Gender differences of airway dimensions in anatomically matched sites on CT in smokers.

PubMed

Kim, Yu-Il; Schroeder, Joyce; Lynch, David; Newell, John; Make, Barry; Friedlander, Adam; Estépar, Raúl San José; Hanania, Nicola A; Washko, George; Murphy, James R; Wilson, Carla; Hokanson, John E; Zach, Jordan; Butterfield, Kiel; Bowler, Russell P; Copdgene Investigators

2011-08-01

There are limited data on, and controversies regarding gender differences in the airway dimensions of smokers. Multi-detector CT (MDCT) images were analyzed to examine whether gender could explain differences in airway dimensions of anatomically matched airways in smokers. We used VIDA imaging software to analyze MDCT scans from 2047 smokers (M:F, 1021:1026) from the COPDGene® cohort. The airway dimensions were analyzed from segmental to subsubsegmental bronchi. We compared the differences of luminal area, inner diameter, wall thickness, wall area percentage (WA%) for each airway between men and women, and multiple linear regression including covariates (age, gender, body sizes, and other relevant confounding factors) was used to determine the predictors of each airway dimensions. Lumen area, internal diameter and wall thickness were smaller for women than men in all measured airway (18.4 vs 22.5 mm(2) for segmental bronchial lumen area, 10.4 vs 12.5 mm(2) for subsegmental bronchi, 6.5 vs 7.7 mm(2) for subsubsegmental bronchi, respectively p < 0.001). However, women had greater WA% in subsegmental and subsubsegmental bronchi. In multivariate regression, gender remained one of the most significant predictors of WA%, lumen area, inner diameter and wall thickness. Women smokers have higher WA%, but lower luminal area, internal diameter and airway thickness in anatomically matched airways as measured by CT scan than do male smokers. This difference may explain, in part, gender differences in the prevalence of COPD and airflow limitation.

Tachykinin receptors and noncholinergic bronchoconstriction in the guinea-pig isolated bronchi.

PubMed

Maggi, C A; Patacchini, R; Rovero, P; Santicioli, P

1991-08-01

The aim of the study was to assess which type(s) of tachykinin receptor mediate the noncholinergic bronchoconstriction produced by activation (electrical field stimulation) of capsaicin-sensitive primary afferents in epithellum-denuded guinea-pig isolated bronchi. Experiments with natural and synthetic tachykinin agonists indicated the presence of both NK-1 and NK-2 receptors at this level. Experiments with the putative NK-1 (L668, 169) or NK-2 (MEN 10,207, MEN 10,376, L659,877, and R396) selective antagonists against NK-1 and NK-2 selective agonists further supported this conclusion. All the tachykinin antagonists tested reduced the noncholinergic bronchoconstriction to field stimulation with the order of potency MEN 10,207 = MEN 10,376 greater than L659,877 greater than L668,169 congruent to R396. In the presence of peptidase inhibitors, the activity of MEN 10,376 toward the noncholinergic bronchoconstriction was slightly reduced, whereas that of L668,169 was increased. These findings demonstrate that both NK-1 and NK-2 receptors mediate the noncholinergic constriction produced by endogenous tachykinins in guinea-pig bronchi and that the relative contribution of NK-2 receptors is greater than that of NK-1. These findings implicate a major role for neurokinin A rather than for substance P as an endogenous bronchoconstrictor in the guinea-pig isolated bronchi. In the presence of peptidase inhibitors, the relative contribution of NK-1 receptors is increased.

Anatomical dimensions of trachea, main bronchi, subcarinal and bronchial angles in fetuses measured ex vivo.

PubMed

Harjeet; Sahni, Daisy; Batra, Yatindra Kumar; Rajeev, Subramanyam

2008-11-01

The increasing opportunities to consider fetal intervention in selected cases of life-threatening malformations have necessitated airway management of fetuses with low gestational age. This study is aimed to determine the anatomical dimensions of trachea, main bronchi, subcarinal and bronchial angles and their correlation to age and crown rump length (CRL) in fetuses. Measurements of tracheo-bronchial dimensions including the subcarinal and bronchial angles with the vertical were taken in specimens obtained from 40 fetuses, varying in CRL from 61 to 270 mm. The incidence of different shapes at the upper end of trachea was studied. The subcarinal and angles of main bronchi with the vertical were measured radiographically with 20% barium sulfate, in another group of 21 fetuses varying in CRL from 63 to 129 mm. Forty fetuses (22 males, 18 females) were analyzed for the dimensions based on CRL (61-130 mm; 131-200 mm; 201-270 mm--CRL 1, 2, and 3 respectively). The internal transverse diameter of trachea was found to increase steadily from 1.87 +/- 0.56 to 2.67 +/- 0.7 mm (P < 0.001) and 3.68 +/- 0.39 mm (P < 0.001) with increasing CRL. Similarly the outer transverse and antero-posterior diameter of the trachea increased steadily with age. Tracheal length was found to increase significantly to 17.48 +/- 2.89 mm and 24.17 +/- 2.3 from 12.72 +/- 2.5 mm (P < 0.001). The length of paries membranaceous increased with gestational age. Although the length of bronchi increased significantly and linearly, subcarinal and bronchial angles did not show any significant changes with age. There was no sexual dimorphism in measurements in the fetuses of corresponding CRL. Oval shaped trachea was found in 60% and circular in 40% of fetuses. The measurements of subcarinal and bronchial angles performed by radiology were almost the same as those measured in trachea separated from fetuses. The internal transverse, outer transverse and antero-posterior diameters, length of trachea and bronchi and circumference of trachea, relate in a linear fashion to CRL and age. However, subcarinal and bronchial angles remained constant.

Gender Differences of Airway Dimensions in Anatomically Matched Sites on CT in Smokers

PubMed Central

Kim, Yu-Il; Schroeder, Joyce; Lynch, David; Newell, John; Make, Barry; Friedlander, Adam; Estépar, Raúl San José; Hanania, Nicola A.; Washko, George; Murphy, James R.; Wilson, Carla; Hokanson, John E.; Zach, Jordan; Butterfield, Kiel; Bowler, Russell P.

2013-01-01

Rationale and Objectives There are limited data on, and controversies regarding gender differences in the airway dimensions of smokers. Multi-detector CT (MDCT) images were analyzed to examine whether gender could explain differences in airway dimensions of anatomically matched airways in smokers. Materials and Methods We used VIDA imaging software to analyze MDCT scans from 2047 smokers (M:F, 1021:1026) from the COPDGene® cohort. The airway dimensions were analyzed from segmental to subsubsegmental bronchi. We compared the differences of luminal area, inner diameter, wall thickness, wall area percentage (WA%) for each airway between men and women, and multiple linear regression including covariates (age, gender, body sizes, and other relevant confounding factors) was used to determine the predictors of each airway dimensions. Results Lumen area, internal diameter and wall thickness were smaller for women than men in all measured airway (18.4 vs 22.5 mm2 for segmental bronchial lumen area, 10.4 vs 12.5 mm2 for subsegmental bronchi, 6.5 vs 7.7 mm2 for subsubsegmental bronchi, respectively p < 0.001). However, women had greater WA% in subsegmental and subsubsegmental bronchi. In multivariate regression, gender remained one of the most significant predictors of WA%, lumen area, inner diameter and wall thickness. Conclusion Women smokers have higher WA%, but lower luminal area, internal diameter and airway thickness in anatomically matched airways as measured by CT scan than do male smokers. This difference may explain, in part, gender differences in the prevalence of COPD and airflow limitation. PMID:21756032

Tachykinin receptors in the guinea-pig isolated bronchi.

PubMed

Maggi, C A; Patacchini, R; Quartara, L; Rovero, P; Santicioli, P

1991-05-17

The aim of the study was to assess which tachykinin receptors mediate the contractile response in the guinea-pig isolated bronchi. Experiments with natural tachykinins and receptor-selective tachykinin agonists were performed in the absence or presence of peptidase inhibitors and in bronchi pretreated with phenoxybenzamine. Both NK-1 (substance P, substance P methylester and septide) and NK-2 (neurokinin A, [beta-Ala8]neurokinin A-(4-10) and MDL 28,564) receptor agonists produced concentration-dependent contraction. NK-3 agonists (senktide and [MePhe7]neurokinin B) were active only at high concentrations. Phenoxybenzamine pretreatment reduced the maximal response to NK-1 agonists and produced a rightward shift of the curve to NK-2 agonists, without depression of the maximum. Five tachykinin antagonists selective for the NK-1 (L 668,169) or the NK-2 (MEN 10,207, MEN 10,376, L 659,877 and R 396) receptor were tested against substance P methylester and [beta-Ala8]neurokinin A-(4-10). The results indicated that these receptor-selective antagonists maintain their characteristic even when tested in a multireceptor assay such as the guinea-pig bronchus. The rank order of potency of NK-2 antagonists against [beta-Ala8]neurokinin A-(4-10) was MEN 10,207 = MEN 10,376 greater than L 659,877 much greater than R 396. This pattern, with the observation of the full agonist activity of MDL 28,564, indicates that in addition to NK-1 receptors, NK-2 receptors also are present in the guinea-pig bronchi and belong to the same subtype (NK-2A) as present in the rabbit pulmonary artery.

beta2-Agonist modulates epithelial gene expression involved in the T- and B-cell chemotaxis and induces airway sensitization in human isolated bronchi.

PubMed

Faisy, Christophe; Pinto, Francisco M; Blouquit-Laye, Sabine; Danel, Claire; Naline, Emmanuel; Buenestado, Amparo; Grassin Delyle, Stanislas; Burgel, Pierre-Régis; Chapelier, Alain; Advenier, Charles; Candenas, Maria-Luz; Devillier, Philippe

2010-02-01

Regular use of beta(2)-adrenoceptor agonists may enhance non-specific airway responsiveness and inflammation. In earlier experimental studies, we showed that prolonged in vitro fenoterol exposure induced airway sensitization via perturbed epithelial regulation of bronchoconstriction. The aim of the present work was to examine the involvement of inflammatory mediator genes and proinflammatory cells and to investigate the role of the bronchial epithelium in these untoward effects. Bronchial tissues were surgically removed from 17 ex-smokers. Bronchial rings and primary cultures of bronchial epithelial cells were incubated with 0.1microM fenoterol for 15h. Levels of mRNA-expression were analyzed using a real-time quantitative reverse transcription-polymerase chain reaction array. Bronchial rings were contracted with endothelin-1 and immune cell infiltration was assessed by immunohistochemistry. Compared to paired controls, fenoterol up-regulated the mRNAs of cytokines/proteins implicated in the recruitment of T and B cells or the activation and proliferation of bronchial epithelial cells (CCL20/MIP-3alpha, FOXA2, PPAR-gamma) in isolated bronchi and in cultured epithelial cells. Fenoterol exposure significantly enhanced CD8(+)-T and differentiated CD138(+)-B-cells infiltration into the bronchi, especially the subepithelial area. Increase in CD8 or CD138 labeling-intensity strongly correlated with rise in maximal contraction to endothelin-1 induced by fenoterol exposure. In summary, our results show that fenoterol modulates the T and B cells chemotaxis possibly via the epithelial chemokine secretion in isolated bronchi from ex-smokers. They also suggest that the infiltration of resident T and B cells into the subepithelial area is associated with an increase in airway responsiveness due to fenoterol exposure. Copyright 2009 Elsevier Ltd. All rights reserved.

Contribution of sensory nerves to LPS-induced hyperresponsiveness of human isolated bronchi.

PubMed

Calzetta, Luigino; Luongo, Livio; Cazzola, Mario; Page, Clive; Rogliani, Paola; Facciolo, Francesco; Maione, Sabatino; Capuano, Annalisa; Rinaldi, Barbara; Matera, Maria Gabriella

2015-06-15

Bacterial lipopolysaccharide (LPS) can induce bronchial hyperresponsiveness (BHR), but the underlying mechanisms remain to be determined. Here, the possible contribution of sensory nerves to LPS-induced BHR was examined in human isolated bronchi to pharmacologically identify the mechanisms underlying this phenomenon. Human isolated bronchial tone was induced by electrical field stimulation (EFS). The responses of airways to LPS, with or without capsaicin desensitization or thiorphan treatment were studied and the transient receptor potential vanilloid type 1 (TRPV1) expression was assessed. We performed similar experiments in the presence of a TRPV1 or a neurokinin (NK) 2 receptor antagonist using SB366791 and GR159897, respectively. LPS increased (≃2.3-fold, P<0.001) the contraction induced by EFS, compared to control tissues. Acute administration of capsaicin enhanced (≃2.3-fold, P<0.001) the EFS-mediated contraction, but did not potentiate the effect of LPS. Thiorphan increased (≃1.3-fold, P<0.05) the contractile response of LPS treated tissues and, at lower frequencies, it enhanced (≃1.7-fold, P<0.001) the capsaicin-induced contraction. In capsaicin-desensitized bronchi, LPS did not modify (P>0.05) the EFS contractile response, nor after treatment with thiorphan. Capsaicin desensitization reduced (≃0.4-fold, P<0.001) the LPS-induced BHR. SB366791 and GR159897 prevented the LPS-induced BHR and the release of NKA. LPS increased (+85.3±9.5%, P<0.01) the surface membrane expression of TRPV1 in parasympathetic ganglia. Our results demonstrate the involvement of capsaicin-sensitive sensory nerves and neutral endopeptidases in LPS-induced BHR of the human bronchi, associated with an upregulation of TRPV1 and release of NKA. Copyright © 2015. Published by Elsevier Inc.

Nerve growth factor enhances cough via a central mechanism of action.

PubMed

El-Hashim, Ahmed Z; Jaffal, Sahar M; Al-Rashidi, Fatma T; Luqmani, Yunus A; Akhtar, Saghir

2013-08-01

The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5h post-treatment. TrkA mRNA was elevated at 0.5h in the bronchi and at 24h in the brainstem while TRPV1 mRNA was elevated from 0.5h to 24h in brainstem and at 24h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough. Copyright © 2013 Elsevier Ltd. All rights reserved.

Experimenatal analysis of the effect of cartilaginous rings on human tracheobronchial flow

NASA Astrophysics Data System (ADS)

Montoya Segnini, Jose; Bocanegra Evans, Humberto; Castillo, Luciano

2016-11-01

We present a set of high-resolution PIV experiments carried out in a refractive index-matched model of a trachea with cartilage rings at Re 2800. Results show a higher vorticity along the walls of the trachea in the model with cartilaginous rings as well as small recirculation areas on the upstream side of the wall cavities created by the rings. Furthermore, the ringed model experiences higher shear stress in the trachea due to the sudden change in the wall position created by the rings. Additionally, small recirculation areas are identified in the cavities between rings. For the smooth model, a stronger separation bubble is observed at the bronchi entrance, generating a stronger shear layer and increasing the wall shear stress on the bottom bronchi wall. The differences observed go against the notion that the main airway, i.e. trachea and main bronchi, may be modeled as smooth. Our results suggest that cartilage rings will have an impact on the wall shear stress and may affect particle deposition, which is of importance in inhaled drug delivery and pollutant deposition in the airway. Additionally, the effects introduced by the rings may change the flow characteristics in further generations.

[Geographical distribution of mortality caused by stomach, trachea, bronchi and lung malignant tumors in Chile].

PubMed

Icaza N, M Gloria; Núñez F, M Loreto; Torres A, Francisco J; Díaz S, Nora L; Várela G, David E

2007-11-01

Maps have played a critical role in public health since 1855, when John Snow associated a cholera outbreak with contaminated water source in London. After cardiovascular diseases, cancer is the second leading cause of death in Chile. Cancer was responsible for 22.7% of all deaths in 1997-2004 period. To describe the geographical distribution of stomach, trachea, bronchi and lung cancer mortality. Mortality statistics for the years 1997-2004, published by the National Statistics Institute and Chilean Ministry of Health, were used. The standardized mortality ratio (SMR) for sex and age quinquennium was calculated for 341 counties in the country. A hierarchical Bayesian analysis of Poisson regression models for SMR was performed. The maps were developed using adjusted SMR (or smoothed) by the Poisson model. There is an excess mortality caused by stomach cancer in south central Chile, from Teno to Valdivia. There is an excess mortality caused by trachea, bronchi and lung cancer in northern Chile, from Copiapó to Iquique. The geographical analysis of mortality caused by cancer shows cluster of counties with an excess risk. These areas should be considered for health care decision making and resource allocation.

Interleukin-1beta-induced hyperresponsiveness to [Sar9,Met(O2)11]substance P in isolated human bronchi.

PubMed

Barchasz, E; Naline, E; Molimard, M; Moreau, J; Georges, O; Emonds-Alt, X; Advenier, C

1999-08-20

Interleukin-1beta has been reported to induce airway hyperresponsiveness in several animal models. In this study, we have investigated whether interleukin-1beta was able to potentiate the contractions of human isolated small bronchi (internal diameter < or = 1 mm) provoked by a specific tachykinin NK1 receptor agonist, [Sar9,Met(O2)11]substance P. Pre-incubation of human isolated small bronchi with interleukin-1beta (10 ng/ml, in Krebs-Henseleit solution, at 21 degrees C for 15 h) potentiated the contractile response to [Sar9,Met(O2)11]substance P. It also increased the [Sar9,Met(O2)11]substance P-induced release of thromboxane B2, the stable metabolite of thromboxane A2. Indomethacin (10(-6) M), a non-specific cyclooxygenase inhibitor, or GR 32191 ((1R-(1alpha(Z)),2beta,3beta,5alpha))-(+)-7-(5-(((1,1' -biphenyl)-4-yl)-methoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl)-4-hept enoic acid, hydrochloride) (10(-6) M), a prostanoid TP-receptor antagonist, blocked the contractions induced by [Sar9,Met(O2)11]substance P both in control experiments and after interleukin-1beta pre-treatment, indicating that prostanoids and thromboxane receptors are directly implicated in the [Sar9,Met(O2)11]substance P-induced contractile response. The thromboxane mimetic U-46619 (10(-8)-10(-6) M) (9,11-dideoxy-11alpha,9alpha-epoxymethano-prostaglandin F2alpha)-induced contractions of human isolated small bronchi were not enhanced by interleukin-1beta pre-treatment, suggesting that no up-regulation of thromboxane receptors occurred. Furthermore, the cyclooxygenase-2 inhibitor CGP 28238 (6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanon e) (10(-6) M) had no direct effect on [Sar9,Met(O2)11]substance P-provoked contractions, but inhibited the interleukin-1beta-induced potentiation of [Sar9,Met(O2)11]substance P response. In conclusion, our results show that interleukin-1beta pre-treatment is able to potentiate the contractions of isolated human small bronchi provoked by [Sar9,Met(O2)11]substance P both by increasing prostanoid synthesis and by inducing a cyclooxygenase-2 pathway.

Scanning electron microscopic study on the microarchitecture of the vascular system in the pigeon lung.

PubMed

Nasu, Tetsuo

2005-10-01

The resin casts of the respiratory and vascular systems in pigeon lung were examined using a scanning electron microscope. The primary bronchi branched to form many secondary bronchi that anastomosed with each other via the parabronchi. Numerous infundibula protruded from the parabronchi via the atria and ramified into the air capillaries. The pulmonary artery entered into the lung and branched into three vessels that coursed the interparabronchial parts. The intraparabronchial arterioles penetrated the gas-exchange tissue to form the anastomosing networks of blood capillaries. The observation of the double casts of the respiratory and vascular systems revealed three-dimensional complicated networks of air capillaries and blood capillaries.

[Virtual reality in video-assisted thoracoscopic lung segmentectomy].

PubMed

Onuki, Takamasa

2009-07-01

The branching patterns of pulmonary arteries and veins vary greatly in the pulmonary hilar region and are very complicated. We attempted to reconstruct anatomically correct images using a freeware program. After uploading the images to a personal computer, bronchi, pulmonary arteries and veins were traced by moving up and down in the images and the location and thickness of the bronchi and pulmonary vasculture were indicated as different-sized cylinders. Next, based on the resulting numerical data, a 3D image was reconstructed using Metasequoia shareware. The reconstructed images can be manipulated by virtual surgical procedures such as reshaping, cutting and moving. These system would be very helpful in complicated video-assisted thoracic surgery such as lung segmentectomy.

Anthracosis and anthracofibrosis.

PubMed

Sigari, Naseh; Mohammadi, Shilan

2009-08-01

To define the clinical, radiographic, and bronchoscopic features, and to describe the occupations of the largest group of patients with anthracosis. All patients who underwent flexible bronchoscopy at 2 Iranian hospitals (Imam Hospital [Tehran], and Tohid Hospital [Sanandaj]), Iran, between April 1982 and June 2006 were considered for inclusion in the study. The demographic data, clinical, and radiographic findings of anthracotic and anthracofibrotic patients were recorded. Of the 14,300 patients, 487 cases of simple anthracosis, and 291 of anthracofibrosis were found. A total of 98.4% female patients were housewives, and 86.4% lived in rural areas. Of the male patients, 40.6% were farmers, 29.6% were manual workers, and 7.5% were miners. Of these, 96% of patients had abnormal chest radiography. On bronchoscopic examination, bilateral bronchial involvement was found in 62.5% of the patients. The condition was confined to the trachea in 0.38% of patients, the bronchi involved were the main bronchus in 37%, the lobar bronchi in 83.2%, and segmental bronchi in 35%. Bronchial narrowing and obstruction was observed in 37.4% of the patients. Anthracosis and anthracofibrosis are neglected conditions that are a common finding on routine bronchoscopic examination. Given the demographic findings, and a review of other reports from developing countries, exposure to combustion of biomass fuel in rural areas is a possible risk factor.

Cellular morphometry of the bronchi of human and dog lungs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, E.S.

1991-03-01

One hundred and thirty-one bronchial samples from 62 patients have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. Complete patient records including occupational and smoking histories, as well as possible exposure to radon, are obtained. In addition, one hundred and sixty-two mongol dog bronchi dissected from different lobes of 23 dog lungs have also been similarly prepared. Ninety-four human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 532 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurementmore » of the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 240 micrographs of dog epithelium from 31 bronchial samples have been entered into COSAS. We have, using the COSAS planimetry program, established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the epithelial cell types of dog bronchi. The data are being used to develop weighting factors for dosimetry and radon risk analysis. 26 refs., 7 figs., 4 tabs.« less

Morphology of presumptive rapidly adapting receptors in the rat bronchus.

PubMed Central

Kappagoda, C T; Skepper, J N; McNaughton, L; Siew, E E; Navaratnam, V

1990-01-01

The present investigation was undertaken in rats to determine whether sensory nerves exist in apposition to the bronchial microvessels which may function as rapidly adapting receptors (RAR). The primary and secondary bronchi on both sides were removed and processed for light and electron microscopy. Nerves were frequently found in relation to venules external to the muscle coat of bronchi. They comprised myelinated axons which ended individually as non-myelinated convoluted terminals enclosed within a loose capsule of attenuated cells. Serial sections showed that these terminals were not related to ganglion cells. Cervical vagal section and injection of HRP-WGA into the nodose ganglion provided corroborative evidence of the sensory nature of these terminals. Vagal section caused degenerative changes in the encapsulated nerve terminals in the bronchial walls and horseradish peroxidase labelling was demonstrable in such terminals. Moreover, immunocytochemical studies demonstrated the presence of calcitonin gene regulated peptide and substance P in these structures. It is suggested that they comprise the RAR. Encapsulated nerve terminals were not found in the epithelial layer, in the submucous coat or in the muscularis of bronchi. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:1691164

A step-by-step development of real-size chest model for simulation of thoracoscopic surgery.

PubMed

Morikawa, Toshiaki; Yamashita, Makoto; Odaka, Makoto; Tsukamoto, Yo; Shibasaki, Takamasa; Mori, Shohei; Asano, Hisatoshi; Akiba, Tadashi

2017-08-01

For the purpose of simulating thoracoscopic surgery, we have conducted stepwise development of a life-like chest model including thorax and intrathoracic organs. First, CT data of the human chest were obtained. First-generation model: based on the CT data, each component of the chest was made from a 3D printer. A hard resin was used for the bony thorax and a rubber-like resin for the vessels and bronchi. Lung parenchyma, muscles and skin were not created. Second-generation model: in addition to the 3D printer, a cast moulding method was used. Each part was casted using a 3D printed master and then assembled. The vasculature and bronchi were casted using silicon resin. The lung parenchyma and mediastinum organs were casted using urethane foam. Chest wall and bony thorax were also casted using a silicon resin. Third-generation model: foamed polyvinyl alcohol (PVA) was newly developed and casted onto the lung parenchyma. The vasculature and bronchi were developed using a soft resin. A PVA plate was made as the mediastinum, and all were combined. The first-generation model showed real distribution of the vasculature and bronchi; it enabled an understanding of the anatomy within the lung. The second-generation model is a total chest dry model, which enabled observation of the total anatomy of the organs and thorax. The third-generation model is a wet organ model. It allowed for realistic simulation of surgical procedures, such as cutting, suturing, stapling and energy device use. This single-use model achieved realistic simulation of thoracoscopic surgery. As the generation advances, the model provides a more realistic simulation of thoracoscopic surgery. Further improvement of the model is needed. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Computed-tomographic and conventional linear-tomographic evaluation of tracheobronchial lesions for laser photoresection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pearlberg, J.L.; Sandler, M.A.; Kvale, P.

1985-03-01

Laser therapy is a new modality for treatment of airway lesions. The authors examined 18 patients prior to laser photoresection of tracheobronchial lesions. Thirteen had cancers involving the distal trachea, carina, and/or proximal bronchi; five had benign lesions of the middle or proximal trachea. Each patient was examined by conventional linear tomography (CLT) and computed tomography (CT). CT was valuable in patients who had lesions of the distal trachea, carina, and/or proximal bronchi. Its particular usefulness, and its advantage relative to CLT, consisted in its ability to delineate vascular structures adjacent to the planned area of photoresection. Neither CLT normore » CT was helpful in evaluation of benign lesions of the proximal trachea.« less

Autoradiographic localization of beta-adrenoceptors in asthmatic human lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spina, D.; Rigby, P.J.; Paterson, J.W.

1989-11-01

The autoradiographic distribution and density of beta-adrenoceptors in human non-diseased and asthmatic bronchi were investigated using (125I)iodocyanopindolol (I-CYP). Analysis of the effects of the beta-adrenoceptor antagonists on I-CYP binding demonstrated that betaxolol (20 nM, beta 1-selective) had no significant effect on specific grain density in either nonasthmatic or asthmatic human bronchus, whereas ICI-118551 (20 nM, beta 2-selective) inhibited I-CYP binding by 85 +/- 9% and 89 +/- 3%, respectively. Thus, homogeneous populations of beta 2-adrenoceptors existed in bronchi from both sources. Large populations of beta-adrenoceptors were localized to the bronchial epithelium, submucosal glands, and airway smooth muscle. Asthmatic bronchial tissuemore » featured epithelial damage with exfoliated cells associated with luminal mucus plugs. A thickened basement membrane and airway smooth muscle hyperplasia were also evident. High levels of specific I-CYP binding were also detected over asthmatic bronchial smooth muscle, as assessed by autoradiography and quantitation of specific grain densities. Isoproterenol and fenoterol were 10- and 13-fold less potent, respectively, in bronchi from asthmatic lung than in those from nonasthmatic lung. However, this attenuated responsiveness to beta-adrenoceptor agonists was not caused by reduced beta-adrenoceptor density in asthmatic airways. A defect may exist in the coupling between beta-adrenoceptors and postreceptor mechanisms in severely asthmatic lung.« less

Second-messenger regulation of sodium transport in mammalian airway epithelia.

PubMed Central

Graham, A; Steel, D M; Alton, E W; Geddes, D M

1992-01-01

1. Sodium absorption is the dominant ion transport process in conducting airways and is a major factor regulating the composition of airway surface liquid. However, little is known about the control of airway sodium transport by intracellular regulatory pathways. 2. In sheep tracheae and human bronchi mounted in Ussing chambers under short circuit conditions, the sodium current can be isolated by pretreating tissues with acetazolamide (100 microM) to inhibit bicarbonate secretion, bumetanide (100 microM) to inhibit chloride secretion and phloridzin (200 microM) to inhibit sodium-glucose cotransport. This sodium current consists of amiloride-sensitive (57%) and amiloride-insensitive (43%) components. 3. The regulation of the isolated sodium current by three second messenger pathways was studied using the calcium ionophore A23187 to elevate intracellular calcium, a combination of forskolin and the phosphodiesterase inhibitor zardaverine to elevate intracellular cyclic AMP, and the phorbol ester 12,13-phorbol dibutyrate (PDB) to stimulate protein kinase C. 4. In sheep trachea, A23187 produces a dose-related inhibition of the sodium current with maximal effect (38% of ISC) at 10 microM and IC50 1 microM. This response affects both the amiloride-sensitive and insensitive components of the sodium current and is not altered by prior stimulation of protein kinase C or elevation of intracellular cyclic AMP. In human bronchi, A23187 (10 microM) produced a significantly greater inhibition of ISC (68%), a response which was unaffected by prior treatment with PDB or forskolin-zardaverine. 5. In sheep trachea, stimulation of protein kinase C with PDB produced a dose-related inhibition of ISC maximal (56% of ISC) at 50 nM (IC50 7 nM). This response was abolished by amiloride (100 microM) pretreatment suggesting a selective effect on the amiloride-sensitive component of the sodium current. The response was not altered by prior elevation of intracellular calcium or cyclic AMP. PDB (10 nM) caused a similar inhibition of ISC in human bronchi (43%). The effect of PKC stimulation following pretreatment with A23187 was diminished in human bronchi. Elevating intracellular cyclic AMP did not alter this response. 6. Addition of forskolin (1 microM) together with the phosphodiesterase inhibitor zardaverine (100 microM) produced a mean 35-fold increase in intracellular cyclic AMP in sheep trachea. This was associated with a small, but significant, 6% transient increase in ISC followed by a significant 4% fall. Neither effect could be abolished by amiloride pretreatment. In human bronchi, a small decrease in ISC which could not be distinguished from that occurring in controls was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1464841

High-resolution CT assessment of the pediatric airways: structure and function

NASA Astrophysics Data System (ADS)

Kramer, Sandra S.; Hoffman, Eric A.; Amirav, Israel

1994-05-01

The airway has always been a central focus for respiratory pathology in infants and children. Imaging of the larynx, trachea, and the central bronchi can be readily accomplished by radiographic or conventional CT techniques. Newer high resolution CT (HRCT) techniques have extended our view of the bronchi peripherally to the limits of scanner resolution, i.e., to bronchial generations 7 - 9, and rapid volumetric CT data acquisitions have made it possible to follow the same lung anatomic level through the rapidly occurring changes in a series of experimental protocols. These techniques together with a custom designed computer software program for image display and analysis have enabled us to objectively study changes in airway caliber and lung density that occurred in an animal mode of airway reactivity and thereby relate structure with function in the airways.

[Expandable stents and composite prosthesis].

PubMed

Baldeyrou, P

1999-11-01

Today, numerous expandable and mixed silicone metallic stents for trachea and bronchi are available. Among the many technical propositions, Nitinol is a new alloy with promising potential, offering the advantage of shape memory. The right stent is the one which best meets the needs of the individual stenotic situation as evaluated by endoscopy and CT. Sufficient experience has been acquired only with the Dumon stent, giving exact information about its qualities and possible complications. The new stents are thinner. Some can be inserted under fluoroscopic and fibroscopic control. They are presumed to produce fewer complications an provide answers to some still unresolved questions such as dyskinesia or stenosis on short bronchi. They appear to be more easily inserted on the tracheo-bronchial tree. More experience is needed to satisfactorily identify specific indications and contraindications. A prospective registry will be important to obtain comparative information more quickly.

Pediatric Pulmonary Artery Rehabilitation: A Review of Our Experience and a Novel Approach Using Bronchial Blockers.

PubMed

Winch, Peter D; Tumin, Dmitry; Moore, Jeffrey; Vizzini, Samantha J; Berman, Darren P; Naguib, Aymen N

2018-05-09

Recent advances in the field of pediatric interventional cardiology have resulted in therapies for patients in need of augmented pulmonary artery (PA) flow. Catheter-based PA rehabilitation can be performed safely but not without the potential risk of pulmonary hemorrhage. When severe, this bleeding has the ability to contaminate the bronchi and trachea, and possibly occlude the endotracheal tube. This can result in a critical inability to ventilate and oxygenate these patients. Herein, we review our institutional experience with pulmonary hemorrhage associated with these procedures and the feasibility of predicting this outcome. The secondary aim was to discuss our novel anesthetic approach to a select group of these patients, involving the use of bronchial blockers to preemptively prevent contamination of bilateral bronchi and occlusion of the endotracheal tube.

Multiple bronchoceles in a non-asthmatic patient with allergic bronchopulmonary aspergillosis.

PubMed

Amin, Muhammad Umar; Mahmood, Rabia

2008-09-01

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction due to a fungus, Aspergillus fumigatus. It is typically seen in patients with long-standing asthma. Our patient was a non-asthmatic 18 years old male who presented with chronic cough for 2 years. Peripheral blood eosinophilia and elevated scrum IgE were observed. His x-ray chest revealed v-shaped opacity in the left upper lobe close to the hilum. High resolution computed tomographic scan of the chest revealed multiple dilated bronchi filled with mucous (bronchoceles) and central bronchiectasis (CB) involving main segmental bronchi. Central bronchiectasis (CB) was typical of ABPA but bronchocele formation was a rare manifestation of the disease. The patient was managed with oral prednisolone and was relieved of his symptoms. Occurrence of ABPA in non-asthmatics is very rare and deserves reporting.

Bronchial abnormalities found in a consecutive series of 40 brachycephalic dogs.

PubMed

De Lorenzi, Davide; Bertoncello, Diana; Drigo, Michele

2009-10-01

To detect abnormalities of the lower respiratory tract (trachea, principal bronchi, and lobar bronchi) in brachycephalic dogs by use of endoscopy, evaluate the correlation between laryngeal collapse and bronchial abnormalities, and determine whether dogs with bronchial abnormalities have a less favorable postsurgical long-term outcome following correction of brachycephalic syndrome. Prospective case series study. 40 client-owned brachycephalic dogs with stertorous breathing and clinical signs of respiratory distress. Brachycephalic dogs anesthetized for pharyngoscopy and laryngoscopy between January 2007 and June 2008 underwent flexible bronchoscopy for systematic evaluation of the principal and lobar bronchi. For dogs that underwent surgical correction of any component of brachycephalic syndrome, owners rated surgical outcome during a follow-up telephone survey. Correlation between laryngeal collapse and bronchial abnormalities and association between bronchial abnormalities and long-term outcome were assessed. Pugs (n = 20), English Bulldogs (13), and French Bulldogs (7) were affected. A fixed bronchial collapse was recognized in 35 of 40 dogs with a total of 94 bronchial stenoses. Abnormalities were irregularly distributed between hemithoraces; 15 of 94 bronchial abnormalities were detected in the right bronchial system, and 79 of 94 were detected in the left. The left cranial bronchus was the most commonly affected structure, and Pugs were the most severely affected breed. Laryngeal collapse was significantly correlated with severe bronchial collapse; no significant correlation was found between severity of bronchial abnormalities and postsurgical outcome. Bronchial collapse was a common finding in brachycephalic dogs, and long-term postsurgical outcome was not affected by bronchial stenosis.

Particle exposures and infections

EPA Science Inventory

Particle exposures increase the risk for human infections. Particles can deposit in the nose, pharynx, larynx, trachea, bronchi, and distal lung and, accordingly, the respiratory tract is the system most frequently infected after such exposure; however, meningitis also occurs. Ci...

LASER BIOLOGY AND MEDICINE: Combination of fluorescence imaging and local spectrophotometry in fluorescence diagnostics of early cancer of larynx and bronchi

NASA Astrophysics Data System (ADS)

Sokolov, Vladimir V.; Filonenko, E. V.; Telegina, L. V.; Boulgakova, N. N.; Smirnov, V. V.

2002-11-01

The results of comparative studies of autofluorescence and 5-ALA-induced fluorescence of protoporphyrin IX, used in the diagnostics of early cancer of larynx and bronchi, are presented. The autofluorescence and 5-ALA-induced fluorescence images of larynx and bronchial tissues are analysed during the endoscopic study. The method of local spectrophotometry is used to verify findings obtained from fluorescence images. It is shown that such a combined approach can be efficiently used to improve the diagnostics of precancer and early cancer, to detect a primary multiple tumours, as well as for the diagnostics of a residual tumour or an early recurrence after the endoscopic, surgery or X-ray treatment. The developed approach allows one to minimise the number of false-positive results and to reduce the number of biopsies, which are commonly used in the white-light bronchoscopy search for occult cancerous loci.

Tracheo-bronchial soft tissue and cartilage resonances in the subglottal acoustic input impedance.

PubMed

Lulich, Steven M; Arsikere, Harish

2015-06-01

This paper offers a re-evaluation of the mechanical properties of the tracheo-bronchial soft tissues and cartilage and uses a model to examine their effects on the subglottal acoustic input impedance. It is shown that the values for soft tissue elastance and cartilage viscosity typically used in models of subglottal acoustics during phonation are not accurate, and corrected values are proposed. The calculated subglottal acoustic input impedance using these corrected values reveals clusters of weak resonances due to soft tissues (SgT) and cartilage (SgC) lining the walls of the trachea and large bronchi, which can be observed empirically in subglottal acoustic spectra. The model predicts that individuals may exhibit SgT and SgC resonances to variable degrees, depending on a number of factors including tissue mechanical properties and the dimensions of the trachea and large bronchi. Potential implications for voice production and large pulmonary airway tissue diseases are also discussed.

Unscheduled DNA synthesis in human bronchial epithelium treated with various chemical carcinogens in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishikawa, T.; Ide, F.; Kodama, K.

1984-07-01

A system was developed in which organ culture of human bronchial epithelium was used in combination with autoradiography for quantitative measurement of unscheduled DNA synthesis (UDS) in bronchial epithelial cells. Human bronchi obtained at surgery were cut into small sections and treated with various carcinogens plus (methyl-/sup 3/H)thymidine in short-term organ culture. Significant numbers of silver grains, indicating UDS, were detected on the nuclei of epithelial cells of human bronchi treated with carcinogens, and the numbers were proportional to the concentrations of carcinogens. In this system seven representative carcinogens induced UDS. Four active metabolites of benzo(a)pyrene, and benz(a)anthracene also weremore » found to induce very active UDS in human bronchial epithelium. These findings suggest that human bronchial epithelial cells can repair different types of DNA modification induced by chemical carcinogens.« less

Nedocromil sodium modulates nonadrenergic, noncholinergic bronchoconstrictor nerves in guinea pig airways in vitro.

PubMed

Verleden, G M; Belvisi, M G; Stretton, C D; Barnes, P J

1991-01-01

Nonadrenergic, noncholinergic (NANC) neural bronchoconstrictor responses in guinea pig airways are due to the release of tachykinins from sensory nerves. We have performed an in vitro study using electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) in guinea pig bronchi to investigate the effect of nedocromil sodium (NS) on NANC bronchoconstrictor responses. NS inhibited NANC bronchoconstriction in bronchi in a concentration-dependent manner, with a maximum inhibition of 40 +/- 4% (p less than 0.001, n = 6) at 100 microM. Cromolyn sodium, however, produced only 9 +/- 8% inhibition at the same molar concentration (p less than 0.05). NS did not affect the contractile response to substance P, nor did it modulate the cholinergic bronchoconstrictor response to EFS in tracheal smooth muscle. These results indicate that NS may modulate the release of tachykinins from airway sensory nerves.

Microscopic anatomy of the lower respiratory tract of the grey short-tailed opossum (Monodelphis domestica).

PubMed

Cope, L A; Henry, R W; Reed, R B

2012-04-01

The respiratory tracts of seven grey short-tailed opossums were histologically examined. Six opossums were prepared by perfusion with buffered formalin. Opossum seven was perfused with gluteraldehyde. Samples taken from the respiratory passages and lungs of specimens 1-6 were stained with haematoxylin and eosin. A mixture of methylene and azure blue was used for specimen 7. The trachea and right and left principal bronchi are lined with a pseudostratified ciliated columnar epithelium with occasional goblet cells. The secondary and tertiary bronchi and the primary and secondary bronchioles are lined by a simple ciliated columnar epithelium. The terminal bronchioles and a portion of the respiratory bronchioles are lined by a simple ciliated cuboidal epithelium. The terminal portion of the respiratory bronchioles and the alveolar ducts are lined with simple squamous epithelium. Alveoli are lined by type I and II pneumocytes. Tracheal glands are present in the tela submucosa. The fibromusculocartilaginous tunic of the trachea consists of c-shaped cartilage rings and the trachealis muscle. A lamina muscularis mucosa begins in the intrapulmonary portion of the principal bronchus and continues into the respiratory bronchioles. Bronchial glands are present in the propria submucosa and tela submucosa of the principal bronchi. The musculocartilaginous tunic is localized to the extrapulmonary portion of the principal bronchus. The bronchial cartilages are irregular shaped plates and limited to the extrapulmonary portion of the principal bronchus. The visceral pleura is a simple squamous mesothelium covering the outer surface of the lung. © 2011 Blackwell Verlag GmbH.

Morphological considerations pertaining to recognition of atrial isomerism. Consequences for sequential chamber localisation.

PubMed Central

Macartney, F J; Zuberbuhler, J R; Anderson, R H

1980-01-01

The atrial morphology and venous connections were assessed "blind" in 51 necropsy specimens from patients with visceral heterotaxy. This was compared with bronchial morphology as established by dissection. Six specimens were found to have both atria and bronchi in situs solitus or inversus, and were rejected. In the remainder, atrial isomerism was diagnosed, though this required minor revision of the atrial assessment in two patients. Thirty-four patients had isomeric right atria and bronchi, while 11 had isomeric left atria and bronchi. In seven cases, splenic status was unknown, but in seven of the remaining 38 (18.4%) atrial isomerism was not associated with either asplenia or polysplenia. Nevertheless, right isomerism was strongly associated with total anomalous pulmonary venous drainage (as is asplenia) and left isomerism was likewise associated with interruption of the inferior vena cava (as is polysplenia). Bilateral superior venae cavae and hepatic veins, and absence of the coronary sinus, were frequent in both forms of isomerism (as they are in asplenia and polysplenia). These findings suggest that atrial situs can be defined as solitus inversus, right isomerism, and left isomerism. This determination of atrial situs is quite independent of any other abnormalities of visceral situs. The high incidence of anomalies of both venous return and common atrium resulted in presumed complete mixing of blood at atrial level in all but one patient (97.8%), making the haemodynamic connection between atria and ventricles almost always ambiguous. To describe this anatomical connection as ambiguous when there are two ventricles present is therefore no more than recognition of anatomical and haemodynamic reality. Images PMID:7459148

High-fidelity simulation of lung isolation with double-lumen endotracheal tubes and bronchial blockers in anesthesiology resident training.

PubMed

Failor, Erin; Bowdle, Andrew; Jelacic, Srdjan; Togashi, Kei

2014-08-01

Demonstrate the feasibility of using the AirSim Bronchi airway simulator to teach residents how to manage lung isolation with double-lumen endotracheal tubes and bronchial blockers and evaluate their performance with a detailed checklist. Prospective observational study. University anesthesiology residency training program. Anesthesiology residents taking a cardiothoracic anesthesiology rotation. Residents were instructed in 7 tasks using the AirSim Bronchi: The use of the fiberoptic bronchoscope, methods for placing left and right double-lumen endotracheal tubes and 3 bronchial blockers (Univent, Arndt, and Cohen), and application of continuous positive airway pressure (CPAP) to the unventilated lung. Two to 3 weeks later, checklists and a detailed scoring system were used to assess performance. Residents rated the curriculum and their own confidence in performing the tasks using a 5-point Likert scale. Thirteen residents completed the curriculum. Their median Likert scale ratings of the curriculum based on a questionnaire with 6 items ranged from 4 to 5 of 5. Resident confidence scores for each lung isolation technique improved after the simulation training, with the median gain ranging from 0.5 to 1.5 Likert levels depending on the task. The largest improvement occurred with the bronchial blockers (p<0.05). The median performance score for the 7 tasks combined was 88% of the maximum possible points. The authors used the AirSim Bronchi simulator in a novel simulation curriculum to teach lung-isolation techniques to anesthesiology residents and evaluated performance using a detailed checklist scoring system. This curriculum is a promising educational tool. Copyright © 2014 Elsevier Inc. All rights reserved.

Cellular morphometry of the bronchi of human and dog lungs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, E.S.

1991-09-01

One hundred and forty-seven bronchial samples (generations 3--6) from 66 patients (62 usable; 36 female, 26 male; median age 61) have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. In addition, one hundred and fifty-six mongol dog bronchi (generations 2--6) dissected from different lobes of 26 dog lungs have also been similarly prepared. One hundred and twenty-seven human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 655 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurement ofmore » the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 328 micrographs of dog epithelium from 33 bronchial samples have been used to measure the distances of basal and mucous cell nuclei to the epithelial free surface and have been entered into COSAS. Using the COSAS planimetry program, we continue to expand our established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the same 5 epithelial cell types of dog bronchi. Our micrographs of human bronchial epithelium have allowed us to analyze the recent suggestion that the DNA of lymphocytes may be subject to significant damage from Rn progeny while within the lung. Since the last progress report three papers have been submitted for publication. 17 refs., 4 tabs.« less

Involvement of the TRPV1 receptor in plasma extravasation in airways of rats treated with an angiotensin-converting enzyme inhibitor.

PubMed

de Oliveira, Janiana Raíza Jentsch Matias; Otuki, Michel Fleith; Cabrini, Daniela Almeida; Brusco, Indiara; Oliveira, Sara Marchesan; Ferreira, Juliano; André, Eunice

2016-12-01

Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of hypertension, congestive heart failure and renal disease, and are considered relatively safe and generally well-tolerated drugs. However, adverse effects of ACEIs have been reported, including non-productive cough and angioedema, which can lead to poor adherence to therapy. The mechanisms by which ACEIs promote adverse effects are not fully elucidated, although increased bradykinin plasma levels following ACEI therapy seem to play an important role. Since bradykinin can sensitise the transient potential vanilloid receptor 1 (TRPV1), we investigated the role of TRPV1 in plasma extravasation in the trachea and bronchi of rats treated with the ACEI captopril. We observed that intravenous (i.v.) administration of captopril did not cause plasma extravasation in the trachea or bronchi of spontaneously breathing rats, but induced plasma extravasation in the trachea and bronchi of artificially ventilated rats. The intratracheal (i.t.) instillation of capsaicin or bradykinin also induced an increase in plasma extravasation in the trachea and bronchi of artificially ventilated rats. As expected, capsaicin-induced plasma extravasation was inhibited by i.t. pretreatment with the TRPV1 selective antagonist capsazepine (CPZ) while bradykinin-induced plasma extravasation was reduced by i.t. pretreatment with the selective B 2 receptor antagonist Icatibant, originally known as HOE 140 (HOE). Interestingly, bradykinin-induced plasma extravasation was also inhibited by CPZ. The pretreatment with HOE and CPZ, singly or in combination and at doses which do not cause inhibitory effects per se, significantly inhibited the plasma extravasation induced by captopril treatment in artificially ventilated rats. In addition, treatment with a high dose of capsaicin in newborn rats, which induces degeneration of TRPV1-expressing sensory neurons, abolished both capsaicin and captopril-induced plasma extravasation in artificially ventilated rats. In conclusion, our study identified that captopril treatment promoted sensitisation of TRPV1, via B 2 receptor activation, inducing plasma extravasation in the airways of mechanically ventilated rats. The present findings add a new view about the role of TRPV1 in the plasma extravasation induced by captopril and could to contribute to the elucidation of mechanisms by which ACEI induces adverse effects on airways. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Treatment by electrocoagulation in malignant tracheobronchial pathology].

PubMed

Frizzelli, R

1986-01-01

The author reports his experience of electrocoagulation used to remove tumoral obstruction of the trachea and primary bronchi. Endoscopic electrocoagulation using a fibrobronchoscope is a useful method. Its results and its cost are of interest, as confirmed by experience in 17 patients.

Differences in the distribution and characteristics of tachykinin NK1 binding sites between human and guinea pig lung.

PubMed Central

Walsh, D A; Salmon, M; Featherstone, R; Wharton, J; Church, M K; Polak, J M

1994-01-01

1. The distribution and characteristics of tachykinin NK1 binding sites have been compared in human and guinea pig lung using quantitative in vitro receptor autoradiography with [125I]-Bolton Hunter-labelled substance P ([125I]-BH-SP). In addition, the effects on these sites of ovalbumin sensitization and challenge have been determined in guinea pig lung. 2. [125I]-BH-SP bound specifically and with high affinity to microvascular endothelium in both human and guinea pig lung, but to bronchial smooth muscle and pulmonary artery media in only guinea pig lung. 3. Specific binding of [125I]-BH-SP to guinea pig bronchial smooth muscle was positively correlated with airway diameter in the range 150-800 microns and was less dense in trachea than in main bronchi. 4. [125I]-BH-SP binding was inhibited by tachykinins with rank orders of affinity of SP > NKA > NKB (human microvessels) and SP > NKA = NKB (guinea pig bronchi and pulmonary arteries). NKA displayed a higher affinity for [125I]-BH-SP binding sites in human microvessels than in guinea pig tissues (P < 0.0001), indicating differences in selectivity for tachykinins between human and guinea pig NK1 receptors. 5. In both human and guinea pig lung, [125I]-BH-SP binding was inhibited by the specific tachykinin receptor antagonists FK888 (NK1 selective antagonist) and FK224 (mixed NK1/NK2 antagonist), with FK888 displaying equal affinity to SP and > 500 times higher affinity than FK224. SP, NKA, NKB and FK888 exhibited similar affinities for [125I]-BH-SP binding sites in both guinea pig arteries and bronchi.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 2 PMID:7534186

Cellular morphometry of the bronchi of human and dog lungs. Progress report, April 1, 1991--October 1, 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robbins, E.S.

1991-09-01

One hundred and forty-seven bronchial samples (generations 3--6) from 66 patients (62 usable; 36 female, 26 male; median age 61) have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. In addition, one hundred and fifty-six mongol dog bronchi (generations 2--6) dissected from different lobes of 26 dog lungs have also been similarly prepared. One hundred and twenty-seven human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 655 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurement ofmore » the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 328 micrographs of dog epithelium from 33 bronchial samples have been used to measure the distances of basal and mucous cell nuclei to the epithelial free surface and have been entered into COSAS. Using the COSAS planimetry program, we continue to expand our established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the same 5 epithelial cell types of dog bronchi. Our micrographs of human bronchial epithelium have allowed us to analyze the recent suggestion that the DNA of lymphocytes may be subject to significant damage from Rn progeny while within the lung. Since the last progress report three papers have been submitted for publication. 17 refs., 4 tabs.« less

Congenital Tracheobronchomegaly (Mounier-Kuhn Syndrome) in a Woman with Human Immunodeficiency Virus: A Case Report.

PubMed

Fletcher, Amanda; Stowell, Justin; Jamoulis, Socrates

2017-04-04

Congenital tracheobronchomegaly (Mounier-Kuhn Syndrome, MKS) is a rare idiopathic disorder characterized by dilation of the central airways, including the trachea and first through fourth order bronchi. MKS disproportionately affects men and results in chronic respiratory tract infections. The diagnosis is made through the synthesis of clinical and radiological data. Here we report a unique case of MKS in a patient with human immunodeficiency virus (HIV) infection. A 45-year-old African American woman with a past medical history of HIV, tobacco and recreational drug abuse, chronic obstructive pulmonary disease, sleep apnea, and a 15-year history of recurrent respiratory infections presented with dyspnea, wheezing, a productive cough, increased yellow-green sputum production, and subjective fevers. Computerized tomography (CT) of the chest revealed striking dilation of the trachea and central bronchi. Fiberoptic bronchoscopy demonstrated a dilated trachea and bronchial tree with complete collapse of the trachea and bilateral mainstem bronchi during expiration. Serial imaging over 14 years allowed the radiologist to confidently diagnose her underlying disorder and recommend appropriate clinical management, which included mucolytics, chest physiotherapy, prophylactic vaccinations, and antibiotics during infectious exacerbations. To the best of our knowledge, there is only one reported case of MKS in the setting of HIV in the English literature. We report the second such case and outline the clinical presentation, diagnostic criteria, and management of MKS with the hope that increased awareness will prevent delayed or misdiagnosis for patients with MKS. This case highlights the common diagnostic delay for MKS and the need to include MKS in the differential diagnosis of recurrent respiratory tract infections.

FLOW SIMULATION IN THE HUMAN UPPER RESPIRATORY TRACT

EPA Science Inventory

ABSTRACT

Computer simulations of airflow patterns within the human upper respiratory tract (URT) are presented. The URT model includes airways of the head (nasal and oral), throat (pharyngeal and laryngeal), and lungs (trachea and main bronchi). The head and throat mor...

Endoscopic tissue autofluorescence measurements in the upper aerodigestive tract and the bronchi

NASA Astrophysics Data System (ADS)

Braichotte, Daniel; Wagnieres, Georges A.; Monnier, Philippe; Savary, Jean-Francois; Bays, Roland; van den Bergh, Hubert; Chatelain, Andre

1991-11-01

A single multimode optical fiber is used to excite and collect tissue autofluorescence as well as the fluorescence of an IV-injected fluorescent tumor marker. Measurements of the relative fluorescence intensity of a tumor marker as a function of the time after IV injection permit measurement of the kinetics of this substance in tumor, normal tissue, and skin. The authors believe that these are the first measurements of this kind in patients. Furthermore, the autofluorescence spectrum generated at several excitation wavelengths in different tissues is compared, for instance in the oesophagus, the bronchi, and the tongue. The measuring system is based on an optical multichannel analyzer which measures the fluorescence excited by monochromatic radiation from a spectrally filtered Xe lamp. A correlation between the observed pharmacokinetics and tumor properties like the degree of vascularization is of fundamental importance for each selected tumor marker. Also, the results of these measurements are used for the optical detection of tumors.

Combination of fluorescence imaging and local spectrophotometry in fluorescence diagnostics of early cancer of larynx and bronchi

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sokolov, Vladimir V; Filonenko, E V; Telegina, L V

2002-11-30

The results of comparative studies of autofluorescence and 5-ALA-induced fluorescence of protoporphyrin IX, used in the diagnostics of early cancer of larynx and bronchi, are presented. The autofluorescence and 5-ALA-induced fluorescence images of larynx and bronchial tissues are analysed during the endoscopic study. The method of local spectrophotometry is used to verify findings obtained from fluorescence images. It is shown that such a combined approach can be efficiently used to improve the diagnostics of precancer and early cancer, to detect a primary multiple tumours, as well as for the diagnostics of a residual tumour or an early recurrence after themore » endoscopic, surgery or X-ray treatment. The developed approach allows one to minimise the number of false-positive results and to reduce the number of biopsies, which are commonly used in the white-light bronchoscopy search for occult cancerous loci. (laser biology and medicine)« less

Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs.

PubMed

Turner, Debra J; Noble, Peter B; Lucas, Matthew P; Mitchell, Howard W

2002-10-01

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0-20 cmH(2)O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls (P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi (P < 0.01) and smooth muscle strips (P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

Particle Deposition in Human Lungs due to Varying Cross-Sectional Ellipticity of Left and Right Main Bronchi

NASA Astrophysics Data System (ADS)

Roth, Steven; Oakes, Jessica; Shadden, Shawn

2015-11-01

Particle deposition in the human lungs can occur with every breathe. Airbourne particles can range from toxic constituents (e.g. tobacco smoke and air pollution) to aerosolized particles designed for drug treatment (e.g. insulin to treat diabetes). The effect of various realistic airway geometries on complex flow structures, and thus particle deposition sites, has yet to be extensively investigated using computational fluid dynamics (CFD). In this work, we created an image-based geometric airway model of the human lung and performed CFD simulations by employing multi-domain methods. Following the flow simulations, Lagrangian particle tracking was used to study the effect of cross-sectional shape on deposition sites in the conducting airways. From a single human lung model, the cross-sectional ellipticity (the ratio of major and minor diameters) of the left and right main bronchi was varied systematically from 2:1 to 1:1. The influence of the airway ellipticity on the surrounding flow field and particle deposition was determined.

Estimation of the site of wheezes in pulmonary emphysema: airflow simulation study by the use of A 4D lung model.

PubMed

Kitaoka, Hiroko; Cok, Salim

2013-01-01

Adventitious lung sounds in pulmonary emphysema, wheezes, are continuous musical sounds during expiration with 400 Hz or more. The textbook tells that expiratory airflow limitation in emphysema occurs at the peripheral airways and that wheezes are generated there. We have recently proposed a novel hypothesis based on image analysis and theoretical consideration that expiratory airflow limitation in emphysema occurs at the intra-mediastinal airway (trachea, main bronchi, and right lobar bronchi) due to compression by overinflated lungs. We performed expiratory airflow simulation by the use of a 4D finite element lung model, and found periodical vortex release with 300-900 Hz at the end of protrusion of the the tracheal posterior wall. Relationship between the peak frequency of pressure fluctuation and airflow velocity was in agreement with Strahal's law either in normal or emphysematous condition. Contrarily, airflow simulation in a small bronchus (1.5 mm in diameter) indicated no apparent periodic vortex release.

Can Bronchoscopic Airway Anatomy Be an Indicator of Autism?

ERIC Educational Resources Information Center

Stewart, Barbara A.; Klar, Amar J. S.

2013-01-01

Bronchoscopic evaluations revealed that some children have double branching of bronchi (designated "doublets") in the lower lungs airways, rather than normal, single branching. Retrospective analyses revealed only one commonality in them: all subjects with doublets also had autism or autism spectrum disorder (ASD). That is, 49 subjects exhibited…

Treatment of diffuse tracheomalacia secondary to relapsing polychondritis with continuous positive airway pressure.

PubMed

Adliff, M; Ngato, D; Keshavjee, S; Brenaman, S; Granton, J T

1997-12-01

Relapsing polychondritis (RP) is a rare disease characterized by recurrent inflammation and destruction of the cartilaginous structures. Tracheobronchial chondritis is a dreaded complication of RP. We wish to report a case of RP of the trachea and bronchi which was treated with nasal continuous positive airway pressure.

The Use of Paramecium to Observe the Toxic Effect of Cigarette Smoke.

ERIC Educational Resources Information Center

Bardell, David

1986-01-01

Describes a laboratory experiment in which Paramecium caudatum was used to demonstrate the toxic effect of cigarette smoke on the cilia of epithelium cells lining the trachea and bronchi of smokers. Provides background information and explains the procedure, including how to make a simple mechanical smoking device. (TW)

Pathological Studies of “Sudden Death Syndrome” in Broiler Chickens

PubMed Central

Ononiwu, J.C.; Thomson, R.G.; Carlson, H.C.; Julian, R.J.

1979-01-01

Sudden death syndrome usually occurs in heavy, fast-growing and healthy-looking broilers. Most of the affected birds are males. The characteristic necropsy changes are seen in well-fleshed broilers with edema and generalized pulmonary congestion, recently ingested feed in the crop and gizzard, distended intestine with creamy content and empty gall bladder. The liver and kidneys are slightly enlarged and the latter have patchy areas of subcapsular hemorrhage. The heart contains clotted blood in the atria but the ventricles are often empty and the left ventricle in particular assumes a hypertrophied appearance. Microscopic examination of heart muscle reveals degeneration of fibers, separation of cardiac muscle fibers by edema and infiltration of heterophils. The lungs have severe vascular congestion, inflammatory cell infiltration in the mucosa of the secondary bronchi and edema fluid in the tertiary bronchi and interlobular connective tissue. The liver has moderate bile duct hyperplasia, periportal hepatitis and mononuclear cell infiltration adjacent to bile ducts which possibly leads to bile duct constriction. The kidneys have subcapsular and parenchymatous hemorrhage. ImagesFIGURE 1.FIGURE 2. PMID:436100

[Virtual bronchoscopy: the correlation between endoscopic simulation and bronchoscopic findings].

PubMed

Salvolini, L; Gasparini, S; Baldelli, S; Bichi Secchi, E; Amici, F

1997-11-01

We carried out a preliminary clinical validation of 3D spiral CT virtual endoscopic reconstructions of the tracheobronchial tree, by comparing virtual bronchoscopic images with actual endoscopic findings. Twenty-two patients with tracheobronchial disease suspected at preliminary clinical, cytopathological and plain chest film findings were submitted to spiral CT of the chest and bronchoscopy. CT was repeated after endobronchial therapy in 2 cases. Virtual endoscopic shaded-surface-display views of the tracheobronchial tree were reconstructed from reformatted CT data with an Advantage Navigator software. Virtual bronchoscopic images were preliminarily evaluated with a semi-quantitative quality score (excellent/good/fair/poor). The depiction of consecutive airway branches was then considered. Virtual bronchoscopies were finally submitted to double-blind comparison with actual endoscopies. Virtual image quality was considered excellent in 8 cases, good in 14 and fair in 2. Virtual exploration was stopped at the lobar bronchi in one case only; the origin of segmental bronchi was depicted in 23 cases and that of some subsegmental branches in 2 cases. Agreement between actual and virtual bronchoscopic findings was good in all cases but 3 where it was nevertheless considered satisfactory. The yield of clinically useful information differed in 8/24 cases: virtual reconstructions provided more information than bronchoscopy in 5 cases and vice versa in 3. Virtual reconstructions are limited in that the procedure is long and difficult and needing a strictly standardized threshold value not to alter virtual findings. Moreover, the reconstructed surface lacks transparency, there is the partial volume effect and the branches < or = 4 pixels phi and/or meandering ones are difficult to explore. Our preliminary data are encouraging. Segmental bronchi were depicted in nearly all cases, except for the branches involved by disease. Obstructing lesions could be bypassed in some cases, making an indication for endoscopic laser therapy. Future didactic perspectives and applications to minimally invasive or virtual reality-assisted therapy seem promising, even though actual clinical applications require further studies.

JPRS Report - Science & Technology USSR: Life Sciences.

DTIC Science & Technology

1988-06-17

No 6. Nov-Dec 87] 11 Electron Microscopic and Radioautographic Investigation of Bronchi in Chronic Inflammation Upon Exposure to Helium-Neon...87] 22 Functional and Morphological Characteristics of Stress-Protective Action of Piracetam [V. M. Vinogradov, A. A. Klishov et al; FARMAKOLOGIYA...I TOKSIKOLOGIYA No 6, Nov-Dec 87] 23 Comparative Neurophysiological Studies on Nootropic Agents Piracetam and Centrophenoxine [S. V Krapivin, T. A

Foreign bodies in the aerodigestive tract in pediatric patients.

PubMed

Higo, Ryuzaburo; Matsumoto, Yu; Ichimura, Keiichi; Kaga, Kimitaka

2003-12-01

To investigate pediatric foreign body cases in the aerodigestive tract, and to elucidate the characteristic problems in Japan. A total of 310 pediatric patients (age 15 or below), gathered from two medical university hospitals (University of Tokyo and Jichi Medical School), were included in this study. Data were collected by retrospective chart review and were statistically analyzed. Two-year-olds were the most common patients, and the range from age 1 to age 4 included 67.7% of all the patients. The most involved sites were the nose (39.4%) and the pharynx (38.4%), followed by the esophagus (12.9%) and the trachea-bronchi (6.5%). Fish bones and toys were the representative foreign bodies (30.7 and 13.6%, respectively). Other foreign bodies often encountered included coins, food, candy, peanuts and nuts, and batteries. The type of foreign body was closely related to the site in which foreign bodies were lodged: 77.3% of foreign bodies in the pharynx were fish bones, and toys were the most common impacted foreign body in the nose. In the esophagus, representative impacted foreign bodies were coins (35.7%), but disk-type battery ingestion has been increasing in recent years. Although most foreign bodies in the esophagus were safely removed, one case of a disk-type battery had a serious sequela. In the trachea-bronchi, peanuts, food, cotton, and coins were impacted. A rigid bronchoscope was basically used to remove foreign bodies, but in some cases, a fine flexible endoscope, with a channel for fiber forceps, was useful, because it could be inserted into narrow bronchi. Advance of a flexible endoscope will make it an excellent tool for diagnosis and management of the trachea-bronchial foreign body. Fish bones in the pharynx, which were closely related to Japanese eating habits, and toys in the nose, were the typical foreign bodies encountered in this study. In the esophagus, an increased incidence of disk-type battery ingestion has become a serious problem in recent years. Since prevention is the most essential way to manage foreign body cases, feedback from studies to public education should be encouraged.

Biological Effects of Short, High-Level Exposure to Gases: Sulfur Dioxide.

DTIC Science & Technology

1980-05-01

irritation and moist rales, bilaterally and anteriorly over the large bronchi. One-half of the subjects exposed to sulfur dioxide at concentrations of... burns . The pharyngeal mucosa was hyperemic but without ulceration . These men had decreased breath sounds, diffuse rales and rhonchi, with essentially...workplace have limited appli- cation in the military setting; the basis for their selection is the protection of chronically exposed workers against

Neuronally mediated non-cholinergic contraction of guinea-pig bronchial smooth muscle is inhibited by a substance P antagonist.

PubMed

Leander, S; Grundström, N; Andersson, R G; Håkanson, R

1984-04-01

The isolated main bronchi of the guinea-pig respond to electrical field stimulation with a twitch followed by a slow contraction. Atropine blocked the slow contraction. The substance P antagonist, (D-Pro2, D- Trp7 ,9)-SP, greatly reduced the atropine-resistant contraction. The results suggest the involvement of substance P in non-cholinergic neurotransmission in the guinea-pig airways.

Lower tracheal and carinal resection associated with subtotal oesophagectomy for carcinoma of oesophagus involving trachea

PubMed Central

Thompson, D. T.

1973-01-01

The problem of the patient with a carcinoma of the oesophagus involving the lower trachea and one or other main stem bronchus is discussed. An operation in which the carina was excised and both main bronchi were re-anastomosed to the trachea in association with a subtotal oesophagectomy is described. The criteria for deciding to undertake such an operation are discussed. Images PMID:4731124

Palmitoylethanolamide Supplementation during Sensitization Prevents Airway Allergic Symptoms in the Mouse

PubMed Central

Roviezzo, Fiorentina; Rossi, Antonietta; Caiazzo, Elisabetta; Orlando, Pierangelo; Riemma, Maria A.; Iacono, Valentina M.; Guarino, Andrea; Ialenti, Armando; Cicala, Carla; Peritore, Alessio; Capasso, Raffaele; Di Marzo, Vincenzo; Izzo, Angelo A.

2017-01-01

One important risk factor for the development of asthma is allergen sensitization. Recent increasing evidence suggests a prominent role of mast cells in asthma pathophysiology. Since Palmitoylethanolamide (PEA), an endogenous lipid mediator chemically related to – and co-released with- the endocannabinoid anandamide, behaves as a local autacoid down-regulator of mast cell activation and inflammation, we explored the possible contribution of PEA in allergic sensitization, by using ovalbumin (OVA) as sensitizing agent in the mouse. PEA levels were dramatically reduced in the bronchi of OVA-treated animals. This effect was coupled to a significant up-regulation of CB2 and GPR55 receptors, two of the proposed molecular PEA targets, in bronchi harvested from allergen-sensitized mice. PEA supplementation (10 mg/kg, 15 min before each allergen exposure) prevented OVA-induced bronchial hyperreactivity, but it did not affect IgE plasma increase. On the other hand, PEA abrogated allergen-induced cell recruitment as well as pulmonary inflammation. Evaluation of pulmonary sections evidenced a significant inhibitory action of PEA on pulmonary mast cell recruitment and degranulation, an effect coupled to a reduction of leukotriene C4 production. These findings demonstrate that allergen sensitization negatively affects PEA bronchial levels and suggest that its supplementation has the potential to prevent the development of asthma-like features. PMID:29311913

Computed tomography in pulmonary sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lynch, D.A.; Webb, W.R.; Gamsu, G.

1989-05-01

We studied the high resolution CT (HRCT) scans of 15 patients with biopsy-proven sarcoidosis and correlated the findings with pulmonary function tests (12 patients), 67Ga scans (10 patients), bronchoalveolar lavage (five patients), recent transbronchial biopsy (six patients), and recent open lung biopsy (three patients). The HRCT features included small nodules, thickened interlobular septa, patchy focal increase in lung density, honeycombing, and central conglomeration of vessels and bronchi. Active alveolitis was present by gallium scanning criteria in 5 of 10 cases. By bronchoalveolar lavage criteria, activity was present in three of five cases. Patchy increase in density may correlate with activemore » alveolitis as seen on /sup 67/Ga scanning. High resolution CT was better than chest X-radiography for demonstration of patchy increase in density and for distinguishing nodules from septal thickening. Both nodules and patchy density were partly reversible following therapy. Nodular densities seen on CT correlated with the presence of granulomata on histology. Resting pulmonary function tests correlated poorly with presence and extent of lung disease on HRCT. The presence on HRCT of focal fine nodules, patchy focal increase in lung density, and central crowding of bronchi and vessels should suggest the diagnosis of sarcoidosis. In some patients, HRCT can identify unsuspected parenchymal lung disease and document the reversible components of sarcoid lung disease.« less

The pathophysiology of bronchiectasis

PubMed Central

King, Paul T

2009-01-01

Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This process occurs in the context of chronic airway infection and inflammation. It is usually diagnosed using computed tomography scanning to visualize the larger bronchi. Bronchiectasis is also characterized by mild to moderate airflow obstruction. This review will describe the pathophysiology of noncystic fibrosis bronchiectasis. Studies have demonstrated that the small airways in bronchiectasis are obstructed from an inflammatory infiltrate in the wall. As most of the bronchial tree is composed of small airways, the net effect is obstruction. The bronchial wall is typically thickened by an inflammatory infiltrate of lymphocytes and macrophages which may form lymphoid follicles. It has recently been demonstrated that patients with bronchiectasis have a progressive decline in lung function. There are a large number of etiologic risk factors associated with bronchiectasis. As there is generally a long-term retrospective history, it may be difficult to determine the exact role of such factors in the pathogenesis. Extremes of age and smoking/chronic obstructive pulmonary disease may be important considerations. There are a variety of different pathogens involved in bronchiectasis, but a common finding despite the presence of purulent sputum is failure to identify any pathogenic microorganisms. The bacterial flora appears to change with progression of disease. PMID:20037680

[The rationale for the combined application of cryomassage and silvinite speleotherapy for the rehabilitative treatment of the patients with bronchial asthma].

PubMed

Aĭrapetova, N S; Rassulova, M A; Antonovich, I V; Stiazhkina, E M; Ksenofontova, I V; Nikoda, N V; Derevnina, N A

2011-01-01

The present study is devoted to the estimation of therapeutic and prophylactic effects of cryomassage and silvinite speleotherapy in the patients with partially controlled asthma. Advantages of the combined application of rehabilitative technologies are illustrated by their well-expressed anti-inflammatory and immunocorrecive actions, reduced obstruction and hyper-reactivity of the bronchi, improved pulmonary cardiohemodynamics, enhanced physical tolerance and better psychological adaptation.

Comparison of Aerosol Delivery by Face Mask and Tracheostomy Collar.

PubMed

Bugis, Alaa A; Sheard, Meryl M; Fink, James B; Harwood, Robert J; Ari, Arzu

2015-09-01

The purpose of this study was to compare the performance of a tracheostomy collar, Wright mask, and aerosol mask attached to a jet nebulizer in facilitating aerosolized medication delivery to the lungs. We also compared albuterol delivery with open versus closed fenestration and determined the effect of inspiratory-expiratory ratio (I:E) on aerosol delivery. Albuterol (2.5 mg/3 mL) was administered to an in vitro model consisting of an adult teaching mannequin extrathoracic and upper airway with stoma intubated with an 8-mm fenestrated tracheostomy tube. The cuff was deflated. A collecting filter at the level of the bronchi was connected to a breathing simulator at a tidal volume of 400 mL, breathing frequency of 20 breaths/min, and I:E of 2:1 and 1:2. A jet nebulizer was operated with O2 at 8 L/min. Each interface was tested in triplicate. The flow was discontinued at the end of nebulization. For each test, the nebulizer was attached to a tracheostomy collar with the fenestration open or closed, a Wright mask, or an aerosol mask. Drug was analyzed by spectrophotometry (276 nm). A paired t test and analysis of variance were performed (P < .05). The mean ± SD percent albuterol dose delivered distal to the bronchi was greater with the tracheostomy collar with a closed fenestration (9.4 ± 1.5%) compared with an open fenestration (7.0 ± 0.8%). The doses delivered with the Wright mask (4.1 ± 0.6%) and aerosol mask (3.5 ± 0.04%) were both less than with the tracheostomy collar under either condition (P < .05). Increasing the I:E from 1:2 to 2:1 increased aerosol delivery by 2.5-4%, with significance for the tracheostomy collar with an open fenestration (11.6 ± 1.4%), Wright mask (7.2 ± 0.6%), and aerosol mask (6.1 ± 0.5%). In an adult tracheostomy model, the tracheostomy collar delivered more aerosol to the bronchi than the Wright or aerosol mask. An I:E of 2:1 caused greater aerosol deposition compared with an I:E of 1:2. During aerosol administration via a tracheostomy collar, closing the fenestration improved aerosol delivery. Copyright © 2015 by Daedalus Enterprises.

The impact of low-frequency, low-force cyclic stretching of human bronchi on airway responsiveness.

PubMed

Le Guen, Morgan; Grassin-Delyle, Stanislas; Naline, Emmanuel; Buenestado, Amparo; Brollo, Marion; Longchampt, Elisabeth; Kleinmann, Philippe; Devillier, Philippe; Faisy, Christophe

2016-11-14

In vivo, the airways are constantly subjected to oscillatory strain (due to tidal breathing during spontaneous respiration) and (in the event of mechanical ventilation) positive pressure. This exposure is especially problematic for the cartilage-free bronchial tree. The effects of cyclic stretching (other than high-force stretching) have not been extensively characterized. Hence, the objective of the present study was to investigate the functional and transcriptional response of human bronchi to repetitive mechanical stress caused by low-frequency, low-force cyclic stretching. After preparation and equilibration in an organ bath, human bronchial rings from 66 thoracic surgery patients were stretched in 1-min cycles of elongation and relaxation over a 60-min period. For each segment, the maximal tension corresponded to 80% of the reference contraction (the response to 3 mM acetylcholine). The impact of cyclic stretching (relative to non-stretched controls) was examined by performing functional assessments (epithelium removal and incubation with sodium channel agonists/antagonists or inhibitors of intracellular pathways), biochemical assays of the organ bath fluid (for detecting the release of pro-inflammatory cytokines), and RT-PCR assays of RNA isolated from tissue samples. The application of low-force cyclic stretching to human bronchial rings for 60 min resulted in an immediate, significant increase in bronchial basal tone, relative to non-cyclic stretching (4.24 ± 0.16 g vs. 3.28 ± 0.12 g, respectively; p < 0.001). This cyclic stimulus also increased the affinity for acetylcholine (-log EC50: 5.67 ± 0.07 vs. 5.32 ± 0.07, respectively; p p < 0.001). Removal of airway epithelium and pretreatment with the Rho-kinase inhibitor Y27632 and inward-rectifier K+ or L-type Ca 2+ channel inhibitors significantly modified the basal tone response. Exposure to L-NAME had opposing effects in all cases. Pro-inflammatory pathways were not involved in the response; cyclic stretching up-regulated the early mRNA expression of MMP9 only, and was not associated with changes in organ bath levels of pro-inflammatory mediators. Low-frequency, low-force cyclic stretching of whole human bronchi induced a myogenic response rather than activation of the pro-inflammatory signaling pathways mediated by mechanotransduction.

Robotic Lobectomy Utilizing the Robotic Stapler.

PubMed

Pearlstein, Daryl Phillip

2016-12-01

A drawback of robotic lobectomy is the inability of the operating surgeon to perform stapler division of the pulmonary vessels and bronchi. With the advent of the robotic stapler, the surgeon is able to control this instrument from the console. The robotic stapler presents certain challenges. This article outlines techniques to use the robotic stapler for the safe and predictable performance of lobectomies. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Imaging Findings of Isolated Bronchial Anthracofibrosis: A Computed Tomography Analysis of Patients With Bronchoscopic and Histologic Confirmation.

PubMed

Kahkouee, Shahram; Pourghorban, Ramin; Bitarafan, Mahdi; Najafizadeh, Katayoun; Makki, Seyed Shahabeddin Mohammad

2015-07-01

To evaluate the chest computed tomography (CT) findings of patients with isolated bronchial anthracofibrosis confirmed by bronchoscopy and histopathology. Fifty-eight patients with isolated bronchial anthracofibrosis (29 females; mean age, 70 years) were enrolled in this study. The diagnosis of bronchial anthracofibrosis was made based on both bronchoscopy and pathology findings in all patients. The various chest CT images were retrospectively reviewed by two chest radiologists who reached decisions in consensus. Central peribronchial soft tissue thickening (n=37, 63.8%) causing bronchial narrowing (n=37, 63.8%) or obstruction (n=11, 19%) was identified as an important finding on imaging. Multiple bronchial stenoses with concurrent involvement of 2, 3, and 5 bronchi were seen in 12 (21%), 9 (15%), and 2 (3.4%) patients, respectively. Segmental atelectasis and lobar or multilobar collapse were detected. These findings mostly occurred in the right lung, predominantly in the right middle lobe. Mosaic attenuation patterns, scattered parenchymal nodules, nodular patterns, and calcified or non-calcified lymph nodes were also observed. On chest CT, isolated bronchial anthracofibrosis appeared as peribronchial soft tissue thickening, bronchial narrowing or obstruction, segmental atelectasis, and lobar or multilobar collapse. The findings were more common in the right side, with simultaneous involvement of multiple bronchi in some patients. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: a review.

PubMed

Razavi, Seyed-Mansour; Ghanei, Mostafa; Salamati, Payman; Safiabadi, Mehdi

2013-01-01

To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable.

The use of expandable metallic airway stents for tracheobronchial obstruction in children.

PubMed

Filler, R M; Forte, V; Fraga, J C; Matute, J

1995-07-01

Expandable metallic angioplasty stents (Palmaz stent) have been implanted in the trachea and/or bronchi of seven children. Three children had severe tracheal stenosis after tracheoplasty for congenital tracheal stenosis repair, and four had tracheomalacia or bronchomalacia with or without vascular compression. The mean age at stenting was 9.7 months (range, 2 to 15 months). Balloon expandable stents were inserted into the trachea or bronchus through a 3.5-mm bronchoscope under fluoroscopic control. Initially a single tracheal stent was used for all patients except for one with obstruction in the trachea and both bronchi, in whom three stents were implanted. Three children had recurrent airway obstruction 1 month later; one was cured with a second stent; one child died 1 year later; and the other is being treated for heart disease. The others have no serious respiratory problems. The stents in all have been in place for 1 to 25 (mean, 11) months. No immediate complications were noted. Early and late bronchoscopy showed incomplete epithelialization of the stent and patches of granulation tissue on it. Two stents were removed bronchoscopically, one at the completion of treatment for tracheomalacia and the other at the time of recurrent airway obstruction. This preliminary experience indicates that expandable metallic stents have a useful role in the treatment of selected lower airway obstructions.

Smooth muscle in human bronchi is disposed to resist airway distension.

PubMed

Gazzola, Morgan; Henry, Cyndi; Couture, Christian; Marsolais, David; King, Gregory G; Fredberg, Jeffrey J; Bossé, Ynuk

2016-07-15

Studying airway smooth muscle (ASM) in conditions that emulate the in vivo environment within which the bronchi normally operate may provide important clues regarding its elusive physiological function. The present study examines the effect of lengthening and shortening of ASM on tension development in human bronchial segments. ASM from each bronchial segment was set at a length approximating in situ length (Linsitu). Bronchial tension was then measured during a slow cyclical strain (0.004Hz, from 0.7Linsitu to 1.3Linsitu) in the relaxed state and at graded levels of activation by methacholine. In all cases, tension was greater at longer ASM lengths, and greater during lengthening than shortening. The threshold of methacholine concentration that was required for ASM to account for bronchial tension across the entire range of ASM lengths tested was on average smaller by 2.8 logs during lengthening than during shortening. The length-dependency of ASM tension, together with this lower threshold of methacholine concentration during lengthening versus shortening, suggest that ASM has a greater ability to resist airway dilation during lung inflation than to narrow the airways during lung deflation. More than serving to narrow the airway, as has long been thought, these data suggest that the main function of ASM contraction is to limit airway wall distension during lung inflation. Copyright © 2016 Elsevier B.V. All rights reserved.

Neurogenic airway microvascular leakage induced by toluene inhalation in rats.

PubMed

Sakamoto, Tatsuo; Kamijima, Michihiro; Miyake, Mio

2012-06-15

Toluene is a representative airborne occupational and domestic pollutant that causes eye and respiratory tract irritation. We investigated whether a single inhalation of toluene elicits microvascular leakage in the rat airway. We also evaluated the effects of CP-99,994, a tachykinin NK(1) receptor antagonist, and ketotifen, a histamine H1 receptor antagonist with mast cell-stabilizing properties, on the airway response. The content of Evans blue dye that extravasated into the tissues was measured as an index of plasma leakage. Toluene (18-450 ppm, 10 min) concentration-dependently induced dye leakage into the trachea and main bronchi of anesthetized and mechanically ventilated rats. Toluene at concentrations of ≥ 50 and ≥ 30 ppm caused significant responses in the trachea and main bronchi, respectively, which both peaked after exposure to 135 ppm toluene for 10 min. This response was abolished by CP-99,994 (5 mg/kg i.v.), but not by ketotifen (1mg/kg i.v.). Nebulized phosphoramidon (1 mM, 1 min), a neutral endopeptidase 24.11 inhibitor, significantly enhanced the response induced by toluene (135 ppm, 10 min) compared with nebulized 0.9% saline (1 min). These results show that toluene can rapidly increase airway plasma leakage that is predominantly mediated by tachykinins endogenously released from airway sensory nerves. However, mast cell activation might not be important in this airway response. Copyright © 2012 Elsevier B.V. All rights reserved.

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

DTIC Science & Technology

2010-09-01

and interstitial fibrosis, and fibrous pleural adhesions. Other lesions included lymphoid hyperplasia and plasmacytosis, and chronic periadnexal and...inflammation in the lung and mediastinal lymph nodes, chronic inflammation centered on bronchi and vessels, type II pneumocyte hyperplasia , pleural...2/6 33 1/6 16 1/3 33 spleen splenitis, necrotizing 1/3 33 2/6 33 4/6 66 2/3 66 lymphoid depletion 2/3 66 3/6 50 3/6 50 2/3 66 lymphoid hyperplasia * 0

Postmortem CT versus forensic autopsy: frequent discrepancies of tracheobronchial content findings.

PubMed

Zech, Wolf-Dieter; Jackowski, Christian; Schwendener, Nicole; Brencicova, Eva; Schuster, Frederick; Lombardo, Paolo

2016-01-01

In their daily forensic casework, the authors experienced discrepancies of tracheobronchial content findings between postmortem computed tomography (PMCT) and autopsy to an extent previously unnoticed in the literature. The goal of this study was to evaluate such discrepancies in routine forensic cases. A total of 327 cases that underwent PMCT prior to routine forensic autopsy were retrospectively evaluated for tracheal and bronchial contents according to PMCT and autopsy findings. Hounsfield unit (HU) values of tracheobronchial contents, causes of death, and presence of pulmonary edema were assessed in mismatching and matching cases. Comparing contents in PMCT and autopsy in each of the separately evaluated compartments of the respiratory tract low positive predictive values were assessed (trachea, 38.2%; main bronchi, 40%; peripheral bronchi, 69.1%) indicating high discrepancy rates. The majority of tracheobronchial contents were viscous stomach contents in matching cases and low radiodensity materials (i.e., HU < 30) in mismatching cases. The majority of causes of death were cardiac related in the matching cases and skull/brain trauma in the mismatching cases. In mismatching cases, frequency of pulmonary edema was significantly higher than in matching cases. It can be concluded that discrepancies in tracheobronchial contents observed between PMCT and routine forensic autopsy occur in a considerable number of cases. Discrepancies may be explained by the runoff of contents via nose and mouth during external examination and the flow back of tracheal and main bronchial contents into the lungs caused by upright movement of the respiratory tract at autopsy.

COMPUTED TOMOGRAPHIC ANATOMY AND CHARACTERISTICS OF RESPIRATORY ASPERGILLOSIS IN JUVENILE WHOOPING CRANES

PubMed Central

Kelley, Cristin; Pinkerton, Marie E.; Hartup, Barry K.

2015-01-01

Respiratory diseases are a leading cause of morbidity and mortality in captivity reared, endangered whooping cranes (Grus americana). Objectives of this retrospective, case series, cross‐sectional study were to describe computed tomography (CT) respiratory anatomy in a juvenile whooping crane without respiratory disease, compare CT characteristics with gross pathologic characteristics in a group of juvenile whooping cranes with respiratory aspergillosis, and test associations between the number of CT tracheal bends and bird sex and age. A total of 10 juvenile whooping cranes (one control, nine affected) were included. Seven affected cranes had CT characteristics of unilateral extrapulmonary bronchial occlusion or wall thickening, and seven cranes had luminal occlusion of the intrapulmonary primary or secondary bronchi. Air sac membrane thickening was observed in three cranes in the cranial and caudal thoracic air sacs, and air sac diverticulum opacification was observed in four cranes. Necropsy lesions consisted of severe, subacute to chronic, focally extensive granulomatous pathology of the trachea, primary bronchi, lungs, or air sacs. No false positive CT scan results were documented. Seven instances of false negative CT scan results occurred; six of these consisted of subtle, mild air sacculitis including membrane opacification or thickening, or the presence of small plaques found at necropsy. The number of CT tracheal bends was associated with bird age but not sex. Findings supported the use of CT as a diagnostic test for avian species with respiratory disease and tracheal coiling or elongated tracheae where endoscopic evaluation is impractical. PMID:26592357

Neoplastic disease in a medicolegal autopsy material. A retrospective study in northern Sweden.

PubMed

Gezelius, C; Eriksson, A

1988-01-01

Only a small fraction of sudden unexpected deaths are caused by neoplastic disease and thus subject ot medicolegal autopsy. The medicolegal autopsy forms an opportunity to study not only medically diagnosed and treated neoplasms, but also the natural evolution of untreated disease. In a series of 7,020 consecutive medicolegal autopsies in northern Sweden, we found 171 cases with malignant and/or intracranial neoplasms. In 41 cases, sudden death was caused by previously unknown tumors. The most common mechanisms of death in this group were disseminated cancer, intracranial tumors, pulmonary thromboembolism, hemoptysis, and aspiration of blood, and the most common locations were the bronchi and the lung. In some of these cases, the mechanism was sometimes dramatic, raising a question of violent death or intoxication. In 30 cases, sudden unexpected death was caused by previously known tumors, and also in this group disseminated cancer was the most common cause of death, and the most common locations were the bronchi and the lung. In 22 cases, tumors were found suicidal cases; in 14 of these, the tumor was considered to be a major causative factor to the suicide, while in eight cases the tumor was considered to be an incidental finding. The expected number of cancers in the 1,060 suicides investigated in this series was 27, according to the official cancer prevalence data. Thus, a possible over-representation of suicides among persons with cancer seems doubtful and needs further exploration.

Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: functional and biochemical study.

PubMed

Cortijo, J; Naline, E; Ortiz, J L; Berto, L; Girard, V; Malbezin, M; Advenier, C; Morcillo, E J

1998-01-02

We have investigated the role of human bronchial cyclic nucleotide phosphodiesterases in the effects of fenspiride, a drug endowed with bronchodilator and anti-inflammatory properties. Functional studies on human isolated bronchi showed that fenspiride (10(-6)-3 x 10(-3) M, 30 min) induced a shift to the left of the concentration-response curves for isoprenaline and sodium nitroprusside with -logEC50 values of 4.1+/-0.1 (n = 7) and 3.5+/-0.2 (n = 8), respectively. Biochemical studies were carried out on three human bronchi in which separation of cyclic nucleotide phosphodiesterase isoenzymes was performed by ion exchange chromatography followed by determination of phosphodiesterase activity with a radioisotopic method. Phosphodiesterase 4 (cyclic AMP-specific) and phosphodiesterase 5 (cyclic GMP-specific) were the major phosphodiesterase isoforms present in the human bronchial tissue. The presence of phosphodiesterase 1 (Ca2+/calmodulin-stimulated), phosphodiesterase 2 (cyclic GMP-stimulated) and, in two cases, phosphodiesterase 3 (cyclic GMP-inhibited) was also identified. Fenspiride inhibited phosphodiesterase 4 and phosphodiesterase 3 activities with -logIC50 values of 4.16+/-0.09 and 3.44+/-0.12, respectively. Phosphodiesterase 5 activity was also inhibited with a -logIC50 value of approximately 3.8. Fenspiride (< or = 10(-3) M) produced less than 25% inhibition of phosphodiesterase 1 and phosphodiesterase 2 activities. In conclusion, fenspiride is an effective inhibitor of both cyclic AMP and cyclic GMP hydrolytic activity in human bronchial tissues and this action may contribute to its airway effects.

The effect of compound 48/80 on contractions induced by toluene diisocyanate in isolated guinea-pig bronchus.

PubMed

Mapp, C E; Boniotti, A; Papi, A; Chitano, P; Coser, E; Di Stefano, A; Saetta, M; Ciaccia, A; Fabbri, L M

1993-06-01

We have investigated the ability of compound 48/80 and of histamine H1 and H2 receptor antagonists to inhibit toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. Compound 48/80 (100 micrograms/ml) significantly inhibited toluene diisocyanate-induced contractions. By contrast, the two histamine H1 and H2 receptor antagonists, chlorpheniramine (10 microM) and cimetidine, (10 microM) did not affect toluene diisocyanate-induced contractions, but significantly inhibited contractions induced by exogenously applied histamine (100 microM) and by 48/80. We investigated which mechanisms 48/80 used to inhibit toluene diisocyanate-induced contractions, paying particular attention to the possible involvement of capsaicin-sensitive primary afferents. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced compound 48/80-induced contractions. A capsaicin-resistant component of contraction was also evident. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, did not affect 48/80-induced contraction. MEN 10,207 (Tyr5,D-Trp6,8,9,Arg10)-neurokinin A (4-10) (3 microM) a selective antagonist of NK2-tachykinin receptors significantly reduced 48/80-induced contractions. These results show that compound 48/80 inhibits toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. It is likely that two mechanisms are involved in the inhibition: (1) the release of mediators other than histamine by mast cells, (2) an effect of 48/80 on sensory nerves.

Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boorman, G.A.; Uraih, L.C.; Gupta, B.N.

1987-06-01

B6C3F1 mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 90-day recovery period. Sixteen of eight (20%) male mice in the 30 ppm group died following exposure. There were no other unscheduled deaths in the mice. Five mice/sex/group were examined at 2 hr or at 1, 3, 7, 14, 28, 49, or 91 days following exposure. Chemical-related changes were restricted to the respiratory system. At 30 ppm there were extensive necrosis and erosion of the respiratory and olfactory epithelium in the nasal cavity. Severe necrosis and epithelial erosion weremore » also found in the trachea and main bronchi. Regeneration of the mucosal epithelium occurred rapidly in the nasal cavity and airways. In the turbinates, mild incomplete olfactory epithelial regeneration persisted to day 91 in the male mice. Intraluminal fibrotic projections covered by respiratory epithelium and bronchial fibrosis were found in the major airways of the 30 ppm male and female mice by day 7. The intraluminal fibrosis persisted to day 91. In males with severe bronchial fibrosis, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, persistent pulmonary changes were not found. These studies indicate that methyl isocyanate inhalation at or near lethal concentrations can cause persistent fibrosis of the major bronchi in mice.« less

Palliative treatment of malignant stenoses of the lower airways with the FIBERTOM Nd:YAG laser

NASA Astrophysics Data System (ADS)

Pirozynski, Michal; Polubiec-Kownacka, Malgorzata; Strojecki, Krzysztof; Blachnio, Antoni; Pawlak, Wieslaw; Krusiewicz, Jan

1996-03-01

Neodymium yttrium aluminum garnet (Nd:YAG) laser, with its infrared wavelength of 1064 nm, is at present the most useful modality in treatment of lower airways obstruction of the lower airways by malignant and benign lesions. In fact that was the first indication for a successful restoration of a narrowed airway by Toty et al. The therapeutical effects of this laser are based on thermal action. The exposed tissue undergoes a progressive transformation by a localized increase in the temperature from warming, protein coagulation, to evaporation of water and vaporization of the tissue. This study represents the initial experience with the use of the FIBERTOMTM Nd:YAG laser in removal of obstructing malignant and non- malignant lesions of the lower airways. Twenty-six patients (mean age 55.7 plus or minus 17.4 years) were included in the study. The main indications for laser therapy were in 16 patients exophytic cancerous lesions of the trachea and main bronchi, benign tumors of the major airways in 6, and in 4 cancerous lesions of the lobar bronchi. Squamous cell lung cancer and adenocarcinoma were diagnosed most often. The degree of obstruction ranged from 70% to 99%. Complete recanalization was achieved in 19 of the 26 patients, in only one patient recanalization was not achieved. The major complication was fever -- seen in 17 (65.4%) patients and cough (19.2%). Long term observation identified 18 patients alive after 52 weeks following laser therapy.

Immunohistochemical demonstration of enkephalin-containing nerve fibers in guinea pig and rat lungs.

PubMed

Shimosegawa, T; Foda, H D; Said, S I

1989-08-01

Met-enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk), the opioid peptides originally isolated from the brain, are believed to act as inhibitory neuromodulators at various synaptic sites. In this immunohistochemical study, we have investigated the localization and distribution of Met- and Leu-Enk immunoreactivities in airways and pulmonary vessels of guinea pigs and rats. Immunoreactivities to both peptides were found in nerve fibers and nerve terminals distributed mainly to the trachea and major bronchi, and were especially prevalent in the smooth muscle layer, in the lamina propria, and around tracheal and bronchial glands, but not in the epithelium. Few immunoreactive nerve fibers were detected in smaller bronchi, bronchioles, and alveoli. Enkephalin-immunoreactive nerve fibers were also localized in the walls of pulmonary and bronchial vessels. Within airway microganglia, immunoreactivity was observed in a few nerve terminals, but not in ganglion cell bodies. Met- and Leu-Enk immunoreactive nerve fibers showed similar distribution patterns, though minor differences were noted between the two species: Enk-immunoreactive nerve fibers in the smooth muscle layer were more abundant in guinea pigs than in rats, whereas those in mucous glands were richer in rats than in guinea pigs. These results document the presence of Met- and Leu-Enk immunoreactivity in nerve fibers supplying guinea pig and rat airways and pulmonary vessels, and provide a morphologic basis for the view that enkephalins are likely neurotransmitters or neuromodulators in the lung.

Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists.

PubMed

Ortiz, Jose Luis; Ortiz, Amparo; Milara, Javier; Armengot, Miguel; Sanz, Celia; Compañ, Desamparados; Morcillo, Esteban; Cortijo, Julio

2016-01-01

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis.

A rare cause of pleural effusion: ruptured primary pleural hydatid cyst.

PubMed

Erkoç, Mustafa Fatih; Öztoprak, Bilge; Alkan, Sevil; Okur, Aylin

2014-03-06

Hydatidosis is an endemic parasitic disease in Mediterranean countries, often caused by the dog tapeworm Echinococcus granulosus. The disease predominantly affects the liver (60-70%) and lungs (30%), and the surgical management is considered as the gold standard for treatment. Besides anaphylactic reactions, the most frequent complication of the hydatid disease is rupture into neighbouring structures, often affecting the bronchi, gastrointestinal tract and peritoneal/pleural cavities, according to its location. Primary pleural hydatidosis is an extremely rare entity and we present a ruptured pleural hydatid cyst with unusual location.

A powered vascular staple for the application of segmental bronchial closure in thoracoscopic anatomic segmentectomy.

PubMed

Kuroda, Hiroaki; Yoshida, Tatsuya; Sakao, Yukinori

2017-12-01

We used the powered vascular staple (PVS) instead of the conventional staple technique [the utilization of the powered linier cutter (PLC)] or ligation for total 23 segmental or subsegmental bronchi with less than 10 mm in the bronchial luminal size on computed tomography (CT) in thoracoscopic segmentectomy. Our results suggested that the availability of the PVS represents a novel advance in the armamentarium and may have a possibility of being pervasive widely however, more observative periods and further sample accumulation are needed.

Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses.

PubMed

Karlsson, J A; Persson, C G

1983-07-01

Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone.

[Second primary cancers of the bronchi treated surgically (recurrence excluded). Results of a national survey (1987)].

PubMed

Levasseur, P; Delambre, J F

1989-01-01

A multicentre study conducted by a number of French Thoracic Surgery centres has collected a total of 88 cases of operated metachronous cancers. After defining the concept of metachronous cancer, the reporters of this survey successively analyse the frequency, histological type and clinical course of such lesions. The various types of resection and the results (postoperative course and long-term acturial survival) are also examined in detail. The good long-term survival of such metachronous cancers justifies a deliberately "aggressive" surgical approach.

Pharmacologic Studies on the In Vitro Bronchodilating Vasoactive Actions of Oligo-PGB (Prostaglandin B)

DTIC Science & Technology

1988-01-06

kotriene D4 (LTD4) 1x10-9M and carbachol . lxlO- M induced similar contrac-tions. The degree of relaxation induced by O-PGB was dependent upon the...contra ti1 agoinst (36% of par---erine when •he bronchi were precontrated with SJ, 25%-against LTD4 and ,.ily 15% agairst carbachol ) suggesting that the...18 or 24 hours. In protl1, we either tested HMW and oligo-PGB in the absencE of a contractile agent or afier exposing the tissue to carbachol (Cch

Fully covered self-expandable metal stent in tracheobronchial disorders: clinical experience.

PubMed

Marchese, Roberto; Poidomani, Grazia; Paglino, Giuseppe; Crimi, Claudia; Lo Nigro, Chiara; Argano, Vincenzo

2015-01-01

The third-generation fully covered self-expandable metallic stent (SEMS) has been developed to solve the problems of difficult removal and in-stent granuloma formation related to the uncovered or partially covered type. There are few written reports about the performance of this type of stents with early encouraging results. To report and analyse our experience with the Silmet® stent in the management of malignant and benign tracheobronchial disorders. We retrospectively reviewed medical records of patients who underwent fully covered SEMS Silmet placement at the Interventional Pulmonology Unit, La Maddalena Cancer Center, Palermo, Italy, between May 2010 and August 2013. Stents were placed in 52 patients with malignant (n = 49) and benign airway obstruction (n = 2) and broncho-oesophageal fistula (n = 1). SEMSs were inserted into the trachea (n = 19), the main bronchi (n = 21) and the peripheral bronchi (n = 31). Besides 1 procedural dislocation, the deployment was successful in all patients with an immediate significant improvement of symptoms (Barthel Index p < 0.001; Medical Research Council score p < 0.001). A radiographic improvement was detected in 48% of patients. The mean follow-up duration was 119 ± 120 days (range 22-549 days). Complications observed were: migration (7.6%), tumour overgrowth (15%), infections (5.7%), granulation tissue formation (3.8%) and mucus plug (3.8%). The Silmet stent is effective, safe and simple to implant and remove. We suggest its use in cases of tight stenoses, in the treatment of small- to medium-caliber airways or in cases of tortuous airways. © 2015 S. Karger AG, Basel.

Reference Values for Central Airway Dimensions on CT Images of Children and Adolescents.

PubMed

Kuo, Wieying; Ciet, Pierluigi; Andrinopoulou, Eleni-Rosalina; Chen, Yong; Pullens, Bas; Garcia-Peña, Pilar; Fleck, Robert J; Paoletti, Matteo; McCartin, Michael; Vermeulen, Francois; Morana, Giovanni; Lee, Edward Y; Tiddens, Harm A W M

2018-02-01

The purpose of this study was to acquire normative data on central airway dimensions on chest CT scans in the pediatric population. Chest CT findings reported as normal by a radiologist were collected retrospectively at 10 international centers. An experienced and independent thoracic radiologist reevaluated all CT scans for image quality and for normal findings. Semiautomated image analysis was performed to measure dimensions of the trachea and right and left main bronchi at inspiration. Intrathoracic tracheal length was measured from carina to thorax inlet. Cross-sectional area and short and long axes were measured perpendicular to the longitudinal airway axis starting from the carina every centimeter upward for the trachea and every 0.5 cm downward for the main bronchi. The effects on airway diameters of age, sex, intrathoracic tracheal length, and distance from the carina were investigated by use of mixed-effects models analysis. Among 1160 CT scans collected, 388 were evaluated as normal by the independent radiologist with sufficient image quality and adequate inspiratory volume level. Central airways were successfully semiautomatically analyzed in 294 of 388 CT studies. Age, sex, intrathoracic tracheal length, and distance from carina were all significant predictors in the models for tracheal and right and left main bronchial diameters (p < 0.001). The central airway dimensions increased with age up to 20 years, and dimensions were larger in male than in female adolescents. Normative data were determined for the central airways of children and adolescents. Central airway dimensions depended on distance from the carina and on intrathoracic tracheal length.

Effect of Perinatal secondhand tobacco smoke exposure on in vivo and intrinsic airway structure/function in non-human primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joad, Jesse P.; Kott, Kayleen S.; Bric, John M.

Infants exposed to second hand smoke (SHS) experience more problems with wheezing. This study was designed to determine if perinatal SHS exposure increases intrinsic and/or in vivo airway responsiveness to methacholine and whether potential structural/cellular alterations in the airway might explain the change in responsiveness. Pregnant rhesus monkeys were exposed to filtered air (FA) or SHS (1 mg/m{sup 3} total suspended particulates) for 6 h/day, 5 days/week starting at 50 days gestational age. The mother/infant pairs continued the SHS exposures postnatally. At 3 months of age each infant: 1) had in vivo lung function measurements in response to inhaled methacholine,more » or 2) the right accessory lobe filled with agarose, precision-cut to 600 {mu}m slices, and bathed in increasing concentrations of methacholine. The lumenal area of the central airway was determined using videomicrometry followed by fixation and histology with morphometry. In vivo tests showed that perinatal SHS increases baseline respiratory rate and decreases responsiveness to methacholine. Perinatal SHS did not alter intrinsic airway responsiveness in the bronchi. However in respiratory bronchioles, SHS exposure increased airway responsiveness at lower methacholine concentrations but decreased it at higher concentrations. Perinatal SHS did not change eosinophil profiles, epithelial volume, smooth muscle volume, or mucin volume. However it did increase the number of alveolar attachments in bronchi and respiratory bronchioles. In general, as mucin increased, airway responsiveness decreased. We conclude that perinatal SHS exposure alters in vivo and intrinsic airway responsiveness, and alveolar attachments.« less

COMPUTED TOMOGRAPHIC ANATOMY AND CHARACTERISTICS OF RESPIRATORY ASPERGILLOSIS IN JUVENILE WHOOPING CRANES.

PubMed

Schwarz, Tobias; Kelley, Cristin; Pinkerton, Marie E; Hartup, Barry K

2016-01-01

Respiratory diseases are a leading cause of morbidity and mortality in captivity reared, endangered whooping cranes (Grus americana). Objectives of this retrospective, case series, cross-sectional study were to describe computed tomography (CT) respiratory anatomy in a juvenile whooping crane without respiratory disease, compare CT characteristics with gross pathologic characteristics in a group of juvenile whooping cranes with respiratory aspergillosis, and test associations between the number of CT tracheal bends and bird sex and age. A total of 10 juvenile whooping cranes (one control, nine affected) were included. Seven affected cranes had CT characteristics of unilateral extrapulmonary bronchial occlusion or wall thickening, and seven cranes had luminal occlusion of the intrapulmonary primary or secondary bronchi. Air sac membrane thickening was observed in three cranes in the cranial and caudal thoracic air sacs, and air sac diverticulum opacification was observed in four cranes. Necropsy lesions consisted of severe, subacute to chronic, focally extensive granulomatous pathology of the trachea, primary bronchi, lungs, or air sacs. No false positive CT scan results were documented. Seven instances of false negative CT scan results occurred; six of these consisted of subtle, mild air sacculitis including membrane opacification or thickening, or the presence of small plaques found at necropsy. The number of CT tracheal bends was associated with bird age but not sex. Findings supported the use of CT as a diagnostic test for avian species with respiratory disease and tracheal coiling or elongated tracheae where endoscopic evaluation is impractical. © 2015 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Radiology.

Inhibitors of neutral endopeptidase potentiate electrically and capsaicin-induced noncholinergic contraction in guinea pig bronchi.

PubMed

Djokic, T D; Nadel, J A; Dusser, D J; Sekizawa, K; Graf, P D; Borson, D B

1989-01-01

To evaluate the role of airway neutral endopeptidase (NEP) in the regulation of contraction of airway smooth muscle in response to endogenous tachykinins, we studied the effects of the NEP inhibitor phosphoramidon on contractions of guinea pig bronchial smooth muscle strips induced by either electrical field stimulation (EFS) or by capsaicin. In the presence of atropine (10(-6) M), propranolol (10(-6) M), phentolamine (10(-5) M), indomethacin (10(-6) M) and pyrilamine (5 x 10(-6) M) EFS (biphasic; pulse width, 1.0 msec; frequency 0.5-5 Hz for 30 sec; intensity, 20 V) produced noncholinergic, nonadrenergic muscle contraction in a frequency-dependent fashion (P less than .001). Phosphoramidon potentiated the contractile responses to EFS (P less than .01). Leucine-thiorphan (10(-5) M), another NEP inhibitor, potentiated EFS-induced contraction in a similar fashion as phosphoramidon (186 and 182% of control, respectively; each comparison, P less than .025). Captopril, bestatin, leupeptin and physostigmine (each drug, 10(-5) M) were without effect (P greater than .5, N = 5). Capsaicin (1.5 x 10(-8) M) produced long-lasting atropine-resistant smooth muscle contraction, an effect potentiated by phosphoramidon (10(-5) M (P less than .001). Removal of the epithelium slightly but significantly (P less than .05) increased the contractile responses to capsaicin and to EFS at impulse frequencies of 2 and 5 Hz, and phosphoramidon substantially increased contractions in tissues without epithelium. The trachea, bronchi and lungs each contained significant NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrospective cohort study of bronchial doses and radiation-induced atelectasis after stereotactic body radiation therapy of lung tumors located close to the bronchial tree.

PubMed

Karlsson, Kristin; Nyman, Jan; Baumann, Pia; Wersäll, Peter; Drugge, Ninni; Gagliardi, Giovanna; Johansson, Karl-Axel; Persson, Jan-Olov; Rutkowska, Eva; Tullgren, Owe; Lax, Ingmar

2013-11-01

To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D(0.1cm3)) was used for further analysis. The median value of D(0.1cm3) (α/β = 3 Gy) was EQD(2,LQ) = 147 Gy3 (range, 20-293 Gy3). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy3, and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy3. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown. Copyright © 2013 Elsevier Inc. All rights reserved.

High-resolution computed tomography evaluation of the bronchial lumen to vertebral body diameter and pulmonary artery to vertebral body diameter ratios in anesthetized ventilated normal cats.

PubMed

Lee-Fowler, Tekla M; Cole, Robert C; Dillon, A Ray; Tillson, D Michael; Garbarino, Rachel; Barney, Sharron

2017-10-01

Objectives Bronchial lumen to pulmonary artery diameter (BA) ratio has been utilized to investigate pulmonary pathology on high-resolution CT images. Diseases affecting both the bronchi and pulmonary arteries render the BA ratio less useful. The purpose of the study was to establish bronchial lumen diameter to vertebral body diameter (BV) and pulmonary artery diameter to vertebral body diameter (AV) ratios in normal cats. Methods Using high-resolution CT images, 16 sets of measurements (sixth thoracic vertebral body [mid-body], each lobar bronchi and companion pulmonary artery diameter) were acquired from young adult female cats and 41 sets from pubertal female cats. Results Young adult and pubertal cat BV ratios were not statistically different from each other in any lung lobe. Significant differences between individual lung lobe BV ratios were noted on combined age group analysis. Caudal lung lobe AV ratios were significantly different between young adult and pubertal cats. All other lung lobe AV ratios were not significantly different. Caudal lung lobe AV ratios were significantly different from all other lung lobes but not from each other in both the young adult and pubertal cats. Conclusions and relevance BV ratio reference intervals determined for individual lung lobes could be applied to both young adult and pubertal cats. Separate AV ratios for individual lung lobes would be required for young adult and pubertal cats. These ratios should allow more accurate evaluation of cats with concurrent bronchial and pulmonary arterial disease.

Image quality of mixed convolution kernel in thoracic computed tomography.

PubMed

Neubauer, Jakob; Spira, Eva Maria; Strube, Juliane; Langer, Mathias; Voss, Christian; Kotter, Elmar

2016-11-01

The mixed convolution kernel alters his properties geographically according to the depicted organ structure, especially for the lung. Therefore, we compared the image quality of the mixed convolution kernel to standard soft and hard kernel reconstructions for different organ structures in thoracic computed tomography (CT) images.Our Ethics Committee approved this prospective study. In total, 31 patients who underwent contrast-enhanced thoracic CT studies were included after informed consent. Axial reconstructions were performed with hard, soft, and mixed convolution kernel. Three independent and blinded observers rated the image quality according to the European Guidelines for Quality Criteria of Thoracic CT for 13 organ structures. The observers rated the depiction of the structures in all reconstructions on a 5-point Likert scale. Statistical analysis was performed with the Friedman Test and post hoc analysis with the Wilcoxon rank-sum test.Compared to the soft convolution kernel, the mixed convolution kernel was rated with a higher image quality for lung parenchyma, segmental bronchi, and the border between the pleura and the thoracic wall (P < 0.03). Compared to the hard convolution kernel, the mixed convolution kernel was rated with a higher image quality for aorta, anterior mediastinal structures, paratracheal soft tissue, hilar lymph nodes, esophagus, pleuromediastinal border, large and medium sized pulmonary vessels and abdomen (P < 0.004) but a lower image quality for trachea, segmental bronchi, lung parenchyma, and skeleton (P < 0.001).The mixed convolution kernel cannot fully substitute the standard CT reconstructions. Hard and soft convolution kernel reconstructions still seem to be mandatory for thoracic CT.

Structural basis for pulmonary functional imaging.

PubMed

Itoh, H; Nakatsu, M; Yoxtheimer, L M; Uematsu, H; Ohno, Y; Hatabu, H

2001-03-01

An understanding of fine normal lung morphology is important for effective pulmonary functional imaging. The lung specimens must be inflated. These include (a) unfixed, inflated lung specimen, (b) formaldehyde fixed lung specimen, (c) fixed, inflated dry lung specimen, and (d) histology specimen. Photography, magnified view, radiograph, computed tomography, and histology of these specimens are demonstrated. From a standpoint of diagnostic imaging, the main normal lung structures consist of airways (bronchi and bronchioles), alveoli, pulmonary vessels, secondary pulmonary lobules, and subpleural pulmonary lymphatic channels. This review summarizes fine radiologic normal lung morphology as an aid to effective pulmonary functional imaging.

Swyer-James syndrome associated with Noonan syndrome: report of a case.

PubMed

Lin, Y M; Huang, W L; Hwang, J J; Ko, Y L; Lien, W P

1995-12-01

A 28-year-old man with Noonan syndrome associated with unilateral hyperlucent lung is reported. He had the typical craniofacial appearance and short stature of Noonan syndrome; he had mild mental retardation, atrophic testis, mild funnel chest and kyphosis. cardiovascular abnormalities included asymmetric hypertrophic cardiomyopathy and a significantly different caliber of the left and right pulmonary arteries. The unilateral hyperlucent lung was shown to result from acquired nondestructive emphysema caused by nonvalvular obstruction of the bronchi (Swyer-James syndrome or Macleod's syndrome). To the authors' knowledge, this is the first reported case of Noonan syndrome associated with Swyer-James syndrome.

Immune Organs and Haemopoietic System Under Modelling of the Mission Factors

NASA Astrophysics Data System (ADS)

Sapin, M. R.; Grigoriev, A. I.; Erofeeva, L. M.; Grigorenko, D. E.; Fedorenko, B. S.

1997-07-01

Literary and experimental data on the character of changes in immune organs and lymphoid tissue of respiratory system and digestive system in laboratory animals during the mission factors model are given. Inhibition of reproductive function in bone marrow, thymus and spleen under irradiation of gamma-rays and accelerated carbon ions, tensity of immune response in the lymphoid structures of larynx, trachea and bronchi under the influence of acetaldehyde vapors and decrease of lymphoid tissue square on histological series in spleen and small intestine with an increase of concentration of microbial bodies in the drinking water were estimated.

Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses.

PubMed Central

Karlsson, J. A.; Persson, C. G.

1983-01-01

Propranolol-resistant neurogenic relaxation persisted in (carbachol-contracted) guinea-pig tracheae already relaxed by supramaximal concentrations of vasoactive intestinal polypeptide (VIP). Also, VIP relaxed preparations that were under neurogenic inhibition. In hilus bronchi, about 60% of a neurogenic contraction was atropine-resistant. (Arg5, D-Trp7.9) SP 5-11 specifically antagonized this contraction and those produced by exogenous substance P. Substance P, but not VIP, seems to be involved in nerve-mediated effects on guinea-pig airway tone. PMID:6197124

Particle deposition due to turbulent diffusion in the upper respiratory system

NASA Technical Reports Server (NTRS)

Hamill, P.

1979-01-01

Aerosol deposition in the upper respiratory system (trachea to segmental bronchi) is considered and the importance of turbulent diffusion as a deposition mechanism is evaluated. It is demonstrated that for large particles (diameter greater than about 5 microns), turbulent diffusion is the dominant deposition mechanism in the trachea. Conditions under which turbulent diffusion may be important in successive generations of the pulmonary system are determined. The probability of particle deposition is compared with probabilities of deposition, as determined by the equations generally used in regional deposition models. The analysis is theoretical; no new experimental data is presented.

Effects of Heat and Moisture Exchangers and Exhaled Humidity on Aerosol Deposition in a Simulated Ventilator-Dependent Adult Lung Model.

PubMed

Ari, Arzu; Alwadeai, Khalid S; Fink, James B

2017-05-01

Many in vitro models report higher inhaled dose with dry versus heated humidity. Heat-and-moisture exchangers (HMEs) provide passive humidity in ventilator-dependent patients but act as a barrier to aerosol. The HMEs designed to allow aerosol delivery (HME-ADs) have not been well described. The purpose of this study is to determine the impact on aerosol deposition of HME-ADs with and without active exhaled humidity in a simulated ventilator-dependent adult model. We used an in vitro lung model consisting of an intubated teaching mannequin with an endotracheal tube of 8.0 mm inner diameter with bronchi directly attached to a collecting filter and passive rubber test lung to provide testing without active exhaled humidity. To simulate exhaled humidity, a Cascade humidifier (37°C and 100% relative humidity) was placed between the collecting filter and test lung, simulating body temperature and pressure saturated exhaled humidity at the bronchi. Albuterol sulfate (2.5 mg/3 mL) was administered with a mesh nebulizer (Aerogen Solo) placed in the inspiratory limb of the ventilator circuit at the Y-piece, with no HME in place (control) and with 3 HME-AD devices, including the CircuVent, Humid-Flo, and AirLife, with and without exhaled humidity. Drug was eluted from the collecting filter and analyzed with spectrophotometry. Student t tests and analysis of variance were used for data analysis ( P < .05). The percentage of drug dose delivered (mean ± SD) distal to the bronchi in the control experiments was greater than all of the HME-ADs without exhaled humidity 18 ± 0.7 and with active exhaled humidity 10.8 ± 0.2% ( P < .005). Without exhaled humidity, aerosol delivery with the CircuVent (12.6 ± 0.8), Humid-Flo (15.3 ± 0.8), and AirLife (12.0 ± 0.5) was less than control ( P < .001, P = .01 and P < .001, respectively). In contrast, with exhaled humidity, no difference was found between control and HME-ADs ( P = .89). Also, a greater variation between control and the 3 HME-ADs was observed without exhaled humidity. Drug delivery without exhaled humidity exceeded aerosol deposition obtained with exhaled humidity in all conditions tested in this study. In this model simulating active exhaled humidity, aerosol drug delivery was lower and more consistent with both control and the HME-ADs than with the standard nonhumidified model. Further studies are needed to determine whether greater deposition in a dry model is an artifact of the model that does not simulate exhaled humidity. Copyright © 2017 by Daedalus Enterprises.

The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.

PubMed

Raju, S Vamsee; Lin, Vivian Y; Liu, Limbo; McNicholas, Carmel M; Karki, Suman; Sloane, Peter A; Tang, Liping; Jackson, Patricia L; Wang, Wei; Wilson, Landon; Macon, Kevin J; Mazur, Marina; Kappes, John C; DeLucas, Lawrence J; Barnes, Stephen; Kirk, Kevin; Tearney, Guillermo J; Rowe, Steven M

2017-01-01

Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-μm resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis.

Evidence of solitary chemosensory cells in a large mammal: the diffuse chemosensory system in Bos taurus airways

PubMed Central

Tizzano, Marco; Merigo, Flavia; Sbarbati, Andrea

2006-01-01

The diffuse chemosensory system (DCS) of the respiratory apparatus is composed of solitary chemosensory cells (SCCs) that resemble taste cells but are not organized in end organs. The discovery of the DCS may open up new approaches to respiratory diseases. However, available data on mammalian SCCs have so far been collected from rodents, the airways of which display some differences from those of large mammals. Here we investigated the presence of the DCS and of SCCs in cows and bulls (Bos taurus), in which the airway cytology is similar to that in humans, focusing our attention on detection in the airways of molecules involved in the transduction cascade of taste [i.e. α-gustducin and phospholipase C of the β2 subtype (PLCβ2)]. The aim of the research was to extend our understanding of airway chemoreceptors and to compare the organization of the DCS in a large mammal with that in rodents. Using immunocytochemistry for α-gustducin, the taste buds of the tongue and arytenoid were visualized. In the trachea and bronchi, α-gustducin-immunoreactive SCCs were frequently found. Using immunocytochemistry for PLCβ2, the staining pattern was generally similar to those seen for α-gustducin. Immunoblotting confirmed the expression of α-gustducin in the tongue and in all the airway regions tested. The study demonstrated the presence of SCCs in cows and bulls, suggesting that DCSs are present in many mammalian species. The description of areas with a high density of SCCs in bovine bronchi seems to indicate that the view of the DCS as made up of isolated cells totally devoid of ancillary elements is probably an oversimplification. PMID:16928202

Hypoxic Gene Expression of Donor Bronchi Linked to Airway Complications after Lung Transplantation.

PubMed

Kraft, Bryan D; Suliman, Hagir B; Colman, Eli C; Mahmood, Kamran; Hartwig, Matthew G; Piantadosi, Claude A; Shofer, Scott L

2016-03-01

Central airway stenosis (CAS) after lung transplantation has been attributed in part to chronic airway ischemia; however, little is known about the time course or significance of large airway hypoxia early after transplantation. To evaluate large airway oxygenation and hypoxic gene expression during the first month after lung transplantation and their relation to airway complications. Subjects who underwent lung transplantation underwent endobronchial tissue oximetry of native and donor bronchi at 0, 3, and 30 days after transplantation (n = 11) and/or endobronchial biopsies (n = 14) at 30 days for real-time polymerase chain reaction of hypoxia-inducible genes. Patients were monitored for 6 months for the development of transplant-related complications. Compared with native endobronchial tissues, donor tissue oxygen saturations (Sto2) were reduced in the upper lobes (74.1 ± 1.8% vs. 68.8 ± 1.7%; P < 0.05) and lower lobes (75.6 ± 1.6% vs. 71.5 ± 1.8%; P = 0.065) at 30 days post-transplantation. Donor upper lobe and subcarina Sto2 levels were also lower than the main carina (difference of -3.9 ± 1.5 and -4.8 ± 2.1, respectively; P < 0.05) at 30 days. Up-regulation of hypoxia-inducible genes VEGFA, FLT1, VEGFC, HMOX1, and TIE2 was significant in donor airways relative to native airways (all P < 0.05). VEGFA, KDR, and HMOX1 were associated with prolonged respiratory failure, prolonged hospitalization, extensive airway necrosis, and CAS (P < 0.05). These findings implicate donor bronchial hypoxia as a driving factor for post-transplantation airway complications. Strategies to improve airway oxygenation, such as bronchial artery re-anastomosis and hyperbaric oxygen therapy merit clinical investigation.

Morbidity, Disability and Death Rates of The Population Due to Malignant Neoplasms in Uralsk City in The Republic of Kazakhstan

PubMed

Umarova, Gulmira; Mamyrbayev, Аrstan; Bermagambetova, Saule; Baspakova, Akmaral; Satybaldieva, Umyt; Sabyrakhmetova, Valentina; Abilov, Talgar; Sultanova, Gulnar; Uraz, Raisa

2016-12-01

Objective: The dynamics of morbidity, disability and death rates due to malignant neoplasms in the population in Uralsk city of the Republic of Kazakhstan were studied for 2011-2015, with a focus on age and sex, as well as tumor location. Methods: Statistics for total morbidity, primary disability and mortality from cancer in the adult population of the city of Uralsk for 2011-2015 were calculated per 100 thousand. Estimation of morbidity was based on data from form - №12 «Report on the number of diseases registered in patients living in the area of health care organizations and patient population under medical observation”. Evaluation of primary disability was based on form №7 «The distribution of newly recognized disabled by disease class, age, sex and disability groups” for 2011-2015 in Ural city and analysis of cancer was carried out using annual form 7 “Report on the sick, and diseases of malignant neoplasms”. Result: The most common localizations of cancer were the trachea, bronchi, lungs, stomach and mammary glands. High death rates were noted for patients with cancer of the trachea, bronchi, lung, as compared to stomach and esophagus. Conclusion: The results of our investigation and data in the literature indicate that regional characteristics influence the impact of risk factors associated with cancer. An unfavorable environmental background contributes to ill health of urban populations, contributing to development of cancer. Moreover behavioral risk factors are very important, such as smoking, alcohol drinking, and an unhealthy diet. All these factors require urgent adoption of a package of measures for prevention, early detection and timely treatment. Detailed study of cancer is necessary to develop national programs and activities for prevention and control. Creative Commons Attribution License

Pre- and postjunctional inhibitory effects of fenspiride on guinea-pig bronchi.

PubMed

Girard, V; Naline, E; Crambes, O; Malbezin, M; Malmström, R E; Lundberg, J M; Advenier, C

1997-05-01

Fenspiride is a drug with potential benefits in the treatment of obstructive airways disease. It has antibronchoconstriction and anti-inflammatory properties. The aim of this study was to investigate the effect of this drug on the contractions induced in the guinea-pig isolated main bronchus and perfused lung by electrical field stimulation (EFS) or exogenously added agents. Bronchi were stimulated transmurally in the presence of indomethacin 10(-6) M and propranolol 10(-6) M, and isometric tension was measured. In the perfused lung model calcitonin gene-related peptide (CGRP) release was determined in the perfusate fractions as a measure of neuropeptide production. Two successive contractile responses were observed: a rapid cholinergic contraction, followed by a long-lasting contraction due to local release of neuropeptides from C-fibre endings. Fenspiride (10(-6) to 10(-4) M) inhibited the nonadrenergic, noncholinergic (NANC) component of the contraction of the guinea-pig isolated main bronchus induced by EFS. Fenspiride significantly affected contractions induced by exogenously added substance P or [Nle10]-NKA(4-10) only at concentrations higher than 10(-3) M. In the guinea-pig perfused lung, fenspiride inhibited low pH- but not capsaicin-evoked release of CGRP. At higher concentrations (10(-4) M to 3x10(-4) M) fenspiride exhibited a significant inhibitory effect both on the cholinergic component of contractile response induced by EFS in the guinea-pig isolated main bronchus and on exogenously added acetylcholine. In conclusion, the result of this study suggests that fenspiride, in moderate concentrations, reduces the release of neuropeptides, including tachykinins, from sensory nerve endings at a prejunctional level. At higher concentrations, postjunctional actions on bronchial smooth muscle are also present.

Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karlsson, Kristin, E-mail: kristin.karlsson@karolinska.se; Department of Oncology-Pathology, Karolinska Institute, Stockholm; Nyman, Jan

2013-11-01

Purpose: To evaluate the dose–response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm{sup 3} up to 2.0 cm{sup 3}]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showedmore » a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm{sup 3} (D{sub 0.1cm3}) was used for further analysis. The median value of D{sub 0.1cm3} (α/β = 3 Gy) was EQD{sub 2,LQ} = 147 Gy{sub 3} (range, 20-293 Gy{sub 3}). For patients who developed atelectasis the median value was EQD{sub 2,LQ} = 210 Gy{sub 3}, and for patients who did not develop atelectasis, EQD{sub 2,LQ} = 105 Gy{sub 3}. Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose–response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.« less

Morphometry of the distribution of hydrostatic pulmonary oedema in dogs.

PubMed Central

Michel, R. P.; Meterissian, S.; Poulsen, R. S.

1986-01-01

Light microscopic morphometry was utilized to examine the distribution of fluid in the interstitium around arteries, veins and within bronchovascular bundles in hydrostatic oedema, comparing it with previous control and permeability oedema experiments. Pulmonary artery wedge pressure was raised with fluid overload and an aortic balloon in five anaesthetized dogs to produce oedema (wet weight to dry weight ratios of 11.66 +/- 0.84). Lung lobes were fixed by freeze-substitution at 20 mmHg airway pressure. Photomicrographs of arteries, veins and bronchovascular bundles were taken, and areas were digitized to obtain the following: for arteries and veins, an oedema ratio=perivascular oedema cuff area/vessel area; for bronchovascular bundles, T=total bundle area, A1=interstitial area around airways, B=airway (respiratory bronchiole, bronchiole, or bronchus) area, A2=periarterial interstitium, V=artery area. From these, oedema ratios were calculated as A1/B and A2/V. We found that the oedema ratios were greater (P less than 0.01) for arteries (1.18, n=675) than veins (0.56, n=263), and were greater for the larger vessels; A1 rose significantly (P less than 0.01) only in bronchovascular bundles with bronchioles and bronchi, not in those with respiratory bronchioles; A2 increased from three- to 25-fold (P less than 0.01) in all bundles; A1/B only increased in bundles with bronchi while A2/V increased two- to six-fold in all bundles with oedema compared with controls. We conclude that these preferential patterns of distribution resemble those reported in permeability oedema, and may shed light on mechanisms of accumulation, and on the physiological effects of oedema on airways and vessels of the lung. Images Fig. 1 Fig. 2 PMID:3801300

High-resolution three-dimensional 19F-magnetic resonance imaging of rat lung in situ: evaluation of airway strain in the perfluorocarbon-filled lung.

PubMed

Weigel, Julia K; Steinmann, Daniel; Emerich, Philipp; Stahl, Claudius A; v Elverfeldt, Dominik; Guttmann, Josef

2011-02-01

Perfluorocarbons (PFC) are biologically and chemically inert fluids with high oxygen and CO(2) carrying capacities. Their use as liquid intrapulmonary gas carriers during liquid ventilation has been investigated. We established a method of high resolution 3D-(19)F-MRI of the totally PFC-filled lung. The goal of this study was to investigate longitudinal and circumferential airway strain in the setting of increasing airway pressures on 3D-(19)F-MR images of the PFC-filled lung. Sixteen female Wistar rats were euthanized and the liquid perfluorocarbon FC-84 instilled into their lungs. 3D-(19)F-MRI was performed at various intrapulmonary pressures. Measurements of bronchial length and cross-sectional area were obtained from transversal 2D images for each pressure range. Changes in bronchial area were used to determine circumferential strain, while longitudinal strain was calculated from changes in bronchial length. Our method of 3D-(19)F-MRI allowed clear visualization of the great bronchi. Longitudinal strain increased significantly up to 31.1 cmH(2)O. The greatest strain could be found in the range of low airway pressures. Circumferential strain increased strongly with the initial pressure rise, but showed no significant changes above 10.4 cmH(2)O. Longitudinal strain was generally higher in distal airways, while circumferential strain showed no difference. Analysis of mechanical characteristics showed that longitudinal and circumferential airway expansion occurred in an anisotropic fashion. Whereas longitudinal strain still increased with higher pressures, circumferential strain quickly reached a 'strain limit'. Longitudinal strain was higher in distal bronchi, as dense PFCs gravitate to dependent, in this case to dorso-basal parts of the lung, acting as liquid positive end expiratory pressure.

Oral frostbite injury from intentional abuse of a fluorinated hydrocarbon.

PubMed

Kuspis, D A; Krenzelok, E P

1999-01-01

A serious but rarely reported complication of halogenated hydrocarbon inhalation abuse is severe mucosal frostbite. A 16-year-old male attempted to "get high" by inhaling airbrush propellant which contained 1,1-difluoroethane (CAS #75-376). The patient lost consciousness and upon awakening his lips and tongue were frozen. He suffered first- and second-degree burns of the larynx with vocal cord involvement and first-degree burns of the trachea, main stem bronchi, and esophagus. The oral cavity had second- and third-degree burns which required debridement. This case demonstrates the unusual but severe damage that can occur with the abuse of fluorinated hydrocarbons.

Cardiovascular safety of antihistamines

PubMed Central

Olasiński, Jerzy; Grajek, Stefan

2014-01-01

Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the ‘rapid’ IKr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk. PMID:25097491

Bioprosthetics and repair of complex aerodigestive defects

PubMed Central

Udelsman, Brooks; Mathisen, Douglas J.

2018-01-01

Aerodigestive defects involving the trachea, bronchi and esophagus are a result of prolonged intubation, operative complications, congenital defects, trauma, radiation and neoplastic disease. The vast majority of these defects may be repaired primarily. Rarely, due the size of the defect, underlying complexity, or unfavorable patient characteristics, primary repair is not possible. One alternative to primary repair is bioprosthetic repair. Materials such as acellular dermal matrix and aortic homograft have been used in a variety of applications, including closure of tracheal, bronchial and esophageal defects. Herein, we review the use of bioprosthetics in the repair of aerodigestive defects, along with the unique advantages and disadvantages of these repairs. PMID:29707507

Three-dimensional pulmonary model using rapid-prototyping in patient with lung cancer requiring segmentectomy.

PubMed

Akiba, Tadashi; Nakada, Takeo; Inagaki, Takuya

2014-01-01

Thoracoscopic pulmonary segmentectomy of the lung is sometime adopted for the lung cancer, but a problem with segmentectomy is variable anatomy. Recently, we are exploring the impact of three-dimensional models using rapid-prototyping technique. It is useful for decision making, surgical planning, and intraoperative orientation for surgical treatment in patient with lung cancer who underwent pulmonary segmentectomy. These newly created models allow us to clearly identify the surgical margin and the intersegmental plane, vessels, and bronchi related to the cancer in the posterior segment. To the best of our knowledge, there are few reports describing a pulmonary model so far.

[Development of a virtual model of fibro-bronchoscopy].

PubMed

Solar, Mauricio; Ducoing, Eugenio

2011-09-01

A virtual model of fibro-bronchoscopy is reported. The virtual model represents in 3D the trachea and the bronchi creating a virtual world of the bronchial tree. The bronchoscope is modeled to look over the bronchial tree imitating the displacement and rotation of the real bronchoscope. The parameters of the virtual model were gradually adjusted according to expert opinion and allowed the training of specialists with a virtual bronchoscope of great realism. The virtual bronchial tree provides clues of reality regarding the movement of the bronchoscope, creating the illusion that the virtual instrument is behaving as the real one with all the benefits in costs that this means.

Mammomonogamus roundworm (Nematoda: Syngamidae) recovered from the duodenum of a Thai patient: a first and unusual case originating in Thailand.

PubMed

Eamsobhana, Praphathip; Mongkolporn, Thawat; Punthuprapasa, Phaibulaya; Yoolek, Adisak

2006-04-01

A pair of Mammomonogamus laryngeus roundworms in copula was recovered from the duodenum of a 72-year-old male Thai patient from Kanchanaburi Province. Eggs were also found in the stool of the patient. This is the first case of Mammomonogamus infection originating in Thailand, as the previous two reports from Thailand attributed the infection as originating in Malaysia. The occurrence of adult worms in the duodenum is unusual and differs from previous findings in the larynx, posterior pharynx, tracheal wall and bronchi. This adds a new dimension to the manifestation of the infection.

Characterization of NK1 and NK2 tachykinin receptors in guinea-pig and rat bronchopulmonary and vascular systems.

PubMed Central

Floch, A.; Fardin, V.; Cavero, I.

1994-01-01

1. NK1 and NK2 tachykinin receptors were characterized in guinea-pig and rat bronchopulmonary systems and in the vasculature of the rat by use of radioligand binding and/or functional studies. 2. The radioligands for NK1 and NK2 receptors ([3H]-SP and [3H]-pNKA, respectively) did not label tachykinin receptors in homogenates of rat lungs or bronchi. In contrast, in the guinea-pig, [3H]-SP bound with high affinity to these tissues (KD = 0.23 +/- 0.08 nM and 0.34 +/- 0.05 nM, for lungs and bronchi, respectively). The total number of binding sites was 4.6 fold greater in bronchus (Bmax = 135 +/- 27 fmol mg-1 protein) than in lung homogenates (Bmax = 29.3 +/- 0.1 fmol mg-1 protein). Furthermore, this binding was markedly displaced by CP-96,345 (pKi = 9.5 +/- 0.1) and RP 67580 (pKi = 7.6 +/- 0.1), antagonists of NK1 receptors, slightly displaced by SR 48968 (pKi = 6.6 +/- 0.1), but not affected by actinomycin D or L-659,877, antagonists of NK2 receptors. Specific binding of [3H]-pNKA, detected in guinea-pig bronchi (KD = 5.2 +/- 0.1 nM, and Bmax = 203 +/- 19 fmol mg-1 protein) but not in lungs, was similarly (40 to 53%) displaced by RP 67580 (1 microM), CP-96,345 (10 and 100 nM) or SR 48968 (10 and 100 nM). The displacement approximately doubled (87 to 91%) when SR 48968 (10 nM) was combined with either RP 67580 (1 microM) or CP-96,345 (10 nM), but not when RP 67580 was combined with CP-96,345. 3. In urethane-anaesthetized guinea-pigs, i.v. injections of the NK1 receptor agonists SP, [Pro9]-SP, [Sar9,Met(O2)11]-SP and septide, as well as the NK2 receptor agonists NKA and [Lys5,MeLeu9,NLeu10]-NKA(4-10) (0.1-10 micrograms kg-1, i.v.), dose-dependently increased lung inflation pressure. The most potent of these peptides were septide and [Lys5, MeLeu9,NLeu10]-NKA(4-10) (EC50 = 0.38 +/- 0.07 and 0.07 +/- 0.02 microgram kg-1, respectively). Interestingly, septide was 130 fold less potent than SP in displacing [3H]-SP from its binding sites in the guinea-pig lung, whereas it was 14 fold more potent than SP as a bronchoconstrictor. RP 67580 (0.3-5 mg kg-1, i.v.) and CP-96,345 (0.01-3 mg kg-1, i.v.) dose-dependently reduced the bronchoconstriction produced by the NK1 receptor agonists.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7517328

Toward the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction

PubMed Central

Mauroy, Benjamin; Flaud, Patrice; Pelca, Dominique; Fausser, Christian; Merckx, Jacques; Mitchell, Barrett R.

2015-01-01

Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions. We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increase any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two a dimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation. PMID:26300780

Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.

PubMed

van den Brand, Judith M A; Wohlsein, Peter; Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M; van de Bildt, Marco W G; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A M; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D M E; Kuiken, Thijs; Baumgärtner, Wolfgang

2016-01-01

Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans.

Observational study of sleep, respiratory mechanics and quality of life in patients with non-cystic fibrosis bronchiectasis: a protocol study

PubMed Central

Faria Júnior, Newton Santos; Oliveira, Luis Vicente Franco; Perez, Eduardo Araújo; de Oliveira, Ezequiel Fernandes; Apostolico, Nadua; Pereira, Nixon Alves; dos Santos, Israel dos Reis; Urbano, Jessica Julioti; Souza, Ismael Dias; Polonio, Igor Bastos; Romaldini, José Gustavo Barian; Pereira, Déborah Madeu; Alves, Vera Lúcia dos Santos; Souza, Ângela Honda; Nascimento, Oliver Augusto; Jardim, José Roberto; Stirbulov, Roberto

2015-01-01

Introduction Bronchiectasis is a chronic disorder characterised by permanent and irreversible abnormal dilation of the bronchi and bronchioles, primarily caused by repeated cycles of pulmonary infections and inflammation, which lead to reduced mucociliary clearance and to the excessive production of sputum. Patients with non-cystic fibrosis bronchiectasis may be predisposed to hypoxemia during sleep, or to symptoms that may lead to arousals and thereby reduce the quality of life, because of the irreversible dilation of the bronchi and the presence of secretions and airflow obstruction. Methods and analysis For this cross-sectional observational study, patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis will be recruited from the Bronchiectasis Clinic of the Pneumology Department of the Santa Casa de Misericordia Hospital and the Federal University of São Paulo (São Paulo, Brazil). Patients of either sex will be included if high-resolution CT of the thorax and classic sweat test confirms they have non-cystic fibrosis bronchiectasis, are between 18 and 80 years old, use long-acting bronchodilators, are clinically stable for a least 1 month, agree to participate in the study and they sign a statement of informed consent. The first part of the study will involve a clinical evaluation, maximal respiratory pressures, spirometry and the Saint George's Respiratory Questionnaire. The Sleep Laboratory of the Master's and Doctoral Postgraduate Program in Rehabilitation Sciences of the Nove de Julho University (São Paulo, Brazil) will perform the polysomnographic studies, Berlin Questionnaire, Epworth Sleepiness Scale, waist and neck circumferences, modified Mallampati classification and tonsil index. Ethics and dissemination This protocol has been approved by the Human Research Ethics Committees of Santa Casa de Misericordia Hospital (process number 178/2012) and Human Research Ethics Committee of Nove de Julho University (process number 370474/2010). All participants will sign a statement of informed consent. The study findings will be published in peer-reviewed journals and presented at conferences. PMID:26169808

Effects of two novel tachykinin antagonists, FK224 and FK888, on neurogenic airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo.

PubMed Central

Hirayama, Y.; Lei, Y. H.; Barnes, P. J.; Rogers, D. F.

1993-01-01

1. We compared the effects of two novel tachykinin receptor antagonists, FK888 (selective at the tachykinin NK1 receptor) and FK224 (dual antagonist at NK1 and NK2 tachykinin receptors) on stimulus-evoked airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo. Plasma exudation was induced by substance P (SP), synthetic tachykinin receptor agonists, platelet activating factor (PAF), electrical stimulation of the cervical vagus nerves or by inhalation of cigarette smoke. Changes in airway tone and in carotid artery blood pressure (BP) were induced by synthetic tachykinin agonists, PAF and vagal stimulation. 2. Both FK224 and FK888 dose-dependently inhibited SP-induced plasma exudation in the lower trachea and main bronchi (ID50 values respectively of 1.1 and 0.1 mumol kg-1 in lower trachea, and of 0.5 and 0.1 mumol kg-1 in main bronchi) with complete inhibition at both airway levels at 10 mumol kg-1 for FK224 and at 2 mumol kg-1 for FK888. 3. The NK1-selective tachykinin receptor agonist, [Sar9,Met(O2)11]substance P ([Sar]SP), induced plasma exudation, a response which was blocked by both FK888 and FK224. The NK2-selective agonist, [beta-Ala8]neurokinin A-(4-10) ([beta-Ala]NKA), did not induce plasma exudation: neither FK888 nor FK224 affected this lack of response to [beta-Ala]NKA. 4. [beta-Ala]NKA induced bronchoconstriction, a response which was blocked by FK224 but which was completely unaffected by FK888. [Sar]SP induced a small but significant bronchoconstriction which was completely inhibited by both tachykinin antagonists. 5. In animals pretreated with capsaicin to deplete sensory neuropeptides, PAF induced both plasma exudation and bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682142

Distribution of (/sup 14/C)acrylamide in male and pregnant Swiss-Webster mice studied by whole-body autoradiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marlowe, C.; Clark, M.J.; Mast, R.W.

1986-12-01

Male and 13.5- and 17.5-day pregnant Swiss-Webster mice were administered 120 mg/kg (2,3-14C)acrylamide orally. The male mice were frozen 0.33, 1, 3, 9, 24, 72, and 216 hr later, and the pregnant mice at each gestational period were frozen at 3 and 24 hr. Whole-body autoradiographs from the male mice at early time intervals revealed accumulation of radioactivity in the contents of the gastrointestinal tract, liver, pancreas, testis, brain and gallbladder, and epithelia of oral cavity, esophagus, and bronchi. The distribution appears to be similar in the male and pregnant mice. Absorption from the stomach was virtually complete by 3more » hr; renal and hepatic elimination was essentially complete at 24 hr. Radioactivity in the male reproductive tract appeared in the parenchyma of the testis at 1 hr, moved to the seminiferous tubules and head of the epididymis at 9 hr, and by 9 days remained only in the tail of the epididymis and the crypts of the epithelium of the glans penis. This movement parallels that of spermatids. The 13.5-day fetuses were uniformly labeled except for a slightly increased uptake in fetal brain. The distribution of radioactivity in the 17.5-day fetal tissues resembled that in maternal tissues; the remarkable exception was an intense accumulation in fetal skin. This study indicates that acrylamide is efficiently absorbed from the stomach and eliminated by the liver, kidney, and possibly the pancreas. A previously unrecognized affinity of acrylamide or a metabolic product was demonstrated for fetal skin in late gestation and for adult epithelia of oral cavity, esophagus, forestomach, and bronchi. Also, acrylamide or a metabolite appears to bind to spermatids at a specific stage near maturation.« less

Impact of endobronchial coiling on segmental bronchial lumen in treated and untreated lung lobes: Correlation with changes in lung volume, clinical and pulmonary function tests.

PubMed

Kloth, C; Thaiss, W M; Hetzel, J; Ditt, H; Grosse, U; Nikolaou, K; Horger, M

2016-07-01

To assess the impact of endobronchial coiling on the segment bronchus cross-sectional area and volumes in patients with lung emphysema using quantitative chest-CT measurements. Thirty patients (female = 15; median age = 65.36 years) received chest-CT before and after endobronchial coiling for lung volume reduction (LVR) between January 2010 and December 2014. Thin-slice (0.6 mm) non-enhanced image data sets were acquired both at end-inspiration and end-expiration using helical technique and 120 kV/100-150 mAs. Clinical response was defined as an increase in the walking distance (Six-minute walk test; 6MWT) after LVR-therapy. Additionally, pulmonary function test (PFT) measurements were used for clinical correlation. In the treated segmental bronchia, the cross-sectional lumen area showed significant reduction (p < 0.05) in inspiration and tendency towards enlargement in expiration (p > 0.05). In the ipsilateral lobes, the lumina showed no significant changes. In the contralateral lung, we found tendency towards increased cross-sectional area in inspiration (p = 0.06). Volumes of the treated segments correlated with the treated segmental bronchial lumina in expiration (r = 0.80, p < 0.001). Clinical correlation with changes in 6MWT/PFT showed a significant decrease of the inspiratory volume of the treated lobe in responders only. Endobronchial coiling causes significant decrease in the cross-sectional area of treated segment bronchi in inspiration and a slight increase in expiration accompanied by a volume reduction. • Endobronchial coiling has indirect impact on cross-sectional area of treated segment bronchi • Volume changes of treated lobes correlate with changes in bronchial cross-sectional area • Coil-induced effects reflect their stabilizing and stiffening impact on lung parenchyma • Endobronchial coiling reduces bronchial collapsing compensating the loss of elasticity.

[Pulmonary manifestations in systemic lupus erythematosus].

PubMed

Vincze, Krisztina; Odler, Balázs; Müller, Veronika

2016-07-01

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

Suicidal choking caused by a bizarre combination of inhalation to the bronchi and external neck compression.

PubMed

Pampin, J B; Varela, L G

2001-06-01

We report a remarkable case of suicidal choking in an elderly man with depressive episodes and one previous attempt of suicide. Initially, the presence of a sweater around his neck and blunt injuries on his head, left elbow and sacrum region seemed to indicate a suspicious violent death. During the necropsy study, a fragment of newspaper was discovered inside his lower respiratory tract. Autopsy findings showed minimal punctata haemorrhages on the larynx and trachea. The subsequent toxicological investigation was negative. This case is extremely rare, because the deceased was not a schizophrenic patient and the peculiar foreign object was found in the lower level. To the best of our knowledge, in medicolegal literature, few similar cases have been reported.

Endoscopic low coherence interferometry in upper airways

NASA Astrophysics Data System (ADS)

Delacrétaz, Yves; Boss, Daniel; Lang, Florian; Depeursinge, Christian

2009-07-01

We introduce Endoscopic Low Coherence Interferometry to obtain topology of upper airways through commonly used rigid endoscopes. Quantitative dimensioning of upper airways pathologies is crucial to provide maximum health recovery chances, for example in order to choose the correct stent to treat endoluminal obstructing pathologies. Our device is fully compatible with procedures used in day-to-day examinations and can potentially be brought to bedside. Besides this, the approach described here can be almost straightforwardly adapted to other endoscopy-related field of interest, such as gastroscopy and arthroscopy. The principle of the method is first exposed, then filtering procedure used to extract the depth information is described. Finally, demonstration of the method ability to operate on biological samples is assessed through measurements on ex-vivo pork bronchi.

[Tracheomalacia (TM) or bronchomalacia (BM) in children: conservative or invasive therapy].

PubMed

Fayon, M; Donato, L

2010-01-01

Tracheomalacia (TM) or bronchomalacia (BM) refers to softness or weakness of the trachea or the bronchi. Its management is not evidenced-based. Conservative therapy is preferred in milder cases, since the outcome is usually favourable within the first 2 years of life. The clinical utility of non-specific treatments (anti-inflammatory agents, bronchodilators, antibiotics, physiotherapy) has not been proven by clinical trials. Treatment of symptomatic cases should be discussed on an individual basis. Airway surgery should be avoided, and non-invasive ventilation may be proposed as a temporary measure. In case of very severe cases, aortopexy, trachostomy or stent placement are the preferred treatments. Regular respiratory monitoring until remission is mandatory. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Pulmonary atelectasis manifested after induction of anesthesia: a contribution of sinobronchial syndrome?

PubMed

Igarashi, Ayuko; Amagasa, Sumio; Oda, Shinya; Yokoo, Noriko

2007-01-01

A 31-year-old man underwent general anesthesia for sinus surgery. Anesthesia was induced with midazolam and butorphanol, and an endotracheal tube was orally placed with a bronchoscope, due to difficulty with temporomandibular joint opening. Ventilation difficulty and increased peak inspiratory pressure were noticed shortly after tracheal intubation, and bronchoscopy was performed for diagnosis. The bronchi were filled with a clear mucous secretion. Removal of the secretion improved respiration and decreased the peak inspiratory pressure. A chest roentgenogram taken prior to extubation showed right upper lobe atelectasis. A diagnosis of sinobronchial syndrome was made postoperatively. The etiology of the acutely developed atelectasis was unclear. However, the latent syndrome may have induced excessive airway secretion with stimuli such as endotracheal intubation.

Endobronchial Mucosal Neuroma with Sarcoidosis.

PubMed

Erdem, Ipek; Duman, Dildar; Eroglu, Selma; Agca, Meltem; Erdagi, Aykut; Turker, Hatice; Hazar, Armagan

2018-02-01

A first case of endobronchial mucosal neuroma with sarcoidosis is hereby reported. A 67-year female patient, who was diagnosed as sarcoidosis previously, was admitted to our hospital with symptoms of dyspnea, chest pain and fatigue. Middle lobe atelectasis and endobronchial lesion were observed in thorax computed tomography (CT). Fiberoptic bronchoscopy revealed polypoid lesions and histopathological examination of biopsy material showed clustered nerve bundles consistent with mucosal neuroma and non-necrotising granulomas consistent with sarcoidosis. Mucosal neuromas are pathognomonic features of multiple endocrine neoplasia (MEN) type 2B. But other components of MEN type 2B such as medullary tyroid carcinoma or pheochromocytoma were not detected in our patient. Hence, a diagnosis of solitary mucosal neuroma and sarcoidosis in the bronchi was made.

[Particular aspects of rhinitis and rhino-conjunctivitis].

PubMed

Favennec, F; Sonneville, A; De Luca, H; Castros, A

2003-03-01

The authors report their experience of 28 years of practice in the opthalmology service of the CHRU at Rennes. The describe certain particular aspects of rhinitis and rhino-conjuctivitis where the danger resides in an extensive risk to the uvula or the bronchi. They insist on the importance of understanding polyvalents in internal medicine (rôle of the seat of gingivodentary "ideas", value of research into indicative markers of protection A2 and B40 in the HLA system. In the region of nutrition, they emphasize the importance of the rôle of zinc, of vitamin C and of magnesium. They base their hopes on study of the local markers of sensitivity, in order to assess the elements of preventative action for an eventual ocular and bronchial extension.

Endobronchial occlusive disease: Nd:YAG or PDT?

NASA Astrophysics Data System (ADS)

Regal, Anne-Marie; Takita, Hiroshi

1991-06-01

Patients with endobronchial occlusion commonly experience dyspnea, cough, hemoptysis, pneumonitis, and atelectasis. If luminal patency is not re-established, obstructive symptoms may progress to sepsis and death. Although the overall survival of patients with lung cancer may not be altered by relief of airway obstruction, the prognosis for this subset of patients may be improved by eliminating the septic complications of bronchial occlusion. Techniques to treat occluded bronchi include electro-fulguration, cryotherapy, brachytherapy, laser (CO2, Nd-YAG) therapy, and photodynamic therapy (PDT). These represent local forms of treatment and are intended to be palliative. Nd-YAG and PDT are the modalities more frequently utilized in this setting. Comparison of the two treatment forms may furnish insight regarding the appropriate role for each as individual therapies and as part of the armamentarium of cancer therapies.

Variations in the morphology of Rhizomucor pusillus in granulomatous lesions of a Magellanic penguin (Spheniscus magellanicus).

PubMed

Suzuta, Fumiko; Kimura, Kumiko; Urakawa, Ryo; Kusuda, Yukio; Tanaka, Shogo; Hanafusa, Yasuko; Haritani, Makoto

2015-08-01

This report presents a new case of mucormycosis encountered in penguin characterized by morphological variation of hyphae and presence of sporangia with numerous sporangiospores. A 4.5-year-old Magellanic penguin (Spheniscus magellanicus) died after exhibiting anorexia, poor nutritional condition and dyspnea. Multiple nodular lesions were observed in the thoracic and abdominal regions. Histopathologically, hyphae of various sizes were seen in the lungs, air sac and nodular lesions. Myriad sporangiospores and several sporangia were observed in/around the bronchi or parabronchi. The very narrow and short hyphae in the nodules were not consistent with the characteristics of Mucorales. However, for most hyphae, including those in the nodules, sporangiospores and sporangia, immunohistochemistry revealed Mucorales-positive reactions. In addition, these fungi were identified as Rhizomucor pusillus by gene analysis.

Beta-blocker-induced psoriasis: a rare side effect--a case report.

PubMed

Yilmaz, Mehmet Birhan; Turhan, Hasan; Akin, Yesim; Kisacik, Halil L; Korkmaz, Sule

2002-01-01

Beta blockers are one of the oral agents shown to decrease cardiovascular morbidity and mortality rates in randomized, controlled trials, and hence, they are widely used for the management of many cardiovascular situations. In terms of side effects there are 3 major modes of action: (1) contraction of smooth muscles, particularly of bronchi with nonselective agents; (2) exaggerated cardiac effects; and (3) central nervous system effects. There are also some rare side effects of beta blockers, some of which are unpredictable, but the others are related to mode of action at the cellular level. Beta-blocking agents may cause psoriaform eruptions and worsen existing psoriasis. Psoriasis may be an inconvenient side effect of beta blockade. Herein, we report a case of beta-blocker-induced psoriasis.

Tracheal worms

USGS Publications Warehouse

Cole, Rebecca A.

1999-01-01

Infection by tracheal worms often results in respiratory distress due to their location in the trachea or bronchi and their obstruction of the air passage. Infections by these parasitic nematodes or roundworms in waterbirds, primarily ducks, geese, and swans, are usually due to Cyathostoma bronchialis and infection of land birds are usually due to Syngamus trachea. However, both genera infect a variety of species, including both land and waterbirds. Infections with S. trachea have been more extensively studied than infections with Cyathostoma sp. because of its previous importance as a disease-causing parasite of poultry in many parts of the world. Changes in husbandry practices to modern intensive methods for poultry production have essentially eliminated S. trachea as an agent of disease in chickens, but it is an occasional cause of disease in turkeys raised on range.

Endoscopic low-coherence topography measurement for upper airways and hollow samples

NASA Astrophysics Data System (ADS)

Delacrétaz, Yves; Shaffer, Etienne; Pavillon, Nicolas; Kühn, Jonas; Lang, Florian; Depeursinge, Christian

2010-11-01

To evaluate the severity of airway pathologies, quantitative dimensioning of airways is of utmost importance. Endoscopic vision gives a projective image and thus no true scaling information can be directly deduced from it. In this article, an approach based on an interferometric setup, a low-coherence laser source and a standard rigid endoscope is presented, and applied to hollow samples measurements. More generally, the use of the low-coherence interferometric setup detailed here could be extended to any other endoscopy-related field of interest, e.g., gastroscopy, arthroscopy and other medical or industrial applications where tri-dimensional topology is required. The setup design with a multiple fibers illumination system is presented. Demonstration of the method ability to operate on biological samples is assessed through measurements on ex vivo pig bronchi.

[Tracheobronchoplasty for Severe Diffuse Tracheomalacia].

PubMed

Hoffmann, H; Gompelmann, D; Heußel, C P; Dienemann, H; Eberhardt, R

2016-09-01

Patients with diffuse airway instability due to tracheobronchomalacia or excessive dynamic airway collapse are typically highly symptomatic, with marked dyspnoea, recurrent bronchopulmonary infections and excruciating intractable cough. Silicone stents achieve immediate symptom control, but are - due to the typical complications associated with stent treatment - usually not an option for long-term treatment. The aim of surgical intervention is definitive stabilisation of the trachea and of both main bronchi by posterior splinting of the Paries membranaceus with a polypropylene mesh. This operation is an appropriate treatment option for patients with documented severe tracheobronchomalacia or excessive dynamic airway collapse and is ultimately the only therapy that can achieve permanent symptom control. The success of the operation, however, depends on many factors and requires close interdisciplinary collaboration. Georg Thieme Verlag KG Stuttgart · New York.

Monitoring the state of the human airways by analysis of respiratory sound

NASA Technical Reports Server (NTRS)

Hardin, J. C.; Patterson, J. L., Jr.

1978-01-01

A mechanism whereby sound is generated by the motion of vortices in the human lung is described. This mechanism is believed to be responsible for most of the sound which is generated both on inspiration and expiration in normal lungs. Mathematical expressions for the frequencies of sound generated, which depend only upon the axial flow velocity and diameters of the bronchi, are derived. This theory allows the location within the bronchial tree from which particular sounds emanate to be determined. Redistribution of pulmonary blood volume following transition from earth gravity to the weightless state probably alters the caliber of certain airways and doubtless alters sound transmission properties of the lung. We believe that these changes can be monitored effectively and non-invasively by spectral analysis of pulmonary sound.

Monitoring the state of the human airways by analysis of respiratory sound

NASA Technical Reports Server (NTRS)

Hardin, J. C.; Patterson, J. L. Jr

1979-01-01

A mechanism whereby sound is generated by the motion of vortices in the human lung is described. This mechanism is believed to be responsible for most of the sound which is generated both on inspiration and expiration in normal lungs. Mathematical expressions for the frequencies of sound generated, which depend only upon the axial flow velocity and diameters of the bronchi, are derived. This theory allows the location within the bronchial tree from which particular sounds emanate to be determined. Redistribution of pulmonary blood volume following transition from Earth gravity to the weightless state probably alters the caliber of certain airways and doubtless alters sound transmission properties of the lung. We believe that these changes can be monitored effectively and non-invasively by spectral analysis of pulmonary sound.

Binocular stereo-navigation for three-dimensional thoracoscopic lung resection.

PubMed

Kanzaki, Masato; Isaka, Tamami; Kikkawa, Takuma; Sakamoto, Kei; Yoshiya, Takehito; Mitsuboshi, Shota; Oyama, Kunihiro; Murasugi, Masahide; Onuki, Takamasa

2015-05-08

This study investigated the efficacy of binocular stereo-navigation during three-dimensional (3-D) thoracoscopic sublobar resection (TSLR). From July 2001, the authors' department began to use a virtual 3-D pulmonary model on a personal computer (PC) for preoperative simulation before thoracoscopic lung resection and for intraoperative navigation during operation. From 120 of 1-mm thin-sliced high-resolution computed tomography (HRCT)-scan images of tumor and hilum, homemade software CTTRY allowed sugeons to mark pulmonary arteries, veins, bronchi, and tumor on the HRCT images manually. The location and thickness of pulmonary vessels and bronchi were rendered as diverse size cylinders. With the resulting numerical data, a 3-D image was reconstructed by Metasequoia shareware. Subsequently, the data of reconstructed 3-D images were converted to Autodesk data, which appeared on a stereoscopic-vision display. Surgeons wearing 3-D polarized glasses performed 3-D TSLR. The patients consisted of 5 men and 5 women, ranging in age from 65 to 84 years. The clinical diagnoses were a primary lung cancer in 6 cases and a solitary metastatic lung tumor in 4 cases. Eight single segmentectomies, one bi-segmentectomy, and one bi-subsegmentectomy were performed. Hilar lymphadenectomy with mediastinal lymph node sampling has been performed in 6 primary lung cancers, but four patients with metastatic lung tumors were performed without lymphadenectomy. The operation time and estimated blood loss ranged from 125 to 333 min and from 5 to 187 g, respectively. There were no intraoperative complications and no conversion to open thoracotomy and lobectomy. Postoperative courses of eight patients were uneventful, and another two patients had a prolonged lung air leak. The drainage duration and hospital stay ranged from 2 to 13 days and from 8 to 19 days, respectively. The tumor histology of primary lung cancer showed 5 adenocarcinoma and 1 squamous cell carcinoma. All primary lung cancers were at stage IA. The organs having metastatic pulmonary tumors were kidney, bladder, breast, and rectum. No patients had macroscopically positive surgical margins. Binocular stereo-navigation was able to identify the bronchovascular structures accurately and suitable to perform TSLR with a sufficient margin for small pulmonary tumors.

Wnt/β-Catenin Signaling Modulates Human Airway Sensitization Induced by β2-Adrenoceptor Stimulation

PubMed Central

Faisy, Christophe; Grassin-Delyle, Stanislas; Blouquit-Laye, Sabine; Brollo, Marion; Naline, Emmanuel; Chapelier, Alain; Devillier, Philippe

2014-01-01

Background Regular use of β2-agonists may enhance non-specific airway responsiveness. The wingless/integrated (Wnt) signaling pathways are responsible for several cellular processes, including airway inflammation and remodeling while cAMP–PKA cascade can activate the Wnt signaling. We aimed to investigate whether the Wnt signaling pathways are involved in the bronchial hyperresponsiveness induced by prolonged exposure to β2-adrenoceptor agonists in human isolated airways. Methods Bronchi were surgically removed from 44 thoracic surgery patients. After preparation, bronchial rings and primary cultures of bronchial epithelial cells were incubated with fenoterol (0.1 µM, 15 hours, 37°C), a β2-agonist with high intrinsic efficacy. The effects of inhibitors/blockers of Wnt signaling on the fenoterol-induced airway sensitization were examined and the impact of fenoterol exposure on the mRNA expression of genes interacting with Wnt signaling or cAMP–PKA cascade was assessed in complete bronchi and in cultured epithelial cells. Results Compared to paired controls, fenoterol-sensitization was abolished by inhibition/blockage of the Wnt/β-catenin signaling, especially the cell-surface LRP5/6 co-receptors or Fzd receptors (1 µM SFRP1 or 1 µM DKK1) and the nuclear recruitment of TCF/LEF transcriptions factors (0.3 µM FH535). Wnt proteins secretion did not seem to be involved in the fenoterol-induced sensitization since the mRNA expression of Wnt remained low after fenoterol exposure and the inactivator of Wnt secretion (1 µM IWP2) had no effect on the fenoterol-sensitization. Fenoterol exposure did not change the mRNA expression of genes regulating Wnt signaling or cAMP–PKA cascade. Conclusions Collectively, our pharmacological investigations indicate that fenoterol-sensitization is modulated by the inhibition/blockage of canonical Wnt/β-catenin pathway, suggesting a phenomenon of biased agonism in connection with the β2-adrenoceptor stimulation. Future experiments based on the results of the present study will be needed to determine the impact of prolonged fenoterol exposure on the extra- and intracellular Wnt signaling pathways at the protein expression level. PMID:25360795

Wnt/β-catenin signaling modulates human airway sensitization induced by β2-adrenoceptor stimulation.

PubMed

Faisy, Christophe; Grassin-Delyle, Stanislas; Blouquit-Laye, Sabine; Brollo, Marion; Naline, Emmanuel; Chapelier, Alain; Devillier, Philippe

2014-01-01

Regular use of β2-agonists may enhance non-specific airway responsiveness. The wingless/integrated (Wnt) signaling pathways are responsible for several cellular processes, including airway inflammation and remodeling while cAMP-PKA cascade can activate the Wnt signaling. We aimed to investigate whether the Wnt signaling pathways are involved in the bronchial hyperresponsiveness induced by prolonged exposure to β2-adrenoceptor agonists in human isolated airways. Bronchi were surgically removed from 44 thoracic surgery patients. After preparation, bronchial rings and primary cultures of bronchial epithelial cells were incubated with fenoterol (0.1 µM, 15 hours, 37 °C), a β2-agonist with high intrinsic efficacy. The effects of inhibitors/blockers of Wnt signaling on the fenoterol-induced airway sensitization were examined and the impact of fenoterol exposure on the mRNA expression of genes interacting with Wnt signaling or cAMP-PKA cascade was assessed in complete bronchi and in cultured epithelial cells. Compared to paired controls, fenoterol-sensitization was abolished by inhibition/blockage of the Wnt/β-catenin signaling, especially the cell-surface LRP5/6 co-receptors or Fzd receptors (1 µM SFRP1 or 1 µM DKK1) and the nuclear recruitment of TCF/LEF transcriptions factors (0.3 µM FH535). Wnt proteins secretion did not seem to be involved in the fenoterol-induced sensitization since the mRNA expression of Wnt remained low after fenoterol exposure and the inactivator of Wnt secretion (1 µM IWP2) had no effect on the fenoterol-sensitization. Fenoterol exposure did not change the mRNA expression of genes regulating Wnt signaling or cAMP-PKA cascade. Collectively, our pharmacological investigations indicate that fenoterol-sensitization is modulated by the inhibition/blockage of canonical Wnt/β-catenin pathway, suggesting a phenomenon of biased agonism in connection with the β2-adrenoceptor stimulation. Future experiments based on the results of the present study will be needed to determine the impact of prolonged fenoterol exposure on the extra- and intracellular Wnt signaling pathways at the protein expression level.

Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer model

PubMed Central

2013-01-01

Background Sonography has become the imaging technique of choice for guiding intraoperative interventions in abdominal surgery. Due to artefacts from residual air content, however, videothoracoscopic and open intraoperative ultrasound-guided thermoablation of lung malignancies are impossible. Lung flooding is a new method that allows complete ultrasound imaging of lungs and their tumours. Methods Fourteen resected tumourous human lung lobes were examined transpleurally with B-mode ultrasound before (in atelectasis) and after lung flooding with isotonic saline solution. In two swine, the left lung was filled with 15 ml/kg isotonic saline solution through the left side of a double-lumen tube. Lung tumours were simulated by transthoracic ultrasound-guided injection of 5 ml of purified bovine serum albumin in glutaraldehyde, centrally into the left lower lung lobe. The rate of tumour detection, the severity of disability caused by residual gas, and sonomorphology of the lungs and tumours were assessed. Results The ex vivo tumour detection rate was 100% in flooded human lung lobes and 43% (6/14) in atelectatic lungs. In all cases of atelectasis, sonographic tumour imaging was impaired by residual gas. Tumours and atelectatic tissue were isoechoic. In 28% of flooded lungs, a little residual gas was observed that did not impair sonographic tumour imaging. In contrast to tumours, flooded lung tissue was hyperechoic, homogeneous, and of fine-grained structure. Because of the bronchial wall three-laminar structure, sonographic differentiation of vessels and bronchi was possible. In all cases, malignant tumours in the flooded lung appeared well-demarcated from the lung parenchyma. Adenocarcinoma, squamous, and large cell carcinomas were hypoechoic. Bronchioloalveolar cell carcinoma was slightly hyperechoic. Transpleural sonography identifies endobronchial tumour growth and bronchial wall destruction. With transthoracic sonography, the flooded animal lung can be completely examined in vivo. There is no residual gas, which interferes with ultrasound. Pulmonary vessels and bronchi are clearly differentiated. Simulated lung lesions can easily be detected inside the lung lobe. Conclusions Lung flooding enables complete lung sonography and tumour detection. We have developed a novel method that efficiently uses ultrasound for guiding intraoperative interventions in open and endoscopic lung surgery. PMID:23841910

[Consequences of short term fluctuations of the environmental temperatures in calves--Part 2: Effects on the health status of animals within three weeks after exposure].

PubMed

Reinhold, P; Elmer, S

2002-04-01

The aim of the present study was to examine consequences of sudden changes in ambient temperature over a 4-hour period (see part 1 [ELMER & REINHOLD, 2002]) on respiratory health in clinically healthy calves. Therefore, the relationship between short-term changes in ambient temperature and the occurrence of clinical respiratory disease was checked over a period of 3 weeks after exposure in 10 calves exposed to 5 degrees C, in 9 calves exposed to 35 degrees C and in 8 control calves (kept at 18-20 degrees C). Within the period beginning 3 days before exposure and lasting until up to 21 days after exposure, each calf was examined clinically. Rectal temperature and respiratory rate were measured daily. All calves were euthanised on day 21 after exposure. Macroscopically visible pneumonic lesions were evaluated using a semiquantitative system. Tissue samples from tonsils, bronchi, trachea, lung and mediastinal lymph nodes were examined bacteriologically. In contrast to non-exposed control calves, severe respiratory illness was observed in individual calves of both exposed groups (5 degrees C, 35 degrees C). Significant increases in body temperature, respiratory rate and animal losses (2 calves died in the group exposed to 5 degrees C, one calf died in the group exposed to 35 degrees C) were the main clinical findings. At necropsy (3 weeks after exposure), no pneumonic lesions were observed in control calves--despite the fact that this group had the highest microbiological colonisation rates in tonsils and in large airways, i.e. trachea and bronchi, within all groups. However, variable pneumonic lung lesions were seen in remaining calves exposed to cold or warm air (5 degrees C, 35 degrees C). The microbiological examination confirmed that mainly Mycoplasma spp. were identified in the lung tissue of calves exposed to 5 degrees C while Pasteurella multocida and/or Mannheimia haemolytica were the only germs found in the lung tissue of calves exposed to 35 degrees C. The results of parts 1 and 2 of the present study related to health issues of calves should be taken into account for future legislation on animal welfare.

The First Korean Case of Cutaneous Lung Tissue Heterotopia

PubMed Central

Jeon, Ga Won; Han, Seong Woo; Jung, Ji Mi; Kang, Mi Seon

2010-01-01

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea. PMID:20808688

Blood sinuses in the submucosa of the large airways of the sheep.

PubMed Central

Hill, P; Goulding, D; Webber, S E; Widdicombe, J G

1989-01-01

We have studied the airway vasculature in sheep using light and transmission electron microscopy, as well as arterial and venous (retrograde) injections of anatomical corrosion compound and latex. Vascular casts were viewed by scanning electron microscopy. There is a complex network of blood sinuses of large diameter (up to 500 microns) in the submucosa of the large airways. The vessels have thin walls formed by a single layer of flattened endothelium with tight junctions and without pericytes or smooth muscle cells. Characteristically the sinuses lie between the cartilage and lamina propria of the trachea or between cartilage and smooth muscle in the bronchi. Sinuses of greater than 50 microns transverse diameter are not found in airways less than 1.0 mm across. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 PMID:2808119

[Bronchopulmonary ACTH-producing tumors].

PubMed

Pikunov, M Iu; Kuznetsov, N S; Latkina, N V; Dobreva, E A; Remizov, O V

2014-01-01

Neuroendocrine tumors have the ability to produce the hormones and vasoactive peptides. Excess of these hormones leads to different symptoms and syndromes because of organs' injuries. Detection of ACTH origin by using of modern diagnostic methods is not always possible. Lungs and bronchi are one of the most frequent localization of ACTH-producing tumors. It is considered that carcinoids with bronchopulmonary localization like a benign tumors in the clinical course. But at the same time carcinoid tends to metastasize, so timely diagnostics and treatment improve quality of life significant and increase the life expectancy of patients. The modern state of diagnostics and surgical treatment problem of ACTH-producing tumors with bronchopulmonary localization is presented in the article. It was described the brief historical background, clinical symptoms, instrumental and biochemical methods of diagnosis. The principles of surgical treatment are presented in the article.

The role of egg drop syndrome virus in acute respiratory disease of goslings.

PubMed

Ivanics, E; Palya, V; Glavits, R; Dan, A; Palfi, V; Revesz, T; Benko, M

2001-06-01

An outbreak of severe acute respiratory disease characterized by tracheitis and bronchitis was observed in young goslings on a large-scale goose farm in Hungary. Histological examination revealed amphophilic intranuclear inclusion bodies in the superficial epithelial cells of the trachea and bronchi. Adenovirus-like particles were detected by electron microscopy, and the virus isolated from the trachea and the lungs was identified as egg drop syndrome (EDS) virus by serological and genomic examination. The clinical and pathological signs were reproduced by intratracheal administration of the virus isolate to 1-day-old goslings free of EDS antibodies. The presence of EDS virus DNA in different organs of the naturally and experimentally infected goslings was detected by polymerase chain reaction. This is the first report on the involvement of EDS virus in severe respiratory disease of geese.

Toxic smoke inhalation in fire victim dogs.

PubMed

Stern, A W; Lewis, R J; Thompson, K S

2014-11-01

Fifteen dogs were found dead in a house that was on fire. Several of these dogs were partially burned. Four dogs were submitted for postmortem examination, 2 of which were determined to have died prior to the fire. Of the 2 submitted fire fatalities, only 1 dog had burns on its body (dorsum and right side of body). Internally, both dogs had soot deposits mixed with mucus in the larynx, trachea, and primary bronchi. Microscopically, soot was identified within both airways and alveolar spaces. There were no macroscopic or microscopic indications of vital heat exposure. High levels of carboxyhemoglobin were detected in the 2 dogs tested. The findings in this case support the use of postmortem examination and toxicology testing to allow for determination of vital reaction to heat and fire fumes. © The Author(s) 2014.

Tracheobronchial foreign body aspiration in children.

PubMed

Burton, E M; Brick, W G; Hall, J D; Riggs, W; Houston, C S

1996-02-01

In this retrospective study, we reviewed the demographic and radiographic findings of 155 children with bronchoscopy-proven tracheobronchial foreign body aspiration (FBA). Two thirds of the patients were male, and most were children between 1 and 2 years of age. An aspirated peanut accounted for one third of all cases. Foreign body location was distributed nearly evenly to the right and left primary bronchi; tracheal foreign body was noted in 16 patients. The most frequent symptoms of FBA were cough (85 patients) and wheezing (60 patients). Although most patients were seen within 1 day of aspiration, 30 patients had symptoms that lasted at least 1 week before diagnosis. The most common radiographic findings were unilateral or segmental hyperlucency (59) or atelectasis (38). The trachea was the site of the foreign body in one half of children with a normal chest radiograph and FBA.

First Case Report of Metastatic Squamous Cell Carcinoma of Lung Associated with Mounier-Kuhn Syndrome and Review of Literature.

PubMed

Ayub, Fatima; Saif, Muhammad W

2017-06-26

Mounier-Kuhn syndrome is a relatively rare condition, mostly involving the trachea and main stem bronchi. It is caused either by the atrophy of elastic fibers or faulty fetal development of cartilage and smooth muscles, hence leading to an overall increase in the diameter of lower respiratory tract. No certain etiology was found in the majority of cases reported previously, however, several other connective tissue diseases have also been implicated with the congenital tracheobronchomegaly. One anecdotal case report mentioned the development of lung malignancy in a patient who had previously received external beam radiotherapy. Herein, we report the first case of Mounier-Kuhn syndrome in a 62-year-old male with a recent diagnosis of metastatic squamous cell carcinoma (SCC) of the lung.

Foreign bodies in the larynx and tracheobronchial tree in children. A review of 225 cases.

PubMed

Rothmann, B F; Boeckman, C R

1980-01-01

In a study of 225 patients with foreign bodies in the larynx, trachea and bronchi, 77% were 36 months of age or less. The male-female ratio was 2:1. Food or food derivatives were the causative agent in 70% of the cases, with 38% due to a portion of nut. The foreign body involved the right and left bronchus with equal frequency. A choking episode followed by an audible wheeze (55%) was the most common presenting complaint. Obstructive emphysema was demonstrated in 60% and was best demonstrated by inspiration-expiration chest roentgenograms or fluoroscopy. A radio-opaque object was seen in 13%. Two hundred ten foreign objects (93%) were removed by endoscopy. Four patients required pulmonary resection for bronchiectasis and in three patients bronchotomy was performed. Five patients expelled the foreign body spontaneously, two patients were transferred to another hospital, and one foreign body was not recovered. There was no mortality.

CHANGES IN LUNG PARENCHYMA WITH PREOPERATIVE Co$sup 60$-IRRADIATION OF BRONCHIAL CARCINOMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widow, W.

1959-01-01

Histologic studies were made of resected lung tissue of 24 patients subjected to radiotherapy. Radiation pneumonitis with incipient fibrosis was observed in 14 cases. In only five of these cases could the histologic findings be confirmed radiologically. The histologic changes included swelling of alveolar septa, interstitial edema, increase of connective tissue components, giant cell formation, exfoliation of alveolar cells, intra-alveolar edema, depositio of cellular debris in small bronchi with apparent injury to the ciliated epithelial and mucous cells, and swelling of the peribronchial and perivascular tissue and pleura. Only a sparse inflammatory cell infiltrate was noted. These responses could notmore » be closely correlated with the radiation dose. The radiation reaction was most marked in the vicinity of old tuberculous lesions. No permanent impairment of pulmonary function would be expected from the observed histologic changes. (H.H.D.)« less

[Diagnostic and curative bronchoscopy for purulent-destructive pulmonary diseases].

PubMed

Pinchuk, T P; Yasnogorodsky, O O; Guryanova, Yu V; Taldykin, M V; Kachikin, A S; Catane, Yu A

To assess an efficacy of diagnostic and curative bronchoscopy in patients with purulent-destructive pulmonary diseases. Diagnosis and treatment of 34 patients with purulent-destructive pulmonary diseases including small-focal destruction (14) and lung abscesses (19) were analyzed. 33 patients underwent diagnostic fibrobronchoscopy (FBS) with brush and transbronchial biopsy. Curative endoscopy included bronchial tree sanation, peribronchial administration of antibiotics (5) and transbronchial drainage of abscess (14). Atrophic bronchitis and cicatricial deformity of the 2-3rd segmental bronchi were revealed in 81.8% and 15.2% respectively. Transbronchial biopsy confirmed malignant neoplasms (15.2%) and pulmonary tuberculosis (6.1%). Peribronchial administration of amikacin in patients with small-focal pulmonary destruction and transbronchial drainage of abscesses accelerated pulmonary tissue repair and complete recovery. Transbronchial biopsy in patients with destructive pulmonary diseases verifies pathological process and excludes malignant and specific pulmonary damage. Complex use of endoscopic methods is associated with positive clinical result in all patients with pulmonary destruction.

Unusual congenital pulmonary anomaly with presumed left lung hypoplasia in a young dog.

PubMed

Lee, C M; Kim, J H; Kang, M H; Eom, K D; Park, H M

2014-05-01

A seven-month-old, entire, male miniature schnauzer dog was referred with acute vomiting, inappetence and depression primarily as a result of a gastric foreign body (pine cones). During investigations, thoracic radiographs revealed increased volume of the right lung lobes, deviated cardiomediastinal structures and elevation of the heart from the sternum. Thoracic computed tomography revealed left cranial lung lobe hypoplasia and extension of the right cranial lung parenchyma across the midline to the left hemithorax. Branches of the right pulmonary vessels and bronchi also crossed the midline and extended to the left caudal lung lobe. These findings suggested that the right and left lungs were fused. In humans this finding is consistent with horseshoe lung, which is an uncommon congenital malformation. To the authors' knowledge, this case represents the first report of such a pulmonary anomaly in a dog. © 2014 British Small Animal Veterinary Association.

Monitoring of experimental rat lung transplants by high-resolution flat-panel volumetric computer tomography (fpVCT).

PubMed

Greschus, Susanne; Kuchenbuch, Tim; Plötz, Christian; Obert, Martin; Traupe, Horst; Padberg, Winfried; Grau, Veronika; Hirschburger, Markus

2009-01-01

Noninvasive assessment of experimental lung transplants with high resolution would be favorable to exclude technical failure and to follow up graft outcome in the living animal. Here we describe a flat-panel Volumetric Computed Tomography (fpVCT) technique using a prototype scanner. Lung transplantation was performed in allogeneic as well as in corresponding syngeneic rat strain combinations. At different time points post-transplantation, fpVCT was performed. Lung transplants can be visualized in the living rat with high-spatial resolution. FpVCT allows a detailed analysis of the lung and the bronchi. Infiltrates developing during rejection episodes can be diagnosed and follow-up studies can easily be performed. With fpVCT it is possible to control the technical success of the surgical procedure. Graft rejection can be visualized individually in the living animal noninvasively, which is highly advantageous for studying the pathogenesis of chronic rejection or to monitor new therapies.

Anatomy and Neurophysiology of Cough

PubMed Central

Canning, Brendan J.; Chang, Anne B.; Bolser, Donald C.; Smith, Jaclyn A.; Mazzone, Stuart B.; Adams, Todd M.; Altman, Kenneth W.; Barker, Alan F.; Birring, Surinder S.; Blackhall, Fiona; Bolser, Donald, C.; Boulet, Louis-Philippe; Braman, Sidney S.; Brightling, Christopher; Callahan-Lyon, Priscilla; Canning, Brendan; Chang, Anne Bernadette; Coeytaux, Remy; Cowley, Terrie; Davenport, Paul; Diekemper, Rebecca L.; Ebihara, Satoru; El Solh, Ali A.; Escalante, Patricio; Feinstein, Anthony; Field, Stephen K.; Fisher, Dina; French, Cynthia T.; Gibson, Peter; Gold, Philip; Grant, Cameron; Harding, Susan M.; Harnden, Anthony; Hill, Adam T.; Irwin, Richard S.; Kahrilas, Peter J.; Keogh, Karina A.; Lane, Andrew P.; Lewis, Sandra Zelman; Lim, Kaiser; Malesker, Mark A.; Mazzone, Peter; Mazzone, Stuart; Molasiotis, Alex; Murad, M. Hassan; Newcombe, Peter; Nguyen, Huong Q.; Oppenheimer, John; Prezant, David; Pringsheim, Tamara; Restrepo, Marcos I.; Rosen, Mark; Rubin, Bruce; Ryu, Jay H.; Smith, Jaclyn; Tarlo, Susan M.; Turner, Ronald B.; Vertigan, Anne; Wang, Gang; Weir, Kelly

2014-01-01

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human. PMID:25188530

Importance of preoperative imaging with 64-row three-dimensional multidetector computed tomography for safer video-assisted thoracic surgery in lung cancer.

PubMed

Akiba, Tadashi; Marushima, Hideki; Harada, Junta; Kobayashi, Susumu; Morikawa, Toshiaki

2009-01-01

Video-assisted thoracic surgery (VATS) has recently been adopted for complicated anatomical lung resections. During these thoracoscopic procedures, surgeons view the operative field on a two-dimensional (2-D) video monitor and cannot palpate the organ directly, thus frequently encountering anatomical difficulties. This study aimed to estimate the usefulness of preoperative three-dimensional (3-D) imaging of thoracic organs. We compared the preoperative 64-row three-dimensional multidetector computed tomography (3DMDCT) findings of lung cancer-affected thoracic organs to the operative findings. In comparison to the operative findings, the branches of pulmonary arteries, veins, and bronchi were well defined in the 3D-MDCT images of 27 patients. 3D-MDCT imaging is useful for preoperatively understanding the individual thoracic anatomy in lung cancer surgery. This modality can therefore contribute to safer anatomical pulmonary operations, especially in VATS.

Improvement with Infliximab of a Disseminated Sarcoidosis in a Patient with Crohn's Disease

PubMed Central

Piégay, Fabrice; Traclet, Julie; Mion, François; Mornex, Jean-François

2014-01-01

Sarcoidosis and Crohn's disease are systemic granulomatous disorders affecting the lung and the intestine, respectively, with variable involvement of other organs and are seldom associated. While anti-TNFα is a recognized treatment of Crohn's disease, its usage is discussed in sarcoidosis. A 42-year-old man presented with an 11-year-long history of Crohn's disease; upon discovery of an abnormal chest CT scan the diagnosis of multivisceral sarcoidosis was made and, later, a treatment with an anti-TNFα agent, infliximab, was started, because of worsening Crohn's disease recurrences. CT scan demonstrated net regression of pulmonary opacities and hepatosplenic lesions. Pathologies obtained from the intestinal tract and the bronchi of the patient were, respectively, characteristic of Crohn's disease and sarcoidosis leading to the diagnosis of both diseases. We report a rare case of steroid resistant Crohn's disease associated with multivisceral sarcoidosis, treated successfully by an anti-TNFα agent, infliximab. PMID:24653848

Treatment of Adult Primary Alveolar Proteinosis.

PubMed

Rodríguez Portal, José Antonio

2015-07-01

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

[Bronchoscopy in ventilated patients: full narcosis or local anesthesia?].

PubMed

Konrad, F; Wiedeck, H; Winter, H; Kilian, J

1990-04-01

In a prospective, randomised trial bronchoscopy was performed either in local anaesthesia (LA) or general anaesthesia, each on 15 ventilated patients. LA was carried out with oxybuprocain-hydrochloride 1% in repeated doses injected into the trachea and main bronchi, general anaesthesia with midazolam, piritramide and vecuronium bromide. Measurements were performed before, 3 minutes after induction of anaesthesia, immediately after bronchoscopy and 15 and 60 minutes after bronchoscopy. There was no effect on cardiocirculatory function during bronchoscopy in both groups, but we found a decrease in paO2 from 97 to 80 mmHg (median) after application of LA. Subsequent bronchoscopy did not significantly influence paO2. The present study shows that in ventilation patients undergoing fibreoptic bronchoscopy, the application of LA will usually result in a decline of arterial oxygen tension. This procedure should therefore only be performed if general anaesthesia is undesirable, as e.g. in patients being weaned from ventilation.

Carcinoid Tumour of Caecum: an Unusual Palpable Mass in the Right Iliac Fossa.

PubMed

Agrawal, Mohit M; Sude, Nandkishor S

2016-04-01

Carcinoid tumour represents 0.8-1.5 % of malignant digestive tumours. Gastrointestinal (GI) carcinoids account for 95 % of all the carcinoids, and caecal carcinoids account for 5 % of all the carcinoids. These tumours are frequent in women (2-4:1) as reported by Spallitta and Termine (Minerva Chir 55:77-87, 2002). In order of frequency, they may occur in the appendix (35 %), ileum (28 %), rectum (13 %) and bronchi. Incidence is less than 1 % in the pancreas, gall bladder, liver, larynx, testes and ovaries. The colon and ileocaecal region are rare sites of origin for gastrointestinal carcinoids as reported by Soga (J Exp Clin Cancer Res 17:139-48, 1998). They remain asymptomatic for years and many a times are diagnosed endoscopically, intraoperatively or during autopsy, based on their histopathological findings. We present a rare case of caecal carcinoid.

Diagnostic Value of Multidetector CT and Its Multiplanar Reformation, Volume Rendering and Virtual Bronchoscopy Postprocessing Techniques for Primary Trachea and Main Bronchus Tumors.

PubMed

Luo, Mingyue; Duan, Chaijie; Qiu, Jianping; Li, Wenru; Zhu, Dongyun; Cai, Wenli

2015-01-01

To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors. Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology. Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm-56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm-68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19), distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n = 1; low density without obvious enhancement, n = 1). MDCT and its MPR, VR and VB images have respective advantages and disadvantages. Their combination could complement to each other to accurately detect locations, natures (benignancy, malignancy or low malignancy), and quantities (extramural invasions, longitudinal involvements, extents of luminal stenoses, distances between main bronchus tumors and trachea carinae) of primary trachea and main bronchus tumors with crucial information for surgical treatment, are highly useful diagnostic methods for primary trachea and main bronchus tumors.

[Virtual endoscopy with a volumetric reconstruction technic: the technical aspects].

PubMed

Pavone, P; Laghi, A; Panebianco, V; Catalano, C; Giura, R; Passariello, R

1998-06-01

We analyze the peculiar technical features of virtual endoscopy obtained with volume rendering. Our preliminary experience is based on virtual endoscopy images from volumetric data acquired with spiral CT (Siemens, Somatom Plus 4) using acquisition protocols standardized for different anatomic areas. Images are reformatted at the CT console, to obtain 1 mm thick contiguous slices, and transferred in DICOM format to an O2 workstation (Silicon Graphics, Mountain View CA, USA) with processor speed of 180 Mhz, 256 Mbyte RAM memory and 4.1 Gbyte hard disk. The software is Vitrea 1.0 (Vital Images, Fairfield, Iowa), running on a Unix platform. Image output is obtained through the Ethernet network to a Macintosh computer and a thermic printer (Kodak 8600 XLS). Diagnostic quality images were obtained in all the cases. Fly-through in the airways allowed correct evaluation of the main bronchi and of the origin of segmentary bronchi. In the vascular district, both carotid strictures and abdominal aortic aneurysms were depicted, with the same accuracy as with conventional reconstruction techniques. In the colon studies, polypoid lesions were correctly depicted in all the cases, with good correlation with endoscopic and double-contrast barium enema findings. In a case of lipoma of the ascending colon, virtual endoscopy allowed to study the colon both cranially and caudally to the lesion. The simultaneous evaluation of axial CT images permitted to characterize the lesion correctly on the basis of its density values. The peculiar feature of volume rendering is the use of the whole information inside the imaging volume to reconstruct three-dimensional images; no threshold values are used and no data are lost as opposite to conventional image reconstruction techniques. The different anatomic structures are visualized modifying the reciprocal opacities, showing the structures of no interest as translucent. The modulation of different opacities is obtained modifying the shape of the opacity curve, either using pre-set curves or in a completely independent way. Other technical features of volume rendering are the perspective evaluation of the objects, color and lighting. In conclusion, volume rendering is a promising technique to elaborate three-dimensional images, offering very realistic endoscopic views. At present, the main limitation is represented by the need of powerful and high-cost workstations.

Transcriptional elements from the human SP-C gene direct expression in the primordial respiratory epithelium of transgenic mice.

PubMed

Wert, S E; Glasser, S W; Korfhagen, T R; Whitsett, J A

1993-04-01

Transgenic animals bearing a chimeric gene containing 5'-flanking regions of the human surfactant protein C (SP-C) gene ligated to the bacterial chloramphenicol acetyltransferase (CAT) gene were analyzed by in situ hybridization histochemistry to determine the temporal and spatial distribution of transgene expression during organogenesis of the murine lung. Ontogenic expression of the SP-C-CAT gene was compared to that of the endogenous SP-C gene and to the Clara cell CC10 gene. High levels of SP-C-CAT expression were observed as early as Day 10 of gestation in epithelial cells of the primordial lung buds. Low levels of endogenous SP-C mRNA were detected a day later, but only in the more distal epithelial cells of the newly formed, primitive, lobar bronchi. On Gestational Days 13 through 16, transcripts for both the endogenous and chimeric gene were restricted to distal epithelial elements of the branching bronchial tubules and were no longer detected in the more proximal regions of the bronchial tree. Although high levels of SP-C-CAT expression were maintained throughout organogenesis, endogenous SP-C expression increased dramatically on Gestational Day 15, coincident with acinar tubule differentiation at the lung periphery. Low levels of endogenous CC10 expression were detected by Gestational Day 16 in both lobar and segmental bronchi. By the time of birth, CC10 transcripts were expressed at high levels in the trachea and at all levels of the bronchial tree; endogenous SP-C mRNA was restricted to epithelial cells of the terminal alveolar saccules; and SP-C-CAT expression was now detected in both alveolar and bronchiolar epithelial cells. These results indicate that (1) cis-acting regulatory elements of the human SP-C gene can direct high levels of foreign gene expression to epithelial cells of the embryonic mouse lung; (2) expression of the human SP-C-CAT chimeric gene is developmentally regulated, exhibiting a morphogenic expression pattern similar, but not identical, to that of the endogenous murine SP-C gene; (3) the embryonic expression of endogenous SP-C and chimeric SP-C-CAT transcripts identifies progenitor cells of the distal respiratory epithelium; and (4) differentiation of bronchial epithelium is coincident with loss of SP-C expression and subsequent acquisition of CC10 expression in proximal regions of the developing bronchial tubules.

Distribution of sialic acid receptors and influenza A virus of avian and swine origin in experimentally infected pigs.

PubMed

Trebbien, Ramona; Larsen, Lars E; Viuff, Birgitte M

2011-09-08

Pigs are considered susceptible to influenza A virus infections from different host origins because earlier studies have shown that they have receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SA-alpha-2,3)) and swine/human (SA-alpha-2,6) influenza viruses in the upper respiratory tract. Furthermore, experimental and natural infections in pigs have been reported with influenza A virus from avian and human sources. This study investigated the receptor distribution in the entire respiratory tract of pigs using specific lectins Maackia Amurensis (MAA) I, and II, and Sambucus Nigra (SNA). Furthermore, the predilection sites of swine influenza virus (SIV) subtypes H1N1 and H1N2 as well as avian influenza virus (AIV) subtype H4N6 were investigated in the respiratory tract of experimentally infected pigs using immunohistochemical methods. SIV antigen was widely distributed in bronchi, but was also present in epithelial cells of the nose, trachea, bronchioles, and alveolar type I and II epithelial cells in severely affected animals. AIV was found in the lower respiratory tract, especially in alveolar type II epithelial cells and occasionally in bronchiolar epithelial cells. SA-alpha-2,6 was the predominant receptor in all areas of the respiratory tract with an average of 80-100% lining at the epithelial cells. On the contrary, the SA-alpha-2,3 was not present (0%) at epithelial cells of nose, trachea, and most bronchi, but was found in small amounts in bronchioles, and in alveoli reaching an average of 20-40% at the epithelial cells. Interestingly, the receptor expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza infected areas compared to non-infected areas. A difference in predilection sites between SIV and AIV virus was found, and this difference was in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3 receptor, respectively. The results indicated that the distribution of influenza A virus receptors in pigs are similar to that of humans and therefore challenge the theory that the pig acts as a mixing vessel between human and avian influenza viruses. Furthermore, it was shown that AIV prefers to infect alveolar type II epithelial cells in pigs. This corresponds with findings in humans emphasising the resemblance between the two species.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ar Latin-Small-Letter-Dotless-I bas, Bilgin Kadri, E-mail: bilginaribas@hotmail.com; Dingil, Guerbuez; Koeroglu, Mert

The aim of this case study is to present effectiveness of percutaneous drainage as a treatment option of ruptured lung and liver hydatid cysts. A 65-year-old male patient was admitted with complicated liver and lung hydatid cysts. A liver hydatid cyst had ruptured transdiaphragmatically, and a lung hydatid cyst had ruptured both into bronchi and pleural space. The patient could not undergo surgery because of decreased respiratory function. Both cysts were drained percutaneously using oral albendazole. Povidone-iodine was used to treat the liver cyst after closure of the diaphragmatic rupture. The drainage was considered successful, and the patient had nomore » recurrence of signs and symptoms. Clinical, laboratory, and radiologic recovery was observed during 2.5 months of catheterization. The patient was asymptomatic after catheter drainage. No recurrence was detected during 86 months of follow-up. For inoperable patients with ruptured liver and lung hydatid cysts, percutaneous drainage with oral albendazole is an alternative treatment option to surgery. The percutaneous approach can be life-saving in such cases.« less

Differential and relaxed image foresting transform for graph-cut segmentation of multiple 3D objects.

PubMed

Moya, Nikolas; Falcão, Alexandre X; Ciesielski, Krzysztof C; Udupa, Jayaram K

2014-01-01

Graph-cut algorithms have been extensively investigated for interactive binary segmentation, when the simultaneous delineation of multiple objects can save considerable user's time. We present an algorithm (named DRIFT) for 3D multiple object segmentation based on seed voxels and Differential Image Foresting Transforms (DIFTs) with relaxation. DRIFT stands behind efficient implementations of some state-of-the-art methods. The user can add/remove markers (seed voxels) along a sequence of executions of the DRIFT algorithm to improve segmentation. Its first execution takes linear time with the image's size, while the subsequent executions for corrections take sublinear time in practice. At each execution, DRIFT first runs the DIFT algorithm, then it applies diffusion filtering to smooth boundaries between objects (and background) and, finally, it corrects possible objects' disconnection occurrences with respect to their seeds. We evaluate DRIFT in 3D CT-images of the thorax for segmenting the arterial system, esophagus, left pleural cavity, right pleural cavity, trachea and bronchi, and the venous system.

The high opening of the right bronchial artery with a non-typical course.

PubMed

Maciejewski, R; Madej, B; Anasiewicz, A

1995-01-01

Authors describing the bronchial vessels agree to the fact that they are characterised by a great variability in regard to their number and the place where they leave aorta (1, 2, 6). The characteristic feature of the right bronchial artery is that it often forms common trunks with other vessels (mainly with the first right aortic intercostal branch or with one of the upper oesophageal arteries). It can also have a common let-out trunk with the left upper bronchial artery (4). Bearing in mind that the operations on trachea and bronchi are difficult, and that it is very important to maintain the blood supply of the walls in the operated organs we have decided to publish our observations. They refer to a case, not described before, in which the right bronchial artery left the aortic arch in a high position making the vascular supply to the front lower half of the trachea and its bifurcation. Then, it went down to the membranous part of the right bronchus.

Recurrent Pneumonia due to Fibrosing Mediastinitis in a Teenage Girl: A Case Report with Long-Term Follow-Up

PubMed Central

Springer, Chaim; Wasser, Oren; Avital, Avraham; Koplewitz, Benjamin Z.

2018-01-01

A teenage girl was evaluated for recurrent right pneumonia. The evaluation revealed a calcified mediastinal mass that compressed the right intermediate and middle lobar bronchi, as well as the right pulmonary artery and veins. The clinical picture together with imaging studies and borderline positive serology testing suggested a diagnosis of fibrosing mediastinitis associated with histoplasmosis. This rare condition is characterized by the local proliferation of invasive fibrous tissue within the mediastinum due to a hyperimmune reaction to Histoplasma capsulatum. Antifungal and anti-inflammatory therapies are usually ineffective, and surgical intervention contains a high morbidity risk. Palliative surgery and stenting of the compressed airway have been suggested. In the past, the prognosis was thought to be poor, but recent studies demonstrate a more positive outcome. Our patient had been radiologically and functionally stable under follow-up for over thirteen years and has married and delivered two healthy children, both following an uneventful pregnancy. PMID:29744231

Haemophilus influenzae and the lung (Haemophilus and the lung)

PubMed Central

2012-01-01

Haemophilus influenzae is present as a commensal organism in the nasopharynx of most healthy adults from where it can spread to cause both systemic and respiratory tract infection. This bacterium is divided into typeable forms (such as type b) or nontypeable forms based on the presence or absence of a tough polysaccharide capsule. Respiratory disease is predominantly caused by the nontypeable forms (NTHi). Haemophilus influenzae has evolved a number of strategies to evade the host defense including the ability to invade into local tissue. Pathogenic properties of this bacterium as well as defects in host defense may result in the spread of this bacterium from the upper airway to the bronchi of the lung. This can result in airway inflammation and colonization particularly in chronic obstructive pulmonary disease. Treatment of respiratory tract infection with Haemophilus influenzae is often only partially successful with ongoing infection and inflammation. Improvement in patient outcome will be dependent on a better understanding of the pathogenesis and host immune response to this bacterium. PMID:23369277

Respiratory response of guinea pigs to sulfuric acid mist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amdur, M.O.

1958-01-01

Guinea pigs were exposed to 23 to 42 mg/m/sup 3/ acid mist with a mass median diameter of 0.8, 2.5, or 7 ..mu..m for 1-h periods. Significant increase in resistance at all levels and sizes was observed. There was a concurrent decrease in compliance for 2.5- and 7-..mu..m sizes with exception of lowest level of exposure. Dose-effect with resistance vs concentration shows smaller sizes were more deleterious. The 2.5 ..mu..m were more harmful at higher concentrations (above approx. 15 mg/m/sup 3/). The 0.8-..mu..m particles produced a rapid response suggesting bronchoconstriction as the mechanism (change in resistance proportionately greater than changemore » in compliance). This was similar to irritant gases. Conversely, 2.5- and 7-..mu..m particles acted slower and change in resistance paralleled the drop in compliance. High concentrations evoked edema and atelectasis. This was interpreted as closure of main bronchi rather than general constriction. Response was consistent with expected penetration.« less

Structure of the syringeal muscles in jungle crow (Corvus macrorhynchos).

PubMed

Tsukahara, Naoki; Yang, Qian; Sugita, Shoei

2008-09-01

Birds' vocalizations are produced by the syrinx, which is located between the trachea and the two primary bronchi. Oscine birds have multiple pairs of syringeal muscles in the syrinx. To determine the detailed structure of the syringeal muscle in jungle crows, an oscine bird, a histological study and gross examination of the syrinx were performed. In the histological study, sections of the syrinxes from four jungle crows were stained with Azan and observed. Each syringeal muscle was classified by the limit of the fascia from neighbor fascicules. From the gross examination a 3-D image of the structure of the syringeal muscles was generated. The combined histological and anatomical results show that there are seven pairs of syringeal muscles in jungle crows. Muscle fusions were observed in some of the syringeal muscles. It is likely that each syringeal muscle has a specific role. Jungle crows may be able to generate various calls because they have several pairs of syringeal muscles.

Orange-Pigmented Sputum as a Manifestation of Smoke Grenade Inhalation Injury.

PubMed

Chatzivasiloglou, Fotini; Katsenos, Stamatis; Psara, Anthoula; Tsintiris, Konstantinos

2016-01-01

A 34-year-old man presented with scanty hemoptysis, orange-colored expectoration, and mild dyspnea. He was in an enclosed building taking part in a military training exercise inhaling an orange-colored smoke from a smoke grenade ignition. His symptoms developed immediately after the initial exposure but he sought medical assistance 20 hours later because of their persistence. Fiberoptic bronchoscopy was performed revealing diffuse inflammatory tracheobronchial tree with streaky orange-pigmented secretions in the trachea and both main-stem bronchi. Acute tracheobronchitis was diagnosed and the patient was treated with nebulized bronchodilators and intravenous corticosteroids showing complete recovery. To our knowledge, this is the first well-documented report of inhalation injury induced by a smoke bomb explosion including potassium chlorate oxidizer and Sudan I and presenting with orange-pigmented sputum production. Smoke inhalation injury is associated with significant morbidity and mortality. The heterogeneity of the smoke and the large variety of the resulting symptoms may be the reason why a definition, specific diagnostic criteria, and therapeutic guidelines are still lacking.

Myosin VIIa as a common component of cilia and microvilli.

PubMed

Wolfrum, U; Liu, X; Schmitt, A; Udovichenko, I P; Williams, D S

1998-01-01

The distribution of myosin VIIa, which is defective or absent in Usher syndrome 1B, was studied in a variety of tissues by immunomicroscopy. The primary aim was to determine whether this putative actin-based mechanoenzyme is a common component of cilia. Previously, it has been proposed that defective ciliary function might be the basis of some forms of Usher syndrome. Myosin VIIa was detected in cilia from cochlear hair cells, olfactory neurons, kidney distal tubules, and lung bronchi. It was also found to cofractionate with the axonemal fraction of retinal photoreceptor cells. Immunolabeling appeared most concentrated in the periphery of the transition zone of the cilia. This general presence of a myosin in cilia is surprising, given that cilia are dominated by microtubules, and not actin filaments. In addition to cilia, myosin VIIa was also found in actin-rich microvilli of different types of cell. We conclude that myosin VIIa is a common component of cilia and microvilli.

Nociceptin effects in the airways.

PubMed

Peiser, C; Undem, B J; Fischer, A

2000-07-01

The opioid-like heptadecapeptide nociceptin (NC) has the following effects in the airways (investigated in isolated tracheae and bronchi from guinea pig or rat): the electric field stimulation (EFS)-induces release of acetylcholine (ACh), the tachykinin substance P (SP) and calcitonin gene-related peptide (CGRP) is reduced after pretreatment with NC, and EFS-induced tachykinergic nonadrenergic-noncholinergic (NANC) bronchoconstriction is inhibited by NC. Both the NC-mediated inhibition of neurotransmission and of smooth muscle contraction occurred in a concentration-dependent manner. Because these effects were naloxone-insensitive, were blocked by the NC receptor antagonist [F/G]NC(1-13)NH(2), and could be mimicked by the NC analogs, NCNH(2) and NC(1-13)NH(2), it is thought that they are distinct from the classic opioid receptors. That these pharmacological actions of NC are of relevance for airway physiology is highly probable given the presence of NC-immunoreactivity in the nerve fibers of the airways and of opioid-like receptor (ORL-1) transcripts in the jugular ganglia, from where the tachykinin-containing afferents arise.

Diagnostic Value of Multidetector CT and Its Multiplanar Reformation, Volume Rendering and Virtual Bronchoscopy Postprocessing Techniques for Primary Trachea and Main Bronchus Tumors

PubMed Central

Luo, Mingyue; Duan, Chaijie; Qiu, Jianping; Li, Wenru; Zhu, Dongyun; Cai, Wenli

2015-01-01

Purpose To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors. Methods Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology. Results Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm—56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm—68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19), distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n = 1; low density without obvious enhancement, n = 1). Conclusion MDCT and its MPR, VR and VB images have respective advantages and disadvantages. Their combination could complement to each other to accurately detect locations, natures (benignancy, malignancy or low malignancy), and quantities (extramural invasions, longitudinal involvements, extents of luminal stenoses, distances between main bronchus tumors and trachea carinae) of primary trachea and main bronchus tumors with crucial information for surgical treatment, are highly useful diagnostic methods for primary trachea and main bronchus tumors. PMID:26332466

Caveolin-1: Functional Insights into Its Role in Muscarine- and Serotonin-Induced Smooth Muscle Constriction in Murine Airways

PubMed Central

Keshavarz, Maryam; Schwarz, Heike; Hartmann, Petra; Wiegand, Silke; Skill, Melanie; Althaus, Mike; Kummer, Wolfgang; Krasteva-Christ, Gabriela

2017-01-01

An increased bronchoconstrictor response is a hallmark in the progression of obstructive airway diseases. Acetylcholine and 5-hydroxytryptamine (5-HT, serotonin) are the major bronchoconstrictors. There is evidence that both cholinergic and serotonergic signaling in airway smooth muscle (ASM) involve caveolae. We hypothesized that caveolin-1 (cav-1), a structural protein of caveolae, plays an important regulatory role in ASM contraction. We analyzed airway contraction in different tracheal segments and extra- and intrapulmonary bronchi in cav-1 deficient (cav-1−/−) and wild-type mice using organ bath recordings and videomorphometry of methyl-beta-cyclodextrin (MCD) treated and non-treated precision-cut lung slices (PCLS). The presence of caveolae was investigated by electron microscopy. Receptor subtypes driving 5-HT-responses were studied by RT-PCR and videomorphometry after pharmacological inhibition with ketanserin. Cav-1 was present in tracheal epithelium and ASM. Muscarine induced a dose dependent contraction in all airway segments. A significantly higher Emax was observed in the caudal trachea. Although, caveolae abundancy was largely reduced in cav-1−/− mice, muscarine-induced airway contraction was maintained, albeit at diminished potency in the middle trachea, in the caudal trachea and in the bronchus without changes in the maximum efficacy. MCD-treatment of PLCS from cav-1−/− mice reduced cholinergic constriction by about 50%, indicating that cholesterol-rich plasma domains account for a substantial portion of the muscarine-induced bronchoconstriction. Notably, cav-1-deficiency fully abrogated 5-HT-induced contraction of extrapulmonary airways. In contrast, 5-HT-induced bronchoconstriction was fully maintained in cav-1-deficient intrapulmonary bronchi, but desensitization upon repetitive stimulation was enhanced. RT-PCR analysis revealed 5-HT1B, 5-HT2A, 5-HT6, and 5-HT7 receptors as the most prevalent subtypes in the airways. The 5-HT-induced-constriction in PCLS could be antagonized by ketanserin, a 5-HT2A receptor inhibitor. In conclusion, the role of cav-1, caveolae, and cholesterol-rich plasma domains in regulation of airway tone are highly agonist-specific and dependent on airway level. Cav-1 is indispensable for serotonergic contraction of extrapulmonary airways and modulates cholinergic constriction of the trachea and main bronchus. Thus, cav-1/caveolae shall be considered in settings such as bronchial hyperreactivity in common airway diseases and might provide an opportunity for modulation of the constrictor response. PMID:28555112

Nd:YAG laser therapy in bronchogenic tumors

NASA Astrophysics Data System (ADS)

Benov, Emil; Kostadinov, D.; Mitchev, K.; Vlasov, V.

1993-03-01

In 2 years 53 patients with tumors of the tracheobronchial tree have been treated by photocoagulation therapy. Forty cases of them were with different types of cancer and 13 cases with benign lesions of the trachea or bronchi. As a laser source we used an Nd:YAG laser, MBB, Germany. At first the tumor was irradiated with a power of 25 - 30 W, following power up to 90 W. The median energy dose was 3,500 J/sq cm for each patient. The treatment was executed under local anesthesia with a rigid or flexible bronchoscope. In all of the cases with benign tumors we obtained a stable positive effect. In 15 cases of carcinoma we attained a recanalization and restoration of the ventilation to the treated area -- 37.5%. The only complication due to the procedure was the death of one patient with a tracheal cancer and myasthenia gravis. Photocoagulation therapy is an effective method for benign tumors. In cases with carcinoma this therapy is used with palliative purpose -- recanalization of the bronchus. Laser endobronchial therapy shows an immediate positive effect in the treatment of airway obstruction.

Foods and respiratory allergy.

PubMed

Novembre, E; de Martino, M; Vierucci, A

1988-05-01

Foods may induce respiratory symptoms by both reaginic and nonreaginic mechanisms. Asthma is one of the most common respiratory manifestations in children, and it is well known that many factors may provoke an attack. When considering the relationship between foods and asthma, we must keep in mind that food allergy may coexist with an inhalant allergy and that other nonallergens, such as pollutants, smoke, or additives, may modulate or modify bronchial reactivity and thus favor the food allergen action. In a study using clinical history, prick test, radioallergosorbent test, and double-blind food challenge, we demonstrated respiratory symptoms related to food allergy in 13 of 140 (9.2%) children with asthma. Asthma, in particular, was demonstrated in 8 of 140 (5.7%) patients. Food allergy respiratory symptoms are, in our experience, almost always associated with other clinical manifestations (e.g., cutaneous, gastrointestinal). The recognition of food-dependent IgE-mediated respiratory symptoms is essentially limited to those cases characterized by food allergy with asthmatic expression. It is possible, however, that in many cases foods may have a nonspecific role in the determination of asthma or in the preparation of bronchi for the possible consequent stimulus.

Morphology of the Oligoryzomys nigripes respiratory system.

PubMed

Mario, Lara Carolina; Borghesi, Jéssica; G Hayashi, Rafael; O Favaron, Phelipe; N Rodrigues, Marcio; C Carvalho, Rafael; Miglino, Maria A

2018-06-04

Rodents are important in the transmission of infectious diseases that affect the respiratory tract, including simple infections and those caused by specific pathogens. These animals are natural reservoirs of zoonoses that cause many public health diseases. Basic knowledge on the morphology of these animals is important as basic research is useful for applied studies, such as the development of clinical, therapeutic, surgical and clinical models. Morphological data of respiratory tract in Oligoryzomys nigripes are absent in the literature. Therefore, the aim of this study was to perform a morphological analysis of the respiratory tract of O. nigripes. Five adult females from the environmental reserve in São Joaquim da Barra, São Paulo were used, donated to the Museum of Veterinary Anatomy (FMVZ/USP). Several morphological features follow the same pattern seen in rodents; however, this species showed some differences such as the presence of three lobar bronchi, nonlobed left lung and the right lung constituted by two lobes. Respiratory epithelium lined the whole respiratory tract and was seen using scanning electron microscopy the oval shape of the parenchyma and alveoli. © 2018 Blackwell Verlag GmbH.

Rabies among African wild dogs (Lycaon pictus) in the Masai Mara, Kenya.

PubMed

Kat, P W; Alexander, K A; Smith, J S; Richardson, J D; Munson, L

1996-10-01

A pack of African wild dogs (Lycaon pictus) ranging to the north of the Masai Mara National Reserve in southwestern Kenya was monitored from 1988 to 1989. During a 6-week period (August 1-September 13, 1989), 21 of 23 members of this pack died. Seven carcasses were retrieved, of which 4 were suitable for necropsy and histopathologic examination. Gross findings varied among individuals and included multiple bite wounds, synovitis, lymphadenopathy, submandibular, cervical, and vocal cord edema, blood in bronchi, bronchioles, stomach, and intestine, and interioventral lung lobe consolidation. Histologic examination of 2 available brain samples revealed nonsuppurative encephalitis with eosinophilic intracytoplasmic inclusions (Negri bodies). An additional brain sample tested positive for rabies via a fluorescent antibody test. Other histologic features included severe suppurative bronchopneumonia, myocarditis, and lymphoid depletion of the lymph nodes, tonsils, and spleen. A 304-base pair (bp) nucleotide sequence from the N gene and a 310-bp sequence from the G gene from rabies isolates of 4 wild dogs indicated that infection was with a rabies variant common among domestic dogs in Kenya and Tanzania.

The Role of the Immune Response in the Pathogenesis of Bronchiectasis.

PubMed

King, Paul T

2018-01-01

Bronchiectasis is a prevalent respiratory condition characterised by permanent and abnormal dilation of the lung airways (bronchi). There are a large variety of causative factors that have been identified for bronchiectasis; all of these compromise the function of the immune response to fight infection. A triggering factor may lead to the establishment of chronic infection in the lower respiratory tract. The bacteria responsible for the lower respiratory tract infection are usually found as commensals in the upper respiratory tract microbiome. The consequent inflammatory response to infection is largely responsible for the pathology of this condition. Both innate and adaptive immune responses are activated. The literature has highlighted the central role of neutrophils in the pathogenesis of bronchiectasis. Proteases produced in the lung by the inflammatory response damage the airways and lead to the pathological dilation that is the pathognomonic feature of bronchiectasis. The small airways demonstrate infiltration with lymphoid follicles that may contribute to localised small airway obstruction. Despite aggressive treatment, most patients will have persistent disease. Manipulating the immune response in bronchiectasis may potentially have therapeutic potential.

Common Cold - an Umbrella Term for Acute Infections of Nose, Throat, Larynx and Bronchi.

PubMed

Kardos, P; Malek, F A

2017-04-01

Acute respiratory tract infections, i. e. rhinitis, sinusitis, pharyngitis, laryngitis, bronchitis, belong to the most common medical conditions with a high economic burden. Nonetheless, there is little agreement concerning their differential diagnosis.This paper will discuss to what extent different anatomical sites of acute respiratory tract infections can be uniquely identified or whether the overlap and consecutive development in signs and symptoms renders these distinctions meaningless.Acute respiratory tract infections are variable but definition of diagnostic categories based on the anatomical sites of the dominant complaints shows that signs and symptoms both overlap to a great extent and/or emerge successively. Thus, in common cold distinguishing between acute symptom-based diagnoses arising from different anatomical sites of the aerodigestive system remains elusive. Therefore, preferred symptomatic treatments should foster a resolution of all possible symptoms as opposed to an isolated treatment of a single symptom (e. g. mucus hypersecretion) according to the presumed anatomical site (i. e. acute bronchitis). © Georg Thieme Verlag KG Stuttgart · New York.

Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

PubMed Central

Yarova, Polina L.; Stewart, Alecia L.; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A.; Lowe, Alexander P. P.; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C.; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J.; Ford, William R.; Broadley, Kenneth J.; Rietdorf, Katja; Chang, Wenhan; Khayat, Mohd E. Bin; Ward, Donald T.; Corrigan, Christopher J.; Ward, Jeremy P. T.; Kemp, Paul J.; Pabelick, Christina M.; Prakash, Y. S.; Riccardi, Daniela

2016-01-01

Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyper-reactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744

Rapid prototyping raw models on the basis of high resolution computed tomography lung data for respiratory flow dynamics.

PubMed

Giesel, Frederik L; Mehndiratta, Amit; von Tengg-Kobligk, Hendrik; Schaeffer, A; Teh, Kevin; Hoffman, E A; Kauczor, Hans-Ulrich; van Beek, E J R; Wild, Jim M

2009-04-01

Three-dimensional image reconstruction by volume rendering and rapid prototyping has made it possible to visualize anatomic structures in three dimensions for interventional planning and academic research. Volumetric chest computed tomography was performed on a healthy volunteer. Computed tomographic images of the larger bronchial branches were segmented by an extended three-dimensional region-growing algorithm, converted into a stereolithography file, and used for computer-aided design on a laser sintering machine. The injection of gases for respiratory flow modeling and measurements using magnetic resonance imaging were done on a hollow cast. Manufacturing the rapid prototype took about 40 minutes and included the airway tree from trackea to segmental bronchi (fifth generation). The branching of the airways are clearly visible in the (3)He images, and the radial imaging has the potential to elucidate the airway dimensions. The results for flow patterns in the human bronchial tree using the rapid-prototype model with hyperpolarized helium-3 magnetic resonance imaging show the value of this model for flow phantom studies.

SPDEF regulates goblet cell hyperplasia in the airway epithelium

PubMed Central

Park, Kwon-Sik; Korfhagen, Thomas R.; Bruno, Michael D.; Kitzmiller, Joseph A.; Wan, Huajing; Wert, Susan E.; Khurana Hershey, Gurjit K.; Chen, Gang; Whitsett, Jeffrey A.

2007-01-01

Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo. PMID:17347682

Bronchovascular anatomy of the upper lobes: evaluation with thin-section CT.

PubMed

Lee, K S; Bae, W K; Lee, B H; Kim, I Y; Choi, E W; Lee, B H

1991-12-01

The anatomy of the bronchovascular trees of the upper lobes was evaluated with thin-section computed tomography (CT) in 50 patients. In all patients, the subsegmental bronchi could be seen, except the right B2b, left B1 + 2c, and left B3c. Regular anatomic relationships were seen between the right A3b and B3b (A3b was seen along the medial aspect of B3b in 45 patients [90%]), right A2a and B2a (A2a was seen along the posteromedial aspect of B2a in 45 patients [90%]), and left A1 + 2c and B1 + 2c (A1 + 2c was seen along the posterior aspect of B1 + 2c in 41 patients [82%]). Four patterns of bronchial branching were seen in the left upper lobe. The lateral branch of the posterior segmental vein of the upper lobes was an anatomic landmark dividing the anterior and posterior segments of the upper lobes. Three kinds of venous drainage patterns were identified in both the right and left upper lobes.

Relapsing polychondritis: A 2016 update on clinical features, diagnostic tools, treatment and biological drug use.

PubMed

Mathian, Alexis; Miyara, Makoto; Cohen-Aubart, Fleur; Haroche, Julien; Hie, Miguel; Pha, Micheline; Grenier, Philippe; Amoura, Zahir

2016-04-01

Relapsing polychondritis (RP) is a very rare autoimmune disease characterised by a relapsing inflammation of the cartilaginous tissues (joints, ears, nose, intervertebral discs, larynx, trachea and cartilaginous bronchi), which may progress to long-lasting atrophy and/or deformity of the cartilages. Non-cartilaginous tissues may also be affected, such as the eyes, heart, aorta, inner ear and skin. RP has a long and unpredictable course. Because no randomised therapeutic trials are available, the treatment of RP remains mainly empirical. Minor forms of the disease can be treated with non-steroidal anti-inflammatory drugs, whereas more severe forms are treated with systemic corticosteroids. Life-threatening diseases and corticosteroid-dependent or resistant diseases are an indication for immunosuppressant therapy such as methotrexate, azathioprine, mycophenolate mofetil and cyclophosphamide. Biologics could be given as second-line treatment in patients with an active disease despite the use of steroids and immunosuppressive drugs. Although the biologics represent new potential treatment for RP, very scarce information is available to draw any firm conclusion on their use in RP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Susceptibility of openbill storks (Anastomius oscitans) to highly pathogenic avian influenza virus subtype H5N1.

PubMed

Chaichoun, Kridsada; Wiriyarat, Withawat; Phonaknguen, Rassmeepen; Sariya, Ladawan; Taowan, Nam-aoy; Chakritbudsabong, Warunya; Chaisilp, Natnapat; Eiam-ampai, Krirat; Phuttavatana, Pilaipan; Ratanakorn, Parntep

2013-09-01

This investigation detailed the clinical disease, gross and histologic lesions in juvenile openbill storks (Anastomus oscitans) intranasally inoculated with an avian influenza virus, A/chicken/Thailand/vsmu-3 (H5N1), which is highly pathogenic for chickens. High morbidity and mortality were observed in openbill storks inoculated with HPAI H5N1 virus. Gross lesions from infected birds were congestion and brain hemorrhage (10/20), pericardial effusions, pericarditis and focal necrosis of the cardiac muscle (2/20), pulmonary edema and pulmonary necrosis, serosanguineous fluid in the bronchis (16/20), liver congestion (6/20), bursitis (5/20), subcutaneous hemorrhages (2/20) and pinpoint proventiculus hemorrhage (2/20). Real time RT-PCR demonstrated the presence of viral RNA in organs associated with the lesions: brain, trachea, lungs, liver, spleen and intestines. Similar to viral genome detection, virus was also isolated from these vital organs. Antibodies to influenza virus detected with a hemagglutination inhibition test, were found only in the openbill storks who died 8 days post-inoculation.

What evidence implicates airway smooth muscle in the cause of BHR?

PubMed

Dulin, Nickolai O; Fernandes, Darren J; Dowell, Maria; Bellam, Shashi; McConville, John; Lakser, Oren; Mitchell, Richard; Camoretti-Mercado, Blanca; Kogut, Paul; Solway, Julian

2003-02-01

Bronchial hyperresponsiveness (BHR), the occurrence of excessive bronchoconstriction in response to relatively small constrictor stimuli, is a cardinal feature of asthma. Here, we consider the role that airway smooth muscle might play in the generation of BHR. The weight of evidence suggests that smooth muscle isolated from asthmatic tissues exhibits normal sensitivity to constrictor agonists when studied during isometric contraction, but the increased muscle mass within asthmatic airways might generate more total force than the lesser amount of muscle found in normal bronchi. Another salient difference between asthmatic and normal individuals lies in the effect of deep inhalation (DI) on bronchoconstriction. DI often substantially reverses induced bronchoconstriction in normals, while it often has much less effect on spontaneous or induced bronchoconstriction in asthmatics. It has been proposed that abnormal dynamic aspects of airway smooth muscle contraction velocity of contraction or plasticity- elasticity balance might underlie the abnormal DI response in asthma. We suggest a speculative model in which abnormally long actin filaments might account for abnormally increased elasticity of contracted airway smooth muscle.

Pulmonary actions of the neurokinin1-specific agonist [Sar9,Met(O2)11]-substance P.

PubMed

Yiamouyiannis, C A; Stengel, P W; Cockerham, S L; Silbaugh, S A

1995-01-01

We examined the relationship between airway obstruction and plasma extravasation produced by the intravenous administration of the selective NK1 receptor agonist [Sar9, Met(O2)11]-substance P(SP). Conscious guinea-pigs were injected with Evans' blue dye followed by intravenous [Sar9,Met(O2)11]-SP. Animals were killed 3 min later and airway obstruction, determined via excised lung gas volumes, and plasma extravasation in the trachea, mainstem bronchi and intrapulmonary airways quantitated. Maximal plasma protein extravasation occurred at a dose about 30 times less than that required to elicit airway obstruction. Neither the neutral endopeptidase (NEP) inhibitor, thiorphan, or the angiotensin-converting enzyme (ACE) inhibitor, captopril, altered the extravasation response to [Sar9,Met(O2)11]-SP. However, thiorphan alone or combined with captopril produced a small but significant potentiation of the airway obstructive response. The marked difference between pulmonary gas trapping and Evans' blue extravasation responses suggest that [Sar9,Met(O2)11]-SP-induced airway obstruction is not secondary to increased pulmonary edema.

Protective effect of fenspiride on the bronchi in rats with chronic obstructive pulmonary disease.

PubMed

Kuzubova, N A; Lebedeva, E S; Fedin, A N; Dvorakovskaya, I V; Titova, O N

2013-06-01

We studied the effect of a non-steroidal anti-inflammatory drug fenspiride on contractive activity of bronchial smooth muscles on the model of chronic obstructive pulmonary disease of rats induced by 60-day exposure to nitrogen dioxide. The administration of fenspiride during the acute stage of the disease (day 15) abolished the constricting effect of the pollutant on the bronchial smooth muscles. Dilatation effect of fenspiride in a low dose (0.15 mg/kg) was mediated by its interaction with nerve endings of bronchial capsaicin-sensitive nerve C-fibers. The interaction of drug with receptors of C-fibers prevented neurogenic inflammation, which was confirmed by the absence of structural changes in the lungs typical of this pathology. The broncholytic effect of fenspiride in a high dose (15 mg/kg) was mediated by not only afferent pathways, but also its direct relaxing action on smooth muscle cells. The observed anti-inflammatory and bronchodilatation effect of fenspiride in very low doses can be used for prevention of chronic obstructive pulmonary disease in risk-group patients contacting with aggressive environmental factors.

Tracheobronchial Manifestations of Aspergillus Infections

PubMed Central

Krenke, Rafal; Grabczak, Elzbieta M.

2011-01-01

Human lungs are constantly exposed to a large number of Aspergillus spores which are present in ambient air. These spores are usually harmless to immunocompetent subjects but can produce a symptomatic disease in patients with impaired antifungal defense. In a small percentage of patients, the trachea and bronchi may be the main or even the sole site of Aspergillus infection. The clinical entities that may develop in tracheobronchial location include saprophytic, allergic and invasive diseases. Although this review is focused on invasive Aspergillus tracheobronchial infections, some aspects of allergic and saprophytic tracheobronchial diseases are also discussed in order to present the whole spectrum of tracheobronchial aspergillosis. To be consistent with clinical practice, an approach basing on specific conditions predisposing to invasive Aspergillus tracheobronchial infections is used to present the differences in the clinical course and prognosis of these infections. Thus, invasive or potentially invasive Aspergillus airway diseases are discussed separately in three groups of patients: (1) lung transplant recipients, (2) highly immunocompromised patients with hematologic malignancies and/or patients undergoing hematopoietic stem cell transplantation, and (3) the remaining, less severely immunocompromised patients or even immunocompetent subjects. PMID:22194666

Clearance of polonium-210-enriched cigarette smoke from the rat trachea and lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, B.S.; Harley, N.H.; Tso, T.C.

The distribution and clearance of alpha radioactivity in the lungs of rats were measured after inhalation of smoke from cigarettes highly enriched in /sup 210/Po. Female Fischer rats were exposed daily for 6 months to smoke from cigarettes with 500 times the normal content of /sup 210/Po. Control rats were exposed to standard cigarette smoke. Animals were serially withdrawn and killed. After necropsy the trachea, major bronchi, larynx, and nasopharynx were examined for surface alpha activity by an etched track technique utilizing cellulose nitrate detectors. Areas of accumulated activity were seen on samples of larynx from rats exposed to themore » /sup 210/Po-enriched cigarettes. No other local accumulations were seen on the airways. The lower lungs were analyzed radiochemically for /sup 210/Po. Both radiochemical analysis and track measurements showed highly elevated activity concentrations in rats exposed to the /sup 210/Po-enriched cigarettes. Following withdrawal from smoking, both short- and long-term clearance components were seen. The parameters which fit the postexposure data for clearance of the lung burden cannot fit the buildup during the exposure period.« less

Clearance of polonium-210-enriched cigarette smoke from the rat trachea and lung.

PubMed

Cohen, B S; Harley, N H; Tso, T C

1985-06-30

The distribution and clearance of alpha radioactivity in the lungs of rats were measured after inhalation of smoke from cigarettes highly enriched in 210Po. Female Fischer rats were exposed daily for 6 months to smoke from cigarettes with 500 times the normal content of 210Po. Control rats were exposed to standard cigarette smoke. Animals were serially withdrawn and killed. After necropsy the trachea, major bronchi, larynx, and nasopharynx were examined for surface alpha activity by an etched track technique utilizing cellulose nitrate detectors. Areas of accumulated activity were seen on samples of larynx from rats exposed to the 210Po-enriched cigarettes. No other local accumulations were seen on the airways. The lower lungs were analyzed radiochemically for 210Po. Both radiochemical analysis and track measurements showed highly elevated activity concentrations in rats exposed to the 210Po-enriched cigarettes. Following withdrawal from smoking, both short- and long-term clearance components were seen. The parameters which fit the postexposure data for clearance of the lung burden cannot fit the buildup during the exposure period.

Three dimensional computed tomography lung modeling is useful in simulation and navigation of lung cancer surgery.

PubMed

Ikeda, Norihiko; Yoshimura, Akinobu; Hagiwara, Masaru; Akata, Soichi; Saji, Hisashi

2013-01-01

The number of minimally invasive operations, such as video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy, has enormously increased in recent years. These operations require extreme knowledge of the anatomy of pulmonary vessels and bronchi in each patient, and surgeons must carefully dissect the branches of pulmonary vessels during operation. Thus, foreknowledge of the anatomy of each patient would greatly contribute to the safety and accuracy of the operation. The development of multi-detector computed tomography (MDCT) has promoted three dimensional (3D) images of lung structures. It is possible to see the vascular and bronchial structures from the view of the operator; therefore, it is employed for preoperative simulation as well as navigation during operation. Due to advances in software, even small vessels can be accurately imaged, which is useful in performing segmentectomy. Surgical simulation and navigation systems based on high quality 3D lung modeling, including vascular and bronchial structures, can be used routinely to enhance the safety operation, education of junior staff, as well as providing a greater sense of security to the operators.

Off-the-job training for VATS employing anatomically correct lung models.

PubMed

Obuchi, Toshiro; Imakiire, Takayuki; Miyahara, Sou; Nakashima, Hiroyasu; Hamanaka, Wakako; Yanagisawa, Jun; Hamatake, Daisuke; Shiraishi, Takeshi; Moriyama, Shigeharu; Iwasaki, Akinori

2012-02-01

We evaluated our simulated major lung resection employing anatomically correct lung models as "off-the-job training" for video-assisted thoracic surgery trainees. A total of 76 surgeons voluntarily participated in our study. They performed video-assisted thoracic surgical lobectomy employing anatomically correct lung models, which are made of sponges so that vessels and bronchi can be cut using usual surgical techniques with typical forceps. After the simulation surgery, participants answered questionnaires on a visual analogue scale, in terms of their level of interest and the reality of our training method as off-the-job training for trainees. We considered that the closer a score was to 10, the more useful our method would be for training new surgeons. Regarding the appeal or level of interest in this simulation surgery, the mean score was 8.3 of 10, and regarding reality, it was 7.0. The participants could feel some of the real sensations of the surgery and seemed to be satisfied to perform the simulation lobectomy. Our training method is considered to be suitable as an appropriate type of surgical off-the-job training.

Mounier Kuhn syndrome presenting with recurrent atelectasis.

PubMed

Quentin, Christine; Lefevre, Nicolas; Bodart, Eddy; Hanssens, Laurence

2017-09-11

Objective and importance Mounier Kuhn syndrome is usually diagnosed in adulthood, and only a few cases have been described in childhood. Clinical presentation We present the case of a seven-year-old boy suffering from recurrent pneumonia and atelectasis. Intervention Previously performed chest X-rays showed bilateral hyperinflation and tracheobronchomegaly. Chest computed tomography (CT) confirmed the presence of distal enlargement of trachea and bronchi. Tracheobronchomegaly associated with recurrent respiratory tract infections is consistent with Mounier Kuhn syndrome. Pseudomonas aeruginosa was isolated from the sputum of the patient. He was then treated according to the guidelines for P. aeruginosa management in cystic fibrosis patients considering the similarities in clinical presentations and pathophysiology of both diseases. Antibiotic treatment resulted in a remarkable reduction of events of pulmonary exacerbation and hospitalizations. There are no specific guidelines for treatment options in case of pulmonary exacerbation of Mounier Kuhn syndrome. Case reports discussing the choice and efficiency of antibiotic treatment are random. Conclusion headings We share our experience of treating pulmonary exacerbation caused by P. aeruginosa in a patient with Mounier Kuhn syndrome suggesting a possible treatment option of pseudomonas infections in this syndrome.

Conditional Deletion of Pten Causes Bronchiolar Hyperplasia

PubMed Central

Davé, Vrushank; Wert, Susan E.; Tanner, Tiffany; Thitoff, Angela R.; Loudy, Dave E.; Whitsett, Jeffrey A.

2008-01-01

Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (PtenΔ/Δ) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as indicated by β-tubulin and FOXJ1 expression in ciliated cells and by CCSP expression in nonciliated cells, cell proliferation (detected by expression of Ki-67, phospho-histone-H3, and cyclin D1) was increased and associated with activation of the AKT/mTOR survival pathway. Deletion of Pten caused papillary epithelial hyperplasia characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protruded into the airway lumens. Cell polarity, as assessed by subcellular localization of cadherin, β-catenin, and zonula occludens-1, was unaltered. PTEN is required for regulation of epithelial cell proliferation in the lung and for the maintenance of the normal simple columnar epithelium characteristics of bronchi and bronchioles. PMID:17921358

Conditional deletion of Pten causes bronchiolar hyperplasia.

PubMed

Davé, Vrushank; Wert, Susan E; Tanner, Tiffany; Thitoff, Angela R; Loudy, Dave E; Whitsett, Jeffrey A

2008-03-01

Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (Pten(Delta/Delta)) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as indicated by beta-tubulin and FOXJ1 expression in ciliated cells and by CCSP expression in nonciliated cells, cell proliferation (detected by expression of Ki-67, phospho-histone-H3, and cyclin D1) was increased and associated with activation of the AKT/mTOR survival pathway. Deletion of Pten caused papillary epithelial hyperplasia characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protruded into the airway lumens. Cell polarity, as assessed by subcellular localization of cadherin, beta-catenin, and zonula occludens-1, was unaltered. PTEN is required for regulation of epithelial cell proliferation in the lung and for the maintenance of the normal simple columnar epithelium characteristics of bronchi and bronchioles.

Virtual endoscopic imaging of the spine.

PubMed

Kotani, Toshiaki; Nagaya, Shigeyuki; Sonoda, Masaru; Akazawa, Tsutomu; Lumawig, Jose Miguel T; Nemoto, Tetsuharu; Koshi, Takana; Kamiya, Koshiro; Hirosawa, Naoya; Minami, Shohei

2012-05-20

Prospective trial of virtual endoscopy in spinal surgery. To investigate the utility of virtual endoscopy of the spine in conjunction with spinal surgery. Several studies have described clinical applications of virtual endoscopy to visualize the inside of the bronchi, paranasal sinus, stomach, small intestine, pancreatic duct, and bile duct, but, to date, no study has described the use of virtual endoscopy in the spine. Virtual endoscopy is a realistic 3-dimensional intraluminal simulation of tubular structures that is generated by postprocessing of computed tomographic data sets. Five patients with spinal disease were selected: 2 patients with degenerative disease, 2 patients with spinal deformity, and 1 patient with spinal injury. Virtual endoscopy software allows an observer to explore the spinal canal with a mouse, using multislice computed tomographic data. Our study found that virtual endoscopy of the spine has advantages compared with standard imaging methods because surgeons can noninvasively explore the spinal canal in all directions. Virtual endoscopy of the spine may be useful to surgeons for diagnosis, preoperative planning, and postoperative assessment by obviating the need to mentally construct a 3-dimensional picture of the spinal canal from 2-dimensional computed tomographic scans.

Association of childhood perennial allergic rhinitis with subclinical airflow limitation.

PubMed

Ciprandi, G; Capasso, M

2010-03-01

Allergic rhinitis (AR) is a relevant risk factor for the onset of asthma, and a close association exists between the nose and the bronchi. Recently, it has been evidenced that the duration of AR and mite allergy represent high risks for spirometric impairment in allergic adults. To evaluate a group of AR children, without bronchial symptoms, to investigate spirometric impairments. Two hundred children with moderate-severe AR were consecutively evaluated. Clinical examination, skin prick test, and spirometry were performed in all children. Thirty-one percent of the children had forced expiratory flow at 25% and 75% of the pulmonary volume (FEF25-75%)<80% of the predicted values and 11% had both forced expiratory volume in 1 s and FEF25-75%<80% of the predicted values. Rhinitis duration and sensitization to house dust mites were significantly associated with impaired values of these spirometric parameters. This study highlights the close link between the upper and the lower airways and the role of some risk factors, such as long duration and mite sensitization, as early prognostic markers of bronchial involvement in children with AR and perceiving nasal symptoms alone.

Airway extraction from 3D chest CT volumes based on iterative extension of VOI enhanced by cavity enhancement filter

NASA Astrophysics Data System (ADS)

Meng, Qier; Kitasaka, Takayuki; Oda, Masahiro; Mori, Kensaku

2017-03-01

Airway segmentation is an important step in analyzing chest CT volumes for computerized lung cancer detection, emphysema diagnosis, asthma diagnosis, and pre- and intra-operative bronchoscope navigation. However, obtaining an integrated 3-D airway tree structure from a CT volume is a quite challenging task. This paper presents a novel airway segmentation method based on intensity structure analysis and bronchi shape structure analysis in volume of interest (VOI). This method segments the bronchial regions by applying the cavity enhancement filter (CEF) to trace the bronchial tree structure from the trachea. It uses the CEF in each VOI to segment each branch and to predict the positions of VOIs which envelope the bronchial regions in next level. At the same time, a leakage detection is performed to avoid the leakage by analysing the pixel information and the shape information of airway candidate regions extracted in the VOI. Bronchial regions are finally obtained by unifying the extracted airway regions. The experiments results showed that the proposed method can extract most of the bronchial region in each VOI and led good results of the airway segmentation.

Dynamics of airflow in a short inhalation

PubMed Central

Bates, A. J.; Doorly, D. J.; Cetto, R.; Calmet, H.; Gambaruto, A. M.; Tolley, N. S.; Houzeaux, G.; Schroter, R. C.

2015-01-01

During a rapid inhalation, such as a sniff, the flow in the airways accelerates and decays quickly. The consequences for flow development and convective transport of an inhaled gas were investigated in a subject geometry extending from the nose to the bronchi. The progress of flow transition and the advance of an inhaled non-absorbed gas were determined using highly resolved simulations of a sniff 0.5 s long, 1 l s−1 peak flow, 364 ml inhaled volume. In the nose, the distribution of airflow evolved through three phases: (i) an initial transient of about 50 ms, roughly the filling time for a nasal volume, (ii) quasi-equilibrium over the majority of the inhalation, and (iii) a terminating phase. Flow transition commenced in the supraglottic region within 20 ms, resulting in large-amplitude fluctuations persisting throughout the inhalation; in the nose, fluctuations that arose nearer peak flow were of much reduced intensity and diminished in the flow decay phase. Measures of gas concentration showed non-uniform build-up and wash-out of the inhaled gas in the nose. At the carina, the form of the temporal concentration profile reflected both shear dispersion and airway filling defects owing to recirculation regions. PMID:25551147

Demographic and Clinical Findings in Children Undergoing Bronchoscopy for Foreign Body Aspiration.

PubMed

Safari, Mojgan; Manesh, Mohammad Reza Hashemi

2016-01-01

Foreign body aspiration (FBA) is a significant cause of airway distress, mortality, and morbidity in children. Diagnosis of FBA can be challenging and is sometimes delayed for weeks or even months. If not diagnosed and treated promptly, FBA can result in serious consequences. For this retrospective study, we investigated the medical records of 89 children who underwent bronchoscopy for suspected FBA and recorded relevant demographic, clinical, and treatment data. Of the 89 patients identified for this study, 51 had a definitive diagnosis of FBA. Among these patients, choking, chronic cough and wheezing, cyanosis, and dyspnea were the most frequent symptoms of FBA. The foreign bodies were located in the left bronchus (45.1%), the right bronchus (35.3%), the trachea (15.7%), and in both the right and left bronchi (3.9%). Seeds were the most prevalent foreign body, found in 39.2% of the patients. Lack of complete medical history in patients with suspected FBA is one of the main causes of delayed FBA diagnosis. Bronchoscopy is considered the definitive diagnostic method for FBA and should be conducted in all patients with suspected FBA because of the low risk of complications and reduced probability that FBA diagnosis and treatment will be delayed.

Disentangling interoception: insights from focal strokes affecting the perception of external and internal milieus

PubMed Central

Couto, Blas; Adolfi, Federico; Sedeño, Lucas; Salles, Alejo; Canales-Johnson, Andrés; Alvarez-Abut, Pablo; Garcia-Cordero, Indira; Pietto, Marcos; Bekinschtein, Tristan; Sigman, Mariano; Manes, Facundo; Ibanez, Agustin

2015-01-01

Interoception is the moment-to-moment sensing of the physiological condition of the body. The multimodal sources of interoception can be classified into two different streams of afferents: an internal pathway of signals arising from core structures (i.e., heart, blood vessels, and bronchi) and an external pathway of body-mapped sensations (i.e., chemosensation and pain) arising from peripersonal space. This study examines differential processing along these streams within the insular cortex (IC) and their subcortical tracts connecting frontotemporal networks. Two rare patients presenting focal lesions of the IC (insular lesion, IL) or its subcortical tracts (subcortical lesion, SL) were tested. Internally generated interoceptive streams were assessed through a heartbeat detection (HBD) task, while those externally triggered were tapped via taste, smell, and pain recognition tasks. A differential pattern was observed. The IC patient showed impaired internal signal processing while the SL patient exhibited external perception deficits. Such selective deficits remained even when comparing each patient with a group of healthy controls and a group of brain-damaged patients. These outcomes suggest the existence of distinguishable interoceptive streams. Results are discussed in relation with neuroanatomical substrates, involving a fronto-insulo-temporal network for interoceptive and cognitive contextual integration. PMID:25983697

[Virtual endoscopic navigation and body transparency based on computed tomography. A step towards in vivo imaging].

PubMed

Cabanis, Emmanuel-Alain; Gombergh, Rodolphe; Castro, Albert; Gandjbakhch, Iradj; Iba-Zizen, Marie-Thérèse; Dubois, François

2011-06-01

Progress in HR-CTdata processing has led to lower X-ray exposure and to better diagnostic performance. We describe 19 adult patients (among 5000) examined by HR CT with 64 detectors, acquisition and exposure protocols in mSv, spiral, 0.6-mm slices, 5To PACS. After the two usual processing steps (60 gray values, 5122 and 10242 matrices, dedicated workstations for coronaroscopy and virtual coloscopy, 2D multiplanar reformation, surfacic, 3D volumes with dissection and navigation), a third original data processing step on additional workstations was added. Variable matrix extrapolated images, flexible colored curves (different from anatomical conventions), lighting (sources) and transparencies (unavailable with traditional endoscopy) were used. The digital film is a 16-minute "journey "consisting of 19 endo-body navigations in 5 regions, from the head to the bronchi, from the heart to the coronary arteries, and from the digestive tract to the abdomen and pelvis. One possible application is post-operative verification of an aortic graft. The movie is illustrated here with ten plates. This new approach is cost-effective and beneficial for the patient, in terms of early diagnosis and therapeutic follow-up. Ethical issues are also examined.

Surgical treatment of late-diagnosed bronchial foreign body aspiration: a report of 23 cases.

PubMed

Duan, Liang; Chen, Xiaofeng; Wang, Hao; Hu, Xuefei; Jiang, Gening

2014-07-01

Late-diagnosed bronchial foreign bodies can lead to irreversible changes in the bronchi and the lungs. To date, few reports are available concerning surgical treatment for this condition. The present report summarizes clinicopathological features and surgical treatment options for late-diagnosed bronchial foreign body aspiration. Clinical data of 23 patients who underwent surgical treatment for late-diagnosed bronchial foreign body aspiration in our hospital from 1980 to 2010 were reviewed. The patients included 17 male and six female patients, aged 6 to 66 years. To remove the foreign body, bronchotomy was performed in six patients and pulmonary resection in 17 patients. Foreign bodies were located on the right side in 17 cases and on the left side in six cases. The majority of the foreign bodies were of food origin. Postoperative bronchopleural fistula occurred in two patients. One patient died of renal failure subsequent to lung infections. Detailed history, awareness of potential foreign body aspiration and thorough bronchoscopic examination are helpful to avoid pulmonary resection. However, the latter is necessary in patients with the associated substantial lung lesions to prevent these from progressing into serious lung infections such as pulmonary suppuration or empyema. © 2013 John Wiley & Sons Ltd.

Three-dimensional computed tomography reconstruction for operative planning in robotic segmentectomy: a pilot study

PubMed Central

Le Moal, Julien; Peillon, Christophe; Dacher, Jean-Nicolas

2018-01-01

Background The objective of our pilot study was to assess if three-dimensional (3D) reconstruction performed by Visible Patient™ could be helpful for the operative planning, efficiency and safety of robot-assisted segmentectomy. Methods Between 2014 and 2015, 3D reconstructions were provided by the Visible Patient™ online service and used for the operative planning of robotic segmentectomy. To obtain 3D reconstruction, the surgeon uploaded the anonymized computed tomography (CT) image of the patient to the secured Visible Patient™ server and then downloaded the model after completion. Results Nine segmentectomies were performed between 2014 and 2015 using a pre-operative 3D model. All 3D reconstructions met our expectations: anatomical accuracy (bronchi, arteries, veins, tumor, and the thoracic wall with intercostal spaces), accurate delimitation of each segment in the lobe of interest, margin resection, free space rotation, portability (smartphone, tablet) and time saving technique. Conclusions We have shown that operative planning by 3D CT using Visible Patient™ reconstruction is useful in our practice of robot-assisted segmentectomy. The main disadvantage is the high cost. Its impact on reducing complications and improving surgical efficiency is the object of an ongoing study. PMID:29600049

Three-dimensional computed tomography reconstruction for operative planning in robotic segmentectomy: a pilot study.

PubMed

Le Moal, Julien; Peillon, Christophe; Dacher, Jean-Nicolas; Baste, Jean-Marc

2018-01-01

The objective of our pilot study was to assess if three-dimensional (3D) reconstruction performed by Visible Patient™ could be helpful for the operative planning, efficiency and safety of robot-assisted segmentectomy. Between 2014 and 2015, 3D reconstructions were provided by the Visible Patient™ online service and used for the operative planning of robotic segmentectomy. To obtain 3D reconstruction, the surgeon uploaded the anonymized computed tomography (CT) image of the patient to the secured Visible Patient™ server and then downloaded the model after completion. Nine segmentectomies were performed between 2014 and 2015 using a pre-operative 3D model. All 3D reconstructions met our expectations: anatomical accuracy (bronchi, arteries, veins, tumor, and the thoracic wall with intercostal spaces), accurate delimitation of each segment in the lobe of interest, margin resection, free space rotation, portability (smartphone, tablet) and time saving technique. We have shown that operative planning by 3D CT using Visible Patient™ reconstruction is useful in our practice of robot-assisted segmentectomy. The main disadvantage is the high cost. Its impact on reducing complications and improving surgical efficiency is the object of an ongoing study.

Mortality associated with melarsomine dihydrochloride administration in two North American river otters (Lontra canadensis) and a red panda (Ailurus fulgens fulgens).

PubMed

Neiffer, Donald L; Klein, Edwin C; Calle, Paul P; Linn, Michael; Terrell, Scott P; Walker, Rodney L; Todd, Donna; Vice, Carol C; Marks, Steven K

2002-09-01

Two adult North American river otters (Lontra canadensis) and an adult red panda (Ailurus fulgens fulgens) at three separate institutions died within 22 hr after receiving single 2.5- to 2.7-mg/kg doses of melarsomine dihydrochloride administered in the epaxial musculature as a treatment for filarid nematodes. One otter had a suspected Dirofilaria immitis infection, the other had a confirmed D. lutrae infection, and the red panda had a confirmed Dirofilaria sp. infection, presumably with D. immitis. Postmortem examinations revealed similar gross lesions, although they were less severe in the red panda. The trachea and primary bronchi contained abundant foamy fluid, the lungs were mottled with areas of consolidation, and the pulmonary parenchyma exuded abundant fluid at the cut section. Histologic evaluation revealed acute pulmonary edema, which resulted in respiratory failure and death. There may have been direct pulmonary cellular toxicity of melarsomine dihydrochloride or a severe systemic anaphylactic reaction to antigens released after parasite death. An idiosyncratic drug reaction or a low therapeutic index of melarsomine probably caused the death of the three individuals. Melarsomine dihydrochloride use should be avoided in North American river otters and red pandas.

Surgical treatment of tracheal collapse using pliable total ring prostheses: results in one experimental and 4 clinical cases.

PubMed Central

Ayres, S A; Holmberg, D L

1999-01-01

Pliable total ring prostheses were created from the polyvinyl chloride drip chambers of intravenous administration sets. The total ring prostheses were placed in one clinically normal research dog and in 4 client-owned dogs diagnosed with tracheal collapse. The research dog was euthanized one month after placement of the prostheses. Histopathological analysis of the trachea adjacent to the prostheses revealed a mild inflammatory response. The follow-up period for the clinical cases was from 4 months to 11 years. Radiographs taken and fluoroscopy performed 1 day to 5 months after surgery revealed improvement or resolution of the tracheal collapse. One dog was asymptomatic 28 weeks following surgery. Two dogs died 7 and 9 years after surgery, with one requiring intermittent medical management for coughing. They were euthanized for nonrespiratory illness. One dog had a persistent nonproductive cough, due to collapse of the mainstem bronchi, when last evaluated 4 months postoperatively. Pliable total ring prostheses provided adequate stability to the trachea and had the advantage of conforming to the trachea and being easy to create, place, and suture. Images Figure 1. Figure 2. PMID:10563237

Parametric Study of Wall Shear Stress in Idealized Avian Airways

NASA Astrophysics Data System (ADS)

Farnsworth, Michael S.; Riede, Tobias; Thomson, Scott L.

2017-11-01

Because wall shear stress (WSS) affects cell response, WSS patterns in avian respiratory airways may be related to the origin of the syrinx and corresponding voice-producing tissue structures (e.g., membranes or vocal folds) in birds. To explore possible linkages between WSS patterns and the locations of avian voice-producing structures, a computational model of flow through an idealized portion of the avian respiratory airway, including trachea and primary bronchi sections, has been developed. The flow is governed by the Navier-Stokes equations, with velocity boundary conditions derived from pressure-flow data in an adult zebra finch during quiet respiration. Geometric parameters such as tracheal/bronchial diameter and length, as well as bronchial branching angle, are parametrically varied based on data for different avian species. Simulation results predict elevated WSS in the vicinity of the tracheobronchial juncture, the location at which voice-producing tissues are found in avian species. In this presentation, the model will be described and spatial distributions of WSS during inspiration and expiration will be presented and compared for different geometric configurations and respiration rates and waveforms. Funding for this project from the Gordon and Betty Moore Foundation (Grant 4498) is gratefully acknowledged.

Virtual 3D Modeling of Airways in Congenital Heart Defects

PubMed Central

Speggiorin, Simone; Durairaj, Saravanan; Mimic, Branko; Corno, Antonio F.

2016-01-01

The involvement of the airway is not uncommon in the presence of complex cardiovascular malformations. In these cases, a careful inspection of the relationship between the airway and the vasculature is paramount to plan the surgical procedure. Three-dimensional printing enhanced the visualization of the cardiovascular structure. Unfortunately, IT does not allow to remove selected anatomy to improve the visualization of the surrounding ones. Computerized modeling has the potential to fill this gap by allowing a dynamic handling of different anatomies, increasing the exposure of vessels or bronchi to show their relationship. We started to use this technique to plan the surgical repair in these complex cases where the airway is affected. This technique is routinely used in our Institution as an additional tool in the presurgical assessment. We report four cases in which the airways were compressed by vascular structures – ascending aorta in one, left pulmonary artery sling in one, patent ductus arteriosus in one, and major aorto-pulmonary collateral artery in one. We believe this technique can enhance the understanding of the causes of airway involvement and facilitate the creation of an appropriate surgical plan. PMID:27833903

Crystallization of recombinant Haemophilus influenzaee (P4) acid phosphatase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ou, Zhonghui; Felts, Richard L.; Reilly, Thomas J.

2006-05-01

Lipoprotein e (P4) is a class C acid phosphatase and a potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. Haemophilus influenzae infects the upper respiratory tract of humans and can cause infections of the middle ear, sinuses and bronchi. The virulence of the pathogen is thought to involve a group of surface-localized macromolecular components that mediate interactions at the host–pathogen interface. One of these components is lipoprotein e (P4), which is a class C acid phosphatase and amore » potential vaccine candidate for nontypeable H. influenzae infections. This paper reports the crystallization of recombinant e (P4) and the acquisition of a 1.7 Å resolution native X-ray diffraction data set. The space group is P4{sub 2}2{sub 1}2, with unit-cell parameters a = 65.6, c = 101.4 Å, one protein molecule per asymmetric unit and 37% solvent content. This is the first report of the crystallization of a class C acid phosphatase.« less

Experimental models of tracheobronchial stenoses: a useful tool for evaluating airway stents.

PubMed

Marquette, C H; Mensier, E; Copin, M C; Desmidt, A; Freitag, L; Witt, C; Petyt, L; Ramon, P

1995-09-01

Stent implantation is a conservative alternative to open operation for treating benign tracheobronchial strictures. Most of the presently available stents were primarily designed for endovascular use. Their respiratory use entails a risk of iatrogenic complications. From a scientific and from an ethical point of view these risks justify preclinical evaluation of new respiratory stents in experimental models of central airway stenoses. Therefore, an attempt was made to develop such models in piglets and adult minipigs. Tracheal stenoses were obtained by creating first a segmental tracheomalacia through extramucosal resection of cartilaginous arches. The fibrous component of the stenoses was then obtained through bronchoscopic application of a caustic agent causing progressive deep mucosal and submucosal injury. Stenoses of the main bronchi were created by topical application of the caustic agent only. These models demonstrated the typical features of benign fibromalacic tracheobronchial stenoses with constant recurrence after mechanical dilation. Preliminary experiments showed that short-term problems of tolerance of stent prototypes are easily demonstrable in these models. These experimental models, which simulate quite realistically human diseases, offer the opportunity to perfect new tracheobronchial stents specifically designed for respiratory use and to evaluate their long-term tolerance before their use in humans.

Adverse health effects of indoor moulds.

PubMed

Piecková, Elena

2012-12-01

Building associated illnesses - sick building syndrome (SBS) as a common example - are associated with staying in buildings with poor indoor air quality. The importance of indoor fungal growth in this phenomenon continues to be evident, even though no causative relation has been established so far. Indoor humidity is strongly associated with the symptoms of SBS. Fungal metabolites that may induce ill health in susceptible occupants comprise beta-D-glucan, mycotoxins, and volatile organic compounds as known irritants and/or immunomodulators. Indoor toxic fungal metabolites might be located in micromycetal propagules (endometabolites), in (bio-)aerosol, detritus, and house dust (exometabolites) as their particular carriers. It is highly probable that hyphal fragments, dust, and particles able to reach the alveoli have the strongest depository and toxic potential. Most fungal spores are entrapped by the upper respiratory tract and do not reach further than the bronchi because of their size, morphology, and the mode of propagation (such as slime heads and aggreggation). This is why studies of the toxic effects of fungal spores prefer directly applying metabolite mixtures over mimicking real exposure. Chronic low-level exposure to a mixture of fungal toxicants and other indoor stressors may have synergistic effects and lead to severe neuroendocrineimmune changes.

Bronchial ulceration as a prognostic indicator for varicella pneumonia: case report and systematic literature review.

PubMed

Inokuchi, Ryota; Nakamura, Kensuke; Sato, Hajime; Shinohara, Kazuaki; Aoki, Yuta; Doi, Kent; Gunshin, Masataka; Ishii, Takeshi; Matsubara, Takehiro; Hiruma, Takahiro; Nakajima, Susumu; Yahagi, Naoki

2013-04-01

Adult varicella pneumonia is a common and serious complication of varicella zoster virus (VZV) infection in pregnant woman and immunocompromised individuals, with mortality rates of 30-50%. The poor prognosis is attributable to very aggressive disease progression and delayed onset of treatment. Here, we present a case of varicella pneumonia in a 69-year-old woman following long-term immunosuppressive treatment for kidney transplant. Respiratory failure developed within 3 d after admission for skin rash, and the patient died 28 d later despite acyclovir and foscarnet treatment. The autopsy showed extensive mucosal airway ulcerations from the pharynx to the main bronchi and numerous VZV-infected cells. We searched PubMed, Web of Science, and EMBASE (1980 through February 2012), as well as several medical report databases created by Japanese healthcare professionals, for all reported cases of varicella pneumonia for which bronchoscopy findings were documented. Twenty-four cases were included and we found that patients with limited or shallow ulcers had favorable outcomes, whereas patients with vast and deep ulcerations had fatal outcomes. These findings indicate that bronchoscopy findings, particularly those showing bronchial involvement, may be useful for evaluating varicella pneumonia. Copyright © 2012 Elsevier B.V. All rights reserved.

Intermittent Haemoptysis due to an Aortobronchial Fistula in a Warmblood Mare.

PubMed

Versnaeyen, H; Saey, V; Vermeiren, D; Chiers, K; Ducatelle, R

2016-01-01

A 7-year-old warmblood mare showed sudden onset of mild intermittent haemoptysis. Clinical examination revealed no significant abnormalities. Haematological examination showed mild anaemia, hypoalbuminaemia and neutrophilia. Coagulation tests were normal. Endoscopic examination revealed unilateral pulmonary haemorrhage with blood clots in the bronchi and trachea. Treatment with antibiotics was started and the horse was given stable rest. Two weeks later, the horse was found dead with blood and frothy sputum leaking from the nostrils. Post-mortem examination revealed a large thoracic aortic aneurysm communicating with a pseudoaneurysm that had formed a fistula into a right bronchial branch. Microscopical examination of the aneurysm showed extensive medial fibrosis with prominent degeneration, fragmentation and mineralization of the elastic fibres and deposition of mucoid material in the tunica media. The pseudoaneurysm was lined by collagen bundles admixed with fibroblasts and a small amount of adipose tissue. Aortobronchial fistula is a rare condition in man that is usually associated with primary aortic pathology, most often aneurysms. To the authors' knowledge this is the first case of a fatal aortobronchial fistula in a horse or any other animal species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Infection of the upper respiratory tract of hamsters by the bovine parainfluenza virus type 3 BN-1 strain expressing enhanced green fluorescent protein.

PubMed

Ohkura, Takashi; Minakuchi, Moeko; Sagai, Mami; Kokuho, Takehiro; Konishi, Misako; Kameyama, Ken-Ichiro; Takeuchi, Kaoru

2015-02-01

Bovine parainfluenza virus type 3 (BPIV3) is an important pathogen associated with bovine respiratory disease complex (BRDC). We have generated a recombinant BPIV3 expressing enhanced green fluorescent protein (rBPIV3-EGFP) based on the BN-1 strain isolated in Japan. After intranasal infection of hamsters with rBPIV3-EGFP, EGFP fluorescence was detected in the upper respiratory tract including the nasal turbinates, pharynx, larynx, and trachea. In the nasal turbinates, rBPIV3-EGFP attained high titers (>10(6) TCID50/g of tissue) 2-4 days after infection. Ciliated epithelial cells in the nasal turbinates and trachea were infected with rBPIV3-EGFP. Histopathological analysis indicated that mucosal epithelial cells in bronchi were shed by 6 days after infection, leaving non-ciliated cells, which may have increased susceptibility to bacterial infection leading to the development of BRDC. These data indicate that rBPIV3-EGFP infection of hamsters is a useful small animal model for studying the development of BPIV3-associated BRDC. Copyright © 2014 Elsevier Inc. All rights reserved.

Numerical simulation of magnetic nano drug targeting in patient-specific lower respiratory tract

NASA Astrophysics Data System (ADS)

Russo, Flavia; Boghi, Andrea; Gori, Fabio

2018-04-01

Magnetic nano drug targeting, with an external magnetic field, can potentially improve the drug absorption in specific locations of the body. However, the effectiveness of the procedure can be reduced due to the limitations of the magnetic field intensity. This work investigates this technique with the Computational Fluid Dynamics (CFD) approach. A single rectangular coil generates the external magnetic field. A patient-specific geometry of the Trachea, with its primary and secondary bronchi, is reconstructed from Digital Imaging and Communications in Medicine (DICOM) formatted images, throughout the Vascular Modelling Tool Kit (VMTK) software. A solver, coupling the Lagrangian dynamics of the magnetic nanoparticles with the Eulerian dynamics of the air, is used to perform the simulations. The resistive pressure, the pulsatile inlet velocity and the rectangular coil magnetic field are the boundary conditions. The dynamics of the injected particles is investigated without and with the magnetic probe. The flow field promotes particles adhesion to the tracheal wall. The particles volumetric flow rate in both cases has been calculated. The magnetic probe is shown to increase the particles flow in the target region, but at a limited extent. This behavior has been attributed to the small particle size and the probe configuration.

Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis.

PubMed

Choi, Yo Won; Munden, Reginald F; Erasmus, Jeremy J; Park, Kyung Joo; Chung, Woo Kyung; Jeon, Seok Chol; Park, Choong-Ki

2004-01-01

Radiation-induced lung disease (RILD) due to radiation therapy is common. Radiologic manifestations are usually confined to the lung tissue within the radiation port and are dependent on the interval after completion of treatment. In the acute phase, RILD typically manifests as ground-glass opacity or attenuation or as consolidation; in the late phase, it typically manifests as traction bronchiectasis, volume loss, and scarring. However, the use of oblique beam angles and the development of newer irradiation techniques such as three-dimensional conformal radiation therapy can result in an unusual distribution of these findings. Awareness of the atypical manifestations of RILD can be useful in preventing confusion with infection, recurrent malignancy, lymphangitic carcinomatosis, and radiation-induced tumors. In addition, knowledge of radiologic findings that are outside the expected pattern for RILD can be useful in diagnosis of infection or recurrent malignancy. Such findings include the late appearance or enlargement of a pleural effusion; development of consolidation, a mass, or cavitation; and occlusion of bronchi within an area of radiation-induced fibrosis. A comprehensive understanding of the full spectrum of these manifestations is important to facilitate diagnosis and management in cancer patients treated with radiation therapy. Copyright RSNA, 2004

Respiratory herpesvirus infection in two Indian Ringneck parakeets.

PubMed

Lazic, Tatjana; Ackermann, Mark R; Drahos, Jo M; Stasko, Judith; Haynes, Joseph S

2008-03-01

A flock of Indian Ringneck parakeets (Psittacula krameri manillensis) was imported to the United States from Australia. Soon after, 1 parakeet suddenly died, and a second parakeet died after a 2-day course of illness, which consisted of anorexia, lethargy, emaciation, and dyspnea. At necropsy, the affected birds had diffuse consolidation and red discoloration of the lungs, as well as thickened, congested air sacs. The microscopic examination revealed multifocal, necrotizing bronchitis, parabronchitis, and interstitial pneumonia. The lumen of the affected airways contained numerous, large syncytial cells with up to 15 nuclei. The nuclei of these syncytial cells often contained large, eosinophilic inclusion bodies, consistent with herpesvirus. The epithelium of the trachea and air sacs was hypertrophied and contained syncytial cells with intranuclear inclusion bodies similar to the bronchi. In addition, a few intranuclear inclusion bodies were also present in the epithelial cells that line the air capillaries. On ultrastructural examination, the nuclei of degenerating epithelial cells contained clusters of viral nucleocapsid proteins and unenveloped, icosahedral, viral particles that were approximately 90 nm in diameter. In addition, some epithelial cells contained clusters of enveloped viral particles approximately 105 nm in diameter, within the cytocavitary network. These lesions are characteristic of those caused by respiratory herpesvirus of parakeets.

Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis.

PubMed

Chandrasekaran, Ravishankar; Mac Aogáin, Micheál; Chalmers, James D; Elborn, Stuart J; Chotirmall, Sanjay H

2018-05-22

Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.

Implication of dipeptidylpeptidase IV activity in human bronchial inflammation and in bronchoconstriction evaluated in anesthetized rabbits.

PubMed

Landis, B N; Grouzmann, E; Monod, M; Busso, N; Petak, F; Spiliopoulos, A; Robert, J H; Szalay-Quinodoz, I; Morel, D R; Lacroix, J S

2008-01-01

Decreased dipeptidylpeptidase IV (DPPIV) activity within the human nasal mucosa has previously been shown to contribute to the severity of chronic inflammatory rhinosinusitis. To investigate and correlate the role of DPPIV activity with regard to bronchial inflammation. DPPIV/CD26 activity/concentration was investigated in the bronchial tissue of human subjects suffering from chronic bronchial inflammation. In addition, the effect of a recombinant Aspergillus fumigatus DPPIV (fuDPPIV) was investigated on histamine-induced bronchoconstriction in anesthetized rabbits. DPPIV/CD26 was present in submucosal seromucous glands, in leukocytes and to a very low degree in endothelial cells of human bronchi. DPPIV activity was correlated with tissue CD26 content measured by immunoassay. As previously reported for the nasal mucosa, DPPIV/CD26 activity was inversely correlated with the degree of airway inflammation. Systemic pretreatment with recombinant fuDPPIV markedly reduced the increase in histamine-induced airway resistance in rabbits. In conclusion, DPPIV activity modulates lower airway tone by degrading unknown peptidic substrates released by histamine in response to an allergen. Contrasting with our observations in the nose, this modulation is apparently not mediated via a neurokinin (NK1) receptor. (c) 2007 S. Karger AG, Basel.

Effect of ONO-1078, a leukotriene antagonist, on capsaicin- and substance P-induced bronchoconstriction and airway microvascular leakage in guinea pigs.

PubMed

Wei, E Q; Liu, J W; Zhang, L F; Zhang, W P; Bian, R L

1996-05-01

To study the effect of 4-oxo-8-[p-(4-phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate (ONO-1078), a specific leukotriene antagonist, on capsaicin (Cap)-sensitive sensory nerve functions in the airways, and clarify the modulating roles of endogenous peptido-leukotrienes. Changes in intrapulmonary pressure (IPP), Evans blue extravasation in airways, and contraction of bronchial smooth muscles of guinea pigs induced by Cap, substance P (SP) and leukotriene C4 (LTC4) were observed. Cap (0.05 mg.kg-1, i.v.), SP (1 microgram.kg-1, i.v.) and LTC4 (0.5 microgram.kg-1, i.v.) enhanced IPP, and Evans blue extravasation in bronchi and intrapulmonary airways. ONO-1078 0.03 mg.kg-1, i.v. completely blocked the responses to LTC4, attenuated those to Cap, but had no effect to SP. In isolated bronchial smooth muscles, ONO-1078 (1 mumol.L-1) inhibited the contractile response to Cap, but not to SP. ONO-1078 partly inhibits Cap-sensitive sensory nerve actions in airways, but has no direct effect on SP, a sensory neuropeptide.

Nuts and seed: a natural yet dangerous foreign body.

PubMed

Sih, Tania; Bunnag, Chaweewan; Ballali, Simonetta; Lauriello, Maria; Bellussi, Luisa

2012-05-14

This paper has the object to present the impact of nuts' and seeds' injuries withdrawing data from the Susy Safe registry, highlighting that as for other foreign bodies the main item efficiently and substantially susceptible to changes to decrease the accidents' rates is the education of adults and children, that can be shared with parents both from pediatricians and general practitioners. Indeed labeling and age related warnings have also a fundamental relevance in prevention. The present study draws its data from the Susy Safe registry. Details on injuries are entered in the Susy Safe Web-registry through a standardized case report form, that includes information regarding: children age and gender, features of the object, circumstances of injury (presence of parents and activity) and hospitalization's details (lasting, complications and removal details). Cases are prospectively collected using the Susy Safe system from 06/2005; moreover, also information regarding past consecutive cases available in each centre adhering to the project have been entered in the Susy Safe registry. Nuts and seeds are one of the most common food item retrieved in foreign bodies injuries in children. In Susy Safe registry they represent the 38% in food group, and almost the 10% in general cases. Trachea, bronchi and lungs were the main location of FB's retrieval, showing an incidence of 68%. Hospitalization occurred in 83% of cases, showing the major frequency for foreign bodies located in trachea. This location was also the principal site of complications, with a frequency of 68%. There were no significant associations between these outcomes and the age class of the children. The most common complications seen (22.4%) was bronchitis, followed by pneumonia (19.7%). Adult presence was recorded as positive in 71.2% of cases, showing an association (p value 0.009) between the adult supervision and the hospitalization outcome. On the contrary there was a non significant association between adult presence and the occurrence of complications. In 80.7% of cases, the incident happened while the child was eating. Among those cases, 88.6% interested trachea, lungs and bronchi. Food-related aspiration injuries are common events for young children, particularly under 4 years of age, and may lead to severe complication. There is a need to study in more depth specific characteristics of foreign bodies associated with increased hazard, such as size, shape, hardness or firmness, lubricity, pliability and elasticity, in order to better identify risky foods, and more precisely described the pathogenetic pathway. Parents are not adequately conscious and aware toward this risk; therefore, the number and severity of the injuries could be reduced by educating parents and children. Information about food safety should be included in all visits to pediatricians in order to make parents able to understand, select, and identify key characteristics of hazardous foods and better control the hazard level of various foods. Finally, preventive measures including warning labels on high-risk foods could be implemented. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

New CO2 laser waveguide systems: advances in surgery of tracheal stenosis

NASA Astrophysics Data System (ADS)

Stasche, Norbert; Bernecker, Frank; Hoermann, Karl

1996-01-01

The carbon dioxide laser is a well established tool in the surgical treatment of laryngeal and tracheal stenosis. Usually the laser beam is applied by a microscope/micromanipulator device. Different types of rigid laryngoscopes and bronchoscopes provide access to nearly every area of larynx, trachea and main bronchi. In order to be treated with this equipment the target tissue has to be in a straight optical axis with the laser beam output at the micromanipulator. We report about one patient who presented with severe dyspnea due to granulation tissue directly below his left vocal cord. He was suffering from tracheomalacia for several years and was successfully treated by tracheostomy and a Montgomery's silicone T-tube as a stent. Then granulation tissue blocked the upper orifice of the Montgomery's T-tube. First removal by a carbon dioxide laser beam through the laryngoscope would have required sacrificing his intact left vocal cord. We removed the obstructing tissue by using the ArthroLaseTM System: the carbon dioxide laser beam was conducted through a 90 degree bent rigid probe, using the tracheostomy as an access. This ArthroLaseTM System was originally designed for arthroscopic surgery. In this special case however it successfully extends the use of the carbon dioxide laser in otolaryngology.

Air sac nematode Monopetalonema alcedinis in a Belted Kingfisher (Megaceryle alcyon) in Maryland, USA.

PubMed

Bronson, Ellen; Kelly, Kathleen; Hoberg, Eric P

2014-10-01

Sporadic and geographically widespread reports of parasites affecting the Belted Kingfisher (Megaceryle alcyon) have been published but few have described details of the pathology. A female, adult kingfisher was found dead in a heavily wooded area of a zoo in Maryland, USA. At necropsy, numerous sexually dimorphic, 4.4-40.5-cm adult Monopetalonema alcedinis nematodes were found tightly wound within the coelomic cavity between organs and completely filling the caudal thoracic and abdominal air sacs. Abundant, 30-60-µm diameter, larvated, thick-walled ova were found in the bronchi and parabronchi, within the mesentery, and in the serosa of multiple coelomic organs. Monopetalonema alcedinis is a characteristic member of the superfamily Diplotriaenoidea, a group of nematodes occurring in birds and reptiles. Infective larvae within an invertebrate intermediate host are ingested and penetrate the intestine, traveling to the lungs and then into the air sacs, where the adult females release eggs. The ova are coughed up by the avian host and passed in feces. Specimens of M. alcedinis have been found in the Belted Kingfisher, although typically intensity of infection is low and infections remain asymptomatic. In contrast, we report the second documented case of high numbers of M. alcedinis resulting in pathologic changes in which parasitism contributed to host mortality.

Demographic and Clinical Findings in Children Undergoing Bronchoscopy for Foreign Body Aspiration

PubMed Central

Safari, Mojgan; Manesh, Mohammad Reza Hashemi

2016-01-01

Background: Foreign body aspiration (FBA) is a significant cause of airway distress, mortality, and morbidity in children. Diagnosis of FBA can be challenging and is sometimes delayed for weeks or even months. If not diagnosed and treated promptly, FBA can result in serious consequences. Methods: For this retrospective study, we investigated the medical records of 89 children who underwent bronchoscopy for suspected FBA and recorded relevant demographic, clinical, and treatment data. Results: Of the 89 patients identified for this study, 51 had a definitive diagnosis of FBA. Among these patients, choking, chronic cough and wheezing, cyanosis, and dyspnea were the most frequent symptoms of FBA. The foreign bodies were located in the left bronchus (45.1%), the right bronchus (35.3%), the trachea (15.7%), and in both the right and left bronchi (3.9%). Seeds were the most prevalent foreign body, found in 39.2% of the patients. Conclusion: Lack of complete medical history in patients with suspected FBA is one of the main causes of delayed FBA diagnosis. Bronchoscopy is considered the definitive diagnostic method for FBA and should be conducted in all patients with suspected FBA because of the low risk of complications and reduced probability that FBA diagnosis and treatment will be delayed. PMID:27303219

Synthesized interstitial lung texture for use in anthropomorphic computational phantoms

NASA Astrophysics Data System (ADS)

Becchetti, Marc F.; Solomon, Justin B.; Segars, W. Paul; Samei, Ehsan

2016-04-01

A realistic model of the anatomical texture from the pulmonary interstitium was developed with the goal of extending the capability of anthropomorphic computational phantoms (e.g., XCAT, Duke University), allowing for more accurate image quality assessment. Contrast-enhanced, high dose, thorax images for a healthy patient from a clinical CT system (Discovery CT750HD, GE healthcare) with thin (0.625 mm) slices and filtered back- projection (FBP) were used to inform the model. The interstitium which gives rise to the texture was defined using 24 volumes of interest (VOIs). These VOIs were selected manually to avoid vasculature, bronchi, and bronchioles. A small scale Hessian-based line filter was applied to minimize the amount of partial-volumed supernumerary vessels and bronchioles within the VOIs. The texture in the VOIs was characterized using 8 Haralick and 13 gray-level run length features. A clustered lumpy background (CLB) model with added noise and blurring to match CT system was optimized to resemble the texture in the VOIs using a genetic algorithm with the Mahalanobis distance as a similarity metric between the texture features. The most similar CLB model was then used to generate the interstitial texture to fill the lung. The optimization improved the similarity by 45%. This will substantially enhance the capabilities of anthropomorphic computational phantoms, allowing for more realistic CT simulations.

Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

PubMed Central

Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

2016-01-01

Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

Autoradiographic localization of specific (/sup 3/H)dexamethasone binding in fetal lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beer, D.G.; Butley, M.S.; Cunha, G.R.

1984-10-01

The cellular and subcellular localization of specific (/sup 3/H)dexamethasone binding was examined in fetal mouse lung at various stages of development and in human fetal lung at 8 weeks of gestation using a rapid in vitro steroid incubation technique followed by thaw-mount autoradiography. Competition studies with unlabeled steroids demonstrate the specificity of (/sup 3/H)dexamethasone labeling, and indicate that fetal lung mesenchyme is a primary glucocorticoid target during lung development. Autoradiographs of (/sup 3/H)dexamethasone binding in lung tissue at early stages of development demonstrate that the mesenchyme directly adjacent to the more proximal portions of the bronchiolar network is heavily labeled.more » In contrast, the epithelium which will later differentiate into bronchi and bronchioles, is relatively unlabeled. Distal portions of the growing epithelium, destined to become alveolar ducts and alveoli, do show nuclear localization of (/sup 3/H)dexamethasone. In addition, by utilizing a technique which allows the simultaneous examination of extracellular matrix components and (/sup 3/H)dexamethasone binding, a relationship is observed between extensive mesenchymal (/sup 3/H)dexamethasone binding and extensive extracellular matrix accumulation. Since glucocorticoids stimulate the synthesis of many extracellular matrix components, these results suggest a role for these hormones in affecting mesenchymal-epithelial interactions during lung morphogenesis.« less

Lysyl Oxidase Is Essential for Normal Development and Function of the Respiratory System and for the Integrity of Elastic and Collagen Fibers in Various Tissues

PubMed Central

Mäki, Joni M.; Sormunen, Raija; Lippo, Sari; Kaarteenaho-Wiik, Riitta; Soininen, Raija; Myllyharju, Johanna

2005-01-01

Lysyl oxidases, a family comprising LOX and four LOX-like enzymes, catalyze crosslinking of elastin and collagens. Mouse Lox was recently shown to be crucial for development of the cardiovascular system because null mice died perinatally of aortic aneurysms and cardiovascular dysfunction. We show here that Lox is also essential for development of the respiratory system and the integrity of elastic and collagen fibers in the lungs and skin. The lungs of E18.5 Lox−/− embryos showed impaired development of the distal and proximal airways. Elastic fibers in E18.5 Lox−/− lungs were markedly less intensely stained and more disperse than in the wild type, especially in the mesenchyme surrounding the distal airways, bronchioles, bronchi, and trachea, and were fragmented in pulmonary arterial walls. The organization of individual collagen fibers into tight bundles was likewise abnormal. Similar elastic and collagen fiber abnormalities were seen in the skin. Lysyl oxidase activity in cultured Lox−/− skin fibroblasts and aortic smooth muscle cells was reduced by ∼80%, indicating that Lox is the main isoenzyme in these cells. LOX abnormalities may thus be critical for the pathogenesis of several common diseases, including pulmonary, skin, and cardiovascular disorders. PMID:16192629

Gene Expression Programs of Human Smooth Muscle Cells: Tissue-Specific Differentiation and Prognostic Significance in Breast Cancers

PubMed Central

Chi, Jen-Tsan; Rodriguez, Edwin H; Wang, Zhen; Nuyten, Dimitry S. A; Mukherjee, Sayan; van de Rijn, Matt; van de Vijver, Marc J.; Hastie, Trevor; Brown, Patrick O

2007-01-01

Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression. PMID:17907811

Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts.

PubMed

Stittelaar, Koert J; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J B; Fraaij, Pieter L A; van Baalen, Carel A; van Kampen, Jeroen J A; van der Vries, Erhard; Osterhaus, Albert D M E; de Swart, Rik L

2016-06-14

Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (10⁵ TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin.

PubMed

Keitsch, Simone; Riethmüller, Joachim; Soddemann, Matthias; Sehl, Carolin; Wilker, Barbara; Edwards, Michael J; Caldwell, Charles C; Fraunholz, Martin; Gulbins, Erich; Becker, Katrin Anne

2018-05-01

Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. aureus are poorly characterized. Therefore, we aimed to identify the role of α-toxin, a major S. aureus toxin, for pulmonary infection of CF mice. Infection with S. aureus JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of α-toxin in JE2-Δhla reduced the pathogenicity of S. aureus in CF mice. However, CF mice were still more susceptible to the mutant S. aureus strain than wildtype mice. The S. aureus JE2 induced a marked increase of ceramide and a downregulation of sphingosine and acid ceramidase expression in bronchi of CF mice. Deletion of α-toxin reduced these changes after infection of CF mice. Similar changes were observed in wildtype mice, but at much lower levels. Our data indicate that expression of α-toxin is a major factor causing S. aureus infections in CF mice. Wildtype S. aureus induces a marked increase of ceramide and a reduction of sphingosine and acid ceramidase expression in bronchial epithelial cells of wildtype and CF mice, changes that determine infection susceptibility.

Treatment of laryngeotracheal papillomatosis with the CO2 and Nd:YAG laser

NASA Astrophysics Data System (ADS)

Sedlmaier, Benedikt W.; Jovanovic, Sergije

2000-06-01

Papillomas are the most common benign neoplasms of the larynx and trachea. There are two types with different biological behavior, both caused by the human papilloma virus: the form that usually manifest itself in adults as a solitary, rarely recurring lesion, whereas one form that manifests in children and adults. It involves multiple lesions with a tendency to spread and recur. There is still no alternative to repeated surgical removal of the papillomas. In a retrospective study the results of laser surgery are compared with the results of instrumental removal of papillomas. The larynges were treated with the CO2 laser applied via high-precision micromanipulators combined with different scanner systems. In cases where the disease has spread into the cervical trachea, the papilloma foci were exposed by special subglottoscopes prior to transglottic removal with the CO2 laser via the operating microscope. The Nd:YAG laser applied through a jet ventilation tracheoscope via optical fibers has proven useful for involvement of the intrathoracic trachea. The use of the laser has not reduce the recurrency rate but the rate of late complications such as anterior synechia. Furthermore in extensive disease laser therapy enables a controlled bloodless removal even in the thoracic trachea and bronchi.

A solitary bronchial papilloma with unusual endoscopic presentation: case study and literature review

PubMed Central

Paganin, Fabrice; Prevot, Martine; Noel, Jean Baptiste; Frejeville, Marie; Arvin-Berod, Claude; Bourdin, Arnaud

2009-01-01

Background Solitary endobronchial papillomas (SEP) are rare tumors and most of them are described by case report. A misdiagnosis is common with viral related papillomas. A histopathological classification has recently permitted a major advancement in the understanding of the disease. Case Presentation We report a case of a mixed bronchial papilloma with an unusual endoscopic presentation. The literature was extensively reviewed to ascertain the unusual characteristics of the current case. A 39-year of age male was referred to our institution for the investigation of a slight hemoptysis. Routine examination was normal. A fibroscopy revealed an unusual feature of the right main bronchus. The lesion was a plane, non-bleeding, non-glistering sub-mucosal proliferation. No enhanced coloration was noticed. Biopsies revealed a mixed solitary bronchial papilloma. In situ HPV hybridization was negative. Endoscopic treatment (electrocautery) was effective with no relapse. Conclusion This lesion contrasts with the data of the literature where papilloma were described as wart-like lesions or cauliflower tumors, with symptoms generally related to bronchial obstruction. We advise chest physicians to be cautious with unusually small swollen lesions of the bronchi that may reveal a solitary bronchial papilloma. Endoscopic imaging can significantly contribute to the difficult diagnosis of SEP by pulmonary physicians and endoscopists. PMID:19689808

[Allergic rhinitis and ashtma: 2 illnesses. The same disease?].

PubMed

González Díaz, Sandra N; Arias Cruz, Alfredo

2002-01-01

Disturbances of the upper and lower airways frequently coexist, and the association between allergic rhinitis and asthma is an example of that. The relationship between allergic rhinitis and asthma probably occurs because both, nasal and bronchial mucosas are elements of a "united airway", and on the other hand, allergic rhinitis and asthma are manifestations of a common allergic disease. Allergic rhinitis and asthma are not only statistically associated, but have pathophysiological and clinical similarities. Allergic rhinitis is itself a risk factor for the development of asthma, but additionally may confound the diagnosis of asthma and may exacerbate coexisting asthma. The management of allergic rhinitis, mainly with the use of intranasal corticosteroids, improve asthma symptoms and lung function in asthmatic patients. Several mechanisms have been proposed to link the nose and bronchi, which include: postnasal drip of inflammatory cells and pro-inflammatory molecules; a possible nasobronchial neural reflex; an increased exposure of the lower airways to dry and cold air as well as aeroallergens because the mouth breathing secondary to nasal obstruction; and an increased susceptibility to rhinovirus infection secondary to an increased ICAM-1 expression in the nasal mucosa of patients with allergic rhinitis. A better understanding of the rhinitis-asthma relationship nature might allow the creation of better strategies for the integral treatment of patients with these diseases.

Respiratory Conditions Associated with Tracheobronchomegaly (Mounier-Kuhn Syndrome): A Study of Seventeen Cases.

PubMed

Schmitt, Pierre; Dalar, Levent; Jouneau, Stéphane; Toublanc, Bénédicte; Camuset, Juliette; Chatte, Gérard; Cellerin, Laurent; Dutau, Hervé; Sanchez, Stéphane; Sauvage, Maxime; Vergnon, Jean-Michel; Dury, Sandra; Deslée, Gaetan; Lebargy, François

2016-01-01

Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by enlargement of the trachea and main bronchi and associated with recurrent respiratory tract infections. This multicenter, retrospective study was carried out to describe respiratory conditions associated with tracheobronchomegaly. Nine institutions involved in the 'Groupe d'Endoscopie de Langue Française' (GELF) participated in this study. A standard form was used to record patient characteristics, treatments and follow-up from medical charts. Seventeen patients, 53% male, aged 58 ± 18 years at diagnosis were included. Recurrent infections revealed MKS in 88% of cases. Main comorbid conditions were diffuse bronchiectasis in 88% of patients and tracheobronchomalacia in 67% of cases. The exacerbation rate was 1.5 exacerbations/patient/year. The main non-respiratory morbid condition was gastroesophageal reflux disease in 29% of cases. Interventional bronchoscopy was performed in seven patients (41%), consisting of laser (n = 2) and tracheal stenting (n = 5). Complications related to stents were observed in 80% of cases with a mean stent duration of 8 months. Four deaths, including three due to respiratory causes, occurred during follow-up. This is the largest series of MKS reported in the literature, showing that bronchiectasis and tracheobronchomalacia are the main associated morbid conditions that constitute a challenge for treatment. © 2016 S. Karger AG, Basel.

Tachykinin antagonists have potent local anaesthetic actions.

PubMed

Post, C; Butterworth, J F; Strichartz, G R; Karlsson, J A; Persson, C G

1985-11-19

Contrary to what would have been expected, an antagonist of substance P (SP) [Arg5,D-Trp7,9]SP-(5-11) inhibited the neurogenic contraction of isolated guinea-pig hilus bronchi more readily than a contraction produced by exogenous SP. Furthermore, it has previously been shown that a tachykinin antagonist given intrathecally produced motor blockade as do local anaesthetic drugs. We therefore examined whether tachykinin antagonists had a depressant action on axonal neurotransmission. The compound action potential (APc) of the frog isolated sciatic nerve was suppressed in a concentration-dependent manner by the tachykinin antagonists [D-Pro2,D-Trp7,9]SP and [Arg5,D-Trp7,9]Sp-(5-11), both being about 4 times more potent than lidocaine. SP itself was without effect. Similarly in the rat isolated sciatic nerve [D-Pro2,D-Trp7,9]SP suppressed the APc. It was more potent in the A alpha- than in the C-fibres. SP did not affect conduction in either fibre type. In conscious guinea-pigs [D-Pro2,D-Trp7,9]SP injected adjacent to the sciatic nerve was found to block motor but not sensory functions of the limb. Thus, commonly used tachykinin antagonists, but not SP itself, have potent local anaesthetic properties. This should be considered when these agents are employed as pharmacological tools.

Substance P antagonists and the role of tachykinins in non-cholinergic bronchoconstriction.

PubMed

Karlsson, J A; Finney, M J; Persson, C G; Post, C

1984-12-24

Electrical field stimulation of guinea-pig isolated hilus bronchi induced tetrodotoxin-sensitive contractions of which only a minor part could be inhibited by atropine. The remaining non-cholinergic bronchoconstriction was antagonized by a heptapeptide and an undecapeptide substance P (SP) analogue (Arg5, D-Trp7,9) SP5-11, IC50 = 24.0 microM and (D-Pro2, D-Trp 7,9) SP, IC50 = 10.0 microM. Of the exogenously added tachykinins, both eledoisin (8 times) and physalaemin (3 times) were more potent bronchoconstrictors than SP. Pretreatment with the SP-analogues shifted concentration-response curves to the tachykinins to the right, eledoisin being most readily antagonized. (Arg5, D-Trp 7,9) SP 5-11 also antagonized the neural response more readily than that of SP. In addition, in the frog isolated sciatic nerve preparation the two SP-analogues were found to possess potent lidocaine-like neurodepressant actions which further complicated the interpretation of the neural inhibitory effects of these compounds. It is concluded that if a tachykinin contributes to non-cholinergic bronchoconstriction, an eledoisin-like peptide is a more likely candidate than SP itself. Since SP-antagonists may have local anaesthetic properties their value as tools in neurophysiology seems limited. Inferentially, the non-cholinergic bronchoconstrictive neurotransmitter remains to be identified.

Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.

PubMed

Chi, Jen-Tsan; Rodriguez, Edwin H; Wang, Zhen; Nuyten, Dimitry S A; Mukherjee, Sayan; van de Rijn, Matt; van de Vijver, Marc J; Hastie, Trevor; Brown, Patrick O

2007-09-01

Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression.

Bronchocarcinogenic properties of welding and thermal spraying fumes containing chromium in the rat.

PubMed

Berg, N O; Berlin, M; Bohgard, M; Rudell, B; Schütz, A; Warvinge, K

1987-01-01

The possible bronchocarcinogenic effects of fumes released during the shielded metal arc welding of stainless steel and the thermal spraying of chromium oxide (Cr2O3) have been studied on the rat. The fume particles were shown to contain tri- and hexavalent chromium in soluble and low soluble forms; they were collected and implanted as pellets in the bronchi of groups of 100 rats by the method of Laskin et al. A negative control group of 100 rats was included, as well as positive controls receiving pellets containing benz(a)pyrene. The experiment was continued for 34 months; no differences of biological significance were noted between the growth rates, survival times, and terminal organ weights of the test and negative control groups. At autopsy, the macroscopic and microscopic appearance of the organs in the three groups, including the local reaction to the implanted pellet, were similar. No precancerous changes were observed at the implantation sites; one rat, who received a pellet containing welding fumes, showed squamous cell carcinoma remote from the implantation site and not associated with the bronchus. It had the appearance of a metastasis. All three benz(a)pyrene control rats developed cancer at the implantation site. The occupational health implications of these findings are discussed.

The role of substance P release in the lung with esophageal acid.

PubMed

Kohrogi, H; Hamamoto, J; Kawano, O; Iwagoe, H; Fujii, K; Hirata, N; Ando, M

2001-12-03

To investigate whether tachykinins are released in the airways by stimulating the esophagus, airway plasma extravasation induced by intraesophageal hydrochloric acid (HCl) in the presence or absence of the neutral endopeptidase (NEP) inhibitor phosphoramidon and the neurokinin-1-receptor antagonist FK888 was studied in anesthetized guinea pigs. Airway plasma extravasation also was studied in the presence of the NEP inhibitor in guinea pigs pretreated with capsaicin or bilateral vagotomy. Propranolol and atropine were used in all animals to block adrenergic and cholinergic nerve effects. Airway plasma leakage was evaluated by measuring extravasated Evans blue dye. One normal HCl infusion into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation induced by HCl infusion into the esophagus in the trachea and main bronchi, and FK888 significantly inhibited extravasation in a dose-related manner. In capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilaterally vagotomized animals. These results suggest that locally acting substances are released by intraesophageal HCl stimulation that cause airway plasma extravasation. These substances are generated through activation of neural pathways, including some that traffic through the vagus nerves that link the esophagus or airways.

Changes in cross-sectional airway areas induced by methacholine, histamine, and LTC4 in asthmatic subjects.

PubMed

Molfino, N A; Slutsky, A S; Hoffstein, V; McClean, P A; Rebuck, A S; Drazen, J M; Zamel, N

1992-09-01

To examine whether leukotrienes, histamine, and methacholine have different sites of bronchoconstrictor action, we studied 8 stable asthmatic subjects (mean age +/- SD, 26 +/- 5 yr) on 3 different days. On each day, a randomized challenge with LTC4, methacholine, or histamine was performed until the dose that provoked a fall of 20% in FEV1 (PC20) was obtained. Complete and partial flow-volume curves as well as area-distance profiles generated by the acoustic reflection technique (ART) at a fixed lung volume were obtained in all subjects before and after each inhalation challenge. No significant differences were found in pulmonary function or baseline cross-sectional airway areas for the different study days. The three agonists provoked significant (p less than 0.05) bronchoconstriction at the level of the main bronchi when identical falls of FEV1 were achieved. Similarly, equal reductions of V30p were elicited by the three agonists. However, LTC4 and methacholine induced additional tracheal constriction but histamine inhalation did not. These differences in the degree of tracheal constriction were statistically significant (p less than 0.05; ANOVA). These results may be explained by distinct pharmacologic properties of the agents used and may have relevance in the understanding of the pathophysiology of asthma.

Induction of humoral immunity and pulmonary mast cells in mice and rats after immunization with aerosolized antigen.

PubMed Central

Ahlstedt, S; Björkstén, B; Nygren, H; Smedegård, G

1983-01-01

Rats (BN X Wistar) and mice (CBA/Ca) were immunized by exposure in 10-day periods to an aerosol of ovalbumin (OA). In rats this immunization resulted in IgE antibodies detectable at very low levels in bronchial washings, whereas IgG, IgA and IgM antibodies were recorded both in serum and in bronchial washings. In mice, exposure to aerosolized antigen resulted in specific IgE and IgG antibodies in serum. The levels of IgM antibodies were low and no IgA antibodies could be recorded with the enzyme-linked immunosorbent assay (ELISA). Histological examination of lung tissue from immunized rats and mice revealed increased numbers of cells with characteristics of both immature and mature mast cells. In addition, in the rats these cells were more closely located to the bronchi in immunized than in control animals. In the latter animals the mast cells were located around the blood vessels. Immature mast cells were located in the bronchiole-associated lymphatic tissue (BALT) which showed a marked proliferation in immunized animals. The findings indicate that sensitization via the airways provides possibilities to develop a model in rodents for studies of IgE-mediated allergy in the lung. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:6822403

A three-microphone acoustic reflection technique using transmitted acoustic waves in the airway.

PubMed

Fujimoto, Yuki; Huang, Jyongsu; Fukunaga, Toshiharu; Kato, Ryo; Higashino, Mari; Shinomiya, Shohei; Kitadate, Shoko; Takahara, Yutaka; Yamaya, Atsuyo; Saito, Masatoshi; Kobayashi, Makoto; Kojima, Koji; Oikawa, Taku; Nakagawa, Ken; Tsuchihara, Katsuma; Iguchi, Masaharu; Takahashi, Masakatsu; Mizuno, Shiro; Osanai, Kazuhiro; Toga, Hirohisa

2013-10-15

The acoustic reflection technique noninvasively measures airway cross-sectional area vs. distance functions and uses a wave tube with a constant cross-sectional area to separate incidental and reflected waves introduced into the mouth or nostril. The accuracy of estimated cross-sectional areas gets worse in the deeper distances due to the nature of marching algorithms, i.e., errors of the estimated areas in the closer distances accumulate to those in the further distances. Here we present a new technique of acoustic reflection from measuring transmitted acoustic waves in the airway with three microphones and without employing a wave tube. Using miniaturized microphones mounted on a catheter, we estimated reflection coefficients among the microphones and separated incidental and reflected waves. A model study showed that the estimated cross-sectional area vs. distance function was coincident with the conventional two-microphone method, and it did not change with altered cross-sectional areas at the microphone position, although the estimated cross-sectional areas are relative values to that at the microphone position. The pharyngeal cross-sectional areas including retropalatal and retroglossal regions and the closing site during sleep was visualized in patients with obstructive sleep apnea. The method can be applicable to larger or smaller bronchi to evaluate the airspace and function in these localized airways.

[Tracheobronchomalacia].

PubMed

Majid, Adnan; Fernández, Liliana; Fernández-Bussy, Sebastián; Herth, Felix; Ernst, Armin

2010-04-01

Tracheobronchomalacia is a central airway disease characterised by weakness of the wall and dynamic decrease in the tracheal lumen and the large bronchi, particularly while exhaling. It is more common in middle age and the elderly with previous exposure to cigarettes. It causes chronic symptoms such as cough, dyspnea, increase in recurrent infections, and poor secretion management, but it can also progress to chronic respiratory failure and death. It is usually confused with other common diseases like chronic obstructive pulmonary disease (COPD) or asthma. Its causes can be congenital or acquired and its diagnosis involves the dynamic assessment of the airway with tomography and fibrobronchoscopy. It is classified as mild, moderate or severe depending on the degree of collapse of the airway when exhaling. Management consists of a primary phase, in which concomitant diseases must be controlled, such as COPD, asthma or gastro-oesophageal reflux. In diffuse moderate to severe symptomatic tracheobronchomalacia tracheobronchoplasty must be considered with strengthening of the posterior wall. Silicone and "Y" stents can be used to identify patients who could potentially benefit from surgical treatment as well as being used for the definitive symptomatic treatment with high surgical risk. More prospective studies need to be done in order to standardise certain common criteria for the management of this usually under-diagnosed disease. Copyright (c) 2009 SEPAR. Published by Elsevier Espana. All rights reserved.

Polonium and lung cancer.

PubMed

Zagà, Vincenzo; Lygidakis, Charilaos; Chaouachi, Kamal; Gattavecchia, Enrico

2011-01-01

The alpha-radioactive polonium 210 (Po-210) is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226) and its decay products, lead 210 (Pb-210) and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties.

A Numerical Model of Viscoelastic Layer Entrainment by Airflow in Cough

NASA Astrophysics Data System (ADS)

Mitran, Sorin M.

2008-07-01

Coughing is an alternative mode of ensuring mucus clearance in the lung when normal cilia induced flow breaks down. A numerical model of this process is presented with the following aspects. (1) A portion of the airway comprising the first three bronchus generations is modeled as radially reinforced elastic tubes. Elasticity equations are solved to predict airway deformation under effect of airway pressure. (2) The compressible, turbulent flow induced by rapid lung contraction is modeled by direct numerical simulation for Reynolds numbers in the range 5,000-10,000 and by Large Eddy Simulation for Reynolds numbers in the range 5,000-40,000. (3) A two-layer model of the airway surface liquid (ASL) covering the airway epithelial layer is used. The periciliary liquid (PCL) in direct contact with the epithelial layer is considered to be a Newtonian fluid. Forces modeling cilia beating can act upon this layer. The mucus layer between the PCL and the interior airflow is modeled as an Oldroyd-B fluid. The overall computation is a fluid-structure interaction simulation that tracks changes in ASL thickness and airway diameters that result from impulsive airflow boundary conditions imposed at bronchi ends. In particular, the amount of mucus that is evacuated from the system is computed as a function of cough intensity and mucus rheological properties.

[Butamirate citrate in control of cough in respiratory tract inflammation].

PubMed

Płusa, Tadeusz

2017-08-21

Cough is the reflex defense response of the respiratory tract to the present secretions in the throat, trachea and bronchi, and ongoing inflammation in the mucous membranes of the upper and lower respiratory tract. From a practical point of view, cough is dry (unproductive) and productive cough with expulsion of significant amounts of secretion. Drugs used to treat cough differ in both mechanism of action and pharmacokinetic activity. Butamirate citrate belongs to a new class of cough suppressants acting centrally through the receptors in the brainstem. In addition, it has a very beneficial effect, because it reduces the resistance in the airways by inhibiting bronchospasm and anti-inflammatory effect. It is rapidly absorbed after oral administration and its therapeutic plasma concentration is determined after 5-10 minutes of administration, irrespective of the dose. Possible side effects are rarely seen in 0.5-1% of patients, mainly in the form of skin rash, nausea, diarrhea, dizziness, which usually resolves during treatment. The cough effect of most cough suppressants is good, but their mechanisms are different and for that reason they should be individually selected. An important asset of this group of drugs is peripheral activity and effects on bronchodilator muscles, such as in the case of butamirate. Inclusion of this feature is particularly beneficial in chronic inflammatory bronchial diseases.

Two years of surveillance of influenza a virus infection in a swine herd. Results of virological, serological and pathological studies.

PubMed

Cappuccio, Javier; Dibarbora, Marina; Lozada, Inés; Quiroga, Alejandra; Olivera, Valeria; Dángelo, Marta; Pérez, Estefanía; Barrales, Hernán; Perfumo, Carlos; Pereda, Ariel; Pérez, Daniel R

2017-02-01

Swine farms provide a dynamic environment for the evolution of influenza A viruses (IAVs). The present report shows the results of a surveillance effort of IAV infection in one commercial swine farm in Argentina. Two cross-sectional serological and virological studies (n=480) were carried out in 2011 and 2012. Virus shedding was detected in nasal samples from pigs from ages 7, 21 and 42-days old. More than 90% of sows and gilts but less than 40% of 21-days old piglets had antibodies against IAV. In addition, IAV was detected in 8/17 nasal swabs and 10/15 lung samples taken from necropsied pigs. A subset of these samples was further processed for virus isolation resulting in 6 viruses of the H1N2 subtype (δ2 cluster). Pathological studies revealed an association between suppurative bronchopneumonia and necrotizing bronchiolitis with IAV positive samples. Statistical analyses showed that the degree of lesions in bronchi, bronchiole, and alveoli was higher in lungs positive to IAV. The results of this study depict the relevance of continuing long-term active surveillance of IAV in swine populations to establish IAV evolution relevant to swine and humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Polonium and Lung Cancer

PubMed Central

Zagà, Vincenzo; Lygidakis, Charilaos; Chaouachi, Kamal; Gattavecchia, Enrico

2011-01-01

The alpha-radioactive polonium 210 (Po-210) is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226) and its decay products, lead 210 (Pb-210) and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties. PMID:21772848

Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

PubMed

Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

Allergic Asthma Induced in Rhesus Monkeys by House Dust Mite (Dermatophagoides farinae)

PubMed Central

Schelegle, Edward S.; Gershwin, Laurel J.; Miller, Lisa A.; Fanucchi, Michelle V.; Van Winkle, Laura S.; Gerriets, Joan P.; Walby, William F.; Omlor, Amanda M.; Buckpitt, Alan R.; Tarkington, Brian K.; Wong, Viviana J.; Joad, Jesse P.; Pinkerton, Kent B.; Wu, Reen; Evans, Michael J.; Hyde, Dallas M.; Plopper, Charles G.

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4+ lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA. PMID:11141508

Lesions associated with Halocercus brasiliensis Lins de Almeida, 1933 in the lungs of dolphins stranded in the Northeast of Brazil.

PubMed

Guimarães, J P; Febronio, A M B; Vergara-Parente, J E; Werneck, M R

2015-04-01

The parasitic fauna of cetaceans is an important tool for ecological studies, including analyses on the causes of death. Halocercus brasiliensis is a nematode frequently found in the bronchi and bronchioles of some cetaceans, and it is commonly associated with focal inflammation of the respiratory tract leading to bacterial pneumonia and septicemia and, sometimes, to death. The objective of this study was to report infections by H. brasiliensis in the respiratory tract of Delphinidae stranded on the northern seaside of Bahia, Sergipe, and south of Alagoas, all states in the northeast region of Brazil. A total of 30 individuals, 1 Feresa attenuate (pygmy killer whale), 9 Stenella clymene (Clymene dolphin), and 20 Sotalia guianensis (Guiana dolphin) were studied. In 16 of them, the presence of H. brasiliensis was observed with a mean intensity of 3.5 ± 0.6 (range 1-9) in the hosts. Macroscopically, parasitic calcified nodules, lung congestion, edema, and emphysema were observed. Histopathological examination showed interstitial and granulomatous pneumonia with multifocal infiltrates, discrete to moderate edema, congestion, diffuse hemorrhage, and foci of calcification. We conclude that parasitic pneumonia in the sampled individuals may have directly contributed to stranding and death of the animals.

Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

PubMed Central

Mukhopadhyay, Indranil; Kulkarni, Abhay; Khairatkar-Joshi, Neelima

2016-01-01

Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists. PMID:27827953

Air pollution as a determinant of rheumatoid arthritis.

PubMed

Sigaux, Johanna; Biton, Jérôme; André, Emma; Semerano, Luca; Boissier, Marie-Christophe

2018-03-07

Pollution has long been incriminated in many cardiovascular and respiratory diseases. More recently, studies evaluated the potential role for particulate pollutants in autoimmune diseases, including rheumatoid arthritis (RA). The incidence of RA was found to be higher in urban areas. Living near air pollution emitters was associated with higher risks of developing RA and of producing RA-specific autoantibodies. Nevertheless, no strong epidemiological evidence exists to link one or more specific air pollution particles to RA. The presence in the bronchi of lymphoid satellite islands (inducible bronchus-associated lymphoid tissue, iBALT) is strongly associated with both inflammatory lung disease and RA-associated lung disease. Diesel exhaust particles can stimulate iBALT formation. The induction by air pollution of an inflammatory environment with high citrullination levels in the lung may induce iBALT formation, thereby causing a transition toward a more specific immune response via the production of anti-citrullinated peptide antibodies. Air pollution not only triggers innate immune responses at the molecular level, increasing the levels of proinflammatory cytokines and reactive oxygen species, but is also involved in adaptive immune responses. Thus, via the aryl hydrocarbon receptor (AHR), diesel exhaust particles can trigger a T-cell switch to the Th17 profile. Finally, in the murine collagen-induced arthritis model, animals whose lymphocytes lack the AHR develop milder arthritis. Copyright © 2018. Published by Elsevier SAS.

Transpleural ventilation of explanted human lungs

PubMed Central

Choong, Cliff K; Macklem, Peter T; Pierce, John A; Lefrak, Stephen S; Woods, Jason C; Conradi, Mark S; Yablonskiy, Dimitry A; Hogg, James C; Chino, Kimiaki; Cooper, Joel D

2007-01-01

Background The hypothesis that ventilation of emphysematous lungs would be enhanced by communication with the parenchyma through holes in the pleural surface was tested. Methods Fresh human lungs were obtained from patients with emphysema undergoing lung transplantation. Control human lungs were obtained from organ donors whose lungs, for technical reasons, were not considered suitable for implantation. Lungs were ventilated through the bronchial tree or transpleurally via a small hole communicating with the underlying parenchyma over which a flanged silicone tube had been cemented to the surface of the lung (spiracle). Measurements included flow‐volume‐time curves during passive deflation via each pathway; volume of trapped gas recovered from lungs via spiracles when no additional gas was obtainable passively from the airways; and magnetic resonance imaging assessment of spatial distribution of hyperpolarised helium (3He) administered through either the airways or spiracles. Results In emphysematous lungs, passively expelled volumes at 20 s were 94% greater through spiracles than via the airways. Following passive deflation from the airways, an average of 1.07 litres of trapped gas volume was recoverable via spiracles. Regions were ventilated by spiracles that were less well ventilated via bronchi. Conclusions Because of the extensive collateral ventilation present in emphysematous lungs, direct communication with the lung parenchyma through non‐anatomical pathways has the potential to improve the mechanics of breathing and hence ventilation. PMID:17412776

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses

PubMed Central

Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-01-01

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma. PMID:28775364

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

PubMed

Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-08-04

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

Efficiency of use endobronchial laser doppler-flowmetry in patients with chronic leukemia

NASA Astrophysics Data System (ADS)

Vanina, E. A.; Voitsekhovskiy, V. V.; Landyshev, Y. S.; Tkacheva, S. I.

2016-11-01

In this work indicatorsendobronchial microcirculation were investigated in patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), polycythemia vera (PV), idiopathic myelofibrosis (IMF). A diagnostic bronchoscopy was performed using fibreoptic «Olympus» (Japan).Endobronchial laser Doppler flowmetry was carried out on the laser analyzer capillary blood LAK-02 (Russia). Laser Doppler flowmetry indicators such as parameter of microcirculation, the oscillation amplitude in the endothelial, neurogenic, myogenic, cardiac and respiratory ranges were calculated by continuous the Wavelet transforms. Reduced cardiac and respiratory amplitudes in CML and CLL are primarily due to the development leukostasis. If PV is the case, this is due to sludge syndrome. And when MM occurs, it is caused by protein stasis in the vessels of the bronchial tubes. Increased endothelial oscillation amplitudes in the range in CML, PV, IMF and their reduction in MM indicate the presence of endothelial dysfunction in these patients. Increasing the amplitude of oscillations in the range of neurogenic indicates the development of arteriolar vasodilation as a compensatory response to the violation of blood flow. Increasing the amplitude of oscillations of myogenic tone indicating decrease precapillaries as a compensatory reaction to improve blood flow. It is concluded that endobronchial laser Doppler flowmetry is an important method allowing diagnosing the pathology of the microvasculature of the bronchi in chronic leukemia.

Pathophysiology and Genetics of Bronchiectasis Unrelated to Cystic Fibrosis.

PubMed

Nikolic, Aleksandra

2018-05-12

Bronchiectasis is characterized by deregulated inflammatory response and recurrent bacterial infection resulting in progressive lung damage and an irreversible dilatation of bronchi and bronchioles. Generally accepted model of the development of bronchiectasis is the "vicious cycle hypothesis" that proposes compromising of the mucociliary clearance by an initial event, which leads to the infection of the respiratory tract followed by further impairment of mucociliary function, bacterial proliferation, and more inflammation. Bronchiectasis is a very common symptom in patients with cystic fibrosis (CF), while bronchiectasis unrelated to CF is heterogeneous pathology of unknown cause with a large number of potential contributory factors and poorly understood pathogenesis. It is presumed that bronchiectasis unrelated to CF is a multifactorial condition predisposed by genetic factors. Different molecules have been implicated in the onset and development of idiopathic bronchiectasis, as well as modulation of the disease severity and response to therapy. Most of these molecules are involved in the processes that contribute to the homeostasis of the lung tissue, especially mucociliary clearance, protease-antiprotease balance, and immunomodulation. Evaluation of the studies performed towards investigation of the role these molecules play in bronchiectasis identifies genetic variants that may be of potential importance for clinical management of the disease, and also of interest for future research efforts. This review focuses on the molecules with major roles in lung homeostasis and their involvement in bronchiectasis unrelated to CF.

Spirometer-controlled cine magnetic resonance imaging used to diagnose tracheobronchomalacia in paediatric patients.

PubMed

Ciet, Pierluigi; Wielopolski, Piotr; Manniesing, Rashindra; Lever, Sandra; de Bruijne, Marleen; Morana, Giovanni; Muzzio, Pier Carlo; Lequin, Maarten H; Tiddens, Harm A W M

2014-01-01

Tracheobronchomalacia (TBM) is defined as an excessive collapse of the intrathoracic trachea. Bronchoscopy is the gold standard for diagnosing TBM; however it has major disadvantages, such as general anaesthesia. Cine computed tomography (CT) is a noninvasive alternative used to diagnose TBM, but its use in children is restricted by ionising radiation. Our aim was to evaluate the feasibility of spirometer-controlled cine magnetic resonance imaging (MRI) as an alternative to cine-CT in a retrospective study. 12 children with a mean age (range) of 12 years (7-17 years), suspected of having TBM, underwent cine-MRI. Static scans were acquired at end-inspiration and expiration covering the thorax using a three-dimensional spoiled gradient echo sequence. Three-dimensional dynamic scans were performed covering only the central airways. TBM was defined as a decrease of the trachea or bronchi diameter >50% at end-expiration in the static and dynamic scans. The success rate of the cine-MRI protocol was 92%. Cine-MRI was compared with bronchoscopy or chest CT in seven subjects. TBM was diagnosed by cine-MRI in seven (58%) out of 12 children and was confirmed by bronchoscopy or CT. In four patients, cine-MRI demonstrated tracheal narrowing that was not present in the static scans. Spirometer controlled cine-MRI is a promising technique to assess TBM in children and has the potential to replace bronchoscopy.

Hypervitaminosis D3 in broiler chicks: histopathological, immunomodulatory and immunohistochemical approach

PubMed Central

Kumar, R.; Brar, R. S.; Banga, H. S.

2017-01-01

The present study was undertaken to investigate the toxic effects of higher doses (1,00,000 IU i.e. 2.5 mg/kg body weight (BW)) of vitamin D3, concomitantly with bacterial endotoxins (lipopolysaccharides: LPS) to study the immunomodulatory potential of vitamin D3 in IBL-80 broiler chicks. The chicks were divided into four groups [group I (NSS), group II (LPS), group III (Vit. D3 + NSS), and group IV (Vit. D3 + LPS)] containing eight chicks in each group, treated accordingly for 21 days. Birds were kept under close observation for apparent clinical signs and symptoms. Clinically, vitamin D3 treated chicks were dull, off feed, showed polydipsia, polyuria, watery faeces, rigidity of limbs, severe dehydration, weakness and significant progressive emaciation. Grossly, the bones were soft whereas most organs revealed congestion and hemorrhages in visceral organs. Histopathologically, renal tubular epithelium showed coagulative necrosis and metastatic calcification. The lung parenchyma and bronchi showed hemorrhages, congestion with diffuse heterophilic cell infiltration in inter-alveolar septa and infiltration of heterophils in alveoli along with proteinacious fluid in LPS treated chicks of treatment group, suggesting immunomodulatory action of vitamin D3. Vitamin D3 treated chicks showed strong expression of Calbindin D28k in intestine and kidney but weak expression in lung, which can be linked to nephrocalcinosis seen in kidney and from its prospective role in cellular calcium homeostasis. PMID:29163645

Hypervitaminosis D3 in broiler chicks: histopathological, immunomodulatory and immunohistochemical approach.

PubMed

Kumar, R; Brar, R S; Banga, H S

2017-01-01

The present study was undertaken to investigate the toxic effects of higher doses (1,00,000 IU i.e. 2.5 mg/kg body weight (BW)) of vitamin D 3 , concomitantly with bacterial endotoxins (lipopolysaccharides: LPS) to study the immunomodulatory potential of vitamin D 3 in IBL-80 broiler chicks. The chicks were divided into four groups [group I (NSS), group II (LPS), group III (Vit. D 3 + NSS), and group IV (Vit. D 3 + LPS)] containing eight chicks in each group, treated accordingly for 21 days. Birds were kept under close observation for apparent clinical signs and symptoms. Clinically, vitamin D 3 treated chicks were dull, off feed, showed polydipsia, polyuria, watery faeces, rigidity of limbs, severe dehydration, weakness and significant progressive emaciation. Grossly, the bones were soft whereas most organs revealed congestion and hemorrhages in visceral organs. Histopathologically, renal tubular epithelium showed coagulative necrosis and metastatic calcification. The lung parenchyma and bronchi showed hemorrhages, congestion with diffuse heterophilic cell infiltration in inter-alveolar septa and infiltration of heterophils in alveoli along with proteinacious fluid in LPS treated chicks of treatment group, suggesting immunomodulatory action of vitamin D 3 . Vitamin D 3 treated chicks showed strong expression of Calbindin D28k in intestine and kidney but weak expression in lung, which can be linked to nephrocalcinosis seen in kidney and from its prospective role in cellular calcium homeostasis.

Accurate airway segmentation based on intensity structure analysis and graph-cut

NASA Astrophysics Data System (ADS)

Meng, Qier; Kitsaka, Takayuki; Nimura, Yukitaka; Oda, Masahiro; Mori, Kensaku

2016-03-01

This paper presents a novel airway segmentation method based on intensity structure analysis and graph-cut. Airway segmentation is an important step in analyzing chest CT volumes for computerized lung cancer detection, emphysema diagnosis, asthma diagnosis, and pre- and intra-operative bronchoscope navigation. However, obtaining a complete 3-D airway tree structure from a CT volume is quite challenging. Several researchers have proposed automated algorithms basically based on region growing and machine learning techniques. However these methods failed to detect the peripheral bronchi branches. They caused a large amount of leakage. This paper presents a novel approach that permits more accurate extraction of complex bronchial airway region. Our method are composed of three steps. First, the Hessian analysis is utilized for enhancing the line-like structure in CT volumes, then a multiscale cavity-enhancement filter is employed to detect the cavity-like structure from the previous enhanced result. In the second step, we utilize the support vector machine (SVM) to construct a classifier for removing the FP regions generated. Finally, the graph-cut algorithm is utilized to connect all of the candidate voxels to form an integrated airway tree. We applied this method to sixteen cases of 3D chest CT volumes. The results showed that the branch detection rate of this method can reach about 77.7% without leaking into the lung parenchyma areas.

Sexual Dimorphism in the Regulation of Estrogen, Progesterone, and Androgen Receptors by Sex Steroids in the Rat Airway Smooth Muscle Cells

PubMed Central

Zarazúa, Abraham; González-Arenas, Aliesha; Ramírez-Vélez, Gabriela; Bazán-Perkins, Blanca; Guerra-Araiza, Christian; Campos-Lara, María G.

2016-01-01

The role of sex hormones in lung is known. The three main sex steroid receptors, estrogen, progesterone, and androgen, have not been sufficiently studied in airway smooth muscle cells (ASMC), and the sex hormone regulation on these receptors is unknown. We examined the presence and regulation of sex hormone receptors in female and male rat ASMC by Western blotting and flow cytometry. Gonadectomized rats were treated with 17β-estradiol, progesterone, 17β-estradiol + progesterone, or testosterone. ASMC were enzymatically isolated from tracheas and bronchi. The experiments were performed with double staining flow cytometry (anti-α-actin smooth muscle and antibodies to each hormone receptor). ERα, ERβ, tPR, and AR were detected in females or males. ERα was upregulated by E2 and T and downregulated by P4 in females; in males, ERα was downregulated by P4, E + P, and T. ERβ was downregulated by each treatment in females, and only by E + P and T in males. tPR was downregulated by P4, E + P, and T in females. No hormonal regulation was observed in male receptors. AR was downregulated in males treated with E + P and T. We have shown the occurrence of sex hormone receptors in ASMC and their regulation by the sex hormones in female and male rats. PMID:27110242

Oslerus osleri (metastrongyloidea; filaroididae) in gray wolves (Canis lupus) from Banff National Park, Alberta, Canada.

PubMed

Verocai, Guilherme G; Schock, Danna M; Lejeune, Manigandan; Warren, Amy L; Duignan, Pádraig J; Kutz, Susan J

2013-04-01

Oslerus osleri is a filaroid parasite of the respiratory tract of canids. In North America, it is most commonly reported from coyotes (Canis latrans) and domestic dogs (Canis lupus familiaris), but reports in gray wolves (Canis lupus) are infrequent. We report a new geographic record for O. osleri in four gray wolves from Banff National Park, Alberta, Canada. Adult nematodes found in nodules in the submucosa of the trachea and bronchi were identified as O. osleri based on morphometry of spicules of males. We sequenced two segments of the genome of adult nematodes: a 1,111-base pair (bp) segment of the 18S region that was 100% identical to the 18S region of O. osleri from a coyote in California and a 537-bp segment that included the ITS-2 region and partial 5.8S and 28S genes. Histopathologically, there were submucosal nodules of adult nematodes surrounded by fibrosis and lymphoplasmacytic inflammation. These findings are consistent with O. osleri infections in other canids. The importance of this parasite in wild canid populations is unknown, but prevalence may be underestimated because many studies have focused on gastrointestinal parasites or used routine fecal flotation that has low sensitivity for this parasite. The ecology and population genetics of this parasite where multiple species of canids are sympatric warrant closer investigation to determine potential for interspecies transmission.

Rapid non-genomic effects of glucocorticoids on oxidative stress in a guinea pig model of asthma.

PubMed

Long, Fei; Wang, Yan; Qi, Hui-Hui; Zhou, Xin; Jin, Xian-Qiao

2008-03-01

Glucocorticoids (GC) may exert therapeutic effects in asthma by a rapid non-genomic mechanism. The lungs of asthmatic patients are exposed to oxidative stress, which is believed to be critical in the pathogenesis of asthma. The aim of this study was to investigate whether GC exert a rapid non-genomic effect on oxidative stress in asthmatic guinea pigs. The guinea pig asthma model was used to assess inhibitory effects of budesonide (BUD) on oxidative stress. BAL fluid (BALF), trolox equivalent antioxidant capacity and lung manganese superoxide dismutase (MnSOD) activity were measured by spectrophotometry. Superoxide anion production was measured by cytochrome c reduction assay. Oxidative stress occurred within minutes following antigen challenge and BUD reduced the severity of oxidative stress in asthmatic guinea pigs within 15 min. BUD significantly decreased BALF trolox equivalent antioxidant capacity and lung MnSOD activity, as compared with those of vehicle-treated asthmatic guinea pigs (P < 0.05). Additionally, BUD rapidly inhibited in vitro superoxide anion production by BALF cells and bronchi harvested from sensitized animals. These rapid effects were not blocked by the GC receptor antagonist RU486 and/or the protein synthesis inhibitor cycloheximide. BUD reduced oxidative stress in a guinea pig model of asthma by a rapid non-genomic mechanism. These data suggest new mechanisms whereby GC treatments may benefit asthma.

Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma.

PubMed

Rivera, Dagmar García; Hernández, Ivones; Merino, Nelson; Luque, Yilian; Álvarez, Alina; Martín, Yanet; Amador, Aylin; Nuevas, Lauro; Delgado, René

2011-10-01

The aim was to study the effects of Mangifera indica extract and its major component mangiferin on lung inflammation response and Th2 cytokine production using a murine experimental model of allergic asthma. BALB/c mice were intraperitoneally sensitized with 10 µg of ovoalbumin (OVA) adsorbed on aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on day 21 and continuing until day 24. To evaluate the protective effect, mice were orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50 mg/kg) from days 0 to 24. Anti-OVA immunoglobulin E, interleukin (IL)-4 and IL-5 were determined by ELISA and lungs were analysed by histology. M. indica extract and mangiferin produced a marked reduction of airway inflammation around vessels and bronchi, inhibition of IL-4 and IL-5 cytokines in bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and lymphocyte proliferation. This is the first pre-clinical report of the anti-inflammatory properties of M. indica extract and mangiferin in experimental asthma and it could be an important part of pre-clinical requirement necessary for its use to complement the treatment of this complex disease. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Virtual landmarks

NASA Astrophysics Data System (ADS)

Tong, Yubing; Udupa, Jayaram K.; Odhner, Dewey; Bai, Peirui; Torigian, Drew A.

2017-03-01

Much has been published on finding landmarks on object surfaces in the context of shape modeling. While this is still an open problem, many of the challenges of past approaches can be overcome by removing the restriction that landmarks must be on the object surface. The virtual landmarks we propose may reside inside, on the boundary of, or outside the object and are tethered to the object. Our solution is straightforward, simple, and recursive in nature, proceeding from global features initially to local features in later levels to detect landmarks. Principal component analysis (PCA) is used as an engine to recursively subdivide the object region. The object itself may be represented in binary or fuzzy form or with gray values. The method is illustrated in 3D space (although it generalizes readily to spaces of any dimensionality) on four objects (liver, trachea and bronchi, and outer boundaries of left and right lungs along pleura) derived from 5 patient computed tomography (CT) image data sets of the thorax and abdomen. The virtual landmark identification approach seems to work well on different structures in different subjects and seems to detect landmarks that are homologously located in different samples of the same object. The approach guarantees that virtual landmarks are invariant to translation, scaling, and rotation of the object/image. Landmarking techniques are fundamental for many computer vision and image processing applications, and we are currently exploring the use virtual landmarks in automatic anatomy recognition and object analytics.

Airway segmentation and analysis for the study of mouse models of lung disease using micro-CT

NASA Astrophysics Data System (ADS)

Artaechevarria, X.; Pérez-Martín, D.; Ceresa, M.; de Biurrun, G.; Blanco, D.; Montuenga, L. M.; van Ginneken, B.; Ortiz-de-Solorzano, C.; Muñoz-Barrutia, A.

2009-11-01

Animal models of lung disease are gaining importance in understanding the underlying mechanisms of diseases such as emphysema and lung cancer. Micro-CT allows in vivo imaging of these models, thus permitting the study of the progression of the disease or the effect of therapeutic drugs in longitudinal studies. Automated analysis of micro-CT images can be helpful to understand the physiology of diseased lungs, especially when combined with measurements of respiratory system input impedance. In this work, we present a fast and robust murine airway segmentation and reconstruction algorithm. The algorithm is based on a propagating fast marching wavefront that, as it grows, divides the tree into segments. We devised a number of specific rules to guarantee that the front propagates only inside the airways and to avoid leaking into the parenchyma. The algorithm was tested on normal mice, a mouse model of chronic inflammation and a mouse model of emphysema. A comparison with manual segmentations of two independent observers shows that the specificity and sensitivity values of our method are comparable to the inter-observer variability, and radius measurements of the mainstem bronchi reveal significant differences between healthy and diseased mice. Combining measurements of the automatically segmented airways with the parameters of the constant phase model provides extra information on how disease affects lung function.

Bronchiectasis diagnosed after renal transplantation: a retrospective multicenter study.

PubMed

Dury, Sandra; Colosio, Charlotte; Etienne, Isabelle; Anglicheau, Dany; Merieau, Elodie; Caillard, Sophie; Rivalan, Joseph; Thervet, Eric; Essig, Marie; Babinet, François; Subra, Jean-François; Toubas, Olivier; Rieu, Philippe; Launois, Claire; Perotin-Collard, Jeanne-Marie; Lebargy, François; Deslée, Gaëtan

2015-11-07

Bronchiectasis is characterized by abnormal, permanent and irreversible dilatation of the bronchi, usually responsible for daily symptoms and frequent respiratory complications. Many causes have been identified, but only limited data are available concerning the association between bronchiectasis and renal transplantation. We conducted a retrospective multicenter study of cases of bronchiectasis diagnosed after renal transplantation in 14 renal transplantation departments (French SPIESSER group). Demographic, clinical, laboratory and CT scan data were collected. Forty-six patients were included (mean age 58.2 years, 52.2 % men). Autosomal dominant polycystic kidney disease (32.6 %) was the main underlying renal disease. Chronic cough and sputum (50.0 %) were the major symptoms leading to chest CT scan. Mean duration of symptoms before diagnosis was 1.5 years [0-12.1 years]. Microorganisms were identified in 22 patients, predominantly Haemophilus influenzae. Hypogammaglobulinemia was observed in 46.9 % patients. Bronchiectasis was usually extensive (84.8 %). The total bronchiectasis score was 7.4 ± 5.5 with a significant gradient from apex to bases. Many patients remained symptomatic (43.5 %) and/or presented recurrent respiratory tract infections (37.0 %) during follow-up. Six deaths (13 %) occurred during follow-up, but none were attributable to bronchiectasis. These results highlight that the diagnosis of bronchiectasis should be considered in patients with de novo respiratory symptoms after renal transplantation. Further studies are needed to more clearly understand the mechanisms underlying bronchiectasis in this setting.

Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography.

PubMed

Karayama, M; Inui, N; Mori, K; Kono, M; Hozumi, H; Suzuki, Y; Furuhashi, K; Hashimoto, D; Enomoto, N; Fujisawa, T; Nakamura, Y; Watanabe, H; Suda, T

2018-03-01

Respiratory impedance comprises the resistance and reactance of the respiratory system and can provide detailed information on respiratory function. However, details of the relationship between impedance and morphological airway changes in asthma are unknown. We aimed to evaluate the correlation between imaging-based airway changes and respiratory impedance in patients with asthma. Respiratory impedance and spirometric data were evaluated in 72 patients with asthma and 29 reference subjects. We measured the intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi using three-dimensional computed tomographic analyses, and values were adjusted by body surface area (BSA, Ai/BSA, and WT/the square root (√) of BSA). Asthma patients had significantly increased respiratory impedance, decreased Ai/BSA, and increased WT/√BSA, as was the case in those without airflow limitation as assessed by spirometry. Ai/BSA was inversely correlated with respiratory resistance at 5 Hz (R5) and 20 Hz (R20). R20 had a stronger correlation with Ai/BSA than did R5. Ai/BSA was positively correlated with forced expiratory volume in 1 second/forced vital capacity ratio, percentage predicted forced expiratory volume in 1 second, and percentage predicted mid-expiratory flow. WT/√BSA had no significant correlation with spirometry or respiratory impedance. Respiratory resistance is associated with airway narrowing. © 2018 John Wiley & Sons Ltd.

Loop diuretics inhibit cholinergic and noncholinergic nerves in guinea pig airways.

PubMed

Elwood, W; Lötvall, J O; Barnes, P J; Chung, K F

1991-06-01

Furosemide, a loop diuretic, is known to inhibit the response to a variety of indirect bronchial challenges in humans but does not inhibit bronchoconstriction induced by inhaled methacholine or histamine. We have investigated the effects of the two loop diuretics, furosemide (10(-6) to 10(-3) M) and bumetanide (10(-7) to 10(-4) M), on airway smooth muscle contraction in vitro induced by electrical field stimulation (EFS), or exogenously applied acetylcholine (ACh) or substance P (SP) in guinea pig tracheal and bronchial smooth muscle strips pretreated with indomethacin (10(-5) M) and propranolol (10(-6) M). Both furosemide and bumetanide caused a concentration-dependent inhibition of cholinergically mediated neural contraction in the trachea. The effect of furosemide was not influenced by the presence of airway epithelium. Furthermore, both furosemide and bumetanide inhibited in a concentration-dependent fashion nonadrenergic, noncholinergic (NANC) contraction induced by electrical field stimulation of bronchi pretreated with atropine (10(-5) M). Neither drug at the highest concentration inhibited the responses to exogenous acetylcholine (10(-8) to 10(-2) M) or substance P (10(-9) to 10(-5) M). Thus loop diuretics inhibit the neurally induced contraction of guinea pig airways without a direct effect on airway smooth muscle. We conclude that loop diuretics inhibit both cholinergic and excitatory NANC neurotransmission in guinea pig airways and that this effect may be related to their inhibitory effects on the sodium-potassium-chloride cotransporter.

Foetal airway motor tone in prenatal lung development of the pig.

PubMed

Sparrow, M P; Warwick, S P; Mitchell, H W

1994-08-01

The terminal airways from embryonic lung in situ or as explants exhibit rhythmic spontaneous contractions. Our objective was to see whether narrowing responses of the airways occurred throughout the bronchial tree in the first trimester foetus and, if so, to characterize them. The bronchial tree was freed of vasculature and parenchyma from the lungs of 20-35 g pig foetuses (44-48 days gestation). The airway lumen was visualized directly with transmitted light, and narrowing was recorded in real time by video-imaging microscopy. From the main stem bronchi to the terminal regions of late generation branches (20-35 microns i.d.) strong bronchoconstrictor responses to micromolar concentrations of acetylcholine (ACh), histamine, substance P and K+ depolarizing solution were seen, whilst inhibition of narrowing with beta-adrenoceptor agonists was evidence of beta-receptors on the smooth muscle. Moreover, strong narrowing responses to electrical field stimulation, which were blocked by atropine, indicated that functional cholinergic nerves were present. A remarkable display of spontaneous narrowing in the airways of many of the bronchial tree preparations caused the movement of lung liquid to and fro. We speculate that the bronchomotor tone and associated spontaneous activity, which move the lung fluid along the airways, serve to maintain an even positive pressure in localized areas of the bronchial tree which is essential to provide the stimulus for continued growth of the lung.

Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs.

PubMed

Kageyama, N; Ichinose, M; Igarashi, A; Miura, M; Yamauchi, H; Sasaki, Y; Ishikawa, J; Tomaki, M; Shirato, K

1996-07-01

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.

Chronic obstructive sleep apnea accelerates pulmonary remodeling via TGF-β/miR-185/CoLA1 signaling in a canine model.

PubMed

Ding, Xue; Yu, Chengyuan; Liu, Yang; Yan, Sen; Li, Wenpeng; Wang, Dingyu; Sun, Li; Han, Yu; Li, Minghui; Zhang, Song; Yun, Fengxiang; Zhao, Hongwei; Li, Yue

2016-09-06

Chronic obstructive sleep apnea syndrome (OSAS) is considered to be associated with pulmonary diseases. However, the roles and mechanisms of OSA in pulmonary remodeling remain ambiguous. Thus, this study was aimed to elucidate the morphological and mechanical action of OSA in lung remodeling. In the present study, we employed a novel OSA model to mimic the OSA patient and investigate the role of OSA in pulmonary remodeling. We showed that pulmonary artery pressure of OSA group has no significant increased compared with the sham group. Nevertheless, we found that fibrotic tissue was predominantly located around the bronchi and vascular in the lung. Additionally, inflammatory cell infiltration was also detected in the peribonchial and perivascular space. The morphological change in OSA canines was ascertained by ultrastructure variation characterized by mitochondrial swelling, lamellar bodies degeneration and vascular smooth muscle incrassation. Moreover, sympathetic nerve sprouting was markedly increased in OSA group. Mechanistically, we showed that several pivotal proteins including collagen type I(CoLA1), GAP-43, TH and NGF were highly expressed in OSA groups. Furthermore, we found OSA could activated the expression of TGF-β, which subsequently suppressed miR-185 and promoted CoL A1 expression. This signaling cascade leads to pulmonary remodeling. In conclusion, Our data demonstrates that OSA can accelerate the progression of pulmonary remodeling through TGF-β/miR-185/CoLA1 signaling, which would potentially provide therapeutic strategies for chronic OSAS.

Evolution of the dinosauriform respiratory apparatus: new evidence from the postcranial axial skeleton.

PubMed

Schachner, Emma R; Farmer, C G; McDonald, Andrew T; Dodson, Peter

2011-09-01

Examination of the thoracic rib and vertebral anatomy of extant archosaurs indicates a relationship between the postcranial axial skeleton and pulmonary anatomy. Lung ventilation in extant crocodilians is primarily achieved with a hepatic piston pump and costal rotation. The tubercula and capitula of the ribs lie on the horizontal plane, forming a smooth thoracic "ceiling" facilitating movement of the viscera. Although the parietal pleura is anchored to the dorsal thoracic wall, the dorsal visceral pleura exhibits a greater freedom of movement. The air sac system and lungs of birds are associated with bicapitate ribs with a ventrally positioned capitular articulation, generating a rigid and furrowed rib cage that minimizes dorsoventral changes in volume in the dorsal thorax. The thin walled bronchi are kept from collapsing by fusion of the lung to the thorax on all sides. Data from this study suggest a progression from a dorsally rigid, heterogeneously partitioned, multichambered lung in basal dinosauriform archosaurs towards the small entirely rigid avian-style lung that was likely present in saurischian dinosaurs, consistent with a constant volume cavum pulmonale, thin walled parabronchi, and distinct air sacs. There is no vertebral evidence for a crocodilian hepatic piston pump in any of the taxa reviewed. The evidence for both a rigid lung and unidirectional airflow in dinosauriformes raises the possibility that these animals had a highly efficient lung relative to other Mesozoic vertebrates, which may have contributed to their successful radiation during this time period. Copyright © 2011 Wiley-Liss, Inc.

Real-time endoscopic image orientation correction system using an accelerometer and gyrosensor.

PubMed

Lee, Hyung-Chul; Jung, Chul-Woo; Kim, Hee Chan

2017-01-01

The discrepancy between spatial orientations of an endoscopic image and a physician's working environment can make it difficult to interpret endoscopic images. In this study, we developed and evaluated a device that corrects the endoscopic image orientation using an accelerometer and gyrosensor. The acceleration of gravity and angular velocity were retrieved from the accelerometer and gyrosensor attached to the handle of the endoscope. The rotational angle of the endoscope handle was calculated using a Kalman filter with transmission delay compensation. Technical evaluation of the orientation correction system was performed using a camera by comparing the optical rotational angle from the captured image with the rotational angle calculated from the sensor outputs. For the clinical utility test, fifteen anesthesiology residents performed a video endoscopic examination of an airway model with and without using the orientation correction system. The participants reported numbers written on papers placed at the left main, right main, and right upper bronchi of the airway model. The correctness and the total time it took participants to report the numbers were recorded. During the technical evaluation, errors in the calculated rotational angle were less than 5 degrees. In the clinical utility test, there was a significant time reduction when using the orientation correction system compared with not using the system (median, 52 vs. 76 seconds; P = .012). In this study, we developed a real-time endoscopic image orientation correction system, which significantly improved physician performance during a video endoscopic exam.

Doses from beta radiation in sensitive layers of human lung and dose conversion factors due to 222Rn/220Rn progeny.

PubMed

Markovic, V M; Stevanovic, N; Nikezic, D

2011-08-01

Great deal of work has been devoted to determine doses from alpha particles emitted by (222)Rn and (220)Rn progeny. In contrast, contribution of beta particles to total dose has been neglected by most of the authors. The present work describes a study of the detriment of (222)Rn and (220)Rn progeny to the human lung due to beta particles. The dose conversion factor (DCF) was introduced to relate effective dose and exposure to radon progeny; it is defined as effective dose per unit exposure to inhaled radon or thoron progeny. Doses and DCFs were determined for beta radiation in sensitive layers of bronchi (BB) and bronchioles (bb), taking into account inhaled (222)Rn and (220)Rn progeny deposited in mucus and cilia layer. The nuclei columnar secretory and short basal cells were considered to be sensitive target layers. For dose calculation, electron-absorbed fractions (AFs) in the sensitive layers of the BB and bb regions were used. Activities in the fast and slow mucus of the BB and bb regions were obtained using the LUNGDOSE software developed earlier. Calculated DCFs due to beta radiation were 0.21 mSv/WLM for (222)Rn and 0.06 mSv/WLM for (220)Rn progeny. In addition, the influence of Jacobi room parameters on DCFs was investigated, and it was shown that DCFs vary with these parameters by up to 50%.

Variations of right bronchial tree: a study with multi-detector CT.

PubMed

Wang, Tao; Meng, Min; Huang, Min; Zhao, Xinya

2018-05-03

The aim was to display variations of right bronchial tree. The bronchial tree images of 238 patients were reconstructed using the postprocessing technique of CT. We revealed four cases rare bronchial branching patterns of right superior lobe. 1 case was referred to as tracheal bronchus. In 1 case, B1 was located in the place of the right superior lobar bronchus and B2 + 3 arose from the right merge of the IB. In 1 case, the right superior lobar bronchus has only two divisions for B1 and B3, and the bronchus B2 arose from the right merge of the IB. In 1 case, B1 branched into four bronchi. We revealed 15 cases of rare bronchial branching patterns of right inferior lobe. In nine cases, the basal trunk bronchus bifurcated into B7 + 8 and B9 + l0. In three cases, B8 branched from the basal trunk bronchus before B7. In two cases, basal trunk bronchus bifurcated into B7 + 8 + 9 and B10. In 1 case, the basal trunk bronchus bifurcated into the common stem of B7 + 10 and B8 + 9. Variations of right bronchial tree were displayed in the present study. This information may have important implications for diagnosis of symptomatic patients and performing certain procedures, including bronchoscopy, endotracheal intubation, and lung resection.

Ceftazidime improves hemodynamics and oxygenation in ovine smoke inhalation injury and septic shock.

PubMed

Maybauer, Marc O; Maybauer, Dirk M; Fraser, John F; Traber, Lillian D; Westphal, Martin; Cox, Robert A; Huda, Ruksana; Nakano, Yoshimitsu Y; Enkhbaatar, Perenlei; Hawkins, Hal K; Herndon, David N; Traber, Daniel L

2007-07-01

To investigate ceftazidime in acute lung injury (ALI) and sepsis. Prospective, randomized, controlled animal study in an investigational ICU at a university hospital. Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol. Whereas global hemodynamics and oxygenation remained stable in sham animals (no injury, no treatment), the injury contributed to a hypotensive-hyperdynamic circulation in the control group (smoke inhalation and sepsis, no treatment), as indicated by a significant increase in cardiac index) and heart rate and a drop in mean arterial pressure. Treatment with ceftazidime (smoke inhalation and sepsis, treatment group) stabilized cardiac index and heart rate and attenuated the decrease in mean arterial pressure. The deterioration in PaO2/FiO2 ratio and pulmonary shunt fraction (Qs/Qt) was significantly delayed and blunted by ceftazidime. At 24 h after injury a significant increase in airway obstruction scores of bronchi and bronchioles in both injured groups was observed. Ceftazidime significantly reduced airway obstruction vs. control animals. Whereas plasma nitrate/nitrite levels increased similarly in the two injured groups, lung 3-nitrotyrosine content remained at the baseline level in the ceftazidime group. In ovine lung injury ceftazidime improves global hemodynamics and oxygenation not only by bacterial clearance but also via reduction in toxic nitrogen species such as 3-nitrotyrosine. Therefore ceftazidime appears as a clinically relevant adjunct in the common setting of sepsis-associated lung injury.

Medical waste tissues - breathing life back into respiratory research.

PubMed

BéruBé, Kelly A

2013-12-01

With the advent of biobanks to store human lung cells and tissues from patient donations and from the procurement of medical waste tissues, it is now possible to integrate (both spatially and temporally) cells into anatomically-correct and physiologically-functional tissues. Modern inhalation toxicology relies on human data on exposure and adverse effects, to determine the most appropriate risk assessments and mitigations for beneficial respiratory health. A point in case is the recapitulation of airway tissue, such as the bronchial epithelium, to investigate the impact of air pollution on human respiratory health. The bronchi are the first point of contact for inhaled substances that bypass defences in the upper respiratory tract. Animal models have been used to resolve such inhalation toxicology hazards. However, the access to medical waste tissues has enabled the Lung Particle Research Group to tissue-engineer the Micro-Lung (TM) and Metabo-Lung(TM) cell culture models, as alternatives to animals in basic research and in the safety testing of aerosolised consumer goods. The former model favours investigations focused on lung injury and repair mechanisms, and the latter model provides the element of metabolism, through the co-culturing of lung and liver (hepatocyte) cells. These innovations represent examples of the animal-free alternatives advocated by the 21st century toxicology paradigm, whereby human-derived cell/tissue data will lead to more-accurate and more-reliable public health risk assessments and therapeutic mitigations (e.g. exposure to ambient air pollutants and adverse drug reactions) for lung disease. 2013 FRAME.

Thoracic stomach-right main bronchus fistula treated with dual Y-shaped covered airway stents.

PubMed

Li, Z-M; Lu, H-B; Ren, K-W; Han, X-W; Wu, G; Jiao, D-C

2017-06-01

To determine the efficacy of dual Y-shaped covered airway stents to treat thoracic stomach-right main bronchus fistulae. Fifteen patients who developed thoracic stomach-right main bronchus fistula after oesophageal cancer resection and postoperative irradiation were retrospectively analysed. All fistulae were close to the right upper lobe bronchus. Two Y-shaped covered airway stents were designed for each patient. Under radiographic guidance, one stent was placed from the right main bronchus into the bifurcation of upper lobe and intermediate bronchus, the other was placed from the trachea into both main bronchi. All fistulae were closed immediately after stenting. All patients could eat a semi-solid diet. The symptom of coughing while lying down resolved in all patients, and no complications, such as airway bleeding or pneumothorax, occurred. The average survival time was 26.65 months (range 2-40 months, 11 patients were still alive at the study end). Two patients died of tumour recurrence. Another two patients died of pulmonary infections. In one of these patients, there was a long delay between symptom onset and stenting. In the other patient, a small rupture occurred in the silicone membrane covering the stent, which allowed the leakage of gastric contents into the lung. Dual Y-shaped covered airway stent placement is feasible and safe to treat thoracic stomach-right main bronchus fistulae. Improvements to the material covering the stents is required. Copyright © 2017. Published by Elsevier Ltd.

Metallic stents for tracheobronchial pathology treatment.

PubMed

Serrano, Carolina; Laborda, Alicia; Lozano, Juan M; Caballero, Hugo; Sebastián, Antonio; Lopera, Jorge; de Gregorio, Miguel Ángel

2013-12-01

To present the 7-year experience of the treatment of benign and malignant tracheobronchial stenoses using metallic stents. One hundred twenty-three stents were inserted in 86 patients (74 benign and 12 malignant stenoses). Ninety-seven stents were placed in the trachea and 26 in the bronchi. The procedures were performed under fluoroscopic and flexible bronchoscopic guidance with the patient under light sedation. In cases of severe stenotic lesions or obstructions, laser resection was performed before stent placement. Clinical and functional pulmonary data were recorded before and 3 months after the procedure. Follow-up involved clinical data and radiographic techniques at 48 h and at 1-, 3-, 6-, and 12-month intervals. The technical success was 100 %. Dyspnea disappearance, forced expiratory volume in the first second, and pulmonary functional data improvement was observed in all patients (p < 0.001). Complications were detected in 23 patients (26.7 %). Mean follow-up time was 6.3 ± 1.2 months in patients with malignant lesions and 76.2 ± 2.3 months patients with in benign lesions. By the end of the study, 100 % of patients with malignant pathology and 6.7 % of patients with benign lesions had died. Endoluminal treatment of tracheobronchial stenosis with metallic stents is a therapeutic alternative in patients who are poor candidates for surgery. In unresectable malignant lesions, the benefit of metallic stenting is unquestionable. In benign lesions, the results are satisfactory, but sometimes other interventions are required to treat complications. New stent technology may improve these results.

Effect of Cilia Beat Frequency on Muco-ciliary Clearance

PubMed Central

Sedaghat, M.H.; Shahmardan, M.M.; Norouzi, M.; Heydari, M.

2016-01-01

Background: The airway surface liquid (ASL), which is a fluid layer coating the interior epithelial surface of the bronchi and bronchiolesis, plays an important defensive role against foreign particles and chemicals entering lungs. Objective: Numerical investigation has been employed to solve two-layer model consisting of mucus layer as a viscoelastic fluid and periciliary liquid layer as a Newtonian fluid to study the effects of cilia beat frequency (CBF) at various amounts of mucus properties on muco-ciliary transport problem. Methods: Hybrid finite difference-lattice Boltzmann-method (FB-LBM) has been used to solve the momentum equations and to simulate cilia forces, and also the PCL-mucus interface more accurately, immersed boundary method (IBM) has been employed. The main contribution of the current study is to use an Oldroyd-B model as the constitutive equation of mucus. Results: Our results show that increasing CBF and decreasing mucus viscosity ratio have great effects on mucus flow, but the effect of viscosity ratio is more significant. The results also illustrate that the relation between cilia beat frequency and mean mucus velocity is almost linear and it has similar behavior at different values of viscosity ratio. Conclusion: Numerical investigation based on hybrid IB-FD-LBM has been used to study the effect of CBF at various mounts of mucus viscosity ratio on the muco-ciliary clearance. The results showed that the effect of viscosity ratio on the muco-ciliary transport process is more significant compared with CBF. PMID:28144596

Allergic Bronchopulmonary Aspergillosis: A Perplexing Clinical Entity

PubMed Central

Panjabi, Chandramani

2016-01-01

In susceptible individuals, inhalation of Aspergillus spores can affect the respiratory tract in many ways. These spores get trapped in the viscid sputum of asthmatic subjects which triggers a cascade of inflammatory reactions that can result in Aspergillus-induced asthma, allergic bronchopulmonary aspergillosis (ABPA), and allergic Aspergillus sinusitis (AAS). An immunologically mediated disease, ABPA, occurs predominantly in patients with asthma and cystic fibrosis (CF). A set of criteria, which is still evolving, is required for diagnosis. Imaging plays a compelling role in the diagnosis and monitoring of the disease. Demonstration of central bronchiectasis with normal tapering bronchi is still considered pathognomonic in patients without CF. Elevated serum IgE levels and Aspergillus-specific IgE and/or IgG are also vital for the diagnosis. Mucoid impaction occurring in the paranasal sinuses results in AAS, which also requires a set of diagnostic criteria. Demonstration of fungal elements in sinus material is the hallmark of AAS. In spite of similar histopathologic features, co-existence of ABPA and AAS is still uncommon. Oral corticosteroids continue to be the mainstay of management of allergic aspergillosis. Antifungal agents play an adjunctive role in ABPA as they help reduce the fungal load. Saprophytic colonization in cavitary ABPA may lead to aspergilloma formation, which could increase the severity of the disease. The presence of ABPA, AAS, and aspergilloma in the same patient has also been documented. All patients with Aspergillus-sensitized asthma must be screened for ABPA, and AAS should always be looked for. PMID:27126721

Fine and ultrafine particle doses in the respiratory tract from digital printing operations.

PubMed

Voliotis, Aristeidis; Karali, Irene; Kouras, Athanasios; Samara, Constantini

2017-01-01

In this study, we report for the first time particle number doses in different parts of the human respiratory tract and real-time deposition rates for particles in the 10 nm to 10 μm size range emitted by digital printing operations. Particle number concentrations (PNCs) and size distribution were measured in a typical small-sized printing house using a NanoScan scanning mobility particle sizer and an optical particle sizer. Particle doses in human lung were estimated applying a multiple-path particle dosimetry model under two different breathing scenarios. PNC was dominated by the ultrafine particle fractions (UFPs, i.e., particles smaller than 100 nm) exhibiting almost nine times higher levels in comparison to the background values. The average deposition rate fοr each scenario in the whole lung was estimated at 2.0 and 2.9 × 10 7 particles min -1 , while the respective highest particle dose in the tracheobronchial tree (2.0 and 2.9 × 10 9 particles) was found for diameter of 50 nm. The majority of particles appeared to deposit in the acinar region and most of them were in the UFP size range. For both scenarios, the maximum deposition density (9.5 × 10 7 and 1.5 × 10 8 particles cm -2 ) was observed at the lobar bronchi. Overall, the differences in the estimated particle doses between the two scenarios were 30-40% for both size ranges.

A fire death with a rare finding: anthracosis or soot embolism?

PubMed

Rahimi, Razuin; Omar, Effat; Md Noor, Shahidan

2015-04-01

Charred human remains were found in the smoking ambers of a dying fire in an oil palm plantation in Selangor, Malaysia in the midnight of January 28, 2013. Investigations showed that palm fronds and rubber tires were used to light and sustain the blaze. At least four to five tires were estimated to be used based on the residual burnt metal wires at the site. The remains were brought to the Department of Forensic Medicine, Hospital Sungai Buloh, Selangor for post-mortem examination. Pre-autopsy imaging showed a fractured skull with presence of a bullet in the head. The body belonged to a male with unrecognizable facial features, pugilistic attitude, and reduced body size caused by fire damage with sparing of the posterior surface. A large fracture was present at the skull vault. An entry gunshot wound was observed on the left side of the body of mandible, which was associated with base of skull fracture. Heat-related fractures were also noted on the right side of the frontal bone. A projectile was retrieved from the right side of the occipital lobe. Further examination showed presence of soot and hyperaemic larynx, trachea, main bronchi, and oesophagus. Black spots measuring 1 to 2 mm were present on the surface and parenchyma of the heart, liver, pancreas and kidneys. Histopathology examination showed black particles within the vessels in the affected organs. We report this rare finding in a charred body and present a discussion based on published literature on this issue.

Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside.

PubMed

Cazzola, Mario; Calzetta, Luigino; Ora, Josuel; Puxeddu, Ermanno; Rogliani, Paola; Matera, Maria Gabriella

2015-10-01

Aim of our study was to understand if the interaction between aclidinium and formoterol administered at therapeutic doses leads to a synergistic rather than additive broncholytic effect. We tested the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. The analysis of the interaction between aclidinium and formoterol in vitro was measured by applying the Unified Theory, whereas that in COPD patients was measured by applying the Bliss Independence criterion. Aclidinium and formoterol administered alone completely relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 ± 0.78 nM, formoterol 2.71 ± 0.21), whereas the interaction of aclidinium plus formoterol produced moderate to strong synergism. Changes in FEV1 values showed that inhaled aclidinium and formoterol induced a significant and time-dependent bronchodilatory effect during the study time. The inhalation of aclidinium and formoterol in combination significantly anticipated at 5 min post-administration the bronchodilatory effect of FEV1, compared with the effect of drugs administered alone. There was a synergistic interaction for FEV1 at 5 min and from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post-administration the drug interaction was additive. This study shows that aclidinium and formoterol can produce a significant synergistic interaction that may have a role also in the clinic setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

Airway Obstruction Due to Bronchial Vascular Injury after Sulfur Mustard Analog Inhalation

PubMed Central

Veress, Livia A.; O'Neill, Heidi C.; Hendry-Hofer, Tara B.; Loader, Joan E.; Rancourt, Raymond C.; White, Carl W.

2010-01-01

Rationale: Sulfur mustard (SM) is a frequently used chemical warfare agent, even in modern history. SM inhalation causes significant respiratory tract injury, with early complications due to airway obstructive bronchial casts, akin to those seen after smoke inhalation and in single-ventricle physiology. This process with SM is poorly understood because animal models are unavailable. Objectives: To develop a rat inhalation model for airway obstruction with the SM analog 2-chloroethyl ethyl sulfide (CEES), and to investigate the pathogenesis of bronchial cast formation. Methods: Adult rats were exposed to 0, 5, or 7.5% CEES in ethanol via nose-only aerosol inhalation (15 min). Airway microdissection and confocal microscopy were used to assess cast formation (4 and 18 h after exposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were done to evaluate vascular permeability. Measurements and Main Results: Bronchial casts, composed of abundant fibrin and lacking mucus, occluded dependent lobar bronchi within 18 hours of CEES exposure. BALF contained elevated concentrations of IgM, protein, and fibrin. Accumulation of fibrin-rich fluid in peribronchovascular regions (4 h) preceded cast formation. Monastral blue dye leakage identified bronchial vessels as the site of leakage. Conclusions: After CEES inhalation, increased permeability from damaged bronchial vessels underlying damaged airway epithelium leads to the appearance of plasma proteins in both peribronchovascular regions and BALF. The subsequent formation of fibrin-rich casts within the airways then leads to airways obstruction, causing significant morbidity and mortality acutely after exposure. PMID:20639443

NK2 tachykinin receptors and contraction of circular muscle of the human colon: characterization of the NK2 receptor subtype.

PubMed

Giuliani, S; Barbanti, G; Turini, D; Quartara, L; Rovero, P; Giachetti, A; Maggi, C A

1991-10-22

The contractile effect of substance P, neurokinin A, receptor selective agonists for tachykinin receptors and NK2 tachykinin receptor antagonists was investigated in mucosa-free circular strips of the human isolated colon. Neurokinin A and substance P produced concentration-dependent contractions which approached 80-90% of the maximal response to carbachol. Neurokinin A was about 370 times more potent than substance P. The action of neurokinin A and substance P was not modified by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). The NK2 receptor selective agonist, [beta-Ala8]neurokinin A-(4-10) closely mimicked the response to neurokinin A while NK1 and NK3 receptor selective agonists were active only at microM concentrations. The pseudopeptide, MDL 28,564, which is one of the most selective NK2 ligands available, behaved as a full agonist. Responses to [beta-Ala8]neurokinin A were antagonized by NK2 receptor selective antagonists, with the rank order of potency MEN 10,376 greater than L 659,877 much greater than R 396. These data indicate that NK2 tachykinin receptors play a dominant role in determining the contraction of the circular muscle of the human colon to peptides of this family. The NK2 receptor subtype responsible for this effect belongs to the same subtype (NK2A) previously identified in the rabbit pulmonary artery and guinea-pig bronchi.

Creation of an in vitro biomechanical model of the trachea using rapid prototyping.

PubMed

Walenga, Ross L; Longest, P Worth; Sundaresan, Gobalakrishnan

2014-06-03

Previous in vitro models of the airways are either rigid or, if flexible, have not matched in vivo compliance characteristics. Rapid prototyping provides a quickly evolving approach that can be used to directly produce in vitro airway models using either rigid or flexible polymers. The objective of this study was to use rapid prototyping to directly produce a flexible hollow model that matches the biomechanical compliance of the trachea. The airway model consisted of a previously developed characteristic mouth-throat region, the trachea, and a portion of the main bronchi. Compliance of the tracheal region was known from a previous in vivo imaging study that reported cross-sectional areas over a range of internal pressures. The compliance of the tracheal region was matched to the in vivo data for a specific flexible resin by iteratively selecting the thicknesses and other dimensions of tracheal wall components. Seven iterative models were produced and illustrated highly non-linear expansion consisting of initial rapid size increase, a transition region, and continued slower size increase as pressure was increased. Thickness of the esophageal interface membrane and initial trachea indention were identified as key parameters with the final model correctly predicting all phases of expansion within a value of 5% of the in vivo data. Applications of the current biomechanical model are related to endotracheal intubation and include determination of effective mucus suctioning and evaluation of cuff sealing with respect to gases and secretions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig.

PubMed Central

Lötvall, J. O.; Elwood, W.; Tokuyama, K.; Barnes, P. J.; Chung, K. F.

1991-01-01

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators. PMID:1725766

Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig.

PubMed

Lötvall, J O; Elwood, W; Tokuyama, K; Barnes, P J; Chung, K F

1991-12-01

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators.

Airway morphometry in the lungs as depicted in chest CT examinations variability of measurements

NASA Astrophysics Data System (ADS)

Leader, J. K.; Zheng, Bin; Scuirba, Frank C.; Coxson, Harvey O.; Weissfeld, Joel L.; Fuhrman, Carl R.; Maitz, Glenn S.; Gur, David

2006-03-01

The purpose of the study was to decrease the variability of computed tomographic airway measurements. We to developed and evaluated a novel computer scheme to automatically segment airways depicted on chest CT examinations at the level of the lobar and segmental bronchi and to decrease. The computer scheme begins with manual selection of a seed point within the airway from which the airway wall and lumen are automatically segmented and airway pixels were assigned full or partial membership to the lumen or wall. Airway pixels not assigned full membership to the lumen (< -900 HU) or wall (> 0 HU) were assigned partial membership to the lumen and wall. In fifteen subjects with no visible signs of emphysema and a range of pulmonary obstruction from none to severe, airway measures were compared to pulmonary function parameters in a rank order analysis to evaluate measuring a single airway versus multiple airways. The quality of the automated airway segmentation was visually acceptable. The Pearson Correlation coefficients for the ranking of FEV I versus wall area percent (percent of total airway size) and FVC versus wall area percent were 0.164 and 0.175 for a single measurement, respectively, and were 0.243 and 0.239 for multiple measurements, respectively. Our preliminary results suggest that averaging the measurements from multiple airways may improve the relation between airway measures and lung function compared to measurement from a single airway, which improve quantification of airway remodeling in COPD patients.

Short-term effects of subchronic low-level hydrogen sulfide exposure on oil field workers.

PubMed

Mousa, Haider Abdul-Lateef

2015-01-01

To investigate the short-term effects of low-level hydrogen sulfide (H2S) exposure on oil field workers. Observational study included 34 patients who work at an oil field. All patients were males with age range of 22-60 years (mean 37 years). The data were collected by systematic questionnaire about symptoms. The inclusion criteria of patients were symptoms related to inhalation of H2S gas in the oil field. The complaints should be frequent and relapsed after each gas exposure and disappeared when there was no gas exposure. Exclusion criteria were the symptoms which experienced with or without H2S exposure. The presence of H2S gas was confirmed by valid gas detector devices. The most frequent presenting symptom was nasal bleeding. It was revealed in 18 patients (52.9%). This followed by pharyngeal bleeding, gum bleeding, and bloody saliva (mouth bleeding) which were encountered in five cases for each complaint (14.7%). Other less frequent presenting symptoms were tongue bleeding, bloody sputum, headache, abdominal colic, pharyngeal soreness, fatigue, and sleepiness. Nasal mucosa was the most vulnerable part to H2S effect. Inhalation of H2S produced upper respiratory tract epithelial damage that led to bleeding from nose, pharynx, gum, tongue, trachea, and bronchi. There were no complaints of asthmatic attack upon exposure to low level of H2S. Sunlight had a significant role in reduction of ambient air H2S level.

The effects of emphysema on airway disease: correlations between multi-detector CT and pulmonary function tests in smokers.

PubMed

Yahaba, Misuzu; Kawata, Naoko; Iesato, Ken; Matsuura, Yukiko; Sugiura, Toshihiko; Kasai, Hajime; Sakurai, Yoriko; Terada, Jiro; Sakao, Seiichiro; Tada, Yuji; Tanabe, Nobuhiro; Tatsumi, Koichiro

2014-06-01

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV1. No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. A significant correlation exists between airway parameters and FEV1 in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

High expression of neutral endopeptidase in idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells.

PubMed

Cohen, A J; King, T E; Gilman, L B; Magill-Solc, C; Miller, Y E

1998-11-01

Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells (IDHPNC) is a clinicopathological entity characterized by a diffuse hyperplasia of neuroendocrine cells involving distal bronchi and bronchioles. The pathogenesis of this syndrome remains unknown. The hyperplastic neuroendocrine (NE) cells contain multiple neuropeptides, including the bombesinlike peptides (BLP), which are likely important in the pathogenesis of the disorder by stimulating proliferation of fibroblasts in a paracrine fashion and the NE cells themselves in an autocrine manner. Neutral endopeptidase (NEP) is a cell-surface enzyme that hydrolyzes BLP and other bioactive peptides. Low or undetectable NEP is present in many primary lung cancers and cell lines. Low NEP expression could increase neuropeptide-induced autocrine effects by increasing local levels of neuropeptides. We hypothesized that IDHPNC was associated with low or absent NEP expression. NEP expression was assayed in patients with IDHPNC (n = 3) and was compared with expression in patients with idiopathic pulmonary fibrosis (n = 5), hypersensitivity pneumonitis (n = 5), and normal lung (n = 4) using immunohistochemistry, ELISA, activity assay, and Western blot analysis. By these assays, NEP expression was highest in lungs affected by IDHPNC. NEP mRNA, as assessed in IDHPNC lung tissue by RT-PCR, was the expected size and free of mutation between bp 238-2437. Therefore, IDHPNC is unlikely to be the result of a defect in NEP expression. The apparent increase in NEP expression in lung tissue from patients with IDHPNC may reflect a compensatory increase that partly counteracts abundant neuropeptides, including BLP, present in this disorder.

Misplacement of left-sided double-lumen tubes into the right mainstem bronchus: incidence, risk factors and blind repositioning techniques.

PubMed

Seo, Jeong-Hwa; Bae, Jun-Yeol; Kim, Hyun Joo; Hong, Deok Man; Jeon, Yunseok; Bahk, Jae-Hyon

2015-10-28

Double-lumen endobronchial tubes (DLTs) are commonly advanced into the mainstem bronchus either blindly or by fiberoptic bronchoscopic guidance. However, blind advancement may result in misplacement of left-sided DLTs into the right bronchus. Therefore, incidence, risk factors, and blind repositioning techniques for right bronchial misplacement of left-sided DLTs were investigated. This was an observational cohort study performed on the data depository consecutively collected from patients who underwent intubation of left-sided DLTs for 2 years. Patients' clinical and anatomical characteristics were analyzed to investigate risk factors for DLT misplacements with logistic regression analysis. Moreover, when DLTs were misplaced into the right bronchus, the bronchial tube was withdrawn into the trachea and blindly readvanced without rotation, or with 90° or 180° counterclockwise rotation while the patient's head was turned right. DLTs were inadvertently advanced into the right bronchus in 48 of 1135 (4.2 %) patients. DLT misplacements occurred more frequently in females, in patients of short stature or with narrow trachea and bronchi, and when small-sized DLTs were used. All of these factors were significantly inter-correlated each other (P < 0.001). In 40 of the 48 (83.3 %) patients, blind repositioning was successful. Smaller left-sided DLTs were more frequently misplaced into the right mainstem bronchus than larger DLTs. Moreover, we were usually able to reposition the misplaced DLTs into the left bronchus by using the blind techniques. ClinicalTrials.gov Identifier: NCT01371773.

Management of acute cough by Zataria multiflora Boiss as an alternative treatment.

PubMed

Mahboubi, Mohaddese

2018-01-01

Cough, as a defensive reflux mechanism, removes foreign objects and secretions from bronchi and bronchioles of airways. Zataria multiflora is a popular plant for treatment of cough in Iranian traditional medicine. The aim of this review was to evaluate the potency of Z. multiflora as an alternative treatment in management of acute cough and its possible mechanisms of action. Here the authors compiled information about Z. multiflora in the treatment of cough from all accessible resources and books. The results of this investigation showed that there were five clinical studies that evaluated the efficacy of Z. multiflora essential oil or extract alone (n = 1), in combination with Althaea officinalis (n = 2) or Foeniculum vulgare essential oil (n = 1), in the form of syrup (n = 3), oral drop (n = 1) and soft capsule (n = 1), for the treatment of acute cough in comparison with placebo or synthetic drugs (bromhexine, dextromethorphan and clobutinol). All clinical studies confirmed the efficacy of Z. multiflora in the amelioration of acute cough in pediatric (n = 1) and adult patients (n = 4) without any adverse effects. Different mechanisms, such as anti-inflammatory, analgesic, antimicrobial, relaxant and immune-enhancement, may be responsible for the efficacy of Z. multiflora in cough relief. Other clinical trials can be performed with Z. multiflora in combination with ivy leaf extract or primrose root extract on patients with cough. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Longitudinal dispersion in model of central airways during high-frequency ventilation.

PubMed

van der Kooij, A M; Luijendijk, S C

1991-04-01

We have measured the longitudinal dispersion of boluses of helium, acetylene and sulphur hexafluoride in a plastic model of the human airways--generations zero through six--during high frequency ventilation (HFV). HFV was maintained by a piston pump. Frequency f and tidal volume VT ranged from 2.5 to 25 Hz and from 5 to 20 ml, respectively. Boluses were injected near the entrance of the zeroth generation (trachea), and the dispersion curves were measured by mass spectrometry at the end of the sixth airway generation. The shapes of the bolus dispersion curves could be well described with Gaussian distribution functions. With the exception of the HFV-conditions with VT = 5 ml, the effective dispersion coefficient DDISP appeared to be independent of the molecular diffusion coefficient. This independency was also found by other investigators in studies with dogs and human subjects. The measured results for DDISP for different f and VT could be satisfactorily described with the empirical equation DDISP = 0.0617 f0.8VT1.38 [cm2S-1]. Application of this equation to f and VT values normally applied in man resulted in DDISP values which should be considered to be too small for maintaining eucapnic ventilation in vivo. On the basis of this result we believe that during HFV in intubated subjects gas transport by longitudinal dispersion will be limited to the instrumental dead space--the endotracheal tube inclusive--and a few generations of large bronchi.

Characterization of primary cilia in human airway smooth muscle cells.

PubMed

Wu, Jun; Du, Hui; Wang, Xiangling; Mei, Changlin; Sieck, Gary C; Qian, Qi

2009-08-01

Considerable evidence indicates a key role for primary cilia of mammalian cells in mechanochemical sensing. Dysfunctions of primary cilia have been linked to the pathogenesis of several human diseases. However, cilia-related research has been limited to a few cell and tissue types; to our knowledge, no literature exists on primary cilia in airway smooth muscle (ASM). The aim of this study was to characterize primary cilia in human ASM. Primary cilia of human bronchial smooth muscle cells (HBSMCs) were examined using immunofluorescence confocal microscopy, and scanning and transmission electron microscopy. HBSMC migration and injury repair were examined by scratch-wound and epidermal growth factor (EGF)-induced migration assays. Cross-sectional images of normal human bronchi revealed that primary cilia of HBSMCs within each ASM bundle aggregated at the same horizontal level, forming a "cilium layer." Individual cilia of HBSMCs projected into extracellular matrix and exhibited varying degrees of deflection. Mechanochemical sensing molecules, polycystins, and alpha2-, alpha5-, and beta1-integrins were enriched in cilia, as was EGF receptor, known to activate jointly with integrins during cell migration. Migration assays demonstrated a ciliary contribution to HBSMC migration and wound repair. The primary cilia of ASM cells exert a role in sensing and transducing extracellular mechanochemical signals and in ASM injury repair. Defects in ASM ciliary function could potentially affect airway wall maintenance and/or remodeling, possibly relating to the genesis of bronchiectasis in autosomal dominant polycystic kidney disease, a disease of ciliopathy.

Mounier-Kuhn syndrome (tracheobronchomegaly): An analysis of eleven cases.

PubMed

Akgedik, Recep; Karamanli, Harun; Kizilirmak, Deniz; Kurt, Ali Bekir; Öztürk, Hasan; Yildirim, Berna Botan; Çakir, Lütfullah

2018-03-01

Mounier-Kuhn syndrome (MKS) is a congenital disorder characterized by tracheobronchomegaly resulting from the absence of elastic fibers in the trachea and main bronchi or atrophy and thinning of the smooth muscle layer. In this syndrome, dead space associated with tracheobronchomegaly increases and discharge of secretions decreases because of ineffective coughing. The most common complications are recurrent lower respiratory tract infections and bronchiectasis. We examined the clinical characteristics, radiological features, and related complications of patients with MKS. The cases were obtained between September 2007 and November 2015. Computed tomography scans of the chest were used to diagnose tracheobronchomegaly. All cases (a total of 11) were males with a mean age of 63 ± 13 (range, 38-80) years. The mean diameter of the trachea was 31.53 ± 2.99 mm; the mean transverse diameter was 31.69 ± 3.10 mm and the mean sagittal diameter was 31.36 ± 3.01 mm. Complaints at the time of presentation included chronic cough, purulent sputum, dyspnea, and hemoptysis. There were recurrent pulmonary infections in seven cases, bronchiectasis in six, and tracheal diverticulum in four at the time of diagnosis. In this article, 11 cases with various rarely seen complications are presented and evaluated in the light of current literature. We recommend that if chronic cough, recurrent pulmonary infections, and bronchiectasis seen in a patient, MKS should be kept in mind. © 2017 John Wiley & Sons Ltd.

Physiologic control. Anatomy and physiology of the airway circulation.

PubMed

Widdicombe, J

1992-11-01

Both for the nose and the lower airways there is an extensive subepithelial capillary network. That for the nose is fenestrated, and this is true for the tracheobronchial tree of rats, guinea pigs, and hamsters, and for that of human asthmatics. However, healthy humans, dogs, and sheep have capillaries without fenestrations except for those close to neuroepithelial bodies and submucosal glands. Deeper in the mucosa there is a capacitance system of vessels, conspicuous in the nose but present also in the lower airways of rabbits and sheep and, to a lesser extent, in those of dogs and humans. Both for the nose and the lower airways, parasympathetic nerves are vasodilator, sympathetic nerves are vasoconstrictor, and sensory nerves are able to release dilator neuropeptides. Most inflammatory and immunologic mediators are vasodilator. A conspicuous difference between the nasal and lower airway vasculatures is the presence of arteriovenous anastomoses only in the former. Countercurrent mechanisms also exist in the nose to increase its efficiency in air conditioning, but they have not been established for the trachea. The pulmonary vasculature could be part of such a system for the bronchi. Distension of the airway vasculature thickens the mucosa, probably both by vascular distension and by edema formation. The latter can lead to exudation into the airway lumen. These processes have not been well quantitated, and the balance sheet of capillary and capacitance vessel volumes, interstitial liquid volume, and exudate volume needs to be worked out in physiologic and pathologic conditions.

Air trapping and airflow obstruction in newborn cystic fibrosis piglets.

PubMed

Adam, Ryan J; Michalski, Andrew S; Bauer, Christian; Abou Alaiwa, Mahmoud H; Gross, Thomas J; Awadalla, Maged S; Bouzek, Drake C; Gansemer, Nicholas D; Taft, Peter J; Hoegger, Mark J; Diwakar, Amit; Ochs, Matthias; Reinhardt, Joseph M; Hoffman, Eric A; Beichel, Reinhard R; Meyerholz, David K; Stoltz, David A

2013-12-15

Air trapping and airflow obstruction are being increasingly identified in infants with cystic fibrosis. These findings are commonly attributed to airway infection, inflammation, and mucus buildup. To learn if air trapping and airflow obstruction are present before the onset of airway infection and inflammation in cystic fibrosis. On the day they are born, piglets with cystic fibrosis lack airway infection and inflammation. Therefore, we used newborn wild-type piglets and piglets with cystic fibrosis to assess air trapping, airway size, and lung volume with inspiratory and expiratory X-ray computed tomography scans. Micro-computed tomography scanning was used to assess more distal airway sizes. Airway resistance was determined with a mechanical ventilator. Mean linear intercept and alveolar surface area were determined using stereologic methods. On the day they were born, piglets with cystic fibrosis exhibited air trapping more frequently than wild-type piglets (75% vs. 12.5%, respectively). Moreover, newborn piglets with cystic fibrosis had increased airway resistance that was accompanied by luminal size reduction in the trachea, mainstem bronchi, and proximal airways. In contrast, mean linear intercept length, alveolar surface area, and lung volume were similar between both genotypes. The presence of air trapping, airflow obstruction, and airway size reduction in newborn piglets with cystic fibrosis before the onset of airway infection, inflammation, and mucus accumulation indicates that cystic fibrosis impacts airway development. Our findings suggest that early airflow obstruction and air trapping in infants with cystic fibrosis might, in part, be caused by congenital airway abnormalities.

[Measures to be taken in adults with bronchiolitis].

PubMed

De Crémoux, Hubert

2003-02-22

The majority of bronchial and interstitial diseases of the adult are accompanied by bronchiolar inflammation, but over time the use of the term "bronchiolitis" has been limited to a few specific affections. Bronchiolitis with predominantly alveolar involvement Some "bronchiolites" emphasize the problem of an interstitial pneumopathy, since the disease predominantly involves the alveolar spaces. Only a few bronchiolites are severely damaging: bronchiolitis obliterans with organizing pneumonia and interstitial pneumopathy with respiratory bronchiolitis. These predominantly alveolar affections reveal the clinical (crepitant rales), radiographic (multiple or even diffuse opacities), and functional aspects (restrictive ventilation problems). Brochiolitis with obstructive airway problems In this case the disease predominantly involves the bronchioles and spares the alveolar tissue. The term "bronchiolitis" is in this case perfectly justified. The clinical picture is evocative with obstructed airway and a clear pulmonary parenchyma on the thoracic x-ray. These affections belong to the obstructive broncho-pneumopathy group. The prototype is brochiolitis obliterans, the anatomic correlation of which is generally constrictive bronchiolitis obliterans. Occasionally primitive, it frequently complicates the progression of many morbid states (transplants, collagenosis, inhaled or ingested toxic substances.). Diffuse panbronchiolitis Other "bronchiolites" deviate from this framework and are accompanied by marked lesions of other respiratory tracts (membrane bronchioles, cartilage bronchi, mucosa, ear nose and throat). The prototype is panbronchiolitis, described in the Far East. It is exceptional in Europe, where similar but nosologically different clinical aspects are observed during various diseases: cystic fibrosis, Young's syndrome, hypogammaglobulinemia, bone marrow transplant, context of HIV or haemorrhagic recto-colitis.

Contractile effects of bradykinin on the isolated human small bronchus.

PubMed

Molimard, M; Martin, C A; Naline, E; Hirsch, A; Advenier, C

1994-01-01

Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.

KF19514, a phosphodieterase 4 and 1 inhibitor, inhibits PAF-induced lung inflammatory responses by inhaled administration in guinea pigs.

PubMed

Manabe, H; Akuta, K; Okamura, K; Ohmori, K

1997-12-01

Phosphodiesterase (PDE) 4 inhibitors are well known for their inhibitory effect on bronchoconstriction and inflammation and may be promising anti-asthma drugs. Platelet-activating factor (PAF) has been proposed as an inflammatory mediator to be relevant to asthma. It causes bronchoconstriction, airway microvascular leakage, inflammatory cell accumulation in the lung and hyperresponsiveness. In this study, we therefore have investigated the anti-asthmatic effects of the inhaled KF19514 [5-phenyl-3'-(3-pyridyl)methyl-3H-imidazo(4,5-c)(1,8) naphthyridin-4(5H)-one], a PDE 4 and 1 inhibitor, on PAF-induced lung inflammatory responses in guinea pigs. The inhaled KF19514 (0.0001-0.01%) significantly inhibited PAF-induced eosinophil and neutrophil accumulation into the airway and hyperresponsiveness in guinea pigs. The IC50 value of KF19514 against eosinophil accumulation was 14.8 microM (0.00063%). Moreover, the effect of KF19514 on the electrical field stimulation-induced bronchial contraction was examined using the main bronchi of guinea pigs in vitro. KF19514 inhibited both cholinergic and tachykininergic contraction and, in particular, produced a potent inhibitory effect on tachykininergic contraction (IC50 = 0.49 microM). The mechanism by which KF19514 inhibited the PAF-induced hyperresponsiveness may in part be the suppression of the tachykinin release. Based on these results, it was demonstrated that the inhaled KF19514 might have a significant potential effect on the inflammatory cell accumulation and hyperresponsiveness induced by PAF.

Effects of the tripeptide substance P antagonist, FR113680, on airway constriction and airway edema induced by neurokinins in guinea-pigs.

PubMed

Murai, M; Morimoto, H; Maeda, Y; Fujii, T

1992-06-24

FR113680 is a newly developed tripeptide substance P (SP) receptor antagonist. The effects of FR113680 on airway constriction and airway edema induced by neurokinins were investigated in guinea-pigs. In in vitro experiments, FR113680 inhibited the contraction of isolated guinea-pig trachea induced by SP and neurokinin A (NKA) in a dose-dependent manner with IC50 values of 2.3 x 10(-6) and 1.5 x 10(-5) M, respectively. The tracheal contraction induced by histamine and acetylcholine was not affected by FR113680. FR113680 (5 x 10(-5) M) also significantly inhibited the atropine-resistant contraction of isolated guinea-pig bronchi induced by electrical field stimulation. In in vivo experiments, FR113680 given i.v. inhibited SP-induced airway constriction in guinea-pigs at doses of 1 and 10 mg kg-1. However, FR113680 only inhibited NKA- and capsaicin-induced airway constriction by 40-50% even at a dose of 10 mg kg-1. FR113680 also inhibited SP-induced airway edema in guinea-pigs with the same potency as it inhibited SP-induced airway constriction. Histamine-induced airway constriction and airway edema were not affected at a dose of 10 mg kg-1. These results suggest that FR113680 preferentially inhibits responses induced by NK1 receptor activation (SP-induced airway constriction and airway edema), but is less effective on a NK2 receptor-induced response (airway constriction by NKA and neurogenic stimulation).

Helminth component community of the loggerhead sea turtle, Caretta caretta, from Madeira Archipelago, Portugal.

PubMed

Valente, Ana Luisa; Delgado, Cláudia; Moreira, Cláudia; Ferreira, Sandra; Dellinger, Thomas; Pinheiro de Carvalho, Miguel A A; Costa, Graça

2009-02-01

The helminth fauna of pelagic-stage loggerhead sea turtles, Caretta caretta, is still poorly known. Here, we describe the helminth-component community of healthy, free-ranging juvenile loggerhead sea turtles captured in the waters around Madeira Island, Portugal. Fifty-seven were used in this study. The esophagus, stomach, intestine, liver, gallbladder, spleen, kidneys, trachea, bronchi, urinary bladder, heart, left and right aortas, and coelomic cavity were macroscopically inspected; organs and tissues were removed and washed through a sieve. A search for parasites was made using a stereoscopic microscope; recovered parasites were fixed and stored in 70% alcohol until staining and identification. Prevalence, mean intensity, and mean abundance values were recorded. In total, 156 parasite specimens belonging to 9 species were found: nematodes included Anisakis simplex s.l. (larvae) and an unidentified species; digenetic trematodes present were Enodiotrema megachondrus, Rhytidodes gelatinosus, Pyelosomum renicapite, and Calycodes anthos; acanthocephalans included Bolbosoma vasculosum and Rhadinorhynchus pristis; a single cestode, Nybelinia sp., was present. Parasite infections were found to have both low prevalences and intensities. Possible reasons for this include the oligotrophic conditions of the pelagic habitat around Madeira; a 'dilution effect' because of the vastness of the area; and the small size, and thus ingestion rate, of the turtles. Results are discussed in terms of the various turtle populations that may use the waters surrounding Madeira. This work provides valuable information on the parasite fauna of a poorly known stage in the life of loggerhead sea turtles, thereby filling a fundamental gap with regard to features of the parasite fauna in this species.

Tuberculosis as a three-act play: A new paradigm for the pathogenesis of pulmonary tuberculosis.

PubMed

Hunter, Robert L

2016-03-01

Lack of access to human tissues with untreated tuberculosis (TB) has forced generations of researchers to use animal models and to adopt a paradigm that granulomas are the characteristic lesion of both primary and post primary TB. An extended search of studies of human lung tissues failed to find any reports that support this paradigm. We found scores of publications from gross pathology in 1804 through high resolution CT scans in 2015 that identify obstructive lobular pneumonia, not granulomas, as the characteristic lesion of developing post-primary TB. This paper reviews this literature together with other relevant observations to formulate a new paradigm of TB with three distinct stages: a three-act play. First, primary TB, a war of attrition, begins with infection that spreads via lymphatics and blood stream before inducing systemic immunity that contains and controls the organisms within granulomas. Second, post-primary TB, a sneak attack, develops during latent TB as an asymptomatic obstructive lobular pneumonia in persons with effective systemic immunity. It is a paucibacillary process with no granulomas that spreads via bronchi and accumulates mycobacterial antigens and host lipids for 1-2 years before suddenly undergoing caseous necrosis. Third, the fallout, is responsible for nearly all clinical post primary disease. It begins with caseous necrotic pneumonia that is either retained to become the focus of fibrocaseous disease or is coughed out to leave a cavity. This three-stage paradigm suggests testable hypotheses and plausible answers to long standing questions of immunity to TB. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Investigation on the potential of thulium-fibre-laser irradiation for in-stent tissue ablation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sroka, Ronald; Frank, Johannes; Reichenberger, Frank; Behr, J.; Gesierich, Wolfgang

2017-04-01

Granulation and tumor regrowth in the area of bronchi stent implants may result in restenosis. It had been shown that by means of Thulium-Fibre-Laser (TFL) a controlled ablation and reduction of the tissue within the stent could be performed. When using Nd:YAG irradiation there is risk for explosive flames, burns of fibre and stent, ruptures of stent meshes as well as perforation of stent and cover. Therefore it was the aim to investigate the safety margin when using TFL. Four different types of clinical used stents (with/without cover) were fixed to pig trachea tissue. Irradiation was performed by fibre assisted TFL-1940nm-laser irradiation while laser power, light application duration and distance, as well as oxygen percentage and contamination were varied. In case of Nitinol-stents rupture were observed at power levels >=7W or distances of <5mm, oxygen conc. of 40% result in increased flame appearance. Polyurethan-covers were ruptured at each variable, flame appeared at 5W. Silicon-stents were destroyed at power levels of about 5W and distances of <5mm and additionally 30%-oxygen or contamination either by blood or soot result in increased appearance of burns and flames. Based upon these observations in clinical TFL-irradiation the distance should >=5 mm and the power level should be <=6W. Furthermore the oxygen conc. should not exceed 30% and short term continuous irradiation of less than 15s exposition should be considered. In case of Silicon-stents light application on contaminated area should be avoided.

Expression of inducible nitric oxide synthase in spontaneous bovine bronchopneumonia.

PubMed

Fligger, J M; Waldvogel, A S; Pfister, H; Jungi, T W

1999-09-01

The expression of inducible nitric oxide synthase (iNOS), major histocompatibility class II molecules (MHC-II), CD68, and the calcium-binding proteins S100A8 and S100A9 (also called MRP8 and MRP14, respectively) was assessed in lung tissues from cattle that succumbed to pneumonia. Expression patterns of these markers were related to the types of lung lesion. iNOS expression was only observed in lungs infected with Arcanobacterium pyogenes or Pasteurella haemolytica but not in lungs from cattle with subacute chronic interstitial pneumonia and acute interstitial pneumonia due to Escherichia coli infection. High levels of iNOS were expressed by cells (probably leukocytes) surrounding necrotic foci. Occasionally, iNOS was expressed by intraalveolar macrophages in viable parenchyma, by leukocytes within the airways, and by some chondrocytes in the supporting cartilage of bronchi. Cells expressing MHC-II were distributed relatively evenly throughout areas of inflammation and did not display any clear association with necrotic foci. Cell types expressing MHC-II included type II alveolar epithelial cells, spindle-shaped cells of the interstitium, cells in bronchus-associated lymphoid tissue, and leukocytes in lymph and blood vessels but largely excluded iNOS-positive cells. Likewise, CD68-positive cells were rarely positive for iNOS and were not confined to the areas surrounding necrotic tissue. As with MHC-II and CD68, there was little if any coexpression of iNOS and either of the S100 proteins tested. Thus, in cattle with necrotizing bronchopneumonia, iNOS-expressing cells were largely restricted to the cellular zone surrounding necrotic areas.

Foreign bodies in tracheobronchial tree in children: a review of cases over a twenty-year period.

PubMed

Yeh, L C; Li, H Y; Huang, T S

1998-03-01

Foreign body inhalation into the tracheobronchial tree of children is rather rare but serious problem. It may be hazardous and even cause fatal sequelae in the children if misdiagnosed and not managed promptly. We retrospectively reviewed the records of 81 patients with foreign bodies inhaled into the larynx, trachea and bronchi. The children were all treated during the 20-year period from July 1976 through June 1996 at Chang Gung Memorial Hospital. Of these patients, 82% were 36 months of age or younger. The male to female ratio was 3:1. All of the patients initially received flexible fiberoptic bronchoscopy to identify the foreign objects. The foreign bodies were removed by jet ventilation bronchoscopy with apneic techniques under general anesthesia. Peanuts were found to be the most common causative foreign body agent which occurred in 53 instances (65%). The most common manifestation was coughing, with subsequent dyspnea and audible wheezing. The foreign bodies were lodged in the left bronchus more than in the right. The most obvious radiologic evidence observed in aspirated children were emphysematous changes at same side of the foreign bodies caused by "expansile check-valve" phenomenon. Four patients showed radio-opaque objects on chest roentgenograms. Six patients required second extraction procedures due to the retained foreign bodies. Neither serious complications nor deaths occurred in these patients due to the foreign body inhalation. Early diagnosis and management is essential in children with foreign bodies in the airways to prevent morbidity or death. Small materials or food bits should be kept far away from young child.

Factors predicting early diagnosis of pediatric laryngotracheobronchial foreign bodies.

PubMed

Parida, Pradipta; Nirmal, Nirmal Shanmugasundaram; Gopalakrishnan, Surianarayanan; Saxena, Sunil Kumar

2015-01-01

To study the clinical and radiological findings to make early diagnosis of foreign body (FB) aspiration in children. This prospective study was conducted on 45 children below 12 years of age with a clinical diagnosis of FB aspiration undergone rigid bronchoscopy from September 2008 to may 2010. Bronchoscopy was positive for FB in 37 children. The results of these 37 children (15 female and 22 male) were analyzed. 81% of children were in age group of 1-3 years. Penetration syndrome (sudden onset coughing, choking and gagging when the child is having something in the mouth) (89.2%) and decreased breath sounds (86.5%) were the most common clinical features. Cough, respiratory difficulty and fever were present in 83.8%, 78.4% and 27% respectively. Tachypnoea, tachycardia, chest retractions, decreased chest movements and wheeze were present in 83.3%, 83.3%, 83.3%, 51.4% and 43.2% respectively. Unilateral hyperinflation (64.9%), mediastinal shift (45.9%), and collapse (21.6%) were common radiological sign on chest radiograph and in 13.5% patients the chest X-rays were normal. Sites of FB lodgments were larynx, trachea, right main bronchus, left main bronchus and bilateral bronchi in 10.8%, 10.8%, 35.1%, 37.8 and 5.5% respectively. Food related FBs were present in 30 cases (peanut in 54.1%) and inorganic FBs were present in 7 cases. FBs were removed successfully by rigid bronchoscopy in all cases without any mortality. Penetration syndrome, localized decreased breath sounds, unilateral hyperinflation and/or mediastinal shift on radiology are predictors for early diagnosis of FB aspiration.

Anesthetic Management of Patients Undergoing Right Lung Surgery After Left Upper Lobectomy: Selection of Tubes for One-Lung Ventilation (OLV) and Oxygenation During OLV.

PubMed

Kawagoe, Izumi; Hayashida, Masakazu; Suzuki, Kenji; Kitamura, Yoshitaka; Oh, Shiaki; Satoh, Daizoh; Inada, Eiichi

2016-08-01

To investigate anesthesia management in patients undergoing right lung surgery after a previous left upper lobectomy (LUL) that may require special precautions since angulation of the left bronchus can hamper correct placement of a left-sided double-lumen tube (DLT), and one-lung ventilation (OLV) depending solely on the left lower lobe may lead to inadequate oxygenation. A retrospective data analysis. Single university hospital. Patients underwent right lung surgery after previous LUL. None. Anesthesia management was investigated in 18 patients who underwent right lung surgery following LUL. All intubation procedures were performed under bronchoscopic guidance to prevent airway trauma. OLV could be achieved with a left-sided DLT in 12 patients, while tubes other than this were required in 6 patients, including a right-sided DLT (n = 3) and a bronchial blocker (n = 3). The presence or absence of remarkable bronchial angulation, characterized by a combination of a wide (>140°) angle between the trachea and left main bronchus and a narrow (<100°) angle between the left main and lower bronchi critically affected tube selections. The minimum SpO2 during OLV was 90.9±4.1%. In 2 patients, intermittent bilateral ventilation was required to treat desaturation. In all the patients, the scheduled surgery could be completed. Extent of left bronchial angulations had a critical impact on whether or not a left-sided DLT could be used in patients undergoing right lung surgery after LUL. Copyright © 2016 Elsevier Inc. All rights reserved.

Embryonic Wnt gene expression in the nitrofen-induced hypoplastic lung using 3-dimensional imaging.

PubMed

Takayasu, Hajime; Murphy, Paula; Sato, Hideaki; Doi, Takashi; Puri, Prem

2010-11-01

Wnts have been reported to play a key role in the lung morphogenesis. We have previously reported that pulmonary gene expression of Wnt2 and Wnt7b is downregulated on day 15 of gestation in the nitrofen-induced congenital diaphragmatic hernia (CDH) model. However, the distribution pattern of gene expression of Wnts in the very early lung development remains unclear. Optical projection tomography (OPT) is a new technique for 3-dimensional imaging of small developing organs and gene distribution combined with whole-mount in situ hybridization. We designed this study to investigate the distribution pattern of Wnts gene expression in lung buds of nitrofen-induced CDH model using OPT. Embryos from normal and nitrofen-treated dams were harvested on embryonic day 10 (E10), and divided into controls and nitrofen group, respectively. Whole-mount in situ hybridization to detect transcripts of Wnt2 and Wnt7b was performed, analyzed, and reconstructed using OPT. The expression of Wnt2 transcripts was detected in the lung bud mesenchyme and markedly diminished in nitrofen group compared to controls, whereas Wnt7b transcripts were expressed in the mesoderm of bronchi and the lung bud with no detectable difference between 2 groups. We provide evidence for the first time that Wnt2 expression is downregulated at lung bud stage in the nitrofen model. Optical projection tomography is potentially a useful approach to visualize both gene expression and morphology during very early stages of lung development. Copyright © 2010 Elsevier Inc. All rights reserved.

A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma.

PubMed

Catal, F; Mete, E; Tayman, C; Topal, E; Albayrak, A; Sert, H

2015-01-01

A few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model. Twelve-week-old BALB/c (H-2d/d) female rats (n=18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab (n=6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed. Severity of lung damage was found to be reduced significantly in the asthma induced with OVA+treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score=1, p=0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration. Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Allergen challenge-induced extravasation of plasma in mouse airways.

PubMed

Erjefält, J S; Andersson, P; Gustafsson, B; Korsgren, M; Sonmark, B; Persson, C G

1998-08-01

Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice. This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin. Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma. Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent. The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation

An iterative method for airway segmentation using multiscale leakage detection

NASA Astrophysics Data System (ADS)

Nadeem, Syed Ahmed; Jin, Dakai; Hoffman, Eric A.; Saha, Punam K.

2017-02-01

There are growing applications of quantitative computed tomography for assessment of pulmonary diseases by characterizing lung parenchyma as well as the bronchial tree. Many large multi-center studies incorporating lung imaging as a study component are interested in phenotypes relating airway branching patterns, wall-thickness, and other morphological measures. To our knowledge, there are no fully automated airway tree segmentation methods, free of the need for user review. Even when there are failures in a small fraction of segmentation results, the airway tree masks must be manually reviewed for all results which is laborious considering that several thousands of image data sets are evaluated in large studies. In this paper, we present a CT-based novel airway tree segmentation algorithm using iterative multi-scale leakage detection, freezing, and active seed detection. The method is fully automated requiring no manual inputs or post-segmentation editing. It uses simple intensity based connectivity and a new leakage detection algorithm to iteratively grow an airway tree starting from an initial seed inside the trachea. It begins with a conservative threshold and then, iteratively shifts toward generous values. The method was applied on chest CT scans of ten non-smoking subjects at total lung capacity and ten at functional residual capacity. Airway segmentation results were compared to an expert's manually edited segmentations. Branch level accuracy of the new segmentation method was examined along five standardized segmental airway paths (RB1, RB4, RB10, LB1, LB10) and two generations beyond these branches. The method successfully detected all branches up to two generations beyond these segmental bronchi with no visual leakages.

Structural Development, Cellular Differentiation and Proliferation of the Respiratory Epithelium in the Bovine Fetal Lung.

PubMed

Drozdowska, J; Cousens, C; Finlayson, J; Collie, D; Dagleish, M P

2016-01-01

Fetal bovine lung samples of 11 different gestational ages were assigned to a classical developmental stage based on histological morphology. Immunohistochemistry was used to characterize the morphology of forming airways, proliferation rate of airway epithelium and the presence of epithelial cell types (i.e. ciliated cells, club cells, neuroepithelial cells (NECs) and type II pneumocytes). Typical structural organization of pseudoglandular (84-98 days gestational age [DGA]), canalicular (154-168 DGA) and alveolar (224-266 DGA) stages was recognized. In addition, transitional pseudoglandular-canalicular (112-126 DGA) and canalicular-saccular (182 DGA) morphologies were present. The embryonic stage was not observed. A significantly (P <0.05) higher proliferation rate of pulmonary epithelium, on average 5.5% and 4.4% in bronchi and bronchioles, respectively, was present in the transitional pseudoglandular-canalicular phase (112-126 DGA) compared with all other phases, while from 8 weeks before term (224-266 DGA) proliferation had almost ceased. The first epithelial cells identified by specific marker proteins in the earliest samples available for study (84 DGA) were ciliated cells and NECs. Club cells were present initially at 112 DGA and type II pneumocytes at 224 DGA. At the latest time points (224-226 DGA) these latter cell types were still present at a much lower percentage compared with adult cattle. This study characterized bovine fetal lung development by histological morphology and cellular composition of the respiratory epithelium and suggests that the apparent structural anatomical maturity of the bovine lung at term is not matched by functional maturity of the respiratory epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Observation of cardiogenic flow oscillations in healthy subjects with hyperpolarized 3He MRI

PubMed Central

Collier, Guilhem J.; Marshall, Helen; Rao, Madhwesha; Stewart, Neil J.; Capener, David

2015-01-01

Recently, dynamic MRI of hyperpolarized 3He during inhalation revealed an alternation of the image intensity between left and right lungs with a cardiac origin (Sun Y, Butler JP, Ferrigno M, Albert MS, Loring SH. Respir Physiol Neurobiol 185: 468–471, 2013). This effect is investigated further using dynamic and phase-contrast flow MRI with inhaled 3He during slow inhalations (flow rate ∼100 ml/s) to elucidate airflow dynamics in the main lobes in six healthy subjects. The ventilation MR signal and gas inflow in the left lower lobe (LLL) of the lungs were found to oscillate clearly at the cardiac frequency in all subjects, whereas the MR signals in the other parts of the lungs had a similar oscillatory behavior but were smaller in magnitude and in anti-phase to the signal in the left lower lung. The airflow in the main bronchi showed periodic oscillations at the frequency of the cardiac cycle. In four of the subjects, backflows were observed for a short period of time of the cardiac cycle, demonstrating a pendelluft effect at the carina bifurcation between the left and right lungs. Additional 1H structural MR images of the lung volume and synchronized ECG recording revealed that maximum inspiratory flow rates in the LLL of the lungs occurred during systole when the corresponding left lung volume increased, whereas the opposite effect was observed during diastole, with gas flow redirected to the other parts of the lung. In conclusion, cardiogenic flow oscillations have a significant effect on regional gas flow and distribution within the lungs. PMID:26338461

Application of adjusted subpixel method (ASM) in HRCT measurements of the bronchi in bronchial asthma patients and healthy individuals.

PubMed

Mincewicz, Grzegorz; Rumiński, Jacek; Krzykowski, Grzegorz

2012-02-01

Recently, we described a model system which included corrections of high-resolution computed tomography (HRCT) bronchial measurements based on the adjusted subpixel method (ASM). To verify the clinical application of ASM by comparing bronchial measurements obtained by means of the traditional eye-driven method, subpixel method alone and ASM in a group comprised of bronchial asthma patients and healthy individuals. The study included 30 bronchial asthma patients and the control group comprised of 20 volunteers with no symptoms of asthma. The lowest internal and external diameters of the bronchial cross-sections (ID and ED) and their derivative parameters were determined in HRCT scans using: (1) traditional eye-driven method, (2) subpixel technique, and (3) ASM. In the case of the eye-driven method, lower ID values along with lower bronchial lumen area and its percentage ratio to total bronchial area were basic parameters that differed between asthma patients and healthy controls. In the case of the subpixel method and ASM, both groups were not significantly different in terms of ID. Significant differences were observed in values of ED and total bronchial area with both parameters being significantly higher in asthma patients. Compared to ASM, the eye-driven method overstated the values of ID and ED by about 30% and 10% respectively, while understating bronchial wall thickness by about 18%. Results obtained in this study suggest that the traditional eye-driven method of HRCT-based measurement of bronchial tree components probably overstates the degree of bronchial patency in asthma patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The role of substance P in inflammatory disease.

PubMed

O'Connor, Terence M; O'Connell, Joseph; O'Brien, Darren I; Goode, Triona; Bredin, Charles P; Shanahan, Fergus

2004-11-01

The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease. Copyright 2004 Wiley-Liss, Inc.

A volumetric pulmonary CT segmentation method with applications in emphysema assessment

NASA Astrophysics Data System (ADS)

Silva, José Silvestre; Silva, Augusto; Santos, Beatriz S.

2006-03-01

A segmentation method is a mandatory pre-processing step in many automated or semi-automated analysis tasks such as region identification and densitometric analysis, or even for 3D visualization purposes. In this work we present a fully automated volumetric pulmonary segmentation algorithm based on intensity discrimination and morphologic procedures. Our method first identifies the trachea as well as primary bronchi and then the pulmonary region is identified by applying a threshold and morphologic operations. When both lungs are in contact, additional procedures are performed to obtain two separated lung volumes. To evaluate the performance of the method, we compared contours extracted from 3D lung surfaces with reference contours, using several figures of merit. Results show that the worst case generally occurs at the middle sections of high resolution CT exams, due the presence of aerial and vascular structures. Nevertheless, the average error is inferior to the average error associated with radiologist inter-observer variability, which suggests that our method produces lung contours similar to those drawn by radiologists. The information created by our segmentation algorithm is used by an identification and representation method in pulmonary emphysema that also classifies emphysema according to its severity degree. Two clinically proved thresholds are applied which identify regions with severe emphysema, and with highly severe emphysema. Based on this thresholding strategy, an application for volumetric emphysema assessment was developed offering new display paradigms concerning the visualization of classification results. This framework is easily extendable to accommodate other classifiers namely those related with texture based segmentation as it is often the case with interstitial diseases.

Quantitative and qualitative computed tomographic characteristics of bronchiectasis in 12 dogs.

PubMed

Cannon, Matthew S; Johnson, Lynelle R; Pesavento, Patricia A; Kass, Philip H; Wisner, Erik R

2013-01-01

Bronchiectasis is an irreversible dilatation of the bronchi resulting from chronic airway inflammation. In people, computed tomography (CT) has been described as the noninvasive gold standard for diagnosing bronchiectasis. In dogs, normal CT bronchoarterial ratios have been described as <2.0. The purpose of this retrospective study was to describe quantitative and qualitative CT characteristics of bronchiectasis in a cohort of dogs with confirmed disease. Inclusion criteria for the study were thoracic radiography, thoracic CT, and a diagnosis of bronchiectasis based on bronchoscopy and/or histopathology. For each included dog, a single observer measured CT bronchoarterial ratios at 6 lobar locations. Qualitative thoracic radiography and CT characteristics were recorded by consensus opinion of two board-certified veterinary radiologists. Twelve dogs met inclusion criteria. The mean bronchoarterial ratio from 28 bronchiectatic lung lobes was 2.71 ± 0.80 (range 1.4 to 4.33), and 23/28 measurements were >2.0. Averaged bronchoarterial ratios from bronchiectatic lung lobes were significantly larger (P < 0.01) than averaged ratios from nonbronchiectatic lung lobes. Qualitative CT characteristics of bronchiectasis included lack of peripheral airway tapering (12/12), lobar consolidation (11/12), bronchial wall thickening (7/12), and bronchial lumen occlusion (4/12). Radiographs detected lack of airway tapering in 7/12 dogs. In conclusion, the most common CT characteristics of bronchiectasis were dilatation, a lack of peripheral airway tapering, and lobar consolidation. Lack of peripheral airway tapering was not visible in thoracic radiographs for some dogs. For some affected dogs, bronchoarterial ratios were less than published normal values. © 2013 Veterinary Radiology & Ultrasound.

Deletion of Pten Expands Lung Epithelial Progenitor Pools and Confers Resistance to Airway Injury

PubMed Central

Tiozzo, Caterina; De Langhe, Stijn; Yu, Mingke; Londhe, Vedang A.; Carraro, Gianni; Li, Min; Li, Changgong; Xing, Yiming; Anderson, Stewart; Borok, Zea; Bellusci, Saverio; Minoo, Parviz

2009-01-01

Rationale: Pten is a tumor-suppressor gene involved in stem cell homeostasis and tumorigenesis. In mouse, Pten expression is ubiquitous and begins as early as 7 days of gestation. Pten−/− mouse embryos die early during gestation indicating a critical role for Pten in embryonic development. Objectives: To test the role of Pten in lung development and injury. Methods: We conditionally deleted Pten throughout the lung epithelium by crossing Ptenflox/flox with Nkx2.1-cre driver mice. The resulting PtenNkx2.1-cre mutants were analyzed for lung defects and response to injury. Measurements and Main Results: PtenNkx2.1-cre embryonic lungs showed airway epithelial hyperplasia with no branching abnormalities. In adult mice, PtenNkx2.1-cre lungs exhibit increased progenitor cell pools composed of basal cells in the trachea, CGRP/CC10 double-positive neuroendocrine cells in the bronchi, and CC10/SPC double-positive cells at the bronchioalveolar duct junctions. Pten deletion affected differentiation of various lung epithelial cell lineages, with a decreased number of terminally differentiated cells. Over time, PtenNxk2.1-cre epithelial cells residing in the bronchioalveolar duct junctions underwent proliferation and formed uniform masses, supporting the concept that the cells residing in this distal niche may also be the source of procarcinogenic stem cells. Finally, increased progenitor cells in all the lung compartments conferred an overall selective advantage to naphthalene injury compared with wild-type control mice. Conclusions: Pten has a pivotal role in lung stem cell homeostasis, cell differentiation, and consequently resistance to lung injury. PMID:19574443

Global impact of bronchiectasis and cystic fibrosis

PubMed Central

Redondo, Margarida; Keyt, Holly; Dhar, Raja

2016-01-01

Educational aims To recognise the clinical and radiological presentation of the spectrum of diseases associated with bronchiectasis. To understand variation in the aetiology, microbiology and burden of bronchiectasis and cystic fibrosis across different global healthcare systems. Bronchiectasis is the term used to refer to dilatation of the bronchi that is usually permanent and is associated with a clinical syndrome of cough, sputum production and recurrent respiratory infections. It can be caused by a range of inherited and acquired disorders, or may be idiopathic in nature. The most well recognised inherited disorder in Western countries is cystic fibrosis (CF), an autosomal recessive condition that leads to progressive bronchiectasis, bacterial infection and premature mortality. Both bronchiectasis due to CF and bronchiectasis due to other conditions are placing an increasing burden on healthcare systems internationally. Treatments for CF are becoming more effective leading to more adult patients with complex healthcare needs. Bronchiectasis not due to CF is becoming increasingly recognised, particularly in the elderly population. Recognition is important and can lead to identification of the underlying cause, appropriate treatment and improved quality of life. The disease is highly diverse in its presentation, requiring all respiratory physicians to have knowledge of the different “bronchiectasis syndromes”. The most common aetiologies and presenting syndromes vary depending on geography, with nontuberculous mycobacterial disease predominating in some parts of North America, post-infectious and idiopathic disease predominating in Western Europe, and post-tuberculosis bronchiectasis dominating in South Asia and Eastern Europe. Ongoing global collaborative studies will greatly advance our understanding of the international impact of bronchiectasis and CF. PMID:28210295

Unique characteristics of the trachea of the juvenile leatherback turtle facilitate feeding, diving and endothermy

USGS Publications Warehouse

Davenport, John; Jones, T. Todd; Work, Thierry M.; Balazs, George H.

2014-01-01

The adult leatherback turtle Dermochelys coriacea overlaps in body size (300–500 kg) with many marine mammals, yet develops from a 50 g hatchling. Adults can dive deeper than 1200 m and have core body temperatures of 25 °C; hatchlings are near-surface dwellers. Juvenile leatherbacks have rarely been studied; here we present anatomical information for the upper respiratory tract of 3 turtles (66.7–83.0 cm straight carapace length; 33.2–53.4 kg body mass) incidentally captured by long-line fisheries. Combined with existing information from adults and hatchlings, our data show that there is an ontogenic shift in tracheal structure, with cartilaginous rings becoming broader and eventually fusing anteriorly. This ontogenic shift during independent existence is unique among extant deep-diving air breathing vertebrates. Tract wall thickness is graded, becoming progressively thinner from larynx to bronchi. In addition, cross-sectional shape becomes increasingly dorsoventrally flattened (more elliptical) from anterior to posterior. These characteristics ensure that the tract will collapse from posterior to anterior during dives. This study contains the first report of a double (= internally bifurcated) posterior section of the trachea; it is suggested that this allows continuous food movement along the esophagus without tracheal collapse. The whole upper respiratory tract (from larynx to lungs) has a vascular lining (thicker anteriorly than posteriorly) that appears to be a simple analog of the complex turbinates of birds and mammals. Our study confirmed that the leatherback tracheal structure represents a distinctive way of dealing with the challenges of diving in deep, cold sea water.

Metallic Stents for Tracheobronchial Pathology Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serrano, Carolina, E-mail: carolina.serrano@unizar.es; Laborda, Alicia, E-mail: alaborda@unizar.es; Lozano, Juan M., E-mail: juamauloz@gmail.com

2013-12-15

Purpose: To present the 7-year experience of the treatment of benign and malignant tracheobronchial stenoses using metallic stents. Patients and Methods: One hundred twenty-three stents were inserted in 86 patients (74 benign and 12 malignant stenoses). Ninety-seven stents were placed in the trachea and 26 in the bronchi. The procedures were performed under fluoroscopic and flexible bronchoscopic guidance with the patient under light sedation. In cases of severe stenotic lesions or obstructions, laser resection was performed before stent placement. Clinical and functional pulmonary data were recorded before and 3 months after the procedure. Follow-up involved clinical data and radiographic techniquesmore » at 48 h and at 1-, 3-, 6-, and 12-month intervals. Results: The technical success was 100 %. Dyspnea disappearance, forced expiratory volume in the first second, and pulmonary functional data improvement was observed in all patients (p < 0.001). Complications were detected in 23 patients (26.7 %). Mean follow-up time was 6.3 {+-} 1.2 months in patients with malignant lesions and 76.2 {+-} 2.3 months patients with in benign lesions. By the end of the study, 100 % of patients with malignant pathology and 6.7 % of patients with benign lesions had died. Conclusion: Endoluminal treatment of tracheobronchial stenosis with metallic stents is a therapeutic alternative in patients who are poor candidates for surgery. In unresectable malignant lesions, the benefit of metallic stenting is unquestionable. In benign lesions, the results are satisfactory, but sometimes other interventions are required to treat complications. New stent technology may improve these results.« less

Upregulation of Mas-related G Protein coupled receptor X2 in asthmatic lung mast cells and its activation by the novel neuropeptide hemokinin-1.

PubMed

Manorak, Wichayapha; Idahosa, Chizobam; Gupta, Kshitij; Roy, Saptarshi; Panettieri, Reynold; Ali, Hydar

2018-01-03

Hemokinin-1 (HK-1) is a novel neuropeptide produced by human bronchial cells and macrophages and causes contraction of human bronchi ex vivo. It is also generated by antigen/IgE-activated murine mast cells (MCs) and contributes to experimental chronic allergic airway inflammation via the activation of the neurokinin receptor-1 (NK-1R) expressed on murine MCs. We found elevated MC numbers in the lungs of individuals who died from asthma (asthma) when compared to lungs of individuals who died from other causes (non-asthma). Mas-related G Protein coupled receptor X2 (MRGPRX2) is a novel G-protein coupled receptor (GPCR) that is expressed predominantly on human MCs. We detected low level of MRGPRX2 in non-asthma lung MCs but its expression was significantly upregulated in asthma lung MCs. HK-1 caused degranulation in a human MC line (LAD2) and RBL-2H3 cells stably expressing MRGPRX2 and this response was resistant to inhibition by an NK-1R antagonist. However, knockdown of MRGPRX2 in LAD2 cells resulted in substantial inhibition of HK-1-induced degranulation. These findings suggest that while HK-1 contributes to the development of experimental asthma in mice via NK-1R on murine MCs the effect of this neuropeptide on human bronchoconstriction likely reflects the activation of MRGPRX2 on lung MCs. Thus, development of selective MRGPRX2 antagonists could serve as novel target for the modulation of asthma.

Airway hyperresponsiveness; smooth muscle as the principal actor

PubMed Central

Lauzon, Anne-Marie; Martin, James G.

2016-01-01

Airway hyperresponsiveness (AHR) is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM) contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway. PMID:26998246

The effect of inhaled K+ channel openers on bronchoconstriction and airway microvascular leakage in anaesthetised guinea pigs.

PubMed

Kidney, J C; Lotvall, J O; Lei, Y; Chung, K F; Barnes, P J

1996-01-18

Since orally administered K+ channel openers may have cardiovascular side effects, it is possible that inhaled administration would be preferred for the treatment of asthma. We have investigated whether inhaled levcromakalim and HOE 234 inhibit histamine-induced bronchoconstriction and airway plasma exudation in anaesthetised guinea pigs. We have also investigated whether inhaled HOE 234 inhibits the bronchoconstriction and plasma exudation induced by vagus nerve stimulation, which is due to the release of tachykinins from sensory nerves. Lung resistance was measured by airway resistance (RL) computed from airway and transpulmonary pressures and plasma exudation by measurement of Evans blue dye extravasation. Inhaled levcromakalim (25 mu g/ml) had a short duration of action, being effective against histamine-induced bronchoconstriction 2 min after pretreatment, but not at 10 min. Inhaled HOE 234 (25 mu g/ml) was similarly effective against histamine-induced bronchoconstriction but had a longer duration of action. Inhaled levcromakalim partially attenuated histamine-induced plasma extravasation in small airways, but not in the trachea or main bronchi, whereas inhaled HOE 234 had no effect. HOE 234 protected against non-adrenergic non-cholinergic nerve-induced bronchoconstriction, but had no effect on neurogenic- or substance P-induced plasma extravasation in the airway. Inhaled K+ channel openers protect against induced bronchoconstriction, but provide little or no protection against plasma exudation, possibly because of an increase in airway blood flow. In addition, inhaled HOE 234 had no effect on neurogenic leakage, suggesting that its vagal inhibitory effect on bronchoconstriction was on airway smooth muscle, rather than on release of neuropeptides from sensory nerves.

Effects of sodium metabisulphite on guinea pig contractile airway smooth muscle responses in vitro.

PubMed

Sun, J; Sakamoto, T; Chung, K F

1995-08-01

Sodium metabisulphite (MBS) is known to induce bronchoconstriction in asthmatic patients. The effects of MBS on guinea pig airway smooth muscle and on neurally mediated contraction in vitro have been examined. Tracheal and bronchial airway segments were placed in oxygenated buffer solution and electrical field stimulation was performed in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M) for the measurement of isometric tension. Atropine (10(-6) M) was added to bronchial tissues. Concentrations of MBS up to 10(-3) M had no direct effect on airway smooth muscle contraction and did not alter either tracheal smooth muscle contraction induced by electrical field stimulation at all frequencies or acetylcholine-induced tracheal smooth muscle contraction. There was a similar response in the absence of epithelium, except for potentiation of the response induced by electrical field stimulation at 0.5 Hz (24 (10)% increase). However, MBS (10(-5), 10(-6) and 10(-7) M) augmented neurally-mediated non-adrenergic non-cholinergic contractile responses in the bronchi (13.3 (3.2)%, 23.8 (9.6)%, and 6.4 (1.6)%, respectively). MBS had no effect on the contractile response induced by substance P, but at higher concentrations (10(-3) M and 10(-4) M) it caused a time-dependent attenuation of responses induced by either electrical field stimulation or exogenously applied acetylcholine or substance P. MBS had no direct contractile responses but enhanced bronchoconstriction induced by activation of non-cholinergic neural pathways in the bronchus, probably through increased release of neuropeptides. At high concentrations MBS inhibited contractile responses initiated by receptor or neural stimulation.

Attenuation of tachykinin-induced airflow obstruction and microvascular leakage in immature airways.

PubMed Central

Tokuyama, K.; Yokoyama, T.; Morikawa, A.; Mochizuki, H.; Kuroume, T.; Barnes, P. J.

1993-01-01

1. To study the effect of maturation on substance P (SP)- and neurokinin A (NKA)-induced airflow obstruction and airway microvascular leakage (MVL), we have measured changes in both lung resistance (RL) and extravasation of Evans blue dye in anaesthetized immature (aged 14 +/- 1 days) and adult guinea-pigs (aged 80 +/- 3 days). 2. RL and its recovery after hyperinflation at 5 min were measured for 6 min after i.v. SP (0.2, 1 and 30 nmol kg-1), NKA (1 and 10 nmol kg-1) or vehicle (0.9% NaCl). After measurement of RL, MVL in trachea, main bronchi and intrapulmonary airways was also examined. 3. The order of potency in inducing airflow obstruction did not change with age (NKA > SP) but immature animals required a larger dose of SP or NKA than adults to cause a significant increase in RL. 4. The order of potency in inducing airway microvascular leakage was SP > NKA in both immature and adult animals. The amount of extravasated dye after SP was significantly less in immature airways, especially in central airways. 5. Phosphoramidon (2.5 mg kg-1), a neutral endopeptidase (NEP) inhibitor, significantly increased RL after 0.2 nmol kg-1 SP only in adult airways. Phosphoramidon enhanced the dye extravasation after 0.2 nmol kg-1 SP in both immature and adult airways with a significantly greater amount of dye in adult animals, suggesting that mechanisms other than changes in NEP activity may be responsible for this age-related difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7679033

Inhibition of excitatory non-adrenergic non-cholinergic bronchoconstriction in guinea-pig airways in vitro by activation of an atypical 5-HT receptor.

PubMed

Ward, J K; Fox, A J; Barnes, P J; Belvisi, M G

1994-04-01

1. The effect of 5-hydroxytryptamine (5-HT) was studied on excitatory neurally mediated non-adrenergic non-cholinergic (NANC) contractions evoked by electrical field stimulation (EFS) in guinea-pig isolated bronchi. 2. 5-HT (0.1-100 microM) produced a concentration-dependent inhibition of the excitatory NANC response with 50.9 +/- 5.0% (n = 5, P < 0.01) inhibition at 100 microM. This inhibition was not significantly affected by the 5-HT2 antagonist, ketanserin (1 microM) when inhibitions (+/- ketanserin) at each concentration of 5-HT were compared by unpaired t tests; however, this concentration appeared to produce a leftward shift (approximately 10 fold) of the 5-HT concentration-inhibition curve. Ketanserin (1 microM) was effective in blocking bronchoconstriction evoked by activation of 5-HT2A receptors on airway smooth muscle. In the presence of ketanserin (1 microM) 5-HT (100 microM) evoked an inhibition of 57.4 +/- 5.9% (n = 5, P < 0.01) with an EC50 of 0.57 microM. 3. Inhibition evoked by 5-HT (0.1-100 microM) was unaffected by the alpha-adrenoceptor antagonist phentolamine (1 microM), the beta 2-adrenoceptor antagonist, ICI 118551 (0.1 microM), the 5-HT1A/B antagonist, cyanopindolol (1 microM) or the 5-HT3/4 antagonist, ICS 205-930 (1 microM). 4. Methiothepin (0.1 microM) produced an insurmountable inhibition of the effect of 5-HT (0.1-100 microM), reducing the maximum inhibition produced by 5-HT (100 microM) to 30.2 +/- 5.0% (n = 5, P < 0.001) and suggesting a non-competitive antagonism. Methiothepin inhibited the effect of 5-HT (10 microM) in a concentration-dependent manner with an IC50 of 81 nM. 5. Selective 5-HT receptor agonists were also tested on excitatory NANC responses. 5-Carboxamidotryptamine (5-CT, 0.1-100 MicroM) was the most potent, producing a concentration-dependent inhibition with an EC50 of 0.13 MicroM. Calculation of approximate IC25 values (concentration of the agonist required to give a 25% inhibition of the excitatory NANC response) gave a rank order of potency 5-CT > 5-HT> > 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) >alpha-methyl-5-hydroxytryptamine (alpha-Me-5HT). Sumatriptan, 5-methoxytryptamine (5-MeOT) and 2-methyl-5-hydroxytryptamine (2-Me-5HT) were essentially inactive with IC25> 100 MicroM.6. 5-HT (10 microM) did not significantly affect contractile responses to exogenously applied substance P(1 nM-10 Microm).7. The effect of 5-HT was unchanged after incubation with the nitric oxide (NO) synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 100 Microm). However, pretreatment with charybdotoxin (ChTX,0.1-30 nM), a blocker of the large conductance Ca2+-activated K+channel (K+ca), produced a concentration-dependent inhibition of the effect of 5-HT (10 MicroM).8. 5-HT evokes a concentration-dependent inhibition of e-NANC bronchoconstriction in guinea-pig isolated bronchi but does not affect cumulative concentration-dependent contractile responses to substance P, suggesting that inhibition is via a prejunctional receptor. Effects of selective antagonists and agonists suggest that an atypical 5-HT receptor mediates this inhibition. The inhibitory effect of 5-HT does not involve the production of NO, but may involve the opening a ChTX-sensitive K+ca channel.These data suggest that an atypical 5-HT receptor inhibits the release of neuropeptides from sensory C fibres and may act as other inhibitory neuromodulators via the opening of a common K'channel.

Automated extraction of pleural effusion in three-dimensional thoracic CT images

NASA Astrophysics Data System (ADS)

Kido, Shoji; Tsunomori, Akinori

2009-02-01

It is important for diagnosis of pulmonary diseases to measure volume of accumulating pleural effusion in threedimensional thoracic CT images quantitatively. However, automated extraction of pulmonary effusion correctly is difficult. Conventional extraction algorithm using a gray-level based threshold can not extract pleural effusion from thoracic wall or mediastinum correctly, because density of pleural effusion in CT images is similar to those of thoracic wall or mediastinum. So, we have developed an automated extraction method of pulmonary effusion by use of extracting lung area with pleural effusion. Our method used a template of lung obtained from a normal lung for segmentation of lungs with pleural effusions. Registration process consisted of two steps. First step was a global matching processing between normal and abnormal lungs of organs such as bronchi, bones (ribs, sternum and vertebrae) and upper surfaces of livers which were extracted using a region-growing algorithm. Second step was a local matching processing between normal and abnormal lungs which were deformed by the parameter obtained from the global matching processing. Finally, we segmented a lung with pleural effusion by use of the template which was deformed by two parameters obtained from the global matching processing and the local matching processing. We compared our method with a conventional extraction method using a gray-level based threshold and two published methods. The extraction rates of pleural effusions obtained from our method were much higher than those obtained from other methods. Automated extraction method of pulmonary effusion by use of extracting lung area with pleural effusion is promising for diagnosis of pulmonary diseases by providing quantitative volume of accumulating pleural effusion.

Visualization of ex vivo human ciliated epithelium and induced flow using optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ling, Yuye; Gamm, Uta A.; Yao, Xinwen; Arteaga-Solis, Emilio; Emala, Charles W.; Choma, Michael A.; Hendon, Christine P.

2017-04-01

The ciliated epithelium is important to the human respiratory system because it clears mucus that contains harmful microorganisms and particulate matter. We report the ex vivo visualization of human trachea/bronchi ciliated epithelium and induced flow characterized by using spectral-domain optical coherence tomography (SD-OCT). A total number of 17 samples from 7 patients were imaged. Samples were obtained from Columbia University Department of Anesthesiology's tissue bank. After excision, the samples were placed in Gibco Medium 199 solution with oxygen at 4°C until imaging. The samples were maintained at 36.7°C throughout the experiment. The imaging protocol included obtaining 3D volumes and 200 consecutive B-scans parallel to the head-to-feet direction (superior-inferior axis) of the airway, using Thorlabs Telesto system at 1300 nm at 28 kHz A-line rate and a custom built high resolution SDOCT system at 800nm at 32 kHz A-line rate. After imaging, samples were processed with H and E histology. Speckle variance of the time resolved datasets demonstrate significant contrast at the ciliated epithelium sites. Flow images were also obtained after injecting 10μm polyester beads into the solution, which shows beads traveling trajectories near the ciliated epithelium areas. In contrary, flow images taken in the orthogonal plane show no beads traveling trajectories. This observation is in line with our expectation that cilia drive flow predominantly along the superior-inferior axis. We also observed the protective function of the mucus, shielding the epithelium from the invasion of foreign objects such as microspheres. Further studies will be focused on the cilia's physiological response to environmental changes such as drug administration and physical injury.

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Increases the Yield of Transbronchial Lung Biopsy for the Evaluation of Peribronchial Lesions

PubMed Central

Chen, Cheng; Mu, Chuan-Yong; Su, Mei-Qin; Mao, Jing-Yu; Zhu, Ye-Han; Huang, Jian-An

2017-01-01

Background: Due to absence of visible endobronchial target, the diagnostic yield of flexible bronchoscopy for peribronchial lesions has been unsatisfactory. Convex probe endobronchial ultrasound (CP-EBUS) has allowed for performing real-time transbronchial needle aspiration (TBNA) of enlarged hilar and mediastinal lymph nodes and therefore could also be used as a means of diagnosing proximal peribronchial lesions. Methods: We retrospectively analyzed the results related to 72 patients who underwent CP-EBUS for peribronchial lesions without endobronchial involvement and adjacent to three-grade bronchi based on chest computed tomography (CT) scan. We recorded the images during EBUS as well as the diagnostic results of TBNA and conventional-transbronchial lung biopsy/brush (C-TBLB/b), and final diagnoses were based on pathologic analysis and follow-up. Results: In all cases, the mass was able to be identified using EBUS in 97.2% patients (70/72) who were performed with EBUS-TBNA + C-TBLB/b. Sixty-six patients had a final diagnosis, 80.0% patients (56/70) had malignancies, and 14.3% patients (10/70) had benign disease. In malignancies, the diagnostic yield of C-TBLB/b was 57.1% (32/56) and in EBUS-TBNA was 85.7% (48/56), whereas pathologic diagnosis reached 94.6% when EBUS-TBNA was combined with C-TBLB/b. C-TBLB/b + EBUS-TBNA also exhibited stronger potency of histolytic diagnosis for malignancies than either EBUS-TBNA or C-TBLB/b alone. Furthermore, there are data supporting the value of EBUS-TBNA for the diagnosis of benign lung disease. Conclusion: The combined endoscopic approach with EBUS-TBNA and C-TBLB/b is an accurate and effective method for the evaluation of peribronchial lesions, with better results than using each technique alone. PMID:28051017

Chronic Obstructive Pulmonary Disease Exacerbations in the COPDGene Study: Associated Radiologic Phenotypes

PubMed Central

Kazerooni, Ella A.; Lynch, David A.; Liu, Lyrica X.; Murray, Susan; Curtis, Jeffrey L.; Criner, Gerard J.; Kim, Victor; Bowler, Russell P.; Hanania, Nicola A.; Anzueto, Antonio R.; Make, Barry J.; Hokanson, John E.; Crapo, James D.; Silverman, Edwin K.; Martinez, Fernando J.; Washko, George R.

2011-01-01

Purpose: To test the hypothesis—given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)—that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease. Materials and Methods: This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a −950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements. Results: In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047). Conclusion: Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110173/-/DC1 PMID:21788524

Relationship between Quantitative CT Metrics and Health Status and Bode in COPD

PubMed Central

Martinez, Carlos H.; Chen, Ya-Hong; Westgate, Phillip M.; Liu, Lyrica X.; Murray, Susan; Curtis, Jeffrey L.; Make, Barry J.; Kazerooni, Ella A.; Lynch, David A.; Marchetti, Nathaniel; Washko, George R.; Martinez, Fernando J.; Han, MeiLan K.

2013-01-01

Background The value of quantitative computed tomography (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. We hypothesized that QCT-defined emphysema and airway abnormalities relate to St. George's Respiratory Questionnaire (SGRQ) and BODE. Methods 1,200 COPDGene subjects meeting GOLD criteria for COPD with QCT analysis were included. Total lung emphysema was measured using density mask technique with a -950 HU threshold. An automated program measured mean wall thickness (WT), wall area percent (WA%) and pi10 in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE. Results In separate models predicting SGRQ score, a one unit standard deviation (SD) increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p<0.001). The comparable increase in SGRQ for a one unit SD increase in percent emphysema in these models was relatively weaker, significant only in the pi10 model (for percent emphysema, 1.45 points higher, p=0.01). In separate models predicting BODE, a one unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07 fold increase, p<0.001; for WA%, 1.20 fold increase, p<0.001; for pi10, 1.16 fold increase, p<0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26 fold increase, p<0.001). Conclusion Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE. PMID:22514236

Multiple endocrine neoplasia type 1

PubMed Central

Marini, Francesca; Falchetti, Alberto; Monte, Francesca Del; Sala, Silvia Carbonell; Gozzini, Alessia; Luzi, Ettore; Brandi, Maria Luisa

2006-01-01

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. PMID:17014705

Bronchoscopy, Imaging, and Concurrent Diseases in Dogs with Bronchiectasis: (2003-2014).

PubMed

Johnson, L R; Johnson, E G; Vernau, W; Kass, P H; Byrne, B A

2016-01-01

Bronchiectasis is a permanent and debilitating sequel to chronic or severe airway injury, however, diseases associated with this condition are poorly defined. To evaluate results of diagnostic tests used to document bronchiectasis and to characterize underlying or concurrent disease processes. Eighty-six dogs that had bronchoscopy performed and a diagnosis of bronchiectasis. Retrospective case series. Radiographs, computed tomography, and bronchoscopic findings were evaluated for features of bronchiectasis. Clinical diagnoses of pneumonia (aspiration, interstitial, foreign body, other), eosinophilic bronchopneumopathy (EBP), and inflammatory airway disease (IAD) were made based on results of history, physical examination, and diagnostic testing, including bronchoalveolar lavage fluid analysis and microbiology. Bronchiectasis was diagnosed in 14% of dogs (86/621) that had bronchoscopy performed. Dogs ranged in age from 0.5 to 14 years with duration of signs from 3 days to 10 years. Bronchiectasis was documented during bronchoscopy in 79/86 dogs (92%), thoracic radiology in 50/83 dogs (60%), and CT in 34/34 dogs (100%). Concurrent airway collapse was detected during bronchoscopy in 50/86 dogs (58%), and focal or multifocal mucus plugging of segmental or subsegmental bronchi was found in 41/86 dogs (48%). Final diagnoses included pneumonia (45/86 dogs, 52%), EBP (10/86 dogs, 12%) and IAD (31/86 dogs, 36%). Bacteria were isolated in 24/86 cases (28%), with Streptococcus spp, Pasteurella spp, enteric organisms, and Stenotrophomonas isolated most frequently. Bronchiectasis can be anticipated in dogs with infectious or inflammatory respiratory disease. Advanced imaging and bronchoscopy are useful in making the diagnosis and identifying concurrent respiratory disease. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Non-adrenergic, non-cholinergic neural activation in guinea-pig bronchi: powerful and frequency-dependent stabilizing effect on tone.

PubMed Central

Lindén, A.; Ullman, A.; Löfdahl, C. G.; Skoogh, B. E.

1993-01-01

1. We examined non-adrenergic, non-cholinergic (NANC) stimulation for its stabilizing effect on bronchial smooth-muscle tone with respect to its regulatory power and the effect of variations in neural impulse frequency. 2. The guinea-pig isolated main bronchus (n = 4-12) was pretreated with indomethacin (10 microM) and incubated with atropine (1 microM) and guanethidine (10 microM). Electrical field stimulation (EFS: 1200 mA, 0.5 ms, 240 s) was applied at various levels of tone prior to EFS: first without tone, then at a moderate tone induced by histamine (0.3 microM) and, finally, at a high tone induced by histamine (6 microM). Three different stimulation frequencies (1, 3 or 10 Hz) were used in order to produce moderate to near-maximum contractile and relaxant NANC neural responses. Both the contractile and the relaxant NANC responses were tetrodotoxin-sensitive in the guinea-pig isolated main bronchus (3 Hz). 3. Without tone prior to EFS, NANC activation (1, 3 or 10 Hz) induced a pronounced contractile response. At a moderate level of tone prior to EFS, NANC activation induced a less pronounced contractile response. At the highest level of tone prior to EFS, NANC activation induced a relaxant response. All these NANC responses adjusted the tone towards a similar level and this 'stabilization level' was 56(6)% at 1 Hz, 65(3)% at 3 Hz and 56(5)% at 10 Hz, expressed as a percentage of the maximum histamine-induced (0.1 mM) tone in each airway preparation. 4. There was a difference of approximately 90% of maximum between the highest and the lowest tone level prior to NANC activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8358575

Expression of alveolar type II cell markers in acinar adenocarcinomas and adenoid cystic carcinomas arising from segmental bronchi. A study in a heterotopic bronchogenic carcinoma model in dogs.

PubMed Central

TenHave-Opbroek, A. A.; Hammond, W. G.; Benfield, J. R.; Teplitz, R. L.; Dijkman, J. H.

1993-01-01

The type II alveolar epithelial cell is one of two pluripotential stem cell phenotypes in normal mammalian lung morphogenesis; cells manifesting this phenotype have been found to constitute bronchioloalveolar regions of canine adenocarcinomas. We now studied type II cell expression in canine acinar adenocarcinomas and adenoid cystic (bronchial gland) carcinomas, using the same bronchogenic carcinoma model (subcutaneous bronchial autografts treated with 3-methylcholanthrene). Distinctive features of type II cells are the approximately cuboid cell shape, large and roundish nucleus, immunofluorescent staining of the cytoplasm for the surfactant protein SP-A, and presence of multilamellar bodies or their precursory forms. Cells with these type II cell characteristics were found in the basal epithelial layer of all tumor lesions and in upper layers as far as the lumen, singly or in clusters; they were also found in early invasive carcinomatous lesions but not in bronchial glands or bronchial epithelium before carcinogen exposure. Immunoblots of tumor homogenates showed reactive proteins within size classes of SP-A (28 to 36 kd) or its dimeric form (56 to 72 kd). These findings and those previously reported are consistent with the concept that chemical carcinogenesis in the adult bronchial epithelium may lead to type II cell carcinomas of varying glandular (acinar, adenoidcystic or bronchioloalveolar) growth patterns. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22 PMID:8386445

Airway remodeling in murine asthma correlates with a defect in PGE2 synthesis by lung fibroblasts

PubMed Central

Stumm, Camila Leindecker; Wettlaufer, Scott H.; Jancar, Sonia

2011-01-01

Asthma is a chronic lung disease characterized by local inflammation that can result in structural alterations termed airway remodeling. One component of airway remodeling involves fibroblast accumulation and activation, resulting in deposition of collagen I around small bronchi. Prostaglandin E2 (PGE2) is the main eicosanoid lipid mediator produced by lung fibroblasts, and it exerts diverse anti-fibrotic actions. Dysregulation of the PGE2 synthesis/response axis has been identified in human pulmonary fibrotic diseases and implicated in the pathogenesis of animal models of lung parenchymal fibrosis. Here we investigated the relationship between the fibroblast PGE2 axis and airway fibrosis in an animal model of chronic allergic asthma. Airway fibrosis increased progressively as the number of airway challenges with antigen increased from 3 to 7 to 12. Compared with cells from control lungs, fibroblasts grown from the lungs of asthmatic animals, regardless of challenge number, exhibited no defect in the ability of PGE2 or its analogs to inhibit cellular proliferation and collagen I expression. This correlated with intact expression of the EP2 receptor, which is pivotal for PGE2 responsiveness. However, cytokine-induced upregulation of PGE2 biosynthesis as well as expression of cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 declined with increasing numbers of antigen challenges. In addition, treatment with the COX-2-selective inhibitor nimesulide potentiated the degree of airway fibrosis following repeated allergen challenge. Because endogenous COX-2-derived PGE2 acts as a brake on airway fibrosis, the inability of fibroblasts to upregulate PGE2 generation in the inflammatory milieu presented by repeated allergen exposure could contribute to the airway remodeling and fibrosis observed in chronic asthma. PMID:21873451

Three-dimensional image reconstruction with free open-source OsiriX software in video-assisted thoracoscopic lobectomy and segmentectomy.

PubMed

Yao, Fei; Wang, Jian; Yao, Ju; Hang, Fangrong; Lei, Xu; Cao, Yongke

2017-03-01

The aim of this retrospective study was to evaluate the practice and the feasibility of Osirix, a free and open-source medical imaging software, in performing accurate video-assisted thoracoscopic lobectomy and segmentectomy. From July 2014 to April 2016, 63 patients received anatomical video-assisted thoracoscopic surgery (VATS), either lobectomy or segmentectomy, in our department. Three-dimensional (3D) reconstruction images of 61 (96.8%) patients were preoperatively obtained with contrast-enhanced computed tomography (CT). Preoperative resection simulations were accomplished with patient-individual reconstructed 3D images. For lobectomy, pulmonary lobar veins, arteries and bronchi were identified meticulously by carefully reviewing the 3D images on the display. For segmentectomy, the intrasegmental veins in the affected segment for division and the intersegmental veins to be preserved were identified on the 3D images. Patient preoperative characteristics, surgical outcomes and postoperative data were reviewed from a prospective database. The study cohort of 63 patients included 33 (52.4%) men and 30 (47.6%) women, of whom 46 (73.0%) underwent VATS lobectomy and 17 (27.0%) underwent VATS segmentectomy. There was 1 conversion from VATS lobectomy to open thoracotomy because of fibrocalcified lymph nodes. A VATS lobectomy was performed in 1 case after completing the segmentectomy because invasive adenocarcinoma was detected by intraoperative frozen-section analysis. There were no 30-day or 90-day operative mortalities CONCLUSIONS: The free, simple, and user-friendly software program Osirix can provide a 3D anatomic structure of pulmonary vessels and a clear vision into the space between the lesion and adjacent tissues, which allows surgeons to make preoperative simulations and improve the accuracy and safety of actual surgery. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Foreign bodies in the upper airways causing complications and requiring hospitalization in children aged 0-14 years: results from the ESFBI study.

PubMed

Gregori, Dario; Salerni, Lorenzo; Scarinzi, Cecilia; Morra, Bruno; Berchialla, Paola; Snidero, Silvia; Corradetti, Roberto; Passali, Desiderio

2008-08-01

Foreign body (FB) aspiration/inhalation is a serious problem because it is still a cause of death in children, especially among those younger than 4 years. The objective of this paper is to characterize the risk of complications and prolonged hospitalization due to foreign bodies (FB) in the upper airways in terms of the characteristics of the injured patients (age, gender), typology and features of the FBs, the circumstances of the accident and the hospitalization details. A retrospective study in the major hospitals of 19 European countries was realized on injuries occurred in the years 2000-2002 and identified by means of the International Classification of Diseases, Ninth Revision (ICD-9) codes listed on hospital discharge records. In 170 cases, it was reported an injury due to the presence of a FB in the pharynx and larynx (ICD933) and in 552 records, it was reported a FB located in the trachea, bronchi and lungs (ICD934). Unlike the complications that occurred in 70 (12.7%) of cases, the hospitalizations were present in 433 (77.6) of the total injuries. One patient died. A higher incidence in males (63%) was observed. Median age for children who experienced complications was 2 years. The most common FB removal technique was laryngoscopy and bronchoscopy. In majority of the cases, children were treated by ENT department. The most common FBs were nuts, seeds, berries, corn and beans. In general, small, round crunchy foods pose a risk of choking. Since prevention is the most essential key to deal with these types of injuries, more effort in caregivers' public education is warranted.

A Diagnostic Dilemma for the Pediatrician: Radiolucent Tracheobronchial Foreign Body.

PubMed

Taşkınlar, Hakan; Bahadır, Gökhan Berktuğ; Erdoğan, Cankat; Yiğit, Doğakan; Avlan, Dinçer; Naycı, Ali

2017-06-01

The purpose of this study is to determine the role of clinical history, physical examinations, and radiological findings in the evaluation of patients with suspected radiolucent foreign body aspiration. The medical records of 236 children (under the age of 18 years), on whom a rigid bronchoscopy was performed between 1999 and 2015 because of suspected radiolucent foreign body aspiration, were analyzed retrospectively. Sensitivity, specificity, positive and negative predictive values of clinical history, physical examinations, and radiological findings were evaluated. In 71.1% of all cases, the children were under the age of 3 years. The bronchoscopy showed the presence of a foreign body in 52.9% of cases, with the locations of the foreign bodies being as follows: (1) right main bronchus, 47.2%; (2) left main bronchus, 36.0%; (3) trachea, 11.2%; (4) both bronchi, 5.6%. Organic foreign bodies were found in 78% of the patients, whereas inorganic foreign bodies were detected in 22% of the patients. The sensitivity and specificity of clinical history, physical examinations, and radiological findings were 98.4% and 54.9%, 47.2% and 74.7%, and 35.2% and 92.7%, respectively. Tracheobronchial foreign body aspirations usually occur prior to the age of 3 years, with the most frequently aspirated foreign bodies being food or items of a radiolucent nature. Clinical history, physical examinations, and radiological findings are not able to detect the presence of a radiolucent foreign body aspiration in children. Therefore, a bronchoscopy should be performed on children in whom a choking event has been witnessed, even in cases of normal radiological and clinical findings. Copyright © 2016. Published by Elsevier B.V.

EG-VEGF, BV8, and their receptor expression in human bronchi and their modification in cystic fibrosis: Impact of CFTR mutation (delF508).

PubMed

Chauvet, Sylvain; Traboulsi, Wael; Thevenon, Laura; Kouadri, Amal; Feige, Jean-Jacques; Camara, Boubou; Alfaidy, Nadia; Benharouga, Mohamed

2015-08-01

Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca(2+) and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion. Copyright © 2015 the American Physiological Society.

Ultra-High-Resolution Computed Tomography of the Lung: Image Quality of a Prototype Scanner.

PubMed

Kakinuma, Ryutaro; Moriyama, Noriyuki; Muramatsu, Yukio; Gomi, Shiho; Suzuki, Masahiro; Nagasawa, Hirobumi; Kusumoto, Masahiko; Aso, Tomohiko; Muramatsu, Yoshihisa; Tsuchida, Takaaki; Tsuta, Koji; Maeshima, Akiko Miyagi; Tochigi, Naobumi; Watanabe, Shun-Ichi; Sugihara, Naoki; Tsukagoshi, Shinsuke; Saito, Yasuo; Kazama, Masahiro; Ashizawa, Kazuto; Awai, Kazuo; Honda, Osamu; Ishikawa, Hiroyuki; Koizumi, Naoya; Komoto, Daisuke; Moriya, Hiroshi; Oda, Seitaro; Oshiro, Yasuji; Yanagawa, Masahiro; Tomiyama, Noriyuki; Asamura, Hisao

2015-01-01

The image noise and image quality of a prototype ultra-high-resolution computed tomography (U-HRCT) scanner was evaluated and compared with those of conventional high-resolution CT (C-HRCT) scanners. This study was approved by the institutional review board. A U-HRCT scanner prototype with 0.25 mm x 4 rows and operating at 120 mAs was used. The C-HRCT images were obtained using a 0.5 mm x 16 or 0.5 mm x 64 detector-row CT scanner operating at 150 mAs. Images from both scanners were reconstructed at 0.1-mm intervals; the slice thickness was 0.25 mm for the U-HRCT scanner and 0.5 mm for the C-HRCT scanners. For both scanners, the display field of view was 80 mm. The image noise of each scanner was evaluated using a phantom. U-HRCT and C-HRCT images of 53 images selected from 37 lung nodules were then observed and graded using a 5-point score by 10 board-certified thoracic radiologists. The images were presented to the observers randomly and in a blinded manner. The image noise for U-HRCT (100.87 ± 0.51 Hounsfield units [HU]) was greater than that for C-HRCT (40.41 ± 0.52 HU; P < .0001). The image quality of U-HRCT was graded as superior to that of C-HRCT (P < .0001) for all of the following parameters that were examined: margins of subsolid and solid nodules, edges of solid components and pulmonary vessels in subsolid nodules, air bronchograms, pleural indentations, margins of pulmonary vessels, edges of bronchi, and interlobar fissures. Despite a larger image noise, the prototype U-HRCT scanner had a significantly better image quality than the C-HRCT scanners.

Serial volumetric registration of pulmonary CT studies

NASA Astrophysics Data System (ADS)

Silva, José Silvestre; Silva, Augusto; Sousa Santos, Beatriz

2008-03-01

Detailed morphological analysis of pulmonary structures and tissue, provided by modern CT scanners, is of utmost importance as in the case of oncological applications both for diagnosis, treatment, and follow-up. In this case, a patient may go through several tomographic studies throughout a period of time originating volumetric sets of image data that must be appropriately registered in order to track suspicious radiological findings. The structures or regions of interest may change their position or shape in CT exams acquired at different moments, due to postural, physiologic or pathologic changes, so, the exams should be registered before any follow-up information can be extracted. Postural mismatching throughout time is practically impossible to avoid being particularly evident when imaging is performed at the limiting spatial resolution. In this paper, we propose a method for intra-patient registration of pulmonary CT studies, to assist in the management of the oncological pathology. Our method takes advantage of prior segmentation work. In the first step, the pulmonary segmentation is performed where trachea and main bronchi are identified. Then, the registration method proceeds with a longitudinal alignment based on morphological features of the lungs, such as the position of the carina, the pulmonary areas, the centers of mass and the pulmonary trans-axial principal axis. The final step corresponds to the trans-axial registration of the corresponding pulmonary masked regions. This is accomplished by a pairwise sectional registration process driven by an iterative search of the affine transformation parameters leading to optimal similarity metrics. Results with several cases of intra-patient, intra-modality registration, up to 7 time points, show that this method provides accurate registration which is needed for quantitative tracking of lesions and the development of image fusion strategies that may effectively assist the follow-up process.

Airflow in Tracheobronchial Tree of Subjects with Tracheal Bronchus Simulated Using CT Image Based Models and CFD Method.

PubMed

Qi, Shouliang; Zhang, Baihua; Yue, Yong; Shen, Jing; Teng, Yueyang; Qian, Wei; Wu, Jianlin

2018-03-01

Tracheal Bronchus (TB) is a rare congenital anomaly characterized by the presence of an abnormal bronchus originating from the trachea or main bronchi and directed toward the upper lobe. The airflow pattern in tracheobronchial trees of TB subjects is critical, but has not been systemically studied. This study proposes to simulate the airflow using CT image based models and the computational fluid dynamics (CFD) method. Six TB subjects and three health controls (HC) are included. After the geometric model of tracheobronchial tree is extracted from CT images, the spatial distribution of velocity, wall pressure, wall shear stress (WSS) is obtained through CFD simulation, and the lobar distribution of air, flow pattern and global pressure drop are investigated. Compared with HC subjects, the main bronchus angle of TB subjects and the variation of volume are large, while the cross-sectional growth rate is small. High airflow velocity, wall pressure, and WSS are observed locally at the tracheal bronchus, but the global patterns of these measures are still similar to those of HC. The ratio of airflow into the tracheal bronchus accounts for 6.6-15.6% of the inhaled airflow, decreasing the ratio to the right upper lobe from 15.7-21.4% (HC) to 4.9-13.6%. The air into tracheal bronchus originates from the right dorsal near-wall region of the trachea. Tracheal bronchus does not change the global pressure drop which is dependent on multiple variables. Though the tracheobronchial trees of TB subjects present individualized features, several commonalities on the structural and airflow characteristics can be revealed. The observed local alternations might provide new insight into the reason of recurrent local infections, cough and acute respiratory distress related to TB.

[The randomized study of efficiency of preoperative photodynamic].

PubMed

Akopov, A L; Rusanov, A A; Molodtsova, V P; Gerasin, A V; Kazakov, N V; Urtenova, M A; Chistiakov, I V

2013-01-01

The authors made a prospective randomized comparison of results of preoperative photodynamic therapy (PhT) with chemotherapy, preoperative chemotherapy in initial unresectable central non-small cell lung cancer in stage III. The efficiency and safety of preoperative therapy were estimated as well as the possibility of subsequent surgical treatment. The research included patients in stage IIIA and IIIB of central non-small cell lung cancer with lesions of primary bronchi and lower section of the trachea, which initially were unresectable, but potentially the patients could be operated on after preoperative treatment. The photodynamic therapy was performed using chlorine E6 and the light of wave length 662 nm. Since January 2008 till December 2011,42 patients were included in the research, 21 patients were randomized in the group for photodynamic therapy and 21--in group without PhT. These groups were compared according to their sex, age, stage of the disease and histological findings. After nonadjuvant treatment the remissions were reached in 19 (90%) patients of the group with PhT and in 16 (76%) patients without PhT and all the patients were operated on. The explorative operations were made on 3 patients out of 16 operated on in the group without PhT (19%). In the group PhT 14 pneumonectomies and 5 lobectomies were perfomed opposite 10 pneumonectomies and 3 lobectomies in group without PhT. The degree of radicalism of resection appears to be reliably higher in the group PhT (RO-89%, R1-11% as against RO-54%, R1-46% in group without PhT), p = 0.038. The preoperative endobronchial PhT conducted with chemotherapy was characterized by efficiency and safety, allowed the surgical treatment and elevated the degree of radicalism of this treatment in selected patients, initially assessed as unresectable.

PATHOLOGY of POST PRIMARY TUBERCULOSIS of the LUNG: AN ILLUSTRATED CRITICAL REVIEW

PubMed Central

Hunter, Robert L.

2011-01-01

Post primary tuberculosis occurs in immunocompetent adults, is restricted to the lungs and accounts for 80% of all clinical cases and nearly 100% of transmission of infection. The supply of human tissues with post primary tuberculosis plummeted with the introduction of antibiotics decades before the flowering of research using molecular methods in animal models. Unfortunately, the paucity of human tissues prevented validation of the models. As a result, it is a paradigm of contemporary research that caseating granulomas are the characteristic lesion of all tuberculosis and that cavities form when they erode into bronchi. This differs from descriptions of the preantibiotic era when many investigators had access to thousands of cases. They reported that post primary tuberculosis begins as an exudative reaction: a tuberculous lipid pneumonia of foamy alveolar macrophages that undergoes caseation necrosis and fragmentation to produce cavities. Granulomas in post primary disease arise only in response to old caseous pneumonia and produce fibrosis, not cavities. We confirmed and extended these observations with study of 104 cases of untreated tuberculosis. In addition, studies of the lungs of infants and immunosuppressed adults revealed a second type of tuberculous pneumonia that seldom produces cavities. Since the concept that cavities arise from caseating granulomas was supported by studies of animals infected with Mycobacterium bovis, we investigated its pathology. We found that M. bovis does not produce post primary tuberculosis in any species. It only produces an aggressive primary tuberculosis that can develop small cavities by erosion of caseating granulomas. Consequently, a key unresolved question in the pathogenesis of tuberculosis is identification of the mechanisms by which Mycobacterium tuberculosis establish a localized safe haven in alveolar macrophages in an otherwise solidly immune host where it can develop conditions for formation of cavities and transmission to new hosts. PMID:21733755

Unidirectional pulmonary airflow patterns in the savannah monitor lizard.

PubMed

Schachner, Emma R; Cieri, Robert L; Butler, James P; Farmer, C G

2014-02-20

The unidirectional airflow patterns in the lungs of birds have long been considered a unique and specialized trait associated with the oxygen demands of flying, their endothermic metabolism and unusual pulmonary architecture. However, the discovery of similar flow patterns in the lungs of crocodilians indicates that this character is probably ancestral for all archosaurs--the group that includes extant birds and crocodilians as well as their extinct relatives, such as pterosaurs and dinosaurs. Unidirectional flow in birds results from aerodynamic valves, rather than from sphincters or other physical mechanisms, and similar aerodynamic valves seem to be present in crocodilians. The anatomical and developmental similarities in the primary and secondary bronchi of birds and crocodilians suggest that these structures and airflow patterns may be homologous. The origin of this pattern is at least as old as the split between crocodilians and birds, which occurred in the Triassic period. Alternatively, this pattern of flow may be even older; this hypothesis can be tested by investigating patterns of airflow in members of the outgroup to birds and crocodilians, the Lepidosauromorpha (tuatara, lizards and snakes). Here we demonstrate region-specific unidirectional airflow in the lungs of the savannah monitor lizard (Varanus exanthematicus). The presence of unidirectional flow in the lungs of V. exanthematicus thus gives rise to two possible evolutionary scenarios: either unidirectional airflow evolved independently in archosaurs and monitor lizards, or these flow patterns are homologous in archosaurs and V. exanthematicus, having evolved only once in ancestral diapsids (the clade encompassing snakes, lizards, crocodilians and birds). If unidirectional airflow is plesiomorphic for Diapsida, this respiratory character can be reconstructed for extinct diapsids, and evolved in a small ectothermic tetrapod during the Palaeozoic era at least a hundred million years before the origin of birds.

Variable p-CREB expression depicts different asthma phenotypes.

PubMed

Chiappara, G; Chanez, P; Bruno, A; Pace, E; Pompeo, F; Bousquet, J; Bonsignore, G; Gjomarkaj, M

2007-07-01

Chromatin modification may play a role in inflammatory gene regulation in asthma. Cyclic adenosine mono-phosphate response element-binding protein (CREB), with the specific co-activator, the CREB-binding protein (CBP), contributes to the acetylation of chromatin and to the transcription of pro-inflammatory genes. To evaluate the expression of CBP and of phospho-CREB (p-CREB) in bronchial biopsies and in peripheral blood mononuclear cells (PBMC) of controls (C), untreated (UA), inhaled steroid treated (ICS) and steroid-dependent asthmatic (SDA) patients. We used immunohistochemistry in bronchial biopsies and western blot analysis and immunocytochemistry in PBMC. Cyclic adenosine mono-phosphate response element-binding protein expression, in the epithelium was similar in all groups, while p-CREB expression was increased in UA and in SDA in comparison with ICS and C subjects (C vs UA P = 0.002, C vs SDA P = 0.007), (ICS vs SDA P = 0.005), (ICS vs UA P = 0.001). Interestingly, also in the submucosa, p-CREB was increased in UA and SDA in comparison with ICS and C subjects (C vs UA P = 0.0004) (C vs SDA P < 0.0001) (ICS vs UA P = 0.002) (ICS vs SDA P < 0.0001) and positively correlated with leukocyte infiltration within the bronchi (CD45RB+ cells). Similar results were obtained with PBMC isolated from the same patient groups. Incubation of PBMC in vitro, with fluticasone propionate, decreased the p-CREB expression induced by cytokine activation (interferon-gamma, tumor necrosis factor-alpha). This study demonstrates that the expression of p-CREB is related, in asthma, to the persistent inflammation according to the disease severity. p-CREB expression can be modulated by glucocorticoids in responsive patients.

Parasites of small Indian mongoose, Herpestes auropunctatus, on St. Kitts, West Indies.

PubMed

Cheng, Trista; Halper, Brandon; Siebert, Jennifer; Cruz-Martinez, Luis; Chapwanya, Aspinas; Kelly, Patrick; Ketzis, Jennifer K; Vessell, Jeffrey; Köster, Liza; Yao, Chaoqun

2018-04-01

Herpestes auropunctatus, the small Indian mongoose, is an invasive omnivore introduced to the Caribbean, including the island of St. Kitts over 150 years ago. It has played a role in changing native fauna and can carry zoonotic pathogens of public health importance. The aim of the current study was to estimate the prevalence of parasites harbored by mongooses. In total, 87 mongooses trapped from April to July 2015 were examined for parasites using (1) hair plucks (N = 79), ear swabs (N = 79), and general coat and skin examination (N = 87) for mites, ticks, lice, and fleas; (2) dissection of the trachea, bronchi, and lungs for lungworms and flukes (N = 76); (3) a double centrifugation fecal flotation method for parasites of the gastrointestinal tract (N = 75); and (4) PCR of heart homogenates for Toxoplasma gondii (N = 60). The only ectoparasite seen was Ctenocephalides felis (79.3%; 69/87), with most mongooses having > 10 fleas (based on a subjective assessment) but insufficient numbers to result in signs of pruritus or anemia. On fecal flotation, coccidial oocysts were found with a prevalence of 69.3% (52/75). Neither T. gondii, lungworm, nor fluke infections were detected with the methods used. The high number of C. felis-infested mongooses and the infestation level of the individual mongooses suggest that they could serve as a reservoir for these potential vectors of pathogens. No evidence was found to support that mongooses are a component of T. gondii cycles on St. Kitts, although this finding needs to be confirmed with a larger sample size from other geographic locations.

Bronchial fenestration improves expiratory flow in emphysematous human lungs.

PubMed

Lausberg, Henning F; Chino, Kimiaki; Patterson, G Alexander; Meyers, Bryan F; Toeniskoetter, Patricia D; Cooper, Joel D

2003-02-01

The crippling effects of emphysema are due in part to dynamic hyperinflation, resulting in altered respiratory mechanics, an increased work of breathing, and a pervasive sense of dyspnea. Because of the extensive collateral ventilation present in emphysematous lungs, we hypothesize that placement of stents between pulmonary parenchyma and large airways could effectively improve expiratory flow, thus reducing dynamic hyperinflation. Twelve human emphysematous lungs, removed at the time of lung transplantation, were placed in an airtight ventilation chamber with the bronchus attached to a tube traversing the chamber wall, and attached to a pneumotachometer. The chamber was evacuated to -10 cm H2O pressure for lung inflation. A forced expiratory maneuver was simulated by rapidly pressurizing the chamber to 20 cm H2O, while the expiratory volume was continuously recorded. A flexible bronchoscope was then inserted into the airway and a radiofrequency catheter (Broncus Technologies) was used to create a passage through the wall of three separate segmental bronchi into the adjacent lung parenchyma. An expandable stent, 1.5 cm in length and 3 mm in diameter, was then inserted through each passage. Expiratory volumes were then remeasured as above. In six experiments, two additional stents were then inserted and forced expiratory volumes again determined. The forced expiratory volume in 1 second (FEV1) increased from 245 +/- 107 mL at baseline to 447 +/- 199 mL after placement of three bronchopulmonary stents (p < 0.001). With two additional stents, the FEV1 increased to 666 +/- 284 mL (p < 0.001). Creation of extra-anatomic bronchopulmonary passages is a potential therapeutic option for emphysematous patients with marked hyperinflation and severe homogeneous pulmonary destruction.

[USE OF PROTECTIVE LUNG VENTILATION REGIMEN IN CARDIAC SURGERY PATIENTS.

PubMed

Pshenichniy, T A; Akselrod, B A; Titova, I V; Trekova, N A; Khrustaleva, M V

2017-09-01

In cardiac surgery, protective lung ventilation and/or preventive brdnchoscopy (PB) are able to decrease lung injury effects of cardiopulmonary bypass (CPB) and mechanical ventilation. define lung complication risks, evaluate the effect ofprotective lung ventilation (PLV) on lung functioning, and investigate the feasibility ofpreventive PB in higher pulmonary risk (PR) patients. 66 patients participated in prospective randomized research. Allocation was based on PR and intraoperative mechanical ventilation type. PLV includedfollowing parameters: PCK PIP - up to 20 cm H20, Vt - 6 ml/ kg of PBW, PEEP - 5-10 cm H20, IE ratio - 1:1.5-1:1, EtCO2 - 35-42 mm Hg, FiO2 - 45-60%, lung ventilation during CPB, alveolar recruitment. Four groups were formed: A - higher PR plus PLV- B - higher PR plus conventional LV (CLV), C - lower PR plus PLV- D - lower PR plus CLV PIP PEEP dynamic compliance, p/f ratio and intrapulmonary shunt (Qs/Qt) were recorded. Seventeen patients of group A underwent PB. Advanced dynamic compliance, higher p/f ratio and lower Qs/Qt were seen in group A, in comparison with group B (p< 0.05). Lower Qs/Qt was seen in group C, in comparison with group D (p<0.05). Mucus obstruction of subsegmental bronchi was observed in 53.3% of higher PR patients. More than half ofpatients without PB sufferedfrom postoperative lung complications (70.4 vs. 34.2 7%, p

Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction

PubMed Central

Namkung, Wan; Yao, Zhen; Finkbeiner, Walter E.; Verkman, A. S.

2011-01-01

TMEM16A (ANO1) is a calcium-activated chloride channel (CaCC) expressed in secretory epithelia, smooth muscle, and other tissues. Cell-based functional screening of ∼110,000 compounds revealed compounds that activated TMEM16A CaCC conductance without increasing cytoplasmic Ca2+. By patch-clamp, N-aroylaminothiazole “activators” (Eact) strongly increased Cl− current at 0 Ca2+, whereas tetrazolylbenzamide “potentiators” (Fact) were not active at 0 Ca2+ but reduced the EC50 for Ca2+-dependent TMEM16A activation. Of 682 analogs tested, the most potent activator (Eact) and potentiator (Fact) produced large and more sustained CaCC Cl− currents than general agonists of Ca2+ signaling, with EC50 3–6 μM and Cl− conductance comparable to that induced transiently by Ca2+-elevating purinergic agonists. Analogs of activators were identified that fully inhibited TMEM16A Cl− conductance, providing further evidence for direct TMEM16A binding. The TMEM16A activators increased CaCC conductance in human salivary and airway submucosal gland epithelial cells, and IL-4 treated bronchial cells, and stimulated submucosal gland secretion in human bronchi and smooth muscle contraction in mouse intestine. Small-molecule, TMEM16A-targeted activators may be useful for drug therapy of cystic fibrosis, dry mouth, and gastrointestinal hypomotility disorders, and for pharmacological dissection of TMEM16A function.—Namkung, W., Yao, Z., Finkbeiner, W. E., Verkman, A. S. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. PMID:21836025

Algorithm for Video Summarization of Bronchoscopy Procedures

PubMed Central

2011-01-01

Background The duration of bronchoscopy examinations varies considerably depending on the diagnostic and therapeutic procedures used. It can last more than 20 minutes if a complex diagnostic work-up is included. With wide access to videobronchoscopy, the whole procedure can be recorded as a video sequence. Common practice relies on an active attitude of the bronchoscopist who initiates the recording process and usually chooses to archive only selected views and sequences. However, it may be important to record the full bronchoscopy procedure as documentation when liability issues are at stake. Furthermore, an automatic recording of the whole procedure enables the bronchoscopist to focus solely on the performed procedures. Video recordings registered during bronchoscopies include a considerable number of frames of poor quality due to blurry or unfocused images. It seems that such frames are unavoidable due to the relatively tight endobronchial space, rapid movements of the respiratory tract due to breathing or coughing, and secretions which occur commonly in the bronchi, especially in patients suffering from pulmonary disorders. Methods The use of recorded bronchoscopy video sequences for diagnostic, reference and educational purposes could be considerably extended with efficient, flexible summarization algorithms. Thus, the authors developed a prototype system to create shortcuts (called summaries or abstracts) of bronchoscopy video recordings. Such a system, based on models described in previously published papers, employs image analysis methods to exclude frames or sequences of limited diagnostic or education value. Results The algorithm for the selection or exclusion of specific frames or shots from video sequences recorded during bronchoscopy procedures is based on several criteria, including automatic detection of "non-informative", frames showing the branching of the airways and frames including pathological lesions. Conclusions The paper focuses on the challenge of generating summaries of bronchoscopy video recordings. PMID:22185344

Radiomic texture-curvature (RTC) features for precision medicine of patients with rheumatoid arthritis-associated interstitial lung disease

NASA Astrophysics Data System (ADS)

Watari, Chinatsu; Matsuhiro, Mikio; Näppi, Janne J.; Nasirudin, Radin A.; Hironaka, Toru; Kawata, Yoshiki; Niki, Noboru; Yoshida, Hiroyuki

2018-03-01

We investigated the effect of radiomic texture-curvature (RTC) features of lung CT images in the prediction of the overall survival of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We retrospectively collected 70 RA-ILD patients who underwent thin-section lung CT and serial pulmonary function tests. After the extraction of the lung region, we computed hyper-curvature features that included the principal curvatures, curvedness, bright/dark sheets, cylinders, blobs, and curvature scales for the bronchi and the aerated lungs. We also computed gray-level co-occurrence matrix (GLCM) texture features on the segmented lungs. An elastic-net penalty method was used to select and combine these features with a Cox proportional hazards model for predicting the survival of the patient. Evaluation was performed by use of concordance index (C-index) as a measure of prediction performance. The C-index values of the texture features, hyper-curvature features, and the combination thereof (RTC features) in predicting patient survival was estimated by use of bootstrapping with 2,000 replications, and they were compared with an established clinical prognostic biomarker known as the gender, age, and physiology (GAP) index by means of two-sided t-test. Bootstrap evaluation yielded the following C-index values for the clinical and radiomic features: (a) GAP index: 78.3%; (b) GLCM texture features: 79.6%; (c) hypercurvature features: 80.8%; and (d) RTC features: 86.8%. The RTC features significantly outperformed any of the other predictors (P < 0.001). The Kaplan-Meier survival curves of patients stratified to low- and high-risk groups based on the RTC features showed statistically significant (P < 0.0001) difference. Thus, the RTC features can provide an effective imaging biomarker for predicting the overall survival of patients with RA-ILD.

Acute bronchiolitis in a paediatric emergency department of Northern Greece. Comparisons between two decades

PubMed Central

Emporiadou, Maria; Aivazis, Victor; Mauromixalis, John; Hatzistilianou, Maria

2012-01-01

Introduction Acute bronchiolitis is the most common lower respiratory tract infection in infants and toddlers concerning small bronchi or bronchioli. This retrospective study aimed to evaluate the incidence of acute bronchiolitis and the use of β2-agonists between two different decades. Material and methods During 1990-1991 and 2001-2002, the files of the 2nd Paediatric Emergency Department of Aristotle University of Thessaloniki, AHEPA Hospital were reviewed and cases of acute bronchiolitis were recorded and analysed. Results During 1990-1991, 14 538 children were identified with respiratory infections and bronchiolitis was diagnosed in 519/14 538 children (3.56%). Only 34 out of 519 patients received nebulised salbutamol (6.6%) and 221/519 were hospitalized (42.6%). During 2001-2002, 9001 children were found to have respiratory tract infections and acute bronchiolitis was diagnosed in 641/9001 of them (7.12%). In total, 411/641 children (64.1%) received salbutamol and ipratropium, and 89/641 patients (13.88%) were hospitalized. There was a predominance of male sex in both decades (p = 0.509). There was a statistically significant difference (p < 0.001) concerning the use of nebulised salbutamol with nebulised ipratropium between the two decades. Finally, during 2001-2002, the use of bronchodilators with or without corticosteroids was more frequent and it appears to be correlated with the reduced number of admissions to hospital (p < 0.05) compared with 1990-1991. Conclusions There was an increase in the incidence of acute bronchiolitis during the last decade. The admission rate decreased probably due to the use of nebulized salbutamol and ipratropium, but further multicentre comparative trials are required to define the role of bronchodilators in the treatment of acute bronchiolitis. PMID:22852008

Bronchoarterial ratio in never-smokers adults: Implications for bronchial dilation definition.

PubMed

Diaz, Alejandro A; Young, Thomas P; Maselli, Diego J; Martinez, Carlos H; Maclean, Erick S; Yen, Andrew; Dass, Chandra; Simpson, Scott A; Lynch, David A; Kinney, Gregory L; Hokanson, John E; Washko, George R; San José Estépar, Raul

2017-01-01

Bronchiectasis manifests as recurrent respiratory infections and reduced lung function. Airway dilation, which is measured as the ratio of the diameters of the bronchial lumen (B) and adjacent pulmonary artery (A), is a defining radiological feature of bronchiectasis. A challenge to equating the bronchoarterial (BA) ratio to disease severity is that the diameters of airway and vessel in health are not established. We sought to explore the variability of BA ratio in never-smokers without pulmonary disease and its associations with lung function. Objective measurements of the BA ratio on volumetric computed tomography (CT) scans and pulmonary function data were collected in 106 never-smokers. The BA ratio was measured in the right upper lobe apical bronchus (RB1) and the right lower lobe basal posterior bronchus. The association between the BA ratio and forced expiratory volume in 1 s (FEV 1 ) was assessed using regression analysis. The BA ratio was 0.79 ± 0.16 and was smaller in more peripheral RB1 bronchi (P < 0.0001). The BA ratio was >1, a typical threshold for bronchiectasis, in 10 (8.5%) subjects. Subjects with a BA ratio >1 versus ≤1 had smaller artery diameters (P < 0.0001) but not significantly larger bronchial lumens. After adjusting for age, gender, race and height, the BA ratio was directly related to FEV 1 (P = 0.0007). In never-smokers, the BA ratio varies by airway generation and is associated with lung function. A BA ratio >1 is driven by small arteries. Using artery diameter as reference to define bronchial dilation seems inappropriate. © 2016 Asian Pacific Society of Respirology.

Barium sulfate micro- and nanoparticles as bioinert reference material in particle toxicology.

PubMed

Loza, Kateryna; Föhring, Isabell; Bünger, Jürgen; Westphal, Götz A; Köller, Manfred; Epple, Matthias; Sengstock, Christina

2016-12-01

The inhalation of particles and their exposure to the bronchi and alveoli constitute a major public health risk. Chemical as well as particle-related properties are important factors for the biological response but are difficult to separate from each other. Barium sulfate is a completely inert chemical compound, therefore it is ideally suited to separate these two factors. The biological response of rat alveolar macrophages (NR8383) was analyzed after exposure to barium sulfate particles with three different diameters (40 nm, 270 nm, and 1.3 μm, respectively) for 24 h in vitro (particle concentrations from 12.5 to 200 μg mL - 1 ). The particles were colloidally stabilized as well as fluorescently-labeled by carboxymethylcellulose, conjugated with 6-aminofluorescein. All kinds of barium sulfate particles were efficiently taken up by NR8383 cells and found inside endo-lysosomes, but never in the cell nucleus. Neither an inflammatory nor a cytotoxic response was detected by the ability of dHL-60 and NR8383 cells to migrate towards a chemotactic gradient (conditioned media of NR8383 cells) and by the release of inflammatory mediators (CCL2, TNF-α, IL-6). The particles neither caused apoptosis (up to 200 μg mL - 1 ) nor necrosis (up to 100 μg mL - 1 ). As only adverse reaction, necrosis was found at a concentration of 200 μg mL - 1 of the largest barium sulfate particles (1.3 μm). Barium sulfate particles are ideally suited as bioinert control to study size-dependent effects such as uptake mechanisms of intracellular distributions of pure particles, especially in nanotoxicology.

Acoustic phenomena observed in lung auscultation

NASA Astrophysics Data System (ADS)

Korenbaum, V. I.; Tagil'Tsev, A. A.; Kulakov, Yu. V.

2003-05-01

The results of studying respiratory noise at the chest wall by the method of acoustic intensimetry reveal the presence of frequency components with different signs of the real and imaginary parts of the cross spectrum obtained for the responses of the receivers of vibratory displacement and dynamic force. An acoustic model is proposed to explain this difference on the basis of the hypothesis that the contributions of both air-borne and structure-borne sound are significant in the transmission of respiratory noise to the chest wall. It is shown that, when considered as an acoustic channel for the basic respiratory noise, the respiratory system of an adult subject has two resonances: in the frequency bands within 110 150 and 215 350 Hz. For adults in normal condition, the air-borne component of the basic respiratory noise predominates in the region 100 300 Hz in the lower parts of lungs. At forced respiration of healthy adults, the sounds of vesicular respiration are generated by the turbulent air flow in the 11th-through 13th-generation bronchi, and the transmission of these sounds to the chest wall in normal condition is mainly through air and is determined by the resonance of the vibratory system formed by the elasticity of air in the respiratory ducts of lungs and by the surface mass density of the chest wall. It is demonstrated that the distance from the chest wall to the sources of structure-borne additional respiratory noise, namely, wheezing with frequencies above 300 Hz, can be estimated numerically from the ratio between the real and imaginary parts of the cross spectrum on the assumption that the source is of the quadrupole type.

Tachykinin receptors in rabbit airways--characterization by functional, autoradiographic and binding studies.

PubMed Central

Black, J. L.; Diment, L. M.; Alouan, L. A.; Johnson, P. R.; Armour, C. L.; Badgery-Parker, T.; Burcher, E.

1992-01-01

1. In many species, both NK1 and NK2 tachykinin receptors appear to be important in mediating the contraction of airway smooth muscle. We have examined the distribution and characterization of receptors for tachykinins in rabbit airways using functional length tension studies, autoradiography and radioligand binding studies. 2. Contractile responses to tachykinins were elicited in four different areas of the respiratory tree--trachea, and three progressively more distal areas of the right bronchus. The NK2 receptor-preferring agonists, neurokinin A (NKA), neuropeptide gamma (NP gamma) and the NK2-selective [Lys5 MeLeu9, Nle10]-NKA(4-10) [NKA (4-10) analogue] produced similar contraction in all four areas. Substance P (SP) and the NK1-selective [Sar9,Met(O2)11]-SP (Sar-SP) exhibited a marked location-dependence in the magnitude of contraction, producing minimal contraction in the trachea and more proximal bronchi with contractions becoming progressively larger in the more distal airways. Senktide (which is selective for the NK3 receptor) produced negligible contraction in all areas. 3. The NK2-selective antagonist, MDL29,913, was a weak antagonist of NKA and NKA(4-10) analogue. At a concentration of 2 microM, it produced a small but significant shift in the response curve to NKA and a greater shift (8 fold) in the curve to NKA(4-10) analogue, but it had no effect on responses to Sar-SP. The non peptide NK1 receptor antagonist, CP-96,345, was also unexpectedly weak in this preparation. The pD2 value for Sar-SP was decreased 27 fold by CP-96,345 at a concentration of 1 microM, without alteration in the maximum response.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 4 PMID:1384914

Activation of the nociceptin/orphanin FQ receptor reduces bronchoconstriction and microvascular leakage in a rabbit model of gastroesophageal reflux

PubMed Central

D'Agostino, Bruno; Marrocco, Giuseppina; De Nardo, Marilisa; Calò, Girolamo; Guerrini, Remo; Gallelli, Luca; Advenier, Charles; Rossi, Francesco

2005-01-01

Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide ligand for a specific G-protein coupled receptor, the N/OFQ peptide receptor (NOP). The N/OFQ-NOP receptor system has been reported to play an important role in pain, anxiety and appetite regulation. In airways, N/OFQ was found to inhibit the release of tachykinins and the bronchoconstriction and cough provoked by capsaicin. Here we evaluated the effects of NOP receptor activation in bronchoconstriction and airway microvascular leakage induced by intraesophageal (i.oe.) hydrochloric acid (HCl) instillation in rabbits. We also tested the effects of NOP receptor activation in SP-induced plasma extravasation and bronchoconstriction. In anesthetized New Zealand rabbits bronchopulmonary function (total lung resistance (RL) and dynamic compliance (Cdyn)) and airway microvascular leakage (extravasation of Evans blue dye) were evaluated. Infusion of i.oe. HCl (1 N) led to a significant increase in bronchoconstriction and plasma extravasation in the main bronchi and trachea of rabbits pretreated with propranolol, atropine and phosphoramidon. Bronchoconstriction and airway microvascular leakage were inhibited by N/OFQ (3–30 μg kg−1 i.v.) in a dose-dependent manner. The NOP receptor agonist [Arg14,Lys15]N/OFQ mimicked the inhibitory effect of N/OFQ, being 10-fold more potent, UFP-101, a peptide selective NOP receptor antagonist, blocked the inhibitory effects of both agonists. Under the same experimental conditions, N/OFQ and [Arg14,Lys15]N/OFQ did not counteract the bronchoconstriction and airway microvascular leakage induced by substance P. These results suggest that bronchoconstriction and airway plasma extravasation induced by i.oe. HCl instillation are inhibited by activation of prejunctional NOP receptors. PMID:15685213

Facilitatory effects of selective agonists for tachykinin receptors on cholinergic neurotransmission: evidence for species differences.

PubMed Central

Belvisi, M. G.; Patacchini, R.; Barnes, P. J.; Maggi, C. A.

1994-01-01

1. Exogenous tachykinins modulate cholinergic neurotransmission in rabbit and guinea-pig airways. We have investigated the effect of selective tachykinin receptor agonists and antagonists on cholinergic neurotransmission evoked by electrical field stimulation (EFS) of bronchial rings in rabbit, guinea-pig and human airways in vitro to assess which type of tachykinin receptor is mediating this facilitatory effect. 2. Bronchial rings were set up for isometric tension recording. Contractile responses to EFS (60 V, 0.4 ms, 2 Hz for 10 s every min) and exogenous acetylcholine (ACh) were obtained and the effects of selective tachykinin agonists and antagonists were investigated. 3. In rabbit bronchi the endogenous tachykinins, substance P (SP) and neurokinin A (NKA) (10 nM) potentiated cholinergic responses to EFS (by 287.6 +/- 121%, P < 0.01 and 181.4 +/- 56.5%, P < 0.001 respectively). 4. The NK1 receptor selective agonist, [Sar9]SP sulphone (10 nM) evoked a maximal facilitatory action on cholinergic responses of 334.9 +/- 63% (P < 0.01) (pD2 = 8.5 +/- 0.06) an effect which was blocked by the selective NK1-receptor antagonist, CP 96,345 (100 nM) (P < 0.05) but not by the NK2 receptor antagonist, MEN 10,376 (100 nM). The NK2 receptor selective agonist, [beta Ala8]NKA(4-10) (10 nM), produced a maximum enhancement of 278 +/- 83.5% (P < 0.01) (pD2 = 8.7 +/- 0.1) an effect which was blocked by MEN 10,376 (100 nM) (P < 0.05) and not by CP 96,345. [MePhe7]NKB, an NK3 receptor selective agonist was without effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7516799

[Sleeve resection of right main bronchus for posttraumatic bronchial stenosis].

PubMed

Bobocea, Andrei Cristian; Matache, Radu; Codreşi, Mihaela; Bolca, Ciprian; Cordoş, Ioan

2011-01-01

Tracheobronchial disruption is one of the most severe injuries caused by blunt chest trauma. A high index of clinical suspicion and accurate interpretation of radiological findings are necessary for prompt surgical intervention with primary repair of the airway. Delays in treatment increases the risk of partial to complete bronchial stenosis. A 21 years old male was admitted to our hospital following a workplace accident. A chest radiograph showed bilateral pneumothorax, cephalic and mediastinal emphysema. Chest tubes were placed on each side, with full pulmonary expansion and remission of emphysema. Minimal lesions of the right main bronchus were found at fiberoptic bronchoscopy. Daily chest X-rays showed an uncomplicated recovery. A stenosis was suspected due to right lung pneumonia evolving under specific antibiotherapy. Right main bronchus posttraumatic stricture was diagnosed by fiberoptic bronchoscopy. He underwent a right lateral thoracotomy with sleeve resection of stenotic bronchi. Control bronchoscopy reveals main bronchus widely patent with untraceable suture line. Main bronchus rupture in blunt chest trauma is an additive effect of chest wall compression between two solid surfaces, traction on the carina and sudden increase in intraluminal pressure. Symptoms may vary: soft air leak, pneumothorax or limited mediastinal emphysema. Bronchoscopy should be performed immediately or when available. Granulation tissue leads to progressive bronchial obstruction, with distal infection and permanent parenchymal damage. Sleeve resection of the stenosed segment is the treatment of choice and restores fully the lung function. Rupture of main bronchus is a complication of blunt chest trauma. Flexible bronchoscopy is useful and reliable for early diagnosis of traumatic tracheobronchial injuries. Delayed diagnosis can lead to lung parenchyma alteration due to retrostenotic pneumonia. Resection and end-to-end anastomosis is the key of successful in these cases.

[Tracheobronchial lavage--a supplementary measure in the initial management of meconium aspiration syndrome].

PubMed

Rosegger, H; Engele, H; Haas, J

1987-12-18

Pulmonary lavage - a supplementary measure of resuscitation in newborn infants with severe aspiration of meconium stained amniotic fluid. During 1984-1985 150 mature newborn infants who had aspirated heavily-stained or pea soup-like amniotic fluid were resuscitated at the University Hospital of Obstetrics and Gynaecology in Graz. In 109 of these infants (controls) routine aspiration of both the upper and lower airways was accomplished as soon as possible, whilst in the remaining 41 infants (lavaged) pulmonary lavage with saline was additionally performed via an endotracheal tube after aspiration to clear the trachea and the upper bronchi from thick meconium which could not have been removed as efficiently otherwise. The incidence of manifest meconium aspiration syndrome was significantly higher (22%) in the lavaged infants than in the controls (8%). Mechanical ventilation was performed in 36% of the lavaged infants, whereas only 5.5% of the controls had to be ventilated for more than 1 hour. The mean duration of ventilation, however, was shorter (Mh = 5.1 hrs vs Mh = 69 hrs) and the average age at discharge lower in the lavaged. Three infants died, two of whom had severe malformations. Only one death in the lavaged infants was attributable to severe meconium aspiration syndrome already manifest at birth. Three infants (two lavaged, one control) showed radiological evidence of pneumothorax, but without clinical appearance of respiratory distress. Since the lavaged group naturally contained the more severely distressed infants, with a high incidence of caesarean section on account of intrauterine asphyxia and lower Apgar scores at one and five minutes, the high incidence of radiologically confirmed meconium aspiration syndrome was not surprising.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory distress syndrome.

PubMed

de Lima, Flávia Mafra; Moreira, Leonardo M; Villaverde, A B; Albertini, Regiane; Castro-Faria-Neto, Hugo C; Aimbire, Flávio

2011-05-01

The aim of this work was to investigate if the low-level laser therapy (LLLT) on acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar lavage fluid (BALF) of mice. LLLT has been reported to actuate positively for relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased TNF mRNA expression and dysfunction of cAMP generation observed in ALI can be influenced by LLLT. For in vivo studies, Balb/c mice (n = 5 for group) received LPS inhalation or TNF intra nasal instillation and 3 h after LPS or TNF-α, leukocytes in BALF were analyzed. LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 660 nm and a dose of 4.5 J/cm(2). The mice were irradiated 15 min after ALI induction. In vitro AM from mice were cultured for analyses of TNF mRNA expression and protein and adenosine3':5'-cyclic monophosphate (cAMP) levels. One hour after LPS, the TNF and cAMP levels in AM were measured by ELISA. RT-PCR was used to measure TNF mRNA in AM. The LLLT was inefficient in potentiating the rolipram effect in presence of a TNF synthesis inhibitor. LLLT attenuated the neutrophil influx and TNF in BALF. In AM, the laser increased the cAMP and reduced the TNF-α mRNA. LLLT increases indirectly the cAMP in AM by a TNF-dependent mechanism.

Low-level laser therapy (LLLT) attenuates RhoA mRNA expression in the rat bronchi smooth muscle exposed to tumor necrosis factor-alpha.

PubMed

de Lima, Flávia Mafra; Bjordal, Jan M; Albertini, Regiane; Santos, Fábio V; Aimbire, Flavio

2010-09-01

Low-level laser therapy (LLLT) has been found to produce anti-inflammatory effects in a variety of disorders. Bronchial smooth muscle (BSM) hyperreactivity is associated with increased Ca+2 sensitivity and increased RhoA mRNA expression. In the current study, we investigated if LLLT could reduce BSM contraction force and RhoA mRNA expression in tumor necrosis factor-alpha (TNF-alpha)-induced BSM hyperreactivity. In the study, 112 male Wistar rats were divided randomly into 16 groups, and BSM was harvested and suspended in TNF-alpha baths for 6 and 24 h, respectively. Irradiation with LLLT was performed with a wavelength of 660 nm for 42 s with a dose of 1.3 J/cm2. This LLLT dose was administered once in the 6-h group and twice in the 24-h group. LLLT significantly decreased contraction force in BSM at 6 h (TNF-alpha + LLLT: 11.65+/-1.10 g/100 mg of tissue) (F=3115) and at 24 h (TNF-alpha+ LLLT: 14.15+/-1.1 g/100 mg of tissue) (F=3245, p<0.05) after TNF-alpha, respectively, when compared to vehicle-bathed groups (control). LLLT also significantly decreased the expression of RhoA mRNA in BSM segments at 6 h (1.22+/-0.20) (F=2820, p<0.05) and 24 h (2.13+/-0.20) (F=3324, p<0.05) when compared to BSM segments incubated with TNF-alpha without LLLT irradiation. We conclude that LLLT administered with this protocol, reduces RhoA mRNA expression and BSM contraction force in TNF-alpha-induced BSM hyperreactivity.

The use of balloon-expandable metallic stents in the treatment of pediatric tracheomalacia and bronchomalacia.

PubMed

Furman, R H; Backer, C L; Dunham, M E; Donaldson, J; Mavroudis, C; Holinger, L D

1999-02-01

To evaluate the use of balloon-expandable metallic stents in the treatment of children with tracheomalacia and bronchomalacia in whom conventional therapy has failed. Retrospective case series. Tertiary pediatric otolaryngology and cardiothoracic surgery referral center. Six patients were identified as having undergone bronchoscopic placement of metallic balloon-expandable stents between 1994 and 1997. The age at stent placement, prior surgical interventions, and indications for and sites of stent placement were noted. Also, the complications related to stent placement and the current airway status of the patients were reviewed. Twelve balloon-expandable metallic angioplasty stents (Palmaz; Johnson & Johnson Interventional Systems Co, Warren, NJ) were placed bronchoscopically in 6 patients. Six stents were placed in the lower trachea, and 6 were placed in the main bronchi. The stents were balloon expanded under fluoroscopic guidance. Discontinuation of mechanical ventilation. The age at stent placement ranged from 1.5 to 38 months (mean age at placement, 10 months). The indications for stent placement were (1) tracheomalacia or bronchomalacia, (2) pericardial patch or slide tracheoplasty failure, and (3) bronchomalacia caused by tetralogy of Fallot and large pulmonary arteries. The primary complication of stent placement was postoperative granulation tissue formation. One patient required the removal of 2 tracheal stents because of granulation tissue formation. There were 2 deaths in the series, 1 possibly related to stent placement. Four of the 6 patients were weaned from mechanical ventilation, and 3 experienced prolonged relief of airway obstruction. Metallic balloon-expandable stents are effective in relieving lower tracheomalacia and bronchomalacia in select patients. Only patients in whom conventional therapy has failed should be considered for stent placement.

Interaction between gas cooking and GSTM1 null genotype in bronchial responsiveness: results from the European Community Respiratory Health Survey

PubMed Central

Amaral, André F S; Ramasamy, Adaikalavan; Castro-Giner, Francesc; Minelli, Cosetta; Accordini, Simone; Sørheim, Inga-Cecilie; Pin, Isabelle; Kogevinas, Manolis; Jõgi, Rain; Balding, David J; Norbäck, Dan; Verlato, Giuseppe; Olivieri, Mario; Probst-Hensch, Nicole; Janson, Christer; Zock, Jan-Paul; Heinrich, Joachim; Jarvis, Deborah L

2014-01-01

Background Increased bronchial responsiveness is characteristic of asthma. Gas cooking, which is a major indoor source of the highly oxidant nitrogen dioxide, has been associated with respiratory symptoms and reduced lung function. However, little is known about the effect of gas cooking on bronchial responsiveness and on how this relationship may be modified by variants in the genes GSTM1, GSTT1 and GSTP1, which influence antioxidant defences. Methods The study was performed in subjects with forced expiratory volume in one second at least 70% of predicted who took part in the multicentre European Community Respiratory Health Survey, had bronchial responsiveness assessed by methacholine challenge and had been genotyped for GSTM1, GSTT1 and GSTP1-rs1695. Information on the use of gas for cooking was obtained from interviewer-led questionnaires. Effect modification by genotype on the association between the use of gas for cooking and bronchial responsiveness was assessed within each participating country, and estimates combined using meta-analysis. Results Overall, gas cooking, as compared with cooking with electricity, was not associated with bronchial responsiveness (β=−0.08, 95% CI −0.40 to 0.25, p=0.648). However, GSTM1 significantly modified this effect (β for interaction=−0.75, 95% CI −1.16 to −0.33, p=4×10−4), with GSTM1 null subjects showing more responsiveness if they cooked with gas. No effect modification by GSTT1 or GSTP1-rs1695 genotypes was observed. Conclusions Increased bronchial responsiveness was associated with gas cooking among subjects with the GSTM1 null genotype. This may reflect the oxidant effects on the bronchi of exposure to nitrogen dioxide. PMID:24613990

Involvement of the Tyr kinase/JNK pathway in carbachol-induced bronchial smooth muscle contraction in the rat.

PubMed

Sakai, Hiroyasu; Watanabe, Yu; Honda, Mai; Tsuiki, Rika; Ueda, Yusuke; Nagai, Yuki; Narita, Minoru; Misawa, Miwa; Chiba, Yoshihiko

2013-05-01

Tyrosine (Tyr) kinases and mitogen-activated protein kinases have been thought to participate in the contractile response in various smooth muscles. The aim of the current study was to investigate the involvement of the Tyr kinase pathway in the contraction of bronchial smooth muscle. Ring preparations of bronchi isolated from rats were suspended in an organ bath. Isometric contraction of circular smooth muscle was measured. Immunoblotting was used to examine the phosphorylation of c-Jun N-terminal kinasess (JNKs) in bronchial smooth muscle. To examine the role of mitogen-activated protein kinase(s) in bronchial smooth muscle contraction, the effects of MPAK inhibitors were investigated in this study. The contraction induced by carbachol (CCh) was significantly inhibited by pretreatment with selective Tyr kinase inhibitors (genistein and ST638, n = 6, respectively), and a JNK inhibitor (SP600125, n = 6). The contractions induced by high K depolarization (n = 4), orthovanadate (a potent Tyr phosphatase inhibitor) and sodium fluoride (a G protein activator; NaF) were also significantly inhibited by selective Tyr kinase inhibitors and a JNK inhibitor (n = 4, respectively). However, the contraction induced by calyculin-A was not affected by SP600125. On the other hand, JNKs were phosphorylated by CCh (2.2 ± 0,4 [mean±SEM] fold increase). The JNK phosphorylation induced by CCh was significantly inhibited by SP600125 (n = 4). These findings suggest that the Tyr kinase/JNK pathway may play a role in bronchial smooth muscle contraction. Strategies to inhibit JNK activation may represent a novel therapeutic approach for diseases involving airway obstruction, such as asthma and chronic obstructive pulmonary disease.

Apoptotic cell death in rat lung following mustard gas inhalation.

PubMed

Andres, Devon K; Keyser, Brian M; Melber, Ashley A; Benton, Betty J; Hamilton, Tracey A; Kniffin, Denise M; Martens, Margaret E; Ray, Radharaman

2017-06-01

To investigate apoptosis as a mechanism of sulfur mustard (SM) inhalation injury in animals, we studied different caspases (caspase-8, -9, -3, and -6) in the lungs from a ventilated rat SM aerosol inhalation model. SM activated all four caspases in cells obtained from bronchoalveolar lavage fluid (BALF) as early as 6 h after exposure. Caspase-8, which is known to initiate the extrinsic Fas-mediated pathway of apoptosis, was increased fivefold between 6 and 24 h, decreasing to the unexposed-control level at 48 h. The initiator, caspase-9, in the intrinsic mitochondrial pathway of apoptosis as well as the executioner caspases, caspase-3 and -6, all peaked ( P < 0.01) at 24 h; caspase-3 and -6 remained elevated, but caspase-9 decreased to unexposed-control level at 48 h. To study further the Fas pathway, we examined soluble as well as membrane-bound Fas ligand (sFas-L and mFas-L, respectively) and Fas receptor (Fas-R) in both BALF cells and BALF. At 24 h after SM exposure, sFas-L increased significantly in both BALF cells ( P < 0.01) and BALF ( P < 0.05). However, mFas-L increased only in BALF cells between 24 and 48 h ( P < 0.1 and P < 0.001, respectively). Fas-R increased only in BALF cells by 6 h ( P < 0.01) after SM exposure. Apoptosis in SM-inhaled rat lung specimens was also confirmed by both immunohistochemical staining using cleaved caspase-3 and -9 antibodies and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining as early as 6 h in the proximal trachea and bronchi, but not before 48 h in distal airways. These findings suggest pathogenic mechanisms at the cellular and molecular levels and logical therapeutic target(s) for SM inhalation injury in animals.

Quantitative analysis of rib movement based on dynamic chest bone images: preliminary results

NASA Astrophysics Data System (ADS)

Tanaka, R.; Sanada, S.; Oda, M.; Mitsutaka, M.; Suzuki, K.; Sakuta, K.; Kawashima, H.

2014-03-01

Rib movement during respiration is one of the diagnostic criteria in pulmonary impairments. In general, the rib movement is assessed in fluoroscopy. However, the shadows of lung vessels and bronchi overlapping ribs prevent accurate quantitative analysis of rib movement. Recently, an image-processing technique for separating bones from soft tissue in static chest radiographs, called "bone suppression technique", has been developed. Our purpose in this study was to evaluate the usefulness of dynamic bone images created by the bone suppression technique in quantitative analysis of rib movement. Dynamic chest radiographs of 10 patients were obtained using a dynamic flat-panel detector (FPD). Bone suppression technique based on a massive-training artificial neural network (MTANN) was applied to the dynamic chest images to create bone images. Velocity vectors were measured in local areas on the dynamic bone images, which formed a map. The velocity maps obtained with bone and original images for scoliosis and normal cases were compared to assess the advantages of bone images. With dynamic bone images, we were able to quantify and distinguish movements of ribs from those of other lung structures accurately. Limited rib movements of scoliosis patients appeared as reduced rib velocity vectors. Vector maps in all normal cases exhibited left-right symmetric distributions, whereas those in abnormal cases showed nonuniform distributions. In conclusion, dynamic bone images were useful for accurate quantitative analysis of rib movements: Limited rib movements were indicated as a reduction of rib movement and left-right asymmetric distribution on vector maps. Thus, dynamic bone images can be a new diagnostic tool for quantitative analysis of rib movements without additional radiation dose.

Improved accuracy of markerless motion tracking on bone suppression images: preliminary study for image-guided radiation therapy (IGRT)

NASA Astrophysics Data System (ADS)

Tanaka, Rie; Sanada, Shigeru; Sakuta, Keita; Kawashima, Hiroki

2015-05-01

The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images obtained by the dual-energy subtraction technique. This study was performed to evaluate the usefulness of bone suppression image processing in image-guided radiation therapy. We demonstrated the improved accuracy of markerless motion tracking on bone suppression images. Chest fluoroscopic images of nine patients with lung nodules during respiration were obtained using a flat-panel detector system (120 kV, 0.1 mAs/pulse, 5 fps). Commercial bone suppression image processing software was applied to the fluoroscopic images to create corresponding bone suppression images. Regions of interest were manually located on lung nodules and automatic target tracking was conducted based on the template matching technique. To evaluate the accuracy of target tracking, the maximum tracking error in the resulting images was compared with that of conventional fluoroscopic images. The tracking errors were decreased by half in eight of nine cases. The average maximum tracking errors in bone suppression and conventional fluoroscopic images were 1.3   ±   1.0 and 3.3   ±   3.3 mm, respectively. The bone suppression technique was especially effective in the lower lung area where pulmonary vessels, bronchi, and ribs showed complex movements. The bone suppression technique improved tracking accuracy without special equipment and implantation of fiducial markers, and with only additional small dose to the patient. Bone suppression fluoroscopy is a potential measure for respiratory displacement of the target. This paper was presented at RSNA 2013 and was carried out at Kanazawa University, JAPAN.

Observation of cardiogenic flow oscillations in healthy subjects with hyperpolarized 3He MRI.

PubMed

Collier, Guilhem J; Marshall, Helen; Rao, Madhwesha; Stewart, Neil J; Capener, David; Wild, Jim M

2015-11-01

Recently, dynamic MRI of hyperpolarized (3)He during inhalation revealed an alternation of the image intensity between left and right lungs with a cardiac origin (Sun Y, Butler JP, Ferrigno M, Albert MS, Loring SH. Respir Physiol Neurobiol 185: 468-471, 2013). This effect is investigated further using dynamic and phase-contrast flow MRI with inhaled (3)He during slow inhalations (flow rate ∼100 ml/s) to elucidate airflow dynamics in the main lobes in six healthy subjects. The ventilation MR signal and gas inflow in the left lower lobe (LLL) of the lungs were found to oscillate clearly at the cardiac frequency in all subjects, whereas the MR signals in the other parts of the lungs had a similar oscillatory behavior but were smaller in magnitude and in anti-phase to the signal in the left lower lung. The airflow in the main bronchi showed periodic oscillations at the frequency of the cardiac cycle. In four of the subjects, backflows were observed for a short period of time of the cardiac cycle, demonstrating a pendelluft effect at the carina bifurcation between the left and right lungs. Additional (1)H structural MR images of the lung volume and synchronized ECG recording revealed that maximum inspiratory flow rates in the LLL of the lungs occurred during systole when the corresponding left lung volume increased, whereas the opposite effect was observed during diastole, with gas flow redirected to the other parts of the lung. In conclusion, cardiogenic flow oscillations have a significant effect on regional gas flow and distribution within the lungs. Copyright © 2015 the American Physiological Society.

Imaging demonstration of a flexible micro-OCT endobronchial probe (Conference Presentation)

NASA Astrophysics Data System (ADS)

Cui, Dongyao; Chu, Kengyeh K.; Ford, Timothy N.; Hyun, Daryl Chulho; Leung, Hui Min; Yin, Biwei; Birket, Susan E.; Solomon, George M.; Rowe, Steven M.; Tearney, Guillermo J.

2017-04-01

The human respiratory system is protected by a defense mechanism termed mucociliary clearance (MCC). Deficiency in MCC leads to respiratory obstruction and pulmonary infection, which often are the main causes of morbidity and mortality in diseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD). Studying key parameters that govern MCC, including ciliary beat frequency, velocity and volume of airway mucus transport, as well as periciliary liquid layer thickness are therefore of great importance in understanding human respiratory health. However, direct, in vivo visualization of ciliary function and MCC has been challenging, hindering the diagnosis of disease pathogenesis and mechanistic evaluation of novel therapeutics. Our laboratory has previously developed a 1-µm resolution optical coherence tomography method, termed Micro-OCT, which is a unique tool for visualizing the spatiotemporal features of ciliary function and MCC. We have previously described the design of a flexible 2.5 mm Micro-OCT probe that is compatible with standard flexible bronchoscopes. This device utilizes a common-path interferometer and annular sample arm apodization to attain a sharply focused spot over an extended depth of focus. Here, we present the most recent iteration of this probe and demonstrate its imaging performance in a mouse trachea tissue culture model. In addition, we have developed an ergonomic assembly for attaching the probe to a standard bronchoscope. The ergonomic assembly fixes the Micro-OCT probe's within the bronchoscope and contains a means transducing linear motion through the sheath so that the Micro-OCT beam can be scanned along the trachea. We have tested the performance of these devices for Micro-OCT imaging in an anatomically correct model of the human airway. Future studies are planned to use this technology to conduct Micro-OCT in human trachea and bronchi in vivo.

Neutron equivalent doses and associated lifetime cancer incidence risks for head & neck and spinal proton therapy

NASA Astrophysics Data System (ADS)

Athar, Basit S.; Paganetti, Harald

2009-08-01

In this work we have simulated the absorbed equivalent doses to various organs distant to the field edge assuming proton therapy treatments of brain or spine lesions. We have used computational whole-body (gender-specific and age-dependent) voxel phantoms and considered six treatment fields with varying treatment volumes and depths. The maximum neutron equivalent dose to organs near the field edge was found to be approximately 8 mSv Gy-1. We were able to clearly demonstrate that organ-specific neutron equivalent doses are age (stature) dependent. For example, assuming an 8-year-old patient, the dose to brain from the spinal fields ranged from 0.04 to 0.10 mSv Gy-1, whereas the dose to the brain assuming a 9-month-old patient ranged from 0.5 to 1.0 mSv Gy-1. Further, as the field aperture opening increases, the secondary neutron equivalent dose caused by the treatment head decreases, while the secondary neutron equivalent dose caused by the patient itself increases. To interpret the dosimetric data, we analyzed second cancer incidence risks for various organs as a function of patient age and field size based on two risk models. The results show that, for example, in an 8-year-old female patient treated with a spinal proton therapy field, breasts, lungs and rectum have the highest radiation-induced lifetime cancer incidence risks. These are estimated to be 0.71%, 1.05% and 0.60%, respectively. For an 11-year-old male patient treated with a spinal field, bronchi and rectum show the highest risks of 0.32% and 0.43%, respectively. Risks for male and female patients increase as their age at treatment time decreases.

Effects of sodium metabisulphite on guinea pig contractile airway smooth muscle responses in vitro.

PubMed Central

Sun, J.; Sakamoto, T.; Chung, K. F.

1995-01-01

BACKGROUND--Sodium metabisulphite (MBS) is known to induce bronchoconstriction in asthmatic patients. The effects of MBS on guinea pig airway smooth muscle and on neurally mediated contraction in vitro have been examined. METHODS--Tracheal and bronchial airway segments were placed in oxygenated buffer solution and electrical field stimulation was performed in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M) for the measurement of isometric tension. Atropine (10(-6) M) was added to bronchial tissues. RESULTS--Concentrations of MBS up to 10(-3) M had no direct effect on airway smooth muscle contraction and did not alter either tracheal smooth muscle contraction induced by electrical field stimulation at all frequencies or acetylcholine-induced tracheal smooth muscle contraction. There was a similar response in the absence of epithelium, except for potentiation of the response induced by electrical field stimulation at 0.5 Hz (24 (10)% increase). However, MBS (10(-5), 10(-6) and 10(-7) M) augmented neurally-mediated non-adrenergic non-cholinergic contractile responses in the bronchi (13.3 (3.2)%, 23.8 (9.6)%, and 6.4 (1.6)%, respectively). MBS had no effect on the contractile response induced by substance P, but at higher concentrations (10(-3) M and 10(-4) M) it caused a time-dependent attenuation of responses induced by either electrical field stimulation or exogenously applied acetylcholine or substance P. CONCLUSIONS--MBS had no direct contractile responses but enhanced bronchoconstriction induced by activation of non-cholinergic neural pathways in the bronchus, probably through increased release of neuropeptides. At high concentrations MBS inhibited contractile responses initiated by receptor or neural stimulation. Images PMID:7570440

Human respiratory tract model for radiological protection: a revision of the ICRP Dosimetric Model for the Respiratory System.

PubMed

Bair, W J

1989-01-01

In 1984, the International Commission on Radiological Protection (ICRP) appointed a task group of Committee 2 to review and revise, as necessary, the ICRP Dosimetric Model for the Respiratory System. The model was originally published in 1966, modified slightly in Publication No. 19, and again in Publication No. 30 (in 1979). The task group concluded that research during the past 20 y suggested certain deficiencies in the ICRP Dosimetric Model for the Respiratory System. Research has also provided sufficient information for a revision of the model. The task group's approach has been to review, in depth, morphology and physiology of the respiratory tract; deposition of inhaled particles in the respiratory tract; clearance of deposited materials; and the nature and specific sites of damage to the respiratory tract caused by inhaled radioactive substances. This review has led to a redefinition of the regions of the respiratory tract for dosimetric purposes. The redefinition has a morphologic and physiological basis and is consistent with observed deposition and clearance of particles and with resultant pathology. Regions, as revised, are the extrathoracic (E-T) region, comprising the nasal and oral regions, the pharynx, larynx, and upper part of the trachea; the fast-clearing thoracic region (T[f]), comprising the remainder of the trachea and bronchi; and the slow-clearing thoracic region (T[s]), comprising the bronchioles, alveoli, and thoracic lymph nodes. A task group report will include models for calculating radiation doses to these regions of the respiratory tract following inhalation of representative alpha-, beta-, and gamma-emitting particulate and gaseous radionuclides. The models may be implemented as a package of computer codes available to a wide range of users. This should facilitate application of the revised human respiratory tract model to worldwide radiation protection needs.

[EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

PubMed

Shostak, Yael; Kramer, Mordechai R

2017-11-01

Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients' quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

Endotracheal tube biofilm translocation in the lateral Trendelenburg position.

PubMed

Li Bassi, Gianluigi; Fernandez-Barat, Laia; Saucedo, Lina; Giunta, Valeria; Marti, Joan Daniel; Tavares Ranzani, Otavio; Aguilera Xiol, Eli; Rigol, Montserrat; Roca, Ignasi; Muñoz, Laura; Luque, Nestor; Esperatti, Mariano; Saco, Maria Adela; Ramirez, Jose; Vila, Jordi; Ferrer, Miguel; Torres, Antoni

2015-02-27

Laboratory studies demonstrated that the lateral Trendelenburg position (LTP) is superior to the semirecumbent position (SRP) in the prevention of ventilator-associated pulmonary infections. We assessed whether the LTP could also prevent pulmonary colonization and infections caused by an endotracheal tube (ETT) biofilm. Eighteen pigs were intubated with ETTs colonized by Pseudomonas aeruginosa biofilm. Pigs were positioned in LTP and randomized to be on mechanical ventilatin (MV) up to 24 hour, 48 hour, 48 hour with acute lung injury (ALI) by oleic acid and 72 hour. Bacteriologic and microscopy studies confirmed presence of biofilm within the ETT. Upon autopsy, samples from the proximal and distal airways were excised for P.aeruginosa quantification. Ventilator-associated tracheobronchitis (VAT) was confirmed by bronchial tissue culture ≥3 log colony forming units per gram (cfu/g). In pulmonary lobes with gross findings of pneumonia, ventilator-associated pneumonia (VAP) was confirmed by lung tissue culture ≥3 log cfu/g. P.aeruginosa colonized the internal lumen of 16 out of 18 ETTs (88.89%), and a mature biofilm was consistently present. P.aeruginosa colonization did not differ among groups, and was found in 23.6% of samples from the proximal airways, and in 7.1% from the distal bronchi (P = 0.001). Animals of the 24 hour group never developed respiratory infections, whereas 20%, 60% and 25% of the animals in group 48 hour, 48 hour-ALI and 72 hour developed P.aeruginosa VAT, respectively (P = 0.327). Nevertheless, VAP never developed. Our findings imply that during the course of invasive MV up to 72 hour, an ETT P.aeruginosa biofilm hastily colonizes the respiratory tract. Yet, the LTP compartmentalizes colonization and infection within the proximal airways and VAP never develops.

Pulmonary Abnormalities in Mice with Paracoccidioidomycosis: A Sequential Study Comparing High Resolution Computed Tomography and Pathologic Findings

PubMed Central

Hidalgo, José Miguel; de Oliveira Pascarelli, Bernardo Miguel; Patiño, Jairo Hernando; Lenzi, Henrique Leonel; Restrepo, Angela; Cano, Luz Elena

2010-01-01

Background Human paracoccidioidomycosis (PCM) is an endemic fungal disease of pulmonary origin. Follow-up of pulmonary lesions by image studies in an experimental model of PCM has not been previously attempted. This study focuses on defining patterns, topography and intensity of lung lesions in experimentally infected PCM mice by means of a comparative analysis between High Resolution Computed Tomography (HRCT) and histopathologic parameters. Methodology Male BALB/c mice were intranasally inoculated with 3×106 Paracoccidioides brasiliensis (Pb) conidia (n = 50) or PBS (n = 50). HRCT was done every four weeks to determine pulmonary lesions, quantify lung density, reconstruct and quantify lung air structure. Lungs were also analyzed by histopathology and histomorphometry. Results Three different patterns of lesions were evidenced by HRCT and histopathology, as follows: nodular-diffuse, confluent and pseudo-tumoral. The lesions were mainly located around the hilus and affected more frequently the left lung. At the 4th week post-challenge HRCT showed that 80% of the Pb-infected mice had peri-bronchial consolidations associated with a significant increase in upper lung density when compared with controls, (−263±25 vs. −422±10 HU, p<0.001). After the 8th and 12th weeks, consolidation had progressed involving also the middle regions. Histopathology revealed that consolidation as assessed by HRCT was equivalent histologically to a confluent granulomatous reaction, while nodules corresponded to individual compact granulomas. At the 16th week of infection, confluent granulomas formed pseudotumoral masses that obstructed large bronchi. Discrete focal fibrosis was visible gradually around granulomas, but this finding was only evident by histopathology. Conclusions/Significance This study demonstrated that conventional HRCT is a useful tool for evaluation and quantification of pulmonary damage occurring in experimental mouse PCM. The experimental design used decreases the need to sacrifice a large number of animals, and serves to monitor treatment efficacy by means of a more rational approach to the study of human lung disease. PMID:20614019

Evaluation of obstructive sleep apnea in non-cystic fibrosis bronchiectasis: A cross-sectional study

PubMed Central

Urbano, Jessica Julioti; Santos, Israel Reis; Silva, Anderson Soares; Perez, Eduardo Araújo; Souza, Ângela Honda; Nascimento, Oliver Augusto; Jardim, José Roberto; Insalaco, Giuseppe; Oliveira, Luis Vicente Franco; Stirbulov, Roberto

2017-01-01

The relationship between sleep disorders and bronchiectasis has not been well described. We hypothesize that, due to the irreversible dilatation of the bronchi, the presence of secretions, and airflow obstruction, patients with non-cystic fibrosis bronchiectasis may be predisposed to hypoxemia during sleep, or to symptoms that may lead to arousal. A cross-sectional observational study was performed involving 49 patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis (NCFB). All patients underwent clinical evaluation, spirometry, and polysomnography, and were evaluated for the presence of excessive daytime sleepiness (EDS) and risk of obstructive sleep apnea (OSA). The mean age of the participants was 50.3 ± 13.6 years; 51.1% of patients were male and had a mean body mass index of 23.8 ± 3.4 kg/m2. The mean total sleep time (TST) was 325.15 ± 64.22 min with a slight reduction in sleep efficiency (84.01 ± 29.2%). Regarding sleep stages, stage 1 sleep and REM sleep were abnormal. OSA was present in 40.82% of the patients. The mean arousal index was 5.6 ± 2.9/h and snoring was observed in 71.43% of the patients. The oxygen desaturation index (ODI) was 14.35 ± 15.36/h, mean minimum oxygen saturation (SpO2 nadir) was 83.29 ± 7.99%, and mean TST with an SpO2 less than 90% was 30.21 ± 60.48 min. EDS was exhibited by 53.06% of the patients and 55.1% were at high risk of developing OSA. The patients infected by Pseudomonas aeruginosa had higher apnea-hypopnea indices, ODI, and TST with SpO2 < 90%, and lower values of SpO2 nadir. Adult patients with clinically stable NCFB, especially those infected by Pseudomonas aeruginosa, display EDS and a high prevalence of OSA, associated with considerable oxygen desaturation during sleep. PMID:28972989

Evaluation of obstructive sleep apnea in non-cystic fibrosis bronchiectasis: A cross-sectional study.

PubMed

Faria Júnior, Newton Santos; Urbano, Jessica Julioti; Santos, Israel Reis; Silva, Anderson Soares; Perez, Eduardo Araújo; Souza, Ângela Honda; Nascimento, Oliver Augusto; Jardim, José Roberto; Insalaco, Giuseppe; Oliveira, Luis Vicente Franco; Stirbulov, Roberto

2017-01-01

The relationship between sleep disorders and bronchiectasis has not been well described. We hypothesize that, due to the irreversible dilatation of the bronchi, the presence of secretions, and airflow obstruction, patients with non-cystic fibrosis bronchiectasis may be predisposed to hypoxemia during sleep, or to symptoms that may lead to arousal. A cross-sectional observational study was performed involving 49 patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis (NCFB). All patients underwent clinical evaluation, spirometry, and polysomnography, and were evaluated for the presence of excessive daytime sleepiness (EDS) and risk of obstructive sleep apnea (OSA). The mean age of the participants was 50.3 ± 13.6 years; 51.1% of patients were male and had a mean body mass index of 23.8 ± 3.4 kg/m2. The mean total sleep time (TST) was 325.15 ± 64.22 min with a slight reduction in sleep efficiency (84.01 ± 29.2%). Regarding sleep stages, stage 1 sleep and REM sleep were abnormal. OSA was present in 40.82% of the patients. The mean arousal index was 5.6 ± 2.9/h and snoring was observed in 71.43% of the patients. The oxygen desaturation index (ODI) was 14.35 ± 15.36/h, mean minimum oxygen saturation (SpO2 nadir) was 83.29 ± 7.99%, and mean TST with an SpO2 less than 90% was 30.21 ± 60.48 min. EDS was exhibited by 53.06% of the patients and 55.1% were at high risk of developing OSA. The patients infected by Pseudomonas aeruginosa had higher apnea-hypopnea indices, ODI, and TST with SpO2 < 90%, and lower values of SpO2 nadir. Adult patients with clinically stable NCFB, especially those infected by Pseudomonas aeruginosa, display EDS and a high prevalence of OSA, associated with considerable oxygen desaturation during sleep.

Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiyoshi, Kyoko; Ichinose, Takamichi; Sadakane, Kaori

Asian sand dust (ASD) containing sulfate (SO{sub 4} {sup 2-}) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO{sub 4} {sup 2-} toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO{sub 4} {sup 2-} (ASD-SO{sub 4}); OVA+ASD; OVA+ASD-SO{sub 4}. ASD or ASD-SO{sub 4} alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO{sub 4} increased pro-inflammatorymore » mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO{sub 4} enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO{sub 4} {sup 2-} was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO{sub 4} group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils.« less

[Occult bronchial foreign bodies - analysis of own material].

PubMed

Szafrański, Wojciech; Dobielski, Jarosław; Papiewski, Wojciech; Czechowska, Urszula

2013-01-01

The aspiration of a foreign body is usually combined with acute clinical symptoms requiring immediate medical intervention. Nevertheless, in approximately one third of patients the symptoms of aspiration are less prominent; such a clinical condition is called occult bronchial foreign body (OBFB). The aim of our study was to assess the frequency of OBFB in the pulmonary unit of a district hospital and to evaluate the diagnostic difficulties and treatment modalities in such patients. The examined group consisted of patients hospitalized in the Department of Lung Diseases in Radom District Hospital. A retrospective analysis of medical records was preformed. In the period 1978-2008 - 12 patients (10 males, 2 females) were hospitalized due to OBFB. The foreign bodies occluded the bronchi over 2 months (3 to 7) in 4 patients. The moment of aspiration was not remembered by 8 patients. Cases of OBFB were rare. In the presented material the frequency was 4 per 10,000 hospitalizations and 8 per 10,000 bronchoscopies. In our region of 600,000 population the index of hospitalization due to OBFB in adults (〉 14 years of age) was 0.07 per 100,000 inhabitants/year. Foreign bodies mainly included bone fragments (5 cases), vegetal remnants - clove of garlic, ear of corn (3 patients), and other food remnants (2 patients). Occasionally other aspirates were found, such as a wooden peg or a piece of plastic. The aspiration took place mostly during meals. The patients developed one or more of the following symptoms: purulent pneumonia (3 cases), pleural empyema (1 case), atelectasis (5 cases), and recurrent bronchitis and pneumonia (2 cases). The foreign body (fragments of plants) was mimicking a bronchial tumour in 4 patients. Fibre optic or rigid bronchoscopy was applied successfully in 11 patients. Only one patient needed surgical intervention. OBFB is a rare condition, but has to be taken into consideration as a cause of chest radiological pathology and in patients with chronic and/or recurrent inflammatory disease of the respiratory system.

Effect of venous (gut) CO2 loading on intrapulmonary gas fractions and ventilation in the tegu lizard.

PubMed

Ballam, G O; Donaldson, L A

1988-01-01

Studies were conducted to determine regional pulmonary gas concentrations in the tegu lizard lung. Additionally, changes in pulmonary gas concentrations and ventilatory patterns caused by elevating venous levels of CO2 by gut infusion were measured. It was found that significant stratification of lung gases was present in the tegu and that dynamic fluctuations of CO2 concentration varied throughout the length of the lung. Mean FCO2 was greater and FO2 less in the posterior regions of the lung. In the posterior regions gas concentrations remained nearly constant, whereas in the anterior regions large swings were observed with each breath. In the most anterior sections of the lung near the bronchi, CO2 and O2 concentrations approached atmospheric levels during inspiration and posterior lung levels during expiration. During gut loading of CO2, the rate of rise of CO2 during the breathing pause increased. The mean level of CO2 also increased. Breathing rate and tidal volume increased to produce a doubling of VE. These results indicate that the method of introduction of CO2 into the tegu respiratory system determines the ventilatory response. If the CO2 is introduced into the venous blood a dramatic increase in ventilation is observed. If the CO2 is introduced into the inspired air a significant decrease in ventilation is produced. The changes in pulmonary CO2 environment caused by inspiratory CO2 loading are different from those caused by venous CO2 loading. We hypothesize that the differences in pulmonary CO2 environment caused by either inspiratory CO2 loading or fluctuations in venous CO2 concentration act differently on the IPC. The differing response of the IPC to the two methods of CO2 loading is the cause of the opposite ventilatory response seen during either venous or inspiratory loading.

The Relationships Between Weather and Climate and Attacks of Bronchitis

NASA Astrophysics Data System (ADS)

Talaia, M. A. R.; Saraiva, M. A. C.; Vieira da Cruz, A. A.

The area of Aveiro, more concretely Aveiro lagoon, a natural laboratory has been con- sidered, for promoting the development and the application of several investigations worked. The importance of the influences of weather and climate on human health has been well known since ancient teams and many decisions concerning human be- haviour it are clearly weather related. However, decisions related to weather criteria can be important and economically significant, but the real economic effect of the weather is difficult to assess. Talaia et al. (2000) and Talaia and Vieira da Cruz (2001) have shown the possible harmful effect of certain meteorological factors on respiratory conditions. Bronchitis is a disease caused by inflammation of the bronchi as a result of infectious agents or air pollutants. In this study our attention is to relate, the be- ginning of bronchitis attacks in the services of urgency of the Hospital of Aveiro with meteorological factors, and the risk group are studied. We used the medical records and the database of meteorological factors. The obtained analysis allows to conclude that some meteorological factors have correlation with the occurrences of the disease and to allow improving the work in the urgency services in the requested periods. The knowledge that will be extracted of this study can be used later in studies that inte- grate other important components for the characterisation of the environmental impact in the area. References: Talaia, M.A.R., Vieira da Cruz, A.A., Saraiva, M.A.C., Amaro, G.S., Oliveira, C.J. and Carvalho, C.F., 2000, The Influence of Meteorological Fac- tors on Pneumonia Emergencies in Aveiro, International Symposium on Human- Biometeorology, St. Petersburg (Pushkin), Russia, pp. 67-68. Talaia, M.A.R. and Vieira of Cruz, A.A., (2001), Meteorological Effects on the Resistance of the Body to Influenza - One Study in Aveiro Region, Proceedings 2nd Symposium of Meteorol- ogy and Geophysics of APMG and 3rd Meeting Portuguese-Spanish of Meteorology (in press).

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates.

PubMed

Longest, P Worth; Tian, Geng; Khajeh-Hosseini-Dalasm, Navvab; Hindle, Michael

2016-12-01

The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition. The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region. It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data. The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro-in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate.

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

PubMed Central

Tian, Geng; Khajeh-Hosseini-Dalasm, Navvab; Hindle, Michael

2016-01-01

Abstract Background: The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition. Methods: The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region. Results: It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data. Conclusions: The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro–in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate. PMID:27082824

Management of cystic echinococcosis complications and dissemination: where is the evidence?

PubMed

Dziri, Chadli; Haouet, Karim; Fingerhut, Abe; Zaouche, Abdeljelil

2009-06-01

This systematic review was designed to provide "evidence-based" answers to identify the best treatment for a complicated hydatid cyst of the liver and the appropriate management of disseminated cystic echinococcosis. An extensive electronic search of the relevant literature was performed using Medline and the Cochrane Library. This systematic review enabled us make to determine the best treatment options for the following conditions. Liver hydatid cysts ruptured into the biliary tract: Common bile duct exploration should be conducted using intraoperative cholangiography and choledoscopy. When the biliary tract is cleared of all cystic content, T-tube drainage should be sufficient. The principal difficulty concerned the management of the large biliocystic fistula: suture or internal transfistulary drainage or fistulization. Medical treatment is indicated in association with surgery for 3 months postoperatively. During the preoperative period, endoscopic retrograde cholangiopancreatography (ERCP) combined with preoperative endoscopic sphincterotomy (ES) may decrease the incidence of postoperative external fistula. Liver hydatid cysts involving the thorax: An abdominal approach is mandatory when common bile duct drainage is required, and it may be sufficient to treat a direct rupture into bronchi. An acute abdomen, owing to Liver hydatid cysts ruptured into peritoneum, requires an emergent operation. Medical treatment should be associated. Cystic echinococcosis of the lung: Surgery is still the main therapeutic option to remove the cyst, suture bronchial fistula if necessary, followed by capitonnage. Osseous cystic echinococcosis: Wide surgical excision is recommended. Cystic echinococcosis of the heart: Cystopericystectomy is the "gold standard" procedure but is sometimes unsuitable for particular sites. Cystic echinococcosis of the kidney: Cystectomy with pericystectomy is feasible in 75% of cases; nephrectomy must be reserved for destroyed kidney. Multiple associated cystic echinococcosis locations: Complicated cysts should be treated with high priority. In case of several cysts in the liver, spleen, and peritoneum, removal of all cysts in the same intervention is indicated when there is no threat to the life of the patient. Otherwise, a planned reoperation should be considered.

Troglostrongylus brevior and Troglostrongylus subcrenatus (Strongylida: Crenosomatidae) as agents of broncho-pulmonary infestation in domestic cats

PubMed Central

2012-01-01

Background Aelurostrongylus abstrusus is currently regarded as the main metastrongyloid infesting domestic cats, whereas the reports of Troglostrongylus spp. in domestic and wild felids largely remain anecdotic. This paper reports on pulmonary infestation caused by Troglostrongylus brevior and Troglostrongylus subcrenatus in two kittens and describes, for the first time, associated clinical presentations and pathological features. Morphometrical, molecular and phylogenetic analyses have also been conducted to differentiate here the examined Troglostrongylus species from A. abstrusus, towards a clearer delineation of metastrongyloids affecting cats. Methods Two kittens were referred for respiratory distress and hospitalized with a diagnosis of severe aelurostrongylosis, based on the presence of metastrongyloid larvae in the faeces. Despite prompt treatment, kittens died within 48 hours. Both kittens were submitted to necropsy to determine the cause of death. Results At necropsy, nematode specimens were found in the trachea, bronchi and bronchioles and were associated with respiratory signs (i.e., dyspnoea, polypnea, severe coughing and nasal discharge). Morphology and measurements of adult parasites found allowed the unequivocal identification of T. brevior and T. subcrenatus, even if first stage larvae were rather similar to those of A. abstrusus. Briefly, T. brevior and T. subcrenatus larvae were shorter in length and lacking the typical knob-like terminal end of A. abstrusus. Molecular and phylogenetic analyses corroborated morphological identification and provided data on mitochondrial and ribosomal DNA genes of T. brevior. Conclusions Data presented here indicate that T. brevior and T. subcrenatus may cause major respiratory distress in domestic cats. Consequently, these two species should be included, along with A. abstrusus, in the differential diagnosis of cat bronchopulmonary affections and treatment protocols need to be evaluated. Through research on the biology, epidemiology and control of Troglostrongylus spp. infestations in domestic cats are advisable to implement current knowledge on these neglected metastrongyloids. PMID:22916686

Surgical anatomy of the supracarinal esophagus based on a minimally invasive approach: vascular and nervous anatomy and technical steps to resection and lymphadenectomy.

PubMed

Cuesta, Miguel A; van der Wielen, Nicole; Weijs, Teus J; Bleys, Ronald L A W; Gisbertz, Suzanne S; van Duijvendijk, Peter; van Hillegersberg, Richard; Ruurda, Jelle P; van Berge Henegouwen, Mark I; Straatman, Jennifer; Osugi, Harushi; van der Peet, Donald L

2017-04-01

During esophageal dissection and lymphadenectomy of the upper mediastinum by thoracoscopy in prone position, we observed a complex anatomy in which we had to resect the esophagus, dissect vessels and nerves, and take down some of these in order to perform a complete lymphadenectomy. In order to improve the quality of the dissection and standardization of the procedure, we describe the surgical anatomy and steps involved in this procedure. We retrospectively evaluated twenty consecutive and unedited videos of thoracoscopic esophageal resections. We recorded the vascular anatomy of the supracarinal esophagus, lymph node stations and the steps taken in this procedure. The resulting concept was validated in a prospective study including five patients. Seventy percent of patients in the retrospective study had one right bronchial artery (RBA) and two left bronchial arteries (LBA). The RBA was divided at both sides of the esophagus in 18 patients, with preservation of one LBA or at least one esophageal branch in all cases. Both recurrent laryngeal nerves were identified in 18 patients. All patients in the prospective study had one RBA and two LBA, and in four patients the RBA was divided at both sides of the esophagus and preserved one of the LBA. Lymphadenectomy was performed of stations 4R, 4L, 2R and 2L, with a median of 11 resected lymph nodes. Both recurrent laryngeal nerves were identified in four patients. In three patients, only the left recurrent nerve could be identified. Two patients showed palsy of the left recurrent laryngeal nerve, and one showed neuropraxia of the left vocal cord. Knowledge of the surgical anatomy of the upper mediastinum and its anatomical variations is important for standardization of an adequate esophageal resection and paratracheal lymphadenectomy with preservation of any vascularization of the trachea, bronchi and the recurrent laryngeal nerves.

Ultra-High-Resolution Computed Tomography of the Lung: Image Quality of a Prototype Scanner

PubMed Central

Kakinuma, Ryutaro; Moriyama, Noriyuki; Muramatsu, Yukio; Gomi, Shiho; Suzuki, Masahiro; Nagasawa, Hirobumi; Kusumoto, Masahiko; Aso, Tomohiko; Muramatsu, Yoshihisa; Tsuchida, Takaaki; Tsuta, Koji; Maeshima, Akiko Miyagi; Tochigi, Naobumi; Watanabe, Shun-ichi; Sugihara, Naoki; Tsukagoshi, Shinsuke; Saito, Yasuo; Kazama, Masahiro; Ashizawa, Kazuto; Awai, Kazuo; Honda, Osamu; Ishikawa, Hiroyuki; Koizumi, Naoya; Komoto, Daisuke; Moriya, Hiroshi; Oda, Seitaro; Oshiro, Yasuji; Yanagawa, Masahiro; Tomiyama, Noriyuki; Asamura, Hisao

2015-01-01

Purpose The image noise and image quality of a prototype ultra-high-resolution computed tomography (U-HRCT) scanner was evaluated and compared with those of conventional high-resolution CT (C-HRCT) scanners. Materials and Methods This study was approved by the institutional review board. A U-HRCT scanner prototype with 0.25 mm x 4 rows and operating at 120 mAs was used. The C-HRCT images were obtained using a 0.5 mm x 16 or 0.5 mm x 64 detector-row CT scanner operating at 150 mAs. Images from both scanners were reconstructed at 0.1-mm intervals; the slice thickness was 0.25 mm for the U-HRCT scanner and 0.5 mm for the C-HRCT scanners. For both scanners, the display field of view was 80 mm. The image noise of each scanner was evaluated using a phantom. U-HRCT and C-HRCT images of 53 images selected from 37 lung nodules were then observed and graded using a 5-point score by 10 board-certified thoracic radiologists. The images were presented to the observers randomly and in a blinded manner. Results The image noise for U-HRCT (100.87 ± 0.51 Hounsfield units [HU]) was greater than that for C-HRCT (40.41 ± 0.52 HU; P < .0001). The image quality of U-HRCT was graded as superior to that of C-HRCT (P < .0001) for all of the following parameters that were examined: margins of subsolid and solid nodules, edges of solid components and pulmonary vessels in subsolid nodules, air bronchograms, pleural indentations, margins of pulmonary vessels, edges of bronchi, and interlobar fissures. Conclusion Despite a larger image noise, the prototype U-HRCT scanner had a significantly better image quality than the C-HRCT scanners. PMID:26352144

Quantification of Pulmonary Fibrosis in a Bleomycin Mouse Model Using Automated Histological Image Analysis.

PubMed

Gilhodes, Jean-Claude; Julé, Yvon; Kreuz, Sebastian; Stierstorfer, Birgit; Stiller, Detlef; Wollin, Lutz

2017-01-01

Current literature on pulmonary fibrosis induced in animal models highlights the need of an accurate, reliable and reproducible histological quantitative analysis. One of the major limits of histological scoring concerns the fact that it is observer-dependent and consequently subject to variability, which may preclude comparative studies between different laboratories. To achieve a reliable and observer-independent quantification of lung fibrosis we developed an automated software histological image analysis performed from digital image of entire lung sections. This automated analysis was compared to standard evaluation methods with regard to its validation as an end-point measure of fibrosis. Lung fibrosis was induced in mice by intratracheal administration of bleomycin (BLM) at 0.25, 0.5, 0.75 and 1 mg/kg. A detailed characterization of BLM-induced fibrosis was performed 14 days after BLM administration using lung function testing, micro-computed tomography and Ashcroft scoring analysis. Quantification of fibrosis by automated analysis was assessed based on pulmonary tissue density measured from thousands of micro-tiles processed from digital images of entire lung sections. Prior to analysis, large bronchi and vessels were manually excluded from the original images. Measurement of fibrosis has been expressed by two indexes: the mean pulmonary tissue density and the high pulmonary tissue density frequency. We showed that tissue density indexes gave access to a very accurate and reliable quantification of morphological changes induced by BLM even for the lowest concentration used (0.25 mg/kg). A reconstructed 2D-image of the entire lung section at high resolution (3.6 μm/pixel) has been performed from tissue density values allowing the visualization of their distribution throughout fibrotic and non-fibrotic regions. A significant correlation (p<0.0001) was found between automated analysis and the above standard evaluation methods. This correlation establishes automated analysis as a novel end-point measure of BLM-induced lung fibrosis in mice, which will be very valuable for future preclinical drug explorations.

Quantification of Pulmonary Fibrosis in a Bleomycin Mouse Model Using Automated Histological Image Analysis

PubMed Central

Gilhodes, Jean-Claude; Kreuz, Sebastian; Stierstorfer, Birgit; Stiller, Detlef; Wollin, Lutz

2017-01-01

Current literature on pulmonary fibrosis induced in animal models highlights the need of an accurate, reliable and reproducible histological quantitative analysis. One of the major limits of histological scoring concerns the fact that it is observer-dependent and consequently subject to variability, which may preclude comparative studies between different laboratories. To achieve a reliable and observer-independent quantification of lung fibrosis we developed an automated software histological image analysis performed from digital image of entire lung sections. This automated analysis was compared to standard evaluation methods with regard to its validation as an end-point measure of fibrosis. Lung fibrosis was induced in mice by intratracheal administration of bleomycin (BLM) at 0.25, 0.5, 0.75 and 1 mg/kg. A detailed characterization of BLM-induced fibrosis was performed 14 days after BLM administration using lung function testing, micro-computed tomography and Ashcroft scoring analysis. Quantification of fibrosis by automated analysis was assessed based on pulmonary tissue density measured from thousands of micro-tiles processed from digital images of entire lung sections. Prior to analysis, large bronchi and vessels were manually excluded from the original images. Measurement of fibrosis has been expressed by two indexes: the mean pulmonary tissue density and the high pulmonary tissue density frequency. We showed that tissue density indexes gave access to a very accurate and reliable quantification of morphological changes induced by BLM even for the lowest concentration used (0.25 mg/kg). A reconstructed 2D-image of the entire lung section at high resolution (3.6 μm/pixel) has been performed from tissue density values allowing the visualization of their distribution throughout fibrotic and non-fibrotic regions. A significant correlation (p<0.0001) was found between automated analysis and the above standard evaluation methods. This correlation establishes automated analysis as a novel end-point measure of BLM-induced lung fibrosis in mice, which will be very valuable for future preclinical drug explorations. PMID:28107543

Digital Longitudinal Tomosynthesis

NASA Astrophysics Data System (ADS)

Rimkus, Daniel Steven

1985-12-01

The purpose of this dissertation was to investigate the clinical utility of digital longitudinal tomosynthesis in radiology. By acquiring a finite group of digital images during a longitudinal tomographic exposure, and processing these images, tomographic planes, other than the fulcrum plane, can be reconstructed. This process is now termed "tomosynthesis". A prototype system utilizing this technique was developed. Both phantom and patient studies were done with this system. The phantom studies were evaluated by subjective, visual criterion and by quantitative analysis of edge sharpness and noise in the reconstructions. Two groups of patients and one volunteer were studied. The first patient group consisted of 8 patients undergoing intravenous urography (IVU). These patients had digital tomography and film tomography of the abdomen. The second patient group consisted of 4 patients with lung cancer admitted to the hospital for laser resection of endobronchial tumor. These patients had mediastinal digital tomograms to evaluate the trachea and mainstem bronchi. The knee of one volunteer was imaged by film tomography and digital tomography. The results of the phantom studies showed that the digital reconstructions accurately produced images of the desired planes. The edge sharpness of the reconstructions approached that of the acquired images. Adequate reconstructions were achieved with as few as 5 images acquired during the exposure, with the quality of the reconstructions improving as the number of images acquired increased. The IVU patients' digital studies had less contrast and spatial resolution than the film tomograms. The single renal lesion visible on the film tomograms was also visible in the digital images. The digital mediastinal studies were felt by several radiologists to be superior to a standard chest xray in evaluating the airways. The digital images of the volunteer's knee showed many of the same anatomic features as the film tomogram, but the digital images had less spatial and contrast resolution. With the equipment improvements discussed in the thesis, digital tomography may have an important role in radiology.

Theoretical deposition of carcinogenic particle aggregates in the upper respiratory tract.

PubMed

Sturm, Robert

2013-10-01

Numerous particles suspended in the atmosphere are composed of smaller particular components that form aggregates with highly irregular shape. Such aggregates, among which dusts and soot are the most prominent examples, may be taken up into the respiratory tract and, in the worst case, initiate a malignant transformation of lung cells. Particle aggregates were theoretically modelled by using small spheres with equal diameters (1 nm) and arranging them randomly. This procedure resulted in the generation of various aggregate shapes (chain-like, loose, compact), for which essential parameters such as dynamic shape factors, χ, and aerodynamic diameters, dae , were computed. Deposition of aggregates consisting of 10, 50, 100, and 1,000 nano-spheres was simulated for the uppermost parts of the human respiratory system (extrathoracic region and airway generation 0 to 4), thereby distinguishing between sitting and light-work breathing as well as between nasal and oral inhalation. Based upon the modelling results, aggregate deposition in the human respiratory system can be described as a function of (I) aerodynamic diameter; (II) inhaled particle position within the airway system; and (III) breathing conditions. Therefore, highest deposition values were obtained for nano-scale aggregates (<10 nm), whereas larger aggregates exhibited slightly to significantly reduced deposition probabilities. Extrathoracic regions and uppermost bronchi (generations 0 to 1) were marked by most effective particle capture. Any increase of inhaled air volumes and reduction of breathing times resulted in an enhancement of deposition probabilities of larger particles. Based on the results derived from this study it may be concluded that small particle aggregates are accumulated in the uppermost compartments of the human respiratory tract, where they may unfold their unwholesome potential. In the case of carcinogenic particles being stored in epithelial cells for a longer time span, malignant transformations starting with the formation of cancerous cells and ending with the growth of a tumour have to be assumed.

[Life-threatening hemoptysis. Treatment with transcatheter embolization].

PubMed

Gimeno Peribáñez, M J; Madariaga, B; Alfonso Aguirán, E R; Medrano Peña, J; Fernández Gómez, J A; Herrera, M; de Gregorio Ariza, M A

1999-09-01

To evaluate the immediate and long-term efficacy of transcatheter embolization of bronchial, systemic and pulmonary arteries to treat life-threatening hemoptysis. Likewise, we propose the systematic treatment of life-threatening hemoptysis by means of transcatheter embolization. One hundred seven angiographies were performed on the same number of patients experiencing life-threatening hemoptysis with bleeding exceeding 150 ml in 24 hours. Before angiography, we rinsed the vessels with cold saline solution and adrenalin through the catheter. Thirty-three patients were female and 74 were male. Mean age was 52.3 years (range 12 to 75 years). Embolization was performed in 104 (3 in patients with recurrent hemoptysis) using polyvinyl alcohol and micro-coils. Bronchial and systemic arteries of the affected hemithorax (mammary and lateral thoracic arteries) were checked in all patients. If findings were negative or bleeding was recurrent, we also performed pulmonary arteriography. In two cases we were unable to catheterize the artery theoretically responsible for bleeding. Examination of both arterial and systemic vessels proved normal in one patient. The embolization technique was successful in 99% (103/104) of the cases and the rate of immediate clinical success was 95.1% (99/104). The mean time of follow-up was 43.2 months (range 3 to 66 months). Hemoptysis recurred in 15.3% (16 cases) within a mean 8.3 months (range 15 days to 48 months); embolization was repeated in 14 of these patients with satisfactory results, while two underwent surgery. In five patients (4.8%) we observed complications requiring no additional medical treatment: one instance of coil migration to the deep femoral artery, from which the coil was removed in a basket; two cases of bronchial artery extravasation with small mediastinal hematomas; and two hematomas at the points of puncture. Selective or supra-selective embolization of the arteries that feed the bronchi provides effective management of life-threatening hemoptysis. No additional medical treatment is usually required.

Neurogenic plasma leakage in mouse airways

PubMed Central

Baluk, Peter; Thurston, Gavin; Murphy, Thomas J; Bunnett, Nigel W; McDonald, Donald M

1999-01-01

This study sought to determine whether neurogenic inflammation occurs in the airways by examining the effects of capsaicin or substance P on microvascular plasma leakage in the trachea and lungs of male pathogen-free C57BL/6 mice. Single bolus intravenous injections of capsaicin (0.5 and 1 μmol kg−1, i.v.) or substance P (1, 10 and 37 nmol kg−1, i.v.) failed to induce significant leakage in the trachea, assessed as extravasation of Evans blue dye, but did induce leakage in the urinary bladder and skin. Pretreatment with captopril (2.5 mg kg−1, i.v.), a selective inhibitor of angiotensin converting enzyme (ACE), either alone or in combination with phosphoramidon (2.5 mg kg−1, i.v.), a selective inhibitor of neutral endopeptidase (NEP), increased baseline leakage of Evans blue in the absence of any exogenous inflammatory mediator. The increase was reversed by the bradykinin B2 receptor antagonist Hoe 140 (0.1 mg kg−1, i.v.). After pretreatment with phosphoramidon and captopril, capsaicin increased the Evans blue leakage above the baseline in the trachea, but not in the lung. This increase was reversed by the tachykinin (NK1) receptor antagonist SR 140333 (0.7 mg kg−1, i.v.), but not by the NK2 receptor antagonist SR 48968 (1 mg kg−1, i.v.). Experiments using Monastral blue pigment as a tracer localized the leakage to postcapillary venules in the trachea and intrapulmonary bronchi, although the labelled vessels were less numerous in mice than in comparably treated rats. Blood vessels of the pulmonary circulation were not labelled. We conclude that neurogenic inflammation can occur in airways of pathogen-free mice, but only after the inhibition of enzymes that normally degrade inflammatory peptides. Neurogenic inflammation does not involve the pulmonary microvasculature. PMID:10077247

First Evaluation of the New Thin Convex Probe Endobronchial Ultrasound Scope: A Human Ex Vivo Lung Study.

PubMed

Patel, Priya; Wada, Hironobu; Hu, Hsin-Pei; Hirohashi, Kentaro; Kato, Tatsuya; Ujiie, Hideki; Ahn, Jin Young; Lee, Daiyoon; Geddie, William; Yasufuku, Kazuhiro

2017-04-01

Endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration allows for sampling of mediastinal lymph nodes. The external diameter, rigidity, and angulation of the convex probe EBUS renders limited accessibility. This study compares the accessibility and transbronchial needle aspiration capability of the prototype thin convex probe EBUS against the convex probe EBUS in human ex vivo lungs rejected for transplant. The prototype thin convex probe EBUS (BF-Y0055; Olympus, Tokyo, Japan) with a thinner tip (5.9 mm), greater upward angle (170 degrees), and decreased forward oblique direction of view (20 degrees) was compared with the current convex probe EBUS (6.9-mm tip, 120 degrees, and 35 degrees, respectively). Accessibility and transbronchial needle aspiration capability was assessed in ex vivo human lungs declined for lung transplant. The distance of maximum reach and sustainable endoscopic limit were measured. Transbronchial needle aspiration capability was assessed using the prototype 25G aspiration needle in segmental lymph nodes. In all evaluated lungs (n = 5), the thin convex probe EBUS demonstrated greater reach and a higher success rate, averaging 22.1 mm greater maximum reach and 10.3 mm further endoscopic visibility range than convex probe EBUS, and could assess selectively almost all segmental bronchi (98% right, 91% left), demonstrating nearly twice the accessibility as the convex probe EBUS (48% right, 47% left). The prototype successfully enabled cytologic assessment of subsegmental lymph nodes with adequate quality using the dedicated 25G aspiration needle. Thin convex probe EBUS has greater accessibility to peripheral airways in human lungs and is capable of sampling segmental lymph nodes using the aspiration needle. That will allow for more precise assessment of N1 nodes and, possibly, intrapulmonary lesions normally inaccessible to the conventional convex probe EBUS. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Inhibition of excitatory non-adrenergic non-cholinergic bronchoconstriction in guinea-pig airways in vitro by activation of an atypical 5-HT receptor.

PubMed Central

Ward, J. K.; Fox, A. J.; Barnes, P. J.; Belvisi, M. G.

1994-01-01

1. The effect of 5-hydroxytryptamine (5-HT) was studied on excitatory neurally mediated non-adrenergic non-cholinergic (NANC) contractions evoked by electrical field stimulation (EFS) in guinea-pig isolated bronchi. 2. 5-HT (0.1-100 microM) produced a concentration-dependent inhibition of the excitatory NANC response with 50.9 +/- 5.0% (n = 5, P < 0.01) inhibition at 100 microM. This inhibition was not significantly affected by the 5-HT2 antagonist, ketanserin (1 microM) when inhibitions (+/- ketanserin) at each concentration of 5-HT were compared by unpaired t tests; however, this concentration appeared to produce a leftward shift (approximately 10 fold) of the 5-HT concentration-inhibition curve. Ketanserin (1 microM) was effective in blocking bronchoconstriction evoked by activation of 5-HT2A receptors on airway smooth muscle. In the presence of ketanserin (1 microM) 5-HT (100 microM) evoked an inhibition of 57.4 +/- 5.9% (n = 5, P < 0.01) with an EC50 of 0.57 microM. 3. Inhibition evoked by 5-HT (0.1-100 microM) was unaffected by the alpha-adrenoceptor antagonist phentolamine (1 microM), the beta 2-adrenoceptor antagonist, ICI 118551 (0.1 microM), the 5-HT1A/B antagonist, cyanopindolol (1 microM) or the 5-HT3/4 antagonist, ICS 205-930 (1 microM). 4. Methiothepin (0.1 microM) produced an insurmountable inhibition of the effect of 5-HT (0.1-100 microM), reducing the maximum inhibition produced by 5-HT (100 microM) to 30.2 +/- 5.0% (n = 5, P < 0.001) and suggesting a non-competitive antagonism. Methiothepin inhibited the effect of 5-HT (10 microM) in a concentration-dependent manner with an IC50 of 81 nM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7518294

An in vitro evaluation of aerosol delivery through tracheostomy and endotracheal tubes using different interfaces.

PubMed

Ari, Arzu; Harwood, Robert J; Sheard, Meryl M; Fink, James B

2012-07-01

Previous research reporting factors influencing aerosol delivery in intubated patients has been largely focused on the endotracheal tube (ETT) during mechanical ventilation, with little comparative analysis of effect of types of artificial airways and their interfaces on aerosol delivery during spontaneous breathing. The purpose of this study was to compare aerosol delivery via tracheostomy tube (TT) and ETT, using interfaces such as T-piece, tracheostomy collar, and manual resuscitation bag. A teaching manikin was intubated with either an ETT (8.0 mm inner diameter) and TT (8 mm inner diameter). Both bronchi were connected to a collecting filter, attached to a sinusoidal pump simulating the breathing pattern of a spontaneously breathing adult (tidal volume 450 mL, respiratory rate 20 breaths/min, inspiratory-expiratory ratio 1:2). Albuterol sulfate (2.5 mg/3 mL) was nebulized through a jet nebulizer, using each airway and interface as appropriate (n = 3). Drug on the filter was eluted and analyzed with spectrophotometry, and expressed as mean percent of loaded dose delivered. Descriptive statistics, the Student t test, and one-way analysis of variance were applied. A greater percentage of nominal dose was delivered via TT than ETT with both T-piece (13.79 ± 2.59% vs 9.05 ± 0.70%) and manual resuscitation bag (45.75 ± 1.8% vs 27.23 ± 8.98%, P = .038 and P = .025, respectively). Use of manual resuscitation bag with both TT and ETT increased lung dose more than 3-fold. Inhaled dose with tracheostomy collar was (6.92 ± 0.81%) less than T-piece with TT (P = .01). In this adult model of spontaneous ventilation, aerosol therapy through ETT was less efficient than TT, while the manual resuscitation bag was more efficient than T-piece or tracheostomy collar.

ASM-024, a Piperazinium Compound, Promotes the In Vitro Relaxation of β2-Adrenoreceptor Desensitized Tracheas

PubMed Central

Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon

2015-01-01

Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short—acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024 could potentially provide clinical benefit when used adjunctively with inhaled β2-adrenoreceptor agonists in those patients exhibiting a reduced response to their chronic use. PMID:25799096

ASM-024, a piperazinium compound, promotes the in vitro relaxation of β2-adrenoreceptor desensitized tracheas.

PubMed

Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon

2015-01-01

Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-Adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short-acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024 could potentially provide clinical benefit when used adjunctively with inhaled β2-adrenoreceptor agonists in those patients exhibiting a reduced response to their chronic use.

A 72-hour study to test the efficacy and safety of the "Mucus Slurper" in mechanically ventilated sheep.

PubMed

Li Bassi, Gianluigi; Curto, Francesco; Zanella, Alberto; Stylianou, Mario; Kolobow, Theodor

2007-03-01

In patients intubated with endotracheal tubes (ETTs), suctioning is routinely performed to remove mucus from within the ETT and trachea. The Mucus Slurper is a novel ETT with built-in suction ports arranged radially at its tip. We evaluated the safety and efficacy of the Mucus Slurper, compared with conventional tracheal suction, to prevent airway obstruction in sheep with the ETT and trachea oriented below horizontal. Prospective randomized animal study. Animal research facility at the National Institutes of Health. Twelve healthy sheep. Sheep were randomized to be intubated with either the Mucus Slurper (study group) or a Hi-Lo Tracheal Tube (Mallinckrodt, St. Louis, MO) (control group) and mechanically ventilated for 72 hrs. In the study group, automatic, timed tracheal aspiration lasted 0.3 secs, was repeated every 2 mins, and was synchronized with the early expiratory phase. In the control group, tracheal suction was performed every 6 hrs or as required. In the control group, tracheal secretions accumulated progressively within the ETT and the trachea. In the study group, all mucus that reached the tip of the Mucus Slurper was aspirated, keeping the lumen of the ETT, and proximal trachea, free from secretions. In the study group, expiratory water trap protein concentration, a crude index to measure mucus drainage through the ETT, was consistently less than the control group (p < .001). At autopsy, no macroscopic injury to the tracheal mucosa was found in either group. In the study group, the respiratory circuit was less colonized than in the control group. There were no statistically significant differences between the two groups in bacterial colonization of the lungs/bronchi. The Mucus Slurper, combined with orientation of the trachea below horizontal, prevents accumulation of secretions within the lumen of the ETT and trachea, without need for conventional tracheal suctioning.

Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lino dos Santos Franco, Adriana; Damazo, Amilcar Sabino; Post-Graduation in Morphology, UNIFESP, EPM, Sao Paulo

2006-07-01

We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also,more » FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects.« less

Continuous quantitative measurement of the proximal airway dimensions and lung density on four-dimensional dynamic-ventilation CT in smokers

PubMed Central

Yamashiro, Tsuneo; Moriya, Hiroshi; Tsubakimoto, Maho; Matsuoka, Shin; Murayama, Sadayuki

2016-01-01

Purpose Four-dimensional dynamic-ventilation computed tomography (CT) imaging demonstrates continuous movement of the airways and lungs, which cannot be depicted with conventional CT. We aimed to investigate continuous changes in lung density and airway dimensions and to assess the correlation with spirometric values in smokers. Materials and methods This retrospective study was approved by the Institutional Review Board, and informed consent was waived. Twenty-one smokers including six patients with COPD underwent four-dimensional dynamic-ventilation CT during free breathing (160 mm in length). The mean lung density (MLD) of the scanned lung and luminal areas (Ai) of fixed points in the trachea and the right proximal bronchi (main bronchus, upper bronchus, bronchus intermedius, and lower bronchus) were continuously measured. Concordance between the time curve of the MLD and that of the airway Ai values was expressed by cross-correlation coefficients. The associations between these quantitative measurements and the forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) values were assessed by Spearman’s rank correlation analysis. Results On the time curve for the MLD, the Δ-MLD1.05 values between the peak inspiratory frame to the later third frame (1.05 seconds later) were strongly correlated with the FEV1/FVC (ρ=0.76, P<0.0001). The cross-correlation coefficients between the airway Ai and MLD values were significantly correlated with the FEV1/FVC (ρ=−0.56 to −0.66, P<0.01), except for the right upper bronchus. This suggested that the synchrony between the airway and lung movement was lost in patients with severe airflow limitation. Conclusion Respiratory changes in the MLD and synchrony between the airway Ai and the MLD measured with dynamic-ventilation CT were correlated with patient’s spirometric values. PMID:27110108

Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

PubMed

Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

2015-12-01

Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P < .05). The tumor necrosis factor alpha and interleukin-8 levels in the BALF reached baseline levels when the humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P < .05). Moreover, humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

Total artificial heart in the pediatric patient with biventricular heart failure.

PubMed

Park, S S; Sanders, D B; Smith, B P; Ryan, J; Plasencia, J; Osborn, M B; Wellnitz, C M; Southard, R N; Pierce, C N; Arabia, F A; Lane, J; Frakes, D; Velez, D A; Pophal, S G; Nigro, J J

2014-01-01

Mechanical circulatory support emerged for the pediatric population in the late 1980s as a bridge to cardiac transplantation. The Total Artificial Heart (TAH-t) (SynCardia Systems Inc., Tuscon, AZ) has been approved for compassionate use by the Food and Drug Administration for patients with end-stage biventricular heart failure as a bridge to heart transplantation since 1985 and has had FDA approval since 2004. However, of the 1,061 patients placed on the TAH-t, only 21 (2%) were under the age 18. SynCardia Systems, Inc. recommends a minimum patient body surface area (BSA) of 1.7 m(2), thus, limiting pediatric application of this device. This unique case report shares this pediatric institution's first experience with the TAH-t. A 14-year-old male was admitted with dilated cardiomyopathy and severe biventricular heart failure. The patient rapidly decompensated, requiring extracorporeal life support. An echocardiogram revealed severe biventricular dysfunction and diffuse clot formation in the left ventricle and outflow tract. The decision was made to transition to biventricular assist device. The biventricular failure and clot formation helped guide the team to the TAH-t, in spite of a BSA (1.5 m(2)) below the recommendation of 1.7 m(2). A computed tomography (CT) scan of the thorax, in conjunction with a novel three-dimensional (3D) modeling system and team, assisted in determining appropriate fit. Chest CT and 3D modeling following implantation were utilized to determine all major vascular structures were unobstructed and the bronchi were open. The virtual 3D model confirmed appropriate device fit with no evidence of compression to the left pulmonary veins. The postoperative course was complicated by a left lung opacification. The left lung anomalies proved to be atelectasis and improved with aggressive recruitment maneuvers. The patient was supported for 11 days prior to transplantation. Chest CT and 3D modeling were crucial in assessing whether the device would fit, as well as postoperative complications in this smaller pediatric patient.

The Rationale and Evidence for Use of Inhaled Antibiotics to Control Pseudomonas aeruginosa Infection in Non-cystic Fibrosis Bronchiectasis

PubMed Central

2018-01-01

Abstract Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic inflammatory lung disease characterized by irreversible dilation of the bronchi, symptoms of persistent cough and expectoration, and recurrent infective exacerbations. The prevalence of NCFBE is on the increase in the United States and Europe, but no licensed therapies are currently available for its treatment. Although there are many similarities between NCFBE and cystic fibrosis (CF) in terms of respiratory symptoms, airway microbiology, and disease progression, there are key differences, for example, in response to treatment, suggesting differences in pathogenesis. This review discusses possible reasons underlying differences in response to inhaled antibiotics in people with CF and NCFBE. Pseudomonas aeruginosa infections are associated with the most severe forms of bronchiectasis. Suboptimal levels of antibiotics in the lung increase the mutation frequency of P. aeruginosa and lead to the development of mucoid strains characterized by formation of a protective polysaccharide biofilm. Mucoid strains of P. aeruginosa are associated with a chronic infection stage, requiring long-term antibiotic therapy. Inhaled antibiotics provide targeted delivery to the lung with minimal systemic toxicity and adverse events compared with oral/intravenous routes of administration, and they could be alternative treatment options to help address some of the treatment challenges in the management of severe cases of NCFBE. This review provides an overview of completed and ongoing trials that evaluated inhaled antibiotic therapy for NCFBE. Recently, several investigators conducted phase 3 randomized controlled trials with inhaled aztreonam and ciprofloxacin in patients with NCFBE. While the aztreonam trial results were not associated with significant clinical benefit in NCFBE, initial results reported from the inhaled ciprofloxacin (dry powder for inhalation and liposome-encapsulated/dual-release formulations) trials hold promise. A more targeted approach could identify specific populations of NCFBE patients who benefit from inhaled antibiotics. PMID:29077527

Postnatal remodeling of the neural components of the epithelial-mesenchymal trophic unit in the proximal airways of infant rhesus monkeys exposed to ozone and allergen.

PubMed

Larson, Shawnessy D; Schelegle, Edward S; Walby, William F; Gershwin, Laural J; Fanuccihi, Michelle V; Evans, Michael J; Joad, Jesse P; Tarkington, Brian K; Hyde, Dallas M; Plopper, Charles G

2004-02-01

Nerves and neuroendocrine cells located within the airway epithelium are ideally situated to sample a changing airway environment, to transmit that information to the central nervous system, and to promote trophic interactions between epithelial and mesenchymal cellular and acellular components. We tested the hypothesis that the environmental stresses of ozone (O(3)) and house dust mite allergen (HDMA) in atopic infant rhesus monkeys alter the distribution of airway nerves. Midlevel bronchi and bronchioles from 6-month-old infant monkeys that inhaled filtered air (FA), house dust mite allergen HDMA, O(3), or HDMA + O(3) for 11 episodes (5 days each, 0.5 ppm O(3), 8 h/day followed by 9 days recovery) were examined using immunohistochemistry for the presence of Protein gene product 9.5 (PGP 9.5), a nonspecific neural indicator, and calcitonin gene-related peptide (CGRP). Along the axial path between the sixth and the seventh intrapulmonary airway generations, there were small significant (P < 0.05) decrements in the density of epithelial nerves in monkeys exposed to HDMA or O(3), while in monkeys exposed to HDMA + O(3) there was a greater significant (P < 0.05) reduction in epithelial innervation. In animals exposed to O(3) or HDMA + O(3) there was a significant increase in the number of PGP 9.5 positive/CGRP negative cells that were anchored to the basal lamina and emitted projections in primarily the lateral plain and often intertwined with projections and cell bodies of other similar cells. We conclude that repeated cycles of acute injury and repair associated with the episodic pattern of ozone and allergen exposure alter the normal development of neural innervation of the epithelial compartment and the appearance of a new population of undefined PGP 9.5 positive cells within the epithelium.

Effect of Matrix Size on the Image Quality of Ultra-high-resolution CT of the Lung: Comparison of 512 × 512, 1024 × 1024, and 2048 × 2048.

PubMed

Hata, Akinori; Yanagawa, Masahiro; Honda, Osamu; Kikuchi, Noriko; Miyata, Tomo; Tsukagoshi, Shinsuke; Uranishi, Ayumi; Tomiyama, Noriyuki

2018-01-16

This study aimed to assess the effect of matrix size on the spatial resolution and image quality of ultra-high-resolution computed tomography (U-HRCT). Slit phantoms and 11 cadaveric lungs were scanned on U-HRCT. Slit phantom scans were reconstructed using a 20-mm field of view (FOV) with 1024 matrix size and a 320-mm FOV with 512, 1024, and 2048 matrix sizes. Cadaveric lung scans were reconstructed using 512, 1024, and 2048 matrix sizes. Three observers subjectively scored the images on a three-point scale (1 = worst, 3 = best), in terms of overall image quality, noise, streak artifact, vessel, bronchi, and image findings. The median score of the three observers was evaluated by Wilcoxon signed-rank test with Bonferroni correction. Noise was measured quantitatively and evaluated with the Tukey test. A P value of <.05 was considered significant. The maximum spatial resolution was 0.14 mm; among the 320-mm FOV images, the 2048 matrix had the highest resolution and was significantly better than the 1024 matrix in terms of overall quality, solid nodule, ground-glass opacity, emphysema, intralobular reticulation, honeycombing, and clarity of vessels (P < .05). Both the 2048 and 1024 matrices performed significantly better than the 512 matrix (P < .001), except for noise and streak artifact. The visual and quantitative noise decreased significantly in the order of 512, 1024, and 2048 (P < .001). In U-HRCT scans, a large matrix size maintained the spatial resolution and improved the image quality and assessment of lung diseases, despite an increase in image noise, when compared to a 512 matrix size. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

[Ultrahigh dose-rate, "flash" irradiation minimizes the side-effects of radiotherapy].

PubMed

Favaudon, V; Fouillade, C; Vozenin, M-C

2015-10-01

Pencil beam scanning and filter free techniques may involve dose-rates considerably higher than those used in conventional external-beam radiotherapy. Our purpose was to investigate normal tissue and tumour responses in vivo to short pulses of radiation. C57BL/6J mice were exposed to bilateral thorax irradiation using pulsed (at least 40 Gy/s, flash) or conventional dose-rate irradiation (0.03 Gy/s or less) in single dose. Immunohistochemical and histological methods were used to compare early radio-induced apoptosis and the development of lung fibrosis in the two situations. The response of two human (HBCx-12A, HEp-2) tumour xenografts in nude mice and one syngeneic, orthotopic lung carcinoma in C57BL/6J mice (TC-1 Luc+), was monitored in both radiation modes. A 17 Gy conventional irradiation induced pulmonary fibrosis and activation of the TGF-beta cascade in 100% of the animals 24-36 weeks post-treatment, as expected, whereas no animal developed complications below 23 Gy flash irradiation, and a 30 Gy flash irradiation was required to induce the same extent of fibrosis as 17 Gy conventional irradiation. Cutaneous lesions were also reduced in severity. Flash irradiation protected vascular and bronchial smooth muscle cells as well as epithelial cells of bronchi against acute apoptosis as shown by analysis of caspase-3 activation and TUNEL staining. In contrast, the antitumour effectiveness of flash irradiation was maintained and not different from that of conventional irradiation. Flash irradiation shifted by a large factor the threshold dose required to initiate lung fibrosis without loss of the antitumour efficiency, suggesting that the method might be used to advantage to minimize the complications of radiotherapy. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin

PubMed Central

Foster, Derek M.; Martin, Luke G.; Papich, Mark G.

2016-01-01

Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points. PMID:26872361

A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig

PubMed Central

Lundberg, J. M.; Saria, A.; Brodin, E.; Rosell, S.; Folkers, K.

1983-01-01

Electrical stimulation of the cervical vagus nerve in anesthetized guinea pigs induced a rapid increase in respiratory insufflation pressure, suggesting increased airway resistance. After intravenous administration of a substance P (SP) antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, the insufflation pressure response to vagal stimulation was reduced by 78% while the cardiovascular effects were unchanged. Histamine receptor-blocking agents were used to inhibit the effects of histamine release induced by the SP-antagonist. [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP also reduced the increase in insufflation pressure caused by intravenous SP or capsaicin. The long-lasting noncholinergic contraction of the main and hilus bronchi induced by field stimulation in vitro, as well as the contractile effects of SP and capsaicin, were also blocked by the SP antagonist. The cholinergic contractions and the noncholinergic tracheal relaxation on field stimulation in vitro were, however, not blocked by the antagonist. Vagal stimulation in vivo also increased vascular permeability in the respiratory tract and esophagus, causing a subepithelial edema as indicated by Evans blue extravasation. Previous treatment with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP inhibited the permeability increase induced by both vagus nerve stimulation and exogenous SP. SP release from vagal sensory nerves was indirectly shown by reduction in the bronchial levels of SP after nerve stimulation in vivo. The data suggest that a major portion of the vagally or capsaicin-induced increase in smooth muscle tone is caused by SP release from sensory neurons. In addition, activation of vagal SP-containing sensory nerves induces local edema. Tracheobronchial afferent SP-containing C fibers may thus exert local control of smooth muscle tone and vascular permeability in normal and pathophysiological conditions. Images PMID:6189120

Pathogenic Link Between Postextubation Pneumonia and Ventilator-Associated Pneumonia: An Experimental Study.

PubMed

Rezoagli, Emanuele; Zanella, Alberto; Cressoni, Massimo; De Marchi, Lorenzo; Kolobow, Theodor; Berra, Lorenzo

2017-04-01

The presence of an endotracheal tube is the main cause for developing ventilator-associated pneumonia (VAP), but pneumonia can still develop in hospitalized patients after endotracheal tube removal (postextubation pneumonia [PEP]). We hypothesized that short-term intubation (24 hours) can play a role in the pathogenesis of PEP. To test such hypothesis, we initially evaluated the occurrence of lung colonization and VAP in sheep that were intubated and mechanically ventilated for 24 hours. Subsequently, we assessed the incidence of lung colonization and PEP at 48 hours after extubation in sheep previously ventilated for 24 hours. To simulate intubated intensive care unit patients placed in semirecumbent position, 14 sheep were intubated and mechanically ventilated with the head elevated 30° above horizontal. Seven of them were euthanized after 24 hours (Control Group), whereas the remaining were euthanized after being awaken, extubated, and left spontaneously breathing for 48 hours after extubation (Awake Group). Criteria of clinical diagnosis of pneumonia were tested. Microbiological evaluation was performed on autopsy in all sheep. Only 1 sheep in the Control Group met the criteria of VAP after 24 hours of mechanical ventilation. However, heavy pathogenic bacteria colonization of trachea, bronchi, and lungs (range, 10-10 colony-forming unit [CFU]/g) was reported in 4 of 7 sheep (57%). In the Awake Group, 1 sheep was diagnosed with VAP and 3 developed PEP within 48 hours after extubation (42%), with 1 euthanized at 30 hours because of respiratory failure. On autopsy, 5 sheep (71%) confirmed pathogenic bacterial growth in the lower respiratory tract (range, 10-10 CFU/g). Twenty-four hours of intubation and mechanical ventilation in semirecumbent position leads to significant pathogenic colonization of the lower airways, which can promote the development of PEP. Strategies directed to prevent pathogenic microbiological colonization before and after mechanical ventilation should be considered to avert the onset of PEP.

Anaesthesia in Chest Surgery, with Special Reference to Controlled Respiration and Cyclopropane: (Section of Anaesthetics).

PubMed

Nosworthy, M D

1941-06-01

Problems in chest surgery: Cases with prolonged toxaemia or amyloid disease require an anaesthetic agent of low toxicity. When sputum or blood are present in the tracheobronchial tree the anaesthesia should abolish reflex distrubances and excessive sputum be removed by suction. The technique should permit the use of a high oxygen atmosphere; controlled respiration with cyclopropane or ether fulfil these requirements. Open pneumothorax is present when a wound of the chest wall allows air to pass in and out of the pleural cavity. The lung on the affected side collapses and the mediastinum moves over and partly compresses the other lung.The dangers of an open pneumothorax: (1) Paradoxical respiration-the lung on the affected side partially inflates on expiration and collapses on inspiration. Part of the air entering the good lung has been shuttled back from the lung on the affected side and is therefore vitiated. Full expansion of the sound lung is handicapped by the initial displacement of the mediastinum which increases on inspiration. The circulation becomes embarrassed.(2) Vicious circle coughing. During a paroxysm of coughing dyspnoea will occur. This accentuates paradoxical respiration and starts a vicious circle. Death from asphyxia may result.Special duties of the anaesthetist: (1) To carry out or supervise continuous circulatory resuscitation. During a thoracotomy a drip blood transfusion maintains normal blood-pressure and pulse-rate.(2) To maintain effcient respiration.Positive pressure anaesthesia: Risk of impacting secretions in smaller bronchi with subsequent atelectasis; eventual risk of CO(2) poisoning without premonitory signs.Controlled respiration: (1) How it is produced. (2) Its uses in chest surgery.Controlled respiration means that the anaesthetist, having abolished the active respiratory efforts of the patient, maintains an efficient tidal exchange by rhythmic squeezing of the breathing bag. This may be done mechanically by Crafoord's modification of Frenkner's spiropulsator or by hand.Active respiration will cease (i) if the patient's CO(2) is lowered sufficiently by hyperventilation, (ii) if the patient's respiratory centre is depressed sufficiently by sedative and anaesthetic drugs, and (iii) by a combination of (i) and (ii) of less degree.The author uses the second method, depressing the respiratory centre with omnoponscopolamine, pentothal sodium, and then cyclopropane. The CO(2) absorption method is essential for this technique, and this and controlled respiration should be mastered by the anaesthetist with a familiar agent and used at first only in uncomplicated cases.The significance of cardiac arrhythmias occuring with cyclopropane is discussed.The place of the other available anaesthetic agents is discussed particularly on the advisability of using local anaesthesia for the drainage of empyema or lung abscess.Pharyngeal airway or endotracheal tube? Anaesthesia may be maintained with a pharyngeal airway in many cases but intubation must be used when tracheobronchial suction may be necessary and when there may be difficulty in maintaining an unobstructed airway.A one-lung anaesthesia is ideal for pneumonectomy. This may be obtained by endotracheal anaesthesia after bronchial tamponage of the affected side (Crafoord, v. fig. 6b) or by an endobronchial intubation of the sound side (v. figs. 9b and 9c). Endobronchial placing of the breathing tube may be performed "blind". Before deciding on blind bronchial intubation, the anaesthetist must examine X-ray films for any abnormality deviating the trachea or bronchi. Though the right bronchus may be easily intubated blindly as a rule, there is the risk of occluding the orifice of the upper lobe bronchus (fig. 9d) when the patient will become cyanosed. If the tube bevel is facing its orifice the risk of occlusion will be decreased (fig. 9c).Greater accuracy in placing the tube can be effected by inserting it under direct vision. Instruments for performing this manoeuvre are described.In lobectomy for bronchiectasis the anaesthetist must try to prevent the spread of infection to other parts. Ideally, the bronchus of the affected lobe should be plugged with ribbon gauze (Crafoord, v. fig. 6c) or a suction catheter with a baby balloon on it placed in the affected bronchus. In the presence of a large bronchopleural fistula controlled respiration cannot be established during operation. As the surgeon is rarely able to plug the fistula, if pneumonectomy is to be performed intubation for a one-lung anaesthesia is the best method. During other procedures it is essential to maintain quiet respiration.In war casualties it is almost always possible, with the technique described, to leave the lung on the affected side fully expanded and thus frequently to restore normal respiratory physiology. Co-operation between surgeon and anaesthetist is essential.

The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higginson, Daniel S., E-mail: daniel.higginson@gmail.com; Chen, Ronald C.; Tracton, Gregg

2012-11-01

Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods andmore » Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1.54; P=.022) remained significant. Conclusions: Patients with bulky central disease, bronchial/vascular compression, and/or pulmonary symptoms exhibited worse overall survival after first-line, platinum-based chemotherapy. A subset of these patients may be studied to determine whether early, planned palliative thoracic radiation could also be of benefit.« less

Food foreign body injuries.

PubMed

Sebastian van As, Arjan B; Yusof, Abdullah M; Millar, Alastair J W

2012-05-14

The purpose of this study is to acquire a better understanding of Food Foreign Bodies (FFB) injuries in children characterizing the risk of complications and prolonged hospitalization due to food items according to patients' characteristics, circumstances of the accident, Foreign Body (FB) features and FB location, as emerging from the SUSY Safe Web-Registry. The present study uses data provided by the SUSY Safe Project, a DG SANCO co-funded project started in February 2005, which was aimed at establishing an international registry of cases of Foreign Bodies (FB) injuries in children aged 0-14 years. The analysis was carried out on injuries due to a food item. FB location was reported according to ICD9-CM code: ears (ICD931), nose (ICD932), pharynx and larynx (ICD933) trachea, bronchi and lungs (ICD934), mouth, esophagus and stomach (ICD935). Age and gender injury distributions were assessed. Data regarding adult supervision and activity before injury were also evaluated. FBs which most frequently cause complications were identified. The association between children age, adult presence, object characteristics and hospitalization/complications was computed using unweighted odds ratios and the related 95% confidence intervals. 16,878 FB injuries occurred in children aged 0-14 years have been recorded in the SUSY Safe databases. FB type was specified in 10,564 cases; among them 2744 (26%) were due to a food item. FB site was recorded in 1344 cases: FB was located in the ears in 99 patients, while 1140 occurred in the upper and lower respiratory tract; finally, 105 food items were removed from mouth, esophagus and stomach. Complications occurred in 176 cases and the most documented was pulmonary or bronchial infections (23%) followed emphysema or atelectasis and by and asthma (7%). Bones were the commonest retrieved FFB encountered in this study, while nuts seem to be the FFB most frequently associated to complications. On the basis of this study we make the strong recommendation that parents should be adequately educated and provide age-appropriate food to their children and be present in order to supervise them during eating especially during a critical period ranging from 2 to 3 years of age. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Bronchial Thermoplasty in Severe Asthma: Best Practice Recommendations from an Expert Panel.

PubMed

Bonta, Peter I; Chanez, Pascal; Annema, Jouke T; Shah, Pallav L; Niven, Robert

2018-01-01

Bronchial thermoplasty (BT) is a bronchoscopic treatment for patients with severe asthma who remain symptomatic despite optimal medical therapy. In this "expert best practice" paper, the background and practical aspects of BT are highlighted. Randomized, controlled clinical trials have shown BT to be safe and effective in reducing severe exacerbations, improving quality of life, and decreasing emergency department visits. Five-year follow-up studies have provided evidence of the functional stability of BT-treated patients with persistence of a clinical benefit. The Global Initiative for Asthma (GINA) guidelines state that BT can be considered as a treatment option for adult asthma patients at step 5. Patient selection for BT requires close collaboration between interventional pulmonologists and severe asthma specialists. Key patient selection criteria for BT will be reviewed. BT therapy is delivered in 3 separate bronchoscopy sessions at least 3 weeks apart, covering different regions of the lung separately. Patients are treated with 50 mg/day of prednisolone or equivalent for 5 days, starting treatment 3 days prior to the procedure. The procedure is performed under moderate-to-deep sedation or general anesthesia. At bronchos-copy a single-use catheter with a basket design is inserted through the instrument channel and the energy is delivered by a radiofrequency (RF) generator (AlairTM Bronchial Thermoplasty System). BT uses temperature-controlled RF energy to impact airway remodeling, including a reduction of excessive airway smooth muscle within the airway wall, which has been recognized as a predominant feature of asthma. The treatment should be performed in a systemic manner, starting at the most distal part of the (sub)segmental airway, then moving proximally to the main bronchi, ensuring that the majority of the airways are treated. In general, 40-70 RF activations are provided in the lower lobes, and between 50 and 100 activations in the upper lobes combined. The main periprocedural adverse events are exacerbation of asthma symptoms and increased cough and sputum production. Occasionally, atelectasis has been observed following the procedure. The long-term safety of BT is excellent. An optimized BT responder profile - i.e., which specific asthma phenotype benefits most - is a topic of current research. © 2018 S. Karger AG, Basel.

Production and Assessment of Decellularized Pig and Human Lung Scaffolds

PubMed Central

Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-01-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production. PMID:23638920

Production and assessment of decellularized pig and human lung scaffolds.

PubMed

Nichols, Joan E; Niles, Jean; Riddle, Michael; Vargas, Gracie; Schilagard, Tuya; Ma, Liang; Edward, Kert; La Francesca, Saverio; Sakamoto, Jason; Vega, Stephanie; Ogadegbe, Marie; Mlcak, Ronald; Deyo, Donald; Woodson, Lee; McQuitty, Christopher; Lick, Scott; Beckles, Daniel; Melo, Esther; Cortiella, Joaquin

2013-09-01

The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production.

MO-AB-BRA-09: Temporally Realistic Manipulation a 4D Biomechanical Lung Phantom for Evaluation of Simultaneous Registration and Segmentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markel, D; Levesque, I R.; Larkin, J

Purpose: To produce multi-modality compatible, realistic datasets for the joint evaluation of segmentation and registration with a reliable ground truth using a 4D biomechanical lung phantom. The further development of a computer controlled air flow system for recreation of real patient breathing patterns is incorporated for additional evaluation of motion prediction algorithms. Methods: A pair of preserved porcine lungs was pneumatically manipulated using an in-house computer controlled respirator. The respirator consisted of a set of bellows actuated by a 186 W computer controlled industrial motor. Patient breathing traces were recorded using a respiratory bellows belt during CT simulation and inputmore » into a control program incorporating a proportional-integral-derivative (PID) feedback controller in LabVIEW. Mock tumors were created using dual compartment vacuum sealed sea sponges. 65% iohexol,a gadolinium-based contrast agent and 18F-FDG were used to produce contrast and thus determine a segmentation ground truth. The intensity distributions of the compartments were then digitally matched for the final dataset. A bifurcation tracking pipeline provided a registration ground truth using the bronchi of the lung. The lungs were scanned using a GE Discovery-ST PET/CT scanner and a Phillips Panorama 0.23T MRI using a T1 weighted 3D fast field echo (FFE) protocol. Results: The standard deviation of the error between the patient breathing trace and the encoder feedback from the respirator was found to be ±4.2%. Bifurcation tracking error using CT (0.97×0.97×3.27 mm{sup 3} resolution) was found to be sub-voxel up to 7.8 cm displacement for human lungs and less than 1.32 voxel widths in any axis up to 2.3 cm for the porcine lungs. Conclusion: An MRI/PET/CT compatible anatomically and temporally realistic swine lung phantom was developed for the evaluation of simultaneous registration and segmentation algorithms. With the addition of custom software and mock tumors, the entire package offers ground truths for benchmarking performance with high fidelity.« less

Immunomodulation of afferent neurons in guinea-pig isolated airway.

PubMed

Riccio, M M; Myers, A C; Undem, B J

1996-03-01

1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P < 0.005). Mechanical sensitivities of afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) from non-immunized control guinea-pig airways were unaffected by antigen (n = 13). 4. Antigen did not overtly cause action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in excitability persisted beyond the duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent nerve terminals projecting from the airway and thus may contribute to the pathophysiology of allergic airway diseases.

Bronchial mucus properties in lung cancer: relationship with site of lesion.

PubMed

Zayas, J G; Rubin, B K; York, E L; Lien, D C; King, M

1999-01-01

To compare the biophysical properties of mucus from the left and right mainstem bronchi in patients undergoing diagnostic bronchoscopy because of a unilateral radiological abnormality. It was hypothesized that abnormalities in the properties of mucus would be greater on the side with the lesion and that this would be most obvious in patients with unilateral lung cancer. Bilateral paired samples of bronchial mucus were taken from 38 nonatopic patients (aged 59.8+/-12.6 years) including 16 nonsmokers, 14 current smokers and eight exsmokers (more than one year). Twenty of the 38 patients had a radiologically defined unilateral abnormality. Eight of these 20, including one nonsmoker, had lung cancer. The viscoelastic properties of the collected mucus were determined by magnetic microrheometry, and the analysis was carried out without knowledge of the histological diagnosis or source. The rheological properties of mucus strongly suggested which was the abnormal side. Within the group of 20 patients with a unilateral radiological abnormality, mucus from the side of the lesion had a lower value of the loss tangent, tan d100 (P=0.004), indicating greater mucus recoil. This is consistent with poor mucus cough clearability on the lesion side. All eight cancer patients fit this mucus rheological pattern with a lower value of tan d100 on the affected side (P=0.007). Four of the five other patients with a similar mucus abnormality were categorized as high cancer risk by other criteria, while six of seven patients with mucus that did not have this abnormality were considered to be lower risk. Based on the mucus analysis done at the time of the bronchoscopy, two of the 'noncancer' patients initially designated as high risk had cancer detected after several months of follow- up. Only two of the 18 patients without a defined unilateral lesion fit the mucus 'cancer pattern'. These findings are consistent with the hypothesis that either abnormalities in mucus properties may represent a risk factor for the development of lung cancer or that bronchial mucus abnormalities may be associated with products secreted by the tumours that, in turn, may suppress mucus clearance.

WE-AB-207B-01: Dose Tolerance for SBRT/SABR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grimm, J

Purpose: Stereotactic body radiation therapy (SBRT) / stereotactic ablative body radiotherapy (SABR) is gaining popularity, but quantitative dose tolerance has still been lacking. To improve this, the April 2016 issue of Seminars in Radiation Oncology will have normal tissue complication probability (NTCP) models for 10 critical structures: optic pathway, cochlea, oral mucosa, esophagus, chestwall, aorta, bronchi, duodenum, small bowel, and spinal cord. Methods: The project included more than 1500 treatments in 1–5 fractions using CyberKnife, Gamma Knife, or LINAC, with 60 authors from 15 institutions. NTCP models were constructed from the 97 grade 2–3 complications, predominantly scored using the commonmore » terminology criteria for adverse events (CTCAEv4). Dose volume histogram (DVH) data from each institutional dataset was loaded into the DVH Evaluator software (DiversiLabs, LLC, Huntingdon Valley, Pa) for modeling. The current state of the literature for the critical structures was depicted using DVH Risk Maps: comparative graphs of dose tolerance limits that can include estimated risk levels, reported complications, DVH data for study patients, as well as high- and low-risk dose tolerance limits. Results: For relatively acceptable toxicity like grade 1–3 rib fractures and chestwall pain, the high-risk limits have 50% risk and the low-risk limits have 5% risk. Emami et al (IJROBP 1991 May 15;21(1):109–22) used 50% and 5% risk levels for all structures, whereas this effort used clinically acceptable ranges for each: in structures like aorta or spinal cord where complications must be avoided, the high- and low-risk limits have about 3% and 1% risk, respectively, in this issue of Seminars. These statistically based guidelines can help ensure plan quality for each patient. Conclusion: NTCP for SBRT is now becoming available. Hypofractionated dose tolerance can be dramatically different than extrapolations of conventional fractionation so NTCP analysis of the SBRT/SBRT data is important to ensure safe clinical practice. Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA-cleared product in commercial use, and was used to analyze the data.« less

The efficacy of 320-detector row computed tomography for the assessment of preoperative pulmonary vasculature of candidates for pulmonary segmentectomy.

PubMed

Tane, Shinya; Ohno, Yoshiharu; Hokka, Daisuke; Ogawa, Hiroyuki; Tauchi, Shunsuke; Nishio, Wataru; Yoshimura, Masahiro; Okita, Yutaka; Maniwa, Yoshimasa

2013-12-01

The purpose of this study was to compare the efficacy of 320-detector row computed tomography (CT) with that of 64-detector row CT for three-dimensional assessment of pulmonary vasculature of candidates for pulmonary segmentectomy. We included 32 patients who underwent both 320- and 64-detector CT before pulmonary segmentectomy, which was performed by cutting the pulmonary artery and bronchi of the affected segment followed by dissection of the intersegmental plane along the intersegmental vein. Before the operation, three-dimensional pulmonary vasculature images were obtained for each patient, and the arteries and intersegmental veins of the affected segments were identified. Two thoracic surgeons independently assessed the vessels with visual scoring systems, and kappa analysis was used to determine interobserver agreement. The Wilcoxon signed-rank test was used to compare the visual scores for the assessment of the visualization capabilities of the two methods. In addition, the final determination of pulmonary vasculature at a given site was made by consensus from thoracic surgeons during operation, and receiver operating characteristic analysis was performed to compare their efficacy of pulmonary vasculature assessment. Sensitivity, specificity and accuracy of either method were also compared by means of McNemar's test. Of the 32 cases, there were no operative complications, but 1 patient died of postoperative idiopathic interstitial pneumonia. Visualization scores for the pulmonary vessels were significantly higher for 320- than those for 64-detector CT (P < 0.0001 for the affected arteries and P < 0.0001 for the intersegmental veins). As for pulmonary vasculature assessment, the areas under the curve showed no statistically significant differences in between the two methods, while the specificity and accuracy of intersegemental vein assessment were significantly better for 320- than those for 64-detector row CT (P < 0.05). Interobserver agreement for the assessment yielded by either method was almost perfect for all cases. Three hundred and twenty-detector row CT is more useful than conventional 64-detector row CT for preoperative three-dimensional assessment of pulmonary vasculature, especially when we identify the intersegmental veins, in candidates for pulmonary segmentectomy.

Impact of Powered and Tissue-Specific Endoscopic Stapling Technology on Clinical and Economic Outcomes of Video-Assisted Thoracic Surgery Lobectomy Procedures: A Retrospective, Observational Study.

PubMed

Miller, Daniel L; Roy, Sanjoy; Kassis, Edmund S; Yadalam, Sashi; Ramisetti, Sushama; Johnston, Stephen S

2018-05-01

Video-assisted thoracic surgery (VATS) lung resections are complex procedures with a critical role played by endoscopic staplers in the transection of vessels, bronchi, and lung tissue. This retrospective, observational study compared hospital resource use, costs, and complications of VATS lobectomy procedures for whom powered versus manual endoscopic surgical staplers were used. Patients ≥ 18 years of age undergoing elective VATS lobectomy during an inpatient admission from January 1, 2012 to September 30, 2016 were identified from the Premier Healthcare Database (first admission = index admission). Use of either powered or manual endoscopic staplers during the index admission was identified from hospital administrative records. Multivariable regression analyses adjusting for patient, hospital, and provider characteristics and hospital-level clustering were carried out to compare the following outcomes between the powered and manual stapler groups: hospital length of stay (LOS), operating room time (ORT), hospital costs, complications (bleeding and/or transfusions, air leak complications, pneumonia, and infection), discharge status, and 30-, 60-, and 90-day all-cause readmissions. The powered and manual stapler groups comprised 659 patients (mean age 66.1 years; 53.6% female) and 3100 patients (mean age 66.7 years; 54.8% female), respectively. In the multivariable analyses, the powered stapler group had shorter LOS (4.9 vs. 5.9 days, P < 0.001), lower total hospital costs ($23,841 vs. $26,052, P = 0.009), and lower rates of combined hemostasis complications (bleeding and/or transfusions; 8.5% vs. 16.0%, P < 0.001) and transfusions (5.4% vs. 10.9%, P = 0.002), compared with the manual stapler group. Other outcomes did not differ significantly between the study groups. Similar trends were observed in subanalyses comparing devices across predominant manufacturers in each group, and in subanalyses of patients with comorbid chronic obstructive pulmonary disease. In this analysis of VATS lobectomy procedures, powered staplers were associated with significant benefits with respect to selected types of hospital resource use, costs, and clinical outcomes when compared with manual staplers. Johnson & Johnson.

Efficacy of High-Dose Amoxicillin-Clavulanate against Experimental Respiratory Tract Infections Caused by Strains of Streptococcus pneumoniae

PubMed Central

Woodnutt, Gary; Berry, Valerie

1999-01-01

The purpose of the present investigation was to determine if the efficacy of amoxicillin-clavulanate against penicillin-resistant Streptococcus pneumoniae could be improved by increasing the pediatric amoxicillin unit dose (90 versus 45 mg/kg of body weight/day) while maintaining the clavulanate unit dose at 6.4 mg/kg/day. A rat pneumonia model was used. In that model approximately 6 log10 CFU of one of four strains of S. pneumoniae (amoxicillin MICs, 2 μg/ml [one strain], 4 μg/ml [two strains], and 8 μg/ml [one strain]) were instilled into the bronchi of rats. Amoxicillin-clavulanate was given by computer-controlled intravenous infusion to approximate the concentrations achieved in the plasma of children following the administration of oral doses of 45/6.4 mg/kg/day or 90/6.4 mg/kg/g/day divided every 12 h or saline as a control for a total of 3 days. Infusions continued for 3 days, and 2 h after the cessation of infusion, bacterial numbers in the lungs were significantly reduced by the 90/6.4-mg/kg/day equivalent dosage for strains for which amoxicillin MICs were 2 or 4 μg/ml. The 45/6.4-mg/kg/day equivalent dosage was fully effective only against the strain for which the amoxicillin MIC was 2 μg/ml and had marginal efficacy against one of the two strains for which amoxicillin MICs were 4 μg/ml. The bacterial load for the strain for which the amoxicillin MIC was 8 μg/ml was not reduced with either dosage. These data demonstrate that regimens which achieved concentrations in plasma above the MIC for at least 34% of a 24-h dosing period resulted in significant reductions in the number of viable bacteria, indicating that the efficacy of amoxicillin-clavulanate can be extended to include efficacy against less susceptible strains of S. pneumoniae by increasing the amoxicillin dose. PMID:9869562

Neurokinin A-LI release after antigen challenge in guinea-pig bronchial tubes: influence of histamine and bradykinin

PubMed Central

Lindström, Eva G; Andersson, Rolf G G

1997-01-01

Our aim was to determine if antigen challenge stimulates sensory nerves and provokes the release of tachykinins. The involvement of histamine and bradykinin was studied by using specific receptor antagonists. Capsaicin-induced responses were also examined. Experiments were performed in vitro on tracheal and bronchial preparations from ovalbumin-sensitized guinea-pigs. Characterization of ovalbumin-induced contraction, with regard to histamine and bradykinin, was carried out on airway ring preparations in the presence of phosphoramidon. The histamine H1 receptor antagonist pyrilamine reduced allergen-induced bronchial contractions by about 30%, whereas the bradykinin B2 receptor antagonist icatibant (Hoe 140) did not significantly affect the response. Combined treatment with pyrilamine (1 μM) and icatibant (0.1 μM) reduced the contractions by about 80%, indicating a synergistic inhibitory action. Tracheal preparations were not significantly affected by treatments, neither were capsaicin-induced contractions. To study the outflow of tachykinins, we used a perfused bronchial-tube preparation, allowing simultaneous measurement of smooth muscle tension and mediator release. Neurokinin A-like immunoreactivity (NKA-LI) and substance P-like immunoreactivity (SP-LI) were determined by radioimmunoassay. The results of the perfusion study showed an increased outflow of NKA-LI into the perfusate in response to ovalbumin (127% of basal) challenge. SP-LI determined in some of the samples showed a much lower amount (40 to 70 times lower) of SP-LI than NKA-LI. Treatment with icatibant and pyrilamine, separately and in combination, significantly reduced the ovalbumin-induced NKA-LI outflow by 38%, 26% and 22%, respectively. Capsaicin-induced outflow (124% of basal) was not significantly affected by treatments (icatibant 121%, pyrilamine 107% and combined treatment 111% of basal). However, when pyrilamine was present the increased outflow was not statistically significant. In conclusion, we found that allergen provocation of guinea-pig bronchi caused an increased outflow of NKA-LI that was reduced by treatment with both pyrilamine and icatibant. These findings demonstrate that the allergen-induced release of histamine and bradykinin stimulate sensory nerves and thereby increase outflow of tachykinins that contribute to the allergic reaction. PMID:9351496

Thoracoscopic Lobectomy in Infants and Children Utilizing a 5 mm Stapling Device.

PubMed

Rothenberg, Steven

2016-12-01

Thoracoscopic lobectomy for congenital cystic lung disease has become an accepted and in many institutions the preferred technique. However, the technical challenges are many. Previous endoscopic staplers (12 mm) used commonly in adults are too large for use in infants This study evaluates the safety and efficacy of using a 5 mm stapling device to seal and divide major pulmonary structures. From July 2014 to March 2016, 26 patients of age 6 weeks to 13 months underwent thoracoscopic lobectomy for CPAM or sequestration. Weights ranged from 3.2 to 11.4 kg. There were 7 upper lobectomies, 2 middle, and 17 lower lobectomies. In each case, the 5 mm stapler (Justright Surgical; Louisville, Colorado) was the primary device for vessel and bronchial sealing and division. It is 4.8 mm in diameter with an anvil length of 25 mm and lays down four rows of staples and divides between them. A 3 mm sealing device was used for dissection and to take smaller segmental vessels as necessary. Stump lines were evaluated for bleeding or air leak in all cases. All procedures were accomplished successfully thoracoscopically. The stapler was used on the main lobar artery cases and vein in 24 cases, a large systemic sequestration vessel in 5 cases, and the bronchus in all 26. The stapler was also used to complete the minor fissure in 1 case and the major fissure in 1 case. A total of 96 staple loads were fired. Operative times ranged from 35 to 135 minutes. There was no significant bleeding of any vascular stump. In 1 case, the edge of the bronchial stump had to be reinforced, this was thought to be secondary to too much tissue being enclosed in the jaws. There were no postoperative complications. The use of a 5 mm stapling device appears to be safe and effective in thoracoscopic lobectomy in infants. It allows for safe management of major pulmonary vessels and bronchi in the confined chest of an infant through a single 5 mm port.

Therapeutic arthropods and other, largely terrestrial, folk-medicinally important invertebrates: a comparative survey and review.

PubMed

Meyer-Rochow, V Benno

2017-02-07

Traditional healing methods involving hundreds of insect and other invertebrate species are reviewed. Some of the uses are based on the tenet of "similia similibus" (let likes be cured by likes), but not all non-conventional health promoting practices should be dismissed as superstition or wishful thinking, for they have stood the test of time. Two questions are addressed: how can totally different organ systems in a human possibly benefit from extracts, potions, powders, secretions, ashes, etc. of a single species and how can different target organs, e.g. bronchi, lungs, the urinary bladder, kidneys, etc. apparently respond to a range of taxonomically not even closely related species? Even though therapeutically used invertebrates are generally small, they nevertheless possess organs for specific functions, e.g. digestion, gas exchange, reproduction. They have a nervous system, endocrine glands, a heart and muscle tissue and they contain a multitude of different molecules like metabolites, enzymes, hormones, neurotransmitters, secretions, etc. that have come under increased scientific scrutiny for pharmacological properties. Bearing that in mind it seems likely that a single species prepared and used in different ways could have a multitude of uses. But how, for example, can there be remedies for breathing and other problems, involving earthworms, molluscs, termites, beetles, cockroaches, bugs, and dragonflies? Since invertebrates themselves can suffer from infections and cancers, common defence reactions are likely to have evolved in all invertebrates, which is why it would be far more surprising to find that each species had evolved its own unique disease fighting system. To obtain a more comprehensive picture, however, we still need information on folk medicinal uses of insects and other invertebrates from a wider range of regions and ethnic groups, but this task is hampered by western-based medicines becoming increasingly dominant and traditional healers being unable and sometimes even unwilling to transmit their knowledge to the younger generation. However, collecting and uncontrolled uses of therapeutic invertebrates can put undue pressure on certain highly sought after species and this is something that has to be borne in mind as well.

The role of airway stenting in pediatric tracheobronchial obstruction.

PubMed

Antón-Pacheco, Juan L; Cabezalí, Daniel; Tejedor, Raquel; López, María; Luna, Carmen; Comas, Juan V; de Miguel, Eduardo

2008-06-01

Tracheobronchial obstruction is infrequent in the pediatric age group but it is associated with significant morbidity and mortality. The purpose of this study is to review the results of a single institution experience with endoscopic stent placement in children with benign tracheobronchial obstruction, and with special concern on safety and clinical effectiveness. Twenty-one patients with severe airway stenosing disease in which stent placement was performed between 1993 and 2006. Inclusion criteria according to the clinical status were: failure to wean from ventilation, episode of apnea, frequent respiratory infections (>3 pneumonia/year), and severe respiratory distress. Additional criteria for stent placement were: failure of surgical treatment, bronchomalacia, and tracheomalacia refractory to previous tracheostomy. Selection of the type of stent depended on the site of the lesion, the patient's age, and the stent availability when time of presentation. The following variables were retrospectively evaluated: age, type of obstruction, associated malformations, stent properties, technical and clinical success, complications and related reinterventions, outcome and follow-up period. Thirty-three stents were placed in the trachea (n=18) and/or bronchi (n=15) of 21 patients with a median age of 6 months (range, 9 days-19 years). Etiology of the airway obstruction included severe tracheomalacia and/or bronchomalacia in 19 cases (90%), and postoperative tracheal stenosis in two. Twelve children had a total of 20 balloon-expandable metallic stents placed, and 10 had 13 silicone-type stents (one patient had both). In nine patients (42%) more than one device was placed. Stent positioning was technically successful in all but one patient. Clinical improvement was observed in 18 patients (85%) but complications occurred in five of them (27%). Eight patients died during follow-up but only in one case it was related to airway stenting. Thirteen patients (62%) are alive and in good condition with a mean follow-up of 39 months (1-13.8 years). Although the results were based on a small series, placement of stents in the pediatric airway to treat tracheobronchial obstruction seems to be safe and effective. Stenting is a satisfactory therapeutic option when other procedures have failed or are not indicated.

Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.

PubMed

Van de Laar, Emily; Clifford, Monica; Hasenoeder, Stefan; Kim, Bo Ram; Wang, Dennis; Lee, Sharon; Paterson, Josh; Vu, Nancy M; Waddell, Thomas K; Keshavjee, Shaf; Tsao, Ming-Sound; Ailles, Laurie; Moghal, Nadeem

2014-12-31

The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~ < 6%) groups. Microarray gene expression profiling supported the heterogeneous expression of these markers in the total population, and immunostaining of large airway tissue suggested that some of these markers are relevant in vivo. 24 markers were enriched in lung SQCCs relative to adenocarcinomas, with four markers having prognostic significance in SQCCs. We also identified 33 signaling receptors, including the MST1R/RON growth factor receptor, whose ligand MST1/MSP was mitogenic for basal cells. This work provides the largest description to date of molecular diversity among human large airway basal cells. Furthermore, these markers can be used to further study basal cell function in repair and disease, and may aid in the classification and study of SQCCs.

Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro

PubMed Central

Capra, Valérie; Bolla, Manlio; Angelo Belloni, Pier; Mezzetti, Maurizio; Carlo Folco, G; Nicosia, Simonetta; Enrico Rovati, G

1998-01-01

Cysteinyl-leukotrienes (cysteinyl-LTs) are important mediators in the pathogenesis of asthma. They cause bronchoconstriction, mucus hypersecretion, increase in microvascular permeability, plasma extravasation and eosinophil recruitment. We investigated the pharmacological profile of the cysteinyl-LT antagonists CGP 45715A (iralukast), a structural analogue of LTD4 and CGP 57698, a quinoline type antagonist, in human airways in vitro, by performing binding studies on human lung parenchyma membranes and functional studies on human isolated bronchial strips. Competition curves vs [3H]-LTD4 on human lung parenchyma membranes demonstrated that: (a) both antagonists were able to compete for the two sites labelled by [3H]-LTD4; (b) as in all the G-protein coupled receptors, iralukast and CGP 57698 did not discriminate between the high and the low affinity states of the CysLT receptor labelled by LTD4 (Ki1=Ki2=16.6 nM±36% CV and Ki1= Ki2=5.7 nM±19% CV, respectively); (c) iralukast, but not CGP 57698, displayed a slow binding kinetic, because preincubation (15 min) increased its antagonist potency. In functional studies: (a) iralukast and CGP 57698 antagonized LTD4-induced contraction of human bronchi, with pA2 values of 7.77±4.3% CV and 8.51±1.6% CV, respectively, and slopes not significantly different from unity; (b) the maximal LTD4 response in the presence of CGP 57698 was actually increased, thus clearly deviating from apparent simple competition. Both antagonists significantly inhibited antigen-induced contraction of human isolated bronchial strips in a concentration-dependent manner, lowering the upper plateau of the anti-IgE curves. In conclusion, the results of the present in vitro investigation indicate that iralukast and CGP 57698 are potent antagonists of LTD4 in human airways, with affinities in the nanomolar range, similar to those obtained for ICI 204,219 and ONO 1078, two of the most clinically advanced CysLT receptor antagonists. Thus, these compounds might be useful drugs for the therapy of asthma and other allergic diseases. PMID:9504401

Anæsthesia in Chest Surgery, with Special Reference to Controlled Respiration and Cyclopropane: (Section of Anæsthetics).

PubMed

Nosworthy, M D

1941-06-01

Problems in chest surgery: Cases with prolonged toxæmia or amyloid disease require an anæsthetic agent of low toxicity. When sputum or blood are present in the tracheobronchial tree the anæsthesia should abolish reflex distrubances and excessive sputum be removed by suction. The technique should permit the use of a high oxygen atmosphere; controlled respiration with cyclopropane or ether fulfil these requirements. Open pneumothorax is present when a wound of the chest wall allows air to pass in and out of the pleural cavity. The lung on the affected side collapses and the mediastinum moves over and partly compresses the other lung.The dangers of an open pneumothorax: (1) Paradoxical respiration-the lung on the affected side partially inflates on expiration and collapses on inspiration. Part of the air entering the good lung has been shuttled back from the lung on the affected side and is therefore vitiated. Full expansion of the sound lung is handicapped by the initial displacement of the mediastinum which increases on inspiration. The circulation becomes embarrassed.(2) Vicious circle coughing. During a paroxysm of coughing dyspnœa will occur. This accentuates paradoxical respiration and starts a vicious circle. Death from asphyxia may result.Special duties of the anæsthetist: (1) To carry out or supervise continuous circulatory resuscitation. During a thoracotomy a drip blood transfusion maintains normal blood-pressure and pulse-rate.(2) To maintain effcient respiration.Positive pressure anæsthesia: Risk of impacting secretions in smaller bronchi with subsequent atelectasis; eventual risk of CO(2) poisoning without premonitory signs.Controlled respiration: (1) How it is produced. (2) Its uses in chest surgery.Controlled respiration means that the anæsthetist, having abolished the active respiratory efforts of the patient, maintains an efficient tidal exchange by rhythmic squeezing of the breathing bag. This may be done mechanically by Crafoord's modification of Frenkner's spiropulsator or by hand.Active respiration will cease (i) if the patient's CO(2) is lowered sufficiently by hyperventilation, (ii) if the patient's respiratory centre is depressed sufficiently by sedative and anæsthetic drugs, and (iii) by a combination of (i) and (ii) of less degree.The author uses the second method, depressing the respiratory centre with omnoponscopolamine, pentothal sodium, and then cycloprȯpane. The CO(2) absorption method is essential for this technique, and this and controlled respiration should be mastered by the anæsthetist with a familiar agent and used at first only in uncomplicated cases.The significance of cardiac arrhythmias occuring with cyclopropane is discussed.The place of the other available anæsthetic agents is discussed particularly on the advisability of using local anæsthesia for the drainage of empyema or lung abscess.Pharyngeal airway or endotracheal tube? Anæsthesia may be maintained with a pharyngeal airway in many cases but intubation must be used when tracheobronchial suction may be necessary and when there may be difficulty in maintaining an unobstructed airway.A one-lung anæsthesia is ideal for pneumonectomy. This may be obtained by endotracheal anæsthesia after bronchial tamponage of the affected side (Crafoord, v. fig. 6b) or by an endobronchial intubation of the sound side (v. figs. 9b and 9c). Endobronchial placing of the breathing tube may be performed "blind". Before deciding on blind bronchial intubation, the anæsthetist must examine X-ray films for any abnormality deviating the trachea or bronchi. Though the right bronchus may be easily intubated blindly as a rule, there is the risk of occluding the orifice of the upper lobe bronchus (fig. 9d) when the patient will become cyanosed. If the tube bevel is facing its orifice the risk of occlusion will be decreased (fig. 9c).Greater accuracy in placing the tube can be effected by inserting it under direct vision. Instruments for performing this manœuvre are described.In lobectomy for bronchiectasis the anæsthetist must try to prevent the spread of infection to other parts. Ideally, the bronchus of the affected lobe should be plugged with ribbon gauze (Crafoord, v. fig. 6c) or a suction catheter with a baby balloon on it placed in the affected bronchus. In the presence of a large bronchopleural fistula controlled respiration cannot be established during operation. As the surgeon is rarely able to plug the fistula, if pneumonectomy is to be performed intubation for a one-lung anæsthesia is the best method. During other procedures it is essential to maintain quiet respiration.In war casualties it is almost always possible, with the technique described, to leave the lung on the affected side fully expanded and thus frequently to restore normal respiratory physiology. Co-operation between surgeon and anæsthetist is essential.

Anæsthesia in Chest Surgery, with Special Reference to Controlled Respiration and Cyclopropane

PubMed Central

Nosworthy, M. D.

1941-01-01

Problems in chest surgery: Cases with prolonged toxæmia or amyloid disease require an anæsthetic agent of low toxicity. When sputum or blood are present in the tracheobronchial tree the anæsthesia should abolish reflex distrubances and excessive sputum be removed by suction. The technique should permit the use of a high oxygen atmosphere; controlled respiration with cyclopropane or ether fulfil these requirements. Open pneumothorax is present when a wound of the chest wall allows air to pass in and out of the pleural cavity. The lung on the affected side collapses and the mediastinum moves over and partly compresses the other lung. The dangers of an open pneumothorax: (1) Paradoxical respiration—the lung on the affected side partially inflates on expiration and collapses on inspiration. Part of the air entering the good lung has been shuttled back from the lung on the affected side and is therefore vitiated. Full expansion of the sound lung is handicapped by the initial displacement of the mediastinum which increases on inspiration. The circulation becomes embarrassed. (2) Vicious circle coughing. During a paroxysm of coughing dyspnœa will occur. This accentuates paradoxical respiration and starts a vicious circle. Death from asphyxia may result. Special duties of the anæsthetist: (1) To carry out or supervise continuous circulatory resuscitation. During a thoracotomy a drip blood transfusion maintains normal blood-pressure and pulse-rate. (2) To maintain effcient respiration. Positive pressure anæsthesia: Risk of impacting secretions in smaller bronchi with subsequent atelectasis; eventual risk of CO2 poisoning without premonitory signs. Controlled respiration: (1) How it is produced. (2) Its uses in chest surgery. Controlled respiration means that the anæsthetist, having abolished the active respiratory efforts of the patient, maintains an efficient tidal exchange by rhythmic squeezing of the breathing bag. This may be done mechanically by Crafoord's modification of Frenkner's spiropulsator or by hand. Active respiration will cease (i) if the patient's CO2 is lowered sufficiently by hyperventilation, (ii) if the patient's respiratory centre is depressed sufficiently by sedative and anæsthetic drugs, and (iii) by a combination of (i) and (ii) of less degree. The author uses the second method, depressing the respiratory centre with omnoponscopolamine, pentothal sodium, and then cycloprȯpane. The CO2 absorption method is essential for this technique, and this and controlled respiration should be mastered by the anæsthetist with a familiar agent and used at first only in uncomplicated cases. The significance of cardiac arrhythmias occuring with cyclopropane is discussed. The place of the other available anæsthetic agents is discussed particularly on the advisability of using local anæsthesia for the drainage of empyema or lung abscess. Pharyngeal airway or endotracheal tube? Anæsthesia may be maintained with a pharyngeal airway in many cases but intubation must be used when tracheobronchial suction may be necessary and when there may be difficulty in maintaining an unobstructed airway. A one-lung anæsthesia is ideal for pneumonectomy. This may be obtained by endotracheal anæsthesia after bronchial tamponage of the affected side (Crafoord, v. fig. 6b) or by an endobronchial intubation of the sound side (v. figs. 9b and 9c). Endobronchial placing of the breathing tube may be performed “blind”. Before deciding on blind bronchial intubation, the anæsthetist must examine X-ray films for any abnormality deviating the trachea or bronchi. Though the right bronchus may be easily intubated blindly as a rule, there is the risk of occluding the orifice of the upper lobe bronchus (fig. 9d) when the patient will become cyanosed. If the tube bevel is facing its orifice the risk of occlusion will be decreased (fig. 9c). Greater accuracy in placing the tube can be effected by inserting it under direct vision. Instruments for performing this manœuvre are described. In lobectomy for bronchiectasis the anæsthetist must try to prevent the spread of infection to other parts. Ideally, the bronchus of the affected lobe should be plugged with ribbon gauze (Crafoord, v. fig. 6c) or a suction catheter with a baby balloon on it placed in the affected bronchus. In the presence of a large bronchopleural fistula controlled respiration cannot be established during operation. As the surgeon is rarely able to plug the fistula, if pneumonectomy is to be performed intubation for a one-lung anæsthesia is the best method. During other procedures it is essential to maintain quiet respiration. In war casualties it is almost always possible, with the technique described, to leave the lung on the affected side fully expanded and thus frequently to restore normal respiratory physiology. Co-operation between surgeon and anæsthetist is essential. PMID:19992357

Retrieval of AOD and PM2.5 Concentrations over Urban Areas of Shenyang City using MODIS Data

NASA Astrophysics Data System (ADS)

Wang, Z.

2016-12-01

Atmospheric aerosols play an important part in the Earth's radiation balance as well as global climate change, aerosols also have very important impact on environment as well as human and other organisms' health, PM2.5 and other small particle aerosols, can enter bronchi directly, thus causing bronchitis, cardiovascular disease, asthma and so on.Detection of AOD by satellite and remote sensing is currently one of the hotest issues , diffierent from the traditional monitoring method, this method has much more advantanges, for emample wide area coverage, fast and convenient etc. So it is possible for people to know the regional changes of AOD real time over large area. Now, detection aerosol by RS technology has reached a high level in marine and dense vegetation land areas, but result is not ideal for urban areas, the higher surface reflectance in urban areas is a bottleneck of AOD retrieval. Focus on the high surface reflectance and low accuracy of the AOD products of urban areas, this paper propose an algorithm coupled with surface reflectance to get red band surface reflectance, based on Dens Dark Vegetation algorithm and geometrical optics model theory, to distinguish urban reflectivity from other targets. Considering the appropriate aerosol model which adapt to season and other proper parameters, this paper uses 6S model to establish look-up table, thus retrieve AOD for urban as well as other high reflectance areas. This paper take Shenyang region as pilot area, then retrieve the AOD and PM2.5 concentration of Shenyang in 2015 based on MODIS data, thus get 1km resolution distribution map, and then analyzed the results in spatial, intensity and temporal. At last, real-time monitoring data from the ground monitor station is used to verify the outcome, the results have good accuracy and the the correlation reached 0.9004 when the weather is sunny. The research shows that this algorithm has relatively higher precision and certain universality. This method has better applicability to retrieve AOD and PM2.5 concentration by remote sensing in Shenyang and Liaoning Provience, and owes guiding and reference significance, and it has a high value in terms of atmospheric environment monitoring.

Ventilator-associated pneumonia: current status and future recommendations.

PubMed

Efrati, Shai; Deutsch, Israel; Antonelli, Massimo; Hockey, Peter M; Rozenblum, Ronen; Gurman, Gabriel M

2010-04-01

Ventilator-associated pneumonia (VAP) is a common hazardous complication in ICU patients. The aim of the current review is to give an update on the current status and future recommendations for VAP prevention. This article gives an updated review of the current literature on VAP. The first part briefly reviews pathogenesis and epidemiology while the second includes an in-depth review of evidence-based practice guidelines (EBPG) and new technologies developed for prevention of VAP. VAP remains a frequent and costly complication of critical illness with a pooled relative risk of 9-27% and mortality of 25-50%. Strikingly, VAP adds an estimated cost of more than $40,000 to a typical hospital admission. An important aetiological mechanism of VAP is gross or micro-aspiration of oropharyngeal organisms around the cuff of the endotracheal tube (ETT) into the distal bronchi. Prevention of VAP is preferable. Preventative measures can be divided into two main groups: the implemen- tation of EBPGs and use of device-based technologies. EBPGs have been authored jointly by the American Thoracic Society and the Infectious Diseases Society of America. The Canadian Critical Care Trials group also published VAP Guidelines in 2008. Their recommendations are detailed in this review. The current device-based technologies include drainage of subglottic secretions, silver coated ETTs aiming to influence the internal bio-layer of the ETT, better sealing of the lower airways with ultrathin cuffs and loops for optimal cuff pressure control. EBPG consensus includes: elevation of the head of the bed, use of daily "sedation vacations" and decontamination of the oropharynx. Technological solutions should aim to use the most comprehensive combination of subglottic suction of secretions, optimization of ETT cuff pressure and ultrathin cuffs. VAP is a type of hospital-acquired pneumonia that develops more than 48 h after endotracheal intubation. Its incidence is estimated to be 9-27%, with a mortality of 25-50% [Am J Respir Crit Care Med 171:388-416 (2005), Am J Med 85:499-506 (1988), Chest 122:2115-2121 (2002), Intensive Care Med 35:9-29 (2009)]. The most important target in VAP handling is its prevention. The aim of this article is to review the pathogenesis, epidemiology and the different strategies/technologies for prevention of VAP.

Local Intratracheal Delivery of Perfluorocarbon Nanoparticles to Lung Cancer Demonstrated with Magnetic Resonance Multimodal Imaging

PubMed Central

Wu, Lina; Wen, Xiaofei; Wang, Xiance; Wang, Chunan; Sun, Xilin; Wang, Kai; Zhang, Huiying; Williams, Todd; Stacy, Allen J.; Chen, Junjie; Schmieder, Anne H.; Lanza, Gregory M.; Shen, Baozhong

2018-01-01

Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications. Methods: This proof-of-concept study compared intratumoral localization of fluorescent paramagnetic (M) PFC NP in the Vx2 rabbit model using proton (1H) and fluorine (19F) magnetic resonance (MR) imaging (3T) following intratracheal (IT) or IV administration. MRI results were corroborated by fluorescence microscopy. Results: Dynamic 1H-MR and 19F-MR images (3T) obtained over 72 h demonstrated marked and progressive accumulation of M-PFC NP within primary lung Vx2 tumors during the first 12 h post IT administration. Marked 1H and 19F MR signal persisted for over 72 h. In contradistinction, IV M-PFC NP produced a modest transient signal during the initial 2 h post-injection that was consistent circumferential blood pool tumor enhancement. Fluorescence microscopy of excised tumors corroborated the MR results and revealed enormous intratumor NP deposition on day 3 after IT but not IV treatment. Rhodamine-phospholipid incorporated into the PFC nanoparticle surfactant was distributed widely within the tumor on day 3, which is consistent with a hemifusion-based contact drug delivery mechanism previously reported. Fluorescence microscopy also revealed similar high concentrations of M-PFC NP given IT for metastatic Vx2 lung tumors. Biodistribution studies in mice revealed that M-PFC NP given IV distributed into the reticuloendothelial organs, whereas, the same dosage given IT was basically not detected beyond the lung itself. PFC NP given IT did not impact rabbit behavior or impair respiratory function. PFC NP effects on cells in culture were negligible and when given IV or IT no changes in rabbit hematology nor serum clinical chemistry parameters were measured. Conclusion: IT delivery of PFC NP offered unique opportunity to locally deliver PFC NP in high concentrations into lung cancers with minimal extratumor systemic exposure. PMID:29290827

Pathology and pathogenesis of disseminated visceral coccidiosis in cranes.

PubMed

Novilla, Meliton N; Carpenter, James W

2004-06-01

Disseminated visceral coccidiosis (DVC) caused by Eimeria spp. was recognized as a disease entity in captive sandhill cranes (Grus canadensis) and whooping cranes (Grus americana) in the late 1970s. While most avian species of Eimeria inhabit the intestinal tract of its host, the crane eimerians, Eimeria reichenowi and Eimeria gruis, invade and multiply systemically and complete their development in both digestive and respiratory tracts. In DVC, cranes, especially chicks, may succumb to acute infections resulting in hepatitis, bronchopneumonia, myocarditis, splenitis, and enteritis. Cranes may also develop chronic, subclinical infections characterized by granulomatous nodules in various organs and tissues. This paper reviews the pathology and pathogenicity of natural and experimental DVC in sandhill and whooping cranes. Naturally infected birds appeared clinically normal, but progressive weakness, emaciation, greenish diarrhea, and recumbency before death were observed in birds administered doses > or = 10 x 10(3) sporulated oocysts per os. At necropsy, naturally infected birds had nodules in the mucosa of the oral cavity and the esophagus, and in thoracic and abdominal viscera. Experimentally infected birds necropsied less than 7 days after infection (a.i.) had no gross lesions. Birds examined later had hepatosplenomegaly, liver mottling, lung congestion and consolidation with frothy fluid in airways, and turgid intestinal tracts with hyperemic mucosa. From 28 days a.i., grossly visible granulomatous nodules were seen in the esophagus, heart, liver, cloaca, and eyelids. By light microscopy, the basic host response was a granulomatous inflammation with non-suppurative vasculitis affecting many organs and tissues. With time, multifocal aggregates of mononuclear cells, many laden with asexual coccidial stages, increased in size and number. Widespread merogony resulted in morbidity and death, particularly in birds administered 20 x 10(3) sporulated oocysts. Ultrastructural examination revealed developing asexual coccidian stages in the cytoplasm of large lymphocytes or monocytes within a parasitophorous vacuole, often indenting the nucleus. Oocysts and gametocytes were found in the intestines by 12 days a.i., and in the esophagus, trachea, bronchi, and lung by 14 days a.i., indicating that crane eimerians can complete their life cycle at these sites. Thus, DVC in cranes could be a useful animal model for the study of eimerian extra-intestinal stages and the evaluation of potential systemic anticoccidial drugs.

To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE). Methods/Design This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year. Discussion We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung function parameters, and total scores judged by the St George’s respiratory questionnaire, Leicester cough questionnaire, and inflammatory index. We hope that this study will provide new information on the preventive effects of OM-85 on bronchiectasis exacerbations and will address a knowledge gap for this understudied disease. Trial registration This study is registered at http://www.clinicaltrials.gov (identifier NCT01968421) on 19 October 2013. PMID:24773830

Effects of formaldehyde gas on the respiratory tract of rhesus monkeys. Pathology and cell proliferation.

PubMed Central

Monticello, T. M.; Morgan, K. T.; Everitt, J. I.; Popp, J. A.

1989-01-01

Formaldehyde is a nasal carcinogen in rats but it remains to be determined what cancer risk this chemical poses in humans. Molecular dosimetry studies of formaldehyde and cellular proliferative responses to formaldehyde-induced cytotoxicity have been studied in the rodent and are important components of the authors' ongoing research, which has now been extended to nonhuman primates, a species more analogous to humans. The present study was designed to characterize formaldehyde injury in the respiratory tract of nonhuman primates to provide a direct comparison to the toxic effects of formaldehyde in rodents. Groups of three rhesus monkeys were exposed to room air, or 6 ppm formaldehyde for 5 days per week for 1 or 6 weeks, and the respiratory tract was assessed for nature and extent of histologic responses, and changes in epithelial cell proliferation rate. Lesions were characterized by mild degeneration and early squamous metaplasia confined to specific regions of the transitional and respiratory epithelia of the nasal passages and the respiratory epithelium of the trachea and major bronchi. There was minimal progression of histologic changes between 1 and 6 weeks; however, the percent of nasal surface area affected significantly increased in the 6-week exposure group. Formaldehyde-induced lesions were associated with increases in cell proliferation rates up to 18-fold over controls, which remained significantly elevated after 6 weeks of exposure. Histologic lesions and increases in cell proliferation were most extensive in the nasal passages and were minimal in the lower airways, whereas the maxillary sinuses exhibited no evidence of a response to formaldehyde exposure. Based on the extent of lesions and cell proliferation data, it appears that the monkey is more sensitive than the rat to the acute and subacute effects of formaldehyde at 6 ppm. The absence of response in the maxillary sinuses in the monkey suggests that combining tumors of the nasal cavity and sinuses in epidemiologic studies may not be appropriate for formaldehyde cancer risk assessment. Results of this study also have provided important information for tissue sample site selection in the monkey respiratory tract for ongoing molecular dosimetry studies. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 9 PMID:2923182

Cigarette smoke-inhibition of neurogenic bronchoconstriction in guinea-pigs in vivo: involvement of exogenous and endogenous nitric oxide

PubMed Central

Emms, Joanne C; Rogers, Duncan F

1997-01-01

We investigated the effect of acute inhalation of cigarette smoke on subsequent non-adrenergic, non-cholinergic (NANC) neural bronchoconstriction in anaesthetized guinea-pigs in vivo by use of pulmonary insufflation pressure (PIP) as an index of airway tone. The contribution of endogenous nitric oxide (NO) was investigated with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The contribution of plasma exudation to the response was investigated with Evans blue dye as a plasma marker. Inhalation of 50 tidal volumes of cigarette smoke or air had no significant effect on baseline PIP. In the presence of propranolol and atropine (1 mg kg−1 each), electrical stimulation of the vagus nerves in animals given air 30 min previously induced a frequency-dependent increase in PIP above sham stimulated controls (16 fold increase at 2.5 Hz, 24 fold increase at 10 Hz). In contrast, in smoke-exposed animals, the increase in subsequent vagally-induced PIP was markedly less than in the air controls (90% less at 2.5 Hz, 76% less at 10 Hz). L-NAME (10 mg kg−1), given 10 min before air or smoke, potentiated subsequent vagally-induced (2.5 Hz) NANC bronchoconstriction by 338% in smoke-exposed animals, but had no significant effect in air-exposed animals. The inactive enantiomer D-NAME (10 mg kg−1) had no effect, and the potentiation by L-NAME was partially reversed by the NO-precursor L-arginine (100 mg kg−1). Vagal stimulation did not affect the magnitude of vagally-induced bronchoconstriction 30 min later. Cigarette smoke exposure reduced the magnitude of subsequent bronchoconstriction induced by neurokinin A (NKA) by 37% compared with the effect of NKA in air-exposed animals. L-NAME had no significant effect on the smoke-induced inhibition of NKA-induced bronchoconstriction. Vagally-induced plasma exudation in the main bronchi was greater in smoke-exposed animals compared with air-exposed animals (120% greater at 2.5 Hz, 82% greater at 10 Hz). We conclude that cigarette smoke-induced inhibition of subsequent NANC neurogenic bronchoconstriction is not associated with inhibition of airway plasma exudation and is mediated in part via exogenous smoke-derived NO, or another bronchoprotective molecule, and by endogenous NO. PMID:9375977

Particle deposition in a realistic geometry of the human conducting airways: Effects of inlet velocity profile, inhalation flowrate and electrostatic charge.

PubMed

Koullapis, P G; Kassinos, S C; Bivolarova, M P; Melikov, A K

2016-07-26

Understanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200kg/m(3)). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects of inlet flow conditions, particle size, electrostatic charge, and flowrate. While most computer simulations assume a uniform velocity at the mouth inlet, we found that using a more realistic inlet profile based on Laser Doppler Anemometry measurements resulted in enhanced deposition, mostly on the tongue. Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected. Nevertheless, at the higher flowrates turbulent intensities persisted further downstream in the main bronchi. For dp>2.5μm, the overall Deposition Fractions (DF) increased with flowrate due to greater inertial impaction in the oropharynx. Below dp=1.0μm, the DF was largely independent of particle size; it also increased with flowrate, but remained significantly lower. Electrostatic charge increased the overall DF of smaller particles by as much as sevenfold, with most of the increase located in the mouth-throat. Moreover, significant enhancement in deposition was found in the left and right lung sub-regions of our reconstructed geometry. Although there was a relatively small impact of inhalation flowrate on the deposition of charged particles for sizes dp<2.5μm, impaction prevailed over electrostatic deposition for larger particles as the flowrate was increased. Overall, we report a significant interplay between particle size, electrostatic charge, and flowrate. Our results suggest that in silico models should be customized for specific applications, ensuring all relevant physical effects are accounted for in a self-consistent fashion. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cancer incidence and mortality in Chukotka, 1997-2010.

PubMed

Dudarev, Alexey A; Chupakhin, Valery S; Odland, Jon Øyvind

2013-01-01

The general aim was to assess cancer incidence and mortality among the general population of Chukotka in 1997-2010 and to compare it with the population of Russia. Cancer data were abstracted from the annual statistical reports of the P.A. Hertzen Research Institute of Oncology in Moscow. The annual number and percent of cases, crude and age-standardized cancer incidence (ASIR) and mortality (ASMR) rates per 100,000 among men and women in the Chukotka Autonomous Okrug were determined for the period 1997-2010 for incidence and 1999-2010 for mortality. Two years' data were aggregated to generate temporal trends during the period. In age-standardization, the Segi-Doll world standard population used by the International Agency for Research on Cancer was used. The higher incidence and mortality rate of cancer (all sites combined) among men compared to women, which was observed in Russia nationally, was reflected also in Chukotka, although the difference between men and women was not statistically significant. Overall, the patterns of cancer sites are similar between Chukotka and Russia, with cancer of the lung/trachea/bronchus and stomach occupying the top ranks among men. Oesophageal cancer is common in Chukotka but not in Russia, whereas prostate cancer is common in Russia but not in Chukotka. Among women, breast cancer is either the commonest or second commonest cancer in terms of incidence or mortality in both Chukotka and Russia. Cancer of the lung/trachea/bronchi ranks higher in Chukotka than in Russia. The rate of cancer incidence and mortality for all sites combined during the 13-year period was relatively stable in Russia. Dividing the period into two halves, an increase among both men and women was observed in Chukotka for all sites combined, and also for colorectal cancer. This paper presents previously unavailable cancer epidemiological data on Chukotka. They provide a basis for comparative studies across circumpolar regions and countries. With its small population, cancer rates in Chukotka tend to be highly unstable and fluctuate widely from year to year. Even when aggregated over a decade or more, only broad conclusions regarding patterns and trends can be made regarding some of the commonest cancer sites, or with all sites combined. Chukotka experienced substantial social and economic dislocations during the period under study, which could conceivably affect risk factor distribution and the quality of medical care.

Quantification and visualization of injury and regeneration in the developing ciliated epithelium using quantitative flow imaging and speckle variance optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Gamm, Ute A.; Huang, Brendan K.; Mis, Emily K.; Khokha, Mustafa K.; Choma, Michael A.

2017-02-01

Premature infants are at a high risk for respiratory diseases owing to an underdeveloped respiratory system that is very susceptible to infection and inflammation. One aspect of respiratory health is the state of the ciliated respiratory epithelium which lines the trachea and bronchi. The ciliated epithelium is responsible for trapping and removing pathogens and pollutants from the lungs and an impairment of ciliary functionality can lead to recurring respiratory infections and subsequent lung damage. Mechanisms of cilia-driven fluid flow itself but also factors influenced by development like ciliary density and flow generation are incompletely understood. Furthermore, medical interventions like intubation and accidental aspiration can lead to focal or diffuse loss of cilia and disruption of flow. In this study we use two animal models, Xenopus embryo and ex vivo mouse trachea, to analyze flow defects in the injured ciliated epithelium. Injury is generated either mechanically with a scalpel or chemically by calcium chloride (CaCl2) shock, which efficiently but reversibly deciliates the embryo skin. In this study we used optical coherence tomography (OCT) and particle tracking velocimetry (PTV) to quantify cilia driven fluid flow over the surface of the Xenopus embryo. We additionally visualized damage to the ciliated epithelium by capturing 3D speckle variance images that highlight beating cilia. Mechanical injury disrupted cilia-driven fluid flow over the injured site, which led to a reduction in cilia-driven fluid flow over the whole surface of the embryo (n=7). The calcium chloride shock protocol proved to be highly effective in deciliating embryos (n=6). 3D speckle variance images visualized a loss of cilia and cilia-driven flow was halted immediately after application. We also applied CaCl2-shock to cultured ex vivo mouse trachea (n=8) and found, similarly to effects in Xenopus embryo, an extensive loss of cilia with resulting cessation of flow. We investigated the regeneration of the ciliated epithelium after an 8 day incubation period, and found that cilia had regrown and flow was completely restored. In conclusion, OCT is a valuable tool to visualize injury of the ciliated epithelium and to quantify reduction of generated flow. This method allows for systematic investigation of focal and diffuse injury of the ciliated epithelium and the assessment of mechanisms to compensate for loss of flow.

Genotoxic effects and oxidative stress induced by organic extracts of particulate matter(PM 10)collected from a subway tunnel in Seoul, Korea.

PubMed

Jung, Mi Hyun; Kim, Ha Ryong; Park, Yong Joo; Park, Duck Shin; Chung, Kyu Hyuck; Oh, Seung Min

2012-12-12

Particulate matter (PM) has become an important health risk factor in our society. PM can easily deposit in the bronchi and lungs, causing diverse diseases such as respiratory infections, lung cancers and cardiovascular diseases. In recent days, more and more toxicological studies have been dealing with air particles in distinctive areas including industrial areas, transportation sites, or indoors. Studies on subway PM in particular, have been recognizing PM as an important health risk factor because many people use subways as a major mode of public transportation (4 million people a day in Korea). The main aim of the present study was to evaluate the genotoxic effects of organic extract (OE) of subway PM10 and potential attribution of PAHs to these effects. Particles were collected in the subway tunnel at Kil-eum station(Line 4) for one month and then extracted with Dichloromethane (DCM). Chinese Hamster Ovary cells(CHO-K1) and human normal bronchial cells (BEAS-2B) were exposed to OE, and MN and Comet assays were conducted to analyze the genotoxicity. The results showed that OE increased DNA or chromosome damages in both cell lines. In the modified Comet assay and MN assay with free radical scavengers, we confirmed that the genotoxic effect of OE was partially due to the oxidative damage on DNA. DCFHD Aassay also indicated that OE induced ROS generation in BEAS-2B cells. PAHs [benzo(a)anthracene,benzo(k)fluoranthrene, etc.], the most well-known carcinogens in polluted air, were detected in Kil-eum PM10. In conclusion, our findings confirmed that OE of subway PM10 has genotoxic effects on normal human lung cells, and oxidative stress could be one of the major mechanisms of these genotoxic effects.In addition, some genotoxic and carcinogenic PAHs were detected in OE by GC/MS/MS, even though PAHs level was not enough to increase CYP1A1 gene. Therefore, we suggest that additive or synergistic effects by unidentified chemicals as well as PAHs contained in OE of subway PM10 may induce genotoxic effects and further researches are needed to identify the genotoxic compounds in subway PM.

Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs.

PubMed

Lundberg, J M; Brodin, E; Saria, A

1983-11-01

The origin of substance P (SP)-immunoreactive neurons in the lower respiratory tract, esophagus and heart of guinea-pigs was demonstrated by surgical denervation or capsaicin pretreatment with subsequent determination of the tissue levels of SP by radioimmunoassay. In other experiments the effect of vagal nerve stimulation on the SP levels in these tissues was studied. The effects of capsaicin-sensitive afferents in the respiratory tract mucosa and bronchial smooth muscle was also studied by analysis of vascular permeability to Evans blue and insufflation-pressure changes. Our present data indicate that all SP nerves in the trachea and lung are afferent and capsaicin-sensitive. The trachea and stem bronchi receive SP afferents mainly from the right vagus nerve with cell bodies located in both the nodose and jugular ganglia. The SP innervation of the lung seems to have a dual origin: 1. Afferents from both vagal nerves with a crossed type of innervation pattern. 2. A non-vagal source which consists of about 40% of the SP nerves in the lung. These nerves probably originate from thoracic spinal ganglia. The effects of ether and capsaicin on insufflation pressure and increase in vascular permeability were dependent on the integrity of capsaicin-sensitive afferents of both vagal and non-vagal origin. In the guinea pig, systemic capsaicin pretreatment to adult animals seemed to result in irreversible changes in the respiratory tract, while in the rat a successive recovery of the functional response of capsaicin-sensitive afferents occurred. Different regimes of systemic capsaicin pretreatment induced different effects on the cholinergic (atropine-sensitive) insufflation-pressure response. Capsaicin pretreatment, using multiple injections over two days, depressed the cholinergic insufflation-pressure increase, while the cholinergic vagal component was unaffected in animals which received a single dose of capsaicin or local pretreatment with capsaicin on the vagal nerves. The local treatment was more effective with regard to SP depletion in target areas when using alcohol as solvent than when capsaicin was dissolved in paraffin oil, while the functional deficits were similar. The SP nerves in the esophagus were mainly of vagal afferent origin, while the heart atrium seemed to have a dual innervation by both vagal and non-vagal SP nerves.

Selective inhibition by dactinomycin of NANC sensory bronchoconstriction and [125I]NKA binding due to NK-2 receptor antagonism.

PubMed

Lou, Y P; Delay-Goyet, P; Lundberg, J M

1992-03-01

In the present study, dactinomycin (10(-5) M) inhibited the non-adrenergic, non-cholinergic bronchoconstriction upon antidromic vagal nerve stimulation (1 Hz for 1 min) in the isolated perfused guinea-pig lung by 84%. The release of calcitonin gene-related peptide was unchanged, however, suggesting a postjunctional action. Dactinomycin (10(-5), 5 x 10(-5) M) also reduced non-adrenergic non-cholinergic bronchial contractions (maximally by 75%) induced by electrical field stimulation or capsaicin, while the cholinergic component and non-adrenergic non-cholinergic relaxation remained intact. The neurokinin-2 receptor antagonist L-659,877 (10(-6) M) had a similar effect as dactinomycin, inhibiting the non-adrenergic non-cholinergic bronchial contractions by 69%, while the neurokinin-1 receptor antagonist CP-96,345 (10(-6) M) had no effect. The bronchoconstriction evoked by neurokinin A, the selective neurokinin-2 receptor agonist Nle10neurokinin A (4-10) and capsaicin was markedly inhibited by dactinomycin while the contraction induced by substance P (SP), the selective neurokinin-1 receptor agonist Sar9Met(O2)11SP, endothelin-1 and acetylcholine was not affected. In autoradiographic experiments on guinea-pig lung, [125I]neurokinin A-labelled sections showed dense binding in the bronchial smooth muscle layer. Dactinomycin inhibited the specific binding of [125I]neurokinin A in a concentration-dependent manner (IC50 = 6.3 x 10(-6) M) and 66% of [125I]neurokinin A total binding was inhibited by 10(-4) M dactinomycin. In the rat colon, [125I]neurokinin A binding to neurokinin-2 sites on circular smooth muscle was inhibited by dactinomycin with an IC50 value of 7.9 x 10(-6) M. Dactinomycin failed to reduce increased nerve-evoked contractions or those caused by Nle10neurokinin A (4-10) per se in the rat vas deferens, which are considered to be mediated by neurokinin-2 receptor activation. In the rat portal vein, dactinomycin did not influence the contractions caused by the neurokinin-3 selective agonist Pro7neurokinin B. In conclusion, dactinomycin selectively inhibited neurokinin-2 receptor activation in guinea-pig lung and rat colon, but not in rat vas deferens, which may depend on the existence of different neurokinin-2 receptor subtypes. Neurokinin A is most likely the main endogenous excitatory non-adrenergic non-cholinergic transmitter in guinea-pig bronchi.

Subjective and objective comparisons of image quality between ultra-high-resolution CT and conventional area detector CT in phantoms and cadaveric human lungs.

PubMed

Yanagawa, Masahiro; Hata, Akinori; Honda, Osamu; Kikuchi, Noriko; Miyata, Tomo; Uranishi, Ayumi; Tsukagoshi, Shinsuke; Tomiyama, Noriyuki

2018-05-29

To compare the image quality of the lungs between ultra-high-resolution CT (U-HRCT) and conventional area detector CT (AD-CT) images. Image data of slit phantoms (0.35, 0.30, and 0.15 mm) and 11 cadaveric human lungs were acquired by both U-HRCT and AD-CT devices. U-HRCT images were obtained with three acquisition modes: normal mode (U-HRCT N : 896 channels, 0.5 mm × 80 rows; 512 matrix), super-high-resolution mode (U-HRCT SHR : 1792 channels, 0.25 mm × 160 rows; 1024 matrix), and volume mode (U-HRCT SHR-VOL : non-helical acquisition with U-HRCT SHR ). AD-CT images were obtained with the same conditions as U-HRCT N . Three independent observers scored normal anatomical structures (vessels and bronchi), abnormal CT findings (faint nodules, solid nodules, ground-glass opacity, consolidation, emphysema, interlobular septal thickening, intralobular reticular opacities, bronchovascular bundle thickening, bronchiectasis, and honeycombing), noise, artifacts, and overall image quality on a 3-point scale (1 = worst, 2 = equal, 3 = best) compared with U-HRCT N . Noise values were calculated quantitatively. U-HRCT could depict a 0.15-mm slit. Both U-HRCT SHR and U-HRCT SHR-VOL significantly improved visualization of normal anatomical structures and abnormal CT findings, except for intralobular reticular opacities and reduced artifacts, compared with AD-CT (p < 0.014). Visually, U-HRCT SHR-VOL has less noise than U-HRCT SHR and AD-CT (p < 0.00001). Quantitative noise values were significantly higher in the following order: U-HRCT SHR (mean, 30.41), U-HRCT SHR-VOL (26.84), AD-CT (16.03), and U-HRCT N (15.14) (p < 0.0001). U-HRCT SHR and U-HRCT SHR-VOL resulted in significantly higher overall image quality than AD-CT and were almost equal to U-HRCT N (p < 0.0001). Both U-HRCT SHR and U-HRCT SHR-VOL can provide higher image quality than AD-CT, while U-HRCT SHR-VOL was less noisy than U-HRCT SHR . • Ultra-high-resolution CT (U-HRCT) can improve spatial resolution. • U-HRCT can reduce streak and dark band artifacts. • U-HRCT can provide higher image quality than conventional area detector CT. • In U-HRCT, the volume mode is less noisy than the super-high-resolution mode. • U-HRCT may provide more detailed information about the lung anatomy and pathology.

Sequence of pathogenic events in cynomolgus macaques infected with aerosolized monkeypox virus.

PubMed

Tree, J A; Hall, G; Pearson, G; Rayner, E; Graham, V A; Steeds, K; Bewley, K R; Hatch, G J; Dennis, M; Taylor, I; Roberts, A D; Funnell, S G P; Vipond, J

2015-04-01

To evaluate new vaccines when human efficacy studies are not possible, the FDA's "Animal Rule" requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (10(5) PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it would be unethical and field trials are not feasible. To overcome this, the FDA may grant marketing approval of a new product based upon the "Animal Rule," in which interventions are tested for efficacy in well-characterized animal models. Monkeypox virus infection of nonhuman primates (NHPs) presents a potential surrogate disease model for smallpox. Previously, the later stages of monkeypox infection were defined, but the early course of infection remains unstudied. Here, the early pathogenic events of inhalational monkeypox infection in NHPs were characterized, and the results support the use of this surrogate model for testing human smallpox interventions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Investigations of initial airtightness after non-anatomic resection of lung parenchyma using a thulium-doped laser with different optical fibres.

PubMed

Kirschbaum, Andreas; Höchsmann, N; Steinfeldt, T; Seyfer, P; Pehl, A; Bartsch, D K; Palade, E

2016-08-01

Lung metastases in healthy patients should be removed non-anatomically whenever possible. This can be done with a laser. Lung parenchyma can be cut very well, because of its high energy absorption at a wavelength of 1940 nm. A coagulation layer is created on the resected surface. It is not clear, whether this surface also needs to be sutured to ensure that it remains airtight even at higher ventilation pressures. It would be helpful, if suturing could be avoided, because the lung can become too puckered, especially with multiple resections, resulting in considerable restriction. We carried out our experiments on isolated and ventilated paracardiac lung lobes of pigs. Non-anatomic resection was carried out reproducibly using three different thulium laser fibres (230, 365 and 600 μm) at two different laser power levels (10 W, 30 W) and three different resection depths (0.5, 1.0 and 2.0 cm). Initial airtightness was investigated while ventilating at normal frequency. We also investigated the bursting pressures of the resected areas by increasing the inspiratory pressure. When 230- and 365-μm fibres were used with a power of 10 W, 70 % of samples were initially airtight up to a resection depth of 1 cm. This rate fell at depths of up to 2 cm. All resected surfaces remained airtight during ventilation when 600-μm fibres were used at both laser power levels (10 and 30 W). The bursting pressures achieved with 600-μm fibres were higher than with the other fibres used: 0.5 cm, 41.6 ± 3.2 mbar; 1 cm, 38.2 ± 2.5 mbar; 2 cm, 33.7 ± 4.8 mbar. As laser power and thickness of laser fibre increased, so the coagulation zone became thicker. With a 600-μm fibre, it measured 145.0 ± 8.2 μm with 10 W power and 315.5 ± 6.4 μm with 30 W power. Closure with sutures after non-anatomic resection of lung parenchyma is not necessary when a thulium laser is used provided a 600-μm fibre and adequate laser power (30 W) are employed. At deeper resection levels, the risk of cutting small segmental bronchi is considerably increased. They must always be closed with sutures.

Cancer incidence and mortality in Chukotka, 1997–2010

PubMed Central

Dudarev, Alexey A.; Chupakhin, Valery S.; Odland, Jon Øyvind

2013-01-01

Objectives The general aim was to assess cancer incidence and mortality among the general population of Chukotka in 1997–2010 and to compare it with the population of Russia. Methods Cancer data were abstracted from the annual statistical reports of the P.A. Hertzen Research Institute of Oncology in Moscow. The annual number and percent of cases, crude and age-standardized cancer incidence (ASIR) and mortality (ASMR) rates per 100,000 among men and women in the Chukotka Autonomous Okrug were determined for the period 1997–2010 for incidence and 1999–2010 for mortality. Two years’ data were aggregated to generate temporal trends during the period. In age-standardization, the Segi-Doll world standard population used by the International Agency for Research on Cancer was used. Results The higher incidence and mortality rate of cancer (all sites combined) among men compared to women, which was observed in Russia nationally, was reflected also in Chukotka, although the difference between men and women was not statistically significant. Overall, the patterns of cancer sites are similar between Chukotka and Russia, with cancer of the lung/trachea/bronchus and stomach occupying the top ranks among men. Oesophageal cancer is common in Chukotka but not in Russia, whereas prostate cancer is common in Russia but not in Chukotka. Among women, breast cancer is either the commonest or second commonest cancer in terms of incidence or mortality in both Chukotka and Russia. Cancer of the lung/trachea/bronchi ranks higher in Chukotka than in Russia. The rate of cancer incidence and mortality for all sites combined during the 13-year period was relatively stable in Russia. Dividing the period into two halves, an increase among both men and women was observed in Chukotka for all sites combined, and also for colorectal cancer. Conclusions This paper presents previously unavailable cancer epidemiological data on Chukotka. They provide a basis for comparative studies across circumpolar regions and countries. With its small population, cancer rates in Chukotka tend to be highly unstable and fluctuate widely from year to year. Even when aggregated over a decade or more, only broad conclusions regarding patterns and trends can be made regarding some of the commonest cancer sites, or with all sites combined. Chukotka experienced substantial social and economic dislocations during the period under study, which could conceivably affect risk factor distribution and the quality of medical care. PMID:23518507

Sequence of Pathogenic Events in Cynomolgus Macaques Infected with Aerosolized Monkeypox Virus

PubMed Central

Hall, G.; Pearson, G.; Rayner, E.; Graham, V. A.; Steeds, K.; Bewley, K. R.; Hatch, G. J.; Dennis, M.; Taylor, I.; Roberts, A. D.; Funnell, S. G. P.; Vipond, J.

2015-01-01

ABSTRACT To evaluate new vaccines when human efficacy studies are not possible, the FDA's “Animal Rule” requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (105 PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. IMPORTANCE Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it would be unethical and field trials are not feasible. To overcome this, the FDA may grant marketing approval of a new product based upon the “Animal Rule,” in which interventions are tested for efficacy in well-characterized animal models. Monkeypox virus infection of nonhuman primates (NHPs) presents a potential surrogate disease model for smallpox. Previously, the later stages of monkeypox infection were defined, but the early course of infection remains unstudied. Here, the early pathogenic events of inhalational monkeypox infection in NHPs were characterized, and the results support the use of this surrogate model for testing human smallpox interventions. PMID:25653439

Particulate Concentration Levels in Chinatown, Oakland, California

NASA Astrophysics Data System (ADS)

Chen, B.; Yeung, A.; Yu, J. F.

2007-12-01

Chinatown is located near the center of the busy business district of downtown Oakland, California. It is one of the most inhabited and congested areas in the City of Oakland, averaging 4,000 vehicles and 3,000 pedestrians per hour at a key intersection in the center of the neighborhood. Particles produced by automobiles and construction can settle into the bronchi of lungs and induce asthma attacks, irritate cardiovascular tissue, and possibly lead to lung cancer and death. Particulate pollution is a serious problem that is estimated to cause between 20,000 and 50,000 deaths per year in the US alone. Hence, evaluation of the air quality of the Chinatown neighborhood is important, because it helps to address issues that are of great concern to residents of the area. The primary goal of our project was to measure particulate concentration levels at various intersections in Oakland's Chinatown to determine if the air quality met U.S. EPA standards, and to take note of any trends that may occur over a period of months. We were primarily concerned with particles that are 2.5 micrometers diameter and smaller, as smaller particles are easily inhaled and directly affect the respiratory system. We were interested in identifying any intersections that may have had significantly higher levels than other intersections. Using a map of Chinatown, we chose 12 intersections and made measurements at these points over the course of six months, beginning in February and ending in July of 2007. Particulate matter measurements were made using a FLUKE 893 Particle Counter. Measurements recorded on the first day of our study, February 4, 2007, which was the day of an annual street festival, yielded the highest values for particulate matter concentration in our dataset. This was followed by a significant drop in concentration the following week, and then a gradual increase of concentration as the months progressed. No one location yielded values significantly higher than any other, and, except for the first and last day (where there was experimental error), recorded values seem to meet EPA standards. We conclude that the high particulate matter levels we observed were due to heavy crowding and traffic jams near street corners during the time of the festival. We also conclude that particulate pollution levels in the Chinatown neighborhood are generally acceptable, except during festivities that generate heavy congestion. We intend conduct further investigations, particularly at next year's street festival, to confirm observations made thus far.

KW-4679-induced inhibition of tachykininergic contraction in the guinea-pig bronchi by prejunctional inhibition of peripheral sensory nerves.

PubMed

Ikemura, T; Okarmura, K; Sasaki, Y; Ishi, H; Ohmori, K

1996-03-01

1. Sensory mechanisms play an important role in the vagal regulation of tracheobronchial smooth muscle tone. We examined the effect of KW-4679, an anti-allergic drug, on guinea-pig tachykinin-mediated contractile responses induced by electrical field stimulation (EFS) in guinea-pig bronchial muscles. 2. EFS (8 Hz, 0.5 ms, 15 V, for 15 s) evoked biphasic contractile responses in the guinea-pig isolated main bronchus in the presence of 5 microM indomethacin. The contractions consisted of a fast phase of an atropine-sensitive transient contraction and a slow phase of a sustained contraction which was inhibited by a combination of the tachykinin NK1 receptor antagonist, (+/-)-CP-96,345 (1 microM) and the NK2 receptor antagonist, SR 48969 (0.1 microM). 3. KW-4679 preferentially inhibited the slow phase in a concentration-dependent manner by 43.2 +/- 7.7% at 10 microM, whereas the drug had no effect on the fast phase at concentrations up to 10 microM. KW-4679, at a concentration of 100 microM, inhibited not only the slow phase by 49.2 +/- 11.4%, but also the fast phase by 36.8 +/- 9.3% [corrected]. 4. KW-4679 (10 microM and 100 microM) did not affect the substance P-induced or neurokinin A-induced contraction. Against the acetylcholine-induced contractile responses, 100 microM KW-4679 had a marked effect producing a 10.2 fold shift to the right in the curve. 5. The inhibitory effect of KW-4679 (10 microM) on the slow phase contraction was not influenced by treatment with naloxone (100 nM), propranolol (1 microM), thioperamide (1 microM), saclofen (50 microM), yohimbine (1 microM), methiothepin (1 microM) or methysergide (1 microM). 6. The inhibitory effect of KW-4679 (10 microM) on the slow phase contraction was not influenced by treatment with intermediate or large conductance Ca(2+)-activated K+ channel blockers (charybdotoxin (10 nM) or iberiotoxin (10 nM)), but suppressed by treatment with small conductance Ca(2+)-activated K+ channel blockers, apamin (500 nM) or scyllatoxin (300 nM). Apamin or scyllatoxin per se did not influence the slow phase contractions. 7. The results suggest that KW-4679 preferentially inhibits the release of tachykinins from the bronchial sensory nerves through activation of small conductance Ca(2+)-activated K+ channels.

Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study

PubMed Central

2014-01-01

Background Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB. Methods We divided 2703 GOLD 1–4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org). Results There were no differences in % emphysema (11.4 ± 12.0 vs. 12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs. 36.3 ± 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 ± 3.2 vs. 62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs. 3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs. 5.17 ± 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB. Conclusions Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB. PMID:24766722

Effect of Heat Moisture Exchanger on Aerosol Drug Delivery and Airway Resistance in Simulated Ventilator-Dependent Adults Using Jet and Mesh Nebulizers.

PubMed

Ari, Arzu; Dang, Truong; Al Enazi, Fahad H; Alqahtani, Mohammed M; Alkhathami, Abdulrahman; Qoutah, Rowaida; Almamary, Ahmad S; Fink, James B

2018-02-01

Placement of a heat moisture exchanger (HME) between aerosol generator and patient has been associated with greatly reduced drug delivery. The purpose of this study was to evaluate the effect of filtered and nonfiltered HMEs placed between nebulizer and patient on aerosol deposition and airway resistance (Raw) in simulated ventilator-dependent adults. An in vitro lung model was developed to simulate a mechanically ventilated adult (Vt 500 mL, RR 15/min, and PEEP 5 cmH 2 O, using two inspiratory flow rates 40 and 50 L/min) using an intubated adult manikin with an endotracheal tube (8 mmID). The bronchi of the manikin were connected to a Y-adapter through a collecting filter (Respirgard II) attached to a test lung through a heated humidifier (37°C producing 100% relative humidity) to simulate exhaled humidity. For treatment conditions, a nonfiltered HME (ThermoFlo™ 6070; ARC Medical) and filtered HMEs (ThermoFlo™ Filter; ARC Medical and PALL Ultipor; Pall Medical) were placed between the ventilator circuit at the endotracheal tube and allowed to acclimate to the exhaled heat and humidity for 30 minutes before aerosol administration. Airway resistance (cmH 2 O/L/s) was taken at 0, 10, 20, and 30 minutes after HME placement and after each of four aerosol treatments. Albuterol sulfate (2.5 mg/3 mL) was administered with jet (Misty Max 10; Airlife) and mesh (Aerogen Solo; Aerogen) nebulizers positioned in the inspiratory limb proximal to the Y-adapter. Control consisted of nebulization with no HME. Drug was eluted from filter at the end of the trachea and measured using spectrophotometry (276 nm). Greater than 60% of the control dose was delivered through the ThermoFlo. No significant difference was found between the first four treatments given by the jet (p = 0.825) and the mesh (p = 0.753) nebulizers. There is a small increase in Raw between pre- and post-four treatments with the jet (p = 0.001) and mesh (p = 0.015) nebulizers. Aerosol delivery through filtered HMEs was similar (<0.5%) across the four treatments. Airway resistance was similar using the ThermoFlo Filter. With the PALL Ultipor, changes in Raw increased with mesh nebulizer after treatment (p = 0.005). Changes in resistance pre- and post-treatment were similar with both filtered HMEs. The ThermoFlo™ nonfilter HME allowed the majority of the control dose to be delivered to the airway. Increases in Raw would likely not be outside of a tolerable range in ventilated patients. In contrast, filtered HMEs should not be placed between nebulizers and patient airways. Further research with other HMEs and materials is warranted.

Comparison of Macintosh and Intubrite laryngoscopes for intubation performed by novice physicians in a difficult airway scenario.

PubMed

Szarpak, Lukasz; Smereka, Jacek; Ladny, Jerzy R

2017-05-01

In the difficult airway, the intubation skills are critically important. In selected cases, particularly in airway edema, laryngeal or tongue edema, endotracheal intubation can turn out very difficult, and repeated attempts may even worsen the airway edema, causing trauma and bleeding, and finally leading to complete airway obstruction and inability to ventilate the patient. The aim of the study was to compare the efficacy of endotracheal intubation performed by novice physicians using a standard Macintosh laryngoscope and an Intubrite videolaryngoscope. The study was designed as a prospective, randomized, crossover, simulation study and continues our research assessing the effectiveness of selected endotracheal intubation techniques in prehospital settings. All participants were experienced with the Macintosh direct laryngoscope but remained novice to videolaryngoscopy. Instructions on the correct use of the Macintosh and Intubrite laryngoscopes were given before the procedure, and all the 30 novice physicians were allowed to practice at least 10 times before the study on manikin with normal airways. We employed an airway manikin (Trucorp Airsim Bronchi; Trucorp Ltd., Belfast, Northern Ireland) to simulate difficult airway, with was obtained by inflating the tongue with 50mL of air. The participants were asked to perform tracheal intubation using an endotracheal tube with 7.5mm of internal diameter (Portex; Smiths Medical, Hythe, UK) through the vocal cords, applying either a conventional Macintosh laryngoscope with a size 3 blade (MAC; Mercury Medical, Clearwater, FL, USA) or the Intubrite videolaryngoscope, also with a Macintosh No. 3 blade (INT; Intubrite Llc, Vista, CA, USA). In both intubation techniques, a guide stylet (Rusch Inc., Duluth, GA, USA) was introduced into the endotracheal tube in order to obtain a C-shape curve to facilitate tracheal intubation. Each participating physician was randomly assigned to three attempts of tracheal intubation with each device. The effectiveness of the first intubation attempt using MAC and INT was 63.6% and 53.4%, respectively (p=0.023), and the total percentage of intubation was 100% for both methods. The median time to intubation was 29.5 (interquartile range [IQR], 27-35.5) s with MAC, and 229 (IQR, 25.5-37) s with INT. The total of 24 physicians out of all study participants would choose MAC as a device to intubate with in real terms, while only 6 physicians would choose INT. During the simulation study, the novice physicians were able to perform endotracheal intubation at the same time using both the Macintosh and Intubrite videolaryngoscope. However, the efficacy of the first intubation attempt was higher for MAC. Further studies are needed to confirm the results. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study.

PubMed

Kim, Victor; Davey, Adam; Comellas, Alejandro P; Han, Meilan K; Washko, George; Martinez, Carlos H; Lynch, David; Lee, Jin Hwa; Silverman, Edwin K; Crapo, James D; Make, Barry J; Criner, Gerard J

2014-04-27

Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB. We divided 2703 GOLD 1-4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org). There were no differences in % emphysema (11.4 ± 12.0 vs. 12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs. 36.3 ± 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 ± 3.2 vs. 62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs. 3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs. 5.17 ± 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB. Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB.

STUDIES ON EXPERIMENTAL PNEUMONIA : IX. PRODUCTION IN MONKEYS OF AN ACUTE RESPIRATORY DISEASE RESEMBLING INFLUENZA BY INOCULATION WITH BACILLUS INFLUENZAE.

PubMed

Blake, F G; Cecil, R L

1920-11-30

Twelve normal monkeys inoculated on the mucous membranes of the nose or nose and mouth with a strain of Bacillus influenzae; originally isolated in pure culture from the pleural exudate of a case of empyema following influenzal pneumonia in man and subsequently raised in virulence by animal passage, developed an acute self-limited respiratory disease of from 3 to 5 days duration, characterized by sudden onset with profound prostration, the development of rhinitis and tracheobronchitis, with sneezing, cough, and the outpouring of a scanty mucoid, or mucopurulent exudate, a variable febrile reaction, and either a leucopenia or no significant change in the leucocyte count. This disease was complicated in five instances by purulent sinusitis of one or both antra, in three by bronchopneumonia. Bacillus influenzae was recovered at autopsy from the lesions of the disease either in pure culture or in association with organisms that are normal inhabitants of the upper respiratory tract of monkeys. Of ten normal monkeys injected intratracheally with the same strain of Bacillus influenzae, seven developed bronchopneumonia, two developed tracheobronchitis without pneumonia, and one resisted infection. The general symptoms and duration of the disease were similar to those of the preceding group. There were a severe cough and accelerated respirations. Bacillus influenzae was recovered in pure culture from the lungs, bronchi, or trachea in the animals killed during the active stage of the disease. It disappeared promptly from the respiratory tract with recovery. The significance of the first series of experiments in which monkeys were inoculated in the upper respiratory tract is twofold. First, they establish the fact that Bacillus influenzae can initiate in monkeys an acute infection of the normal mucous membranes of the upper respiratory tract; that is, it can act as a primary incitant of respiratory infection without the assistance of a preceding or concomitant contributing cause. In this respect it differs radically from the pneumococcus and Streptococcus haemolyticus, since experiments previously reported(2, 4) have shown that neither of these organisms possesses the property of initiating an infection of the normal mucous membranes of the upper respiratory tract of monkeys, even though the strains used were incalculably more virulent for monkeys than the strain of Bacillus influenzae used in the foregoing experiments. Secondly, the experiments show that Bacillus influenzae infection of the mucous membranes of the upper respiratory tract may spread by continuity to the paranasal sinuses, setting up an acute sinusitis, that it spreads readily to the lower respiratory tract, producing a tracheobronchitis and permitting the ready invasion of secondary bacteria, and that it may penetrate as far as the terminal bronchioles, alveolar ducts, atria, and alveoli, there setting up a bronchiolitis and true bronchopneumonia. In these respects it likewise differs radically from the pneumococcus and Streptococcus haemolyticus which do not possess these pathogenic properties as previous experiments have shown.(2, 4) The bearing of these facts on the possible etiologic relation of Bacillus influenzae to influenza is important, since they show that Bacillus influenzae possesses certain definite primary pathogenic properties which distinguish it and therefore separate it from the group of recognized secondary organisms in influenzal complications, of which the pneumococcus and the streptococcus are the most frequent. The possible etiologic relation of Bacillus influenzae to influenza is further supported by the character of the respiratory disease that occurred in the monkeys. The sudden onset with profound prostration, the absence of leucocytosis or often a leucopenia, the congestion of the mucous membranes of the respiratory tract, the development on the 2nd or 3rd day of an irritative cough due to an inflammatory tracheitis or tracheobronchitis, the brief self-limited course of the infection, and the irregular febrile reactions are all characteristic of influenza. Many of these symptoms were in striking contrast with the symptoms and course of pneumococcus or streptococcus infections in monkeys in which there were no prostration at onset, invariable leucocytosis, and infrequent cough developing only late in the disease. While all the above features of the disease produced in monkeys are characteristic of influenza in man, none are pathognomonic and, in fact, it is doubtful whether uncomplicated influenza possesses any pathognomonic features by which it may be diagnosed certainly in the absence of an epidemic. Even during epidemic times many respiratory infections arise which, though presumably influenza, it is impossible to diagnose as such with certainty. Nor does pathology help in this respect, since there would appear to be no established distinctive lesions of uncomplicated influenza in man, nor for that matter of the complications of influenza, apart from the complications which have been ascribed by Pfeiffer,(5) MacCallum,(6) Wolbach,(7) and others to infection with Bacillus influenzae because of the association of Bacillus influenzae in pure culture with these complications. For these reasons, although the disease produced in monkeys appears to be essentially identical with influenza in man with respect to its clinical course and complications, it is impossible to determine certainly whether it is actually so. The experiments are advanced, therefore, as evidence in favor of the etiologic relation of Bacillus influenzae to influenza, though they do not permit of a definite conclusion in this respect. Their bearing upon the relation of Bacillus influenzae to certain of the complications of influenza would appear to be reasonably conclusive. The recovery of Bacillus influenzae in pure culture at autopsy from the antra, from the trachea and bronchi, and from the lungs in some of the animals developing sinusitis, bronchiolitis, and a characteristic type of bronchopneumonia confirms by animal experiment the etiologic relation of Bacillus influenzae to these complications of influenza, which hitherto has rested solely upon the frequent association of the influenza bacillus with these lesions in man. The production of tracheobronchitis and the same type of bronchopneumonia by the intratracheal injection of Bacillus influenzae in the second series of experiments serves as additional confirmation of this, but has no direct bearing on the etiologic relation of Bacillus influenzae to uncomplicated influenzae.

The clinical and integrated management of COPD. An official document of AIMAR (Interdisciplinary Association for Research in Lung Disease), AIPO (Italian Association of Hospital Pulmonologists), SIMER (Italian Society of Respiratory Medicine), SIMG (Italian Society of General Medicine)

PubMed Central

2014-01-01

COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60% predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2 < 88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with "severe" or "very severe" COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneously published in Sarcoidosis Vasc Diffuse Lung Dis 2014, 31(Suppl. 1);3-21. PMID:25057359

Changing prevalence and resistance patterns in children with drug-resistant tuberculosis in Mumbai.

PubMed

Shah, Ira; Shah, Forum

2017-05-01

The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B. J. Wadia Hospital for Children, Mumbai. Children were defined as having DR TB on the basis of drug susceptibility testing (DST) of Mycobacterium tuberculosis grown on culture of body fluids (in the case of extra pulmonary TB) or from gastric lavage/bronchi-alveolar lavage/sputum in patients with pulmonary TB or from DST of the contacts. The prevalence of DR TB was calculated and the type of DR was evaluated yearly and in the pre-2010 and post-2010 eras. The overall prevalence of DR TB was 86 (6.6%) with an increase from 23 (5.6%) patients pre-2010 to 63 (7%) post-2010 (P = 0.40). Nine (10.4%) patients were diagnosed on the basis of contact with a parent with DR TB. Overall fluoroquinolone resistance increased from 9 (39.1%) pre-2010 to 59 (93.7%) post-2010 (P = 0.0001): moxifloxacin resistance increased from 2 (8.7%) to 29 (46%) (P = 0.0018) and ofloxacin resistance increased from 7 (30.4%) to 30 (47.6%) (P = 0.14). Ethionamide resistance also increased from 6 (26.1%) to 31 (49.2%) (P = 0.04), aminoglycoside resistance was one (4.3%) pre-2010 and 12 (19%) post-2010 (P = 0.17) and resistance remained virtually the same for both amikacin [0 pre-2010 and 6 (9.5%) after 2010] and kanamycin [one (4.3%) pre- and 6 (9.5%) post-2010]. Of the first-line drugs, resistance remained the same for isoniazid [23 (100%) to 61 (96.8%)], rifampicin [22 (95.7%) to 51 (80.9%),P = 0.17], pyrazinamide [15 (65.2%) to 35 (55.6%), P = 0.47], ethambutol [14 (60.9%) to 38 (60.3%), P = 1.00] and streptomycin [19 (82.6%) to 50 (79.4%), P = 1.00]. Resistance to PAS remained unchanged [2 (8.7%) to 5 (7.9%), P = 1.00]. There is increasing resistance to second-line anti-tuberculosis (ATT) drugs, particularly flouroquinolones and ethionamide. Hence, there is an urgent need to avoid the use of ATT drugs for non-tuberculous infection and to increase surveillance for DR TB in adults as MDR TB in children is usually through contact with an adult with infectious MDR TB.

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

PubMed Central

Larios Mora, Alejandro; Detalle, Laurent; Van Geelen, Albert; Davis, Michael S.; Stohr, Thomas; Gallup, Jack M.; Ackermann, Mark R.

2015-01-01

Rationale Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. Methods Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 107 FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. Results Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and hyperplasia, peribronchial lymphocyte infiltration, and syncytial cells, were consistent with those described previously for lambs and infants. Conclusion This work demonstrates that M37 hRSV replication in the lower airways of newborn lambs is robust with peak replication on day 3 and sustained until day 6. These findings, along with the similarities of lamb lung to those of infants in terms of alveolar development, airway branching and epithelium, susceptibility to human RSV strains, lesion characteristics (bronchiolitis), lung size, clinical parameters, and immunity, further establish the neonatal lamb as a model with key features that mimic RSV infection in infants. PMID:26641081

[Decrease in paO2 following intratracheal application of a local anesthetic and a 0.9% sodium chloride solution. A prospective study on the use of fiberoptic bronchoscopy in ventilated patients during local anesthesia].

PubMed

Konrad, F; Deller, A; Diatzko, J; Schmitz, J E; Kilian, J

1989-04-01

Flexible fiberoptic bronchoscopy of intubated patients can be performed in general or local anesthesia (LA). Up to now, no results have been published on the effects of LA for bronchoscopy in ventilated patients. We studied the hemodynamic changes caused by bronchoscopy under LA in mechanically ventilated patients and the effect of LA on the endoscopic decline in arterial pO2. Differences between the widely used agents lidocaine and oxybuprocaine hydrochloride were also studied. We found a decline in paO2 after the administration of LA and further investigated the influence of bronchial lavage on paO2. METHOD. A total of 70 ventilator patients, excluding patients with atelectasis, massive mucous-plug retention, and those under muscle relaxants, were examined in a surgical intensive care unit. In 40 long-term ventilator patients bronchoscopy was performed with either oxybuprocaine hydrochloride 1% (Novesin) (group 1; n = 20) or Lidocaine 1% (Xylocaine) (group 2; n = 20) (2-3 ml LA in repeated doses into the trachea and main bronchi; total amount 10 ml). We looked for hemodynamic changes and effects of LA on the bronchoscopic decline in paO2. In 15 long-term ventilator patients (group 3), LA was applied without bronchoscopy to investigate the duration of the LA-caused decline in paO2. In 15 intubated patients (group 4), the influence of intratracheal administration of 10 ml normal saline was examined. Patient data are shown in Table 2. Measurements were performed in groups 1 and 2 before and after LA, immediately after bronchoscopy and 15, 30, and 60 min after bronchoscopy and in groups 3 and 4 before and 5, 15, 30, and 60 min after LA. RESULTS. There was no effect on cardiocirculatory function during bronchoscopy in LA, but we found a decrease in paO2 after administration of LA in all patients (median in group 1 from 100 to 78 mmHg in group 2 from 104 to 86 mmHg). The subsequent bronchoscopy caused only a small, nonsignificant further decline in paO2. The administration of LA without bronchoscopy (group 3) was followed by a fall in paO2 from 86 +/- 12.5 to 69 +/- 11.7 mmHg (mean +/- SD) with oxybuprocaine hydrochloride and from 87 +/- 12.4 to 72 +/- 8.7 mmHg with lidocaine. Even after 30 min the paO2 had not returned to the initial value. The intratracheal application of 10 ml 0.9% NaCl caused a decline in paO2 from 101 +/- 20 to 78 +/- 12 mmHg (mean +/- SD), which also persisted for more than 30 min. CONCLUSIONS. The study shows that in ventilator patients undergoing fiberoptic bronchoscopy in LA, the administration of the LA is an essential factor in the decline in paO2 associated with bronchoscopy. A similar fall in paO2 is observed by intratracheal

[Regulative mechanism of dexamethasone on Toll-like receptor 4 signal transduction of infant asthma rat].

PubMed

Su, Miao-shang; Li, Chang-chong; Lin, Li; Zheng, Ji-shan; Zheng, Yang-ming; Guan, Xiao-jun; Zhang, Wei-xi; Luo, Yun-chun

2006-12-01

Eosinophilic airway inflammation is one of the basic characteristics of allergic asthma. Toll-like receptor is one of the most important innate immunity pattern recognition receptors. Glucocorticoids (GCS) are still the most effective treatment for asthma. However, few reports of studies on regulatory mechanism of GCS on the innate immunity system are available. The mechanism of effects of GCS on TLR4 is unclear. The present study aimed at understanding the effect of dexamethasone (DXM) on change of TLR4 and mechanism of regulatory effect of TLR4 on eosinophil (EOS) apoptosis. Twenty-seven Sprague-Dawley (SD) rats (age 28 to 42 days, body weight 120 to 180 gram) were randomly divided into the control group, asthma group and DXM group with 9 in each. Asthma model rats were sensitized with the mixture of ovalbumin (OVA, 1 mg) and Al (OH)(3), 100 mg on day 1 and day 8, repeatedly exposed to aerosolized OVA after day 15, once a day for three days and continued for 30 minutes at every time. During the sensitization stage, 100 microg/ml DXM were prepared with DXM group for every other day, and the same doses DXM were prepared for every day on the stage of challenge. The histopathological changes of lung tissues were observed with light microscope (LM). EOS and other inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted; the concentrations of OVA-sIgE in serum were measured by using "sandwich" ELISA; The expressions of TLR4 mRNA were determined by in situ hybridization, the apoptosis of EOS was detected by TUNEL. (1) LM showed many inflammatory cells infiltration around the bronchi and blood vessels, bronchus mucus increased, airway epithelium damage and desquamation, and airway mucous plugs in asthma group, whereas DXM group showed significantly milder changes. (2) Inflammationary cells count in BALF of asthma group was significantly higher as compared to control group (P < 0.01); compared with asthma group, the total cell count, EOS absolute count and EOS% were all significantly decreased in DXM group [(2.14 +/- 0.10) x 10(9)/L, (4.78 +/- 1.23) x 10(7)/L, (2.17 +/- 0.25)%]. (3) Levels of OVA-sIgE in serum of asthma group [(83.40 +/- 6.80) microg/ml] were significantly higher than those of the control group [(14.38 +/- 4.25) microg/ml] (P < 0.01), while those of DXM group [(45.02 +/- 7.47) microg/ml] were significantly lower than asthma group (P < 0.0 1). (4) There were no significant differences in TLR4 mRNA detected by in situ hybridization between control group (24.71 +/- 0.85) and asthma group (25.81 +/- 3.56) (P > 0.05); but it significantly increased in DXM group (29.86 +/- 3.92) as compared to asthma group. (5) The percentages of apoptotic EOS in asthma group [(7.39 +/- 1.93)%] were significantly lower than those in control group [(9.06 +/- 1.52)%] (P < 0.01); and significantly higher in DXM group [(13.33 +/- 1.09)%] than in asthma group (P < 0.01). There were significantly positive correlations between TLR4 mRNA and the percentage of apoptotic EOS (r = 0.612, P < 0.01). DXM can decrease OVA-sIgE level, induce EOS apoptosis, which may correlate with the activation of TLR4 signal transduction.

Pharmacokinetics and pharmacodynamics of tetra(m-hydroxyphenyl)chlorin in the hamster cheek pouch tumor model: comparison with clinical measurements.

PubMed

Glanzmann, T; Forrer, M; Blant, S A; Woodtli, A; Grosjean, P; Braichotte, D; van den Bergh, H; Monnier, P; Wagnières, G

2000-08-01

The pharmacokinetics (PK) of the photosensitizer tetra(m-hydroxyphenyl)chlorin (mTHPC) was measured by optical fiber-based light-induced fluorescence spectroscopy (LIFS) in the normal and tumoral cheek pouch mucosa of 29 Golden Syrian hamsters with chemically induced squamous cell carcinoma. Similar measurements were carried out on the normal oral cavity mucosa of five patients up to 30 days after injection. The drug doses were between 0.15 and 0.3 mg per kg of body weight (mg/kg), and the mTHPC fluorescence in the tissue was excited at 420 nm. The PK in both human and hamster exhibited similar behavior although the PK in the hamster mucosa was slightly delayed in comparison with that of its human counterpart. The mTHPC fluorescence signal of the hamster mucosa was smaller than that of the human mucosa by a factor of about 3 for the same injected drug dose. A linear correlation was found between the fluorescence signal and the mTHPC dose in the range from 0.075 to 0.5 mg/kg at times between 8 and 96 h after injection. No significant selectivity in mTHPC fluorescence between the tumoral and normal mucosa of the hamsters was found at any of the applied conditions. The sensitivity of the normal and tumoral hamster cheek pouch mucosa to mTHPC photodynamic therapy as a function of the light dose was determined by light irradiation at 650 nm and 150 mW/cm2, 4 days after the injection of a drug dose of 0.15 mg/kg. These results were compared with irradiations of the normal oral and normal and tumoral bronchial mucosa of 37 patients under the same conditions. The reaction to PDT of both types of human mucosae was considerably stronger than that of the hamster cheek pouch mucosa. The sensitivity to PDT became comparable between hamster and human mucosa when the drug dose for the hamster was increased to 0.5 mg/kg. A significant therapeutic selectivity between the normal and neoplastic hamster cheek pouch was observed. Less selectivity was found following irradiations of normal mucosa and early carcinomas in the human bronchi. The pharmacodynamic behavior of mTHPC was determined by test irradiations of the normal mucosa of hamsters and patients between 6 h and 8 days after injection of 0.5 and 0.15 mg/kg in the hamsters and the patients, respectively. The normal hamster cheek pouch showed a maximum response to irradiation 6 h after injection and then decreased continuously to no observable reaction at 8 days after injection. The reaction of the normal human oral mucosa, however, showed an increasing sensitivity to the applied light between 6 h and 4 days after mTHPC injection and then decreased again at 8 days. The hamster model with the chemically induced early squamous cell cancer in the cheek pouch thus showed some similarity to the early squamous cell cancer of the human oral mucosa considering the PK. However, a quantitative difference in fluorescence signal for identical mTHPC doses as well as a significant difference in pharmacodynamic behavior were also observed. The suitability of this animal model for the optimization of PDT parameters in the clinic is therefore limited. Hence great care must be taken in screening new dyes for PDT of early squamous cell cancer of the upper aerodigestive tract based upon observables in the hamster cheek pouch model.

Performance Comparisons of Jet and Mesh Nebulizers Using Different Interfaces in Simulated Spontaneously Breathing Adults and Children.

PubMed

Ari, Arzu; de Andrade, Armele Dornelas; Sheard, Meryl; AlHamad, Bshayer; Fink, James B

2015-08-01

Different types of nebulizers and interfaces are used for the treatment of adults and children with pulmonary diseases. The purpose of this study was to determine the efficiency of a mesh nebulizer (MN) with a proprietary adapter and a jet nebulizer (JN) under different configurations in adult and pediatric models of spontaneous breathing. We hypothesize that delivery efficiency of JN and MN will differ depending on the interface used during aerosol therapy in simulated spontaneously breathing adult and pediatric models. While we expect that aerosol delivery with JN will be less efficient than MN, we also hypothesize that lung deposition obtained with the adult lung model will be more than that with the pediatric lung model in all conditions tested in this study. A lung model using a teaching manikin connected to a sinusoidal pump via a collecting filter at the level of the bronchi simulating a spontaneously breathing adult (Vt 500 mL, RR 15 bpm, I:E ratio 1:2) or pediatric patient (Vt 150 mL, RR 25 bpm, I:E ratio 1:2). Albuterol sulfate (2.5 mg/3 mL) was aerosolized with JN (Mistymax 10, Airlife) or MN (Aerogen Solo(®), Aerogen) with the Adapter (Aerogen Solo(®) Adapter, Aerogen Ltd, Galway, Ireland) using mouthpiece, aerosol mask, and valved-mask in adults and the dragon mask, aerosol mask, and valved-mask in pediatrics (n=3). The Adapter, specifically designed for MN, was attached to all the interfaces used in this study with supplemental oxygen of 2 lpm, and in addition, the MP was tested with no additional flow in the adult model. The JN was driven with 10 lpm based on the manufacturer's label. Drug was eluted from the filter and analyzed via spectrophotometry. Descriptive statistics, dependent t-test and one-way analysis of variance were used for data analysis. Significant level was set at 0.05. In adults, delivery efficiency of JN with the valved mask was significantly greater than that with the aerosol mask (p=0.01). Aerosol delivery of JN with the mouthpiece was not statistically significant from the valved mask (p=0.123) and the aerosol mask (p=0.193). Drug delivery with MN with mouthpiece (15.42±1.4%) and valved-mask (15.15±1.1%) was greater than the open aerosol mask (7.54±0.39%; p=0.0001) in the adult lung model. With no flow mouthpiece delivery increased>2 fold (34.9±3.1%; p=.0001) compared to use of 2 lpm of flow. Using the JN with the pediatric model deposition with valved-mask (5.3±0.8%), dragon mask (4.7±0.9%), and aerosol mask (4.1±0.3%) were similar (p>0.05); while drug delivery with MN via valved-mask (11.1±0.7%) was greater than the dragon mask (6.44±0.3%; p=0.002) and aerosol mask (4.6±0.4%; p=0.002), and the dragon mask was more efficient than the open aerosol mask (p=0.009) CONCLUSION: The type of nebulizer and interface used for aerosol therapy affects delivery efficiency in these simulated spontaneously breathing adult and pediatric models. Drug delivery was greatest with the valved-mouthpiece and mask with JN and MN, while the standard aerosol mask was least efficient in these simulated spontaneously breathing adult and pediatric lung models. Delivery efficiency of JN was less than MN in all conditions tested in this study except in the aerosol mask. Lung deposition obtained with the adult lung model was more than that with the pediatric lung model.

Serum lipoproteins are not associated with the severity of asthma.

PubMed

Scaduto, Federica; Giglio, Rosaria Vincenza; Benfante, Alida; Nikolic, Dragana; Montalto, Giuseppe; Rizzo, Manfredi; Scichilone, Nicola

2018-06-01

Asthma is a chronic inflammatory disorder of the bronchi with a complicated and largely unknown pathogenesis. In this context, an emerging role is attributed to the apolipoproteins which serve as structural components of plasma lipoproteins. Low density lipoproteins (LDL) may be involved in the inflammatory pathways of the asthmatic airways; in particular, small dense LDL (sdLDL) particles were associated with increased oxidative susceptibility compared to medium and large sized LDL. In our previous study, we found a positive correlation between forced expiratory volume 1 s (FEV 1 ) % predicted and larger LDL particles (LDL-1), and an inverse correlation between FEV 1 % predicted and sdLDL (LDL-3) in mild, untreated asthmatics. Although LDL appear to be important modulators of inflammation, data on their clinical implications are still lacking. The aim of the study is to investigate whether LDL subclasses correlate with the severity of asthma, assuming that the atherogenic and most pro-inflammatory LDL contribute to ignite and perpetuate the airway inflammatory processes. The study was conducted in one visit, and included clinical and lung functional assessments, as well as measurements of serum concentrations of the LDL subclasses. Non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL subclasses, with the LipoPrint © System (Quantimetrix Corporation, Redondo Beach, CA, USA). LDL subclasses were distributed as seven bands (LDL-1 to LDL-7), LDL-1 and -2 being defined as large LDL (least pro-inflammatory), and LDL-3 to 7 defined as sdLDL (most pro-inflammatory). 70 asthmatics under inhaled treatment (M/F: 35/35) were enrolled; 10 healthy subjects (M/F: 3/7) served as controls. In the asthmatic group, FEV 1 % predicted was 81 ± 22% (mean ± SD), vital capacity (VC) % predicted was 97 ± 18%, and FEV 1 /FVC was 0.68 ± 0.1. The mean asthma control test (ACT) score was 18 ± 5. LDL-1 were significantly lower in asthmatics as compared to controls (18 ± 4% vs. 22 ± 4%, p = 0.008). On the contrary, LDL-2 (12 ± 4% vs. 12 ± 5%) and LDL-3 (3 ± 3% vs. 2 ± 2%) were not statistically different between the two groups; smaller subclasses were undetectable. To comply with the design of the study, subjects were classified according to their degree of severity into the 5 Global Initiative for Asthma (GINA) steps: Step 1 (M/F: 4/3, 44 ± 12 yrs), Step 2 (M/F: 1/2, 37 ± 11 yrs), Step 3 (M/F: 12/7, 47 ± 12 yrs), Step 4 (M/F: 8/15, 54 ± 12 yrs), and Step 5 (M/F: 7/9, 56 ± 9 yrs). None of the LDL subclasses showed significant differences between classes of severity: LDL-1 were 16.1 ± 5.6% in Step 1, 18 ± 2.8% in Step 2, 16.7 ± 3.7% in Step 3, 18 ± 3.3% in Step 4, and 19.5 ± 3.2% in Step 5 (p = NS); LDL2 were 14 ± 3.6%, 15 ± 3.4%, 12.4 ± 5.3%, 12.7 ± 4.4% and 11.3 ± 4.2%, respectively (p = NS); LDL3 were 5 ± 5.2%, 4.4 ± 2.6%, 3.3 ± 3.6%, 3.2 ± 2.6% and 2.4 ± 1.8%, p = NS. Finally, no relationship was detected between LDL subclasses and lung function parameters as well as the ACT scores. The current findings confirm a role of LDL as a potential biomarker in the diagnostic process for asthma, and suggest that LDL cannot be used as marker of severity of the disease. Copyright © 2018. Published by Elsevier Ltd.

TISSUE CHANGES FOLLOWING DEPRIVATION OF FAT-SOLUBLE A VITAMIN

PubMed Central

Wolbach, S. Burt; Howe, Percy R.

1925-01-01

The specific tissue changes which follow the deprivation of fat-soluble vitamin A in albino white rats and in the human concerns epithelial tissues. This effect is the substitution of stratified keratinizing epithelium for normal epithelium in various parts of the respiratory tract, alimentary tract, eyes, and paraocular glands and the genitourinary tract. We have described the morphological sequences which clearly show that the replacement of epithelium arises from focal proliferation of cells arising from the original epithelium and not by differentiation or change of preexisting cells. Young rats respond to the deficiency more promptly than adults. Growth activity of epithelium is not diminished. On the contrary, there is convincing evidence that it is greatly augmented. In a few of our animals the behavior of the replacing epithelium in respect to numbers of mitotic figures and response on the part of connective tissue and blood vessels suggests the acquisition of neoplastic properties. While the epitheliums which are the seats of these changes are largely of covering types, glandular epithelium is involved, specifically in the paraocular glands and salivary glands. It is highly probable also that the epithelium of gland ducts, respiratory mucosa, and genitourinary tract have secretory functions so that we conclude that the deficiency results in loss of specific (chemical) functions of the epitheliums concerned, while the power of growth becomes augmented. Explanation for the substitution of a chemically inactive (nonsecretory) epithelium, common in type for all locations, remains a matter of speculation. We can only speculate also in regard to the absence of change in the epithelium of such organ as the liver, parenchyma of the kidney, stomach, and intestines. The significance of the order or sequence in which different organs exhibit this change has not been determined. In general the respiratory mucosa in nares, trachea, and bronchi respond first, then the salivary glands, eye, genitourinary tract, then paraocular glands and pancreas, although as has been noted there are exceptions to this order. Our studies show that the mitochondrial apparatus is not primarily affected. Study of individual cells indicates that the first morphological evidence of avitaminosis will be found in the nucleus. We have not devoted sufficient study to be certain, but an increase of chromatin and in some instances in size of nucleoli are early morphological manifestations. Other important effects of fat-soluble A deficiency are atrophy of glandular organs, emaciation, localized edema of testes, submaxillary gland, and connective tissue structures of the lungs and focal myocardial lesions. From our own limited experience with rats fed on a water-soluble B deficient diet and from work by Cramer, Drew, and Mottram, the loss of fat in water-soluble B deficiency is as great, if not greater than in vitamin A deuciency, so that tor tne present we assume that this is not a specific manifestation of any one avitaminosis. The same applies to glandular atrophy. Both of these effects probably concern the nutrition as a whole and may be ascribed to inanition. The occurrence of transient edema in testes and salivary gland coinciding with a period of maximum atrophic change, suggests the hypothesis that this edema is the result of failure of epithelium to utilize transported material, which leads further to the hypothesis that the capillaries of these organs are differentiated in regard to permeability to the respective materials utilized by the cells. It would seem that in the case of the testis we have a unique instance of complete atrophy producible at will without impairment of circulation and supporting tissues. This phenomenon may possibly be followed with advantage in the study of the mechanism of edema. Vascularization of the cornea, as we have shown it to be independent of infection, must be a physiological response to the increased demands of the rapidly growing epithelium which has replaced the corneal epithelium. We have assumed throughout this work that the diet on which we kept our animals was deficient in respect to a single substance or group of substances having similar physiological properties, designated by the term fat-soluble vitamin A. Whether or not more than one so called vitamin or accessory substance was missing in the diet we employed does not affect the theoretical importance of the morphological results. Work by Evans and Bishop would indicate that other factors affecting fertility in addition to the so called antixerophthalmic or vitamin A factor may have been missing. Our own experience leads us to believe the specific effects we have described upon epithelial tissues were in all probability due to withdrawal of a single factor. We have shown how these effects, that is the replacement of uterine epithelium by keratinizing epithelium can account for sterility in the female. Whether or not the atrophy of the testis is due to the same factor remains to be proved, but presumptive evidence is strong that this is the case. The study of the reverse changes that follow in the rapid amelioration when the rats are restored to an adequate diet has been begun and will be reported later. We have shown that the substitution of keratinizing epithelium in all locations is not secondary to infections, and presumably is a primary effect of the withdrawal of factors essential for the chemical activities or maintenance of differentiation of the epitheliums concerned. It is, of course, possible that the phenomenon is produced in a roundabout way in that it may be secondary to the effects of the avitaminosis upon the metabolism of tissue-sustaining substances. This possibility is supported by the cessation of growth of the skeleton and teeth, although we know that other avitaminoses produce retardation of growth. PMID:19869087

Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

NASA Technical Reports Server (NTRS)

Deatly, Anne M.; Lin, Yen-Huei; McCarthy, Maureen; Chen, Wei; Miller, Lynn Z.; Quiroz, Jorge; Nowak, Becky M.; Lerch, Robert A.; Udem, Stephen A.; Goodwin, Thomas J.

2012-01-01

Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse, cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses recapitulated by mimicking the structural organization of the HRE. In vivo, airway epithelial cells play a significant and dynamic role in host defense by blocking paracellular permeability and modulating airway function through cellular interactions or tight junctions. As regulators of the innate immune response, epithelial cells constitutively express cytokines, chemokines, and colony stimulating factors including RANTES, IL-8, IL-6, GM-CSF, and G-CSF for proactive host defense. In response to viral infection, epithelial cells induce potent immuno-modulatory and pro-inflammatory cytokines that recruit phagocytic and inflammatory cells to clear the virus and enhance protection. Although disease pathogenesis is classically attributed to the cytopathic effects of the pathogen, severe disease states associated with RSV and PIV3 are attributed to the inflammatory response, especially in infants. RSV is a potent inducer of cytokines and pro-inflammatory mediators in epithelial cells in vivo. A differentiated human epithelial model independent of the complete functional immune system will help elucidate the role of epithelial cells in respiratory disease. We reported here, virus and host cell interactions in 3D HBE TLAs are similar to that in vivo. Because the epithelial cell organization of the TLAs impacts not only the expression of airway epithelial characteristics, but also cellular communication, the TLAs represent a more physiologically relevant model of the HRE than BEAS-2B or other non-tumour monolayer models of respiratory disease. As a result, wild type respiratory viruses have a clear growth advantage over attenuated viruses in TLAs unlike traditional monolayers. In addition, the TLAs respond to wild type virus infection by secreting pro-inflammatory mediators characteristic of infected HRE. TLAs expressing microbial defense mechanisms provide an excellent model to study the interactions of respiratory pathogens with their host and to identify the innate immunity mediators. Therefore, 3D HBE TLAs offer advantages for the study of respiratory viruses and the development of viral vaccine candidates.

Toxicology and carcinogenesis studies of diethylamine (CAS No. 109-89-7) in F344/N rats and B6C3F1 mice (inhalation studies).

PubMed

2011-10-01

Diethylamine is used mainly as a chemical intermediate to produce the corrosion inhibitor N,N-diethylethanolamine and a lesser amount is used to produce pesticides and insect repellants and in rubber processing. Diethylamine was nominated for study by the National Institute of Environmental Health Sciences based upon its high production volume and ubiquitous natural occurrence in trace amounts and because of the lack of chronic toxicity and carcinogenicity data on the chemical. Male and female F344/N rats and B6C3F1 mice were exposed to diethylamine (approximately 99.9% pure) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in bacterial mutagenicity tester strains and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to diethylamine vapor at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 16 days. All rats survived to the end of the study. The mean body weights of 250 and 500 ppm males and females and 125 ppm males were significantly less than those of the chamber controls. Clinical findings included lethargy, nasal/eye discharge, abnormal breathing, thinness, eye abnormalities, and discolored urine. The thymus weights of males exposed to 125 ppm or greater and females exposed to 500 ppm were significantly less than those of the chamber controls. Focal eye lesions were noted at necropsy in four males and three females exposed to 500 ppm and one male exposed to 250 ppm. Crusty noses were observed in most 500 ppm males and females and in two 250 ppm males. Suppurative inflammation, necrosis of the turbinates (except in one 125 ppm female), and squamous metaplasia of the respiratory epithelium of the nose were present in all rats exposed to 125 ppm or greater. Ulcer of the respiratory epithelium and atrophy of the olfactory epithelium occurred in all rats exposed to 250 or 500 ppm, and ulcer of the nasopharyngeal duct was present in all 500 ppm rats. Suppurative inflammation of the cornea was present in most rats exposed to 500 ppm. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were exposed to diethylamine vapor at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 17 days. Two males and three females exposed to 500 ppm died during the first week of the study. The mean body weights of males and females exposed to 125 ppm or greater were significantly less than those of the chamber controls. Males and females exposed to 250 or 500 ppm lost weight during the study. Lethargy, abnormal breathing, and thinness were observed in most mice exposed to 250 or 500 ppm. Eye irritation and discharge, nasal discharge, and low fecal and urine output were noted in 500 ppm mice. Thymus weights of 250 and 500 ppm males and 125 ppm or greater females were significantly less than those of the chamber controls. Suppurative inflammation of the nose occurred in all males exposed to 250 or 500 ppm and all females exposed to 125 ppm or greater, and most males exposed to 125 ppm. Turbinate necrosis occurred in all exposed mice except one 31 ppm female. Squamous metaplasia of the respiratory epithelium and olfactory epithelial atrophy were seen in mice exposed to 125 ppm or greater. In the lung, the incidence of minimal chronic active inflammation of mainstem bronchi was significantly increased in 500 ppm males. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to diethylamine vapor at concentrations of 0, 8, 16, 32, 62, or 125 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 14 weeks. All rats survived to the end of the study. Mean body weights of all exposed groups were similar to those of the chamber control groups. There were significant exposure concentration-related decreases in sperm motility in 32, 62, and 125 ppm males; there were no significant differences in the lengths of estrous cycles between chamber control and exposed groups of females. Exposure-related nasal lesions were seen primarily in rats exposed to 62 or 125 ppm. These lesions included turbinate necrosis, suppurative inflammation, respiratory epithelial hyperplasia, squamous metaplasia of the respiratory epithelium, and olfactory epithelial atrophy. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to diethylamine vapor at concentrations of 0, 8, 16, 32, 62, or 125 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 14 weeks. All mice survived to the end of the study. The mean body weights of 125 ppm males and females were significantly less than those of the chamber controls. There were significant exposure concentration-related decreases in sperm motility in males exposed to 32, 62, or 125 ppm; the estrous cycle of 125 ppm females was significantly longer than that of the chamber controls but only by half a day. Histopathologic changes were noted primarily in the nasal cavity and involved both the respiratory and olfactory epithelium of males and females principally in the 62 or 125 ppm groups. These lesions included suppurative inflammation, squamous metaplasia of the respiratory epithelium, olfactory epithelial atrophy, and necrosis of the turbinates. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to diethylamine vapor at concentrations of 0, 31, 62.5, or 125 ppm, 6 hours plus T90 (15 minutes) per day, 5 days per week for 105 weeks. Survival of exposed groups of rats was similar to that of the chamber control groups. Mean body weights of males and females exposed to 125 ppm were less than those of the chamber controls after week 57. Increased incidences of eye abnormality occurred in exposed males and females. A spectrum of nonneoplastic lesions was observed in the respiratory and olfactory epithelium of the nose in exposed rats. The lesions included suppurative inflammation, ulceration of the respiratory epithelium, hyaline droplet accumulation in the glands of the respiratory epithelium, necrosis of the turbinates, squamous metaplasia of the respiratory epithelium, hyperplasia of the respiratory epithelium, atrophy of the olfactory epithelium, hyaline droplet accumulation in the respiratory and olfactory epithelium, basal cell hyperplasia of the olfactory epithelium, respiratory metaplasia of the olfactory epithelium, and goblet cell hyperplasia. The incidence of chronic inflammation of the pleura was significantly increased in 125 ppm females. The incidences of histiocytic cellular infiltration of the alveolus of the lung were significantly increased in all exposed groups of females and the incidence of chronic inflammation was significantly increased in 125 ppm females. In 125 ppm males, the incidence of suppurative inflammation of the cornea was significantly increased. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to diethylamine vapor at concentrations of 0, 16, 31, or 62.5 ppm, 6 hours plus T90 (15 minutes) per day, 5 days per week for 105 weeks. Survival of exposed groups of mice was similar to that of the chamber control groups. Mean body weights of males and females were similar to those of the chamber controls. Eye abnormality was observed in greater incidence in exposed groups of males than in the chamber controls, and torso/ventral ulcer/abscess was observed in six 62.5 ppm males compared to none in the chamber controls. A similar spectrum of nonneoplastic lesions was seen in the nose of exposed mice as was seen in rats. Diethylamine was not mutagenic in either of two independent bacterial mutagenicity assays, each conducted with and without exogenous metabolic activation enzymes. Bacterial strains tested included Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2 uvrA/pKM101. In addition to the negative results in the two bacterial assays, no significant increases in the frequencies of micronucleated erythrocytes were seen in peripheral blood of male or female B6C3F1 mice from the 3-month study. Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of diethylamine in male or female F344/N rats exposed to 31, 62.5, or 125 ppm. There was no evidence of carcinogenic activity of diethylamine in male or female B6C3F1 mice exposed to 16, 31, or 62.5 ppm. Exposure to diethylamine resulted in increased incidences of nonneoplastic lesions of the nose in male and female rats and mice, of the cornea in male rats, and of the pleura and lung in female rats.