A new biomarker panel in bronchoalveolar lavage for an improved lung cancer diagnosis.

PubMed

Uribarri, María; Hormaeche, Itsaso; Zalacain, Rafael; Lopez-Vivanco, Guillermo; Martinez, Antonio; Nagore, Daniel; Ruiz-Argüello, M Begoña

2014-10-01

The enormous biological complexity and high mortality rate of lung cancer highlights the need for new global approaches for the discovery of reliable early diagnostic biomarkers. The study of bronchoalveolar lavage samples by proteomic techniques could identify new lung cancer biomarkers and may provide promising noninvasive diagnostic tools able to enhance the sensitivity of current methods. First, an observational prospective study was designed to assess protein expression differences in bronchoalveolar lavages from patients with (n = 139) and without (n = 49) lung cancer, using two-dimensional gel electrophoresis and subsequent protein identification by mass spectrometry. Second, validation of candidate biomarkers was performed by bead-based immunoassays with a different patient cohort (204 patients, 48 controls). Thirty-two differentially expressed proteins were identified in bronchoalveolar lavages, 10 of which were confirmed by immunoassays. The expression levels of APOA1, CO4A, CRP, GSTP1, and SAMP led to a lung cancer diagnostic panel that reached 95% sensitivity and 81% specificity, and the quantification of STMN1 and GSTP1 proteins allowed the two main lung cancer subtypes to be discriminated with 90% sensitivity and 57% specificity. Bronchoalveolar lavage represents a promising noninvasive source of lung cancer specific protein biomarkers with high diagnostic accuracy. Measurement of APOA1, CO4A, CRP, GSTP1, SAMP, and STMN1 in this fluid may be a useful tool for lung cancer diagnosis, although a further validation in a larger clinical set is required for early stages.

Test Characteristics of Acridine Orange, Gram, and May-Grünwald-Giemsa Stains for Enumeration of Intracellular Organisms in Bronchoalveolar Lavage Fluid

PubMed Central

De Brauwer, Els; Jacobs, Jan; Nieman, Fred; Bruggeman, Cathrien; Drent, Marjolein

1999-01-01

For enumeration of intracellular organisms (ICO) in bronchoalveolar lavage fluid samples, the May-Grünwald-Giemsa (MGG) stain displayed higher interobserver agreement than the acridine orange and Gram stains. The MGG stain offered a reliable enumeration of ICO when 200 cells were counted by one observer. PMID:9889233

Diagnostic value of (1 → 3)-β-D-glucan in bronchoalveolar lavage fluid for invasive fungal disease: A meta-analysis.

PubMed

Shi, Xin-Yu; Liu, Yao; Gu, Xian-Min; Hao, Sheng-Yu; Wang, Yu-Hong; Yan, Di; Jiang, Shu-Juang

2016-08-01

The serum (1 → 3)-β-D-glucan (BG) assay has been approved for diagnosing invasive fungal diseases (IFDs). However, the performance of (1 → 3)-β-D-glucan assay in bronchoalveolar lavage (BAL) fluid is various among studies. The present study aimed to assess the accuracy of (1 → 3)-β-D-glucan assay in bronchoalveolar lavage fluid for the diagnosis of invasive fungal diseases by means of meta-analysis and systematic review of relevant studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (OR) and a summary receiver-operating characteristic curve of BAL-BG for diagnosing invasive fungal diseases were pooled using meta-analysis. We also performed meta-regression analysis. A total of 838 patients (138 with proven or probable invasive fungal diseases), included in 6 studies, were analyzed. The pooled sensitivity, specificity, PLR, NLR and diagnostic odds ratio were 0.52 (95%CI, 0.38-0.53), 0.58 (95%CI, 0.55-0.61), 1.34 (95%CI, 1.08-1.66), 0.82 (95% CI, 0.63-1.07) and 1.71 (95%CI, 1.01-2.92) respectively. The area under the summary receiver operating characteristic curve, with 95% confidence intervals was 0.61 (95%CI, 0.67-0.55). The accuracy of (1 → 3)-β-D-glucan test in bronchoalveolar lavage fluid is marginal, so that the results should not be interpreted alone but can be used as a part of full assessment with clinical features, image findings and other laboratory results for the diagnosis of invasive fungal diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gallium-67 activity in bronchoalveolar lavage fluid in sarcoidosis

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

Trauth, H.A.; Heimes, K.; Schubotz, R.

1986-01-01

Roentgenograms and gallium-67 scans and gallium-67 counts of BAL fluid samples, together with differential cell counts, have proved to be useful in assessing activity and lung involvement in sarcoidosis. In active pulmonary sarcoidosis gallium-67 scans are usually positive. Quantitation of gallium-67 uptake in lung scans, however, may be difficult. Because gallium-67 uptake and cell counts in BAL fluid may be correlated, we set out to investigate gallium-67 activity in BAL fluid recovered from patient of different groups. Sixteen patients with recently diagnosed and untreated sarcoidosis, nine patients with healthy lungs, and five patients with CFA were studied. Gallium-67 uptake ofmore » the lung, gallium-67 activity in the lavage fluid, SACE and LACE levels, and alpha 1-AT activity were measured. Significantly more gallium-67 activity was found in BAL fluid from sarcoidosis patients than in that from CFA patients (alpha = .001) or patients with healthy lungs (alpha = .001). Gallium-67 activity in BAL fluid could be well correlated with the number of lymphocytes in BAL fluid, but poorly with the number of macrophages. Subjects with increased levels of SACE or serum alpha 1-AT showed higher lavage gallium-67 activity than did normals, but no correlation could be established. High gallium-67 activity in lavage fluid may be correlated with acute sarcoidosis or physiological deterioration; low activity denotes change for the better. The results show that gallium-67 counts in BAL fluid reflects the intensity of gallium-67 uptake and thus of activity of pulmonary sarcoidosis.« less

Asbestos bodies in bronchoalveolar lavage fluid. A study of 20 asbestos-exposed individuals and comparison to patients with other chronic interstitial lung diseases

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

Roggli, V.L.; Piantadosi, C.A.; Bell, D.Y.

1986-09-01

We studied the asbestos body (AB) content of bronchoalveolar lavage fluid from 20 patients with a history of occupational asbestos exposure, 31 patients with sarcoidosis and 5 patients with idiopathic pulmonary fibrosis. The cellular lavage pellet was digested in sodium hypochlorite and filtered onto Nuclepore filters for AB quantification by light microscopy. ABs were found in 15 of 20 asbestos-exposed individuals, 9 of 31 sarcoidosis cases and 2 of 5 patients with idiopathic pulmonary fibrosis. There was a statistically significant difference in the number of ABs per million cells recovered or per milliliter of recovered lavage fluid in the asbestos-exposedmore » group as compared to the other categories of chronic interstitial lung disease. The highest levels occurred in patients with asbestosis. Large numbers of asbestos bodies in the lavage fluid (greater than 1 AB/10(6) cells) were indicative of considerable occupational asbestos exposure, whereas occasional bodies were a nonspecific finding.« less

Polymerase chain reaction-based detection of Pneumocystis jirovecii in bronchoalveolar lavage fluid for the diagnosis of pneumocystis pneumonia.

PubMed

Oren, Ilana; Hardak, Emilia; Finkelstein, Renato; Yigla, Mordechai; Sprecher, Hannah

2011-09-01

The diagnosis of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected immunocompromised patients is notoriously difficult. The recent advent of polymerase chain reaction (PCR)-based detection systems, based on the identification of single fungal genes, has markedly improved diagnostic accuracy in this ominous disease. In an attempt to further improve diagnostic yield, the authors used a PCR-based detection system for Pneumocystis jirovecii, based on targeting 3 distinct genes. During the 4-year period (January 2005 to January 2009), all consecutive immunocompromised patients suspected of having PCP in the differential diagnosis underwent bronchoscopy with bronchoalveolar lavage sampling for the evaluation of the etiology of pulmonary infiltrates. Bronchoalveolar fluid was tested for the presence of a wide variety of possible etiological microorganisms. In a cohort of 214 immunocompromised patients (of which 198 were non-HIV immunocompromised patients) who underwent bronchoscopy with bronchoalveolar lavage for evaluation of pulmonary infiltrates, PCR correctly diagnosed PCP in 75% (42/56) compared with 14% (8/56) diagnosed by traditional stains, and increased diagnostic yield 5.4-fold. Given the absence of a sensitive gold standard, this study demonstrates the usefulness of a multigene PCR-based detection of Pneumocystis jirovecii DNA for supporting the clinical diagnosis of PCP, with high sensitivity and negative predictive value rates compared with direct stains, especially in non-HIV immunocompromised patients.

Non-fibrous inorganic particles in bronchoalveolar lavage fluid of pottery workers.

PubMed Central

Falchi, M; Paoletti, L; Mariotta, S; Giosue, S; Guidi, L; Biondo, L; Scavalli, P; Bisetti, A

1996-01-01

AIM: To study the actual exposure of pottery workers to silica particles, as their risk of silicosis is potentially high because of the presence of inhalable crystalline silica particles in the workplace. METHODS: Nine pottery workers underwent bronchoalveolar lavage. The recovered fluid was analysed for cytological and mineralogical content by analytical transmission electron microscopy. The data were compared with those obtained from a control group composed of seven patients with sarcoidosis and six patients with haemoptysis. RESULTS: Cytological results showed a similar profile in exposed workers and controls, whereas in patients with sarcoidosis a lymphocytic alveolitis was found. Microanalysis of the particulate identified the presence of silicates, CRSs, and metals. Pottery workers had higher numbers of total particles and CRSs, and had a higher silicate/metal ratio. In five workers, the presence of zirconium silicate was also detected. Patients with sarcoidosis had the lowest number of particles, and an inverted silicate/metal ratio. CONCLUSION: Microanalysis by transmission electron microscope can provide useful information to assess occupational exposure to dusts. PMID:9038801

Blood and bronchoalveolar lavage fluid acetylcholinesterase levels following microinstillation inhalation exposure to sarin in Guinea pigs.

PubMed

Che, Magnus M; Conti, Michele; Boylan, Megan; Sciuto, Alfred M; Gordon, Richard K; Nambiar, Madhusoodana P

2008-07-01

We determined acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition in the bronchoalveolar lavage fluid (BALF) following inhalation exposure to chemical threat nerve agent (CTNA) sarin. Age- and weight-matched male guinea pigs were exposed to five different doses of sarin (169.3, 338.7, 508, 677.4, and 846.5 mg/m(3)) using a microinstillation inhalation exposure technique for 4 min. The technique involves aerosolization of the agent in the trachea using a microcatheter with a center hole that delivers the agent and multiple peripheral holes that pumps air to aerosolize the agent at the tip. Animals exposed to higher doses of sarin occasionally developed seizures and succumbed to death within 15 min after exposure. The LCt(50) for sarin using the microinstillation technique was determined to be close to 677.4 mg/m(3). Ear blood AChE activity showed a dose-dependent inhibition at 15 min postexposure. The inhibition of blood AChE remained constant over 35 and 55 min after sarin exposure indicating that there was no lung depot effect. Cardiac blood AChE and butyrylcholinesterase (BChE) activity in surviving animals euthanized at 24 h postexposure showed a dose-dependent inhibition with an inhibition of 60% at 677.4 and 846.5 mg/m(3) sarin exposure. AChE and BChE activity in bronchoalveolar lavage fluid (BALF) showed a slight increase at 338.7 to 677.4 mg/m(3) sarin exposure but a marginal inhibition at 169.3 mg/m(3). In contrast, the AChE protein levels determined by immunoblotting showed an increase at 169.3 mg/m(3) in the BALF. The BALF protein level, a biomarker of lung injury, was increased maximally at 338.7 mg/m(3) and that increase was dropped with an increase in the dose of sarin. The BALF protein levels correlated with the AChE and BChE activity. These data suggest that sarin microinstillation inhalation exposure results in respiratory toxicity and lung injury characterized by changes in lavage AChE, BChE, and protein levels.

Presumed lupus erythematosus cells identified in bronchoalveolar lavage fluid from a Mexican Hairless dog.

PubMed

Black, Laura J; Hechler, Ashley C; Duffy, Maura E; Beatty, Sarah S K

2017-06-01

A neutered male Mexican Hairless dog was presented for generalized weight loss and weakness. Initial laboratory testing and diagnostic imaging revealed thrombocytopenia and an interstitial to miliary lung pattern affecting all lung fields. Mild joint effusion was found on physical examination affecting the stifle, tarsal, carpal, and elbow joints. Examination of synovial fluid demonstrated an inflammatory polyarthropathy in 3 joints. Cytocentrifuged and direct preparations of the bronchoalveolar lavage (BAL) fluid sample were made and cells consistent with lupus erythematosus (LE) cells and ragocytes were found. Based on these findings, the anti-nuclear antibody (ANA) titer was determined as 1:640. A clinical diagnosis of systemic LE was made based on the satisfaction of 2 major criteria (thrombocytopenia and inflammatory polyarthritis), 4 minor criteria (central nervous system signs, lymphadenopathy, fever of unknown origin, and pleuritis), positive ANA titer, and the identification of presumed LE cells in BAL fluid. This case report highlights a novel finding of LE cells in respiratory secretions and provides a review of diagnostic criteria of systemic LE. © 2017 American Society for Veterinary Clinical Pathology.

Mild hypothermia attenuates changes in respiratory system mechanics and modifies cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation.

PubMed

Dostál, P; Senkeřík, M; Pařízková, R; Bareš, D; Zivný, P; Zivná, H; Cerný, V

2010-01-01

Hypothermia was shown to attenuate ventilator-induced lung injury due to large tidal volumes. It is unclear if the protective effect of hypothermia is maintained under less injurious mechanical ventilation in animals without previous lung injury. Tracheostomized rats were randomly allocated to non-ventilated group (group C) or ventilated groups of normothermia (group N) and mild hypothermia (group H). After two hours of mechanical ventilation with inspiratory fraction of oxygen 1.0, respiratory rate 60 min(-1), tidal volume 10 ml x kg(-1), positive end-expiratory pressure (PEEP) 2 cm H2O or immediately after tracheostomy in non-ventilated animals inspiratory pressures were recorded, rats were sacrificed, pressure-volume (PV) curve of respiratory system constructed, bronchoalveolar lavage (BAL) fluid and aortic blood samples obtained. Group N animals exhibited a higher rise in peak inspiratory pressures in comparison to group H animals. Shift of the PV curve to right, higher total protein and interleukin-6 levels in BAL fluid were observed in normothermia animals in comparison with hypothermia animals and non-ventilated controls. Tumor necrosis factor-alpha was lower in the hypothermia group in comparison with normothermia and non-ventilated groups. Mild hypothermia attenuated changes in respiratory system mechanics and modified cytokine concentration in bronchoalveolar lavage fluid during low lung volume ventilation in animals without previous lung injury.

Diagnostic value of bronchoalveolar lavage fluid and serum tumor markers for lung cancer.

PubMed

Wang, Hongmin; Zhang, Xiaohong; Liu, Xinkui; Liu, Kangdong; Li, Yuexia; Xu, Haijiang

2016-01-01

To analyze the changes of bronchoalveolar lavage fluid (BALF) and serum tumor markers in lung cancer. Fifty patients with lung cancer (study group) and 50 cases with benign lung lesions (control group) were selected from May, 2010 to May, 2013. The observation group included squamous cell carcinoma subgroup (n = 25), adenocarcinoma subgroup (n = 19), and small cell undifferentiated carcinoma subgroup (n = 6). The carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CYFRA21-1) concentration were compared; and the comparisons among subgroups were also performed. Three kinds of tumor markers in BALF and serum of the observation group were higher than that of the control group. NSE concentration of small.cell lung cancer was the highest, CYFRA21.1 concentration was highest in the squamous cell carcinoma, and CEA concentration was highest in the adenocarcinoma group; the former increased more significantly. BALF and serum NSE, CEA, and CYFRA21.1 elevated in lung cancer, which had prompt value for pathology, especially significant for BALF.

OPTIMIZATION OF REPEATED BRONCHOALVEOLAR LAVAGE IN RABBITS

EPA Science Inventory

Background. Bronchoalveolar lavage (BAL) is a relatively non-invasive technique used to obtain diagnostic samples from the lower airways of companion animals with respira¬tory disease. BAL is also commonly used in laboratory animals to assess pulmo¬nary changes after expos...

Glycoproteomic analysis of bronchoalveolar lavage (BAL) fluid identifies tumor-associated glycoproteins from lung adenocarcinoma.

PubMed

Li, Qing Kay; Shah, Punit; Li, Yan; Aiyetan, Paul O; Chen, Jing; Yung, Rex; Molena, Daniela; Gabrielson, Edward; Askin, Frederic; Chan, Daniel W; Zhang, Hui

2013-08-02

Cytological examination of cells from bronchoalveolar lavage (BAL) is commonly used for the diagnosis of lung cancer. Proteins released from lung cancer cells into BAL may serve as biomarkers for cancer detection. In this study, N-glycoproteins in eight cases of BAL fluid, as well as eight lung adenocarcinoma tissues and eight tumor-matched normal lung tissues, were analyzed using the solid-phase extraction of N-glycoprotein (SPEG), iTRAQ labeling, and liquid chromatography tandem mass spectrometry (LC-MS/MS). Of 80 glycoproteins found in BAL specimens, 32 were identified in both cancer BAL and cancer tissues, with levels of 25 glycoproteins showing at least a 2-fold difference between cancer and benign BAL. Among them, eight glycoproteins showed greater than 2-fold elevations in cancer BAL, including Neutrophil elastase (NE), Integrin alpha-M, Cullin-4B, Napsin A, lysosome-associated membrane protein 2 (LAMP2), Cathepsin D, BPI fold-containing family B member 2, and Neutrophil gelatinase-associated lipocalin. The levels of Napsin A in cancer BAL were further verified in independently collected 39 BAL specimens using an ELISA assay. Our study demonstrates that potential protein biomarkers in BAL fluid can be detected and quantified.

Predictive Role of ADA in Bronchoalveolar Lavage Fluid in Making the Diagnosis of Pulmonary Tuberculosis.

PubMed

Binesh, Fariba; Halvani, Abolhassan

2013-01-01

Current diagnostic tests for tuberculosis (TB) are time-consuming. The aim of this study was to evaluate the diagnostic usefulness of ADA in bronchoalveolar lavage fluid in patients with pulmonary TB. A cross-sectional study was performed in Yazd, Iran, between 2009 and 2010. Patients suspected of pulmonary TB with negative sputum smear for AFB were included in the study. Mean ADA levels in BAL fluids were measured and compared between study groups. Sixty-three patients were enrolled in the study among which 15 cases had pulmonary TB, 33 had pulmonary diseases other than TB, and 15 subjects with normal bronchoscopy results were considered as controls. Mean ADA levels in BAL fluid were 4.13 ± 2.55, 2.42 ± 1.06, and 1.93 ± 0.88, respectively. This rate was significantly higher in the pulmonary TB group compared to the other two groups (P = 0.001). Using ROC curve with a cut-off value of 3.5 IU/L, the highest sensitivity (57%) and specificity (84%) were obtained in diagnosis of TB. The results showed that although ADA activity in BAL fluid of pulmonary TB patients was higher than those seen in other diseases, a negative test does not rule out pulmonary TB.

Bronchoalveolar lavage for diagnosis of tuberculosis infection in elephants.

PubMed

Hermes, R; Saragusty, J; Moser, I; Holtze, S; Nieter, J; Sachse, K; Voracek, T; Bernhard, A; Bouts, T; Göritz, F; Hildebrandt, T B

2018-03-01

Tuberculosis (TB) has been known to affect elephants for thousands of years. It was put into spotlight when few circus elephants were diagnosed carrying Mycobacterium (M.) tuberculosis. Because of the zoonotic risk and high susceptibility to M. tuberculosis, periodic testing was enacted since, in captive breeding programmes. Presently, trunk wash is the recommended diagnostic procedure for TB. Trunk wash, however, puts the operator at risk, has low sensitivity, and is prone to contamination. Here, bronchoalveolar lavage is described for the first time for TB diagnosis in elephants. Bronchial, trunk and mouth fluids were investigated using bacterial culture, M. tuberculosis complex (MTC)-specific real-time quantitative PCR (qPCR) and mycobacterial genus-specific qPCR for overall presence of mycobacteria or mycobacterial DNA including bacteria or DNA of closely related genera, respectively, in 14 elephants. Neither bacteria of the MTC nor their DNA were identified in any of the elephants. Yet, 25% of the cultures grew non-tuberculous mycobacteria (NTM) or closely related bacterial species. Furthermore, 85% of the samples contained DNA of NTM or closely related bacterial genera. This finding might explain continued false-positive results from various serological tests. From a zoonotic point of view, bronchoalveolar lavage is safer for the testing personal, has higher probability of capturing MTC and, through PCR, identifies DNA NTM in elephants. Yet, necessary endoscopic equipment, animal sedation and access to a TB reference laboratory might pose challenging requirements in remote conditions in some elephant range countries.

Translational research in pediatrics III: bronchoalveolar lavage.

PubMed

Radhakrishnan, Dhenuka; Yamashita, Cory; Gillio-Meina, Carolina; Fraser, Douglas D

2014-07-01

The role of flexible bronchoscopy and bronchoalveolar lavage (BAL) for the care of children with airway and pulmonary diseases is well established, with collected BAL fluid most often used clinically for microbiologic pathogen identification and cellular analyses. More recently, powerful analytic research methods have been used to investigate BAL samples to better understand the pathophysiological basis of pediatric respiratory disease. Investigations have focused on the cellular components contained in BAL fluid, such as macrophages, lymphocytes, neutrophils, eosinophils, and mast cells, as well as the noncellular components such as serum molecules, inflammatory proteins, and surfactant. Molecular techniques are frequently used to investigate BAL fluid for the presence of infectious pathologies and for cellular gene expression. Recent advances in proteomics allow identification of multiple protein expression patterns linked to specific respiratory diseases, whereas newer analytic techniques allow for investigations on surfactant quantification and function. These translational research studies on BAL fluid have aided our understanding of pulmonary inflammation and the injury/repair responses in children. We review the ethics and practices for the execution of BAL in children for translational research purposes, with an emphasis on the optimal handling and processing of BAL samples. Copyright © 2014 by the American Academy of Pediatrics.

Mass spectrometry-based analysis of murine bronchoalveolar lavage fluid following respiratory exposure to 4,4'-methylene diphenyl diisocyanate aerosol.

PubMed

Hettick, Justin M; Law, Brandon F; Lin, Chen-Chung; Wisnewski, Adam V; Siegel, Paul D

2018-06-01

1. Diisocyanates are highly reactive electrophiles utilized in the manufacture of a wide range of polyurethane products and have been identified as causative agents of occupational allergic respiratory disease. However, in spite of the significant occupational health burden associated with diisocyanate-induced asthma, the mechanism of disease pathogenesis remains largely unknown. 2. To better understand the fate of inhaled diisocyanates, a nose-only aerosol exposure system was constructed and utilized to expose a BALB/c mouse model to an aerosol generated from 4,4'-methylene diphenyl diisocyanate (MDI). Tissue and bronchoalveolar lavage samples were evaluated 4 and 24 h post-exposure for evidence of diisocyanate-protein haptenation, and a label-free quantitative proteomics strategy was employed to evaluate relative changes to the protein content of the cellular fraction of the lavage fluid. 3. Following MDI aerosol exposure, expression of the number of proteins with immunological or xenobiotic metabolism relevance is increased, including endoplasmin, cytochrome P450 and argininosuccinate synthase. Western blot analysis indicated MDI-conjugated protein in the lavage fluid, which was identified as serum albumin. 4. Tandem mass spectrometry analysis of MDI-albumin revealed MDI conjugation occurs at a dilysine motif at Lys525, as well as at a glutamine-lysine motif at Lys414, in good agreement with previously published in vitro data on diisocyanate-conjugated serum albumin.

[A case of legionellesis pneumonia verified by isolation of Legionella pneumophila serogroup 1 from bronchoalveolar lavage fluid treated with levofloxacine and tigecycline].

PubMed

Galstian, G M; Drokov, M Iu; Katrysh, S A; Kliasova, G A; Giliazitdinova, E A; Karpova, T I; Marakusha, B I; Tartakovskiĭ, I S

2011-01-01

A male patient received non-chemotherapeutic drugs which induced deep neutropenia complicated with sepsis, bilateral pneumonia, acute respiratory insufficiency. Artificial pulmonary ventilation was applied. The examination of bronchoalveolar lavage showed the presence of the culture L. pneumophila (serogroup 1) in a concentration 2 x 10(3) CFU/ml. Antibacterial therapy with levofloxacin in a dose 1000 mg/day was conducted. In a week not only L.pneumophila but also Acinetobacter baumanii was isolated from bronchoalveolar lavage. Tigecyclin was added to levofloxacin treatment. Two air cavities were found in the left lung. The treatment reduced the size of these cavities, infiltrative changes in the lungs and respiratory insufficiency regressed. The patient was discharged from hospital This case is the first case in Russia of L.pneumophila isolation from bronchoalveolar lavage. The case is also characterized by use of tigecycline for treatment of combined legionella and akinetobacterial infection and cavities in the lungs in legionella pneumonia.

Utility of galactomannan antigen detection in bronchoalveolar lavage fluid in immunocompromised patients.

PubMed

Brownback, Kyle R; Pitts, Lucas R; Simpson, Steven Q

2013-09-01

Diagnosis of invasive pulmonary aspergillosis (IPA) is a challenging process in immunocompromised patients. Galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) fluid is a method to detect IPA with improved sensitivity over conventional studies. We sought to determine the diagnostic yield of BAL GM assay in a diverse population of immunocompromised patients. A retrospective review of 150 fiberoptic bronchoscopy (FOB) with BAL for newly diagnosed pulmonary infiltrate in immunocompromised patients was performed. Patient information, procedural details and laboratory studies were collected. BAL and serum samples were evaluated for GM using enzyme-linked immunoassay. Of 150 separate FOB with BAL, BAL GM was obtained in 143 samples. There were 31 positive BAL GM assays. In those 31 positive tests, 13 were confirmed as IPA, giving a positive predictive value of 41.9%. There was one false negative BAL GM. Of the 18 false positive BAL GM, 4 were receiving piperacillin-tazobactam and 11 were receiving an alternative beta-lactam antibiotic. BAL GM assay shows excellent sensitivity for diagnosing IPA. There was a significant number of false positive BAL GM assays and several of those patients were receiving beta-lactam antibiotics at the time of bronchoscopy. © 2013 Blackwell Verlag GmbH.

Evaluation of VEGF-C and tumor markers in bronchoalveolar lavage fluid for lung cancer diagnosis.

PubMed

Cao, Chao; Chen, Zhong-Bo; Sun, Shi-Fang; Yu, Yi-Ming; Ding, Qun-Li; Deng, Zai-Chun

2013-12-11

A total of 87 patients were enrolled and bronchoalveolar lavage fluid (BALF) samples were obtained from all subjects. A significant difference was found in BALF VEGF-C level between patients with squamous cell carcinoma and benign diseases (P = 0.043). In addition, the concentration of NSE in BALF form the malignant group was significantly higher compared with that of the benign groups (P = 0.018). However, no statistical difference was observed in BALF CEA (P = 0.375) or CYFRA21-1 (P = 0.838) between lung cancer patients and nonmalignant controls. With a cut-off value of 2.06 ng/ml, NSE had a sensitivity of 72.9%, a specificity of 69.2%, respectively, in predicting the malignant nature of pulmonary mass. Our study observed that the level of VEGF-C was increased in BALF of patients with squamous cell carcinoma. Moreover, we found that NSE was significantly higher in BALF of lung cancer patients than in benign diseases.

Determination of albumin in bronchoalveolar lavage fluid by flow-injection fluorometry using chromazurol S.

PubMed

Sato, Takaji; Saito, Yoshihiro; Chikuma, Masahiko; Saito, Yutaka; Nagai, Sonoko

2008-03-01

A highly sensitive flow injection fluorometry for the determination of albumin was developed and applied to the determination of albumin in human bronchoalveolar lavage fluids (BALF). This method is based on binding of chromazurol S (CAS) to albumin. The calibration curve was linear in the range of 5-200 microg/ml of albumin. A highly linear correlation (r=0.986) was observed between the albumin level in BALF samples (n=25) determined by the proposed method and by a conventional fluorometric method using CAS (CAS manual method). The IgG interference was lower in the CAS flow injection method than in the CAS manual method. The albumin level in BALF collected from healthy volunteers (n=10) was 58.5+/-13.1 microg/ml. The albumin levels in BALF samples obtained from patients with sarcoidosis and idiopathic pulmonary fibrosis were increased. This finding shows that the determination of albumin levels in BALF samples is useful for investigating lung diseases and that CAS flow injection method is promising in the determination of trace albumin in BALF samples, because it is sensitive and precise.

Discovery of potential protein biomarkers of lung adenocarcinoma in bronchoalveolar lavage fluid by SWATH MS data-independent acquisition and targeted data extraction.

PubMed

Ortea, I; Rodríguez-Ariza, A; Chicano-Gálvez, E; Arenas Vacas, M S; Jurado Gámez, B

2016-04-14

Lung cancer currently ranks as the neoplasia with the highest global mortality rate. Although some improvements have been introduced in recent years, new advances in diagnosis are required in order to increase survival rates. New mildly invasive endoscopy-based diagnostic techniques include the collection of bronchoalveolar lavage fluid (BALF), which is discarded after using a portion of the fluid for standard pathological procedures. BALF proteomic analysis can contribute to clinical practice with more sensitive biomarkers, and can complement cytohistological studies by aiding in the diagnosis, prognosis, and subtyping of lung cancer, as well as the monitoring of treatment response. The range of quantitative proteomics methodologies used for biomarker discovery is currently being broadened with the introduction of data-independent acquisition (DIA) analysis-related approaches that address the massive quantitation of the components of a proteome. Here we report for the first time a DIA-based quantitative proteomics study using BALF as the source for the discovery of potential lung cancer biomarkers. The results have been encouraging in terms of the number of identified and quantified proteins. A panel of candidate protein biomarkers for adenocarcinoma in BALF is reported; this points to the activation of the complement network as being strongly over-represented and suggests this pathway as a potential target for lung cancer research. In addition, the results reported for haptoglobin, complement C4-A, and glutathione S-transferase pi are consistent with previous studies, which indicates that these proteins deserve further consideration as potential lung cancer biomarkers in BALF. Our study demonstrates that the analysis of BALF proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS), combining a simple sample pre-treatment and SWATH DIA MS, is a useful method for the discovery of potential lung cancer biomarkers. Bronchoalveolar lavage fluid (BALF

Bacteria from bronchoalveolar lavage fluid from children with suspected chronic lower respiratory tract infection: results from a multi-center, cross-sectional study in Spain.

PubMed

Escribano Montaner, Amparo; García de Lomas, Juan; Villa Asensi, José Ramón; Asensio de la Cruz, Oscar; de la Serna Blázquez, Olga; Santiago Burruchaga, Mikel; Mondéjar López, Pedro; Torrent Vernetta, Alba; Feng, Yang; Van Dyke, Melissa K; Reyes, Janet; Garcia-Corbeira, Pilar; Talarico, Carla A

2018-02-01

This cross-sectional study assessed the prevalence of bacteria isolated from Spanish children with suspected chronic lower respiratory tract infection (LRTI) for whom bronchoalveolar lavage (BAL) was indicated. BAL fluid (BALF) was collected from 191 children (aged ≥ 6 months to < 6 years, with persistent or recurrent respiratory symptoms, non-responders to usual treatment) and cultured. Nasopharyngeal swabs (NPSs) were also obtained and cultured to assess concordance of BALF and NPS findings in the same patient. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis were identified from BALF with a bacterial load indicative of infection (> 10 4  colony-forming units/mL) in 10.5, 8.9, and 6.3% of children, respectively. Clinical characteristics were similar among participants, regardless of positivity status for any of the bacteria. Approximately 26% of pneumococcal isolates were PCV13 serotypes, and 96% of H. influenzae isolates were non-typeable (NTHi). Concordance between BALF and NPS isolates was 51.0% for S. pneumoniae, 52.1% for H. influenzae, and 22.0% for M. catarrhalis. S. pneumoniae, NTHi, and M. catarrhalis were the main bacteria detected in BALF and NPS. Children with suspected chronic LRTI may benefit from a vaccine protecting against NTHi. What is Known: • Chronic lower respiratory tract infection (LRTI) in children can cause high morbidity and is a major use of healthcare resources worldwide. Despite this, their etiology or potential preventive measures are poorly assessed. • Bronchoalveolar lavage can be used to determine bacterial etiology of chronic LRTI. What is New: • We used conventional and molecular techniques to show that Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis were present in the LRT of Spanish children with suspected chronic LRTI • Concordance between isolates from bronchoalveolar lavage fluid and nasopharyngeal swabs was low, suggesting that samples from the

Myeloperoxidase concentration in bronchoalveolar lavage fluid from healthy horses and those with recurrent airway obstruction

PubMed Central

Art, Tatiana; Franck, Thierry; Lekeux, Pierre; de Moffarts, Brieuc; Couëtil, Laurent; Becker, Martine; Kohnen, Serge; Deby-Dupont, Ginette; Serteyn, Didier

2006-01-01

The aim of this work was to measure the myeloperoxidase (MPO) concentration in bronchoalveolar lavage (BAL) fluid collected from horses with recurrent airway obstruction (RAO), both in crisis and in remission, as well as from healthy horses. Seven horses with RAO were exposed to moldy hay until the maximum change in pleural pressure was greater than 1.5 kPa. At that point, BAL was performed, and the total cell counts and percentages in the fluid were immediately determined. To measure the MPO concentration in BAL-fluid supernatant, we used a specific enzyme-linked immunosorbent assay with polyclonal antibodies against equine MPO. The tests were repeated on the horses with RAO after they had spent 2 mo on pasture. Six healthy horses serving as controls underwent the same tests. The absolute and relative neutrophil counts and the MPO concentration in the BAL fluid were significantly greater in the horses with an RAO crisis than in the control horses. After 2 mo on pasture, the horses that had been in RAO crisis were clinically normal, and their neutrophil counts and MPO levels in BAL fluid had significantly decreased; during remission their neutrophil counts were not significantly different from those in the healthy horses, but their MPO concentration remained significantly higher. This study showed that determining the MPO concentration in a horse’s BAL fluid is technically possible and that during remission from RAO the concentration remains higher than normal. Thus, MPO may be a marker of neutrophil presence and activation in the lower airways. PMID:17042382

Non-small cell lung cancer detection using microRNA expression profiling of bronchoalveolar lavage fluid and sputum.

PubMed

Kim, Julian O; Gazala, Sayf; Razzak, Rene; Guo, Linghong; Ghosh, Sunita; Roa, Wilson H; Bédard, Eric L R

2015-04-01

To assess if miRNA expression profiling of bronchoalveolar lavage (BAL) fluid and sputum could be used to detect early-stage non-small cell lung cancer (NSCLC). Hierarchical cluster analysis was performed on the expression levels of 5 miRNAs (miR-21, miR-143, miR-155, miR-210, and miR-372) which were quantified using RNA reverse transcription and quantitative real-time polymerase chain reaction in sputum and BAL samples from NSCLC cases and cancer-free controls. Cluster analysis of the miRNA expression levels in BAL samples from 21 NSCLC cases and sputum samples from 10 cancer-free controls yielded a diagnostic sensitivity of 85.7% and specificity of 100%. Cluster analysis of sputum samples from the same patients yielded a diagnostic sensitivity of 67.8% and specificity of 90%. miRNA expression profiling of sputum and BAL fluids represent a potential means to detect early-stage NSCLC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Comparative assessment of the diagnostic value of transbronchial lung biopsy and bronchoalveolar lavage fluid cytology in lung cancer.

PubMed

Binesh, Fariba; Pirdehghan, Azar; Mirjalili, Mohammad Reza; Samet, Mohammad; Majomerd, Zahra Amini; Akhavan, Ali

2015-01-01

This study was designed to determine the accuracy of bronchoalveolar lavage fluid cytology (BAL) using histopathologic examination of transbronchial biopsy specimens as the gold standard in diagnosis of lung carcinoma at our center. A retrospective study was conducted to investigate a total of 388 patients who were suspected of having lung cancer and had undergone fiberoptic bronchoscopy in Shahid Sadoughi hospital from 2006 to 2011. Lung masses were proven to be malignant by histology. Transbronchial lung biopsy (TBLB) identified malignancy in 183 of the 388 cases, including 48 cases (26.2%) with adenocarcinoma, 4(2.1%) with bronchioloalveolar carcinoma, 47(25.6%)with squamous cell carcinoma, 34(18.5%) with well-diffentiated neuroendocrine carcinoma, 35(19.1%) with small cell carcinoma, 14 (7.6%) with non-small cell carcinoma, and 1 (0.54%) with large cell carcinoma. A total of 205 cases were correctly classified as negative. BAL was also performed in 388 patients; 86/103 cases were consistent with the final diagnosis of lung cancer and 188/285 cases were correctly classified as negative. The sensitivity of BAL was 46.9%(CI:41.9%, 51.8%)) and its specificity was 91.6%(CI:88.8%, 94.3%). BAL had a positive predictive value (PPV) of 83.4%(CI:79.7%, 87.1%) and a negative predictive value (NPV) of 65.8%(CI:61%, 70.5%). The overall accuracy of BAL was 70.5% and the exact concordance was 39%. Our findings suggest that BAL cytology is not sensitive but is a specific test for diagnosis of lung carcinoma. If transbronchial lung biopsy is combined with bronchoalveolar lavage, the positive diagnostic rate will be further elevated.

De Novo Assembly of the Pneumocystis jirovecii Genome from a Single Bronchoalveolar Lavage Fluid Specimen from a Patient

PubMed Central

Cissé, Ousmane H.; Pagni, Marco; Hauser, Philippe M.

2012-01-01

ABSTRACT Pneumocystis jirovecii is a fungus that causes severe pneumonia in immunocompromised patients. However, its study is hindered by the lack of an in vitro culture method. We report here the genome of P. jirovecii that was obtained from a single bronchoalveolar lavage fluid specimen from a patient. The major challenge was the in silico sorting of the reads from a mixture representing the different organisms of the lung microbiome. This genome lacks virulence factors and most amino acid biosynthesis enzymes and presents reduced GC content and size. Together with epidemiological observations, these features suggest that P. jirovecii is an obligate parasite specialized in the colonization of human lungs, which causes disease only in immune-deficient individuals. This genome sequence will boost research on this deadly pathogen. PMID:23269827

Decreased phosphatidyl choline content in bronchoalveolar lavage fluids of children with bronchopulmonary dysplasia: a preliminary investigation.

PubMed

Clement, A; Masliah, J; Housset, B; Just, J; Garcia, J; Grimfeld, A; Tournier, G

1987-01-01

Bronchoalveolar lavage (BAL) was performed on 12 infants who had recovered from neonatal acute respiratory failure and on 12 patients with bronchopulmonary dysplasia (BPD) in order to evaluate the concentration of phosphatidyl choline (PC) in BAL fluid. These two groups were similar at birth (mean birth weight: 1,980 and 1,750 g, respectively; mean gestational age: 33.4 and 32.1 weeks respectively). Mechanical ventilation based on oxygen requirement lasted longer in the group with BPD. BAL was performed at the end of the first year of life (at 8.5 and 10.3 months, respectively) and the results were compared to control values (from infants of the same age without neonatal disease). Whereas the protein concentration in BAL fluid was similar in the two groups, a dramatic decrease of the BAL PC was found in BPD: The mean values of BAL-PC over protein ratio were 0.9 in the group without pulmonary sequelae and 0.3 in the group with BPD. These preliminary results suggest an impairment of the pulmonary surfactant metabolism in this chronic lung disease following neonatal acute respiratory failure.

Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

PubMed

Norris, C R; Byerly, J R; Decile, K C; Berghaus, R D; Walby, W F; Schelegle, E S; Hyde, D M; Gershwin, L J

2003-12-15

Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

PubMed

Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

2016-06-21

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

[Simple evaluation of numbers of asbestos bodies in bronchoalveolar lavage fluid under light microscopy: analysis of 35 pulmonary nodular lesions].

PubMed

Kawahara, Kunimitsu; Kawasumi, Hiromi; Nagano, Teruaki; Sasada, Shinji; Okamoto, Norio

2008-04-01

More than 1 asbestos body (AB) per ml of bronchoalveolar lavage fluid (BALF) under light microscopy was defined as AB positive (ABP) and suggests an occupational asbestos exposure. We microscopically evaluated the AB number per one ml of BALF, which we defined as the AB concentration (ABC), using bronchoalveolar lavage (BAL) cytocentrifuge slides obtained from 35 patients having pulmonary nodular lesions (20 carcinoma and 15 nonneoplastic disease) and examined the correlation between ABC and clinicopathological data including findings on Helical computed tomography scan (HCTS) and occupational history of asbestos exposure (OHAE). BAL was performed by the standard technique without removing mucous with a gauze filter. AB was microscopically defined as a structure consisting of a core of transparent asbestos surrounded by an iron-protein coat. Twenty of 35 patients were ABP (ABP rate; 57%) and ABC ranged from 0 to 207.98/ml (mean ABC; 11.33/ml). Mean ABC was significantly higher in patients with OHAE (15.04/ml) compared to that in patients without OHAE (3.23/ml). Twenty-two of 35 patients (63%) lacked abnormality on HCTS and among these, 12 patients (55%) were ABP. In 20 pulmonary carcinoma patients, the ABP rate was 85% and ABC ranged from 0 to 31.1/ml (Mean ABC; 2.99/ml). The ABP rate of pulmonary carcinoma patients was 40% (8 patients) and among these, 5 patients (63%) did not show any abnormality on HCTS. In conclusion, our method was simple and useful and should be applied to patients with pulmonary nodular lesions and OHAE, even if there are no abnormalities on HCTS.

Diagnosis of a case of lipoid pneumonia by bronchoalveolar lavage.

PubMed

Spatafora, M; Bellia, V; Ferrara, G; Genova, G

1987-01-01

Exogenous lipoid pneumonia (ELP) was diagnosed by bronchoalveolar lavage (BAL) in a 57-year-old woman with a long history of using oily nose drops. Since clinical and roentgenological presentations are nonspecific, BAL, along with specific staining of recovered alveolar macrophages, represents a safe alternative to more invasive diagnostic procedures whenever a diagnosis of ELP is suspected.

Evaluation of plasma, erythrocytes, and bronchoalveolar lavage fluid antioxidant defense system in sulfur mustard-injured patients.

PubMed

Jafari, Mahvash; Ghanei, Mostafa

2010-03-01

Sulfur mustard (SM) is a strong alkylating agent that causes acute and chronic effects on different organs following exposure. Main late respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, asthma, and bronchiolitis obliterans. It seems that oxidative stress plays a major role in pathogenesis of diseases. This study was undertaken to evaluate the long-term effect of SM on plasma, erythrocytes, and brochoalveolar lavage fluid antioxidant defense system in SM-injured patients. Brochoalveolar lavage fluid, plasma, and erythrocyte samples were taken from 54 patients in the case group exposed to SM and 25 controls with chronic respiratory disease without a history of exposure to SM. Superoxide dismutase, catalase, and glutathione peroxidase activities in lavage fluid, plasma, and erythrocytes were significantly higher in case group. The increased glutathione S-transferase activity in lavage fluid was associated with a depletion of glutathione and an increase of malondialdehyde levels. There was no significant change observed in glutathione reductase activity. The data suggest that oxidative damage might have an important role for patients exposed to SM. SM may induce an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in lung cells.

Analysis of Trace Elements in Rat Bronchoalveolar Lavage Fluid by Inductively Coupled Plasma Mass Spectrometry.

PubMed

Qamar, Wajhul; Al-Ghadeer, Abdul Rahman; Ali, Raisuddin; Abuelizz, Hatem A

2017-08-01

The main objective was to determine the elemental profile of the lung lining fluid of rats which are used as model animals in various experiments. Lung lining fluid elemental constitution obtained after bronchoalveolar lavage fluid (BALF) was analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine the biological trace elements along with calcium and magnesium. BALF was collected from healthy rats using a tracheal cannula. However, cells in BALF were counted to monitor any underlying inflammatory lung condition. Cell free BALF samples were processed and analyzed for the elements including magnesium (Mg), calcium (Ca), chromium (Cr), manganese (Mn), iron (Fe), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), bromine (Br), and iodine (I). In view of this, calcium concentration was the highest (6318.08 ± 3094.3 μg/L) and copper concentration was the lowest (0.89 ± 0.21 μg/L). The detected elements, from high to low concentration, include Ca > Mg > Fe > Br > I > Cr > Ni > Zn > Mn > Se > Cu. Pearson's correlation analysis revealed no significant correlation between cell count and concentration of any of the element detected in BALF. Correlation analysis also revealed significant positive correlation among Fe, I, Cr, Ni, and Mn. Ca was found to be correlated negatively with Cu and positively with Se. Br and Mg found to be positively correlated with each other. Zn remained the only element that was not found to be correlated with any of the elements in the rat BALF.

Bronchoalveolar lavage for the treatment of neonatal pulmonary atelectasis under lung ultrasound monitoring.

PubMed

Liu, Jing; Ren, Xiao-Ling; Fu, Wei; Liu, Ying; Xia, Rong-Ming

2017-10-01

Pulmonary atelectasis (PA) is a common clinical complication among newborns, and it is one of the most common causes of neonatal dyspnea, a condition with no specific effective treatment. This study examined the effectiveness and security of bronchoalveolar lavage (BL) regarding the treatment of neonatal PA under ultrasound monitoring. A total of 57 patients diagnosed with PA via lung ultrasound (LUS) were included in this study. All patients received BL via a tracheal intubation injection of lavage fluid. The LUS was conducted immediately after each lavage to understand the conditions of lung re-expansion. Irrigation was repeated two to three times as one course of treatment. BL was provided as one to two courses of treatment daily for several days according to atelectasis and lung recruitment status. Of the 57 patients, BL was very effective in 44 cases (77.2%), marginally effective in nine cases (15.8%) and ineffective in four cases (7.0%), showing a total effective rate of 93.0%. The four ineffective cases showed a long disease duration and severe pulmonary consolidation. BL showed significant effectiveness for the treatment of neonatal PA under ultrasound monitoring. This treatment is easy to operate, and no adverse side effects were observed. Thus, BL should be considered for clinical application.

Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity.

PubMed

Dailey, Lea Ann; Hernández-Prieto, Raquel; Casas-Ferreira, Ana Maria; Jones, Marie-Christine; Riffo-Vasquez, Yanira; Rodríguez-Gonzalo, Encarnación; Spina, Domenico; Jones, Stuart A; Smith, Norman W; Forbes, Ben; Page, Clive; Legido-Quigley, Cristina

2015-02-01

Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.e. pegylated lipid nanocapsules, polyvinyl acetate nanoparticles and polystyrene beads; listed in order of increasing hydrophobicity). Broncho-alveolar lavage (BAL) fluid was collected from mice exposed to nanoparticles at a surface area dose of 220 cm(2) and metabolite fingerprints were acquired via ultra pressure liquid chromatography-mass spectrometry-based metabolomics. Particles with high surface hydrophobicity were pro-inflammatory. Multivariate analysis of the resultant small molecule fingerprints revealed clear discrimination between the vehicle control and polystyrene beads (p < 0.05), as well as between nanoparticles of different surface hydrophobicity (p < 0.0001). Further investigation of the metabolic fingerprints revealed that adenosine monophosphate (AMP) concentration in BAL correlated with neutrophilia (p < 0.01), CXCL1 levels (p < 0.05) and nanoparticle surface hydrophobicity (p < 0.001). Our results suggest that extracellular AMP is an intermediary metabolite involved in adenine nucleotide-regulated neutrophilic inflammation as well as tissue damage, and could potentially be used to monitor nanoparticle-induced responses in the lung following pulmonary administration.

Comparison of the diagnostic performance of bacterial culture of nasopharyngeal swab and bronchoalveolar lavage fluid samples obtained from calves with bovine respiratory disease

USDA-ARS?s Scientific Manuscript database

Objective: Examine the culture results, gamithromycin susceptibility, predictive values, and agreement of pooled bilateral nasopharyngeal swabs (NPS) and bronchoalveolar lavages (BAL) for identification of Mannheimia haemolytica genotypes, Pasteurella multocida, and Histophilus somni in calves treat...

Usefulness of Cellular Analysis of Bronchoalveolar Lavage Fluid for Predicting the Etiology of Pneumonia in Critically Ill Patients

PubMed Central

Hong, Hyo-Lim; Kim, Sung-Han; Huh, Jin Won; Sung, Heungsup; Lee, Sang-Oh; Kim, Mi-Na; Jeong, Jin-Yong; Lim, Chae-Man; Kim, Yang Soo; Woo, Jun Hee; Koh, Younsuck

2014-01-01

Background The usefulness of bronchoalveolar lavage (BAL) fluid cellular analysis in pneumonia has not been adequately evaluated. This study investigated the ability of cellular analysis of BAL fluid to differentially diagnose bacterial pneumonia from viral pneumonia in adult patients who are admitted to intensive care unit. Methods BAL fluid cellular analysis was evaluated in 47 adult patients who underwent bronchoscopic BAL following less than 24 hours of antimicrobial agent exposure. The abilities of BAL fluid total white blood cell (WBC) counts and differential cell counts to differentiate between bacterial and viral pneumonia were evaluated using receiver operating characteristic (ROC) curve analysis. Results Bacterial pneumonia (n = 24) and viral pneumonia (n = 23) were frequently associated with neutrophilic pleocytosis in BAL fluid. BAL fluid median total WBC count (2,815/µL vs. 300/µL, P<0.001) and percentage of neutrophils (80.5% vs. 54.0%, P = 0.02) were significantly higher in the bacterial pneumonia group than in the viral pneumonia group. In ROC curve analysis, BAL fluid total WBC count showed the best discrimination, with an area under the curve of 0.855 (95% CI, 0.750–0.960). BAL fluid total WBC count ≥510/µL had a sensitivity of 83.3%, specificity of 78.3%, positive likelihood ratio (PLR) of 3.83, and negative likelihood ratio (NLR) of 0.21. When analyzed in combination with serum procalcitonin or C-reactive protein, sensitivity was 95.8%, specificity was 95.7%, PLR was 8.63, and NLR was 0.07. BAL fluid total WBC count ≥510/µL was an independent predictor of bacterial pneumonia with an adjusted odds ratio of 13.5 in multiple logistic regression analysis. Conclusions Cellular analysis of BAL fluid can aid early differential diagnosis of bacterial pneumonia from viral pneumonia in critically ill patients. PMID:24824328

Cytomegalovirus (CMV) DNA quantification in bronchoalveolar lavage fluid of immunocompromised patients with CMV pneumonia.

PubMed

Beam, Elena; Germer, Jeffrey J; Lahr, Brian; Yao, Joseph D C; Limper, Andrew Harold; Binnicker, Matthew J; Razonable, Raymund R

2018-01-01

Cytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA-approved PCR assay (Cobas ® AmpliPrep/Cobas TaqMan ® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsy-proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/10 6 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Elevated uric acid and adenosine triphosphate concentrations in bronchoalveolar lavage fluid of eosinophilic pneumonia.

PubMed

Kobayashi, Takehito; Nakagome, Kazuyuki; Noguchi, Toru; Kobayashi, Kiyoko; Ueda, Yutaka; Soma, Tomoyuki; Ikebuchi, Kenji; Nakamoto, Hidetomo; Nagata, Makoto

2017-09-01

Recent evidence has suggested that the innate immune response may play a role in the development of eosinophilic airway inflammation. We previously reported that uric acid (UA) and adenosine triphosphate (ATP), two important damage-associated molecular pattern molecules (DAMPs), activate eosinophil functions, suggesting that these molecules may be involved in the development of eosinophilic airway inflammation. The objective of this study was to measure the concentrations of DAMPs including UA and ATP in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP). BAL was performed in patients with EP including acute and chronic eosinophilic pneumonia, and in patients with hypersensitivity pneumonia, and sarcoidosis. UA, ATP, and cytokine concentrations in the BALF were then measured. The UA concentration was increased in the BALF of EP patients. UA concentrations correlated with eosinophil numbers, and with eosinophil-derived neurotoxin and interleukin (IL)-5 concentrations. Furthermore, the ATP concentration was increased in the BALF of EP patients and ATP concentrations correlated with UA concentrations. Moreover, IL-33 was increased in EP patients and IL-33 concentrations correlated with UA and ATP concentrations. The UA and ATP concentration was increased in the BALF of EP patients. UA concentrations correlated with eosinophil numbers, and with ATP and IL-33 concentrations. Our findings suggest that DAMPs such as UA and ATP play a role in the pathogenesis of EP. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Increased level of annexin A1 in bronchoalveolar lavage fluid as a potential diagnostic indicator for lung cancer.

PubMed

Biaoxue, Rong; Xiguang, Cai; Hua, Liu; Tian, Fu; Wenlong, Gao

2017-03-02

Annexin A1 has been implicated in various tumor types, but few studies have investigated its involvement in lung cancer. The purpose of this investigation was to quantify the annexin A1 level in bronchoalveolar lavage fluid (BALF) and analyze its usefulness in lung cancer diagnosis. Annexin A1 expression was measured by immunohistochemistry and enzyme immunoassay. The sensitivity and specificity of annexin A1 for distinguishing lung cancer were determined by receiver operator characteristic (ROC) curves. Tumor tissues, BALF and serum of patients with lung cancer contained higher levels of annexin A1 than those of the control group of patients with benign lung diseases. Moreover, an increased level of BALF annexin A1 was closely correlated with lymphatic invasion and malignant progression of lung cancer. The sensitivity and specificity of BALF annexin A1 for distinguishing lung cancer were 94.2% and 90.2%, respectively. Increased annexin A1 in BALF was correlated with lymphatic invasion and malignant progression of lung cancer, suggesting that it could be an indicator for discerning lung cancer and predicting outcome.

Effective assessment of egfr mutation status in bronchoalveolar lavage and pleural fluids by next-generation sequencing.

PubMed

Buttitta, Fiamma; Felicioni, Lara; Del Grammastro, Maela; Filice, Giampaolo; Di Lorito, Alessia; Malatesta, Sara; Viola, Patrizia; Centi, Irene; D'Antuono, Tommaso; Zappacosta, Roberta; Rosini, Sandra; Cuccurullo, Franco; Marchetti, Antonio

2013-02-01

The therapeutic choice for patients with lung adenocarcinoma depends on the presence of EGF receptor (EGFR) mutations. In many cases, only cytologic samples are available for molecular diagnosis. Bronchoalveolar lavage (BAL) and pleural fluid, which represent a considerable proportion of cytologic specimens, cannot always be used for molecular testing because of low rate of tumor cells. We tested the feasibility of EGFR mutation analysis on BAL and pleural fluid samples by next-generation sequencing (NGS), an innovative and extremely sensitive platform. The study was devised to extend the EGFR test to those patients who could not get it due to the paucity of biologic material. A series of 830 lung cytology specimens was used to select 48 samples (BAL and pleural fluid) from patients with EGFR mutations in resected tumors. These samples included 36 cases with 0.3% to 9% of neoplastic cells (series A) and 12 cases without evidence of tumor (series B). All samples were analyzed by Sanger sequencing and NGS on 454 Roche platform. A mean of 21,130 ± 2,370 sequences per sample were obtained by NGS. In series A, EGFR mutations were detected in 16% of cases by Sanger sequencing and in 81% of cases by NGS. Seventy-seven percent of cases found to be negative by Sanger sequencing showed mutations by NGS. In series B, all samples were negative for EGFR mutation by Sanger sequencing whereas 42% of them were positive by NGS. The very sensitive EGFR-NGS assay may open up to the possibility of specific treatments for patients otherwise doomed to re-biopsies or nontargeted therapies.

Proteomic analysis of bronchoalveolar lavage fluid proteins from mice infected with Francisella tularensis ssp novicida

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

Varnum, Susan M.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.

2012-07-06

Francisella tularensis causes the zoonosis tularemia in humans and is one of the most virulent bacterial pathogens. We utilized a global proteomic approach to characterize protein changes in bronchoalveolar lavage fluid from mice exposed to one of three organisms, F. tularensis ssp. novicida, an avirulent mutant of F. tularensis ssp. novicida (F.t. novicida-ΔmglA); and Pseudomonas aeruginosa. The composition of BALF proteins was altered following infection, including proteins involved in neutrophil activation, oxidative stress and inflammatory responses. Components of the innate immune response were induced including the acute phase response and the complement system, however the timing of their induction varied.more » Francisella tularensis ssp. novicida infected mice do not appear to have an effective innate immune response in the first hours of infection, however within 24 hours they show an upregulation of innate immune response proteins. This delayed response is in contrast to P. aeruginosa infected animals which show an early innate immune response. Likewise, F.t. novicida-ΔmglA infection initiates an early innate immune response, however this response is dimished by 24 hours. Finally, this study identifies several candidate biomarkers, including Chitinase 3-like-1 (CHI3L1 or YKL-40) and peroxiredoxin 1, that are associated with F. tularensis ssp. novicida but not P. aeruginosa infection.« less

TGF-β1, IL-6, and TNF-α in bronchoalveolar lavage fluid: useful markers for lung cancer?

PubMed

Chen, Zhongbo; Xu, Zhiwei; Sun, Shifang; Yu, Yiming; Lv, Dan; Cao, Chao; Deng, Zaichun

2014-07-07

Changes of cytokines in bronchoalveolar lavage fluid (BALF) reflect immunologic reactions of the lung in pulmonary malignancies. Detection of biomarkers in BALF might serve as an important method for differential diagnosis of lung cancer. A total of 78 patients admitted into hospital with suspected lung cancer were included in our study. BALF samples were obtained from all patients, and were analyzed for TGF-β1, IL-6, and TNF-α using commercially available sandwich ELISA kits. The levels of TGF-β1 in BALF were significantly higher in patients with lung cancer compared with patients with benign diseases (P = 0.003). However, no significant difference of IL-6 (P = 0.61) or TNF-α (P = 0.72) in BALF was observed between malignant and nonmalignant groups. With a cut-off value of 10.85 pg/ml, TGF-β1 showed a sensitivity of 62.2%, and a specificity of 60.6%, in predicting the malignant nature of pulmonary disease. Our data suggest that TGF-β1 in BALF might be a valuable biomarker for lung cancer. However, measurement of IL-6 or TNF-α in BALF has poor diagnostic value in lung cancer.

Periodontitis-associated septic pulmonary embolism caused by Actinomyces species identified by anaerobic culture of bronchoalveolar lavage fluid: a case report.

PubMed

Endo, Shun; Mishima, Eikan; Takeuchi, Yoichi; Ohi, Takashi; Ishida, Masatsugu; Yanai, Masaru; Kiyomoto, Hideyasu; Nagasawa, Tasuku; Ito, Sadayoshi

2015-12-01

Periodontal disease is a less common but important cause of septic pulmonary embolism (SPE). However, the pathogens causing periodontal disease-associated SPE (PD-SPE) have been poorly understood. Actinomyces species are resident microbiota in the oral cavity. Here we report a case of PD-SPE caused by Actinomyces species, which was identified by anaerobic culture of bronchoalveolar lavage fluid (BAL). A 64-year-old Asian man, complicated with severe chronic periodontitis, was admitted with chest pain and fever. Chest CT revealed multiple bilateral pulmonary nodules located subpleurally. We diagnosed the case as SPE associated with periodontitis. Although blood cultures were negative for the usual 5-day incubation, anaerobic culture of the BAL fluid sample yielded Actinomyces species. Antibacterial therapy alone did not ameliorate the symptoms; however, additional dental treatment, including tooth extraction, promptly did. The patient was discharged 23 days after admission. The 3-month follow-up revealed no recurrence of the symptoms and complete resolution of the lung lesions. This case demonstrated that Actinomyces species can cause PD-SPE. Additionally, clinicians should consider performing appropriate anaerobic culture of BAL fluid to identify the pathogen of SPE, and to ordering dental treatment, if necessary, in addition to antibiotics for the initial management of PD-SPE.

Relationship between secretory leukocyte protease inhibitor levels in bronchoalveolar lavage fluid and postoperative pulmonary complications in patients with esophageal cancer.

PubMed

Tsukada, Katsuhiko; Miyazaki, Tatsuya; Katoh, Hiroyuki; Masuda, Norihiro; Ojima, Hitoshi; Fukuchi, Minoru; Manda, Ryokuhei; Fukai, Yasuyuki; Nakajima, Masanobu; Sohda, Makoto; Kuwano, Hiroyuki

2005-04-01

We investigated whether secretory leukocyte protease inhibitor (SLPI) is associated with pulmonary complications after esophagectomy. We measured serial changes in the SLPI concentration in the bronchoalveolar lavage fluid (BALF) of 34 patients who underwent and examined the relationship between SLPI and postoperative morbidity. Fifteen (44%) of 34 patients (high group) had a BALF SLPI concentration >90,000 pg/mL at the end of the surgery (postoperative day [POD] 0). There was no significant difference between the high group and other 19 patients (low group) with respect to age, sex, preoperative comorbid conditions, tumor stage, surgical technique, operating time, or blood loss volume. Days of intubation and pulmonary complication rate were significantly increased in the high group compared with the low group. Logistic regression analysis revealed that the BALF SLPI level on POD 0 was significant for pulmonary complications. Our results indicate that assaying SLPI levels in BALF can be useful for the prediction of pulmonary complications after esophagectomy.

Neutrophil and macrophage apoptosis in bronchoalveolar lavage fluid from healthy horses and horses with recurrent airway obstruction (RAO)

PubMed Central

2014-01-01

Background Dysregulation of apoptosis has been implicated in a range of diseases including tumors, neurodegenerative and autoimmine diseases, as well as allergic asthma and chronic obstructive pulmonary disease (COPD) in humans. Although it has a different pathophysiology, delayed apoptosis of various inflammatory cells may play a pivotal role in the development of recurrent airway obstruction (RAO) in horses. Reduction of inflammatory cell apoptosis or a dysregulation of this process could lead to chronic inflammation and tissue injury. Therefore, the aim of this study was to investigate the rate of apoptosis and necrosis of neutrophils and macrophages in bronchoalveolar lavage fluid obtained from seven horses suffering from RAO (study group) and seven control horses. Results We demonstrated that neutrophil/macrophage apoptosis is altered in RAO-affected horses compared with the control group in the BAL fluid. We found a significant difference between the median percentage of early and late apoptosis of neutrophils between the study and control group of horses. Moreover, we found a positive correlation between the rate of apoptosis and the median percentage of macrophages in RAO-affected horses. Conclusion The findings suggest that apoptosis dysregulation may play a significant role in the pathogenesis of RAO. However, further studies are needed to clarify the role of altered apoptosis in the course of equine recurrent airway obstruction. PMID:24460911

A prototypic small molecule database for bronchoalveolar lavage-based metabolomics

NASA Astrophysics Data System (ADS)

Walmsley, Scott; Cruickshank-Quinn, Charmion; Quinn, Kevin; Zhang, Xing; Petrache, Irina; Bowler, Russell P.; Reisdorph, Richard; Reisdorph, Nichole

2018-04-01

The analysis of bronchoalveolar lavage fluid (BALF) using mass spectrometry-based metabolomics can provide insight into lung diseases, such as asthma. However, the important step of compound identification is hindered by the lack of a small molecule database that is specific for BALF. Here we describe prototypic, small molecule databases derived from human BALF samples (n=117). Human BALF was extracted into lipid and aqueous fractions and analyzed using liquid chromatography mass spectrometry. Following filtering to reduce contaminants and artifacts, the resulting BALF databases (BALF-DBs) contain 11,736 lipid and 658 aqueous compounds. Over 10% of these were found in 100% of samples. Testing the BALF-DBs using nested test sets produced a 99% match rate for lipids and 47% match rate for aqueous molecules. Searching an independent dataset resulted in 45% matching to the lipid BALF-DB compared to<25% when general databases are searched. The BALF-DBs are available for download from MetaboLights. Overall, the BALF-DBs can reduce false positives and improve confidence in compound identification compared to when general databases are used.

CD4+/CD25(high)/FoxP3+/CD127- regulatory T cells in bronchoalveolar lavage fluid of lung cancer patients.

PubMed

Osińska, Iwona; Stelmaszczyk-Emmel, Anna; Polubiec-Kownacka, Małgorzata; Dziedzic, Dariusz; Domagała-Kulawik, Joanna

2016-10-01

The aim of the study was to compare the presence of regulatory T cells (Tregs) in the local lung cancer environment versus systemic immune response based on the examination of bronchoalveolar lavage fluid (BALf) and peripheral blood (PB) from the same patient. 35 patients with lung cancer were investigated. Flow cytometry method with panel of antibodies: anti CD4/CD25/FoxP3/CD127 for Tregs identification was used. We observed significantly higher proportion of Tregs in the BALF than in PB (median 9.4 vs. 5.4%, p<0.05). The increased proportion of Tregs in patients with advanced disease and in adenocarcinoma was found. This study confirmed the usefulness of BALF analysis in evaluation of immune response in lung cancer. Detection of Tregs in the local tumour environment may have therapeutic relevance in individual indication for anti-cancer immune-therapies. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

T-cell phenotypes in bronchoalveolar lavage fluid, blood and lymph nodes in pulmonary sarcoidosis--indication for an airborne antigen as the triggering factor in sarcoidosis.

PubMed

Darlington, P; Haugom-Olsen, H; von Sivers, K; Wahlström, J; Runold, M; Svjatoha, V; Porwit, A; Eklund, A; Grunewald, J

2012-11-01

An increased percentage of CD4+ T cells is usually observed in bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis. In HLA-DRB1*03-positive patients, such T cells express the T-cell receptor (TCR) AV2S3+ gene segment. It is not known whether cells found in BALF reflect those in enlarged regional lymph nodes (LNs). Therefore, the aim of this study was to compare T-cell phenotypes in BALF, blood and mediastinal LNs. Fifteen patients underwent clinical investigation including bronchoscopy with bronchoalveolar lavage. Blood samples were drawn, and endoscopic ultrasound-guided fine-needle aspiration of enlarged mediastinal LNs was performed via the oesophagus. T cells from all three compartments were analysed by flow cytometry for markers of activity, differentiation and T regulatory function. The CD4/CD8 ratio was significantly higher in BALF compared with regional LNs and was also significantly higher in LNs than in blood. The CD4+ T cells were recently activated and more differentiated in BALF than in blood and LNs. There was an accumulation of T regulatory cells (FOXP3+) in LNs and a correlation between high levels of FOXP3+ cells in BALF and in LNs. In HLA-DRB1*03-positive patients, TCR AV2S3+ CD4+ T cells were predominantly localized within BALF. The CD4+ T-cell phenotype in BALF indicates an active ongoing specific immune response primarily localized to the alveolar space. © 2012 The Association for the Publication of the Journal of Internal Medicine.

Comparison of gallium-67 scanning, bronchoalveolar lavage, and serum angiotensin-converting enzyme levels in pulmonary sarcoidosis. Predicting response to therapy

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

Baughman, R.P.; Fernandez, M.; Bosken, C.H.

1984-05-01

Patients with active pulmonary sarcoidosis underwent bronchoalveolar lavage, gallium scan, and serum angiotensin-converting enzyme (ACE) level determination prior to treatment with corticosteroids. Pulmonary function was tested before and after therapy. Increase in vital capacity after treatment ranged from 40 to 1,030 ml; 12 of the 16 patients studied had an increase of more than 200 ml. There was a close correlation between the percentage uptake of gallium scan and the increase of the vital capacity after therapy (r . 0.95, p less than 0.01). There was no relationship between the percentage of lymphocytes obtained on lavage and the changes inmore » vital capacity with therapy (r . 0.05). There was a positive correlation between the changes in vital capacity and the ratio of T4(+):T8(+)lymphocytes (r . 0.62, p less than 0.05) and number of T4 (+) lymphocytes (r . 0.92, p less than 0.01) in the bronchoalveolar fluid. There was a low correlation between the pretreatment ACE level and the change in vital capacity (r . 0.368, p greater than 0.05).« less

Intratracheal fiber glass instillation in rats: IL8 and lymphocytes levels in bronchoalveolar lavage, correlation with the histopathological findings

PubMed Central

HANCU, BIANCA DOMOKOS; POP, MONICA

2013-01-01

Introduction Fiberglass (FG) is the largest category of man –made mineral fibers. Many types of FG are manufactured for specific uses building insulation, air handling, and sound absorption. Because of increasing use and potential for widespread human exposure, a chronic toxicity instillation study was conducted in Wistar rats, which were found to be sensitive to the induction of mesotheliomas with another MMVF. Aim The present study is focused on the effect of fiber glass on lung through intratracheal exposure, the analysis of bronchoalveolar lavage and measurement of IL 8 levels, lymphocytes number and histopathological finding after the exposure period. Material and method Four groups of 8 female Wistar rats were included in the study. The animals were divided into three groups of 8 each, exposed to different doses of FG and one control group. The first group (1–8) was exposed to 6 mg dose/0.2 ml saline 5 days/week for 10 weeks, the second (9–16) group was exposed to 10 mg/0.2 ml saline 5 days/week 10 weeks, the third group (17–24) was exposed to 12 mg FG/0.2 ml saline solution 5 days/week 10 weeks and the control group (25–32) was exposed to the same volume of saline. The fibers had been size selected to be rat respirable. At the end of the exposure period of 10 weeks the rats were killed one week after the last exposure. Following preparation of the lungs, they were lavaged with 2x5 ml saline without massage. The lavage fluid was collected in calibrated tubes and harvested volume was recorded. Supernatant was obtained after centrifugation at 1,500 r.p.m for 5 minutes and IL8 levels and lymphocytes number were measured. Results The IL8 levels were found to be dose related; the first group had values ranging from 10 to 19.8 pg/ml and the total lymphocytes number in the bronchoalveolar lavage fluid ranging from 1,500–1,900 and minimal/slight inflammatory lesions. The second group had the IL8 levels ranging between 60.4–80.4 pg/ml, lymphocytes number

Eicosanoids in exhaled breath condensate and bronchoalveolar lavage fluid of patients with primary lung cancer.

PubMed

Ciebiada, Maciej; Górski, Paweł; Antczak, Adam

2012-01-01

Although eicosanoids are involved in lung carcinogenesis they were poorly investigated in exhaled breath condensate (EBC) and bronchoalveolar lavage fluid (BALf) in patients with primary lung cancer. In this study 17 patients with diagnosed non-small cell lung cancer, 10 healthy smokers and 12 healthy nonsmokers were included. The levels of cys-LTs, 8-isoprostane, LTB4 and PGE2 were measured before any treatment in the EBC of all patients and in BALf of patients with lung cancer by enzyme linked immunosorbent assay. 8-isoprostane, LTB4, cys-LTs and PGE2 were detectable in the EBC and BALf. There were no significant differences between healthy smokers and nonsmokers in concentrations of all measured mediators. Compared with both healthy controls, patients with diagnosed lung cancer displayed higher concentrations of cys-LTs (p< 0.05) and LTB4 (p < 0.05) in EBC. In patients with lung cancer, the mean concentrations of all measured mediators were significantly higher in BALf compared with EBC and there was a significant, positive correlation between concentration of cys-LTs, LTB(4) and 8-isoprostane in BALf and their concentrations in the EBC (r=0.64, p < 0.05, r=0.59, p< 0.05, r=0.53, p< 0.05 respectively). Since cys-LT, LTB4 and 8-isoprostane concentrations in EBC from patients with lung cancer reflect their concentrations in BALf, they may serve as a possible non-invasive method to monitor the disease and to assess the effectiveness of therapy.

Analysis of Culture-Dependent versus Culture-Independent Techniques for Identification of Bacteria in Clinically Obtained Bronchoalveolar Lavage Fluid

PubMed Central

Dickson, Robert P.; Erb-Downward, John R.; Prescott, Hallie C.; Martinez, Fernando J.; Curtis, Jeffrey L.; Lama, Vibha N.

2014-01-01

The diagnosis and management of pneumonia are limited by the use of culture-based techniques of microbial identification, which may fail to identify unculturable, fastidious, and metabolically active viable but unculturable bacteria. Novel high-throughput culture-independent techniques hold promise but have not been systematically compared to conventional culture. We analyzed 46 clinically obtained bronchoalveolar lavage (BAL) fluid specimens from symptomatic and asymptomatic lung transplant recipients both by culture (using a clinical microbiology laboratory protocol) and by bacterial 16S rRNA gene pyrosequencing. Bacteria were identified in 44 of 46 (95.7%) BAL fluid specimens by culture-independent sequencing, significantly more than the number of specimens in which bacteria were detected (37 of 46, 80.4%, P ≤ 0.05) or “pathogen” species reported (18 of 46, 39.1%, P ≤ 0.0001) via culture. Identification of bacteria by culture was positively associated with culture-independent indices of infection (total bacterial DNA burden and low bacterial community diversity) (P ≤ 0.01). In BAL fluid specimens with no culture growth, the amount of bacterial DNA was greater than that in reagent and rinse controls, and communities were markedly dominated by select Gammaproteobacteria, notably Escherichia species and Pseudomonas fluorescens. Culture growth above the threshold of 104 CFU/ml was correlated with increased bacterial DNA burden (P < 0.01), decreased community diversity (P < 0.05), and increased relative abundance of Pseudomonas aeruginosa (P < 0.001). We present two case studies in which culture-independent techniques identified a respiratory pathogen missed by culture and clarified whether a cultured “oral flora” species represented a state of acute infection. In summary, we found that bacterial culture of BAL fluid is largely effective in discriminating acute infection from its absence and identified some specific limitations of BAL fluid culture in

Analysis of culture-dependent versus culture-independent techniques for identification of bacteria in clinically obtained bronchoalveolar lavage fluid.

PubMed

Dickson, Robert P; Erb-Downward, John R; Prescott, Hallie C; Martinez, Fernando J; Curtis, Jeffrey L; Lama, Vibha N; Huffnagle, Gary B

2014-10-01

The diagnosis and management of pneumonia are limited by the use of culture-based techniques of microbial identification, which may fail to identify unculturable, fastidious, and metabolically active viable but unculturable bacteria. Novel high-throughput culture-independent techniques hold promise but have not been systematically compared to conventional culture. We analyzed 46 clinically obtained bronchoalveolar lavage (BAL) fluid specimens from symptomatic and asymptomatic lung transplant recipients both by culture (using a clinical microbiology laboratory protocol) and by bacterial 16S rRNA gene pyrosequencing. Bacteria were identified in 44 of 46 (95.7%) BAL fluid specimens by culture-independent sequencing, significantly more than the number of specimens in which bacteria were detected (37 of 46, 80.4%, P ≤ 0.05) or "pathogen" species reported (18 of 46, 39.1%, P ≤ 0.0001) via culture. Identification of bacteria by culture was positively associated with culture-independent indices of infection (total bacterial DNA burden and low bacterial community diversity) (P ≤ 0.01). In BAL fluid specimens with no culture growth, the amount of bacterial DNA was greater than that in reagent and rinse controls, and communities were markedly dominated by select Gammaproteobacteria, notably Escherichia species and Pseudomonas fluorescens. Culture growth above the threshold of 10(4) CFU/ml was correlated with increased bacterial DNA burden (P < 0.01), decreased community diversity (P < 0.05), and increased relative abundance of Pseudomonas aeruginosa (P < 0.001). We present two case studies in which culture-independent techniques identified a respiratory pathogen missed by culture and clarified whether a cultured "oral flora" species represented a state of acute infection. In summary, we found that bacterial culture of BAL fluid is largely effective in discriminating acute infection from its absence and identified some specific limitations of BAL fluid culture in the

Evaluation of diagnostic value of four tumor markers in bronchoalveolar lavage fluid of peripheral lung cancer.

PubMed

Li, Jian; Chen, Ping; Mao, Chao-Ming; Tang, Xing-Ping; Zhu, Li-Rong

2014-06-01

The diagnostic role of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, Cyfra 21-1 and neuron-specific enolase (NSE) in the bronchoalveolar lavage fluid (BALF) for lung cancer is still controversial. The aim of this study was to evaluate the diagnostic value of these four tumor markers in BALF for peripheral lung cancer. We measured and compared the levels of CEA, SCC, Cyfra21-1 and NSE in BALF in 42 patients with peripheral lung cancer and 22 patients with benign lung disease. In the patients with peripheral lung cancer, the BAL was separately performed in the bronchus of the tumor-bearing lung and in the corresponding bronchus of the opposite healthy lung. The levels of CEA, SCC, Cyfra21-1 and NSE were significantly elevated in BALF from the tumor-bearing lung compared with the opposite healthy lung in the lung cancer patients (P < 0.001) or the benign lung disease patients (P < 0.005). The diagnostic sensitivities of Cyfra21-1 (86 and 76%), with a specificity of 91%, were the highest among the four tumor markers for the tumor-bearing lung versus the opposite healthy lung and benign lung disease. The combination of Cyfra21-1 and CEA increased the sensitivity to 93 and 86 percent, respectively. The assay of these tumor markers in BALF may be used as a diagnostic tool to complement a cytological examination in the diagnosis of peripheral lung cancer. © 2013 Wiley Publishing Asia Pty Ltd.

Pentraxin 3 levels in bronchoalveolar lavage fluid of lung transplant recipients with invasive aspergillosis.

PubMed

Kabbani, Dima; Bhaskaran, Archana; Singer, Lianne G; Bhimji, Alyajahan; Rotstein, Coleman; Keshavjee, Shaf; Liles, W Conrad; Husain, Shahid

2017-09-01

Invasive aspergillosis is the most common invasive fungal infection in lung transplant recipients. The use of galactomannan testing in bronchoalveolar lavage (BAL) fluid has improved diagnosis of invasive aspergillosis; however, false-positive results can lead to overdiagnosis and unnecessary treatment. The use of proinflammatory markers such as pentraxin 3 (PTX3) may help differentiate between Aspergillus colonization and disease. BAL PTX3 concentrations were measured by enzyme-linked immunosorbent assay in 151 lung transplant recipients and 9 healthy control subjects. Patients were characterized as having Aspergillus colonization or invasive disease according to International Society of Heart and Lung Transplantation criteria. Concomitant PTX3values were compared using Mann-Whitney U and Kruskal-Wallis tests. We analyzed 322 BAL stored samples and identified 15 invasive aspergillosis events, 38 Aspergillus colonizations, and 17 positive galactomannan with negative Aspergillus cultures. Median BAL PTX3 level was significantly higher in patients with invasive aspergillosis compared with patients with Aspergillus colonization and healthy control subjects (439.20 pg/ml [interquartile range (IQR) 168.18-778.90], 68.93 pg/ml [IQR 13.67-156.74], and 13.67 pg/ml [IQR 13.67-121.18]; p < 0.001). Patients with BAL PTX3 value >319 pg/ml with positive galactomannan and patients with BAL PTX3 value >312 pg/ml with positive Aspergillus culture were 4.5 and 5.5 times more likely to have invasive pulmonary aspergillosis, respectively. Our study shows that PTX3 measurements in BAL samples were significantly higher among patients with invasive aspergillosis and may help to identify patients with Aspergillus colonization and false-positive galactomannan in BAL samples. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

The diagnostic value of tumor markers in bronchoalveolar lavage fluid for the peripheral pulmonary carcinoma.

PubMed

Zhang, Shi; Zhao, Yun-Feng; Zhang, Ming-Zhou; Wu, Xue-Ling

2017-07-01

To investigate the value of Ubiquitin specific peptidase 8 (USP8), Chitinase 3-like 1 (YKL40), Heat shock protein 90a (HSP90α), glutathione S-transferase P1 (GSTP1), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and cytokeratin fragment antiogen 21-1 (CYFRA21-1) in bronchoalveolar lavage fluid (BALF) and serum for diagnosis in patients with peripheral lung cancer. The concentration of these markers were measured in 50 patients with peripheral lung cancer and 50 patients with benign lung diseases by using enzyme-linked immuno sorbent assay methods. There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the BALF of USP8, YKL40, HSP90α, CEA, NSE and CYFRA21-1. There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the serum of HSP90α and CEA. There were no differences in others. There were no correlation between the concentration of all markers and age, histological type, TNM stage (I-IV). There was a weak correlation between the primary foci diameters and the concentration of YKL40 in BALF. (Pearson's correlation: 0.203, P = 0.048) The diagnostic efficiencies of USP8, YKL40, HSP90α were superior to CYFRA21-1 and NSE, being lower CEA. Detection of tumor markers in BALF was superior to serum specimens. The measurement of USP8, HSP90α and YKL40 in BALF had more clinical value for the diagnosis of peripheral pulmonary carcinoma. © 2015 John Wiley & Sons Ltd.

Recovery of rat alveolar macrophages by bronchoalveolar lavage under normal and activated conditions.

PubMed Central

Rehn, B; Bruch, J; Zou, T; Hobusch, G

1992-01-01

When rat (female Wistar) lungs were lavaged (bronchoalveolar lavage, BAL) six times with physiological saline, approximately the same number of alveolar macrophages (AM) were found in the first and second BAL, whereas in the third fourth, fifth, and sixth BAL, the number of AM decreased exponentially. Morphometric counting of the number of AM in histological sections of lung tissue showed that only 14% of the AM population had been recovered by BAL. Although additives to the BAL fluid such as lidocaine and/or fetal calf serum increased the AM count in the first washing considerably, the total number of AM washed out remained unaltered. Addition of the phagocytosis stimulant zymosan increased the AM count in BAL by a factor of more than 2. On stimulation of the lungs with an inert dust (silicon carbide), the AM count in the BAL and the lung was only slightly increased 8 weeks after intratracheal instillation. In contrast, after exposure to fibrogenic and cytotoxic quartz, the AM count in BAL and lung was significantly increased, and the recovery of AM had also increased by a factor of approximately 2. The experiments show that it is the micromilieu of the alveoli and the condition of the AM (certain physiological activation states, such as phagocytic activity) that essentially determine the degree of recovery. PMID:1396444

Diagnostic Performance of Bronchoalveolar Lavage Fluid CD4/CD8 Ratio for Sarcoidosis: A Meta-analysis.

PubMed

Shen, Yongchun; Pang, Caishuang; Wu, Yanqiu; Li, Diandian; Wan, Chun; Liao, Zenglin; Yang, Ting; Chen, Lei; Wen, Fuqiang

2016-06-01

The usefulness of bronchoalveolar lavage fluid (BALF) CD4/CD8 ratio for diagnosing sarcoidosis has been reported in many studies with variable results. Therefore, we performed a meta-analysis to estimate the overall diagnostic accuracy of BALF CD4/CD8 ratio based on the bulk of published evidence. Studies published prior to June 2015 and indexed in PubMed, OVID, Web of Science, Scopus and other databases were evaluated for inclusion. Data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled from included studies. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deeks's funnel plot was used to detect publication bias. Sixteen publications with 1885 subjects met our inclusion criteria and were included in this meta-analysis. Summary estimates of the diagnostic performance of the BALF CD4/CD8 ratio were as follows: sensitivity, 0.70 (95%CI 0.64-0.75); specificity, 0.83 (95%CI 0.78-0.86); PLR, 4.04 (95%CI 3.13-5.20); NLR, 0.36 (95%CI 0.30-0.44); and DOR, 11.17 (95%CI 7.31-17.07). The area under the SROC curve was 0.84 (95%CI 0.81-0.87). There was no evidence of publication bias. Measuring the BALF CD4/CD8 ratio may assist in the diagnosis of sarcoidosis when interpreted in parallel with other diagnostic factors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Concentrations of cysteinyl leukotrienes in urine and bronchoalveolar lavage fluid of cats with experimentally induced asthma.

PubMed

Norris, Carol R; Decile, Kendra C; Berghaus, Londa J; Berghaus, Roy D; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2003-11-01

To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma. 19 cats with experimentally induced asthma and 5 control cats. Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LT-to-TP ratios were calculated. Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergen-sensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points. Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study.

Occult exposure to asbestos in steel workers revealed by bronchoalveolar lavage

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

Corhay, J.-L.; Delavignette, J.-P.; Bury, T.

To investigate the asbestos burden in a steelplant environment, we counted asbestos bodies (ABs) in the bronchoalveolar lavage fluid (BALF) of 65 steel workers who had retired during the previous 5 y. They had worked for at least 15 y in the same area of the plant (coke oven or blast furnace) as maintenance or production workers. On the basis of occupational anamnesis, 28 had occasional past professional exposure to asbestos; the remaining 37 workers denied any contact with asbestos. A total of 54 white-collar workers who had no occupational exposure to asbestos were included in the study as controls.more » An increased prevalence and concentration of ABs was found in the BALF of steel workers. Electron microscopy and EDAX analysis of AB from steel workers revealed that the core fibers were mainly amphiboles. More ABs were found in the BALF of maintenance workers than in production workers. However, the BALF from steel workers who denied any contact with asbestos revealed an increased AB burden v. controls. This demonstrates that steel workers may be subject to an occult exposure to amphiboles in the steelplant environment.« less

Utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid for differential diagnosis of primary lung cancer.

PubMed

Cao, Chao; Sun, Shi-Fang; Lv, Dan; Chen, Zhong-Bo; Ding, Qun-Li; Deng, Zai-Chun

2013-01-01

Published data have shown that the levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sVEGFR-1) in plasma and pleural effusion might be usefulness for lung cancer diagnosis. Here, we performed a prospective study to investigate the utility of VEGF and sVEGFR-1 in bronchoalveolar lavage fluid (BALF) for differential diagnosis of primary lung cancer. A total of 56 patients with solitary pulmonary massed by chest radiograph or CT screening were enrolled in this study. BALF and plasma samples were obtained from all patients and analyzed for VEGF and sVEGFR-1 using a commercially available sandwich ELISA kit. The results showed that the levels of VEGF in BALF were significantly higher in patients with a malignant pulmonary mass compared with patients with a benign mass (P < 0.001). However, no significant difference of sVEGFR-1 in BALF was found between malignant and non-malignant groups (P = 0.43). With a cut-off value of 214 pg/ml, VEGF showed a sensitivity and specificity of 81.8% and 84.2%, respectively, in predicting the malignant nature of a solitary pulmonary mass. Our study suggests that VEGF is significantly increased in BALF among patients with lung cancer than in benign diseases. Measurement of VEGF in BALF might be helpful for differential diagnosis of primary lung cancer.

Response of rodents to inhaled diluted diesel exhaust: biochemical and cytological changes in bronchoalveolar lavage fluid and in lung tissue

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

Henderson, R.F.; Pickrell, J.A.; Jones, R.K.

1988-10-01

The effect of long-term (24 months) inhalation of diesel exhaust on the bronchoalveolar region of the respiratory tract of rodents was assessed by serial (every 6 months) analysis of bronchoalveolar lavage fluid (BALF) and of lung tissue from F344/Crl rats and CD-1 mice (both sexes) exposed to diesel exhaust diluted to contain 0, 0.35, 3.5, or 7.0 mg soot/m3. The purpose of the study was twofold. One was to assess the potential health effects of inhaling diluted exhaust from light-duty diesel engines. The second was to determine the usefulness of BALF analysis in detecting the early stages in the developmentmore » of nononcogenic lung disease and differentiating them from the normal repair processes. No biochemical or cytological changes in BALF or in lung tissue were noted in either species exposed to the lowest, and most environmentally relevant, concentration of diesel exhaust. In the two higher levels of exposure, a chronic inflammatory response was measured in both species by dose-dependent increases in inflammatory cells, cytoplasmic and lysosomal enzymes, and protein in BALF. Histologically, after 1 year of exposure, the rats had developed focal areas of fibrosis associated with the deposits of soot, while the mice, despite a higher lung burden of soot than the rats, had only a fine fibrillar thickening of an occasional alveolar septa in the high-level exposure group. Higher increases in BALF beta-glucuronidase activity and in hydroxyproline content accompanied the greater degree of fibrosis in the rat. BALF levels of glutathione (GSH) and glutathione reductase activity increased in a dose-dependent fashion and were higher in mice than in rats. Lung tissue GSH was depleted in a dose-dependent fashion in rats but was slightly increased in mice.« less

Aspergillus Galactomannan Enzyme Immunoassay and Quantitative PCR for Diagnosis of Invasive Aspergillosis with Bronchoalveolar Lavage Fluid

PubMed Central

Musher, Benjamin; Fredricks, David; Leisenring, Wendy; Balajee, S. Arunmozhi; Smith, Caitlin; Marr, Kieren A.

2004-01-01

Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in hematopoietic stem cell transplant patients. Diagnosis requires microbiological or histopathologic demonstration of the organism in tissues; however, cultivation of Aspergillus species from respiratory secretions has low diagnostic sensitivity. Assays to detect Aspergillus antigen or DNA in bronchoalveolar lavage (BAL) fluid could facilitate earlier diagnosis, thereby guiding optimal therapy and obviating the need for additional costly and potentially morbid diagnostic evaluation. We evaluated the performance of a galactomannan enzyme immunoassay (GM EIA; Bio-Rad) by using a range of index cutoffs to define positivity and a quantitative PCR (qPCR) assay for the detection of Aspergillus species from BAL samples of patients with proven and probable IPA (case patients; n = 49) and without IPA (control patients; n = 50). The sensitivity of the GM EIA was 61% with an index cutoff of 1.0 and 76% with an index cutoff of 0.5; the corresponding specificities were 98 and 94%, respectively. The sensitivity and specificity of qPCR assay were 67 and 100%, respectively. The sensitivity with 22 culture-negative BAL specimens from patients with IPA was 41% for GM EIA with an index cutoff of 1.0, 59% for GM EIA with an index cutoff of 0.5, and 36% for qPCR assay. GM EIA indices and DNA quantities corresponded to BAL fungal burdens, with culture-positive samples having larger amounts of antigen and DNA compared to culture-negative samples. GM EIA and qPCR assay add to the sensitivity of BAL for diagnosing IPA in high-risk patients, with excellent specificity. Adjunctive use of these tests may reduce dependence on invasive diagnostic procedures. PMID:15583275

Utility of Bronchoalveolar Lavage for the Diagnosis of Asbestos-Related Diseases.

PubMed

Cruz, María Jesús; Curull, Victor; Pijuan, Lara; Álvarez-Simón, Daniel; Sánchez-Font, Albert; de Gracia, Javier; Culebras, Mario; Ferrer, Jaume

2017-06-01

Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD). BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue. Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002). BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion

PubMed Central

Andreasson, Anders S.I.; Karamanou, Danai M.; Gillespie, Colin S.; Özalp, Faruk; Butt, Tanveer; Hill, Paul; Jiwa, Kasim; Walden, Hannah R.; Green, Nicola J.; Borthwick, Lee A.; Clark, Stephen C.; Pauli, Henning; Gould, Kate F.; Corris, Paul A.; Ali, Simi; Dark, John H.

2017-01-01

Abstract OBJECTIVES: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study. PMID:28082471

Effects of tylosin, tilmicosin and tulathromycin on inflammatory mediators in bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury.

PubMed

Er, Ayse; Yazar, Enver

2012-12-01

The aim of this study was to determine the anti-inflammatory effects of macrolides through kinetic parameters in bronchoalveolar lavage fluid (BALF) of lipopolysaccharide-induced lung injury. Rats were divided into four groups: lipopolysaccharide (LPS), LPS + tylosin, LPS + tilmicosin and LPS + tulathromycin. BALF samples were collected at sampling times. TNF, IL-1β, IL-6, IL-10 and 13,14-dihydro-15-keto-prostaglandin F2α (PGM) and C-reactive protein (CRP) were analysed. Area under the curve (AUC) and maximum plasma concentration (Cmax) values of inflammatory mediators were determined by a pharmacokinetic computer programme. When inflammatory mediator concentrations were compared between the LPS group and other groups for each sampling time, the three macrolides had no pronounced depressor effect on cytokine levels, but they depressed PGM and CRP levels. In addition, tylosin and tilmicosin decreased the AUC0-24 level of TNF, while tilmicosin decreased the AUC0-24 level of IL-10. Tylosin and tulathromycin decreased the AUC0-24 of PGM, and all three macrolides decreased the AUC0-24 of CRP. Especially tylosin and tulathromycin may have more expressed anti-inflammatory effects than tilmicosin, via depressing the production of inflammatory mediators in the lung. The AUC may be used for determining the effects of drugs on inflammation. In this study, the antiinflammatory effects of these antibiotics were evaluated with kinetic parameters as a new and different approach.

Cytokine expression in severe pneumonia: a bronchoalveolar lavage study.

PubMed

Montón, C; Torres, A; El-Ebiary, M; Filella, X; Xaubet, A; de la Bellacasa, J P

1999-09-01

To assess the cytokine expression (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, and IL-6) in severe pneumonia, both locally (in the lungs) and systemically (in blood). Prospective sequential study with bronchoalveolar lavage (BAL) and blood sampling. Six-bed respiratory intensive care unit of a 1,000-bed teaching hospital. Thirty mechanically ventilated patients (>48 hrs) were allocated to either the pneumonia group (n = 20) or a control group (n = 10). Protected specimen brush and BAL samples for quantitative cultures, and serum and BAL fluid TNF-alpha, IL-1beta, and IL-6 levels were measured on days 1, 3, and 7. In the control group, the procedure was done on day 1 only. Serum TNF-alpha levels were significantly higher in patients with pneumonia compared with controls (35 +/- 4 vs. 17 +/- 3 pg/mL, respectively, p = .001). IL-6 levels in serum and BAL fluid were higher in pneumonia than in control patients (serum, 837 +/- 260 vs. 94 +/- 35 pg/mL, respectively, p = .017; BAL fluid, 1176 +/- 468 vs. 234 +/- 83 pg/mL, respectively, p = .05). On days 1, 3, and 7 in patients with pneumonia, IL-1beta levels turned out to be higher in BAL fluid than in serum (71 +/- 17 vs. 2 +/-1 pg/mL on day 1; 49 +/- 8 vs. 6 +/- 2 pg/mL on day 3; and 47 +/- 16 vs. 3 +/- 2 pg/mL on day 7 for BAL fluid and serum, respectively, p < .05). No significant correlation between BAL fluid cytokine levels and lung bacterial burden was shown in presence of antibiotic treatment. Although no clear relationship was found between BAL fluid and serum cytokines and mortality, there was a trend toward higher serum IL-6 levels in nonsurvivors (1209 +/- 433 pg/mL) with pneumonia compared with survivors (464 +/- 260 pg/mL). In addition, serum TNF-alpha and IL-6 correlated with multiple organ failure score (r2 = .36, p = .004 for both) and with lung injury score (r2 = .30, p = .01, and r2 = .22, p = .03, for TNF-alpha and IL-6, respectively). The present study describes the lung and

Cytokine profile of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during seasonal H1N1 infection.

PubMed

Hasegawa, Shunji; Wakiguchi, Hiroyuki; Okada, Seigo; Gui Kang, Yu; Fujii, Nao; Hasegawa, Masanari; Hasegawa, Hideki; Ainai, Akira; Atsuta, Ryo; Shirabe, Komei; Toda, Shoichi; Wakabayashi-Takahara, Midori; Morishima, Tsuneo; Ichiyama, Takashi

2014-10-01

Several studies support the role of viral infections in the pathogenesis of asthma exacerbation. However, several pediatricians believe that influenza virus infection does not exacerbate bronchial asthma, except for influenza A H1N1 2009 pandemic [A(H1N1)pdm09] virus infection. We previously reported that A(H1N1)pdm09 infection possibly induces severe pulmonary inflammation or severe asthmatic attack in a mouse model of bronchial asthma and in asthmatic children. However, the ability of seasonal H1N1 influenza (H1N1) infection to exacerbate asthmatic attacks in bronchial asthma patients has not been previously reported, and the differences in the pathogenicity profiles, such as cytokine profiles, remains unclear in bronchial asthma patients after A(H1N1)pdm09 and H1N1 infections. The cytokine levels and viral titers in the bronchoalveolar lavage (BAL) fluid from mice with and without asthma after H1N1 infection (A/Yamagata and A/Puerto Rico strains) were compared. The interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, IL-5, interferon (IFN)-α, IFN-β, and IFN-γ levels were significantly higher in the BAL fluids from the control/H1N1 mice than from the asthmatic/H1N1 mice. The viral titers in the BAL fluid were also significantly higher in the control/H1N1mice than in the asthmatic/H1N1 mice infected with either A/Yamagata or A/Puerto Rico. A(H1N1)pdm09 infection, but not H1N1 infection, can induce severe pulmonary inflammation through elevated cytokine levels in a mouse model of asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia

PubMed Central

Stevens-Ayers, Terry; Travi, Giovanna; Huang, Meei-Li; Cheng, Guang-Shing; Xie, Hu; Leisenring, Wendy; Erard, Veronique; Seo, Sachiko; Kimball, Louise; Corey, Lawrence; Pergam, Steven A; Jerome, Keith R.

2017-01-01

Abstract Background. Quantitative cytomegalovirus (CMV) DNA–specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding. Methods. We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA–specific PCR. Results. Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6–6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0–1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0–2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values. Conclusion. CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding. PMID:28181657

Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.

PubMed

Andreasson, Anders S I; Karamanou, Danai M; Gillespie, Colin S; Özalp, Faruk; Butt, Tanveer; Hill, Paul; Jiwa, Kasim; Walden, Hannah R; Green, Nicola J; Borthwick, Lee A; Clark, Stephen C; Pauli, Henning; Gould, Kate F; Corris, Paul A; Ali, Simi; Dark, John H; Fisher, Andrew J

2017-03-01

Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.

Clinical utility of Aspergillus galactomannan and PCR in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies.

PubMed

Heng, Siow-Chin; Chen, Sharon C-A; Morrissey, C Orla; Thursky, Karin; Manser, Renee L; De Silva, Harini D; Halliday, Catriona L; Seymour, John F; Nation, Roger L; Kong, David C M; Slavin, Monica A

2014-07-01

Interpretation of Aspergillus galactomannan (GM) and PCR results in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with haematological malignancies requires clarification. A total of 116 patients underwent BAL for investigation of new lung infiltrates: 40% were neutropenic, 68% and 36% were receiving mould-active antifungal agents and β-lactam antibiotics. The diagnosis of proven IPA (n = 3), probable IPA (n = 15), and possible invasive fungal disease (IFD, n = 50) was made without inclusion of GM results. BAL GM (at cut-off of 0.8) had lower diagnostic sensitivity for IPA than PCR (61% versus 78%) but higher specificity (93% versus 79%). Both tests had excellent negative predictive values (85-90%), supporting their utility in excluding IPA. The use of BAL GM and PCR results increased the certainty of Aspergillus aetiology in 7 probable IPA cases where fungal hyphae were detected in respiratory samples by microscopy, and upgraded 24 patients from possible IFD to probable IPA. Use of BAL GM and PCR improves the diagnosis of IPA. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Increased β-glucuronidase activity in bronchoalveolar lavage fluid of children with bacterial lung infection: A case-control study.

PubMed

Panagiotopoulou, Evgenia C; Fouzas, Sotirios; Douros, Konstantinos; Triantaphyllidou, Irene-Eva; Malavaki, Christina; Priftis, Kostas N; Karamanos, Nikos K; Anthracopoulos, Michael B

2015-11-01

β-Glucuronidase is a lysosomal enzyme released into the extracellular fluid during inflammation. Increased β-glucuronidase activity in the cerebrospinal and peritoneal fluid has been shown to be a useful marker of bacterial inflammation. We explored the role of β-glucuronidase in the detection of bacterial infection in bronchoalveolar lavage fluid (BALF) of paediatric patients. In this case-control study, % polymorphonuclear cell count (PMN%), β-glucuronidase activity, interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α) and elastase were measured in culture-positive (≥10(4) cfu/mL, C+) and -negative (C-) BALF samples obtained from children. A total of 92 BALF samples were analysed. The median β-glucuronidase activity (measured in nanomoles of 4-methylumbelliferone (4-MU)/mL BALF/h) was 246.4 in C+ (interquartile range: 71.2-751) and 21.9 in C- (4.0-40.8) (P < 0.001). The levels of TNF-α and IL-8 were increased in C+ as compared with C- (5.4 (1.7-12.6) vs 0.7 (0.2-6.2) pg/mL, P < 0.001 and 288 (76-4300) vs 287 (89-1566) pg/mL, P = 0.042, respectively). Elastase level and PMN% did not differ significantly (50 (21-149) vs 26 (15-59) ng/mL, P = 0.051 and 20 (9-40) vs 18 (9-34) %, P = 0.674, respectively). The area under the curve of β-glucuronidase activity (0.856, 95% confidence interval (CI): 0.767-0.920) was higher than that of TNF-α (0.718; 95% CI: 0.614-0.806; P = 0.040), IL-8 (0.623; 95% CI: 0.516-0.722; P = 0.001), elastase (0.645; 95% CI: 0.514-0.761; P = 0.008) and PMN% (0.526; 95 % CI: 0.418-0.632; P < 0.001). This study demonstrates a significant increase of β-glucuronidase activity in BALF of children with culture-positive bacterial inflammation. In our population β-glucuronidase activity showed superior predictive ability for bacterial lung infection than other markers of inflammation. © 2015 Asian Pacific Society of Respirology.

Bronchoalveolar lavage, serum angiotensin-converting enzyme, and /sup 67/Ga scanning in extrathoracic sarcoidosis

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

Wallaert, B.; Ramon, P.; Fournier, E.

1982-11-01

Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis.

Euthanasia and Lavage Mediated Effects on Bronchoalveolar Measures of Lung Injury and Inflammation.

PubMed

Tighe, Robert M; Birukova, Anastasiya; Yeager, Michael J; Reece, Sky W; Gowdy, Kymberly M

2018-02-26

Accurate and reproducible assessments of experimental lung injury and inflammation are critical to basic and translational research. In particular, investigators use varied methods of bronchoalveolar lavage and euthanasia but their impact to assessments of injury and inflammation are unknown. To define potential effects, we compared methods of lavage and euthanasia in uninjured mice and following a mild lung injury model (ozone). C57BL/6J male mice age 8-10 weeks underwent BAL following euthanasia with ketamine/xylazine, carbon dioxide (C0 2 ), or isoflurane. BAL methods included 800-μL instilled and withdrawn three times, and 1 or 3 passive fill(s) and drainage to 20cm H20. Parallel experiments were performed 24hr following 3hr of ozone (O 3 ) exposure at 2 parts per million (ppm). BAL total cell counts/differentials and total protein/albumin were determined. Lung histology was evaluated for lung inflammation/injury. BAL cells were cultured and stimulated with PBS, phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) for 4hr and supernatants were evaluated for cytokine content. In uninjured mice, we observed differences due to the lavage and euthanasia methods. The lavage method increased uninjured and O 3 exposure total cells and total protein/albumin with 800-μL instillation having the highest values. Isoflurane increased uninjured total BAL cells, while C0 2 euthanasia increased the uninjured total protein/albumin levels. These effects limited the ability to detect differences in BAL injury measures following O 3 exposure. In conclusion, the method of lavage and euthanasia affects measures of lung inflammation/injury and should be considered a variable in model assessment.

Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia.

PubMed

Boeckh, Michael; Stevens-Ayers, Terry; Travi, Giovanna; Huang, Meei-Li; Cheng, Guang-Shing; Xie, Hu; Leisenring, Wendy; Erard, Veronique; Seo, Sachiko; Kimball, Louise; Corey, Lawrence; Pergam, Steven A; Jerome, Keith R

2017-05-15

Quantitative cytomegalovirus (CMV) DNA-specific polymerase chain reaction (PCR) analysis is widely used as a surveillance method for hematopoietic stem cell transplant (HCT) recipients. However, no CMV DNA threshold exists in bronchoalveolar lavage (BAL) to differentiate pneumonia from pulmonary shedding. We tested archived BAL fluid samples from 132 HCT recipients with CMV pneumonia and 139 controls (100 patients with non-CMV pneumonia, 18 with idiopathic pneumonia syndrome [IPS], and 21 who were asymptomatic) by quantitative CMV and β-globin DNA-specific PCR. Patients with CMV pneumonia had higher median viral loads (3.9 log10 IU/mL; interquartile range [IQR], 2.6-6.0 log10 IU/mL) than controls (0 log10 IU/mL [IQR, 0-1.6 log10 IU/mL] for patients with non-CMV pneumonia, 0 log10 IU/mL [IQR, 0-1.6 log10 IU/mL] for patients with IPS, and 1.63 log10 IU/mL [IQR, 0-2.5 log10 IU/mL] for patients who were asymptomatic; P < .001 for all comparisons to patients with CMV pneumonia). Receiver operating characteristic curve analyses and predictive models identified a cutoff CMV DNA level of 500 IU/mL to differentiate between CMV pneumonia and pulmonary shedding, using current CMV pneumonia prevalence figures. However, different levels may be appropriate in settings of very high or low CMV pneumonia prevalence. The presence of pulmonary copathogens, radiographic presentation, or pulmonary hemorrhage did not alter predictive values. CMV DNA load in BAL can be used to differentiate CMV pneumonia from pulmonary shedding. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Increased pro-angiogenic factors, infiltrating neutrophils and CD163(+) macrophages in bronchoalveolar lavage fluid from lung cancer patients.

PubMed

Chen, Lu; Li, Qian; Zhou, Xiang-dong; Shi, Yu; Yang, Lang; Xu, Sen-lin; Chen, Cong; Cui, You-hong; Zhang, Xia; Bian, Xiu-wu

2014-05-01

Infiltration of inflammatory cells and production of pro-angiogenic factors are important in lung cancer immunity. The distributions of those cells and their contributions to the production of pro-angiogenic factors and the activation phenotype of macrophages in bronchoalveolar lavage fluid (BALF) from lung cancer patients remain unclear. We analyzed the presence of distinct inflammatory cells and the macrophage activation phenotype together with the levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) within BALF from 54 smoking lung cancer patients including 36 squamous cell carcinoma (SCC), 9 adenocarcinoma (AC), and 9 small cell lung cancer (SCLC) in comparison with those from 13 non-smoking and 7 smoking patients with nonspecific chronic inflammation and 8 non-smoking normal controls. We found a significantly lower percentage of total macrophages and a much higher percentage of neutrophils among all inflammatory cells in BALF from lung cancer and non-specific chronic inflammation patients. BALF from AC patients had a significantly higher percentage of lymphocytes. CD163(+)) macrophages predominantly existed in BALF from SCLC patients. BALF of lung cancer patients had markedly higher levels of IL-8 and VEGF. Interestingly, IL-8 level was positively correlated to the numbers of neutrophils and lymphocytes. VEGF level was inversely correlated to the number of lymphocytes but positively to cancer cells in SCC cases, whereas no correlation existed between CD163(+)) macrophages and the levels of IL-8 and VEGF. Our results suggest that the detection of infiltrating inflammatory cells and pro-angiogenic factors in BALF will be helpful for diagnosis of cancerous inflammation in lungs. Copyright © 2014 Elsevier B.V. All rights reserved.

Detection of disease specific sialoglycoconjugate specific antibodies in bronchoalveolar lavage fluid of non-small cell lung cancer patients.

PubMed

Mehta, Sangeeta; Chhetra, Rakhee; Srinivasan, Radhika; Sharma, Suresh C; Behera, Digambar; Ghosh, Sujata

2010-07-01

In this study, we report the presence of significantly higher level of GM3 specific IgG antibodies (IgG(TL)) in the bronchoalveolar lavage fluid obtained from tumor bearing lung of non-small cell lung cancer (NSCLC) patients as compared to other non-neoplastic controls. The antibodies were isolated using DEAE-cellulose anion exchange chromatography and molecular weight of the subunits of IgG(TL) was confirmed in SDS-PAGE. IgG(TL) revealed high specificity to GM3 and the IgG distribution was confined to IgG1. Furthermore, IgG(TL) showed strong reactivity with NSCLC cell lines as well as the tissue biopsies and cells obtained from fine needle aspirations of NSCLC patients. A 66 kDa membrane glycoprotein of NSCLC cell lines was found to interact specifically with IgG(TL), the intensity of which was drastically reduced in presence of GM3. Further, binding of Maackia amurensis agglutinin [specific for NeuAcalpha(2-->3)Gal unit , the same disaccharide unit also known to be present in GM3] to the 66 kDa band confirmed it to be a sialoglycoprotein in nature. IgG(TL) could not show any reactivity to alkaline borohydrate treated or periodate oxidised membrane fractions, suggesting the probable involvement of the carbohydrate moiety of the 66 kDa glycoprotein in the interaction with IgG(TL). Thus, the 66 kDa sialoglycoprotein seems to be the NSCLC specific sialoglycoconjugate. Taken together, IgG(TL) antibodies may have the potential to serve as a unique probe for detail investigation of NSCLC specific cell surface sialoglycoconjugate. Further, due to high specificity of IgG(TL) to GM3, it may be possible to develop a simple alternative diagnostic approach (GM3-ELISA) for NSCLC.

Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

PubMed

Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

2015-12-01

Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

Comparison of bronchoalveolar lavage cytology and transbronchial biopsy in the diagnosis of carcinoma of lung.

PubMed

Ahmed, Ayesha; Ahmed, Sajjad

2004-01-01

The objectives of this study were to compare bronchoalveolar lavage (BAL) cytology and transbronchial biopsy in the diagnosis of carcinoma lung and to determine accuracy of BAL cytology using histopathlologic examination of transbronchial biopsy as gold standard at our center. This study was carried out at Department of Histopathology, Ayub Medical College, Abbottabad, from 1.09.2000 to 28.02.2003. BAL fluid and bronchial biopsy were received and processed simultaneously. Four cytology and a set of histopathology slides were prepared. These were screened and diagnosis recorded. Sensitivity, Specificity, False Positive, False Negative, Positive predictive value and Negative predictive value of BAL cytology were determined using histopathology of transbronchial biopsy as gold standard. We found the sensitivity of BAL cytology to be 93.44% as compared with transbronchial biopsy. The specificity was 100%. There was no false positive while false negative results were 6.55 %. The positive predictive value was 100 %, while the negative predictive value was 75 %. The overall diagnostic efficacy of BAL cytology was 94.52 %. BAL cytology is a highly sensitive and specific test for diagnosis of carcinoma lung. It can be used as a quick and reliable diagnostic method for diagnosis of lung malignancy.

Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis.

PubMed

Tan, Susanna K; Burgener, Elizabeth B; Waggoner, Jesse J; Gajurel, Kiran; Gonzalez, Sarah; Chen, Sharon F; Pinsky, Benjamin A

2016-01-01

Background.  Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods.  Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results.  Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV-positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P ≤ .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions.  Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis.

Correlation of levels of alpha-defensins determined by HPLC-ESI-MS in bronchoalveolar lavage fluid with the diagnosis of pneumonia in premature neonates.

PubMed

Tirone, Chiara; Boccacci, Simona; Inzitari, Rosanna; Tana, Milena; Aurilia, Claudia; Fanali, Chiara; Cabras, Tiziana; Messana, Irene; Castagnola, Massimo; Romagnoli, Costantino; Vento, Giovanni

2010-08-01

The presence of alpha-defensins in bronchoalveolar lavage fluid (BALF) was investigated in a cohort of preterm newborns with gestational age (GA) < or =30 wk. Specimens were collected during the first week of life from 24 preterm neonates mechanically ventilated. The studied population was divided into two groups: pneumonia group of nine neonates suffering from pulmonary infection (GA: 26.1 +/- 2.1 wk; birth weight: 787.4 +/- 309.9 g), with or without associated bloodstream infection, and nonpneumonia group of 15 neonates (GA: 27.7 +/- 2.0 wk; birth weight: 1019.0 +/- 319.8 g). BALF culture was positive for CONS (n = 5), Staphylococcus aureus (n = 1), and Candida spp (n = 3). BALF samples were analyzed by HPLC-electrospray Ionization-mass spectrometer. The alpha-defensins 1-4 concentration, absolute and differential white cells count were measured. Relative amounts of alpha-defensins 1-4 and the absolute number of neutrophils were found significantly higher in the pneumonia group with respect to the nonpneumonia group (p < 0.05). Moreover, positive significant correlations between the number of neutrophils and the alpha-defensins 1-3 levels were observed. In conclusion, our data show that preterm newborns, also at the lower GA, are able to produce alpha-defensins, underlining that their innate defense system is already active before the at-term delivery date.

A Prospective Randomized Study Comparing Manual and Wall Suction in the Performance of Bronchoalveolar Lavage.

PubMed

Seijo, Luis M; Flandes, Javier; Somiedo, Maria V; Naya, Alba; Manjón, Josefina; Álvarez, Susana; Fernández-Navamuel, Iker

2016-01-01

Bronchoalveolar lavage (BAL) may be performed using a hand-held syringe or wall suction. The aim was to study BAL volume and diagnostic yields based on BAL technique. A total of 220 consecutive patients undergoing BAL at our center were included. Manual aspiration was performed in 115 patients (group 1), and wall suction (<50 mm Hg of negative pressure) was used in 105 patients (group 2). All bronchoscopies were performed under conscious sedation applying topical anesthesia with lidocaine. Three 50-ml sterile saline aliquots were instilled in all patients. The mean total amount of fluid recovered was 67 ± 20 ml in group 1 and 55 ± 22 ml in group 2 (p < 0.001). More patients in the manual aspiration group met American Thoracic Society criteria (recovery of ≥30% of instilled fluid) for an optimal BAL (81 vs. 59%; p < 0.001). The quantity of recovered fluid was also related to BAL location (p < 0.001) and radiologic findings (p = 0.002). Forty-eight (22%) BALs were diagnostic (23 in group 1 and 25 in group 2), including 37 positive bacterial cultures, 6 positive stains for Pneumocystis, and 5 cases of malignancy. No statistically significant difference in diagnostic yield was observed between the two groups. A BAL diagnosis was more likely in patients with certain radiologic (p = 0.033) and endoscopic findings (p = 0.001). When taking into account all bronchoscopic techniques performed during the procedure (e.g. biopsies, brushing, etc.), bronchoscopy was diagnostic in 37% of patients. Manual aspiration is superior to wall suction during BAL yielding a larger quantity of aspirate. Diagnostic yields are similar for both techniques. © 2016 S. Karger AG, Basel.

Analysis of bronchoalveolar lavage fluid (Balf) from patients with adult respiratory distress syndrome (ARDS)

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

Henderson, R.F.; Baughman, R.P.; Waide, J.J.

1995-12-01

The pathogenesis of ARDS is largely unknown, but many factors are known to predispose one to ARDS: sepsis, aspiration of gastric contents, pneumonia, fracture, multiple transfusions, cardiopulmonary bypass, burn, dissemination intravascular coagulation, pulmonary contusion, near drowning, and pancreatitis. ARDS is characterized by severe hypoxemia, diffuse pulmonary infiltrates, and decreased pulmonary compliance. Current treatment methods still result in 50% mortality. Studies are underway at the University of Cincinnati to determine if treatment with a synthetic pulmonary surfactant, Exosurf{sup {reg_sign}} (contains dipalmitoyl phosphatidyl choline, Burroughs-Wellcome), improves the prognosis of these patients. BALF from these patients, before and after treatment, was analyzed tomore » determine if the treatment resulted in an increase in disaturated phospholipids (surfactant phospholipids) in the epithelial lining fluid and if the treatments reduced the concentration of markers of inflammation and toxicity in the BALF. This study indicates that the method of administering Exosurf{sup {reg_sign}} did not lead to an increase in surfactant lipid or protein in the bronchoalveolar region of the respiratory tract.« less

Characterization and Comparison of Galactomannan Enzyme Immunoassay and Quantitative Real-Time PCR Assay for Detection of Aspergillus fumigatus in Bronchoalveolar Lavage Fluid from Experimental Invasive Pulmonary Aspergillosis

PubMed Central

Francesconi, Andrea; Kasai, Miki; Petraitiene, Ruta; Petraitis, Vidmantas; Kelaher, Amy M.; Schaufele, Robert; Hope, William W.; Shea, Yvonne R.; Bacher, John; Walsh, Thomas J.

2006-01-01

Bronchoalveolar lavage (BAL) is widely used for evaluation of patients with suspected invasive pulmonary aspergillosis (IPA). However, the diagnostic yield of BAL for detection of IPA by culture and direct examination is limited. Earlier diagnosis may be facilitated by assays that can detect Aspergillus galactomannan antigen or DNA in BAL fluid. We therefore characterized and compared the diagnostic yields of a galactomannan enzyme immunoassay (GM EIA), quantitative real-time PCR (qPCR), and quantitative cultures in experiments using BAL fluid from neutropenic rabbits with experimentally induced IPA defined as microbiologically and histologically evident invasion. The qPCR assay targeted the rRNA gene complex of Aspergillus fumigatus. The GM EIA and qPCR assay were characterized by receiver operator curve analysis. With an optimal cutoff of 0.75, the GM EIA had a sensitivity and specificity of 100% in untreated controls. A decline in sensitivity (92%) was observed when antifungal therapy (AFT) was administered. The optimal cutoff for qPCR was a crossover of 36 cycles, with sensitivity and specificity of 80% and 100%, respectively. The sensitivity of qPCR also decreased with AFT to 50%. Quantitative culture of BAL had a sensitivity of 46% and a specificity of 100%. The sensitivity of quantitative culture decreased with AFT to 16%. The GM EIA and qPCR assay had greater sensitivity than culture in detection of A. fumigatus in BAL fluid in experimentally induced IPA (P ± 0.04). Use of the GM EIA and qPCR assay in conjunction with culture-based diagnostic methods applied to BAL fluid could facilitate accurate diagnosis and more-timely initiation of specific therapy. PMID:16825367

Interrogating Bronchoalveolar Lavage Samples via Exclusion-Based Analyte Extraction.

PubMed

Tokar, Jacob J; Warrick, Jay W; Guckenberger, David J; Sperger, Jamie M; Lang, Joshua M; Ferguson, J Scott; Beebe, David J

2017-06-01

Although average survival rates for lung cancer have improved, earlier and better diagnosis remains a priority. One promising approach to assisting earlier and safer diagnosis of lung lesions is bronchoalveolar lavage (BAL), which provides a sample of lung tissue as well as proteins and immune cells from the vicinity of the lesion, yet diagnostic sensitivity remains a challenge. Reproducible isolation of lung epithelia and multianalyte extraction have the potential to improve diagnostic sensitivity and provide new information for developing personalized therapeutic approaches. We present the use of a recently developed exclusion-based, solid-phase-extraction technique called SLIDE (Sliding Lid for Immobilized Droplet Extraction) to facilitate analysis of BAL samples. We developed a SLIDE protocol for lung epithelial cell extraction and biomarker staining of patient BALs, testing both EpCAM and Trop2 as capture antigens. We characterized captured cells using TTF1 and p40 as immunostaining biomarkers of adenocarcinoma and squamous cell carcinoma, respectively. We achieved up to 90% (EpCAM) and 84% (Trop2) extraction efficiency of representative tumor cell lines. We then used the platform to process two patient BAL samples in parallel within the same sample plate to demonstrate feasibility and observed that Trop2-based extraction potentially extracts more target cells than EpCAM-based extraction.

Clinical impact of methicillin-resistant staphylococcus aureus on bacterial pneumonia: cultivation and 16S ribosomal RNA gene analysis of bronchoalveolar lavage fluid.

PubMed

Kawanami, Toshinori; Yatera, Kazuhiro; Yamasaki, Kei; Noguchi, Shingo; Fukuda, Kazumasa; Akata, Kentarou; Naito, Keisuke; Kido, Takashi; Ishimoto, Hiroshi; Taniguchi, Hatsumi; Mukae, Hiroshi

2016-04-16

Determining whether methicillin-resistant Staphylococcus aureus (MRSA) is a true causative pathogen or reflective of colonization when MRSA is cultured from the respiratory tract remains important in treating patients with pneumonia. We evaluated the bacterial microbiota in bronchoalveolar lavage fluid (BALF) using the clone library method with a 16S ribosomal RNA (rRNA) gene analysis in 42 patients from a pneumonia registry who had MRSA cultured from their sputum or BALF samples. Patients were divided into two groups: those treated with (Group A) or without (Group B) anti-MRSA agents, and their clinical features were compared. Among 248 patients with pneumonia, 42 patients who had MRSA cultured from the respiratory tract were analyzed (Group A: 13 patients, Group B: 29 patients). No clones of S. aureus were detected in the BALF of 20 out of 42 patients. Twenty-eight of 29 patients in Group B showed favorable clinical outcomes, indicating that these patients had non-MRSA pneumonia. Using a microflora analysis of the BALF, the S. aureus phylotype was predominant in 5 of 28 (17.9%) patients among the detected bacterial phylotypes, but a minor population (the percentage of clones ≤ 10%) in 19 (67.9%) of 28 patients. A statistical analysis revealed no positive relationship between the percentage of clones of the S. aureus phylotype and risk factors of MRSA pneumonia. The molecular method using BALF specimens suggests that conventional cultivation method results may mislead true causative pathogens, especially in patients with MRSA pneumonia. Further studies are necessary to elucidate these clinically important issues.

Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways

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

Denner, Darcy R.; Sangwan, Naseer; Becker, Julia B.

The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. OBJECTIVES: We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. METHODS: DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencingmore » was used to compare the relative abundance of bacterial genera with clinical characteristics. RESULTS: Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus, Pseudomonas, and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella, Streptococcus, and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV1 and the proportion of lavage eosinophils. CONCLUSION: The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.« less

Analysis of insulin like growth factor 1 and insulin like growth factor binding protein 3 levels in bronchoalveolar lavage fluid and serum of patients with lung cancer.

PubMed

Unsal, Ebru; Köksal, Deniz; Yurdakul, Ahmet Selim; Atikcan, Sükran; Cinaz, Peyami

2005-05-01

Insulin like growth factor 1 (IGF-1) is recognized as a potent mitogen for many cancer cell lines and there is good evidence that lung cancer cells produce both IGF-1 and insulin like growth factor binding protein 3 (IGFBP-3). The aim of this study was to investigate the clinical significance of IGF-1 and IGFBP-3 levels in serum and in bronchoalveolar lavage (BAL) fluid by comparing lung cancer patients with healthy controls. BAL fluid and serum samples were obtained from 24 lung cancer patients and 12 healthy controls, and were analyzed for IGF-1 and IGFBP-3 levels by a two site immunoradiometric assay. The recovered BAL fluid was standardized by albumin to remove the variable of dilution and the data was expressed in epithelial lining fluid (ELF). Serum IGF-1 and IGFBP-3 levels were lower in lung cancer patients, but the difference between the groups did not reach a statistical significance. IGF-1/IGFBP-3 ratio in ELF was significantly lower in lung cancer patients (P=0.035). Mean IGF-1 level in ELF was determined to be significantly lower in patients with distant metastasis (P=0.04). Serum IGF-1/IGFBP-3 ratio was found to be significantly lower in patients with distant (P=0.04) and nodal metastasis (P=0.03). Tumor stage was negatively correlated with IGF-1 level in ELF (P=0.05, r=-0.4) and serum IGF-1/IGFBP-3 ratio (P=0.04, r=-0.4). IGF-1 and IGFBP-3 levels both in serum and ELF might serve a clinical significance in patients with lung cancer. However, further studies comprising more cases are needed to investigate the clinical significance of IGF-1 and IGFBP-3 in lung cancer.

Effect of a syringe aspiration technique versus a mechanical suction technique and use of N-butylscopolammonium bromide on the quantity and quality of bronchoalveolar lavage fluid samples obtained from horses with the summer pasture endophenotype of equine asthma.

PubMed

Bowser, Jacquelyn E; Costa, Lais R R; Rodil, Alba U; Lopp, Christine T; Johnson, Melanie E; Wills, Robert W; Swiderski, Cyprianna E

2018-03-01

OBJECTIVE To evaluate the effect of 2 bronchoalveolar lavage (BAL) sampling techniques and the use of N-butylscopolammonium bromide (NBB) on the quantity and quality of BAL fluid (BALF) samples obtained from horses with the summer pasture endophenotype of equine asthma. ANIMALS 8 horses with the summer pasture endophenotype of equine asthma. PROCEDURES BAL was performed bilaterally (right and left lung sites) with a flexible videoendoscope passed through the left or right nasal passage. During lavage of the first lung site, a BALF sample was collected by means of either gentle syringe aspiration or mechanical suction with a pressure-regulated wall-mounted suction pump. The endoscope was then maneuvered into the contralateral lung site, and lavage was performed with the alternate fluid retrieval technique. For each horse, BAL was performed bilaterally once with and once without premedication with NBB (21-day interval). The BALF samples retrieved were evaluated for volume, total cell count, differential cell count, RBC count, and total protein concentration. RESULTS Use of syringe aspiration significantly increased total BALF volume (mean volume increase, 40 mL [approx 7.5% yield]) and decreased total RBC count (mean decrease, 142 cells/μL), compared with use of mechanical suction. The BALF nucleated cell count and differential cell count did not differ between BAL procedures. Use of NBB had no effect on BALF retrieval. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that retrieval of BALF by syringe aspiration may increase yield and reduce barotrauma in horses at increased risk of bronchoconstriction and bronchiolar collapse. Further studies to determine the usefulness of NBB and other bronchodilators during BAL procedures in horses are warranted.

Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage fluids as early detection of acute GVHD following BMT: evidence of a significant relationship.

PubMed

Takemoto, Y; Takatsuka, H; Wada, H; Mori, A; Saheki, K; Okada, M; Tamura, S; Fujimori, Y; Okamoto, T; Kakishita, E; Kanamaru, A

2000-07-01

We evaluated the relationship between CMV and human herpes virus-6 (HHV-6) reactivation and the incidence of grades 2 to 4 acute GVHD post BMT. Bronchoalveolar lavage fluid (BALF) samples extracted from 54 BMT recipients on post-BMT day 35 were analyzed by PCR for detection of CMV DNA, HHV-6 DNA and CMV plus HHV-6 DNA. CMV DNA was detected in 26 patients and 13 (50%) developed grades 2 to 4 acute GVHD. Of the 28 who were CMV negative, only six (21.4%) developed grades 2 to 4 acute GVHD. HHV-6 was detected in 18 patients, and 11 (61.1%) developed grades 2 to 4 acute GVHD. Of the 36 who were HHV-6 negative, only eight (22.2%) developed grades 2 to 4 acute GVHD. CMV and HHV-6 were detected in 13 patients, and eight (61.5%) developed grades 2 to 4 acute GVHD. Of the 23 who were negative for both CMV and HHV-6, only three (13%) developed grades 2 to 4 acute GVHD. In all experiments, the difference between the groups was significant (P<0.05, P<0.05 and P<0.01, respectively). We conclude that herpes virus infection, in particular CMV concurrent with HHV-6 reactivation, is predictive of moderate to severe acute GVHD.

Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey

PubMed Central

Tanriverdi, Hakan; Erboy, Fatma; Altinsoy, Bulent; Uygur, Firat; Arasli, Mehmet; Ozel Tekin, Ishak; Tor, Muge Meltem; Atalay, Figen

2015-01-01

Background: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs. Objectives: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort. Patients and Methods: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups. Results: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16+56+, CD103+, CD8+103+, and CD3+16+56+ cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0

Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

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

Line, B.R.; Hunninghake, G.W.; Keogh, B.A.

1981-04-01

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, we studied 41 patients with this disorder and correlated estimates of pulmonary 67Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of 67Ga accumulation in the lung compared with control subjects, only weak correlations (r lessmore » than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of 67Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because 67Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.« less

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and β-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis

PubMed Central

Urabe, Naohisa; Sano, Go; Suzuki, Junko; Hebisawa, Akira; Nakamura, Yasuhiko; Koyama, Kazuya; Ishii, Yoshikazu; Tateda, Kazuhiro; Homma, Sakae

2017-01-01

ABSTRACT We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a β-d-glucan (βDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and βDG testing of BALF, respectively. The sensitivity and specificity of the GM test, βDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and βDG tests had the highest diagnostic odds ratio. The combination of the GM and βDG tests on BALF was more useful than any single test for diagnosing CPA. PMID:28330887

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and β-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis.

PubMed

Urabe, Naohisa; Sakamoto, Susumu; Sano, Go; Suzuki, Junko; Hebisawa, Akira; Nakamura, Yasuhiko; Koyama, Kazuya; Ishii, Yoshikazu; Tateda, Kazuhiro; Homma, Sakae

2017-06-01

We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a β-d-glucan (βDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and βDG testing of BALF, respectively. The sensitivity and specificity of the GM test, βDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and βDG tests had the highest diagnostic odds ratio. The combination of the GM and βDG tests on BALF was more useful than any single test for diagnosing CPA. Copyright © 2017 American Society for Microbiology.

Ultrastructural examination of broncho-alveolar lavage for diagnosis of pulmonary histiocytosis X: Preliminary report on 4 cases.

PubMed Central

Basset, F; Soler, P; Jaurand, M C; Bignon, J

1977-01-01

Fibreoptic broncho-alveolar lavage was used in four patients; the diagnosis of histiocytosis X had been established by lung biopsy in three and was suggested on clinical grounds in the remaining patient. Characteristic cells with an ultrastructural cytoplasmic marker (X body) were found in the washes of all four patients. In the patient without biopsy confirmation, the findings in the broncho-aleolar washes supplied the corroborating evidence for the diagnosis. From this preliminary study the technique seems able to provide a diagnosis in pulmonary histiocytosis X without the need for an open lung biopsy. Images PMID:302040

Comparison of the diagnostic performance of bacterial culture of nasopharyngeal swab and bronchoalveolar lavage fluid samples obtained from calves with bovine respiratory disease.

PubMed

Capik, Sarah F; White, Brad J; Lubbers, Brian V; Apley, Michael D; DeDonder, Keith D; Larson, Robert L; Harhay, Greg P; Chitko-McKown, Carol G; Harhay, Dayna M; Kalbfleisch, Ted S; Schuller, Gennie; Clawson, Michael L

2017-03-01

OBJECTIVE To compare predictive values, extent of agreement, and gamithromycin susceptibility between bacterial culture results of nasopharyngeal swab (NPS) and bronchoalveolar lavage fluid (BALF) samples obtained from calves with bovine respiratory disease (BRD). ANIMALS 28 beef calves with clinical BRD. PROCEDURES Pooled bilateral NPS samples and BALF samples were obtained for bacterial culture from calves immediately before and at various times during the 5 days after gamithromycin (6 mg/kg, SC, once) administration. For each culture-positive sample, up to 12 Mannheimia haemolytica, 6 Pasteurella multocida, and 6 Histophilus somni colonies underwent gamithromycin susceptibility testing. Whole-genome sequencing was performed on all M haemolytica isolates. For paired NPS and BALF samples collected 5 days after gamithromycin administration, the positive and negative predictive values for culture results of NPS samples relative to those of BALF samples and the extent of agreement between the sampling methods were determined. RESULTS Positive and negative predictive values of NPS samples were 67% and 100% for M haemolytica, 75% and 100% for P multocida, and 100% and 96% for H somni. Extent of agreement between results for NPS and BALF samples was substantial for M haemolytica (κ, 0.71) and H somni (κ, 0.78) and almost perfect for P multocida (κ, 0.81). Gamithromycin susceptibility varied within the same sample and between paired NPS and BALF samples. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated culture results of NPS and BALF samples from calves with BRD should be interpreted cautiously considering disease prevalence within the population, sample collection relative to antimicrobial administration, and limitations of diagnostic testing methods.

Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.

PubMed

Theron, Grant; Peter, Jonny; Meldau, Richard; Khalfey, Hoosain; Gina, Phindile; Matinyena, Brian; Lenders, Laura; Calligaro, Gregory; Allwood, Brian; Symons, Gregory; Govender, Ureshnie; Setshedi, Mashiko; Dheda, Keertan

2013-11-01

The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (∼10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18-41) to 0 (0-0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1-49) versus 7 (0-21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.

Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid

PubMed Central

Theron, Grant; Peter, Jonny; Meldau, Richard; Khalfey, Hoosain; Gina, Phindile; Matinyena, Brian; Lenders, Laura; Calligaro, Gregory; Allwood, Brian; Symons, Gregory; Govender, Ureshnie; Setshedi, Mashiko; Dheda, Keertan

2017-01-01

Rationale The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. Methods South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (~10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. Results 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18–41) to 0 (0–0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1–49) versus 7 (0–21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. Conclusions MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment. PMID:23811536

Diagnostic value of sTREM-1 in bronchoalveolar lavage fluid in ICU patients with bacterial lung infections: a bivariate meta-analysis.

PubMed

Shi, Jia-Xin; Li, Jia-Shu; Hu, Rong; Li, Chun-Hua; Wen, Yan; Zheng, Hong; Zhang, Feng; Li, Qin

2013-01-01

The serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a useful biomarker in differentiating bacterial infections from others. However, the diagnostic value of sTREM-1 in bronchoalveolar lavage fluid (BALF) in lung infections has not been well established. We performed a meta-analysis to assess the accuracy of sTREM-1 in BALF for diagnosis of bacterial lung infections in intensive care unit (ICU) patients. We searched PUBMED, EMBASE and Web of Knowledge (from January 1966 to October 2012) databases for relevant studies that reported diagnostic accuracy data of BALF sTREM-1 in the diagnosis of bacterial lung infections in ICU patients. Pooled sensitivity, specificity, and positive and negative likelihood ratios were calculated by a bivariate regression analysis. Measures of accuracy and Q point value (Q*) were calculated using summary receiver operating characteristic (SROC) curve. The potential between-studies heterogeneity was explored by subgroup analysis. Nine studies were included in the present meta-analysis. Overall, the prevalence was 50.6%; the sensitivity was 0.87 (95% confidence interval (CI), 0.72-0.95); the specificity was 0.79 (95% CI, 0.56-0.92); the positive likelihood ratio (PLR) was 4.18 (95% CI, 1.78-9.86); the negative likelihood ratio (NLR) was 0.16 (95% CI, 0.07-0.36), and the diagnostic odds ratio (DOR) was 25.60 (95% CI, 7.28-89.93). The area under the SROC curve was 0.91 (95% CI, 0.88-0.93), with a Q* of 0.83. Subgroup analysis showed that the assay method and cutoff value influenced the diagnostic accuracy of sTREM-1. BALF sTREM-1 is a useful biomarker of bacterial lung infections in ICU patients. Further studies are needed to confirm the optimized cutoff value.

A Comparison of Aspergillus and Mucorales PCR Testing of Different Bronchoalveolar Lavage Fluid Fractions from Patients with Suspected Invasive Pulmonary Fungal Disease.

PubMed

Springer, Jan; White, P Lewis; Kessel, Johanna; Wieters, Imke; Teschner, Daniel; Korczynski, Daniel; Liebregts, Tobias; Cornely, Oliver A; Schwartz, Stefan; Elgeti, Thomas; Meintker, Lisa; Krause, Stefan W; Posso, Raquel B; Heinz, Werner J; Fuhrmann, Sandra; Vehreschild, Jörg Janne; Einsele, Hermann; Rickerts, Volker; Loeffler, Juergen

2018-02-01

In patients with hematological malignancies, bronchoalveolar lavage fluid (BALF) specimens are commonly used for the diagnosis of mold infections. However, it is not clear whether the cell pellet (P) or the supernatant fraction (S) of the BALF specimen is optimal for molecular diagnostic testing. Thus, 99 BALF specimens were collected from 96 hematology patients with or without allogeneic hematopoietic stem cell transplant. The cell pellets and supernatants were processed alone and in combination (S/P) for testing by two fungus-specific real-time PCR assays compliant with international recommendations. The results achieved with S/P were revealed to be superior in comparison to those achieved with S and P alone, with the use of each single fraction showing a reduced sensitivity for the detection of Aspergillus DNA (82% and 43% for S and P, respectively). In 57% of the samples, testing of the combination of S and P generated a lower quantification cycle value than testing of S or P alone. Molds would have been missed in 5 and 16 out of 28 samples if only S or P, respectively, was analyzed. No sample was positive by testing of S or P only. Similar results were obtained for the detection of Mucorales DNA in BALF specimens (reduced sensitivity of 67% and 50% for S and P, respectively). Study patients were categorized according to the current European Organization for the Research and Treatment of Cancer/Mycoses Study Group classification for invasive fungal disease (IFD), revealing that 35 patients had proven/probable IFD (36%), 47 patients had possible IFD (49%), and 14 patients had undetermined IFD (15%). Copyright © 2018 American Society for Microbiology.

Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

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

Line, B.R.; Hunninghake, G.W.; Keogh, B.A.

1981-04-01

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, researchers studied 41 patients with this disorder and correlated estimates of pulmonary /sup 67/Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of /sup 67/Ga accumulation in the lung compared with control subjects, only weak correlationsmore » (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of /sup 67/Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because /sup 67/Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.« less

DNA Methylation Analysis of the SHOX2 and RASSF1A Panel in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

PubMed Central

Zhang, Chenzi; Yu, Wenjun; Wang, Lin; Zhao, Mingna; Guo, Qiaomei; Lv, Shaogang; Hu, Xiaomeng; Lou, Jiatao

2017-01-01

Introduction: Currently the majority of lung cancer patients are diagnosed as advanced diseases for no sensitive and specific biomarkers exist, noninvasive biomarkers with high sensitivity and specificity are urgently needed in lung cancer diagnosis. Bronchoscopy is a standard procedure of the diagnostic work-up of patients with suspected lung cancer despite of the limited diagnostic accuracy. Besides, epigenetic changes through DNA methylation play an important role in tumorigenesis. Thus, we examined the aberrant methylation of the SHOX2 and RASSF1A in bronchoalveolar lavage fluid (BALF) in comparing with conventional cytology examination and serum CEA in order to evaluate the new diagnostic method. Patients and Methods: BALF and serum samples were collected from 322 patients at the time of diagnosis, 284 of them were pathologically confirmed lung cancer, 35 were benign lung diseases and 3 were malignancies in other systems. For all of the 322 patients, the methylation status of the SHOX2 and RASSF1A gene were detected by a new RT-PCR platform and then confirmed by sanger sequencing. Serum CEA were detected using electrochemiluminescence immunoassay. Results: Profiling data showed the consistency of RT-PCR and sanger sequencing in detecting the methylation of the SHOX2 and RASSF1A. Besides, the combination of SHOX2 and RASSF1A methylation in BALF yielded a diagnostic sensitivity of 81.0% and specificity of 97.4%. When compared with established cytology examination (sensitivity: 68.3%, specificity: 97.4%) and serum biomarker carcinoembryonic antigen (CEA) (sensitivity: 30.6%, specificity: 100.0%), the SHOX2 and RASSF1A methylation panel showed the highest diagnostic efficiency. Notably, the combination of cytology and the SHOX2 and RASSF1A methylation panel could significantly improve the diagnostic efficacy. Conclusion: The methylation analysis of the SHOX2 and RASSF1A panel in BALF with RT-PCR achieved a satisfactory sensitivity and specificity in lung cancer

Inflammatory and Repair Pathways Induced in Human Bronchoalveolar Lavage Cells with Ozone Inhalation

PubMed Central

Wong, Hofer; Tenney, Rachel; Chen, Chun; Stiner, Rachel; Balmes, John R.; Paquet, Agnès C.; Arjomandi, Mehrdad

2015-01-01

Background Inhalation of ambient levels of ozone causes airway inflammation and epithelial injury. Methods To examine the responses of airway cells to ozone-induced oxidative injury, 19 subjects (7 with asthma) were exposed to clean air (0ppb), medium (100ppb), and high (200ppb) ambient levels of ozone for 4h on three separate occasions in a climate-controlled chamber followed by bronchoscopy with bronchoalveolar lavage (BAL) 24h later. BAL cell mRNA expression was examined using Affymetrix GeneChip Microarray. The role of a differentially expressed gene (DEG) in epithelial injury was evaluated in an in vitro model of injury [16HBE14o- cell line scratch assay]. Results Ozone exposure caused a dose-dependent up-regulation of several biologic pathways involved in inflammation and repair including chemokine and cytokine secretion, activity, and receptor binding; metalloproteinase and endopeptidase activity; adhesion, locomotion, and migration; and cell growth and tumorigenesis regulation. Asthmatic subjects had 1.7- to 3.8-fold higher expression of many DEGs suggestive of increased proinflammatory and matrix degradation and remodeling signals. The most highly up-regulated gene was osteopontin, the protein level of which in BAL fluid increased in a dose-dependent manner after ozone exposure. Asthmatic subjects had a disproportionate increase in non-polymerized osteopontin with increasing exposure to ozone. Treatment with polymeric, but not monomeric, osteopontin enhanced the migration of epithelial cells and wound closure in an α9β1 integrin-dependent manner. Conclusions Expression profiling of BAL cells after ozone exposure reveals potential regulatory genes and pathways activated by oxidative stress. One DEG, osteopontin, promotes epithelial wound healing in an in vitro model of injury. PMID:26035830

Technical considerations and precautions in in situ bronchoalveolar lavage and alveolar infiltrating cells isolation in rats.

PubMed

Qamar, Wajhul

2015-01-01

Bronchoalveolar lavage fluid (BALF) is an important tool in experimental toxicology and pharmacology. A number of researchers have utilized BAL in studies involving rodents. However, the detailed procedure of performing BAL in rodents has rarely been reported. In the present article, in situ BAL in rats has been described with technical points that ensure the quality and validity of BALF samples. BAL was performed in rats of Wistar strain. Flow cytometry and microscopy were utilized to analyze the BAL cells. The collected volume of BALF was 84.32 ± 2.7% of instilled volume. Alveolar macrophages were found to be prevalent in normal lungs when analyzed under microscope and by flow cytometry. The main problem that one may face is the accidental contamination of BALF samples with blood of the animal itself. Presence of blood in BALF certainly adds a significant number of cells and other biochemical variables. No blood contamination was detected in BALF. Here, a simple procedure for BAL and collection of alveolar cells (macrophages in the present study) is explained with an emphasis on technical steps and precautions, which ensures the quality of the BALF samples. Data exhibit that there is no blood contamination in the BALF and provide evidence that the technical points considered in the procedure here are successful in maintaining the quality and validity of BALF samples.

Evaluation of a multiplex real-time PCR for detection of four bacterial agents commonly associated with bovine respiratory disease in bronchoalveolar lavage fluid.

PubMed

Wisselink, Henk J; Cornelissen, Jan B W J; van der Wal, Fimme J; Kooi, Engbert A; Koene, Miriam G; Bossers, Alex; Smid, Bregtje; de Bree, Freddy M; Antonis, Adriaan F G

2017-07-13

Pasteurella multocida, Mannheimia haemolytica, Histophilus somni and Trueperella pyogenes are four bacterial agents commonly associated with bovine respiratory disease (BRD). In this study a bacterial multiplex real-time PCR (the RespoCheck PCR) was evaluated for the detection in bronchoalveolar lavage fluid (BALF) of these four bacterial agents. The analytical sensitivity of the multiplex real-time PCR assay determined on purified DNA and on bacterial cells of the four target pathogens was one to ten fg DNA/assay and 4 × 10 -1 to 2 × 10 0  CFU/assay. The analytical specificity of the test was, as evaluated on a collection of 118 bacterial isolates, 98.3% for M. haemolytica and 100% for the other three target bacteria. A set of 160 BALF samples of calves originating from ten different herds with health problems related to BRD was examined with bacteriological methods and with the RespoCheck PCR. Using bacteriological examination as the gold standard, the diagnostic sensitivities and specificities of the four bacterial agents were respectively between 0.72 and 1.00 and between 0.70 and 0.99. Kappa values for agreement between results of bacteriological examination and PCRs were low for H. somni (0.17), moderate for P. multocida (0.52) and M. haemolytica (0.57), and good for T. pyogenes (0.79). The low and moderate kappa values seemed to be related to limitations of the bacteriological examination, this was especially the case for H. somni. It was concluded that the RespoCheck PCR assay is a valuable diagnostic tool for the simultaneous detection of the four bacterial agents in BALF of calves.

Detection and identification of Toxocara canis DNA in bronchoalveolar lavage of infected mice using a novel real-time PCR.

PubMed

Pinelli, E; Roelfsema, J H; Brandes, S; Kortbeek, T

2013-04-15

Toxocarosis is a zoonosis with worldwide distribution caused by Toxocara spp. of dogs and cats. In humans, diagnosis relies mainly on detection of parasite-specific antibodies. Although serological assays in current use have defined sensitivity and specificity, the problem of cross-reactivity still remains, particularly in areas of endemic polyparasitism. Microscopic detection of the parasite in tissue biopsies is not recommended for diagnosis because larvae can be difficult to locate, and finding the parasite eggs in faeces is not applicable since the larvae do not develop to the adult stage in the human host. In this study we describe a novel real-time PCR ('Nemo-PCR') that, in combination with DNA sequencing, allows the detection and identification of Toxocara canis and other nematodes in the Superfamily Ascaridoidea. Results indicate that this approach can detect Toxocara spp. DNA in bronchoalveolar lavage (BAL) of experimentally-infected mice. For diagnostic purposes further studies are necessary to evaluate this assay including testing human BAL fluid. The availability of such a direct assay would improve diagnosis of toxocarosis particularly for patients with pulmonary signs and symptoms. Copyright © 2013. Published by Elsevier B.V.

Detection of Bacterial Pathogens from Broncho-Alveolar Lavage by Next-Generation Sequencing.

PubMed

Leo, Stefano; Gaïa, Nadia; Ruppé, Etienne; Emonet, Stephane; Girard, Myriam; Lazarevic, Vladimir; Schrenzel, Jacques

2017-09-20

The applications of whole-metagenome shotgun sequencing (WMGS) in routine clinical analysis are still limited. A combination of a DNA extraction procedure, sequencing, and bioinformatics tools is essential for the removal of human DNA and for improving bacterial species identification in a timely manner. We tackled these issues with a broncho-alveolar lavage (BAL) sample from an immunocompromised patient who had developed severe chronic pneumonia. We extracted DNA from the BAL sample with protocols based either on sequential lysis of human and bacterial cells or on the mechanical disruption of all cells. Metagenomic libraries were sequenced on Illumina HiSeq platforms. Microbial community composition was determined by k-mer analysis or by mapping to taxonomic markers. Results were compared to those obtained by conventional clinical culture and molecular methods. Compared to mechanical cell disruption, a sequential lysis protocol resulted in a significantly increased proportion of bacterial DNA over human DNA and higher sequence coverage of Mycobacterium abscessus , Corynebacterium jeikeium and Rothia dentocariosa , the bacteria reported by clinical microbiology tests. In addition, we identified anaerobic bacteria not searched for by the clinical laboratory. Our results further support the implementation of WMGS in clinical routine diagnosis for bacterial identification.

[Microbiology of bronchoalveolar lavage in infants with bacterial community-acquired pneumonia with poor outcome].

PubMed

García-Elorriaga, Guadalupe; Palma-Alaniz, Laura; García-Bolaños, Carlos; Ruelas-Vargas, Consuelo; Méndez-Tovar, Socorro; Del Rey-Pineda, Guillermo

Community-acquired pneumonia (CAP) is one of the most common infectious causes of morbidity and mortality in children <5 years of age. The aim of the study was to clarify the bacterial etiologic diagnosis in infants with CAP. A prospective, cross-sectional and descriptive study in patients 6 months to 2 years 11 months of age with CAP with poor outcome was conducted. Patients were admitted to the Pediatric Pneumology Service and underwent bronchoscopy with bronchoalveolar lavage (BAL), taking appropriate measures during the procedure to limit the risk of contamination. Aerobic bacteria isolated were Moraxella sp. 23%, Streptococcus mitis 23%, Streptococcus pneumoniae 18%, Haemophilus influenzae 12%, Streptococcus oralis 12%, and Streptococcus salivarius 12%. In contrast to other reports, we found Moraxella sp. to be a major bacterial pathogen, possibly because of improved detection with bronchoscopy plus BAL. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Gene Expression Profiling of Bronchoalveolar Lavage Cells During Aspergillus Colonization of the Lung Allograft.

PubMed

Weigt, S Samuel; Wang, Xiaoyan; Palchevskiy, Vyacheslav; Patel, Naman; Derhovanessian, Ariss; Shino, Michael Y; Sayah, David M; Lynch, Joseph P; Saggar, Rajan; Ross, David J; Kubak, Bernie M; Ardehali, Abbas; Palmer, Scott; Husain, Shahid; Belperio, John A

2018-06-01

Aspergillus colonization after lung transplant is associated with an increased risk of chronic lung allograft dysfunction (CLAD). We hypothesized that gene expression during Aspergillus colonization could provide clues to CLAD pathogenesis. We examined transcriptional profiles in 3- or 6-month surveillance bronchoalveolar lavage fluid cell pellets from recipients with Aspergillus fumigatus colonization (n = 12) and without colonization (n = 10). Among the Aspergillus colonized, we also explored profiles in those who developed CLAD (n = 6) or remained CLAD-free (n = 6). Transcription profiles were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression was based on an absolute fold difference of 2.0 or greater and unadjusted P value less than 0.05. We used NIH Database for Annotation, Visualization and Integrated Discovery for functional analyses, with false discovery rates less than 5% considered significant. Aspergillus colonization was associated with differential expression of 489 probe sets, representing 404 unique genes. "Defense response" genes and genes in the "cytokine-cytokine receptor" Kyoto Encyclopedia of Genes and Genomes pathway were notably enriched in this list. Among Aspergillus colonized patients, CLAD development was associated with differential expression of 69 probe sets, representing 64 unique genes. This list was enriched for genes involved in "immune response" and "response to wounding", among others. Notably, both chitinase 3-like-1 and chitotriosidase were associated with progression to CLAD. Aspergillus colonization is associated with gene expression profiles related to defense responses including cytokine signaling. Epithelial wounding, as well as the innate immune response to chitin that is present in the fungal cell wall, may be key in the link between Aspergillus colonization and CLAD.

Bronchoalveolar lavage with diluted porcine surfactant in mechanically ventilated term infants with meconium aspiration syndrome.

PubMed

Lista, Gianluca; Bianchi, Silvia; Castoldi, Francesca; Fontana, Paola; Cavigioli, Francesco

2006-01-01

To evaluate the efficacy and safety of bronchoalveolar lavage (BAL) with diluted porcine surfactant in mechanically ventilated term infants with severe acute respiratory distress syndrome (ARDS) due to meconium aspiration syndrome (MAS). Eight consecutive mechanically ventilated term infants with severe ARDS due to MAS underwent BAL with 15 mL/kg of diluted (5.3mg phospholipid/mL) surfactant saline suspension (porcine surfactant [Curosurf]). Treatment was administered slowly in aliquots of 2.5 mL. The mean age of neonates at treatment was 3.5 (range 1-8) hours. Heart rate, systemic blood pressure and oxygen saturation were monitored continuously. Arterial blood gases were measured immediately before treatment, and again at 3 and 6 hours post-treatment. Chest x-rays were taken 6 and 24 hours after treatment. Radiological improvement was evident in all eight patients 6 hours post-treatment. Compared with pre-BAL values, significant improvements (p < 0.05) in mean values for partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, arterial/alveolar O2 ratio and oxygenation index were documented at 3 and 6 hours after BAL. In all patients, tracheal fluids that had been meconium-stained prior to BAL were clear of meconium after BAL. Only one patient required nitric oxide therapy for transient pulmonary hypertension. No adverse sequelae of treatment occurred during the study. BAL with dilute porcine surfactant administered slowly in 2.5 mL aliquots improved oxygenation and chest x-ray findings, without causing major adverse effects, in mechanically ventilated term infants with ARDS due to MAS.

Patients referred to an indoor air health clinic: exposure to water-damaged buildings causes an increase of lymphocytes in bronchoalveolar lavage and a decrease of CD19 leucocytes in peripheral blood.

PubMed

Wolff, Henrik; Mussalo-Rauhamaa, Helena; Raitio, Hanna; Elg, Peter; Orpana, Arto; Piilonen, Anneli; Haahtela, Tari

2009-01-01

Respiratory and other symptoms are often associated with exposure to microbes present in water-damaged buildings. We examined 82 consecutive patients referred to the Indoor Air Clinic, Helsinki University Hospital, due to symptoms suspected of having been caused by long-term exposure to water damage in the home or workplace. Exposure to water damage was assessed by building inspections and microbial analyses as needed. Bronchoalveolar lavage, lung function measurements, skin prick tests to inhalant allergens and radiological examinations were performed in all patients. Leucocyte subsets in peripheral blood were analysed in 35 patients. Marked water damage was detected in the homes or workplaces of 47 (59%) patients; the remaining 34 patients formed the control group. The exposed group expressed more symptoms in total than the control group: fatigue, conjunctival symptoms, rhinitis with sinusitis, recurrent bronchitis and asthma were more common in the exposed group, but a significant difference was seen only for headache. In BAL (bronchoalveolar lavage) samples, lymphocytes represented 25% of the total cell population in non-smoking-exposed patients compared with 12% in control patients (p=0.004). In peripheral blood, CD19 leucocytes were significantly decreased in the exposed group (7.5% versus 12.3%; p<0.01). Confirmed exposure to water damage was associated with an increase in symptoms. Exposure to water damage caused a significant change in the cellular composition in BAL fluid (lymphocytosis) and blood (decrease of CD19 cells). The depletion of CD19 leucocytes in peripheral blood may indicate an active immune response in the lungs.

Design of a multi-center immunophenotyping analysis of peripheral blood, sputum and bronchoalveolar lavage fluid in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

PubMed

Freeman, Christine M; Crudgington, Sean; Stolberg, Valerie R; Brown, Jeanette P; Sonstein, Joanne; Alexis, Neil E; Doerschuk, Claire M; Basta, Patricia V; Carretta, Elizabeth E; Couper, David J; Hastie, Annette T; Kaner, Robert J; O'Neal, Wanda K; Paine, Robert; Rennard, Stephen I; Shimbo, Daichi; Woodruff, Prescott G; Zeidler, Michelle; Curtis, Jeffrey L

2015-01-27

Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multi-center longitudinal, observational study to identify novel phenotypes and biomarkers of chronic obstructive pulmonary disease (COPD). In a subset of 300 subjects enrolled at six clinical centers, we are performing flow cytometric analyses of leukocytes from induced sputum, bronchoalveolar lavage (BAL) and peripheral blood. To minimize several sources of variability, we use a "just-in-time" design that permits immediate staining without pre-fixation of samples, followed by centralized analysis on a single instrument. The Immunophenotyping Core prepares 12-color antibody panels, which are shipped to the six Clinical Centers shortly before study visits. Sputum induction occurs at least two weeks before a bronchoscopy visit, at which time peripheral blood and bronchoalveolar lavage are collected. Immunostaining is performed at each clinical site on the day that the samples are collected. Samples are fixed and express shipped to the Immunophenotyping Core for data acquisition on a single modified LSR II flow cytometer. Results are analyzed using FACS Diva and FloJo software and cross-checked by Core scientists who are blinded to subject data. Thus far, a total of 152 sputum samples and 117 samples of blood and BAL have been returned to the Immunophenotyping Core. Initial quality checks indicate useable data from 126 sputum samples (83%), 106 blood samples (91%) and 91 BAL samples (78%). In all three sample types, we are able to identify and characterize the activation state or subset of multiple leukocyte cell populations (including CD4+ and CD8+ T cells, B cells, monocytes, macrophages, neutrophils and eosinophils), thereby demonstrating the validity of the antibody panel. Our study design, which relies on bi-directional communication between clinical centers and the Core according to a pre-specified protocol, appears to reduce several sources of variability often seen in flow cytometric

IL-11 and CCL-1: Novel Protein Diagnostic Biomarkers of Lung Adenocarcinoma in Bronchoalveolar Lavage Fluid (BALF).

PubMed

Pastor, Maria Delores; Nogal, Ana; Molina-Pinelo, Sonia; Quintanal-Villalonga, Álvaro; Meléndez, Ricardo; Ferrer, I; Romero-Romero, Beatrice; De Miguel, Maria José; López-Campos, José Luis; Corral, Jesús; García-Carboner, Rocío; Carnero, Amancio; Paz-Ares, Luis

2016-12-01

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are smoking-related diseases, with the presence of COPD itself increasing the risk for development of LC, probably owing to underlying inflammation. LC is typically detected at late stages of the disease and carries a poor prognosis. There is an unmet need for methods to facilitate the early detection of LC in high-risk subjects such as smokers. The expression of inflammatory proteins in bronchoalveolar lavage fluid (BALF) samples was studied by antibody arrays in a prospective cohort of 60 smokers of more than 30 pack-years divided into four groups (control, patients with LC, patients with COPD, and patients with LC plus COPD). Relevant biomarkers were validated by Western blot. Additional validation with enzyme-linked immunosorbent assay (ELISA) was carried out on two independent controlled cohorts of 139 patients (control, patients with LC, patients with COPD, and patients with LC plus COPD) and 160 patients (control and patients with LC of all histological types). A total of 16 differentially expressed proteins in samples from patients with LC, COPD, and LC plus COPD were identified by antibody arrays and validated by Western blot and ELISA. C-C motif chemokine ligand 1 (CCL-1) and interleukin-11 (IL)-11 were selectively expressed in samples from patients with adenocarcinoma with or without COPD (p < 0.005). These proteins exhibited a remarkable diagnostic performance for lung adenocarcinoma in an independent cohort of 139 patients. Receiver operating characteristic curves showed that the optimum diagnostic cutoff value for IL-11 was 42 pg/mL (area under the curve = 0.93 [95% confidence interval: 0.896-0.975], sensitivity 90%, specificity 86%), whereas for CCL-1 it was 39.5 pg/mL (0.83 [95% confidence interval: 0.749-0.902], sensitivity 83%, and specificity 74%). Further validation of the ELISA biomarkers at the aforementioned cutoffs was performed in an additional cohort of 160 patients (20

Gene mutation analysis in non-small cell lung cancer patients using bronchoalveolar lavage fluid and tumor tissue as diagnostic markers.

PubMed

Li, Jian; Hu, Yi-Ming; Wang, Yi; Tang, Xing-Ping; Shi, Wei-Lin; Du, Yong-Jie

2014-12-09

Non-small cell lung cancer (NSCLC) is one of the main causes of cancer death in the world. Early detection of NSCLC can improve its outcome. The aim of this study was to identify the mutations of the KRAS and p53 genes in bronchoalveoar lavage (BAL) fluid for the early detection of peripheral NSCLC. We examined the DNA obtained from the tumor, nearby normal lung tissue, and matched BAL fluid for mutations in the KRAS and p53 genes; the material was obtained from 48 patients with peripheral NSCLC, and was analyzed by PCR-single strand conformation polymorphism and DNA sequencing. BAL fluids from 26 patients with benign lung disease were used as controls. Positive rates of KRAS and p53 mutations were distributed as follows: in NSCLC tissue, 52% and 58%; in BAL fluid of NSCLC patients, 38% and 44%; in normal lung tissue, 6% and 4%; and in BAL fluid of patients with benign lung disease, 8% and 4%. The combined detection of both KRAS and p53 mutations yielded a sensitivity of 66% for the diagnosis of peripheral NSCLC, which is markedly higher than that of cytology plus histology by first bronchoscopy (38%, p=0.008). In each patient with the 2 gene mutations in BAL fluid, mutation type and location were the same as those of the primary tumor. Our study indicates that the detection of the KRAS and p53 mutations in BAL fluids could be a helpful addition to cytology and histology examination for the diagnosis of peripheral NSCLC.

Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen

PubMed Central

Hohenadel, I; Kiworr, M; Genitsariotis, R; Zeidler, D; Lorenz, J

2001-01-01

BACKGROUND—In a retrospective study the value of bronchoalveolar lavage (BAL) in the diagnosis of pneumonia was investigated in 95 immunocompromised patients suffering from haematological disorders and receiving a regimen of broad spectrum antibiotics and antifungal agents (BSAR).
METHODS—With the exception of four afebrile patients, all had fever, raised C reactive protein (CRP) levels, and new infiltrates visible on chest radiography. All patients underwent BAL to identify the organism causing the pneumonia and surveillance cultures were performed regularly for pathogens at different sites. Following classification of the isolates, patients with positive cultures were subdivided into two groups, pathogenic or contaminated. We investigated whether relevant pathogens were cultured only from the BAL fluid and whether they were susceptible to BSAR.
RESULTS—Although 77 of the 95 patients were thrombocytopenic, bleeding during BAL occurred in only 15% of all patients. Ten days after the procedure the fever improved in 88% of patients, radiographic findings improved in 71%, and CRP levels improved in 75% of patients; 22% of patients died within 28 days. Pathologically relevant isolates were found in 65% of all patients. Respiratory pathogens were detected only in the BAL fluid of 29 of the 95 patients (35% Gram positive species, 40% Gram negative species, 11% Mycobacterium, 11% fungi, and 3% cytomegalovirus). In 16 of these 29 patients (55%) the pathogens cultured only from the BAL fluid were resistant to treatment. Pathogens detected only in the BAL fluid were not susceptible to a standard broad spectrum antibiotic and antifungal regimen including teicoplanin, ceftriaxon, tobramycin, and amphotericin B in 12 of the 29 patients (41%).
CONCLUSIONS—Our data suggest that 12 patients were treated with broad spectrum antimicrobial agents which were not directed at the appropriate organism on in vitro sensitivity tests without BAL. BAL is a relatively safe

Culture-independent Analysis of Pediatric Broncho-alveolar Lavage (BAL) Specimens.

PubMed

Zachariah, Philip; Ryan, Chanelle; Nadimpalli, Sruti; Coscia, Gina; Kolb, Michelle; Smith, Hannah; Foca, Marc; Saiman, Lisa; Planet, Paul J

2018-06-07

The clinical utility of culture-independent testing of pediatric bronchoalveolar lavage (BAL) specimens is unknown. Additionally, the variability of the pediatric pulmonary microbiome with patient characteristics is not well understood. Study subjects were ≤22 years old and underwent BAL from May 2013 - July 2015 as part of clinical care. DNA extracted from BAL specimens was used for 16S rRNA gene-based (16S-based) microbiome analysis, and results compared to routine cultures from the same samples. Indices of microbial diversity and relative taxon abundances were compared based on subject characteristics. From 81 participants (51% male, median age 9 years), 89 samples were collected and the 16S rRNA genes of 77 (86.5%) samples were successfully analyzed. Subjects included 23 cystic fibrosis (CF), 19 immunocompromised (IC), and 28 non-immunocompromised (nIC) patients. Of 68 organisms identified in culture, 16S-based analyses were concordant with culture results in 66 (97.1%), and also identified potentially clinically significant taxa missed by cultures (e.g. Staphylococcus, Legionella, Pseudomonas). Significant differences in abundance were noted mostly for non-cultured taxa with diagnosis and antibiotic use (Veillonella, Corynebacterium, Haemophilus). The microbiota of CF samples was less diverse and a "core" group of fifteen taxa shared across samples was identified. 16S-based culture independent analysis was concordant with routine cultures and showed potential to detect non-cultured pathogens. While 16S- based testing identified relative changes in organism abundance associated with clinical characteristics, distinct microbiome profiles associated with disease states were not identified.

Different exosome cargo from plasma/bronchoalveolar lavage in non-small-cell lung cancer.

PubMed

Rodríguez, Marta; Silva, Javier; López-Alfonso, Ana; López-Muñiz, María Belen; Peña, Cristina; Domínguez, Gemma; García, Jose Miguel; López-Gónzalez, Ana; Méndez, Miriam; Provencio, Mariano; García, Vanesa; Bonilla, Félix

2014-09-01

Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth, metastasis, development of drug resistance, and immunosuppression. However, little is known about the exosomes isolated from bronchoalveolar lavage (BAL) in patients with lung neoplasm. Exosomes isolated in plasma and BAL from 30 and 75 patients with tumor and nontumor pathology were quantified by acetylcholinesterase activity and characterized by Western Blot, Electron Microscopy, and Nanoparticle Tracking Analysis. Differences in exosome cargo were analyzed by miRNA quantitative PCR in pooled samples and validated in a second series of patients. More exosomes were detected in plasma than in BAL in both groups (P < 0.001). The most miRNAs evaluated by PCR array were detected in tumor plasma, tumor BAL, and nontumor BAL pools, but only 56% were detected in the nontumor plasma pool. Comparing the top miRNAs with the highest levels detected in each pool, we found close homology only between the BAL samples of the two pathologies. In tumor plasma, we found a higher percentage of miRNAs with increased levels than in tumor BAL or in nontumor plasma. The data reveal differences between BAL and plasma exosome amount and miRNA content. © 2014 Wiley Periodicals, Inc.

[Effect of bronchoalveolar lavage with fiberoptic bronchoscopy combined with vibration sputum drainage on mechanically ventilated patients with severe pneumonia: a prospective randomized controlled trial in 286 patients].

PubMed

Shi, Zeya; Qin, Yuelan; Zhu, Yimin; Pan, Xiaoji; Zhou, Xu; Tan, Yuting; Liu, Yanhui

2017-01-01

To investigate the curative effect of bronchoalveolar lavage with fiberoptic bronchoscopy combined with vibration sputum drainage in the treatment of severe pneumonia patients undergoing mechanical ventilation (MV). A prospective randomized controlled trial was conducted. 286 severe pneumonia patients undergoing MV admitted to intensive care unit (ICU) of Hunan People's Hospital from January 2014 to July 2016 were enrolled, and they were divided into control group and observation group according to random number table, with 143 patients in each group. Patients in both groups received sensitive antibiotics for anti-infection, etiological treatment, and calefacient and humidifying treatment. The patients in the control group received bronchoalveolar lavage with fiberoptic bronchoscopy, and those in the observation group received bronchoalveolar lavage combined with vibration sputum drainage. The parameters of respiratory function and inflammation before and after treatment, curative effect, and prognosis were compared between the two groups. (1) There were no significant differences in respiratory function parameters between the two groups before treatment, 2 hours after treatment, the parameters were improved in both groups. Moreover, oxygenation index (PaO 2 /FiO 2 ) in observation group was significantly higher than that of control group [mmHg (1 mmHg = 0.133 kPa): 379.1±20.2 vs. 351.8±24.7], and arterial partial pressure of carbon dioxide (PaCO 2 ) and airway resistance (Raw) were significantly lower than those of the control group [PaCO 2 (mmHg): 36.5±5.8 vs. 45.3±6.9, Raw (cmH 2 O, 1 cmH 2 O = 0.098 kPa): 12.9±0.6 vs. 13.1±0.8, all P < 0.01]. (2) There were no significant differences in inflammation parameters between the two groups before treatment, 24 hours after intervention, which were significantly decreased in both groups. Moreover, white blood cell count (WBC), procalcitonin (PCT) and C-reactive protein (CRP) in the observation group were

A Deep Nasopharyngeal Swab Versus Nonendoscopic Bronchoalveolar Lavage for Isolation of Bacterial Pathogens from Preweaned Calves With Respiratory Disease.

PubMed

Van Driessche, L; Valgaeren, B R; Gille, L; Boyen, F; Ducatelle, R; Haesebrouck, F; Deprez, P; Pardon, B

2017-05-01

Nonendoscopic bronchoalveolar lavage (BAL) is a practical alternative for a deep nasopharyngeal swab (DNS) to sample the airways of a large number of calves in a short period of time. The extent of commensal overgrowth and agreement of BAL with DNS culture results in preweaned calves are unknown. To compare commensal overgrowth and bacterial culture results between DNS and BAL samples. A total of 183 preweaned calves (144 with bovine respiratory disease and 39 healthy animals). Cross-sectional study. Deep nasopharyngeal swab and BAL samples were taken from each calf and cultured to detect Pasteurellaceae and Mycoplasma bovis. Agreement and associations between culture results of DNS and BAL samples were determined by kappa statistics and logistic regression. Bronchoalveolar lavage samples were less often polymicrobial, more frequently negative and yielded more pure cultures compared to DNS, leading to a clinically interpretable culture result in 79.2% of the cases compared to only in 31.2% of the DNS samples. Isolation rates were lower in healthy animals, but not different between DNS and BAL samples. Only Histophilus somni was more likely to be isolated from BAL samples. In clinical cases, a polymicrobial DNS culture result did not increase the probability of a polymicrobial BAL result by ≥30%, nor did it influence the probability of a negative culture. A significant herd effect was noted for all observed relationships. Nonendoscopic BAL samples are far less overgrown by bacteria compared to DNS samples under the conditions of this study, facilitating clinical interpretation and resulting in a higher return on investment in bacteriologic culturing. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection.

PubMed

Fujimoto, Yousuke; Hasegawa, Shunji; Matsushige, Takeshi; Wakiguchi, Hiroyuki; Nakamura, Tamaki; Hasegawa, Hideki; Nakajima, Noriko; Ainai, Akira; Oga, Atsunori; Itoh, Hiroshi; Shirabe, Komei; Toda, Shoichi; Atsuta, Ryo; Morishima, Tsuneo; Ohga, Shouichi

2017-08-22

Asthmatic patients present more rapid progression of respiratory distress after A(H1N1)pdm09 influenza infection than after seasonal infection. Here, we sought to clarify the pathophysiology of early deterioration in asthmatic patients after A(H1N1)pdm09 infection. Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. In asthma/A(H1N1)pdm09 mice, IL-6 and TNF-α levels peaked at 3 days post-infection and were higher than those in all other groups. IFN-γ levels in asthma/A(H1N1)pdm09 mice at 3 days post-infection were higher than in all other mice at any time point, whereas at 7 days post-infection, the levels were lowest in asthma/A(H1N1)pdm09 mice. Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group. Histopathological examination showed more inflammatory cell infiltration and lung tissue destruction in the asthma/A(H1N1)pdm09 group than in any other group. The distinct cytokine profiles in A(H1N1)pdm09-infected asthmatic mice indicated excessive inflammation and virus replication within a few days after infection. Thus, bronchial asthma could be a more exacerbating factor for pandemic influenza infection than for seasonal influenza infection.

Assessment of CCL2 and CXCL8 chemokines in serum, bronchoalveolar lavage fluid and lung tissue samples from dogs affected with canine idiopathic pulmonary fibrosis.

PubMed

Roels, Elodie; Krafft, Emilie; Farnir, Frederic; Holopainen, Saila; Laurila, Henna P; Rajamäki, Minna M; Day, Michael J; Antoine, Nadine; Pirottin, Dimitri; Clercx, Cecile

2015-10-01

Canine idiopathic pulmonary fibrosis (CIPF) is a progressive disease of the lung parenchyma that is more prevalent in dogs of the West Highland white terrier (WHWT) breed. Since the chemokines (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 8 (CXCL8) have been implicated in pulmonary fibrosis in humans, the aim of the present study was to investigate whether these same chemokines are involved in the pathogenesis of CIPF. CCL2 and CXCL8 concentrations were measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) from healthy dogs and WHWTs affected with CIPF. Expression of the genes encoding CCL2 and CXCL8 and their respective receptors, namely (C-C motif) receptor 2 (CCR2) and (C-X-C motif) receptor 2 (CXCR2), was compared in unaffected lung tissue and biopsies from dogs affected with CIPF by quantitative PCR and localisation of CCL2 and CXCL8 proteins were determined by immunohistochemistry. Significantly greater CCL2 and CXCL8 concentrations were found in the BALF from WHWTs affected with CIPF, compared with healthy dogs. Significantly greater serum concentrations of CCL2, but not CXCL8, were found in CIPF-affected dogs compared with healthy WHWTs. No differences in relative gene expression for CCL2, CXCL8, CCR2 or CXCR2 were observed when comparing lung biopsies from control dogs and those affected with CIPF. In affected lung tissues, immunolabelling for CCL2 and CXCL8 was observed in bronchial airway epithelial cells in dogs affected with CIPF. The study findings suggest that both CCL2 and CXCL8 are involved in the pathogenesis of CIPF. Further studies are required to determine whether these chemokines might have a clinical use as biomarkers of fibrosis or as targets for therapeutic intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bacteriological incidence in pneumonia patients with pulmonary emphysema: a bacterial floral analysis using the 16S ribosomal RNA gene in bronchoalveolar lavage fluid.

PubMed

Naito, Keisuke; Yamasaki, Kei; Yatera, Kazuhiro; Akata, Kentaro; Noguchi, Shingo; Kawanami, Toshinori; Fukuda, Kazumasa; Kido, Takashi; Ishimoto, Hiroshi; Mukae, Hiroshi

2017-01-01

Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, Moraxella catarrhalis was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of Haemophilus influenzae and Pseudomonas aeruginosa were unrelated to the severity of pulmonary emphysematous changes, and Streptococcus species - except for the S. anginosus group and S. pneumoniae - were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that M. catarrhalis is more frequently detected in pneumonia patients with moderate or

Bacteriological incidence in pneumonia patients with pulmonary emphysema: a bacterial floral analysis using the 16S ribosomal RNA gene in bronchoalveolar lavage fluid

PubMed Central

Naito, Keisuke; Yamasaki, Kei; Yatera, Kazuhiro; Akata, Kentaro; Noguchi, Shingo; Kawanami, Toshinori; Fukuda, Kazumasa; Kido, Takashi; Ishimoto, Hiroshi; Mukae, Hiroshi

2017-01-01

Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, Moraxella catarrhalis was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of Haemophilus influenzae and Pseudomonas aeruginosa were unrelated to the severity of pulmonary emphysematous changes, and Streptococcus species – except for the S. anginosus group and S. pneumoniae – were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that M. catarrhalis is more frequently detected in pneumonia patients with moderate

Comparison of Tracheal Wash and Bronchoalveolar Lavage Cytology in 154 Horses With and Without Respiratory Signs in a Referral Hospital Over 2009−2015

PubMed Central

Rossi, Heini; Virtala, Anna-Maija; Raekallio, Marja; Rahkonen, Emmi; Rajamäki, Minna M.; Mykkänen, Anna

2018-01-01

Most equine lower respiratory diseases present as increased airway neutrophilia, which can be detected in tracheal wash (TW) or bronchoalveolar lavage fluid (BALF) cytology samples. The aim was to compare the TW and BALF results in a population of client-owned horses with and without clinical respiratory disease signs. A secondary aim was to determine the sensitivity (Se) and specificity (Sp) of TW and BALF neutrophilia in detecting respiratory disease. The cutoff values for neutrophils were also evaluated. Retrospective data from 154 horses of various breeds that had been subject to both TW and bronchoalveolar lavage (BAL) sampling at rest during 2009−2015 were used. The horses were divided into three groups based on the presenting signs, physical examination, and endoscopy mucus score. Neutrophil counts of >20% in TW and >5% in BAL were considered abnormal. Cytology results between groups, correlations between TW and BALF cell types, and tracheal mucus score were analyzed. Two graph receiving operating characteristic (ROC) curves of the neutrophil percentage values of TW and BALF were created to determine the optimal cutoff values and to calculate the diagnostic Se and Sp for diagnosing airway inflammation in horses with and without clinical respiratory signs. The Se and Sp of TW and BALF neutrophil percentages were further estimated using a two-test one-population Bayesian latent class model. The two tests showed substantial agreement, and only 17.5% of the horses were classified differently (healthy vs. diseased). The neutrophil percentage was found to correlate between TW and BALF. The Se and Sp of TW were generally higher than for BAL when estimated with area under the curve or Bayesian model. Cutoff values of 17.7% for TW and 7% for BALF were indicated by the ROCs. We conclude that TW is a more sensitive and specific method in our patient population. We suggest that the current neutrophil cutoff values of 20% for TW and 5% for BALF would still be

Evaluation of CD30 as a marker for th2 lymphocytes in bronchoalveolar lavage in interstitial lung diseases.

PubMed

Petkova, D; Xaubet, A; Picado, C; Filella, X; Agusti, C; Luburich, P; Rodriguez-Roisin, R

2000-04-01

Several studies have been carried out to clarify the relationship between CD30 expression and Th2 lymphocytes, although the results have been controversial. To investigate whether CD30 is a useful marker for Th2 lymphocytes in bronchoalveolar lavage (BAL) in interstitial lung diseases (ILD), we studied six control subjects and 31 patients with ILD (12 with idiopathic pulmonary fibrosis, seven with hypersensitivity pneumonitis, three with chronic eosinophilic pneumonia and nine with sarcoidosis). The levels of interleukin-5 (IL-5) (secreted by Th2 cells), interferon-gamma (IFNgamma) (secreted by Th1 cells) and the expression of CD30 on lymphocytes were determined in BAL fluid. There were no differences in the percentage of CD30+ lymphocytes between controls and patients with ILD (0.8+0.4% vs. 2+/-0.4%). In order to determine the relationship between Th2 cells and CD30 expression, we divided the patients into two groups according to BAL IL-5 levels. Group I consisted of eight patients (three chronic eosinophilic pneumonia, three hypersensitivity pneumonitis, two idiopathic pulmonary fibrosis) with high IL-5 levels (298+/-138 pg ml(-1)). Group II consisted of the remaining 23 ILD patients with normal IL-5 levels (0.9+/-0.6 pg ml(-1)). The percentage of eosinophils in BAL fluid was significantly higher in group I compared with group 11 (34+/-16% vs. 3+/-1%, P < 0.05). A correlation between CD30+ lymphocytes and IL-5 in group 1 was not shown. There were no differences in the number of CD30+ I we found a significant correlation between IL-5 levels and the percentage of eosinophils (r = 0.95, P < 0.0001). Our results suggest that CD30 does not appear to be a useful marker for Th2 lymphocytes in BAL from patients with ILD.

Lung malignancy: Diagnostic accuracies of bronchoalveolar lavage, bronchial brushing, and fine needle aspiration cytology

PubMed Central

Sareen, Rateesh; Pandey, C L

2016-01-01

Background: Early diagnosis of lung cancer plays a pivotal role in reducing lung cancer death rate. Cytological techniques are safer, economical and provide quick results. Bronchoscopic washing, brushing and fine needle aspirations not only complement tissue biopsies in the diagnosis of lung cancer but also comparable. Objectives: (1) To find out diagnostic yields of bronchioalveolar lavage, bronchial brushings, FNAC in diagnosis of lung malignancy. (2) To compare relative accuracy of these three cytological techniques. (3) To correlate the cytologic diagnosis with clinical, bronchoscopic and CT findings. (4) Cytological and histopathological correlation of lung lesions. Methods: All the patients who came with clinical or radiological suspicion of lung malignancy in two and a half year period were included in study. Bronchoalveolar lavage was the most common type of cytological specimen (82.36%), followed by CT guided FNAC (9.45%) and bronchial brushings (8.19%). Sensitivity, specificity, positive and negative predictive value for all techniques and correlation with histopathology was done using standard formulas. Results: The most sensitive technique was CT FNAC – (87.25%) followed by brushings (77.78%) and BAL (72.69%). CT FNAC had highest diagnostic yield (90.38%), followed by brushings (86.67%) and BAL (83.67%). Specificity and positive predictive value were 100 % each of all techniques. Lowest false negatives were obtained in CT FNAC (12.5%) and highest in BAL (27.3%). Highest negative predictive value was of BAL 76.95 % followed by BB 75.59% and CT FNAC 70.59%. Conclusion: Before administering antitubercular treatment every effort should be made to rule out malignancy. CT FNAC had highest diagnostic yield among three cytological techniques. BAL is an important tool in screening central as well as in accessible lesions. It can be used at places where CT guided FNAC is not available or could not be done due to technical or financial limitations PMID:27890992

Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure.

PubMed

Gouveia-Figueira, Sandra; Karimpour, Masoumeh; Bosson, Jenny A; Blomberg, Anders; Unosson, Jon; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Nording, Malin L

2017-04-01

The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 μg/m 3 ) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, N-acylethanolamines, and related lipid metabolites in the collected BW and BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE 2 , 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

Performance of 2 commercial real-time polymerase chain reaction assays for the detection of Aspergillus and Pneumocystis DNA in bronchoalveolar lavage fluid samples from critical care patients.

PubMed

Orsi, Carlotta Francesca; Gennari, William; Venturelli, Claudia; La Regina, Annunziata; Pecorari, Monica; Righi, Elena; Machetti, Marco; Blasi, Elisabetta

2012-06-01

This article investigates the performance of 2 commercial real-time polymerase chain reaction (PCR) assays, MycAssay™ Aspergillus (Myc(Asp)Assay) and MycAssay™ Pneumocystis (Myc(PCP)Assay), on the ABI 7300 platform for the detection of Aspergillus (Asp) or Pneumocystis jirovecii (Pj) DNA in bronchoalveolar lavage (BAL) samples from 20 patients. Operationally, patients enrolled were clustered into 3 groups: invasive aspergillosis group (IA, 7 patients), Pj pneumonia group (PCP, 8 patients), and negative control group (5 patients). All the IA patients were Myc(Asp)Assay positive, whereas 12 non-IA patients returned negative PCR results. Furthermore, 7 of 8 PCP patients were Myc(PCP)Assay positive, while 9 non-PCP patients were PCR negative. In conclusion, these data provide an early indication of the effectiveness of both the Myc(Asp)Assay and Myc(PCP)Assay on the ABI 7300 platform for the detection of either Asp or Pj DNA in BAL from patients with deep fungal infections. Copyright © 2012 Elsevier Inc. All rights reserved.

Usefulness of bronchoalveolar lavage and flow cytometry in patients with hematological malignancies and respiratory failure.

PubMed

Ferrà, Christelle; Xicoy, Blanca; Castillo, Nerea; Morgades, Mireia; Juncà, Jordi; Andreo, Felipe; Millá, Fuensanta; Feliu, Evarist; Ribera, Josep-María

2017-04-07

Strategies to improve the efficiency of bronchoalveolar lavage (BAL) are needed. We conducted a study to establish the diagnostic value of BAL in patients with hematological malignancies and pulmonary infiltrates. The correlation of cytologic and flow cytometric study of BAL with the microbiological findings and the clinical evolution was determined. Seventy BAL were performed and flow cytometric study was analyzed in 23 of them. Fifty-three patients did not present any adverse event attributable to BAL. Anti-infectious therapy was modified in 64 (91%) patients. T lymphocyte count >0.3×10 9 /l in peripheral blood was associated with longer OS at 3 years (53 vs. 22%, p=.009). Higher CD4 (>20/μL) and CD8 (>35/μL) lymphocyte counts in the BAL were associated with a longer OS at 3 years: 82 vs. 21% (p=.030) and 80 vs. 23% (p=.059). Our study confirms the clinical value of BAL for treatment decision making in patients with hematological malignancies and acute respiratory failure. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Use of vitamin B12 in joint lavage for determination of dilution factors of canine synovial fluid.

PubMed

de Bruin, Tanya; de Rooster, Hilde; van Bree, Henri; Cox, Eric

2005-11-01

To test a modified saline (0.9% NaCl) solution joint washing (lavage) technique that includes the use of vitamin B12 as an internal marker for the evaluation of synovial fluid dilution in lavage samples from canine joints. 9 plasma samples obtained from blood samples of 9 healthy dogs and 9 synovial fluid samples aspirated from stifle joints of 9 cadaveric dogs. Photometric absorbances of 25% vitamin B12 solution, canine synovial fluid, and canine plasma were measured in a spectrophotometer to establish an optimal wavelength for analysis. Canine synovial fluid and plasma samples were mixed with the 25% vitamin B12 solution to obtain 1%, 3%, 5%, 10%, 20%, and 50% solutions of synovial fluid or plasma. Diluted synovial fluid and plasma samples were used to simulate joint lavage samples and to examine the possible interference of these substances (synovial fluid or plasma) with the absorbance of the 25% vitamin B12 solution in photometric analysis. The optimal wavelength was found to be at 550 nm. Canine synovial fluid and plasma samples did not interfere with the absorbance measurements of the 25% vitamin B12 solution up to a 50% dilution of plasma or synovial fluid. The modified saline solution joint lavage method with the use of a 25% vitamin B12 solution as an internal standard provides an accurate and reliable technique for the evaluation of synovial fluid dilution in lavage samples from canine joints.

Correlation between viral loads of cytomegalovirus in blood and bronchoalveolar lavage specimens from lung transplant recipients determined by histology and immunohistochemistry.

PubMed

Chemaly, Roy F; Yen-Lieberman, Belinda; Castilla, Elias A; Reilly, Amy; Arrigain, Susana; Farver, Carol; Avery, Robin K; Gordon, Steven M; Procop, Gary W

2004-05-01

Cytomegalovirus (CMV) is an important pathogen in lung transplant recipients. Early detection of CMV end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.

[Interleukin 8 concentrations in donor bronchoalveolar lavage: impact on primary graft failure in double lung transplant].

PubMed

Almenar, María; Cerón, José; Gómez, M A Dolores; Peñalver, Juan C; Jiménez, M A José; Padilla, José

2009-01-01

The purpose of this study was to determine concentrations of interleukin 8 (IL-8) in the bronchoalveolar lavage (BAL) fluid from donor lungs and assess the role of IL-8 levels in the development of primary graft failure. Twenty patients who received a double lung transplant were studied. A series of data, including BAL fluid concentrations of IL-8, were collected for the donors. Data collected for the recipients included arterial blood gases after 6, 24, and 48 hours, and intubation time. Patients with a ratio of PaO(2) to the fraction of inspired oxygen (FiO(2)) of less than 300 during the first 48 hours were diagnosed with primary graft failure. IL-8 levels were determined by enzyme-linked immunosorbent assay. Associations between the donor variables and IL-8 concentrations were evaluated using the Spearman rank correlation coefficient (rho) and the Mann-Whitney test for categorical and continuous variables, respectively. Logistic regression was used for multivariate analysis. Fifteen of the 20 donors were men. The cause of brain death was trauma in 9 donors, 7 were smokers, 13 required inotropic support, and pathogens were isolated in the BAL fluid of 18. The median age was 35 years (interquartile range [IQR], 23.5-51.25y), the median ventilation time was 1 day (IQR, 1-2d), the median PaO(2)/FiO(2) was 459.5 (IQR, 427-510.25), and the median IL-8 concentration in BAL fluid was 49.01ng/L (IQR, 7.86-94.05ng/mL). Ten of the recipients were men and the median age was 48.43 years (IQR, 25.4-56.81y). The median ischemic time was 210 minutes (IQR, 176.25-228.75 min) for the first lung and 300 minutes (IQR, 273.75-333.73 min) for the second lung. The median PaO(2)/FiO(2) ratio for the implant at 6, 14, and 48 hours was 329 (IQR, 190.25-435), 363.5 (IQR, 249-434.75), and 370.5 (IQR, 243.25-418.25), respectively. The median intubation time was 39.5 hours (IQR, 19.25-68.5h) and the correlation with IL-8 values was positive: higher IL-8 concentrations in BAL fluid

Bronchoalveolar lavage fluid in Standardbred racehorses: influence of unilateral/bilateral profiles and cut-off values on lower airway disease diagnosis.

PubMed

Depecker, Marianne; Richard, Eric A; Pitel, Pierre-Hugues; Fortier, Guillaume; Leleu, Claire; Couroucé-Malblanc, Anne

2014-01-01

The aim of this study was to determine whether the lung side being sampled would significantly influence bronchoalveolar lavage (BAL) cytological profiles and subsequent diagnosis in Standardbred racehorses. One hundred and thirty-eight French Trotters in active training and racing were included in a prospective observational study. BAL was performed using videoendoscopy in both right and left lungs during summer meetings in 2011 (64 horses) and 2012 (74 horses). Cytological data performed 24h later from right and left lungs were compared and specifically used to classify horses as affected with exercise-induced pulmonary haemorrhage (EIPH), inflammatory airway disease (IAD), or were 'controls'. For IAD, cytological definition was based on two different cut off values. Neutrophil percentages, haemosiderophage percentages and the haemosiderophage/macrophage (H/M) ratios were significantly higher in the right compared to the left lung. Measures of intra-class correlation coefficients revealed a fair agreement between left and right lungs for percentages of mast cells, eosinophils, and for the H/M ratio, and a moderate agreement for neutrophil percentages. Fair to moderate agreements were observed between left and right lungs for the diagnosis of IAD and/or EIPH based on kappa coefficients. When sampling one lung only, the risk of incorrectly classifying a horse as a 'control' increased with the use of the restraint cut-off values for IAD. As BAL from one lung is not representative of the other lung in the same horse, both lungs should be sampled for a better assessment of lung cellularity and for a precise diagnosis of lower airway diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Proteomic analysis of bronchoalveolar lavage fluid (BALF) from lung cancer patients using label-free mass spectrometry.

PubMed

Hmmier, Abduladim; O'Brien, Michael Emmet; Lynch, Vincent; Clynes, Martin; Morgan, Ross; Dowling, Paul

2017-06-01

Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC). Validation of candidate biomarkers identified in BALF was performed in a larger cohort of plasma samples by detection with enzyme-linked immunoassay. Four proteins (Cystatin-C, TIMP-1, Lipocalin-2 and HSP70/HSPA1A) were selected as a representative group from discovery phase mass spectrometry BALF analysis. Plasma levels of TIMP-1, Lipocalin-2 and Cystatin-C were found to be significantly elevated in AD and SqCC compared to control. The results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers. There is good correlation between the trend of protein abundance levels in BALF and that of plasma which validates this approach to develop a blood biomarker to aid lung cancer diagnosis, particularly in the era of lung cancer screening. The protein signatures identified also provide insight into the molecular mechanisms associated with lung malignancy.

CYFRA 21.1 in bronchoalveolar lavage of idiopathic pulmonary fibrosis patients.

PubMed

Vercauteren, Inge M; Verleden, Stijn E; McDonough, John E; Vandermeulen, Elly; Ruttens, David; Lammertyn, Elise J; Bellon, Hannelore; De Dycker, Els; Dooms, Christophe; Yserbyt, Jonas; Verleden, Geert M; Vanaudenaerde, Bart M; Wuyts, Wim A

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases, however, clinically relevant biomarkers of diagnosis or prognosis are lacking. In this study, we investigated the levels of a fragment of Cytokeratin 19 (CYFRA 21.1) in bronchoalveolar lavage (BAL) of IPF patients at time of diagnosis. We further evaluated associations between CYFRA 21.1, pulmonary function evolution, mortality, and BAL cell count. Using the Lumipulse® G1200, CYFRA 21.1 was measured in BAL samples of 81 IPF patients and 9 controls. Based upon the median detected level (1.2 ng/mL) of CYFRA 21.1 in IPF patients, they were subdivided into an IPF CYFRA 21.1 low group (≤ 1.2 ng/mL) and IPF CYFRA 21.1 high group (> 1.2 ng/mL). The CYFRA 21.1 levels were significantly higher in BAL of IPF patients compared to controls (P = .0015).Worse survival was observed, but no changes in pulmonary function, for IPF patients with high CYFRA 21.1 levels versus patients with low CYFRA 21.1 levels [P = .030, HR: 0.41, (0.18-0.92)[. The CYFRA 21.1 level correlated with both neutrophils (%: R = 0.60, P < .0001; #: R = 0.47, P < .0001) and eosinophils (%: R = 0.38, P = .0005; #: R = 0.30, P < .0072). CYFRA 21.1 is increased in BAL of IPF patients. IPF patients with a high CYFRA 21.1 concentration have a worse survival. CYFRA 21.1 levels correlate with eosinophils and neutrophils. Further studies are warranted in using CYFRA 21.1 as a biomarker for IPF prognosis.

[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer].

PubMed

Grünewaldt, A; Hügel, C; Hermann, E; Wagner, T O F

2017-02-01

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods  In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results  We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion  We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison of surfactant lipids between pleural and pulmonary lining fluids.

PubMed

Mills, P C; Chen, Y; Hills, Y C; Hills, B A

2006-01-01

Saturated phospholipids (PCs), particularly dipalmitoylphosphatidylcholine (DPPC), predominate in surfactant lining the alveoli, although little is known about the relationship between saturated and unsaturated PCs on the outer surface of the lung, the pleura. Seven healthy cats were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately followed by a pleural lavage (PL). Lipid was extracted from lavage fluid and then analyzed for saturated, primarily dipalmitoylphosphatidylcholine (DPPC), and unsaturated PC species using high-performance liquid chromatography (HPLC) with combined fluorescence and ultraviolet detection. Dilution of epithelial lining fluid (ELF) in lavage fluids was corrected for using the urea method. The concentration of DPPC in BAL fluid (85.3+/-15.7 microg/mL) was significantly higher (P=0.021) than unsaturated PCs ( approximately 40 microg/mL). However, unsaturated PCs ( approximately 34 microg/mL), particularly stearoyl-linoleoyl-phosphatidylcholine (SLPC; 17.4+/-6.8), were significantly higher (P=0.021) than DPPC (4.3+/-1.8 microg/mL) in PL fluid. These results show that unsaturated PCs appear functionally more important in the pleural cavity, which may have implications for surfactant replenishment following pleural disease or thoracic surgery.

Analysis of Lung Microbiota in Bronchoalveolar Lavage, Protected Brush and Sputum Samples from Subjects with Mild-To-Moderate Cystic Fibrosis Lung Disease

PubMed Central

Hogan, Deborah A.; Willger, Sven D.; Dolben, Emily L.; Hampton, Thomas H.; Stanton, Bruce A.; Morrison, Hilary G.; Sogin, Mitchell L.; Czum, Julianna; Ashare, Alix

2016-01-01

Individuals with cystic fibrosis (CF) often acquire chronic lung infections that lead to irreversible damage. We sought to examine regional variation in the microbial communities in the lungs of individuals with mild-to-moderate CF lung disease, to examine the relationship between the local microbiota and local damage, and to determine the relationships between microbiota in samples taken directly from the lung and the microbiota in spontaneously expectorated sputum. In this initial study, nine stable, adult CF patients with an FEV1>50% underwent regional sampling of different lobes of the right lung by bronchoalveolar lavage (BAL) and protected brush (PB) sampling of mucus plugs. Sputum samples were obtained from six of the nine subjects immediately prior to the procedure. Microbial community analysis was performed on DNA extracted from these samples and the extent of damage in each lobe was quantified from a recent CT scan. The extent of damage observed in regions of the right lung did not correlate with specific microbial genera, levels of community diversity or composition, or bacterial genome copies per ml of BAL fluid. In all subjects, BAL fluid from different regions of the lung contained similar microbial communities. In eight out of nine subjects, PB samples from different regions of the lung were also similar in microbial community composition, and were similar to microbial communities in BAL fluid from the same lobe. Microbial communities in PB samples were more diverse than those in BAL samples, suggesting enrichment of some taxa in mucus plugs. To our knowledge, this study is the first to examine the microbiota in different regions of the CF lung in clinically stable individuals with mild-to-moderate CF-related lung disease. PMID:26943329

Differences in surfactant lipids collected from pleural and pulmonary lining fluids.

PubMed

Mills, Paul C; Chen, Yi; Hills, Yvette C; Hills, Brian A

2005-11-01

The type and relative importance of saturated and unsaturated phospholipid components of surfactant within the epithelial lining fluid (ELF) of the inner and outer surfaces of the lung is not known. Seven healthy dogs were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately followed by a pleural lavage (PL). Lipid was extracted from lavage fluid and then analyzed for saturated, primarily dipalmitoylphosphatidylcholine (DPPC), and unsaturated phosphatidylcholine (PC) species using high-performance liquid chromatography (HPLC) with combined fluorescence and ultraviolet detection. Dilution of ELF in lavage fluids was corrected for using the urea method. DPPC (494.7 +/- 213.9 microg/mL) was the predominant PC present in ELF collected from the alveolar surface. In contrast, significantly higher (p = 0.028) proportions of unsaturated PC species were measured in PL fluid (approximately 105 microg/mL), particularly stearoyl-linoleoyl-phosphatidylcholine (SLPC), which could not be measured in fluid collected from the alveoli, compared to DPPC (2.6 +/- 2.0 microg/mL). This study indicates that unsaturated PC species seem to be more important than saturated species, particularly DPPC, in the pleural cavity, which has implications for surfactant replenishment following pleural disease or thoracic surgery.

PAR-2, IL-4R, TGF-β and TNF-α in bronchoalveolar lavage distinguishes extrinsic allergic alveolitis from sarcoidosis.

PubMed

Matěj, Radoslav; Smětáková, Magdalena; Vašáková, Martina; Nováková, Jana; Sterclová, Martina; Kukal, Jaromír; Olejár, Tomáš

2014-08-01

Sarcoidosis (SARC) and extrinsic allergic alveolitis (EAA) share certain markers, making a differential diagnosis difficult even with histopathological investigation. In lung tissue, proteinase-activated receptor-2 (PAR-2) is primarily investigated with regard to epithelial and inflammatory perspectives. Varying levels of certain chemokines can be a useful tool for distinguishing EAA and SARC. Thus, in the present study, differences in the levels of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin-4 receptor (IL-4R) and PAR-2 in bronchoalveolar lavage fluid (BALF) were compared, using an ELISA method, between 14 patients with EAA and six patients with SARC. Statistically significant higher levels of IL-4R, PAR-2 and the PAR-2/TGF-β1 and PAR-2/TNF-α ratios were observed in EAA patients as compared with SARC patients. Furthermore, the ratios of TNF-α/total protein, TGF-β1/PAR-2 and TNF-α/PAR-2 were significantly lower in EAA patients than in SARC patients. The results indicated a higher detection of PAR-2 in EAA samples in association with TNF-α and TGF-β levels. As EAA and PAR-2 in parallel belong to the Th2-mediated pathway, the results significantly indicated an association between this receptor and etiology. In addition, the results indicated that SARC is predominantly a granulomatous inflammatory disease, thus, higher levels of TNF-α are observed. Therefore, the detection of PAR-2 and investigated chemokines in BALF may serve as a useful tool in the differential diagnosis between EAA and SARC.

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

PubMed Central

2014-01-01

Background We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions Candidate proteins and mi

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea.

PubMed

Brown, Joseph N; Brewer, Heather M; Nicora, Carrie D; Weitz, Karl K; Morris, Michael J; Skabelund, Andrew J; Adkins, Joshua N; Smith, Richard D; Cho, Ji-Hoon; Gelinas, Richard

2014-10-05

We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Candidate proteins and miRNAs associated with the general diagnosis of

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

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

Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbonmore » monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

DOE PAGES

Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.; ...

2014-10-05

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbonmore » monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins

Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia.

PubMed

Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik; Kirkby, Nikolai; Perch, Michael; Andersen, Claus; Lundgren, Jens D; Iversen, Martin

2018-02-01

The diagnostic yield for cytomegalovirus (CMV) polymerase chain reaction (PCR) viral load in bronchoalveolar lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain and was investigated in a large cohort of consecutive lung transplant recipients. Bronchoscopies within the first year of lung transplantation with CMV detectable in BAL by PCR (ie, viral load, ≥273 IU/mL) were included (66 recipients; 145 bronchoscopies); at each bronchoscopy episode, 2 independent experts reviewed clinical and laboratory information to determine whether the patient at that time fulfilled the criteria for CMV pneumonia per current international recommendations. Corresponding plasma CMV PCR viral load determined at time of the bronchoscopy (n = 126) was also studied. Optimal CMV PCR viral load cutoff for CMV pneumonia diagnosis was determined using receiver operating characteristics. CMV was detected in BAL with CMV PCR in 145 episodes, and 34 (23%) of these episodes fulfilled the criteria for CMV pneumonia. The area under the curve-receiver operating characteristics for CMV in BAL was 90% at the optimum cutoff (4545 IU/mL) with a corresponding sensitivity of 91% and specificity of 77% (in plasma the corresponding values were 274 IU/mL, 63% and 76%, respectively). CMV PCR viral load in BAL had a high performance to diagnose CMV pneumonia in lung transplant recipients; plasma CMV viral load did not reliably aid as a diagnostic tool.

Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines.

PubMed

Brasier, Allan R; Victor, Sundar; Boetticher, Gary; Ju, Hyunsu; Lee, Chang; Bleecker, Eugene R; Castro, Mario; Busse, William W; Calhoun, William J

2008-01-01

Asthma is a heterogeneous clinical disorder. Methods for objective identification of disease subtypes will focus on clinical interventions and help identify causative pathways. Few studies have explored phenotypes at a molecular level. We sought to discriminate asthma phenotypes on the basis of cytokine profiles in bronchoalveolar lavage (BAL) samples from patients with mild-moderate and severe asthma. Twenty-five cytokines were measured in BAL samples of 84 patients (41 severe, 43 mild-moderate) using bead-based multiplex immunoassays. The normalized data were subjected to statistical and informatics analysis. Four groups of asthmatic profiles could be identified on the basis of unsupervised analysis (hierarchical clustering) that were independent of treatment. One group, enriched in patients with severe asthma, showed differences in BAL cellular content, reductions in baseline pulmonary function, and enhanced response to methacholine provocation. Ten cytokines were identified that accurately predicted this group. Classification methods for predicting methacholine sensitivity were developed. The best model analysis predicted hyperresponders with 88% accuracy in 10 trials by using a 10-fold cross-validation. The cytokines that contributed to this model were IL-2, IL-4, and IL-5. On the basis of this classifier, 3 distinct hyperresponder classes were identified that varied in BAL eosinophil count and PC20 methacholine. Cytokine expression patterns in BAL can be used to identify distinct types of asthma and identify distinct subsets of methacholine hyperresponders. Further biomarker discovery in BAL may be informative.

An assay for the assessment of lipocortin 1 levels in human lung lavage fluid.

PubMed

Smith, S F; Goulding, N J; Godolphin, J L; Tetley, T D; Roberts, C M; Guz, A; Flower, R J

1990-07-20

The physiological function of the lipocortins, proteins which are thought to be glucocorticoid-regulated, is unclear. An improved assay for lipocortins might help to elucidate their role. A rapid and specific sandwich enzyme-linked immunosorbent assay (ELISA) for lipocortin 1 with a working range of 1-2000 ng/ml and an interrun coefficient of variation of less than 10% is described and used in this pilot study to quantify human lipocortin 1 for the first time in acellular bronchoalveolar lavage fluid (BALF), and in media conditioned by BAL cells, from control patients and those with pulmonary sarcoidosis. Using this assay a statistically significant relationship, not previously observed in man, has been demonstrated between concentrations of lipocortin 1/ml of BALF and serum cortisol levels (n = 10, rs = 0.6939, P less than 0.05). Although lipocortin 1 levels in acellular BALF were the same in control and sarcoid patients, significantly more lipocortin 1 was released from sarcoid BAL cells in culture (median 21.6, range 8.1-45.4 ng lipocortin/10(6) cells/h in culture) than from control cells (2.5, 1.5-7.6 ng lipocortin/10(6) cells/h in culture). The possible clinical significance of these data is discussed, but remains to be established.

Human body fluid proteome analysis

PubMed Central

Hu, Shen; Loo, Joseph A.; Wong, David T.

2010-01-01

The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future. PMID:17083142

Human body fluid proteome analysis.

PubMed

Hu, Shen; Loo, Joseph A; Wong, David T

2006-12-01

The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.

Bronchoalveolar inflammation after exposure to diesel exhaust: comparison between unfiltered and particle trap filtered exhaust

PubMed Central

Rudell, B.; Blomberg, A.; Helleday, R.; Ledin, M. C.; Lundback, B.; Stjernberg, N.; Horstedt, P.; Sandstrom, T.

1999-01-01

OBJECTIVES: Air pollution particulates have been identified as having adverse effects on respiratory health. The present study was undertaken to further clarify the effects of diesel exhaust on bronchoalveolar cells and soluble components in normal healthy subjects. The study was also designed to evaluate whether a ceramic particle trap at the end of the tail pipe, from an idling engine, would reduce indices of airway inflammation. METHODS: The study comprised three exposures in all 10 healthy never smoking subjects; air, diluted diesel exhaust, and diluted diesel exhaust filtered with a ceramic particle trap. The exposures were given for 1 hour in randomised order about 3 weeks apart. The diesel exhaust exposure apperatus has previously been carefully developed and evaluated. Bronchoalveolar lavage was performed 24 hours after exposures and the lavage fluids from the bronchial and bronchoalveolar region were analysed for cells and soluble components. RESULTS: The particle trap reduced the mean steady state number of particles by 50%, but the concentrations of the other measured compounds were almost unchanged. It was found that diesel exhaust caused an increase in neutrophils in airway lavage, together with an adverse influence on the phagocytosis by alveolar macrophages in vitro. Furthermore, the diesel exhaust was found to be able to induce a migration of alveolar macrophages into the airspaces, together with reduction in CD3+CD25+ cells. (CD = cluster of differentiation) The use of the specific ceramic particle trap at the end of the tail pipe was not sufficient to completely abolish these effects when interacting with the exhaust from an idling vehicle. CONCLUSIONS: The current study showed that exposure to diesel exhaust may induce neutrophil and alveolar macrophage recruitment into the airways and suppress alveolar macrophage function. The particle trap did not cause significant reduction of effects induced by diesel exhaust compared with unfiltered diesel

Bronchoalveolar inflammation after exposure to diesel exhaust: comparison between unfiltered and particle trap filtered exhaust.

PubMed

Rudell, B; Blomberg, A; Helleday, R; Ledin, M C; Lundbäck, B; Stjernberg, N; Hörstedt, P; Sandström, T

1999-08-01

Air pollution particulates have been identified as having adverse effects on respiratory health. The present study was undertaken to further clarify the effects of diesel exhaust on bronchoalveolar cells and soluble components in normal healthy subjects. The study was also designed to evaluate whether a ceramic particle trap at the end of the tail pipe, from an idling engine, would reduce indices of airway inflammation. The study comprised three exposures in all 10 healthy never smoking subjects; air, diluted diesel exhaust, and diluted diesel exhaust filtered with a ceramic particle trap. The exposures were given for 1 hour in randomised order about 3 weeks apart. The diesel exhaust exposure apperatus has previously been carefully developed and evaluated. Bronchoalveolar lavage was performed 24 hours after exposures and the lavage fluids from the bronchial and bronchoalveolar region were analysed for cells and soluble components. The particle trap reduced the mean steady state number of particles by 50%, but the concentrations of the other measured compounds were almost unchanged. It was found that diesel exhaust caused an increase in neutrophils in airway lavage, together with an adverse influence on the phagocytosis by alveolar macrophages in vitro. Furthermore, the diesel exhaust was found to be able to induce a migration of alveolar macrophages into the airspaces, together with reduction in CD3+CD25+ cells. (CD = cluster of differentiation) The use of the specific ceramic particle trap at the end of the tail pipe was not sufficient to completely abolish these effects when interacting with the exhaust from an idling vehicle. The current study showed that exposure to diesel exhaust may induce neutrophil and alveolar macrophage recruitment into the airways and suppress alveolar macrophage function. The particle trap did not cause significant reduction of effects induced by diesel exhaust compared with unfiltered diesel exhaust. Further studies are warranted to

Multi-platform metabolomics assays for human lung lavage fluids in an air pollution exposure study.

PubMed

Surowiec, Izabella; Karimpour, Masoumeh; Gouveia-Figueira, Sandra; Wu, Junfang; Unosson, Jon; Bosson, Jenny A; Blomberg, Anders; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Trygg, Johan; Nording, Malin L

2016-07-01

Metabolomics protocols are used to comprehensively characterize the metabolite content of biological samples by exploiting cutting-edge analytical platforms, such as gas chromatography (GC) or liquid chromatography (LC) coupled to mass spectrometry (MS) assays, as well as nuclear magnetic resonance (NMR) assays. We have developed novel sample preparation procedures combined with GC-MS, LC-MS, and NMR metabolomics profiling for analyzing bronchial wash (BW) and bronchoalveolar lavage (BAL) fluid from 15 healthy volunteers following exposure to biodiesel exhaust and filtered air. Our aim was to investigate the responsiveness of metabolite profiles in the human lung to air pollution exposure derived from combustion of biofuels, such as rapeseed methyl ester biodiesel, which are increasingly being promoted as alternatives to conventional fossil fuels. Our multi-platform approach enabled us to detect the greatest number of unique metabolites yet reported in BW and BAL fluid (82 in total). All of the metabolomics assays indicated that the metabolite profiles of the BW and BAL fluids differed appreciably, with 46 metabolites showing significantly different levels in the corresponding lung compartments. Furthermore, the GC-MS assay revealed an effect of biodiesel exhaust exposure on the levels of 1-monostearylglycerol, sucrose, inosine, nonanoic acid, and ethanolamine (in BAL) and pentadecanoic acid (in BW), whereas the LC-MS assay indicated a shift in the levels of niacinamide (in BAL). The NMR assay only identified lactic acid (in BW) as being responsive to biodiesel exhaust exposure. Our findings demonstrate that the proposed multi-platform approach is useful for wide metabolomics screening of BW and BAL fluids and can facilitate elucidation of metabolites responsive to biodiesel exhaust exposure. Graphical Abstract Graphical abstract illustrating the study workflow. NMR Nuclear Magnetic Resonance, LC-TOFMS Liquid chromatography-Time Of Flight Mass Spectrometry, GC Gas

Lung fibrosis-associated soluble mediators and bronchoalveolar lavage from idiopathic pulmonary fibrosis patients promote the expression of fibrogenic factors in subepithelial lung myofibroblasts.

PubMed

Bouros, Evangelos; Filidou, Eirini; Arvanitidis, Konstantinos; Mikroulis, Dimitrios; Steiropoulos, Paschalis; Bamias, George; Bouros, Demosthenes; Kolios, George

2017-10-01

Idiopathic pulmonary fibrosis (IPF) is characterized by infiltration of inflammatory cells, excessive collagen production and accumulation of myofibroblasts. We explored the possible role of subepithelial lung myofibroblasts (SELMs) in the development of fibrosis in IPF. SELMs, isolated from surgical specimens of healthy lung tissue, were cultured with pro-inflammatory factors or bronchoalveolar lavage fluid (BALF) from patients with IPF or idiopathic non-specific interstitial pneumonia (iNSIP) and their fibrotic activity was assessed. Stimulation of SELMs with pro-inflammatory factors induced a significant increase of Tissue Factor (TF) and Tumor necrosis factor-Like cytokine 1 A (TL1A) expression and collagen production in culture supernatants. Stimulation with BALF from IPF patients with mild to moderate, but not severe disease, and from iNSIP patients induced a significant increase of TF expression. BALF from all IPF patients induced a significant increase of TL1A expression and collagen production, while BALF from iNSIP patients induced a significant increase of TL1A, but not of collagen production. Interestingly, TGF-β1 and BALF from all IPF, but not iNSIP patients, induced a significant increase in SELMs migration. In conclusion, BALF from IPF patients induces fibrotic activity in lung myofibroblasts, similar to mediators associated with lung fibrosis, indicating a key role of SELMs in IPF. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of Two Commercial Real-Time PCR Kits for Aspergillus DNA Detection in Bronchoalveolar Lavage Fluid in Patients with Invasive Pulmonary Aspergillosis.

PubMed

Denis, Julie; Forouzanfar, Faezeh; Herbrecht, Raoul; Toussaint, Elise; Kessler, Romain; Sabou, Marcela; Candolfi, Ermanno; Letsher-Bru, Valérie

2018-05-01

Invasive pulmonary aspergillosis (IPA) is a common complication of immunosuppression. Rapid diagnosis using molecular techniques is essential to improve patient survival. PCR techniques are promising in enhancing Aspergillus detection in blood and respiratory samples. We evaluate for the first time the performances of two commercial real-time PCR kits, the A. fumigatus Bio-Evolution and the MycoGENIE A. fumigatus for the detection of A. fumigatus DNA in bronchoalveolar lavage (BAL) from patients with and without IPA. Seventy-three BAL samples were included. Thirty-one of them corresponded to patients with probable IPA, 11 to patients with possible IPA, and 31 to patients without aspergillosis, according to the 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. In the probable IPA group, A. fumigatus Bio-Evolution and the MycoGENIE A. fumigatus real-time PCR kits showed a specificity of 100% and a sensitivity of 81% and 71%, respectively. The A. fumigatus Bio-Evolution detected Aspergillus DNA in the 14 BAL samples with a positive Aspergillus culture result, whereas the MycoGENIE A. fumigatus PCR result was positive only for 12. In the possible IPA group, there were no positive real-time PCR or positive Aspergillus culture results. For the patients without aspergillosis, no positive result was observed for real-time PCR kit, despite the presence of various other non-Aspergillus pathogens in this group. Our study demonstrates an excellent specificity and a good sensitivity of A. fumigatus DNA detection in BAL samples with both kits. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Immunoglobulin concentrations in nasal lavage fluids in dogs with non-specific rhinitis.

PubMed

Wolschrijn, C F; Macri, R M; Bernadina, W E; Willemse, T; van den Brom, W E; Venker-van Haagen, A J

1996-03-01

The pathophysiology of non-specific chronic rhinitis(NSCR) in dogs is still unknown. In this study the possible role of immunological mechanisms in NSCR is examined, by comparing immunoglobulin concentrations in nasal lavage fluids of dogs with NSCR with those of healthy dogs. The immunoglobulin IgA was detected in nasal lavage fluids of both groups of dogs and the differences in relative levels of IgA in dogs with NSCR were not significant. IgM, IgG(a,b), and IgG(d) were detected more frequently in dogs with NSCR (P<0.05), and the relative levels were higher. The presence of IgG(a,b) may indicate the chronic character of rhinitis, and the presence of IgG(d) the possibility of an allergic component in its pathophysiology. The role of IgM is not completely clear.

Diagnostic Value of Bronchoalveolar Lavage for Diagnosis of Suspected Peripheral Lung Cancer.

PubMed

Bezel, Pascal; Tischler, Verena; Robinson, Cecile; Baumueller, Stephan; Bode-Lesniewska, Beata; Kohler, Malcolm; Freitag, Lutz; Franzen, Daniel

2016-09-01

There is a paucity of data concerning the benefit of bronchoalveolar lavage (BAL) for the diagnosis of suspected peripheral lung cancer (PLC). The aim of this study was to investigate the diagnostic value of BAL for the diagnosis of suspected PLC. All flexible bronchoscopies that included BAL among other modalities (brush, forceps, washing) for the diagnosis of a suspected PLC performed between 2009 and 2013 were analyzed in this retrospective study. A total of 260 patients were included. Malignancy was present in 61%. BAL's sensitivity for the diagnosis of malignancy was 29%, and overall diagnostic yield of BAL was 46%. However, only 1% of cancer diagnoses would have been missed in the absence of BAL. In the multivariable analysis, the size of lesion (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.02-1.33; P = .023), the presence of bronchus sign (OR, 4.73; 95% CI, 1.06-21.08; P = .042), and the presence of mediastinal/hilar lymphadenopathy (OR, 3.37; 95% CI, 1.53-7.41; P = .002) were associated with improved BAL true-positive ratio relating to diagnosis of malignancy. However, the effect of lesion size on sensitivity was small (area under the curve, 0.31; 95% CI, 0.23-0.40; P < .001). Ground-glass lesions were not associated with improved BAL diagnostic value. The number needed to test for BAL for the diagnosis of malignancy or pulmonary infection was 37. Conventional BAL has a low diagnostic value for the diagnosis of suspected PLC, and the low number needed to test does not qualify BAL as a recommended routine investigation for the diagnosis of suspected PLC for either solid or ground-glass lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of Gene Expression in Actinobacillus pleuropneumoniae Exposed to Bronchoalveolar Fluid

PubMed Central

Lone, Abdul G.; Deslandes, Vincent; Nash, John H. E.; Jacques, Mario; MacInnes, Janet I.

2009-01-01

Background Actinobacillus pleuropneumoniae, the causative agent of porcine contagious pleuropneumonia, is an important pathogen of swine throughout the world. It must rapidly overcome the innate pulmonary immune defenses of the pig to cause disease. To better understand this process, the objective of this study was to identify genes that are differentially expressed in a medium that mimics the lung environment early in the infection process. Methods and Principal Findings Since bronchoalveolar lavage fluid (BALF) contains innate immune and other components found in the lungs, we examined gene expression of a virulent serovar 1 strain of A. pleuropneumoniae after a 30 min exposure to BALF, using DNA microarrays and real-time PCR. The functional classes of genes found to be up-regulated most often in BALF were those encoding proteins involved in energy metabolism, especially anaerobic metabolism, and in cell envelope, DNA, and protein biosynthesis. Transcription of a number of known virulence genes including apxIVA and the gene for SapF, a protein which is involved in resistance to antimicrobial peptides, was also up-regulated in BALF. Seventy-nine percent of the genes that were up-regulated in BALF encoded a known protein product, and of these, 44% had been reported to be either expressed in vivo and/or involved in virulence. Conclusions The results of this study suggest that in early stages of infection, A. pleuropneumoniae may modulate expression of genes involved in anaerobic energy generation and in the synthesis of proteins involved in cell wall biogenesis, as well as established virulence factors. Given that many of these genes are thought to be expressed in vivo or involved in virulence, incubation in BALF appears, at least partially, to simulate in vivo conditions and may provide a useful medium for the discovery of novel vaccine or therapeutic targets. PMID:19578537

Soluble Human Leukocyte Antigen-G in the Bronchoalveolar Lavage of Lung Cancer Patients.

PubMed

Montilla, Dayana; Pérez, Mario; Borges, Lérida; Bianchi, Guillermo; Cova, José-Angel

2016-08-01

The main function of the HLA-G molecule in its membrane-bound and soluble forms is to inhibit the immune response by acting on CD4+ T cells, cytotoxic T cells, NK cells and dendritic cells. Lung cancer is a leading cause of death worldwide, and annual incidence is high in both women and men. Some studies have reported an increase of HLA-G serum levels in lung cancer, probably generated by tumor cells escaping the antitumor immune response. In this study the concentration of soluble HLA-G in bronchoalveolar lavage (BAL) in patients with primary and metastatic lung cancer was measured to determine its relation with tumor histological type and overall patient status according to the Karnofsky scale. Thirty-one lung cancer patients were included. A tumor biopsy was obtained by bronchoscopy and the tumor type was determined by hematoxylin and eosin staining. BAL samples were obtained to measure soluble HLA-G concentrations in an ELISA sandwich assay. The average value of soluble HLA-G was 49.04ng/mL. No correlation between soluble HLA-G levels and age, gender or smoking was observed. A highly significant difference was observed in the levels of soluble HLA-G in BAL from patients with different histological types of lung cancer, especially in metastatic tumors. The Karnofsky index showed a significant and inverse correlation with soluble HLA-G levels in BAL. Soluble HLA-G protein is significantly associated with metastatic tumors and patients with lower Karnofsky index and may be useful as a prognostic marker in lung cancer. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

The significance of oral streptococci in patients with pneumonia with risk factors for aspiration: the bacterial floral analysis of 16S ribosomal RNA gene using bronchoalveolar lavage fluid.

PubMed

Akata, Kentaro; Yatera, Kazuhiro; Yamasaki, Kei; Kawanami, Toshinori; Naito, Keisuke; Noguchi, Shingo; Fukuda, Kazumasa; Ishimoto, Hiroshi; Taniguchi, Hatsumi; Mukae, Hiroshi

2016-05-11

Aspiration pneumonia has been a growing interest in an aging population. Anaerobes are important pathogens, however, the etiology of aspiration pneumonia is not fully understood. In addition, the relationship between the patient clinical characteristics and the causative pathogens in pneumonia patients with aspiration risk factors are unclear. To evaluate the relationship between the patient clinical characteristics with risk factors for aspiration and bacterial flora in bronchoalveolar lavage fluid (BALF) in pneumonia patients, the bacterial floral analysis of 16S ribosomal RNA gene was applied in addition to cultivation methods in BALF samples. From April 2010 to February 2014, BALF samples were obtained from the affected lesions of pneumonia via bronchoscopy, and were evaluated by the bacterial floral analysis of 16S rRNA gene in addition to cultivation methods in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). Factors associated with aspiration risks in these patients were analyzed. A total of 177 (CAP 83, HCAP 94) patients were enrolled. According to the results of the bacterial floral analysis, detection rate of oral streptococci as the most detected bacterial phylotypes in BALF was significantly higher in patients with aspiration risks (31.0 %) than in patients without aspiration risks (14.7 %) (P = 0.009). In addition, the percentages of oral streptococci in each BALF sample were significantly higher in patients with aspiration risks (26.6 ± 32.0 %) than in patients without aspiration risks (13.8 ± 25.3 %) (P = 0.002). A multiple linear regression analysis showed that an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≥3, the presence of comorbidities, and a history of pneumonia within a previous year were significantly associated with a detection of oral streptococci in BALF. The bacterial floral analysis of 16S rRNA gene revealed that oral streptococci were mostly

Usefulness of FTA® cards as a Pneumocystis-DNA extraction method in bronchoalveolar lavage samples.

PubMed

Rodiño, Jenniffer M; Aguilar, Yudy A; Rueda, Zulma Vanessa; Vélez, Lázaro A

2016-01-01

FTA® cards (Fast Technology for Analysis of Nucleic Acids) are an alternative DNA extraction method in bronchoalveolar lavage (BAL) samples for Pneumocystis jirovecii molecular analyses. The goal was to evaluate the usefulness of FTA® cards to detect P. jirovecii-DNA by PCR in BAL samples compared to silica adsorption chromatography (SAC). This study used 134 BAL samples from immunocompromised patients previously studied to establish microbiological aetiology of pneumonia, among them 15 cases of Pneumocystis pneumonia (PCP) documented by staining and 119 with other alternative diagnoses. The FTA® system and SAC were used for DNA extraction and then amplified by nested PCR to detect P. jirovecii. Performance and concordance of the two DNA extraction methods compared to P. jirovecii microscopy were calculated. The influence of the macroscopic characteristics, transportation of samples and the duration of the FTA® card storage (1, 7, 10 or 12 months) were also evaluated. Among 134 BAL samples, 56% were positive for P. jirovecii-DNA by SAC and 27% by FTA®. All 15 diagnosed by microscopy were detected by FTA® and SAC. Specificity of the FTA® system and SAC were 82.4% and 49.6%, respectively. Compared to SAC, positivity by FTA® decreased with the presence of blood in BAL (62% vs 13.5%). The agreement between samples at 7, 10 and 12 months was 92.5% for FTA®. Positive cases by FTA® remained the same after shipment by mail. Results suggest that FTA® is a practical, safe and economical method to preserve P. jirovecii-DNA in BAL samples for molecular studies.

Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.

PubMed

Bewig, B; Haacke, T C; Tiroke, A; Bastian, A; Böttcher, H; Hirt, S W; Rautenberg, P; Haverich, A

2000-01-01

Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. Evaluation of methods for the rapid diagnosis of CMV pneumonitis. The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis. Copyright 2000 S. Karger AG, Basel.

Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial.

PubMed

Wainwright, Claire E; Vidmar, Suzanna; Armstrong, David S; Byrnes, Catherine A; Carlin, John B; Cheney, Joyce; Cooper, Peter J; Grimwood, Keith; Moodie, Marj; Robertson, Colin F; Tiddens, Harm A

2011-07-13

Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking. To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009. BAL-directed (n = 84) or standard (n = 86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P. aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results. Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan. Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P. aeruginosa in final BAL cultures (risk difference, -1.7% [95% confidence interval, -11.6% to 8.1%]; P = .73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95

[Comparative study of protein markers in serum and bronchoalveolar lavage fluid from patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry].

PubMed

Zhou, Ji-hong; Liu, Guang-nan; Huang, Si-ming; Zhong, Xiao-ning; Su, Hong; Zhou, Yi

2011-04-01

To detect the protein markers in serum and bronchoalveolar lavage fluid (BALF) of the patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technology, and to explore if they can be used as markers for the diagnosis of lung cancer. SELDI-TOF-MS technology and protein chips weak cation exchange (WCX-2 chip) were used to detect the protein mass spectrum in serum and BALF of 35 patients with lung cancer and 18 cases of benign pulmonary diseases. The different protein markers were analyzed by Biomarker Pattern Software and the initial diagnosis models were set up. The diagnosis models were verified further by blind screen to confirm the efficacy of diagnosis. Five protein peaks in the sera of the patients with lung cancer were significantly higher (P < 0.05). The protein peak with a mass/charge ratio (M/Z) of 5639 was selected to establish the classification tree model. The sensitivity of diagnosis was 80% (28/35) and the specificity was 78% (14/18). The results verified by blind screen showed a sensitivity of 85% (17/20), a specificity of 90% (9/10), a crude accuracy (CA) of 87% (26/30) and Youden's index (γ) of 0.7. Eight protein peaks in the BALF of the patients with lung cancer were significantly higher (P < 0.05). The different protein peaks with M/Z of 7976 and 11 809 respectively were selected to establish the classification tree model. The sensitivity of diagnosis was 86% (30/35) and the specificity was 72% (13/18). The results verified by blind screen showed a sensitivity of 90% (18/20), a specificity of 90% (9/10), a CA of 90% (27/30) and γ of 0.8. There was a complementary role in combination of differential proteins in serum and BALF and the sensitivity, specificity and accuracy of diagnosis for lung cancer were 100% by parallel test. The SELDI-TOF-MS technology can screen out the differential protein markers in serum and BALF of the patients with lung cancer, which show high sensitivity

Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

PubMed

Foster, D M; Sylvester, H J; Papich, M G

2017-12-01

Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p < .05). The concentrations of tilmicosin in DS and BAL samples exceeded plasma drug concentrations by 567 ± 189% and 776 ± 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

Sys-BodyFluid: a systematical database for human body fluid proteome research

PubMed Central

Li, Su-Jun; Peng, Mao; Li, Hong; Liu, Bo-Shu; Wang, Chuan; Wu, Jia-Rui; Li, Yi-Xue; Zeng, Rong

2009-01-01

Recently, body fluids have widely become an important target for proteomic research and proteomic study has produced more and more body fluid related protein data. A database is needed to collect and analyze these proteome data. Thus, we developed this web-based body fluid proteome database Sys-BodyFluid. It contains eleven kinds of body fluid proteomes, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, seminal fluid, human milk and amniotic fluid. Over 10 000 proteins are presented in the Sys-BodyFluid. Sys-BodyFluid provides the detailed protein annotations, including protein description, Gene Ontology, domain information, protein sequence and involved pathways. These proteome data can be retrieved by using protein name, protein accession number and sequence similarity. In addition, users can query between these different body fluids to get the different proteins identification information. Sys-BodyFluid database can facilitate the body fluid proteomics and disease proteomics research as a reference database. It is available at http://www.biosino.org/bodyfluid/. PMID:18978022

Sys-BodyFluid: a systematical database for human body fluid proteome research.

PubMed

Li, Su-Jun; Peng, Mao; Li, Hong; Liu, Bo-Shu; Wang, Chuan; Wu, Jia-Rui; Li, Yi-Xue; Zeng, Rong

2009-01-01

Recently, body fluids have widely become an important target for proteomic research and proteomic study has produced more and more body fluid related protein data. A database is needed to collect and analyze these proteome data. Thus, we developed this web-based body fluid proteome database Sys-BodyFluid. It contains eleven kinds of body fluid proteomes, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, seminal fluid, human milk and amniotic fluid. Over 10,000 proteins are presented in the Sys-BodyFluid. Sys-BodyFluid provides the detailed protein annotations, including protein description, Gene Ontology, domain information, protein sequence and involved pathways. These proteome data can be retrieved by using protein name, protein accession number and sequence similarity. In addition, users can query between these different body fluids to get the different proteins identification information. Sys-BodyFluid database can facilitate the body fluid proteomics and disease proteomics research as a reference database. It is available at http://www.biosino.org/bodyfluid/.

Cytoprotection: Immune and Matrix Modulation of Tissue Repair

DTIC Science & Technology

2012-04-01

bronchoalveolar lavage (BAL) fluid for cytokines, cell counts and eosinophilia, and histological analysis of airway hyper-responsiveness and remodeling...OVA administered intra-nasally on Days 21–25 with or without 0.1% XHA. B) Total leukocyte and eosinophil counts in bronchoalveolar lavage (BAL) fluid...and different doses of HA peptide. The absolute number of Tmr+ and FOXP3+ populations was determined using total cell counts and flow cytometry for Tmr

Polarized type 1 cytokine profile in bronchoalveolar lavage T cells of patients with hypersensitivity pneumonitis.

PubMed

Yamasaki, H; Ando, M; Brazer, W; Center, D M; Cruikshank, W W

1999-09-15

Hypersensitivity pneumonitis (HP) is characterized by an inflammatory lymphocytic alveolitis comprised of both CD8+ and CD4+ T cells. Animal models suggest that HP is facilitated by overproduction of IFN-gamma, and that IL-10 ameliorates severity of the disease, indicating a Th1-type response. To determine whether a Th1 phenotype in HP also exists clinically, bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells were obtained from HP individuals and analyzed for Th1 vs Th2 cytokine profiles. It was determined that soluble OKT3-stimulated BAL T cells cocultured with alveolar macrophages produced more IFN-gamma and less IL-10 than PB T cells cocultured with monocytes, but no difference was observed in IL-4 production. The monocytic cells did not account for this difference, as CD80 and CD86 expressions were similar, and coculturing PB T cells with alveolar macrophages resulted in no difference in IFN-gamma production. Similarly, there was no difference in IL-12 production between stimulated BAL or PB T cells; however, addition of rIL-12 significantly increased production of IFN-gamma by BAL T cells, but not by PB T cells. This effect was due to a difference in IL-12R expression. High affinity IL-12R were only present in association with BAL T cells. These studies indicate that clinical HP is characterized by a predominance of IFN-gamma-producing T cells, perhaps resulting from a reduction in IL-10 production and an increase in high affinity IL-12R compared with blood T cells.

PCR examination of bronchoalveolar lavage samples is a useful tool in pre-clinical diagnosis of ovine pulmonary adenocarcinoma (Jaagsiekte).

PubMed

Voigt, K; Brügmann, M; Huber, K; Dewar, P; Cousens, C; Hall, M; Sharp, J M; Ganter, M

2007-12-01

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The disease is a particular problem in flocks in many parts of the world. The aim of the study was to assess screening methods for individual animals as a prelude to future eradication trials. Results of histological examination were used as the standard to evaluate the relative sensitivity and specificity of an established heminested polymerase chain reaction (PCR) test for JSRV proviral DNA from blood and bronchoalveolar lavage (BAL) samples. PCR results from tissue samples are included as control data. PCR testing of blood samples was found to have an estimated sensitivity of only 10% (95% confidence interval (CI) 3-20) while the sensitivity of the PCR test on BAL samples was 89% (CI 79-96) in comparison to the results of histological examination. We conclude that PCR testing of BAL samples is an effective confirmatory test for sheep with suspected clinical OPA. It is also a useful tool for the pre-clinical identification of individual infected sheep within an infected flock and therefore may prove beneficial in future control or eradication programmes.

Broad-Range Detection of Microorganisms Directly from Bronchoalveolar Lavage Specimens by PCR/Electrospray Ionization-Mass Spectrometry

PubMed Central

Ullberg, Måns; Lüthje, Petra; Mölling, Paula; Strålin, Kristoffer

2017-01-01

The clinical demand on rapid microbiological diagnostic is constantly increasing. PCR coupled to electrospray ionization-mass spectrometry, PCR/ESI-MS, offers detection and identification of over 750 bacteria and Candida species directly from clinical specimens within 6 hours. In this study, we investigated the clinical performance of the IRIDICA BAC LRT Assay for detection of bacterial pathogens in 121 bronchoalveolar lavage (BAL) samples that were received consecutively at our bacterial laboratory for BAL culture. Commensal or pathogenic microorganisms were detected in 118/121 (98%) BAL samples by PCR/ESI-MS, while in 104/121 (86%) samples by routine culture (P<0.01). Detection of potentially pathogenic microorganisms by PCR/ESI-MS was evaluated in comparison with conventional culture-based or molecular methods. The agreement between positive findings was overall good. Most Staphylococcus aureus-positive PCR/ESI-MS results were confirmed by culture or species-specific PCR (27/33, 82%). The identity of Streptococcus pneumoniae could however be confirmed for only 6/17 (35%) PCR/ESI-MS-positive samples. Non-cultivable and fastidious pathogens, which were not covered by standard culture procedures were readily detected by PCR/ESI-MS, including Legionella pneumophila, Bordetella pertussis, Norcadia species and Mycoplasma pneumoniae. In conclusion, PCR/ESI-MS detected a broad range of potential pathogens with equal or superior sensitivity compared to conventional methods within few hours directly from BAL samples. This novel method might thus provide a relevant tool for diagnostics in critically ill patients. PMID:28085931

A Comprehensive Evaluation of Xpert MTB/RIF Assay With Bronchoalveolar Lavage Fluid as a Single Test or Combined With Conventional Assays for Diagnosis of Pulmonary Tuberculosis in China: A Two-Center Prospective Study

PubMed Central

Pan, Xiaofu; Yang, Shoufeng; Deighton, Margaret A.; Qu, Yue; Hong, Liang; Su, Feifei

2018-01-01

Introduction: The Xpert MTB/RIF is recommended by the World Health Organization as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB); however, China does not routinely use this test, partially due to the lack of a sufficient number of systematic evaluations of this assay in local patients. The aims of this study were to comprehensively assess the diagnostic performance of Xpert MTB/RIF, either alone or in combination with conventional assays for the diagnosis of pulmonary TB in adult Chinese patients. Methods: Xpert MTB/RIF tests were performed in 190 adult patients with suspected pulmonary TB, using bronchoalveolar lavage fluid (BALF) as test specimens. In parallel, conventional tests were carried out using the same BALF samples. Using two different reference standards, the performance of Xpert MTB/RIF, conventional assays and their combinations were evaluated. Results: Using mycobacterial culture as the reference comparator, Xpert MTB/RIF was found to be superior to smear-microscopy in detecting Mycobacterium tuberculosis. When final diagnosis, based on clinical criteria, was employed as the reference standard, Xpert MTB/RIF showed an even higher accuracy of 72.1%, supported by a sensitivity of 61.1% and specificity of 96.6%. Xpert MTB/RIF also demonstrated a powerful capability to identify pulmonary TB cases undetected by culture or smear-microscopy. Combining smear-microscopy and Xpert MTB/RIF was found to be the most accurate early predictor for pulmonary TB. Rifampicin resistance reported by Xpert MTB/RIF slightly deviated from that by phenotypic antibiotic susceptibility testing and requires further study with a larger sample size. Conclusion: This two-center prospective study highlights the value of Xpert MTB/RIF with BALF in diagnosing pulmonary TB in adult Chinese patients. These findings might contribute to the optimization of current diagnostic algorithms for pulmonary TB in China. PMID:29593688

A Comprehensive Evaluation of Xpert MTB/RIF Assay With Bronchoalveolar Lavage Fluid as a Single Test or Combined With Conventional Assays for Diagnosis of Pulmonary Tuberculosis in China: A Two-Center Prospective Study.

PubMed

Pan, Xiaofu; Yang, Shoufeng; Deighton, Margaret A; Qu, Yue; Hong, Liang; Su, Feifei

2018-01-01

Introduction: The Xpert MTB/RIF is recommended by the World Health Organization as a first line rapid test for the diagnosis of pulmonary tuberculosis (TB); however, China does not routinely use this test, partially due to the lack of a sufficient number of systematic evaluations of this assay in local patients. The aims of this study were to comprehensively assess the diagnostic performance of Xpert MTB/RIF, either alone or in combination with conventional assays for the diagnosis of pulmonary TB in adult Chinese patients. Methods: Xpert MTB/RIF tests were performed in 190 adult patients with suspected pulmonary TB, using bronchoalveolar lavage fluid (BALF) as test specimens. In parallel, conventional tests were carried out using the same BALF samples. Using two different reference standards, the performance of Xpert MTB/RIF, conventional assays and their combinations were evaluated. Results: Using mycobacterial culture as the reference comparator, Xpert MTB/RIF was found to be superior to smear-microscopy in detecting Mycobacterium tuberculosis . When final diagnosis, based on clinical criteria, was employed as the reference standard, Xpert MTB/RIF showed an even higher accuracy of 72.1%, supported by a sensitivity of 61.1% and specificity of 96.6%. Xpert MTB/RIF also demonstrated a powerful capability to identify pulmonary TB cases undetected by culture or smear-microscopy. Combining smear-microscopy and Xpert MTB/RIF was found to be the most accurate early predictor for pulmonary TB. Rifampicin resistance reported by Xpert MTB/RIF slightly deviated from that by phenotypic antibiotic susceptibility testing and requires further study with a larger sample size. Conclusion: This two-center prospective study highlights the value of Xpert MTB/RIF with BALF in diagnosing pulmonary TB in adult Chinese patients. These findings might contribute to the optimization of current diagnostic algorithms for pulmonary TB in China.

The diagnostic value of gastroesophageal reflux disease (GERD) symptoms and detection of pepsin and bile acids in bronchoalveolar lavage fluid and exhaled breath condensate for identifying lung transplantation patients with GERD-induced aspiration.

PubMed

Reder, Nicholas P; Davis, Christopher S; Kovacs, Elizabeth J; Fisichella, P Marco

2014-06-01

Gastroesophageal reflux disease (GERD) is thought to lead to aspiration and bronchiolitis obliterans syndrome after lung transplantation. Unfortunately, the identification of patients with GERD who aspirate still lacks clear diagnostic indicators. The authors hypothesized that symptoms of GERD and detection of pepsin and bile acids in the bronchoalveolar lavage fluid (BAL) and exhaled breath condensate (EBC) are effective for identifying lung transplantation patients with GERD-induced aspiration. From November 2009 to November 2010, 85 lung transplantation patients undergoing surveillance bronchoscopy were prospectively enrolled. For these patients, self-reported symptoms of GERD were correlated with levels of pepsin and bile acids in BAL and EBC and with GERD status assessed by 24-h pH monitoring. The sensitivity and specificity of pepsin and bile acids in BAL and EBC also were compared with the presence of GERD in 24-h pH monitoring. The typical symptoms of GERD (heartburn and regurgitation) had modest sensitivity and specificity for detecting GERD and aspiration. The atypical symptoms of GERD (aspiration and bronchitis) showed better identification of aspiration as measured by detection of pepsin and bile acids in BAL. The sensitivity and specificity of pepsin in BAL compared with GERD by 24-h pH monitoring were respectively 60 and 45 %, whereas the sensitivity and specificity of bile acids in BAL were 67 and 80 %. These data indicate that the measurement of pepsin and bile acids in BAL can provide additional data for identifying lung transplantation patients at risk for GERD-induced aspiration compared with symptoms or 24-h pH monitoring alone. These results support a diagnostic role for detecting markers of aspiration in BAL, but this must be validated in larger studies.

Clearance of bile and trypsin in rat lungs following aspiration of human gastric fluid.

PubMed

Leung, Jason H; Chang, Jui-Chih; Foltz, Emily; Bell, Sadé M; Pi, Cinthia; Azad, Sassan; Everett, Mary Lou; Holzknecht, Zoie E; Sanders, Nathan L; Parker, William; Davis, R Duane; Keshavjee, Shaf; Lin, Shu S

2016-01-01

In the clinical setting, there is no reliable tool for diagnosing gastric aspiration. A potential way of diagnosing gastric fluid aspiration entails bronchoalveolar lavage (BAL) with subsequent examination of the BAL fluid for gastric fluid components that are exogenous to the lungs. The objective of this study was to determine the longevity of the gastric fluid components bile and trypsin in the lung, in order to provide an estimate of the time frame in which assessment of these components in the BAL might effectively be used as a measure of aspiration. Human gastric fluid (0.5 mg/kg) was infused in the right lung of intubated male Fischer 344 rats (n = 30). Animals were sacrificed at specified times following the experimentally induced aspiration, and bronchoalveolar lavage fluid (BALF) was collected. Bile concentrations were analyzed by an enzyme-linked chromatogenic method, and the concentration of trypsin was quantified using an ELISA. Data were analyzed using non-linear regression and a one-phase decay equation. In this experimental model, the half-life of bile was 9.3 hours (r(2) = 0.81), and the half-life of trypsin was 9.0 hours (r(2) = 0.68). The half-lives of bile and trypsin in the rodent aspiration model suggest that the ability to detect aspiration may be limited to a few days post-aspiration. If studies using rats are any indication, it may be most effective to collect BAL samples within the first 24 hours of suspected aspiration events in order to detect aspiration.

Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

PubMed Central

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L.; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-01-01

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis. PMID:23389041

Identification of oxidative stress related proteins as biomarkers for lung cancer and chronic obstructive pulmonary disease in bronchoalveolar lavage.

PubMed

Pastor, Maria Dolores; Nogal, Ana; Molina-Pinelo, Sonia; Meléndez, Ricardo; Romero-Romero, Beatriz; Mediano, Maria Dolores; López-Campos, Jose L; García-Carbonero, Rocío; Sanchez-Gastaldo, Amparo; Carnero, Amancio; Paz-Ares, Luis

2013-02-06

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

[Effect of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) on gas exgange in patients after cardiac surgery].

PubMed

Benova, A; Dimitrov, N; Stoilova, M; Evstatiev, I; Tsarianski, G; Chirkov, A

2005-01-01

Fiberoptic bronchoscopy (FOB) has become a commonplace procedure in ICUs in patients after operation. We studied the outcomes of 35 FOBs performed in 26 patients (18 male and 8 female) during their stay in the ICU of "St. Ekaterina" University Hospital in Sofia after cardiac surgery with Cardiopulmonary Bypass. 33 (95%) of our patients were receiving mechanical ventilation at the time of the FOB. Bronchoalveolar lavage (BAL) was added to all procedures. 21 (60%) patients demonstrated an improvement after FOB. We defined improvement as either an increase of PaO2 with 10 or more mmHg in 6 hours after the procedure or better aeration on the follow-up chest radiograph (CXR). In 19 (54%) FOBs a great amount of secretions, plugging up bronchial lumens was seen. 14 (73%) of these patients were improved after the FOB. From the rest 16 patients, in whom such increased amount of secretions was not seen on FOB, only 7 (43%) demonstrated an improvement after the FOB. 16 procedures were performed on indications of atelectasis. 9 (56%) of them showed an improvement after the FOB. When atelectasis was not present on the CXR, an improvement was found in 12 (63%) cases. 1. FOB is most effective in removing retained secretions. 2. Although not so effective in resolving atelectasis that is not caused by central plugging, FOB should not be neglected because of the additional benefit of BAL for clearing more distal airways.

Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles.

PubMed

Klier, John; May, Anna; Fuchs, Sebastian; Schillinger, Ulrike; Plank, Christian; Winter, Gerhard; Gehlen, Heidrun; Coester, Conrad

2011-11-15

Recurrent airway obstruction (RAO) in horses has become a common problem in stabled horses in industrialized countries and deserves new therapeutic strategies. CpG-oligodeoxynucleotides (CpG-ODNs) were developed as effective immunostimulating agents to induce a Th2/Th1 shift. These agents showed a beneficial therapeutic effect in allergic diseases with predominant Th2 immunoresponse. CpG-ODN delivery by gelatin nanoparticles (GNPs) resulted in enhanced cellular uptake in murine and human in vitro studies and was a starting point for the present trial. The aim of this study was to identify an optimal stimulating CpG motif in horses with regard to species specificity on equine bronchoalveolar lavage (BAL) cells, in terms of a possible specific immunomodulation effect (Th2/Th1 shift) by used CpG-ODN. Accordingly, GNPs were evaluated as a delivery system to improve CpG-ODN immunostimulation in equine BAL cells. BAL fluid (BALF) was obtained from seven horses with moderate RAO and from four healthy horses and was subsequently incubated with five different CpG-ODN sequences (from A-, B- and C-class) and one ODN without any CpG motif. Release of three key cytokines (IL-4, IL-10 and IFN-γ) was quantified by ELISA to detect an allergy mediated Th2 immunoresponse (IL-4) as well as a proinflammatory Th1 response (IFN-γ). Due to its specific anti-inflammatory and anti-allergic effects, IL-10 was considered as a beneficial agent in pathophysiology of RAO. Results showed a significant upregulation of IL-10 and IFN-γ on the one hand and a downregulation of IL-4 on the other hand in RAO affected horses. Cell cultures from healthy horses had a significantly stronger response in cytokine release to all the applied stimuli in contrast to RAO derived cells. Comparing all five CpG sequences, A-class 2216 significantly showed the highest immunomodulatory effects on equine BALF cells and, hence, was chosen for follow-up preliminary clinical studies. Copyright © 2011 Elsevier B.V. All

Clearance of bile and trypsin in rat lungs following aspiration of human gastric fluid

PubMed Central

Leung, Jason H.; Chang, Jui-Chih; Foltz, Emily; Bell, Sadé M.; Pi, Cinthia; Azad, Sassan; Everett, Mary Lou; Holzknecht, Zoie E.; Sanders, Nathan L.; Parker, William; Davis, R. Duane; Keshavjee, Shaf; Lin, Shu S.

2016-01-01

ABSTRACT Purpose: In the clinical setting, there is no reliable tool for diagnosing gastric aspiration. A potential way of diagnosing gastric fluid aspiration entails bronchoalveolar lavage (BAL) with subsequent examination of the BAL fluid for gastric fluid components that are exogenous to the lungs. The objective of this study was to determine the longevity of the gastric fluid components bile and trypsin in the lung, in order to provide an estimate of the time frame in which assessment of these components in the BAL might effectively be used as a measure of aspiration. Materials and Methods: Human gastric fluid (0.5 mg/kg) was infused in the right lung of intubated male Fischer 344 rats (n = 30). Animals were sacrificed at specified times following the experimentally induced aspiration, and bronchoalveolar lavage fluid (BALF) was collected. Bile concentrations were analyzed by an enzyme-linked chromatogenic method, and the concentration of trypsin was quantified using an ELISA. Data were analyzed using non-linear regression and a one-phase decay equation. Results: In this experimental model, the half-life of bile was 9.3 hours (r 2 = 0.81), and the half-life of trypsin was 9.0 hours (r 2 = 0.68). Conclusions: The half-lives of bile and trypsin in the rodent aspiration model suggest that the ability to detect aspiration may be limited to a few days post-aspiration. If studies using rats are any indication, it may be most effective to collect BAL samples within the first 24 hours of suspected aspiration events in order to detect aspiration. PMID:26873328

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

PubMed Central

Clarke, R W; Coull, B; Reinisch, U; Catalano, P; Killingsworth, C R; Koutrakis, P; Kavouras, I; Murthy, G G; Lawrence, J; Lovett, E; Wolfson, J M; Verrier, R L; Godleski, J J

2000-01-01

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur

Release of MicroRNAs into Body Fluids from Ten Organs of Mice Exposed to Cigarette Smoke

PubMed Central

Izzotti, Alberto; Longobardi, Mariagrazia; La Maestra, Sebastiano; Micale, Rosanna T.; Pulliero, Alessandra; Camoirano, Anna; Geretto, Marta; D'Agostini, Francesco; Balansky, Roumen; Miller, Mark Steven; Steele, Vernon E.; De Flora, Silvio

2018-01-01

Purpose: MicroRNAs are small non-coding RNAs that regulate gene expression, thereby playing a role in a variety of physiological and pathophysiological states. Exposure to cigarette smoke extensively downregulates microRNA expression in pulmonary cells of mice, rats, and humans. Cellular microRNAs are released into body fluids, but a poor parallelism was previously observed between lung microRNAs and circulating microRNAs. The purpose of the present study was to validate the application of this epigenetic biomarker by using less invasive collection procedures. Experimental design: Using microarray analyses, we measured 1135 microRNAs in 10 organs and 3 body fluids of mice that were either unexposed or exposed to mainstream cigarette smoke for up to 8 weeks. The results obtained with selected miRNAs were validated by qPCR. Results: The lung was the main target affected by smoke (190 dysregulated miRNAs), followed by skeletal muscle (180), liver (138), blood serum (109), kidney (96), spleen (89), stomach (36), heart (33), bronchoalveolar lavage fluid (32), urine (27), urinary bladder (12), colon (5), and brain (0). Skeletal muscle, kidney, and lung were the most important sources of smoke-altered microRNAs in blood serum, urine, and bronchoalveolar lavage fluid, respectively. Conclusions: microRNA expression analysis was able to identify target organs after just 8 weeks of exposure to smoke, well before the occurrence of any detectable histopathological alteration. The present translational study validates the use of body fluid microRNAs as biomarkers applicable to human biomonitoring for mechanistic studies, diagnostic purposes, preventive medicine, and therapeutic strategies. PMID:29721069

Angiogenic axis angiopoietin-1 and angiopoietin-2/Tie-2 in non-small cell lung cancer: a bronchoalveolar lavage and serum study.

PubMed

Naumnik, W; Naumnik, B; Niewiarowska, K; Ossolinska, M; Chyczewska, E

2013-01-01

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), ligands for the Tie-2 receptor expressed on endothelial cells, play a critical role in angiogenesis, in concert with vascular endothelial growth factor (VEGF). Angiogenesis is important for tumor growth and development and also is implicated in the pathogenesis of interstitial lung diseases. The aim of this study was to evaluate the concentration of Ang-1, Ang-2, Tie-2, interleukin-18 (IL-18), transforming growth factor beta-1 (TGF β1), and VEGF domain in both serum and bronchoalveolar lavage fluid (BALF) of lung cancer patients before chemotherapy. We studied 45 non-small cell lung cancer (NSCLC) patients (M/F; 38/7; mean age 62 ± 4 years). The age-matched control groups consisted of 15 sarcoidosis (BBS), 15 hypersensivity pneumonitis (HP), and 15 healthy subjects. The patients with NSCLC had a significantly higher level of Ang-1 compared with the BBS and healthy subjects, and a higher level of Ang-2 compared with the healthy subjects in both serum and BALF. BALF level of IL-18 was lower in the NSCLC than that in the HP group, but higher than that in the BBS patients. Serum level of IL-18 was higher in the NSCLC than in the healthy subjects. The NSCLC group had lower VEGF in BALF than that in healthy subjects. Receiver-operating characteristics (ROC) curves were applied to find the cut-off the serum levels of Ang-1 and Ang-2 levels in BALF. We did not find any correlation between the levels of Ang-1, Ang-2, Tie-2, and the stage of tumor or treatment response (prospectively). We conclude that the angiogenic axis Ang-1 and Ang-2/Tie-2 may play an important role in lung cancer development and their concentrations may be a useful marker at the time of initial diagnosis of lung cancer.

Aspergillus colonization in patients with bronchogenic carcinoma.

PubMed

Ali, Sana; Malik, Abida; Bhargava, Rakesh; Shahid, Mohammad; Fatima, Nazish

2014-05-01

Aspergillus antigens such as galactomannan antigen, a cell wall polysaccharide, can be detected in patient's serum or bronchoalveolar lavage. To study the prevalence of Aspergillus infection in patients with bronchogenic carcinoma, we measured galactomannan antigen in serum and bronchoalveolar lavage samples of patients with bronchogenic carcinoma. The study was conducted on 45 bronchogenic carcinoma patients. The diagnosis of lung cancer was confirmed by bronchoscopy, histopathological and radiological examinations. Bronchoalveolar lavage fluid collected from each patient by fiberoptic bronchoscopy was subjected to direct microscopy and culture on Sabouraud's dextrose agar and Czapek-Dox agar, and Aspergillus galactomannan antigen was measured in serum and bronchoalveolar lavage samples. The majority of patients were male (93.3%) in the age group 51-60 years, 88.9% were addicted to gutka chewing, and 82.1% were addicted to smoking. Most patients complained of cough (73%) and shortness of breath (51.1%). Squamous cell carcinoma (64.4%) was the most common malignancy, followed by adenocarcinoma (13.3%). On culture of bronchoalveolar lavage samples, 35.5% showed growth of Aspergillus spp. (Aspergillus fumigatus in 17.8%, Aspergillus flavus in 13.3%, and Aspergillus niger in 4.4%). Galactomannan antigen was detected in 58.3% of bronchoalveolar lavage samples and 47.2% of serum samples. There is a high prevalence of aspergillosis in patients with lung carcinoma, especially among smokers and gutka chewers.

The Prevalence of Pneumocystis jiroveci in Bronchoalveolar Lavage Specimens of Lung Transplant Recipients Examined by the Nested PCR.

PubMed

Izadi, Morteza; Jonaidi Jafari, Nematollah; Sadraei, Javid; Mahmoodzadeh Poornaki, Abbas; Rezavand, Babak; Zarrinfar, Hossein; Abdi, Jahangir; Mohammadi, Younes

2014-12-01

The use of immune suppressive drugs for organ transplant recipients predisposes them to opportunistic infections, especially by fungal agents. Pneumocystis jiroveci, as an opportunistic pathogen, endangers the patients' life in those with immune system disorders. Early detection of latent Pneumocystis infection in susceptible patients may help choose the optimal treatment for these patients. The aim of this study was to identify and determine the colonization of latent P. jiroveci infection among lung transplant recipients. This cross-sectional descriptive study was conducted on lung transplant recipients. Bronchoalveolar lavage (BAL) specimens were collected from 32 patients undergoing bronchoscopy. The samples were aseptically homogenized by 10 mM dithiothreitol, and their DNA was extracted. The mtLSUrRNA gene of P. jiroveci was amplified using nested PCR in two stages. Nested PCR was performed using external primers of pAZ-102-E and pAZ102-H followed by using the PCR product of the first stage and internal primers of pAZ-102-E and pAZ102-L2. The genome of P. jiroveci was revealed by a 346 bp PCR product in the initial amplification and a 120 bp product in the nested PCR. The results showed that seven BAL specimens (21.9%) from lung transplant recipients were positive for P. jiroveci. In molecular epidemiology studies, nested PCR has higher sensitivity than PCR. Results of this study support the colonization of P. jiroveci in patients receiving lung transplantation. Patients who are carriers of P. jiroveci are at a higher risk of P. jiroveci pneumonia.

Lung lavage with oxygenated perfluorochemical liquid in acute lung injury.

PubMed

Richman, P S; Wolfson, M R; Shaffer, T H

1993-05-01

To investigate the effects of lung lavage with oxygenated liquid perfluorochemical on gas exchange, lung mechanics, and cardiac function in animals with acute lung injury. Prospective, randomized, controlled trial. Animal laboratory. Eight adult cats (2 to 4 kg, random sex). Two insults were combined to cause lung injury: oleic acid infusion and saline whole-lung wash. Animals were assigned to either the control or treatment group which consisted of a perfluorochemical liquid (Rimar 101) lavage. Perfluorochemical liquid lavage was performed three times at hourly intervals after lung injury. Three other cats with identical injury but no perfluorochemical liquid lavage served as control animals. All cats were ventilated with an FIO2 of 0.95 and positive end-expiratory pressure of 2 cm H2O continuously. Arterial blood gas tensions and pH, dynamic pulmonary compliance were measured at 15-min intervals. Cardiac index was assessed hourly, and lung fluid was collected after each of the three perfluorochemical liquid lavages. Arterial oxygen tension and pulmonary compliance deteriorated abruptly after lung injury in all cats, and improved significantly (p < .001, two-way analysis of variance) 15 mins after perfluorochemical liquid lavage. These parameters gradually returned to their baseline over 60 mins. Arterial blood pressure and cardiac index decreased after injury in all cats, and were not significantly changed after perfluorochemical liquid lavage. Hemorrhagic fluid was recovered from distal airways by perfluorochemical liquid lavage, despite prior suctioning of the airway. Perfluorochemical liquid lavage removes pulmonary edema fluid and improves gas exchange and the mechanical properties of the lung, after acute severe lung injury.

Use of EPR Spin-Trapping Techniques to Detect Radicals from Rat Lung Lavage Fluid Following Sulfur Mustard Vapor Exposure

DTIC Science & Technology

1993-05-13

lung injury. Anesthetized rats were intratracheally intubated and exposed to 0.35 mg HD vapor over 50 min, Immediately, 1 hr or 24 hr after exposure...lungs were lavaged with the spin trap, alpha-phenyl-t-butyl nitrone (PBN; 0.35 mg/ml). Recovered lavage fluid was assayed by EPR spectroscopy for...in EtOH (100 Ml), or EtOH alone (control), was placed in a water Jacketed (37° C) vapor generator and the rats .ere exposed for 50 min. by which time

Prediction of therapeutic response in steroid-treated pulmonary sarcoidosis. Evaluation of clinical parameters, bronchoalveolar lavage, gallium-67 lung scanning, and serum angiotensin-converting enzyme levels

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

Hollinger, W.M.; Staton, G.W. Jr.; Fajman, W.A.

1985-07-01

To find a pretreatment predictor of steroid responsiveness in pulmonary sarcoidosis the authors studied 21 patients before and after steroid treatment by clinical evaluation, pulmonary function tests, bronchoalveolar lavage (BAL), gallium-67 lung scan, and serum angiotensin-converting enzyme (SACE) level. Although clinical score, forced vital capacity (FVC), BAL percent lymphocytes (% lymphs), quantitated gallium-67 lung uptake, and SACE levels all improved with therapy, only the pretreatment BAL % lymphs correlated with the improvement in FVC (r = 0.47, p less than 0.05). Pretreatment BAL % lymphs of greater than or equal to 35% predicted improvement in FVC of 10/11 patients, whereasmore » among 10 patients with BAL % lymphs less than 35%, 5 patients improved and 5 deteriorated. Clinical score, pulmonary function parameters, quantitated gallium-67 lung uptake, and SACE level used alone, in combination with BAL % lymphs or in combination with each other, did not improve this predictive value. The authors conclude that steroid therapy improves a number of clinical and laboratory parameters in sarcoidosis, but only the pretreatment BAL % lymphs are useful in predicting therapeutic responsiveness.« less

Physiological and lavage fluid cytological and biochemical endpoints of toxicity in the rat

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

Lehnert, B.E.

1992-01-01

Exposure of the respiratory tract to toxic materials can result in a variety of physiologic disturbances that can serve as endpoints of toxicity. In addition to a brief review of commonly assessed physiologic endpoints, attention is given in the first component of this report to the use of both nose breathing and mouth'' breathing rats in toxicity studies that involve measurements of ventilatory functional changes in response to test atmospheres. Additionally, the usefulness of maximum oxygen consumption, or VO[sub 2max], as a physiologic endpoint of toxicity that uses exercising rats after exposure to test atmospheres is described, along with anmore » introduction to post-exposure exercise as an important behavioral activity that can markedly impact on the severity of acute lung injury caused by pneumoedematogenic materials. The second component of this report focuses on bronchoalveolar lavage and cytological and biochemical endpoints that can be assessed in investigations of the toxicities of test materials. As will be shown herein, some of the biochemical endpoints of toxicity, especially, can sensitively detect subtle injury to the lower respiratory tract that may escape detection by changes in some other conventional endpoints of toxicity, including lung gravimetric increases and histopathological alterations.« less

Physiological and lavage fluid cytological and biochemical endpoints of toxicity in the rat

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

Lehnert, B.E.

1992-12-31

Exposure of the respiratory tract to toxic materials can result in a variety of physiologic disturbances that can serve as endpoints of toxicity. In addition to a brief review of commonly assessed physiologic endpoints, attention is given in the first component of this report to the use of both nose breathing and ``mouth`` breathing rats in toxicity studies that involve measurements of ventilatory functional changes in response to test atmospheres. Additionally, the usefulness of maximum oxygen consumption, or VO{sub 2max}, as a physiologic endpoint of toxicity that uses exercising rats after exposure to test atmospheres is described, along with anmore » introduction to post-exposure exercise as an important behavioral activity that can markedly impact on the severity of acute lung injury caused by pneumoedematogenic materials. The second component of this report focuses on bronchoalveolar lavage and cytological and biochemical endpoints that can be assessed in investigations of the toxicities of test materials. As will be shown herein, some of the biochemical endpoints of toxicity, especially, can sensitively detect subtle injury to the lower respiratory tract that may escape detection by changes in some other conventional endpoints of toxicity, including lung gravimetric increases and histopathological alterations.« less

Identification of Candida albicans and Candida dubliniensis Species Isolated from Bronchoalveolar Lavage Samples Using Genotypic and Phenotypic Methods.

PubMed

Kianipour, Sahar; Ardestani, Mohammad Emami; Dehghan, Parvin

2018-01-01

Candida dubliniensis is a newly diagnosed species very similar to Candida albicans phenotypically and first discovered in the mouth of people with AIDS in 1995. Among the different phenotypic and genotypic methods, a cost-effective method should be selected which makes it possible to differentiate these similar species. Polymerase chain reaction (PCR)-restriction fragment length polymorphism with MspI enzyme and the Duplex-PCR method were done by DNA extraction using boiling. The sequencing of the amplified ribosomal region was used to confirm the C. dubliniensis species. Direct examination and colony count of the yeasts were applied for bronchoalveolar lavage (BAL) samples and the growth rate of the yeasts were studied at 45°C. To understand the ability formation of chlamydoconidia in yeast isolates, they were separately cultured on the sunflower seed agar, wheat flour agar, and corn meal agar media. Fifty-nine (49.2%) yeast colonies were identified from the total of 120 BAL specimens. Twenty-nine isolated yeasts; including 17 (58.6%) of C. albicans / dubliniensis complex and 12 (41.4%) of nonalbicans isolates produced pseudohypha or blastoconidia in direct smear with a mean colony count of 42000 CFU/mL. C. albicans with the frequency of 15 (42.9%) were the most common isolated yeasts, whereas C. dubliniensis was identified in two nonHIV patients. Sequencing of the replicated gene fragment is the best method for identifying the yeasts, but the determination of the species by phenotypic methods such as the creation of chlamydoconidia in sunflower seeds agar and wheat flour agar media can be cost-effective, have sensitivity and acceptable quality.

Levels of IL-32 in Serum, Induced Sputum Supernatant, and Bronchial Lavage Fluid of Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Gasiuniene, Edita; Lavinskiene, Simona; Sakalauskas, Raimundas; Sitkauskiene, Brigita

2016-10-01

Interleukin-32 (IL-32) is a newly described cytokine which is expected to have an important role in autoimmune disorders. It was shown that chronic obstructive pulmonary disease (COPD) has a component of autoimmunity, though the role of IL-32 in its pathogenesis is not known. The aim of this study was to estimate IL-32 concentrations in serum, induced sputum (IS) supernatant and bronchoalveolar lavage (BAL) fluid from patients with COPD, and to compare asthma patients with and healthy subjects. Outpatients with COPD (63.7 ± 8.4 years, n = 51), asthma (58.3 ± 12.4 years, n = 31), and healthy subjects (59.8 ± 8.2 years, n = 9) were studied. The levels of IL-32 in serum, BAL fluid, and IS supernatant samples were analyzed by ELISA. Concentrations of IL-32 were higher in all the studied materials from patients with COPD (BAL 22.46 ± 2.48 pg/ml, IS 19.66 ± 1.69 pg/ml, serum 26.77 ± 2.56 pg/ml) in comparison with patients with asthma (BAL 6.25 ± 1.08 pg/ml, IS 5.82 ± 1.15 pg/ml, serum 6.09 ± 1.16 pg/ml, p < 0.05 respectively) as well as healthy subjects (BAL 4.21 ± 1.13 pg/ml, IS 3.59 ± 0.66 pg/ml, serum 4.63 ± 1.03 pg/ml, p < 0.05 respectively). Moreover, the level of IL-32 was higher in COPD smokers than in COPD ex-smokers in investigated respiratory tissue compartments and serum, and correlated with smoking history. Increased level of IL-32 in serum, IS supernatant, and BAL fluid from patients with COPD in comparison with asthma patients and healthy subjects suggest that IL-32 may play an important role in the pathogenesis of COPD, which depends on the smoking history.

The secretory IgA system of lung secretions in chronic obstructive bronchitis: comparison of sputum with secretions obtained during fibreoptic bronchoscopy.

PubMed Central

Wiggins, J; Hill, S L; Stockley, R A

1984-01-01

The constituents of the secretory immunoglobulin A system (dimeric IgA, total secretory component and free secretory component) were measured in sputum sol phase, tracheal aspirates, and bronchoalveolar lavage fluids from 15 patients undergoing fibreoptic bronchoscopy. All of the proteins showed a progressive decrease in concentration from sputum to the bronchoalveolar lavage fluids (2p less than 0.001). Standardisation of samples by means of protein concentration ratios showed that all secretions were generally similar in respect of their secretory IgA profiles, although major differences remained in some individual patients. The between patient variability of the results was generally reduced by the use of protein concentration ratios, allowing closer comparison between subjects. When the secretion albumin concentration was used as a standard, however, it increased the variability of the sputum sol phase IgA components (2p less than 0.01), whereas it decreased the variability of the IgA components in the bronchoalveolar lavage fluid (2p less than 0.05). The role of albumin as a standard protein for assessing the secretory IgA system in lung secretions remains uncertain. PMID:6463931

Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

PubMed Central

Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.

2014-01-01

We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

Distinction between mesothelioma and lung adenocarcinoma based on immunohistochemistry in a patient with asbestos bodies in bronchoalveolar fluid - case report.

PubMed

Raşcu, Agripina; Naghi, Eugenia; OŢelea, Marina Ruxandra; NiŢu, Floarea Mimi; Arghir, Oana Cristina

2016-01-01

Asbestos is a mineral-mined form the rocks, consisting in amosite (brown asbestos), crocidolite (blue asbestos) and÷or chrysotile (white asbestos) used in many industries. Researches about the exposure to asbestos dust and asbestosis related diseases started almost a century ago. The first case report of fatal asbestosis disease was published in 1906, in England, by Dr. Hubert Montague Murray. A decade after, asbestos "curious bodies" were firstly described in the lung tissue by Cooke (1926) and McDonald (1927). Occupational exposure to asbestos is now regulated in Romania, but past exposure is still a cause of asbestosis-related diseases (ARDs), including lung cancer. A peculiar association between a lung adenocarcinoma, a previously healed pulmonary tuberculosis (PTB) disease, is reported in a 61-year-old nonsmoker white man, a former factory worker with 29 years of occupational exposure history to cement and asbestos fibers. The positive diagnosis of asbestos exposure was facilitated by asbestos bodies determined in bronchoalveolar lavage fluid. The main purpose of this case report is to describe the development of a right pleural effusion which was not revelatory for a mesothelioma but for an adenocarcinoma of the lung. An accurate morphologic and immunohistochemistry assessment of a pleural biopsy sample excluded mesothelioma and was crucial in the positive diagnosis of adenocarcinoma. In conclusion, unilateral paraneoplastic pleural effusion in a nonsmoker male with occupational exposure to asbestosis fibers was suggestive for adenocarcinoma related asbestosis of the lung. Lung cancer and malignant pleural exudate developed after a long latency cumulative retention time of asbestos fibers.

Asbestos bodies in bronchoalveolar lavage in the 21st century: a time-trend analysis in a clinical population.

PubMed

Nuyts, Valerie; Vanhooren, Hadewijch; Begyn, Sarah; Nackaerts, Kristiaan; Nemery, Benoit

2017-01-01

Asbestos bodies (AB) in bronchoalveolar lavage (BAL) can be detected by light microscopy and their concentration is indicative of past cumulative asbestos exposure. We assessed clinical and exposure characteristics, as well as possible time trends, among patients in whom AB had been quantified in BAL. BAL samples obtained from 578 participants between January 1997 and December 2014 were available for analysis. The processing of samples and the microscopic analysis were performed by a single expert and 76% of samples came from a single tertiary care hospital, allowing clinical and exposure data to be extracted from patient files. The study population (95% males) had a mean age of 62.5 (±12.4) years. AB were detected in 55.2% of the samples, giving a median concentration of 0.5 AB/mL (95th centile: 23.6 AB/mL; highest value: 164.5 AB/mL). The AB concentration exceeded 1 AB/mL in 39.4% and 5 AB/mL in 17.8%. A significant decrease from a geometric mean of 0.93 AB/mL in 1997 to 0.2 AB/mL in 2014 was apparent. High AB concentrations generally corresponded with occupations with (presumed) high asbestos exposure. AB concentrations were higher among patients with asbestosis and pleural plaques, when compared with other disease groups. Nevertheless, a substantial proportion of participants with likely exposure to asbestos did not exhibit high AB counts. This retrospective study of a large clinical population supports the value of counting AB in BAL as a complementary approach to assess past exposure to asbestos. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Costs of bronchoalveolar lavage-directed therapy in the first 5 years of life for children with cystic fibrosis.

PubMed

Moodie, Marj; Lal, Anita; Vidmar, Suzanna; Armstrong, David S; Byrnes, Catherine A; Carlin, John B; Cheney, Joyce; Cooper, Peter J; Grimwood, Keith; Robertson, Colin F; Tiddens, Harm A; Wainwright, Claire E

2014-09-01

To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P = .90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P = .48). BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings. Copyright © 2014 Elsevier Inc. All rights reserved.

Does molecular analysis increase the efficacy of bronchoalveolar lavage in the diagnosis and management of respiratory infections in hemato-oncological patients?

PubMed

Oren, Ilana; Hardak, Emilia; Zuckerman, Tsila; Geffen, Yuval; Hoffman, Ron; Yigla, Mordechai; Avivi, Irit

2016-09-01

The identification of the specific pathogen responsible for a respiratory infection in patients with hematological malignancies (HM) would ensure relevant treatment and prevent toxicity associated with anti-infective therapy. This large-scale study aimed to explore the clinical impact of fiberoptic bronchoscopy with bronchoalveolar lavage (FOB-BAL) in conjunction with molecular analysis on the diagnosis and management of respiratory infections in hemato-oncological patients. All consecutive patients with HM and pulmonary infiltrates, who underwent FOB-BAL between January 2008 and January 2013, were included in the analysis. Clinical characteristics, FOB-BAL results, and treatment adjustments were recorded, and factors predicting a positive BAL were assessed. Four hundred and twenty-five FOB-BAL procedures were analyzed. BAL revealed a specific diagnosis in 219 (51.5%) patients, 208 of them with a pulmonary infection. Infectious etiological agents found were mainly Aspergillus spp (n=142), bacterial species (n=44), and Pneumocystis jirovecii (n=34). Multivariate analysis showed that a lymphoproliferative disease, ≥2 symptoms (dyspnea/cough/hemoptysis/pleuritic pain), and less than 4 days between symptom appearance and FOB-BAL, predicted a positive FOB-BAL result. BAL results prompted a treatment modification in 48% of subjects. FOB-BAL in conjunction with molecular assays is efficient in the rapid detection of life-threatening infections, allowing for adjustment of anti-infective therapy, which may result in better outcomes and reduce treatment-related toxicity. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Differential modulation of leukotriene B4 synthesis and degradation in human bronchoalveolar lavage cells by lipopolysaccharide and tobacco smoke.

PubMed

Mao, Jenny T; Tashkin, Donald P; Tsu, I-Hsien; Serio, Kenneth J

2008-09-01

Leukotrienes have been implicated to play a prominent inductive role in carcinogenesis. We previously reported that bronchoalveolar lavage (BAL) cells from smokers manifested higher levels of leukotriene B4 (LTB4) production than ex-smokers. This study aims to elucidate the underlying mechanism(s). BAL cells from current and former smokers were exposed to lipopolysaccharide (LPS) for up to 7 days. LPS induced the release of LTB4 from BAL cells and down-regulated 5-lipoxygenase (5-LOX) mRNA expression in a dose-dependent manner, followed by a decrease in 5-LOX protein production and normalization of LTB4 levels. Exogenous LTB4 inhibited LPS-induced 5-LOX activity and accentuated the down-regulation of 5-LOX mRNA, whereas suppression of 5-LOX abrogated the LPS-induced changes, suggesting a negative feedback mechanism. LPS concomitantly induced expression and activity of the LTB4 metabolizing enzyme LTB4 omega-hydroxylase (LTB4OH) in ex-smokers' BAL cells, but not in smokers' BAL cells. In vitro smoke exposure of ex-smokers' BAL cells also abrogated the LPS-induced up-regulation of LTB4OH mRNA expression. Furthermore, ex-smokers' BAL cells expressed significantly higher LTB4OH mRNA levels than smokers' BAL cells. Such differential modulation of LTB4 synthesis and degradation by LPS in the setting of tobacco smoke exposure suggests that mechanisms responsible for sustained elevation of LTB4 levels in the lung microenvironment may contribute to the pathogenesis of tobacco-related respiratory diseases such as lung cancer. By regulating the balance of LTB4 in the lung, LTB4OH may function as a suppressor of lung carcinogenesis.

Phase I study of adenovirus p53 administered by bronchoalveolar lavage in patients with bronchioloalveolar cell lung carcinoma: ECOG 6597.

PubMed

Keedy, Vicki; Wang, Wei; Schiller, Joan; Chada, Sunil; Slovis, Bonnie; Coffee, Keith; Worrell, John; Thet, Lyn A; Johnson, David H; Carbone, David P

2008-09-01

This pilot phase I trial evaluated the safety and maximum-tolerated dose of p53 gene transfer using an adenovirus vector (Ad-p53) delivered via bronchoalveolar lavage (BAL) to patients with bronchioloalveolar lung carcinoma (BAC). Patients were initially administered two treatments of Ad-p53 to a single involved lobe, beginning at 2 x 10(9) viral particles (vp) per dose and escalated to a maximum of 2 x 10(12) vp. If a clinical benefit was seen and the treatment was well tolerated, additional doses could be administered to additional lobes. Twenty-five patients were treated at doses between 2 x 10(9) and 2 x 10(12) vp. At 2 x 10(12) vp, one patient experienced grade 4 pulmonary toxicity, and one patient died 25 days after his second cycle; therefore, a cohort of 10 patients was treated at the recommended phase II dose of 5 x 10(11) vp, with no grade 4 toxicity observed. The most frequent toxicities included low-grade fever, hypoxia, and dyspnea. Of the 23 assessable patients, 16 had stable disease as their best response. Subjective improvement in breathing was noted in eight patients. Limited distribution of vector was observed, with transient detection in patient sputum for 1 to 2 days after administration. Ad-p53 can be administered safely by BAL at 5 x 10(11) vp with repeated dosing. Stabilization of disease and symptomatic improvement may warrant further studies of Ad-p53 or other adenoviruses administered by BAL in patients with BAC.

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

PubMed

Ribeiro, Alison; Ferraz-de-Paula, Viviane; Pinheiro, Milena L; Vitoretti, Luana B; Mariano-Souza, Domenica P; Quinteiro-Filho, Wanderley M; Akamine, Adriana T; Almeida, Vinícius I; Quevedo, João; Dal-Pizzol, Felipe; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Palermo-Neto, João

2012-03-05

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor. Copyright © 2012 Elsevier B.V. All rights

Bronchogenic carcinoma and secondary aspergillosis--common yet unexplored: evaluation of the role of bronchoalveolar lavage-polymerase chain reaction and some nonvalidated serologic methods to establish early diagnosis.

PubMed

Shahid, Mohammed; Malik, Abida; Bhargava, Rakesh

2008-08-01

More cases of bronchogenic carcinoma have been reported in recent years, and these patients are more prone to secondary aspergillosis. However, the frequency of secondary aspergillosis in bronchogenic carcinoma still has not been defined clearly in the literature. The current study population was comprised of 69 patients with bronchogenic carcinoma and 16 healthy controls. Histopathologic examination was done to identify carcinoma cell types and to categorize aspergillosis types. Bronchoalveolar lavage (BAL) fluids were collected for direct fungal examination, culture, Aspergillus polymerase chain reaction (PCR), and galactomannan (GM) detection using a 1-stage immunoenzymatic sandwich microplate assay; and blood samples were collected for fungal serology by double immunodiffusion (DID), enzyme-linked immunosorbent assay (ELISA), and dot blot assay (DBA). The sensitivity, specificity, positive predictive value, and negative predictive value were analyzed for various nonvalidated tests. Twenty-five patients had follow-up data available for an analysis of clinical and diagnostic outcomes. The cohort included patients with squamous cell carcinoma (n = 47), adenocarcinoma (n = 16), small cell carcinoma (n = 3), large cell carcinoma (n = 2), and undiagnosed type (n = 1), and patients were categorized with definite invasive pulmonary aspergillosis (IPA) (n = 6), probable IPA (n = 17), possible IPA (n = 13), and non-IPA (n = 33). Most patients were in the group ages 45 years to <60 years, and there was a preponderance of men (10.5:1). Cultures from 20 of 69 patients (29%) revealed the growth of Aspergillus species. Anti-Aspergillus antibodies were detected in 26 of 69 patients (37.7%) each by DID and DBA, whereas antibodies were detected in 28 of 69 patients (40.6%) by ELISA. GM was detected in BAL fluids from 25 of 69 patients (36.2%), whereas Aspergillus DNA was detected in 32 of 69 patients (46.4%) by PCR. The sensitivity of PCR and serologic tests (ELISA, DID, and DBA

Proteomic Changes of Alveolar Lining Fluid in Illnesses Associated with Exposure to Inhaled Non-Infectious Microbial Particles

PubMed Central

Teirilä, Laura; Karvala, Kirsi; Ahonen, Niina; Riska, Henrik; Pietinalho, Anne; Tuominen, Päivi; Piirilä, Päivi

2014-01-01

Background Hyperresponsiveness to inhaled non-infectious microbial particles (NIMPs) has been associated with illnesses in the airways. Hypersensitivity pneumonitis (HP) is considered to be the prototype for these NIMPs-related diseases; however, there is no consensus on the definitions or diagnostic criteria for HP and the spectrum of related illnesses. Methods and Findings In order to identify the possible diagnostic markers for illnesses associated with NIMPs in alveolar lining fluid, we performed a proteomic analysis using a two-dimensional difference gel electrophoresis on bronchoalveolar lavage (BAL) fluid from patients with exposure to NIMPs in the context of damp building-related illness (DBRI) or conditions on the borderline to acute HP, designated here as agricultural type of microbial exposure (AME). Samples from patients with HP and sarcoidosis (SARC) were included for reference. Results were compared to results of healthy subjects (CTR). Western blot was used for validation of potential marker proteins from BAL fluid and plasma. Protein expression patterns suggest a close similarity between AME and HP, while DBRI was similar to CTR. However, in DBRI the levels of the inflammation associated molecules galectin-3 and alpha-1-antitrypsin were increased. A novel finding emerging from this study was the increases of semenogelin levels in BAL fluid from patients with AME, HP and SARC. Histone 4 levels were increased in AME, HP and SARC. Elevated plasma levels of histone 2B were detected in HP and SARC, suggesting it to be a potential blood indicator for inflammatory diseases of the lungs. Conclusions In this study, the proteomic changes in bronchoalveolar lavage of DBRI patients were distinct from other NIMP exposure associated lung diseases, while changes in AME overlapped those observed for HP patient samples. Some of the proteins identified in this study, semenogelin and histone 4, could function as diagnostic markers for differential diagnosis between

Detection of ozone-induced DNA single strand breaks in murine bronchoalveolar lavage cells acutely exposed in vivo.

PubMed

Haney, J T; Connor, T H; Li, L

1999-04-01

Single-strand breaks (SSBs) in DNA have been used a biomarker of oxidative damage. The comet assay, also known as single-cell gel electrophoresis, was used to investigate the ability of ozone (O(3)) to induce DNA SSBs in murine bronchoalveolar lavage (BAL) cells. The comet assay is more sensitive than other techniques currently utilized for detecting SSBs and requires fewer cells. In the present study, 3 mice were exposed for 3 h to 0.25 ppm of O(3), and 3 to 0.5 ppm of O(3) for 3 h. Two air-exposed mice served as negative controls. All mice were euthanized 3 h after exposure, at which time BAL cells were recovered from the lungs and stained with ethidium bromide. BAL cells recovered from an air-exposed mouse were exposed to various concentrations of H(2)O(2) in vitro for 1 h at 4 degrees C. Excluding cells from the H(2)O(2) group (n = 25), 50 randomly selected BAL cells were graded by comet tail length into 1 of 4 categories: no damage (0 mm), low damage (1-10 mm), medium damage (11-30 mm), and high damage (31 + mm). The nonparametric Wilcoxon rank-sum test was used for statistical analysis, and p values lower than .05 were considered significant. The H(2)O(2) and the 0.25 and 0.5 ppm O3 groups showed statistically significant increases in DNA SSBs as compared to air-exposed controls. The results of this study indicate that (1) O(3) induces DNA strand breaks in murine BAL cells at 0.25 and 0.5 ppm, as evidenced by statistically significant increases in the length of comet tails for O(3)-exposed groups, and (2) the comet assay can be used to assess O(3)-induced SSBs for in vivo exposures. Therefore, it has the potential as a biomarker for in vivo oxidant exposures.

The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome

PubMed Central

2009-01-01

Background Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A) plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s) responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood. Methods We employed 2-dimensional difference gel electrophoresis (2D-DIGE), a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL) proteomes in wild type (WT) and SP-A knockout (KO) mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups. Results We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours) there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice. Conclusion We postulate that SP-A plays a role in reactive oxidant

Comparison of endotracheal aspirate and non-bronchoscopic bronchoalveolar lavage in the diagnosis of ventilator-associated pneumonia in a pediatric intensive care unit.

PubMed

Yıldız-Atıkan, Başak; Karapınar, Bülent; Aydemir, Şöhret; Vardar, Fadıl

2015-01-01

Ventilator-associated pneumonia (VAP) is defined as pneumonia occuring in any period of mechanical ventilation. There is no optimal diagnostic method in current use and in this study we aimed to compare two non-invasive diagnostic methods used in diagnosis of VAP in children. This prospective study was conducted in 8 bedded Pediatric Intensive Care Unit at Ege University Children´s Hospital. Endotracheal aspiration (ETA) and non-bronchoscopic bronchoalveolar lavage (BAL) were performed in case of developing VIP after 48 hours of ventilation. Quantitative cultures were examined in Ege University Department of Diagnostic Microbiology, Bacteriology Laboratory. Fourty-one patients were enrolled in the study. The mean age of study subjects was 47.2±53.6 months. A total of 28 in 82 specimens taken with both methods were negative/negative; 28 had positive result with ETA and a negative result with non-bronchoscopic BAL and both results were negative in 26 specimens. There were no patients whose respiratory specimen culture was negative with ETA and positive with non-bronchoscopic BAL. These results imply that there is a significant difference between two diagnostic methods (p < 0.001). Negative non-bronchoscopic BAL results are recognized as absence of VAP; therefore, ETA results were compared with this method. ETA's sensitivity, specificity, negative and positive predictive values were 100%, 50%, 100% and 48% respectively. The study revealed the ease of usability and the sensitivity of non-bronchoscopic BAL, in comparison with ETA.

Bovine milk exosome proteome

USDA-ARS?s Scientific Manuscript database

Exosomes are 40-100 nm membrane vesicles of endocytic origin and are found in blood, urine, amniotic fluid, bronchoalveolar lavage (BAL) fluid, as well as human and bovine milk. Exosomes are extracellular organelles important in intracellular communication/signaling, immune function, and biomarkers ...

Assessing the activity of sarcoidosis: quantitative /sup 67/Ga-citrate imaging

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

Fajman, W.A.; Greenwald, L.V.; Staton, G.

1984-04-01

Three different methods of quantitating /sup 67/Ga-citrate lung images - a visual index, a computer-assisted index, and the total-lung-to-background ratio - were compared in 71 studies of patients with biopsy-proven sarcoidosis. Fifty consecutive cases were analyzed independently by two different observers using all three methods. In these studies, each index was correlated with the cell differential in the bronchoalveolar lavage fluid. The total-lung-to-background ratio proved to be the simplest to perform; correlated best with the original visual index and the percentage of lymphocytes obtained in bronchoalveolar lavage fluid. Sensitivity for detecting active disease was 84% compared with 64% and 58%more » for the visual and computer-assisted indices, respectively, with no sacrifice in specificity.« less

[The bactericidal effect of oxybuprocaine. A possible cause of false negative results in bronchoalveolar lavage].

PubMed

Anding, K; Albrecht, P; Heilmann, C; Daschner, F

1993-09-01

New approaches in the diagnosis of pneumonia, especially in intensive care units, are quantitative cultures of bronchoalveolar (BAL) fluid or the protected specimen brush. The sensitivity of these methods, however, has often been found to be as low as 50-60%. One possible explanation for the low sensitivity of these diagnostic tools is the antimicrobial activity of local anaesthetics used in bronchoscopy. Therefore, we investigated the bactericidal properties of oxybuprocaine, a topical anaesthetic used for bronchoscopy in our clinic, in order to test the reliability of specimens obtained from BAL. METHODS. The bactericidal activity of oxybuprocaine in concentrations of 1%, 0.1%, 0.05% and 0.01% was tested by constructing time-kill curves for Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa and Escherichia coli. Five stains of each bacterial species were tested. The inoculum size was 10(4) ml, and bacteria were counted after 10, 20, 30, 60 and 120 min. RESULTS. The resulting time-kill curves are demonstrated in Figs. 1-4. The most sensitive bacteria were S. pneumoniae and H. influenzae, in which significant bactericidal activity could be shown even with a 0.01% solution of oxybuprocaine. E. coli and P. aeruginosa were also inhibited, but only at the highest concentration of 1%. CONCLUSIONS. The use of local anaesthetics before material is taken for culture, e.g. from BAL, may give rise to false-negative results and should therefore be avoided or reduced. For each local anaesthetic used in bronchoscopy, the concentrations that can be used without the risk of false-negative results should be determined.

Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma.

PubMed

Planagumà, Anna; Kazani, Shamsah; Marigowda, Gautham; Haworth, Oliver; Mariani, Thomas J; Israel, Elliot; Bleecker, Eugene R; Curran-Everett, Douglas; Erzurum, Serpil C; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Gaston, Benjamin; Jarjour, Nizar N; Busse, William W; Wenzel, Sally E; Levy, Bruce D

2008-09-15

Airway inflammation is common in severe asthma despite antiinflammatory therapy with corticosteroids. Lipoxin A(4) (LXA(4)) is an arachidonic acid-derived mediator that serves as an agonist for resolution of inflammation. Airway levels of LXA(4), as well as the expression of lipoxin biosynthetic genes and receptors, in severe asthma. Samples of bronchoalveolar lavage fluid were obtained from subjects with asthma and levels of LXA(4) and related eicosanoids were measured. Expression of lipoxin biosynthetic genes was determined in whole blood, bronchoalveolar lavage cells, and endobronchial biopsies by quantitative polymerase chain reaction, and leukocyte LXA(4) receptors were monitored by flow cytometry. Individuals with severe asthma had significantly less LXA(4) in bronchoalveolar lavage fluids (11.2 +/- 2.1 pg/ml) than did subjects with nonsevere asthma (150.1 +/- 38.5 pg/ml; P < 0.05). In contrast, levels of cysteinyl leukotrienes were increased in both asthma cohorts compared with healthy individuals. In severe asthma, 15-lipoxygenase-1 mean expression was decreased fivefold in bronchoalveolar lavage cells. In contrast, 15-lipoxgenase-1 was increased threefold in endobronchial biopsies, but expression of both 5-lipoxygenase and 15-lipoxygenase-2 in these samples was decreased. Cyclooxygenase-2 expression was decreased in all anatomic compartments sampled in severe asthma. Moreover, LXA(4) receptor gene and protein expression were significantly decreased in severe asthma peripheral blood granulocytes. Mechanisms underlying pathological airway responses in severe asthma include lipoxin underproduction with decreased expression of lipoxin biosynthetic enzymes and receptors. Together, these results indicate that severe asthma is characterized, in part, by defective lipoxin counterregulatory signaling circuits.

Effects of inhaled corticosteroids on airway inflammation in chronic obstructive pulmonary disease: a systematic review and meta-analysis

PubMed Central

Jen, Rachel; Rennard, Stephen I; Sin, Don D

2012-01-01

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD. Methods: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences (SMD) to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across the original studies. If significant heterogeneity was present (P < 0.1), then a random effects model was used to pool the original data; otherwise, a fixed effects model was used. Results: We identified eight original studies that met the inclusion criteria. Four studies used bronchial biopsies (n =102 participants) and showed that ICS were effective in reducing CD4 and CD8 cell counts (SMD, −0.52 units and −0.66 units, 95% confidence interval). The five studies used bronchoalveolar lavage fluid (n =309), which together showed that ICS reduced neutrophil and lymphocyte counts (SMD, −0.64 units and −0.64 units, 95% confidence interval). ICS on the other hand significantly increased macrophage counts (SMD, 0.68 units, 95% confidence interval) in bronchoalveolar lavage fluid. Conclusion: ICS has important immunomodulatory effects in airways with COPD that may explain its beneficial effect on exacerbations and enhanced risk of pneumonia. PMID:23055709

Effectiveness and Safety of High-Flow Nasal Cannula Oxygen Delivery during Bronchoalveolar Lavage in Acute Respiratory Failure Patients.

PubMed

Kim, Eun Jin; Jung, Chi Young; Kim, Kyung Chan

2018-06-19

Bronchoalveolar lavage (BAL) is a necessary procedure for diagnosis of various lung diseases. High-flow nasal cannula (HFNC) oxygen delivery was recently introduced. This study aimed to investigate the safety and effectiveness of HFNC oxygen supply during BAL procedure in patients with acute respiratory failure (ARF). Patients who underwent BAL while using HFNC at a partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO₂/FiO₂; PF) ratio of 300 or below among patients who had been admitted from March 2013 to May 2017 were retrospectively investigated. Thirty-three BAL procedures were confirmed. Their baseline PF ratio was 166.1±46.7. FiO₂ values before, during, and after BAL were 0.45±0.12, 0.74±0.19, and 0.57±0.14, respectively. Flow (L/min) values before, during, and after BAL were 26.5±20.3, 49.0±7.2, and 40.8±14.2, respectively. Both FiO₂ and flow during and after the procedure were significantly different from those before the procedure (both p<0.001). Oxygen saturation levels before, during, and after BAL measured by pulse oximeter were 94.8±2.9, 94.6±3.5, and 95.2±2.8%, respectively. There were no significant differences in oxygen saturation among the three groups. Complications of BAL procedure included transient hypoxemia, hypotension, and fever. However, there was no endotracheal intubation within 24 hours. Baseline PF ratio in "without HFNC" group was significantly higher than that in "with HFNC" group. There were no differences in complications between the two groups. The use of HFNC during BAL procedure in ARF patients was effective and safe. However, there were no significant differences in oxygen saturation level and complications comparing "without HFNC" group in mild ARF. More studies are needed for moderate to severe ARF patients. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

Protein profiles of nasal lavage fluid from individuals with work-related upper airway symptoms associated with moldy and damp buildings.

PubMed

Wåhlén, K; Fornander, L; Olausson, P; Ydreborg, K; Flodin, U; Graff, P; Lindahl, M; Ghafouri, B

2016-10-01

Upper airway irritation is common among individuals working in moldy and damp buildings. The aim of this study was to investigate effects on the protein composition of the nasal lining fluid. The prevalence of symptoms in relation to work environment was examined in 37 individuals working in two damp buildings. Microbial growth was confirmed in one of the buildings. Nasal lavage fluid was collected from 29 of the exposed subjects and 13 controls, not working in a damp building. Protein profiles were investigated with a proteomic approach and evaluated by multivariate statistical models. Subjects from both workplaces reported upper airway and ocular symptoms. Based on protein profiles, symptomatic subjects in the two workplaces were discriminated from each other and separated from healthy controls. The groups differed in proteins involved in inflammation and host defense. Measurements of innate immunity proteins showed a significant increase in protein S100-A8 and decrease in SPLUNC1 in subjects from one workplace, while alpha-1-antitrypsin was elevated in subjects from the other workplace, compared with healthy controls. The results show that protein profiles in nasal lavage fluid can be used to monitor airway mucosal effects in personnel working in damp buildings and indicate that the profile may be separated when the dampness is associated with the presence of molds. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A competitive enzyme-linked immunosorbent assay for quantification of tetrastatin in body fluids and tumor extracts.

PubMed

Dupont-Deshorgue, A; Oudart, J B; Brassart, B; Deslee, G; Perotin, J M; Diebold, M D; Monboisse, J C; Ramont, L; Brassart-Pasco, S

2015-08-01

Basement membrane collagens or derived fragments are measured in biological fluids such as blood and urine of patients and appear to be useful for diagnosis, prognostication, or treatment monitoring as proposed for endostatin, a fragment of collagen XVIII, or tumstatin, a fragment of collagen IV. Tetrastatin, the NC1 alpha 4 collagen IV domain, was previously reported to inhibit tumor growth and angiogenesis. The aim of this study was to develop and validate a method to measure tetrastatin concentrations in human fluids. We developed a competitive enzyme-linked immunosorbent assay (ELISA). It allowed measuring tetrastatin levels in human serum, bronchial aspiration and bronchoalveolar lavage fluids, and lung tissue extracts. The tetrastatin level was significantly higher in tumor tissues than in healthy lung tissues. Tetrastatin competitive ELISA could be useful to quantify tetrastatin in tissues and biological fluids for the diagnosis or prognostication of diseases in which basement membrane metabolism may be altered, especially tumor progression. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of intra-articular chlorhexidine diacetate lavage on the stifle in healthy dogs.

PubMed

Anderson, M A; Payne, J T; Kreeger, J M; Wagner-Mann, C C; Schmidt, D A; Mann, F A

1993-10-01

Eight dogs were determined to be orthopedically normal on the basis of prelavage physical examination, stifle radiography, synovial fluid analysis, and force plate analysis (peak vertical force normalized for body weight, and time on the force plate). Each dog had 1 stifle randomly assigned to be lavaged with 100 ml of a commercially available 0.05% (w/v) chlorhexidine diacetate solution, and the contralateral stifle was lavaged with lactated Ringer's solution. Difference was not detected between the chlorhexidine diacetate and lactated Ringer's solution-treated joints, with regard to results of synovial fluid analysis and clinical lameness evaluations on days 4 and 8 after lavage. Chlorhexidine diacetate caused a more intense synovitis than did lactated Ringer's solution, as determined by histologic evaluation of synovial membrane specimens after necropsy on day 8; however, a difference in the intensity of toluidine blue staining of articular cartilage was not found between treatments. Chlorhexidine diacetate, as a 0.05% (w/v) solution, cannot be recommended as a joint lavage fluid until the duration of inflammatory changes in the synovial membrane are determined or until the chemical constituents of chlorhexidine diacetate causing the synovitis can be identified and removed.

Improvements in lung lavage to increase its effectiveness in removing inhaled radionuclides

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

Muggenburg, B.A.; Guilmette, R.A.; Romero, L.M.

Lung lavage has been shown to be an effective method to remove insoluble radionuclides deposited and retained in the lung, but the treatment has been limited to the effective removal of only about 50% of the retained material. Reported here is change in lavage technique that slightly increases the effectiveness and the addition of high-frequency chest wall oscillation. The latter increased the effectiveness of the lavage procedure but also caused significant physiological complications. These studies were conducted in adult male and female beagles. The aerosol in the first study was {sup 239}PuO{sub 2} heat-treated at 850{degrees}C, obtained as powder frommore » a commercial V-blending process. The dogs briefly inhaled the aerosol per nasi. The tissue content at death and the amount of {sup 239}Pu excreted and in the recovered lung lavage fluid was determined by radiochemical methods{sup 5}. These values were used to reconstruct the initial pulmonary burden of {sup 239} and the amount of {sup 239}Pu removed by lavage. In the second study, with the HFCWO, the aerosol was {sup 85}Sr fused in aluminosilicate particles. The IPB of {sup 85}Sr was determined by whole-body counting. The excreta and recovered lung lavage fluids were also assayed for {sup 85}Sr activity.« less

Fluid lavage of open wounds (FLOW): a multicenter, blinded, factorial pilot trial comparing alternative irrigating solutions and pressures in patients with open fractures.

PubMed

Petrisor, Bradley; Sun, Xin; Bhandari, Mohit; Guyatt, Gordon; Jeray, Kyle J; Sprague, Sheila; Tanner, Stephanie; Schemitsch, Emil; Sancheti, Parag; Anglen, Jeff; Tornetta, Paul; Bosse, Michael; Liew, Susan; Walter, Stephen

2011-09-01

Open fractures are an important source of morbidity and are associated with delayed union, nonunion, and infection. Preventing infection through meticulous irrigation and debridement is an important goal in management, and different lavage fluids and irrigation techniques (e.g., high- or low-pressure lavage) have been described for this purpose. However, there are a limited number of randomized trials comparing irrigating solutions or irrigating technique. We compared the use of castile soap versus normal saline and high- versus low-pressure pulsatile lavage on the rates of reoperations and complications in patients with open fracture wounds. We conducted a multicenter, blinded, randomized 2 × 2 factorial pilot trial of 111 patients in whom an open fracture wound was treated with either castile soap solution or normal saline and either high- or low-pressure pulsatile lavage. The primary composite outcome of reoperation, measured at 12 months after initial operative procedure, included infection, wound healing problems, and nonunion. Planned reoperations were not included. Secondary outcomes included all infection, all wound healing problems, and nonunion as well as functional outcomes scores (EuroQol-5 dimensions and short form-12). Eighty-nine patients completed the 1-year follow-up. Among all patients, 13 (23%) in the castile soap group and 13 (24%) in the saline group had a primary outcome event (hazard ratio, 0.91, 95% confidence interval: 0.42-2.00, p = 0.52). Sixteen patients (28%) in the high-pressure group and 10 patients (19%) in the low-pressure group had a primary outcome event (hazard ratio 0.55, 95% confidence interval: 0.24-1.27, p = 0.17). Functional outcome scores showed no significant differences at any time point between groups. The fluid lavage of open wounds pilot randomized controlled trial demonstrated the possibility that the use of low pressure may decrease the reoperation rate for infection, wound healing problems, or nonunion. We have

Levels of cytokines in broncho-alveolar lavage fluid, but not in plasma, are associated with levels of markers of lipid peroxidation in breath of ventilated ICU patients.

PubMed

Boshuizen, Margit; Leopold, Jan Hendrik; Zakharkina, Tetyana; Knobel, Hugo H; Weda, Hans; Nijsen, Tamara M E; Vink, Teunis J; Sterk, Peter J; Schultz, Marcus J; Bos, Lieuwe D J

2015-09-03

Alkanes and alkenes in the breath are produced through fatty acid peroxidation, which is initialized by reactive oxygen species. Inflammation is an important cause and effect of reactive oxygen species. We aimed to evaluate the association between fatty acid peroxidation products and inflammation of the alveolar and systemic compartment in ventilated intensive care unit (ICU) patients.Volatile organic compounds were measured by gas chromatography and mass spectrometry in the breath of newly ventilated ICU patients within 24 h after ICU admission. Cytokines were measured in non-directed bronchial lavage fluid (NBL) and plasma by cytometric bead array. Correlation coefficients were calculated and presented in heatmaps.93 patients were included. Peroxidation products in exhaled breath were not associated with markers of inflammation in plasma, but were correlated with those in NBL. IL-6, IL-8, IL-1β and TNF-α concentration in NBL showed inverse correlation coefficients with the peroxidation products of fatty acids. Furthermore, NBL IL-10, IL-13, GM-CSF and IFNγ demonstrated positive associations with breath alkanes and alkenes. Correlation coefficients for NBL cytokines were high regarding peroxidation products of n-6, n-7 and particularly in n-9 fatty acids.Levels of lipid peroxidation products in the breath of ventilated ICU patients are associated with levels of inflammatory markers in NBL, but not in plasma. Alkanes and alkenes in breath seems to be associated with an anti-inflammatory, rather than a pro-inflammatory state in the alveoli.

The IRIDICA PCR/Electrospray Ionization-Mass Spectrometry Assay on Bronchoalveolar Lavage for Bacterial Etiology in Mechanically Ventilated Patients with Suspected Pneumonia.

PubMed

Strålin, Kristoffer; Ehn, Fredrik; Giske, Christian G; Ullberg, Måns; Hedlund, Jonas; Petersson, Johan; Spindler, Carl; Özenci, Volkan

2016-01-01

We studied the diagnostic performance of the IRIDICA PCR/electrospray ionization-mass spectrometry (PCR/ESI-MS) assay applied on bronchoalveolar lavage (BAL) samples, from 51 mechanically ventilated patients with suspected pneumonia, in a prospective study. In 32 patients with X-ray verified pneumonia, PCR/ESI-MS was positive in 66% and BAL culture was positive in 38% (p = 0.045), and either of the methods was positive in 69%. The following BAL result combinations were noted: PCR/ESI-MS+/culture+, 34%; PCR/ESI-MS+/culture-, 31%; PCR/ESI-MS-/culture+, 3.1%; PCR/ESI-MS-/culture-, 31%; kappa 0.36 (95% confidence interval (CI), 0.10-0.63). In pneumonia patients without prior antibiotic treatment, optimal agreement was noted with 88% PCR/ESI-MS+/culture+ and 12% PCR/ESI-MS-/culture- (kappa 1.0). However, in patients with prior antibiotic treatment, the test agreement was poor (kappa 0.16; 95% CI, -0.10-0.44), as 10 patients were PCR/ESI-MS+/culture-. In 8/10 patients the pathogens detected by PCR/ESI-MS could be detected by other conventional tests or PCR tests on BAL. Compared with BAL culture, PCR/ESI-MS showed specificities and negative predictive values of ≥87% for all individual pathogens, an overall sensitivity of 77% and positive predictive value (PPV) of 42%. When other conventional tests and PCR tests were added to the reference standard, the overall PPV increased to 87%. The PCR/ESI-MS semi-quantitative level tended to be higher for PCR/ESI-MS positive cases with pneumonia compared with cases without pneumonia (p = 0.074). In conclusion, PCR/ESI-MS applied on BAL showed a promising performance and has potential to be clinically useful in mechanically ventilated patients with suspected pneumonia. The usefulness of the method for establishment of pneumonia etiology and selection of antibiotic therapy should be further studied.

Comparison of ozone-specific (OZAC) and oxygen radical (ORAC) antioxidant capacity assays for use with nasal lavage fluid.

PubMed

Rutkowski, Joseph M; Santiag, Lizzie Y; Ben-Jebria, Abdellaziz; Ultman, James S

2011-10-01

Antioxidants in respiratory mucus protect the underlying airway epithelium from damage by ozone (O(3)), a common outdoor air pollutant. To understand O(3)-antioxidant interactions and the variation of these interactions among individuals, in vitro assays are needed to measure the total antioxidant capacity of airway lavage fluid, a convenient source of (diluted) mucous samples. Here, we compare the oxygen radical absorbance capacity (ORAC), a general method that uses peroxyl radicals as a reactive substance, to the recently developed ozone specific antioxidant capacity (OZAC), a procedure that directly employs O(3). For prepared model mucous antioxidant solutions containing uric acid, ascorbic acid or glutathione, the ORAC and OZAC methods yielded comparable antioxidant capacities. The addition of EDTA or DETAPAC, necessary to prevent auto-oxidation of test solutions during the ORAC assay, unpredictably altered ORAC measurements. EDTA did not have a significant effect on OZAC measurements in either prepared uric acid or ascorbic acid solutions. When assessing antioxidant capacities of nasal lavage samples, the ORAC and OZAC assays were no longer comparable. Because the OZAC of nasal lavage samples was positively related to measured uric acid concentrations whereas the ORAC data were not, the OZAC method appears to provide more realistic mucous antioxidant capacities than the ORAC method. Copyright © 2011 Elsevier Ltd. All rights reserved.

[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)

Diagnostic peritoneal lavage: volume of lavage effluent needed for accurate determination of a negative lavage.

PubMed

Sweeney, J F; Albrink, M H; Bischof, E; McAllister, E W; Rosemurgy, A S

1994-12-01

While the ability of diagnostic peritoneal lavage (DPL) to 'rule out' occult intra-abdominal injuries has been well established, the volume of lavage effluent necessary for accurate prediction of a negative lavage has not been determined. To address this, 60 injured adults with blunt (N = 45) or penetrating (N = 15) trauma undergoing DPL were evaluated prospectively through protocol. After infusion of 1l of Ringer's lactate solution, samples of lavage effluent were obtained at 100 cm3, 250 cm3, 500 cm3, and 759 cm3, and when no more effluent could be returned (final sample). DPL was considered negative if final sample RBC count was < or = 100,000/mm3 for blunt injury and < 50,000/mm3 for penetrating injury. The conclusion is that at 100 cm3 of lavage effluent returned, negative results are highly predictive of a negative DPL (98 per cent), though 250 cm3 of lavage effluent is required to predict a negative DPL uniformly (100 per cent).

Biomarkers of Oxidative Stress Study IV. Are Antioxidants Markers of Ozone Exposure?

EPA Science Inventory

To determine whether the oxidative effects of ozone would result in losses of antioxidants from plasma, and possibly bronchoalveolar lavage fluid (BALF). This research is part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative ...

Advances in the analysis of "less-conventional" human body fluids: An overview of the CE- and HPLC-MS applications in the years 2015-2017.

PubMed

Di Venere, Monica; Viglio, Simona; Cagnone, Maddalena; Bardoni, Anna; Salvini, Roberta; Iadarola, Paolo

2018-01-01

Aim of this article is to focus the attention of the reader on the application of CE/MS and LC/MS to the analysis of human body fluids not currently used for the diagnosis of disorders and, for this reason, catalogued as "less/nonconventional" fluids, that is, tears, nasal secretions, cerumen, bronchoalveolar lavage fluid, sputum, exhaled breath condensate, nipple aspirate, breast milk, amniotic fluid, bile, seminal plasma, liposuction aspirate fluid, and synovial fluid. The pool of articles presented in this report demonstrates that, rather than being neglected, these fluids are an important resource for the evaluation of possible pathologic conditions. Thus, being a sort of mirror that reflects the normal internal characteristics and disease state of an individual, they benefit of an increasing appreciation. This review follows a previous report of this series and covers the latest developments in this field that have been published in specialist journals in the years 2015-2017. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone

EPA Science Inventory

We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to 03 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH ...

Silicosis in Workers Exposed to Artificial Quartz Conglomerates: Does It Differ From Chronic Simple Silicosis?

PubMed

Paolucci, Valentina; Romeo, Riccardo; Sisinni, Antonietta Gerardina; Bartoli, Dusca; Mazzei, Maria Antonietta; Sartorelli, Pietro

2015-12-01

Recently, a number of reports have been published on silicosis in workers exposed to artificial quartz conglomerates containing high levels of crystalline silica particles (70-90%) used in the construction of kitchen and bathroom surfaces. Three cases of silicosis in workers exposed to artificial quartz conglomerates are reported. The diagnosis was derived from both the International Labour Office and the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD) classifications and cytological analysis of bronchoalveolar lavage fluid. In 2 cases, levels of respirable silica greatly in excess of recommended standards were measured in the workplace, and cytological analysis of bronchoalveolar lavage fluid highlighted a prevalence of lymphocytes, meeting criteria for the diagnosis of accelerated silicosis. The prevention of pneumoconiosis caused by the use of innovative materials, such as artificial conglomerates with high crystalline silica content must be addressed. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

[Effects of dexamethasone on the expression of muscarinic receptor mRNA in asthmatic guinea pig airway smooth muscle and eosinophil infiltration in bronchoalveolar lavage fluid].

PubMed

Shi, Liang; Luo, Ya-ling; Lai, Wen-yan; Luo, Liang

2005-08-01

To investigate the effect of dexamethasone on the expression of muscarinic receptor (MR) mRNA in smooth muscle and infiltration of eosinophils (Eos) in the airway of asthmatic guinea pigs. Thirty healthy guinea pigs were randomized into 3 equal groups, the control group, asthmatic group and dexamethasone therapy group. Asthma was induced in the latter 2 groups with the asthma-inducing agents and received treatments as indicated. Bronchial alveolar lavage fluid(BALF) were collected subsequently from the guinea pigs for examining the total cell number and cell classification, and histopathologic examination of the lung tissue was performed. Semi-quantitative analysis with reverse transcriptional- polymerase chain reaction (RT-PCR) was performed for M(2) and M(3) receptor mRNA in airway smooth muscle. Compared with the control and the asthmatic group, the number of Eos in the BALF of dexamethasone therapy group was significantly lower (P<0.01). In spite of the presence of hyperemia and edema in the lung tissues of the dexamethasone therapy group, Eos infiltration was less severe than that in the asthmatic group. As found by RT-PCR, the quantity of M(2) receptor mRNA in the airway smooth muscle of the dexamethasone therapy group was significantly higher than those in both the control and asthmatic groups (P<0.01), and the quantity of M(3) receptor mRNA in the airway smooth muscle of dexamethasone therapy group was significantly higher than that in the asthmatic group, but did not significantly differ from that in the control group. The quantities of M(2) and M(3) receptor mRNAs in the control group were both significantly higher than that in asthmatic group (P<0.01). The expression of M(2) receptor is increased in antigen- challenged guinea pigs, and that of M(3) receptor decreased. Dexamethasone can treat asthma by inhibiting inflammatory action involving Eos infiltration, regulating the expressions of M(2) and M(3) receptors and restoring the function of M(2

Effects of clinical and environmental factors on bronchoalveolar antibody responses to Pneumocystis jirovecii: A prospective cohort study of HIV+ patients.

PubMed

Blount, Robert J; Daly, Kieran R; Fong, Serena; Chang, Emily; Grieco, Katherine; Greene, Meredith; Stone, Stephen; Balmes, John; Miller, Robert F; Walzer, Peter D; Huang, Laurence

2017-01-01

Humoral immunity plays an important role against Pneumocystis jirovecii infection, yet clinical and environmental factors that impact bronchoalveolar antibody responses to P. jirovecii remain uncertain. From October 2008-December 2011 we enrolled consecutive HIV-infected adults admitted to San Francisco General Hospital (SFGH) who underwent bronchoscopy for suspected Pneumocystis pneumonia (PCP). We used local air quality monitoring data to assign ozone, nitrogen dioxide, and fine particulate matter exposures within 14 days prior to hospital admission. We quantified serum and bronchoalveolar lavage fluid (BALF) antibody responses to P. jirovecii major surface glycoprotein (Msg) recombinant constructs using ELISA. We then fit linear regression models to determine whether PCP and ambient air pollutants were associated with bronchoalveolar antibody responses to Msg. Of 81 HIV-infected patients enrolled, 47 (58%) were diagnosed with current PCP and 9 (11%) had a prior history of PCP. The median CD4+ count was 51 cells/μl (IQR 15-129) and 44% were current smokers. Serum antibody responses to Msg were statistically significantly predictive of BALF antibody responses, with the exception of IgG responses to MsgC8 and MsgC9. Prior PCP was associated with increased BALF IgA responses to Msg and current PCP was associated with decreased IgA responses. For instance, among patients without current PCP, those with prior PCP had a median 73.2 U (IQR 19.2-169) IgA response to MsgC1 compared to a 5.00 U (3.52-12.6) response among those without prior PCP. Additionally, current PCP predicted a 22.5 U (95%CI -39.2, -5.82) lower IgA response to MsgC1. Ambient ozone within the two weeks prior to hospital admission was associated with decreased BALF IgA responses to Msg while nitrogen dioxide was associated with increased IgA responses. PCP and ambient air pollutants were associated with BALF IgA responses to P. jirovecii in HIV-infected patients evaluated for suspected PCP.

Effects of clinical and environmental factors on bronchoalveolar antibody responses to Pneumocystis jirovecii: A prospective cohort study of HIV+ patients

PubMed Central

Daly, Kieran R.; Fong, Serena; Chang, Emily; Grieco, Katherine; Greene, Meredith; Stone, Stephen; Balmes, John; Miller, Robert F.; Walzer, Peter D.; Huang, Laurence

2017-01-01

Background Humoral immunity plays an important role against Pneumocystis jirovecii infection, yet clinical and environmental factors that impact bronchoalveolar antibody responses to P. jirovecii remain uncertain. Methods From October 2008—December 2011 we enrolled consecutive HIV-infected adults admitted to San Francisco General Hospital (SFGH) who underwent bronchoscopy for suspected Pneumocystis pneumonia (PCP). We used local air quality monitoring data to assign ozone, nitrogen dioxide, and fine particulate matter exposures within 14 days prior to hospital admission. We quantified serum and bronchoalveolar lavage fluid (BALF) antibody responses to P. jirovecii major surface glycoprotein (Msg) recombinant constructs using ELISA. We then fit linear regression models to determine whether PCP and ambient air pollutants were associated with bronchoalveolar antibody responses to Msg. Results Of 81 HIV-infected patients enrolled, 47 (58%) were diagnosed with current PCP and 9 (11%) had a prior history of PCP. The median CD4+ count was 51 cells/μl (IQR 15–129) and 44% were current smokers. Serum antibody responses to Msg were statistically significantly predictive of BALF antibody responses, with the exception of IgG responses to MsgC8 and MsgC9. Prior PCP was associated with increased BALF IgA responses to Msg and current PCP was associated with decreased IgA responses. For instance, among patients without current PCP, those with prior PCP had a median 73.2 U (IQR 19.2–169) IgA response to MsgC1 compared to a 5.00 U (3.52–12.6) response among those without prior PCP. Additionally, current PCP predicted a 22.5 U (95%CI -39.2, -5.82) lower IgA response to MsgC1. Ambient ozone within the two weeks prior to hospital admission was associated with decreased BALF IgA responses to Msg while nitrogen dioxide was associated with increased IgA responses. Conclusions PCP and ambient air pollutants were associated with BALF IgA responses to P. jirovecii in HIV

The IRIDICA PCR/Electrospray Ionization–Mass Spectrometry Assay on Bronchoalveolar Lavage for Bacterial Etiology in Mechanically Ventilated Patients with Suspected Pneumonia

PubMed Central

Ehn, Fredrik; Giske, Christian G.; Ullberg, Måns; Hedlund, Jonas; Petersson, Johan; Spindler, Carl; Özenci, Volkan

2016-01-01

We studied the diagnostic performance of the IRIDICA PCR/electrospray ionization–mass spectrometry (PCR/ESI-MS) assay applied on bronchoalveolar lavage (BAL) samples, from 51 mechanically ventilated patients with suspected pneumonia, in a prospective study. In 32 patients with X-ray verified pneumonia, PCR/ESI-MS was positive in 66% and BAL culture was positive in 38% (p = 0.045), and either of the methods was positive in 69%. The following BAL result combinations were noted: PCR/ESI-MS+/culture+, 34%; PCR/ESI-MS+/culture-, 31%; PCR/ESI-MS-/culture+, 3.1%; PCR/ESI-MS-/culture-, 31%; kappa 0.36 (95% confidence interval (CI), 0.10–0.63). In pneumonia patients without prior antibiotic treatment, optimal agreement was noted with 88% PCR/ESI-MS+/culture+ and 12% PCR/ESI-MS-/culture- (kappa 1.0). However, in patients with prior antibiotic treatment, the test agreement was poor (kappa 0.16; 95% CI, -0.10–0.44), as 10 patients were PCR/ESI-MS+/culture-. In 8/10 patients the pathogens detected by PCR/ESI-MS could be detected by other conventional tests or PCR tests on BAL. Compared with BAL culture, PCR/ESI-MS showed specificities and negative predictive values of ≥87% for all individual pathogens, an overall sensitivity of 77% and positive predictive value (PPV) of 42%. When other conventional tests and PCR tests were added to the reference standard, the overall PPV increased to 87%. The PCR/ESI-MS semi-quantitative level tended to be higher for PCR/ESI-MS positive cases with pneumonia compared with cases without pneumonia (p = 0.074). In conclusion, PCR/ESI-MS applied on BAL showed a promising performance and has potential to be clinically useful in mechanically ventilated patients with suspected pneumonia. The usefulness of the method for establishment of pneumonia etiology and selection of antibiotic therapy should be further studied. PMID:27463099

Clinical Implications of Hepatocyte Growth Factor, Interleukin-20, and Interleukin-22 in Serum and Bronchoalveolar Fluid of Patients with Non-Small Cell Lung Cancer.

PubMed

Naumnik, W; Naumnik, B; Niklińska, W; Ossolińska, M; Chyczewska, E

2016-01-01

Hepatocyte growth factor (HGF) is involved in tumorigenesis, interleukin-20 (IL-20) is an inhibitor of angiogenesis, and interleukin-22 (IL-22) stimulates tumor growth. The aim of this study was to determine the level of HGF, IL-20, and IL-22 in both serum and bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients before onset of chemotherapy, the nature of the interrelationships between these markers, and their prognostic significance regarding post-chemotherapy survival time. We studied 46 NSCLC patients and 15 healthy subjects as a control group. We found significantly higher serum levels of HGF and IL-22 in the NSCLC patients than those in controls [pg/ml: HGF - 1911 (693-6510) vs. 1333 (838-3667), p = 0.0004; IL-22 - 10.66 (1.44-70.34) vs. 4.69 (0.35-12.29), p = 0.0007]. In contrast, concentrations of HGF and IL-22 in BALF were lower in NSCLC patients than those in controls [pg/ml: HGF - 72 (6-561) vs. 488 (14-2003), p = 0.0002; IL-22 - 2.28 (0.70-6.52) vs. 3.72 (2.76-5.64), p = 0.002]. In the NSCLC patients, there was a negative correlation between the serum level of IL-20 and time to tumor progression (r = -0.405, p = 0.04) and between the serum level of HGF and survival time (r = -0.41, p = 0.005). In addition, a higher serum level of HGF and a higher BALF level of IL-22 in patients were linked with a shorter overall survival. We conclude that HGF, IL-20, and IL-22 in the serum and BALF of NSCLC patients before chemotherapy may be a prognostic of cancer progression.

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

Lieske, T.R.; Sunderrajan, E.V.; Passamonte, P.M.

A patient with chronic eosinophilic pneumonia was evaluated using bronchoalveolar lavage, technetium-99m glucoheptonate, and transbronchial lung biopsy. Bronchoalveolar lavage revealed 43 percent eosinophils and correlated well with results of transbronchial lung biopsy. Technetium-99m glucoheptonate lung imaging demonstrated intense parenchymal uptake. After eight weeks of corticosteroid therapy, the bronchoalveolar lavage eosinophil population and the technetium-99m glucoheptonate uptake had returned to normal. We suggest that bronchoalveolar lavage, with transbronchial lung biopsy, is a less invasive way than open lung biopsy to diagnose chronic eosinophilic pneumonia. The mechanism of uptake of technetium-99m glucoheptonate in this disorder remains to be defined.

Fluorescent microscopy and Ziehl-Neelsen staining of bronchoalveolar lavage, bronchial washings, bronchoscopic brushing and post bronchoscopic sputum along with cytological examination in cases of suspected tuberculosis.

PubMed

Bodal, Vijay Kumar; Bal, Manjit S; Bhagat, Sunita; Kishan, Jai; Brar, Rupinder K

2015-01-01

Ever since the discovery of Mycobacterium tuberculosis in 1882, many diagnostic methods have been developed. However "The gold standard" for the diagnosis of tuberculosis (TB) is still the demonstration of acid fast Bacilli (AFB) by microscopic examination of smear or bacteriological confirmation by culture method. In suspected 75 patients with active pulmonary TB, the materials obtained bronchoscopically, were bronchoalveolar lavage (BAL), bronchial brushings, bronchial washings and post bronchoscopic sputum. Four smears were made from each of the specimen. Fluorescent Staining, Ziehl-Neelsen (ZN), Pap and May Grunwald-Giemsa (MGG) stains were carried out for cytological examination. Fluorescent stain yielded maximum AFB positivity in all the methods, that is 36 (48%) in post fibre-optic bronchoscopy (FOB) sputum and 19 (25.33%) by fluorescence microscopy in both bronchial brushings and bronchial washings. Maximum yield of AFB with ZN staining 12 (16%) was equal to the post FOB sputum and bronchial brushings samples. It was followed by 6 cases (8%) in BAL and 4 (5.3%) in bronchial washings. The cytological examination was suggestive of TB in only 8 (10.66%) cases in bronchial washings and 6 (8%) cases in post FOB collection. It was equal in BAL and Bronchial brushings each that is 5 (6.67%). Bronchoscopy is a useful diagnostic tool and fluorescent microscopy is more sensitive than ZN and cytology. On X-ray examination, other diseases like malignancy or fungus can also mimick TB. So apart from ZN staining or fluorescence microscopy, Pap and MGG stain will be worthwhile to identify other microorganisms.

Intra-operative peritoneal lavage for colorectal cancer

PubMed Central

Passot, Guillaume; Mohkam, Kayvan; Cotte, Eddy; Glehen, Olivier

2014-01-01

Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies. PMID:24616569

Synovitis induced by joint lavage with hypertonic saline solutions in healthy dairy calves

PubMed Central

Achard, Damien; Francoz, David; Desrochers, André; Girard, Christiane; Piché, Caroline

2012-01-01

The objective of this study was to evaluate the effect of a single joint lavage with 7.2% or 15% hypertonic saline solutions (HSS) on the tarsocrural joints of healthy calves. The tarsi of 10 calves were randomly lavaged with 7.2% HSS, 15% HSS, or isotonic saline. Synovial fluid samples were collected aseptically on days 1 (before joint lavage), 2, 3, 4, and 8 for complete cytological analysis. Lameness, joint swelling, and pain were recorded daily. Calves were euthanized on day 8 for gross and histological analyses of synovial membranes and articular cartilage. Synovitis was evaluated using a scoring system reflecting inflammatory changes in synovial membranes. Joints irrigated with HSS were more distended and painful compared with isotonic control joints. Swelling decreased consistently in the joints lavaged with 7.2% HSS, whereas it remained unchanged in joints lavaged with 15% HSS. Slight to moderate lameness was observed in the joints lavaged with 15% HSS. In comparison to isotonic saline joints, total protein concentration was significantly increased on day 2 and 3 for the joints lavaged with 7.2% HSS (P ≤ 0.01) and on days 2, 3, and 4 in the joints lavaged with 15% HSS (P ≤ 0.0006). Gross and histological findings revealed that synovitis was more severe in the joints lavaged with 15% HSS but variable in the joints lavaged with 7.2% HSS. No significant differences were observed for the articular cartilage. Fifteen percent HSS is not recommended for joint lavage. Although irrigation with 7.2% HSS may induce a variable synovitis, it was found appropriate for joint lavage. Its effects on septic joints remain undetermined. PMID:23024450

Association between the miRNA signatures in plasma and bronchoalveolar fluid in respiratory pathologies.

PubMed

Molina-Pinelo, Sonia; Suárez, Rocío; Pastor, María Dolores; Nogal, Ana; Márquez-Martín, Eduardo; Martín-Juan, José; Carnero, Amancio; Paz-Ares, Luis

2012-01-01

The identification of new less invasive biomarkers is necessary to improve the detection and prognostic outcome of respiratory pathological processes. The measurement of miRNA expression through less invasive techniques such as plasma and serum have been suggested to analysis of several lung malignancies including lung cancer. These studies are assuming a common deregulated miRNA expression both in blood and lung tissue. The present study aimed to obtain miRNA representative signatures both in plasma and bronchoalveolar cell fraction that could serve as biomarker in respiratory diseases. Ten patients were evaluated to assess the expression levels of 381 miRNAs. We found that around 50% miRNAs were no detected in both plasma and bronchoalveolar cell fraction and only 20% of miRNAs showed similar expression in both samples. These results show a lack of association of miRNA signatures between plasma and bronchoalveolar cytology in the same patient. The profiles are not comparable; however, there is a similarity in the relative expression in a very small subset of miRNAs (miR-17, miR-19b, miR-195 and miR-20b) between both biological samples in all patients. This finding supports that the miRNAs profiles obtained from different biological samples have to be carefully validated to link with respiratory diseases.

Association between the miRNA Signatures in Plasma and Bronchoalveolar Fluid in Respiratory Pathologies

PubMed Central

Molina-Pinelo, Sonia; Suárez, Rocío; Pastor, María Dolores; Nogal, Ana; Márquez-Martín, Eduardo; Martín-Juan, José; Carnero, Amancio; Paz-Ares, Luis

2012-01-01

The identification of new less invasive biomarkers is necessary to improve the detection and prognostic outcome of respiratory pathological processes. The measurement of miRNA expression through less invasive techniques such as plasma and serum have been suggested to analysis of several lung malignancies including lung cancer. These studies are assuming a common deregulated miRNA expression both in blood and lung tissue. The present study aimed to obtain miRNA representative signatures both in plasma and bronchoalveolar cell fraction that could serve as biomarker in respiratory diseases. Ten patients were evaluated to assess the expression levels of 381 miRNAs. We found that around 50% miRNAs were no detected in both plasma and bronchoalveolar cell fraction and only 20% of miRNAs showed similar expression in both samples. These results show a lack of association of miRNA signatures between plasma and bronchoalveolar cytology in the same patient. The profiles are not comparable; however, there is a similarity in the relative expression in a very small subset of miRNAs (miR-17, miR-19b, miR-195 and miR-20b) between both biological samples in all patients. This finding supports that the miRNAs profiles obtained from different biological samples have to be carefully validated to link with respiratory diseases. PMID:22430188

Surfactant protein B deficiency and gene mutations for neonatal respiratory distress syndrome in China Han ethnic population

PubMed Central

Yin, Xiaojuan; Meng, Fanping; wang, Yan; Xie, Lu; Kong, Xiangyong; Feng, Zhichun

2013-01-01

Objective: To determine whether the SP-B deficiency and gene mutations in exon 4 is associated with neonatal RDS in China Han ethnic population. Methods: The study population consisted of 40 neonates with RDS and 40 neonates with other diseases as control in China Han ethnic population. We Compared SP-B expression in lung tissue and bronchoalveolar lavage fluid with immunoblotting, and analyzed mutations in the SP-B gene with polymerase chain reaction (PCR) and gene sequencing. Results: In RDS group, low mature Surfactant protein B was found in both lung tissue and bronchoalveolar lavage fluid in 8 neonates. In control group, only 4 neonates with low mature Surfactant protein B in both lung tissue and bronchoalveolar lavage fluid. In RDS group, 20 neonates were found to have mutations in exon 4, 12 homozygous mutations with C/C genotype and 8 heterozygous mutations with C/T genotype in surfactant protein B gene+1580 polymorphism. There were 8 cases mutations in control group, 1 in C/C and 7 in C/T genotype. The frequency of homozygotes with C/C genotype was 0.3 and frequency of heterozygotes with C/T genotype was 0.02 in RDS group. In control group, frequency of homozygotes with C/C genotype was 0.025 and frequency of heterozygote with C/T genotype was 0.175. Conclusion: Low mature Surfactant protein B is associated with the pathogenesis of neonatal respiratory distress syndrome (RDS) in China Han ethnic population. Mutations in exon 4 of the surfactant protein B gene demonstrate an association between homozygous mutations with C/C genotype in SP-B gene and neonatal RDS. PMID:23330012

Effects of positive end-expiratory pressure and 30% inspired oxygen on pulmonary mechanics and atelectasis in cats undergoing non-bronchoscopic bronchoalveolar lavage.

PubMed

Bernhard, Christa; Masseau, Isabelle; Dodam, John; Outi, Hilton; Krumme, Stacy; Bishop, Kaitlin; Graham, Amber; Reinero, Carol

2017-06-01

Objectives The objective of this study was to determine if modification of inspired oxygen concentration or positive end-expiratory pressure (PEEP) would alter bronchoalveolar lavage (BAL)-induced changes in pulmonary mechanics or atelectasis, as measured using ventilator-acquired pulmonary mechanics and thoracic CT. Methods Six experimentally asthmatic cats underwent anesthesia and non-bronchoscopic BAL, each under four randomized treatment conditions: 100% oxygen, zero PEEP; 30% oxygen, zero PEEP; 100% oxygen, PEEP 2 cmH 2 O; and 30% oxygen, PEEP 2 cmH 2 O. Pulse oximetry was used to estimate oxygen saturation (SpO 2 ). Ventilator-acquired pulmonary mechanics and thoracic CT scans were collected prior to BAL and at 1, 5 and 15 mins post-BAL. Results While receiving 100% oxygen, no cat had SpO 2 <91%. Some cats receiving 30% oxygen had decreased saturation immediately post-BAL (mean ± SD 70.8 ± 31%), but 6/8 of these had SpO 2 >90% by 1 min later. There was a significant increase in airway resistance and a decrease in lung compliance following BAL, but there was no significant difference between treatment groups. Cats receiving no PEEP and 30% oxygen conserved better aeration of the lung parenchyma in BAL-sampled areas than those receiving no PEEP and 100% oxygen. Conclusions and relevance Alterations in pulmonary mechanics or atelectasis may not be reflected by SpO 2 following BAL. The use of 30% inspired oxygen concentration failed to show any significant improvement in pulmonary mechanics but did diminish atelectasis. In some cats, it was also associated with desaturation of hemoglobin. The use of PEEP in this study did not show any effect on our outcome parameters. Further studies using higher PEEP (5-10 cmH 2 O) and intermediate inspired oxygen concentration (40-60%) are warranted to determine if they would confer clinical benefit in cats undergoing diagnostic BAL.

Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX.

PubMed

Graham, Jacob R; Wright, Benjamin S; Rezk, Peter E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P

2006-06-01

Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea pig BALF has a significant amount of cholinesterase activity. Treatment with Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity, indicating the predominance of BChE in BALF. A predominance of BChE expression in the lung lavage was seen in both genders. Substrate specific inhibition indicated that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and lung tissue AChE and BChE activities were strongly inhibited in guinea pigs exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15 min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity was increased 77% and 88% after 24 h of recovery following 5 min inhalation exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver and present in the plasma, an increase in BALF indicates endothelial barrier injury and leakage of plasma into lung interstitium. Therefore, a measure of increased levels of AChE and BChE in the lung lavage can be used to determine the chronology of barrier damage as well as the extent of lung injury following exposure to chemical warfare nerve agents.

Genomic Analysis of Uterine Lavage Fluid Detects Early Endometrial Cancers and Reveals a Prevalent Landscape of Driver Mutations in Women without Histopathologic Evidence of Cancer: A Prospective Cross-Sectional Study

PubMed Central

Camacho, Sandra Catalina; Schumacher, Cassie A.; Irish, Jonathan C.; Harkins, Timothy T.; Belfer, Rachel; Kalir, Tamara; Reva, Boris; Dottino, Peter; Martignetti, John A.

2016-01-01

Background Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA) revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis. Methods and Findings Uterine lavage and paired blood samples were collected and analyzed from 107 consecutive patients who were undergoing hysteroscopy and curettage for diagnostic evaluation from this single-institution study. The lavage fluid was separated into cellular and acellular fractions by centrifugation. Cellular and cell-free DNA (cfDNA) were isolated from each lavage. Two targeted next-generation sequencing (NGS) gene panels, one composed of 56 genes and the other of 12 genes, were used for ultra-deep sequencing. To rule out potential NGS-based errors, orthogonal mutation validation was performed using digital PCR and Sanger sequencing. Seven patients were diagnosed with endometrial cancer based on classic histopathologic analysis. Six of these patients had stage IA cancer, and one of these cancers was only detectable as a microscopic focus within a polyp. All seven patients were found to have significant cancer-associated gene mutations in both cell pellet and cfDNA fractions. In the four patients in whom adequate tumor sample was available, all tumor mutations above a specific allele fraction were present in the uterine lavage DNA samples. Mutations originally only detected in lavage fluid fractions were later confirmed to be present

Type XVIII collagen degradation products in acute lung injury

PubMed Central

Perkins, Gavin D; Nathani, Nazim; Richter, Alex G; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, W; McAuley, Danny; Gao, Fang; Thickett, David R

2009-01-01

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods Endostatin was measured by ELISA and western blotting. Results Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation. PMID:19358707

In vitro gallium-67 lung index for the evaluation of sarcoidosis

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

Braude, A.C.; Cohen, R.; Rahmani, R.

1984-11-01

In the evaluation of the active alveolitis of pulmonary sarcoidosis, both the proportional lymphocyte count obtained by bronchoalveolar lavage and state of activation of the alveolar macrophage by gallium scanning are required. We injected 6 mCi (200 MBq) of /sup 67/Ga intravenously on 24 occasions in 13 patients with biopsy-proved sarcoidosis. Forty-eight hours later, patients were scanned with a rectilinear scanner and the generated scintigrams were evaluated using the NIH index. Seventy-two hours after injection, bronchoalveolar lavage was performed, and venous blood was sampled. The harvested lavage fluid was analyzed for absolute and proportional cell counts, and radioactivity was measuredmore » in blood and BAL fluid. An in vitro /sup 67/Ga index was generated and expressed as counts/100,000 alveolar macrophages/ml blood (mean, 0.0146 +/- 0.0087 SD). There was a significant relationship between the in vitro index and proportional lymphocyte BAL counts (r . 0.79; p less than 0.002) that was comparable to that obtained using the NIH index (r . 0.74; p less than 0.005). These data suggest that the in vitro index might offer a more objective assessment of /sup 67/Ga uptake by the lung, but this would require validation against clinical parameters in a prospective study.« less

Depletion by styrene of glutathione in plasma and bronchioalveolar lavage fluid of non-Swiss albino (NSA) mice.

PubMed

Carlson, Gary P

2010-01-01

Styrene is a widely used chemical, but it is known to produce lung and liver damage in mice. This may be related to oxidative stress associated with the decrease in the levels of reduced glutathione (GSH) in the target tissues. The purpose of this study was to investigate the effect of styrene and its primary metabolites R-styrene oxide (R-SO) and S-styrene oxide (S-SO) on GSH levels in the lung lumen, as determined by amounts of GSH in bronchioalveolar lavage fluid (BALF) and in plasma. When non-Swiss albino (NSA) mice were administered styrene (600 mg/kg, ip), there was a significant fall in GSH levels in both BALF and plasma within 3 h. These returned to control levels by 12 h. The active metabolite R-SO (300 mg/kg, ip) also produced significant decreases in GSH in both BALF and plasma, but S-SO was without marked effect. Since GSH is a principal antioxidant in the lung epithelial lining fluid, this fall due to styrene may exert a significant influence on the ability of the lung to buffer oxidative damage.

Neutrophil alveolitis following endotoxemia. Enhancement by previous exposure to hyperoxia.

PubMed

Rinaldo, J E; Dauber, J H; Christman, J; Rogers, R M

1984-12-01

We injected Escherichia coli endotoxin, 2.5 mg/kg, intraperitoneally in rats, sequentially quantified alveolar inflammation during a 6-day period by several techniques, and observed the effect of previous exposure to hyperoxia on the intensity of alveolitis in this model. As noted in other models of endotoxemia, we found intravascular sequestration of leukocytes and an increase in the retention of 125I albumin in the lung 4 to 6 h after the injection of endotoxin. Bronchoalveolar lavage fluid (BALF) obtained at this time only slightly stimulated the migration of neutrophils in vitro, and the numbers and types of cells recovered by lavage were normal. Fifteen h after the injection of endotoxin, however, bronchoalveolar lavage fluid stimulated both random and directed migration of neutrophils in vitro, although recovery of neutrophils by lavage was increased only slightly. By 24 h, 125I albumin retention had returned to normal levels, but the chemotactic activity of BALF remained high, and the percentage and absolute number of neutrophils recovered by lung lavage were increased markedly. The recovery of neutrophils remained significantly elevated for 3 days but declined to control levels by 6 days, whereas the recovery of alveolar macrophages was increased at this time. Exposure to 100% O2 for 36 h prior to endotoxemia accelerated and intensified neutrophil influx into the lung and increased the stimulatory effect of BALF on neutrophil migration in vitro. We conclude that a single episode of endotoxemia in the rat causes a multi-phasic alveolar inflammatory response, and that this response is accelerated and intensified by prior, mild exposure to hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx.

PubMed

Marsh, R L; Kaestli, M; Chang, A B; Binks, M J; Pope, C E; Hoffman, L R; Smith-Vaughan, H C

2016-07-07

Invasive methods requiring general anaesthesia are needed to sample the lung microbiota in young children who do not expectorate. This poses substantial challenges to longitudinal study of paediatric airway microbiota. Non-invasive upper airway sampling is an alternative method for monitoring airway microbiota; however, there are limited data describing the relationship of such results with lung microbiota in young children. In this study, we compared the upper and lower airway microbiota in young children to determine whether non-invasive upper airway sampling procedures provide a reliable measure of either lung microbiota or clinically defined differences. The microbiota in oropharyngeal (OP) swabs, nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) from 78 children (median age 2.2 years) with and without lung disease were characterised using 16S rRNA gene sequencing. Permutational multivariate analysis of variance (PERMANOVA) detected significant differences between the microbiota in BAL and those in both OP swabs (p = 0.0001, Pseudo-F = 12.2, df = 1) and NP swabs (p = 0.0001; Pseudo-F = 21.9, df = 1) with the NP and BAL microbiota more different than the OP and BAL, as indicated by a higher Pseudo-F value. The microbiota in combined OP and NP data (upper airways) provided a more comprehensive representation of BAL microbiota, but significant differences between the upper airway and BAL microbiota remained, albeit with a considerably smaller Pseudo-F (PERMANOVA p = 0.0001; Pseudo-F = 4.9, df = 1). Despite this overall difference, paired BAL and upper airway (OP and NP) microbiota were >50 % similar among 69 % of children. Furthermore, canonical analysis of principal coordinates (CAP analysis) detected significant differences between the microbiota from clinically defined groups when analysing either BAL (eigenvalues >0.8; misclassification rate 26.5 %) or the combined OP and NP data (eigenvalues >0

Obesity is Associated with Atypia in Breast Ductal Lavage of Women with Proliferative Breast Disease

PubMed Central

Djuric, Zora; Edwards, Ann; Madan, Shashi; Darga, Linda; Ren, Jianwei; Koletsky, Mathew; Heilbrun, Lance K.

2009-01-01

Background Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. Methods We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. Results There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity) as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index also was significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Conclusions Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk. PMID:19683484

Obesity is associated with atypia in breast ductal lavage of women with proliferative breast disease.

PubMed

Djuric, Zora; Edwards, Ann; Madan, Shashi; Darga, Linda; Ren, Jianwei; Blake, Cassann; Koletsky, Mathew; Heilbrun, Lance K

2009-10-01

Benign proliferative breast disease without atypia slightly increases breast cancer risk but there are currently few clinical options for breast cancer prevention in this group of women. We conducted a pilot study of women with a past diagnosis of proliferative breast disease with a goal to determine if the characteristics of cells obtained by breast ductal lavage were related to nutritional factors. There were 57 women who enrolled. A total of 39 women yielded nipple aspirate fluid (NAF) samples and 36 underwent breast ductal lavage. Five of the lavage samples were acellular and 28 had at least 200 cells. Surprisingly, atypia was present in 11 women. Presence of atypia was associated with slight changes in morphometric features of the epithelial cells such as measures of circularity as obtained by image analysis, but the only variable significantly different in women with atypia (versus no atypia) was a higher mean body mass index. Body mass index was also significantly correlated with C-reactive protein (CRP) levels in the nipple aspirate fluid, indicating that obesity might have a pro-inflammatory effect on the breast that can contribute to increased rates of atypia. Although the clinical significance of atypia in breast ductal lavage is uncertain, these results support further work on prevention of obesity as a strategy for reducing breast cancer risk.

Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome.

PubMed

Chang, Dong W; Hayashi, Shinichi; Gharib, Sina A; Vaisar, Tomas; King, S Trevor; Tsuchiya, Mitsuhiro; Ruzinski, John T; Park, David R; Matute-Bello, Gustavo; Wurfel, Mark M; Bumgarner, Roger; Heinecke, Jay W; Martin, Thomas R

2008-10-01

Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.

BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6

PubMed Central

2014-01-01

Background Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. Case presentation We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no acid-fast bacillus could be identified in recovered BALF or pleural effusion. The lymphocyte stimulation test of BCG was strongly positive. However, levels of serum and bronchoalveolar lavage fluid KL-6, a useful marker for hypersensitivity pneumonitis (HP), were within normal ranges. Conclusion We speculate that the pathogenesis of our case may be a hypersensitive reaction to the proteic component of BCG entering the lung and pleural space, which is different from the etiology of the common type of HP. PMID:24593234

Protein corona formation in bronchoalveolar fluid enhances diesel exhaust nanoparticle uptake and pro-inflammatory responses in macrophages.

PubMed

Shaw, Catherine A; Mortimer, Gysell M; Deng, Zhou J; Carter, Edwin S; Connell, Shea P; Miller, Mark R; Duffin, Rodger; Newby, David E; Hadoke, Patrick W F; Minchin, Rodney F

2016-09-01

In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences biological activity and fate of nanoparticle in vivo. Corona composition is often determined by the biological milieu encountered at the entry portal into the body, and, can therefore, depend on the route of exposure to the nanoparticle. For environmental nanoparticles where exposure is by inhalation, this will be lung lining fluid. This study examined plasma and bronchoalveolar fluid (BALF) protein binding to engineered and environmental nanoparticles. We hypothesized that protein corona on nanoparticles would influence nanoparticle uptake and subsequent pro-inflammatory biological response in macrophages. All nanoparticles bound plasma and BALF proteins, but the profile of bound proteins varied between nanoparticles. Focusing on diesel exhaust nanoparticles (DENP), we identified proteins bound from plasma to include fibrinogen, and those bound from BALF to include albumin and surfactant proteins A and D. The presence on DENP of a plasma-derived corona or one of purified fibrinogen failed to evoke an inflammatory response in macrophages. However, coronae formed in BALF increased DENP uptake into macrophages two fold, and increased nanoparticulate carbon black (NanoCB) uptake fivefold. Furthermore, a BALF-derived corona increased IL-8 release from macrophages in response to DENP from 1720 ± 850 pg/mL to 5560 ± 1380 pg/mL (p = 0.014). These results demonstrate that the unique protein corona formed on nanoparticles plays an important role in determining biological reactivity and fate of nanoparticle in vivo. Importantly, these findings have implications for the mechanism of detrimental properties of environmental nanoparticles since the principle route of exposure to such particles is via the lung.

Postexposure Application of Fas Receptor Small-Interfering RNA to Suppress Sulfur Mustard-Induced Apoptosis in Human Airway Epithelial Cells: Implication for a Therapeutic Approach

DTIC Science & Technology

2013-01-01

bronchiolitis, bronchopneumo- nia, chronic obstructive pulmonary disease, bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis ... pulmonary fibrosis , acute lung injury [ALI], acute respiratory distress syndrome, etc.) (Beheshti et al., 2006; Emmler et al., 2007; Kuwano, 2008...cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. J In- terferon Cytokine Res 27:38

Ceramides: a potential therapeutic target in pulmonary emphysema.

PubMed

Tibboel, Jeroen; Reiss, Irwin; de Jongste, Johan C; Post, Martin

2013-10-01

The aim of this manuscript was to characterize airway ceramide profiles in a rodent model of elastase-induced emphysema and to examine the effect of pharmacological intervention directed towards ceramide metabolism. Adult mice were anesthetized and treated with an intratracheal instillation of elastase. Lung function was measured, broncho-alveolar lavage fluid collected and histological and morphometrical analysis of lung tissue performed within 3 weeks after elastase injection, with and without sphingomyelinase inhibitors or serine palmitoyltransferase inhibitor. Ceramides in broncho-alveolar lavage (BAL) fluid were quantified by tandem mass spectrometry. BAL fluid showed a transient increase in total protein and IgM, and activated macrophages and neutrophils. Ceramides were transiently upregulated at day 2 after elastase treatment. Histology showed persistent patchy alveolar destruction at day 2 after elastase installation. Acid and neutral sphingomyelinase inhibitors had no effect on BAL ceramide levels, lung function or histology. Addition of a serine palmitoyltransferase inhibitor ameliorated lung function changes and reduced ceramides in BAL. Ceramides were increased during the acute inflammatory phase of elastase-induced lung injury. Since addition of a serine palmitoyltransferase inhibitor diminished the rise in ceramides and ameliorated lung function, ceramides likely contributed to the early phase of alveolar destruction and are a potential therapeutic target in the elastase model of lung emphysema.

Radiographic appearance of bronchoalveolar carcinoma in nine cats.

PubMed

Ballegeer, Elizabeth A; Forrest, Lisa J; Stepien, Rebecca L

2002-01-01

Thoracic radiographs of nine cats with confirmed bronchoalveolar carcinoma (BAC) were reviewed retrospectively. Radiographic appearance of BAC was divided into three categories: mixed bronchoalveolar pattern, ill-defined alveolar mass, or mass with cavitation. In addition to these radiographic signs, all nine cats had evidence of some form of bronchial disease. Cavitary lesions were the most common finding (n = 5). In addition, three cats in this category had diffuse bronchointerstitial opacity and one cat had focal peribronchial cuffing. Five cats had either a mixed bronchoalveolar pattern with bronchiectasis (n = 3) or an ill-defined alveolar mass with peribronchial cuffing (n = 2). One cat had both a mixed bronchoalveolar pattern and a cavitary mass. Each of these nine cats had some form of bronchial disease (bronchointerstitial pattern, peribronchial cuffing, or bronchiectasis), which aids in the radiographic diagnosis of bronchoalveolar carcinoma and may represent airway metastasis.

LADTAG Progress 2010 and Plans for 2011 and Provisional PELs from Lavage and Blood Data

NASA Technical Reports Server (NTRS)

James, John T.

2010-01-01

This viewgraph presentation reviews the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) plans and progress for 2010 and 2011. Provisional Permissible Exposure Limits (PPELs) from lavage fluid and blood data are also presented.

Pulmonary bioavailability of ascorbic acid in an ascorbate-synthesising species, the horse.

PubMed

Deaton, Christopher M; Marlin, David J; Smith, Nicola C; Roberts, Colin A; Harris, Pat A; Kelly, Frank J; Schroter, Robert C

2003-04-01

Vitamin C (ascorbic acid) is a non-enzymatic antioxidant important in protecting the lung against oxidative damage and is decreased in lung lining fluid of horses with airway inflammation. To examine possible therapeutic regimens in a species with ascorbate-synthesising capacity, we studied the effects of oral supplementation of two forms of ascorbic acid, (each equivalent to 20 mg ascorbic acid per kg body weight) on the pulmonary and systemic antioxidant status of six healthy ponies in a 3 x 3 Latin square design. Two weeks supplementation with ascorbyl palmitate significantly increased mean plasma ascorbic acid concentrations compared to control (29 +/- 5 and 18 +/- 7 micromol/l, respectively; p < 0.05). Calcium ascorbyl-2-monophosphate, a more stable form of ascorbic acid, also increased mean plasma ascorbic acid concentrations, but not significantly (23 +/- 1 micromol/l; p = 0.07). The concentration of ascorbic acid in bronchoalveolar lavage fluid increased in five out of six ponies following supplementation with either ascorbyl palmitate or calcium ascorbyl-2-monophosphate compared with control (30 +/- 10, 25 +/- 4 and 18 +/- 8 micromol/l, respectively; p < 0.01). Neither supplement altered the concentration of glutathione, uric acid or alpha-tocopherol in plasma or bronchoalveolar lavage fluid. In conclusion, the concentration of lung lining fluid ascorbic acid is increased following ascorbic acid supplementation (20 mg/kg body weight) in an ascorbate-synthesising species.

Ghrelin Ameliorates Asthma by Inhibiting Endoplasmic Reticulum Stress.

PubMed

Fu, Tian; Wang, Lei; Zeng, Qingdi; Zhang, Yan; Sheng, Baowei; Han, Liping

2017-12-01

This study aimed to confirm the ameliorative effect of ghrelin on asthma and investigate its mechanism. The murine model of asthma was induced by ovalbumin (OVA) treatment and assessed by histological pathology and airway responsiveness to methacholine. The total and differential leukocytes were counted. Tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 levels in bronchoalveolar lavage fluid were quantified by commercial kits. The protein levels in pulmonary tissues were measured by Western blot analysis. Ghrelin ameliorated the histological pathology and airway hyperresponsiveness in the OVA-induced asthmatic mouse model. Consistently, OVA-increased total and differential leukocytes and levels of tumor necrosis factor α, interferon γ, interleukin-5 and interleukin-13 in bronchoalveolar lavage fluid were significantly attenuated by ghrelin. Ghrelin prevented the increased protein levels of the endoplasmic reticulum stress markers glucose regulated protein 78 and CCAAT/enhancer binding protein homologous protein and reversed the reduced levels of p-Akt in asthmatic mice. Ghrelin might prevent endoplasmic reticulum stress activation by stimulating the Akt signaling pathway, which attenuated inflammation and ameliorated asthma in mice. Ghrelin might be a new target for asthma therapy. Copyright © 2017. Published by Elsevier Inc.

The importance of interleukin-8 as a neutrophil chemoattractant in the lungs of cattle with pneumonic pasteurellosis.

PubMed Central

Caswell, J L; Middleton, D M; Gordon, J R

2001-01-01

Interleukin-8 (IL-8), an in vitro and in vivo neutrophil chemoattractant, is expressed at high levels in the lesions observed in bovine pneumonic pasteurellosis. Because of the role of neutrophils in the pathogenesis of pneumonic pasteurellosis, we investigated the relative importance of IL-8 as a neutrophil chemoattractant in this disease. Bronchoalveolar lavage (BAL) fluid was harvested from calves experimentally infected with bovine herpesvirus-1 and challenged with Mannheimia haemolytica. Neutrophil chemotactic activity was measured in pneumonic BAL fluid samples treated with a neutralizing monoclonal antibody to ovine IL-8, and compared to the activity in samples treated with an isotype-matched control antibody. Bronchoalveolar lavage fluid was analyzed at a dilution which induced a half-maximal response, and the concentrations of antibody were optimized in a preliminary experiment. Following incubation of replicate samples of diluted pneumonic bovine BAL fluid with 70 microg/mL of IL-8-neutralizing antibody or control antibody, the neutrophil chemotactic activities of the samples were determined using an in vitro microchemotaxis assay. Overall, pretreatment of BAL fluid samples with neutralizing anti-IL-8 antibody reduced neutrophil chemotactic activity by 15% to 60%, compared to pretreatment with control antibody. This effect was highly significant (P < 0.001), and was present in 5 of 5 samples. These data indicate that IL-8 is an important neutrophil chemoattractant in calves with pneumonic pasteurellosis, but that mediators with actions redundant to those of IL-8 must also be present in the lesions. PMID:11768129

Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD.

PubMed

Yang, Mingxing; Kohler, Maxie; Heyder, Tina; Forsslund, Helena; Garberg, Hilde K; Karimi, Reza; Grunewald, Johan; Berven, Frode S; Magnus Sköld, C; Wheelock, Åsa M

2018-03-08

Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV 1 /FVC as well as the percentage of CD8 + T-cells and CD8 + CD69 + T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV 1 /FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. ClinicalTrials.gov identifier NCT02627872 ; Retrospectively registered on December 9, 2015.

[The effect of the intratracheal administration of americium-241 on rat alveolar macrophages].

PubMed

Shopova, V; Sŭlovski, P; Dancheva, V

1996-01-01

In experiments in rats it was found that 241Am transitory decreases the total cell number and alveolar macrophage's percentage in bronchoalveolar lavage fluid (BALF): increases the macrophages size and nuclear size; and increases acid phosphatase and lactate dehydrogenase activities in BALF. It was suggested that 241Am causes and activation in the alveolar macrophages which probably appears as one of factors provoking lung injuries.

21 CFR 880.5475 - Jet lavage.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Jet lavage. 880.5475 Section 880.5475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... Jet lavage. (a) Identification. A jet lavage is a device used to clean a wound by a pulsatile jet of...

21 CFR 880.5475 - Jet lavage.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Jet lavage. 880.5475 Section 880.5475 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... Jet lavage. (a) Identification. A jet lavage is a device used to clean a wound by a pulsatile jet of...

Streptococcal Toxic Shock Syndrome: Life Saving Role of Peritoneal Lavage and Drainage.

PubMed

Yokoyama, Minako; Oyama, Fumie; Ito, Asami; Yokota, Megumi; Matsukura, Daisuke; Tsutsumi, Shinji; Kasai, Tomonori; Nitobe, Yohshiro; Morikawa, Akiko; Ozaki, Takashi; Yokoyama, Yoshihito

2016-01-01

We encountered a case where an infection with group A streptococcus (GAS; ie, Streptococcus pyogenes) initially caused primary peritonitis and then subsequently caused streptococcal toxic shock syndrome. The patient's life was likely saved by an emergency laparotomy followed by extensive peritoneal lavage and drainage. A 40-year-old woman was admitted to the Emergency Department for lower abdominal pain and numbness in the extremities. She presented with systemic inflammatory response syndrome. An emergency laparotomy was performed, and ascites that resembled pus and general peritonitis were noted. Peritoneal lavage and drainage were performed, and GAS was isolated from peritoneal fluid. Gram staining of cervical polyp specimens revealed Gram-positive bacteria. The patient was diagnosed with streptococcal toxic shock syndrome due to an ascending GAS infection originating from vagina.

Genetics of Eosinophilic Esophagitis

DTIC Science & Technology

2011-03-01

cellular content (total cells, left panel, and differential cell counts , right panel) in bronchoalveolar lavage fluid (BALF) in IL-21R-/- mice compared...group (30%) had multiple sensitivities to foods and pollens (GM total IgE 285 IU/ ml). Tests for IgE to carbohydrate antigens were negative in all...those with multiple pollen allergies. The frequent occurrence of multiple associated sensitivities to grains, legumes, molds, and pollens suggests that

Analysis of inflammatory markers and metals in nasal lavage fluid of welders.

PubMed

Raulf, Monika; Weiss, Tobias; Lotz, Anne; Lehnert, Martin; Hoffmeyer, Frank; Liebers, Verena; Van Gelder, Rainer; Udo Käfferlein, Heiko; Hartwig, Andrea; Pesch, Beate; Brüning, Thomas

2016-01-01

Welding fumes may produce adverse health effects in the respiratory tract. To assess the relationship between exposure to welding fumes and inflammation in the upper airways, 190 male welders were examined from the WELDOX study (median age 40 yr, 54.7% smokers, and 32.9% atopics). Inhalable welding fumes were collected in the breathing zone of welders during a single shift. Chromium (Cr), nickel (Ni), manganese (Mn), and iron (Fe) were measured in the welding-fume samples and in postshift nasal lavage fluid (NALF). In addition, the numbers of particles and inflammatory biomarkers, including total and differential cell counts, interleukin (IL)-8, leukotriene (LT) B 4 , 8-isoprostane (8-iso-PGF 2α ), tissue inhibitor of metalloproteinase-1 (TIMP-1), and immunoreactive matrix metalloproteinase (MMP)-9, were determined. Metal concentrations in NALF correlated with airborne concentrations. No significant association was found between airborne metal concentrations and biomarkers of inflammation in NALF, whereas increasing metal concentrations in NALF resulted in increased concentrations of total protein, IL-8, MMP-9, and TIMP-1. LTB 4 and 8-iso PGF 2α were elevated at higher concentrations of Cr or Ni in NALF. The same was true for Fe, although the effects were less pronounced and of borderline significance. In conclusion, our results showed a significant association between the concentrations of metals and soluble inflammatory markers in the NALF of welders. The noninvasive collection of NALF is applicable in field studies, where it may serve as a suitable matrix to simultaneously assess biomarkers of exposure and effect in the upper respiratory tract in workers who are occupationally exposed to airborne hazardous substances.

Diffuse consolidation form of bronchoalveolar carcinoma.

PubMed

Khalil, Kanwal Fatima; Saeed, Waseem; Zill-e-Hamayun

2010-03-01

This case report describes a patient with diffuse consolidation form of bronchoalveolar carcinoma (BAC) which is a rare type of adenocarcinoma of lung. He was diagnosed on the basis of findings on X-ray and high resolution CT(HRCT) chest later confirmed by open lung biopsy and immuno-histochemical staining. Only supportive treatment could be provided and the patient expired during the subsequent month of follow-up. Traditionally, diffuse consolidation is the radiological presentation in only 20% of patients with bronchoalveolar carcinoma.

Evaluation of the concentration of marbofloxacin in alveolar macrophages and pulmonary epithelial lining fluid after administration in dogs.

PubMed

Boothe, Harry W; Jones, Sarah A; Wilkie, W Scott; Boeckh, Albert; Stenstrom, Kristol K; Boothe, Dawn M

2005-10-01

To determine concentrations of marbofloxacin in alveolar macrophages (AMs) and epithelial lining fluid (ELF) and compare those concentrations with plasma concentrations in healthy dogs. 12 adult mixed-breed and purebred hounds. 10 dogs received orally administered marbofloxacin at a dosage of 2.75 mg/kg every 24 hours for 5 days. Two dogs served as nontreated controls. Fiberoptic bronchoscopy and bronchoalveolar lavage procedures were performed while dogs were anesthetized with propofol, approximately 6 hours after the fifth dose. The concentrations of marbofloxacin in plasma and bronchoalveolar fluid (cell and supernatant fractions) were determined by use of high-performance liquid chromatography with detection of fluorescence. Mean +/- SD plasma marbofloxacin concentrations 2 and 6 hours after the fifth dose were 2.36 +/- 0.52 microg/mL and 1.81 +/- 0.21 microg/mL, respectively. Mean +/- SD marbofloxacin concentration 6 hours after the fifth dose in AMs (37.43 +/- 24.61 microg/mL) was significantly greater than that in plasma (1.81 +/- 0.21 microg/mL) and ELF (0.82 +/- 0.34 microg/mL), resulting in a mean AM concentration-to-plasma concentration ratio of 20.4, a mean AM:ELF ratio of 60.8, and a mean ELF-to-plasma ratio of 0.46. Marbofloxacin was not detected in any samples from control dogs. Marbofloxacin concentrations in AMs were greater than the mean inhibitory concentrations of major bacterial pathogens in dogs. Results indicated that marbofloxacin accumulates in AMs at concentrations exceeding those reached in plasma and ELF The accumulation of marbofloxacin in AMs may facilitate treatment for susceptible intracellular pathogens or infections associated with pulmonary macrophage infiltration.

Effect of peritoneal lavage solution temperature on body temperature in anaesthetised cats and small dogs.

PubMed

Barnes, D C; Leece, E A; Trimble, T A; Demetriou, J L

2017-05-20

A prospective, randomised, non-blinded, clinical study to assess the effect of peritoneal lavage using warmed fluid on body temperature in anesthetised cats and dogs of less than 10 kg body mass undergoing coeliotomy. A standardised anaesthetic protocol was used. Oesophageal and rectal temperatures were measured at various time points. At the end of surgery, group 1 patients (n=10) were lavaged with 200 ml/kg sterile isotonic saline at 34±1°C and group 2 (n=10) at 40±1°C. Groups were similar with respect to age, mass, body condition and surgical incision length. Duration of anaesthesia, surgical procedures and peritoneal lavage was similar between groups. Linear regression showed no significant change in oesophageal temperature during the lavage period for group 1 (P=0.64), but a significant increase for group 2 patients (P<0.0001), with mean temperature changes of -0.5°C (from (36.3°C to 35.9°C) and +0.9°C (from 35.4°C to 36.3°C), respectively. Similar results were found for rectal temperature, with mean changes of -0.5°C and +0.8°C (P=0.922 and 0.045), respectively. The use of isotonic crystalloid solution for peritoneal lavage at a temperature of 40±1°C significantly warms small animal patients, when applied in a clinical setting, compared with lavage solution at 34±1°C. British Veterinary Association.

miR-185 and miR-29a are similarly expressed in the bronchoalveolar lavage cells in IPF and lung cancer but common targets DNMT1 and COL1A1 show disease specific patterns

PubMed Central

Bibaki, Eleni; Tsitoura, Eliza; Vasarmidi, Eirini; Margaritopoulos, George; Trachalaki, Athina; Koutoulaki, Chara; Georgopoulou, Theodora; Spandidos, Demetrios A.; Tzanakis, Nikos; Antoniou, Katerina M.

2018-01-01

Idiopathic pulmonary fibrosis (IPF) and lung cancer (LC) constitute two progressively devastating lung diseases with common risk factors including aging and smoking. There is an increasing interest in the investigation of common pathogenic mechanisms between IPF and LC with therapeutic implications. Several oncomirs, microRNAs associated with malignancy, are also linked with IPF. miR-29a and miR-185 downregulation is probably involved both in carcinogenesis and fibrogenesis. We have previously observed miR-29a and miR-185 downregulation in IPF cells from bronchoalveolar lavage (BAL) and in this study we investigated their expression in LC BAL cells. Common targets of miR-29a and miR-185 such as DNA methyltransferase (DNMT)1, DNMT3b, COL1A1, AKT1 and AKT2 were measured. Potential correlations with pulmonary function tests, smoking status and endobronchial findings were investigated. Similar levels of miR-29a and miR-185 were detected in IPF and LC while their common targets AKT1 and DNMT3b were not found to differ, suggesting potential pathogenetic similarities at the level of key epigenetic regulators. By conrast, COL1A1 mRNA levels were increased in IPF suggesting a disease-specific mRNA signature. Notably, DNMT1 was downregulated in the LC group and its expression was further reduced in the presence of increasing malignant burden as it was implied by the endobronchial findings. PMID:29568927

[Efficacy of bronchoalveolar lavage and its influence factors in the treatment of Mycoplasma pneumoniae pneumonia with atelectasis].

PubMed

Yang, M; Yang, D H; Yang, X; Wang, Y S; Wu, L; Chen, Z M

2018-05-02

Objective: To investigate the efficacy of bronchoalveolar lavage (BAL) and its influence factors in the treatment of Mycoplasma pneumoniae pneumonia (MPP) with atelectasis. Methods: A retrospective case control study was performed on hospitalized MPP patients with atelectasis and received BAL in the Department of Pulmonology, Children's Hospital Zhejiang University School of Medicine from January 1, 2015 to July 31, 2017. Fever relieved in 48 hours and chest imaging improved in one week after BAL were considered effective. Clinical data, including age, sex, blood routine tests, lactate dehydrogenase (LDH), cytokines, complications, fever duration before BAL, course of disease before BAL, sputum plug, atelectasis area and its CT values of atelectasis site were collected. Student's t test, Mann-Whitney U test, or chi square test were used. Results: (1) A total of 163 patients were enrolled, including 69 boys and 94 girls, with the ratio of 1∶1.36. Their ages ranged from 6 months to 12.6 years. (2) On the day of bronchoscope, 113 patients still had fever. They were divided into effective group ( n= 66) and ineffective group ( n= 47) according to whether fever was relieved in 48 hours after BAL. The effective group were found to have less sputum plug compared with the ineffective group (33% (22/66) vs . 57% (27/47), χ(2)=6.499, P= 0.011). The other factors such as sex, age, fever duration before BAL, course of disease before BAL, C reactive protein (CRP), LDH, IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, atelectasis area and CT value showed no significant difference between the two groups (all P >0.05). (3)A total of 122 cases had chest imaging after BAL. According to chest imaging improvement, they were divided into effective group ( n= 81) and ineffective group ( n= 41). The effective group showed lower CT value ((58±9) vs. (63±8) HU, t= -2.436, P= 0.017), IL-6 and IL-10 ( M ( Q (1), Q (3))) (21.0 (1.9, 48.4) vs . 36.4(21.8, 93.6), 4.9 (3.7, 9.6) vs . 7.7 (4.4, 12

A role for MCP-1/CCR2 in interstitial lung disease in children

PubMed Central

Hartl, Dominik; Griese, Matthias; Nicolai, Thomas; Zissel, Gernot; Prell, Christine; Reinhardt, Dietrich; Schendel, Dolores J; Krauss-Etschmann, Susanne

2005-01-01

Background Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies. PMID:16095529

Increase of matrix metalloproteinases in woodsmoke-induced lung emphysema in guinea pigs.

PubMed

Ramos, Carlos; Cisneros, Jose; Gonzalez-Avila, Georgina; Becerril, Carina; Ruiz, Víctor; Montaño, Martha

2009-02-01

Elastolysis, collagenolysis and gelatinolysis are essential in the pathogenesis of tobacco smoke-induced emphysema; however, these activities have been scantily studied in emphysema secondary to woodsmoke. The aim of this study was to analyze elastolysis, collagenolysis and gelatinolysis, MMP-1, MMP-2, and MMP-9 expression, and apoptosis in guinea pigs exposed to smoke produced by 60 g/day of pine wood, 5 days/week, from 1 to 7 months. Histological analysis after 4 to 7 months in smoke exposed guinea pigs showed alveolar mononuclear phagocyte and lymphocytic peribronchiolar inflammation, epithelial and smooth muscle hyperplasia, and pulmonary arterial hypertension. Mild to moderate emphysematous lesions were observed in woodsmoke-exposed animals at 4 to 7 months by increase of mean linear intercepts. A higher percentage of whole blood carboxyhemoglobin (COHb) and elastolytic activity in bronchoalveolar lavage macrophages and lung tissue homogenates was observed at all times. Collagenolysis was increased after 4 to 7 months in woodsmoke-exposed animals, although collagen concentration did not change. Zymography revealed increase in lysis bands of the active MMP-2 and MMP-9 at 4 and 7 months in bronchoalveolar lavage fluid and lung tissue homogenate. Positive immunostaining for MMP-1 and MMP-9 was observed in epithelial cells and macrophages in wood exposed animals at 4 to 7 months. Real-time PCR showed MMP-2 and MMP-9 expression at 3 to 7 months in exposed animals. Furthermore, apoptosis was increased at all times in bronchoalveolar lavage macrophages and lung tissue from exposed animals. Results support a role of metalloproteinases and apoptosis in emphysema secondary to woodsmoke exposure.

Immune cell landscape in therapy-naïve squamous cell and adenocarcinomas of the lung.

PubMed

Brcic, Luka; Stanzer, Stefanie; Krenbek, Dagmar; Gruber-Moesenbacher, Ulrike; Absenger, Gudrun; Quehenberger, Franz; Valipour, Arschang; Lindenmann, Joerg; Stoeger, Herbert; Al Effah, Mohamed; Fediuk, Melanie; Balic, Marija; Popper, Helmut H

2018-04-01

Squamous cell and adenocarcinomas of the lung develop different mechanisms during carcinogenesis to evade attacks of the immune system. Besides the well-known check-point control programmed death 1 and its ligand, many more mechanisms, acting either tumoricidal or in favor of tumor progression, exist. Analysis of the immune cell profiles in resected tissues and bronchoalveolar lavage samples and correlation between them and with overall survival data was performed. In all tumor samples in this study, cells of the immune system expressed a tumor-cooperating phenotype. High numbers of regulatory T cells, or alternatively expression of Vista on lymphocytes was present. Tumoricidal dendritic cells were absent in tumor tissue, and barely present in bronchoalveolar lavage, whereas tumor-friendly monocytoid and plasmocytoid dendritic cells were seen in both. Alveolar macrophages were predominantly differentiated into tumor-cooperating M2 types, whereas tumoricidal M1 macrophages were absent or rare. The expression of PDL1 on tumor cells did not correlate with any other immune cells. Expression of PD1 on lymphocytes was frequently encountered. None of analyzed immune cells showed correlation with overall survival. Immune cells in bronchoalveolar lavage and tissue did not correlate. For the first time, a tissue-based analysis of different immune cells in squamous cell and adenocarcinomas of the lung is provided, trying to explain their potential role in tumor development and progression. Discordant numbers of cells with bronchoalveolar lavage are most probably due to the fact that bronchoalveolar lavage reflects the situation in the whole lung, where chronic obstructive lung disease and other conditions are present.

Comparative Proteomic Analysis of Whole-Gut Lavage Fluid and Pancreatic Juice Reveals a Less Invasive Method of Sampling Pancreatic Secretions

PubMed Central

Rocker, Jana M; Tan, Marcus C; Thompson, Lee W; Contreras, Carlo M; DiPalma, Jack A; Pannell, Lewis K

2016-01-01

OBJECTIVES: There are currently no reliable, non-invasive screening tests for pancreatic ductal adenocarcinoma. The fluid secreted from the pancreatic ductal system (“pancreatic juice”) has been well-studied as a potential source of cancer biomarkers. However, it is invasive to collect. We recently observed that the proteomic profile of intestinal effluent from the bowel in response to administration of an oral bowel preparation solution (also known as whole-gut lavage fluid, WGLF) contains large amounts of pancreas-derived proteins. We therefore hypothesized that the proteomic profile is similar to that of pancreatic juice. In this study, we compared the proteomic profiles of 77 patients undergoing routine colonoscopy with the profiles of 19 samples of pure pancreatic juice collected during surgery. METHODS: WGLF was collected from patients undergoing routine colonoscopy, and pancreatic juice was collected from patients undergoing pancreatic surgery. Protein was isolated from both samples using an optimized method and analyzed by LC-MS/MS. Identified proteins were compared between samples and groups to determine similarity of the two fluids. We then compared our results with literature reports of pancreatic juice-based studies to determine similarity. RESULTS: We found 104 proteins in our pancreatic juice samples, of which 90% were also found in our WGLF samples. The majority (67%) of the total proteins found in the WGLF were common to pancreatic juice, with intestine-specific proteins making up a smaller proportion. CONCLUSIONS: WGLF and pancreatic juice appear to have similar proteomic profiles. This supports the notion that WGLF is a non-invasive, surrogate bio-fluid for pancreatic juice. Further studies are required to further elucidate its role in the diagnosis of pancreatic cancer. PMID:27228405

Genetics of Eosinophilic Esophagitis

DTIC Science & Technology

2012-03-01

cells, left panel, and differential cell counts , right panel) in bronchoalveolar lavage fluid (BALF) in IL- 21R-/- mice compared to wild-type (WT). A...positive skin tests. A third group (30%) had multiple sensitivities to foods and pollens (GM total IgE 285 IU/ ml). Tests for IgE to carbohydrate antigens...milk sensitized, and those with multiple pollen allergies. The frequent occurrence of multiple associated sensitivities to grains, legumes, molds, and

A case report on bronchoalveolar carcinoma presenting as non-resolving consolidation.

PubMed

Shoib, Sheikh; Malik, Javid A; Arif, Tasleem; Bashir, Haamid

2012-08-01

Bronchoalveolar carcinoma presenting as non-resolving consolidation is an uncommon presentation. The typical presentation of bronchoalveolar carcinoma is asymptomatic (solitary nodule) and remains without symptoms even as disease disseminates. We report a case of bronchoalveolar carcinoma presenting as non-resolving consolidation in a young male with productive cough, exertional breathlessness and physical examination revealing the features of right lower consolidation on x-ray chest, with subsequent CT of the chest and bronchoscopic examination revealed bronchoalveolar carcinoma. Patient had a good score and was managed conservatively.

Invasive adenocarcinoma with bronchoalveolar features: a population-based evaluation of the extent of resection in bronchoalveolar cell carcinoma.

PubMed

Whitson, Bryan A; Groth, Shawn S; Andrade, Rafael S; Mitiek, Mohi O; Maddaus, Michael A; D'Cunha, Jonathan

2012-03-01

We used a population-based data set to assess the association between the extent of pulmonary resection for bronchoalveolar carcinoma and survival. The reports thus far have been limited to small, institutional series. Using the Surveillance, Epidemiology, and End Results database (1988-2007), we identified patients with bronchoalveolar carcinoma who had undergone wedge resection, segmentectomy, or lobectomy. The bronchoalveolar carcinoma histologic findings were mucinous, nonmucinous, mixed, not otherwise specified, and alveolar carcinoma. To adjust for potential confounders, we used a Cox proportional hazards regression model. A total of 6810 patients met the inclusion criteria. Compared with the sublobar resections (wedge resections and segmentectomies), lobectomy conferred superior 5-year overall (59.5% vs 43.9%) and cancer-specific (67.1% vs 53.1%) survival (P < .0001). After adjusting for potential confounding patient and tumor characteristics, we found that patients who underwent an anatomic resection had significantly better overall (segmentectomy: hazard ratio, 0.59; 95% confidence interval, 0.43-0.81; lobectomy: hazard ratio, 0.50; 95% confidence interval, 0.44-0.57) and cancer-specific (segmentectomy: hazard ratio, 0.51; 95% confidence interval, 0.34-0.75; lobectomy: hazard ratio, 0.46; 95% confidence interval, 0.40-0.53) survival compared with patients who underwent wedge resection. Additionally, gender, race, tumor size, and degree of tumor de-differentiation were negative prognostic factors. Our results were unchanged when we limited our analysis to early-stage disease. Using a population-based data set, we found that anatomic resections for bronchoalveolar carcinoma conferred superior overall and cancer-specific survival rates compared with wedge resection. Bronchoalveolar carcinoma's propensity for intraparenchymal spread might be the underlying biologic basis of our observation of improved survival after anatomic resection. Copyright © 2012

Sudden generalized lung atelectasis during thoracotomy following thoracic lavage in 3 dogs.

PubMed

Drynan, Eleanor; Musk, Gabrielle; Raisis, Anthea

2012-08-01

To describe sudden onset of generalized pulmonary atelectasis following thoracic lavage in 3 dogs. Thoracic lavage was performed following ligation of a patent ductus arteriosus in case 1, prior to closure of a large traumatic full thickness wound in the chest wall in case 2, and during investigation of an idiopathic spontaneous pneumothorax in case 3. In each case anesthesia and surgery were uneventful until thoracic lavage was performed, after which sudden generalized pulmonary atelectasis was observed. The atelectasis was visualized and was associated with oxyhemoglobin desaturation, decreased end-tidal carbon dioxide partial pressure (ETCO(2)), and a marked increase in the peak inspiratory pressure (PIP) required to achieve visible lung inflation. Occlusion of the endotracheal tube and cervical trachea was directly eliminated as the cause of atelectasis in cases 1 and 2, and indirectly eliminated in case 3. Improvement in pulmonary function occurred in all cases in response to increased PIP ± positive end expiratory pressure (PEEP). Generalized atelectasis should be considered a possible complication of thoracic lavage performed during thoracotomy. In the cases presented here, it is suspected that pre-existing reduction in lung volume (due to inadequate ventilation, surgical compression, absorption atelectasis) was exacerbated by the addition of the lavage fluid to the thoracic cavity. This pre-existing lung collapse is believed to have resulted in reduction of lung volume and that further reduction below the critical closing volume occurred following instillation of saline into the thorax resulting in the subsequent development of generalized atelectasis. The performance of regular arterial blood gas analyses and different ventilation protocols may have prevented the marked atelectasis that was observed in these cases. © Veterinary Emergency and Critical Care Society 2012.

Conservative fluid management prevents age-associated ventilator induced mortality.

PubMed

Herbert, Joseph A; Valentine, Michael S; Saravanan, Nivi; Schneck, Matthew B; Pidaparti, Ramana; Fowler, Alpha A; Reynolds, Angela M; Heise, Rebecca L

2016-08-01

Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hospital mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. 2month old and 20month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4h with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. At 4h, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1h in advanced age HVT subjects. In 4h ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in

Conservative Fluid Management Prevents Age-Associated Ventilator Induced Mortality

PubMed Central

Herbert, Joseph A.; Valentine, Michael S.; Saravanan, Nivi; Schneck, Matthew B.; Pidaparti, Ramana; Fowler, Alpha A.; Reynolds, Angela M.; Heise, Rebecca L.

2017-01-01

Background Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hosptial mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. Methods 2 month old and 20 month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4 hours with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. Results At 4hrs, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1hr in advanced age HVT subjects. In 4hr ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in

Repeated measurement of nasal lavage fluid chemokines in school-age children with asthma.

PubMed

Noah, Terry L; Tudor, Gail E; Ivins, Sally S; Murphy, Paula C; Peden, David B; Henderson, Frederick W

2006-02-01

Inflammatory processes at the mucosal surface may play a role in maintenance of asthma pathophysiology. Cross-sectional studies in asthmatic patients suggest that chemokines such as interleukin 8 (IL-8) are overproduced by respiratory epithelium. To test the hypothesis that chemokine levels are persistently elevated in the respiratory secretions of asthmatic children at a stable baseline. We measured nasal lavage fluid (NLF) levels of chemokines and other mediators at 3- to 4-month intervals in a longitudinal study of asthmatic children, with nonasthmatic siblings as controls. In a linear mixed-model analysis, both family and day of visit had significant effects on nasal mediators. Thus, data for 12 asthmatic-nonasthmatic sibling pairs who had 3 or more same-day visits were analyzed separately. For sibling pairs, median eosinophil cationic protein levels derived from serial measurements in NLF were elevated in asthmatic patients compared with nonasthmatic patients, with a near-significant tendency for elevation of total protein and eotaxin levels as well. However, no significant differences were found for IL-8 or several other chemokines. Ratios of IL-13 or IL-5 to interferon-gamma released by house dust mite antigen-stimulated peripheral blood mononuclear cells, tested on a single occasion, were significantly increased for asthmatic patients. Substantial temporal and family-related variability exists in nasal inflammation in asthmatic children. Although higher levels of eosinophil cationic protein are usually present in NLF of patients with stable asthma compared with patients without asthma, chemokines other than eotaxin are not consistently increased. Eosinophil activation at the mucosal surface is a more consistent predictor of asthmatic symptoms than nonspecific elevation of epithelium-derived inflammatory chemokine levels.

IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines.

PubMed

Molet, S; Hamid, Q; Davoine, F; Nutku, E; Taha, R; Pagé, N; Olivenstein, R; Elias, J; Chakir, J

2001-09-01

IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibro-blasts and macrophages for the secretion of GM-CSF, TNF-alpha, IL-1beta, and IL-6. A number of these cytokines are involved in the airway remodeling that is observed within the lungs of asthmatic individuals. In this study, we investigated the expression of IL-17 in sputum and bronchoalveolar lavage specimens obtained from asthmatic subjects and from nonasthmatic control subjects. IL-17 was detected through use of immunocytochemistry, in situ hybridization, and Western blot. Bronchial fibroblasts were stimulated with IL-17, and cytokine production and chemokine production were detected through use of ELISA and RT-PCR. Using immunocytochemistry, we demonstrated that the numbers of cells positive for IL-17 are significantly increased in sputum and bronchoalveolar lavage fluids of subjects with asthma in comparison with control subjects (P <.001 and P <.005, respectively). We demonstrated that in addition to T cells, eosinophils in sputum and bronchoalveolar lavage fluids expressed IL-17. Peripheral blood eosinophils were also positive for IL-17, and the level of IL-17 in eosinophils purified from peripheral blood was significantly higher in subjects with asthma than in controls (P <.01). To further investigate the mechanism of action of IL-17 in vivo, we examined the effect of this cytokine on fibroblasts isolated from bronchial biopsies of asthmatic and nonasthmatic subjects. IL-17 did enhance the production of pro-fibrotic cytokines (IL-6 and IL-11) by fibroblasts, and this was inhibited by dexamethasone. Similarly, IL-17 increased the level of other fibroblast-derived inflammatory mediators, such as the alpha-chemokines, IL-8, and growth-related oncogene-alpha. Our results, which demonstrate for the first time that eosinophils are a potential source of IL-17 within asthmatic airways, suggest that IL-17 might have the potential to amplify inflammatory

Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against Methicillin Resistant Staphylococcus aureus.

PubMed

Kiem, Sungmin; Schentag, Jerome J

2014-12-01

Although antibiotics whose epithelial lining fluid (ELF) concentrations are reported high tend to be preferred in treatment of pneumonia, measurement of ELF concentrations of antibiotics could be misled by contamination from lysis of ELF cells and technical errors of bronchoalveolar lavage (BAL). In this review, ELF concentrations of anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics were interpreted considering above confounding factors. An equation used to explain antibiotic diffusion into CSF (cerebrospinal fluid) was adopted: ELF/free serum concentration ratio = 0.96 + 0.091 × ln (partition coefficient / molecular weight(1/2)). Seven anti-MRSA antibiotics with reported ELF concentrations were fitted to this equation to see if their ELF concentrations were explainable by the penetration capacity only. Then, outliers were modeled under the assumption of varying contamination from lysed ELF cells (test range 0-10% of ELF volume). ELF concentrations of oritavancin, telavancin, tigecycline, and vancomycin were well described by the diffusion equation, with or without additional impact from cell lysis. For modestly high ELF/free serum concentration ratio of linezolid, technical errors of BAL should be excluded. Although teicoplanin and iclaprim showed high ELF/free serum ratios also, their protein binding levels need to be cleared for proper interpretation. At the moment, it appears very premature to use ELF concentrations of anti-MRSA antibiotics as a relevant guide for treatment of lung infections by MRSA.

Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against Methicillin Resistant Staphylococcus aureus

PubMed Central

Schentag, Jerome J

2014-01-01

Although antibiotics whose epithelial lining fluid (ELF) concentrations are reported high tend to be preferred in treatment of pneumonia, measurement of ELF concentrations of antibiotics could be misled by contamination from lysis of ELF cells and technical errors of bronchoalveolar lavage (BAL). In this review, ELF concentrations of anti-methicillin resistant Staphylococcus aureus (MRSA) antibiotics were interpreted considering above confounding factors. An equation used to explain antibiotic diffusion into CSF (cerebrospinal fluid) was adopted: ELF/free serum concentration ratio = 0.96 + 0.091 × ln (partition coefficient / molecular weight1/2). Seven anti-MRSA antibiotics with reported ELF concentrations were fitted to this equation to see if their ELF concentrations were explainable by the penetration capacity only. Then, outliers were modeled under the assumption of varying contamination from lysed ELF cells (test range 0-10% of ELF volume). ELF concentrations of oritavancin, telavancin, tigecycline, and vancomycin were well described by the diffusion equation, with or without additional impact from cell lysis. For modestly high ELF/free serum concentration ratio of linezolid, technical errors of BAL should be excluded. Although teicoplanin and iclaprim showed high ELF/free serum ratios also, their protein binding levels need to be cleared for proper interpretation. At the moment, it appears very premature to use ELF concentrations of anti-MRSA antibiotics as a relevant guide for treatment of lung infections by MRSA. PMID:25566401

The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial.

PubMed

Ronchetti, Katherine; Tame, Jo-Dee; Paisey, Christopher; Thia, Lena P; Doull, Iolo; Howe, Robin; Mahenthiralingam, Eshwar; Forton, Julian T

2018-06-01

Pathogen surveillance is challenging but crucial in children with cystic fibrosis-who are often non-productive of sputum even if actively coughing-because infection and lung disease begin early in life. The role of sputum induction as a diagnostic tool for infection has not previously been systematically addressed in young children with cystic fibrosis. We aimed to assess the pathogen yield from sputum induction compared with that from cough swab and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage. This prospective internally controlled interventional trial was done at the Children's Hospital for Wales (Cardiff, UK) in children with cystic fibrosis aged between 6 months and 18 years. Samples from cough swab, sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage were matched for within-patient comparisons. Primary outcomes were comparative pathogen yield between sputum induction and cough swab for stage 1, and between sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage for stage 2. Data were analysed as per protocol. This study is registered with the UK Clinical Research Network (14615) and with the International Standard Randomised Controlled Trial Network Registry (12473810). Between Jan 23, 2012, and July 4, 2017, 124 patients were prospectively recruited to the trial and had 200 sputum induction procedures for stage 1. 167 (84%) procedures were successful and the procedure was well tolerated. Of the 167 paired samples, 63 (38%) sputum-induction samples were pathogen positive compared with 24 (14%) cough swabs (p<0·0001; odds ratio [OR] 7·5; 95% CI 3·19-17·98). More pathogens were isolated from sputum induction than cough swab (79 [92%] of 86 vs 27 [31%] of 86; p<0·0001). For stage 2, 35 patients had a total of 41 paired sputum-induction and bronchoalveolar lavage procedures. Of the 41 paired samples, 28 (68%) were positive for at least one of the concurrent samples. 39 pathogens were

Ma Huang Tang ameliorates asthma though modulation of Th1/Th2 cytokines and inhibition of Th17 cells in ovalbumin-sensitized mice.

PubMed

Ma, Chun-Hua; Ma, Zhan-Qiang; Fu, Qiang; Ma, Shi-Ping

2014-05-01

Ma Huang Tang (Ephedra decoction, MHT) is a famous classical formula from Shang Han Lun by Zhang Zhongjing in the Han Dynasty. The anti-asthmatic effects of MHT and the possible mechanisms were tested. An asthma model was established by ovalbumin (OVA)-induction in mice. A total of forty-eight mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg·kg(-1)) and MHT (5, 10, and 20 mg·kg(-1)). Airway resistance (Raw) was measured by the forced oscillation technique, histological studies were evaluated by hematoxylin and eosin (HE) staining, Th1/Th2 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA), and Th17 cells were evaluated by flow cytometry (FCM). This study demonstrated that MHT inhibited OVA-induced increases in Raw and eosinophil count; interleukin (IL)-4 and IL-17 levels were recovered in bronchoalveolar lavage fluid, increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that MHT substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry studies demonstrated that MHT substantially inhibited Th17 cells. These findings suggest that MHT may effectively ameliorate the progression of asthma, and could be further investigated for potential use as a therapy for patients with allergic asthma. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Ayanin, a non-selective phosphodiesterase 1-4 inhibitor, effectively suppresses ovalbumin-induced airway hyperresponsiveness without affecting xylazine/ketamine-induced anesthesia.

PubMed

Lee, Fei-Peng; Shih, Chwen-Ming; Shen, Hsin-Yi; Chen, Chien-Ming; Chen, Chi-Ming; Ko, Wun-Chang

2010-06-10

In recent in vitro reports, the IC(50) value of ayanin (quercetin-3,7,4'-O-trimethylether) was 2.2microM for inhibiting interleukin (IL)-4 production from purified basophils, and its therapeutic ratio was >19. Therefore, we were interested in investigating the effects on ovalbumin induced airway hyperresponsiveness in vivo, and to clarify its potential for treating asthma. Ayanin (30-100micromol/kg, orally (p.o.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid of these mice. However, at 100micromol/kg, it significantly enhanced the level of interferon (IFN)-gamma. In addition, ayanin (30-100micromol/kg, p.o.) dose-dependently and significantly suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and bronchoalveolar lavage fluid, and enhanced the IgG(2a) level in serum of these mice. In the present results, ayanin did not affect xylazine/ketamine-induced anesthesia, suggesting that ayanin has few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, the above results suggest that ayanin may have the potential for use in treating allergic asthma.

Inhibition of poly(ADP-ribose) polymerase prevents allergen-induced asthma-like reaction in sensitized Guinea pigs.

PubMed

Suzuki, Ylenia; Masini, Emanuela; Mazzocca, Cosimo; Cuzzocrea, Salvatore; Ciampa, Anna; Suzuki, Hisanori; Bani, Daniele

2004-12-01

Poly(ADP-ribose) polymerase (PARP) plays an important role in tissue injury in conditions associated with oxidative stress and inflammation. Because asthma is a chronic inflammatory disorder of the airways, we designed the present experimental study to evaluate the effects of PARP inhibition on allergen-induced asthma-like reaction in ovalbumin-sensitized guinea pigs. Cough and dyspnea in response to ovalbumin aerosol were absent in naive guinea pigs, whereas they became severe in the sensitized animals. In the latter ones, ovalbumin aerosol also induced a rapid increase in PARP activity, bronchiolar constriction, pulmonary air space inflation, mast cell degranulation, poly(ADP-ribose) and nitrotyrosine immunostaining, myeloperoxidase activity, and malondialdehyde in lung tissue, as well as a rise in the amounts of nitrites and tumor necrosis factor-alpha in bronchoalveolar lavage fluid. Pretreatment with the PARP inhibitors 3-aminobenzamide (10 mg/kg b.wt.) or 5-aminoisoquinolinone (0.5 mg/kg b.wt.) given i.p. 3 h before ovalbumin challenge significantly reduced the severity of cough and the occurrence of dyspnea and delayed the onset of respiratory abnormalities. Both PARP inhibitors were also able to prevent the above morphological and biochemical changes of lung tissue or bronchoalveolar lavage fluid induced by ovalbumin challenge. Conversely, p-aminobenzoic acid, the inactive analog of 3-aminobenzamide, had no effects.

Neurokinin-1 receptor mediates stress-exacerbated allergic airway inflammation and airway hyperresponsiveness in mice.

PubMed

Joachim, Ricarda A; Sagach, Viktoriya; Quarcoo, David; Dinh, Q Thai; Arck, Petra C; Klapp, Burghard F

2004-01-01

A wealth of clinical observation has suggested that stress and asthma morbidity are associated. We have previously established a mouse model of stress-exacerbated allergic airway inflammation, which reflects major clinical findings. The aim of the current study was to investigate the role of the neurokinin- (NK-)1 receptor in the mediation of stress effects in allergic airway inflammation. BALB/c mice were systemically sensitized with ovalbumin (OVA) on assay days 1, 14, and 21 and repeatedly challenged with OVA aerosol on days 26 and 27. Sound stress was applied to the animals for 24 hours, starting with the first airway challenge. Additionally, one group of stressed and one group of nonstressed mice received the highly specific NK-1 receptor antagonist RP 67580. Bronchoalveolar lavage fluid was obtained, and cell numbers and differentiation were determined. Airway hyperreactivity was measured in vitro by electrical field stimulation of tracheal smooth-muscle elements. Application of stress in sensitized and challenged animals resulted in a significant increase in leukocyte number in the bronchoalveolar lavage fluid. Furthermore, stressed animals showed enhanced airway reactivity. The increase of inflammatory cells and airway reactivity was blocked by treatment of animals with the NK-1 receptor antagonist. These data indicate that the NK-1 receptor plays an important role in mediating stress effects in allergen-induced airway inflammation.

Pretreatment with simvastatin reduces lung injury related to intestinal ischemia-reperfusion in rats.

PubMed

Pirat, Arash; Zeyneloglu, Pinar; Aldemir, Derya; Yücel, Muammer; Ozen, Ozlem; Candan, Selim; Arslan, Gülnaz

2006-01-01

In this rat model study we evaluated whether pretreatment with simvastatin affects the severity of acute lung injury caused by intestinal ischemia-reperfusion (I/R). Twenty-four animals were randomly allocated to three equal groups (sham, control, simvastatin). The simvastatin group was pretreated with simvastatin 10 mg x kg(-1) x day(-1) for 3 days, whereas the other groups received placebo. The simvastatin and control groups underwent 60 min of superior mesenteric artery occlusion and 90 min of reperfusion. Compared with the simvastatin group, the control group exhibited significantly more severe intestinal I/R-induced acute lung injury, as indicated by lower Pao2 and oxygen saturation (P = 0.01 and P = 0.005, respectively) and higher mean values for neutrophil infiltration of the lungs (P = 0.003), total lung histopathologic injury score (P = 0.003), lung wet-to-dry weight ratio (P = 0.009), and lung-tissue malondialdehyde levels (P = 0.016). The control and simvastatin groups had similar serum levels and similar bronchoalveolar lavage fluid levels of cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) and P-selectin at all measurements, except for a significantly higher level of bronchoalveolar lavage fluid P-selectin in the control group (P = 0.006). Pretreatment with simvastatin reduces the severity of acute lung injury induced by intestinal I/R in rats.

The Alveolar Microenvironment of Patients Infected with Human Immunodeficiency Virus Does Not Modify Alveolar Macrophage Interactions with Streptococcus pneumoniae

PubMed Central

Jagoe, R. Thomas; Jarman, Elizabeth R.; North, James C.; Pridmore, Alison; Musaya, Janelisa; French, Neil; Zijlstra, Eduard E.; Molyneux, Malcolm E.; Read, Robert C.

2013-01-01

We tested the hypothesis that HIV infection results in activation of alveolar macrophages and that this might be associated with impaired defense against pneumococcus. We compared alveolar macrophages and lymphocytes in 131 bronchoalveolar lavage samples from HIV-infected and healthy controls using inflammatory gene microarrays, flow cytometry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA) to determine the pattern of macrophage activation associated with HIV infection and the effect of this activation on defense against pneumococcus. We used gamma interferon (IFN-γ) priming to mimic the cellular milieu in HIV-infected lungs. InnateDB and BioLayout 3D were used to analyze the interactions of the upregulated genes. Alveolar macrophages from HIV-infected adults showed increased gene expression and cytokine production in a classical pattern. Bronchoalveolar lavage from HIV-infected subjects showed excess CD8+ lymphocytes with activated phenotype. Toll-like receptor 4 (TLR4) expression was increased in macrophages from HIV-infected subjects, but function was similar between the groups; lung lavage fluid did not inhibit TLR function in transfected HeLa cells. Alveolar macrophages from HIV-infected subjects showed normal binding and internalization of opsonized pneumococci, with or without IFN-γ priming. Alveolar macrophages from HIV-infected subjects showed classical activation compared to that of healthy controls, but this does not alter macrophage interactions with pneumococci. PMID:23576675

Gastric Lavage in Acute Organophosphorus Pesticide poisoning (GLAOP) – a randomised controlled trial of multiple vs. single gastric lavage in unselected acute organophosphorus pesticide poisoning

PubMed Central

Li, Yi; Yu, XueZhong; Wang, Zhong; Wang, HouLi; Zhao, XiangHuai; Cao, YuPing; Wang, WeiZhan; Eddleston, Michael

2006-01-01

Background Organophosphorus (OP) pesticide poisoning is the most common form of pesticide poisoning in many Asian countries. Guidelines in western countries for management of poisoning indicate that gastric lavage should be performed only if two criteria are met: within one hour of poison ingestion and substantial ingested amount. But the evidence on which these guidelines are based is from medicine overdoses in developed countries and may be irrelevant to OP poisoning in Asia. Chinese clinical experience suggests that OP remains in the stomach for several hours or even days after ingestion. Thus, there may be reasons for doing single or multiple gastric lavages for OP poisoning. There have been no randomised controlled trials (RCTs) to assess this practice of multiple lavages. Since it is currently standard therapy in China, we cannot perform a RCT of no lavage vs. a single lavage vs. multiple lavages. We will compare a single gastric lavage with three gastric lavages as the first stage to assess the role of gastric lavage in OP poisoning. Methods/Design We have designed an RCT assessing the effectiveness of multiple gastric lavages in adult OP self-poisoning patients admitted to three Chinese hospitals within 12 hrs of ingestion. Patients will be randomised to standard treatment plus either a single gastric lavage on admission or three gastric lavages at four hour intervals. The primary outcome is in-hospital mortality. Analysis will be on an intention-to-treat basis. On the basis of the historical incidence of OP at the study sites, we expect to enroll 908 patients over three years. This projected sample size provides sufficient power to evaluate the death rate; and a variety of other exposure and outcome variables, including particular OPs and ingestion time. Changes of OP level will be analyzed in order to provide some toxic kinetic data. Discussion the GLAOP study is a novel, prospective cohort study that will explore to the toxic kinetics of OP and effects

The expediency of peritoneal lavage for blunt trauma in children.

PubMed

Drew, R; Perry, J F; Fischer, R P

1977-12-01

Two hundred and thirty children, ten years of age or younger, suspected of having blunt abdominal injuries underwent diagnostic peritoneal lavage. Peritoneal lavage was 99.1 per cent accurate in determining the presence or absence of abdominal injuries. One patient had a false-positive peritoneal lavage. Sixty-nine of the 70 patients with blunt abdominal injuries, who underwent peritoneal lavage, had a positive peritoneal lavage; one patient had a false-negative peritoneal levage. Ninety-one per cent of the positive peritoneal lavages were grossly positive for hemoperitoneum. All 11 children with extraperitoneal abdominal injuries had positive peritoneal lavages from associated intraperitoneal injeries. The mortality for children with blunt abdominal injuries was 19.4 per cent. Intra-abdominal injuries were solely responsible for 29 per cent of the deaths and were a major contributing factor in an additional 21 per cent of the deaths. The routine use of diagnostic peritoneal lavage during the initial evaluation of blunt abdominal trauma was, in large part, responsible for the rapid, definitive treatment which -he children with abdominal injuries received. Sixty-five per cent of the children underwent exploratory laparotomy within one hour of admission to the hospital.

Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival.

PubMed

Okubo, K; Mark, E J; Flieder, D; Wain, J C; Wright, C D; Moncure, A C; Grillo, H C; Mathisen, D J

1999-10-01

The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed. We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed. Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P <.0001). Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P =.006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P =.003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection. Mitosis or nuclear grade of tumor cells did not correlate with survival. Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures. Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival.

A quantitative PCR method for assessing the presence of Pasteurella testudinis DNA in nasal lavage samples from the desert tortoise (Gopherus agassizii).

PubMed

duPre', S A; Tracy, C R; Sandmeier, F C; Hunter, K W

2012-12-01

Pasteurella testudinis has been associated with upper respiratory tract disease (URTD) in the threatened desert tortoise (Gopherus agassizii). Our goal was to develop a sensitive and specific qPCR method for detecting DNA from P. testudinis in nasal lavage fluid collected from desert tortoises in the field. Probes for 16S ribosomal RNA and RNA polymerase β-subunit (rpoB) genes were designed. A standard curve generated with DNA extracted from known numbers of bacterial cells determined by flow cytometry revealed a lower detection limit of 50 fg/ml (10 bacteria/ml). The nasal lavage fluid contained no interfering substances, and the qPCR method did not recognize normal flora DNA. The nasal lavage samples from 20 desert tortoises captured in Clark County, Nevada, USA in 2007 and housed at the Desert Tortoise Conservation Center, were all positive for P. testudinis DNA by qPCR. Another set of 19 lavage samples collected in 2010 from wild desert tortoises in the Mojave Desert were tested and 84% were positive for P. testudinis DNA. Fully validated, this qPCR method will provide a means of determining colonization rate. When used in conjunction with serological methods and clinical evaluations, both infection rate and disease rate can be determined for this potential URTD pathogen. This new assay provides an important tool for managing the threatened populations of the Mojave Desert tortoise. Copyright © 2012 Elsevier B.V. All rights reserved.

Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients.

PubMed Central

Muller-Serieys, C; Bancal, C; Dombret, M C; Soler, P; Murciano, G; Aubier, M; Bergogne-Berezin, E

1992-01-01

The pulmonary disposition of cefpodoxime was studied in 12 patients with pulmonary opacities after a single oral dose of 260 mg of cefpodoxime-proxetil, which is equivalent to 200 mg of cefpodoxime. Blood and lung tissue samples were collected during surgery, and bronchoalveolar lavage was carried out 3 h (group A) or 6 h (group B) after drug administration. Urea was used as an endogenous marker for measurement of the volume of epithelial lining fluid (ELF). Concentrations were measured by using a microbiological assay. The mean concentrations of cefpodoxime in plasma, ELF, and lung tissue were, respectively, 1.85 +/- 0.82 mg/liter, 0.22 +/- 0.13 mg/liter, and 0.89 +/- 0.80 mg/kg of body weight in group A and 1.40 +/- 1.25 mg/liter, 0.12 +/- 0.14 mg/liter, and 0.84 +/- 0.61 mg/kg in group B. Concentrations in lung parenchyma 6 h after dosing were at least equal to or above the MICs for 90% of the strains of most organisms commonly found in respiratory tract infections, whereas data for ELF suggest levels of drug insufficient to inhibit bacteria. PMID:1444291

Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust.

PubMed

Rom, William N; Weiden, Michael; Garcia, Roberto; Yie, Ting An; Vathesatogkit, Pratan; Tse, Doris B; McGuinness, Georgeann; Roggli, Victor; Prezant, David

2002-09-15

We report a sentinel case of acute eosinophilic pneumonia in a firefighter exposed to high concentrations of World Trade Center dust during the rescue effort from September 11 to 24. The firefighter presented with a Pa(O2) of 53 mm Hg and responded to oxygen and corticosteroids. Computed tomography scan showed patchy ground glass density, thickened bronchial walls, and bilateral pleural effusions. Bronchoalveolar lavage recovered 70% eosinophils, with only 1% eosinophils in peripheral blood. Eosinophils were not degranulated and increased levels of interleukin-5 were measured in bronchoalveolar lavage and serum. Mineralogic analysis counted 305 commercial asbestos fibers/10(6) macrophages including those with high aspect ratios, and significant quantities of fly ash and degraded fibrous glass. Acute eosinophilic pneumonia is a rare consequence of acute high dust exposure. World Trade Center dust consists of large particle-size silicates, but fly ash and asbestos fibers may be found in bronchoalveolar lavage cells.

Synchronous B3 thymoma and lung bronchoalveolar carcinoma.

PubMed

Patella, Miriam; Anile, Marco; Vitolo, Domenico; Venuta, Federico

2011-01-01

The association between thymic tumors and other intrathoracic or extrathoracic neoplasms is relatively rare; the synchronous occurrence of thymoma and bronchoalveolar carcinoma of the lung has never been described so far. A huge B3 cystic thymoma was found at thoracotomy to be associated with stage IV bronchoalveolar carcinoma (intraparenchymal and pleural metastases). The thymic tumor was completely resected; lung cancer was biopsied only for diagnosis and staging purposes. After an uneventful postoperative course the patient underwent chemotherapy; she is still alive and well one year after surgery.

Peroperative Gastrograffin bowel lavage in gastroschisis.

PubMed

Cherian, Abraham; Hallows, Ruth M; Singh, Shalinder J; McCallion, William A; Stewart, Richard J

2006-10-01

The aim of the study was to evaluate potential benefits in the use of peroperative bowel lavage with Gastrograffin in neonates with gastroschisis. A retrospective analysis of newborns with gastroschisis was performed over a 10-year period in 2 centers in the United Kingdom. Two groups were studied wherein one had peroperative bowel lavage with Gastrograffin and the other did not. Data were collected on 116 patients of whom 93 were suitable for analysis. There were no statistically significant differences in primary closure rate, duration of ventilation, parenteral nutrition, or hospital stay. Intestinal obstruction occurred more frequently in the nonlavage group. Gastrograffin lavage peroperatively in gastroschisis offers no potential advantage in reducing ventilatory requirements, parenteral nutrition, and hospital stay. It also does not achieve greater primary closure rates, but may reduce the incidence of intestinal obstruction.

[Expression of vascular endothelial growth factor and its significance in pulmonary bronchoalveolar carcinoma].

PubMed

Song, Weian; Li, Hui; Wang, Huasheng; Zhang, Weidong; Zhao, Xiaogang

2004-02-20

To study the relationship between the vascular endothelial growth factor (VEGF) and the clinicopathological characteristics of the patients with pulmonary bronchoalveolar carcinoma, and to research the possible role of VEGF in the malignant growth of pulmonary bronchoalveolar carcinoma. The expression of VEGF and MVD were detected in 38 pulmonary bronchoalveolar carcinoma and 20 normal lung tissues by immunohistochemical method. The positive rate of VEGF expression (73.68%,28/38) and MVD (63.81±19.26) in pulmonary bronchoalveolar carcinoma tissues were both remarkably higher than those in normal lung tissues (0, 18.44±6.53)( P < 0.005,P < 0.001). The positive rate of VEGF expression was significantly related to the size of tumor ( P < 0.05), lymphatic metastasis ( P < 0.025) and TNM stage ( P < 0.05), and so did the MVD ( P < 0.05, P < 0.05, P < 0.05). MVD was remarkably higher in VEGF (+) carcinoma tissues than that in VEGF (-) carcinoma tissues ( P < 0.05). VEGF correlates with the clinicopathological characteristics of pulmonary bronchoalveolar carcinoma. It may play an important role in the development of pulmonary bronchoalveolar carcinoma.

[Application of continuous intra-arterial blood gas monitoring system "Paratrend 7" for pulmonary lavage of a patient with alveolar proteinosis].

PubMed

Harigae, M; Hirose, Y; Gamo, M; Hirose, M; Fujiwara, C; Matsuo, K

1999-03-01

We applied a continuous intra-arterial blood gas monitoring system (Paratrend 7) to a patient with pulmonary alveolar proteinosis during pulmonary lavage. Lavage was performed under general anesthesia with one lung ventilation. We inserted the sensor of Patatrend 7 through a 20 G catheter into the radial artery, and monitored pH, PaCO2 and PaO2 continuously throughout the procedure. SpO2 and EtCO2 were also monitored. Saline 1000-1500 ml was instilled and drained repeatedly by volume limited methods. PaO2 values by Paratrend 7 increased during instillation and decreased during drainage of the irrigating fluid. In contrast, PaCO2 value by Paratrend 7 decreased slightly during instillation and increased during drainage. The change of SpO2 was almost the same as that by Paratrend 7, but the response time of pulse oxymetry was a little quicker than Paratrend 7. During the lavage procedure, respiratory and circulatory condition changed very rapidly, and it is necessary to monitor blood gas change intensively. Paratrend 7 is useful as a perioperative monitoring system, but pulse oxymetry might be sufficient during pulmonary lavage considering its cost.

G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production.

PubMed

Queto, Túlio; Vasconcelos, Zilton F M; Luz, Ricardo Alves; Anselmo, Carina; Guiné, Ana Amélia A; e Silva, Patricia Machado R; Farache, Júlia; Cunha, José Marcos T; Bonomo, Adriana C; Gaspar-Elsas, Maria Ignez C; Xavier-Elsas, Pedro

2011-05-09

Granulocyte Colony-Stimulating Factor (G-CSF), which mobilizes hemopoietic stem cells (HSC), is believed to protect HSC graft recipients from graft-versus-host disease by enhancing Th2 cytokine secretion. Accordingly, G-CSF should aggravate Th2-dependent allergic pulmonary inflammation and the associated eosinophilia. We evaluated the effects of G-CSF in a model of allergic pulmonary inflammation. Allergic pulmonary inflammation was induced by repeated aerosol allergen challenge in ovalbumin-sensitized C57BL/6J mice. The effects of allergen challenge and of G-CSF pretreatment were evaluated by monitoring: a) eosinophilia and cytokine/chemokine content of bronchoalveolar lavage fluid, pulmonary interstitium, and blood; b) changes in airway resistance; and c) changes in bone-marrow eosinophil production. Contrary to expectations, G-CSF pretreatment neither induced nor enhanced allergic pulmonary inflammation. Instead, G-CSF: a) suppressed accumulation of infiltrating eosinophils in bronchoalveolar, peribronchial and perivascular spaces of challenged lungs; and b) prevented ovalbumin challenge-induced rises in airway resistance. G-CSF had multiple regulatory effects on cytokine and chemokine production: in bronchoalveolar lavage fluid, levels of IL-1 and IL-12 (p40), eotaxin and MIP-1a were decreased; in plasma, KC, a neutrophil chemoattractant, was increased, while IL-5 was decreased and eotaxin was unaffected. In bone-marrow, G-CSF: a) prevented the increase in bone-marrow eosinophil production induced by ovalbumin challenge of sensitized mice; and b) selectively stimulated neutrophil colony formation. These observations challenge the view that G-CSF deviates cytokine production towards a Th2 profile in vivo, and suggest that this neutrophil-selective hemopoietin affects eosinophilic inflammation by a combination of effects on lung cytokine production and bone-marrow hemopoiesis. Copyright © 2011 Elsevier Inc. All rights reserved.

IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema.

PubMed

Fujii, Utako; Miyahara, Nobuaki; Taniguchi, Akihiko; Waseda, Koichi; Morichika, Daisuke; Kurimoto, Etsuko; Koga, Hikari; Kataoka, Mikio; Gelfand, Erwin W; Cua, Daniel J; Yoshimura, Akihiko; Tanimoto, Mitsune; Kanehiro, Arihiko

2016-11-01

We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23 -/- ) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23 -/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid of WT mice was attenuated in IL-23 -/- mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.

Short term inhalation toxicity of a liquid aerosol of glutaraldehyde-coated CdS/Cd(OH)2 core shell quantum dots in rats.

PubMed

Ma-Hock, L; Farias, P M A; Hofmann, T; Andrade, A C D S; Silva, J N; Arnaud, T M S; Wohlleben, W; Strauss, V; Treumann, S; Chaves, C R; Gröters, S; Landsiedel, R; van Ravenzwaay, B

2014-02-10

Quantum dots exhibit extraordinary optical and mechanical properties, and the number of their applications is increasing. In order to investigate a possible effect of coating on the inhalation toxicity of previously tested non-coated CdS/Cd(OH)2 quantum dots and translocation of these very small particles from the lungs, rats were exposed to coated quantum dots or CdCl2 aerosol (since Cd(2+) was present as impurity), 6h/d for 5 consecutive days. Cd content was determined in organs and excreta after the end of exposure and three weeks thereafter. Toxicity was determined by examination of broncho-alveolar lavage fluid and microscopic evaluation of the entire respiratory tract. There was no evidence for translocation of particles from the respiratory tract. Evidence of a minimal inflammatory process was observed by examination of broncho-alveolar lavage fluid. Microscopically, minimal to mild epithelial alteration was seen in the larynx. The effects observed with coated quantum dots, non-coated quantum dots and CdCl2 were comparable, indicating that quantum dots elicited no significant effects beyond the toxicity of the Cd(2+) ion itself. Compared to other compounds with larger particle size tested at similarly low concentrations, quantum dots caused much less pronounced toxicological effects. Therefore, the present data show that small particle sizes with corresponding high surfaces are not the only factor triggering the toxic response or translocation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Decreased sialidase activity in alveolar macrophages of guinea pigs exposed to coal mine dust.

PubMed Central

Terzidis-Trabelsi, H; Lefèvre, J P; Bignon, J; Lambré, C R

1992-01-01

The origin of immune dysfunctions that are observed in pneumoconiotic miners still remains unknown. There is evidence that the carbohydrate moiety of membrane glycoconjugates is of primary importance in many functions of immunocompetent cells. The glycosylation, and especially the sialylation level of membrane components of various lymphocyte and macrophage subsets, vary depending on the state of cellular differentiation and activation. Sialidases, which may regulate the amount of sialic acids exposed on the cell membrane, can thus be considered as immunoregulatory enzymes. In this report, the sialidase activity has been measured in alveolar macrophages (AM) and in cell-free bronchoalveolar lavage fluid (BALF) from guinea pigs exposed for 4 months to coal mine dust at a concentration of 300 mg/m3. The samples were collected by bronchoalveolar lavage 2 months after cessation of exposure. The sialidase activity in the cell-free fluid and in the purified alveolar macrophages showed a 10-fold decrease (p less than 0.001). Kinetic parameters of the enzyme such as Km and optimum pH did not change. This changed activity was specific for sialidase, as two other lysosomal glycosidases, beta-galactosidase and N-acetylglucosaminidase, showed unchanged activities. These results suggest the possibility that, by inducing a decreased sialidase activity, exposure to coal mine dust may lead to a modified expression of AM membrane-associated sialic acids giving rise to altered immune functions (i. e., phagocytosis, antigen processing, response to cytokines, etc.). PMID:1396442

Effect of treatment with geraniol on ovalbumin-induced allergic asthma in mice.

PubMed

Xue, Zheng; Zhang, Xin-Guang; Wu, Jie; Xu, Wan-Chao; Li, Li-Qing; Liu, Fei; Yu, Jian-Er

2016-06-01

Asthma, a complex highly prevalent airway disease, is a major public health problem for which current treatment options are inadequate. To evaluate the antiasthma activity of geraniol and investigate its underlying molecular mechanisms. In a standard experimental asthma model, Balb/c mice were sensitized with ovalbumin, treated with geraniol (100 or 200 mg/kg) or a vehicle control, during ovalbumin challenge. Treatment of ovalbumin-sensitized/challenged mice with geraniol significantly decreased airway hyperresponsiveness to inhaled methacholine. Geraniol treatment reduced eotaxin levels in bronchoalveolar lavage fluid and attenuated infiltration of eosinophils induced by ovalbumin. Geraniol treatment reduced TH2 cytokines (including interleukins 4, 5, and 13), increased TH1 cytokine interferon γ in bronchoalveolar lavage fluid, and reduced ovalbumin-specific IgE in serum. In addition, treatment of ovalbumin-sensitized/challenged mice with geraniol enhanced T-bet (TH1 response) messenger RNA expression and reduced GATA-3 (TH2 response) messenger RNA expression in lungs. Furthermore, treatment of ovalbumin -sensitized/challenged mice with geraniol further enhanced Nrf2 protein expression and activated Nrf2-directed antioxidant pathways, such as glutamate-cysteine ligase, superoxide dismutase, and glutathione S-transferase, and enhanced formation of reduced glutathione and reduced formation of malondialdehyde in lungs. Geraniol attenuated important features of allergic asthma in mice, possibly through the modulation of TH1/TH2 balance and activation the of Nrf2/antioxidant response element pathway. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Markers of cartilage and synovial metabolism in joint fluid and serum of patients with chondromalacia of the patella.

PubMed

Väätäinen, U; Lohmander, L S; Thonar, E; Hongisto, T; Agren, U; Rönkkö, S; Jaroma, H; Kosma, V M; Tammi, M; Kiviranta, I

1998-03-01

To further our understanding of the pathogenesis of chondromalacia of the patella (CM), we have studied the release into knee joint fluid and serum, obtained from patients with CM, of molecules associated with the metabolism of joint cartilage matrix and synovium. Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), stromelysin-1 (MMP-3), interstitial collagenase (MMP-1), tissue inhibitor for metalloproteinases-1 (TIMP-1), phospholipase activity A2 (PLA2), hyaluronan (HA), aggrecan fragments (AGN) and antigenic keratan sulfate (KS) were quantified in knee joint lavage fluid from 96 patients with CM; KS and HA also was measured in serum. Chondromalacia was graded on a scale of I to IV according to Outerbridge (1961). The histopathology of the synovial membrane close to the patellofemoral joint was evaluated. Control samples were obtained from nine patients with knee pain presenting with arthroscopically normal knee joints. The concentrations of MMP-3, MMP-1 and TIMP-1 proteins in joint lavage fluid were increased in advanced (grade IV) CM, compared with controls. Levels of MMP-1 in lavage fluid correlated with the severity of CM (r = 0.38, P < 0.01) and MMP-1 and MMP-3 concentrations correlated with each other (r = 0.45, P < 0.001). TIMP-1 was elevated in grade IV CM compared with grades II and III CM (P < 0.02, P < 0.01). Interleukins (IL-1 alpha, IL-1 beta and IL-6) showed no significant change in CM. The lavage fluid level of PLA2 increased with the severity of CM (r = 0.40, P < 0.001). Serum KS was higher in CM IV than in controls (P = 0.05), while lavage fluid KS concentration was elevated in CM I (P = 0.04). There were no differences in the lavage fluid levels of AGN and HA between the different study groups. Synovium showed slight or moderate histological signs of inflammation in 9% of CM patients. The changes in the release and activity of these marker molecules from serum and synovial fluid may reflect changes in the

The effects of physical exercise and smoking habits on the expression of SPLUNC1 in nasal lavage fluids from allergic rhinitis subjects.

PubMed

Irander, K; Borres, M P; Ghafouri, B

2014-04-01

Palate lung nasal epithelial clone (PLUNC) is a family of proteins, which are proposed to participate in the innate immune defense against infections in the upper aero-digestive tract. The aim of this study was to investigate the expression of SPLUNC1 in allergic rhinitis subjects with considerations taken to the mucosal function and smoking habits. The participants, recruited from a cohort followed from infancy, were re-examined at the age of 18 years regarding allergy development. Based on medical histories and skin prick tests the participants were classified into groups with persistent allergic rhinitis (n=18), intermittent allergic rhinitis (n = 8) and healthy controls (n = 13). Seven subjects (3, 2 and 2 in each group, respectively) reported smoking habits. The SPLUNC1 levels in nasal lavage fluids were analyzed by Western blot. Changes in the volume of the proper nasal cavity before and after physical exercise (Vol2(increase)) were analyzed by acoustic rhinometry. Compared to the control group the SPLUNC1 level was significantly lower in the persistent allergy group (3.8 ± 3.4 OD vs. 1.3 ± 1.5 OD; p = 0.02), but not in the intermittent allergy group without current exposure to allergens (3.6 ± 4.7 OD). No differences were found in Vol2(increase) between any of the allergy groups and controls. In smokers Vol2(increase) was significantly reduced (p < 0.01) and the SPLUNC1 levels were lower compared to non-smokers. A significant correlation was found between SPLUNC1 and Vol2(increase) (p < 0.01; r = 0.53) in non-smokers. Current allergen exposure has an impact on SPLUNC1 expression in nasal lavage fluid, why allergy ought to be considered in study populations where analyses of SPLUNC1 levels are included in the reports. The normal nasal decongestion after exercise was not affected by allergy in contrast to smoking habits. The correlation between SPLUNC1 levels and Vol2(increase) in non-smokers may indicate involvement of SPLUNC1in the regulation of the

Diffuse Alveolar Hemorrhage Induced by Irinotecan for a Patient with Metastatic Thymic Carcinoma: A Case Report and Literature Review.

PubMed

Kim, Sung-Ho; Minami, Seigo; Ogata, Yoshitaka; Yamamoto, Suguru; Komuta, Kiyoshi

2017-01-01

We herein report a 73-year-old Japanese woman with metastatic thymic carcinoma who developed diffuse alveolar hemorrhage (DAH) during irinotecan chemotherapy. She presented with a mild fever and exertional dyspnea after the second cycle of weekly irinotecan monotherapy. Chest images showed diffuse ground-glass opacities. The diagnosis of DAH was based on the findings of the bronchoalveolar lavage fluid, which was bloody and contained hemosiderin-laden macrophages. The discontinuation of irinotecan and introduction of oral prednisolone improved her symptoms and chest abnormal shadows. This is the first case of DAH caused by irinotecan.

The utility of ductal lavage in breast cancer detection and risk assessment

PubMed Central

Domchek, Susan M

2002-01-01

Ductal lavage (DL) permits noninvasive retrieval of epithelial cells from the breast. Clinical development of this technique has been fueled largely by its potential, as yet unproven, to improve detection of breast cancer and definition of individual risk for development of breast cancer. Early studies demonstrate the feasibility of performing this technique, provide data on cellular yield and findings, and demonstrate the ability to measure molecular markers in DL fluid. However, the sensitivity and specificity of DL for the detection of breast cancer remains unknown, as does the significance of atypia, particularly mild atypia, when found in DL fluid. Although DL appears safe and the device is approved by the US Food and Drug Administration, DL is still best utilized in the setting of clinical trials designed to resolve issues of sensitivity, specificity, and localization. PMID:11879562

[Pre-analytical quality in fluid samples cytopathology: Results of a survey from the French Society of Clinical Cytology].

PubMed

Courtade-Saïdi, Monique; Fleury Feith, Jocelyne

2015-10-01

The pre-analytical step includes sample collection, preparation, transportation and storage in the pathology unit where the diagnosis is performed. The pathologist ensures that pre-analytical conditions are in line with expectations. The lack of standardization for handling cytological samples makes this pre-analytical step difficult to harmonize. Moreover, this step depends on the nature of the sample: fresh liquid or fixed material, air-dried smears, liquid-based cytology. The aim of the study was to review the different practices in French structures of pathology on the pre-analytical phase concerning cytological fluids such as broncho-alveolar lavage (BALF), serous fluids and urine. A survey was conducted on the basis of the pre-analytical chapter of the ISO 15189 and sent to 191 French pathological structures (105 public and 86 private). Fifty-six laboratories replied to the survey. Ninety-five per cent have a computerized management system and 70% a manual on sample handling. The general instructions requested for the patients and sample identification were highly correctly filled with a short time routing and additional tests prescription. By contrast, information are variable concerning the clinical information requested and the type of tubes for collecting fluids and the volumes required as well as the actions taken in case of non-conformity. For the specific items concerning BALF, serous fluids and urine, this survey has shown a great heterogeneity according to sample collection, fixation and of clinical information. This survey demonstrates that the pre-analytical quality for BALF, serous fluids and urine is not optimal and that some corrections of the practices are recommended with a standardization of numerous steps in order to increase the reproducibility of additional tests such as immunocytochemistry, cytogenetic and molecular biology. Some recommendations have been written. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Methylene blue attenuates ischemia--reperfusion injury in lung transplantation.

PubMed

Abreu, Marcus da Matta; Pazetti, Rogerio; Almeida, Francine Maria de; Correia, Aristides Tadeu; Parra, Edwin Roger; Silva, Laís Pereira da; Vieira, Rodolfo de Paula; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli

2014-12-01

Ischemia-reperfusion injury (IRI) is one of the principal obstacles for the lung transplantation (LTx) success. Several strategies have been adopted to minimize the effects of IRI in lungs, including ex vivo conditioning of the grafts and the use of antioxidant drugs, such as methylene blue (MB). We hypothesized that MB could minimize the effects of IRI in a LTx rodent model. Forty rats were divided into four groups (n = 10) according to treatment (saline solution or MB) and graft cold ischemic time (3 or 6 h). All animals underwent unilateral LTx. Recipients received 2 mL of saline or MB intraperitoneally before transplantation. After 2 h of reperfusion, arterial blood and exhaled nitric oxide samples were collected and bronchoalveolar lavage performed. Then animals were euthanized, and histopathology analysis as well as cell counts and cytokine levels measurements in bronchoalveolar lavage fluid were performed. There was a significant decrease in exhaled nitric oxide, neutrophils, interleukin-6, and tumor necrosis factor-α in MB-treated animals. PaO2 and uric acid levels were higher in MB group. MB was able in attenuating IRI in this LTx model. Copyright © 2014 Elsevier Inc. All rights reserved.

Randomized clinical trial of peritoneal lavage for preventing surgical site infection in elective liver surgery.

PubMed

Tanaka, Kuniya; Matsuo, Kenichi; Kawaguchi, Daisuke; Murakami, Takashi; Hiroshima, Yukihiko; Hirano, Atsushi; Sato, Sho; Endo, Itaru; Taguri, Masataka; Koda, Keiji

2015-06-01

Although intraoperative peritoneal lavage is often performed routinely with the aim of reducing peritoneal contamination, little evidence of lavage benefits in elective liver resection without bile duct resection is available. We addressed the issue with a randomized clinical trial. We prospectively and randomly assigned consecutive patients undergoing liver resection to a lavage group or a non-lavage group. Peritoneal lavage was performed at the end of operation for patients in the lavage group. The primary endpoint was the rate of surgical site infection. Ninety-six patients were assigned to the lavage group and 97 to the non-lavage group. When superficial/deep incisional infection and organ/space infection were considered together, no significant difference in surgical site infection rate was evident between lavage (21.9%) and non-lavage groups (13.4%, P = 0.135). However, organ/space infection was significantly more frequent in the lavage group (16.7%) than the non-lavage group (7.2%, P = 0.048). Peritoneal lavage was identified as a risk factor for organ/space infection by multivariate analysis (relative risk, 2.977; confidence interval, 1.094 to 8.100; P = 0.033). Intraoperative peritoneal lavage does not reduce overall incidence of surgical site infection and may increase risk of organ/space infection. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

[Establishment and evaluation of extracorporeal circulation model in rats].

PubMed

Xie, Xiao-Jun; Tao, Kai-Yu; Tang, Meng-Lin; Du, Lei; An, Qi; Lin, Ke; Gan, Chang-Ping; Chen, You-Wen; Luo, Shu-Hua

2012-09-01

To establish an extracorporeal circulation (ECC) rat model, and evaluate the inflammatory response and organ injury induced in the model. SD rats were anesthetized and cannulated from right common carotid artery to left femoral vein to establish the bypass of extracorporeal circulation. Then the rats were randomly divided into ECC group and sham group. The rats in ECC group were subjected to extracorporeal circulation for 2 hours and then rest for 2 hours, while the rats in sham group were only observed for 4 hours without extracorporeal circulation. After that, blood routine examination, blood gas analysis, the measurement of pro-inflammatory factors in bronchoalveolar lavage fluid and lung tissue were performed to evaluate the lung injury induced by ECC. Circulating endothelial cells were also calculated by flow cytometry to assess the vascular endothelial injury. At 2 hours after ECC, red blood cell counts in both groups kept normal, while leukocyte and neutrophil counts, plasmatic tumor necrosis factor-a level and neutrophil elastase level, circulating endothelial cells in the rats of ECC group were significantly higher than those in sham group. Tumor necrosis factor-alpha in bronchoalveolar lavage fluid and water content in lung of the ECC rats were also significantly higher, while the oxygenation index was significantly lower. Neutrophil infiltration was also observed in lung tissues with increased thickness of alveolar membrane in ECC group. The ECC model established from right common carotid artery to left femoral vein in our study can successfully induce systemic inflammatory response, and acute lung injury associated with inflammation.

Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB.

PubMed

Goh, Fera Y; Upton, Nadine; Guan, Shouping; Cheng, Chang; Shanmugam, Muthu K; Sethi, Gautam; Leung, Bernard P; Wong, W S Fred

2012-03-15

Persistent activation of nuclear factor-κB (NF-κB) has been associated with the development of asthma. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring bioactive flavonol, has been shown to inhibit NF-κB activity. We hypothesized that fisetin may attenuate allergic asthma via negative regulation of the NF-κB activity. Female BALB/c mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Fisetin dose-dependently inhibited ovalbumin-induced increases in total cell count, eosinophil count, and IL-4, IL-5 and IL-13 levels recovered in bronchoalveolar lavage fluid. It attenuated ovalbumin-induced lung tissue eosinophilia and airway mucus production, mRNA expression of adhesion molecules, chitinase, IL-17, IL-33, Muc5ac and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. Fisetin blocked NF-κB subunit p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of ovalbumin-challenged mice. In normal human bronchial epithelial cells, fisetin repressed TNF-α-induced NF-κB-dependent reporter gene expression. Our findings implicate a potential therapeutic value of fisetin in the treatment of asthma through negative regulation of NF-κB pathway. Copyright © 2012 Elsevier B.V. All rights reserved.

Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation.

PubMed

Sayah, David M; Mallavia, Beñat; Liu, Fengchun; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; DerHovanessian, Ariss; Ross, David J; Lynch, Joseph P; Saggar, Rajan; Ardehali, Abbas; Ware, Lorraine B; Christie, Jason D; Belperio, John A; Looney, Mark R

2015-02-15

Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, although both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. To study NETs in experimental models of PGD and in lung transplant patients. Two experimental murine PGD models were studied: hilar clamp and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with DNaseI. NETs were also measured in bronchoalveolar lavage fluid and plasma from lung transplant patients with and without PGD. NETs were increased after either hilar clamp or OLT-PCI compared with surgical control subjects. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury, and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In bronchoalveolar lavage fluid from human lung transplant recipients, NETs were more abundant in patients with PGD. NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD.

Neutrophil Extracellular Traps Are Pathogenic in Primary Graft Dysfunction after Lung Transplantation

PubMed Central

Mallavia, Beñat; Liu, Fengchun; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; DerHovanessian, Ariss; Ross, David J.; Lynch III, Joseph P.; Saggar, Rajan; Ardehali, Abbas; Ware, Lorraine B.; Christie, Jason D.; Belperio, John A.; Looney, Mark R.

2015-01-01

Rationale: Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, although both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. Objectives: To study NETs in experimental models of PGD and in lung transplant patients. Methods: Two experimental murine PGD models were studied: hilar clamp and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with DNaseI. NETs were also measured in bronchoalveolar lavage fluid and plasma from lung transplant patients with and without PGD. Measurements and Main Results: NETs were increased after either hilar clamp or OLT-PCI compared with surgical control subjects. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury, and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In bronchoalveolar lavage fluid from human lung transplant recipients, NETs were more abundant in patients with PGD. Conclusions: NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD. PMID:25485813

PKCλ/ι regulates Th17 differentiation and house dust mite-induced allergic airway inflammation.

PubMed

Yang, Yingying; Dong, Panpan; Zhao, Jing; Zhou, Wei; Zhou, Yonghua; Xu, Yongliang; Mei, Congjin; Guo, Fukun; Zheng, Yi; Yang, Jun-Qi

2018-03-01

Asthma is a chronic airway inflammation in which Th2 and Th17 cells play critical roles in its pathogenesis. We have reported that atypical protein kinase (PKC) λ/ι is a new regulator for Th2 differentiation and function. However, the role of PKCλ/ι for Th17 cells remains elusive. In this study, we explored the effect of PKCλ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional PKCλ/ι-deficient mice. Our findings indicate that PKCλ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKCλ/ι-deficiency was associated with the downregulation of Stat3 and Rorγt, key Th17 transcription factors. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of house dust mites. PKCλ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional PKCλ/ι-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, PKCλ/ι emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness. Copyright © 2018 Elsevier B.V. All rights reserved.

Does bacteremia occur during high pressure lavage of contaminated wounds?

PubMed

Tabor, O B; Bosse, M J; Hudson, M C; Greene, K G; Nousiainen, M T; Meyer, R A; Sims, S H; Kellam, J F

1998-02-01

The risk of bacteremia secondary to high pressure lavage of contaminated wounds was assessed. Twenty canines were divided randomly into four treatment groups. A 10-cm incision was made over the left shoulder of each dog. The deltoideus muscle was disrupted and traumatized. Groups A and B (n = 8) had wound contamination with 1.4 x 10(9) Staphylococcus aureus followed 75 minutes later by high pressure lavage or bulb syringe irrigation, respectively. Groups C and D (n = 2) had no contamination, followed by the same treatment. Bacterial counts were obtained before and after wound irrigation. Blood cultures were obtained before, during, and 15 minutes after irrigation. Positive control cultures were obtained during injection of bacteria into the antecubital vein. A detectable bacteremia did not occur during or after high pressure lavage or bulb syringe irrigation of acute contaminated wounds but did occur in 18 of 20 positive controls. Bacterial levels were reduced by an average of 70% +/- 10% by high pressure lavage and 44% +/- 50% by bulb irrigation. Reduction of wound bacteria was achieved more consistently with high pressure lavage than with bulb syringe irrigation.

Gastric Cancer Cells in Peritoneal Lavage Fluid: A Systematic Review Comparing Cytological with Molecular Detection for Diagnosis of Peritoneal Metastases and Prediction of Peritoneal Recurrences.

PubMed

Virgilio, Edoardo; Giarnieri, Enrico; Giovagnoli, Maria Rosaria; Montagnini, Monica; Proietti, Antonella; D'Urso, Rosaria; Mercantini, Paolo; Valabrega, Stefano; Balducci, Genoveffa; Cavallini, Marco

2018-03-01

Detecting free tumor cells in the peritoneal lavage fluid of gastric cancer patients permits to assess a more accurate prognosis, predict peritoneal recurrence and select cases for a more aggressive treatment. Currently, cytology and molecular biology comprise the two most popular methods of detection that are under constant study by researchers. We burrowed into the available literature comparing cytological with molecular detection of free intraperitoneal gastric cancer cells. PubMed, Science Direct, Scopus and Google Scholar were the search engines investigated. As of 2017, 51 dedicated studies have been published. Messenger RNA of carcinoembryonic antigen was the genetic target most frequently described. The genetic technique is usually superior to cytology in sensitivity (38-100% vs. 12.3-67% respectively), whereas cytological examination tends to show a slight pre-eminence in specificity (approximately 100%). So far, given the imperfection of each method, employment of both cytology and molecular examination seem to be mandatory. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Nasal lavage, blood or sputum: Which is best for phenotyping asthma?

PubMed

de Farias, Camyla F; Amorim, Maria M F; Dracoulakis, Michel; Caetano, Lilian B; Santoro, Ilka L; Fernandes, Ana L G

2017-05-01

Determination of asthma phenotypes, particularly inflammatory phenotypes, helps guide treatment and management of this heterogeneous disease. Induced sputum cytology has been the gold standard for determination of inflammatory phenotypes, but sputum induction is fairly invasive and technically challenging. Blood and nasal lavage cytology have been suggested as substitutes, but have not been fully verified. The aim of this study is to determine the accuracy of blood and nasal lavage cytometry as indicators of inflammatory phenotypes in asthma. Clinical evaluation, Asthma Control Questionnaire (ACQ) and spirometry were performed for 121 adult asthma patients, and blood, nasal lavage and induced sputum samples were taken. Eosinophils and neutrophils were counted in three samples from each subject. Inflammatory phenotypes (eosinophilic, neutrophilic, mixed and paucicellular) and cells counts were analysed using Venn diagram and receiver operating characteristic (ROC) curve, respectively. ACQ score, spirometry and bronchodilator response did not differ among subjects with different inflammatory phenotypes. Inflammatory phenotypes defined by nasal lavage cytometry were in better concordance than those defined by blood cell counts with phenotypes determined by sputum cytology, and were significantly correlated with sputum phenotypes. For eosinophilia, nasal lavage cytology showed better accuracy than blood cytology (area under the curve (AUC): 0.89 vs 0.65). For all phenotypes, sensitivity and positive and negative predictive power were higher for nasal lavage cytometry than for blood. Blood cell counts gave a high level of false positives for all inflammatory phenotypes. We recommend nasal lavage cytology over blood cell count as a substitute for sputum cytology to identify inflammatory phenotypes in asthma. © 2016 Asian Pacific Society of Respirology.

Gastric phytobezoars may be treated by nasogastric Coca-Cola lavage.

PubMed

Ladas, Spiros D; Triantafyllou, Konstantinos; Tzathas, Charalabos; Tassios, Pericles; Rokkas, Theodore; Raptis, Sotirios A

2002-07-01

Large gastric phytobezoars may occur in patients with gastric dysmotility disorders. Treatment options include dissolution with enzymes, endoscopic fragmentation with removal or aspiration, and surgery. We report our experience with nasogastric cola lavage therapy. Over an 8-year period, five consecutive patients were referred to our unit for endoscopic treatment of large gastric phytobezoars. They included one patient with lobectomy for lung cancer and four patients with diabetic gastroparesis. An initial attempt of endoscopic fragmentation and removal was unsuccessful. Patients were treated with 3 l of Coca-Cola nasogastric lavage over 12 h. Nasogastric lavage was very well tolerated by the patients. Complete phytobezoar dissolution was achieved in one session in all cases. There were no procedure-related complications. The dissolution of large gastric phytobezoars with cola nasogastric lavage is a safe, rapid and effective method. Patients may be treated in the medical ward, avoiding therapeutic endoscopy or surgery.

[Bronchoalveolar carcinoma].

PubMed

Wislez, Marie; Cadranel, Jacques; Milleron, Bernard

2003-04-01

Bronchoalveolar carcinoma is one of the four histologic subtypes of adenocarcinoma and its incidence is increasing. It grows in a lepidic fashion along the alveolar septa without invasive growth. The lack of invasive growth is an essential criterion based on data indicating that patients may be curable by surgical resection. The revised definition seems to be suitable for its solitary nodular form but less for multifocal or pneumonic-type form. High-resolution lung CT-scan is necessary to evaluate pulmonary involvement because of the high frequency of multifocal disease at initial presentation and because of the presence of ground glass opacity that could be one of the first manifestation of cancer bronchiolo-alvéolaireon CT. Therapeutic management does not differ from the one of non small cell lung cancer. Solitary nodules are treated by surgical resection with a good prognosis while multifocal and/or pneumonic forms are treated by systemic chemotherapy with a worse prognosis.

Prediction of Breast Cancer Risk by Aberrant Methylation in Mammary Duct Lavage

DTIC Science & Technology

2006-07-01

Assessment of breast epithelial cells obtained by nipple duct lavage (NDL) may have value for breast cancer risk stratification. NDL was performed in 150...contribute to risk stratification. 15. SUBJECT TERMS breast cancer, DNA methylation, Methylation Specific PCR, Nipple Duct Lavage, Risk assessment 16...carcinogenesis. Nipple duct lavage (NDL) is a minimally invasive approach for obtaining breast epithelial cells. Cytological atypia identified in nipple

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury

PubMed Central

Peters, Dorothea M.; Vadász, István; Wujak, Łukasz; Wygrecka, Małgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P.; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E.

2014-01-01

TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which—together with patch-clamp and flow cytometry studies—identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys43. Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β–dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs. PMID:24324142

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury.

PubMed

Peters, Dorothea M; Vadász, István; Wujak, Lukasz; Wygrecka, Malgorzata; Olschewski, Andrea; Becker, Christin; Herold, Susanne; Papp, Rita; Mayer, Konstantin; Rummel, Sebastian; Brandes, Ralph P; Günther, Andreas; Waldegger, Siegfried; Eickelberg, Oliver; Seeger, Werner; Morty, Rory E

2014-01-21

TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which--together with patch-clamp and flow cytometry studies--identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys(43). Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β-dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs.

Pancreatic-duct-lavage cytology in candidates for surgical resection of branch-duct intraductal papillary mucinous neoplasm of the pancreas: should the International Consensus Guidelines be revised?

PubMed

Sai, Jin Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio; Maehara, Tadayuki

2009-03-01

The International Consensus Guidelines are helpful for the management of branch-duct intraductal papillary mucinous neoplasms (IPMNs), because they allow us to exclude malignancy. However, it is not possible to predict malignancy with certainty, and further preoperative differentiation between benign and malignant IPMNs is required to avoid the false-positive results. To examine the usefulness of pancreatic-duct-lavage cytology by using an originally designed double-lumen catheter for discriminating benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines. Pancreatic-duct-lavage cytology was investigated in 24 patients with branch-duct IPMNs who underwent surgical resection based on the International Consensus Guidelines, namely, they either had intramural nodules or the ectatic branch duct was >30 mm in diameter. Single-center retrospective study. Academic medical center. The sensitivity and specificity of pancreatic-duct-lavage cytology for discriminating benign from malignant IPMNs. More than 30 mL of pancreatic-duct-lavage fluid was obtained from each patient, and there were no patients with noninformative results. The sensitivity, specificity, positive predictive value, and negative predictive value of the cytologic diagnosis were 78%, 93%, 88%, and 88%, respectively. Single-center and small number of patients. Pancreatic-duct-lavage cytology can improve differentiation between benign and malignant IPMNs of the branch-duct type in candidates for surgical resection based on the International Consensus Guidelines.

Trace metals in fluids lining the respiratory system of patients with idiopathic pulmonary fibrosis and diffuse lung diseases.

PubMed

Bargagli, Elena; Lavorini, Federico; Pistolesi, Massimo; Rosi, Elisabetta; Prasse, Antje; Rota, Emilia; Voltolini, Luca

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an undefined etiopathogenesis. Oxidative stress contributes to alveolar injury and fibrosis development and, because transition metals are essential to the functioning of most proteins involved in redox reactions, a better knowledge of metal concentrations and metabolism in the respiratory system of IPF patients may provide a valuable complementary approach to prevent and manage a disease which is often misdiagnosed or diagnosed in later stages. The present review summarizes and discusses literature data on the elemental composition of bronchoalveolar lavage (BAL), induced sputum and exhaled breath condensate (EBC) from patients affected by IPF and healthy subjects. Available data are scanty and the lack of consistent methods for the collection and analysis of lung and airways lining fluids makes it difficult to compare the results of different studies. However, the elemental composition of BAL samples from IPF patients seems to have a specific profile that can be distinguished from that of patients with other interstitial lung diseases (ILD) or control subjects. Suggestions are given towards standard sampling and analytical procedures of BAL samples, in the aim to assess typical element concentration patterns and their potential role as biomarkers of IPF. Copyright © 2017 Elsevier GmbH. All rights reserved.

Cigarette smoke increases BLT2 receptor functions in bronchial epithelial cells: in vitro and ex vivo evidence

PubMed Central

Pace, Elisabetta; Ferraro, Maria; Vincenzo, Serena Di; Bruno, Andreina; Giarratano, Antonino; Scafidi, Valeria; Lipari, Luana; Benedetto, Denise Valentina Di; Sciarrino, Serafina; Gjomarkaj, Mark

2013-01-01

Leukotriene B4 (LTB4) is a neutrophil chemotactic molecule with important involvement in the inflammatory responses of chronic obstructive pulmonary disease (COPD). Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke, the major risk factor for COPD. In this study we have explored whether cigarette smoke extracts (CSE) or soluble mediators present in distal lung fluid samples (mini-bronchoalveolar lavages) from smokers alter the expression of the LTB4 receptor 2 (BLT2) and peroxisome proliferator-activated receptor-α (PPAR-α) in bronchial epithelial cells. We also evaluated the effects of CSE on the expression of intercellular adhesion molecule 1 (ICAM-1) and on the binding of signal transducer and activator of transcription 1 (STAT-1) to ICAM-1 promoter as well as the adhesiveness of neutrophils to bronchial epithelial cells. CSE and mini-bronchoalveolar lavages from smokers increased BLT2 and ICAM-1 expression as well as the adhesiveness of neutrophils to bronchial epithelial cells and decreased PPAR-α expression. CSE induced the activation of STAT-1 and its binding to ICAM-1 promoter. These findings suggest that, in bronchial epithelial cells, CSE promote a prevalent induction of pro-inflammatory BLT2 receptors and activate mechanisms leading to increased neutrophil adhesion, a mechanism that contributes to airway neutrophilia and to tissue damage. PMID:23347335

Exposure to wood smoke particles produces inflammation in healthy volunteers.

PubMed

Ghio, Andrew J; Soukup, Joleen M; Case, Martin; Dailey, Lisa A; Richards, Judy; Berntsen, Jon; Devlin, Robert B; Stone, Susan; Rappold, Ana

2012-03-01

Human exposure to wood smoke particles (WSP) impacts on human health through changes in indoor air quality, exposures from wild fires, burning of biomass and air pollution. This investigation tested the postulate that healthy volunteers exposed to WSP would demonstrate evidence of both pulmonary and systemic inflammation. Ten volunteers were exposed to filtered air and, 3 weeks or more later, WSP. Each exposure included alternating 15 min of exercise and 15 min of rest for a total duration of 2 h. Wood smoke was generated by heating an oak log on an electric element and then delivered to the exposure chamber. Endpoints measured in the volunteers included symptoms, pulmonary function tests, measures of heart rate variability and repolarisation, blood indices and analysis of cells and fluid obtained during bronchoalveolar lavage. Mean particle mass for the 10 exposures to air and WSP was measured using the mass of particles collected on filters and found to be below the detectable limit and 485±84 μg/m(3), respectively (mean±SD). There was no change in either symptom prevalence or pulmonary function with exposure to WSP. At 20 h after wood smoke exposure, blood tests demonstrated an increased percentage of neutrophils, and bronchial and bronchoalveolar lavage revealed a neutrophilic influx. We conclude that exposure of healthy volunteers to WSP may be associated with evidence of both systemic and pulmonary inflammation.

Laparoscopic peritoneal lavage: our experience and review of the literature.

PubMed

Parisi, Amilcare; Gemini, Alessandro; Desiderio, Jacopo; Petrina, Adolfo; Trastulli, Stefano; Grassi, Veronica; Sani, Marco; Pironi, Daniele; Santoro, Alberto

2016-01-01

Over the years various therapeutic techniques for diverticulitis have been developed. Laparoscopic peritoneal lavage (LPL) appears to be a safe and useful treatment, and it could be an effective alternative to colonic resection in emergency surgery. This prospective observational study aims to assess the safety and benefits of laparoscopic peritoneal lavage in perforated sigmoid diverticulitis. We surgically treated 70 patients urgently for complicated sigmoid diverticulitis. Thirty-two (45.7%) patients underwent resection of the sigmoid colon and creation of a colostomy (Hartmann technique); 21 (30%) patients underwent peritoneal laparoscopic lavage; 4 (5.7%) patients underwent colostomy by the Mikulicz technique; and the remaining 13 (18.6%) patients underwent resection of the sigmoid colon and creation of a colorectal anastomosis with a protective ileostomy. The 66 patients examined were divided into 3 groups: 32 patients were treated with urgent surgery according to the Hartmann procedure; 13 patients were treated with resection and colorectal anastomosis; 21 patients were treated urgently with laparoscopic peritoneal lavage. We had no intraoperative complications. The overall mortality was 4.3% (3 patients). In the LPL group the morbidity rate was 33.3%. Currently it cannot be said that LPL is better in terms of mortality and morbidity than colonic resection. These data may, however, be proven wrong by greater attention in the selection of patients to undergo laparoscopic peritoneal lavage.

Effect of bronchopulmonary lavage on lung retention and clearance of particulate material in hamsters

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

Ellender, M.; Hodgson, A.; Wood, K.L.

Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP) labeled with [sup 57]CO. Three groups of animals were given bronchopulmonary lavage, beginning at either 1 week, 1 month, or 6 months after exposure. Each treated group was lavaged eight times over a period of 25 days. Each lavage involved 10 saline washes of the lungs. For each group, about 60-70% of the body content of [sup 57]CO at the start of lavage treatment was removed; nearly half of this was recovered in the first two lavages. A positive correlation was demonstrated between the macrophage content and [sup 57]Comore » activity of the washings. The subsequent fractional clearance rate of [sup 57]Co from lavaged animals was not significantly different from that in a group of untreated control animals. 30 refs., 2 figs., 2 tabs.« less

Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

PubMed

Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

2016-03-01

Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway. Copyright © 2016 by The American Association of Immunologists, Inc.

Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury.

PubMed

Wolthuis, Esther K; Choi, Goda; Dessing, Mark C; Bresser, Paul; Lutter, Rene; Dzoljic, Misa; van der Poll, Tom; Vroom, Margreeth B; Hollmann, Markus; Schultz, Marcus J

2008-01-01

Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury. Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes. Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor alpha, IL-1alpha, IL-1beta, IL-6, macrophage inflammatory protein 1alpha, and macrophage inflammatory protein 1beta in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups. The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.

Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

PubMed

Ramsey, Kathryn A; Ranganathan, Sarath; Park, Judy; Skoric, Billy; Adams, Anne-Marie; Simpson, Shannon J; Robins-Browne, Roy M; Franklin, Peter J; de Klerk, Nick H; Sly, Peter D; Stick, Steve M; Hall, Graham L

2014-11-15

Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis.

PubMed

Coughlan, Catherine A; Chotirmall, Sanjay H; Renwick, Julie; Hassan, Tidi; Low, Teck Boon; Bergsson, Gudmundur; Eshwika, Ahmed; Bennett, Kathleen; Dunne, Katie; Greene, Catherine M; Gunaratnam, Cedric; Kavanagh, Kevin; Logan, Patrick M; Murphy, Philip; Reeves, Emer P; McElvaney, Noel G

2012-11-15

Aspergillus fumigatus (A. fumigatus) in cystic fibrosis (CF) is increasingly recognized. Although allergic bronchopulmonary aspergillosis (ABPA) leads to deterioration of pulmonary function, the effect of A. fumigatus colonization in the absence of ABPA remains unclear. To address this, we examined individuals with CF with A. fumigatus who were ABPA negative to identify the effects of itraconazole therapy on Aspergillus-induced lung inflammation. The effect of A. fumigatus on nuclear vitamin D receptor (VDR) expression was investigated using qRT-PCR and Western blotting. IL-5 and IL-13 levels were quantified by ELISA. The effect of itraconazole was assessed by a combination of high-resolution computed tomography, lung function test, and microbiological analysis. We demonstrate that A. fumigatus down-regulates VDR in macrophages and airway epithelial cells and that the fungal metabolite gliotoxin (Gt) is the main causative agent. Gt overcame the positive effect of 1,25-OH vitamin D(3) on VDR expression in vitro, resulting in increased IL-5 and IL-13 production. In vivo, A. fumigatus positivity was associated with increased Gt in CF bronchoalveolar lavage fluid and increased bronchoalveolar lavage fluid levels of IL-5 and IL-13. After airway eradication of A. fumigatus with itraconazole, we observed decreased Gt, IL-5 and IL-13, improved respiratory symptoms, and diminished high-resolution computed tomography mosaic pattern consistent with sustained pulmonary function. This study provides a rationale for the therapeutic effect of itraconazole and implied that the therapeutic potential of vitamin D supplementation in preventing ABPA is only feasible with concurrent elimination of A. fumigatus to permit VDR expression and its positive functional consequences.

Lethal H1N1 influenza A virus infection alters the murine alveolar type II cell surfactant lipidome.

PubMed

Woods, Parker S; Doolittle, Lauren M; Rosas, Lucia E; Joseph, Lisa M; Calomeni, Edward P; Davis, Ian C

2016-12-01

Alveolar type II (ATII) epithelial cells are the primary site of influenza virus replication in the distal lung. Development of acute respiratory distress syndrome in influenza-infected mice correlates with significant alterations in ATII cell function. However, the impact of infection on ATII cell surfactant lipid metabolism has not been explored. C57BL/6 mice were inoculated intranasally with influenza A/WSN/33 (H1N1) virus (10,000 plaque-forming units/mouse) or mock-infected with virus diluent. ATII cells were isolated by a standard lung digestion protocol at 2 and 6 days postinfection. Levels of 77 surfactant lipid-related compounds of known identity in each ATII cell sample were measured by ultra-high-performance liquid chromatography-mass spectrometry. In other mice, bronchoalveolar lavage fluid was collected to measure lipid and protein content using commercial assay kits. Relative to mock-infected animals, ATII cells from influenza-infected mice contained reduced levels of major surfactant phospholipids (phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine) but increased levels of minor phospholipids (phosphatidylserine, phosphatidylinositol, and sphingomyelin), cholesterol, and diacylglycerol. These changes were accompanied by reductions in cytidine 5'-diphosphocholine and 5'-diphosphoethanolamine (liponucleotide precursors for ATII cell phosphatidylcholine and phosphatidylethanolamine synthesis, respectively). ATII cell lamellar bodies were ultrastructurally abnormal after infection. Changes in ATII cell phospholipids were reflected in the composition of bronchoalveolar lavage fluid, which contained reduced amounts of phosphatidylcholine and phosphatidylglycerol but increased amounts of sphingomyelin, cholesterol, and protein. Influenza infection significantly alters ATII cell surfactant lipid metabolism, which may contribute to surfactant dysfunction and development of acute respiratory distress syndrome in influenza-infected mice

Lethal H1N1 influenza A virus infection alters the murine alveolar type II cell surfactant lipidome

PubMed Central

Woods, Parker S.; Doolittle, Lauren M.; Rosas, Lucia E.; Joseph, Lisa M.; Calomeni, Edward P.

2016-01-01

Alveolar type II (ATII) epithelial cells are the primary site of influenza virus replication in the distal lung. Development of acute respiratory distress syndrome in influenza-infected mice correlates with significant alterations in ATII cell function. However, the impact of infection on ATII cell surfactant lipid metabolism has not been explored. C57BL/6 mice were inoculated intranasally with influenza A/WSN/33 (H1N1) virus (10,000 plaque-forming units/mouse) or mock-infected with virus diluent. ATII cells were isolated by a standard lung digestion protocol at 2 and 6 days postinfection. Levels of 77 surfactant lipid-related compounds of known identity in each ATII cell sample were measured by ultra-high-performance liquid chromatography-mass spectrometry. In other mice, bronchoalveolar lavage fluid was collected to measure lipid and protein content using commercial assay kits. Relative to mock-infected animals, ATII cells from influenza-infected mice contained reduced levels of major surfactant phospholipids (phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine) but increased levels of minor phospholipids (phosphatidylserine, phosphatidylinositol, and sphingomyelin), cholesterol, and diacylglycerol. These changes were accompanied by reductions in cytidine 5′-diphosphocholine and 5′-diphosphoethanolamine (liponucleotide precursors for ATII cell phosphatidylcholine and phosphatidylethanolamine synthesis, respectively). ATII cell lamellar bodies were ultrastructurally abnormal after infection. Changes in ATII cell phospholipids were reflected in the composition of bronchoalveolar lavage fluid, which contained reduced amounts of phosphatidylcholine and phosphatidylglycerol but increased amounts of sphingomyelin, cholesterol, and protein. Influenza infection significantly alters ATII cell surfactant lipid metabolism, which may contribute to surfactant dysfunction and development of acute respiratory distress syndrome in influenza-infected mice

Herpes simplex type 1 pneumonitis and acute respiratory distress syndrome in a patient with chronic lymphatic leukemia: a case report.

PubMed

Luginbuehl, Miriam; Imhof, Alexander; Klarer, Alexander

2017-11-23

Pulmonary pathogenicity of herpes simplex virus type 1 in patients in intensive care without classic immunosuppression as well as the necessity of antiviral treatment in the case of herpes simplex virus detection in respiratory specimens in these patients is controversial. We present a case of acute respiratory distress syndrome in a patient with stable chronic lymphatic leukemia not requiring treatment, in whom we diagnosed herpes simplex virus type 1 bronchopneumonitis based on herpes simplex virus type 1 detection in bronchoalveolar lavage fluid and clinical response to antiviral treatment. A 72-year-old white man presented with symptoms of lower respiratory tract infection. His medical history was significant for chronic lymphatic leukemia, which had been stable without treatment, arterial hypertension, multiple squamous cell carcinomas of the scalp, and alcohol overuse. Community-acquired pneumonia was suspected and appropriate broad-spectrum antibacterial treatment was initiated. Within a few hours, rapid respiratory deterioration led to cardiac arrest. He was successfully resuscitated, but developed acute respiratory distress syndrome. Furthermore, he remained febrile and inflammation markers remained elevated despite antibacterial treatment. Polymerase chain reaction from bronchoalveolar lavage fluid and viral culture from tracheobronchial secretions tested positive for herpes simplex virus type 1. We initiated antiviral treatment with acyclovir. Concomitantly we further escalated the antibacterial treatment, although no bacterial pathogen had been isolated at any point. Defervescence occurred rapidly and his C-reactive protein and leukocyte levels decreased. He was successfully weaned from mechanical ventilation, transferred to the ward, and eventually discharged to home. Herpes simplex virus should be considered a cause for lower respiratory tract infection in critically ill patients, especially in the setting of an underlying disease.

Acute Exposure to Electronic and Combustible Cigarette Aerosols: Effects in an Animal Model and in Human Alveolar Cells

PubMed Central

Husari, Ahmad; Shihadeh, Alan; Talih, Soha; Hashem, Yasmine

2016-01-01

Abstract Background: Smoking electronic cigarettes (ECIG) is promoted as a safer alternative to smoking combustible cigarettes. This study investigates the effects of ECIG aerosol and cigarette smoke (CS) in an animal model and in human alveolar cell cultures (A549). Methods: Mice were divided into Control, ECIG, and CS. Animals were exposed for 6h/d to either lab air, ECIG or CS, for of 3 days. Total particulate matter exposure for the ECIG was set at higher levels compared to CS. Lung injury was determined by: (1) measurement of wet-to-dry ratio; (2) albumin concentration in the bronchoalveolar lavage fluid; (3) transcriptional expression of inflammatory mediators IL-1β, IL-6, TNF-α; (4) oxidative stress; (5) assessment of cell death; and (6) lung histopathology. Human alveolar cell cultures were treated with various concentrations of ECIG and CS aerosol extracts and the effects on cell proliferation were evaluated. Results: Wet-to-dry ratio was higher in CS when compared to ECIG. Albumin leak in bronchoalveolar lavage fluid was evident in CS but not in ECIG. ECIG exposure was only associated with a significant increase in IL-1β. In contrast, CS exposure resulted in significant increases in IL-1β, IL-6, TNF-α expression, and oxidative stress. TUNEL staining demonstrated significant cell death in CS but not in ECIG. At the cellular level, ECIG and CS extracts reduced cell proliferation, however, CS exhibited effects at lower concentrations. Conclusion: Despite higher exposure conditions, ECIG exhibited less toxic effects on lungs of experimental animals and on A549 cell cultures when compared to CS. PMID:26272212

Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice.

PubMed

Kanwar, R K; Macgibbon, A K; Black, P N; Kanwar, J R; Rowan, A; Vale, M; Krissansen, G W

2008-01-01

It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses. C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

PubMed Central

Xu, Dun-quan; Gao, Cao; Niu, Wen; Li, Yan; Wang, Yan-xia; Gao, Chang-jun; Ding, Qian; Yao, Li-nong; Chai, Wei; Li, Zhi-chao

2013-01-01

Aim: To investigate the protective effects of hydrogen sulfide (H2S) against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods: Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35–40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NaHS (28 μmol/kg, ip) was injected before the resuscitation. Results: Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-α, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H2O2 and ·OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin 1 expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NaHS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion: NaHS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway. PMID:24122010

Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties

PubMed Central

Marzaioli, Viviana; Aguilar-Pimentel, Juan Antonio; Weichenmeier, Ingrid; Luxenhofer, Georg; Wiemann, Martin; Landsiedel, Robert; Wohlleben, Wendel; Eiden, Stefanie; Mempel, Martin; Behrendt, Heidrun; Schmidt-Weber, Carsten; Gutermuth, Jan; Alessandrini, Francesca

2014-01-01

Background Silica (SiO2) nanoparticles (NPs) are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems. Objective To assess the potential impact of SiO2 NP exposure and NPs chemical modifications in allergic airway inflammation. Methods Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 μg) over 42 days, then intratracheally instilled with plain or modified SiO2 NPs (50 μg/mouse), and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue. Results Plain SiO2 NPs induced proinflammatory and immunomodulatory effects in vivo, highlighted by enhanced infiltration of inflammatory cells in the bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2) cytokine pattern, differentiation of type 2 macrophages, and by morphological changes in the lung of sensitized mice. These effects were dramatically attenuated using surface-functionalized NPs with amino and phosphate groups, but not with polyethylene glycol. The role of macrophages in taking up SiO2 NPs was confirmed by flow cytometry, confocal microscopy, and gene expression analysis. Conclusion Our data suggest that amino and phosphate surface modifications, but not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory effect of SiO2 NPs in allergic airway inflammation, paving the way for new strategies in the production of nanomaterials with lower health impact for humans. PMID:24940059

Molecular epidemiologic analysis of a Pneumocystis pneumonia outbreak among renal transplant patients.

PubMed

Urabe, N; Ishii, Y; Hyodo, Y; Aoki, K; Yoshizawa, S; Saga, T; Murayama, S Y; Sakai, K; Homma, S; Tateda, K

2016-04-01

Between 18 November and 3 December 2011, five renal transplant patients at the Department of Nephrology, Toho University Omori Medical Centre, Tokyo, were diagnosed with Pneumocystis pneumonia (PCP). We used molecular epidemiologic methods to determine whether the patients were infected with the same strain of Pneumocystis jirovecii. DNA extracted from the residual bronchoalveolar lavage fluid from the five outbreak cases and from another 20 cases of PCP between 2007 and 2014 were used for multilocus sequence typing to compare the genetic similarity of the P. jirovecii. DNA base sequencing by the Sanger method showed some regions where two bases overlapped and could not be defined. A next-generation sequencer was used to analyse the types and ratios of these overlapping bases. DNA base sequences of P. jirovecii in the bronchoalveolar lavage fluid from four of the five PCP patients in the 2011 outbreak and from another two renal transplant patients who developed PCP in 2013 were highly homologous. The Sanger method revealed 14 genomic regions where two differing DNA bases overlapped and could not be identified. Analyses of the overlapping bases by a next-generation sequencer revealed that the differing types of base were present in almost identical ratios. There is a strong possibility that the PCP outbreak at the Toho University Omori Medical Centre was caused by the same strain of P. jirovecii. Two different types of base present in some regions may be due to P. jirovecii's being a diploid species. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Peritoneal lavage with povidone-iodine solution in colorectal cancer-induced rats.

PubMed

Song, Hua-Li; Zhang, Dong-Mei; Wen, Heng; Wang, Meng; Zhao, Na; Gao, Yu-Hua; Ding, Ni

2018-08-01

Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations. Copyright © 2018 Elsevier Inc. All rights reserved.

The effects of heated and room-temperature abdominal lavage solutions on core body temperature in dogs undergoing celiotomy.

PubMed

Nawrocki, Michael A; McLaughlin, Ron; Hendrix, P K

2005-01-01

To document the magnitude of temperature elevation obtained with heated lavage solutions during abdominal lavage, 18 dogs were lavaged with sterile isotonic saline intraoperatively (i.e., during a celiotomy). In nine dogs, room-temperature saline was used. In the remaining nine dogs, saline heated to 43+/-2 degrees C (110+/-4 degrees F) was used. Esophageal, rectal, and tympanic temperatures were recorded every 60 seconds for 15 minutes after initiation of the lavage. Temperature levels decreased in dogs lavaged with room-temperature saline. Temperature levels increased significantly in dogs lavaged with heated saline after 2 to 6 minutes of lavage, and temperatures continued to increase throughout the 15-minute lavage period.

Pleural sarcoidosis diagnosed on the basis of an increased CD4/CD8 lymphocyte ratio in pleural effusion fluid: a case report.

PubMed

Kumagai, Toru; Tomita, Yasuhiko; Inoue, Takako; Uchida, Junji; Nishino, Kazumi; Imamura, Fumio

2015-08-14

Pleural effusion induced by sarcoidosis is rare, and pleural sarcoidosis is often diagnosed by thoracoscopic surgery. The diagnosis of pleural sarcoidosis using thoracentesis may be less invasive when sarcoidosis is already diagnosed histologically in more than one organ specimen. Here we report the case of a 64-year-old woman with pleural sarcoidosis diagnosed on the basis of an increased CD4/CD8 lymphocyte ratio in pleural effusion fluid obtained by thoracentesis. This case report is important because it highlights the usefulness of the CD4/CD8 lymphocyte ratio in pleural effusion as an indicator of pleural involvement of sarcoidosis. A 64-year-old Japanese woman visited our hospital with an initial symptom of dyspnea on exertion for a period of 4 months. Chest computed tomography showed bilateral hilar and multiple mediastinal lymphadenopathy, multiple small nodular shadows in her bilateral lungs, small nodular shadows along the interlobar pleura, and bilateral pleural effusion. Her serum angiotensin-converting enzyme and soluble interleukin-2 receptor levels were elevated. Histological analysis of a resected subcutaneous nodule, and biopsy specimens from a right mediastinal lymph node and from her right lung revealed non-caseous epithelioid granulomas. Her bronchoalveolar lavage fluid exhibited a predominance of lymphocytes together with an increase in the CD4/CD8 lymphocyte ratio. The lymphocytic predominance and the increased CD4/CD8 lymphocyte ratio were also detected in the right-sided pleural effusion fluid obtained by thoracentesis. We diagnosed sarcoidosis with pleural involvement. Because pleural effusion did not resolve spontaneously and her symptom of dyspnea on exertion worsened, corticosteroid therapy was initiated, which ameliorated the sarcoidosis and the pleuritis. Analysis of the CD4/CD8 lymphocyte ratio in pleural effusion fluid obtained by thoracentesis may be helpful for the diagnosis of pleural sarcoidosis when the diagnosis is already made

Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

PubMed

Mokra, D; Kosutova, P; Balentova, S; Adamkov, M; Mikolka, P; Mokry, J; Antosova, M; Calkovska, A

2016-12-01

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO 2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and

Acute eosinophilic pneumonia secondary to heroin inhalation.

PubMed

Eyüpoğlu, Damla; Ortaç Ersoy, Ebru; Rollas, Kazım; Topeli, Arzu

2017-06-01

Smoking heroin (chasing the dragon), is a method of inhaling heroin via heating the drug on a tin-foil above a flame. It also has been associated both with the indirect effects of heroin overdose and with direct pulmonary toxicity. We describe a case of acute eosinophilic pneumonia secondary to heroin inhalation in our medical intensive care unit. She presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed bilateral infiltrations. Examination of bronchoalveolar lavage fluid revealed significant eosinophilia. She was diagnosed with acute eosinophilic pneumonia. After heroin abstinence and corticosteroid therapy, remission was achieved rapidly and the patient was discharge on the fourth day of her hospital stay.

Childhood hypersensitivity pneumonitis associated with fungal contamination of indoor hydroponics.

PubMed

Engelhart, Steffen; Rietschel, Ernst; Exner, Martin; Lange, Lars

2009-01-01

Childhood hypersensitivity pneumonitis (HP) is often associated with exposure to antigens in the home environment. We describe a case of HP associated with indoor hydroponics in a 14-year-old girl. Water samples from hydroponics revealed Aureobasidium pullulans as the dominant fungal micro-organism (10(4)CFU/ml). The diagnosis is supported by the existence of serum precipitating antibodies against A. pullulans, lymphocytic alveolitis on bronchoalveolar lavage (BAL) fluid, a corresponding reaction on a lung biopsy, and the sustained absence of clinical symptoms following the removal of hydroponics from the home. We conclude that hydroponics should be considered as potential sources of fungal contaminants when checking for indoor health complaints.

Hypersensitivity pneumonitis and related conditions in the work environment.

PubMed

Zacharisen, Michael C; Fink, Jordan N

2011-11-01

Hypersensitivity pneumonitis can occur from a wide variety of occupational exposures. Although uncommon and difficult to recognize, through a detailed work exposure history, physical examination, radiography, pulmonary function studies, and selected laboratory studies using sera and bronchoalveolar lavage fluid, workers can be identified early to effect avoidance of the antigen and institute pharmacologic therapy, if necessary. A lung biopsy may be necessary to rule out other interstitial lung diseases. Despite the varied organic antigen triggers, the presentation is similar with acute, subacute, or chronic forms. Systemic corticosteroids are the only reliable pharmacologic treatment but do not alter the long-term outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

Reactivity of airway phagocytes during the development of acute pneumonia under conditions of stimulation of mononuclear phagocyte system with zymosan.

PubMed

Makarova, O P

2008-12-01

Pneumonia was induced in (CBA x C57Bl)F1 mice under conditions of stimulation of the mononuclear phagocyte system with zymosan. The number of neutrophils in airways increased after 3 days; by day 14, the number of cells in the bronchoalveolar lavage fluid further increased due to migration of macrophages. After zymosan prestimulation, the number and functional activity of neutrophils during the early period of inflammation (3 days) did not change, but the increase in phagocytic activity of macrophages was inhibited by 20%. By day 14, the effect of prestimulation manifested in 4.5-fold decreased capacity of neutrophils and macrophages to reduce NBT.

Evaluating the effect of intraoperative peritoneal lavage on bacterial culture in dogs with suspected septic peritonitis.

PubMed

Swayne, Seanna L; Brisson, Brigitte; Weese, J Scott; Sears, William

2012-09-01

This pilot study describes the effect of intraoperative peritoneal lavage (IOPL) on bacterial counts and outcome in clinical cases of septic peritonitis. Intraoperative samples were cultured before and after IOPL. Thirty-three dogs with presumed septic peritonitis on the basis of cytology were managed surgically during the study period. Positive pre-lavage bacterial cultures were found in 14 cases, 13 of which were a result of intestinal leakage. The post-lavage cultures showed fewer isolates in 9 cases and in 1 case became negative. The number of dogs with a decrease in the concentration of bacteria cultured from pre-lavage to post-lavage samples was not statistically significant. There was no significant effect of the change in pre- to post-lavage culture, single versus multiple types of bacteria, selection of an appropriate empiric antimicrobial on survival or the need for subsequent surgery. This pilot study describes the effect of intraoperative peritoneal lavage (IOPL) on bacterial counts and outcome in clinical cases of septic peritonitis. Intraoperative samples were cultured before and after IOPL. Thirty-three dogs with presumed septic peritonitis on the basis of cytology were managed surgically during the study period. Positive pre-lavage bacterial cultures were found in 14 cases, 13 of which were a result of intestinal leakage. The post-lavage cultures showed fewer isolates in 9 cases and in 1 case became negative. The number of dogs with a decrease in the concentration of bacteria cultured from pre-lavage to post-lavage samples was not statistically significant. There was no significant effect of the change in pre- to post-lavage culture, single versus multiple types of bacteria, selection of an appropriate empiric antimicrobial on survival or the need for subsequent surgery.

Acute nose-only exposure of rats to phosgene. Part II. Concentration x time dependence of changes in bronchoalveolar lavage during a follow-up period of 3 months.

PubMed

Pauluhn, Jürgen

2006-08-01

Groups of young adult male Wistar rats were acutely exposed to phosgene gas for either 30 or 240 min using a directed-flow nose-only mode of exposure. In 30-min exposed rats the concentrations were 0.94, 2.02, 3.89, 7.35, and 15.36 mg/m3, which relate to C x t products of 28.2, 60.6, 116.7, 220.5, and 460.8 mg/m3 x min. In 240-min exposed rats the concentrations were 0.96, 0.387, 0.786, 1.567, and 4.2 mg/m3, which relate C x t products of 47.0, 92.9, 188.6, 376, and 1008 mg/m3 x min. Six rats/group were sacrificed on postexposure days 1, 3, 7, 14, and 84, while the rats of the 1008 mg/m3 x min group where sacrificed on postexposure days 1, 7, 14, and 28. The focus of measurements was directed toward indicators of inflammatory response and increased transmucosal permeability in bronchoalveolar lavage (BAL), including lung weights. Lungs from rats sacrificed at the end of the postexposure period were additionally examined by histopathology. Mortality did not occur at any C x t product. The most pronounced changes were related to C x t-dependent increases in the following markers in BAL: protein, soluble collagen, polymorphonuclear leukocytes (PMN) counts, and alveolar macrophages with foamy appearance. These indicators were maximal on the first postexposure day, while total cell counts and alveolar macrophages containing increased phospholipids reached their climax around post-exposure day 3. At 1008 mg/m3 x min the most sensitive indicators in BAL, that is, protein, PMN, and collagen, resolved within 2 wk, whereas at lower C x t products they reached the level of the control by postexposure day 7. At 1008 mg/m3 x min (day 28), histopathology revealed a minimal to slight hypercellularity in terminal bronchioles with focal peribronchiolar inflammatory infiltrates and focal septal thickening. At lower C x t products (day 84) the rats from all groups were indistinguishable and Sirius red-stained lungs did not provide evidence of late-onset sequelae, such as fibrotic

The importance of pulsed lavage on interface temperature and ligament tension force in cemented unicompartmental knee arthroplasty.

PubMed

Clarius, M; Seeger, J B; Jaeger, S; Mohr, G; Bitsch, R G

2012-05-01

Mechanical loosening is the most common cause of revision in unicompartmental knee arthroplasty. We determined the effect of bone lavage on tibial cement penetration and interface temperature with controlled ligament tension forces. We presumed pulsed lavage would allow increased cement penetration compared with syringe lavage. Cemented unicompartmental knee arthroplasty was performed in 12 pairs of fresh-frozen knees. Lavage was performed using pulsed lavage on one side (A) and syringe lavage on the other (B). Cement penetration pressure, interface temperature, and ligament tension forces were continuously monitored during the operation. Screened radiographs were taken and cement penetration under the tibial plateau was measured. The pulsed lavage group showed a mean cement penetration area of 187.24 (SD 36.37) mm², whereas 144.29 (SD 35.74) mm(2) was measured in the group with syringe lavage. Cement penetration pressure was 13.29 (SD 8.69) kPa in Group A and 20.21 (SD 7.78) kPa in Group B. Maximum interface temperatures of 46.99°C were observed in Group A and 45.02°C in Group B. Our data showed pulsed lavage cleansing of the cancellous tibial bone substantially improved cement penetration compared with syringe lavage without reaching the temperature threshold for bone necrosis. We recommend the routine use of pulsed lavage to improve long-term fixation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparison of Irrigation Times Using Gravity and High-Pressure Lavage.

PubMed

Muscatelli, Stefano; Howe, Andrea; O'Hara, Nathan N; O'Toole, Robert V; Sprague, Sheila A; Slobogean, Gerard P

2017-05-01

The benefits of high-pressure pulsatile lavage for open fracture irrigation have been controversial based on conflicting experimental animal research. Recently published data definitively demonstrated that irrigation pressure does not affect the incidence of reoperation for the treatment of open fractures. However, proponents of pulsatile lavage argue a faster irrigation time is an important benefit of the high-pressure treatment. The purpose of this study was to determine the difference in irrigation time between gravity and high-pressure lavage. The experimental setup was designed to mimic clinical practice and compared mean irrigation flow times for high-pressure pulsatile lavage and gravity flow with 2 commonly used tube diameters. Each irrigation setup was tested 5 times at 3 different irrigation bag heights. Analysis of variance and Student's t tests were used to compare the mean flow times of 3 irrigation methods at each height and among the 3 heights for each irrigation method. The mean irrigation flow time in the various experimental models ranged from 161 to 243 seconds. Gravity irrigation with wide tubing was significantly faster than pulsatile lavage or gravity with narrow tubing (P<.001). Increasing irrigation bag height had only a marginal effect on the overall flow times (<9% difference). The difference in mean flow time among the testing techniques was slightly longer than 1 minute, which is unlikely to have a material impact on procedural costs, operating times, and subsequent gains in patient safety. [Orthopedics. 2017; 40(3):e413-e416.]. Copyright 2017, SLACK Incorporated.

The Physical Properties of a Lavage Mixture of Pulmonary Surfactant, Perfluorodecaline, and Methylprednisolone (Perfactant Lavage)

DTIC Science & Technology

2014-05-09

release: distribution unlimited Purpose: To characterize the physical properties of a lavage mixture of pulmonary surfactant, perfluorocarbon and...methylprednisolone. Background: Perfluorocarbons (PFCs) are compounds derived from hydrocarbons by the substitution of hydrogen atoms with fluorine...atoms. Perfluorocarbon liquids are colorless, odorless and biologically inert. They are highly dense, due to their molecular weight. Their low

Fingerprint of Lung Fluid Ultrafine Particles, a Novel Marker of Acute Lung Inflammation.

PubMed

Bar-Shai, Amir; Alcalay, Yifat; Sagiv, Adi; Rotem, Michal; Feigelson, Sara W; Alon, Ronen; Fireman, Elizabeth

2015-01-01

Acute lung inflammation can be monitored by various biochemical readouts of bronchoalveolar lavage fluid (BALF). To analyze the BALF content of ultrafine particles (UFP; <100 nm) as an inflammatory biomarker in early diagnosis of acute and chronic lung diseases. Mice were exposed to different stress conditions and inflammatory insults (acute lipopolysaccharide inhalation, tobacco smoke and lethal dose of total body irradiation, i.e. 950 rad). After centrifugation, the cellular pellet was assessed while cytokines and ultrafine particles were measured in the soluble fraction of the BALF. A characteristic UFP distribution with a D50 (i.e. the dimension of the 50th UFP percentile) was shared by all tested mouse strains in the BALF of resting lungs. All tested inflammatory insults similarly shifted this size distribution, resulting in a unique UFP fingerprint with an averaged D50 of 58.6 nm, compared with the mean UFP D50 of 23.7 nm for resting BALF (p < 0.0001). This UFP profile was highly reproducible and independent of the intensity or duration of the inflammatory trigger. It returned to baseline after resolution of the inflammation. Neither total body irradiation nor induction of acute cough induced this fingerprint. The UFP fingerprint in the BALF of resting and inflamed lungs can serve as a binary biomarker of healthy and acutely inflamed lungs. This marker can be used as a novel readout for the onset of inflammatory lung diseases and for complete lung recovery from different insults.

Analysis of a Panel of 48 Cytokines in BAL Fluids Specifically Identifies IL-8 Levels as the Only Cytokine that Distinguishes Controlled Asthma from Uncontrolled Asthma, and Correlates Inversely with FEV1

PubMed Central

Qi, Huibin; Kurosky, Alexander; Jennings, Kristofer; Sun, Qian; Boldogh, Istvan; Sur, Sanjiv

2015-01-01

We sought to identify cells and cytokines in bronchoalveolar lavage (BAL) fluids that distinguish asthma from healthy control subjects and those that distinguish controlled asthma from uncontrolled asthma. Following informed consent, 36 human subjects were recruited for this study. These included 11 healthy control subjects, 15 subjects with controlled asthma with FEV1≥80% predicted and 10 subjects with uncontrolled asthma with FEV1 <80% predicted. BAL fluid was obtained from all subjects. The numbers of different cell types and the levels of 48 cytokines were measured in these fluids. Compared to healthy control subjects, patients with asthma had significantly more percentages of eosinophils and neutrophils, IL-1RA, IL-1α, IL-1β, IL-2Rα, IL-5, IL-6, IL-7, IL-8, G-CSF, GROα (CXCL1), MIP-1β (CCL4), MIG (CXCL9), RANTES (CCL5) and TRAIL in their BAL fluids. The only inflammatory markers that distinguished controlled asthma from uncontrolled asthma were neutrophil percentage and IL-8 levels, and both were inversely correlated with FEV1. We examined whether grouping asthma subjects on the basis of BAL eosinophil % or neutrophil % could identify specific cytokine profiles. The only differences between neutrophil-normal asthma (neutrophil≤2.4%) and neutrophil-high asthma (neutrophils%>2.4%) were a higher BAL fluid IL-8 levels, and a lower FEV1 in the latter group. By contrast, compared to eosinophil-normal asthma (eosinophils≤0.3%), eosinophil-high asthma (eosinophils>0.3%) had higher levels of IL-5, IL-13, IL-16, and PDGF-bb, but same neutrophil percentage, IL-8, and FEV1. Our results identify neutrophils and IL-8 are the only inflammatory components in BAL fluids that distinguish controlled asthma from uncontrolled asthma, and both correlate inversely with FEV1. PMID:26011707

Inhibition of HMGCoA reductase by simvastatin protects mice from injurious mechanical ventilation.

PubMed

Manitsopoulos, Nikolaos; Orfanos, Stylianos E; Kotanidou, Anastasia; Nikitopoulou, Ioanna; Siempos, Ilias; Magkou, Christina; Dimopoulou, Ioanna; Zakynthinos, Spyros G; Armaganidis, Apostolos; Maniatis, Nikolaos A

2015-02-14

Mortality from severe acute respiratory distress syndrome exceeds 40% and there is no available pharmacologic treatment. Mechanical ventilation contributes to lung dysfunction and mortality by causing ventilator-induced lung injury. We explored the utility of simvastatin in a mouse model of severe ventilator-induced lung injury. Male C57BL6 mice (n = 7/group) were pretreated with simvastatin or saline and received protective (8 mL/kg) or injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20 mg/kg) or saline were injected intraperitoneally on days -2, -1 and 0 of the experiment. Lung mechanics, (respiratory system elastance, tissue damping and airway resistance), were evaluated by forced oscillation technique, while respiratory system compliance was measured with quasi-static pressure-volume curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin-stained lung sections for the presence of lung injury. Pulmonary endothelial dysfunction was ascertained by bronchoalveolar lavage protein content and lung tissue expression of endothelial junctional protein Vascular Endothelial cadherin by immunoblotting. To assess the inflammatory response in the lung, we determined bronchoalveolar lavage fluid total cell content and neutrophil fraction by microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the systemic response, we obtained plasma levels of Tumor Necrosis Factor-α, Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis testing was undertaken using one-way analysis of variance and Tukey's post hoc tests. Ventilation with high tidal volume (HVt) resulted in significantly increased lung elastance by 3-fold and decreased lung compliance by 45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical alterations of HVt. Histologic lung injury score increased four-fold by HVt but not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were

Reaction products of hexamethylene diisocyanate vapors with “self” molecules in the airways of rabbits exposed via tracheostomy

PubMed Central

Wisnewski, Adam V.; Kanyo, Jean; Asher, Jennifer; Goodrich, James A.; Barnett, Grace; Patrylak, Lyn; Liu, Jian; Redlich, Carrie A.; Nassar, Ala F.

2018-01-01

Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma.“Self” molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized.This study employed unique approaches to identify and characterize “self” targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O2, or O2 plus ~200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS.The low-molecular weight (<3 kDa) fraction of HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified 783.26 and 476.18 m/z [M+H]+ ions with high energy collision-induced dissociation (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin.In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with “self” molecules in the lower airways. PMID:28489470

Characterization of Siglec-8 Expression on Lavage Cells after Segmental Lung Allergen Challenge.

PubMed

Johansson, Mats W; Kelly, Elizabeth A; Nguyen, Christopher L; Jarjour, Nizar N; Bochner, Bruce S

2018-06-07

Siglec-8 is present at a high level on human blood eosinophils and low level on blood basophils. Engagement of Siglec-8 on blood eosinophils causes its internalization and results in death. Siglec-8 is a potential therapeutic target in eosinophilic asthma. The aim of this study was to determine Siglec-8 levels on eosinophils and basophils recruited during lung inflammation. We analyzed surface Siglec-8 by flow cytometry on cells obtained by bronchoalveolar lavage (BAL) 48 h after segmental lung allergen challenge of human subjects with mild allergic asthma and used confocal microscopy to compare Siglec-8 distribution on BAL and blood eosinophils. Like their blood counterparts, BAL eosinophils had high unimodal surface Siglec-8, while BAL basophils had lower but detectable surface Siglec-8. BAL macrophages, monocytes, neutrophils, and plasmacytoid dendritic cells did not express surface Siglec-8. Microscopy of freshly isolated blood eosinophils demonstrated homogeneous Siglec-8 distribution over the cell surface. Upon incubation with IL-5, Siglec-8 on the surface of eosinophils became localized in patches both at the nucleopod tip and at the opposite cell pole. BAL eosinophils also had a patchy Siglec-8 distribution. We conclude that 48 h after segmental allergen challenge, overall levels of Siglec-8 expression on airway eosinophils resemble those on blood eosinophils, but with a patchier distribution, a pattern consistent with activation. Thus, therapeutic targeting of Siglec-8 has the potential to impact blood as well as lung eosinophils, which may be associated with an improved outcome in eosinophilic lung diseases. © 2018 S. Karger AG, Basel.

Exogenous surfactant preserves lung function and reduces alveolar Evans blue dye influx in a rat model of ventilation-induced lung injury.

PubMed

Verbrugge, S J; Vazquez de Anda, G; Gommers, D; Neggers, S J; Sorm, V; Böhm, S H; Lachmann, B

1998-08-01

was reduced in the groups that received 200 and 400 mg/kg exogenous surfactant. Exogenous surfactant preceding high peak inspiratory lung volumes prevents impairment of oxygenation, lung mechanics, and minimal surface tension of bronchoalveolar lavage fluid and reduces alveolar influx of Evans blue dye. These data indicate that surfactant has a beneficial effect on ventilation-induced lung injury.

Proinflammatory role of epithelial cell-derived exosomes in allergic airway inflammation.

PubMed

Kulshreshtha, Ankur; Ahmad, Tanveer; Agrawal, Anurag; Ghosh, Balaram

2013-04-01

Exosomes are nanovesicles involved in intercellular communication. Their roles in various diseases are often contextual, depending on the cell type producing them. Although few studies hint toward the proinflammatory role of bronchoalveolar lavage fluid-derived exosomes in asthmatic progression, the cell types in lungs associated with exosome-mediated crosstalk and their resultant effects remain unexplored. It is well established that exosome-mediated cellular communication can influence disease phenotypes. This study explores exosome-mediated cellular crosstalk between structural and immune cells in asthma pathogenesis. Exosomes were isolated and detected from bronchoalveolar lavage fluid of control and asthmatic mice and were quantified by using a bead-based assay. Involvement of epithelial cells and macrophages were established by using immunohistochemical techniques in lung tissue sections. The role of IL-13 in exosome production was ascertained by using various in vitro and in vivo techniques. Exosome secretion was blocked in in vitro and in vivo settings by using a chemical inhibitor, and the effects on various asthmatic features were studied. Using combinatorial in vitro and in vivo approaches, we found that exosome secretion and production of exosome-associated proteins are higher in lungs of asthmatic mice compared with that seen in sham mice. Asthma is marked by enhanced secretion of exosomes by epithelial cells, but not macrophages, under the influence of IL-13. These epithelial cell exosomes induce proliferation and chemotaxis of undifferentiated macrophages. On the other hand, GW4869, which inhibited exosome production, resulted in a reduced population of proliferating monocytes and alleviation of various asthmatic features. Under the influence of IL-13, epithelial cell-derived exosomes can induce enhanced proliferation and chemotaxis of undifferentiated macrophages in the lungs during asthmatic inflammatory conditions. Copyright © 2013 American

Acute respiratory toxicity following inhalation exposure to soman in guinea pigs.

PubMed

Perkins, Michael W; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Kabra, Kareem; Chanda, Soma; Oguntayo, Samuel; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2010-06-01

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m(3) concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m(3) soman survived, while animals exposed to 841, and 1121 mg/m(3) resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt(50) for soman determined by probit analysis was 827.2mg/m(3). A majority of the animals that died at 1121 mg/m(3) developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs. (c) 2010 Elsevier Inc. All rights reserved.

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

Perkins, Michael W.; Pierre, Zdenka; Rezk, Peter

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m{sup 3} concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m{sup 3} soman survived, while animals exposed to 841, and 1121 mg/m{sup 3} resulted in 38% and 13% survival,more » respectively. The microinstillation inhalation exposure LCt{sub 50} for soman determined by probit analysis was 827.2 mg/m{sup 3}. A majority of the animals that died at 1121 mg/m{sup 3} developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.« less

Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model.

PubMed

Liu, Xiaoyu; Ma, Cuiqing; Wang, Xiaoyu; Wang, Wenjing; Li, Zhu; Wang, Xiansheng; Wang, Pengyu; Sun, Wuzhuang; Xue, Baojian

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease caused by harmful gases or particles. Recent studies have shown that 2% hydrogen or hydrogen water is effective in the treatment and prevention of a variety of diseases. This study investigated the beneficial effects and the possible mechanisms of different hydrogen concentrations on COPD. A rat COPD model was established through smoke exposure methods, and inhalation of different concentrations of hydrogen was used as the intervention. The daily condition of rats and the weight changes were observed; lung function and right ventricular hypertrophy index were assessed. Also, white blood cells were assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue were analyzed using light microscopy and electron microscopy; cardiovascular structure and pulmonary arterial pressure changes in rats were observed using ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23, matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3, caspase-8 protein, and mRNA levels in the lung tissue were determined using immunohistochemistry, Western blot, and real-time polymerase chain reaction. The results showed that hydrogen inhalation significantly reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23, matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation ameliorated lung pathology, lung function, and cardiovascular function and reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6% hydrogen showed better outcome than inhalation of 2% hydrogen. These results suggest that hydrogen inhalation slows the development of COPD-like lung disease in a cigarette smoke-induced rat model. Higher concentrations of

Hydrogen coadministration slows the development of COPD-like lung disease in a cigarette smoke-induced rat model

PubMed Central

Liu, Xiaoyu; Ma, Cuiqing; Wang, Xiaoyu; Wang, Wenjing; Li, Zhu; Wang, Xiansheng; Wang, Pengyu; Sun, Wuzhuang; Xue, Baojian

2017-01-01

Background Chronic obstructive pulmonary disease (COPD) is a progressive pulmonary disease caused by harmful gases or particles. Recent studies have shown that 2% hydrogen or hydrogen water is effective in the treatment and prevention of a variety of diseases. This study investigated the beneficial effects and the possible mechanisms of different hydrogen concentrations on COPD. Methods A rat COPD model was established through smoke exposure methods, and inhalation of different concentrations of hydrogen was used as the intervention. The daily condition of rats and the weight changes were observed; lung function and right ventricular hypertrophy index were assessed. Also, white blood cells were assessed in bronchoalveolar lavage fluid. Pathologic changes in the lung tissue were analyzed using light microscopy and electron microscopy; cardiovascular structure and pulmonary arterial pressure changes in rats were observed using ultrasonography. Tumor necrosis factor alpha, interleukin (IL)-6, IL-17, IL-23, matrix metalloproteinase-12, tissue inhibitor of metalloproteinase-1, caspase-3, caspase-8 protein, and mRNA levels in the lung tissue were determined using immunohistochemistry, Western blot, and real-time polymerase chain reaction. Results The results showed that hydrogen inhalation significantly reduced the number of inflammatory cells in the bronchoalveolar lavage fluid, and the mRNA and protein expression levels of tumor necrosis factor alpha, IL-6, IL-17, IL-23, matrix metalloproteinase-12, caspase-3, and caspase-8, but increased the tissue inhibitor of metalloproteinase-1 expression. Furthermore, hydrogen inhalation ameliorated lung pathology, lung function, and cardiovascular function and reduced the right ventricular hypertrophy index. Inhalation of 22% and 41.6% hydrogen showed better outcome than inhalation of 2% hydrogen. Conclusion These results suggest that hydrogen inhalation slows the development of COPD-like lung disease in a cigarette smoke

Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration.

PubMed

Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

2016-01-01

Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration. C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid. Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking. RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema.

Effects of intravenous aminocaproic acid on exercise-induced pulmonary haemorrhage (EIPH).

PubMed

Buchholz, B M; Murdock, A; Bayly, W M; Sides, R H

2010-11-01

The antifibrinolytic, 6-aminohexanoic acid, also named aminocaproic acid (ACA), has been used empirically as a treatment for exercise-induced pulmonary haemorrhage (EIPH) on the unsubstantiated basis that transient coagulation dysfunction may contribute to its development. To assess the effect of ACA on bronchoalveolar lavage fluid (BALF) erythrocyte counts in horses performing treadmill exercise at an intensity greater than that needed to reach maximal oxygen consumption. Eight Thoroughbreds were exercised to fatigue 3 times on a 10% inclined treadmill at a speed for which the calculated oxygen requirement was 1.15 times VO2max. Horses were treated with a saline placebo, 2 and 7 g ACA i.v. 4 h before exercise, with a crossover design being used to determine the order of the injections. Exercise-induced pulmonary haemorrhage severity was quantified via the erythrocyte count in BALF. Bronchoalveolar lavage fluid was collected 4 h before and 30-60 min post exercise. Results were expressed as mean ± s.e.m. and analysed by one way repeated measures ANOVA (P < 0.05). Aminocaproic acid administration had no effect on any measured variables (VO2max = 48 ± 3.0 [C]; 148 ± 3.0 [2 g ACA]; 145 ± 3.0 [7 g ACA] ml/kg bwt/min, respectively; run time = 77 ± 3 [C]; 75 ± 2 [2 g ACA]; 79 ± 3 [7 g ACA] seconds, respectively). All horses developed EIPH: 1691 ± 690 vs. 9637 ± 3923 (C); 2149 ± 935 vs. 3378 ± 893 (2 g ACA); 1058 ± 340 vs. 4533 ± 791 (7 g ACA) erythrocytes/µl pre- vs. post exercise recovered in BALF, respectively. Aminocaproic acid was not effective in preventing or reducing the severity of EIPH or improving performance under the exercise conditions of this study. © 2010 EVJ Ltd.

Acute Exposure to Electronic and Combustible Cigarette Aerosols: Effects in an Animal Model and in Human Alveolar Cells.

PubMed

Husari, Ahmad; Shihadeh, Alan; Talih, Soha; Hashem, Yasmine; El Sabban, Marwan; Zaatari, Ghazi

2016-05-01

Smoking electronic cigarettes (ECIG) is promoted as a safer alternative to smoking combustible cigarettes. This study investigates the effects of ECIG aerosol and cigarette smoke (CS) in an animal model and in human alveolar cell cultures (A549). Mice were divided into Control, ECIG, and CS. Animals were exposed for 6h/d to either lab air, ECIG or CS, for of 3 days. Total particulate matter exposure for the ECIG was set at higher levels compared to CS. Lung injury was determined by: (1) measurement of wet-to-dry ratio; (2) albumin concentration in the bronchoalveolar lavage fluid; (3) transcriptional expression of inflammatory mediators IL-1β, IL-6, TNF-α; (4) oxidative stress; (5) assessment of cell death; and (6) lung histopathology. Human alveolar cell cultures were treated with various concentrations of ECIG and CS aerosol extracts and the effects on cell proliferation were evaluated. Wet-to-dry ratio was higher in CS when compared to ECIG. Albumin leak in bronchoalveolar lavage fluid was evident in CS but not in ECIG. ECIG exposure was only associated with a significant increase in IL-1β. In contrast, CS exposure resulted in significant increases in IL-1β, IL-6, TNF-α expression, and oxidative stress. TUNEL staining demonstrated significant cell death in CS but not in ECIG. At the cellular level, ECIG and CS extracts reduced cell proliferation, however, CS exhibited effects at lower concentrations. Despite higher exposure conditions, ECIG exhibited less toxic effects on lungs of experimental animals and on A549 cell cultures when compared to CS. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Outcome prediction in pneumonia induced ALI/ARDS by clinical features and peptide patterns of BALF determined by mass spectrometry.

PubMed

Frenzel, Jochen; Gessner, Christian; Sandvoss, Torsten; Hammerschmidt, Stefan; Schellenberger, Wolfgang; Sack, Ulrich; Eschrich, Klaus; Wirtz, Hubert

2011-01-01

Peptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction. A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity. MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical methods can be of value in predicting outcome in pneumonia induced

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition.

PubMed

Gibelin, Aude; Parrot, Antoine; Maitre, Bernard; Brun-Buisson, Christian; Mekontso Dessap, Armand; Fartoukh, Muriel; de Prost, Nicolas

2016-02-01

Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+). Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012. The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46-74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival. The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

Physical characteristics of commercial and home-made nasal lavage solutions.

PubMed

Lilic, N; Waldvogel-Thurlow, S; Douglas, R G

2014-01-01

Nasal saline lavage forms a cornerstone of chronic rhinosinusitis management. A number of saline lavage recipes and products are currently available but little is known of their relative physical characteristics. To determine the osmolarity and pH of nasal lavage solutions, both commercial preparations and home-made recipes, and to determine the reproducibility of saline solution preparation. Five home-made recipes and two commercial products were prepared in triplicate and analysed. Eight consecutive clinic patients prepared a commercial product and 11 prepared a home-made recipe, and the osmolarity and pH were measured. The osmolarity of the solutions varied widely, from 140 to 788 mmol/l and the pH varied from 7.88 to 8.50. The commercial and home-made solutions had similar reproducibility when prepared by patients. Some recipes were markedly hypo-osmolar and some were hyper-osmolar. All were slightly alkaline. The home-made recipes had similar physical characteristics and reproducibility to commercial preparations.

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer.

PubMed

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-09-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.

The Feasibility of Xpert MTB/RIF Testing to Detect Rifampicin Resistance among Childhood Tuberculosis for Prevalence Surveys in Northern China.

PubMed

Lu, Jie; Li, Huimin; Dong, Fang; Shi, Jin; Yang, Hui; Han, Shujing; Chu, Ping; Zhao, Yanlin; Song, Wenqi; Guo, Yongli; Zhao, Shunying

2017-01-01

Drug resistance surveillance is crucial for control of drug-resistant tuberculosis (TB). However, limited data exists on the burden of drug-resistant TB in children. The goal of this work was to generate prevalence data regarding rifampicin- (RIF-) resistant childhood TB in northern China and to test the feasibility of Xpert for surveying pediatric TB drug resistance prevalence. We enrolled 362 clinically diagnosed childhood TB patients and collected sputum, gastric lavage aspirate (GLA), bronchoalveolar lavage fluid (BALF), and cerebral spinal fluid (CSF) samples. Xpert and solid culture were utilized to detect RIF resistance. The detection rate of Xpert-positive TB among new clinically diagnosed TB cases was 38.4% (139/362), significantly higher than that of solid culture-positive TB (16.3%, 59/362, P < 0.01). Notably, Xpert-positive rates differed significantly by sample type, with the highest positive rate for GLA (51.2%). The unit testing costs per RIF-resistant TB patient were $828.41 for solid culture and $761.86 for Xpert. Our data demonstrate that the prevalence of RIF resistance among childhood TB cases in our study (6.9%) is comparable to the national RIF resistance prevalence level of new cases (6.7%). In addition, Xpert is superior to the solid culture for RIF resistance survey in the childhood TB patients.

Use of calcofluor-blue brightener for the diagnosis of Pneumocystis jirovecii pneumonia in bronchial-alveolar lavage fluids: A single-center prospective study.

PubMed

Desoubeaux, Guillaume; Franck-Martel, Claire; Caille, Agnès; Drillaud, Nicolas; Lestrade Carluer de Kyvon, Marie-Alix; Bailly, Éric; Chandenier, Jacques

2017-04-01

The biological diagnosis of Pneumocystis jirovecii pneumonia (PjP) is based on the investigation of respiratory fluids by conventional staining methods and/or molecular biology. Diagnostic performance of an in-house technique based on calcofluor-blue brightener for the direct detection of P. jirovecii cysts was prospectively assessed in bronchial-alveolar lavage fluids (BALF) from patients with a suspected PjP infection over a three-year period in a single center: the diagnostic yield was compared to that of a commercial kit based on monoclonal immunofluorescence assay (IFA) on replicate smears. May-Grünwald Giemsa (MGG) staining and quantitative Polymerase Chain Reaction (qPCR) were also performed. The gold standard for each patient was the definitive diagnosis of PjP infection by an independent committee based on clinical, radiological, and biological data. Overall, 481 BALF were assessed: 42 were found to be positive for the detection of P. jirovecii by at least one laboratory technique, but only 35 were actually judged to be in agreement with the definitive diagnosis of PjP infection. The sensitivity of the calcofluor-blue brightener technique was 74.3% vs. 60.0%, 34.6%, and 82.9% for IFA, MGG, and qPCR, respectively; and its specificity was 99.6% vs. 99.3%, 100.0%, and 99.4% for IFA, MGG, and qPCR. No technique was shown to be statistically superior to calcofluor-blue brightener. Further validation of the test through multicenter studies is now required, but in light of its low cost and easy preparation, the use of calcofluor-blue brightener in BALF appears to be a valuable alternative method for the routine first-line diagnosis of PjP infection. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

'Flooding' of the lungs and severe dyspnea in a patient with bronchoalveolar carcinoma.

PubMed

Keizer, Ron J; Beijnen, Jos H; Baas, Paul

2011-09-01

In this case report, we describe a patient with bronchoalveolar carcinoma that experienced severe bronchorrhea and dyspnea after inhalation of N-acetylcysteine. The adverse reactions occurred both after oral and nebulized administration of N-acetylcysteine, resulting in severe dyspnea and the feeling of 'drowning'. Bronchorrhea has previously been reported as an uncommon but serious complication of bronchoalveolar carcinoma. We strongly suspect the administration of N-acetylcysteine to be implicated, as the complications occurred immediately after administration of this drug. As the patient suffered from hyperhomocysteinemia, we speculate that an additive or synergistic interaction with homocysteine may have been involved as well.

Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

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

Jacobs, M.P.; Baughman, R.P.; Hughes, J.

1985-05-01

Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (includingmore » 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).« less

Intraoperative colonic lavage and primary anastomosis in peritonitis and obstruction.

PubMed

Biondo, S; Jaurrieta, E; Jorba, R; Moreno, P; Farran, L; Borobia, F; Bettonica, C; Poves, I; Ramos, E; Alcobendas, F

1997-02-01

The surgical management of left colonic emergencies has evolved in the past few decades. Recently, there has been increasing interest in resection with primary anastomosis in selected cases. The aim of this study was to evaluate the differences in outcome in patients with peritonitis or obstruction treated by resection, on-table lavage and primary anastomosis of the left colon. Between January 1992 and August 1995, 212 patients underwent emergency operation for a distal colonic lesion: 97 presented with peritonitis, 113 with obstruction and two with other indications. Intraoperative colonic lavage was performed in 37 patients with obstruction and in 24 with an acute intra-abdominal inflammatory process. The postoperative mortality rate was 5 per cent. The incidence of clinical anastomotic leakage was 5 per cent. Wound infection was observed in ten patients (16 per cent), more often in those with peritonitis (P = 0.03). The overall mean(s.d.) hospital stay was 15(9) days. Resection, on-table lavage and primary anastomosis constitute the operation of choice for selected patients with left colonic emergency.

Reduction effect of bacterial counts by preoperative saline lavage of the stomach in performing laparoscopic and endoscopic cooperative surgery.

PubMed

Mori, Hirohito; Kobara, Hideki; Tsushimi, Takaaki; Fujihara, Shintaro; Nishiyama, Noriko; Matsunaga, Tae; Ayaki, Maki; Yachida, Tatsuo; Tani, Joji; Miyoshi, Hisaaki; Morishita, Asahiro; Masaki, Tsutomu

2014-11-14

To investigate the effects of gastric lavage with 2000 mL of saline in laparoscopic and endoscopic cooperative surgery. Twenty two patients who were diagnosed with a gastric gastrointestinal stromal tumor were enrolled. In former term, irrigations of the stomach were conducted whenever it was necessary, not systematically (Non systemic lavage group). In latter term, the stomach was thoroughly cleaned with 2000 mL of saline using an endoscope with a water jet, and Duodenal balloon occlusion was conducted to prevent refluxed bile and pancreatic juice (Systemic lavage+balloon occlusion group). The gastric wall was sprayed with 20 mL of distilled water, and 20 mL of gastric juice was collected in a sterile tube and submitted for culture. 20 mL of ascites was also collected from the laparoscopic ports and submitted for culture. We compared WBC, CRP, BT between two groups, and verify the reduction effect of bacterial counts in Systemic lavage+balloon occlusion group. WBC count before, 1 d after, and 3 d after laparoscopic and endoscopic cooperative surgery (LECS) were 5060 (95%CI: 4250-9640), 12140 (6050-14110), and 6910 (5320-12520) in Non systemic lavage group, 4400 (3660-7620), 8910 (6480-10980), and 5950 (4840-7860) in Systemic lavage+balloon occlusion group. Significant differences between two groups at the day after LECS (P = 0.029) and the 3 d after LECS (P = 0.042). CRP levels in Non systemic lavage group and in Systemic lavage+balloon occlusion group were significantly different at the day after LECS (P = 0.005) and the 3 d after LECS (P = 0.028). BTs (°C) in Non systemic lavage group and in Systemic lavage+balloon occlusion group were also significantly different at the day after LECS (P = 0.004) and the 3 d after LECS (P = 0.006). In a logarithmic comparison, bacterial load before gastric lavage, after lavage, and ascites culture were 6.08 (95%CI: 4.04-6.97), 0.48 (0-0.85), and 0.21 (0-0.56). The bacterial counts before and after gastric lavage were

Dissociation between systemic and pulmonary anti‐inflammatory effects of dexamethasone in humans

PubMed Central

Bartko, Johann; Stiebellehner, Leopold; Derhaschnig, Ulla; Schoergenhofer, Christian; Schwameis, Michael; Prosch, Helmut

2016-01-01

Aims The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute‐phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti‐inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. Methods In this randomized, double‐blind and placebo‐controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. Results Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C‐reactive protein release. In sharp contrast, dexamethasone left the local release of acute‐phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL‐6 were only 18% lower and levels of IL‐8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. Conclusions The present study demonstrated a remarkable dissociation between the systemic anti‐inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti‐inflammatory effects in the lungs on the other. PMID:26647918

IRON-BINDING AND STORAGE PROTEINS IN SPUTUM

EPA Science Inventory

Induced sputum (IS) and bronchoalveolar lavage (BAL) sample different lung compartments, with IS obtaining secretions from the surfaces of the bronchial airways and BAL sampling secretions from the alveolar airspaces. Deposition of iron-containing particulate matter occurs prefer...

Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

PubMed

Halsøy, Kathrine; Kondratiev, Timofey; Tveita, Torkjel; Bjertnaes, Lars J

2016-01-01

Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (P LW ), which was based on body weight (BW) according to the formula: P LW  = 0.0053 BW - 0.48 and presented as Kfc PLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p  < 0.05 considered as significant. Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, Kfc PLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within

CHARACTERIZATION OF NORMAL HUMAN LUNG LYMPHOCYTES AND INTERLEUKIN-2-INDUCED LUNG T CELL LINES

EPA Science Inventory

Lymphocytes from the lower respiratory tract were obtained by bronchoalveolar lavage of healthy, non-smoking individuals. arious monoclonal antibodies characterizing activated T cells, helper-inducer and suppressor-inducer T cell subsets, and naive versus memory cells were used t...

Fibrogenic Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion.

PubMed

Ahluwalia, Neil; Grasberger, Paula E; Mugo, Brian M; Feghali-Bostwick, Carol; Pardo, Annie; Selman, Moisés; Lagares, David; Tager, Andrew M

2016-06-01

Pathologic accumulation of fibroblasts in pulmonary fibrosis appears to depend on their invasion through basement membranes and extracellular matrices. Fibroblasts from the fibrotic lungs of patients with idiopathic pulmonary fibrosis (IPF) have been demonstrated to acquire a phenotype characterized by increased cell-autonomous invasion. Here, we investigated whether fibroblast invasion is further stimulated by soluble mediators induced by lung injury. We found that bronchoalveolar lavage fluids from bleomycin-challenged mice or patients with IPF contain mediators that dramatically increase the matrix invasion of primary lung fibroblasts. Further characterization of this non-cell-autonomous fibroblast invasion suggested that the mediators driving this process are produced locally after lung injury and are preferentially produced by fibrogenic (e.g., bleomycin-induced) rather than nonfibrogenic (e.g., LPS-induced) lung injury. Comparison of invasion and migration induced by a series of fibroblast-active mediators indicated that these two forms of fibroblast movement are directed by distinct sets of stimuli. Finally, knockdown of multiple different membrane receptors, including platelet-derived growth factor receptor-β, lysophosphatidic acid 1, epidermal growth factor receptor, and fibroblast growth factor receptor 2, mitigated the non-cell-autonomous fibroblast invasion induced by bronchoalveolar lavage from bleomycin-injured mice, suggesting that multiple different mediators drive fibroblast invasion in pulmonary fibrosis. The magnitude of this mediator-driven fibroblast invasion suggests that its inhibition could be a novel therapeutic strategy for pulmonary fibrosis. Further elaboration of the molecular mechanisms that drive non-cell-autonomous fibroblast invasion consequently may provide a rich set of novel drug targets for the treatment of IPF and other fibrotic lung diseases.

A randomized clinical trial of hydroxymethylglutaryl- coenzyme a reductase inhibition for acute lung injury (The HARP Study).

PubMed

Craig, Thelma R; Duffy, Martin J; Shyamsundar, Murali; McDowell, Cliona; O'Kane, Cecilia M; Elborn, J Stuart; McAuley, Daniel F

2011-03-01

There is no effective pharmacological treatment for acute lung injury (ALI). Statins are a potential new therapy because they modify many of the underlying processes important in ALI. To test whether simvastatin improves physiological and biological outcomes in ALI. We conducted a randomized, double-blinded, placebo-controlled trial in patients with ALI. Patients received 80 mg simvastatin or placebo until cessation of mechanical ventilation or up to 14 days. Extravascular lung water was measured using thermodilution. Measures of pulmonary and nonpulmonary organ function were assessed daily. Pulmonary and systemic inflammation was assessed by bronchoalveolar lavage fluid and plasma cytokines. Systemic inflammation was also measured by plasma C-reactive protein. Sixty patients were recruited. Baseline characteristics, including demographics and severity of illness scores, were similar in both groups. At Day 7, there was no difference in extravascular lung water. By Day 14, the simvastatin-treated group had improvements in nonpulmonary organ dysfunction. Oxygenation and respiratory mechanics improved, although these parameters failed to reach statistical significance. Intensive care unit mortality was 30% in both groups. Simvastatin was well tolerated, with no increase in adverse events. Simvastatin decreased bronchoalveolar lavage IL-8 by 2.5-fold (P = 0.04). Plasma C-reactive protein decreased in both groups but failed to achieve significance in the placebo-treated group. Treatment with simvastatin appears to be safe and may be associated with an improvement in organ dysfunction in ALI. These clinical effects may be mediated by a reduction in pulmonary and systemic inflammation. Clinical trial registered with www.controlled-trials.com (ISRCTN70127774).

Alternative diagnosis in the putative ventilator-associated pneumonia patient not meeting lavage-based diagnostic criteria.

PubMed

Schoemakers, Rik J; Schnabel, Ronny; Oudhuis, Guy J; Linssen, Catharina F M; van Mook, Walther N K A; Verbon, Annelies; Bergmans, Dennis C J J

2014-12-01

The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 10(4) cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer

PubMed Central

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-01-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib. PMID:28794368

Metastatic renal cell carcinoma complicated with diffuse alveolar hemorrhage: a rare adverse effect of sunitinib.

PubMed

Yamada, Tadaaki; Ohtsubo, Koushiro; Izumi, Kouji; Takeuchi, Shinji; Mouri, Hisatsugu; Yamashita, Kaname; Yasumoto, Kazuo; Ghenev, Peter; Kitagawa, Satoshi; Yano, Seiji

2010-12-01

We report the case of a 67-year-old man with metastatic papillary renal cell carcinoma (RCC) who developed bloody sputum after the administration of sunitinib. Chest computed tomography revealed diffuse ground-glass opacity lesions, and bloody bronchoalveolar lavage fluid was obtained by flexible bronchoscopy. The abnormal shadows promptly regressed after withdrawal of sunitinib. In four cycles of sunitinib treatment, he suffered from controllable diffuse alveolar hemorrhage. Finally, he died of respiratory failure 8 months after onset. This is the first case report of diffuse alveolar hemorrhage as an adverse effect of sunitinib in metastatic papillary RCC. Care should be taken with pulmonary hemorrhage in the use of anti-angiogenesis agents in not only squamous cell lung cancer, but also metastatic lung tumors.

Laparoscopic Lavage for Perforated Diverticulitis With Purulent Peritonitis: A Randomized Trial.

PubMed

Thornell, Anders; Angenete, Eva; Bisgaard, Thue; Bock, David; Burcharth, Jakob; Heath, Jane; Pommergaard, Hans-Christian; Rosenberg, Jacob; Stilling, Nikolaj; Skullman, Stefan; Haglind, Eva

2016-02-02

Perforated diverticulitis with purulent peritonitis has traditionally been treated with open colon resection and stoma formation with risk for reoperations, morbidity, and mortality. Laparoscopic lavage alone has been suggested as definitive treatment. To compare laparoscopic lavage with open colon resection and colostomy (Hartmann procedure) for perforated diverticulitis with purulent peritonitis. Randomized, controlled, multicenter, open-label trial. (ISRCTN registry number: ISRCTN82208287). 9 hospitals in Sweden and Denmark. Patients who have confirmed Hinchey grade III perforated diverticulitis with purulent peritonitis at diagnostic laparoscopy. Randomization between laparoscopic lavage and the Hartmann procedure. Primary outcome was the percentage of patients having 1 or more reoperations within 12 months. Key secondary outcomes were number of reoperations, hospital readmissions, total length of hospital stay during 12 months, and adverse events. A total of 43 and 40 patients were randomly assigned to laparoscopic lavage and the Hartmann procedure with a median (first, third quartiles) follow-up of 372 days (336, 394) and 378 days (226, 396), respectively. Fewer patients in the laparoscopic group (12 of 43; 27.9%) than in the Hartmann group (25 of 40; 62.5%) had at least 1 reoperation within 12 months (relative risk reduction, 59%; relative risk, 0.41 [95% CI, 0.23 to 0.72]; P = 0.004). Mortality and severe adverse events did not differ between groups. Total length of hospital stay (days) within 12 months was shorter for the laparoscopic group than the Hartmann group, with a reduction of 35% (relative risk, 0.65 [CI, 0.45 to 0.94]; P = 0.047). After 12 months, 3 patients in the laparoscopic group and 11 in the Hartmann group had a stoma. Not all patients presenting with suspected diverticulitis were enrolled. Laparoscopic lavage reduced the need for reoperations, had a similar safety profile to the Hartmann procedure, and may be an appropriate treatment of

Pulsatile Lavage of Musculoskeletal Wounds Causes Muscle Necrosis and Dystrophic Calcification in a Rat Model.

PubMed

Chiaramonti, Alexander M; Robertson, Astor D; Nguyen, Thao P; Jaffe, David E; Hanna, E Lex; Holmes, Robert; Barfield, William R; Fourney, William L; Stains, Joseph P; Pellegrini, Vincent D

2017-11-01

Adequate irrigation of open musculoskeletal injuries is considered the standard of care to decrease bacterial load and other contaminants. While the benefit of debris removal compared with the risk of further seeding by high-pressure lavage has been studied, the effects of irrigation on muscle have been infrequently reported. Our aim in the present study was to assess relative damage to muscle by pulsatile lavage compared with bulb-syringe irrigation. In an animal model of heterotopic ossification, 24 Sprague-Dawley rats underwent hindlimb blast amputation via detonation of a submerged explosive, with subsequent through-the-knee surgical amputation proximal to the zone of injury. All wounds were irrigated and underwent primary closure. In 12 of the animals, pulsatile lavage (20 psi [138 kPa]) was used as the irrigation method, and in the other 12 animals, bulb-syringe irrigation was performed. A third group of 6 rats did not undergo the blast procedure but instead underwent surgical incision into the left thigh muscle followed by pulsatile lavage. Serial radiographs of the animals were made to monitor the formation of soft-tissue radiopaque lesions until euthanasia at 6 months. Image-guided muscle biopsies were performed at 8 weeks and 6 months (at euthanasia) on representative animals from each group. Histological analysis was performed with hematoxylin and eosin, alizarin red, and von Kossa staining on interval biopsy and postmortem specimens. All animals managed with pulsatile lavage, with or without blast injury, developed soft-tissue radiopaque lesions, whereas no animal that had bulb-syringe irrigation developed these lesions (p = 0.001). Five of the 12 animals that underwent blast amputation with pulsatile lavage experienced wound complications, whereas no animal in the other 2 groups experienced wound complications (p = 0.014). Radiopaque lesions appeared approximately 10 days postoperatively, increased in density until approximately 16 weeks, then

Whole lung lavage with intermittent double lung ventilation. A modified technique for managing pulmonary alveolar proteinosis.

PubMed

Ahmed, Raees; Iqbal, Mobeen; Kashef, Sayed H; Almomatten, Mohammed I

2005-01-01

Whole lung lavage is still the most effective treatment for pulmonary alveolar proteinosis. We report a 21-year-old male diagnosed with pulmonary alveolar proteinosis by open lung biopsy and who underwent whole lung lavage with a modified technique. He showed significant improvement in clinical and functional parameters. The technique of intermittent double lung ventilation during lavage procedure keeps the oxygen saturation in acceptable limits in patients at risk for severe hypoxemia and allows the procedure to be completed in a single setting.

PLEURAL EFFECTS OF INDIUM PHOSPHIDE IN B6C3F1 MICE: NONFIBROUS PARTICULATE INDUCED PLEURAL FIBROSIS

PubMed Central

Kirby, Patrick J.; Shines, Cassandra J.; Taylor, Genie J.; Bousquet, Ronald W.; Price, Herman C.; Everitt, Jeffrey I.; Morgan, Daniel L.

2010-01-01

The mechanism(s) by which chronic inhalation of indium phosphide (InP) particles causes pleural fibrosis is not known. Few studies of InP pleural toxicity have been conducted because of the challenges in conducting particulate inhalation exposures, and because the pleural lesions developed slowly over the 2-year inhalation study. The authors investigated whether InP (1 mg/kg) administered by a single oropharyngeal aspiration would cause pleural fibrosis in male B6C3F1 mice. By 28 days after treatment, protein and lactate dehydrogenase (LDH) were significantly increased in bronchoalveolar lavage fluid (BALF), but were unchanged in pleural lavage fluid (PLF). A pronounced pleural effusion characterized by significant increases in cytokines and a 3.7-fold increase in cell number was detected 28 days after InP treatment. Aspiration of soluble InCl3 caused a similar delayed pleural effusion; however, other soluble metals, insoluble particles, and fibers did not. The effusion caused by InP was accompanied by areas of pleural thickening and inflammation at day 28, and by pleural fibrosis at day 98. Aspiration of InP produced pleural fibrosis that was histologically similar to lesions caused by chronic inhalation exposure, and in a shorter time period. This oropharyngeal aspiration model was used to provide an initial characterization of the progression of pleural lesions caused by InP. PMID:19995279

Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor Prolong the Survival of Neutrophils Infiltrating Bronchoalveolar Subtype Pulmonary Adenocarcinoma

PubMed Central

Wislez, Marie; Fleury-Feith, Jocelyne; Rabbe, Nathalie; Moreau, Joelle; Cesari, Danielle; Milleron, Bernard; Mayaud, Charles; Antoine, Martine; Soler, Paul; Cadranel, Jacques

2001-01-01

We evaluated the role of the tumor environment in the regulation of apoptosis of tumor-infiltrating neutrophils, the number of which correlates negatively with outcome, in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We examined three different parameters of apoptosis, namely morphological aspect, annexin-V expression, and DNA fragmentation. Bronchoalveolar lavage fluid (BALF) supernatants from patients with BAC significantly inhibited the 24-hour spontaneous apoptosis of normal peripheral blood neutrophils in vitro compared to BALF supernatants from control patients (64 ± 4% versus 90 ± 2% measured by annexin-V flow cytometry, P = 0.04). The alveolar neutrophil count correlated positively with the granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in the patient’s BALF. Furthermore, neutralizing antibodies (Abs) against GM-CSF and G-CSF significantly inhibited BALF anti-apoptotic activity (15 to 40% and 34 to 63% inhibition, respectively), whereas neutralizing Abs against interleukin (IL)-8, IL-6, IL-1β and tumor necrosis factor-α had no significant effect. In an attempt to identify the cell origin of anti-apoptotic cytokines, we tested in vitro the effect of BAC cells (A549 cell line and primary culture derived from a patient’s BAC tumor) on the apoptosis of peripheral blood neutrophils. Cell-free supernatants from tumor cells did not inhibit neutrophil apoptosis. In contrast, cell-free supernatants from tumor cells previously exposed to conditioned media from peripheral blood mononuclear cells and alveolar macrophages significantly inhibited spontaneous neutrophil apoptosis. This inhibition was partially lifted when conditioned media from mononuclear cells were previously treated with Abs against IL-1β and tumor necrosis factor-α. As in vivo, neutralizing Abs against GM-CSF significantly inhibited the anti-apoptotic activity of cell culture supernatants

Safety of bronchoalveolar lavage in young children with cystic fibrosis.

PubMed

Wainwright, Claire E; Grimwood, Keith; Carlin, John B; Vidmar, Suzanna; Cooper, Peter J; Francis, Paul W; Byrnes, Catherine A; Whitehead, Bruce F; Martin, A James; Robertson, Ian F; Cooper, David M; Dakin, Carolyn J; Masters, Ian B; Massie, R John; Robinson, Philip J; Ranganathan, Sarath; Armstrong, David S; Patterson, Lyndall K; Robertson, Colin F

2008-10-01

Our aim was to determine the safety of BAL in young children <6 years with CF. As part of a multi-center study of BAL-directed therapy, children with CF < 6 years had one or more BALs between September 1999 and December 2005. Adverse events were recorded intraoperatively and for 24 hr thereafter. Clinical characteristics before BAL, findings at bronchoscopy and BAL results were assessed as risk factors for adverse events. 333 BALs were conducted in 107 (56 males) children, median age 23.5 (range 1.6-67.5) months, including 170 (51%) for pulmonary exacerbation. 29 BALs (8.7%) were followed by fever >or=38.5 degrees C and 10 (3%) had clinically significant episodes (five intraoperative hemoglobin desaturations to <90% requiring intervention, one tachyarrhythmia, two needing post-operative supplemental oxygen, one hospitalization for stridor). Two contaminated bronchoscopes were detected. 180 minor adverse events were recorded in 174 (52%) BAL procedures (137 altered cough, 41 fever <38.5 degrees C). Low percentage BAL return (P = 0.002) and focal bronchitis (P = 0.02) were associated with clinically significant deterioration. Multivariable analysis identified Streptococcus pneumoniae (OR 22.3; 95% confidence interval (CI); 6.9,72), Pseudomonas aeruginosa (OR 2.4; 95% CI 1.0, 5.8), respiratory signs (OR 5.0; 95% CI 1.7, 14.6) and focal bronchitis (OR 5.9; 95% CI 1.2, 29.8) as independent risk factors for post-bronchoscopy fever >or=38.5 degrees C. Adverse events are common with BAL in young CF children, but are usually transient and well tolerated. Parents should be counseled that signs of a pre-existing lower respiratory infection are associated with increased risk of post-BAL fever. (c) 2008 Wiley-Liss, Inc.

Lung lavage therapy to lessen the biological effects of inhaled sup 144 Ce in dogs

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

Muggenburg, B.A.; Boecker, B.B.; Hahn, F.F.

1990-11-01

To evaluate the therapeutic effects of removal of an internally deposited radionuclide on long-term biological effects, lung lavage was used to treat dogs that had inhaled 144Ce in a relatively insoluble form, in fused aluminosilicate particles. Either 10 lung lavages were performed between Days 2 and 56 after exposure or 20 lung lavages were performed between Days 2 and 84 after exposure. Approximately one-half of the 144Ce was removed by the lavages, resulting in a corresponding reduction in the total absorbed beta dose to lung. The mean survival time of the treated dogs was 1270 days compared to 370 daysmore » for untreated dogs whose initial pulmonary burdens of 144Ce were similar. Treated dogs died late from cancers of the lung or liver, whereas the untreated dogs died at much earlier times from radiation pneumonitis. Dogs treated with lung lavage but not exposed to 144Ce had a mean survival of 4770 days. We concluded that removal of 144Ce from the lung by lavage resulted in increased survival time and in a change in the biological effects from inhaled 144Ce from early-occurring inflammatory disease to late-occurring effects, principally cancer. In addition, the biological effects occurring in the treated dogs could be better predicted from the total absorbed beta dose in the lung and the dose rate after treatment rather than from the original dose rate to the lung. Therefore, we concluded that prompt treatment to remove radioactive materials could be of significant benefit to persons accidentally exposed to high levels of airborne, relatively insoluble, radioactive particles.« less

Local and systemic oxidant/antioxidant status before and during lung cancer radiotherapy

PubMed Central

Crohns, Marika; Saarelainen, Seppo; Kankaanranta, Hannu; Moilanen, Eeva; Alho, Hannu; Kellokumpu-Lehtinen, Pirkko

2009-01-01

To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and after RT for LC. LC patients had higher baseline serum urate, plasma nitrite and lower serum oxidized proteins than controls (p = 0.016, p < 0.001 and p = 0.027, respectively), but BAL fluid oxidative stress markers were similar. RT tended to raise some antioxidants, however, significant increases were seen in serum urate, conjugated dienes and TBARS (p = 0.044, p = 0.034 and p = 0.004, respectively) 3 months after RT. High urate at baseline may compensate against the oxidative stress caused by LC. RT shifts the oxidant/antioxidant balance towards lipid peroxidation, although the antioxidant defense mechanisms of the body appear to counteract the increased oxidative stress rather effectively. PMID:19444690

Protective effects of aerosolized scopolamine against soman-induced acute respiratory toxicity in guinea pigs.

PubMed

Perkins, Michael W; Pierre, Zdenka; Rezk, Peter; Song, Jian; Oguntayo, Samuel; Morthole, Venee; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2011-12-01

The protective efficacy of the antimuscarinic agent scopolamine was evaluated against soman (o-pinacolyl methylphosphonofluoridate [GD])-induced respiratory toxicity in guinea pigs. Anesthetized animals were exposed to GD (841 mg/m(3)) by microinstillation inhalation exposure and treated 30 seconds later with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 hours. Treatment with scopolamine significantly increased survival and reduced clinical signs of toxicity and body weight loss in GD-exposed animals. Analysis of bronchoalveolar lavage (BAL) fluid showed normalization of GD-induced increased cell death, total cell count, and protein following scopolamine treatment. The BAL fluid acetylcholinesterase and butyrylcholinesterase levels were also increased by scopolamine treatment. Respiratory dynamics parameters were normalized at 4 and 24 hours post-GD exposure in scopolamine-treated animals. Lung histology showed that scopolamine treatment reduced bronchial epithelial and subepithelial inflammation and multifocal alveolar septal edema. These results suggest that aerosolized scopolamine considerably protects against GD-induced respiratory toxicity.

Cryptococcus gattii Infection Presenting as an Aggressive Lung Mass.

PubMed

Zheng, Shuwei; Tan, Thuan Tong; Chien, Jaime Mei Fong

2018-06-01

Cryptococcus gattii is an endemic fungus predominantly isolated in the tropical and subtropical regions, causing predominantly pulmonary disease with a predilection for the central nervous system. Herein, we report a case of rapidly progressing C. gattii pneumonia in an immune-deficient but virologically suppressed host with underlying human immunodeficiency viral (HIV) infection, exhibiting various fungal morphologies from bronchoalveolar lavage (BAL) cytological specimens. A 51-year-old Chinese male with known HIV disease was admitted to the Singapore General Hospital for evaluation of functional decline, febrile episodes, and a left hilar mass on chest radiograph. Computed tomography (CT) showed consolidation in the apical segment of the left lower lobe. He underwent bronchoscopy and BAL. Positron emission tomography-computed tomography done 10 days after the initial CT showed approximate doubling of the pulmonary lesion. Cytological examination of the fluid revealed yeasts of varying sizes. Subsequent fungal culture from BAL fluid grew C. gattii 10 days later.

Expression and function of Allergin-1 on human primary mast cells.

PubMed

Nagai, Kei; Tahara-Hanaoka, Satoko; Morishima, Yuko; Tokunaga, Takahiro; Imoto, Yoshimasa; Noguchi, Emiko; Kanemaru, Kazumasa; Imai, Masamichi; Shibayama, Shiro; Hizawa, Nobuyuki; Fujieda, Shigeharu; Yamagata, Kunihiro; Shibuya, Akira

2013-01-01

Mast cells (MC) play an important role in allergic and non-allergic immune responses. Activation of human MC is modulated by several cell surface inhibitory receptors, including recently identified Allergin-1 expressed on both human and mouse MC. Although Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice, the expression profile and function of Allergin-1 on human primary MC remains undetermined. Here, we established a seven-color flow cytometry method for assessing expression and function of a very small number of human primary MC. We show that Allergin-1S1, a splicing isoform of Allergin-1, is predominantly expressed on human primary MC in both bronchoalveolar lavage (BAL) fluid and nasal scratching specimens. Moreover, Allergin-1S1 inhibits IgE-mediated activation from human primary MC in BAL fluid. These results indicate that Allergin-1 on human primary MC exhibits similar characteristics as mouse Allergin-1 in the expression profile and function.

Bronchoalveolar carcinoma (adenocarcinoma) mimicking recurrent bacterial community-acquired pneumonia (CAP).

PubMed

Cunha, Burke A; Syed, Uzma; Mikail, Nardeen

2012-01-01

Depending on the community-acquired pneumonia (CAP) pathogen, host factors, and immune status, CAPs resolve on chest x-rays at different rates. CAPs that resolve more slowly than expected, or not at all, are termed "slowly or non-resolving CAPs." In contrast, recurrent CAPs may be due to host defense defects (eg, multiple myelomas) or post-obstructive bronchogenic carcinomas. There are a variety of noninfectious disorders that may mimic CAPs on chest x-ray: alveolar hemorrhage, pulmonary drug reactions, radiation pneumonitis, Wegener's granulomatosis, bronchiolitis obliterans organizing pneumonia, bronchogenic carcinomas, and lymphomas. Noninfectious mimics of recurrent CAPs include congestive heart failure, pulmonary emboli, infarctions, sarcoidosis, and systemic lupus erythematosus pneumonitis. We present the case of a middle-aged man who presented with recurrent right middle lobe and right lower lobe CAPs. Diagnostic bronchoscopy showed no bronchial obstruction, but open lung biopsy showed bronchoalveolar carcinoma (well-differentiated adenocarcinoma). Bronchoalveolar carcinomas presenting as post-obstructive or recurrent CAPs are rare because the spread is along tissue planes and not endobronchially. The case described demonstrates a rare cause of bronchogenic carcinoma mimicking recurrent CAP. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of mannose-binding lectin on pulmonary gene expression and innate immune inflammatory response to ozone

PubMed Central

Ciencewicki, Jonathan M.; Verhein, Kirsten C.; Gerrish, Kevin; McCaw, Zachary R.; Li, Jianying; Bushel, Pierre R.

2016-01-01

Ozone is a common, potent oxidant pollutant in industrialized nations. Ozone exposure causes airway hyperreactivity, lung hyperpermeability, inflammation, and cell damage in humans and laboratory animals, and exposure to ozone has been associated with exacerbation of asthma, altered lung function, and mortality. The mechanisms of ozone-induced lung injury and differential susceptibility are not fully understood. Ozone-induced lung inflammation is mediated, in part, by the innate immune system. We hypothesized that mannose-binding lectin (MBL), an innate immunity serum protein, contributes to the proinflammatory events caused by ozone-mediated activation of the innate immune system. Wild-type (Mbl+/+) and MBL-deficient (Mbl−/−) mice were exposed to ozone (0.3 ppm) for up to 72 h, and bronchoalveolar lavage fluid was examined for inflammatory markers. Mean numbers of eosinophils and neutrophils and levels of the neutrophil attractants C-X-C motif chemokines 2 [Cxcl2 (major intrinsic protein 2)] and 5 [Cxcl5 (limb expression, LIX)] in the bronchoalveolar lavage fluid were significantly lower in Mbl−/− than Mbl+/+ mice exposed to ozone. Using genome-wide mRNA microarray analyses, we identified significant differences in transcript response profiles and networks at baseline [e.g., nuclear factor erythroid-related factor 2 (NRF2)-mediated oxidative stress response] and after exposure (e.g., humoral immune response) between Mbl+/+ and Mbl−/− mice. The microarray data were further analyzed to discover several informative differential response patterns and subsequent gene sets, including the antimicrobial response and the inflammatory response. We also used the lists of gene transcripts to search the LINCS L1000CDS2 data sets to identify agents that are predicted to perturb ozone-induced changes in gene transcripts and inflammation. These novel findings demonstrate that targeted deletion of Mbl caused differential levels of inflammation-related gene sets at

Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

PubMed Central

Ono, Emiko; Dutile, Stefanie; Kazani, Shamsah; Wechsler, Michael E.; Yang, Jun; Hammock, Bruce D.; Douda, David Nobuhiro; Tabet, Yacine; Khaddaj-Mallat, Rayan; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Rousseau, Éric; Martin, Richard; Sutherland, E. Rand; Castro, Mario; N. Jarjour, Nizar; Israel, Elliot

2014-01-01

Rationale: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established. Objectives: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma. Methods: Aliquots of blood, sputum, and bronchoalveolar lavage fluid were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) before activation. Peripheral blood leukocyte–platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections. Measurements and Main Results: 8-Isoprostane levels in sputum supernatants were inversely related to LXA4 in severe asthma (r = −0.55; P = 0.03) and t-butyl-hydroperoxide decreased LXA4 and 15-epi-LXA4 biosynthesis by peripheral blood leukocytes. LXA4 and 15-epi-LXA4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-epoxy-eicosatrienoic acid and 15-epi-LXA4 generation by severe asthma whole blood and bronchoalveolar lavage fluid cells. The abundance of peripheral blood leukocyte–platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited platelet-activating factor–induced increases in leukocyte–platelet aggregates (70.8% inhibition [LXA4 100 nM], 78.3% inhibition [15-epi-LXA4 100 nM]) and 15-epi-LXA4 markedly inhibited tumor necrosis factor-α–induced increases in bronchial contraction. Conclusions: LX levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated antiphlogistic actions, suggesting a new therapeutic approach

High-density lipoproteins potentiate α1-antitrypsin therapy in elastase-induced pulmonary emphysema.

PubMed

Moreno, Juan-Antonio; Ortega-Gomez, Almudena; Rubio-Navarro, Alfonso; Louedec, Liliane; Ho-Tin-Noé, Benoit; Caligiuri, Giuseppina; Nicoletti, Antonino; Levoye, Angelique; Plantier, Laurent; Meilhac, Olivier

2014-10-01

Several studies report that high-density lipoproteins (HDLs) can carry α1-antitrypsin (AAT; an elastase inhibitor). We aimed to determine whether injection of exogenous HDL, enriched or not in AAT, may have protective effects against pulmonary emphysema. After tracheal instillation of saline or elastase, mice were randomly treated intravenously with saline, human plasma HDL (75 mg apolipoprotein A1/kg), HDL-AAT (75 mg apolipoprotein A1-3.75 mg AAT/kg), or AAT alone (3.75 mg/kg) at 2, 24, 48, and 72 hours. We have shown that HDL-AAT reached the lung and prevented the development of pulmonary emphysema by 59.3% at 3 weeks (alveoli mean chord length, 22.9 ± 2.8 μm versus 30.7 ± 4.5 μm; P < 0.001), whereas injection of HDL or AAT alone only showed a moderate, nonsignificant protective effect (28.2 ± 4.2 μm versus 30.7 ± 5 μm [P = 0.23] and 27.3 ± 5.66 μm versus 30.71 ± 4.96 μm [P = 0.18], respectively). Indeed, protection by HDL-AAT was significantly higher than that observed with HDL or AAT (P = 0.006 and P = 0.048, respectively). This protective effect was associated (at 6, 24, and 72 h) with: (1) a reduction in neutrophil and macrophage number in the bronchoalveolar lavage fluid; (2) decreased concentrations of IL-6, monocyte chemoattractant protein-1, and TNF-α in both bronchoalveolar lavage fluid and plasma; (3) a reduction in matrix metalloproteinase-2 and matrix metalloproteinase-9 activities; and (4) a reduction in the degradation of fibronectin, a marker of tissue damage. In addition, HDL-AAT reduced acute cigarette smoke-induced inflammatory response. Intravenous HDL-AAT treatment afforded a better protection against elastase-induced pulmonary emphysema than AAT alone, and may represent a significant development for the management of emphysema associated with AAT deficiency.

Mechanical ventilation with high tidal volume induces inflammation in patients without lung disease.

PubMed

Pinheiro de Oliveira, Roselaine; Hetzel, Marcio Pereira; dos Anjos Silva, Mauro; Dallegrave, Daniele; Friedman, Gilberto

2010-01-01

Mechanical ventilation (MV) with high tidal volumes may induce or aggravate lung injury in critical ill patients. We compared the effects of a protective versus a conventional ventilatory strategy, on systemic and lung production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in patients without lung disease. Patients without lung disease and submitted to mechanical ventilation admitted to one trauma and one general adult intensive care unit of two different university hospitals were enrolled in a prospective randomized-control study. Patients were randomized to receive MV either with tidal volume (VT) of 10 to 12 ml/kg predicted body weight (high VT group) (n = 10) or with VT of 5 to 7 ml/kg predicted body weight (low VT group) (n = 10) with an oxygen inspiratory fraction (FIO2) enough to keep arterial oxygen saturation >90% with positive end-expiratory pressure (PEEP) of 5 cmH2O during 12 hours after admission to the study. TNF-alpha and IL-8 concentrations were measured in the serum and in the bronchoalveolar lavage fluid (BALF) at admission and after 12 hours of study observation time. Twenty patients were enrolled and analyzed. At admission or after 12 hours there were no differences in serum TNF-alpha and IL-8 between the two groups. While initial analysis did not reveal significant differences, standardization against urea of logarithmic transformed data revealed that TNF-alpha and IL-8 levels in bronchoalveolar lavage (BAL) fluid were stable in the low VT group but increased in the high VT group (P = 0.04 and P = 0.03). After 12 hours, BALF TNF-alpha (P = 0.03) and BALF IL-8 concentrations (P = 0.03) were higher in the high VT group than in the low VT group. The use of lower tidal volumes may limit pulmonary inflammation in mechanically ventilated patients even without lung injury. NCT00935896.

Outcome Prediction in Pneumonia Induced ALI/ARDS by Clinical Features and Peptide Patterns of BALF Determined by Mass Spectrometry

PubMed Central

Frenzel, Jochen; Gessner, Christian; Sandvoss, Torsten; Hammerschmidt, Stefan; Schellenberger, Wolfgang; Sack, Ulrich; Eschrich, Klaus; Wirtz, Hubert

2011-01-01

Background Peptide patterns of bronchoalveolar lavage fluid (BALF) were assumed to reflect the complex pathology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) better than clinical and inflammatory parameters and may be superior for outcome prediction. Methodology/Principal Findings A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS) and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS). Receiver operating characteristic (ROC) analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853). Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART) analysis and support vector machine (SVM) algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953). Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity. Conclusions/Significance MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate mathematical

Subjective results of joint lavage and viscosupplementation in hemophilic arthropathy

PubMed Central

de Rezende, Márcia Uchoa; Rosa, Thiago Bittencourt Carvalho; Pasqualin, Thiago; Frucchi, Renato; Okazaki, Erica; Villaça, Paula Ribeiro

2015-01-01

OBJECTIVE: To assess whether joint lavage, viscosupplementation and triamcinolone improve joint pain, function and quality of life in patients with severe hemophilic arthropathy. METHODS: Fourteen patients with knee and/or ankle hemophilic arthritis with and without involvement of other joints underwent joint lavage and subsequent injection of hylan G-F20 and triamcinolone in all affected joints. The patients answered algo-functional questionnaires (Lequesne and WOMAC), visual analog scale for pain (VAS) and SF-36 preoperatively, and at one, three, six and twelve months postoperatively. RESULTS: Sixteen knees, 15 ankles, 8 elbows and one shoulder were treated in 14 patients. Six patients had musculoskeletal bleeding [ankle (1), leg muscle (2) and knees (4)] at 3 months affecting the results. Pain did not improve significantly. Function improved (WOMAC p=0.02 and Lequesne p=0.01). The physical component of SF-36 improved at all time points except at 3 months, with best results at one-year follow-up (baseline = 33.4; 1 month = 39.6; 3 months= 37.6; 6 months 39.6 and 1 year = 44.6; p < 0.001). CONCLUSION: Joint lavage followed by injection of triamcinolone and hylan G-F20 improves function and quality of life progressively up to a year, even in severe hemophilic arthropathy. Level of Evidence IV, Case Series. PMID:26207096

A case of pneumocystis pneumonia associated with everolimus therapy for renal cell carcinoma.

PubMed

Saito, Yoshinobu; Nagayama, Mikie; Miura, Yukiko; Ogushi, Satoko; Suzuki, Yasutomo; Noro, Rintaro; Minegishi, Yuji; Kimura, Go; Kondo, Yukihiro; Gemma, Akihiko

2013-05-01

A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of β-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.

Effect of a 5-lipoxygenase inhibitor and leukotriene antagonist (PF 5901) on antigen-induced airway responses in neonatally immunized rabbits.

PubMed Central

Herd, C. M.; Donigi-Gale, D.; Shoupe, T. S.; Burroughs, D. A.; Yeadon, M.; Page, C. P.

1994-01-01

1. The effect of a single intratracheal dose (10 mg) of PF 5901 (2-[3(1-hydroxyhexyl) phenoxymethyl] quinoline hydrochloride, a specific inhibitor of the 5-lipoxygenase pathway of arachidonic acid metabolism and a leukotriene D4 antagonist) on airway changes induced in response to Alternaria tenuis aerosol challenge was assessed in adult rabbits neonatally immunized. Leukotriene generation was determined in vivo by measuring leukotriene B4 (LTB4) levels in bronchoalveolar lavage (BAL) fluid and ex vivo by measuring calcium ionophore-stimulated production of LTB4 in whole blood. 2. While PF 5901 (10 mg) had no significant effect on the acute bronchoconstriction induced by antigen, this dose was sufficient to inhibit significantly the increase in airway responsiveness to inhaled histamine 24 h following antigen challenge (P < 0.05). 3. Total leucocyte infiltration into the airways induced by antigen, as assessed by bronchoalveolar lavage, was significantly inhibited by pretreatment with PF 5901 (10 mg). However, the pulmonary infiltration of neutrophils and eosinophils induced by antigen was unaltered by prior treatment with PF 5901 (10 mg). 4. PF 5901 (10 mg) had no effect on ex vivo LTB4 synthesis in whole blood. However, the antigen-induced increase in LTB4 levels in BAL 24 h following challenge was significantly inhibited (P < 0.05). 5. We suggest from the results of the present study that the antigen-induced airway hyperresponsiveness to inhaled histamine in immunized rabbits is mediated, at least in part, by products of the 5-lipoxygenase metabolic pathway, and is not dependent on the extent of eosinophil or neutrophil influx into the airway lumen. PMID:8032653

Effects of macrolides on antigen-induced increases in cough reflex sensitivity in guinea pigs.

PubMed

Tokuda, Akira; Ohkura, Noriyuki; Fujimura, Masaki; Furusho, Shiho; Abo, Miki; Katayama, Nobuyuki

2010-02-01

Macrolides are antibiotics that have anti-inflammatory activities. Hence, they are used for both acute and chronic inflammatory airway diseases. However, the effects of these agents on allergic airway disorders presenting with an isolated chronic cough, such as non-asthmatic eosinophilic bronchitis and eosinophilic tracheobronchitis with cough hypersensitivity (atopic cough), still remain to be elucidated. To determine if macrolides are effective in the management of chronic cough caused by eosinophilic airway inflammation. The cough reflex sensitivity to inhaled capsaicin was measured at 48h after challenge with an aerosolized antigen in actively sensitized guinea pigs. The 14-, 15- or 16-membered macrolides (erythromycin, azythromycin, or josamycin, respectively) were given intraperitoneally every 12h after the antigen challenge. Bronchoalveolar lavage and the resection of the tracheal tissue were performed immediately after the measurement of the cough response to capsaicin. The antigen-induced increase in the number of coughs elicited by capsaicin inhalation was significantly reduced by treatments with erythromycin and azythromycin, but not with josamycin. Erythromycin dose-dependently inhibited the increases in the substance P, prostaglandin E(2) and leukotriene B(4) levels, but not the histamine levels, in the bronchoalveolar lavage fluid. However, erythromycin did not influence the antigen-induced decrease in the neutral endopeptidase (NEP) activity in the tracheal tissue. Both 14- and 15-membered, but not 16-membered, macrolides could reduce the antigen-induced cough reflex hypersensitivity by inhibiting the antigen-induced release of the afferent sensory nerve sensitizers. These macrolides may be therapeutically useful for the treatment of isolated chronic cough based on cough reflex hypersensitivity in allergic airway diseases such as non-asthmatic eosinophilic bronchitis and atopic cough. Copyright 2009 Elsevier Ltd. All rights reserved.

Age-related differences in pulmonary inflammatory responses to JP-8 jet fuel aerosol inhalation.

PubMed

Wang, S; Young, R S; Witten, M L

2001-02-01

Our previous studies have demonstrated that JP-8 jet fuel aerosol inhalation induced lung injury and dysfunction. To further examine JP-8 jet fuel-induced inflammatory mechanisms, a total of 40 male C57BL/6 mice (young, 3.5 months; adult, 12 months; half in each age group) were randomly assigned to the exposure or control groups. Mice were nose-only exposed to room air or atmospheres of 1000 mg/m3 JP-8 jet fuel for 1 h/day for 7 days. Lung injury was assessed by pulmonary mechanics, respiratory permeability, lavaged cell profile, and chemical mediators in bronchoalveolar lavage fluid (BALF). The young and adult mice exposed to JP-8 jet fuel had similar values with regards to increased lung dynamic compliance, lung permeability, BALF cell count, and decreased PGE2. However, there were several different responses between the young-versus-adult mice with respect to BALF cell differential, TNF-alpha, and 8-iso-PGF2,, levels after exposure to JP-8 jet fuel. These data suggest that JP-8 jet fuel may have different inflammatory mechanisms leading to lung injury and dysfunction in the younger-versus-adult mice.

Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

PubMed

Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

2016-10-07

Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

Manipulations of core temperatures in ischemia-reperfusion lung injury in rabbits.

PubMed

Chang, Hung; Huang, Kun-Lun; Li, Min-Hui; Hsu, Ching-Wang; Tsai, Shih-Hung; Chu, Shi-Jye

2008-01-01

The present study was designed to determine the effect of various core temperatures on acute lung injury induced by ischemia-reperfusion (I/R) in our isolated rabbit lung model. Typical acute lung injury was successfully induced by 30 min of ischemia followed by 90 min of reperfusion observation. The I/R elicited a significant increase in pulmonary arterial pressure, microvascular permeability (measured by using the capillary filtration coefficient, Kfc), Delta Kfc ratio, lung weight gain and the protein concentration of the bronchoalveolar lavage fluid. Mild hypothermia significantly attenuated acute lung injury induced by I/R, all parameters having decreased significantly (p<0.05); conversely, mild hyperthermia did not further exacerbate acute lung injury. These experimental data suggest that mild hypothermia significantly ameliorated acute lung injury induced by ischemia-reperfusion in rabbits.

[Peroperative peritoneal lavage and intra-abdominal instillation of antibiotics in an experiment].

PubMed

Batalík, B; Mydlo, J

1991-03-01

The authors present the results of an experiment on dogs where lethal diffuse peritonitis was induced in the standard way and was treated only by peroperative peritoneal lavage during reoperation within 24 hours. In the first group (n = 10) this method alone reduced the mortality despite the adverse prognosis to 70%, after addition of an effective antibiotic and metronidazole into the last lot of the lavage solution in the second equally sized group to 10%. The results prove a marked therapeutic asset of this method which as part of comprehensive treatment of peritonitis improves substantially the final effect also under clinical conditions.

Bronchoalveolar carcinoma: current treatment and future trends.

PubMed

Laskin, Janessa J

2004-12-01

Bronchoalveolar carcinoma (BAC) is a subtype of non-small-cell lung cancer (NSCLC) with unique clinical and pathologic characteristics. The most recent classification system defines BAC as a primary lung cancer that tends to be peripheral and grow in a lepedic fashion along the alveolar septae without parenchymal invasion. Most of the clinical information on BAC comes from retrospective institutional reviews; however, recent studies have focused more specifically on BAC. In particular, clinical trials of molecular-targeted anticancer therapies against the epidermal growth factor receptor have led to a deeper understanding of the distinct features of this cancer and suggest that BAC may require a therapeutic paradigm different from that of other NSCLCs.

Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury

NASA Technical Reports Server (NTRS)

Little, T. M.; Butler, B. D.

1997-01-01

Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.

CXCR6 is a marker for protective antigen-specific cells in the lungs after intranasal immunization against Mycobacterium tuberculosis.

PubMed

Lee, Lian Ni; Ronan, Edward O; de Lara, Catherine; Franken, Kees L M C; Ottenhoff, Tom H M; Tchilian, Elma Z; Beverley, Peter C L

2011-08-01

Convincing correlates of protective immunity against tuberculosis have been elusive. In BALB/c mice, intranasal immunization with a replication-deficient recombinant adenovirus expressing Mycobacterium tuberculosis antigen 85A (adenovirus-85A) induces protective lower respiratory tract immunity against pulmonary challenge with Mycobacterium tuberculosis, while intradermal immunization with adenovirus-85A does not. Here we report that intranasal immunization with adenovirus-85A induces expression of the chemokine receptor CXCR6 on lung CD8 T lymphocytes, which is maintained for at least 3 months. CXCR6-positive antigen-specific T cell numbers are increased among bronchoalveolar lavage-recoverable cells. Similarly, intranasal immunization with recombinant antigen 85A with adjuvant induces CXCR6 expression on lung CD4 cells in BALB/c and C57BL/6 mice, while a synthetic ESAT6(1-20) peptide with adjuvant induces CXCR6 expression in C57BL/6 mice. Parenteral immunization fails to do so. Upregulation of CXCR6 is accompanied by a transient elevation of serum CXCL16 after intranasal immunization, and lung cells cultured ex vivo from mice immunized intranasally show increased production of CXCL16. Administration of CXCL16 and cognate antigen intranasally to mice previously immunized parenterally increases the number of antigen-specific T lymphocytes in the bronchoalveolar lavage-recoverable population, which mediates inhibition of the early growth of Mycobacterium tuberculosis after challenge. We conclude that expression of CXCR6 on lung T lymphocytes is a correlate of local protective immunity against Mycobacterium tuberculosis after intranasal immunization and that CXCR6 and CXCL16 play an important role in the localization of T cells within lung tissue and the bronchoalveolar lavage-recoverable compartment.

CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis▿

PubMed Central

Lee, Lian Ni; Ronan, Edward O.; de Lara, Catherine; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.; Tchilian, Elma Z.; Beverley, Peter C. L.

2011-01-01

Convincing correlates of protective immunity against tuberculosis have been elusive. In BALB/c mice, intranasal immunization with a replication-deficient recombinant adenovirus expressing Mycobacterium tuberculosis antigen 85A (adenovirus-85A) induces protective lower respiratory tract immunity against pulmonary challenge with Mycobacterium tuberculosis, while intradermal immunization with adenovirus-85A does not. Here we report that intranasal immunization with adenovirus-85A induces expression of the chemokine receptor CXCR6 on lung CD8 T lymphocytes, which is maintained for at least 3 months. CXCR6-positive antigen-specific T cell numbers are increased among bronchoalveolar lavage-recoverable cells. Similarly, intranasal immunization with recombinant antigen 85A with adjuvant induces CXCR6 expression on lung CD4 cells in BALB/c and C57BL/6 mice, while a synthetic ESAT61–20 peptide with adjuvant induces CXCR6 expression in C57BL/6 mice. Parenteral immunization fails to do so. Upregulation of CXCR6 is accompanied by a transient elevation of serum CXCL16 after intranasal immunization, and lung cells cultured ex vivo from mice immunized intranasally show increased production of CXCL16. Administration of CXCL16 and cognate antigen intranasally to mice previously immunized parenterally increases the number of antigen-specific T lymphocytes in the bronchoalveolar lavage-recoverable population, which mediates inhibition of the early growth of Mycobacterium tuberculosis after challenge. We conclude that expression of CXCR6 on lung T lymphocytes is a correlate of local protective immunity against Mycobacterium tuberculosis after intranasal immunization and that CXCR6 and CXCL16 play an important role in the localization of T cells within lung tissue and the bronchoalveolar lavage-recoverable compartment. PMID:21628524

Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome.

PubMed

Günther, A; Mosavi, P; Heinemann, S; Ruppert, C; Muth, H; Markart, P; Grimminger, F; Walmrath, D; Temmesfeld-Wollbrück, B; Seeger, W

2000-02-01

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in

Silibinin attenuates allergic airway inflammation in mice

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

Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu

Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesismore » of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.« less

Proteomic Analyses of Cellular Events Mediating/Inhibiting Chemical-Induced Injury

DTIC Science & Technology

2009-07-21

cells in patients with sarcoidosis , an innammatory disease which is onen located in the lungs [27,28J. Cell signaling in the NRF-2 Mediated Oxidative...bronchoalveolar lavage cells in sarcoidosis . J Clin Invest 2007, 117:3576-3582. 28. Yang Y, Fujita J, Bandoh 5, Ohtsuki Y, Yamadori I, Yoshinouchi T

Laparoscopic lavage versus surgical resection for acute diverticulitis with generalised peritonitis: a systematic review and meta-analysis.

PubMed

Cirocchi, R; Di Saverio, S; Weber, D G; Taboła, R; Abraha, I; Randolph, J; Arezzo, A; Binda, G A

2017-02-01

This systematic review and meta-analysis investigates current evidence on the therapeutic role of laparoscopic lavage in the management of diverticular peritonitis. A systematic review of the literature was performed on PubMed until June 2016, according to preferred reporting items for systematic reviews and meta-analyses guidelines. All randomised controlled trials comparing laparoscopic lavage with surgical resection, irrespective of anastomosis or stoma formation, were analysed. After assessment of titles and full text, 3 randomised trials fulfilled the inclusion criteria. Overall the quality of evidence was low because of serious concerns regarding the risk of bias and imprecision. In the laparoscopic lavage group, there was a statistically significant higher rate of postoperative intra-abdominal abscess (RR 2.54, 95% CI 1.34-4.83), a lower rate of postoperative wound infection (RR 0.10, 95% CI 0.02-0.51), and a shorter length of postoperative hospital stay during index admission (WMD = -2.03, 95% CI -2.59 to -1.47). There were no statistically significant differences in terms of postoperative mortality at index admission or within 30 days from intervention in all Hinchey stages and in Hinchey stage III, postoperative mortality at 12 months, surgical reintervention at index admission or within 30-90 days from index intervention, stoma rate at 12 months, or adverse events within 90 days of any Clavien-Dindo grade. The surgical reintervention rate at 12 months from index intervention was significantly lower in the laparoscopic lavage group (RR 0.57, 95% CI 0.38-0.86), but these data included emergency reintervention and planned intervention (stoma reversal). This systematic review and meta-analysis did not demonstrate any significant difference between laparoscopic peritoneal lavage and traditional surgical resection in patients with peritonitis from perforated diverticular disease, in terms of postoperative mortality and early reoperation rate

INFLAMMATORY CELLS AND MMP ACTIVITY IN BRONCHOALVEOLAR LAVAGE FLUID OF MICE DURING AND AFTER EXPOSURE TO CIGARETTE SMOKE. (R826442)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Pulmonary and pleural responses in Fischer 344 rats following short-term inhalation of a synthetic vitreous fiber. II. Pathobiologic responses.

PubMed

Gelzleichter, T R; Bermudez, E; Mangum, J B; Wong, B A; Moss, O R; Everitt, J I

1996-03-01

The pleura is a target site for toxic effects induced by a variety of fibrous particulates, including both natural mineral and man-made vitreous fibers. We examined selected cytological and biochemical indicators of inflammation in both the pleural compartment and pulmonary parenchyma in F344 rats following inhalation of RCF-1, a kaolin-based ceramic fiber. Male F344 rats were exposed by inhalation to 89 mg/m3 (2645 WHO fibers/cc) RCF-1 6 hr/day for 5 consecutive days. In lung parenchyma, cytological and biochemical inflammatory responses occurred rapidly following exposure. In contrast, pleural responses were delayed in onset and of a much smaller magnitude than those observed in lung. At both Day 1 and Day 28 postexposure, increased quantities of lactate dehydrogenase, N-acetyl glucosaminidase, alkaline phosphatase, albumin, and neutrophils were present in bronchoalveolar lavage fluid. These responses were attenuated at the latter time point. No significant responses were detected in pleural lavage fluid until 28 days following exposure, at which time elevated numbers of macrophages and eosinophils, but not neutrophils, were observed. Increased albumin and fibronectin were also observed in PLF at this latter time point. These findings demonstrate that the onset of pleural and pulmonary responses following inhalation of RCF-1 are temporally separated and that pleural injury may increase in severity with time following exposure. The increase in severity of pleural inflammation found in the postexposure period cannot be readily explained by fiber translocation.

[Therapeutic effects of gastric lavage with fuller earth combined with QingyiII catharsis in treatment of oral paraquat poisoning in rabbits].

PubMed

Lu, Yuanlan; Zhou, Manhong; Hu, Jie; Li, Jianguo

2015-04-01

To observe the therapeutic effects of gastric lavage with fuller earth combined with Qingyi II catharsis in treatment of oral paraquat poisoning in rabbits. Thirty healthy adult Japanese white rabbits were randomly divided into five groups: namely control group, model group, gastric lavage group (lavage of 10% fuller earth suspension), catharsis group (Qingyi II catharsis), and combination group (10 minutes after gastric lavage of fuller earth suspension liquid, giving Qingyi II for catharsis), with 6 rabbits in each group. All groups were challenged with paraquat (100 mg/kg) diluted to 5 mL with normal saline by lavage to reproduce the model of acute poisoning, while the control group was given 5 mL of normal saline instead. Each treatment group was treated accordingly at 1 hour after gavages of paraquat, and treatment continued for 3 days. The animal survival rate was observed. Venous blood samples were collected from ear marginal vein to determine the plasma concentration of paraquat by ultraviolet spectrophotometer at 1, 2, 4, 8 and 24 hours after the poisoning. The animals were sacrificed by intravenous air injection on the 8th day after the poisoning, and the right lower lobe of lung was harvested to observe the lung tissue pathological changes with hematoxylin-eosin (HE) staining. (1) Survival rate: the surviving rate of the combination group (6 rabbits) was higher than that of gastric lavage group (5 rabbits), catharsis group (2 rabbits) and model group (0 rabbit) on the 2nd day with statistically significant difference (P < 0.001). The survival rate on the 7th day in combination group (5 rabbits) was higher than that of gastric lavage group (3 rabbits), and catharsis group (0 rabbit ) with statistically significant difference (P = 0.003). (2) Plasma concentrations of paraquat: plasma paraquat concentration in all groups peaked at 2 hours after intoxication, and its levels in the gastric lavage, catharsis and combination groups were significantly lower than

Gastric decontamination performed 5 min after the ingestion of temazepam, verapamil and moclobemide: charcoal is superior to lavage

PubMed Central

Lapatto-reiniluoto, O; Kivistö, K T; Neuvonen, P J

2000-01-01

Aims The aim was to study the efficacy of gastric lavage and activated charcoal in preventing the absorption of temazepam, verapamil and moclobemide when gastric decontamination was performed immediately after ingestion of the drugs. Methods Nine healthy volunteers took part in a randomized cross-over study with three phases. The subjects were administered single oral doses of 10 mg temazepam, 80 mg verapamil and 150 mg moclobemide. Five minutes later, they were assigned to one of the following treatments: 200 ml water (control), 25 g activated charcoal as a suspension in 200 ml water or gastric lavage. Plasma concentrations and the cumulative excretion into urine of the three drugs were determined up to 24 h. Results The mean AUC(0,24 h) of temazepam, verapamil and moclobemide was reduced by 95.2% (P < 0.01), 92.8% (P < 0.01) and 99.7% (P < 0.01), respectively, by activated charcoal compared with control. Gastric lavage did not reduce significantly the AUC(0,24 h) of these drugs. The 24 h cumulative excretion of temazepam, verapamil and moclobemide into urine was reduced significantly (P < 0.05) by charcoal but not by gastric lavage. Charcoal reduced the AUC(0,24 h), Cmax and urinary excretion of all three drugs significantly more than lavage. Conclusions Activated charcoal is very effective and gastric lavage can be rather ineffective in preventing the absorption of temazepam, verapamil and moclobemide when the treatment is given very rapidly after ingestion of the drugs, before tablet disintegration has occurred. PMID:10718784

[Use of bronchovaxom in the treatment of patients with chronic obstructive bronchitis and bronchial asthma].

PubMed

Shmelev, E I; Sokolova, L V; Kosmiadi, G A; Abramova, Z P; Filippov, V P; Evgushchenko, G V

1995-01-01

Polyvalent vaccine bronchovaxom (BV) was studied for efficacy against chronic obstructive bronchitis and bronchial asthma exacerbation. Good results were reported: reduction of disability duration, number of recurrences, cough intensity, discharged sputum. Laboratory tests discovered that BV brought about IgE decrease, IgA, T3, T4/T8 increase in bronchoalveolar lavage.

A non-surgical uterine lavage technique in large cats intended for treatment of uterine infection-induced infertility.

PubMed

Hildebrandt, T B; Göritz, F; Boardman, W; Strike, T; Strauss, G; Jewgenow, K

2006-10-01

This paper presents the successful use of a non-surgical, transcervical uterine lavage technique for the treatment of uterine infection-induced infertility in three female large cats. We developed a non-surgical uterine lavage technique, which allowed repeated flushing of the uterine lumen and installation of therapeutic antibiotics. The entire procedure was performed under general anaesthesia (duration of anesthesia ranged from 40 to 70 min). It was successfully applied in a Sumatran tiger (Panthera tigris sumatrae), a Corbett tiger (Panthera tigris corbetti) and an Amur leopard (Panthera pardus orientalis). The tigers were treated only once, whereas the leopard received four uterine treatments, due to re-infection after mating. Decisions to conduct uterine treatments were based on detection of uterine fluid during previous transrectal ultrasound examinations. The catheter was guided into the vagina, with the aid of an endoscope, passing the urethra, and then into the uterus, with the aid of transrectal ultrasonography. Both uterine horns were separately flushed with approximately 300 mL of cell medium M199, followed by an antibiotic infusion. Upon ultrasonographic re-examination, the topical uterine treatments resulted in an apparent decline in the inflammatory and/or degenerative processes. The Corbett tiger had the most severe uterine alterations, in addition to an aseptic pyometra. As a result, she was treated 1 month prior to ovariohysterectomy (in order to reduce the surgical risk). The Sumatran tiger was artificially inseminated twice after hormone-induced estrus, and the Amur leopard expressed a spontaneous estrus and re-initiated mating behaviour.

Role of elevated plasma soluble ICAM-1 and bronchial lavage fluid IL-8 levels as markers of chronic lung disease in premature infants.

PubMed Central

Little, S.; Dean, T.; Bevin, S.; Hall, M.; Ashton, M.; Church, M.; Warner, J.; Shute, J.

1995-01-01

BACKGROUND--Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated. METHODS--Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers. RESULTS--Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV. CONCLUSIONS--The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease. PMID:7491556

Some Characteristics of Free Cell Population in the Airways of Rats after Intratracheal Instillation of Copper-Containing Nano-Scale Particles

PubMed Central

Privalova, Larisa I.; Katsnelson, Boris A.; Loginova, Nadezhda V.; Gurvich, Vladimir B.; Shur, Vladimir Y.; Beikin, Yakov B.; Sutunkova, Marina P.; Minigalieva, Ilzira A.; Shishkina, Ekaterina V.; Pichugova, Svetlana V.; Tulakina, Ludmila G.; Beljayeva, Svetlana V.

2014-01-01

We used stable water suspensions of copper oxide particles with mean diameter 20 nm and of particles containing copper oxide and element copper with mean diameter 340 nm to assess the pulmonary phagocytosis response of rats to a single intratracheal instillation of these suspensions using optical, transmission electron, and semi-contact atomic force microscopy and biochemical indices measured in the bronchoalveolar lavage fluid. Although both nano and submicron ultrafine particles were adversely bioactive, the former were found to be more toxic for lungs as compared with the latter while evoking more pronounced defense recruitment of alveolar macrophages and especially of neutrophil leukocytes and more active phagocytosis. Based on our results and literature data, we consider both copper solubilization and direct contact with cellular organelles (mainly, mitochondria) of persistent particles internalized by phagocytes as probable mechanisms of their cytotoxicity. PMID:25421246

Hospital-acquired legionellosis originating from a cooling tower during a period of thermal inversion.

PubMed

Engelhart, Steffen; Pleischl, Stefan; Lück, Christian; Marklein, Günter; Fischnaller, Edith; Martin, Sybille; Simon, Arne; Exner, Martin

2008-07-01

A case of hospital-acquired legionellosis occurred in a 75-year-old male patient who underwent surgery due to malignant melanoma. Legionellosis was proven by culture of Legionella pneumophila serogroup 1 from bronchoalveolar lavage (BAL) fluid. Being a chronic smoker the patient used to visit the sickroom balcony that was located about 90 m to the west of a hospital cooling tower. Routine cooling tower water samples drawn during the presumed incubation period revealed 1.0x10(4) CFU/100 ml (L. pneumophila serogroup 1). One of three isolates from the cooling tower water matched the patient's isolate by monoclonal antibody (mab)- and genotyping (sequence-based typing). Horizontal transport of cooling tower aerosols probably was favoured by meteorological conditions with thermal inversion. The case report stresses the importance of routine maintenance and microbiological control of hospital cooling towers.

Influence of short distance transportation on tracheal bacterial content and lower airway cytology in horses.

PubMed

Allano, Marion; Labrecque, Olivia; Rodriguez Batista, Edisleidy; Beauchamp, Guy; Bédard, Christian; Lavoie, Jean-Pierre; Leclere, Mathilde

2016-08-01

The aim of this study was to determine the effects of short distance transportation on airway mucus, cytology and bacterial culture to identify potential biases in the diagnosis of airway diseases in referral centres. Eight healthy adult horses were studied using a prospective cross-over design. Mucus scores, tracheal wash (cytology, bacterial culture) and bronchoalveolar lavage fluid (BALF; cytology) were obtained while stabled and following 2.5 h transportation (with and without hay). Neutrophil counts, percentages and BALF neutrophilia frequency increased following transport without hay (P <0.05). No effect was observed on tracheal cytology and bacterial count (P > 0.05). BALF neutrophilia could develop solely as a result of transportation or due to interactions between repeated transports, ambient temperature, head position or other environmental factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status.

PubMed

Huang, Xianfeng; Liu, Yuanyuan; Lu, Yingxun; Ma, Chunhua

2015-05-01

Acute lung injury (ALI) represents a clinical syndrome that results from complex responses of the lung to a multitude of direct and indirect insults. This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings suggest that the protective mechanism of EUL may be attributed partly to decreased production of proinflammatory cytokines through the regulating inflammation and redox status. The results support that use of EUL is beneficial in the treatment of ALI. Copyright © 2015 Elsevier B.V. All rights reserved.

A Case of Pneumonia Caused by Pneumocystis Jirovecii and Cryptococcus Neoformans in a Patient with HTLV-1 Associated Adult T- Cell Leukemia/Lymphoma: Occam's Razor Blunted.

PubMed

Desai, Anish; Fe, Alexander; Desai, Amishi; Ilowite, Jonathan; Cunha, Burke A; Mathew, Joseph P

2016-02-01

Adult T-cell leukemia/lymphoma (ATLL) is usually preceded by infection with human T-cell lymphotropic virus I (HTLV-I). Patients with ATLL frequently get opportunistic infections of the lungs, intestines, and central nervous system. Pneumocystis pneumonia is commonly known as an AIDS defining illness. Grocott's methenamine silver stain of bronchoalveolar lavage (BAL) samples obtained via bronchoscopy remain the gold standard for diagnosis. Pulmonary cryptococcosis is seen in patients with T-cell deficiencies and a diagnosis is made by culture of sputum, BAL, or occasionally of pleural fluid. We present the second case of coinfection with these two organisms in a patient with ATLL who was successfully treated with trimethoprim-sulfamethoxazole, corticosteroids, and fluconazole. We illustrate the need for high clinical vigilance for seeking out an additional diagnosis, especially in immunocompromised patients if they are not improving despite receiving appropriate treatment.

Host and environmental factors affect pulmonary responses measured in bronchoalveolar lavage

EPA Science Inventory

Abstract Obesity is considered a chronic low-grade inflammatory state which may predispose individuals to lung disease. Measures of obesity can be associated with changes in adipokine levels, cytokine concentrations, and indices of iron homeostasis in the serum. To test for an...

Impact of pathogen-directed antimicrobial therapy for ventilator-associated pneumonia in trauma patients on charges and recurrence.

PubMed

Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Swanson, Joseph M; Wood, G Christopher; Fabian, Timothy C; Croce, Martin A

2015-04-01

Ventilator-associated pneumonia (VAP) represents one of the driving forces behind antibiotic use in the ICU. In a previous study, we established a defined algorithm for treatment of hospital-acquired VAP dictated by the causative pathogen. The purpose of the current study was to evaluate the impact of this algorithm for hospital-acquired VAP on recurrence and charges in trauma patients. Patients with VAP secondary to MRSA, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or Enterobacteriaceae during 5 years subsequent to the previous study were evaluated. All VAP were diagnosed using quantitative cultures of the bronchoalveolar lavage effluent. Duration of antimicrobial therapy was dictated by the causative pathogen. If microbiologic resolution, defined as <10(3) colony-forming units/mL, was achieved, therapy was stopped by day 10. The remainder received 14 days of therapy. Recurrence was defined as >10(5) colony-forming units/mL on subsequent bronchoalveolar lavage performed within 2 weeks after completion of appropriate therapy. Five hundred and twenty-nine VAP episodes were identified in 381 patients. Overall recurrence was unchanged compared with the previous study (1.5% vs 2%; p = 0.3). There was a decrease in the number of bronchoalveolar lavages performed per patient compared with the previous study (1.6 vs 2.3; p = 0.24) and a reduction of 4.8 antibiotic days per VAP episode compared with the previous study. Both changes resulted in a cumulative reduction of $3,535.04 per patient, for a savings of $1.35 million during the study period. Hospital-acquired VAP can be managed effectively by a defined course of therapy dictated by the causative pathogen. Adherence to an established algorithm simplified the management of VAP and contributed to a cumulative reduction in patient charges without impacting recurrence. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction.

PubMed

Borthwick, L A; Suwara, M I; Carnell, S C; Green, N J; Mahida, R; Dixon, D; Gillespie, C S; Cartwright, T N; Horabin, J; Walker, A; Olin, E; Rangar, M; Gardner, A; Mann, J; Corris, P A; Mann, D A; Fisher, A J

2016-06-01

Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin-1 alpha (IL-1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4-21.8] vs. 2.8 [0.9-9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4-25.1] vs. 3.6 [0.6-17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL-1α positively correlated with elevated bronchoalveolar lavage IL-8 levels (r(2)  = 0.6095, p < 0.0001) and neutrophil percentage (r(2)  = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro-inflammatory phenotype in fibroblasts via an IL-1α/IL-1R-dependent signaling pathway. In conclusion, we propose that IL-1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation. © Copyright 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of the American Society of Transplantation and the American Society of Transplant Surgeons.

Eucoleus aerophilus respiratory infection in a dog with Addison’s disease

PubMed Central

Burgess, Hilary; Ruotsalo, Kristiina; Peregrine, Andrew S.; Hanselman, Beth; Abrams-Ogg, Anthony

2008-01-01

A 4-year-old, standard poodle was presented to the Ontario Veterinary College for a 3-week history of a moist, productive cough that was first noted while boarding at a kennel. Bronchoalveolar lavage revealed numerous ova identified as Eucoleus aerophilus, previously known as Capillaria aerophila. Clinical signs resolved following treatment with fenbendazole. PMID:18481549