Research Advances in Resistance to Platinum-based Chemotherapy in Lung Cancer.

PubMed

Zhang, Yajuan; Chang, De; Zhang, Jianpeng

2017-02-20

Platinum-based chemotherapy is the the cornerstone of treatment of many cancers. Combinations of platinum drugs with other agents are still the mainstream therapies for non-small cell lung cancer,showing significant effectiveness in an early phase. Along with the treatment,the tumor cells can become resistant to chemotherapy drugs,which affect the efficacy and prognosis. The mechanisms of drug resistance are complicated,including abnormal expressions of membrane proteins,enhanced DNA repair functions,abnormal regulation mechanisms of apoptosis,and enhanced cellular detoxification function. In this article we summarize some of the main mechanisms of platinum resistance in lung cancer cells,with an attempt to identify new potential target analogues or inhibitors and improve the efficacies of the combined use of platinum-based drugs.

Automated lung sound analysis for detecting pulmonary abnormalities.

PubMed

Datta, Shreyasi; Dutta Choudhury, Anirban; Deshpande, Parijat; Bhattacharya, Sakyajit; Pal, Arpan

2017-07-01

Identification of pulmonary diseases comprises of accurate auscultation as well as elaborate and expensive pulmonary function tests. Prior arts have shown that pulmonary diseases lead to abnormal lung sounds such as wheezes and crackles. This paper introduces novel spectral and spectrogram features, which are further refined by Maximal Information Coefficient, leading to the classification of healthy and abnormal lung sounds. A balanced lung sound dataset, consisting of publicly available data and data collected with a low-cost in-house digital stethoscope are used. The performance of the classifier is validated over several randomly selected non-overlapping training and validation samples and tested on separate subjects for two separate test cases: (a) overlapping and (b) non-overlapping data sources in training and testing. The results reveal that the proposed method sustains an accuracy of 80% even for non-overlapping data sources in training and testing.

Prevalence, distribution, and progression of radiographic abnormalities in the lungs of cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii): 89 cases (2002-2005).

PubMed

Stockman, Jonathan; Innis, Charles J; Solano, Mauricio; O'Sullivan Brisson, Jennifer; Kass, Philip H; Tlusty, Michael F; Weber, E Scott

2013-03-01

To evaluate the prevalence, distribution, and progression of radiographic abnormalities in the lungs of cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii) and associations between these abnormalities and body weight, carapace length, and hematologic and plasma biochemical variables. Retrospective case series. 89 cold-stunned juvenile Kemp's ridley sea turtles. Medical records were reviewed. Dorsoventral and horizontal beam craniocaudal radiographs were evaluated for the presence, distribution, and progression of lung abnormalities. Turtles were categorized as having radiographically normal or abnormal lungs; those with abnormalities detected were further categorized according to the distribution of abnormalities (left lung, right lung, or both affected). Body weight, carapace length, and hematologic and plasma biochemical data were compared among categories. 48 of 89 (54%) turtles had radiographic abnormalities of the lungs. Unilateral abnormalities of the right or left lung were detected in 14 (16%) and 2 (2%), respectively; both lungs were affected in 32 (36%). Prevalence of unilateral abnormalities was significantly greater for the right lung than for the left lung. Evaluation of follow-up radiographs indicated clinical improvement over time for most (18/31 [58%]) turtles. Prevalence of bilateral radiographic abnormalities was positively correlated with body weight and carapace length. There was no significant association between radiographic category and hematologic or plasma biochemical variables. Radiographic abnormalities of the lungs were commonly detected in cold-stunned Kemp's ridley turtles. Results of this study may aid clinicians in developing effective diagnostic and treatment plans for these patients.

Lung clearance index is a repeatable and sensitive indicator of radiological changes in bronchiectasis.

PubMed

Rowan, Stephen A; Bradley, Judy M; Bradbury, Ian; Lawson, John; Lynch, Tom; Gustafsson, Per; Horsley, Alex; O'Neill, Katherine; Ennis, Madeleine; Elborn, J Stuart

2014-03-01

In bronchiectasis there is a need for improved markers of lung function to determine disease severity and response to therapy. To assess whether the lung clearance index is a repeatable and more sensitive indicator of computed tomography (CT) scan abnormalities than spirometry in bronchiectasis. Thirty patients with stable bronchiectasis were recruited and lung clearance index, spirometry, and health-related quality of life measures were assessed on two occasions, 2 weeks apart when stable (study 1). A separate group of 60 patients with stable bronchiectasis was studied on a single visit with the same measurements and a CT scan (study 2). In study 1, the intervisit intraclass correlation coefficient for the lung clearance index was 0.94 (95% confidence interval, 0.89 to 0.97; P < 0.001). In study 2, the mean age was 62 (10) years, FEV1 76.5% predicted (18.9), lung clearance index 9.1 (2.0), and total CT score 14.1 (10.2)%. The lung clearance index was abnormal in 53 of 60 patients (88%) and FEV1 was abnormal in 37 of 60 patients (62%). FEV1 negatively correlated with the lung clearance index (r = -0.51, P < 0.0001). Across CT scores, there was a relationship with the lung clearance index, with little evidence of an effect of FEV1. There were no significant associations between the lung clearance index or FEV1 and health-related quality of life. The lung clearance index is repeatable and a more sensitive measure than FEV1 in the detection of abnormalities demonstrated on CT scan. The lung clearance index has the potential to be a useful clinical and research tool in patients with bronchiectasis.

Esophageal motor disease and reflux patterns in patients with advanced pulmonary disease undergoing lung transplant evaluation.

PubMed

Seccombe, J; Mirza, F; Hachem, R; Gyawali, C P

2013-08-01

Advanced pulmonary disorders are linked to esophageal hypomotility and reflux disease. However, characterization of esophageal function using high resolution manometry (HRM) and ambulatory pH monitoring, segregation by pulmonary pathology, and comparison to traditional reflux disease are all limited in the literature. Over a 4 year period, 73 patients (55.2 ± 1.3 years, 44F) were identified who underwent esophageal function testing as part of lung transplant evaluation for advanced pulmonary disease (interstitial lung disease, ILD = 47, obstructive lung disease, OLD = 24, other = 2). Proportions of patients with motor dysfunction (≥ 80% failed sequences = severe hypomotility) and/or abnormal reflux parameters (acid exposure time, AET ≥ 4%) were determined, and compared to a cohort of 1081 patients (48.4 ± 0.4 years, 613F) referred for esophageal function testing prior to antireflux surgery (ARS). The proportion of esophageal body hypomotility was significantly higher within advanced pulmonary disease categories (35.6%), particularly ILD (44.7%), compared to ARS patients (12.1%, P < 0.0001). Abnormal AET was noted in 56.5%, and was similar between ILD and OLD, but less frequent than in the ARS group (P = 0.04). Post-transplant chronic rejection trended towards association with pretransplant elevated AET in OLD (P = 0.08) but not ILD. Mortality was not predicted by esophageal motor pattern or reflux evidence. Interstitial lung disease has a highly significant association with esophageal body hypomotility. Consequently, prevalence of abnormal esophageal acid exposure is high, but implications for post lung transplant chronic rejection remain unclear. © 2013 John Wiley & Sons Ltd.

Pulmonary Screening in Subjects after the Fontan Procedure.

PubMed

Liptzin, Deborah R; Di Maria, Michael V; Younoszai, Adel; Narkewicz, Michael R; Kelly, Sarah L; Wolfe, Kelly R; Veress, Livia A

2018-05-07

To review the pulmonary findings of the first 51 patients who presented to our interdisciplinary single-ventricle clinic after undergoing the Fontan procedure. We performed an Institutional Review Board-approved retrospective review of 51 patients evaluated following the Fontan procedure. Evaluation included history, physical examination, pulmonary function testing, and 6-minute walk. Descriptive statistics were used to describe the population and testing data. Sixty-one percent of the patients had a pulmonary concern raised during the visit. Three patients had plastic bronchitis. Abnormal lung function testing was present in 46% of patients. Two-thirds (66%) of the patients had significant desaturation during the 6-minute walk test. Patients who underwent a fenestrated Fontan procedure and those who underwent unfenestrated Fontan were compared in terms of saturation and 6-minute walk test results. Sleep concerns were present in 45% of the patients. Pulmonary morbidities are common in patients after Fontan surgery and include plastic bronchitis, abnormal lung function, desaturations with walking, and sleep concerns. Abnormal lung function and obstructive sleep apnea may stress the Fontan circuit and may have implications for cognitive and emotional functioning. A pulmonologist involved in the care of patients after Fontan surgery can assist in screening for comorbidities and recommend interventions. Copyright © 2018 Elsevier Inc. All rights reserved.

Longitudinal assessment of spirometry in the World Trade Center medical monitoring program.

PubMed

Skloot, Gwen S; Schechter, Clyde B; Herbert, Robin; Moline, Jacqueline M; Levin, Stephen M; Crowley, Laura E; Luft, Benjamin J; Udasin, Iris G; Enright, Paul L

2009-02-01

Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV(1) and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were lack of bronchodilator responsiveness at examination 1 and weight gain [corrected]. Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, lack of bronchodilator response at examination 1 and weight gain were significantly associated with greater-than-normal lung function declines [corrected]. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

The lung in paracoccidioidomycosis: new insights into old problems

PubMed Central

Costa, Andre Nathan; Benard, Gil; Albuquerque, Andre Luis Pereira; Fujita, Carmem Lucia; Magri, Adriana Satie Kono; Salge, João Marcos; Shikanai-Yasuda, Maria Aparecida; Carvalho, Carlos Roberto Ribeiro

2013-01-01

OBJECTIVES: Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. METHODS: A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. RESULTS: Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life. CONCLUSIONS: Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial serology and more severe emphysema, stressing the importance of adequate treatment associated with tobacco exposure cessation. PMID:23778339

Evolution of cystic fibrosis lung function in the early years.

PubMed

Bush, Andrew; Sly, Peter D

2015-11-01

Most treatment of newborn screening-diagnosed cystic fibrosis is not evidence-based; there are very few randomized controlled trials (RCTs). Furthermore, the advent of novel molecular therapies, which could be started at diagnosis, mandates performing RCTs in very young children. However, unless the natural history of early cystic fibrosis lung disease is known, RCTs are impossible. Here, we review the results of two large prospective cohorts of these infants - London Cystic Fibrosis Collaboration (LCFC) (London, UK) and Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF) (Australia). Nutritional status remained excellent in both the cohorts. Both cohorts reported abnormal lung function aged at 3 months. AREST-CF, which previously reported rapidly declining preschool lung function, now report good conventional school-age spirometry. LCFC reported improvement between 3 months and 1 year, and stability in the second year. AREST-CF also reported a high prevalence of high resolution computed tomographic abnormalities related to free neutrophil elastase in bronchoalveolar lavage; LCFC reported high resolution computed tomographic changes at 1 year, which were too mild to be scored reproducibly. At least in the first 2 years of life, lung function is not a good end-point for RCTs; routine bronchoalveolar lavage and HRCT cannot be justified. Newborn screening has greatly improved outcomes, but we need better point-of-care biomarkers.

Long-Term Exposure to Primary Traffic Pollutants and Lung Function in Children: Cross-Sectional Study and Meta-Analysis.

PubMed

Barone-Adesi, Francesco; Dent, Jennifer E; Dajnak, David; Beevers, Sean; Anderson, H Ross; Kelly, Frank J; Cook, Derek G; Whincup, Peter H

2015-01-01

There is widespread concern about the possible health effects of traffic-related air pollution. Nitrogen dioxide (NO2) is a convenient marker of primary pollution. We investigated the associations between lung function and current residential exposure to a range of air pollutants (particularly NO2, NO, NOx and particulate matter) in London children. Moreover, we placed the results for NO2 in context with a meta-analysis of published estimates of the association. Associations between primary traffic pollutants and lung function were investigated in 4884 children aged 9-10 years who participated in the Child Heart and Health Study in England (CHASE). A systematic literature search identified 13 studies eligible for inclusion in a meta-analysis. We combined results from the meta-analysis with the distribution of the values of FEV1 in CHASE to estimate the prevalence of children with abnormal lung function (FEV1<80% of predicted value) expected under different scenarios of NO2 exposure. In CHASE, there were non-significant inverse associations between all pollutants except ozone and both FEV1 and FVC. In the meta-analysis, a 10 μg/m3 increase in NO2 was associated with an 8 ml lower FEV1 (95% CI: -14 to -1 ml; p: 0.016). The observed effect was not modified by a reported asthma diagnosis. On the basis of these results, a 10 μg/m3 increase in NO2 level would translate into a 7% (95% CI: 4% to 12%) increase of the prevalence of children with abnormal lung function. Exposure to traffic pollution may cause a small overall reduction in lung function and increase the prevalence of children with clinically relevant declines in lung function.

High resolution multidetector CT aided tissue analysis and quantification of lung fibrosis

NASA Astrophysics Data System (ADS)

Zavaletta, Vanessa A.; Karwoski, Ronald A.; Bartholmai, Brian; Robb, Richard A.

2006-03-01

Idiopathic pulmonary fibrosis (IPF, also known as Idiopathic Usual Interstitial Pneumontis, pathologically) is a progressive diffuse lung disease which has a median survival rate of less than four years with a prevalence of 15-20/100,000 in the United States. Global function changes are measured by pulmonary function tests and the diagnosis and extent of pulmonary structural changes are typically assessed by acquiring two-dimensional high resolution CT (HRCT) images. The acquisition and analysis of volumetric high resolution Multi-Detector CT (MDCT) images with nearly isotropic pixels offers the potential to measure both lung function and structure. This paper presents a new approach to three dimensional lung image analysis and classification of normal and abnormal structures in lungs with IPF.

Airway inflammation in cystic fibrosis: molecular mechanisms and clinical implications.

PubMed

Cohen-Cymberknoh, Malena; Kerem, Eitan; Ferkol, Thomas; Elizur, Arnon

2013-12-01

Airway epithelial cells and immune cells participate in the inflammatory process responsible for much of the pathology found in the lung of patients with cystic fibrosis (CF). Intense bronchial neutrophilic inflammation and release of proteases and oxygen radicals perpetuate the vicious cycle and progressively damage the airways. In vitro studies suggest that CF transmembrane conductance regulator (CFTR)-deficient airway epithelial cells display signalling abnormalities and aberrant intracellular processes which lead to transcription of inflammatory mediators. Several transcription factors, especially nuclear factor-κB, are activated. In addition, the accumulation of abnormally processed CFTR in the endoplasmic reticulum results in unfolded protein responses that trigger 'cell stress' and apoptosis leading to dysregulation of the epithelial cells and innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation. Measuring airway inflammation is crucial for initiating treatment and monitoring its effect. No inflammatory biomarker predictive for the clinical course of CF lung disease is currently known, although neutrophil elastase seems to correlate with lung function decline. CF animal models mimicking human lung disease may provide an important insight into the pathogenesis of lung inflammation in CF and identify new therapeutic targets.

Clinical Validation of 4-Dimensional Computed Tomography Ventilation With Pulmonary Function Test Data

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

Brennan, Douglas; Schubert, Leah; Diot, Quentin

Purpose: A new form of functional imaging has been proposed in the form of 4-dimensional computed tomography (4DCT) ventilation. Because 4DCTs are acquired as part of routine care for lung cancer patients, calculating ventilation maps from 4DCTs provides spatial lung function information without added dosimetric or monetary cost to the patient. Before 4DCT-ventilation is implemented it needs to be clinically validated. Pulmonary function tests (PFTs) provide a clinically established way of evaluating lung function. The purpose of our work was to perform a clinical validation by comparing 4DCT-ventilation metrics with PFT data. Methods and Materials: Ninety-eight lung cancer patients withmore » pretreatment 4DCT and PFT data were included in the study. Pulmonary function test metrics used to diagnose obstructive lung disease were recorded: forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity. Four-dimensional CT data sets and spatial registration were used to compute 4DCT-ventilation images using a density change–based and a Jacobian-based model. The ventilation maps were reduced to single metrics intended to reflect the degree of ventilation obstruction. Specifically, we computed the coefficient of variation (SD/mean), ventilation V20 (volume of lung ≤20% ventilation), and correlated the ventilation metrics with PFT data. Regression analysis was used to determine whether 4DCT ventilation data could predict for normal versus abnormal lung function using PFT thresholds. Results: Correlation coefficients comparing 4DCT-ventilation with PFT data ranged from 0.63 to 0.72, with the best agreement between FEV1 and coefficient of variation. Four-dimensional CT ventilation metrics were able to significantly delineate between clinically normal versus abnormal PFT results. Conclusions: Validation of 4DCT ventilation with clinically relevant metrics is essential. We demonstrate good global agreement between PFTs and 4DCT-ventilation, indicating that 4DCT-ventilation provides a reliable assessment of lung function. Four-dimensional CT ventilation enables exciting opportunities to assess lung function and create functional avoidance radiation therapy plans. The present work provides supporting evidence for the integration of 4DCT-ventilation into clinical trials.« less

Lung function in the absence of respiratory symptoms in overweight children and adolescents*

PubMed Central

de Assunção, Silvana Neves Ferraz; Daltro, Carla Hilário da Cunha; Boa Sorte, Ney Christian; Ribeiro, Hugo da Costa; Bastos, Maria de Lourdes; Queiroz, Cleriston Farias; Lemos, Antônio Carlos Moreira

2014-01-01

OBJECTIVE: To describe lung function findings in overweight children and adolescents without respiratory disease. METHODS: This was a cross-sectional study involving male and female overweight children and adolescents in the 8-18 year age bracket, without respiratory disease. All of the participants underwent anthropometric assessment, chest X-ray, pulse oximetry, spirometry, and lung volume measurements. Individuals with respiratory disease were excluded, as were those who were smokers, those with abnormal chest X-rays, and those with an SpO2 = 92%. Waist circumference was measured in centimeters. The body mass index-for-age Z score for boys and girls was used in order to classify the individuals as overweight, obese, or severely obese. Lung function variables were expressed in percentage of the predicted value and were correlated with the anthropometric indices. RESULTS: We included 59 individuals (30 males and 29 females). The mean age was 11.7 ± 2.7 years. Lung function was normal in 21 individuals (35.6%). Of the 38 remaining individuals, 19 (32.2%), 15 (25.4%), and 4 (6.7%) presented with obstructive, restrictive, and mixed ventilatory disorder, respectively. The bronchodilator response was positive in 15 individuals (25.4%), and TLC measurements revealed that all of the individuals with reduced VC had restrictive ventilatory disorder. There were significant negative correlations between the anthropometric indices and the Tiffeneau index in the individuals with mixed ventilatory disorder. CONCLUSIONS: Lung function was abnormal in approximately 65% of the individuals evaluated here, all of whom were overweight. Obstructive ventilatory disorder and positive bronchodilator response predominated. PMID:24831397

Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

PubMed

Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

2018-04-01

Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD

PubMed Central

Cukic, Vesna; Begic, Amela

2014-01-01

Objective: To highlight the importance of the lung ventilation scintigraphy (LVS) to study the regional distribution of lung ventilation and to describe most frequent abnormal patterns of lung ventilation distribution obtained by this technique in COPD and to compare the information obtained by LVS with the that obtained by traditional lung function tests. Material and methods: The research was done in 20 patients with previously diagnosed COPD who were treated in Intensive care unit of Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Center, University of Sarajevo in exacerbation of COPD during first three months of 2014. Each patient was undergone to testing of pulmonary function by body plethysmography and ventilation/perfusion lung scintigraphy with radio pharmaceutics Technegas, 111 MBq Tc -99m-MAA. We compared the results obtained by these two methods. Results: All patients with COPD have a damaged lung function tests examined by body plethysmography implying airflow obstruction, but LVS indicates not only airflow obstruction and reduced ventilation, but also indicates the disorders in distribution in lung ventilation. Conclusion: LVS may add further information to the functional evaluation of COPD to that provided by traditional lung function tests and may contribute to characterizing the different phenotypes of COPD. PMID:25132709

Mini-extracorporeal circulation minimizes coagulation abnormalities and ameliorates pulmonary outcome in coronary artery bypass grafting surgery.

PubMed

Zeitani, J; Buccisano, F; Nardella, S; Flaminio, M; Prati, P; Chiariello, G; Venditti, A; Chiariello, L

2013-07-01

Hemostasis is impaired during CABG and coagulation abnormalities often result in clinically relevant organ dysfunctions, eventually increasing morbidity and mortality rates. Fifteen consecutive patients with coronary artery disease submitted to conventional extracorporeal circulation (cECC) have been compared with 15 matched patients, using mini-ECC (MECC). Postoperative lung function was evaluated according to gas exchange, intubation time and lung injury score. In the MECC group, thrombin-antithrombin complex levels (TaTc), prothrombin fragments (PF1+2) formation and thromboelastography (TEG) clotting times were lower compared to the cECC group (p=0.002 and p<0.001, respectively) whereas postoperative blood loss was higher in the cECC group (p=0.030) and more patients required blood transfusion (p=0.020). In the MECC group, postoperative gas exchange values were better, intubation time shorter and lung injury score lower (p<0.001 for all comparisons). Our study suggests that MECC induces less coagulation disorders, leading to lower postoperative blood loss and better postoperative lung function. This approach may be advantageous in high-risk patients.

Pleural plaques and their effect on lung function in Libby vermiculite miners.

PubMed

Clark, Kathleen A; Flynn, J Jay; Goodman, Julie E; Zu, Ke; Karmaus, Wilfried J J; Mohr, Lawrence C

2014-09-01

Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners. The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure. Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function. Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

Can lung function measurements be used to predict which patients will be at risk of developing interstitial pneumonitis after bone marrow transplantation?

PubMed

Milburn, H J; Prentice, H G; du Bois, R M

1992-06-01

Lung function often deteriorates after bone marrow transplantation for haematological malignancies. Whether pulmonary function measurements are useful for monitoring patients' progress after transplantation and for alerting clinicians to the development of pneumonitis is uncertain. Serial pulmonary function measurements were made in 39 patients with a haematological malignancy, and the values from 18 recipients of T cell depleted allogeneic (n = 17) or autologous (n = 1) bone marrow transplants who developed interstitial pneumonitis were compared retrospectively with values from 21 recipients of allogeneic (n = 17) or autologous (n = 4) transplants who did not develop pneumonitis. Lung function was measured at the onset of a further 18 episodes of pneumonitis. Measurements made before transplantation showed no difference in forced expiratory volume in one second (FEV1), transfer factor for carbon monoxide (TLCO), or total lung capacity between the two groups, but the forced vital capacity (FVC) was slightly higher in those who developed pneumonitis (mean (SD)% predicted 104 (12)) than in those who did not (93 (17%)). Six weeks and three months after transplantation all pulmonary function measurements had fallen slightly in both groups but TLCO had fallen considerably more in those who later developed pneumonitis, being 71% (SD 11%) and 77% (7%) of pretransplant values in patients who later developed pneumonitis compared with 109% (38%) and 96% (26%) in those who did not. All lung function measurements were significantly lower at the onset of pneumonitis than three months after transplantation, even in patients with no abnormal signs and a normal chest radiograph. Serial measurements of gas transfer before and after bone marrow transplantation may be useful for predicting which patients will be at risk of developing pneumonitis and may help to diagnose pneumonitis in breathless patients with no abnormal signs.

Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

PubMed

Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

2016-02-01

Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (p<0.0001) and pulmonary capillary blood volume from 39.7 to 64.1 ml/m2 (p<0.0001); forced expiratory volume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.

PubMed

Speirs, Jennifer J; van der Ent, Cornelis K; Beekman, Jeffrey M

2012-11-01

Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary. A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown. A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.

Pulmonary function abnormalities and airway irritation symptoms of metal fumes exposure on automobile spot welders.

PubMed

Luo, Jiin-Chyuan John; Hsu, Kuang-Hung; Shen, Wu-Shiun

2006-06-01

Spot or resistance welding has been considered less hazardous than other types of welding. Automobile manufacturing is a major industry in Taiwan. Spot and arc welding are common processes in this industry. The respiratory effects on automobile spot welders exposed to metal fumes are investigated. The cohort consisted of 41 male auto-body spot welders, 76 male arc welders, 71 male office workers, and 59 assemblers without welding exposure. Inductivity Coupled Plasma Mass Spectrophotometer (ICP-MS) was applied to detect metals' (zinc, copper, nickel) levels in the post-shift urine samples. Demographic data, work history, smoking status, and respiratory tract irritation symptoms were gathered by a standard self-administered questionnaire. Pulmonary function tests were also performed. There were significantly higher values for average urine metals' (zinc, copper, nickel) levels in spot welders and arc welders than in the non-welding controls. There were 4 out of 23 (17.4%) abnormal forced vital capacity (FVC) among the high-exposed spot welders, 2 out of 18 (11.1%) among the low-exposed spot welders, and 6 out of 130 (4.6%) non-welding-exposed workers. There was a significant linear trend between spot welding exposure and the prevalence of restrictive airway abnormalities (P = 0.036) after adjusting for other factors. There were 9 out of 23 (39.1%) abnormal peak expiratory flow rate (PEFR) among high-exposed spot welders, 5 out of 18 (27.8%) among the low-exposed spot welders, and 28 out of 130 (21.5%) non-welding-exposed workers. There was a borderline significant linear trend between spot welding exposure and the prevalence of obstructive lung function abnormalities (P = 0.084) after adjusting for other factors. There was also a significant dose-response relationship of airway irritation symptoms (cough, phlegm, chronic bronchitis) among the spot welders. Arc welders with high exposure status also had a significant risk of obstructive lung abnormalities (PEFR reduction). There was also a significant dose-response relationship of airway irritation symptoms (cough, phlegm, chest tightness, and chronic bronchitis) among the arc welders. These findings suggest that restrictive and obstructive lung abnormalities, and airway irritation symptoms are associated with spot and arc welding exposures.

A retrospective study of two populations to test a simple rule for spirometry.

PubMed

Ohar, Jill A; Yawn, Barbara P; Ruppel, Gregg L; Donohue, James F

2016-06-04

Chronic lung disease is common and often under-diagnosed. To test a simple rule for conducting spirometry we reviewed spirograms from two populations, occupational medicine evaluations (OME) conducted by Saint Louis and Wake Forest Universities at 3 sites (n = 3260, mean age 64.14 years, 95 % CI 58.94-69.34, 97 % men) and conducted by Wake Forest University preop clinic (POC) at one site (n = 845, mean age 62.10 years, 95 % CI 50.46-73.74, 57 % men). This retrospective review of database information that the first author collected prospectively identified rates, types, sensitivity, specificity and positive and negative predictive value for lung function abnormalities and associated mortality rate found when conducting spirometry based on the 20/40 rule (≥20 years of smoking in those aged ≥ 40 years) in the OME population. To determine the reproducibility of the 20/40 rule for conducting spirometry, the rule was applied to the POC population. A lung function abnormality was found in 74 % of the OME population and 67 % of the POC population. Sensitivity of the rule was 85 % for an obstructive pattern and 77 % for any abnormality on spirometry. Positive and negative predictive values of the rule for a spirometric abnormality were 74 and 55 %, respectively. Patients with an obstructive pattern were at greater risk of coronary heart disease (odds ratio (OR) 1.39 [confidence interval (CI) 1.00-1.93] vs. normal) and death (hazard ratio (HR) 1.53, 95 % CI 1.20-1.84) than subjects with normal spirometry. Restricted spirometry patterns were also associated with greater risk of coronary disease (odds ratio (OR) 1.7 [CI 1.23-2.35]) and death (Hazard ratio 1.40, 95 % CI 1.08-1.72). Smokers (≥ 20 pack years) age ≥ 40 years are at an increased risk for lung function abnormalities and those abnormalities are associated with greater presence of coronary heart disease and increased all-cause mortality. Use of the 20/40 rule could provide a simple method to enhance selection of candidates for spirometry evaluation in the primary care setting.

Interstitial lung abnormalities and self-reported health and functional status.

PubMed

Axelsson, Gisli Thor; Putman, Rachel K; Araki, Tetsuro; Sigurdsson, Sigurdur; Gudmundsson, Elias Freyr; Eiriksdottir, Gudny; Aspelund, Thor; Miller, Ezra R; Launer, Lenore J; Harris, Tamara B; Hatabu, Hiroto; Gudnason, Vilmundur; Hunninghake, Gary Matt; Gudmundsson, Gunnar

2018-01-09

We investigated the association between interstitial lung abnormalities (ILA) and self-reported measures of health and functional status in 5764 participants from the Age, Gene/Environment Susceptibility-Reykjavik study. The associations of ILA to activities of daily living (ADLs), general health status and physical activity were explored using logistic regression models. Participants with ILA were less likely to be independent in ADLs (OR 0.70; 95% CI 0.55 to 0.90) to have good or better self-reported health (OR 0.66; 95% CI 0.52 to 0.82) and to participate in physical activity (OR 0.72; CI 0.56 to 0.91). The results demonstrate ILA's association with worsening self-reported health and functional status. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Computer-aided pulmonary image analysis in small animal models

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

Xu, Ziyue; Mansoor, Awais; Mollura, Daniel J.

Purpose: To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models. Methods: The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next.more » The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray-scale morphological reconstruction filters. Results: 133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set. Conclusions: The authors developed a comprehensive computer-aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.« less

Association of incidental emphysema with annual lung function decline and future development of airflow limitation

PubMed Central

Koo, Hyeon-Kyoung; Jin, Kwang Nam; Kim, Deog Kyeom; Chung, Hee Soon; Lee, Chang-Hoon

2016-01-01

Objectives Emphysema is one of the prognostic factors for rapid lung function decline in patients with COPD, but the impact of incidentally detected emphysema on population without spirometric abnormalities has not been evaluated. This study aimed to determine whether emphysema detected upon computed tomography (CT) screening would accelerate the rate of lung function decline and influence the possibility of future development of airflow limitation in a population without spirometric abnormalities. Materials and methods Subjects who participated in a routine screening for health checkup and follow-up pulmonary function tests for at least 3 years between 2004 and 2010 were retrospectively enrolled. The percentage of low-attenuation area below −950 Hounsfield units (%LAA−950) was calculated automatically. A calculated value of %LAA−950 that exceeded 10% was defined as emphysema. Adjusted annual lung function decline was analyzed using random-slope, random-intercept mixed linear regression models. Results A total of 628 healthy subjects within the normal range of spriometric values were included. Multivariable analysis showed that the emphysema group exhibited a faster decline in forced vital capacity (−33.9 versus −18.8 mL/year; P=0.02). Emphysema was not associated with the development of airflow limitation during follow-up. Conclusion Incidental emphysema quantified using CT scan was significantly associated with a more rapid decline in forced vital capacity in the population with normative spirometric values. However, an association between emphysema and future development of airflow limitation was not observed. PMID:26893550

Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study.

PubMed

Hadchouel, Alice; Marchand-Martin, Laetitia; Franco-Montoya, Marie-Laure; Peaudecerf, Laetitia; Ancel, Pierre-Yves; Delacourt, Christophe

2015-01-01

Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25-75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease.

Screening for Chronic Obstructive Pulmonary Disease (COPD) in an Urban HIV Clinic: A Pilot Study

PubMed Central

Kaner, Robert J.; Glesby, Marshall J.

2015-01-01

Abstract Increased smoking and a detrimental response to tobacco smoke in the lungs of HIV/AIDS patients result in an increased risk for COPD. We aimed to determine the predictive value of a COPD screening strategy validated in the general population and to identify HIV-related factors associated with decreased lung function. Subjects at least 35 years of age at an HIV clinic in New York City completed a COPD screening questionnaire and peak flow measurement. Those with abnormal results and a random one-third of normal screens had spirometry. 235 individuals were included and 89 completed spirometry. Eleven (12%) had undiagnosed airway obstruction and 5 had COPD. A combination of a positive questionnaire and abnormal peak flow yielded a sensitivity of 20% (specificity 93%) for detection of COPD. Peak flow alone had a sensitivity of 80% (specificity 80%). Abnormal peak flow was associated with an AIDS diagnosis (p=0.04), lower nadir (p=0.001), and current CD4 counts (p=0.001). Nadir CD4 remained associated in multivariate analysis (p=0.05). Decreased FEV1 (<80% predicted) was associated with lower CD4 count nadir (p=0.04) and detectable current HIV viral load (p=0.01) in multivariate analysis. Questionnaire and peak flow together had low sensitivity, but abnormal peak flow shows potential as a screening tool for COPD in HIV/AIDS. These data suggest that lung function may be influenced by HIV-related factors. PMID:25723842

Computerized scheme for detection of diffuse lung diseases on CR chest images

NASA Astrophysics Data System (ADS)

Pereira, Roberto R., Jr.; Shiraishi, Junji; Li, Feng; Li, Qiang; Doi, Kunio

2008-03-01

We have developed a new computer-aided diagnostic (CAD) scheme for detection of diffuse lung disease in computed radiographic (CR) chest images. One hundred ninety-four chest images (56 normals and 138 abnormals with diffuse lung diseases) were used. The 138 abnormal cases were classified into three levels of severity (34 mild, 60 moderate, and 44 severe) by an experienced chest radiologist with use of five different patterns, i.e., reticular, reticulonodular, nodular, air-space opacity, and emphysema. In our computerized scheme, the first moment of the power spectrum, the root-mean-square variation, and the average pixel value were determined for each region of interest (ROI), which was selected automatically in the lung fields. The average pixel value and its dependence on the location of the ROI were employed for identifying abnormal patterns due to air-space opacity or emphysema. A rule-based method was used for determining three levels of abnormality for each ROI (0: normal, 1: mild, 2: moderate, and 3: severe). The distinction between normal lungs and abnormal lungs with diffuse lung disease was determined based on the fractional number of abnormal ROIs by taking into account the severity of abnormalities. Preliminary results indicated that the area under the ROC curve was 0.889 for the 44 severe cases, 0.825 for the 104 severe and moderate cases, and 0.794 for all cases. We have identified a number of problems and reasons causing false positives on normal cases, and also false negatives on abnormal cases. In addition, we have discussed potential approaches for improvement of our CAD scheme. In conclusion, the CAD scheme for detection of diffuse lung diseases based on texture features extracted from CR chest images has the potential to assist radiologists in their interpretation of diffuse lung diseases.

Lungs in Heart Failure

PubMed Central

Apostolo, Anna; Giusti, Giuliano; Gargiulo, Paola; Bussotti, Maurizio; Agostoni, Piergiuseppe

2012-01-01

Lung function abnormalities both at rest and during exercise are frequently observed in patients with chronic heart failure, also in the absence of respiratory disease. Alterations of respiratory mechanics and of gas exchange capacity are strictly related to heart failure. Severe heart failure patients often show a restrictive respiratory pattern, secondary to heart enlargement and increased lung fluids, and impairment of alveolar-capillary gas diffusion, mainly due to an increased resistance to molecular diffusion across the alveolar capillary membrane. Reduced gas diffusion contributes to exercise intolerance and to a worse prognosis. Cardiopulmonary exercise test is considered the “gold standard” when studying the cardiovascular, pulmonary, and metabolic adaptations to exercise in cardiac patients. During exercise, hyperventilation and consequent reduction of ventilation efficiency are often observed in heart failure patients, resulting in an increased slope of ventilation/carbon dioxide (VE/VCO2) relationship. Ventilatory efficiency is as strong prognostic and an important stratification marker. This paper describes the pulmonary abnormalities at rest and during exercise in the patients with heart failure, highlighting the principal diagnostic tools for evaluation of lungs function, the possible pharmacological interventions, and the parameters that could be useful in prognostic assessment of heart failure patients. PMID:23365739

Early detection of cystic fibrosis lung disease: multiple‐breath washout versus raised volume tests

PubMed Central

Lum, Sooky; Gustafsson, Per; Ljungberg, Henrik; Hülskamp, Georg; Bush, Andrew; Carr, Siobhán B; Castle, Rosemary; Hoo, Ah‐fong; Price, John; Ranganathan, Sarath; Stroobant, John; Wade, Angie; Wallis, Colin; Wyatt, Hilary; Stocks, Janet

2007-01-01

Background Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple‐breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco–abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow‐volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV0.5 and FEF25–75 ) than boys (mean (95% CI girls–boys): –1.2 (–2.1 to −0.3) for FEV0.5 Z score; FEF25–75: –1.2 (–2.2 to −0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC. PMID:17121870

Assessing Respiratory System Mechanical Function.

PubMed

Restrepo, Ruben D; Serrato, Diana M; Adasme, Rodrigo

2016-12-01

The main goals of assessing respiratory system mechanical function are to evaluate the lung function through a variety of methods and to detect early signs of abnormalities that could affect the patient's outcomes. In ventilated patients, it has become increasingly important to recognize whether respiratory function has improved or deteriorated, whether the ventilator settings match the patient's demand, and whether the selection of ventilator parameters follows a lung-protective strategy. Ventilator graphics, esophageal pressure, intra-abdominal pressure, and electric impedance tomography are some of the best-known monitoring tools to obtain measurements and adequately evaluate the respiratory system mechanical function. Copyright © 2016 Elsevier Inc. All rights reserved.

TU-CD-BRA-11: Application of Bone Suppression Technique to Inspiratory/expiratory Chest Radiography

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

Tanaka, R; Sanada, S; Sakuta, K

Purpose: The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images normally obtained by the dual-energy subtraction technique. This study was performed to investigate the usefulness of bone suppression technique in quantitative analysis of pulmonary function in inspiratory/expiratory chest radiography. Methods: Commercial bone suppression image processing software (ClearRead; Riverain Technologies) was applied to paired inspiratory/expiratory chest radiographs of 107 patients (normal, 33; abnormal, 74) to create corresponding bone suppression images. The abnormal subjects had been diagnosed with pulmonary diseases, such as pneumothorax, pneumonia, emphysema, asthma, and lung cancer.more » After recognition of the lung area, the vectors of respiratory displacement were measured in all local lung areas using a cross-correlation technique. The measured displacement in each area was visualized as displacement color maps. The distribution pattern of respiratory displacement was assessed by comparison with the findings of lung scintigraphy. Results: Respiratory displacement of pulmonary markings (soft tissues) was able to be quantified separately from the rib movements on bone suppression images. The resulting displacement map showed a left-right symmetric distribution increasing from the lung apex to the bottom region of the lung in many cases. However, patients with ventilatory impairments showed a nonuniform distribution caused by decreased displacement of pulmonary markings, which were confirmed to correspond to area with ventilatory impairments found on the lung scintigrams. Conclusion: The bone suppression technique was useful for quantitative analysis of respiratory displacement of pulmonary markings without any interruption of the rib shadows. Abnormal areas could be detected as decreased displacement of pulmonary markings. Inspiratory/expiratory chest radiography combined with the bone suppression technique has potential for predicting local lung function on the basis of dynamic analysis of pulmonary markings. This work was partially supported by Nakatani Foundation, Grant-in-aid for Scientific Research (C) of Ministry of Education, Culture, Sports, Science and Technology, JAPAN (Grant number : 24601007), and Nakatani Foundation, Mitsubishi Foundation, and the he Mitani Foundation for Research and Development. Yasushi Kishitani is a staff of TOYO corporation.« less

Metabolic Syndrome Biomarkers Predict Lung Function Impairment

PubMed Central

Naveed, Bushra; Weiden, Michael D.; Kwon, Sophia; Gracely, Edward J.; Comfort, Ashley L.; Ferrier, Natalia; Kasturiarachchi, Kusali J.; Cohen, Hillel W.; Aldrich, Thomas K.; Rom, William N.; Kelly, Kerry; Prezant, David J.

2012-01-01

Rationale: Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function. Objectives: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure. Methods: A nested case-control study of Fire Department of New York personnel with normal pre–September 11th FEV1 and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV1. FEV1 at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV1 less than lower limit of normal, whereas control subjects had FEV1 greater than or equal to lower limit of normal. Measurements and Main Results: Clinical data and serum sampled at the first monitoring examination within 6 months of September 11, 2001, assessed body mass index, heart rate, serum glucose, triglycerides and high-density lipoprotein (HDL), leptin, pancreatic polypeptide, and amylin. Cases and control subjects had significant differences in HDL less than 40 mg/dl with triglycerides greater than or equal to 150 mg/dl, heart rate greater than or equal to 66 bpm, and leptin greater than or equal to 10,300 pg/ml. Each increased the odds of abnormal FEV1 at pulmonary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the odds by 84%, in a multibiomarker model adjusting for age, race, body mass index, and World Trade Center arrival time. This model had a sensitivity of 41%, a specificity of 86%, and a receiver operating characteristic area under the curve of 0.77. Conclusions: Abnormal triglycerides and HDL and elevated heart rate and leptin are independent risk factors of greater susceptibility to lung function impairment after September 11, 2001, whereas elevated amylin is protective. Metabolic biomarkers are predictors of lung disease, and may be useful for assessing risk of impaired lung function in response to particulate inhalation. PMID:22095549

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

PubMed

Podolanczuk, Anna J; Oelsner, Elizabeth C; Barr, R Graham; Hoffman, Eric A; Armstrong, Hilary F; Austin, John H M; Basner, Robert C; Bartels, Matthew N; Christie, Jason D; Enright, Paul L; Gochuico, Bernadette R; Hinckley Stukovsky, Karen; Kaufman, Joel D; Hrudaya Nath, P; Newell, John D; Palmer, Scott M; Rabinowitz, Dan; Raghu, Ganesh; Sell, Jessica L; Sieren, Jered; Sonavane, Sushil K; Tracy, Russell P; Watts, Jubal R; Williams, Kayleen; Kawut, Steven M; Lederer, David J

2016-11-01

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults. Copyright ©ERS 2016.

Heterozygous Vangl2Looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair

PubMed Central

Poobalasingam, Thanushiyan; Yates, Laura L.; Walker, Simone A.; Pereira, Miguel; Gross, Nina Y.; Ali, Akmol; Kolatsi-Joannou, Maria; Jarvelin, Marjo-Riitta; Pekkanen, Juha; Papakrivopoulou, Eugenia; Long, David A.; Griffiths, Mark; Wagner, Darcy; Königshoff, Melanie; Hind, Matthew; Minelli, Cosetta; Lloyd, Clare M.

2017-01-01

ABSTRACT Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising. The planar cell polarity (PCP) pathway is critical for the embryonic development of many organs, including kidney and lung. We have previously shown that perturbation of the PCP pathway impairs tissue morphogenesis, which disrupts the number and shape of epithelial tubes formed within these organs during embryogenesis. However, very little is known about the role of the PCP pathway beyond birth, partly because of the perinatal lethality of many PCP mouse mutant lines. Here, we investigate heterozygous Looptail (Lp) mice, in which a single copy of the core PCP gene, Vangl2, is disrupted. We show that these mice are viable but display severe airspace enlargement and impaired adult lung function. Underlying these defects, we find that Vangl2Lp/+ lungs exhibit altered distribution of actin microfilaments and abnormal regulation of the actin-modifying protein cofilin. In addition, we show that Vangl2Lp/+ lungs exhibit many of the hallmarks of tissue damage, including an altered macrophage population, abnormal elastin deposition and elevated levels of the elastin-modifying enzyme, Mmp12, all of which are observed in emphysema. In vitro, disruption of VANGL2 impairs directed cell migration and reduces the rate of repair following scratch wounding of human alveolar epithelial cells. Moreover, using population data from a birth cohort of young adults, all aged 31, we found evidence of an interactive effect between VANGL2 and smoking on lung function. Finally, we show that PCP genes VANGL2 and SCRIB are significantly downregulated in lung tissue from patients with emphysema. Our data reveal an important novel role for the PCP pathway in adult lung homeostasis and repair and shed new light on the genetic factors which may modify destructive lung diseases such as emphysema. PMID:28237967

Common cold decreases lung function in infants with recurrent wheezing.

PubMed

Mallol, J; Aguirre, V; Wandalsen, G

2010-01-01

Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. This study shows that common colds cause a marked reduction of lung function in infants with RW. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Segmentation and Image Analysis of Abnormal Lungs at CT: Current Approaches, Challenges, and Future Trends

PubMed Central

Mansoor, Awais; Foster, Brent; Xu, Ziyue; Papadakis, Georgios Z.; Folio, Les R.; Udupa, Jayaram K.; Mollura, Daniel J.

2015-01-01

The computer-based process of identifying the boundaries of lung from surrounding thoracic tissue on computed tomographic (CT) images, which is called segmentation, is a vital first step in radiologic pulmonary image analysis. Many algorithms and software platforms provide image segmentation routines for quantification of lung abnormalities; however, nearly all of the current image segmentation approaches apply well only if the lungs exhibit minimal or no pathologic conditions. When moderate to high amounts of disease or abnormalities with a challenging shape or appearance exist in the lungs, computer-aided detection systems may be highly likely to fail to depict those abnormal regions because of inaccurate segmentation methods. In particular, abnormalities such as pleural effusions, consolidations, and masses often cause inaccurate lung segmentation, which greatly limits the use of image processing methods in clinical and research contexts. In this review, a critical summary of the current methods for lung segmentation on CT images is provided, with special emphasis on the accuracy and performance of the methods in cases with abnormalities and cases with exemplary pathologic findings. The currently available segmentation methods can be divided into five major classes: (a) thresholding-based, (b) region-based, (c) shape-based, (d) neighboring anatomy–guided, and (e) machine learning–based methods. The feasibility of each class and its shortcomings are explained and illustrated with the most common lung abnormalities observed on CT images. In an overview, practical applications and evolving technologies combining the presented approaches for the practicing radiologist are detailed. ©RSNA, 2015 PMID:26172351

Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies.

PubMed

Henderson, Lauren A; Loring, Stephen H; Gill, Ritu R; Liao, Katherine P; Ishizawar, Rumey; Kim, Susan; Perlmutter-Goldenson, Robin; Rothman, Deborah; Son, Mary Beth F; Stoll, Matthew L; Zemel, Lawrence S; Sandborg, Christy; Dellaripa, Paul F; Nigrovic, Peter A

2013-03-01

The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients. Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density. Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density. Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.

Radiographic abnormalities and the risk of lung cancer among workers exposed to silica dust in Ontario.

PubMed Central

Finkelstein, M M

1995-01-01

OBJECTIVE: To determine whether workers in Ontario who had been exposed to silica dust and who have radiographic abnormalities are at increased risk of lung cancer. DESIGN: Cohort and case-control studies of rates of death from lung cancer and cancer incidence rates; data were obtained from the Ontario Silicosis Surveillance Registry. Follow-up was through linkage to the Ontario mortality and cancer registries. SETTING: Ontario. PARTICIPANTS: A total of 523 workers with radiographic abnormalities and 1568 control subjects with normal radiographic findings who had been exposed to silica dust. Matching criteria were year of birth and the requirement that the control subject have a normal radiographic finding either later than or in the same year that the radiographic abnormality was identified in the silicosis subject. OUTCOME MEASURES: Standardized mortality ratios (SMRs), standardized incidence ratios (SIRs) and odds ratios for lung cancer. RESULTS: In the cohort analysis, with the Ontario population rates as reference, the all-cause SMR was 0.96 among the workers with radiographic abnormalities and 0.51 among the control subjects. The corresponding SIRs for lung cancer were 2.49 and 0.87 (p < 0.001). In the case-control analysis the workers with silicosis were more likely than the control subjects to have been smokers, but this difference likely accounted for only a small part of the difference in the incidence of lung cancer. The relative risk of lung cancer was elevated among the workers with silicosis from the foundry, mining and nonmetallic-minerals industries; however, the number of subjects was too small for a significant difference to be detected. Among the miners exposure to radon daughters did not affect the risk of lung cancer attributable to radiographic abnormalities. CONCLUSIONS: Radiographic abnormalities suggestive of exposure to silica dust are markers for increased risk of lung cancer. Physicians might thus wish to warn their patients with silica-associated radiographic abnormalities about the increased risk and to counsel those who smoke to stop. PMID:7804920

Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

PubMed

Thompson, Sophie M; Connell, Marilyn G; van Kuppevelt, Toin H; Xu, Ruoyan; Turnbull, Jeremy E; Losty, Paul D; Fernig, David G; Jesudason, Edwin C

2011-06-14

Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme.We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional consequence of the observed changes in HS in these lungs. These results identify a novel, significant molecular defect in hypoplastic lungs and reveals HS as a potential contributor to hypoplastic lung development in CDH. Finally, these results afford the prospect that HS-mimetic therapeutics could repair defective signalling in hypoplastic lungs, improve lung growth, and reduce CDH mortality.

Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

PubMed Central

2011-01-01

Background Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. Results The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme. We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. Conclusions The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional consequence of the observed changes in HS in these lungs. These results identify a novel, significant molecular defect in hypoplastic lungs and reveals HS as a potential contributor to hypoplastic lung development in CDH. Finally, these results afford the prospect that HS-mimetic therapeutics could repair defective signalling in hypoplastic lungs, improve lung growth, and reduce CDH mortality. PMID:21672206

The Aging Lung: Clinical and Imaging Findings and the Fringe of Physiological State.

PubMed

Schröder, T H; Storbeck, B; Rabe, K F; Weber, C

2015-06-01

Since aspects of demographic transition have become an essential part of socioeconomic, medical and health-care research in the last decades, it is vital for the radiologist to discriminate between normal ageing related effects and abnormal imaging findings in the elderly. This article reviews functional and structural aspects of the ageing lung and focuses on typical ageing related radiological patterns. • The physiological aging process of the thoracic organs shows typical structural and functional aspects.• Mild interstitial fibrosis and focal parenchymal abnormalities like septal thickening can be diagnosed frequently - whereas a clinical correlate is often lacking.• With increasing patient age, the influence by various intrinsic and extrinsic factors (including comorbidities of the patient, and drug inhalation toxicants) also increases.• A growing spectrum of imaging techniques (including functional cardiopulmonary MRI, MRI spectroscopy, hybrid-techniques) is confronted by rare empiric data in the very old people (aging 80 years and older). © Georg Thieme Verlag KG Stuttgart · New York.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities.

PubMed

Ho, Jennifer E; Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O; Hatabu, Hiroto; Latourelle, Jeanne C; Nishino, Mizuki; Dupuis, Josée; Washko, George R; O'Connor, George T; Hunninghake, Gary M

2016-07-01

Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8-2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6-1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3-2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49-4.76; P < 0.001). Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities

PubMed Central

Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O.; Hatabu, Hiroto; Latourelle, Jeanne C.; Nishino, Mizuki; Dupuis, Josée; Washko, George R.; O’Connor, George T.; Hunninghake, Gary M.

2016-01-01

Rationale: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. Objectives: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. Methods: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Measurements and Main Results: Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8–2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6–1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3–2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49–4.76; P < 0.001). Conclusions: Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis. PMID:26771117

Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity.

PubMed

Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M

2016-01-01

Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, p<0.001; r2 = 0.34, p<0.001). Cardiac output and index (cardiac output / body surface area) were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p = 0.03). Subjects with lower DM/VC demonstrated a cardiac output that remained in the normal range despite presence of obesity. Global dysfunction of the distal lung (alveolar membrane and distal airway) is associated with pulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often unrecognized causes of airway dysfunction in obesity.

42 CFR 37.53 - Notification of abnormal roentgenographic findings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer... findings suggesting, abnormality of cardiac shape or size, tuberculosis, lung cancer, or any other...

Early Changes in Clinical, Functional, and Laboratory Biomarkers in Workers at Risk of Indium Lung Disease

PubMed Central

Virji, M. Abbas; Trapnell, Bruce C.; Carey, Brenna; Healey, Terrance; Kreiss, Kathleen

2014-01-01

Rationale: Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods: Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results: Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions: In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease. PMID:25295756

Using K-Nearest Neighbor Classification to Diagnose Abnormal Lung Sounds

PubMed Central

Chen, Chin-Hsing; Huang, Wen-Tzeng; Tan, Tan-Hsu; Chang, Cheng-Chun; Chang, Yuan-Jen

2015-01-01

A reported 30% of people worldwide have abnormal lung sounds, including crackles, rhonchi, and wheezes. To date, the traditional stethoscope remains the most popular tool used by physicians to diagnose such abnormal lung sounds, however, many problems arise with the use of a stethoscope, including the effects of environmental noise, the inability to record and store lung sounds for follow-up or tracking, and the physician’s subjective diagnostic experience. This study has developed a digital stethoscope to help physicians overcome these problems when diagnosing abnormal lung sounds. In this digital system, mel-frequency cepstral coefficients (MFCCs) were used to extract the features of lung sounds, and then the K-means algorithm was used for feature clustering, to reduce the amount of data for computation. Finally, the K-nearest neighbor method was used to classify the lung sounds. The proposed system can also be used for home care: if the percentage of abnormal lung sound frames is > 30% of the whole test signal, the system can automatically warn the user to visit a physician for diagnosis. We also used bend sensors together with an amplification circuit, Bluetooth, and a microcontroller to implement a respiration detector. The respiratory signal extracted by the bend sensors can be transmitted to the computer via Bluetooth to calculate the respiratory cycle, for real-time assessment. If an abnormal status is detected, the device will warn the user automatically. Experimental results indicated that the error in respiratory cycles between measured and actual values was only 6.8%, illustrating the potential of our detector for home care applications. PMID:26053756

Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension.

PubMed

Malenfant, Simon; Potus, François; Fournier, Frédéric; Breuils-Bonnet, Sandra; Pflieger, Aude; Bourassa, Sylvie; Tremblay, Ève; Nehmé, Benjamin; Droit, Arnaud; Bonnet, Sébastien; Provencher, Steeve

2015-05-01

Exercise limitation comes from a close interaction between cardiovascular and skeletal muscle impairments. To better understand the implication of possible peripheral oxidative metabolism dysfunction, we studied the proteomic signature of skeletal muscle in pulmonary arterial hypertension (PAH). Eight idiopathic PAH patients and eight matched healthy sedentary subjects were evaluated for exercise capacity, skeletal muscle proteomic profile, metabolism, and mitochondrial function. Skeletal muscle proteins were extracted, and fractioned peptides were tagged using an iTRAQ protocol. Proteomic analyses have documented a total of 9 downregulated proteins in PAH skeletal muscles and 10 upregulated proteins compared to healthy subjects. Most of the downregulated proteins were related to mitochondrial structure and function. Focusing on skeletal muscle metabolism and mitochondrial health, PAH patients presented a decreased expression of oxidative enzymes (pyruvate dehydrogenase, p < 0.01) and an increased expression of glycolytic enzymes (lactate dehydrogenase activity, p < 0.05). These findings were supported by abnormal mitochondrial morphology on electronic microscopy, lower citrate synthase activity (p < 0.01) and lower expression of the transcription factor A of the mitochondria (p < 0.05), confirming a more glycolytic metabolism in PAH skeletal muscles. We provide evidences that impaired mitochondrial and metabolic functions found in the lungs and the right ventricle are also present in skeletal muscles of patients. • Proteomic and metabolic analysis show abnormal oxidative metabolism in PAH skeletal muscle. • EM of PAH patients reveals abnormal mitochondrial structure and distribution. • Abnormal mitochondrial health and function contribute to exercise impairments of PAH. • PAH may be considered a vascular affliction of heart and lungs with major impact on peripheral muscles.

Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy.

PubMed

Bober, Michael B; Taylor, Megan; Heinle, Robert; Mackenzie, William

2012-09-01

Achondroplasia and hypochondroplasia are two of the most common forms of skeletal dysplasia. They are both caused by activating mutations in FGFR3 and are inherited in an autosomal dominant manner. Our patient was born to parents with presumed achondroplasia, and found on prenatal testing to have p.G380R and p.N540K FGFR3 mutations. In addition to having typical problems associated with both achondroplasia and hypochondroplasia, our patient had several atypical findings including: abnormal lobulation of the lungs with respiratory insufficiency, C1 stenosis, and hypoglycemia following a Nissen fundoplication. After his reflux and aspiration were treated, the persistence of the tachypnea and increased respiratory effort indicated this was not the primary source of the respiratory distress. Our subsequent hypothesis was that primary restrictive lung disease was the cause of his respiratory distress. A closer examination of his chest circumference did not support this conclusion either. Following his death, an autopsy found the right lung had 2 lobes while the left lung had 3 lobes. A literature review demonstrates that other children with achondroplasia-hypochondroplasia complex have been described with abnormal pulmonary function and infants with thanatophoric dysplasia have similar abnormal pulmonary anatomy. We hypothesize that there may be a primary pulmonary phenotype associated with FGFR3-opathies, unrelated to chest size which leads to the consistent finding of increased respiratory signs and symptoms in these children. Further observation of respiratory status, combined with the macroscopic and microscopic analysis of pulmonary branching anatomy and alveolar structure in this patient population will be important to explore this hypothesis. Copyright © 2012 Wiley Periodicals, Inc.

Abnormal pulmonary function in adults with sickle cell anemia.

PubMed

Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

2006-06-01

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

In vivo imaging of pulmonary nodule and vasculature using endoscopic co-registered optical coherence tomography and autofluorescence imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Pahlevaninezhad, Hamid; Lee, Anthony; Hohert, Geoffrey; Schwartz, Carely; Shaipanich, Tawimas; Ritchie, Alexander J.; Zhang, Wei; MacAulay, Calum E.; Lam, Stephen; Lane, Pierre M.

2016-03-01

Peripheral lung nodules found by CT-scans are difficult to localize and biopsy bronchoscopically particularly for those ≤ 2 cm in diameter. In this work, we present the results of endoscopic co-registered optical coherence tomography and autofluorescence imaging (OCT-AFI) of normal and abnormal peripheral airways from 40 patients using 0.9 mm diameter fiber optic rotary pullback catheter. Optical coherence tomography (OCT) can visualize detailed airway morphology endoscopically in the lung periphery. Autofluorescence imaging (AFI) can visualize fluorescing tissue components such as collagen and elastin, enabling the detection of airway lesions with high sensitivity. Results indicate that AFI of abnormal airways is different from that of normal airways, suggesting that AFI can provide a sensitive visual presentation for rapidly identifying possible sites of pulmonary nodules. AFI can also rapidly visualize in vivo vascular networks using fast scanning parameters resulting in vascular-sensitive imaging with less breathing/cardiac motion artifacts compared to Doppler OCT imaging. It is known that tumor vasculature is structurally and functionally different from normal vessels. Thus, AFI can be potentially used for differentiating normal and abnormal lung vasculature for studying vascular remodeling.

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

PubMed

Reynolds, A M; McEvoy, R D

1988-04-01

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Pulmonary function abnormalities in never-smoking flight attendants exposed to secondhand tobacco smoke in the aircraft cabin.

PubMed

Arjomandi, Mehrdad; Haight, Thaddeus; Redberg, Rita; Gold, Warren M

2009-06-01

To determine whether the flight attendants who were exposed to secondhand tobacco smoke in the aircraft cabin have abnormal pulmonary function. We administered questionnaires and performed pulmonary function testing in 61 never-smoking female flight attendants who worked in active air crews before the smoking ban on commercial aircraft (preban). Although the preban flight attendants had normal FVC, FEV1, and FEV1/FVC ratio, they had significantly decreased flow at mid- and low-lung volumes, curvilinear flow-volume curves, and evidence of air trapping. Furthermore, the flight attendants had significantly decreased diffusing capacity (77.5% +/- 11.2% predicted normal) with 51% having a diffusing capacity below their 95% normal prediction limit. This cohort of healthy never-smoking flight attendants who were exposed to secondhand tobacco smoke in the aircraft cabin showed pulmonary function abnormalities suggestive of airway obstruction and impaired diffusion.

Idiopathic pulmonary fibrosis is associated with increased impedance measures of reflux compared to non-fibrotic disease among pre-lung transplant patients.

PubMed

Gavini, S; Finn, R T; Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

2015-09-01

Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF), although the mechanism remains unclear. Gastroesophageal reflux/microaspiration may lead to lung fibrosis, while increased pulmonary workload may also worsen GER. Comparing the GER profile of IPF patients to chronic obstructive pulmonary disease (COPD) patients with similar lung function may help delineate the role of GER in IPF pathogenesis. This was a retrospective cohort study of IPF and COPD patients undergoing pre-lung transplant multichannel intraluminal impedance and pH study (MII-pH) off acid suppression at a tertiary center in 2008-2014. Patients with prior fundoplication were excluded. Baseline demographics, pulmonary function test, and MII-pH results were recorded. Univariate analyses were performed using Fisher's exact (binary variables) and Student's t (continuous variables) tests. Logistic regression was performed to adjust for potential confounders. A total of 90 subjects (54 IPF, 36 COPD) met inclusion criteria. Compared to COPD, IPF patients had increased total reflux episodes (65.9 vs 46.1, p = 0.02), proximal reflux episodes (30.3 vs 20.3, p = 0.04), and prevalence of abnormal total reflux episodes (38.9% vs 16.7%, p = 0.02). On multivariate analyses, abnormal total reflux episodes (OR: 4.9, p = 0.05) and bolus reflux exposure time (OR: 4, p = 0.04) remained significantly associated with IPF. Abnormal reflux was significantly more prevalent among IPF patients after controlling for lung disease severity. Gastroesophageal reflux/microaspiration likely plays a role in fibrosis in IPF. A significant portion of IPF patients had increased non-acid reflux. Therapies aiming to prevent reflux of gastric contents may be more beneficial than antisecretory medications alone in these patients. © 2015 John Wiley & Sons Ltd.

Pectus excavatum in children: pulmonary scintigraphy before and after corrective surgery

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

Blickman, J.G.; Rosen, P.R.; Welch, K.J.

1985-09-01

Regional distribution of pulmonary function was evaluated preoperatively and postoperatively with xenon-133 perfusion and ventilation scintigraphy in 17 patients with pectus excavatum. Ventilatory preoperative studies were abnormal in 12 of 17 patients, resolving in seven of 12 postoperatively. Perfusion scans were abnormal in ten of 17 patients preoperatively; six of ten showed improvement postoperatively. Ventilation-perfusion ratios were abnormal in ten of 17 patients, normalizing postoperatively in six of ten. Symmetry of ventilation-perfusion ratio images improved in six out of nine in the latter group. The distribution of regional lung function in pectus excavatum can be evaluated preoperatively to support indicationsmore » for surgery. Postoperative improvement can be documented by physiological changes produced by the surgical correction.« less

Pemetrexed-Induced Nephrogenic Diabetes Insipidus

PubMed Central

Fung, Enrica; Anand, Shuchi; Bhalla, Vivek

2016-01-01

Pemetrexed is an approved anti-metabolite agent, now widely used for treating locally advanced or metastatic non-squamous, non–small cell lung cancer. Although no electrolyte abnormalities are described in the prescribing information for this drug, several case reports have noted nephrogenic diabetes insipidus with associated acute kidney injury. We present a case of nephrogenic diabetes insipidus without severely reduced kidney function and propose a mechanism for the isolated finding. Severe hypernatremia can lead to encephalopathy and osmotic demyelination, and our report highlights the importance of careful monitoring of electrolytes and kidney function in patients with lung cancer receiving pemetrexed. PMID:27241854

Small Airway Dysfunction and Abnormal Exercise Responses

PubMed Central

Petsonk, Edward L.; Stansbury, Robert C.; Beeckman-Wagner, Lu-Ann; Long, Joshua L.; Wang, Mei Lin

2016-01-01

Rationale Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. Objectives We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. Methods Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. Measurements and Main Results Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. Conclusions Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance. PMID:27073987

Persistent Lung Disease in Adults with NKX2.1 Mutation and Familial Neuroendocrine Cell Hyperplasia of Infancy

PubMed Central

Nevel, Rebekah J.; Garnett, Errine T.; Worrell, John A.; Morton, Ronald L.; Nogee, Lawrence M.; Blackwell, Timothy S.

2016-01-01

Rationale: Neuroendocrine cell hyperplasia of infancy (NEHI) is a diffuse lung disease that presents in infancy and improves during childhood. Long-term outcomes have not previously been described. In one familial cohort, we have reported that NEHI is associated with a heterozygous variant of NKX2.1/TTF1. Objectives: Our objective was to determine whether pulmonary abnormalities persist in adults with NEHI, to aid in elucidating the natural history of this disease. Methods: Four adult relatives with heterozygous NKX2.1 mutation and with clinical histories compatible with NEHI enrolled in a prospective study that included questionnaires, pulmonary function tests, and chest computed tomography scans. Measurements and Main Results: Mild radiologic abnormalities including mosaicism were seen in all four cases. Three individuals had obstruction on pulmonary function tests, two had marked air trapping, and three had symptomatic impairments with exercise intolerance. Conclusions: Although clinical improvement occurs over time, NEHI may result in lifelong pulmonary abnormalities in some cases. Further studies are required to better describe the natural history of this disease and would be facilitated by additional delineation of genetic mechanisms to enable improved case identification. PMID:27187870

Abnormal lung sounds in patients with asthma during episodes with normal lung function.

PubMed

Schreur, H J; Vanderschoot, J; Zwinderman, A H; Dijkman, J H; Sterk, P J

1994-07-01

Even in patients with clinically stable asthma with normal lung function, the airways are characterized by inflammatory changes, including mucosal swelling. In order to investigate whether lung sounds can distinguish these subjects from normal subjects, we compared lung sound characteristics between eight normal and nine symptom-free subjects with mild asthma. All subjects underwent simultaneous recordings of airflow, lung volume changes, and lung sounds during standardized quiet breathing, and during forced maneuvers. Flow-dependent power spectra were computed using fast Fourier transform. For each spectrum we determined lung sound intensity (LSI), frequencies (Q25%, Q50%, Q75%) wheezing (W), and W%. The results were analyzed by ANOVA. During expiration, LSI was lower in patients with asthma than in healthy controls, in particular at relatively low airflow values. During quiet expiration, Q25% to Q75% were higher in asthmatics than in healthy controls, while the change of Q25% to Q75% with flow was greater in asthmatic than in normal subjects. The W and W% were not different between the subject groups. The results indicate that at given airflows, lung sounds are lower in intensity and higher in pitch in asthmatics as compared with controls. This suggests that the generation and/or transmission of lung sounds in symptom-free patients with stable asthma differ from that in normal subjects, even when lung function is within the normal range. Therefore, airflow standardized phonopneumography might reflect morphologic changes in airways of patients with asthma.

Haemodynamics, dyspnoea, and pulmonary reserve in heart failure with preserved ejection fraction.

PubMed

Obokata, Masaru; Olson, Thomas P; Reddy, Yogesh N V; Melenovsky, Vojtech; Kane, Garvan C; Borlaug, Barry A

2018-05-19

Increases in left ventricular filling pressure are a fundamental haemodynamic abnormality in heart failure with preserved ejection fraction (HFpEF). However, very little is known regarding how elevated filling pressures cause pulmonary abnormalities or symptoms of dyspnoea. We sought to determine the relationships between simultaneously measured central haemodynamics, symptoms, and lung ventilatory and gas exchange abnormalities during exercise in HFpEF. Subjects with invasively-proven HFpEF (n = 50) and non-cardiac causes of dyspnoea (controls, n = 24) underwent cardiac catheterization at rest and during exercise with simultaneous expired gas analysis. During submaximal (20 W) exercise, subjects with HFpEF displayed higher pulmonary capillary wedge pressures (PCWP) and pulmonary artery pressures, higher Borg perceived dyspnoea scores, and increased ventilatory drive and respiratory rate. At peak exercise, ventilation reserve was reduced in HFpEF compared with controls, with greater dead space ventilation (higher VD/VT). Increasing exercise PCWP was directly correlated with higher perceived dyspnoea scores, lower peak exercise capacity, greater ventilatory drive, worse New York Heart Association (NYHA) functional class, and impaired pulmonary ventilation reserve. This study provides the first evidence linking altered exercise haemodynamics to pulmonary abnormalities and symptoms of dyspnoea in patients with HFpEF. Further study is required to identify the mechanisms by which haemodynamic derangements affect lung function and symptoms and to test novel therapies targeting exercise haemodynamics in HFpEF.

Outcome of influenza infection managed with oseltamivir in lung transplant recipients.

PubMed

Ison, Michael G; Sharma, Amita; Shepard, Jo-Anne O; Wain, John C; Ginns, Leo C

2008-03-01

Influenza causes significant morbidity and mortality in lung transplant recipients and likely predisposes to obliterative bronchiolitis. Neuraminidase inhibitors shorten the duration of symptoms and virus shedding and the number of antibiotic-requiring complications in ambulatory immunocompetent patients, although the efficacy of these agents in lung transplant recipients has not been assessed previously. In this study, 9 lung transplant patients who were treated with oseltamivir for influenza infections were identified and analyzed retrospectively. Oseltamivir was well tolerated. Infection resolved in all patients and there were no deaths. Two patients developed pneumonia shortly after their influenza infection and both responded to antibiotic therapy. None of the patients had persistent abnormalities noted on chest imaging and most did not show significant changes on pulmonary function testing. Two patients with the lowest pulmonary function test (PFT) values pre-infection had persistent defects after infection. Oseltamivir is well tolerated in lung transplant recipients and may reduce the risk of complications, although further studies are warranted.

[Lung involvement in systemic connective tissue diseases].

PubMed

Plavec, Goran; Tomić, Ilija; Bihorac, Sanela; Kovacević, Gordana; Pavlica, Ljiljana; Cvetković, Gordana; Sikimić, Stevan; Milić, Rade

2008-09-01

Systemic connective tissue diseases (SCTD) are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory sistem. The aim of this study was to find out the frequency of respiratory simptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT) abnormalities, and their correlation with the duration of the disease and the applied treatment. In 47 non-randomised consecutive patients standard chest radiography, HRCT, and lung function tests were done. Hypoxemia was present in nine of the patients with respiratory simptoms (20%). In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had simptoms of lung involment. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung functin disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro). Pulmonary fibrosis occures in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway

PubMed Central

Hwang, Jae-Woong; Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.; Rahman, Irfan

2014-01-01

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 μM) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. PMID:24025728

[Interpretation and use of routine pulmonary function tests: Spirometry, static lung volumes, lung diffusion, arterial blood gas, methacholine challenge test and 6-minute walk test].

PubMed

Bokov, P; Delclaux, C

2016-02-01

Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Longitudinal and Cross-sectional Analyses of Lung Function in Toluene Diisocyanate Production Workers.

PubMed

Wang, Mei Lin; Storey, Eileen; Cassidy, Laura D; Doney, Brent; Conner, Patrick R; Collins, James J; Carson, Michael; Molenaar, Don

2017-12-01

The aim of this study was to investigate lung function among toluene diisocyanate (TDI) production workers. One hundred ninety-seven U.S workers performed spirometry from 2006 through 2012. Results were compared within the study cohort and with U.S. population measures. A mixed-effects model assessed factors affecting repeated forced expiratory volume in 1 second (FEV1) measurements. The cohort's mean FEV1 and forced vital capacity (FVC) percent reference values, although greater than 90%, were significantly lower and the prevalence of abnormal spirometry (predominantly restrictive pattern) was significantly higher than in the U.S. Differences in lung function among workers with higher cumulative TDI exposure were in the direction of an exposure effect, but not significant. We found little evidence of an adverse effect of TDI exposure on longitudinal spirometry in these workers. The association between TDI exposure and the increasing prevalence of a restrictive pattern needs further exploration.

Noninfectious interstitial lung disease during infliximab therapy: Case report and literature review

PubMed Central

Caccaro, Roberta; Savarino, Edoardo; D’Incà, Renata; Sturniolo, Giacomo Carlo

2013-01-01

Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases. However, lung toxicity can be induced by conventional medications used to maintain remission, and similar evidence is also emerging for biologics. We present the case of a young woman affected by colonic Crohn’s disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab. She was referred to our clinic with a severe relapse and was treated with infliximab, an anti-tumor necrosis factor α (TNF-α) antibody, to induce remission. After an initial benefit, with decreases in bowel movements, rectal bleeding and C-reactive protein levels, she experienced shortness of breath after the 5th infusion. Noninfectious interstitial lung disease was diagnosed. Both mesalamine and infliximab were discontinued, and steroids were introduced with slow but progressive improvement of symptoms, radiology and functional tests. This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations. Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases, this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy. PMID:23983443

The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

2017-08-01

Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Abnormal heart rate recovery and chronotropic incompetence on exercise in chronic obstructive pulmonary disease.

PubMed

Gupta, Mansi; Bansal, Vishal; Chhabra, Sunil K

2013-08-01

Chronotropic incompetence (CI; failure to reach the targeted heart rate (HR) on exercise) and a delayed HR recovery (HRR; ≤12 beats decline within the first minute after cessation) reflect autonomic dysfunction (AD) and predict adverse cardiac prognosis. As chronic obstructive pulmonary disease (COPD) is known to be associated with AD, we hypothesized that these patients may manifest these responses on exercise. The prevalence and predictors of these responses in COPD and their association with its severity have not been evaluated. Normoxemic, stable male patients with COPD (n = 39) and 11 healthy controls underwent lung function testing and incremental leg ergometry. HR responses were monitored during exercise and recovery to compute the HRR and CI. Of all the patients, 33 (84.6%) had at least one of the two exercise responses as abnormal, with the majority (23, 58.9%) having both an abnormal HRR and CI. The frequency of abnormal responses increased with increasing Global Initiative for Chronic Obstructive Lung Disease stage and body mass index, airflow obstruction, dyspnoea and exercise capacity index. After adjusting for smoking history and post-bronchodilator forced expiratory volume in 1 second, only a reduced diffusion capacity for carbon monoxide predicted abnormal HRR, though weakly. We concluded that abnormal HRR and CI are common in patients with COPD. These responses are observed with increasing frequency as the severity of disease increases.

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

PubMed Central

Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

2006-01-01

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

PubMed

Sung, Jae Hyuck; Choi, Byung-Gil; Maeng, Seung-Hee; Kim, Soo-Jin; Chung, Yong Hyun; Han, Jeong Hee; Song, Kyung Seuk; Lee, Yong Hwan; Cho, Yong Bong; Cho, Myung-Haing; Kim, Kwang Jong; Hyun, Jin Suk; Yu, Il Je

2004-12-01

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

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

PubMed Central

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

2005-01-01

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

Association between right ventricular dysfunction and restrictive lung disease in childhood cancer survivors as measured by quantitative echocardiography.

PubMed

Patel, Amee; Weismann, Constance; Weiss, Pnina; Russell, Kerry; Bazzy-Asaad, Alia; Kadan-Lottick, Nina S

2014-11-01

Restrictive lung disease is a complication in childhood cancer survivors who received lung-toxic chemotherapy and/or thoracic radiation. Left ventricular dysfunction is documented in these survivors, but less is known about right ventricular (RV) function. Quantitative echocardiography may help detect subclinical RV dysfunction. The aim of this study was to assess RV function quantitatively in childhood cancer survivors after lung-toxic therapy. We identified records of 33 childhood cancer survivors who (1) were treated with lung-toxic therapy and/or radiation, (2) were cancer-free for ≥ one year after therapy, and (3) had pulmonary function tests and echocardiograms from their most recent follow-up visit. Participants' mean age was 11.6 ± 4.5 years at cancer diagnosis and 23 ± 8.6 years at evaluation. The most common diagnosis was lymphoma/leukemia (n = 27). Twenty-nine subjects had anthracycline exposure. Eleven of the 33 subjects demonstrated restrictive pulmonary impairment (total lung capacity 3.69 ± 1.5 L [69.3 ± 22.4% predicted]). Among quantitative measures of RV function, isovolumetric acceleration (IVA), a measure of contractility, was significantly lower in the group with restrictive lung disease (2.42 ± 0.56 vs. 1.83 ± 0.78 m/sec(2); P < 0.05). There was a trend towards lower tissue Doppler derived S' and tricuspid annular plane systolic excursion in the group with restrictive lung disease. Subjects with restrictive lung disease were found to have ≥ 2 abnormal parameters (P < 0.01). IVA may detect early RV dysfunction in childhood cancer survivors with restrictive lung disease. Our findings require confirmation in a larger study population and validation by cardiac MRI. © 2014 Wiley Periodicals, Inc.

High-Risk Infants: Auditory Processing Deficits in Later Childhood.

ERIC Educational Resources Information Center

Gilbride, Kathleen E.; And Others

To determine whether deficits warranting intervention are present in the later functioning of high-risk infants, 22 premature infants who experienced asphyxia or chronic lung disease (CLD) but who had no gross developmental abnormalities were evaluated. Assessments of auditory perception and receptive language ability were made during later…

Post-tuberculous lung function impairment in a tuberculosis reference clinic in Cameroon.

PubMed

Mbatchou Ngahane, Bertrand Hugo; Nouyep, Junior; Nganda Motto, Malea; Mapoure Njankouo, Yacouba; Wandji, Adeline; Endale, Mireille; Afane Ze, Emmanuel

2016-05-01

After completion of treatment, a proportion of pulmonary TB (pTB) patients experience lung function impairment which can influence their quality of life. This study aimed to determine the prevalence of lung function impairment in patients treated for pTB and investigate its associated factors. A cross-sectional study was conducted in TB clinic of the Douala Laquintinie Hospital in Cameroon. Patients aged 15 and above who were treated for pTB between 2008 and 2012 were included in the study. Demographic data, respiratory symptoms prior TB diagnosis, comorbidities and chest radiography findings prior to TB treatment were collected. All participants underwent spirometric measurements. Airflow obstruction was defined as a post-bronchodilation FEV1/FVC <70% with FVC >80%, restrictive defects as an FEV1/FVC ratio of ≥70% with an FVC <80% predicted, and mixed defects as FVC of <80% predicted and an FEV1/FVC ratio of <70%. Lung function impairment was defined by the presence of at least one of these three abnormalities. Logistic regression analysis was employed to investigate risk factors of lung function impairment. Of a total of 269 participants included in the study, 146 (54.3%) were male. The median age of participants was 33 years. The median duration of symptoms before diagnosis of TB was 4 weeks [interquartile range (IQR) 3-8]. The prevalence of lung function impairment was 45.4% (95% CI 39-51). The multivariate analysis identified duration of symptoms [OR 1.08; 95% CI (1.01-1.15)] and fibrotic pattern [OR 3.54; 95% CI (1.40-8.95)] as independent risk factors for lung function impairment. Post-tuberculous pulmonary function impairment is frequent in Douala. Sensitization of patient with symptoms of pulmonary TB for an earlier visit to healthcare facilities could reduce the impact of pTB on lung function of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interpretation of indeterminate lung scintigrams. [/sup 99m/Tc, /sup 133/Xe

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

Biello, D.R.; Mattar, A.G.; Osei-Wusu, A.

1979-10-01

Lung scintigrams and pulmonary angiograms of 111 patients with suspected pulmonary embolism who had matching perfusion defects and radiographic abnormalities (infiltrate, atelectasis, or effusion) were reviewed. In 14 patients perfusion defects were substantially smaller than the corresponding radiographic opacity; only 1 (7%) had pulmonary embolism. In 77 the opacities and perfusion defects were of similar size; the abnormality was due to embolism in 20 (26%). In 18 patients perfusion defects were substantially larger than the radiographic opacities and were not associated with matching ventilation abnormalities; of these, 16 (89%) had pulmonary embolism. Evaluation of the relative size of perfusion defectsmore » and radiographic abnormalities occurring in the same region improves the ability of lung scintigrams to predict pulmonary emboli.« less

Neurologic, neuropsychologic, and computed cranial tomography scan abnormalities in 2- to 10-year survivors of small-cell lung cancer.

PubMed

Johnson, B E; Becker, B; Goff, W B; Petronas, N; Krehbiel, M A; Makuch, R W; McKenna, G; Glatstein, E; Ihde, D C

1985-12-01

In order to evaluate the relationship between neurologic function and cranial irradiation, 20 patients treated on National Cancer Institute (NCI) small-cell lung cancer (SCLC) trials who were alive and free of cancer 2.4 to 10.6 years (median, 6.2) from the start of therapy were studied. All were tested with a neurologic history and examination, mental status examination, neuropsychologic testing, and review of serial computed cranial tomography (CCT) scans. Fifteen patients had been treated with prophylactic cranial irradiation (PCI), two patients with therapeutic cranial irradiation, and three received no cranial irradiation. All patients but one were ambulatory and none were institutionalized. Fifteen patients (75%) had neurologic complaints, 13 (65%) had abnormal neurologic examinations, 12 (60%) had abnormal mental status examinations, 13 (65%) had abnormal neuropsychologic testing, and 15 (75%) had abnormal CCT scans. Compared with those given low-dose maintenance chemotherapy during PCI using 200 to 300 rad per fraction, patients who were given high-dose induction chemotherapy during the time of cranial irradiation or large radiotherapy fractions (400 rad) were more likely to have abnormal mental status examinations (6/6 v 4/9) and abnormal neuropsychologic tests (6/6 v 4/9), but no major difference in CCT findings was present. CCT scans in the majority of cases (11/18) showed progressive ventricular dilatation or cerebral atrophy up to 8 years after stopping therapy. We conclude neurologic abnormalities are common in long-term survivors of SCLC, and may be more prominent in patients given high-dose chemotherapy during cranial irradiation or treated with large radiotherapy fractions. The CCT scan abnormalities are common and progressive years after prophylactic cranial irradiation and chemotherapy are stopped.

Which prognostic indicator should we use for clinical practice in the initial evaluation and follow-up of IIP: should we depend on PFT, HRCT or...what?

PubMed

Caminati, Antonella; Harari, Sergio

2005-12-01

Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and fibrotic disorders of the lung parenchyma that cause restrictive physiology and impair gas exchange. Usual interstitial pneumonia and non-specific interstitial pneumonia comprise the majority of idiopathic interstitial pneumonia cases. Previous studies have identified the histopathologic pattern as the most important baseline factor in determining prognosis. The non-invasive diagnosis of these diseases is sometimes uncertain but histological evaluation is an imperfect gold-standard. In some cases, the biopsy specimen may not be representative of the entire lung. In other cases, there may be differences in interpretation of the histological findings. HRCT has also assumed a greater role in the diagnosis and management of patients with idiopathic interstitial pneumonia. Factors affecting prognosis are discussed controversially. Histological criteria, clinical features, or lung function parameters are not clear prognostic indicators. Increased interstitial abnormalities in the HRCT, parameters indicating restrictive lung function, desaturation at 6MWT and abnormal gas exchange are possible determinants of survival. The prognostic value of pulmonary function trends over time may prove more useful. Longitudinal behavior is a more accurate determinant of outcome than evaluation at a single point in time. It is important to remember that no predictor of survival can ever reliably predict an individual patient's prognosis. Physicians should realize this limitation, and use predictor tools as general prognostic guides, not crystal balls. However, due to the great variability in the natural history of the disease, close monitoring of the patients may be necessary to evaluate the individual course of each patient.

Bronchopulmonary dysplasia: improvement in lung function between 7 and 10 years of age.

PubMed

Blayney, M; Kerem, E; Whyte, H; O'Brodovich, H

1991-02-01

To evaluate the natural history of bronchopulmonary dysplasia, we studied the same 32 patients at a mean age of 7 and 10 years. The group as a whole had normal height and weight percentiles, and each child grew along his or her established somatic growth curve. Although some children had abnormal values, the group maintained a normal mean total lung capacity and functional residual capacity. The mean residual volume and the residual volume/total lung capacity ratios were elevated at both ages. At age 7 years the 19 patients (59%) who had a forced expiratory volume in 1 second (FEV1) of less than 80% had "catch up" improvement by 10 years of age (65 +/- 11% to 72 +/- 16% of predicted value; p less than 0.05). All the children who had a normal FEV1 at 7 years of age continued to have a normal FEV1 at age 10 years. Resting single-breath carbon monoxide uptake by the lung was normal when measured at age 10 years. The majority of patients had a positive methacholine challenge test result at both ages, although there was a low incidence of clinically diagnosed asthma. This study demonstrates that patients with bronchopulmonary dysplasia who have normal lung function at age 7 have had normal lung growth and that those with evidence of mild to moderate lung disease have continued lung growth or repair, or both, during their school years.

[Anomalous systemic arterial supply to normal basal segments of the left lung (Pryce type I)].

PubMed

Ryu, Chusei; Sawada, Takahiro; Machino, Ryusuke

2013-03-01

Patient 1 was a 54-year-old female diagnosed with anomalous systemic arterial supply to normal basal segments of the left lung discovered as an abnormality on chest X-ray radiography. Patient 2 was a 47-year-old male in whom the disease was diagnosed by close examination of bloody sputum. Division of the abnormal artery and left lower lobectomy were performed in patient 1. Arterial congestion and serpentine distribution were noted in the basal segments of the lung, which was the region perfused by the abnormal artery, on histopathological examination. Arteriosclerotic changes were noted in the vascular wall, but no abnormal vascular wall or alveolar structure was noted in S6, which was not included in theperfused region. Based on the above findings, division of the abnormal artery and left basal segmentectomy were performed in patient 2. Bloody sputum disappeared, and activity of daily living( ADL) were not impaired after surgery.

Computerized Lung Sound Analysis as diagnostic aid for the detection of abnormal lung sounds: a systematic review and meta-analysis

PubMed Central

Gurung, Arati; Scrafford, Carolyn G; Tielsch, James M; Levine, Orin S; Checkley, William

2011-01-01

Rationale The standardized use of a stethoscope for chest auscultation in clinical research is limited by its inherent inter-listener variability. Electronic auscultation and automated classification of recorded lung sounds may help prevent some these shortcomings. Objective We sought to perform a systematic review and meta-analysis of studies implementing computerized lung sounds analysis (CLSA) to aid in the detection of abnormal lung sounds for specific respiratory disorders. Methods We searched for articles on CLSA in MEDLINE, EMBASE, Cochrane Library and ISI Web of Knowledge through July 31, 2010. Following qualitative review, we conducted a meta-analysis to estimate the sensitivity and specificity of CLSA for the detection of abnormal lung sounds. Measurements and Main Results Of 208 articles identified, we selected eight studies for review. Most studies employed either electret microphones or piezoelectric sensors for auscultation, and Fourier Transform and Neural Network algorithms for analysis and automated classification of lung sounds. Overall sensitivity for the detection of wheezes or crackles using CLSA was 80% (95% CI 72–86%) and specificity was 85% (95% CI 78–91%). Conclusions While quality data on CLSA are relatively limited, analysis of existing information suggests that CLSA can provide a relatively high specificity for detecting abnormal lung sounds such as crackles and wheezes. Further research and product development could promote the value of CLSA in research studies or its diagnostic utility in clinical setting. PMID:21676606

Computerized lung sound analysis as diagnostic aid for the detection of abnormal lung sounds: a systematic review and meta-analysis.

PubMed

Gurung, Arati; Scrafford, Carolyn G; Tielsch, James M; Levine, Orin S; Checkley, William

2011-09-01

The standardized use of a stethoscope for chest auscultation in clinical research is limited by its inherent inter-listener variability. Electronic auscultation and automated classification of recorded lung sounds may help prevent some of these shortcomings. We sought to perform a systematic review and meta-analysis of studies implementing computerized lung sound analysis (CLSA) to aid in the detection of abnormal lung sounds for specific respiratory disorders. We searched for articles on CLSA in MEDLINE, EMBASE, Cochrane Library and ISI Web of Knowledge through July 31, 2010. Following qualitative review, we conducted a meta-analysis to estimate the sensitivity and specificity of CLSA for the detection of abnormal lung sounds. Of 208 articles identified, we selected eight studies for review. Most studies employed either electret microphones or piezoelectric sensors for auscultation, and Fourier Transform and Neural Network algorithms for analysis and automated classification of lung sounds. Overall sensitivity for the detection of wheezes or crackles using CLSA was 80% (95% CI 72-86%) and specificity was 85% (95% CI 78-91%). While quality data on CLSA are relatively limited, analysis of existing information suggests that CLSA can provide a relatively high specificity for detecting abnormal lung sounds such as crackles and wheezes. Further research and product development could promote the value of CLSA in research studies or its diagnostic utility in clinical settings. Copyright © 2011 Elsevier Ltd. All rights reserved.

Function of the Dräger Oxylog ventilator at high altitude.

PubMed

Thomas, G; Brimacombe, J

1994-06-01

We have assessed the performance of the Dräger Oxylog ventilator at high altitude using a decompression chamber and a lung simulator set to mimic the normal and non-compliant lung. In the normal lung, tidal volume increased by 28% at 2040 metres and by 106% at 9120 metres. A lesser change, but in the opposite direction, occurred in respiratory rate. The net effect was a linear increase in minute volume with altitude. At 2040 and 9144 metres minute volume increased by 13% and by 45%, and rate decreased by 10% and 30% respectively. In the abnormal lung stimulation, similar, but slightly less marked, changes occurred in all variables. These changes are of sufficient magnitude to require frequent observation of tidal volume and respiratory rate during aircraft ascent and descent.

Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient.

PubMed

Davies, Gwyneth; Stocks, Janet; Thia, Lena P; Hoo, Ah-Fong; Bush, Andrew; Aurora, Paul; Brennan, Lucy; Lee, Simon; Lum, Sooky; Cottam, Philippa; Miles, Joanne; Chudleigh, Jane; Kirkby, Jane; Balfour-Lynn, Ian M; Carr, Siobhán B; Wallis, Colin; Wyatt, Hilary; Wade, Angie

2017-11-01

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV 0.5 ), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV 0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45-1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV 0.5 on all test occasions, precluding the ability to identify "high-risk" infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up. Copyright ©ERS 2017.

Redox imbalance and mitochondrial abnormalities in the diabetic lung.

PubMed

Wu, Jinzi; Jin, Zhen; Yan, Liang-Jun

2017-04-01

Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD + redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung. Using STZ induced diabetes in rat as a model, we measured redox-imbalance related parameters including aldose reductase activity, level of poly ADP ribose polymerase (PAPR-1), NAD + content, NADPH content, reduced form of glutathione (GSH), and glucose 6-phophate dehydrogenase (G6PD) activity. For assessment of mitochondrial abnormalities in the diabetic lung, we measured the activities of mitochondrial electron transport chain complexes I to IV and complex V as well as dihydrolipoamide dehydrogenase (DLDH) content and activity. We also measured the protein content of NAD + dependent enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Our results demonstrate that NADH/NAD + redox imbalance occurs in the diabetic lung. This redox imbalance upregulates the activities of complexes I to IV, but not complex V; and this upregulation is likely the source of increased mitochondrial ROS production, oxidative stress, and cell death in the diabetic lung. These results, together with the findings that the protein contents of DLDH, sirt3, and NQO1 all are decreased in the diabetic lung, demonstrate that redox imbalance, mitochondrial abnormality, and oxidative stress contribute to lung injury in diabetes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Changes in Lung Function and Chylous Effusions in Patients With Lymphangioleiomyomatosis Treated With Sirolimus

PubMed Central

Taveira-DaSilva, Angelo M.; Hathaway, Olanda; Stylianou, Mario; Moss, Joel

2011-01-01

Background Lymphangioleiomyomatosis (LAM) is a disorder that affects women and is characterized by cystic lung destruction, chylous effusions, lymphangioleiomyomas, and angiomyolipomas. It is caused by proliferation of abnormal smooth muscle–like cells. Sirolimus is a mammalian target of rapamycin inhibitor that has been reported to decrease the size of neoplastic growths in animal models of tuberous sclerosis complex and to reduce the size of angiomyolipomas and stabilize lung function in humans. Objective To assess whether sirolimus therapy is associated with improvement in lung function and a decrease in the size of chylous effusions and lymphangioleiomyomas in patients with LAM. Design Observational study. Setting The National Institutes of Health Clinical Center. Patients 19 patients with rapidly progressing LAM or chylous effusions. Intervention Treatment with sirolimus. Measurements Lung function and the size of chylous effusions and lymphangioleiomyomas before and during sirolimus therapy. Results Over a mean of 2.5 years before beginning sirolimus therapy, the mean (±SE) FEV1 decreased by 2.8% ± 0.8% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) decreased by 4.8% ± 0.9% predicted per year. In contrast, over a mean of 2.6 years of sirolimus therapy, the mean (± SE) FEV1 increased by 1.8% ± 0.5% predicted and DLCO increased by 0.8% ± 0.5% predicted per year (P < 0.001). After beginning sirolimus therapy, 12 patients with chylous effusions and 11 patients with lymphangioleiomyomas experienced almost complete resolution of these conditions. In 2 of the 12 patients, sirolimus therapy enabled discontinuation of pleural fluid drainage. Limitations This was an observational study. The resolution of effusions may have affected improvements in lung function. Conclusion Sirolimus therapy is associated with improvement or stabilization of lung function and reduction in the size of chylous effusions and lymphangioleiomyomas in patients with LAM. Primary Funding Source Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health. PMID:21690594

42 CFR 37.54 - Notification of abnormal radiographic findings.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., abnormality of cardiac shape or size, tuberculosis, lung cancer, or any other significant abnormal findings... shape or size, tuberculosis, cancer, complicated pneumoconiosis, and any other significant abnormal...

Impact of lung disease on respiratory impedance in young children with cystic fibrosis.

PubMed

Ramsey, Kathryn A; Ranganathan, Sarath C; Gangell, Catherine L; Turkovic, Lidija; Park, Judy; Skoric, Billy; Stick, Stephen M; Sly, Peter D; Hall, Graham L

2015-12-01

This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease. Copyright ©ERS 2015.

Clinical and imaging features in lung torsion and description of a novel imaging sign.

PubMed

Hammer, Mark M; Madan, Rachna

2018-04-01

We set out to identify the clinical and imaging features seen in lung torsion, a rare but emergent diagnosis leading to vascular compromise of a lobe or entire lung. We retrospectively identified 10 patients with torsion who underwent chest CT. We evaluated each case for the presence of bronchial obstruction and abnormal fissure orientation. In seven patients who underwent contrast-enhanced CTs, we assessed for the presence of the antler sign, a novel sign seen on axial images demonstrating abnormal curvature of the artery and branches originating on one side. Five patients had right middle lobe (RML) torsion after right upper lobectomy, and the remaining occurred following thoracentesis, aortic surgery, or spontaneously. Chest CTs demonstrated bronchial obstruction in eight cases and presence of abnormal fissure orientation in four patients. The antler sign was present in three patients with whole-lung torsion and one patient with lobar torsion; vascular swirling was seen on 3-D images in all seven patients with contrast-enhanced CTs. Lung parenchymal imaging findings in lung torsion may be non-specific. Identification of the antler sign on contrast-enhanced chest CT, in combination with other signs such as bronchial obstruction and abnormal fissure orientation, indicates rotation of the bronchovascular pedicle. The presence of this sign should prompt further evaluation with 3-dimensional reconstructions.

Pulmonary function in children and adolescents with sickle cell disease: have we paid proper attention to this problem?

PubMed

Vieira, Ana Karine; Alvim, Cristina Gonçalves; Carneiro, Maria Cristina Marquez; Ibiapina, Cássio da Cunha

2016-01-01

To evaluate pulmonary function and functional capacity in children and adolescents with sickle cell disease. This was a cross-sectional study involving 70 children and adolescents (8-15 years of age) with sickle cell disease who underwent pulmonary function tests (spirometry) and functional capacity testing (six-minute walk test). The results of the pulmonary function tests were compared with variables related to the severity of sickle cell disease and history of asthma and of acute chest syndrome. Of the 64 patients who underwent spirometry, 15 (23.4%) showed abnormal results: restrictive lung disease, in 8 (12.5%); and obstructive lung disease, in 7 (10.9%). Of the 69 patients who underwent the six-minute walk test, 18 (26.1%) showed abnormal results regarding the six-minute walk distance as a percentage of the predicted value for age, and there was a ≥ 3% decrease in SpO2 in 36 patients (52.2%). Abnormal pulmonary function was not significantly associated with any of the other variables studied, except for hypoxemia and restrictive lung disease. In this sample of children and adolescents with sickle cell disease, there was a significant prevalence of abnormal pulmonary function. The high prevalence of respiratory disorders suggests the need for a closer look at the lung function of this population, in childhood and thereafter. Avaliar a função pulmonar e a capacidade funcional em crianças e adolescentes com doença falciforme. Estudo transversal com 70 crianças e adolescentes com doença falciforme (8-15 anos), submetidos a testes de função respiratória (espirometria) e de capacidade funcional (teste de caminhada de seis minutos). Os resultados da avaliação da função pulmonar foram comparados com variáveis relacionadas à gravidade da doença falciforme e à presença de história de asma e de síndrome torácica aguda. Dos 64 pacientes submetidos à espirometria, 15 (23,4%) apresentaram resultados alterados: distúrbio ventilatório restritivo, em 8; (12,5%) e distúrbio respiratório obstrutivo, em 7 (10,9%). Dos 69 pacientes submetidos ao teste de caminhada de seis minutos, 18 (26,1%) apresentaram resultados alterados na distância em % do previsto para a idade, e houve uma queda ≥ 3% na SpO2 em 36 (52,2%) dos pacientes. Não houve associações significativas entre função pulmonar alterada e as outras variáveis analisadas, exceto para hipoxemia e distúrbio ventilatório restritivo. Observou-se uma significativa prevalência de alterações na função pulmonar nesta amostra de crianças e adolescentes com doença falciforme. A elevada prevalência de distúrbios ventilatórios sugere a necessidade de um olhar mais atento à função pulmonar desde a infância nessa população.

Incidental renal tumours on low-dose CT lung cancer screening exams.

PubMed

Pinsky, Paul F; Dunn, Barbara; Gierada, David; Nath, P Hrudaya; Munden, Reginald; Berland, Lincoln; Kramer, Barnett S

2017-06-01

Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P < 0.001). Cases with abnormalities below the diaphragms had shorter median time to diagnosis than those without (71 vs. 160 days, P = 0.004). In the reader study, 64% of renal cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P < 0.001). Conclusion Low-dose computed tomography screens can potentially detect renal cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

Acute tropical pulmonary eosinophilia. Characterization of the lower respiratory tract inflammation and its response to therapy.

PubMed Central

Pinkston, P; Vijayan, V K; Nutman, T B; Rom, W N; O'Donnell, K M; Cornelius, M J; Kumaraswami, V; Ferrans, V J; Takemura, T; Yenokida, G

1987-01-01

Although acute tropical pulmonary eosinophilia (TPE) is well recognized as a manifestation of filarial infection, the processes that mediate the abnormalities of the lung in TPE are unknown. To evaluate the hypothesis that the derangements of the lower respiratory tract in this disorder are mediated by inflammatory cells in the local milieu, we utilized bronchoalveolar lavage to evaluate affected individuals before and after therapy. Inflammatory cells recovered from the lower respiratory tract of individuals with acute, untreated TPE (n = 8) revealed a striking eosinophilic alveolitis, with marked elevations in both the proportion of eosinophils (TPE 54 +/- 5%; normal 2 +/- 5%; P less than 0.001) and the concentration of eosinophils in the recovered epithelial lining fluid (ELF) (TPE 63 +/- 20 X 10(3)/microliter; normal 0.3 +/- 0.1 X 10(3)/microliter; P less than 0.01). Importantly, when individuals (n = 5) with acute TPE were treated with diethylcarbamazine (DEC), there was a marked decrease of the lung eosinophils and concomitant increase in lung function. These observations are consistent with the concept that at least some of the abnormalities found in the lung in acute TPE are mediated by an eosinophil-dominated inflammatory process in the lower respiratory tract. Images PMID:3298321

Abnormal pulmonary function and associated risk factors in children and adolescents with sickle cell anemia

PubMed Central

Arteta, Manuel; Campbell, Andrew; Nouraie, Mehdi; Rana, Sohail; Onyekwere, Onyinye; Ensing, Gregory; Sable, Craig; Dham, Niti; Darbari, Deepika; Luchtman-Jones, Lori; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Minniti, Caterina P.; Gordeuk, Victor R.

2015-01-01

Obstructive and restrictive pulmonary changes develop in children with sickle cell disease, but reports conflict as to the type of change that predominates. We prospectively performed spirometry, plethysmography and lung diffusing capacity in 146 children aged 7–20 years with hemoglobin SS or Sβ0-thalassemia. Nineteen percent of the patients had obstructive physiology as defined according to guidelines of the American Thoracic Society. In addition, 9% had restrictive physiology and 11% had abnormal but not categorized physiology. Increasing age, patient- or family-reported history of asthma or wheezing, and higher lactate dehydrogenase concentration were independent predictors of obstruction as reflected in lower FEV1/FVC. In conclusion, abnormal pulmonary function, most often obstructive, is common in children with hemoglobin SS and Sβ0-thalassemia. Full pulmonary function testing should be performed in children with hemoglobin SS or Sβ0 thalassemia, especially with history of asthma or wheezing and accentuated elevations in hemolytic markers. PMID:24309610

Prevalence of abnormal findings when adopting new national and international Global Lung Function Initiative reference values for spirometry in the Finnish general population

PubMed Central

Kainu, Annette; Lindqvist, Ari; Sovijärvi, Anssi R. A.

2016-01-01

Background New Finnish (Kainu2015) and international Global Lung Function Initiative (GLI2012) reference values for spirometry were recently published. The aim of this study is to compare the interpretative consequences of adopting these new reference values with older, currently used Finnish reference values (Viljanen1982) in the general population of native Finns. Methods Two Finnish general population samples including 1,328 adults (45% males) aged 21–74 years were evaluated. Airway obstruction was defined as a reduced ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), possible restrictive pattern as reduced FVC, and decreased ventilatory capacity as reduced FEV1 below their respective 2.5th percentiles. The severity gradings of reduced lung function were also compared. Results Using the Kainu2015 reference values, the prevalence of airway obstruction in the population was 5.6%; using GLI2012 it was 4.0% and with Viljanen1982 it was 13.0%. Possible restrictive pattern was found in 4.2% using the Kainu2015 values, in 2.0% with GLI2012, and 7.9% with the Viljanen1982 values. The prevalence of decreased ventilatory capacity was 6.8, 4.0, and 13.3% with the Kainu2015, GLI2012 and Viljanen1982 values, respectively. Conclusions The application of the GLI2012 reference values underestimates the prevalence of abnormal spirometric findings in native Finns. The adoption of the Kainu2015 reference values reduces the prevalences of airways obstruction, decreased ventilatory capacity, and restrictive impairment by approximately 50%. Changing from the 2.5th percentile, the previously used lower limit of normal, to the 5th percentile recommended by the American Thoracic Society/European Respiratory Society will not increase the prevalence of abnormal findings in the implementation of spirometry reference values. PMID:27608270

Effect of a Gonadotrophin-Releasing Hormone Analogue on Lung Function in Lymphangioleiomyomatosis

PubMed Central

Harari, Sergio; Cassandro, Roberto; Chiodini, Jacopo; Taveira-DaSilva, Angelo M.; Moss, Joel

2010-01-01

Background Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM. Methods Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed. Results Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density. Conclusions Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density. PMID:18071009

A conserved post-transcriptional BMP2 switch in lung cells.

PubMed

Jiang, Shan; Fritz, David T; Rogers, Melissa B

2010-05-15

An ultra-conserved sequence in the bone morphogenetic protein 2 (BMP2) 3' untranslated region (UTR) markedly represses BMP2 expression in non-transformed lung cells. In contrast, the ultra-conserved sequence stimulates BMP2 expression in transformed lung cells. The ultra-conserved sequence functions as a post-transcriptional cis-regulatory switch. A common single-nucleotide polymorphism (SNP, rs15705, +A1123C), which has been shown to influence human morphology, disrupts a conserved element within the ultra-conserved sequence and altered reporter gene activity in non-transformed lung cells. This polymorphism changed the affinity of the BMP2 RNA for several proteins including nucleolin, which has an increased affinity for the C allele. Elevated BMP2 synthesis is associated with increased malignancy in mouse models of lung cancer and poor lung cancer patient prognosis. Understanding the cis- and trans-regulatory factors that control BMP2 synthesis is relevant to the initiation or progression of pathologies associated with abnormal BMP2 levels. (c) 2010 Wiley-Liss, Inc.

The LISS--a public database of common imaging signs of lung diseases for computer-aided detection and diagnosis research and medical education.

PubMed

Han, Guanghui; Liu, Xiabi; Han, Feifei; Santika, I Nyoman Tenaya; Zhao, Yanfeng; Zhao, Xinming; Zhou, Chunwu

2015-02-01

Lung computed tomography (CT) imaging signs play important roles in the diagnosis of lung diseases. In this paper, we review the significance of CT imaging signs in disease diagnosis and determine the inclusion criterion of CT scans and CT imaging signs of our database. We develop the software of abnormal regions annotation and design the storage scheme of CT images and annotation data. Then, we present a publicly available database of lung CT imaging signs, called LISS for short, which contains 271 CT scans and 677 abnormal regions in them. The 677 abnormal regions are divided into nine categories of common CT imaging signs of lung disease (CISLs). The ground truth of these CISLs regions and the corresponding categories are provided. Furthermore, to make the database publicly available, all private data in CT scans are eliminated or replaced with provisioned values. The main characteristic of our LISS database is that it is developed from a new perspective of CT imaging signs of lung diseases instead of commonly considered lung nodules. Thus, it is promising to apply to computer-aided detection and diagnosis research and medical education.

Abnormal findings in brainstem auditory evoked response at 36-37weeks of postconceptional age in babies with neonatal chronic lung disease.

PubMed

Jiang, Ze D; Wang, Cui

2016-12-01

To examine brainstem auditory function at 36-37weeks of postconceptional age in preterm infants who are diagnosed to have neonatal chronic lung disease (CLD). Preterm infants, born at 31 and less weeks of gestation, were studied at 36-37weeks of postconceptional age when they were diagnosed to have neonatal CLD. Brainstem auditory evoked response (BAER) was recorded and analyzed at different click rates. Compared with healthy controls at the same postconceptional age, the CLD infants showed a slightly increase in BAER wave V latency. However, the I-V, and III-V interpeak intervals in the CLD infants were significantly increased. The III-V/I-III interval ratio was also significantly increased. The amplitudes of BAER waves III and V in the CLD infants tended to be reduced. These BAER findings were similar at all 21, 51 and 91/s clicks, although the abnormalities tended to be more significant at higher than at low click rates. At 36-37weeks of postconceptional age, BAER was abnormal in preterm infants who were diagnosed to have neonatal CLD. This suggests that at time when the diagnosis of CLD is made there is functional impairment, reflecting poor myelination, in the brainstem auditory pathway in preterm infants with neonatal CLD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Time course of lung function changes in atypical pneumonia.

PubMed Central

Benusiglio, L N; Stalder, H; Junod, A F

1980-01-01

We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae. PMID:7444825

The role of ultrasonography in the management of lung and pleural diseases.

PubMed

Rumende, C Martin

2012-04-01

Ultrasonographic examination in pulmonology provides a revolutionary advance because it is very helpful in the diagnosis and management of various pleural and peripheral pulmonary defects. Lung ultrasonography allows the clinicians to diagnose some pulmonary abnormalities more rapidly, including the diagnosis of pleural effusion. Ultrasound examination also provides great assistance for the clinicians to perform invasive techniques in the field of pulmonology, which may increase the success rate and reduce the likelihood of complications. In addition to pleural effusion, other lung disorders can be diagnosed by ultrasound such as peripheral lung tumors and other pleural abnormalities caused by pleural fibrosis and tumor metastasis as well as the primary pleural tumor (mesothelioma). Ultrasound-guided invasive procedures include aspiration of minimal effusion, Transthoracal Needle Aspiration, Transthoracal biopsies and chest tube insertion. Lung ultrasound also offers other advantages, i.e. free from radiation hazards, portable, non-invasive and relatively inexpensive. Ultrasonography in the thorax also has its limitations, especially in detecting mediastinal abnormalities.

IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age

PubMed Central

Lauhkonen, Eero; Koponen, Petri; Teräsjärvi, Johanna; Gröndahl-Yli-Hannuksela, Kirsi; Vuononvirta, Juho; Nuolivirta, Kirsi; Toikka, Jyri O.; Helminen, Merja; He, Qiushui; Korppi, Matti

2015-01-01

Aim Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age. Methods We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children. Results IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise. Conclusion Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients. PMID:26473365

Radiology compared with xenon—133 scanning and bronchoscopic lobar sampling as methods for assessing regional lung function in patients with emphysema

PubMed Central

Barter, C. E.; Hugh-Jones, P.; Laws, J. W.; Crosbie, W. A.

1973-01-01

Regional lung function was assessed by radiographic methods, by regional function studies using xenon-133 scans, and by lobar sampling with a mass spectrometer flow-meter at bronchoscopy in 12 patients who subsequently had bullae resected at operation. The information given by these three methods of regional assessment was subsequently compared with the findings at operation. When only one lobe was abnormal on the radiographs, these alone were adequate to locate the major site of the emphysema and the regional tests gave relatively little extra information. The xenon scan was sometimes helpful in assessing the state of the remaining lung, but this information could be deduced from the radiographs and overall lung function tests, especially the carbon monoxide transfer and mechanical measurements. Bronchoscopic sampling was helpful in determining whether the affected lobe was acting as a ventilated dead-space. When more than one lobe was affected the regional function tests supplemented the radiographs in defining the site of bullous change as well as locating dead space. Xenon scans, although widely employed for such preoperative assessments, added little to the topographical information obtained by careful radiology. The combination of radiology, lobar sampling, and overall function tests is recommended for assessing which emphysematous patients are likely to benefit from surgery. Images PMID:4685209

Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis.

PubMed

Leslie, Kevin O

2012-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal lung disease occurring in older individuals. Despite 50 years of accrued data about the disease, little progress has been made in slowing functional loss or in decreasing patient mortality. To present a novel hypothesis on the etiology and pathogenesis of idiopathic pulmonary fibrosis. Published data are reviewed regarding the epidemiology, clinical presentation, natural history, radiologic findings, and pathologic findings in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis may be predisposed genetically to tractional injury to the peripheral lung. The result is recurrent damage to the epithelial-mesenchymal interface, preferentially at the outer edges of the basilar lung lobules where tractional stress is high during inspiration, compliance is relatively low, and there is a greater tendency for alveolar collapse at end-expiration. A distinctive "reticular network of injury" (the fibroblast focus) forms, attended by a prolonged phase of wound repair (tear and slow repair). Discrete areas of alveolar collapse are observed in scar at the periphery of the lung lobules. The cycle repeats over many years resulting in progressive fibrous remodeling and replacement of the alveoli in a lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in surfactant function are proposed as a potential mechanism of initial lung damage. Age of onset may be a function of a required threshold of environmental exposures (eg, cigarette smoking) or other comorbid injury to the aging lung. Evidence supporting this hypothesis is presented and potential mechanisms are discussed. A potential role for contributing cofactors is presented.

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

Harris, C.C.; Cohen, M.H.; Connor, R.

Scrum alpha/sub 1/-antitrypsin Pi types and trypsin inhibitory capacity (TIC) were measured in 72 patients with lung cancer and in 196 patients with abnormal sputum cytology but no clinical evidence of lung cancer to determine if a genetic deficiency of alpha/sub 1/-antitrypsin (AAT) predisposes to lung cancer. The distributions of Pi types in these two groups of patients and healthy adults are similar. Serum TIC and AAT concentrations are elevated in lung cancer patients. However, patients with abnormal sputum cytology and no clinical lung cancer have normal levels of serum TIC and AAT. A genetic deficiency of AAT probably doesmore » not produce a state of increased susceptibility to the carcinogenic effects of respiratory carcinogens such as tobacco smoke.« less

Impaired pulmonary function after treatment for tuberculosis: the end of the disease?

PubMed Central

Chushkin, Mikhail Ivanovich; Ots, Oleg Nikolayevich

2017-01-01

ABSTRACT Objective: To evaluate the prevalence of pulmonary function abnormalities and to investigate the factors affecting lung function in patients treated for pulmonary tuberculosis. Methods: A total of 214 consecutive patients (132 men and 82 women; 20-82 years of age), treated for pulmonary tuberculosis and followed at a local dispensary, underwent spirometry and plethysmography at least one year after treatment. Results: Pulmonary impairment was present in 102 (47.7%) of the 214 patients evaluated. The most common functional alteration was obstructive lung disease (seen in 34.6%). Of the 214 patients, 60 (28.0%) showed reduced pulmonary function (FEV1 below the lower limit of normal). Risk factors for reduced pulmonary function were having had culture-positive pulmonary tuberculosis in the past, being over 50 years of age, having recurrent tuberculosis, and having a lower level of education. Conclusions: Nearly half of all tuberculosis patients evolve to impaired pulmonary function. That underscores the need for pulmonary function testing after the end of treatment. PMID:28380187

Radiation and Its Health Effects. AIO Red Paper #19.

ERIC Educational Resources Information Center

Duda, Terrie

Radiation has been a serious concern to individuals for over 100 years. A process by which an atomic nucleus emits particles to reach a more stable energy state, radiation harms living cells (usually by inhalation and absorption into the lungs) by causing abnormal cell function and structure. Man is constantly exposed to background radiation, both…

Respirator triggering of electron beam computed tomography (EBCT): evaluation of dynamic changes during mechanical expiration in the traumatized patient

NASA Astrophysics Data System (ADS)

Recheis, Wolfgang A.; Kleinsasser, Axel; Hatschenberger, Robert; Knapp, Rudolf; zur Nedden, Dieter; Hoermann, Christoph

1999-05-01

The purpose of this project is to evaluate the dynamic changes during expiration at different levels of positive end- expiratory pressure (PEEP) in the ventilated patient. We wanted to discriminate between normal lung function and acute respiratory distress syndrome (ARDS). After approval by the local Ethic Committee we studied two ventilated patients: (1) with normal lung function; (2) ARDS). We used the 50 ms scan mode of the EBCT. The beam was positioned 1 cm above the diaphragm. The table position remained unchanged. An electronic trigger was developed, that utilizes the respirators synchronizing signal to start the EBCT at the onset of expiration. During controlled mechanical expiration at two levels of PEEP (0 and 15 cm H2O), pulmonary aeration was rated as: well-aerated (-900HU/-500HU), poorly- aerated (-500HU/-100HU) and non-aerated (-100HU/+100HU). Pathological and normal lung function showed different dynamic changes (FIG.4-12). The different PEEP levels resulted in a significant change of pulmonary aeration in the same patient. Although we studied only a very limited number of patients, respirator triggered EBCT may be accurate in discriminating pathological changes due to the abnormal lung function in the mechanically ventilated patient.

Computer-Aided Diagnostic System For Mass Survey Chest Images

NASA Astrophysics Data System (ADS)

Yasuda, Yoshizumi; Kinoshita, Yasuhiro; Emori, Yasufumi; Yoshimura, Hitoshi

1988-06-01

In order to support screening of chest radiographs on mass survey, a computer-aided diagnostic system that automatically detects abnormality of candidate images using a digital image analysis technique has been developed. Extracting boundary lines of lung fields and examining their shapes allowed various kind of abnormalities to be detected. Correction and expansion were facilitated by describing the system control, image analysis control and judgement of abnormality in the rule type programing language. In the experiments using typical samples of student's radiograms, good results were obtained for the detection of abnormal shape of lung field, cardiac hypertrophy and scoliosis. As for the detection of diaphragmatic abnormality, relatively good results were obtained but further improvements will be necessary.

A General Approach to the Evaluation of Ventilation-Perfusion Ratios in Normal and Abnormal Lungs

ERIC Educational Resources Information Center

Wagner, Peter D.

1977-01-01

Outlines methods for manipulating multiple gas data so as to gain the greatest amount of insight into the properties of ventilation-perfusion distributions. Refers to data corresponding to normal and abnormal lungs. Uses a two-dimensional framework with the respiratory gases of oxygen and carbon dioxide. (CS)

The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise Capacity - Results from the Study of Health in Pomerania (SHIP).

PubMed

Stubbe, Beate; Schipf, Sabine; Schäper, Christoph; Felix, Stephan B; Steveling, Antje; Nauck, Matthias; Völzke, Henry; Wallaschofski, Henri; Friedrich, Nele; Ewert, Ralf; Ittermann, Till; Gläser, Sven

2017-01-01

Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients. Our study is based on population data of the Study of Health in Pomerania (SHIP). Objective: To investigate the influence of metabolic control on pulmonary system function and to establish a decreased pulmonary system function as a late complication of T1DM in a population based setting. Methods: The study is a case matched study with multiple controls based on participants with T1DM (SHIP-DM-1, n=73) and non-diabetics (SHIP-1, n=292) from the population based study of Pomerania. Data on lung function and exercise performance stratified by age, sex, body mass index and smoking habits in participants with T1DM and without diabetes were matched. Results: Participants with T1DM showed a significantly lower total lung capacity, residual volume and forced vital capacity. The transfer factor for carbon monoxide, the maximum power output and oxygen uptake during exercise were significantly decreased in comparison to the general population without diabetes. Conclusion: The pattern of abnormal pulmonary function as observed in the present study with a reduction in lung volume parameters and reduced oxygen uptake in participants with T1DM suggests a restrictive type of lung disease caused by an intrinsic lung tissue derangement as well as pulmonary microangiopathy. © Georg Thieme Verlag KG Stuttgart · New York.

Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk - a re-analysis of eight GWASs

PubMed Central

Zhou, Fei; Wang, Yanru; Liu, Hongliang; Ready, Neal; Han, Younghun; Hung, Rayjean J.; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S.; Caporaso, Neil; Landi, Maria Teresa; Brüske, Irene; Risch, Angela; Ye, Yuanqing; Wu, Xifeng; Christiani, David C.; Goodman, Gary; Chen, Chu; Amos, Christopher I.; Qingyi, Wei

2017-01-01

Purpose mRNA degradation is an important regulatory step for controlling gene expression and cell functions. Genetic abnormalities of the genes involved in mRNA degradation were found to be associated with cancer risks. Therefore, we systematically investigated the roles of genetic variants of genes in the general mRNA degradation pathway in lung cancer risk. Experimental design Meta-analyses were conducted in six lung cancer genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung and additional two GWASs from Harvard University and deCODE in the International Lung Cancer Consortium. Expression quantitative trait loci analysis (eQTL) was used for in silico functional validation of the identified significant susceptibility loci. Results This pathway-based analysis included 4,603 single nucleotide polymorphisms (SNP) in 68 genes in 14,463 lung cancer cases and 44,188 controls, of which 20 SNPs were found to be associated with lung cancer risk with a false discovery rate threshold of <0.05. Among the 11 newly identified SNPs in CNOT6, which were in high linkage disequilibrium, the rs2453176 with a RegulomDB score “1f” was chosen as the tag SNP for further analysis. We found that the rs2453176 T allele was significantly associated with lung cancer risk (odds ratio=1.11, 95% confidence interval=1.04–1.18, P=0.001) in the eight GWASs. In the eQTL analysis, we found that levels of CNOT6 mRNA expression were significantly correlated with the rs2453176 T allele, which provided additional biological basis for the observed positive association. Conclusion The CNOT6 rs2453176 SNP may be a new functional susceptible locus for lung cancer risk. PMID:27805284

Susceptibility loci of CNOT6 in the general mRNA degradation pathway and lung cancer risk-A re-analysis of eight GWASs.

PubMed

Zhou, Fei; Wang, Yanru; Liu, Hongliang; Ready, Neal; Han, Younghun; Hung, Rayjean J; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S; Caporaso, Neil; Landi, Maria Teresa; Brüske, Irene; Risch, Angela; Ye, Yuanqing; Wu, Xifeng; Christiani, David C; Goodman, Gary; Chen, Chu; Amos, Christopher I; Wei, Qingyi

2017-04-01

mRNA degradation is an important regulatory step for controlling gene expression and cell functions. Genetic abnormalities involved in mRNA degradation genes were found to be associated with cancer risks. Therefore, we systematically investigated the roles of genetic variants in the general mRNA degradation pathway in lung cancer risk. Meta-analyses were conducted using summary data from six lung cancer genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung and additional two GWASs from Harvard University and deCODE in the International Lung Cancer Consortium. Expression quantitative trait loci analysis (eQTL) was used for in silico functional validation of the identified significant susceptibility loci. This pathway-based analysis included 6816 single nucleotide polymorphisms (SNP) in 68 genes in 14 463 lung cancer cases and 44 188 controls. In the single-locus analysis, we found that 20 SNPs were associated with lung cancer risk with a false discovery rate threshold of <0.05. Among the 11 newly identified SNPs in CNOT6, which were in high linkage disequilibrium, the rs2453176 with a RegulomDB score "1f" was chosen as the tagSNP for further analysis. We found that the rs2453176 T allele was significantly associated with lung cancer risk (odds ratio = 1.11, 95% confidence interval = 1.04-1.18) in the eight GWASs. In the eQTL analysis, we found that levels of CNOT6 mRNA expression were significantly correlated with the rs2453176 T allele, which provided additional biological basis for the observed positive association. The CNOT6 rs2453176 SNP may be a new functional susceptible locus for lung cancer risk. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

42 CFR 37.54 - Notification of abnormal radiographic findings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... shape or size, tuberculosis, lung cancer, or any other significant abnormal findings other than..., tuberculosis, cancer, complicated pneumoconiosis, and any other significant abnormal findings, NIOSH will...

[Lung is also involved in juvenile dermatomyositis].

PubMed

Pouessel, G; Thumerelle, C; Nève, V; Santangelo, T; Flammarion, S; Pruvot, I; Tillie-Leblond, I; Deschildre, A

2014-07-01

Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children. Lung involvement in inflammatory myopathies is well described in adults, involving mostly interstitial lung disease, aspiration pneumonia and alveolar hypoventilation. We propose to describe its specificities in children. Pulmonary involvement may be asymptomatic and therefore must be systematically screened for. In case of clinical or functional respiratory abnormality, a chest computed tomographic (CT) scan is necessary. In children, a decrease of respiratory muscle strength seems common and should be systematically and specifically searched for by non-invasive and reproducible tests (sniff test). Interstitial lung disease usually associates restrictive functional defect, impairment of carbon monoxide diffusion and interstitial lung disease on CT scan. As in adults, the first-line treatment of juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant forms require corticosteroid bolus or adjuvant immunosuppressive drugs (methotrexate or cyclosporine). There is no consensus in pediatrics for the treatment of diffuse interstitial lung disease. Complications of treatment, including prolonged steroid therapy, are frequent and therefore a careful assessment of the treatments risk-benefit ratio is necessary, especially in growing children. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Hypoxemia, hypercapnia, and breathing pattern in patients with chronic obstructive pulmonary disease.

PubMed

Parot, S; Miara, B; Milic-Emili, J; Gautier, H

1982-11-01

The results of lung function tests (total and functional residual capacities, residual volume/total lung capacity ratio, forced expiratory volume in one second) breathing patterns and arterial PO2 and PCO2 were studied in 651 ambulatory male patients with chronic obstructive pulmonary disease, functionally and clinically stable. Function tests were only loosely correlated with gas tensions: abnormalities in mechanics and in gas exchange are not necessarily related. In patients matched for the degree of obstruction, the breathing pattern depended upon both PaO2 and PaCO2. Isolated hypoxemia was accompanied by increased respiratory frequency without any variation in tidal volume: this suggests that the chemoreceptive systems still responded to changes in PaO2. Isolated hypercapnia was accompanied by a decrease in tidal volume and an increase in respiratory frequency. Consequently, the dead space/tidal volume ratio increased, leading to a drop in alveolar ventilation and to CO2 retention.

[Respiratory function in heroin addicts with or without HIV infection. Study of 107 cases with a 6-month follow-up of 36 subjects].

PubMed

Escamilla, R; Pecoul, J; Hermant, C; Besombes, J P; Krempf, M

1992-01-01

Both intravenous drug addiction (IVDA) and HIV infection can involve respiratory system. So, we have studied pulmonary function in 107 heroin abusers during deprivation to clarify the extent of these two factors respectively. Two groups were separated: 50 subjects without HIV infection (HIV-) and 57 seropositive subjects (HIV+) in early stage of the disease (mean CD4 lymphocytes: 457 +/- 61/mm3). 36 subjects have been investigated 6 months later to evaluate the reversibility of possible observed abnormalities. Altered pulmonary function was encountered similarly in HIV+ and HIV-. DLco was abnormal in 40% of cases both in HIV+ (mean DLco: 63.4 +/- 1.1% of predicted values) and HIV- (mean DLco: 65.4 +/- 1.5% pred); obstructive lung disease was present in 18% of HIV- (FEV1/VC: 63.8 +/- 2.5) and 9% of HIV+ (FEV1/VC: 61 +/- 3.6); restrictive lung disease was found more frequently (16% vs 10%) in HIV+ (FEV1/VC: 81.2 +/- 2.1, TLC: 72.4 +/- 3.6% pred) than in HIV- (FEV1/VC: 84.2 +/- 1.6, TLC: 71.2 +/- 0.9% pred). These abnormalities were not associated with significant arterial blood gas modifications. As a whole, DLco tend to improve in the two groups and this significantly for HIV+ (p less than 0.03). But for individuals initial DLco alteration was persistent in 68% of cases suggesting slow improvement. In conclusion, in this study HIV+ and HIV- IVDA were not different concerning pulmonary function. In this risk group, DLco itself had a poor specificity and only it follow-up may be of interest for pulmonary opportunistic infection screening.

A Review of Clinical and Imaging Findings in Eosinophilic Lung Diseases.

PubMed

Bernheim, Adam; McLoud, Theresa

2017-05-01

The purpose of this article is to review the clinical and imaging findings associated with eosinophilic lung diseases. The spectrum of eosinophilic lung diseases comprises a diverse group of pulmonary disorders that have an association with tissue or peripheral eosinophilia. These diseases have varied clinical presentations and may be associated with several other abnormalities. Characteristic imaging findings are often detected with chest radiography, and CT best shows parenchymal abnormalities. The integration of clinical, radiologic, and pathologic findings facilitates diagnosis and directs appropriate treatment.

Quantification of Dynamic [18F]FDG Pet Studies in Acute Lung Injury.

PubMed

Grecchi, Elisabetta; Veronese, Mattia; Moresco, Rosa Maria; Bellani, Giacomo; Pesenti, Antonio; Messa, Cristina; Bertoldo, Alessandra

2016-02-01

This work aims to investigate lung glucose metabolism using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging in acute lung injury (ALI) patients. Eleven ALI patients and five healthy controls underwent a dynamic [(18)F]FDG PET/X-ray computed tomography (CT) scan. The standardized uptake values (SUV) and three different methods for the quantification of glucose metabolism (i.e., ratio, Patlak, and spectral analysis iterative filter, SAIF) were applied both at the region and the voxel levels. SUV reported a lower correlation than the ratio with the net tracer uptake. Patlak and SAIF analyses did not show any significant spatial or quantitative (R(2) > 0.80) difference. The additional information provided by SAIF showed that in lung inflammation, elevated tracer uptake is coupled with abnormal tracer exchanges within and between lung tissue compartments. Full kinetic modeling provides a multi-parametric description of glucose metabolism in the lungs. This allows characterizing the spatial distribution of lung inflammation as well as returning the functional state of the tissues.

Lung function, diagnosis, and treatment of sleep-disordered breathing in children with achondroplasia.

PubMed

Julliand, Sébastien; Boulé, Michèle; Baujat, Geneviève; Ramirez, Adriana; Couloigner, Vincent; Beydon, Nicole; Zerah, Michel; di Rocco, Federico; Lemerrer, Martine; Cormier-Daire, Valérie; Fauroux, Brigitte

2012-08-01

Children with achondroplasia are at risk of sleep-disordered breathing. The aim of the study was to evaluate lung function and sleep-disordered breathing in children with achondroplasia. An interview, clinical examination, lung function tests with blood gases, and a polygraphic sleep study were obtained as part of routine annual evaluation in consecutive children with achondroplasia. We included 30 children (median age 3.0 years, range: 0.4-17.1) over a period of 21 months. Habitual snoring and witnessed apneas were observed in 77% and 33% of the patients, respectively. Prior to the sleep study, 10/29 (34%) patients had undergone upper airway surgery and 5/29 (17%) craniocervical decompression operation. Arterial blood gases were abnormal in two (7%) patients. Sleep findings were abnormal in 28/30 (93%) patients. Eleven (37%) patients had an apnea index≥1 event/hr and 26 (87%) had an apnea-hypopnea index≥5 events/hr. The ≥3% desaturation index was >5/hr in 22 (73%) patients. Sixteen (53%) patients had a minimal pulse oximetry<90% but only two (7%) patients had a maximal transcutaneous carbon dioxide pressure>50 mmHg during sleep. As a consequence, the following therapeutic interventions were performed: upper airway surgery in four patients and noninvasive positive pressure ventilation (NPPV) in five other patients, resulting in an improvement in sleep studies in all nine patients. Systematic sleep studies are recommended in children with achondroplasia because of the high prevalence of sleep-disordered breathing. Upper airway surgery and NPPV are effective treatments of sleep-disordered breathing. Copyright © 2012 Wiley Periodicals, Inc.

Pulmonary outcome of esophageal atresia patients and its potential causes in early childhood.

PubMed

Dittrich, René; Stock, Philippe; Rothe, Karin; Degenhardt, Petra

2017-08-01

The aim of this study was to illustrate the pulmonary long term outcome of patients with repaired esophageal atresia and to further examine causes and correlations that might have led to this outcome. Twenty-seven of 62 possible patients (43%) aged 5-20years, with repaired esophageal atresia were recruited. Body plethysmography and spirometry were performed to evaluate lung function, and the Bruce protocol treadmill exercise test to assess physical fitness. Results were correlated to conditions such as interpouch distance, gastroesophageal reflux or duration of post-operative mechanical ventilation. Seventeen participants (63%) showed abnormal lung function at rest or after exercise. Restrictive ventilatory defects (solely restrictive or combined) were found in 11 participants (41%), and obstructive ventilatory defects (solely obstructive or combined) in 13 subjects (48%). Twenty-two participants (81%) performed the Bruce protocol treadmill exercise test to standard. The treadmill exercise results were expressed in z-score and revealed to be significantly below the standard population mean (z-score=-1.40). Moreover, significant correlations between restrictive ventilatory defects and the interpouch distance; duration of post-operative ventilation; gastroesophageal reflux disease; plus recurrent aspiration pneumonia during infancy; were described. It was shown that esophageal atresia and associated early complications have significant impact on pulmonary long term outcomes such as abnormal lung function and, in particular restrictive ventilatory defects. Long-running and regular follow-ups of patients with congenital esophageal atresia are necessary in order to detect and react to the development and progression of associated complications such as ventilation disorders or gastroesophageal reflux disease. Prognosis study, Level II. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of gastroesophageal reflux and delayed gastric emptying on pediatric lung transplant outcomes.

PubMed

Jamie Dy, Fei; Freiberger, Dawn; Liu, Enju; Boyer, Debra; Visner, Gary; Rosen, Rachel

2017-08-01

Gastroesophageal reflux disease is thought to predispose to adverse lung allograft outcomes. However, little is known about the burden of gastroesophageal reflux (GER) and gastroparesis in pediatric patients. In this study we describe the burden of reflux and gastroparesis in children undergoing lung transplant, and evaluates their impact on allograft survival and rejection incidence. This study is a retrospective analysis of pediatric lung transplant recipients who had combined pH and multichannel intraluminal impedance testing (pH-MII) and gastric-emptying scans (GES). Hazard ratios with 95% confidence intervals (CIs) estimated from Cox proportional hazard models were used to examine the associations between reflux parameters and adverse allograft outcomes. Covariates considered in the multivariate analysis included abnormal pH-MII testing, abnormal GES and Nissen fundoplication status. Kaplan-Meier curves were created, with log-rank testing employed to assess differences between groups. Thirty lung transplant recipients, aged 1 to 21 years, were identified. Eight of 30 patients (27%) had abnormal reflux by impedance, and 12 (40%) had abnormal pH-metry. Of 19 patients tested, 5 (26.3%) had evidence of gastric dysmotility; however, the severity of GER did not trend with delays in gastric emptying. Neither reflux burden by pH-MII testing nor fundoplication status impacted survival or rejection. However, delayed gastric emptying appeared significantly linked to the development of chronic lung allograft dysfunction, independent of GER. In children, reflux burden and fundoplication status do not impact lung transplant outcomes, but gastric dysmotility may be linked to allograft dysfunction in children. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

HOXA5 plays tissue-specific roles in the developing respiratory system.

PubMed

Landry-Truchon, Kim; Houde, Nicolas; Boucherat, Olivier; Joncas, France-Hélène; Dasen, Jeremy S; Philippidou, Polyxeni; Mansfield, Jennifer H; Jeannotte, Lucie

2017-10-01

Hoxa5 is essential for development of several organs and tissues. In the respiratory system, loss of Hoxa5 function causes neonatal death due to respiratory distress. Expression of HOXA5 protein in mesenchyme of the respiratory tract and in phrenic motor neurons of the central nervous system led us to address the individual contribution of these Hoxa5 expression domains using a conditional gene targeting approach. Hoxa5 does not play a cell-autonomous role in lung epithelium, consistent with lack of HOXA5 expression in this cell layer. In contrast, ablation of Hoxa5 in mesenchyme perturbed trachea development, lung epithelial cell differentiation and lung growth. Further, deletion of Hoxa5 in motor neurons resulted in abnormal diaphragm innervation and musculature, and lung hypoplasia. It also reproduced the neonatal lethality observed in null mutants, indicating that the defective diaphragm is the main cause of impaired survival at birth. Thus, Hoxa5 possesses tissue-specific functions that differentially contribute to the morphogenesis of the respiratory tract. © 2017. Published by The Company of Biologists Ltd.

PET scan

MedlinePlus

... in your lung is cancerous or harmless Normal Results A normal result means there were no problems ... which the tracer has abnormally collected. What Abnormal Results Mean Abnormal results depend on the part of ...

Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice

PubMed Central

Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert; Navarro, Edwin; Jain, Noopur; Carandang, Francis; Peterson, Joanna; Mokres, Lucia; Milla, Carlos; Preuss, Stefanie; Alcazar, Miguel Alejandre; Khan, Suleman; Masumi, Juliet; Ferreira-Tojais, Nancy; Mujahid, Sana; Starcher, Barry; Rabinovitch, Marlene

2014-01-01

Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice (Eln+/−) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type (Eln+/+) and Eln+/− littermates at baseline and after MV with air for 8–24 h. Lungs of unventilated Eln+/− mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln+/+ pups. Eln+/− lungs contained fewer capillaries than Eln+/+ lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln+/+ neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln+/− mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln+/− than in Eln+/+ pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln+/− compared with Eln+/+ mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln+/+ and Eln+/− mice. Paucity of lung capillaries in Eln+/− newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln+/− mice. PMID:25539853

[Lung abscess which needed to be distinguished from lung cancer; report of a case].

PubMed

Kamiya, Kazunori; Yoshizu, Akira; Misumi, Yuki; Hida, Naoya; Okamoto, Hiroaki; Yoshida, Sachiko

2011-12-01

Differential diagnosis of lung abscess from lung cancer is sometimes difficult. In February 2009, a 57-year-old man consulted our hospital complaining of bloody sputum. Chest computed tomography (CT) demonstrated a 2.5 cm nodule with pleural indentation, spicula and vascular involvement in the right S(3). Bronchofiberscope could not establish a definitive diagnosis. Blood test showed no abnormality. Three months later, progression of the nodule to the adjacent middle lobe was demonstrated by follow-up CT, and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed isotope accumulation in the nodule and hilar lymph node. A diagnosis of lung cancer was suspected and surgery was performed. The diagnosis of possible lung cancer was made by needle biopsy, and the patient underwent right upper lobectomy and partial resection of middle lobe with standard nodal dissection. The final pathological diagnosis was lung abscess. Lung abscess must be kept in mind as a possible differential diagnosis when abnormal shadow suspected of lung cancer is observed.

Lung lobe segmentation based on statistical atlas and graph cuts

NASA Astrophysics Data System (ADS)

Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

2012-03-01

This paper presents a novel method that can extract lung lobes by utilizing probability atlas and multilabel graph cuts. Information about pulmonary structures plays very important role for decision of the treatment strategy and surgical planning. The human lungs are divided into five anatomical regions, the lung lobes. Precise segmentation and recognition of lung lobes are indispensable tasks in computer aided diagnosis systems and computer aided surgery systems. A lot of methods for lung lobe segmentation are proposed. However, these methods only target the normal cases. Therefore, these methods cannot extract the lung lobes in abnormal cases, such as COPD cases. To extract lung lobes in abnormal cases, this paper propose a lung lobe segmentation method based on probability atlas of lobe location and multilabel graph cuts. The process consists of three components; normalization based on the patient's physique, probability atlas generation, and segmentation based on graph cuts. We apply this method to six cases of chest CT images including COPD cases. Jaccard index was 79.1%.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

PubMed Central

Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

2016-01-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

Lung texture in serial thoracic CT scans: correlation with radiologist-defined severity of acute changes following radiation therapy

NASA Astrophysics Data System (ADS)

Cunliffe, Alexandra R.; Armato, Samuel G., III; Straus, Christopher; Malik, Renuka; Al-Hallaq, Hania A.

2014-09-01

This study examines the correlation between the radiologist-defined severity of normal tissue damage following radiation therapy (RT) for lung cancer treatment and a set of mathematical descriptors of computed tomography (CT) scan texture (‘texture features’). A pre-therapy CT scan and a post-therapy CT scan were retrospectively collected under IRB approval for each of the 25 patients who underwent definitive RT (median dose: 66 Gy). Sixty regions of interest (ROIs) were automatically identified in the non-cancerous lung tissue of each post-therapy scan. A radiologist compared post-therapy scan ROIs with pre-therapy scans and categorized each as containing no abnormality, mild abnormality, moderate abnormality, or severe abnormality. Twenty texture features that characterize gray-level intensity, region morphology, and gray-level distribution were calculated in post-therapy scan ROIs and compared with anatomically matched ROIs in the pre-therapy scan. Linear regression and receiver operating characteristic (ROC) analysis were used to compare the percent feature value change (ΔFV) between ROIs at each category of visible radiation damage. Most ROIs contained no (65%) or mild abnormality (30%). ROIs with moderate (3%) or severe (2%) abnormalities were observed in 9 patients. For 19 of 20 features, ΔFV was significantly different among severity levels. For 12 features, significant differences were observed at every level. Compared with regions with no abnormalities, ΔFV for these 12 features increased, on average, by 1.5%, 12%, and 30%, respectively, for mild, moderate, and severe abnormalitites. Area under the ROC curve was largest when comparing ΔFV in the highest severity level with the remaining three categories (mean AUC across features: 0.84). In conclusion, 19 features that characterized the severity of radiologic changes from pre-therapy scans were identified. These features may be used in future studies to quantify acute normal lung tissue damage following RT. Presented, in part at the IASLC 15th World Conference on Lung Conference, Sydney, AUS (2013).

[Lung scintigraphy].

PubMed

Schümichen, Carl; Schmidt, Matthias; Krause, Thomas

2018-06-01

The S1 guideline for lung scintigraphy has been updated and extended in order to emphasize the advantages oft the method in detecting acute pulmonary embolism (PE) in the periphery oft the lung (subsegmental PE), in underlying subacute and chronic pulmonary disorders, as well as in detecting chronic LE (CTEPH). Method of choice is ventilation / perfusion (V/P) SPECT or V/P SPECT/CT with even higher specificity. Because of its high sensitivity, a threshold (V/P mismatch in at least one segment or two subsegments) is introduced to avoid overtreatment. In case of a change in the therapeutic approach (observation only instead of anticoaculation) the threshold can be omitted. New data concerning the clinical and therapeutical impact of subsegmental PE are included, the chapters open questions have been extented. Other indications for V/P SPECT (secondary diagnoses, abnormalities in pulmonary perfusion, prediction of postoperative lung function) are presented with new data. Schattauer GmbH.

An essential role of intestinal cell kinase in lung development is linked to the perinatal lethality of human ECO syndrome

PubMed Central

Tong, Yixin; Park, So Hyun; Wu, Di; Xu, Wenhao; Guillot, Stacey J.; Jin, Li; Li, Xudong; Wang, Yalin; Lin, Chyuan-Sheng; Fu, Zheng

2017-01-01

Human endocrine-cerebro-osteodysplasia (ECO) syndrome, caused by the loss-of-function mutation R272Q in the ICK (intestinal cell kinase) gene, is a neonatal-lethal developmental disorder. To elucidate the molecular basis of ECO syndrome, we constructed an Ick R272Q knock-in mouse model that recapitulates ECO pathological phenotypes. Newborns bearing Ick R272Q homozygous mutations die at birth due to respiratory distress. Ick mutant lungs exhibit not only impaired branching morphogenesis associated with reduced mesenchymal proliferation, but also significant airspace deficiency in primitive alveoli concomitant with abnormal interstitial mesenchymal differentiation. ICK dysfunction induces elongated primary cilia and perturbs ciliary Hedgehog signaling and autophagy during lung sacculation. Our study identifies an essential role for ICK in lung development and advances the mechanistic understanding of ECO syndrome. PMID:28380258

An essential role of intestinal cell kinase in lung development is linked to the perinatal lethality of human ECO syndrome.

PubMed

Tong, Yixin; Park, So Hyun; Wu, Di; Xu, Wenhao; Guillot, Stacey J; Jin, Li; Li, Xudong; Wang, Yalin; Lin, Chyuan-Sheng; Fu, Zheng

2017-05-01

Human endocrine-cerebro-osteodysplasia (ECO) syndrome, caused by the loss-of-function mutation R272Q in the intestinal cell kinase (ICK) gene, is a neonatal-lethal developmental disorder. To elucidate the molecular basis of ECO syndrome, we constructed an Ick R272Q knock-in mouse model that recapitulates ECO pathological phenotypes. Newborns bearing Ick R272Q homozygous mutations die at birth due to respiratory distress. Ick mutant lungs exhibit not only impaired branching morphogenesis associated with reduced mesenchymal proliferation but also significant airspace deficiency in primitive alveoli concomitant with abnormal interstitial mesenchymal differentiation. ICK dysfunction induces elongated primary cilia and perturbs ciliary Hedgehog signaling and autophagy during lung sacculation. Our study identifies an essential role for ICK in lung development and advances the mechanistic understanding of ECO syndrome. © 2017 Federation of European Biochemical Societies.

Quantitative assessment of lung ventilation and microstructure in an animal model of idiopathic pulmonary fibrosis using hyperpolarized gas MRI.

PubMed

Stephen, Michael J; Emami, Kiarash; Woodburn, John M; Chia, Elaine; Kadlecek, Stephen; Zhu, Jianliang; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R; Rossman, Milton

2010-11-01

The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). Preliminary results suggest that quantitative (3)He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

Influence of Central Obesity Assessed by Conicity Index on Lung Age in Young Adults.

PubMed

Shenoy, Usha; Jagadamba

2017-04-01

Central obesity is an emerging public health problem in young adults which compromises lung mechanics. Conicity Index (CI) is a simple anthropometric measure to assess central adiposity. The concept of lung age relates to a person's current lung function at which his/her lung function would be considered abnormal in relation to the present actual age. To determine the effect of central obesity by CI on lung age in young adults. A total of 319 young adults in the age group 18-25 years were recruited for this cross-sectional observational study. Written informed consent and Institutional Ethical Clearance (IEC) approval were obtained. Anthropometric parameters were measured and CI was calculated using the following formula: CI = Waist Circumference (WC) (m)/ [0.109 X√ {Bodyweight (kg)/ Height (m)}] where 0.109 is a constant. Spirometry was performed and all the lung volumes and capacities were obtained. There was a significant increase in mean values of CI in obese young adults compared to non obese (1.36±0.15 and 1.16±0.08, p<0.001). The effect of central obesity on lung age in young adults was compared using an independent t-test. Mean of lung age was significantly higher in centrally obese young adults compared to non obese 23.87±3.03 and 21.30±2.6, p<0.001) which was statistically significant. Lung age is significantly increased in centrally obese young adults compared to non obese. Hence, lung age can be used as a potential psychological tool to show an individual with central obesity that there is premature aging of their lungs.

Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load.

PubMed

Davidson, Donald J; Webb, Sheila; Teague, Peter; Govan, John R W; Dorin, Julia R

2004-01-01

To establish the role of defects in murine Cftr in the susceptibility to Staphylococcus aureus lung disease using mouse models of cystic fibrosis (CF), congenic or inbred strains. We describe the histopathological analyses of CF mice repeatedly exposed by aerosolisation to a CF isolate of S. aureus, using residual function Cftr mice and compound heterozygotes generated by intercrossing these with Cftr 'null' mice, all congenic on the C57Bl6/N background. We demonstrate that mice congenic on the C57Bl/6 background develop significantly more severe lung pathology than non-CF littermates in response to repeated exposure to the most frequent early CF lung pathogen S. aureus. Furthermore, reducing the level of Cftr by half in compound heterozygote mice does not impact upon disease severity, even in response to an increased bacterial dose. These results are consistent with an airway clearance defect, or abnormal inflammatory response secondary to Cftr mutation. These studies confirm the primary role for Cftr mutation in the development of this lung phenotype. In addition, these results demonstrate that a further 50% decrease in residual wild-type Cftr mRNA levels in this model does not impact the severity of the histopathological response to S. aureus, suggesting a critical threshold level for functional CFTR. Copyright 2004 S. Karger AG, Basel

Occurrence of neonatal and postnatal mortality in range beef cattle. II. Factors contributing to calf death.

PubMed

Bellows, R A; Patterson, D J; Burfening, P J; Phelps, D A

1987-11-01

Results are summarized of necropsy findings from 798 calves lost from birth to weaning over a 15-yr period. Autopsies determined cause of death and ascertained anatomical normalcy of the skeletal, musculature and organ systems and functinal status of the lungs. Of the 798 calves, 77.7% were anatomically normal and 22.3% were abnormal (P < 0.01) and 75.0% of the total deaths of abnormal calves occurred by Day 2 postpartum. Birth weights of normal calves averaged 4.2 kg heavier (P < 0.05) than that of abnormal calves. Internal hydrocephalus was identified and confirmed heritable as a lethal recessive trait. The number of calves lost from dystocia (406 calves, 50.9%) exceeded losses from all other causes (392 calves, 49.1%). Lung status was determined for 492 calves dying at birth, with 39.6 and 60.4% having functional and nonfunctional lungs, respectively (P < 0.01). Diseases, mainly scours and pneumonia, ranked second in importance as cause of death (12.8%), followed by exposure-chilling (5.6%) due to cold and wet conditions. Abnormalities observed included heart anomalies (24 calves), hydrocephalus (38 calves) and a missing segment of the caudal gut (8 calves). Multiple congenital malformations were found in 15 calves with findings similar to those resulting from maternal consumption of toxins from poison hemlock (Conium maculatum) during gestation. Twelve calves died from peritonitis resulting from a perforated abomasal ulcer caused by accumulated hair. Of the 373 dystocia deaths in anatomically normal calves, 121 (32.4%) involved abnormal presentation, with calves involved in backward or breech presentation accounting for 62.0% of the losses from abnormal presentation. Calves experiencing hiplock or retained forelimb were heavier (P < 0.05) than calves presented in normal, back-ward or breech positions. Dystocia scores were assigned to 253 calves dying at parturition. Percentage losses within score were 52.6, 6.7, 30.8 and 9.9 (P < 0.05) and birth weights were 33.9, 36.1, 39.2 and 37.4 kg (P < 0.05) for scores of 1, 2, 3 and 4, respectively.

[A case of volcanic ash lung: report of a case].

PubMed

Shojima, Junko; Ikushima, Soichiro; Ando, Tsunehiro; Mochida, Akihiko; Yanagawa, Takashi; Takemura, Tamiko; Oritsu, Masaru

2006-03-01

A 57-year-old woman inhaled much volcanic ash without using a mask every day during the eruption of the Miyake Volcano in August 2000. An abnormal shadow was pointed out on her chest radiography by chance, after she sought refuge in Higashimurayama city in September. She had no respiratory symptoms and her chest radiography in an annual health check in July 2000 had showed no abnormality. She was admitted to our hospital and thoracoscopic lung biopsy was performed. We diagnosed it as lung inflammation caused by volcanic ash. The reasons for diagnosis were because the abnormal shadow appeared after the inhalation of volcanic ash, chest computed tomography showed diffuse irregular shadows with air bronchogram, thoracoscopic lung biopsy showed cellular-bronchiolitis around crystals, and the results of mineralogical analysis of the particles in alveolar macrophages detected in the biopsy specimen by scanning electron microscopy (SEM) were very similar to those of volcanic ash. The shadow on her chest radiography disappeared gradually without any treatment, but she avoided further exposure to volcanic ash. It is necessary to consider volcanic ash capable of causing lung inflammation.

CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis.

PubMed

Tarique, Abdullah A; Sly, Peter D; Holt, Patrick G; Bosco, Anthony; Ware, Robert S; Logan, Jayden; Bell, Scott C; Wainwright, Claire E; Fantino, Emmanuelle

2017-07-01

The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. Blood samples were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Predictors of oxygen desaturation during submaximal exercise in 8,000 patients.

PubMed

Hadeli, K O; Siegel, E M; Sherrill, D L; Beck, K C; Enright, P L

2001-07-01

To determine predictors of oxygen desaturation during submaximal exercise in patients with various lung diseases. This retrospective case series used pulmonary function laboratory results from all patients referred to a major tertiary-care center. All patients > or = 35 years old who underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), lung volumes, and pulse oximetry during 3-min submaximal step-test exercise during 1996 were included (4,545 men and 3,472 women). Logistic regression models, correcting for gender, age, and weight, determined the odds ratios (ORs) for oxygen desaturation of > or = 4% during exercise for each category of lung function abnormality (compared to those with entirely normal lung function). Approximately 74% of the patients had airways obstruction, while only 5.6% had restriction of lung volumes. One third of those with obstruction had a low DLCO, compared to 56% with restriction, while 2.7% had a low DLCO without obstruction or restriction. The risk of oxygen desaturation during submaximal exercise was very high (OR, 34) in patients with restriction and low DLCO (as in interstitial lung disease) and in patients with obstruction and low DLCO (as in COPD; OR, 18), intermediate (OR, 9) in patients with only a low DLCO, and lowest in those with a normal DLCO (OR, 4 if restricted; OR, 2 if obstructed). A cut point of DLCO < 62% predicted resulted in 75% sensitivity and specificity for exercise desaturation. No untoward cardiac events occurred in any patients during or following the submaximal exercise tests. The risk of oxygen desaturation during submaximal exercise is very high in patients with a low DLCO. Submaximal exercise tests are safe, even in elderly patients with heart and lung diseases.

Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of distal airway and blood biomarkers that predict FEV1 decline

PubMed Central

Weiden, Michael D.; Kwon, Sophia; Caraher, Erin; Berger, Kenneth I.; Reibman, Joan; Rom, William N.; Prezant, David J.; Nolan, Anna

2016-01-01

Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung’s normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after World Trade Center (WTC) exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1

“Pulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health”

PubMed Central

McEvoy, Cindy T.; Spindel, Eliot R.

2016-01-01

Summary Maternal smoking during pregnancy is the largest preventable cause of abnormal in-utero lung development. Despite well known risks, rates of smoking during pregnancy have only slightly decreased over the last ten years, with rates varying from 5-40% worldwide resulting in tens of millions of fetal exposures. Despite multiple approaches to smoking cessation about 50% of smokers will continue to smoke during pregnancy. Maternal genotype plays an important role in the likelihood of continued smoking during pregnancy and the degree to which maternal smoking will affect the fetus. The primary effects of maternal smoking on offspring lung function and health are decreases in forced expiratory flows, decreased passive respiratory compliance, increased hospitalization for respiratory infections, and an increased prevalence of childhood wheeze and asthma. Nicotine appears to be the responsible component of tobacco smoke that affects lung development, and some of the effects of maternal smoking on lung development can be prevented by supplemental vitamin C. Because nicotine is the key agent for affecting lung development, e-cigarette usage during pregnancy is likely to be as dangerous to fetal lung development as is maternal smoking. PMID:27639458

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

PubMed

Yu, Min; Lou, Jianlin; Xia, Hailing; Zhang, Min; Zhang, Yixiao; Chen, Junqiang; Zhang, Xing; Ying, Shibo; Zhu, Lijin; Liu, Lihong; Jia, Guang

2017-04-01

To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2  = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

Air pollution and environmental risk factors for altered lung function among adult women of an urban slum area of Delhi: A prevalence study.

PubMed

Arora, Shweta; Rasania, S K; Bachani, D; Gandhi, Asha; Chhabra, S K

2018-01-01

Household and ambient air pollution are jointly responsible for about 7 million premature deaths annually. Women living in slums, with unhealthy environment, both indoors and outdoors, particularly those living close to industrial and/or vehicular pollution zones due to multiple sources of air pollution, are at the higher risk of having impaired lung function tests. The aim of this study was to estimate the prevalence of abnormal lung functions and to identify the environmental risk factors associated with them among adult women of 18-59 years. A total of 550 women aged 18-59 years were approached in a representative urban slum. Five hundred consented to participate and 299 had prebronchodilator spirometry satisfying ATS standards. House visits to assess environmental conditions were conducted to determine their association with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Chi-square test was used to test the association of risk factors with lung functions. ANOVA was used to test the association of mean values of FEV1 and FVC with age. Out of 299 participants with acceptable spirometric curves, 5% had reduced FEV1/FVC ratio than the normal and 26.8% and 17.4% had lower values than predicted for FVC and FEV1, respectively. Altered lung function was related to age, tobacco smoking, and history of respiratory disease. Both ambient and household air pollution have a deleterious pulmonary effect on long-term women residents of a representative urban slum in Delhi.

Impact of Lung Cancer Screening Results on Smoking Cessation

PubMed Central

Berg, Christine D.; Riley, Thomas L.; Cunningham, Christopher R.; Taylor, Kathryn L.

2014-01-01

Background Lung cancer screening programs may provide opportunities to reduce smoking rates among participants. This study evaluates the impact of lung cancer screening results on smoking cessation. Methods Data from Lung Screening Study participants in the National Lung Screening Trial (NLST; 2002–2009) were used to prepare multivariable longitudinal regression models predicting annual smoking cessation in those who were current smokers at study entry (n = 15489, excluding those developing lung cancer in follow-up). The associations of lung cancer screening results on smoking cessation over the trial period were analyzed. All hypothesis testing used two sided P values. Results In adjusted analyses, smoking cessation was strongly associated with the amount of abnormality observed in the previous year’s screening (P < .0001). Compared with those with a normal screen, individuals were less likely to be smokers if their previous year’s screen had a major abnormality that was not suspicious for lung cancer (odds ratio [OR] = 0.811; 95% confidence interval [CI] = 0.722 to 0.912; P < .001), was suspicious for lung cancer but stable from previous screens (OR = 0.785; 95% CI = 0.706 to 0.872; P < .001), or was suspicious for lung cancer and was new or changed from the previous screen (OR = 0.663; 95% CI = 0.607 to 0.724; P < .001). Differences in smoking prevalence were present up to 5 years after the last screen. Conclusions Smoking cessation is statistically significantly associated with screen-detected abnormality. Integration of effective smoking cessation programs within screening programs should lead to further reduction in smoking-related morbidity and mortality. PMID:24872540

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

Poulou, Loukia S., E-mail: ploukia@hotmail.com; Tsangaridou, Iris; Filippoussis, Petros

Bronchiolitis obliterans organizing pneumonia (BOOP) is a nonneoplastic, noninfectious lung disease with a diverse spectrum of imaging abnormalities and nonspecific symptoms diagnosed by open lung biopsy, transbroncial biopsy, and/or video-assisted thoracoscopy. The objective of this study was to retrospectively assess the role of percutaneous computed tomography (CT)-guided biopsy in early diagnosis of the disorder. Fourteen BOOP cases diagnosed by CT-guided biopsy were analyzed in terms of imaging abnormalities and complication rate. All had previously undergone a nondiagnostic procedure (bronchoscopy, transbronchial biopsy, bronchoalveolar lavage) to exclude infection or lung cancer. The most common imaging abnormalities in descending order were bilateral consolidationsmore » (5/14), unilateral tumor-like lesions (5/14), unilateral consolidations (3/14), and diffuse reticular pattern (1/14). Coexistent abnormalities (pleural effusions, nodules, ground-glass opacities) were observed in five patients. The complication rate was 4 of 14 (28.6%), including 2 cases of subclinical pneumothorax and 1 case of minor hemoptysis and local lung injury. None required intervention. We conclude that transthoracic CT-guided biopsy may be used in the diagnosis of BOOP in selected patients with mild complications. For the focal consolidation nodule/mass imaging pattern, CT-guided biopsy may prove to be a reasonable alternative to more invasive procedures.« less

Computer Vision Tool and Technician as First Reader of Lung Cancer Screening CT Scans.

PubMed

Ritchie, Alexander J; Sanghera, Calvin; Jacobs, Colin; Zhang, Wei; Mayo, John; Schmidt, Heidi; Gingras, Michel; Pasian, Sergio; Stewart, Lori; Tsai, Scott; Manos, Daria; Seely, Jean M; Burrowes, Paul; Bhatia, Rick; Atkar-Khattra, Sukhinder; van Ginneken, Bram; Tammemagi, Martin; Tsao, Ming Sound; Lam, Stephen

2016-05-01

To implement a cost-effective low-dose computed tomography (LDCT) lung cancer screening program at the population level, accurate and efficient interpretation of a large volume of LDCT scans is needed. The objective of this study was to evaluate a workflow strategy to identify abnormal LDCT scans in which a technician assisted by computer vision (CV) software acts as a first reader with the aim to improve speed, consistency, and quality of scan interpretation. Without knowledge of the diagnosis, a technician reviewed 828 randomly batched scans (136 with lung cancers, 556 with benign nodules, and 136 without nodules) from the baseline Pan-Canadian Early Detection of Lung Cancer Study that had been annotated by the CV software CIRRUS Lung Screening (Diagnostic Image Analysis Group, Nijmegen, The Netherlands). The scans were classified as either normal (no nodules ≥1 mm or benign nodules) or abnormal (nodules or other abnormality). The results were compared with the diagnostic interpretation by Pan-Canadian Early Detection of Lung Cancer Study radiologists. The overall sensitivity and specificity of the technician in identifying an abnormal scan were 97.8% (95% confidence interval: 96.4-98.8) and 98.0% (95% confidence interval: 89.5-99.7), respectively. Of the 112 prevalent nodules that were found to be malignant in follow-up, 92.9% were correctly identified by the technician plus CV compared with 84.8% by the study radiologists. The average time taken by the technician to review a scan after CV processing was 208 ± 120 seconds. Prescreening CV software and a technician as first reader is a promising strategy for improving the consistency and quality of screening interpretation of LDCT scans. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Cardiorespiratory Interactions in Paediatrics: 'It's (almost always) the circulation stupid!'

PubMed

Rigby, M L; Rosenthal, M

2017-03-01

The interaction of the heart and lungs is probably the most important aspect of life and survival. Fortunately, it is not difficult to understand the fundamentals. The purpose of the lungs and their ventilation is to present oxygen to the circulation via the alveoli and to receive carbon dioxide from the circulation and then expel it. The relations of the heart and lungs and the matching of blood flow to the various organs with ventilation and lung perfusion may be disrupted by a variety of congenital or acquired heart malformations. They include those giving rise to an increased or reduced pulmonary blood flow, elevated pulmonary venous pressure or external physical pressure on the airways or lung parenchyma. Respiratory disorders which compromise cardiac function include states with reduced alveolar ventilation, those with a barrier to ventilation or perfusion, ventilation/perfusion mismatch and pulmonary vascular disease. There is also a fascinating group in which congenital disorders of the heart and lung co-exist to produce very particular modes of abnormal cardiopulmonary interaction. Copyright © 2016. Published by Elsevier Ltd.

Evaluation of pulmonary function using breathing chest radiography with a dynamic flat panel detector: primary results in pulmonary diseases.

PubMed

Tanaka, Rie; Sanada, Shigeru; Okazaki, Nobuo; Kobayashi, Takeshi; Fujimura, Masaki; Yasui, Masahide; Matsui, Takeshi; Nakayama, Kazuya; Nanbu, Yuko; Matsui, Osamu

2006-10-01

Dynamic flat panel detectors (FPD) permit acquisition of distortion-free radiographs with a large field of view and high image quality. The present study was performed to evaluate pulmonary function using breathing chest radiography with a dynamic FPD. We report primary results of a clinical study and computer algorithm for quantifying and visualizing relative local pulmonary airflow. Dynamic chest radiographs of 18 subjects (1 emphysema, 2 asthma, 4 interstitial pneumonia, 1 pulmonary nodule, and 10 normal controls) were obtained during respiration using an FPD system. We measured respiratory changes in distance from the lung apex to the diaphragm (DLD) and pixel values in each lung area. Subsequently, the interframe differences (D-frame) and difference values between maximum inspiratory and expiratory phases (D-max) were calculated. D-max in each lung represents relative vital capacity (VC) and regional D-frames represent pulmonary airflow in each local area. D-frames were superimposed on dynamic chest radiographs in the form of color display (fusion images). The results obtained using our methods were compared with findings on computed tomography (CT) images and pulmonary functional test (PFT), which were examined before inclusion in the study. In normal subjects, the D-frames were distributed symmetrically in both lungs throughout all respiratory phases. However, subjects with pulmonary diseases showed D-frame distribution patterns that differed from the normal pattern. In subjects with air trapping, there were some areas with D-frames near zero indicated as colorless areas on fusion images. These areas also corresponded to the areas showing air trapping on computed tomography images. In asthma, obstructive abnormality was indicated by areas continuously showing D-frame near zero in the upper lung. Patients with interstitial pneumonia commonly showed fusion images with an uneven color distribution accompanied by increased D-frames in the area identified as normal on computed tomography images. Furthermore, measurement of DLD was very effective for evaluating diaphragmatic kinetics. This is a rapid and simple method for evaluation of respiratory kinetics for pulmonary diseases, which can reveal abnormalities in diaphragmatic kinetics and regional lung ventilation. Furthermore, quantification and visualization of respiratory kinetics is useful as an aid in interpreting dynamic chest radiographs.

Comparison between conventional and protective one-lung ventilation for ventilator-assisted thoracic surgery.

PubMed

Ahn, H J; Kim, J A; Yang, M; Shim, W S; Park, K J; Lee, J J

2012-09-01

Recent papers suggest protective ventilation (PV) as a primary ventilation strategy during one-lung ventilation (OLV) to reduce postoperative pulmonary morbidity. However, data regarding the advantage of the PV strategy in patients with normal preoperative pulmonary function are inconsistent, especially in the case of minimally invasive thoracic surgery. Therefore we compared conventional OLV (VT 10 ml/kg, FiO2 1.0, zero PEEP) to protective OLV (VT 6 ml/kg, FiO2 0.5, PEEP 5 cmH2O) in patients with normal preoperative pulmonary function tests undergoing video-assisted thoracic surgery. Oxygenation, respiratory mechanics, plasma interleukin-6 and malondialdehyde levels were measured at baseline, 15 and 60 minutes after OLV and 15 minutes after restoration of two-lung ventilation. PaO2 and PaO2/FiO2 were higher in conventional OLV than in protective OLV (P<0.001). Interleukin-6 and malondialdehyde increased over time in both groups (P<0.05); however, the magnitudes of increase were not different between the groups. Postoperatively there were no differences in the number of patients with PaO2/FiO2<300 mmHg or abnormalities on chest radiography. Protective ventilation did not provide advantages over conventional ventilation for video-assisted thoracic surgery in this group of patients with normal lung function.

Immunohistological features related to functional impairment in lymphangioleiomyomatosis.

PubMed

Nascimento, Ellen Caroline Toledo do; Baldi, Bruno Guedes; Mariani, Alessandro Wasum; Annoni, Raquel; Kairalla, Ronaldo Adib; Pimenta, Suzana Pinheiro; da Silva, Luiz Fernando Ferraz; Carvalho, Carlos Roberto Ribeiro; Dolhnikoff, Marisa

2018-05-08

Lymphangioleiomyomatosis (LAM) is a low-grade neoplasm characterized by the pulmonary infiltration of smooth muscle-like cells (LAM cells) and cystic destruction. Patients usually present with airway obstruction in pulmonary function tests (PFTs). Previous studies have shown correlations among histological parameters, lung function abnormalities and prognosis in LAM. We investigated the lung tissue expression of proteins related to the mTOR pathway, angiogenesis and enzymatic activity and its correlation with functional parameters in LAM patients. We analyzed morphological and functional parameters of thirty-three patients. Two groups of disease severity were identified according to FEV1 values. Lung tissue from open biopsies or lung transplants was immunostained for SMA, HMB-45, mTOR, VEGF-D, MMP-9 and D2-40. Density of cysts, density of nodules and protein expression were measured by image analysis and correlated with PFT parameters. There was no difference in the expression of D2-40 between the more severe and the less severe groups. All other immunohistological parameters showed significantly higher values in the more severe group (p ≤ 0.002). The expression of VEGF-D, MMP-9 and mTOR in LAM cells was associated with the density of both cysts and nodules. The density of cysts and nodules as well as the expression of MMP-9 and VEGF-D were associated with the impairment of PFT parameters. Severe LAM represents an active phase of the disease with high expression of VEGF-D, mTOR, and MMP-9, as well as LAM cell infiltration. Our findings suggest that the tissue expression levels of VEGF-D and MMP-9 are important parameters associated with the loss of pulmonary function and could be considered as potential severity markers in open lung biopsies of LAM patients.

Lung abscess mimicking lung cancer developed around staples in a patient with permanent tracheostoma.

PubMed

Watanabe, Yui; Aoki, Masaya; Suzuki, Soichi; Umehara, Tadashi; Harada, Aya; Wakida, Kazuhiro; Nagata, Toshiyuki; Kariatsumari, Kota; Nakamura, Yoshihiro; Sato, Masami

2015-11-01

A 68-year-old male with a tracheostoma due to hypopharyngeal cancer was admitted because his chest computed tomography (CT) showed a small nodule in the right middle lobe. Following a partial resection of the right middle lobe, histopathological diagnosis of the resected sample was that of organizing pneumonia. Eleven months later, chest CT showed a mass with pleural indentation and spiculation in the right middle lobe. 18-Fluorodeoxyglucose-positron emission tomography showed significant accumulation in the middle lobe tumor mass shadow. The abnormal chest shadow that had developed around surgical staples suggested inadequate resection and tumor recurrence. As the abnormal radiological shadow was enlarging, middle lobectomy was carried out. Histological examination revealed that the tumor was a lung abscess without malignant features. This is a unique case of lung abscess mimicking lung cancer which developed around staples used during partial resection of the lung.

Shortness of breath in clinical practice: A case for left atrial function and exercise stress testing for a comprehensive diastolic heart failure workup

PubMed Central

Iyngkaran, Pupalan; Anavekar, Nagesh S; Neil, Christopher; Thomas, Liza; Hare, David L

2017-01-01

The symptom cluster of shortness of breath (SOB) contributes significantly to the outpatient workload of cardiology services. The workup of these patients includes blood chemistry and biomarkers, imaging and functional testing of the heart and lungs. A diagnosis of diastolic heart failure is inferred through the exclusion of systolic abnormalities, a normal pulmonary function test and normal hemoglobin, coupled with diastolic abnormalities on echocardiography. Differentiating confounders such as obesity or deconditioning in a patient with diastolic abnormalities is difficult. While the most recent guidelines provide more avenues for diagnosis, such as incorporating the left atrial size, little emphasis is given to understanding left atrial function, which contributes to at least 25% of diastolic left ventricular filling; additionally, exercise stress testing to elicit symptoms and test the dynamics of diastolic parameters, especially when access to the “gold standard” invasive tests is lacking, presents clinical translational gaps. It is thus important in diastolic heart failure work up to understand left atrial mechanics and the role of exercise testing to build a comprehensive argument for the diagnosis of diastolic heart failure in a patient presenting with SOB. PMID:29354484

SU-F-J-91: Sparing Lung Function in Treatment Planning Using Dual Energy Tomography

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

Lapointe, A; Bahig, H; Zerouali, K

2016-06-15

Purpose: To propose an alternate treatment plan that minimizes the dose to the functional lung tissues. In clinical situation, the evaluation of the lung functionality is typically derived from perfusion scintigraphy. However, such technique has spatial and temporal resolutions generally inferior to those of a CT scan. Alternatively, it is possible to evaluate pulmonary function by analysing the iodine concentration determined via contrast-enhanced dual energy CT (DECT) scan. Methods: Five lung cancer patients underwent a scintigraphy and a contrast-enhanced DECT scan (SOMATOM Definition Flash, Siemens). The iodine concentration was evaluated using the two-material decomposition method to produce a functional mapmore » of the lung. The validation of the approach is realized by comparison between the differential function computed by DECT and scintigraphy. The functional map is then used to redefine the V5 (volume of the organ that received more than 5 Gy during a radiotherapy treatment) to a novel functional parameter, the V5f. The V5f, that uses a volume weighted by its function level, can assist in evaluating optimal beam entry points for a specific treatment plan. Results: The results show that the differential functions obtained by scintigraphy and DECT are in good agreement with a mean difference of 6%. In specific cases, we are able to visually correlate low iodine concentration with abnormal pulmonary lung or cancerous tumors. The comparison between V5f and V5 has shown that some entry points can be better exploited and that new ones are now accessible, 2.34 times more in average, without increasing the V5f - thus allowing easier optimization of other planning objectives. Conclusion: In addition to the high-resolution DECT images, the iodine map provides local information used to detect potential functional heterogeneities in the 3D space. We propose that this information be used to calculate new functional dose parameters such as the V5f. The presenting author, Andreanne Lapointe, received a canadian scholarship from MITACS. Part of the funding is from the compagny Siemens.« less

Perfusion lung imaging in the adult respiratory distress syndrome

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

Pistolesi, M.; Miniati, M.; Di Ricco, G.

1986-07-01

In 29 perfusion lung scans (PLS) of 19 patients with ARDS, 20 of which were obtained within six days from the onset of respiratory symptoms, perfusion abnormalities were the rule. These included focal, nonsegmental defects, mostly peripheral and dorsal, and perfusion redistribution away from the dependent lung zones. PLS were scored for the presence and intensity of perfusion abnormalities and the scores of perfusion redistribution were validated against numerical indices of blood flow distribution per unit lung volume. PLS scores were correlated with arterial blood gas values, hemodynamic parameters, and chest radiographic scores of ARDS. Arterial oxygen tension correlated withmore » the scores of both perfusion defects and redistribution. Perfusion defects correlated better with the radiographic score of ARDS, and perfusion redistribution with PAP and vascular resistance. ARDS patients exhibit peculiar patterns of PLS abnormalities not observed in other disorders. Thus, PLS may help considerably in the detection and evaluation of pulmonary vascular injury in ARDS.« less

Lung Hot Spot Without Corresponding Computed Tomography Abnormality on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Artifactual or Real, Iatrogenic or Pathologic?

PubMed

Liu, Yiyan

Focal lung uptake without corresponding lesions or abnormalities on computed tomography (CT) scan poses a dilemma in the interpretation of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). A limited number of case reports have previously suggested an artifactual or iatrogenic nature of the uptake. In the present study, 8 relevant cases were included within a retrospective search of the database. Medical records were reviewed for follow-up radiological and pathologic information. In 7 of 8 cases with focal increased FDG uptake but no corresponding lesions or abnormalities on CT scan, the lung hot spots were artifactual or iatrogenic upon follow-up diagnostic chest CT or repeated PET/CT or both the scans. Microemboli were most likely a potential cause of the pulmonary uptake, with or without partial paravenous injection. One case in the series had a real pulmonary lesion demonstrated on follow-up PET/CT scans and on surgical pathology, although the initial integrated CT and follow-up diagnostic chest CT scans revealed negative findings to demonstrate pulmonary abnormalities corresponding to the hot spot on the PET scan. In conclusion, the finding of a lung hot spot in the absence of anatomical abnormality on FDG PET/CT was most likely artifactual or iatrogenic, but it might also represent a real pulmonary lesion. Nonvisualization of anatomical abnormality could be because of its small size and position directly overlying a segmental vessel. Further image follow-up is necessary and important to clarify the nature of the uptake. Copyright © 2017 Elsevier Inc. All rights reserved.

Defective parasympathetic innervation is associated with airway branching abnormalities in experimental CDH

PubMed Central

Rhodes, Julie; Saxena, Deeksha; Zhang, GuangFeng; Gittes, George K.

2015-01-01

Developmental mechanisms leading to lung hypoplasia in congenital diaphragmatic hernia (CDH) remain poorly defined. Pulmonary innervation is defective in the human disease and in the rodent models of CDH. We hypothesize that defective parasympathetic innervation may contribute to airway branching abnormalities and, therefore, lung hypoplasia, during lung development in CDH. The murine nitrofen model of CDH was utilized to study the effect of the cholinergic agonist carbachol on embryonic day 11.5 (E11.5) lung explant cultures. Airway branching and contractions were quantified. In a subset of experiments, verapamil was added to inhibit airway contractions. Sox9 immunostaining and 5-bromo-2-deoxyuridine incorporation were used to identify and quantify the number and proliferation of distal airway epithelial progenitor cells. Intra-amniotic injections were used to determine the in vivo effect of carbachol. Airway branching and airway contractions were significantly decreased in nitrofen-treated lungs compared with controls. Carbachol resulted in increased airway contractions and branching in nitrofen-treated lungs. Nitrofen-treated lungs exhibited an increased number of proliferating Sox9-positive distal epithelial progenitor cells, which were decreased and normalized by treatment with carbachol. Verapamil inhibited the carbachol-induced airway contractions in nitrofen-treated lungs but had no effect on the carbachol-induced increase in airway branching, suggesting a direct carbachol effect independent of airway contractions. In vivo treatment of nitrofen-treated embryos via amniotic injection of carbachol at E10.5 resulted in modest increases in lung size and branching at E17.5. These results suggest that defective parasympathetic innervation may contribute to airway branching abnormalities in CDH. PMID:25934671

Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome

PubMed Central

Wu, Wei; Zhang, Junlan; Yang, Wenli; Hu, Bingqian

2016-01-01

Abstract Background and Aim Pulmonary monocyte infiltration plays a significant role in the development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been identified as a major source of monocytes that accumulate in injured tissues. Whether splenic monocytes contribute to monocyte alterations after CBDL is unknown. This study evaluates monocyte distributions and assesses effects of splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities in experimental HPS. Methods Splenectomy was performed in CBDL animals. Monocyte levels in different tissues and circulation were assessed with CD68. Pulmonary alterations of HPS were evaluated with vascular endothelial growth factor‐A (VEGF‐A) levels, angiogenesis, and alveolar–arterial oxygen gradient (AaPO2). Liver abnormalities were evaluated with fibrosis (Sirius red), bile duct proliferation (CK‐19), and enzymatic changes. Results Monocyte levels increased in the lung and liver after CBDL and were accompanied by elevated circulating monocyte numbers. Splenectomy significantly decreased monocyte accumulation, VEGF‐A levels, and angiogenesis in CBDL animal lung and improved AaPO2 levels. In contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were further exacerbated by spleen removal. Conclusions Splenic reservoir monocytes are a major source for lung monocyte accumulation after CBDL, and spleen removal attenuates the development of experimental HPS. Liver monocytes may have different origins, and accumulation is exacerbated after depletion of splenic reservoir monocytes. Tissue specific monocyte alterations, influenced by the spleen reservoir, have a significant impact on pulmonary complications of liver disease. PMID:27029414

Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy

PubMed Central

Burgel, Pierre-Régis; Paugam, André; Hubert, Dominique; Martin, Clémence

2016-01-01

Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus-positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy. PMID:27703383

Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy.

PubMed

Burgel, Pierre-Régis; Paugam, André; Hubert, Dominique; Martin, Clémence

2016-01-01

Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus -positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy.

Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes.

PubMed

Cano Megías, Marta; Guisado Vasco, Pablo; González Albarrán, Olga; Lamas Ferreiro, Adelaida; Máiz Carro, Luis

2015-11-01

Nutritional status is a prognostic factor in cystic fibrosis. Prevention of nutritional impairment and weigh loss are major clinical objectives because they are associated with worsening of lung function and increased mortality. To identify a potential relationship of clinical nutrition parameters, and their relative changes, with lung function (FEV1%) in a cohort of adolescent and adult patients with CF. A retrospective analysis of 64 patients older than 14years. Weight, height, BMI, and lung function data were collected at a period of disease stability, both in the year of the first abnormal oral glucose tolerance test (OGTT) and in the previous year. Relative changes in weight and BMI, and their relationship with FEV1%, were determined by linear regression and ANOVA tests; influence of gender and diabetes was also assessed. Mean age of the series (28 females and 36 males) was 26.8years. Normal glucose tolerance (NGT) was found in 26.7%, while 18.3% had diabetes without impaired fasting glucose (CFRD without FPG). Mean BMI was 20.32, with a mean weight of 53.53kg; 32.8% had BMI<18.5, and only 4.7% were overweight. Overall, a positive relative change in weight (≥6%) was associated with an increase in FEV1% (9.31%), as compared to those with a greater weight loss (at least 2%), who had a 12.09% fall in FEV1. Patients with CFRD without FPG had poorer lung function if they had a negative relative change in weight by at least 2% as compared to NGT. In patients with CF, a relative weight gain is positively associated to FEV1%, while a relative weight loss of at least 2% has a significant negative impact on lung function. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Chest Radiological Findings of Patients With Severe H1N1 Pneumonia Requiring Intensive Care.

PubMed

Rohani, Payam; Jude, Cecilia M; Chan, Kelvin; Barot, Nikhil; Kamangar, Nader

2016-01-01

A new strain of human influenza A (H1N1) virus originated from Mexico in 2009 and spread to more than 190 countries and territories. The World Health Organization (WHO) declared it a level 6 (highest level) pandemic. In August 2010, WHO announced that the H1N1 2009 influenza virus had moved into the postpandemic period. The WHO also declared that this flu strain is expected to continue to circulate as a seasonal virus "for some years to come." The objective of this study is to describe the chest radiographic and computed tomography (CT) findings of patients with severe H1N1 pneumonia admitted to the intensive care unit (ICU) during the 2009 pandemic. Patients with severe H1N1 pneumonia requiring ICU admission have extensive radiographic and CT abnormalities. Eighteen patients, aged 23 to 62 (mean 41), admitted to the ICU at UCLA-Olive View Medical Center with a primary diagnosis of pandemic H1N1 infection, confirmed either via rapid influenza detection test or by real-time reverse transcriptase polymerase chain reaction assay, formed the study population. All patients had chest x-ray (CXR) within 24 hours of admission and 5 patients had CT examinations. In this retrospective study, images were evaluated for the pattern (ground-glass opacities, consolidation, reticular opacities, and nodular opacities), distribution (unilateral/bilateral, upper/middle/lower lung zone, and central/peripheral/peribronchovascular), and extent (focal/multifocal/diffuse; number of lung zones) of abnormalities. All (100%) patients had abnormal CXR and CT studies. The predominant radiographic findings were ground-glass opacities (16 of 18; 89%), consolidation (16 of 18; 89%), and reticular opacities (6 of 18, 33%). The radiographic abnormalities were bilateral in 17 (94%) patients; involved lower lung distribution in 18 (100%) patients, and mid and lower lung distribution in 16 (89%) patients. Radiographic abnormalities were peribronchovascular in 11 (61%) patients and multifocal in 10 (56%). Sixteen (89%) patients had extensive abnormalities involving 3 or more lung zones. The patients requiring mechanical ventilation had a higher incidence of bilateral, diffuse consolidation in a peribronchovascular distribution on chest radiographs. The predominant CT abnormalities were consolidation (5 of 5; 100%), ground-glass opacities (5 of 5; 100%), and nodular opacities (3 of 5, 60%). The CT findings were peribronchovascular and multifocal in 4 (80%) patients and extensive and bilateral in all (100%) patients. Patients with H1N1 pneumonia admitted to the ICU had bilateral, extensive CXR, and CT abnormalities. Consolidations and ground-glass opacities were the most common imaging findings, predominantly affecting mid and lower lung zones. Imaging abnormalities were peribronchovascular and multifocal in a majority of patients. © The Author(s) 2014.

Sarcoidosis: correlation of pulmonary parenchymal pattern at CT with results of pulmonary function tests

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

Bergin, C.J.; Bell, D.Y.; Coblentz, C.L.

1989-06-01

The appearances of the lungs on radiographs and computed tomographic (CT) scans were correlated with degree of uptake on gallium scans and results of pulmonary function tests (PFTs) in 27 patients with sarcoidosis. CT scans were evaluated both qualitatively and quantitatively. Patients were divided into five categories on the basis of the pattern of abnormality at CT: 1 = normal (n = 4); 2 = segmental air-space disease (n = 4); 3 = spherical (alveolar) masslike opacities (n = 4); 4 = multiple, discrete, small nodules (n = 6); and 5 = distortion of parenchymal structures (fibrotic end-stage sarcoidosis) (nmore » = 9). The percentage of the volume judged to be abnormal (CT grade) was correlated with PFT results for each CT and radiographic category. CT grades were also correlated with gallium scanning results and percentage of lymphocytes recovered from bronchoalveolar lavage (BAL). Patients in CT categories 1 and 2 had normal lung function, those in category 3 had mild functional impairment, and those in categories 4 and 5 showed moderate to severe dysfunction. The overall CT grade correlated well with PFT results expressed as a percentage of the predicted value. In five patients, CT scans showed extensive parenchymal disease not seen on radiographs. CT grades did not correlate with the results of gallium scanning or BAL lymphocytes. The authors conclude that patterns of parenchymal sarcoidosis seen at CT correlate with the PFT results and can be used to indicate respiratory impairment.« less

Exploiting unsupervised and supervised classification for segmentation of the pathological lung in CT

NASA Astrophysics Data System (ADS)

Korfiatis, P.; Kalogeropoulou, C.; Daoussis, D.; Petsas, T.; Adonopoulos, A.; Costaridou, L.

2009-07-01

Delineation of lung fields in presence of diffuse lung diseases (DLPDs), such as interstitial pneumonias (IP), challenges segmentation algorithms. To deal with IP patterns affecting the lung border an automated image texture classification scheme is proposed. The proposed segmentation scheme is based on supervised texture classification between lung tissue (normal and abnormal) and surrounding tissue (pleura and thoracic wall) in the lung border region. This region is coarsely defined around an initial estimate of lung border, provided by means of Markov Radom Field modeling and morphological operations. Subsequently, a support vector machine classifier was trained to distinguish between the above two classes of tissue, using textural feature of gray scale and wavelet domains. 17 patients diagnosed with IP, secondary to connective tissue diseases were examined. Segmentation performance in terms of overlap was 0.924±0.021, and for shape differentiation mean, rms and maximum distance were 1.663±0.816, 2.334±1.574 and 8.0515±6.549 mm, respectively. An accurate, automated scheme is proposed for segmenting abnormal lung fields in HRC affected by IP

Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in Chronic Obstructive Pulmonary Disease.

PubMed

El-Tantawi, Gihan A Younis; Imam, Mohamed H; Morsi, Tamer S

2015-01-01

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures. Although phrenic neuropathy is known to cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD. This work aimed at assessing phrenic nerve conduction in COPD and its relation to radiographic hyperinflation and pulmonary function. Forty COPD patients were evaluated. Radiographic parameters of lung hyperinflation were measured on postero-anterior and lateral chest x-ray films. Flow volume loop parameters were obtained from all patients. Motor conduction study of the phrenic nerves was performed and potentials were recorded over the xiphoid process and the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were enrolled as controls. Parameters of phrenic nerve conduction differed significantly in patients compared to controls. Phrenic nerve abnormalities were detected in 17 patients (42.5%). Electrophysiological measures correlated with diaphragmatic angle of depression on lateral view films and with lung height on postero-anterior films. They did not correlate with the flow volume loop data or disease severity score. Phrenic nerve conduction abnormality is an appreciated finding in COPD. Nerve stretching associated with diaphragmatic descent can be a suggested mechanism for nerve lesion. The presence of phrenic neuropathy may be an additional contributing factor to diaphragmatic dysfunction in COPD patients.

[Fetal bone and joint disorders].

PubMed

Jakobovits, Akos

2008-12-21

The article discusses the physiology and pathology of fetal bone and joint development and functions. The bones provide static support for the body. The skull and the bones of spinal column encase the central and part of the peripheral nervous system. The ribs and the sternum shield the heart and the lungs, while the bones of the pelvis protect the intraabdominal organs. Pathological changes of these bony structures may impair the functions of the respective systems or internal organs. Movements of the bones are brought about by muscles. The deriving motions are facilitated by joints. Bony anomalies of the extremities limit their effective functions. Apart from skeletal and joint abnormalities, akinesia may also be caused by neurological, muscular and skin diseases that secondarily affect the functions of bones and joints. Such pathological changes may lead to various degrees of physical disability and even to death. Some of the mentioned anomalies are recognizable in utero by ultrasound. The diagnosis may serve as medical indication for abortion in those instances when the identified abnormality is incompatible with independent life.

Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

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

Venkatramani, Rajkumar, E-mail: rvenkatramani@chla.usc.edu; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; Kamath, Sunil

Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The followingmore » pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed dose should be used to perform risk stratification of patients receiving lung irradiation.« less

Lung function in retired coke oven plant workers.

PubMed Central

Chau, N; Bertrand, J P; Guenzi, M; Mayer, L; Téculescu, D; Mur, J M; Patris, A; Moulin, J J; Pham, Q T

1992-01-01

Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID:1599869

Bronchial mucus properties in lung cancer: relationship with site of lesion.

PubMed

Zayas, J G; Rubin, B K; York, E L; Lien, D C; King, M

1999-01-01

To compare the biophysical properties of mucus from the left and right mainstem bronchi in patients undergoing diagnostic bronchoscopy because of a unilateral radiological abnormality. It was hypothesized that abnormalities in the properties of mucus would be greater on the side with the lesion and that this would be most obvious in patients with unilateral lung cancer. Bilateral paired samples of bronchial mucus were taken from 38 nonatopic patients (aged 59.8+/-12.6 years) including 16 nonsmokers, 14 current smokers and eight exsmokers (more than one year). Twenty of the 38 patients had a radiologically defined unilateral abnormality. Eight of these 20, including one nonsmoker, had lung cancer. The viscoelastic properties of the collected mucus were determined by magnetic microrheometry, and the analysis was carried out without knowledge of the histological diagnosis or source. The rheological properties of mucus strongly suggested which was the abnormal side. Within the group of 20 patients with a unilateral radiological abnormality, mucus from the side of the lesion had a lower value of the loss tangent, tan d100 (P=0.004), indicating greater mucus recoil. This is consistent with poor mucus cough clearability on the lesion side. All eight cancer patients fit this mucus rheological pattern with a lower value of tan d100 on the affected side (P=0.007). Four of the five other patients with a similar mucus abnormality were categorized as high cancer risk by other criteria, while six of seven patients with mucus that did not have this abnormality were considered to be lower risk. Based on the mucus analysis done at the time of the bronchoscopy, two of the 'noncancer' patients initially designated as high risk had cancer detected after several months of follow- up. Only two of the 18 patients without a defined unilateral lesion fit the mucus 'cancer pattern'. These findings are consistent with the hypothesis that either abnormalities in mucus properties may represent a risk factor for the development of lung cancer or that bronchial mucus abnormalities may be associated with products secreted by the tumours that, in turn, may suppress mucus clearance.

I Vivo Characterization of Ultrasonic Backscattering from Normal and Abnormal Lungs.

NASA Astrophysics Data System (ADS)

Jafari, Farhad

The primary goal of this project has been to characterize the lung tissue in its in vivo ultrasonic backscattering properties in normal human subjects, and study the changes in the lung echo characteristics under various pathological conditions. Such a characterization procedure is used to estimate the potential of ultrasound for providing useful diagnostic information about the superficial region of the lung. The results of this study may be divided into three categories: (1) This work has resulted in the ultrasonic characterization of lung tissue, in vivo, and has investigated the various statistical features of the lung echo properties in normal human subjects. The echo properties of the lungs are characterized with respect to the mean echo amplitude relative to a perfect reflector and the mean autocorrelation of normalized echo signals. (2) A theoretical model is developed to simulate the ultrasonic backscattering properties of the lung under normal and various simulated abnormal conditions. This model has been tested on various phantoms simulating the strong acoustic interactions of the lung. When applied to the lung this model has shown excellent agreement to experimental data gathered on a population of normal human subjects. By varying a few of the model parameters, the effect of changes in the lung structural parameters on the detected ultrasonic echoes is investigated. It is found that alveoli size changes of about 50 percent and concentration changes of 40 percent may produce spectral changes exceeding the variability exhibited by normal lungs. (3) Ultrasonic echoes from the lungs of 4 groups of patients were studied. The groups included patients with edema, emphysema, pneumothorax, and patients undergoing radiation therapy for treatment of lung cancer. Significant deviations from normal lung echo characteristics is observed in more than 80 percent of the patients studied. These deviations are intercompared and some qualitative associations between the echo characteristics on each patient group and their pulmonary pathology is made. It is concluded that the technique may provide a potential tool in detecting pulmonary abnormalities. More controlled patient studies, however, are indicated as necessary to determine the sensitivity of the ultrasound technique.

Functional mechanism of lung mosaic CT attenuation: assessment with deep-inspiration breath-hold perfusion SPECT-CT fusion imaging and non-breath-hold Technegas SPECT.

PubMed

Suga, K; Yasuhiko, K; Iwanaga, H; Tokuda, O; Matsunaga, N

2009-01-01

The functional mechanism of lung mosaic computed tomography attenuation (MCA) in pulmonary vascular disease (PVD) and obstructive airway disease (OAD) has not yet been fully clarified. To clarify the mechanism of MCA in these diseases by assessing the relationship between regional lung function and CT attenuation change at MCA sites with the use of automated deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images and non-breath-hold Technegas SPECT. Subjects were 42 PVD patients (31 pulmonary thromboembolism, four primary/two secondary pulmonary hypertension, and five Takayasu arteritis), 12 OAD patients (five acute asthma, four obliterative bronchiolitis, and three bronchiectasis), and 12 normal controls, all of whom had MCA on DIBrH CT. The relationship between regional lung function and CT attenuation change at the lung slices with MCA was assessed using DIBrH perfusion SPECT-CT fusion images and non-breath-hold Technegas SPECT. The severity of perfusion defects with or without MCA was quantified by regions-of-interest analysis. On DIBrH CT and perfusion SPECT, in contrast to no noticeable CT attenuation abnormality and fairly uniform perfusion in controls, 60 MCA and 274 perfusion defects in PVD patients, and 18 MCA and 61 defects in OAD patients were identified, with a total of 77 ventilation defects on Technegas SPECT in all patients. SPECT-CT correlation showed that, throughout the 78 MCA sites of all patients, lung perfusion was persistently decreased at low CT attenuation and preserved at intervening high CT attenuation, while lung ventilation was poorly correlated with CT attenuation change. The radioactivity ratios of reduced perfusion and the intervening preserved perfusion at the 78 perfusion defects with MCA were significantly lower than those at the remaining 257 defects without MCA (P<0.0001). Although further validation is required, our results indicate that heterogeneous pulmonary arterial perfusion may be a dominant mechanism of MCA in PVD and OAD.

Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung

PubMed Central

Yates, Laura L.; Schnatwinkel, Carsten; Hazelwood, Lee; Chessum, Lauren; Paudyal, Anju; Hilton, Helen; Romero, M. Rosario; Wilde, Jonathan; Bogani, Debora; Sanderson, Jeremy; Formstone, Caroline; Murdoch, Jennifer N.; Niswander, Lee A.; Greenfield, Andy; Dean, Charlotte H.

2013-01-01

During lung development, proper epithelial cell arrangements are critical for the formation of an arborized network of tubes. Each tube requires a lumen, the diameter of which must be tightly regulated to enable optimal lung function. Lung branching and lumen morphogenesis require close epithelial cell–cell contacts that are maintained as a result of adherens junctions, tight junctions and by intact apical–basal (A/B) polarity. However, the molecular mechanisms that maintain epithelial cohesion and lumen diameter in the mammalian lung are unknown. Here we show that Scribble, a protein implicated in planar cell polarity (PCP) signalling, is necessary for normal lung morphogenesis. Lungs of the Scrib mouse mutant Circletail (Crc) are abnormally shaped with fewer airways, and these airways often lack a visible, ‘open’ lumen. Mechanistically we show that Scrib genetically interacts with the core PCP gene Vangl2 in the developing lung and that the distribution of PCP pathway proteins and Rho mediated cytoskeletal modification is perturbed in ScribCrc/Crc lungs. However A/B polarity, which is disrupted in Drosophila Scrib mutants, is largely unaffected. Notably, we find that Scrib mediates functions not attributed to other PCP proteins in the lung. Specifically, Scrib localises to both adherens and tight junctions of lung epithelia and knockdown of Scrib in lung explants and organotypic cultures leads to reduced cohesion of lung epithelial cells. Live imaging of Scrib knockdown lungs shows that Scrib does not affect bud bifurcation, as previously shown for the PCP protein Celsr1, but is required to maintain epithelial cohesion. To understand the mechanism leading to reduced cell–cell association, we show that Scrib associates with β-catenin in embryonic lung and the sub-cellular distribution of adherens and tight junction proteins is perturbed in mutant lung epithelia. Our data reveal that Scrib is required for normal lung epithelial organisation and lumen morphogenesis by maintaining cell–cell contacts. Thus we reveal novel and important roles for Scrib in lung development operating via the PCP pathway, and in regulating junctional complexes and cell cohesion. PMID:23195221

Pulmonary changes in liver transplant candidates with hepatitis C cirrhosis.

PubMed

Al-Moamary, M S; Gorka, T; Al-Traif, I H; Al-Jahdali, H H; Al-Shimemeri, A A; Al-Kanway, B; Abdulkareeem, A A; Abdulkareeem, A A

2001-12-01

Several studies have shown that pulmonary abnormalities are common in patients with end-stage liver disease. However, most of these studies were conducted on patients with heterogeneous etiologies. Therefore, we studied these changes in a homogenous group of hepatitis C cirrhotic patients who were potential candidates for liver transplantation. The charts of 81 patients from King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia with hepatitis C cirrhosis who were evaluated for liver transplantation were reviewed. The following data was retrieved: echocardiography with micro-bubble study, arterial blood gases, and pulmonary function tests of 81 candidates and reviewed over 3 years from 1994 to 1997. The mean age was 53 (+/-9) years with male to female ratio of 1.4:1. Echocardiographic micro-bubble study, revealed 4 of 62 (7%) had an intrapulmonary shunt. Arterial blood gases results were pH of 7.44 (+/-0.4), partial arterial tension of carbon dioxide of 33 mm Hg (+/-4), partial arterial tension of oxygen of 84 mm Hg (+/-12), and alveolar-arterial gradient of 30 mm Hg (+/-10). Eleven percent had obstructive airway disease, 17% had restrictive lung impairment, and 43% had reduced diffusion capacity. Seventy five percent of patients with reduced diffusion capacity had normal lung volumes. Various pulmonary function test abnormalities did not lead to significant differences in arterial blood gases. Pulmonary changes were frequent in liver transplant candidates with hepatitis C virus cirrhosis with reduced diffusion capacity being the most. Apart from the effect of hepatopulmonary syndrome on arterial oxygenation, other pulmonary abnormalities were not significantly different.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

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

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com; School of Medicine, University Juarez of Durango, Gomez Palacio, Durango; Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatorymore » biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels • In 275 children chronically exposed to As, 3 biomarkers were measured. • Negative associations were found between DMA, %MMA and %DMA with sRAGE. • Positive associations were found between %DMA with MMP-9 and with the MMP-9/TIMP-1 ratio. • Chronic arsenic exposure-induced alterations in lung inflammatory biomarkers in children.« less

Changes in lung volumes and gas trapping in patients with large hiatal hernia.

PubMed

Naoum, Christopher; Kritharides, Leonard; Ing, Alvin; Falk, Gregory L; Yiannikas, John

2017-03-01

Studies assessing hiatal hernia (HH)-related effects on lung volumes derived by body plethysmography are limited. We aimed to evaluate the effect of hernia size on lung volumes (including assessment by body plethysmography) and the relationship to functional capacity, as well as the impact of corrective surgery. Seventy-three patients (70 ± 10 years; 54 female) with large HH [mean ± standard deviation, intra-thoracic stomach (ITS) (%): 63 ± 20%; type III in 65/73] had respiratory function data (spirometry, 73/73; body plethysmography, 64/73; diffusing capacity, 71/73) and underwent HH surgery. Respiratory function was analysed in relation to hernia size (groups I, II and III: ≤50, 50%-75% and ≥75% ITS, respectively) and functional capacity. Post-operative changes were quantified in a subgroup. Total lung capacity (TLC) and vital capacity (VC) correlated inversely with hernia size (TLC: 97 ± 11%, 96 ± 13%, 88 ± 10% predicted in groups I, II and III, respectively, P = 0.01; VC: 110 ± 17%, 111 ± 14%, 98 ± 14% predicted, P = 0.02); however, mean values were normal and only 14% had abnormal lung volumes. Surgery increased TLC (93 ± 11% vs 97 ± 10% predicted) and VC (105 ± 15% vs 116 ± 18%), and decreased residual volume/total lung capacity (RV/TLC) ratio (39 ± 7% vs 37 ± 6%) (P < 0.01 for all). Respiratory changes were modest relative to the marked functional class improvement. Among parameters that improved following HH surgery, decreased TLC and forced expiratory volume in 1 s and increased RV/TLC ratio correlated with poorer functional class pre-operatively. Increasing HH size correlates with reduced TLC and VC. Surgery improves lung volumes and gas trapping; however, the changes are mild and within the normal range. © 2015 John Wiley & Sons Ltd.

Intermittent hypoxia during recovery from neonatal hyperoxic lung injury causes long-term impairment of alveolar development: A new rat model of BPD.

PubMed

Mankouski, Anastasiya; Kantores, Crystal; Wong, Mathew J; Ivanovska, Julijana; Jain, Amish; Benner, Eric J; Mason, Stanley N; Tanswell, A Keith; Auten, Richard L; Jankov, Robert P

2017-02-01

Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O 2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O 2 until day 14 were recovered in air with or without IH (FI O 2 = 0.10 for 10 min every 6 h) until day 28 Animals exposed to 60% O 2 and recovered in air had no evidence of abnormal lung morphology on day 28 or at 10-12 wk. In contrast, 60% O 2 -exposed animals recovered in IH had persistently increased mean chord length, more dysmorphic septal crests, and fewer peripheral arteries. Recovery in IH also increased pulmonary vascular resistance, Fulton index, and arterial wall thickness. IH-mediated abnormalities in lung structure (but not pulmonary hypertension) persisted when reexamined at 10-12 wk, accompanied by increased pulmonary vascular reactivity and decreased exercise tolerance. Increased mean chord length secondary to IH was prevented by treatment with a peroxynitrite decomposition catalyst [5,10,15,20-Tetrakis(4-sulfonatophenyl)-21H,23H-porphyrin iron (III) chloride, 30 mg/kg/day, days 14-28], an effect accompanied by fewer inflammatory cells. We conclude that IH during recovery from hyperoxia-induced injury prevents recovery of alveologenesis and leads to changes in lung and pulmonary vascular function lasting into adulthood, thus more closely mimicking contemporary BPD. Copyright © 2017 the American Physiological Society.

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

Reiss, T.F.; Golden, J.

Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologicmore » tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population.« less

Pulmonary nocardiosis

MedlinePlus

... you and listen to your lungs using a stethoscope. You may have abnormal lung sounds, called crackles. ... returning. Alternative Names Nocardiosis - pulmonary; Mycetoma; Nocardia Images Respiratory system References Southwick FS. Nocardiosis. In: Goldman L, ...

The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis

PubMed Central

Yates, Laura L.; Schnatwinkel, Carsten; Murdoch, Jennifer N.; Bogani, Debora; Formstone, Caroline J.; Townsend, Stuart; Greenfield, Andy; Niswander, Lee A.; Dean, Charlotte H.

2010-01-01

The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation of either the correct number or shape of epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such as cystadenomatoid malformations, pulmonary hypertension or lung hypoplasia. Defects in lung architecture are also associated with adult lung disease, particularly in cases of idiopathic lung fibrosis. Identifying the signalling pathways which drive epithelial tube formation will likely shed light on both congenital and adult lung disease. Here we show that mutations in the planar cell polarity (PCP) genes Celsr1 and Vangl2 lead to disrupted lung development and defects in lung architecture. Lungs from Celsr1Crsh and Vangl2Lp mouse mutants are small and misshapen with fewer branches, and by late gestation exhibit thickened interstitial mesenchyme and defective saccular formation. We observe a recapitulation of these branching defects following inhibition of Rho kinase, an important downstream effector of the PCP signalling pathway. Moreover, epithelial integrity is disrupted, cytoskeletal remodelling perturbed and mutant endoderm does not branch normally in response to the chemoattractant FGF10. We further show that Celsr1 and Vangl2 proteins are present in restricted spatial domains within lung epithelium. Our data show that the PCP genes Celsr1 and Vangl2 are required for foetal lung development thereby revealing a novel signalling pathway critical for this process that will enhance our understanding of congenital and adult lung diseases and may in future lead to novel therapeutic strategies. PMID:20223754

Effects of marijuana smoking on the lung.

PubMed

Tashkin, Donald P

2013-06-01

Regular smoking of marijuana by itself causes visible and microscopic injury to the large airways that is consistently associated with an increased likelihood of symptoms of chronic bronchitis that subside after cessation of use. On the other hand, habitual use of marijuana alone does not appear to lead to significant abnormalities in lung function when assessed either cross-sectionally or longitudinally, except for possible increases in lung volumes and modest increases in airway resistance of unclear clinical significance. Therefore, no clear link to chronic obstructive pulmonary disease has been established. Although marijuana smoke contains a number of carcinogens and cocarcinogens, findings from a limited number of well-designed epidemiological studies do not suggest an increased risk for the development of either lung or upper airway cancer from light or moderate use, although evidence is mixed concerning possible carcinogenic risks of heavy, long-term use. Although regular marijuana smoking leads to bronchial epithelial ciliary loss and impairs the microbicidal function of alveolar macrophages, evidence is inconclusive regarding possible associated risks for lower respiratory tract infection. Several case reports have implicated marijuana smoking as an etiologic factor in pneumothorax/pneumomediastinum and bullous lung disease, although evidence of a possible causal link from epidemiologic studies is lacking. In summary, the accumulated weight of evidence implies far lower risks for pulmonary complications of even regular heavy use of marijuana compared with the grave pulmonary consequences of tobacco.

Congruence Between Pulmonary Function and Computed Tomography Imaging Assessment of Cystic Fibrosis Severity.

PubMed

Rybacka, Anna; Goździk-Spychalska, Joanna; Rybacki, Adam; Piorunek, Tomasz; Batura-Gabryel, Halina; Karmelita-Katulska, Katarzyna

2018-05-04

In cystic fibrosis, pulmonary function tests (PFTs) and computed tomography are used to assess lung function and structure, respectively. Although both techniques of assessment are congruent there are lingering doubts about which PFTs variables show the best congruence with computed tomography scoring. In this study we addressed the issue by reinvestigating the association between PFTs variables and the score of changes seen in computed tomography scans in patients with cystic fibrosis with and without pulmonary exacerbation. This retrospective study comprised 40 patients in whom PFTs and computed tomography were performed no longer than 3 weeks apart. Images (inspiratory: 0.625 mm slice thickness, 0.625 mm interval; expiratory: 1.250 mm slice thickness, 10 mm interval) were evaluated with the Bhalla scoring system. The most frequent structural abnormality found in scans were bronchiectases and peribronchial thickening. The strongest relationship was found between the Bhalla sore and forced expiratory volume in 1 s (FEV1). The Bhalla sore also was related to forced vital capacity (FVC), FEV1/FVC ratio, residual volume (RV), and RV/total lung capacity (TLC) ratio. We conclude that lung structural data obtained from the computed tomography examination are highly congruent to lung function data. Thus, computed tomography imaging may supersede functional assessment in cases of poor compliance with spirometry procedures in the lederly or children. Computed tomography also seems more sensitive than PFTs in the assessment of cystic fibrosis progression. Moreover, in early phases of cystic fibrosis, computed tomography, due to its excellent resolution, may be irreplaceable in monitoring pulmonary damage.

Restrictive allograft syndrome after lung transplantation: new radiological insights.

PubMed

Dubbeldam, Adriana; Barthels, Caroline; Coolen, Johan; Verschakelen, Johny A; Verleden, Stijn E; Vos, Robin; Verleden, Geert M; De Wever, Walter

2017-07-01

To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities. In 14 patients, non-regressing nodules and reticulations predominantly affecting the upper lobes developed an average of 13.9 months prior to the diagnosis of RAS. Median graft survival after onset of non-regressing abnormalities was 33.5 months, with most patients in follow-up (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly affecting both upper and lower lobes was seen an average of 2.8 months prior to the diagnosis of RAS. Median graft survival was 6.4 months after first onset of non-regressing abnormalities, with graft loss in most patients (6/8). RAS has been previously described as a homogenous group. However, our study shows two different groups of RAS-patients: one with slow progression and one with fast progression. The two groups show different onset and progression patterns of CT abnormalities. • RAS is the newest discovered form of chronic lung allograft dysfunction (CLAD). • RAS is not a homogenous group, as survival varies greatly between patients. • In this study, we see two different CT onset and progression patterns. • These two different CT patterns also correlate with a different survival rate.

42 CFR 37.53 - Notification of abnormal roentgenographic findings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer...

42 CFR 37.53 - Notification of abnormal roentgenographic findings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer...

Pulmonary complications of endocrine and metabolic disorders.

PubMed

Milla, Carlos E; Zirbes, Jacquelyn

2012-03-01

There are many important respiratory manifestations of endocrine and metabolic diseases in children. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes mellitus, although cardiogenic and non-cardiogenic pulmonary oedema are also possible. Pseudohypoaldosteronism type 1 may be indistinguishable from cystic fibrosis (CF) unless serum aldosterone, plasma renin activity, and urinary electrolytes are measured and mutation analysis rules out CF. Hypo- and hyperthyroidism may alter lung function and affect the central respiratory drive. The thyroid hormone plays an essential role in lung development, surfactant synthesis, and lung defence. Complications of hypoparathyroidism are largely due to hypocalcaemia. Laryngospasm can lead to stridor and airway obstruction. Ovarian tumours, benign or malignant, may present with unilateral or bilateral pleural effusions. Metabolic storage disorders, primarily as a consequence of lysosomal dysfunction from enzymatic deficiencies, constitute a diverse group of rare conditions that can have profound effects on the respiratory system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

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

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, Da

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbitsmore » were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. • Acute effects of chlorine were pulmonary edema, hypoxemia and impaired lung function. • Persistent small airway disease developed following recovery from acute injury. • Small airway disease included inflammation and bronchiolitis obliterans lesions. • The model should be useful for studying chlorine lung injury and testing treatments.« less

World Trade Center dyspnea: bronchiolitis obliterans with functional improvement: a case report.

PubMed

Mann, Jack M; Sha, Kenneth K; Kline, Gary; Breuer, Frank-Uwe; Miller, Albert

2005-09-01

Bronchiolitis obliterans is a severe, often progressive, lung disease characterized by cough, exertional dyspnea, and airflow obstruction. It has been ascribed to specific causes such as lung or bone marrow transplant, medications for rheumatoid disease, and most recently in association with exposure to environmental agents. A 42-year-old, previously healthy New York City Highway Patrol officer who arrived at the World Trade Center (WTC), "ground zero," early on September 11, 2001 was evaluated. He has been followed for over 2 years with serial chest radiographs, CT scans, and pulmonary function studies. He eventually underwent an open lung biopsy. His dyspnea started on September 12, 2001 and progressed despite aggressive therapy with inhaled bronchodilator as well as oral and inhaled corticosteroids. At no time did he have any radiographic evidence of pulmonary disease. His forced vital capacity (FVC) decreased from 5.32 L in October 2001 to 2.86 L in January 2003. He underwent an open lung biopsy because of the persistent exertional dyspnea coupled with the loss of over 2 L of lung volume. The pathological findings were chronic bronchiolitis with focal obliterative bronchiolitis and rare non-necrotizing granuloma. Symptoms and pulmonary function improved after therapy with Azithromycin was added to his treatment. This process is believed to be secondary to his massive exposure to the cloud of dust that followed the collapse of the WTC. It is our conviction that many of those present at the WTC on September 11 who have persistent dyspnea and deterioration of pulmonary function may have a similar pathologic process despite absence of abnormalities on CT of the chest. In view of the many signs and symptoms seen in first responders we feel that these findings provide important information about the pathophysiology and treatment of progressive disease resulting from this exposure.

MicroRNA-1285-5p influences the proliferation and metastasis of non-small-cell lung carcinoma cells via downregulating CDH1 and Smad4.

PubMed

Zhou, Shixia; Zhang, Zhongmian; Zheng, Pengyuan; Zhao, Wenchao; Han, Na

2017-06-01

Abnormal expression of microRNAs has been reported to regulate gene expression and cancer cell growth, invasion, and migration. Recently, upregulation of hsa-miR-1285 was demonstrated in bronchoalveolar lavage fluid samples from patients with lung cancer and downregulation in plasma level of stage-I lung cancer patients. However, the function and the underlying mechanism of miR-1285 in non-small-cell lung carcinoma have not been elucidated. In this study, we found that miR-1285-5p, the mature form of miR-1285, was significantly upregulated in human non-small-cell lung carcinoma cell lines A549 and SK-MES-1. Additionally, cells transfected with the miR-1285-5p inhibitor LV-anti-miR-1285-5p demonstrated significantly inhibited proliferation and invasion and depressed migration. Further analysis demonstrated that the miR-1285-5p precursor LV-miR-1285-5p attenuated the expression of Smad4 and cadherin-1 (CDH1) but that LV-anti-miR-1285-5p showed opposite results. A luciferase reporter assay confirmed that miR-1285-5p targeted Smad4 and CDH1. Mechanism analyses revealed that silence of Smad4 and CDH1 significantly attenuated the inhibitory effects of LV-anti-miR-1285-5p on non-small-cell lung carcinoma growth and invasion. Taken together, our data suggest that miR-1285-5p functions as a tumor promoter in the development of non-small-cell lung carcinoma by targeting Smad4 and CDH1, indicating a novel therapeutic strategy for non-small-cell lung carcinoma patients.

Anti-sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia.

PubMed

Wallace, Bradley; Peisl, Amelie; Seedorf, Gregory; Nowlin, Taylor; Kim, Christina; Bosco, Jennifer; Kenniston, Jon; Keefe, Dennis; Abman, Steven H

2018-03-15

Pregnancies complicated by antenatal stress, including preeclampsia (PE) and chorioamnionitis (CA), increase the risk for bronchopulmonary dysplasia (BPD) in preterm infants, but biologic mechanisms linking prenatal factors with BPD are uncertain. Levels of sFlt-1 (soluble fms-like tyrosine kinase 1), an endogenous antagonist to VEGF (vascular endothelial growth factor), are increased in amniotic fluid and maternal blood in PE and associated with CA. Because impaired VEGF signaling has been implicated in the pathogenesis of BPD, we hypothesized that fetal exposure to sFlt-1 decreases lung growth and causes abnormal lung structure and pulmonary hypertension during infancy. To test this hypothesis, we studied the effects of anti-sFlt-1 monoclonal antibody (mAb) treatment on lung growth in two established antenatal models of BPD that mimic PE and CA induced by intraamniotic (i.a.) injections of sFlt-1 or endotoxin, respectively. In experimental PE, mAb was administered by three different approaches, including antenatal treatment by either i.a. instillation or maternal uterine artery infusion, or by postnatal intraperitoneal injections. With each strategy, mAb therapy improved infant lung structure as assessed by radial alveolar count, vessel density, right ventricular hypertrophy, and lung function. As found in the PE model, the adverse lung effects of i.a. endotoxin were also reduced by antenatal or postnatal mAb therapy. We conclude that treatment with anti-sFlt-1 mAb preserves lung structure and function and prevents right ventricular hypertrophy in two rat models of BPD of antenatal stress and speculate that early mAb therapy may provide a novel strategy for the prevention of BPD.

Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

PubMed

Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

2014-06-01

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

Inhalation exposure to sulfur mustard in the guinea pig model: Clinical, biochemical and histopathological characterization of respiratory injuries

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

Allon, Nahum, E-mail: nahuma@iibr.gov.i; Amir, Adina; Manisterski, Eliau

2009-12-01

Guinea pigs (GP) were exposed (head only) in individual plethysmographs to various concentrations of sulfur mustard vapor, determined online, using FTIR attached to flow chamber. The LCt{sub 50} and the inhaled LD{sub 50} were calculated at different time points post exposure. Surviving animals were monitored for clinical symptoms, respiratory parameters and body weight changes for up to 30 days. Clinical symptoms were noted at 3 h post exposure, characterized by erythematic and swelling nose with extensive mucous secretion (with or without bleeding). At 6 h post exposure most of the guinea pigs had breathing difficulties, rhonchi and dyspnea and fewmore » deaths were noted. These symptoms peaked at 48 h and were noted up to 8 days, associated with few additional deaths. Thereafter, a spontaneous healing was noted, characterized by recovery of respiratory parameters and normal weight gain with almost complete apparent healing within 2 weeks. Histopathological evaluation of lungs and trachea in the surviving GPs at 4 weeks post exposure revealed a dose-dependent residual injury in both lung and trachea expressed by abnormal recovery of the tracheal epithelium concomitant with a dose-dependent increase in cellular volume in the lungs. These abnormal epithelial regeneration and lung remodeling were accompanied with significant changes in protein, LDH, differential cell count and glutathione levels in the bronchoalveolar lavage (BAL). It is suggested that the abnormal epithelial growth and cellular infiltration into the lung as well as the continuous lung inflammation could cause recurrent lung injury similar to that reported for HD exposed human casualties.« less

Respiratory profiles of grain handlers and sedentary workers.

PubMed Central

Herbert, F. A.; Woytowich, V.; Schram, E.; Baldwin, D.

1981-01-01

During 1978, grain handlers employed at three large inland grain terminals were studied along with an equal number of office workers matched for sex, age and smoking history. Respiratory symptoms and spirometric abnormalities were no more frequent in 16 grain handlers who were non-smokers than in their controls. However, 20 grain handlers who were smokers complained significantly more (P less than 0.01) of grade 1 dyspnea and had significantly lower ratios of forced expiratory volume in the first second to forced vital capacity (P less than 0.05) than their controls. Only 3% of the grain handlers were sensitive to grain dust, and 18% were found to be atopic but to have good lung function. A family history of asthma or allergic rhinitis was no more frequent in the grain handlers than in the control subjects. We conclude that the combination of cigarette smoking and exposure to grain dust causes a deterioration in lung function. PMID:7260809

Lung diffusion capacity in children with respiratory symptoms and untreated GERD.

PubMed

Mirić, Mirjana; Turkalj, Mirjana; Nogalo, Boro; Erceg, Damir; Perica, Marija; Plavec, Davor

2014-05-12

Gastroesophageal reflux disease (GERD) is associated with many respiratory disorders, among which, chronic cough, laryngitis, and asthma are among the most common. We investigated lung function, including gas diffusion capacity, in children with poor asthma control or chronic laryngitis with untreated GERD. A total of 71 children, aged 6-17 years, with chronic respiratory and other symptoms suggestive for GERD, were enrolled and divided into 2 groups: chronic laryngitis and asthma. Participants underwent 24-hour pH monitoring and lung function assessment, measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FENO) measurement. 24-hour pH monitoring was positive for GERD in 92.1% of preselected children with asthma and 90.1% of children with chronic recurrent laryngitis. All flows (PEF, MEF75, MEF50, and MEF25) were significantly lower in the asthma group, while FENO and DLCO were significantly lower in the laryngitis group. A significant inverse relationship was found between DLCO and all reflux indexes in the laryngitis group. Each unit change of Johnson-DeMeester score and Boix-Ochoa score increased the odds for significantly lower DLCO in laryngitis patients by 3.9% and 5.5%, respectively. In children with uncontrolled asthma and chronic laryngitis, the regurgitation of gastric contents due to GERD contributes to poor asthma control and aggravation of chronic laryngitis. Despite having normal lung function, the gas diffusion capacity should be controlled in patients with GERD and chronic laryngitis, and it might be the very first abnormality in distal airways.

The role of pleiotrophin and β-catenin in fetal lung development

PubMed Central

2010-01-01

Mammalian lung development is a complex biological process, which is temporally and spatially regulated by growth factors, hormones, and extracellular matrix proteins. Abnormal changes of these molecules often lead to impaired lung development, and thus pulmonary diseases. Epithelial-mesenchymal interactions are crucial for fetal lung development. This paper reviews two interconnected pathways, pleiotrophin and Wnt/β-catenin, which are involved in fibroblast and epithelial cell communication during fetal lung development. PMID:20565841

Collagen mimetic peptide engineered M13 bacteriophage for collagen targeting and imaging in cancer.

PubMed

Jin, Hyo-Eon; Farr, Rebecca; Lee, Seung-Wuk

2014-11-01

Collagens are over-expressed in various human cancers and subsequently degraded and denatured by proteolytic enzymes, thus making them a target for diagnostics and therapeutics. Genetically engineered bacteriophage (phage) is a promising candidate for the development of imaging or therapeutic materials for cancer collagen targeting due to its promising structural features. We genetically engineered M13 phages with two functional peptides, collagen mimetic peptide and streptavidin binding peptide, on their minor and major coat proteins, respectively. The resulting engineered phage functions as a therapeutic or imaging material to target degraded and denatured collagens in cancerous tissues. We demonstrated that the engineered phages are able to target and label abnormal collagens expressed on A549 human lung adenocarcinoma cells after the conjugation with streptavidin-linked fluorescent agents. Our engineered collagen binding phage could be a useful platform for abnormal collagen imaging and drug delivery in various collagen-related diseases. Published by Elsevier Ltd.

Physiology of breathlessness associated with pleural effusions

PubMed Central

Thomas, Rajesh; Jenkins, Susan; Eastwood, Peter R.; Lee, Y.C. Gary; Singh, Bhajan

2015-01-01

Purpose of review Pleural effusions have a major impact on the cardiorespiratory system. This article reviews the pathophysiological effects of pleural effusions and pleural drainage, their relationship with breathlessness, and highlights key knowledge gaps. Recent findings The basis for breathlessness in pleural effusions and relief following thoracentesis is not well understood. Many existing studies on the pathophysiology of breathlessness in pleural effusions are limited by small sample sizes, heterogeneous design and a lack of direct measurements of respiratory muscle function. Gas exchange worsens with pleural effusions and improves after thoracentesis. Improvements in ventilatory capacity and lung volumes following pleural drainage are small, and correlate poorly with the volume of fluid drained and the severity of breathlessness. Rather than lung compression, expansion of the chest wall, including displacement of the diaphragm, appears to be the principle mechanism by which the effusion is accommodated. Deflation of the thoracic cage and restoration of diaphragmatic function after thoracentesis may improve diaphragm effectiveness and efficiency, and this may be an important mechanism by which breathlessness improves. Effusions do not usually lead to major hemodynamic changes, but large effusions may cause cardiac tamponade and ventricular diastolic collapse. Patients with effusions can have impaired exercise capacity and poor sleep quality and efficiency. Summary Pleural effusions are associated with abnormalities in gas exchange, respiratory mechanics, respiratory muscle function and hemodynamics, but the association between these abnormalities and breathlessness remains unclear. Prospective studies should aim to identify the key mechanisms of effusion-related breathlessness and predictors of improvement following pleural drainage. PMID:25978627

Physiology of breathlessness associated with pleural effusions.

PubMed

Thomas, Rajesh; Jenkins, Susan; Eastwood, Peter R; Lee, Y C Gary; Singh, Bhajan

2015-07-01

Pleural effusions have a major impact on the cardiorespiratory system. This article reviews the pathophysiological effects of pleural effusions and pleural drainage, their relationship with breathlessness, and highlights key knowledge gaps. The basis for breathlessness in pleural effusions and relief following thoracentesis is not well understood. Many existing studies on the pathophysiology of breathlessness in pleural effusions are limited by small sample sizes, heterogeneous design and a lack of direct measurements of respiratory muscle function. Gas exchange worsens with pleural effusions and improves after thoracentesis. Improvements in ventilatory capacity and lung volumes following pleural drainage are small, and correlate poorly with the volume of fluid drained and the severity of breathlessness. Rather than lung compression, expansion of the chest wall, including displacement of the diaphragm, appears to be the principle mechanism by which the effusion is accommodated. Deflation of the thoracic cage and restoration of diaphragmatic function after thoracentesis may improve diaphragm effectiveness and efficiency, and this may be an important mechanism by which breathlessness improves. Effusions do not usually lead to major hemodynamic changes, but large effusions may cause cardiac tamponade and ventricular diastolic collapse. Patients with effusions can have impaired exercise capacity and poor sleep quality and efficiency. Pleural effusions are associated with abnormalities in gas exchange, respiratory mechanics, respiratory muscle function and hemodynamics, but the association between these abnormalities and breathlessness remains unclear. Prospective studies should aim to identify the key mechanisms of effusion-related breathlessness and predictors of improvement following pleural drainage.

Physiologic assessment before video thoracoscopic resection for lung cancer in patients with abnormal pulmonary function.

PubMed

Benattia, Amira; Debeaumont, David; Guyader, Vincent; Tardif, Catherine; Peillon, Christophe; Cuvelier, Antoine; Baste, Jean-Marc

2016-06-01

Impaired respiratory function may prevent curative surgery for patients with non-small cell lung cancer (NSCLC). Video-assisted thoracoscopic surgery (VATS) reduces postoperative morbility-mortality and could change preoperative assessment practices and therapeutic decisions. We evaluated the relation between preoperative pulmonary function tests and the occurrence of postoperative complications after VATS pulmonary resection in patients with abnormal pulmonary function. We included 106 consecutive patients with ≤80% predicted value of presurgical expiratory volume in one second (FEV1) and/or diffusing capacity of carbon monoxide (DLCO) and who underwent VATS pulmonary resection for NSCLC from a prospective surgical database. Patients (64±9.5 years) had lobectomy (n=91), segmentectomy (n=7), bilobectomy (n=4), or pneumonectomy (n=4). FEV1 and DLCO preoperative averages were 68%±21% and 60%±18%. Operative mortality was 1.89%. Only FEV1 was predictive of postoperative complications [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.926-0.991, P=0.016], but there was no determinable threshold. Twenty-five patients underwent incremental exercise testing. Desaturations during exercise (OR, 0.462; 95% CI, 0.191-0.878, P=0.039) and heart rate (HR) response (OR, 0.953; 95% CI, 0.895-0.993, P=0.05) were associated with postoperative complications. FEV1 but not DLCO was a significant predictor of pulmonary complications after VATS pulmonary resection despite a low rate of severe morbidity. Incremental exercise testing seems more discriminating. Further investigation is required in a larger patient population to change current pre-operative threshold in a new era of minimally invasive surgery.

Does nebulized fentanyl relieve dyspnea during exercise in healthy man?

PubMed Central

Kotrach, Houssam G.; Bourbeau, Jean

2015-01-01

Few therapies exist for the relief of dyspnea in restrictive lung disorders. Accumulating evidence suggests that nebulized opioids selective for the mu-receptor subtype may relieve dyspnea by modulating intrapulmonary opioid receptor activity. Our respective primary and secondary objectives were to test the hypothesis that nebulized fentanyl (a mu-opioid receptor agonist) relieves dyspnea during exercise in the presence of abnormal restrictive ventilatory constraints and to identify the physiological mechanisms of this improvement. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of 250 μg nebulized fentanyl, chest wall strapping (CWS), and their interaction on detailed physiological and perceptual responses to constant work rate cycle exercise (85% of maximum incremental work rate) in 14 healthy, fit young men. By design, CWS decreased vital capacity by ∼20% and mimicked the negative consequences of a mild restrictive lung disorder on exercise endurance time and on dyspnea, breathing pattern, dynamic operating lung volumes, and diaphragmatic electromyographic and respiratory muscle function during exercise. Compared with placebo under both unrestricted control and CWS conditions, nebulized fentanyl had no effect on exercise endurance time, integrated physiological response to exercise, sensory intensity, unpleasantness ratings of exertional dyspnea. Our results do not support a role for intrapulmonary opioids in the neuromodulation of exertional dyspnea in health nor do they provide a physiological rationale for the use of nebulized fentanyl in the management of dyspnea due to mild restrictive lung disorders, specifically those arising from abnormalities of the chest wall and not affiliated with airway inflammation. PMID:26031762

21 CFR 882.5830 - Implanted diaphragmatic/phrenic nerve stimulator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... which an abnormally low amount of air enters the lungs) caused by brain stem disease, high cervical spinal cord injury, or chronic lung disease. The stimulator consists of an implanted receiver with...

21 CFR 882.5830 - Implanted diaphragmatic/phrenic nerve stimulator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... which an abnormally low amount of air enters the lungs) caused by brain stem disease, high cervical spinal cord injury, or chronic lung disease. The stimulator consists of an implanted receiver with...

21 CFR 882.5830 - Implanted diaphragmatic/phrenic nerve stimulator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... which an abnormally low amount of air enters the lungs) caused by brain stem disease, high cervical spinal cord injury, or chronic lung disease. The stimulator consists of an implanted receiver with...

Routine application of lung ultrasonography in the neonatal intensive care unit

PubMed Central

Chen, Shui-Wen; Fu, Wei; Liu, Jing; Wang, Yan

2017-01-01

Abstract The aim of this study was to study the features of lung ultrasonography (LUS) in lung disease and to evaluate the usefulness of LUS in the neonatal intensive care unit (NICU). All of 3405 neonates included in this study underwent an LUS examination. Diagnoses were based on medical history, clinical manifestation, laboratory examination, and signs on chest radiography (CR) and/or computed tomography (CT). A single expert physician performed all LUS examinations. There were 2658 cases (78.9%) with lung disease and 747 cases (21.9%) without lung disease. The main signs of neonates with lung disease on LUS were as follows: absence of A-lines, pleural-line abnormalities, interstitial syndrome, lung consolidation, air bronchograms, pulmonary edema, and lung pulse. These abnormal signs were reduced or eliminated on LUS as patient conditions improved. There were 81 cases that could not be diagnosed as lung disease by CR but were discovered as pneumonia, respiratory distress syndrome (RDS), or transient tachypnea of newborn (TTN) on LUS. Likewise, 23 cases misdiagnosed as RDS by CR were diagnosed as TTN on LUS. Among 212 cases of long-term oxygen dependence (LTOD) that failed to yield signs of pulmonary edema and lung consolidation on CR, 103 cases showed abnormal signs on LUS. Among 747 cases without lung disease, B-lines of 713 neonates (95.4%) could be found within 3 days after birth, and 256 neonates (34.3%) could be observed from 3 days to 1 week after birth. B-lines of 19 cases could be detected from 1 to 2 weeks after birth. The longest time at which B-lines could still be observed was 19 days after birth. LUS has clinical value for the diagnosis of lung disease and the discrimination of causes of LTOP in premature infants, particularly for the diagnosis and identification of RDS and TTN. Moreover, LUS has additional advantages, including its lack of radiation exposure and its ability to noninvasively monitor treatment progress. Therefore, LUS should be routinely used in the NICU. PMID:28079811

The lung in liver disease: old problem, new concepts.

PubMed

Fallon, Michael B; Zhang, Junlan

2013-01-01

Liver dysfunction has been recognized to influence the lung in many different clinical situations, although the mechanisms for these effects are not well understood. One increasingly recognized interaction, the hepatopulmonary syndrome (HPS) occurs in the context of cirrhosis and results when alveolar microvascular dilation causes arterial gas exchange abnormalities and hypoxemia. HPS occurs in up to 30% of patients with cirrhosis and significantly increases mortality in affected patients. Currently, liver transplantation is the only curative therapy. Experimental biliary cirrhosis induced by common bile duct ligation (CBDL) in the rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS and has been contrasted with other experimental models of cirrhosis in which HPS does not develop. Microvascular dilation, intravascular monocyte infiltration, and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Our recent studies have identified biliary epithelium and activation and interaction between the endothelin-1 (ET-1)/endothelial endothelin B (ETB) receptor and CX3CL1/CX3CR1 pathways as important mechanisms for the observed pathologic events. These studies define novel interactions between the lung and liver in cirrhosis and may lead to effective medical therapies.

Association between lung capacity and abnormal glucose metabolism: findings from China and Australia.

PubMed

Yu, Dahai; Chen, Tao; Qin, Rui; Cai, Yamei; Jiang, Zhixin; Zhao, Zhanzheng; Simmons, David

2016-07-01

Restricted pulmonary function is found among people with diabetes. This study aimed to investigate the dose-response relationship between pulmonary function measurements [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)] and risk of metabolic syndrome (MS)/type 2 diabetes. A total of 1454 adults in rural Victoria, Australia, and 5824 adults in Nanjing, China, from randomly selected households provided clinical history, oral glucose tolerance test, lipids, anthropometric, blood pressure and spirometric measurements. MS was defined by International Diabetes Federation criteria. Adjusted odds ratios for MS and type 2 diabetes with lung capacity measurements were estimated using logistic regression. Dose-response relationships were explored using the restricted cubic spline models. There was a nonlinear relationship between FEV1 and the risk of type 2 diabetes and MS (both P < 0·0001) in both the Australian and Chinese populations. The FEV1 associated with the lowest risk of type 2 diabetes and MS was above 2·70 l (95%CI: 2·68 to 2·72 l and 2·65 to 2·76 l in Chinese and Australian populations, respectively). The discrimination of the model could be significantly improved using the FEV1 threshold in both the Australian and Chinese populations. In both the Australian and Chinese populations, the risk of type 2 diabetes and MS is lowest with a FEV1 of 2·65-2·76 l. This might be used in clinical practice in different countries as a prompt to screen for type 2 diabetes and MS in patients with obstructive lung disease and to ensure there was no abnormal glucose metabolism before the commencement of steroids if indicated. © 2015 John Wiley & Sons Ltd.

Iodine deficiency and subclinical hypothyroidism are common in cystic fibrosis patients.

PubMed

Naehrlich, Lutz; Dörr, Helmuth-Günther; Bagheri-Behrouzi, Azadeh; Rauh, Manfred

2013-04-01

Disorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients. We investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges. Subclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function. Dramatic iodine deficiency was found in our cohort of CF patients. This condition can cause subclinical hypothyroidism; therefore, an individual iodine supplementation program is necessary and should be started immediately. Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.

Quartz exposure, retention, and early silicosis in sheep.

PubMed

Bégin, R; Dufresne, A; Cantin, A; Possmayer, F; Sébastien, P; Fabi, D; Bilodeau, G; Martel, M; Bisson, D; Pietrowski, B

1989-05-01

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.

Genetics Home Reference: hereditary antithrombin deficiency

MedlinePlus

... at higher than average risk for developing abnormal blood clots, particularly a type of clot that occurs in ... in the lungs. In hereditary antithrombin deficiency , abnormal blood clots usually form only in veins, although they may ...

CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society

PubMed Central

Austin, John H. M.; Hogg, James C.; Grenier, Philippe A.; Kauczor, Hans-Ulrich; Bankier, Alexander A.; Barr, R. Graham; Colby, Thomas V.; Galvin, Jeffrey R.; Gevenois, Pierre Alain; Coxson, Harvey O.; Hoffman, Eric A.; Newell, John D.; Pistolesi, Massimo; Silverman, Edwin K.; Crapo, James D.

2015-01-01

The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis. © RSNA, 2015 PMID:25961632

The Dynamics and Characteristics of Aeolian Dust in Dryland Central Asia: Possible Impacts on Respiratory Health in the Aral Sea Basin

NASA Astrophysics Data System (ADS)

Wiggs, G. F.; O'Hara, S.; Wegerdt, J.; van der Meer, J.; Small, I.; Hubbard, R.

2003-12-01

Over the last 40 years over 36,000 km2 of the former Aral Sea bed have been exposed creating a potentially significant aeolian dust source. It is widely believed, but little researched, that increased dust storm activity in the region has had a major impact on human health. In this paper we report the findings of a study into the link between dust exposure and respiratory health amongst children in the Autonomous Republic of Karakalpakstan, located on the southern shore of the Aral Sea. Data were collected over a 12 month period at 16 sites located within a broad transect running north to south through Karakalpakstan. At each site monthly measurements of dust deposition were undertaken linked with daily meteorological data at 6 stations. At 3 sites weekly measurements of PM10 were also carried out. Approximately 100 children (aged 7-10 years) were randomly selected within 5 km of each dust trap site and data were collected on their respiratory health and environmental exposures. Lung function data were also collected using a handheld spirometer. A linear regression model was used to predict lung function for the children incorporating variables for Forced Expiratory Volume in one second (FEV1), age, gender, height and weight and we estimated the impact of dust deposition rates on the odds of having abnormal lung function using logistic regression. The findings indicate that dust deposition rates across the region are high with sites located near the former shore of the sea being the worst affected. For these northerly regions the former Aral Sea bed is the most likely source of dust. The situation for the rest of the country seems to be far more complex. In these regions it appears that local sources (agricultural fields, abandoned irrigation grounds, overgrazed dunes, and unpaved roads) and more distant sources to the south and south-west represent significant sediment providers, particularly in the early summer when agricultural fields are ploughed. We found some evidence of a dose-related impact of dust levels on lung function. These associations were statistically significant for all measures of dust exposure but were most marked for levels of winter dust exposure and level of PM2.5 exposure. The results from this study suggest that aeolian dust dynamics in the region are spatially and temporally highly variable and, counter to local and regional perceptions, the former bed of the Aral Sea does not appear to be the only significant source. Nevertheless, there is also evidence of a dose-related impact of airborne dust on the risk of having abnormally low lung function in children living in the Aral Sea Area.

Growth Patterns of Fetal Lung Volumes in Healthy Fetuses and Fetuses With Isolated Left-Sided Congenital Diaphragmatic Hernia.

PubMed

Ruano, Rodrigo; Britto, Ingrid Schwach Werneck; Sananes, Nicolas; Lee, Wesley; Sangi-Haghpeykar, Haleh; Deter, Russell L

2016-06-01

To evaluate fetal lung growth using 3-dimensional sonography in healthy fetuses and those with congenital diaphragmatic hernia (CDH). Right and total lung volumes were serially evaluated by 3-dimensional sonography in 66 healthy fetuses and 52 fetuses with left-sided CDH between 20 and 37 weeks' menstrual age. Functions fitted to these parameters were compared for 2 groups: (1) healthy versus those with CDH; and (2) fetuses with CHD who survived versus those who died. Fetal right and total lung volumes as well as fetal observed-to-expected right and total lung volume ratios were significantly lower in fetuses with CDH than healthy fetuses (P< .001) and in those fetuses with CDH who died (P< .001). The observed-to-expected right and total lung volume ratios did not vary with menstrual age in healthy fetuses or in those with CDH (independent of outcome). Lung volume rates were lower in fetuses with left-sided CDH compared to healthy fetuses, as well as in fetuses with CDH who died compared to those who survived. The observed-to-expected right and total lung volume ratios were relatively constant throughout menstrual age in fetuses with left-sided CDH, suggesting that the origin of their lung growth abnormalities occurred before 20 weeks and did not progress. The observed-to-expected ratios may be useful in predicting the outcome in fetuses with CDH independent of menstrual age. © 2016 by the American Institute of Ultrasound in Medicine.

Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease.

PubMed

Lunt, Alan; Ahmed, Na'eem; Rafferty, Gerrard F; Dick, Moira; Rees, David; Height, Sue; Thein, Swee Lay; Greenough, Anne

2016-02-01

Children with sickle cell disease (SCD) often have obstructive lung function abnormalities which could be due to asthma or increased pulmonary blood volume; it is important to determine the underlying mechanism to direct appropriate treatment. In asthmatics, exhaled nitric oxide (FeNO) is elevated. FeNO, however, can also be raised due to increased alveolar production. Our aim, therefore, was to determine if airway or alveolar NO production differed between SCD children and ethnic and age-matched controls. Lung function, airway NO flux and alveolar NO production, and effective pulmonary blood flow were assessed in 18 SCD children and 18 ethnic and age-matched controls. The SCD children compared to the controls had a higher respiratory system resistance (P = 0.0008), alveolar NO production (P = 0.0224), and pulmonary blood flow (P < 0.0001), but not airway NO flux. There was no significant correlation between FeNO and respiratory system resistance in either group, but in the SCD children, there were correlations between alveolar NO production (P = 0.0006) and concentration (P < 0.0001) and pulmonary blood flow. Airway NO flux was not elevated in the SCD children nor correlated with airways obstruction, suggesting that airways obstruction, at least in some SCD children, is not due to asthma.

Lung function and blood markers of nutritional status in non-COPD aging men with smoking history: a cross-sectional study.

PubMed

Shiozawa, Nobuyoshi; Hayashimoto, Kanae; Suzuki, Etsuji; Kikuchi, Hiroshi; Takata, Shingo; Ashida, Kozo; Watanabe, Masutaka; Hosaki, Yasuhiro; Mitsunobu, Fumihiro

2010-08-09

Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men. This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV(1)/FVC), and 17 with COPD (COPD group). After adjustment for potential confounders, lower FEV(1)/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group. In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.

Lung radiology and pulmonary function of children chronically exposed to air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Fordham, Lynn A; Chung, Charles J; Valencia-Salazar, Gildardo; Flores-Gómez, Silvia; Solt, Anna C; Gomez-del Campo, Alberto; Jardón-Torres, Ricardo; Henríquez-Roldán, Carlos; Hazucha, Milan J; Reed, William

2006-09-01

We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala. In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S. National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters

Incentive spirometry does not enhance recovery after thoracic surgery.

PubMed

Gosselink, R; Schrever, K; Cops, P; Witvrouwen, H; De Leyn, P; Troosters, T; Lerut, A; Deneffe, G; Decramer, M

2000-03-01

To investigate the additional effect of incentive spirometry to chest physiotherapy to prevent postoperative pulmonary complications after thoracic surgery for lung and esophageal resections. Randomized controlled trial. University hospital, intensive care unit, and surgical department. Sixty-seven patients (age, 59 +/- 13 yrs; forced expiratory volume in 1 sec, 93% +/- 22% predicted) undergoing elective thoracic surgery for lung (n = 40) or esophagus (n = 27) resection. Physiotherapy (breathing exercises, huffing, and coughing) (PT) plus incentive spirometry (IS) was compared with PT alone. Lung function, body temperature, chest radiograph, white blood cell count, and number of hospital and intensive care unit days were all measured. Pulmonary function was significantly reduced after surgery (55% of the initial value) and improved significantly in the postoperative period in both groups. However, no differences were observed in the recovery of pulmonary function between the groups. The overall score of the chest radiograph, based on the presence of atelectasis, was similar in both treatment groups. Eight patients (12%) (three patients with lobectomy and five with esophagus resection) developed a pulmonary complication (abnormal chest radiograph, elevated body temperature and white blood cell count), four in each treatment group. Adding IS to regular PT did not reduce hospital or intensive care unit stay. Pulmonary complications after lung and esophagus surgery were relatively low. The addition of IS to PT did not further reduce pulmonary complications or hospital stay. Although we cannot rule out beneficial effects in a subgroup of high-risk patients, routine use of IS after thoracic surgery seems to be ineffective.

Skeletal muscle strength and endurance in recipients of lung transplants.

PubMed

Mathur, Sunita; Levy, Robert D; Reid, W Darlene

2008-09-01

Exercise limitation in recipients of lung transplant may be a result of abnormalities in the skeletal muscle. However, it is not clear whether these abnormalities are merely a reflection of the changes observed in the pretransplant condition. The purpose of this paper was to compare thigh muscle volume and composition, strength, and endurance in lung transplant recipients to people with chronic obstructive pulmonary disease (COPD). Single lung transplant recipients (n=6) and people with COPD (n=6), matched for age, sex, and BMI participated in the study. Subjects underwent MRI to determine muscle size and composition, lower extremity strength testing and an isometric endurance test of the quadriceps. Lung transplant recipients had similar muscle volumes and intramuscular fat infiltration of their thigh muscles and similar strength of the quadriceps and hamstrings to people with COPD who had not undergone transplant. However, quadriceps endurance tended to be lower in transplant recipients compared to people with COPD (15 +/- 7 seconds in transplant versus 31 +/- 12 seconds in COPD, p = 0.08). Recipients of lung transplant showed similar changes in muscle size and strength as people with COPD, however muscle endurance tended to be lower in people with lung transplants. Impairments in muscle endurance may reflect the effects of immunosuppressant medications on skeletal muscle in people with lung transplant.

Arsenite promotes centrosome abnormalities under a p53 compromised status induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

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

Liao, W.-T.; Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

2010-02-15

Epidemiological evidence indicated that residents, especially cigarette smokers, in arseniasis areas had significantly higher lung cancer risk than those living in non-arseniasis areas. Thus an interaction between arsenite and cigarette smoking in lung carcinogenesis was suspected. In the present study, we investigated the interactions of a tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (nicotine-derived nitrosamine ketone, NNK) and arsenite on lung cell transformation. BEAS-2B, an immortalized human lung epithelial cell line, was selected to test the centrosomal abnormalities and colony formation by NNK and arsenite. We found that NNK, alone, could enhance BEAS-2B cell growth at 1-5 muM. Under NNK exposure, arsenite wasmore » able to increase centrosomal abnormality as compared with NNK or arsenite treatment alone. NNK treatment could also reduce arsenite-induced G2/M cell cycle arrest and apoptosis, these cellular effects were found to be correlated with p53 dysfunction. Increased anchorage-independent growth (colony formation) of BEAS-2B cells cotreated with NNK and arsenite was also observed in soft agar. Our present investigation demonstrated that NNK could provide a p53 compromised status. Arsenite would act specifically on this p53 compromised status to induce centrosomal abnormality and colony formation. These findings provided strong evidence on the carcinogenic promotional role of arsenite under tobacco-specific carcinogen co-exposure.« less

Mechanisms of physical activity limitation in chronic lung diseases.

PubMed

Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

2012-01-01

In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients' quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.

The diagnosis of neonatal pulmonary atelectasis using lung ultrasonography.

PubMed

Liu, Jing; Chen, Shui-Wen; Liu, Fang; Li, Qiu-Ping; Kong, Xiang-Yong; Feng, Zhi-Chun

2015-04-01

Ultrasonography has been used for the diagnosis of many kinds of lung conditions, but few studies have investigated ultrasound for the diagnosis of neonatal pulmonary atelectasis (NAP). In this study, we evaluated the usefulness of lung ultrasonography for the diagnosis of NPA. From May 2012 to December 2013, 80 neonates with NPA and 50 neonates without lung disease were enrolled in this study. Each lung of every infant was divided into the anterior, lateral, and posterior regions by the anterior and posterior axillary lines. Each region was scanned carefully with the probe perpendicular or parallel to the ribs. The ultrasound findings were confirmed by chest radiograph (CXR) or CT scan. Sixty of the 80 patients with signs of NPA on lung ultrasound also had signs of NPA on CXR (termed focal-type atelectasis), and the other 20 patients had signs of NPA on chest CT scan while there were no abnormal findings on CXR (termed occult lung atelectasis). In patients with NPA, the main ultrasound findings were large areas of lung consolidation with clearly demarcated borders, air bronchograms, pleural line abnormalities, and absence of A-lines, as well as the presence of lung pulse and absence of lung sliding on real-time ultrasound. The sensitivity of lung ultrasonography for the diagnosis of NPA was 100%, whereas the sensitivity of CXR was 75%. Large areas of lung consolidation with clearly demarcated borders were only observed in patients with NPA. Lung ultrasonography is an accurate and reliable method for diagnosing NPA; most importantly, it can find those occult lung atelectasis that could not be detected on CXR. Routine lung ultrasonography is a useful method of diagnosing or excluding NPA in neonates.

Technetium-99m-HMPAO as a marker of chemical and irradiation lung injury: Experimental and clinical investigations

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

Suga, Kazuyoshi; Uchisako, Hiromichi; Nishigauchi, Kazuya

1994-09-01

The authors evaluated the ability of {sup 99m}Tc-hexamethylpropyleneamine oxime ({sup 99m}Tc-HMPAO) to serve as a sensitive marker of lung injury. Two experiment rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, they clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of {sup 99m}Tc-HMPAO in the lungs. Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of {supmore » 99m}Tc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of {sup 99m}Tc-HMPAO activity in the patients who received chemotherapy (0.649{+-}0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387{+-}0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. These findings suggest that {sup 99m}Tc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury. 53 refs., 5 figs., 3 tabs.« less

Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities.

PubMed

Tamura, Taro; Suganuma, Narufumi; Hering, Kurt G; Vehmas, Tapio; Itoh, Harumi; Akira, Masanori; Takashima, Yoshihiro; Hirano, Harukazu; Kusaka, Yukinori

2015-01-01

The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects' occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades.

Chronic respiratory disfunction due to diffuse alveolar hemorrhage in patients with systemic lupus erythematosus and primary vasculitis.

PubMed

Pérez Aceves, Eva; Pérez Cristóbal, Mario; Espinola Reyna, Gerardo A; Ariza Andraca, Raul; Xibille Fridmann, Daniel; Barile Fabris, Leonor A

2013-01-01

Pulmonary hemorrhage (PH) occurs in 2-5% of SLE patients, and is associated with a high mortality rate (79-90%). Diagnostic criteria for this complication include: 1) Pulmonary infiltrates, with at least ¾ of lung tissue involved in a chest x ray, 2) Acute respiratory failure, 3) A decrease of 3g/dL or more in hemoglobin levels. PH might lead to organized pneumonia, collagen deposition, and pulmonary fibrosis which in time might cause changes in pulmonary function tests with either restrictive or obstructive patterns. To evaluate the existence of abnormalities in pulmonary function tests after a PH episode. We included patients with SLE and primary vasculitis that developed PH. During the acute episode, we measured SLEDAI in SLE patients, five factor score in microscopic polyangiitis (MPA) and Birmingham Vasculitis Activity Store (BVAS) in granulomatosis with polyangiitis (GPA) (Wegener). We determined the number of PH events, treatment, and ventilator assistance requirements and correlated its association with abnormal pulmonary function tests. We included 10 patients, 7 with SLE, 2 with MPA and 1 with GPA (Wegener). The mean activity measures were: SLEDAI 20.4 ± 7.5, FFS 2, and BVAS 36. Treatment consisted in methylprednisolone (MPD) in 3 patients, MPD plus cyclophosphamide (CY) in 6 patients, and MPD, CY, IV immunoglobulin, and plasmapheresis in one patient. Five patients required ventilatory support. We found abnormalities in pulmonary function tests in 8 patients, three had an obstructive pattern and five a restrictive pattern; 2 patients did not show any change. We did not find a significant association with any of the studied variables. PH might cause abnormalities in pulmonary function tests and prolonged immunosuppressive treatment could be required. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Epidemiology and Immediate Indirect Effects of Respiratory Viruses in Lung Transplant Recipients: A 5-Year Prospective Study.

PubMed

Peghin, M; Hirsch, H H; Len, Ó; Codina, G; Berastegui, C; Sáez, B; Solé, J; Cabral, E; Solé, A; Zurbano, F; López-Medrano, F; Román, A; Gavaldá, J

2017-05-01

The epidemiology of respiratory viruses (RVs) in lung transplant recipients (LTRs) and the relationship of RVs to lung function, acute rejection (AR) and opportunistic infections in these patients are not well known. We performed a prospective cohort study (2009-2014) by collecting nasopharyngeal swabs (NPSs) from asymptomatic LTRs during seasonal changes and from LTRs with upper respiratory tract infectious disease (URTID), lower respiratory tract infectious disease (LRTID) and AR. NPSs were analyzed by multiplex polymerase chain reaction. Overall, 1094 NPSs were collected from 98 patients with a 23.6% positivity rate and mean follow-up of 3.4 years (interquartile range 2.5-4.0 years). Approximately half of URTIDs (47 of 97, 48.5%) and tracheobronchitis cases (22 of 56, 39.3%) were caused by picornavirus, whereas pneumonia was caused mainly by paramyxovirus (four of nine, 44.4%) and influenza (two of nine, 22.2%). In LTRs with LRTID, lung function changed significantly at 1 mo (p = 0.03) and 3 mo (p = 0.04). In a nested case-control analysis, AR was associated with RVs (hazard ratio [HR] 6.54), Pseudomonas aeruginosa was associated with LRTID (HR 8.54), and cytomegalovirus (CMV) replication or disease was associated with URTID (HR 2.53) in the previous 3 mo. There was no association between RVs and Aspergillus spp. colonization or infection (HR 0.71). In conclusion, we documented a high incidence of RV infections in LTRs. LRTID produced significant lung function abnormalities. Associations were observed between AR and RVs, between P. aeruginosa colonization or infection and LRTID, and between CMV replication or disease and URTID. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chronic suppurative lung disease in a developing country: impact on child and parent.

PubMed

Nathan, Anna Marie; Muthusamy, Ananthan; Thavagnanam, Surendran; Hashim, Azfawahiza; de Bruyne, Jessie

2014-05-01

To investigate the impact of chronic suppurative lung disease (CSLD) on growth and lung function in the child as well as quality of life of the child and parent. Cross-sectional study in 60 children with CSLD, bronchiectasis (including cystic fibrosis) and bronchiolitis obliterans. Thirty-five parents were interviewed while the remaining patients' data were collated from medical notes. Anthropometric measurements at first diagnosis and at interview were compared. The most recent lung function was also collected. The Parent Cough-Specific Quality of Life (PC-QOL) and the Depression, Anxiety and Stress (DASS21) questionnaires were administered to parents. The median (range) age at diagnosis was 1.3 (0.2-11) years. The median (IQR) duration between anthropometric measurements was 35 (15, 59) months. Children with cystic fibrosis (CF) had improvements both in weight and BMI, whereas children with non-CF CSLD had no improvements in any growth parameter. Seventy-eight percent of children who performed spirometry had values <80% of normal predicted value. PC-QOL scores were low. Frequent exacerbations (more than twice in the past 6 months) and cough (more than 2 days/week) were not associated with significantly lower PC-QOL scores. Seventy-seven percent of interviewed parents had abnormal DASS21 scores with 54% being stressed and 51% being depressed. Mental health was better in parents of children with CF. CSLD had a negative impact on growth, lung function, and quality of life. Children with CF had a better outcome in growth as well as better parental mental health compared to children with other etiologies. Pediatr Pulmonol. 2014; 49:435-440. © 2013 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Pulmonary fibrosis in rheumatoid arthritis: a review of clinical features and therapy.

PubMed

Roschmann, R A; Rothenberg, R J

1987-02-01

During the past four decades there has been a growing appreciation of the frequency of pulmonary abnormalities associated with RA. Approximately 30% to 40% of patients with RA demonstrate either radiographic or pulmonary function abnormalities indicative of interstitial fibrosis or restrictive lung disease. The severity of pulmonary fibrosis is not associated with rheumatologic symptoms or the duration of the associated RA, nor is there any clear relation to the extraarticular features of RA or serologic findings. Survival rates in patients with coexisting RA and pulmonary fibrosis are similar to those of patients with idiopathic pulmonary fibrosis. However, the spectrum of disease activity is quite variable. The majority of patients with progressive pulmonary symptomatology, when treated with corticosteroids, will have equivocal results. Some patients appear to respond to immunosuppressive or cytotoxic medications. The role of macrophages may be central to the injury to lung. Recent studies suggest a potential treatment role for cyclosporine, which may be able to interrupt lymphocyte-stimulated macrophage activation, and thus, fibroblast-mediated fibrosis in patients with pulmonary interstitial fibrosis. Bronchoalveolar lavage studies may delineate subgroups of patients who are more likely to respond to immunosuppressive agents, especially when treatment is started early.

ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term and long-term outcomes.

PubMed

Kenyon, S; Taylor, D J; Tarnow-Mordi, W O

2002-01-01

Preterm prelabour rupture of the foetal membranes (pPROM) is the most common antecedent of preterm birth and can lead to death, neonatal disease and long-term disability. Previous small trials of antibiotics for pPROM suggested some health benefits for the neonate, but the results were inconclusive. A large, randomized, multicentre trial was undertaken to try to resolve this issue. In total, 4826 women with pPROM were randomized to one of four treatments: 325 mg co-amoxiclav plus 250 mg erythromycin, co-amoxiclav plus erythromycin placebo, erythromycin plus co-amoxiclav placebo, or co-amoxiclav placebo plus erythromycin placebo, four times daily for 10 d or until delivery. The primary outcome measure was a composite of neonatal death, chronic lung disease or major cerebral abnormality on ultrasonography before discharge from hospital. The analysis was undertaken by intention to treat. Indications of short-term respiratory function, chronic lung disease and major neonatal cerebral abnormality were reduced with the prescription of erythromycin. In contrast, the use of co-amoxiclav was associated with a significant increase in the occurrence of neonatal necrotizing enterocolitis. Prophylactic antibiotics can play a role in preterm prelabour rupture of the membranes in reducing infant morbidity.

Perivascular fluid cuffs decrease lung compliance by increasing tissue resistance.

PubMed

Lowe, Kevin; Alvarez, Diego F; King, Judy A; Stevens, Troy

2010-06-01

Lung inflammation causes perivascular fluid cuffs to form around extra-alveolar blood vessels; however, the physiologic consequences of such cuffs remain poorly understood. Herein, we tested the hypothesis that perivascular fluid cuffs, without concomitant alveolar edema, are sufficient to decrease lung compliance. Prospective, randomized, controlled study. Research laboratory. One hundred twenty male CD40 rats. To test this hypothesis, the plant alkaloid thapsigargin was used to activate store-operated calcium entry and increase cytosolic calcium in endothelium. Thapsigargin was infused into a central venous catheter of intact, sedated, and mechanically ventilated rats. Static and dynamic lung mechanics and hemodynamics were measured continuously. Thapsigargin produced perivascular fluid cuffs along extra-alveolar vessels but did not cause alveolar flooding or blood gas abnormalities. Lung compliance dose-dependently decreased after thapsigargin infusion, attributable to an increase in tissue resistance that was attributed to increased tissue damping and tissue elastance. Airway resistance was not changed. Neither central venous pressure nor left ventricular end diastolic pressure was altered by thapsigargin. Heart rate did not change, although thapsigargin decreased left ventricular systolic function sufficient to reduce cardiac output by 50%. Infusion of the type 4 phosphodiesterase inhibitor, rolipram, prevented thapsigargin from inducing perivascular cuffs and decreasing lung compliance. Rolipram also normalized pressure over time and corrected the deficit in cardiac output. Our findings resolve for the first time that perivascular cuff formation negatively impacts mechanical coupling between the bronchovascular bundle and the lung parenchyma, decreasing lung compliance without impacting central venous pressure.

Gpr177 regulates pulmonary vasculature development.

PubMed

Jiang, Ming; Ku, Wei-yao; Fu, Jiang; Offermanns, Stefan; Hsu, Wei; Que, Jianwen

2013-09-01

Establishment of the functional pulmonary vasculature requires intimate interaction between the epithelium and mesenchyme. Previous genetic studies have led to inconsistent conclusions about the contribution of epithelial Wnts to pulmonary vasculature development. This discrepancy is possibly due to the functional redundancy among different Wnts. Here, we use Shh-Cre to conditionally delete Gpr177 (the mouse ortholog of Drosophila Wntless, Wls), a chaperon protein important for the sorting and secretion of Wnt proteins. Deletion of epithelial Gpr177 reduces Wnt signaling activity in both the epithelium and mesenchyme, resulting in severe hemorrhage and abnormal vasculature, accompanied by branching defects and abnormal epithelial differentiation. We then used multiple mouse models to demonstrate that Wnt/β-catenin signaling is not only required for the proliferation and differentiation of mesenchyme, but also is important for the maintenance of smooth muscle cells through the regulation of the transcription factor Kruppel-like factor 2 (Klf2). Together, our studies define a novel mechanism by which epithelial Wnts regulate the normal development and maintenance of pulmonary vasculature. These findings provide insight into the pathobiology of congenital lung diseases, such as alveolar capillary dysplasia (ACD), that have abnormal alveolar development and dysmorphic pulmonary vasculature.

Unsupervised segmentation of lungs from chest radiographs

NASA Astrophysics Data System (ADS)

Ghosh, Payel; Antani, Sameer K.; Long, L. Rodney; Thoma, George R.

2012-03-01

This paper describes our preliminary investigations for deriving and characterizing coarse-level textural regions present in the lung field on chest radiographs using unsupervised grow-cut (UGC), a cellular automaton based unsupervised segmentation technique. The segmentation has been performed on a publicly available data set of chest radiographs. The algorithm is useful for this application because it automatically converges to a natural segmentation of the image from random seed points using low-level image features such as pixel intensity values and texture features. Our goal is to develop a portable screening system for early detection of lung diseases for use in remote areas in developing countries. This involves developing automated algorithms for screening x-rays as normal/abnormal with a high degree of sensitivity, and identifying lung disease patterns on chest x-rays. Automatically deriving and quantitatively characterizing abnormal regions present in the lung field is the first step toward this goal. Therefore, region-based features such as geometrical and pixel-value measurements were derived from the segmented lung fields. In the future, feature selection and classification will be performed to identify pathological conditions such as pulmonary tuberculosis on chest radiographs. Shape-based features will also be incorporated to account for occlusions of the lung field and by other anatomical structures such as the heart and diaphragm.

United in prevention-electrocardiographic screening for chronic obstructive pulmonary disease.

PubMed

Lazovic, Biljana; Mazic, Sanja; Stajic, Zoran; Djelic, Marina; Zlatkovic-Svenda, Mirjana; Putnikovic, Biljana

2013-01-01

NONE DECLARED. P-wave abnormalities on the resting electrocardiogram have been associated with cardiovascular or pulmonary disease. So far, "Gothic" P wave and verticalization of the frontal plane axis is related to lung disease, particularly obstructive lung disease. We tested if inverted P wave in AVl as a lone criteria of P wave axis >70° could be screening tool for emphysema. 1095 routine electrocardiograms (ECGs) were reviewed which yielded 478 (82,1%) ECGs with vertical P-axis in sinus rhythm. Charts were reviewed for the diagnosis of COPD and emphysema based on medical history and pulmonary function tests. Electrocardiogram is very effective screening tool not only in cardiovascular field but in chronic obstructive pulmonary disease. The verticality of the P axis is usually immediately apparent, making electrocardiogram rapid screening test for emphysema.

[Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy].

PubMed

Gómez Tejada, Ricardo A; Legarreta, Cora G; Enghelmayer, Juan Ignacio; Dianti, Milagros; Acuña, Silvana; Olmedo, Gloria

2017-01-01

In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect.

PubMed

Peca, Donatella; Petrini, Stefania; Tzialla, Chryssoula; Boldrini, Renata; Morini, Francesco; Stronati, Mauro; Carnielli, Virgilio P; Cogo, Paola E; Danhaive, Olivier

2011-08-25

Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled (2)H(2)O and (13)C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry (2)H and (13)C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and in five ABCA3 mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B synthesis (43.2 vs. 76.5 ± 24.8%/day); conversely, DSPC synthesis was higher (12.4 vs. 6.3 ± 0.5%/day) compared to controls, although there was a marked reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 ± 12.4% of total phospholipid content). Defective TTF-1 signaling may result in profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in other genetic surfactant defects.

Altered surfactant homeostasis and recurrent respiratory failure secondary to TTF-1 nuclear targeting defect

PubMed Central

2011-01-01

Background Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1) - critical for lung, thyroid and central nervous system morphogenesis and function - causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored. We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant. Methods The subject was an infant with severe neonatal respiratory distress syndrome followed by recurrent respiratory failure episodes, hypopituitarism and neurological abnormalities. Lung histology and ultrastructure were assessed by surgical biopsy. Surfactant-related genes were studied by direct genomic DNA sequencing and array chromatine genomic hybridization (aCGH). Surfactant protein expression in lung tissue was analyzed by confocal immunofluorescence microscopy. For kinetics studies, surfactant protein B and disaturated phosphatidylcholine (DSPC) were isolated from serial tracheal aspirates after intravenous administration of stable isotope-labeled 2H2O and 13C-leucine; fractional synthetic rate was derived from gas chromatography/mass spectrometry 2H and 13C enrichment curves. Six intubated infants with no primary lung disease were used as controls. Results Lung biopsy showed desquamative interstitial pneumonitis and lamellar body abnormalities suggestive of genetic surfactant deficiency. Genetic studies identified a heterozygous ABCA3 mutation, L941P, previously unreported. No SFTPB, SFTPC or NKX2.1 mutations or deletions were found. However, immunofluorescence studies showed TTF-1 prevalently expressed in type II cell cytoplasm instead of nucleus, indicating defective nuclear targeting. This pattern has not been reported in human and was not found in two healthy controls and in five ABCA3 mutation carriers. Kinetic studies demonstrated a marked reduction of SP-B synthesis (43.2 vs. 76.5 ± 24.8%/day); conversely, DSPC synthesis was higher (12.4 vs. 6.3 ± 0.5%/day) compared to controls, although there was a marked reduction of DSPC content in tracheal aspirates (29.8 vs. 56.1 ± 12.4% of total phospholipid content). Conclusion Defective TTF-1 signaling may result in profound surfactant homeostasis disruption and neonatal/pediatric diffuse lung disease. Heterozygous ABCA3 missense mutations may act as disease modifiers in other genetic surfactant defects. PMID:21867529

Viral and Mycoplasma pneumoniae pneumonias in school-age children: three-year follow-up of respiratory function.

PubMed

Todisco, T; de Benedictis, F M; Dottorini, M

1989-01-01

We studied the evolution of respiratory function during and for 3 years after the acute onset of viral and Mycoplasma pneumoniae pneumonias in 13 school-age children. A mixed type transient ventilatory defect (restrictive and obstructive, but mainly restrictive) with large and small airway involvement was observed during the acute phase of the pneumonias. Residual small airway involvement was found over the next 12 months, but no pulmonary function abnormalities were present after 3 years. At that time, one of the 13 subjects displayed bronchial hyperreactivity to distilled water mist challenge. The authors concluded that viral and Mycoplasma pneumoniae pneumonia in previously healthy school-age children does not cause impaired lung function in later childhood.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases.

PubMed

Wang, Hui; Liu, Jing-Shi; Peng, Shao-Hua; Deng, Xi-Yun; Zhu, De-Mao; Javidiparsijani, Sara; Wang, Gui-Rong; Li, Dai-Qiang; Li, Long-Xuan; Wang, Yi-Chun; Luo, Jun-Ming

2013-10-28

Pulmonary abnormalities, dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms, and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy, with failure to isolate bacterial pathogens on repeated sputum culture, and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel. Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD, the detailed mechanisms of pulmonary-intestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities, dysfunction, or hyper-reactivity among IBD patients need further evaluation. Here, we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

PubMed Central

Wang, Hui; Liu, Jing-Shi; Peng, Shao-Hua; Deng, Xi-Yun; Zhu, De-Mao; Javidiparsijani, Sara; Wang, Gui-Rong; Li, Dai-Qiang; Li, Long-Xuan; Wang, Yi-Chun; Luo, Jun-Ming

2013-01-01

Pulmonary abnormalities, dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms, and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy, with failure to isolate bacterial pathogens on repeated sputum culture, and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel. Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD, the detailed mechanisms of pulmonary-intestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities, dysfunction, or hyper-reactivity among IBD patients need further evaluation. Here, we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy. PMID:24187454

Prenatally diagnosed fetal lung lesions with associated conotruncal heart defects: is there a genetic association?

PubMed

Hüsler, Margaret R; Wilson, R Douglas; Rychik, Jack; Bebbington, Michael W; Johnson, Mark P; Mann, Stephanie E; Hedrick, Holly L; Adzick, Scott

2007-12-01

Congenital lung malformation can easily be diagnosed by prenatal ultrasound. Associated extrapulmonary malformations such as heart defects and chromosomal aberrations are rare. The objective of this study was to describe the natural history, outcome and other associated malformations in fetuses with lung lesions and an associated heart defect. Retrospective analysis of 4 cases of prenatally diagnosed fetal CCAMs and hybrid lesions with an associated heart defect and review of 8 cases in the literature. At a single referral center 1.9% of the fetuses with Congenital cystic adenomatoid malformation (CCAM) were diagnosed with an associated heart defect. Seven of the total 12 cases (58%) reviewed had a conotruncal heart abnormality. Chromosomal abnormalities were found in 5 (42%) of the cases. This retrospective review shows that karyotyping in fetal lung lesions with an associated heart defect or isolated large lung lesions is indicated. It also suggests that there is a subpopulation of fetuses with CCAMs who have conotruncal heart defects. This finding may suggest a common genetic background. Copyright (c) 2007 John Wiley & Sons, Ltd.

Buoyancy disorders in pet axolotls Ambystoma mexicanum: three cases.

PubMed

Takami, Yoshinori; Une, Yumi

2018-01-31

As far as we are aware, there are no previous reports on the pathologic conditions of buoyancy disorders in Ambystoma mexicanum. Herein, we describe various clinical test results, clinical outcomes, and the pathological findings of an experimental pneumonectomy procedure in 3 A. mexicanum exhibiting abnormal buoyancy. The 3 pet A. mexicanum were adults, and their respective ages and body weights were 1, 5, and 6 yr and 48, 55, and 56 g. Two of these cases were confirmed via radiographic examination to have free air within the body cavity, and all 3 cases were found via ultrasonography to have an acoustic shadow within the body cavity and were diagnosed with pneumocoelom. Lung perforations were detected macroscopically in 2 of the cases, and all 3 cases had fibrosis in the caudal ends of the lungs. Removal of the lung lesions eliminated the abnormal buoyancy in all 3 cases. We concluded that air had leaked into the body cavity from the lungs, and we propose that lung lesions are an important cause of buoyancy disorders in A. mexicanum.

Respiratory damage in children exposed to urban pollution.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Fordham, Lynn A; Valencia-Salazar, Gildardo; Chung, Charles J; Rodriguez-Alcaraz, Antonio; Paredes, Rogelio; Variakojis, Daina; Villarreal-Calderón, Anna; Flores-Camacho, Lourdes; Antunez-Solis, Angelina; Henríquez-Roldán, Carlos; Hazucha, Milan J

2003-08-01

Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life. Copyright 2003 Wiley-Liss, Inc.

Lung boundary detection in pediatric chest x-rays

NASA Astrophysics Data System (ADS)

Candemir, Sema; Antani, Sameer; Jaeger, Stefan; Browning, Renee; Thoma, George R.

2015-03-01

Tuberculosis (TB) is a major public health problem worldwide, and highly prevalent in developing countries. According to the World Health Organization (WHO), over 95% of TB deaths occur in low- and middle- income countries that often have under-resourced health care systems. In an effort to aid population screening in such resource challenged settings, the U.S. National Library of Medicine has developed a chest X-ray (CXR) screening system that provides a pre-decision on pulmonary abnormalities. When the system is presented with a digital CXR image from the Picture Archive and Communication Systems (PACS) or an imaging source, it automatically identifies the lung regions in the image, extracts image features, and classifies the image as normal or abnormal using trained machine-learning algorithms. The system has been trained on adult CXR images, and this article presents enhancements toward including pediatric CXR images. Our adult lung boundary detection algorithm is model-based. We note the lung shape differences during pediatric developmental stages, and adulthood, and propose building new lung models suitable for pediatric developmental stages. In this study, we quantify changes in lung shape from infancy to adulthood toward enhancing our lung segmentation algorithm. Our initial findings suggest pediatric age groupings of 0 - 23 months, 2 - 10 years, and 11 - 18 years. We present justification for our groupings. We report on the quality of boundary detection algorithm with the pediatric lung models.

Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets.

PubMed

Haq, Iram J; Gray, Michael A; Garnett, James P; Ward, Christopher; Brodlie, Malcolm

2016-03-01

Cystic fibrosis (CF) is a life-limiting disease characterised by recurrent respiratory infections, inflammation and lung damage. The volume and composition of the airway surface liquid (ASL) are important in maintaining ciliary function, mucociliary clearance and antimicrobial properties of the airway. In CF, these homeostatic mechanisms are impaired, leading to a dehydrated and acidic ASL. ASL volume depletion in CF is secondary to defective anion transport by the abnormal cystic fibrosis transmembrane conductance regulator protein (CFTR). Abnormal CFTR mediated bicarbonate transport creates an unfavourable, acidic environment, which impairs antimicrobial function and alters mucus properties and clearance. These disease mechanisms create a disordered airway milieu, consisting of thick mucopurulent secretions and chronic bacterial infection. In addition to CFTR, there are additional ion channels and transporters in the apical airway epithelium that play a role in maintaining ASL homeostasis. These include the epithelial sodium channel (ENaC), the solute carrier 26A (SLC26A) family of anion exchangers, and calcium-activated chloride channels. In this review we discuss how the ASL is abnormal in CF and how targeting these alternative channels and transporters could provide an attractive therapeutic strategy to correct the underlying ASL abnormalities evident in CF. 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/

Assessment of pulmonary structure-function relationships in young children and adolescents with cystic fibrosis by multivolume proton-MRI and CT.

PubMed

Pennati, Francesca; Roach, David J; Clancy, John P; Brody, Alan S; Fleck, Robert J; Aliverti, Andrea; Woods, Jason C

2018-02-19

Lung disease is the most frequent cause of morbidity and mortality in patients with cystic fibrosis (CF), and there is a shortage of sensitive biomarkers able to regionally monitor disease progression and to assess early responses to therapy. To determine the feasibility of noncontrast-enhanced multivolume MRI, which assesses intensity changes between expiratory and inspiratory breath-hold images, to detect and quantify regional ventilation abnormalities in CF lung disease, with a focus on the structure-function relationship. Retrospective. Twenty-nine subjects, including healthy young children (n = 9, 7-37 months), healthy adolescents (n = 4, 14-22 years), young children with CF lung disease (n = 10, 7-47 months), and adolescents with CF lung disease (n = 6, 8-18 years) were studied. 3D spoiled gradient-recalled sequence at 1.5T. Subjects were scanned during breath-hold at functional residual capacity (FRC) and total lung capacity (TLC) through noncontrast-enhanced MRI and CT. Expiratory-inspiratory differences in MR signal-intensity (Δ 1 H-MRI) and CT-density (ΔHU) were computed to estimate regional ventilation. MR and CT images were also evaluated using a CF-specific scoring system. Quadratic regression, Spearman's correlation, one-way analysis of variance (ANOVA). Δ 1 H-MRI maps were sensitive to ventilation heterogeneity related to gravity dependence in healthy lung and to ventilation impairment in CF lung disease. A high correlation was found between MRI and CT ventilation maps (R 2  = 0.79, P < 0.001). Globally, Δ 1 H-MRI and ΔHU decrease with increasing morphological score (respectively, R 2  = 0.56, P < 0.001 and R 2  = 0.31, P < 0.001). Locally, Δ 1 H-MRI was higher in healthy regions (median 15%) compared to regions with bronchiectasis, air trapping, consolidation, and to segments fed by airways with bronchial wall thickening (P < 0.001). Multivolume noncontrast-enhanced MRI, as a nonionizing imaging modality that can be used on nearly any MRI scanner without specialized equipment or gaseous tracers, may be particularly valuable in CF care, providing a new imaging biomarker to detect early alterations in regional lung structure-function. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Unique spatial and cellular expression patterns of Hoxa5, Hoxb4 and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia

PubMed Central

Volpe, MaryAnn Vitoria; Wang, Karen Ting Wai; Nielsen, Heber Carl; Chinoy, Mala Romeshchandra

2009-01-01

Background Hox transcription factors modulate signaling pathways controlling organ morphogenesis and maintain cell fate and differentiation in adults. Retinoid signaling, key in regulating Hox expression, is altered in pulmonary hypoplasia. Information on pattern-specific expression of Hox proteins in normal lung development and in pulmonary hypoplasia is minimal. Our objective was to determine how pulmonary hypoplasia alters temporal, spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 proteins compared to normal lung development. Methods Temporal, spatial and cellular Hoxa5, Hoxb4 and Hoxb6 expression was studied in normal (untreated) and nitrofen-induced hypoplastic (NT-PH) lungs from gestational day 13.5, 16, 19 fetuses and neonates using western blot and immunohistochemistry. Results Modification of protein levels and spatial and cellular Hox expression patterns in NT-PH lungs was consistent with delayed lung development. Distinct protein isoforms were detected for each Hox protein. Expression levels of the Hoxa5 and Hoxb6 isoforms changed with development and further in NT-PH lungs. Compared to normal lungs, Gd19 and neonatal NT-PH lungs had decreased Hoxb6 and increased Hoxa5 and Hoxb4. Hoxa5 cellular localization changed from mesenchyme to epithelia earlier in normal lungs. Hoxb4 was expressed in mesenchyme and epithelial cells throughout development. Hoxb6 remained mainly in mesenchymal cells around distal airways. Conclusions Unique spatial and cellular expression of Hoxa5, Hoxb4 and Hoxb6 participates in branching morphogenesis and terminal sac formation. Altered Hox protein temporal and cellular balance of expression either contributes to pulmonary hypoplasia or functions as a compensatory mechanism attempting to correct abnormal lung development and maturation in this condition. PMID:18553509

Diagnosing cystic fibrosis-related diabetes: current methods and challenges.

PubMed

Prentice, Bernadette; Hameed, Shihab; Verge, Charles F; Ooi, Chee Y; Jaffe, Adam; Widger, John

2016-07-01

Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms "Cystic Fibrosis Related Diabetes", "Cystic Fibrosis" AND "glucose", "Cystic Fibrosis" AND "insulin", "Cystic Fibrosis" AND "Diabetes". Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute sampled oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF.

Stratifin regulates stabilization of receptor tyrosine kinases via interaction with ubiquitin-specific protease 8 in lung adenocarcinoma.

PubMed

Kim, Yunjung; Shiba-Ishii, Aya; Nakagawa, Tomoki; Iemura, Shun-Ichiro; Natsume, Tohru; Nakano, Noriyuki; Matsuoka, Ryota; Sakashita, Shingo; Lee, SangJoon; Kawaguchi, Atsushi; Sato, Yukio; Noguchi, Masayuki

2018-06-07

Previously we have reported that stratifin (SFN, 14-3-3 sigma) acts as a novel oncogene, accelerating the tumor initiation and progression of lung adenocarcinoma. Here, pull-down assay and LC-MS/MS analysis revealed that ubiquitin-specific protease 8 (USP8) specifically bound to SFN in lung adenocarcinoma cells. Both USP8 and SFN showed higher expression in human lung adenocarcinoma than in normal lung tissue, and USP8 expression was significantly correlated with SFN expression. Expression of SFN, but not of USP8, was associated with histological subtype, pathological stage, and poor prognosis. USP8 stabilizes receptor tyrosine kinases (RTKs) such as EGFR and MET by deubiquitination, contributing to the proliferative activity of many human cancers including non-small cell lung cancer. In vitro, USP8 binds to SFN and they co-localize at the early endosomes in lung adenocarcinoma cells. Moreover, USP8 or SFN knockdown leads to downregulation of tumor cellular proliferation and upregulation of apoptosis, p-EGFR or p-MET, which are related to the degradation pathway, and accumulation of ubiquitinated RTKs, leading to lysosomal degradation. Additionally, mutant USP8, which is unable to bind to SFN, reduces the expression of RTKs and p-STAT3. We also found that interaction with SFN is critical for USP8 to exert its autodeubiquitination function and avoid dephosphorylation by PP1. Our findings demonstrate that SFN enhances RTK stabilization through abnormal USP8 regulation in lung adenocarcinoma, suggesting that SFN could be a more suitable therapeutic target for lung adenocarcinoma than USP8.

Industrial ammonia gassing

PubMed Central

Walton, M.

1973-01-01

Walton, M. (1972).British Journal of Industrial Medicine,30, 78-86. Industrial ammonia gassing. Seven cases of ammonia gassing are described with follow-up for five years of the six survivors and the post-mortem findings of the fatal case. All the survivors attributed continuing symptoms to the gassing. The study failed to demonstrate permanent ill effects in the one case of mild exposure. Of the more serious cases one has stopped smoking and taken up physical training teaching. He now has above average lung function. Two serious cases who continued to smoke have the lung function abnormalities expected from their smoking. In the other two seriously exposed cases, who also continued to smoke, there is a persistent reduction in ventilation and gas transfer which seems to be due to the ammonia gassing. The post-mortem findings in the fatal case showed acute congestion and oedema of the mucosa of the respiratory tract, the bronchial walls being stripped of their lining epithelium and the alveoli stuffed with red blood cells and oedema fluid. Images PMID:4685304

Pulmonary function tests do not predict mortality in patients undergoing continuous-flow left ventricular assist device implantation.

PubMed

Bedzra, Edo K S; Dardas, Todd F; Cheng, Richard K; Pal, Jay D; Mahr, Claudius; Smith, Jason W; Shively, Kent; Masri, S Carolina; Levy, Wayne C; Mokadam, Nahush A

2017-12-01

To investigate the effect of pulmonary function testing on outcomes after continuous flow left ventricular assist device implantation. A total of 263 and 239 patients, respectively, had tests of forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide preoperatively for left ventricular assist device implantations between July 2005 and September 2015. Kaplan-Meier analysis and multivariable Cox regressions were performed to evaluate mortality. Patients were analyzed in a single cohort and across 5 groups. Postoperative intensive care unit and hospital lengths of stay were evaluated with negative binomial regressions. There is no association of forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide with survival and no difference in mortality at 1 and 3 years between the groups (log rank P = .841 and .713, respectively). Greater values in either parameter were associated with decreased hospital lengths of stay. Only diffusing capacity of the lungs for carbon monoxide was associated with increased intensive care unit length of stay in the group analysis (P = .001). Ventilator times, postoperative pneumonia, reintubation, and tracheostomy rates were similar across the groups. Forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide are not associated with operative or long-term mortality in patients undergoing continuous flow left ventricular assist device implantation. These findings suggest that these abnormal pulmonary function tests alone should not preclude mechanical circulatory support candidacy. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Lung perfusion characteristics in pulmonary arterial hypertension (PAH) and peripheral forms of chronic thromboembolic pulmonary hypertension (pCTEPH): Dual-energy CT experience in 31 patients.

PubMed

Giordano, Jessica; Khung, Suonita; Duhamel, Alain; Hossein-Foucher, Claude; Bellèvre, Dimitri; Lamblin, Nicolas; Remy, Jacques; Remy-Jardin, Martine

2017-04-01

To compare lung perfusion in PAH and pCTEPH on dual-energy CT (DECT) examinations. Thirty-one patients with PAH (group 1; n = 19) and pCTEPH (group 2; n = 12) underwent a dual-energy chest CTA with reconstruction of diagnostic and perfusion images. Perfusion alterations were analysed at a segmental level. V/Q scintigraphy was available in 22 patients (group 1: 13/19; group 2: 9/12). CT perfusion was abnormal in 52.6 % of group 1 patients and in 100 % of group 2 patients (p = 0.0051). The patterns of perfusion alteration significantly differed between the two groups (p < 0.0001): (1) in group 1, 96.6 % of segments with abnormal perfusion showed patchy defects; (2) in group 2, the most frequent abnormalities consisted of patchy (58.5 %) and PE-type (37.5 %) defects. Paired comparison of CT perfusion and scintigraphy showed concordant findings in 76.9 % of group 1 (10/13) and 100 % of group 2 (9/9) patients, with a predominant or an exclusive patchy pattern in group 1 and a mixed pattern of abnormalities in group 2. Lung perfusion alterations at DECT are less frequent and more homogeneous in PAH than in pCTEPH, with a high level of concordant findings with V/Q scintigraphy. • Depiction of chronic pulmonary embolism exclusively located on peripheral arteries is difficult. • The main differential diagnosis of pCTEPH is PAH. • The pattern of DECT perfusion changes can help differentiate PAH and pCETPH. • In PAH, almost all segments with abnormal perfusion showed patchy defects. • In pCTEPH, patchy and PE-type defects were the most frequent abnormalities.

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

PubMed

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p<0.01) and among patients with severe motor dysfunction (90% vs. 35%; p<0.001). Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Analysis of the pattern of expression of the Fanconi anemia group C (Facc) gene during murine development

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

Krasnoshtein, F.; Buchwald, M.

1994-09-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by a variety of congenital and skeletal malformations, progressive pancytopanenia and predisposition to malignancies. FA cells display chromosomal instability and hypersensitivity to DNA-damaging agents. Both the human and the corresponding murine cDNAs have been cloned in our lab. Here we describe the expression of Facc during mouse development, using mRNA in situ hybridization. Our aim is to obtain clues on the possible function of the Facc gene product during development that may help elucidate basic defect(s) in FA. In addition, knowledge of the exact pattern of Facc expression will assist inmore » interpreting the phenotypes of mutant mice, currently being developed. In embryos the gene is diffusely expressed over the entire embryo, with higher hybridization levels in the mesenchyme and in both upper and lower extremities. Specific expression of Facc is seen in the perichondrium and marrow of long bones of hind limbs/hip; long bones of front limbs/shoulder region; developing digits of front and hind paws; and ribs. The signal is also detected in the following regions: cranial/frontal; facial/periorbital and maxillary/mandibular, hair follicles, diaphragm and lung. In addition, generalized Facc expression is seen during these embryonic stages. The pattern of Facc expression is consistent with the known skeletal abnormalities in FA patients, which include radial ray deformities, metacarpal hypoplasia, and abnormalities of lower limbs, ribs, head and face. The signal in the lung is consistent with the lung lobe absence and abnormal pulmonary drainage that have been detected in some FA patients. The sloped forehead and microcephaly in FA patients may have some association with the signal seen in the frontal region of the mouse cranium. Taken together, our results suggest that Facc is directly involved in the development of various embryonic tissues, particularly bone.« less

Pulmonary effects of exposure to fine fibreglass: irregular opacities and small airways obstruction.

PubMed Central

Kilburn, K H; Powers, D; Warshaw, R H

1992-01-01

OBJECTIVE--Man made mineral fibres imitate asbestos and produce tumours of the pleura in animals. To answer the question, Does prolonged exposure to fibreglass adversely affect pulmonary function or produce radiographic abnormalities in human subjects? we studied workers in a midwestern appliance plant where refrigerator doors and previously entire cabinets were insulated with fibreglass sheeting and loose rotary spun fibreglass. METHODS--Spirometry and lung volumes were measured, respiratory and occupational questionnaires were administered, and chest x-ray films were read for pneumoconiosis using International Labour Office (ILO) 1980 criteria in 284 workers with exposure of 20 years or more. RESULTS--Expiratory flows were reduced including FEV1 (mean 90.3% of predicted (pr), FEF25-75 (85.5% pr), and FEF75-85 (76.2% pr). Forced vital capacity was significantly reduced (92.8% pr) and total lung capacity was significantly increased (109.2% pr). In white male smokers, a group large enough for comparisons, parameters of pulmonary function were reduced further in the presence of irregular opacities. Forty three workers (15.1%) had evidence of pneumoconiosis on chest radiographs: 26 of these (9.1%), had no known exposure to asbestos and 17 (6.0%) had some exposure. The best judgement was that in 36 (13.0%), pulmonary opacities or pleural abnormalities were due to fibreglass. CONCLUSION--Commercial rotary spun fibreglass used for insulating appliances appears to produce human disease that is similar to asbestosis. PMID:1419860

Inhibition of cancer growth in vitro and in vivo by a novel ROS-modulating agent with ability to eliminate stem-like cancer cells.

PubMed

Wang, Jiankang; Luo, Bingling; Li, Xiaobing; Lu, Wenhua; Yang, Jing; Hu, Yumin; Huang, Peng; Wen, Shijun

2017-06-22

Reactive oxygen species (ROS) have a crucial role in cell signaling and cellular functions. Mounting evidences suggest that abnormal increase of ROS is often observed in cancer cells and that this biochemical feature can be exploited for selective killing of the malignant cells. A naturally occurring compound phenethyl isothiocyanate (PEITC) has been shown to have promising anticancer activity by modulating intracellular ROS. Here we report a novel synthetic analog of PEITC with superior in vitro and in vivo antitumor effects. Mechanistic study showed that LBL21 induced a rapid depletion of intracellular glutathione (GSH), leading to abnormal ROS accumulation and mitochondrial dysfunction, evident by a decrease in mitochondrial respiration and transmembrane potential. Importantly, LBL21 exhibited the ability to abrogate stem cell-like cancer side population (SP) cells in non-small cell lung cancer A549 cells associated with a downregulation of stem cell markers including OCT4, ABCG2, SOX2 and CD133. Functionally, LBL21 inhibited the ability of cancer cells to form colonies in vitro and develop tumor in vivo. The therapeutic efficacy of LBL21 was further demonstrated in mice bearing A549 lung cancer xenografts. Our study suggests that the novel ROS-modulating agent LBL21 has promising anticancer activity with an advantage of elimination of stem-like cancer cells. This compound merits further study to evaluate its potential for use in cancer treatment.

Abnormal predicted diffusion capacities in healthy Asians: an inequality with a solution.

PubMed

Pesola, Gene R; Huggins, Gladstone; Sherpa, Tsering Y

2006-01-01

Asian lung volumes are 10-15% less than those of Caucasians. To test the hypothesis that healthy Asians might be labeled as abnormal using three commonly used Caucasian-derived prediction equation estimates (PEE) of DLCO currently used. In addition, a Chinese-derived PEE of DLCO was tested to determine its validity in non-Chinese Asians. Forty-one healthy Asians underwent DLCO testing. Controls consisted of the PEE and 12 healthy Caucasians. Measured DLCO was compared with the Miller, Knudson, Crapo and one Chinese PEE. Abnormal was defined as a DLCO <80% predicted. Gas dilution and plethysmography estimated alveolar volume. Proportions in parentheses in the results below are DLCO adjusted for alveolar volume. The average Asian DLCO was 25.75 +/- 5.55 ml/min/mm Hg, no different than the predicted DLCO of 25.29 +/- 5.53 seen with Chinese PEE. This was different (p < 0.01) than the predicted DLCO of 27.82 +/- 5.09, 33.66 +/- 6.29, and 31.64 +/- 5.33 for the Miller, Knudson, and Crapo equations, respectively. This resulted in 4/41 (0/41), 27/39 (2/39), 21/41 (3/41) and 1/41 (0/41) DLCO measurements being defined as abnormal using Miller, Knudson, Crapo and Chinese PEE, respectively. In Caucasians, the measured DLCO was similar to the Miller but significantly lower than the Knudson and Crapo PEE. Measured lung volumes were significantly smaller compared to predicted for the three Caucasian PEE in Asians, with no difference in Caucasians. There was no difference in measured lung volumes and Chinese PEE. Current Caucasian PEE for DLCO when used in healthy Asians result in an abnormal reading that is incorrect from 10 to 50% of the time. This PEE failure is related to a reduction in lung volume not accounted for. The Chinese PEE for DLCO works for non-Chinese Asians and should replace Caucasian PEE in the US in all Asians.

Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene

PubMed Central

2013-01-01

Background To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. Methods Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. Results Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration and proliferation in vitro. Conclusions The two libraries of differentially expressed genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer-related gene. ERGIC3 may play an active role in the development and progression of lung cancer. PMID:23374247

Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

PubMed Central

Wolf, Michael S.; Chadha, Ashley D.; Carroll, Clinton M.; Borinstein, Scott C.

2014-01-01

Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. PMID:25434733

Decrease of pulmonary blood flow detected by phase contrast MRI is correlated with a decrease in lung volume and increase of lung fibrosis area determined by computed tomography in interstitial lung disease.

PubMed

Tsuchiya, Nanae; Yamashiro, Tsuneo; Murayama, Sadayuki

2016-09-01

Lung volume and pulmonary blood flow decrease in patients with interstitial lung disease (ILD). The purpose of this study was to assess the relationship between pulmonary blood flow and lung volume in ILD patients. This research was approved by the institutional review board. Twenty-seven patients (9 men, 18 women; mean age, 59 years; range, 24-79 years) with ILD were included. Blood flow was assessed in the pulmonary trunk and the left and right pulmonary arteries by phase contrast magnetic resonance imaging (MRI). Lung volume and the computed tomography (CT) visual score that indicates the severity of ILD were assessed on the left and right sides by thin-section CT scanning. Lung volume was automatically measured by lung analysis software (VINCENT Ver. 4). The CT visual score was measured by averaging the proportion of abnormal lung area at five anatomic levels. Pearson's correlation coefficient was used to determine the relationship between pulmonary blood flow and lung volume. Pulmonary blood flow showed a significant correlation with lung volume (both: r=0.52, p=0.006; left: r=0.61, p=0.001; right: r=0.54, p=0.004) and CT visual score (both: r=-0.39, p=0.04; left: r=-0.48, p=0.01; right: r=-0.38, p=0.04). Partial correlation analysis, controlled for age, height and weight, showed a significant correlation between pulmonary blood flow and lung volume (both: r=0.43, p=0.03; left: r=0.55, p=0.005; right: r=0.48, p=0.01) and CT visual score (both: r=-0.58, p=0.003; left: r=-0.51, p=0.01; right: r=-0.64, p=0.001). In ILD, reduced pulmonary blood flow is associated with reduced lung volume and increased abnormal lung area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prevalence of renal insufficiency in elderly cancer patients in a tertiary cancer center

PubMed Central

Pontes, Lucíola de Barros; Antunes, Yuri Philippe Pimentel Vieira; Bugano, Diogo Diniz Gomes; Karnakis, Theodora; del Giglio, Auro; Kaliks, Rafael Aliosha

2014-01-01

Objective To estimate the prevalence of abnormal glomerular filtration rate in elderly patients with solid tumors. Methods A retrospective study with patients aged >65 years diagnosed with solid tumors between January 2007 and December 2011 in a cancer center. The following data were collected: sex, age, serum creatinine at the time of diagnosis and type of tumor. Renal function was calculated using abbreviated Modification of Diet in Renal Disease (MDRD) formulae and then staged in accordance with the clinical practice guidelines published by the Working Group of the National Kidney Foundation. Results A total of 666 patients were included and 60% were male. The median age was 74.2 years (range: 65 to 99 years). The most prevalent diagnosis in the study population were colorectal (24%), prostate (20%), breast (16%) and lung cancer (16%). The prevalence of elevated serum creatinine (>1.0mg/dL) was 30%. However, when patients were assessed using abbreviated MDRD formulae, 66% had abnormal renal function, stratified as follows: 45% with stage 2, 18% with stage 3, 3% with stage 4 and 0.3% with stage 5. Conclusion To the best of our knowledge, this was the first study to estimate the frequency of renal insufficiency in elderly cancer patients in Brazil. The prevalence of abnormal renal function among our cohort was high. As suspected, the absolute creatinine level does underestimate renal function impairment and should not be used as predictor of chemotherapy metabolism, excretion and consequent toxicity. PMID:25295449

Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

PubMed Central

2014-01-01

The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers.

PubMed

Selman, Moisés; Pardo, Annie

2006-06-01

Idiopathic pulmonary fibrosis (IPF), a progressive and relentless lung scarring of unknown etiology, has been recognized as the most lethal interstitial lung disease. Despite the growing interest in IPF, the precise molecular mechanisms underlying the development of fibrosis and leading to the irreversible destruction of the lung are still unknown. Recently, it has been proposed that IPF, instead of being a chronic inflammatory disorder, results from multiple cycles of epithelial cell injury and activation. In turn, active alveolar epithelial cells provoke the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci and the exaggerated accumulation of extracellular matrix, mirroring abnormal wound repair. In this article, some characteristics of the alveolar epithelium are briefly outlined, and the fibrogenic mechanisms specifically operated by active abnormal epithelial cells are examined.

Prospective evaluation of changes in computed cranial tomography in patients with small cell lung carcinoma treated with chemotherapy and prophylactic cranial irradiation.

PubMed

Craig, J B; Jackson, D V; Moody, D; Cruz, J M; Pope, E K; Powell, B L; Spurr, C L; Capizzi, R L

1984-10-01

Computed cranial tomographic scans were performed as part of the pretreatment evaluation and at six- to nine-month intervals posttreatment in 13 patients with small cell lung carcinoma. All patients received 3,000 rad of prophylactic cranial irradiation delivered over two weeks in ten treatment fractions in conjunction with multiagent chemotherapy. Posttreatment scans documented an extraordinarily high frequency of abnormalities including cerebral atrophy (100%), ventricular dilatation (70%), and decreased coefficient of absorption in the white matter (15%). Unexplained neurologic abnormalities developed in four of six patients living at least 15 months after institution of therapy. As the number of long-term survivors of this type of lung cancer increases, the need for prospective comprehensive neuropsychologic assessment to determine the clinical significance of these changes is needed.

Evaluation of pulmonary function using single-breath-hold dual-energy computed tomography with xenon

PubMed Central

Kyoyama, Hiroyuki; Hirata, Yusuke; Kikuchi, Satoshi; Sakai, Kosuke; Saito, Yuriko; Mikami, Shintaro; Moriyama, Gaku; Yanagita, Hisami; Watanabe, Wataru; Otani, Katharina; Honda, Norinari; Uematsu, Kazutsugu

2017-01-01

Abstract Xenon-enhanced dual-energy computed tomography (xenon-enhanced CT) can provide lung ventilation maps that may be useful for assessing structural and functional abnormalities of the lung. Xenon-enhanced CT has been performed using a multiple-breath-hold technique during xenon washout. We recently developed xenon-enhanced CT using a single-breath-hold technique to assess ventilation. We sought to evaluate whether xenon-enhanced CT using a single-breath-hold technique correlates with pulmonary function testing (PFT) results. Twenty-six patients, including 11 chronic obstructive pulmonary disease (COPD) patients, underwent xenon-enhanced CT and PFT. Three of the COPD patients underwent xenon-enhanced CT before and after bronchodilator treatment. Images from xenon-CT were obtained by dual-source CT during a breath-hold after a single vital-capacity inspiration of a xenon–oxygen gas mixture. Image postprocessing by 3-material decomposition generated conventional CT and xenon-enhanced images. Low-attenuation areas on xenon images matched low-attenuation areas on conventional CT in 21 cases but matched normal-attenuation areas in 5 cases. Volumes of Hounsfield unit (HU) histograms of xenon images correlated moderately and highly with vital capacity (VC) and total lung capacity (TLC), respectively (r = 0.68 and 0.85). Means and modes of histograms weakly correlated with VC (r = 0.39 and 0.38), moderately with forced expiratory volume in 1 second (FEV1) (r = 0.59 and 0.56), weakly with the ratio of FEV1 to FVC (r = 0.46 and 0.42), and moderately with the ratio of FEV1 to its predicted value (r = 0.64 and 0.60). Mode and volume of histograms increased in 2 COPD patients after the improvement of FEV1 with bronchodilators. Inhalation of xenon gas caused no adverse effects. Xenon-enhanced CT using a single-breath-hold technique depicted functional abnormalities not detectable on thin-slice CT. Mode, mean, and volume of HU histograms of xenon images reflected pulmonary function. Xenon images obtained with xenon-enhanced CT using a single-breath-hold technique can qualitatively depict pulmonary ventilation. A larger study comprising only COPD patients should be conducted, as xenon-enhanced CT is expected to be a promising technique for the management of COPD. PMID:28099359

Evaluation of pulmonary function using single-breath-hold dual-energy computed tomography with xenon: Results of a preliminary study.

PubMed

Kyoyama, Hiroyuki; Hirata, Yusuke; Kikuchi, Satoshi; Sakai, Kosuke; Saito, Yuriko; Mikami, Shintaro; Moriyama, Gaku; Yanagita, Hisami; Watanabe, Wataru; Otani, Katharina; Honda, Norinari; Uematsu, Kazutsugu

2017-01-01

Xenon-enhanced dual-energy computed tomography (xenon-enhanced CT) can provide lung ventilation maps that may be useful for assessing structural and functional abnormalities of the lung. Xenon-enhanced CT has been performed using a multiple-breath-hold technique during xenon washout. We recently developed xenon-enhanced CT using a single-breath-hold technique to assess ventilation. We sought to evaluate whether xenon-enhanced CT using a single-breath-hold technique correlates with pulmonary function testing (PFT) results.Twenty-six patients, including 11 chronic obstructive pulmonary disease (COPD) patients, underwent xenon-enhanced CT and PFT. Three of the COPD patients underwent xenon-enhanced CT before and after bronchodilator treatment. Images from xenon-CT were obtained by dual-source CT during a breath-hold after a single vital-capacity inspiration of a xenon-oxygen gas mixture. Image postprocessing by 3-material decomposition generated conventional CT and xenon-enhanced images.Low-attenuation areas on xenon images matched low-attenuation areas on conventional CT in 21 cases but matched normal-attenuation areas in 5 cases. Volumes of Hounsfield unit (HU) histograms of xenon images correlated moderately and highly with vital capacity (VC) and total lung capacity (TLC), respectively (r = 0.68 and 0.85). Means and modes of histograms weakly correlated with VC (r = 0.39 and 0.38), moderately with forced expiratory volume in 1 second (FEV1) (r = 0.59 and 0.56), weakly with the ratio of FEV1 to FVC (r = 0.46 and 0.42), and moderately with the ratio of FEV1 to its predicted value (r = 0.64 and 0.60). Mode and volume of histograms increased in 2 COPD patients after the improvement of FEV1 with bronchodilators. Inhalation of xenon gas caused no adverse effects.Xenon-enhanced CT using a single-breath-hold technique depicted functional abnormalities not detectable on thin-slice CT. Mode, mean, and volume of HU histograms of xenon images reflected pulmonary function. Xenon images obtained with xenon-enhanced CT using a single-breath-hold technique can qualitatively depict pulmonary ventilation. A larger study comprising only COPD patients should be conducted, as xenon-enhanced CT is expected to be a promising technique for the management of COPD.

Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury

PubMed Central

Mo, Yiqun; Chen, Jing; Humphrey, David M.; Fodah, Ramy A.; Warawa, Jonathan M.

2014-01-01

Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham-exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1 day after chlorine exposure, which was repaired with restoration of a pseudostratified epithelium by day 7. The repaired epithelium contained an abnormal distribution of epithelial cells containing clusters of club or ciliated cells rather than the uniformly interspersed pattern of these cells in unexposed mice. Although the damaged epithelium in A/J mice was repaired rapidly, and minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis characterized by infiltration of alveoli with neutrophils and prominent, large, foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine, granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid from chlorine-exposed mice showed steadily increasing trends over time. BAL protein levels were increased on day 4 and remained elevated out to day 28. The number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after exposure was not increased compared with sham-exposed mice, indicating that the observed pneumonitis was not driven by bacterial infection of the lung. The results indicate that acute chlorine exposure may cause chronic abnormalities in the lungs despite rapid repair of injured epithelium. PMID:25398987

Abnormal epithelial structure and chronic lung inflammation after repair of chlorine-induced airway injury.

PubMed

Mo, Yiqun; Chen, Jing; Humphrey, David M; Fodah, Ramy A; Warawa, Jonathan M; Hoyle, Gary W

2015-01-15

Chlorine is a toxic gas used in a variety of industrial processes and is considered a chemical threat agent. High-level chlorine exposure causes acute lung injury, but the long-term effects of acute chlorine exposure are unclear. Here we characterized chronic pulmonary changes following acute chlorine exposure in mice. A/J mice were exposed to 240 parts per million-hour chlorine or sham-exposed to air. Chlorine inhalation caused sloughing of bronchial epithelium 1 day after chlorine exposure, which was repaired with restoration of a pseudostratified epithelium by day 7. The repaired epithelium contained an abnormal distribution of epithelial cells containing clusters of club or ciliated cells rather than the uniformly interspersed pattern of these cells in unexposed mice. Although the damaged epithelium in A/J mice was repaired rapidly, and minimal airway fibrosis was observed, chlorine-exposed mice developed pneumonitis characterized by infiltration of alveoli with neutrophils and prominent, large, foamy macrophages. Levels of CXCL1/KC, CXCL5/LPS-induced CXC chemokine, granulocyte colony-stimulating factor, and VEGF in bronchoalveolar (BAL) fluid from chlorine-exposed mice showed steadily increasing trends over time. BAL protein levels were increased on day 4 and remained elevated out to day 28. The number of bacteria cultured from lungs of chlorine-exposed mice 4 wk after exposure was not increased compared with sham-exposed mice, indicating that the observed pneumonitis was not driven by bacterial infection of the lung. The results indicate that acute chlorine exposure may cause chronic abnormalities in the lungs despite rapid repair of injured epithelium. Copyright © 2015 the American Physiological Society.

Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity

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

Rinaldo, J.E.; English, D.; Levine, J.

1988-02-01

Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria.more » However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.« less

Relationship between clinical signs and pulmonary function estimated by the single breath diagram for CO(2) (SBD-CO(2)) in horses with chronic obstructive pulmonary disease.

PubMed

Herholz, C; Straub, R; Gerber, V; Wampfler, B; Lüthi, S; Imhof, A; Moens, Y; Busato, A

2002-03-01

The pulmonary health of 66 horses was assessed by a clinical examination and simple supplementary diagnostic methods. Single breath diagrams for CO(2) (SBD-CO(2)) and derived lung function indices were used to determine pulmonary function. The clinical signs in different groups were related to the results of the lung function indices derived from the SBD-CO(2). In horses with moderate to severe chronic obstructive pulmonary disease (COPD), a significant relationship was found between the respiratory frequency and the ratio of Bohr's dead space to the tidal volume (VD(Bohr)/VT), and between the physiological dead space/tidal volume ratio (VD(phys)/VT) and the ratio of the alveolar dead space to the alveolar tidal volume (VD(alv)/VT(alv)), but no significant associations were found between the arterial oxygen tension (P(a)O(2)) and lung function indices derived from the SBD-CO(2). The occurrence of cough, the viscosity of tracheobronchial mucus and the amount of polynuclear neutrophils in tracheobronchial aspirates were significantly related to the expiratory tidal volume (VT), the total expired volume of CO(2) (VCO(2)), VD(Bohr)/VT, VD(phys)/VT and VD(alv)/VT(alv). We conclude that abnormal findings in these clinical parameters indicate a measurable ventilation and perfusion (V(A)/Q) mismatch which is reflected by increases in dead space, VD(Bohr)/VT and VD(phys)/VT as well as VD(alv)/VT(alv). Copyright 2002 Elsevier Science Ltd. All rights reserved.

Nonuniformity of diffusing capacity from small alveolar gas samples is increased in smokers.

PubMed

Cotton, D J; Mink, J T; Graham, B L

1998-01-01

Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSM manoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer. To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLcoSB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity. Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates. Both smokers and nonsmokers performed SBWSM manoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB-3EQ was calculated from the total alveolar gas sample. DLcoSB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB-3EQ from the entire alveolar gas sample. An index of variation (DI) among the small-sample DLcoSB-3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix). For SBWSM, DI was increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and Sn. The decrease in DI with breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVC manoeuvres, there were no differences due to smoking in Sn or Emix, but DI was increased in smokers and correlated with age and smoking pack-years, but not with Sn. For SBWSM manoeuvres the increase in DI in smokers correlated with breath hold time-dependent increases in Sn, suggesting that the changes in DI reflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVC manoeuvres, the increase in DI in smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DI during this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.

Classification of normal and abnormal images of lung cancer

NASA Astrophysics Data System (ADS)

Bhatnagar, Divyesh; Tiwari, Amit Kumar; Vijayarajan, V.; Krishnamoorthy, A.

2017-11-01

To find the exact symptoms of lung cancer is difficult, because of the formation of the most cancers tissues, wherein large structure of tissues is intersect in a different way. This problem can be evaluated with the help of digital images. In this strategy images will be examined with basic operation of PCA Algorithm. In this paper, GLCM method is used for pre-processing of the snap shots and function extraction system and to test the level of diseases of a patient in its premature stage get to know it is regular or unusual. With the help of result stage of cancer will be evaluated. With the help of dataset and result survival rate of cancer patient can be estimated. Result is based totally on the precise and wrong arrangement of the patterns of tissues.

Frequency and distribution of incidental findings deemed appropriate for S modifier designation on low-dose CT in a lung cancer screening program.

PubMed

Reiter, Michael J; Nemesure, Allison; Madu, Ezemonye; Reagan, Lisa; Plank, April

2018-06-01

To describe the frequency, distribution and reporting patterns of incidental findings receiving the Lung-RADS S modifier on low-dose chest computed tomography (CT) among lung cancer screening participants. This retrospective investigation included 581 individuals who received baseline low-dose chest CT for lung cancer screening between October 2013 and June 2017 at a single center. Incidental findings resulting in assignment of Lung-RADS S modifier were recorded as were incidental abnormalities detailed within the body of the radiology report only. A subset of 60 randomly selected CTs was reviewed by a second (blinded) radiologist to evaluate inter-rater variability of Lung-RADS reporting. A total of 261 (45%) participants received the Lung-RADS S modifier on baseline CT with 369 incidental findings indicated as potentially clinically significant. Coronary artery calcification was most commonly reported, accounting for 182 of the 369 (49%) findings. An additional 141 incidentalomas of the same types as these 369 findings were described in reports but were not labelled with the S modifier. Therefore, as high as 69% (402 of 581) of participants could have received the S modifier if reporting was uniform. Inter-radiologist concordance of S modifier reporting in a subset of 60 participants was poor (42% agreement, kappa = 0.2). Incidental findings are commonly identified on chest CT for lung cancer screening, yet reporting of the S modifier within Lung-RADS is inconsistent. Specific guidelines are necessary to better define potentially clinically significant abnormalities and to improve reporting uniformity. Copyright © 2018 Elsevier B.V. All rights reserved.

Prominent Intrapulmonary Bronchopulmonary Anastomoses and Abnormal Lung Development in Infants and Children with Down Syndrome.

PubMed

Bush, Douglas; Abman, Steven H; Galambos, Csaba

2017-01-01

To determine the frequency of histologic features of impaired lung vascular and alveolar development and to identify the presence of intrapulmonary bronchopulmonary anastomoses (IBA) in infants and children who died with Down syndrome. A retrospective review of autopsy reports and lung histology from 13 children with Down syndrome (ages: 0-8 years) was performed. Histologic features of abnormal lung development were identified and semiquantified, including the presence of IBA. Three-dimensional reconstructions of IBA were also performed. Comparisons were made with 4 age-matched patients without Down syndrome with congenital heart defects who underwent autopsies during this time period. Of the 13 subjects with Down syndrome, 69% died from cardiac events, 77% had a congenital heart defect, and 46% had a clinical diagnosis of pulmonary hypertension. Lung histology from all subjects with Down syndrome demonstrated alveolar simplification, and 92% had signs of persistence of a double capillary network in the distal lung. The lungs from the subjects with Down syndrome frequently had features of pulmonary arterial hypertensive remodeling (85%), and prominent bronchial vessels and IBA were observed in all subjects with Down syndrome. These features were more frequent in subjects with Down syndrome compared with control subjects. Children with Down syndrome who died of cardiopulmonary diseases often have histologic evidence of impaired lung alveolar and vascular development, including the presence of prominent IBA and pulmonary hypertension. We speculate that children with Down syndrome are at risk for reduced lung surface area and recruitment of IBA, which may worsen gas exchange in subjects with Down syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

[Lung perfusion studies after percutaneous closure of patent ductus arteriosus using the Amplatzer Duct Occluder in children].

PubMed

Parra-Bravo, José Rafael; Apolonio-Martínez, Adriana; Estrada-Loza, María de Jesús; Beirana-Palencia, Luisa Gracia; Ramírez-Portillo, César Iván

2015-01-01

The closure of patent ductus arteriosus with multiple devices has been associated with a reduction in lung perfusion. We evaluated the pulmonary perfusion after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder device using perfusion lung scan. Thirty patients underwent successful percutaneous patent ductus arteriosus occlusions using the Amplatzer Duct Occluder device were included in this study. Lung perfusion scans were preformed 6 months after the procedure. Peak flow velocities and protrusion of the device were analyzed by Doppler echocardiography. A left lung perfusion<40% was considered abnormal. The device implantation was successful in all patients. Average perfusion of left lung was 44.7±4.9% (37.8-61.4). Five patients (16.6%) showed decreased perfusion of the left lung. Age, low weight, the length of the ductus arteriosus and the minimum and maximum diameter/length of the ductus arteriosus ratio were statistically significant in patients with abnormalities of lung perfusion. It was observed protrusion the device in 6 patients with a higher maximum flow rate in the left pulmonary artery. The left lung perfusion may be compromised after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder. The increased flow velocity in the origin of the left pulmonary artery can be a poor indicator of reduction in pulmonary perfusion and can occur in the absence of protrusion of the device. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Abnormal gallium scan patterns of the salivary gland in pulmonary sarcoidosis

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

Mishkin, F.S.; Tanaka, T.T.; Niden, A.H.

1978-12-01

The findings of gallium imaging suggest that parotid abnormalities in sarcoidosis are common. Correlation with lung and mediastinal uptake suggests that this represents an early disease state and that it responds to steroid administration. That the findings after therapy do not simply represent suppression of the uptake mechanism for gallium is supported by objective improvement in pulmonary function as well as symptomatic relief. Salivary gland accumulation of gallium citrate occurred in one third of our control group patients--in those who had collagen disease and presumably either were alcoholic or had infectious parotitis. This may also be seen in lymphoma andmore » after radiation therapy. Although the combination of salivary gland, pulmonary, and hilar concentration of gallium is not specific, in the appropriate clinical setting the pattern may be helpful in suggesting the correct diagnosis.« less

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results.

PubMed

Amaral, André F S; Coton, Sonia; Kato, Bernet; Tan, Wan C; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D; Buist, Sonia; Burney, Peter G J

2015-10-01

In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high- and low/middle-income countries, according to gross national income.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. Copyright ©ERS 2015.

Tuberculosis associates with both airflow obstruction and low lung function: BOLD results

PubMed Central

Amaral, André F. S.; Coton, Sonia; Kato, Bernet; Tan, Wan C.; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D.; Buist, Sonia; Burney, Peter G. J.

2015-01-01

Background In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. Objective To assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. Methods The study was performed in adults, aged 40 and above, who took part in the multicentre cross-sectional, general population-based, Burden of Obstructive Lung Disease study, had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high and low/middle income countries, according to gross national income. Results A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio = 2.51, 95% confidence interval 1.83-3.42) and spirometric restriction (adjusted odds ratio = 2.13, 95% confidence interval 1.42-3.19). Conclusion A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. PMID:26113680

Chronic eosinophilic pneumonia.

PubMed Central

Fox, B; Seed, W A

1980-01-01

We described three cases of eosinophilic pneumonia of unknown aetiology investigated clinically and by lung biopsy. The illnesses lasted between six and 20 weeks and consisted of cough, dyspnoea, malaise, and in two cases prolonged pyrexia. All had blood eosinophilia and chest radiographs showing widespread bilateral shadowing; in two cases this had a characteristic peripheral distribution. One patient recovered spontaneously and the other two responded to steroids, with disappearance of pyrexia within 12 hours and radiological clearing within 14 days. Lung function tests during the acute illness showed volume restriction or gas transfer defects or both in two cases. After remission all three showed abnormalities if small airways function. Lung biopsies performed during the acute illness were examined histologically and by transmission electron microscopy, and in two cases by immunofluorescence. There was both intra-alveolar and interstitial eosinophilic pneumonia with bronchiolitis obliterans, microgranulomata, and a vasculitis. Electron microscopy showed numerous eosinophils, many degranulated, and macrophages with phagocytosed eosinophilic granules and intracytoplasmic inclusions. In one case IgM, IgG, and IgA were demonstrated in the bronchial walls and interstitium. No IgE or complement was present. We believe that eosinophil granules are responsible for the tissue damage and fever and suggest mechanisms for this and for the response to steroid therapy. Images PMID:7003796

Congenital Lung Agenesis: Incidence and Outcome in the North of England.

PubMed

Thomas, Matthew; Robertson, Nic; Miller, Nicola; Rankin, Judith; McKean, Michael; Brodlie, Malcom

2017-07-03

Unilateral lung agenesis is an uncommon congenital abnormality, with a lack of reported accurate incidence estimates. Prognosis is also uncertain, with older literature reporting poor outcomes. The North of England register of congenital anomalies (Northern Congenital Abnormality Survey) records cases of congenital anomalies to mothers' resident in the region. We used the register to identify all patients with congenital lung agenesis born between 2004 and 2013 to calculate an accurate incidence estimate and report clinical outcomes with contemporary management. Four patients with congenital lung agenesis were born during the study period, giving an estimated incidence in the North of England of 1.22 per 100,000 live births (95% confidence interval, 0.33-3.11). Two patients had associated congenital heart disease requiring corrective surgery, and one had musculoskeletal anomalies. All four patients are alive and well without a regular oxygen requirement. Contrary to previous reports, the medium term outcomes in our patients have been good, even when lung agenesis is associated with other congenital anomalies. Long-term prognosis with modern management remains unknown, and the potential for the development of pulmonary hypertension remains a concern. Birth Defects Research 109:857-859, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Investigation of Lung Structure-Function Relationships Using Hyperpolarized Noble Gases

NASA Astrophysics Data System (ADS)

Thomen, Robert P.

Magnetic Resonance Imaging (MRI) is an application of the nuclear magnetic resonance (NMR) phenomenon to non-invasively generate 3D tomographic images. MRI is an emerging modality for the lung, but it suffers from low sensitivity due to inherent low tissue density and short T(*/2) . Hyperpolarization is a process by which the nuclear contribution to NMR signal is greatly enhanced to more than 100,000 times that of samples in thermal equilibrium. The noble gases 3He and 129Xe are most often hyperpolarized by transfer of light angular momentum through the electron of a vaporized alkali metal to the noble gas nucleus (called Spin Exchange Optical Pumping). The enhancement in NMR signal is so great that the gas itself can be imaged via MRI, and because noble gases are chemically inert, they can be safely inhaled by a subject, and the gas distribution within the interior of the lung can be imaged. The mechanics of respiration is an elegant physical process by which air is is brought into the distal airspaces of the lungs for oxygen/carbon dioxide gas exchange with blood. Therefore proper description of lung function is intricately related to its physical structure , and the basic mechanical operation of healthy lungs -- from pressure driven airflow, to alveolar airspace gas kinetics, to gas exchange by blood/gas concentration gradients, to elastic contraction of parenchymal tissue -- is a process decidedly governed by the laws of physics. This dissertation will describe experiments investigating the relationship of lung structure and function using hyperpolarized (HP) noble gas MRI. In particular HP gases will be applied to the study of several pulmonary diseases each of which demonstrates unique structure-function abnormalities: asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Successful implementation of an HP gas acquisition protocol for pulmonary studies is an involved and stratified undertaking which requires a solid theoretical foundation in NMR and hyperpolarization theory, construction of dedicated hardware, development of dedicated software, and appropriate image analysis techniques for all acquired data. The author has been actively involved in each of these and has dedicated specific chapters of this dissertation to their description. First, a brief description of lung structure-function investigations and pulmonary imaging will be given (chapter 1). Brief discussions of basic NMR, MRI, and hyperpolarization theory will be given (chapters 2 and 3) followed by their particular methods of implementation in this work (chapters 4 and 5). Analysis of acquired HP gas images will be discussed (chapter 6), and the investigational procedures and results for each lung disease examined will be detailed (chapter 7). Finally, a quick digression on the strengths and limitations of HP gas MRI will be provided (chapter 8).

Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats

PubMed Central

Zeidler-Erdely, Patti C.; Meighan, Terence G.; Erdely, Aaron; Fedan, Jeffrey S.; Thompson, Janet A.; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B.; Afshari, Aliakbar; McKinney, Walter; Frazer, David G.; Antonini, James M.

2015-01-01

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID:25140454

Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary Hypertension.

PubMed

Jernigan, Nikki L; Resta, Thomas C; Gonzalez Bosc, Laura V

2017-01-01

Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III). The rise in pulmonary vascular resistance increases right heart afterload causing right ventricular hypertrophy that can ultimately lead to right heart failure in patients with chronic lung disease. PH is typically characterized by diminished paracrine release of vasodilators, antimitogenic factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive oxygen species and endothelin-1) from the endothelium and lung parenchyma. In addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC), including alterations in Ca 2+ homeostasis, Ca 2+ sensitivity, and activation of transcription factors are thought to play prominent roles in the development of both vasoconstrictor and arterial remodeling components of hypoxia-associated PH. These changes in PASMC function are briefly reviewed in Sect. 1 and the influence of altered reactive oxygen species homeostasis on PASMC function discussed in Sects. 2-4.

Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust.

PubMed Central

Soutar, C A; Copland, L H; Thornley, P E; Hurley, J F; Ottery, J; Adams, W G; Bennett, B

1980-01-01

The respiratory health of workers exposed to polyvinylchloride (PVC) dust has been investigated in 818 men sampled from the work force of a factory manufacturing PVC. In a cross-sectional survey, the lung function and prevalences of respiratory symptoms and chest radiographic abnormalities were compared with estimates of individual PVC dust exposures based on detailed occupational histories and current measurements of respirable PVC dust. Complaints of slight exertional dyspnoea were associated with PVC dust exposure, though age and smoking effects were much stronger. The forced expired volume in one second (FEV1) and forced vital capacity (FVC) were inversely related to dust exposure after age, height, and smoking effects had been taken into account. This effect was seen principally in cigarette smokers, and there was suggestive evidence that PVC dust exposure and cigarette smoking interacted in the reduction of FEV1 and FVC. Gas transfer factor was not related to dust exposure. The chest radiographs were read according to the ILO U/C classification by three experienced readers. One reader recorded a low prevalence of small rounded opacities, and these were not related to age or dust exposure. Another reader recorded a higher prevalence of small rounded opacities category 0/1 or more, and these were related to age but not to dust exposure. The third reader recorded the highest prevalence of small rounded opacities (though none greater than category 1/1), and these were independently related both to age and to PVC dust exposure, indicating an effect of PVC dust on the appearance of the chest radiography. These appearances were so slight that only the higher sensitivity of this reader in the interpretation of profusion of small rounded opacities on the ILO U/C scale enabled detection of this effect of PVC dust. In conclusion, exposure to PVC dust is associated with some deterioration of lung function, slight abnormalities of the chest radiograph, and complaints of slight dyspnoea. The mean decline in FEV1 associated with the average dust exposure experienced in the study was small, though some of the men with higher dust exposures may have suffered clinically important loss of lung function as a result of their occupation. PMID:7444838

Clinical, Bronchographic, Radiological, and Physiological Observations in Ten Cases of Asbestosis

PubMed Central

Leathart, G. L.

1960-01-01

Ten cases of asbestosis (eight male, two female), aged 45-65 years have been kept under observation for periods of up to eight years. Bronchiectasis was demonstrated bronchographically in six cases. Clubbing of the fingers and coarse crepitations appeared to be signs of bronchiectasis rather than of uncomplicated asbestosis. It is suggested that the prevalence of bronchiectasis is higher than has been reported previously because the patients survived longer. The radiological findings are tabulated and compared with previous descriptions. In these subjects there was no relationship between radiological and clinical state. Nine patients eventually showed clinical deterioration and it often proceeded rapidly. The radiograph however, usually remained unaltered. Pulmonary function tests, including diffusing capacity, arterial blood analysis and estimation of mechanical properties of the lung, were carried out in these 10 cases, and in 11 asbestos workers (aged 35-64 years) without radiological abnormality. The steady state diffusing capacity for carbon monoxide (Dco) at rest was lower in asbestosis than in the control subjects. The pulmonary compliance was remarkably low in asbestosis and related fairly closely to the vital capacity. The maximum voluntary ventilation was also low and was related to increased pulmonary resistance but it cannot be said whether this is in the airways or in the lung tissue. Indirect evidence of inequalities of ventilation/perfusion ratio was obtained in most cases. There is no convincing evidence that pulmonary fibrosis occurs without radiological abnormality, but a defect of diffusion may occur. There is no test of pulmonary function which is diagnostic, but a low pulmonary compliance, especially if combined with a low diffusing capacity, is confirmatory. It is suggested that the demonstration of a progressive decline in vital capacity, or in diffusing capacity, may enable a diagnosis of asbestosis to be made before radiological abnormality has appeared, but this point has not been proved.

Amniocentesis for Fetal Lung Maturity: Will It Become Obsolete?

PubMed Central

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

Amniocentesis for fetal lung maturity has historically been performed for many reasons: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate. PMID:24826202

Amniocentesis for fetal lung maturity: will it become obsolete?

PubMed

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

AMNIOCENTESIS FOR FETAL LUNG MATURITY HAS HISTORICALLY BEEN PERFORMED FOR MANY REASONS: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate.

Lung densitometry: why, how and when

PubMed Central

Camiciottoli, Gianna; Diciotti, Stefano

2017-01-01

Lung densitometry assesses with computed tomography (CT) the X-ray attenuation of the pulmonary tissue which reflects both the degree of inflation and the structural lung abnormalities implying decreased attenuation, as in emphysema and cystic diseases, or increased attenuation, as in fibrosis. Five reasons justify replacement with lung densitometry of semi-quantitative visual scales used to measure extent and severity of diffuse lung diseases: (I) improved reproducibility; (II) complete vs. discrete assessment of the lung tissue; (III) shorter computation times; (IV) better correlation with pathology quantification of pulmonary emphysema; (V) better or equal correlation with pulmonary function tests (PFT). Commercially and open platform software are available for lung densitometry. It requires attention to technical and methodological issues including CT scanner calibration, radiation dose, and selection of thickness and filter to be applied to sections reconstructed from whole-lung CT acquisition. Critical is also the lung volume reached by the subject at scanning that can be measured in post-processing and represent valuable information per se. The measurements of lung density include mean and standard deviation, relative area (RA) at −970, −960 or −950 Hounsfield units (HU) and 1st and 15th percentile for emphysema in inspiratory scans, and RA at −856 HU for air trapping in expiratory scans. Kurtosis and skewness are used for evaluating pulmonary fibrosis in inspiratory scans. The main indication for lung densitometry is assessment of emphysema component in the single patient with chronic obstructive pulmonary diseases (COPD). Additional emerging applications include the evaluation of air trapping in COPD patients and in subjects at risk of emphysema and the staging in patients with lymphangioleiomyomatosis (LAM) and with pulmonary fibrosis. It has also been applied to assess prevalence of smoking-related emphysema and to monitor progression of smoking-related emphysema, alpha1 antitrypsin deficiency emphysema, and pulmonary fibrosis. Finally, it is recommended as end-point in pharmacological trials of emphysema and lung fibrosis. PMID:29221318

Low-voltage electricity-induced lung injury.

PubMed

Truong, Thai; Le, Thuong Vu; Smith, David L; Kantrow, Stephen P; Tran, Van Ngoc

2018-02-01

We report a case of bilateral pulmonary infiltrates and haemoptysis following low-voltage electricity exposure in an agricultural worker. A 58-year-old man standing in water reached for an electric watering machine and sustained an exposure to 220 V circuit for an uncertain duration. The electricity was turned off by another worker, and the patient was asymptomatic for the next 10 h until he developed haemoptysis. A chest radiograph demonstrated bilateral infiltrates, and chest computed tomography (CT) revealed ground-glass opacities with interstitial thickening. Evaluations, including electrocardiogram, serum troponin, N-terminal pro-B-type natriuretic peptide (NT-pro BNP), coagulation studies, and echocardiogram, found no abnormality. The patient was treated for suspected electricity-induced lung injury and bleeding with tranexamic acid and for rhabdomyolysis with volume resuscitation. He recovered with complete resolution of chest radiograph abnormalities by Day 7. This is the first reported case of bilateral lung oedema and/or injury after electricity exposure without cardiac arrest.

Fuzzy-C-Means Clustering Based Segmentation and CNN-Classification for Accurate Segmentation of Lung Nodules

PubMed

K, Jalal Deen; R, Ganesan; A, Merline

2017-07-27

Objective: Accurate segmentation of abnormal and healthy lungs is very crucial for a steadfast computer-aided disease diagnostics. Methods: For this purpose a stack of chest CT scans are processed. In this paper, novel methods are proposed for segmentation of the multimodal grayscale lung CT scan. In the conventional methods using Markov–Gibbs Random Field (MGRF) model the required regions of interest (ROI) are identified. Result: The results of proposed FCM and CNN based process are compared with the results obtained from the conventional method using MGRF model. The results illustrate that the proposed method can able to segment the various kinds of complex multimodal medical images precisely. Conclusion: However, in this paper, to obtain an exact boundary of the regions, every empirical dispersion of the image is computed by Fuzzy C-Means Clustering segmentation. A classification process based on the Convolutional Neural Network (CNN) classifier is accomplished to distinguish the normal tissue and the abnormal tissue. The experimental evaluation is done using the Interstitial Lung Disease (ILD) database. Creative Commons Attribution License

Fuzzy-C-Means Clustering Based Segmentation and CNN-Classification for Accurate Segmentation of Lung Nodules

PubMed Central

K, Jalal Deen; R, Ganesan; A, Merline

2017-01-01

Objective: Accurate segmentation of abnormal and healthy lungs is very crucial for a steadfast computer-aided disease diagnostics. Methods: For this purpose a stack of chest CT scans are processed. In this paper, novel methods are proposed for segmentation of the multimodal grayscale lung CT scan. In the conventional methods using Markov–Gibbs Random Field (MGRF) model the required regions of interest (ROI) are identified. Result: The results of proposed FCM and CNN based process are compared with the results obtained from the conventional method using MGRF model. The results illustrate that the proposed method can able to segment the various kinds of complex multimodal medical images precisely. Conclusion: However, in this paper, to obtain an exact boundary of the regions, every empirical dispersion of the image is computed by Fuzzy C-Means Clustering segmentation. A classification process based on the Convolutional Neural Network (CNN) classifier is accomplished to distinguish the normal tissue and the abnormal tissue. The experimental evaluation is done using the Interstitial Lung Disease (ILD) database. PMID:28749127

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

[Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer].

PubMed

Kuznetsova, E S; Zinovieva, O L; Oparina, N Yu; Prokofjeva, M M; Spirin, P V; Favorskaya, I A; Zborovskaya, I B; Lisitsyn, N A; Prassolov, V S; Mashkova, T D

2016-01-01

Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.

Pulmonary physiology during pulmonary embolism.

PubMed

Elliott, C G

1992-04-01

Acute pulmonary thromboembolism produces a number of pathophysiologic derangements of pulmonary function. Foremost among these alterations is increased pulmonary vascular resistance. For patients without preexistent cardiopulmonary disease, increased pulmonary vascular resistance is directly related to the degree of vascular obstruction demonstrated on the pulmonary arteriogram. Vasoconstriction, either reflexly or biochemically mediated, may contribute to increased pulmonary vascular resistance. Acute pulmonary thromboembolism also disturbs matching of ventilation and blood flow. Consequently, some lung units are overventilated relative to perfusion (increased dead space), while other lung units are underventilated relative to perfusion (venous admixture). True right-to-left shunting of mixed venous blood can occur through the lungs (intrapulmonary shunt) or across the atrial septum (intracardiac shunt). In addition, abnormalities of pulmonary gas exchange (carbon monoxide transfer), pulmonary compliance and airway resistance, and ventilatory control may accompany pulmonary embolism. Thrombolytic therapy can reverse the hemodynamic derangements of acute pulmonary thromboembolism more rapidly than anticoagulant therapy. Limited data suggest a sustained benefit of thrombolytic treatment on the pathophysiologic alterations of pulmonary vascular resistance and pulmonary gas exchange produced by acute pulmonary emboli.

A role for a lithium-inhibited Golgi nucleotidase in skeletal development and sulfation

PubMed Central

Frederick, Joshua P.; Tafari, A. Tsahai; Wu, Sheue-Mei; Megosh, Louis C.; Chiou, Shean-Tai; Irving, Ryan P.; York, John D.

2008-01-01

Sulfation is an important biological process that modulates the function of numerous molecules. It is directly mediated by cytosolic and Golgi sulfotransferases, which use 3′-phosphoadenosine 5′-phosphosulfate to produce sulfated acceptors and 3′-phosphoadenosine 5′-phosphate (PAP). Here, we identify a Golgi-resident PAP 3′-phosphatase (gPAPP) and demonstrate that its activity is potently inhibited by lithium in vitro. The inactivation of gPAPP in mice led to neonatal lethality, lung abnormalities resembling atelectasis, and dwarfism characterized by aberrant cartilage morphology. The phenotypic similarities of gPAPP mutant mice to chondrodysplastic models harboring mutations within components of the sulfation pathway lead to the discovery of undersulfated chondroitin in the absence of functional enzyme. Additionally, we observed loss of gPAPP leads to perturbations in the levels of heparan sulfate species in lung tissue and whole embryos. Our data are consistent with a model that clearance of the nucleotide product of sulfotransferases within the Golgi plays an important role in glycosaminoglycan sulfation, provide a unique genetic basis for chondrodysplasia, and define a function for gPAPP in the formation of skeletal elements derived through endochondral ossification. PMID:18695242

Histochemical and cellular changes accompanying the appearance of lung fibrosis in an experimental mouse model for Hermansky Pudlak syndrome

PubMed Central

Lyerla, Timothy

2010-01-01

Hermansky Pudlak syndrome (HPS) is a heterogeneous recessive genetic disease with a tendency to develop lung fibrosis with aging. A mouse strain with two mutant HPS genes affecting separate vesicle trafficking pathways, C57BL/6-Hps1ep-Ap3b1pe, exhibits severe lung abnormalities at young ages, including enlarged alveolar type II (ATII) cells with giant lamellar bodies and foamy alveolar macrophages (AMs), which are readily identified histologically. In this study, the appearance of lung fibrosis in older animals was studied using classical histological and biochemical methods. The HPS double mutant mice, but not Chediak Higashi syndrome (C57BL/6-Lystbg-J-J, CHS) or C57BL/6J black control (WT) mice, were found to develop lung fibrosis at about 17 months of age using Masson trichrome staining, which was confirmed by hydroxyproline analysis. TGF β1 levels were elevated in bronchial alveolar lavage samples at all ages tested in the double mutant, but not WT or CHS mice, indicative of a prefibrotic condition in this experimental strain; and AMs were highly positive for this cytokine using immunohistochemistry staining. Prosurfactant protein C staining for ATII cells showed redistribution and dysmorphism of these cells with aging, but there was no evidence for epithelial-mesenchymal transition of ATII cells by dual staining for prosurfactant C protein and α-smooth muscle actin. This investigation showed that the HPS double mutant mouse strain develops interstitial pneumonia (HPSIP) past 1 year of age, which may be initiated by abnormal ATII cells and exacerbated by AM activation. With prominent prefibrotic abnormalities, this double mutant may serve as a model for interventive therapy in HPS. PMID:20603711

Reducing Wait Time for Lung Cancer Diagnosis and Treatment: Impact of a Multidisciplinary, Centralized Referral Program.

PubMed

Common, Jessica L; Mariathas, Hensley H; Parsons, Kaylah; Greenland, Jonathan D; Harris, Scott; Bhatia, Rick; Byrne, SuzanneC

2018-06-04

A multidisciplinary, centralized referral program was established at our institution in 2014 to reduce delays in lung cancer diagnosis and treatment following diagnostic imaging observed with the traditional, primary care provider-led referral process. The main objectives of this retrospective cohort study were to determine if referral to a Thoracic Triage Panel (TTP): 1) expedites lung cancer diagnosis and treatment initiation; and 2) leads to more appropriate specialist consultation. Patients with a diagnosis of lung cancer and initial diagnostic imaging between March 1, 2015, and February 29, 2016, at a Memorial University-affiliated tertiary care centre in St John's, Newfoundland, were identified and grouped according to whether they were referred to the TTP or managed through a traditional referral process. Wait times (in days) from first abnormal imaging to biopsy and treatment initiation were recorded. Statistical analysis was performed using the Wilcoxon rank-sum test. A total of 133 patients who met inclusion criteria were identified. Seventy-nine patients were referred to the TTP and 54 were managed by traditional means. There was a statistically significant reduction in median wait times for patients referred to the TTP. Wait time from first abnormal imaging to biopsy decreased from 61.5 to 36.0 days (P < .0001). Wait time from first abnormal imaging to treatment initiation decreased from 118.0 to 80.0 days (P < .001). The percentage of specialist consultations that led to treatment was also greater for patients referred to the TTP. A collaborative, centralized intake and referral program helps to reduce wait time for diagnosis and treatment of lung cancer. Copyright © 2018 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Consequences of screening in lung cancer: development and dimensionality of a questionnaire.

PubMed

Brodersen, John; Thorsen, Hanne; Kreiner, Svend

2010-08-01

The objective of this study was to extend the Consequences of Screening (COS) Questionnaire for use in a lung cancer screening by testing for comprehension, content coverage, dimensionality, and reliability. In interviews, the suitability, content coverage, and relevance of the COS were tested on participants in a lung cancer screening program. The results were thematically analyzed to identify the key consequences of abnormal and false-positive screening results. Item Response Theory and Classical Test Theory were used to analyze data. Dimensionality, objectivity, and reliability were established by item analysis, examining the fit between item responses and Rasch models. Eight themes specifically relevant for participants in lung cancer screening results were identified: "self-blame,"focus on symptoms,"stigmatization,"introvert,"harm of smoking,"impulsivity,"empathy," and "regretful of still smoking." Altogether, 26 new items for part I and 16 new items for part II were generated. These themes were confirmed to fit a partial-credit Rasch model measuring different constructs including several of the new items. In conclusion, the reliability and the dimensionality of a condition-specific measure with high content validity for persons having abnormal or false-positive lung cancer screening results have been demonstrated. This new questionnaire called Consequences of Screening in Lung Cancer (COS-LC) covers in two parts the psychosocial experience in lung cancer screening. Part I: "anxiety,"behavior,"dejection,"sleep,"self-blame,"focus on airway symptoms,"stigmatization,"introvert," and "harm of smoking." Part II: "calm/relax,"social network,"existential values,"impulsivity,"empathy," and "regretful of still smoking."

Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

PubMed

Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

2011-10-01

Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP).

PubMed

Nascimento, Fábio A; Tseng, Zian H; Palmiere, Cristian; Maleszewski, Joseph J; Shiomi, Takayuki; McCrillis, Aileen; Devinsky, Orrin

2017-08-01

To review studies on structural pulmonary and cardiac changes in SUDEP cases as well as studies showing pulmonary or cardiac structural changes in living epilepsy patients. We conducted electronic literature searches using the PubMed database for articles published in English, regardless of publication year, that included data on cardiac and/or pulmonary structural abnormalities in SUDEP cases or in living epilepsy patients during the postictal period. Fourteen postmortem studies reported pulmonary findings in SUDEP cases. Two focused mainly on assessing lung weights in SUDEP cases versus controls; no group difference was found. The other 12 reported descriptive autopsy findings. Among all SUDEP cases with available descriptive postmortem pulmonary examination, 72% had pulmonary changes, most often pulmonary edema/congestion, and, less frequently, intraalveolar hemorrhage. Eleven studies reported on cardiac pathology in SUDEP. Cardiac abnormalities were found in approximately one-fourth of cases. The most common findings were myocyte hypertrophy and myocardial fibrosis of various degrees. Among living epilepsy patients, postictal pulmonary pathology was the most commonly reported pulmonary abnormality and the most common postictal cardiac abnormality was transient left ventricular dysfunction - Takotsubo or neurogenic stunned myocardium. Cardiac and pulmonary pathological abnormalities are frequent among SUDEP cases, most commonly pulmonary edema/congestion and focal interstitial myocardial fibrosis. Most findings are not quantified, with subjective elements and undefined interobserver reliability, and lack of controls such as matched epilepsy patients who died from other causes. Further, studies have not systematically evaluated potential confounding factors, including postmortem interval to autopsy, paramedic resuscitation and IV fluids administration, underlying heart/lung disease, and risk factors for cardiac or pulmonary disease. Prospective studies with controls are needed to define the heart and lung changes in SUDEP and understand their potential relationship to mechanisms of death in SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.

Impaired Cell Volume Regulation in Intestinal Crypt Epithelia of Cystic Fibrosis Mice

NASA Astrophysics Data System (ADS)

Valverde, M. A.; O'Brien, J. A.; Sepulveda, F. V.; Ratcliff, R. A.; Evans, M. J.; Colledge, W. H.

1995-09-01

Cystic fibrosis is a disease characterized by abnormalities in the epithelia of the lungs, intestine, salivary and sweat glands, liver, and reproductive systems, often as a result of inadequate hydration of their secretions. The primary defect in cystic fibrosis is the altered activity of a cAMP-activated Cl^- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it is not clear how a defect in the CFTR Cl^- channel function leads to the observed pathological changes. Although much is known about the structural properties and regulation of the CFTR, little is known of its relationship to cellular functions other than the cAMP-dependent Cl^- secretion. Here we report that cell volume regulation after hypotonic challenge is also defective in intestinal crypt epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of the regulatory volume decrease in CFTR -/- crypts appears to be related to the inability of a K^+ conductance to provide a pathway for the exit of this cation during the volume adjustments. This provides evidence that the lack of CFTR protein may have additional consequences for the cellular function other than the abnormal cAMP-mediated Cl^- secretion.

Combination therapy for advanced or metastatic non-small cell lung cancer will be tested in new clinical trial | Center for Cancer Research

Cancer.gov

Non-small cell lung cancer (NSCLC) develops when abnormal lung cells begin to grow out of control. These cells can form into a tumor and spread to other areas of the body. David Schrump, M.D., of the Thoracic and Gastrointestinal Oncology Branch is leading a clinical trial of a new combination treatment for patients with advanced or metastatic NSCLC that cannot be treated

The Cell-CT 3D Cell Imaging Technology Platform Enables the Detection of Lung Cancer Using the Non-Invasive LuCED Sputum Test

PubMed Central

Meyer, Michael G.; Hayenga, Jon; Neumann, Thomas; Katdare, Rahul; Presley, Chris; Steinhauer, David; Bell, Timothy; Lancaster, Christy; Nelson, Alan C.

2015-01-01

The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5-year survival rate for lung cancer remains little changed over the past 40 years. Early detection through emerging lung cancer screening programs promises the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Cancer Screening Trial reported that screening by three consecutive low-dose X-ray CT scans provides a 20% reduction in lung cancer mortality compared to chest X-ray. This reduction in mortality, however, comes with an unacceptable false positive rate that increases patient risks and the overall cost of lung cancer screening. This article reviews the LuCED® test for detecting early lung cancer. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell-CT®, which images cells in three dimensions with sub-micron resolution. Algorithms are applied to the 3D cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification which could enable cost effective detection of lung cancer. PMID:26148817

An automatically generated texture-based atlas of the lungs

NASA Astrophysics Data System (ADS)

Dicente Cid, Yashin; Puonti, Oula; Platon, Alexandra; Van Leemput, Koen; Müller, Henning; Poletti, Pierre-Alexandre

2018-02-01

Many pulmonary diseases can be characterized by visual abnormalities on lung CT scans. Some diseases manifest similar defects but require completely different treatments, as is the case for Pulmonary Hypertension (PH) and Pulmonary Embolism (PE): both present hypo- and hyper-perfused regions but with different distribution across the lung and require different treatment protocols. Finding these distributions by visual inspection is not trivial even for trained radiologists who currently use invasive catheterism to diagnose PH. A Computer-Aided Diagnosis (CAD) tool that could facilitate the non-invasive diagnosis of these diseases can benefit both the radiologists and the patients. Most of the visual differences in the parenchyma can be characterized using texture descriptors. Current CAD systems often use texture information but the texture is either computed in a patch-based fashion, or based on an anatomical division of the lung. The difficulty of precisely finding these divisions in abnormal lungs calls for new tools for obtaining new meaningful divisions of the lungs. In this paper we present a method for unsupervised segmentation of lung CT scans into subregions that are similar in terms of texture and spatial proximity. To this extent, we combine a previously validated Riesz-wavelet texture descriptor with a well-known superpixel segmentation approach that we extend to 3D. We demonstrate the feasibility and accuracy of our approach on a simulated texture dataset, and show preliminary results for CT scans of the lung comparing subjects suffering either from PH or PE. The resulting texture-based atlas of individual lungs can potentially help physicians in diagnosis or be used for studying common texture distributions related to other diseases.

Wait Times Experienced by Lung Cancer Patients in the BC Southern Interior to Obtain Oncologic Care: Exploration of the Intervals from First Abnormal Imaging to Oncologic Treatment

PubMed Central

Chowdhury, Rezwan; Boyce, Andrew; Halperin, Ross

2015-01-01

Background: Lung cancer is associated with rapid disease progression, which can significantly progress over a duration of four to eight weeks. This study examines the time interval lung cancer patients from the interior of British Columbia (BC) experience while undergoing diagnostic evaluation, biopsy, staging, and preparation for treatment. Methods: A chart review of lung cancer patients (n=231) referred to the BC Cancer Agency Centre for the Southern Interior between January 1, 2010 and December 31, 2011 was performed. Time zero was defined as the date of the first abnormal chest imaging. Time intervals, expressed as median averages, to specialist consult, biopsy, oncologic referral, initial oncology consultation, and commencement of oncologic treatment were obtained. Results: The median time interval from first abnormal chest imaging to a specialist consultation was 18 days (interquartile range, IQR, 7-36). An additional nine days elapsed prior to biopsy in the form of bronchoscopy, CT-guided biopsy, or sputum cytology (median; IQR, 3-21); if lobectomy was required, 18 days elapsed (median; IQR, 9-28). Eight days were required for pathologic diagnosis and subsequent referral to the cancer centre (median; IQR, 3-16.5). Once referral was received, 10 days elapsed prior to consultation with either a medical or radiation oncologist (median, IQR 5-18). Finally, eight days was required for initiation of radiation and/or chemotherapy (median; IQR, 1-15). The median wait time from detection of lung cancer on imaging to oncologic treatment in the form of radiation and/or chemotherapy was 65.5 days (IQR, 41.5-104.3).  Interpretation: Patients in the BC Southern Interior experience considerable delays in accessing lung cancer care. During this time, the disease has the potential to significantly progress and it is possible that a subset of patients may lose their opportunity for curative intent treatment. PMID:26543688

Optimal graph based segmentation using flow lines with application to airway wall segmentation.

PubMed

Petersen, Jens; Nielsen, Mads; Lo, Pechin; Saghir, Zaigham; Dirksen, Asger; de Bruijne, Marleen

2011-01-01

This paper introduces a novel optimal graph construction method that is applicable to multi-dimensional, multi-surface segmentation problems. Such problems are often solved by refining an initial coarse surface within the space given by graph columns. Conventional columns are not well suited for surfaces with high curvature or complex shapes but the proposed columns, based on properly generated flow lines, which are non-intersecting, guarantee solutions that do not self-intersect and are better able to handle such surfaces. The method is applied to segment human airway walls in computed tomography images. Comparison with manual annotations on 649 cross-sectional images from 15 different subjects shows significantly smaller contour distances and larger area of overlap than are obtained with recently published graph based methods. Airway abnormality measurements obtained with the method on 480 scan pairs from a lung cancer screening trial are reproducible and correlate significantly with lung function.

Respiratory outcomes study (RESPOS) for preterm infants at primary school age.

PubMed

Astle, Valerie; Broom, Margaret; Todd, David A; Charles, Blessy; Ringland, Cathy; Ciszek, Karen; Shadbolt, Bruce

2015-02-01

Pulmonary function abnormalities and hospital re-admissions in survivors of neonatal lung disease remain highly prevalent. The respiratory outcomes study (RESPOS) aimed to investigate the respiratory and associated atopy outcomes in preterm infants <30 weeks gestational age (GA) and/or birth-weight (BWt) <1000 g at primary school age, and to compare these outcomes between infants with and without chronic lung disease (CLD). In the RESPOS 92 parents of preterm infants admitted to the Neonatal unit in Canberra Hospital between 1/1/2001 and 31/12/2003 were sent a questionnaire regarding their respiratory, atopy management and follow-up. Fifty-three parents responded, including 28 preterm infants who had CLD and 25 who had no CLD. The gestational age was significantly lower in the CLD group compared to the non-CLD group [26.9 (26.3-27.5) CLD and 28.6 (28.3-29.0) non-CLD] [weeks [95% confidence interval (CI)

Acute and Perioperative Care of the Burn-Injured Patient

PubMed Central

Bittner, Edward A.; Shank, Erik; Woodson, Lee; Martyn, J.A. Jeevendra

2016-01-01

Care of burn-injured patients requires knowledge of the pathophysiologic changes affecting virtually all organs from the onset of injury until wounds are healed. Massive airway and/or lung edema can occur rapidly and unpredictably after burn and/or inhalation injury. Hemodynamics in the early phase of severe burn injury are characterized by a reduction in cardiac output, increased systemic and pulmonary vascular resistance. Approximately 2–5 days after major burn injury, a hyperdynamic and hypermetabolic state develops. Electrical burns result in morbidity much higher than expected based on burn size alone. Formulae for fluid resuscitation should serve only as guideline; fluids should be titrated to physiologic end points. Burn injury is associated basal and procedural pain requiring higher than normal opioid and sedative doses. Operating room concerns for the burn-injured patient include airway abnormalities, impaired lung function, vascular access, deceptively large and rapid blood loss, hypothermia and altered pharmacology. PMID:25485468

United in Prevention–Electrocardiographic Screening for Chronic Obstructive Pulmonary Disease

PubMed Central

Mazic, Sanja; Stajic, Zoran; Djelic, Marina; Zlatkovic-Svenda, Mirjana; Putnikovic, Biljana

2013-01-01

CONFLICT OF INTEREST: NONE DECLARED Introduction P-wave abnormalities on the resting electrocardiogram have been associated with cardiovascular or pulmonary disease. So far, “Gothic” P wave and verticalization of the frontal plane axis is related to lung disease, particularly obstructive lung disease. Aim We tested if inverted P wave in AVl as a lone criteria of P wave axis >70° could be screening tool for emphysema. Material and method 1095 routine electrocardiograms (ECGs) were reviewed which yielded 478 (82,1%) ECGs with vertical P-axis in sinus rhythm. Charts were reviewed for the diagnosis of COPD and emphysema based on medical history and pulmonary function tests. Conclusion Electrocardiogram is very effective screening tool not only in cardiovascular field but in chronic obstructive pulmonary disease. The verticality of the P axis is usually immediately apparent, making electrocardiogram rapid screening test for emphysema. PMID:24058253

Respiratory Morbidity in a Coffee Processing Workplace With Sentinel Obliterative Bronchiolitis Cases

PubMed Central

Bailey, Rachel L.; Cox-Ganser, Jean M.; Duling, Matthew G.; LeBouf, Ryan F.; Martin, Stephen B.; Bledsoe, Toni A.; Green, Brett J.; Kreiss, Kathleen

2016-01-01

Rationale Obliterative bronchiolitis in former coffee workers prompted a cross-sectional study of current workers. Diacetyl and 2,3-pentanedione levels were highest in areas for flavoring and grinding/packaging unflavored coffee. Methods We interviewed 75 (88%) workers, measured lung function, and created exposure groups based on work history. We calculated standardized morbidity ratios (SMRs) for symptoms and spirometric abnormalities. We examined health outcomes by exposure groups. Results SMRs were elevated 1.6-fold for dyspnea and 2.7-fold for obstruction. The exposure group working in both coffee flavoring and grinding/packaging of unflavored coffee areas had significantly lower mean ratio of forced expiratory volume in 1 s to forced vital capacity and percent predicted mid-expiratory flow than workers without such exposure. Conclusion Current workers have occupational lung morbidity associated with high diacetyl and 2,3-pentanedione exposures, which were not limited to flavoring areas. PMID:26523478

Respiratory morbidity in workers exposed to asbestos in the primary manufacture of building materials.

PubMed

Robins, T G; Green, M A

1988-01-01

Former employees (214) of a plant that manufactured asbestos-containing building materials (wallboard and acoustic tile) from 1958 through 1974 were screened for asbestos-related pulmonary disease. Results are presented on 182 union members whose names appeared on a 1966 seniority list in one of six departments believed to have had substantial asbestos exposure. The study population demonstrated a high frequency of pulmonary abnormalities often associated with asbestos exposure: low mean forced vital capacity percent of predicted (FVC % predicted), low mean forced expiratory volume at one second percent of predicted (FEV1 % predicted), presence of parenchymal abnormalities (40.1% with profusion scores of 1/0 or higher), and 30.5% with bilateral pleural abnormalities on chest roentgenograms. In addition, râles in two or more locations were found in 22.8% on examination of the chest, 30.6% gave a history of chronic bronchitis, and 34.8% of dyspnea grade two or higher. Calculated asbestos exposure scores, based upon participant recall, were not found to be associated with these abnormalities. The abnormal findings were not adequately explained by potential confounders such as cigarette smoking. Other notable findings in this study include the presence of smoking-adjusted decrements in pulmonary function associated with moderate profusion scores (i.e., 1/0 and 1/1) and the presence of a substantial degree of obstructive lung disease (19.2%) in this population.

[Horseshoe lung with normal pulmonary venous return].

PubMed

Gondra Sangroniz, A; Elorz Lambarri, J; Villar Alvarez, M A; Lecumberri Cortes, I; Ayala Curiel, J

2010-09-01

Horseshoe lung is a rare congenital anomaly characterised by a midline isthmus of pulmonary parenchyma connecting the posterior basal segments of the lungs behind the heart in conjunction with unilateral pulmonary hypoplasia. Of all cases, 80% are associated with scimitar syndrome, consisting of right anomalous pulmonary venous drainage, pulmonary hypoplasia of the right lung and systemic arterial perfusion to some lung areas. A six year old girl who had recurrent lower respiratory infections since birth. Chest Rx, angioCT and MR showed: hypoplasia of the right lung, dextrocardia and pulmonary isthmus bridging both lungs behind the pericardium. The right hypoplastic lung had little systemic supply coming from the abdominal aorta. The right pulmonary artery was hypoplastic. The right pulmonary venous drainage was normal. We present a case of horseshoe lung without abnormal venous drainage. 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Respiratory tract disease from thermosetting resins. Study of an outbreak in rubber tire workers.

PubMed

doPico, G A; Rankin, J; Chosy, L W; Reddan, W G; Barbee, R A; Gee, B; Dickie, H A

1975-08-01

An outbreak of upper and lower respiratory tract inflammatory disease and conjunctivitis among synthetic rubber tire workers occurred. The outbreak began after the introduction of a new thermosetting resin, containing resorcinol and a trimere of methylene aminoacetronitrile, into the rubber tire carcass stock formulation. Two hundred ten workers were affected. Characteristically, symptoms improved during periods of sick leave or vacation, recurring upon the workers' return to the plant. Chest radiograms disclosed pneumonic infiltrates in about one fourth of the cases. Pulmonary function studies detected abnormal airways dynamics as well as abnormal diffusing capacity in more than one third of the workers tested. Lung biopsy showed evidence of focal interstitial fibrosis and peribronchiolar and perivascular chronic inflammatory reaction. The illness was ascribed to volatile products released during the manufacture of synthetic rubber tires. The exact chemical nature of these products is unknown.

Major health problems of expressway workers in Thailand: an 8-year cohort study.

PubMed

Charusabha, Chotima; Thongpakdee, Ketsaraporn; Rakmanee, Natefa; Singhasivanon, Pratap; Lawpoolsri, Saranath

2014-02-01

Workers in the transportation sector may be expose to environmental hazards resulting in adverse health outcomes. The present study aimed to assess environmental-hazard-related morbidity among transportation workers over an eight-year period Data were extracted from the registry database of a cohort of workers in the Expressway Authority of Thailand between 2004 and 2011. Annual trends and changes in health status were described. Factors associated with major health problems were also evaluated The cohort consisted of 2,000 to 2,700 workers. The trend of abnormal lung function, abnormal hearing, high blood pressure, high cholesterol, and asthma significantly increased over the period. Very few workers had high serum lead levels. The present study revealed several major occupation-related health problems among transportation workers. In addition to an annual health assessment, other control measures should be instituted to protect workers from occupation-related exposures.

Hand ultrasound: a high-fidelity simulation of lung sliding.

PubMed

Shokoohi, Hamid; Boniface, Keith

2012-09-01

Simulation training has been effectively used to integrate didactic knowledge and technical skills in emergency and critical care medicine. In this article, we introduce a novel model of simulating lung ultrasound and the features of lung sliding and pneumothorax by performing a hand ultrasound. The simulation model involves scanning the palmar aspect of the hand to create normal lung sliding in varying modes of scanning and to mimic ultrasound features of pneumothorax, including "stratosphere/barcode sign" and "lung point." The simple, reproducible, and readily available simulation model we describe demonstrates a high-fidelity simulation surrogate that can be used to rapidly illustrate the signs of normal and abnormal lung sliding at the bedside. © 2012 by the Society for Academic Emergency Medicine.

'TOTAL' (Tracheal Occlusion To Accelerate Lung Growth) Trial

ClinicalTrials.gov

2018-01-25

Hernia; Hernia, Diaphragmatic; Hernia, DIaphragmatic, Congenital; Pathological Conditions, Anatomical; Congenital Abnormalities; Congenital Diaphragmatic Hernia; Fetal Anomaly; Fetal Surgery; Pulmonary Hypoplasia

PD-1/PD-L1 Pathway Mediates the Alleviation of Pulmonary Fibrosis by Human Mesenchymal Stem Cells in Humanized Mice.

PubMed

Ni, Ke; Liu, Ming; Zheng, Jian; Wen, Liyan; Chen, Qingyun; Xiang, Zheng; Lam, Kowk-Tai; Liu, Yinping; Chan, Godfrey Chi-Fung; Lau, Yu-Lung; Tu, Wenwei

2018-06-01

Pulmonary fibrosis is a chronic progressive lung disease with few treatments. Human mesenchymal stem cells (MSCs) have been shown to be beneficial in pulmonary fibrosis because they have immunomodulatory capacity. However, there is no reliable model to test the therapeutic effect of human MSCs in vivo. To mimic pulmonary fibrosis in humans, we established a novel bleomycin-induced pulmonary fibrosis model in humanized mice. With this model, the benefit of human MSCs in pulmonary fibrosis and the underlying mechanisms were investigated. In addition, the relevant parameters in patients with pulmonary fibrosis were examined. We demonstrate that human CD8 + T cells were critical for the induction of pulmonary fibrosis in humanized mice. Human MSCs could alleviate pulmonary fibrosis and improve lung function by suppressing bleomycin-induced human T-cell infiltration and proinflammatory cytokine production in the lungs of humanized mice. Importantly, alleviation of pulmonary fibrosis by human MSCs was mediated by the PD-1/programmed death-ligand 1 pathway. Moreover, abnormal PD-1 expression was found in circulating T cells and lung tissues of patients with pulmonary fibrosis. Our study supports the potential benefit of targeting the PD-1/programmed death-ligand 1 pathway in the treatment of pulmonary fibrosis.

Lung-Kidney Cross-Talk in the Critically Ill Patient.

PubMed

Husain-Syed, Faeq; Slutsky, Arthur S; Ronco, Claudio

2016-08-15

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

Combination therapy for advanced or metastatic non-small cell lung cancer will be tested in new clinical trial | Center for Cancer Research

Cancer.gov

Non-small cell lung cancer (NSCLC) develops when abnormal lung cells begin to grow out of control. These cells can form into a tumor and spread to other areas of the body. David Schrump, M.D., of the Thoracic and Gastrointestinal Oncology Branch is leading a clinical trial of a new combination treatment for patients with advanced or metastatic NSCLC that cannot be treated surgically. Read more... 

A small cell bronchogenic carcinoma associated with tumoral hypophosphataemia and inappropriate antidiuresis.

PubMed Central

Robin, N.; Gill, G.; van Heyningen, C.; Fraser, W.

1994-01-01

A patient is described with small cell carcinoma of the lung, associated with profound hypophosphataemia and hyponatraemia. Increased phosphate excretion and inappropriately high urine osmolality were observed. The abnormalities are consistent with tumoral hypophosphataemia and inappropriate antidiuresis. These tumour-related metabolic abnormalities have only been described once before with this malignancy. PMID:7831175

Respiratory and psychiatric abnormalities in chronic symptomatic hyperventilation.

PubMed Central

Bass, C; Gardner, W N

1985-01-01

Many physicians believe that the hyperventilation syndrome is invariably associated with anxiety or undiagnosed organic disease such as asthma and pulmonary embolus, or both. Twenty one patients referred by specialist physicians with unexplained somatic symptoms and unequivocal chronic hypocapnia (resting end tidal Pco2 less than or equal to 4 kPa (30 mm Hg) on repeated occasions during prolonged measurement) were investigated. All but one complained of inability to take a satisfying breath. Standard lung function test results and chest radiographs were normal in all patients, but histamine challenge showed bronchial hyper-reactivity in two of 20 patients tested, and skin tests to common allergens were positive in three of 18. Ventilation-perfusion scanning was abnormal in a further three of 15 patients studied, with unmatched perfusion defects in two and isolated ventilation defects in one. None of the 21 had thyrotoxicosis, severe coronary heart disease, or other relevant cardiovascular abnormalities. Ten of the 21 patients were neurotic and suffered from chronic psychiatric disturbance characterised by anxiety, panic, and phobic symptoms. The remainder had no detectable psychiatric disorders but reported proportionately more somatic than anxiety symptoms. Severe hyperventilation can occur in the absence of formal psychiatric or detectable respiratory or other organic abnormalities. Asthma and pulmonary embolus must be specifically excluded. PMID:3922504

Technical description of endoscopic ultrasonography with fine-needle aspiration for the staging of lung cancer.

PubMed

Kramer, Henk; van Putten, John W G; Douma, W Rob; Smidt, Alie A; van Dullemen, Hendrik M; Groen, Harry J M

2005-02-01

Endoscopic ultrasonography (EUS) is a novel method for staging of the mediastinum in lung cancer patients. The recent development of linear scanners enables safe and accurate fine-needle aspiration (FNA) of mediastinal and upper abdominal structures under real-time ultrasound guidance. However, various methods and equipment for mediastinal EUS-FNA are being used throughout the world, and a detailed description of the procedures is lacking. A thorough description of linear EUS-FNA is needed. A step-by-step description of the linear EUS-FNA procedure as performed in our hospital will be provided. Ultrasonographic landmarks will be shown on images. The procedure will be related to published literature, with a systematic literature search. EUS-FNA is an outpatient procedure under conscious sedation. The typical linear EUS-FNA procedure starts with examination of the retroperitoneal area. After this, systematic scanning of the mediastinum is performed at intervals of 1-2cm. Abnormalities are noted, and FNA of the abnormalities can be performed. Specimens are assessed for cellularity on-site. The entire procedure takes 45-60 min. EUS-FNA is minimally invasive, accurate, and fast. Anatomical areas can be reached that are inaccessible for cervical mediastinoscopy. EUS-FNA is useful for the staging of lung cancer or the assessment and diagnosis of abnormalities in the posterior mediastinum.

Inflammatory and genotoxic responses during 30-day welding-fume exposure period.

PubMed

Yu, Il Je; Song, Kyung Seuk; Maeng, Seung Hee; Kim, Soo Jin; Sung, Jae Hyuck; Han, Jeong Hee; Chung, Yong Hyun; Cho, Myung Haing; Chung, Kyu Hyuck; Han, Kuy Tae; Hyun, Jin Sook; Kim, Kwang Jong

2004-12-01

Welder's pneumoconiosis has generally been determined to be benign and unassociated with respiratory symptoms based on the absence of pulmonary-function abnormalities in welders with marked radiographic abnormalities. In previous studies, the current authors suggested a three-phase lung fibrosis process to study the pathological process of lung fibrosis and found that the critical point for recovery was after 30 days of welding-fume exposure at a high dose, at which point early and delicate fibrosis was observed in the perivascular and peribronchiolar regions. Accordingly, the current study investigated the inflammatory and genotoxic responses during a 30-day period of welding-fume exposure to elucidate the process of fibrosis. As such, rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes at concentrations of 65.6 +/- 2.9 (low dose) and 116.8 +/- 3.9 mg/m3 (high dose) total suspended particulate for 2 h per day in an inhalation chamber for 30 days. Animals were sacrificed after the initial 2 h exposure, and after 15 and 30 days of exposure. The rats exposed to the welding fumes exhibited a statistically significant (P < 0.05) decrease in body weight when compared to the control during the 30-day exposure period, yet an elevated cellular differential count and higher levels of albumin, LDH, and beta-NAG, but not elevated TNF-alpha, and IL-1beta in the acellular bronchoalveolar lavage fluid. In addition, the DNA damage resulting from 30 days of welding-fume exposure was confirmed by a comet assay and the inmmunohistochemistry for 8-hydroxydeoxyguanine (8-OH-dG). Consequently, the elevated inflammatory and genotoxic indicators confirmed the lung injury and inflammation caused by the MMA-SS welding-fume exposure.

Respiratory physiology during early life.

PubMed

Stocks, J

1999-08-01

Despite the rapid adaptation to extrauterine life, the respiratory system of an infant is not simply a miniaturized version of that of an adult, since the rapid somatic growth that occurs during the first year of life is accompanied by major developmental changes in respiratory physiology. The highly compliant chest wall of the infant results in relatively low transpulmonary pressures at end expiration with increased tendency of the small peripheral airways to close during tidal breathing. This not only impairs gas exchange and ventilation-perfusion balance, particularly in dependent parts of the lung, but, together with the small absolute size of the airways, renders the infant and young child particularly susceptible to airway obstruction. Premature airways are highly compliant structures compared with those of mature newborns or adults. This increased compliance can cause airway collapse, resulting in increased airways resistance, flow limitation, poor gas exchange and increased work of breathing. Although there is clear evidence that airway reactivity is present from birth, its role in wheezing lower respiratory tract illnesses in young infants may be overshadowed by pre-existing abnormalities of airway geometry and lung mechanics, or by pathological changes such as airway oedema and mucus hypersecretion. Attempts to assess age-related changes in airway reactivity or response to aerosol therapy in the very young is confounded by changes in breathing patterns and the fact that infants are preferential nose breathers. There is increasing evidence that pre-existing abnormalities of respiratory function, associated with adverse events during foetal life (including maternal smoking during pregnancy), and familial predisposition to wheezing are important determinants of wheezing illnesses during the first years of life. This emphasizes the need to identify and minimize any factors that threaten the normal development of the lung during this critical period if respiratory morbidity throughout life is to be minimized.

Xenon-enhanced CT using subtraction CT: Basic and preliminary clinical studies for comparison of its efficacy with that of dual-energy CT and ventilation SPECT/CT to assess regional ventilation and pulmonary functional loss in smokers.

PubMed

Ohno, Yoshiharu; Yoshikawa, Takeshi; Takenaka, Daisuke; Fujisawa, Yasuko; Sugihara, Naoki; Kishida, Yuji; Seki, Shinichiro; Koyama, Hisanobu; Sugimura, Kazuro

2017-01-01

To prospectively and directly compare the capability for assessments of regional ventilation and pulmonary functional loss in smokers of xenon-ventilation CT obtained with the dual-energy CT (DE-CT) and subtraction CT (Sub-CT) MATERIALS AND METHODS: Twenty-three consecutive smokers (15 men and 8 women, mean age: 69.7±8.7years) underwent prospective unenhanced and xenon-enhanced CTs, the latter by Sub-CT and DE-CT methods, ventilation SPECT and pulmonary function tests. Sub-CT was generated from unenhanced and xenon-enhanced CT, and all co-registered SPECT/CT data were produced from SPECT and unenhanced CT data. For each method, regional ventilation was assessed by using a 11-point scoring system on a per-lobe basis. To determine the functional lung volume by each method, it was also calculated for individual sublets with a previously reported method. To determine inter-observer agreement for each method, ventilation defect assessment was evaluated by using the χ2 test with weighted kappa statistics. For evaluation of the efficacy of each method for pulmonary functional loss assessment, functional lung volume was correlated with%FEV 1 . Each inter-observer agreement was rated as substantial (Sub-CT: κ=0.69, p<0.0001; DE-CT: κ=0.64, p<0.0001; SPECT/CT: κ=0.64, p<0.0001). Functional lung volume for each method showed significant to good correlation with%FEV 1 (Sub-CT: r=0.72, p=0.0001; DE-CT: r=0.74, p<0.0001; SPECT/CT: r=0.66, p=0.0006). Xenon-enhanced CT obtained by Sub-CT can be considered at least as efficacious as that obtained by DE-CT and SPECT/CT for assessment of ventilation abnormality and pulmonary functional loss in smokers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Automated extraction of pleural effusion in three-dimensional thoracic CT images

NASA Astrophysics Data System (ADS)

Kido, Shoji; Tsunomori, Akinori

2009-02-01

It is important for diagnosis of pulmonary diseases to measure volume of accumulating pleural effusion in threedimensional thoracic CT images quantitatively. However, automated extraction of pulmonary effusion correctly is difficult. Conventional extraction algorithm using a gray-level based threshold can not extract pleural effusion from thoracic wall or mediastinum correctly, because density of pleural effusion in CT images is similar to those of thoracic wall or mediastinum. So, we have developed an automated extraction method of pulmonary effusion by use of extracting lung area with pleural effusion. Our method used a template of lung obtained from a normal lung for segmentation of lungs with pleural effusions. Registration process consisted of two steps. First step was a global matching processing between normal and abnormal lungs of organs such as bronchi, bones (ribs, sternum and vertebrae) and upper surfaces of livers which were extracted using a region-growing algorithm. Second step was a local matching processing between normal and abnormal lungs which were deformed by the parameter obtained from the global matching processing. Finally, we segmented a lung with pleural effusion by use of the template which was deformed by two parameters obtained from the global matching processing and the local matching processing. We compared our method with a conventional extraction method using a gray-level based threshold and two published methods. The extraction rates of pleural effusions obtained from our method were much higher than those obtained from other methods. Automated extraction method of pulmonary effusion by use of extracting lung area with pleural effusion is promising for diagnosis of pulmonary diseases by providing quantitative volume of accumulating pleural effusion.

A comparison of visual and quantitative methods to identify interstitial lung abnormalities.

PubMed

Kliment, Corrine R; Araki, Tetsuro; Doyle, Tracy J; Gao, Wei; Dupuis, Josée; Latourelle, Jeanne C; Zazueta, Oscar E; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Ross, James C; Estépar, Raúl San José; Diaz, Alejandro A; Lederer, David J; Schwartz, David A; Silverman, Edwin K; Rosas, Ivan O; Washko, George R; O'Connor, George T; Hatabu, Hiroto; Hunninghake, Gary M

2015-10-29

Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density metrics and compared these to visual assessments of ILA. To provide a comparison between ILA detection methods based on visual assessment we generated measures of high attenuation areas (HAAs, defined by attenuation values between -600 and -250 Hounsfield Units) in >4500 participants from both the COPDGene and Framingham Heart studies (FHS). Linear and logistic regressions were used for analyses. Increased measures of HAAs (in ≥ 10 % of the lung) were significantly associated with ILA defined by visual inspection in both cohorts (P < 0.0001); however, the positive predictive values were not very high (19 % in COPDGene and 13 % in the FHS). In COPDGene, the association between HAAs and ILA defined by visual assessment were modified by the percentage of emphysema and body mass index. Although increased HAAs were associated with reductions in total lung capacity in both cohorts, there was no evidence for an association between measurement of HAAs and MUC5B promoter genotype in the FHS. Our findings demonstrate that increased measures of lung density may be helpful in determining the severity of lung volume reduction, but alone, are not strongly predictive of ILA defined by visual assessment. Moreover, HAAs were not associated with MUC5B promoter genotype.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

PubMed

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Heterogeneous Pulmonary Phenotypes Associated With Mutations in the Thyroid Transcription Factor Gene NKX2-1

PubMed Central

Deterding, Robin R.; Wert, Susan E.; White, Frances V.; Dishop, Megan K.; Alfano, Danielle N.; Halbower, Ann C.; Planer, Benjamin; Stephan, Mark J.; Uchida, Derek A.; Williames, Lee D.; Rosenfeld, Jill A.; Lebel, Robert Roger; Young, Lisa R.; Cole, F. Sessions; Nogee, Lawrence M.

2013-01-01

Background: Mutations in the gene encoding thyroid transcription factor, NKX2-1, result in neurologic abnormalities, hypothyroidism, and neonatal respiratory distress syndrome (RDS) that together are known as the brain-thyroid-lung syndrome. To characterize the spectrum of associated pulmonary phenotypes, we identified individuals with mutations in NKX2-1 whose primary manifestation was respiratory disease. Methods: Retrospective and prospective approaches identified infants and children with unexplained diffuse lung disease for NKX2-1 sequencing. Histopathologic results and electron micrographs were assessed, and immunohistochemical analysis for surfactant-associated proteins was performed in a subset of 10 children for whom lung tissue was available. Results: We identified 16 individuals with heterozygous missense, nonsense, and frameshift mutations and five individuals with heterozygous, whole-gene deletions of NKX2-1. Neonatal RDS was the presenting pulmonary phenotype in 16 individuals (76%), interstitial lung disease in four (19%), and pulmonary fibrosis in one adult family member. Altogether, 12 individuals (57%) had the full triad of neurologic, thyroid, and respiratory manifestations, but five (24%) had only pulmonary symptoms at the time of presentation. Recurrent respiratory infections were a prominent feature in nine subjects. Lung histopathology demonstrated evidence of disrupted surfactant homeostasis in the majority of cases, and at least five cases had evidence of disrupted lung growth. Conclusions: Patients with mutations in NKX2-1 may present with pulmonary manifestations in the newborn period or during childhood when thyroid or neurologic abnormalities are not apparent. Surfactant dysfunction and, in more severe cases, disrupted lung development are likely mechanisms for the respiratory disease. PMID:23430038

Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1.

PubMed

Hamvas, Aaron; Deterding, Robin R; Wert, Susan E; White, Frances V; Dishop, Megan K; Alfano, Danielle N; Halbower, Ann C; Planer, Benjamin; Stephan, Mark J; Uchida, Derek A; Williames, Lee D; Rosenfeld, Jill A; Lebel, Robert Roger; Young, Lisa R; Cole, F Sessions; Nogee, Lawrence M

2013-09-01

Mutations in the gene encoding thyroid transcription factor, NKX2-1, result in neurologic abnormalities, hypothyroidism, and neonatal respiratory distress syndrome (RDS) that together are known as the brain-thyroid-lung syndrome. To characterize the spectrum of associated pulmonary phenotypes, we identified individuals with mutations in NKX2-1 whose primary manifestation was respiratory disease. Retrospective and prospective approaches identified infants and children with unexplained diffuse lung disease for NKX2-1 sequencing. Histopathologic results and electron micrographs were assessed, and immunohistochemical analysis for surfactant-associated proteins was performed in a subset of 10 children for whom lung tissue was available. We identified 16 individuals with heterozygous missense, nonsense, and frameshift mutations and five individuals with heterozygous, whole-gene deletions of NKX2-1. Neonatal RDS was the presenting pulmonary phenotype in 16 individuals (76%), interstitial lung disease in four (19%), and pulmonary fibrosis in one adult family member. Altogether, 12 individuals (57%) had the full triad of neurologic, thyroid, and respiratory manifestations, but five (24%) had only pulmonary symptoms at the time of presentation. Recurrent respiratory infections were a prominent feature in nine subjects. Lung histopathology demonstrated evidence of disrupted surfactant homeostasis in the majority of cases, and at least five cases had evidence of disrupted lung growth. Patients with mutations in NKX2-1 may present with pulmonary manifestations in the newborn period or during childhood when thyroid or neurologic abnormalities are not apparent. Surfactant dysfunction and, in more severe cases, disrupted lung development are likely mechanisms for the respiratory disease.

The Evaluation of Interstitial Abnormalities in Group B of the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Classification of Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Ohgiya, Masahiro; Matsui, Hirotoshi; Tamura, Atsuhisa; Kato, Takafumi; Akagawa, Shinobu; Ohta, Ken

2017-10-15

Objective In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification categorized chronic obstructive pulmonary disease (COPD) patients into 4 groups. A report demonstrated that the mortality in Group B was higher than that in Group C. Ischemic heart disease and cancer were suggested to be the cause. The aim of the present study was to test the hypothesis that interstitial lung abnormalities (ILAs) are more prevalent in Group B than Group C and that they may be responsible for the higher mortality in Group B. Methods Patients were selected based on their pulmonary function test results. The inclusion criterion was a forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) of <70% after the inhalation of a bronchodilator. Patients without a smoking history or computed tomography (CT) scan were excluded. The medical records of the patients were retrospectively reviewed, and the selected patients were categorized into Groups A to D. High-resolution CT scans were used to investigate the presence of ILAs and determine the low attenuation area (LAA). Results Among the 349 COPD patients, ILAs were detected in 10.3% of the patients in Group A, 22.5% of the patients in Group B, 5.6% of the patients in Group C, and 23.1% of the patients in Group D. In Group B, the frequency of ILAs was significantly higher and the area affected by the ILAs was significantly greater in comparison to Group C. Among the patterns of interstitial abnormalities, the area of honeycombing in Group B was significantly greater than that in Group C. Furthermore, among the patients in Group B, the LAA in the ILA-positive patients was significantly greater than that in the ILA-negative patients. Conclusion In Group B, the area occupied by ILAs-especially honeycombing-was greater than that in Group C. This contributed to the preserved %FEV 1 and possibly to the poorer prognosis of the patients in Group B.

Serum interleukin-17 in Egyptian children with systemic lupus erythematosus: is it related to pulmonary affection?

PubMed

Hammad, A; Osman, E; Mosaad, Y; Wahba, M

2017-04-01

Objective Pulmonary involvement in paediatric systemic lupus erythematosus (pSLE) is not an uncommon finding; however, subclinical affection occurs more frequently. Many studies have reported that cytokine dysregulation as interleukin-17 (IL-17) over-expression plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). We aim to assess serum levels of IL-17 A and their association with pulmonary involvement in children with SLE. Methods Serum IL-17A levels - determined by solid phase sandwich ELISA - were assessed in forty-two pSLE patients and compared to 45 age-matched healthy controls. All patients were subjected to pulmonary function tests to detect subclinical pulmonary affection. High-resolution CT (HRCT) chest scan was carried out in patients with abnormal pulmonary function tests (PFTs) and those with chronic respiratory symptoms. Results Abnormal PFTs were found in 73% of patients; of them, only 25% had abnormal findings in HRCT chest. Serum levels of IL-17 A were significantly elevated in pSLE patients as compared to healthy controls ( p < 0.001). The serum levels of IL-17 A had a highly significant positive correlation with SLEDAI ( r = 0.811 and p < 0.001) Strong negative correlation was found between serum levels of IL-17A with both FEV1 and FVC ( p < 0.05). Conclusions Serum IL-17A is elevated in pSLE patients, which correlates with disease activity. IL-17 seems to have a possible role in the pathogenesis of subclinical lung affection. Abnormal PFTS may be found in pSLE patients even with normal radiology.

Correlation between molecular analysis, diagnosis according to the 2015 WHO classification of unresected lung tumours and TTF1 expression in small biopsies and cytology specimens from 344 non-small cell lung carcinoma patients.

PubMed

Russell, Prudence A; Rogers, Toni-Maree; Solomon, Benjamin; Alam, Naveed; Barnett, Stephen A; Rathi, Vivek; Williams, Richard A; Wright, Gavin M; Conron, Matthew

2017-10-01

We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected. More EGFR-mutant (78%) and ALK-rearranged (75%) tumours had morphologic adenocarcinoma than KRAS-mutant (56%) tumours. Despite no significant difference in the overall rate of any molecular abnormality between morphologic adenocarcinoma (52%) and NSCLC, favour adenocarcinoma (47%) (p = 0.18), KRAS mutations were detected more frequently in the latter group. No significant difference in the overall rate of any molecular abnormality between TTF1 positive (49%) and TTF1 negative tumours (44%) (p = 0.92) was detected, but more EGFR-mutant (97%) and ALK-rearranged tumours (92%) were TTF1 positive than KRAS-mutant tumours (68%). Rates of EGFR, KRAS and BRAF mutations and ALK rearrangements in this Australian NSCLC patient population are consistent with the published international literature. Our findings suggest that 2015 WHO classification of unresected tumours may assist in identifying molecular subsets of advanced NSCLC. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

The effect of methacholine-induced acute airway narrowing on lung sounds in normal and asthmatic subjects.

PubMed

Schreur, H J; Vanderschoot, J; Zwinderman, A H; Dijkman, J H; Sterk, P J

1995-02-01

The association between lung sound alterations and airways obstruction has long been recognized in clinical practice, but the precise pathophysiological mechanisms of this relationship have not been determined. Therefore, we examined the changes in lung sounds at well-defined levels of methacholine-induced airway narrowing in eight normal and nine asthmatic subjects with normal baseline lung function. All subjects underwent phonopneumography at baseline condition and at > or = 20% fall in forced expiratory volume in one second (FEV1), and in asthmatic subjects also at > or = 40% fall in FEV1. Lung sounds were recorded at three locations on the chest wall during standardized quiet breathing, and during maximal forced breathing. Airflow-dependent power spectra were computed using fast Fourier transform. For each spectrum, we determined the intensity and frequency content of lung sounds, together with the extent of wheezing. The results were analysed using analysis of variance (ANOVA). During acute airway narrowing, the intensity and frequency content of the recorded sounds, as well as the extent of wheezing, were higher than at baseline in both groups of subjects. At similar levels of obstruction, both the pitch and the change in sound intensity with airflow were higher in asthmatics than in normal subjects. Wheezing, being nondiscriminative between the subject groups at baseline, was more prominent in asthmatics than in normal subjects at 20% fall in FEV1. We conclude that, at given levels of acute airway narrowing, lung sounds differ between asthmatics and normal subjects. This suggests that airflow-standardized phonopneumography is a sensitive method for detecting abnormalities in airway dynamics in asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Postnatal airway growth in cystic fibrosis piglets.

PubMed

Adam, Ryan J; Abou Alaiwa, Mahmoud H; Bouzek, Drake C; Cook, Daniel P; Gansemer, Nicholas D; Taft, Peter J; Powers, Linda S; Stroik, Mallory R; Hoegger, Mark J; McMenimen, James D; Hoffman, Eric A; Zabner, Joseph; Welsh, Michael J; Meyerholz, David K; Stoltz, David A

2017-09-01

Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis. NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis. Copyright © 2017 the American Physiological Society.

Low‐voltage electricity‐induced lung injury

PubMed Central

Le, Thuong Vu; Smith, David L.; Kantrow, Stephen P.; Tran, Van Ngoc

2017-01-01

We report a case of bilateral pulmonary infiltrates and haemoptysis following low‐voltage electricity exposure in an agricultural worker. A 58‐year‐old man standing in water reached for an electric watering machine and sustained an exposure to 220 V circuit for an uncertain duration. The electricity was turned off by another worker, and the patient was asymptomatic for the next 10 h until he developed haemoptysis. A chest radiograph demonstrated bilateral infiltrates, and chest computed tomography (CT) revealed ground‐glass opacities with interstitial thickening. Evaluations, including electrocardiogram, serum troponin, N‐terminal pro‐B‐type natriuretic peptide (NT‐pro BNP), coagulation studies, and echocardiogram, found no abnormality. The patient was treated for suspected electricity‐induced lung injury and bleeding with tranexamic acid and for rhabdomyolysis with volume resuscitation. He recovered with complete resolution of chest radiograph abnormalities by Day 7. This is the first reported case of bilateral lung oedema and/or injury after electricity exposure without cardiac arrest. PMID:29321936

Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

PubMed

Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

2014-01-01

The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer

PubMed Central

Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

2014-01-01

The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors. PMID:25414829

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

Adelstein, D.J.; Padhya, T.; Tomashefski, J.F. Jr.

We describe a patient with recurrent small cell undifferentiated lung carcinoma after chemotherapy and mediastinal radiation therapy who presented with peripheral pulmonary infiltrates on chest radiograph. At autopsy the patient was found to have carcinomatous pneumonia confined to the radiographically abnormal lung. The descriptive term reverse radiation pneumonitis is applied in view of the striking nonsegmental distribution of these pulmonary infiltrates, which occurred only outside the irradiated field. In this patient, radiation therapy successfully controlled disease in the treated lung parenchyma, thus accounting for this unusual radiologic and histologic picture. Pneumonia carcinomatosa, occurring after lung irradiation, can therefore be addedmore » to the differential diagnosis of radiographic peripheral pulmonary infiltrates.« less

FBXW7 mutations typically found in human cancers are distinct from null alleles and disrupt lung development

PubMed Central

Davis, Hayley; Lewis, Annabelle; Spencer-Dene, Bradley; Tateossian, Hilda; Stamp, Gordon; Behrens, Axel; Tomlinson, Ian

2011-01-01

FBXW7 is the substrate recognition component of a SCF-type E3 ubiquitin ligase. It has multiple targets such as Notch1, c-Jun, and cyclin E that function in critical developmental and signalling pathways. Mutations in FBXW7 are often found in many types of cancer. In most cases, these mutations do not inactivate the protein, but are mono-allelic missense changes at specific arginine resides involved in substrate binding. We have hypothesized that FBXW7 mutations are selected in cancers for reasons other than haploinsufficiency or full loss-of-function. Given that the existing mutant Fbxw7 mice carry null alleles, we created a mouse model carrying one of the commonly occurring point mutations (Fbxw7) in the WD40 substrate recognition domain of Fbxw7. Mice heterozygous for this mutation apparently developed normally in utero, died perinatally due to a defect in lung development, and in some cases showed cleft palate and eyelid fusion defects. By comparison, Fbxw7+/− mice were viable and developed normally. Fbxw7−/− animals died of vascular abnormalities at E10.5. We screened known FBXW7 targets for changes in the lungs of the Fbxw7R482Q/+ mice and found Tgif1 and Klf5 to be up-regulated. Fbxw7 alleles are not functionally equivalent to heterozygous or homozygous null alleles, and we propose that they are selected in tumourigenesis because they cause a selective or partial loss of FBXW7 function. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:21503901

Correlation of ultra-low dose chest CT findings with physiologic measures of asbestosis.

PubMed

Manners, David; Wong, Patrick; Murray, Conor; Teh, Joelin; Kwok, Yi Jin; de Klerk, Nick; Alfonso, Helman; Franklin, Peter; Reid, Alison; Musk, A W Bill; Brims, Fraser J H

2017-08-01

The correlation between ultra low dose computed tomography (ULDCT)-detected parenchymal lung changes and pulmonary function abnormalities is not well described. This study aimed to determine the relationship between ULDCT-detected interstitial lung disease (ILD) and measures of pulmonary function in an asbestos-exposed population. Two thoracic radiologists independently categorised prone ULDCT scans from 143 participants for ILD appearances as absent (score 0), probable (1) or definite (2) without knowledge of asbestos exposure or lung function. Pulmonary function measures included spirometry and diffusing capacity to carbon monoxide (DLCO). Participants were 92% male with a median age of 73.0 years. CT dose index volume was between 0.6 and 1.8 mGy. Probable or definite ILD was reported in 63 (44.1%) participants. Inter-observer agreement was good (k = 0.613, p < 0.001). There was a statistically significant correlation between the ILD score and both forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) (r = -0.17, p = 0.04 and r = -0.20, p = 0.02). There was a strong correlation between ILD score and DLCO (r = -0.34, p < 0.0001). Changes consistent with ILD on ULDCT correlate well with corresponding reductions in gas transfer, similar to standard CT. In asbestos-exposed populations, ULDCT may be adequate to detect radiological changes consistent with asbestosis. • Interobserver agreement for the ILD score using prone ULDCT is good. • Prone ULDCT appearances of ILD correlate with changes in spirometric observations. • Prone ULDCT appearances of ILD correlate strongly with changes in gas transfer. • Prone ULDCT may provide sufficient radiological evidence to inform the diagnosis of asbestosis.

Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats.

PubMed

Zeidler-Erdely, Patti C; Meighan, Terence G; Erdely, Aaron; Fedan, Jeffrey S; Thompson, Janet A; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B; Afshari, Aliakbar; McKinney, Walter; Frazer, David G; Antonini, James M

2014-10-01

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m³ to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline R(L) was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased R(L) and result in endothelial dysfunction, but otherwise had minor effects on the lung.

Human Impairment from Living near Confined Animal (Hog) Feeding Operations

PubMed Central

Kilburn, Kaye H.

2012-01-01

Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neurophysiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neurobehavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neurobehavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas. PMID:22496706

[MicroRNAs in diagnosis and prognosis in lung cancer].

PubMed

Avila-Moreno, Federico; Urrea, Francisco; Ortiz-Quintero, Blanca

2011-01-01

MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that regulate gene expression at the posttranscriptional level by blocking translation or inducing degradation of messenger RNA targets. It has been shown that miRNAs participate in a wide spectrum of essential biologic processes including cell cycle, differentiation, development, apoptosis and hematopoiesis, revealing one of the major regulators of human gene expression. Recent studies have shown evidences of abnormal expression of miRNAs in solid and hematological tumors, as well as the association of altered miRNAs with oncogenic or tumor suppressor functions, suggesting a key role of miRNAs in carcinogenesis. Moreover, unique profiles of altered miRNAs expression seem to allow distinction from normal tissue, prediction of disease outcomes, and evaluation of tumor aggressiveness in several types of cancer, including lung cancer. These unique and highly stable miRNAs patterns seems not to depend of age and race, and these characteristics highlight their potential diagnostic and prognosis utility. These findings are particularly promising for lung cancer, a worldwide leading cause of cancer-related deaths with a poor survival rate, despite the discovery of novel therapies. This review describes the potential of miRNAs as biomarkers for diagnosis, cancer classification and estimation of prognosis in lung cancer; and the approaches used to detect and quantify these miRNAs; including the current information about circulating miRNAs as potential biomarkers in lung cancer. This review also provides a description of miRNAs biogenesis, nomenclature and available database for miRNA sequences.

Netrin-1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin-Induced Pulmonary Fibrosis.

PubMed

Sun, Huanxing; Zhu, Yangyang; Pan, Hongyi; Chen, Xiaosong; Balestrini, Jenna L; Lam, TuKiet T; Kanyo, Jean E; Eichmann, Anne; Gulati, Mridu; Fares, Wassim H; Bai, Hanwen; Feghali-Bostwick, Carol A; Gan, Ye; Peng, Xueyan; Moore, Meagan W; White, Eric S; Sava, Parid; Gonzalez, Anjelica L; Cheng, Yuwei; Niklason, Laura E; Herzog, Erica L

2016-05-01

Fibrocytes are collagen-producing leukocytes that accumulate in patients with systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) via unknown mechanisms that have been associated with altered expression of neuroimmune proteins. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in SSc has not been explored. The aim of this study was to use a novel translational platform based on decellularized human lungs to determine whether the lung ECM of patients with scleroderma controls the development of fibrocytes from peripheral blood mononuclear cells. We performed biomechanical evaluation of decellularized scaffolds prepared from lung explants from healthy control subjects and patients with scleroderma, using tensile testing and biochemical and proteomic analysis. Cells obtained from healthy controls and patients with SSc-related ILD were cultured on these scaffolds, and CD45+pro-ColIα1+ cells meeting the criteria for fibrocytes were quantified. The contribution of the neuromolecule netrin-1 to fibrosis was assessed using neutralizing antibodies in this system and by administering bleomycin via inhalation to netrin-1(+/-) mice. Compared with control lung scaffolds, lung scaffolds from patients with SSc-related ILD showed aberrant anatomy, enhanced stiffness, and abnormal ECM composition. Culture of control cells in lung scaffolds from patients with SSc-related ILD increased production of pro-ColIα1+ cells, which was stimulated by enhanced stiffness and abnormal ECM composition. Cells from patients with SSc-related ILD demonstrated increased pro-ColIα1 responsiveness to lung scaffolds from scleroderma patients but not enhanced stiffness. Enhanced detection of netrin-1-expressing CD14(low) cells in patients with SSc-related ILD was observed, and antibody-mediated netrin-1 neutralization attenuated detection of CD45+pro-ColIα1+ cells in all settings. Netrin-1(+/-) mice were protected against bleomycin-induced lung fibrosis and fibrocyte accumulation. Factors present in the lung matrices of patients with scleroderma regulate fibrocyte accumulation via a netrin-1-dependent pathway. Netrin-1 regulates bleomycin-induced pulmonary fibrosis in mice. Netrin-1 might be a novel therapeutic target in SSc-related ILD. © 2016, American College of Rheumatology.

Hemoglobin (image)

MedlinePlus

... oxygen. In the lungs, oxygen is exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in the normal balance between red blood cell production and destruction. Both ...

Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease

PubMed Central

Jobe, Alan H.

2015-01-01

Bronchopulmonary dysplasia (BPD) is a unique injury syndrome caused by prolonged injury and repair imposed on an immature and developing lung. The decreased septation and decreased microvascular development phenotype of BPD can be reproduced in newborn rodents with increased chronic oxygen exposure and in premature primates and sheep with oxygen and/or mechanical ventilation. The inflammation caused by oxidants, inflammatory agonists, and/or stretch injury from mechanical ventilation seems to promote the anatomic abnormalities. Multiple interventions targeted to specific inflammatory cells or pathways or targeted to decreasing ventilation-mediated injury can substantially prevent the anatomic changes associated with BPD in term rodents and in preterm sheep or primate models. Most of the anti-inflammatory therapies with benefit in animal models have not been tested clinically. None of the interventions that have been tested clinically are as effective as anticipated from the animal models. These inconsistencies in responses likely are explained by the antenatal differences in lung exposures of the developing animals relative to very preterm humans. The animals generally have normal lungs while the lungs of preterm infants are exposed variably to intrauterine inflammation, growth abnormalities, antenatal corticosteroids, and poorly understood effects from the causes of preterm delivery. The animal models have been essential for the definition of the mediators that can cause a BPD phenotype. These models will be necessary to develop and test future-targeted interventions to prevent and treat BPD. PMID:26301222

Thoracoscopic decortication for the management of trapped lung caused by 14-year pneumothorax: A case report.

PubMed

Tian, Yan; Zheng, Wenqi; Zha, Nashunbayaer; Wang, Yufei; Huang, Shaojun; Guo, Zhanlin

2018-05-26

Trapped lung is defined by the lung's inability to expand and fill the thoracic cavity because of a restricting "peel" caused by benign or malignant pleural disease. However, trapped lung secondary to pneumothorax is rarely reported. We present a case of trapped lung caused by a pneumothorax that occurred some 14 years before the patient presented to our hospital with a complaint of incapacitating dyspnea. Computed tomography (CT) scans revealed trapping of the right lung with abnormal thickening of the visceral pleura. In view of the patient's history of pneumothorax, we concluded that his dyspnea was attributable mainly to the trapping of his lung by the earlier pneumothorax. We therefore scheduled thoracoscopic decortication, which was successfully completed. The patient's recovery after the operation was uneventful, and seven weeks after surgery the right lung had re-expanded well. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Challenging embryological theories on congenital diaphragmatic hernia: future therapeutic implications for paediatric surgery.

PubMed Central

Jesudason, E. C.

2002-01-01

Lung hypoplasia is central to the poor prognosis of babies with congenital diaphragmatic hernia (CDH). Prolapse of abdominal organs through a diaphragmatic defect has traditionally been thought to impair lung growth by compression. The precise developmental biology of CDH remains unresolved. Refractory to fetal correction, lung hypoplasia in CDH may instead originate during embryogenesis and before visceral herniation. Resolving these conflicting hypotheses may lead to reappraisal of current clinical strategies. Genetic studies in murine models and the fruitfly, Drosophila melanogaster are elucidating the control of normal respiratory organogenesis. Branchless and breathless are Drosophila mutants lacking fibroblast growth factor (FGF) and its cognate receptor (FGFR), respectively. Sugarless and sulphateless mutants lack enzymes essential for heparan sulphate (HS) biosynthesis. Phenotypically, all these mutants share abrogated airway branching. Mammalian organ culture and transgenic models confirm the essential interaction of FGFs and HS during airway ramification. Embryonic airway development (branching morphogenesis) occurs in a defined spatiotemporal sequence. Unlike the surgically-created lamb model, the nitrofen rat model permits investigation of embryonic lung growth in CDH. Microdissecting embryonic lung primordia from the nitrofen CDH model and normal controls, we demonstrated that disruption of stereotyped airway branching correlates with and precedes subsequent CDH formation. To examine disturbed branching morphogenesis longitudinally, we characterised a system that preserves lung hypoplasia in organ culture. We tested FGFs and heparin (an HS analogue) as potential therapies on normal and hypoplastic lungs. Observing striking differences in morphological response to FGFs between normal and hypoplastic lung primordia, we postulated abnormalities of FGF/HS signalling in the embryonic CDH lung. Evaluating this hypothesis further, we examined effects of an HS-independent growth factor (epidermal growth factor, EGF) on hypoplastic lung development. Visible differences in morphological response indicate an intrinsic abnormality of hypoplastic lung primordia that may involve shared targets of FGFs and EGE. These studies indicate that lung hypoplasia precedes diaphragmatic hernia and may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. What does this imply for human CDH? Fetal surgery may be 'too little, too late' to correct an established lung embryopathy. In utero growth factor therapy may permit antenatal lung rescue. Prevention of the birth defect by preconceptual prophylaxis may represent the ultimate solution. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 PMID:12215028

Pulmonary Function Test Abnormalities in Children With Inflammatory Bowel Disease: Is It Common?

PubMed

El Amrousy, Doaa Mohamed; Hassan, Samir; El-Ashry, Heba; Yousef, Mohamed; Sharshar, Ragia

2018-04-03

The aim of the study was to evaluate the frequency and type of pulmonary dysfunction in newly diagnosed children with inflammatory bowel disease (IBD) and the correlation between pulmonary function tests (PFTs) and IBD activity. It is an observational case-control study. One hundred newly diagnosed children with IBD were enrolled as the patient group, which was subdivided into 52 with Crohn disease (CD) and 48 with ulcerative colitis (UC). Fifty healthy children matched for age, sex, height, and body mass index (BMI) served as the control group. PFTs in the form of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, residual volume (RV), total lung capacity (TLC), mid-forced expiratory flow of 25% to 75% (FEF 25%-75%) and diffusing capacity of the lung for carbon monoxide (DLCO) were evaluated in all studied children. PFTs were measured at diagnosis, every 6 months for a period of 3 years, during remission and at least once during activity in patient group. There was significant progressive deterioration in all PFTs in IBD patients compared with their PFTs at the start of the study (P < 0.05) except for FEV1/FVC, RV, and TLC (P > 0.05). There was significant deterioration during disease activity compared with remission state regarding FEV1, FVC, FEV 25% to 75%, and DLCO (P < 0.05). Significant negative correlation was found between disease activity in both UC and CD groups and FEV1, FVC, FEV 25% to 75%, and DLCO. Subclinical PFT abnormalities are common in pediatric IBD even during remission period. So, periodic PFT evaluation should be considered in the routine follow-up of IBD children.

Anatomical pulmonary magnetic resonance imaging segmentation for regional structure-function measurements of asthma

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

Guo, F.; Graduate Program in Biomedical Engineering, University of Western Ontario, London, Ontario N6A 5B9; Svenningsen, S.

Purpose: Pulmonary magnetic-resonance-imaging (MRI) and x-ray computed-tomography have provided strong evidence of spatially and temporally persistent lung structure-function abnormalities in asthmatics. This has generated a shift in their understanding of lung disease and supports the use of imaging biomarkers as intermediate endpoints of asthma severity and control. In particular, pulmonary {sup 1}H MRI can be used to provide quantitative lung structure-function measurements longitudinally and in response to treatment. However, to translate such biomarkers of asthma, robust methods are required to segment the lung from pulmonary {sup 1}H MRI. Therefore, their objective was to develop a pulmonary {sup 1}H MRI segmentationmore » algorithm to provide regional measurements with the precision and speed required to support clinical studies. Methods: The authors developed a method to segment the left and right lung from {sup 1}H MRI acquired in 20 asthmatics including five well-controlled and 15 severe poorly controlled participants who provided written informed consent to a study protocol approved by Health Canada. Same-day spirometry and plethysmography measurements of lung function and volume were acquired as well as {sup 1}H MRI using a whole-body radiofrequency coil and fast spoiled gradient-recalled echo sequence at a fixed lung volume (functional residual capacity + 1 l). We incorporated the left-to-right lung volume proportion prior based on the Potts model and derived a volume-proportion preserved Potts model, which was approximated through convex relaxation and further represented by a dual volume-proportion preserved max-flow model. The max-flow model led to a linear problem with convex and linear equality constraints that implicitly encoded the proportion prior. To implement the algorithm, {sup 1}H MRI was resampled into ∼3 × 3 × 3 mm{sup 3} isotropic voxel space. Two observers placed seeds on each lung and on the background of 20 pulmonary {sup 1}H MR images in a randomized dataset, on five occasions, five consecutive days in a row. Segmentation accuracy was evaluated using the Dice-similarity-coefficient (DSC) of the segmented thoracic cavity with comparison to five-rounds of manual segmentation by an expert observer. The authors also evaluated the root-mean-squared-error (RMSE) of the Euclidean distance between lung surfaces, the absolute, and percent volume error. Reproducibility was measured using the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for two observers who repeated segmentation measurements five-times. Results: For five well-controlled asthmatics, forced expiratory volume in 1 s (FEV{sub 1})/forced vital capacity (FVC) was 83% ± 7% and FEV{sub 1} was 86 ± 9%{sub pred}. For 15 severe, poorly controlled asthmatics, FEV{sub 1}/FV C = 66% ± 17% and FEV{sub 1} = 72 ± 27%{sub pred}. The DSC for algorithm and manual segmentation was 91% ± 3%, 92% ± 2% and 91% ± 2% for the left, right, and whole lung, respectively. RMSE was 4.0 ± 1.0 mm for each of the left, right, and whole lung. The absolute (percent) volume errors were 0.1 l (∼6%) for each of right and left lung and ∼0.2 l (∼6%) for whole lung. Intra- and inter-CoV (ICC) were <0.5% (>0.91%) for DSC and <4.5% (>0.93%) for RMSE. While segmentation required 10 s including ∼6 s for user interaction, the smallest detectable difference was 0.24 l for algorithm measurements which was similar to manual measurements. Conclusions: This lung segmentation approach provided the necessary and sufficient precision and accuracy required for research and clinical studies.« less

Quantitative analysis of airway abnormalities in CT

NASA Astrophysics Data System (ADS)

Petersen, Jens; Lo, Pechin; Nielsen, Mads; Edula, Goutham; Ashraf, Haseem; Dirksen, Asger; de Bruijne, Marleen

2010-03-01

A coupled surface graph cut algorithm for airway wall segmentation from Computed Tomography (CT) images is presented. Using cost functions that highlight both inner and outer wall borders, the method combines the search for both borders into one graph cut. The proposed method is evaluated on 173 manually segmented images extracted from 15 different subjects and shown to give accurate results, with 37% less errors than the Full Width at Half Maximum (FWHM) algorithm and 62% less than a similar graph cut method without coupled surfaces. Common measures of airway wall thickness such as the Interior Area (IA) and Wall Area percentage (WA%) was measured by the proposed method on a total of 723 CT scans from a lung cancer screening study. These measures were significantly different for participants with Chronic Obstructive Pulmonary Disease (COPD) compared to asymptomatic participants. Furthermore, reproducibility was good as confirmed by repeat scans and the measures correlated well with the outcomes of pulmonary function tests, demonstrating the use of the algorithm as a COPD diagnostic tool. Additionally, a new measure of airway wall thickness is proposed, Normalized Wall Intensity Sum (NWIS). NWIS is shown to correlate better with lung function test values and to be more reproducible than previous measures IA, WA% and airway wall thickness at a lumen perimeter of 10 mm (PI10).

Neutrophilic infiltration within the airway smooth muscle in patients with COPD

PubMed Central

Baraldo, S; Turato, G; Badin, C; Bazzan, E; Beghe, B; Zuin, R; Calabrese, F; Casoni, G; Maestrelli, P; Papi, A; Fabbri, L; Saetta, M

2004-01-01

Background: COPD is an inflammatory disorder characterised by chronic airflow limitation, but the extent to which airway inflammation is related to functional abnormalities is still uncertain. The interaction between inflammatory cells and airway smooth muscle may have a crucial role. Methods: To investigate the microlocalisation of inflammatory cells within the airway smooth muscle in COPD, surgical specimens obtained from 26 subjects undergoing thoracotomy (eight smokers with COPD, 10 smokers with normal lung function, and eight non-smoking controls) were examined. Immunohistochemical analysis was used to quantify the number of neutrophils, macrophages, mast cells, CD4+ and CD8+ cells localised within the smooth muscle of peripheral airways. Results: Smokers with COPD had an increased number of neutrophils and CD8+ cells in the airway smooth muscle compared with non-smokers. Smokers with normal lung function also had a neutrophilic infiltration in the airway smooth muscle, but to a lesser extent. When all the subjects were analysed as one group, neutrophilic infiltration was inversely related to forced expiratory volume in 1 second (% predicted). Conclusions: Microlocalisation of neutrophils and CD8+ cells in the airway smooth muscle in smokers with COPD suggests a possible role for these cells in the pathogenesis of smoking induced airflow limitation. PMID:15047950

Yield of diagnostic procedures for invasive fungal infections in neutropenic febrile patients with chest computed tomography abnormalities.

PubMed

Ho, Dora Y; Lin, Margaret; Schaenman, Joanna; Rosso, Fernando; Leung, Ann N C; Coutre, Steven E; Sista, Ramachandra R; Montoya, Jose G

2011-01-01

Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients. Fifty-six patients received diagnostic procedures, including 46 bronchoscopies, 25 lung biopsies and seven sinus biopsies, with a diagnostic yield for IFI of 12.8%, 35.0% and 83.3%, respectively. In conclusion, chest CT plays an important role in the evaluation of haematological patients with febrile neutropenia and often leads to a change in antimicrobial therapy. Pulmonary nodules are the most common radiological abnormality. Sinus or lung biopsies have a high-diagnostic yield for IFI as compared to bronchoscopy. Patients with IFI may not have sinus/chest symptoms, and thus, clinicians should have a low threshold for performing sinus/chest imaging, and if indicated and safe, a biopsy of the abnormal areas. © 2009 Blackwell Verlag GmbH.

H₂S protecting against lung injury following limb ischemia-reperfusion by alleviating inflammation and water transport abnormality in rats.

PubMed

Qi, Qi Ying Chun; Chen, Wen; Li, Xiao Ling; Wang, Yu Wei; Xie, Xiao Hua

2014-06-01

To investigate the effect of H₂S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism. Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NaHS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS (0.78 mg/kg) as exogenous H₂S donor and PPG (60 mg/kg) which can suppress endogenous H₂S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP₁), aquaporin-5 (AQP₅) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR₄), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-κB as indexes of inflammation. LIR induced lung injury was accompanied with upregulation of TLR₄-Myd88-NF-κB pathway and downregulation of AQP1/AQP₅. NaHS pre-treatment reduced lung injury with increasing AQP₁/AQP₅ expression and inhibition of TLR₄-Myd88-NF-κB pathway, but PPG adjusted AQP₁/AQP₅ and TLR4 pathway to the opposite side and exacerbated lung injury. Endogenous H₂S, TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ were involved in LIR induced lung injury. Increased H₂S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ expression to reduce inflammatory reaction and lessen pulmonary edema. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome

PubMed Central

Schloter-Hai, Brigitte; Kublik, Susanne; Granitsiotis, Michael S.; Boschetto, Piera; Stendardo, Mariarita; Barta, Imre; Dome, Balazs; Deleuze, Jean-François; Boland, Anne; Müller-Quernheim, Joachim; Prasse, Antje; Welte, Tobias; Hohlfeld, Jens; Subramanian, Deepak; Parr, David; Gut, Ivo Glynne; Greulich, Timm; Koczulla, Andreas Rembert; Nowinski, Adam; Gorecka, Dorota; Singh, Dave; Gupta, Sumit; Brightling, Christopher E.; Hoffmann, Harald; Frankenberger, Marion; Hofer, Thomas P.; Burggraf, Dorothe; Heiss-Neumann, Marion; Ziegler-Heitbrock, Loems; Schloter, Michael; zu Castell, Wolfgang

2017-01-01

Background Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. Methods Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. Results We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. Conclusion Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system. PMID:28704452

Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome.

PubMed

Engel, Marion; Endesfelder, David; Schloter-Hai, Brigitte; Kublik, Susanne; Granitsiotis, Michael S; Boschetto, Piera; Stendardo, Mariarita; Barta, Imre; Dome, Balazs; Deleuze, Jean-François; Boland, Anne; Müller-Quernheim, Joachim; Prasse, Antje; Welte, Tobias; Hohlfeld, Jens; Subramanian, Deepak; Parr, David; Gut, Ivo Glynne; Greulich, Timm; Koczulla, Andreas Rembert; Nowinski, Adam; Gorecka, Dorota; Singh, Dave; Gupta, Sumit; Brightling, Christopher E; Hoffmann, Harald; Frankenberger, Marion; Hofer, Thomas P; Burggraf, Dorothe; Heiss-Neumann, Marion; Ziegler-Heitbrock, Loems; Schloter, Michael; Zu Castell, Wolfgang

2017-01-01

Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.

Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: a systematic review and a meta-analysis.

PubMed

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Lococo, Filippo; Cafarotti, Stefano; Prior, John O; Bertagna, Francesco; Ceriani, Luca; Giovanella, Luca

2014-01-01

To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Hematocrit

MedlinePlus

... of the heart Too little water in the body ( dehydration ) Low levels of oxygen in the blood Scarring or thickening of the lungs Bone marrow disease that causes abnormal increase in red blood cells

Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.

PubMed Central

Ray, P; Tang, W; Wang, P; Homer, R; Kuhn, C; Flavell, R A; Elias, J A

1997-01-01

Standard overexpression transgenic approaches are limited in their ability to model waxing and waning diseases and frequently superimpose development-dependent and -independent phenotypic manifestations. We used the clara cell 10-kD protein (CC10) promoter and the reverse tetracycline transactivator (rtTA) to create a lung-specific, externally regulatable, overexpression transgenic system and used this system to express human interleukin 11 (IL-11) in respiratory structures. Gene induction could be achieved in utero, in neonates and in adult animals. Moreover, gene expression could be turned off by removal of the inducing stimulus. When gene activation was initiated in utero and continued into adulthood, subepithelial airway fibrosis, peribronchiolar mononuclear nodules, and alveolar enlargement (emphysema) were noted. Induction in the mature lung caused airway remodeling and peribronchiolar nodules, but alveolar enlargement was not appreciated. In contrast, induction in utero and during the first 14 d of life caused alveolar enlargement without airway remodeling or peribronchiolar nodules. Thus, IL-11 overexpression causes abnormalities that are dependent (large alveoli) and independent (airway remodeling, peribronchiolar nodules) of lung growth and development, and the CC10-rtTA system can be used to differentiate among these effector functions. The CC10-rtTA transgenic system can be used to model waxing and waning, childhood and growth and development-related biologic processes with enhanced fidelity. PMID:9366564

A site-specific genetic modification for induction of pluripotency and subsequent isolation of derived lung alveolar epithelial type II cells.

PubMed

Yan, Qing; Quan, Yuan; Sun, Huanhuan; Peng, Xinmiao; Zou, Zhengyun; Alcorn, Joseph L; Wetsel, Rick A; Wang, Dachun

2014-02-01

Human induced pluripotent stem cells (hiPSCs) have great therapeutic potential in repairing defective lung alveoli. However, genetic abnormalities caused by vector integrations and low efficiency in generating hiPSCs, as well as difficulty in obtaining transplantable hiPSC-derived cell types are still major obstacles. Here we report a novel strategy using a single nonviral site-specific targeting vector with a combination of Tet-On inducible gene expression system, Cre/lox P switching gene expression system, and alveolar epithelial type II cell (ATIIC)-specific Neomycin(R) transgene expression system. With this strategy, a single copy of all of the required transgenes can be specifically knocked into a site immediately downstream of β-2-microglobulin (B2M) gene locus at a high frequency, without causing B2M dysfunction. Thus, the expression of reprogramming factors, Oct4, Sox2, cMyc, and Klf4, can be precisely regulated for efficient reprogramming of somatic cells into random integration-free or genetic mutation-free hiPSCs. The exogenous reprogramming factor transgenes can be subsequently removed after reprogramming by transient expression of Cre recombinase, and the resulting random integration-free and exogenous reprogramming factor-free hiPSCs can be selectively differentiated into a homogenous population of ATIICs. In addition, we show that these hiPSC-derived ATIICs exhibit ultrastructural characteristics and biological functions of normal ATIICs. When transplanted into bleomycin-challenged mice lungs, hiPSC-derived ATIICs efficiently remain and re-epithelialize injured alveoli to restore pulmonary function, preventing lung fibrosis and increasing survival without tumorigenic side effect. This strategy allows for the first time efficient generation of patient-specific ATIICs for possible future clinical applications. © 2013 AlphaMed Press.

A site-specific genetic modification for induction of pluripotency and subsequent isolation of derived lung alveolar epithelial type II cells

PubMed Central

Yan, Qing; Quan, Yuan; Sun, Huanhuan; Peng, Xinmiao; Zou, Zhengyun; Alcorn, Joseph L.; Wetsel, Rick A.; Wang, Dachun

2013-01-01

Human induced pluripotent stem cells (hiPSCs) have great therapeutic potential in repairing defective lung alveoli. However, genetic abnormalities caused by vector-integrations and low efficiency in generating hiPSCs, as well as difficulty in obtaining transplantable hiPSC-derived cell types, are still major obstacles. Here we report a novel strategy using a single non-viral site-specific-targeting vector with a combination of Tet-On inducible gene expression system, Cre/lox P switching gene expression system, and alveolar epithelial type II cell (ATIIC)-specific NeomycinR trangene expression system. With this strategy, a single copy of all of the required transgenes can be specifically knocked into a site immediately downstream of beta-2-microglobulin (B2M) gene locus at a high frequency, without causing B2M dysfunction. Thus, the expression of reprogramming factors, Oct4, Sox2, cMyc and Klf4, can be precisely regulated for efficient reprogramming of somatic cells into random-integration-free or genetic mutation-free hiPSCs. The exogenous reprogramming factor transgenes can be subsequently removed after reprogramming by transient expression of Cre recombinase, and the resulting random-integration-free and exogenous reprogramming-factor-free hiPSCs can be selectively differentiated into a homogenous population of ATIICs. In addition, we show that these hiPSC-derived ATIICs exhibit ultra-structural characteristics and biological functions of normal ATIICs. When transplanted into bleomycin-challenged mice lungs, hiPSC-derived ATIICs efficiently remain and re-epithelialize injured alveoli to restore pulmonary function, preventing lung fibrosis and increasing survival without tumorigenic side effect. This strategy allows for the first time efficient generation of patient-specific ATIICs for possible future clinical applications. PMID:24123810

Nrf2 protects against airway disorders

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

Cho, Hye-Youn, E-mail: cho2@niehs.nih.go; Kleeberger, Steven R.

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver,more » gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.« less

Heart rate recovery after six-minute walk test predicts pulmonary hypertension in patients with idiopathic pulmonary fibrosis.

PubMed

Swigris, Jeffrey J; Olson, Amy L; Shlobin, Oksana A; Ahmad, Shahzad; Brown, Kevin K; Nathan, Steven D

2011-04-01

In patients with IPF, we sought to validate that abnormal heart rate recovery at 1 min (HRR1) after six-minute walk test (6MWT) predicts mortality and to explore the relationship between abnormal HRR1 and pulmonary hypertension (PH). We identified IPF patients who performed a 6MWT as part of their clinical evaluation between 2006 and 2009 and were followed to lung transplantation or death. Right heart catheterization (RHC) data were collated and analysed for the subgroup who had this procedure. There were 160 subjects who qualified for the survival analysis, and those with an abnormal HRR1 had worse survival than subjects with normal HRR1 (log-rank P = 0.01). Eighty-two subjects had a right heart catheter (RHC); among them, abnormal HRR1 was associated with RHC-confirmed PH (χ(2) = 4.83, P = 0.03) and had a sensitivity, specificity, positive predictive value and negative predictive value of 52%, 74%, 41% and 82%, respectively, for PH. In bivariate and multivariable analyses, abnormal HRR1 appeared to be the strongest predictor of RHC-confirmed PH (odds ratio (OR) = 4.0, 95% CI: 1.17-13.69, P = 0.02 in the multivariable analysis). This study adds to data that support the validity of abnormal HRR1 as a predictor of mortality and of RHC-confirmed PH in IPF. Research is needed to further investigate the link between abnormal HRR1 and PH and to elucidate heart-lung interactions at work during exercise and recovery in patients with IPF. © 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.

Smoking Cessation in COPD Causes a Transient Improvement in Spirometry and Decreases Micronodules on High-Resolution CT Imaging

PubMed Central

Dhariwal, Jaideep; Tennant, Rachel C.; Hansell, David M.; Westwick, John; Walker, Christoph; Ward, Simon P.; Pride, Neil; Barnes, Peter J.; Kon, Onn Min

2014-01-01

Background: Smoking cessation is of major importance for all smokers; however, in patients with COPD, little information exists on how smoking cessation influences lung function and high-resolution CT (HRCT) scan appearances. Methods: In this single-center study, we performed screening spirometry in a group of heavy smokers aged 40 to 80 years (N = 358). We then studied the effects of smoking cessation in two groups of selected subjects: smokers with COPD (n = 38) and smokers with normal spirometry (n = 55). In parallel to subjects undergoing smoking cessation, we studied a control group of nonsmokers (n = 19). Results: Subjects with COPD who quit smoking had a marked, but transient improvement in FEV1 at 6 weeks (184 mL, n = 17, P < .01) that was still present at 12 weeks (81 mL, n = 17, P < .05) and only partially maintained at 1 year. In contrast, we saw improvement in the transfer factor of lung for carbon monoxide at 6 weeks in both subjects with COPD who quit smoking (0.47 mmol/min/kPa, n = 17, P < .01) and subjects who quit smoking with normal spirometry (0.40 mmol/min/kPa, n = 35, P < .01). An upper-zone single HRCT image slice reliably identified emphysema at baseline in 74% of smokers with COPD (28 of 38) and 29% of healthy smokers (16 of 55). Smoking cessation had no significant effect on the appearances of emphysema but decreased the presence of micronodules on HRCT imaging. Conclusions: Cigarette smoking causes extensive lung function and HRCT image abnormalities, even in patients with normal spirometry. Smoking cessation has differential effects on lung function (FEV1 and gas transfer) and features on HRCT images (emphysema and micronodules). Cessation of smoking in patients with COPD causes a transient improvement in FEV1 and decreases the presence of micronodules, offering an opportunity for concomitant therapy during smoking cessation to augment these effects. Smoking cessation at the earliest possible opportunity is vital to minimize permanent damage to the lungs. PMID:24522562

Indoor Air Quality and Respiratory Health among Malay Preschool Children in Selangor.

PubMed

Rawi, Nur Azwani Mohd Nor; Jalaludin, Juliana; Chua, Poh Choo

2015-01-01

Indoor air quality (IAQ) has been the object of several studies due to its adverse health effects on children. Methods. A cross-sectional comparative study was carried out among Malay children in Balakong (2 studied preschools) and Bangi (2 comparative preschools), Selangor, with the aims of determining IAQ and its association with respiratory health. 61 and 50 children aged 5-6 years were selected as studied and comparative groups. A questionnaire was used to obtain an exposure history and respiratory symptoms. Lung function test was carried out. IAQ parameters obtained include indoor concentration of particulate matter (PM), volatile organic compounds (VOCs), carbon monoxide (CO), carbon dioxide (CO2), temperature, air velocity (AV), and relative humidity. Results. There was a significant difference between IAQ in studied and comparative preschools for all parameters measured (P < 0.001) except for CO2 and AV. Studied preschools had higher PM and CO concentration. FVC, FEV1, FVC% and FEV1% predicted values were significantly lower among studied group. Exposures to PM, VOCs, and CO were associated with wheezing. Conclusion. The finding concluded that exposures to poor IAQ might increase the risk of getting lung function abnormality and respiratory problems among study respondents.

Indoor Air Quality and Respiratory Health among Malay Preschool Children in Selangor

PubMed Central

Chua, Poh Choo

2015-01-01

Indoor air quality (IAQ) has been the object of several studies due to its adverse health effects on children. Methods. A cross-sectional comparative study was carried out among Malay children in Balakong (2 studied preschools) and Bangi (2 comparative preschools), Selangor, with the aims of determining IAQ and its association with respiratory health. 61 and 50 children aged 5-6 years were selected as studied and comparative groups. A questionnaire was used to obtain an exposure history and respiratory symptoms. Lung function test was carried out. IAQ parameters obtained include indoor concentration of particulate matter (PM), volatile organic compounds (VOCs), carbon monoxide (CO), carbon dioxide (CO2), temperature, air velocity (AV), and relative humidity. Results. There was a significant difference between IAQ in studied and comparative preschools for all parameters measured (P < 0.001) except for CO2 and AV. Studied preschools had higher PM and CO concentration. FVC, FEV1, FVC% and FEV1% predicted values were significantly lower among studied group. Exposures to PM, VOCs, and CO were associated with wheezing. Conclusion. The finding concluded that exposures to poor IAQ might increase the risk of getting lung function abnormality and respiratory problems among study respondents. PMID:25984527

Automated localization of costophrenic recesses and costophrenic angle measurement on frontal chest radiographs

NASA Astrophysics Data System (ADS)

Maduskar, Pragnya; Hogeweg, Laurens; Philipsen, Rick; van Ginneken, Bram

2013-03-01

Computer aided detection (CAD) of tuberculosis (TB) on chest radiographs (CXR) is difficult because the disease has varied manifestations, like opacification, hilar elevation, and pleural effusions. We have developed a CAD research prototype for TB (CAD4TB v1.08, Diagnostic Image Analysis Group, Nijmegen, The Netherlands) which is trained to detect textural abnormalities inside unobscured lung fields. If the only abnormality visible on a CXR would be a blunt costophrenic angle, caused by pleural fluid in the costophrenic recess, this is likely to be missed by texture analysis in the lung fields. The goal of this work is therefore to detect the presence of blunt costophrenic (CP) angles caused by pleural effusion on chest radiographs. The CP angle is the angle formed by the hemidiaphragm and the chest wall. We define the intersection point of both as the CP angle point. We first detect the CP angle point automatically from a lung field segmentation by finding the foreground pixel of each lung with maximum y location. Patches are extracted around the CP angle point and boundary tracing is performed to detect 10 consecutive pixels along the hemidiaphragm and the chest wall and derive the CP angle from these. We evaluate the method on a data set of 250 normal CXRs, 200 CXRs with only one or two blunt CP angles and 200 CXRs with one or two blunt CP angles but also other abnormalities. For these three groups, the CP angle location and angle measurements were accurate in 91%, 88%, and 92% of all the cases, respectively. The average CP angles for the three groups are indeed different with 71.6° +/- 22.9, 87.5° +/- 25.7, and 87.7° +/- 25.3, respectively.

Epithelial to mesenchymal transition-related proteins ZEB1, β-catenin, and β-tubulin-III in idiopathic pulmonary fibrosis.

PubMed

Chilosi, Marco; Caliò, Anna; Rossi, Andrea; Gilioli, Eliana; Pedica, Federica; Montagna, Licia; Pedron, Serena; Confalonieri, Marco; Doglioni, Claudio; Ziesche, Rolf; Grubinger, Markus; Mikulits, Wolfgang; Poletti, Venerino

2017-01-01

Epithelial to mesenchymal transition has been suggested as a relevant contributor to pulmonary fibrosis, but how and where this complex process is triggered in idiopathic pulmonary fibrosis is not fully understood. Beta-tubulin-III (Tubβ3), ZEB1, and β-catenin are partially under the negative control of miR-200, a family of micro-RNAs playing a major role in epithelial to mesenchymal transition, that are reduced in experimental lung fibrosis and idiopathic pulmonary fibrosis. We wonder whether in situ expression of these proteins is increased in idiopathic pulmonary fibrosis, to better understand the significance of miR-200 feedback loop and epithelial to mesenchymal transition. We investigated the immunohistochemical and immunofluorescent expression and precise location of ZEB1, Tubβ3, and β-catenin in tissue samples from 34 idiopathic pulmonary fibrosis cases and 21 controls (5 normal lungs and 16 other interstitial lung diseases). In 100% idiopathic pulmonary fibrosis samples, the three proteins were concurrently expressed in fibroblastic foci, as well in damaged epithelial cells overlying these lesions and in pericytes within neo-angiogenesis areas. These results were also confirmed by immunofluorescence assay. In controls the abnormal expression of the three proteins was absent or limited. This is the first study that relates concurrent expression of Tubβ3, ZEB1, and β-catenin to abnormal epithelial and myofibroblast differentiation in idiopathic pulmonary fibrosis, providing indirect but robust evidence of miR-200 deregulation and epithelial to mesenchymal transition activation in idiopathic pulmonary fibrosis. The abnormal expression and localization of these proteins in bronchiolar fibro-proliferative lesions are unique for idiopathic pulmonary fibrosis, and might represent a disease-specific marker in challenging lung biopsies.

Horner syndrome

MedlinePlus

... to a part of the brain called the brainstem Tumor in the top of the lung Injections ... 424. Thurtell MJ, Rucker JC. Pupillary and eyelid abnormalities. In: Daroff RB, Jankovic J, Mazziotta JC, Pomeroy ...

A Case of Transient Pulmonary Interstitial Lesions in Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorder.

PubMed

Asato, Yuko; Kamitani, Toshiaki; Ootsuka, Kuniyuki; Kuramochi, Mizuki; Nakanishi, Kozo; Shimada, Tetsuya; Takahashi, Toshiyuki; Misu, Tatsuro; Aoki, Masashi; Fujihara, Kazuo; Kawabata, Yoshinori

2018-05-18

We herein report the case of a 76-year old man with aquaporin-4-Immunoglobulin-G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), in whom transient interstitial pulmonary lesions developed at the early stage of the disease. Chest X-ray showed multiple infiltrative shadows in both upper lung fields, and computed tomography revealed abnormal shadows distributed randomly in the lungs. Surgical lung biopsy showed features of unclassifiable interstitial pneumonia, characterized by various types of air-space organization, which resulted in obscure lung structure. This is the first report to describe the pathological findings of interstitial pneumonia, which may represent a rare extra-central nervous system complication of NMOSD.

Multiple myeloma associated with acquired cutis laxa.

PubMed

Cho, S Y; Maguire, R F

1980-08-01

Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

Homogeneous immunoglobulins in the sera of lung carcinoma patients receiving cytotoxic chemotherapy--detection with the use of isoelectric focusing and immunoblotting.

PubMed Central

Haas, H; Lange, A; Schlaak, M

1987-01-01

Using isoelectric focusing (IEF) with immunoblotting, we have analysed serum immunoglobulins of 15 lung cancer patients on cytotoxic chemotherapy. In five of the patients homogeneous immunoglobulins were found which appeared between 9 and 18 months after beginning of treatment and were monoclonal in two and oligoclonal in three cases. These abnormalities were only partially shown by zonal electrophoresis with immunofixation and not detected by immune electrophoresis. Examination of 10 normal and 10 myeloma sera by the three techniques in parallel confirmed the competence and sensitivity of IEF with immunoblotting in detecting homogeneous immunoglobulins. Thus, this method provides a valuable tool for investigating an abnormal regulation of the immunoglobulin synthesis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:3325203

[The value of the x-ray findings in the follow-up of the adult respiratory distress syndrome. A retrospective analysis].

PubMed

Konrad, H; Schild, H; Weilemann, L S; Lorenz, J

1992-09-01

Serial chest x-rays of 23 ARDS patients, taken in an 24 hour interval, were retrospectively analysed. Radiographic patterns of ARDS were divided into five stages and were related to corresponding parameters of respiratory status. Characteristic findings on chest x-ray films occurred after a short latency period following the clinical onset of ARDS. There was a close relationship between the time of maximum radiographic changes and maximum loss of lung function. The progression through successive radiologic stages was in many cases accompanied by a significant deterioration of functional parameters. Distinction between survivors and non-survivors was achieved while considering maximum radiographic abnormalities. The results suggest significance of serial chest x-rays in diagnosis and course estimation of ARDS.

Metabolic Alkalosis in Adults with Stable Cystic Fibrosis

PubMed Central

Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

2012-01-01

Background: The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Methods: Retrospective chart review. Results: Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Conclusions: Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract. PMID:22905070

Metabolic alkalosis in adults with stable cystic fibrosis.

PubMed

Al-Ghimlas, Fahad; Faughnan, Marie E; Tullis, Elizabeth

2012-01-01

The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown. Retrospective chart review. Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis. Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.

Health risk assessment due to biomass smoke exposure in Indian indoor environment: An empirical approach using lung deposition model.

PubMed

Tigala, Snehlata; Sharma, Anu Rani; Sachdeva, Kamna

2018-06-04

The paper subsumes a framework that assesses health risk due to exposure to different fuel combustion through articulation of modern microscopic techniques, empirical equations, lung diagnostic tools and a pre-existing model that has been extrapolated to futuristic aspects (within controlled conditions). The framework was tested on 132 household cooks belonging to different age groups and using different types of fuel. The inhalable fraction released during fuel combustion varied in morphological characteristics and deposition site. Micrographs obtained using Scanning Electron Microscope (SEM) analysis of (biomass smoke) soot indicates aggregate formation attributing to a higher level of health risk. Further, abnormal ventilatory function along with higher risk (RR > 1) was more evident within biomass fuel users. The condition further exacerbates while using dung cakes due to high levels of emissions (294.3 particles/liter) that deposit in the upper respiratory tract (0.0899). Further, the population attributable risk percent (79%) calculated on the basis of cooking behavior suggests a 'rural culture' health determinant as clean fuel usage is not practiced as an outcome of low literacy and poor income in the region. These preliminary findings highlight the drudgery of impuissant women who are exposed to high particulate emissions on a regular basis which results in reduced lung function. Nevertheless, further cogitation is required to eliminate the limitations in this study and explore further linkages between exposure and vulnerable group to generate meaningful policy recommendations. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of innate defense proteins BPIFA1 and BPIFB1 with disease severity in COPD

PubMed Central

De Smet, Elise G; Seys, Leen JM; Verhamme, Fien M; Vanaudenaerde, Bart M; Brusselle, Guy G; Bingle, Colin D; Bracke, Ken R

2018-01-01

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal inflammatory response in the lungs caused by the inhalation of noxious particles and gases. The airway epithelium has a protective function against these harmful agents by maintaining a physical barrier and by secreting defensive proteins, such as bactericidal/permeability-increasing fold-containing (BPIF) proteins, BPIFA1 and BPIFB1. However, inconsistent data regarding BPIFA1 expression in smokers and COPD patients have been reported to date. Therefore, we investigated the expression of BPIFA1 and BPIFB1 in a large cohort of never-smokers and smokers with and without COPD, both on the messenger RNA (mRNA) level in lung tissue and on the protein level in airway epithelium. Furthermore, we examined the correlation between BPIFA1 and BPIFB1 levels, goblet cell hyperplasia, and lung function measurements. BPIFA1 and BPIFB1 mRNA expressions were significantly increased in stage III–IV COPD patients compared with stage II COPD patients and subjects without COPD. In addition, protein levels in COPD patients were significantly increased in comparison with subjects without COPD. BPIFA1 and BPIFB1 levels were inversely correlated with measurements of airflow limitation and positively correlated with goblet cell hyperplasia. In addition, by the use of immunofluorescence double staining, we demonstrated the expression of BPIFB1 in goblet cells. In conclusion, we show that BPIFA1 and BPIFB1 levels are elevated in COPD patients and correlate with disease severity. PMID:29296079

Uterine-Specific Loss of Tsc2 Leads to Myometrial Tumors in Both the Uterus and Lungs

PubMed Central

Prizant, Hen; Sen, Aritro; Light, Allison; Cho, Sung-Nam; DeMayo, Francesco J.; Lydon, John P.

2013-01-01

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by proliferation of abnormal smooth-muscle cells in the lungs, leading to functional loss and sometimes lung transplantation. Although the origin of LAM cells is unknown, several features of LAM provide clues. First, LAM cells contain inactivating mutations in genes encoding Tsc1 or Tsc2, proteins that limit mTORC1 activity. Second, LAM tumors recur after lung transplantation, suggesting a metastatic pathogenesis. Third, LAM is found almost exclusively in women. Finally, LAM shares features with uterine leiomyomas, benign tumors of myometrial cells. From these observations, we proposed that LAM cells might originate from uterine leiomyomas containing Tsc mutations. To test our hypothesis, and to develop mouse models for leiomyoma and LAM, we targeted Tsc2 deletion primarily in uterine cells. In fact, nearly 100% of uteri from uterine-specific Tsc2 knockout mice developed myometrial proliferation and uterine leiomyomas by 12 and 24 weeks, respectively. Myometrial proliferation and mTORC1/S6 activity were abrogated by the mTORC1 inhibitor rapamycin or by elimination of sex steroid production through ovariectomy or aromatase inhibition. In ovariectomized Tsc2 null mice, mTORC1/S6 activity and myometrial growth were restored by estrogen but not progesterone. Thus, even without Tsc2, estrogen appears to be required for myometrial mTORC1/S6 signaling and proliferation. Finally, we found Tsc2 null myometrial tumors in lungs of older Tsc2 uterine-specific knockout females, suggesting that lung LAM-like myometrial lesions may indeed originate from the uterus. This mouse model may improve our understanding of LAM and leiomyomas and might lead to novel therapeutic strategies for both diseases. PMID:23820898

The increasing incidence of foetal echogenic congenital lung malformations: an observational study.

PubMed

Stocker, Linden J; Wellesley, Diana G; Stanton, Michael P; Parasuraman, Rajeswari; Howe, David T

2015-02-01

The aim of this study was to investigate the incidence of congenital lung malformations over the past 19 years. Congenital lung malformations (CLM) are a heterogeneous group of lung abnormalities. The antenatal diagnosis is important for foetal and neonatal management but there have been no studies examining whether the reported incidence of this abnormality is constant. A retrospective cross-sectional study of cases identified from the Wessex Antenatally Detected Anomalies (WANDA) register 1994-2012. One hundred and thirty-three cases of CLM in 524 372 live and stillbirths were identified. All but seven were identified on antenatal ultrasound. During the early registry (1994-1998) the average incidence of CLM was 1.27 per 10,000 births. By the last 4 years (2008-2012) this had risen to 4.15 per 10,000 births, with a progressive increase during the intervening years. There was over a three-fold increase in the antenatally detected CLM in the Wessex region 1994-2012. Comparison with the antenatal detection of diaphragmatic hernia suggests that this is a true rise in incidence rather than an artefactual increase due to increased antenatal recognition secondary to improved ultrasound resolution and operator experience. These results have clinical and cost implications for practitioners of foetal medicine, neonatology and paediatric surgery services. © 2014 John Wiley & Sons, Ltd.

Hair Loss (Alopecia)

MedlinePlus

... Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental ... with certain abnormalities of the nails and the teeth. Later in childhood, hair loss may be due ...

Evaluation of Functional Limitations in Female Soccer Players and Their Relationship with Sports Level – A Cross Sectional Study

PubMed Central

Grygorowicz, Monika; Piontek, Tomasz; Dudzinski, Witold

2013-01-01

The main objective(s) of the study The aim of this study was to analyze: a) abnormalities in the length of lower limb muscles, b) the correctness of movement patterns, and c) the impact of functional limitations of muscles on the correctness of fundamental movement patterns in a group of female soccer players, in relation to their skill level. Materials and Methods 21 female soccer players from Polish Ekstraklasa and 22 players from the 1st Division were tested for lower limb muscle length restrictions and level of fundamental movement skills (with the Fundamental Movement Screen™ test concept by Gray Cook). Chi-square test was used for categorical unrelated variables. Differences between groups in absolute point values were analyzed using the non-parametric Mann-Whitney U test. Statistical significance was set at p<0.05. Results Statistically significant higher number of measurements indicating an abnormal length of rectus femoris was observed in the 1st Division group (p = 0.0433). In the group of Ekstraklasa the authors obtained a significantly higher number of abnormal hamstring test results (p = 0.0006). Ekstraklasa players scored higher in the rotational stability test of the trunk (p = 0.0008), whereas the 1st Division players scored higher in the following tests: deep squat (p = 0.0220), in-line lunge (p = 0.0042) and active straight leg raise (p = 0.0125). The results suggest that there are different functional reasons affecting point values obtained in the FMS™ tests in both analyzed groups. Conclusions The differences in the flexibility of rectus femoris and hamstring muscle observed between female soccer players with different levels of training, may result from a long-term impact of soccer training on the muscle-tendon system and articular structures. Different causes of abnormalities in fundamental movement patterns in both analyzed groups suggest the need for tailoring prevention programs to the level of sport skills represented by the players. PMID:23825579

Computation of ventilation-perfusion ratio with Kr-81m in pulmonary embolism

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

Meignan, M.; Simonneau, G.; Oliveira, L.

1984-02-01

Diagnostic difficulties occur in pulmonary embolism (PE) during visual analysis of ventilation-perfusion images in matched defects or in chronic obstructive lung disease (COPD). In 44 patients with angiographically confirmed PE and in 40 patients with COPD, the regional ventilation-perfusion ratios (V/Q) were therefore computed using krypton-81m for each perfusion defect, and were displayed in a functional image. In patients with PE and mismatched defects, a high V/Q (1.96) was observed. A V/Q > 1.25 was also found in nine of 11 patients having PE and indeterminate studies (studies with perfusion abnormalities matched by radiographic abnormalities). COPD was characterized by matchedmore » defects and low V/Q. The percentage of patients correctly classified as having PE or COPD increased from 56% when considering the match or mismatched character to 88% when based on a V/Q of 1.25 in the region of the perfusion defect. This quantitative analysis, therefore, seems useful in classifying patients with scintigraphic suspicion of PE.« less

Texture classification of lung computed tomography images

NASA Astrophysics Data System (ADS)

Pheng, Hang See; Shamsuddin, Siti M.

2013-03-01

Current development of algorithms in computer-aided diagnosis (CAD) scheme is growing rapidly to assist the radiologist in medical image interpretation. Texture analysis of computed tomography (CT) scans is one of important preliminary stage in the computerized detection system and classification for lung cancer. Among different types of images features analysis, Haralick texture with variety of statistical measures has been used widely in image texture description. The extraction of texture feature values is essential to be used by a CAD especially in classification of the normal and abnormal tissue on the cross sectional CT images. This paper aims to compare experimental results using texture extraction and different machine leaning methods in the classification normal and abnormal tissues through lung CT images. The machine learning methods involve in this assessment are Artificial Immune Recognition System (AIRS), Naive Bayes, Decision Tree (J48) and Backpropagation Neural Network. AIRS is found to provide high accuracy (99.2%) and sensitivity (98.0%) in the assessment. For experiments and testing purpose, publicly available datasets in the Reference Image Database to Evaluate Therapy Response (RIDER) are used as study cases.

Dabrafenib

MedlinePlus

... to treat a certain type of non-small cell lung cancer (NSCLC) that has spread to nearby tissues or ... the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of ...

Trametinib

MedlinePlus

... to treat a certain type of non-small-cell lung cancer (NSCLC) that has spread to nearby tissues or ... the action of an abnormal protein that signals cancer cells to multiply. This helps stop the spread of ...

Brigatinib

MedlinePlus

... to treat a certain type of non-small cell lung cancer (NSCLC) that has spread to other parts of ... the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the ...

Alectinib

MedlinePlus

... to treat a certain type of non-small-cell lung cancer (NSCLC) that has spread to other parts of ... the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the ...

Erlotinib

MedlinePlus

... used to treat certain types of non-small cell lung cancer that has spread to nearby tissues or to ... the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the ...

Do nanoparticles provide a new opportunity for diagnosis of distal airspace disease?

PubMed Central

Löndahl, Jakob; Jakobsson, Jonas KF; Broday, David M; Aaltonen, H Laura; Wollmer, Per

2017-01-01

There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4–1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide (DL,CO), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology. PMID:28053522

Do nanoparticles provide a new opportunity for diagnosis of distal airspace disease?

PubMed

Löndahl, Jakob; Jakobsson, Jonas Kf; Broday, David M; Aaltonen, H Laura; Wollmer, Per

There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4-1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide ( D L,CO ), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology.

[The role of spirometry in encouraging smoking cessation in general practice. A pilot study using "lung age"].

PubMed

Lorenzo, A; Noël, F; Lorenzo, M; Van Den Broucke, J

2017-09-01

Our aim was to investigate whether spirometry, performed in general practitioners' offices would change non-motivated smokers' attitudes toward smoking cessation. We performed an interventional, prospective, before-after single-center study, approved by a research ethics committee. We included 74 smokers older than 18years old, who reported no intention to quit smoking, whatever they were visiting general practitioners for. We performed spirometry and gave them their results, FEV 1 /FVC and lung age together with a comment on it. Nine months later, we called them for another assessment. Fifty-six percent were women with an average-age of 46.5, who smoked 26.3 pack-years. Eighty-two percent of them had normal FEV 1 /FVC but lung age was pathological among 38% of them. Nine months later, 61.1% reported an increased motivation to quit smoking. They smoked 10.9 cigarettes per day versus 13,3 at baseline (P=0.0254). Increase in motivation was not statistically related to age, gender, previous smoking cessations, daily smoking, nicotine dependence or an abnormal FEV 1 /VC ratio (P>0.75) but was significantly related to the presence of an abnormal lung age status (P<0.03). This study suggests that spirometry in general practice, combined with the determination of the lung age, may increase motivation towards smoking cessation in smokers who lack motivation. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Nailfold capillary abnormalities in erectile dysfunction of systemic sclerosis: a EUSTAR group analysis.

PubMed

Keck, Andrea D; Foocharoen, Chingching; Rosato, Edoardo; Smith, Vanessa; Allanore, Yannick; Distler, Oliver; Stamenkovic, Bojana; Pereira Da Silva, José Antonio; Hadj Khelifa, Sondess; Denisov, Lev N; Hachulla, Eric; García de la Peña Lefebvre, Paloma; Sibilia, Jean; Airò, Paolo; Caramaschi, Paola; Müller-Ladner, Ulf; Wiland, Piotr; Walker, Ulrich A

2014-04-01

The objective of this study was to analyse an association between nailfold capillary abnormalities and the presence and severity of erectile dysfunction (ED) in men with SSc. A cross-sectional analysis of the prospective European League Against Rheumatism (EULAR) Scleroderma Trial and Research database was performed. Men with SSc were included if they had undergone nailfold capillaroscopy and simultaneous ED assessment with the 5-item International Index for Erectile Function (IIEF-5). Eighty-six men met the inclusion criteria. Eight men (9.3%) had not had sexual intercourse and could not be assigned an IIEF-5 score. Sixty-nine of the 78 men (88.5%) with an IIEF-5 score had nailfold capillary abnormalities, of whom 54 (78.3%) suffered from ED. Nine men (11.5%) had no nailfold capillary abnormalities, of whom six (66.7%) had ED (P = 0.44). ED was more frequent in older men (P = 0.002) and in men with diffuse disease (P = 0.06). Men with abnormal capillaroscopy had a higher median EULAR disease activity than men without (P = 0.02), a lower diffusing capacity of the lung (P = 0.001) and a higher modified Rodnan skin score (P = 0.04), but mean IIEF-5 scores did not differ [15.7 (S.D. 6.2) vs 15.7 (S.D. 6.3)]. IIEF-5 scores did not differ between men with early (n = 12), active (n = 27) or late (n = 27) patterns (IIEF-5 scores of 17.9, 16.3 and 14.7, respectively). There were no differences in the prevalence of early, active and late capillaroscopy patterns between men with or without ED. Neither the presence or absence of abnormal capillaroscopy findings nor the subdivision into early, active and late patterns is associated with coexistent ED in SSc.

Endoscopic sensing of pH in the distal lung (Conference Presentation)

NASA Astrophysics Data System (ADS)

Choudhury, Debaditya; Tanner, Michael G.; McAughtrie, Sarah; Yu, Fei; Mills, Bethany; Choudhary, Tushar R.; Seth, Sohan; Craven, Thomas; Stone, James M.; Mati, Ioulia K.; Campbell, Colin J.; Bradley, Mark; Williams, Christopher K.; Dhaliwal, Kevin; Birks, Timothy A.; Thomson, Robert R.

2017-04-01

In healthy humans, the physiological state in the distal lung alveolar acinar units is tightly regulated by normal homeostatic mechanisms. Pulmonary abnormalities such as chronic obstructive pulmonary disease, that are characterized by recurrent cycles of inflammation and infection involving dense infiltration by myeloid derived peripheral blood cells, may result in significant perturbation of the homeostatic baselines of physiology in addition to host tissue damage. Therefore, the ability to quantify and monitor physiology (e.g. pH, glucose level, oxygen tension) within the alveolar acinar units would provide a key biomarker of distal lung innate defence. Although in vitro modeling of fundamental biological processes show remarkable sensitivity to physiological aberrations, little is known about the physiological state of the distal lung due to the inability to concurrently access the alveolar sacs and perform real-time sensing. Here we report on previously unobtainable measurements of alveolar pH using a fiber-optic optrode and surface enhanced Raman spectroscopy (SERS) and show that alveolar pH changes in response to ventilation. The endoscope-deployable optrode consisted of para-mercaptobenzoic acid functionalized 150 nm gold nanoshells located at the distal end, and an asymmetric dual-core optical fiber designed for spatially separated optical pump delivery and SERS signal collection in order to circumvent the unwanted Raman signal originating from the fiber itself. We demonstrate a 100-fold increase in SERS signal-to-fiber background ratio and pH sensing at multiple sites in the respiratory acinar units of a whole ex vivo ovine lung model with a measurement accuracy of ± 0.07 pH units.

RGS4 Overexpression in Lung Attenuates Airway Hyperresponsiveness in Mice.

PubMed

Madigan, Laura A; Wong, Gordon S; Gordon, Elizabeth M; Chen, Wei-Sheng; Balenga, Nariman; Koziol-White, Cynthia J; Panettieri, Reynold A; Levine, Stewart J; Druey, Kirk M

2018-01-01

A cardinal feature of asthma is airway hyperresponsiveness (AHR) to spasmogens, many of which activate G protein-coupled receptors (GPCRs) on airway smooth muscle (ASM) cells. Asthma subtypes associated with allergy are characterized by eosinophilic inflammation in the lung due to the type 2 immune response to allergens and proinflammatory mediators that promote AHR. The degree to which intrinsic abnormalities of ASM contribute to this phenotype remains unknown. The regulators of G protein signaling (RGS) proteins are a large group of intracellular proteins that inhibit GPCR signaling pathways. RGS2- and RGS5-deficient mice develop AHR spontaneously. Although RGS4 is upregulated in ASM from patients with severe asthma, the effects of increased RGS4 expression on AHR in vivo are unknown. Here, we examined the impact of forced RGS4 overexpression in lung on AHR using transgenic (Tg) mice. Tg RGS4 was expressed in bronchial epithelium and ASM in vivo, and protein expression in lung was increased at least 4-fold in Tg mice compared with wild-type (WT) mice. Lung slices from Tg mice contracted less in response to the m3 muscarinic receptor agonist methacholine compared with the WT, although airway resistance in live, unchallenged mice of both strains was similar. Tg mice were partially protected against AHR induced by fungal allergen challenge due to weakened contraction signaling in ASM and reduced type 2 cytokine (IL-5 and IL-13) levels in Tg mice compared with the WT. These results provide support for the hypothesis that increasing RGS4 expression and/or function could be a viable therapeutic strategy for asthma.

Toxicity of Paraquat and Diquat Aerosols Generated by a Size-selective Cyclone: Effect of Particle Size Distribution

PubMed Central

Gage, J. C.

1968-01-01

The toxicity of paraquat and diquat aerosols to several species has been investigated. In order to obtain an atmosphere of `respirable' particles, an atomizer has been constructed with an upper cut-off of size by a cyclone separator, and with a calibrated reservoir to enable the concentration output to be estimated by inspection. Paraquat has an irritant action on the lungs, and at lethal concentrations death is delayed and is associated with pulmonary haemorrhage and oedema. After single exposures the LC50 appears to be a function of the duration and of the concentration; in the rat the lethal concentration-time product (CT) is about 6 μg./l.hr. Guinea-pigs and male mice are about as sensitive as rats. Female mice and rabbits are less sensitive. The dog can tolerate a CT product of 25 μg./l. hr without ill-effects. The toxicity is a complex function of particle size. In the rat it appears that the most effective size is in the region of 3 μ, as larger particles do not reach the alveolar regions and finer particles are probably not retained there. Repeated daily 6-hr exposures of rats to paraquat aerosols over a three-week period produce signs of lung irritation but no deaths at 0·4 μg./l., and the no-effect level is about 0·1 μg./litre. Paraquat appears to be poorly absorbed from the lungs. After single exposures death is associated with a paraquat content of about 6 μg. in the lungs. Paraquat is subsequently cleared from the lung with a half-life of about 36 hr. Diquat is much less irritant to the lungs than is paraquat; the no-effect levels on single and repeated exposure are at least five times larger. It is concluded that paraquat and diquat do not present an inhalation hazard under normal conditions of application, but with paraquat under abnormal conditions it may be desirable to provide respiratory protection. Images PMID:5723352

WE-AB-202-04: Statistical Evaluation of Lung Function Using 4DCT Ventilation Imaging: Proton Therapy VS IMRT

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

Huang, Q; Zhang, M; Chen, T

Purpose: Variation in function of different lung regions has been ignored so far for conventional lung cancer treatment planning, which may lead to higher risk of radiation induced lung disease. 4DCT based lung ventilation imaging provides a novel yet convenient approach for lung functional imaging as 4DCT is taken as routine for lung cancer treatment. Our work aims to evaluate the impact of accounting for spatial heterogeneity in lung function using 4DCT based lung ventilation imaging for proton and IMRT plans. Methods: Six patients with advanced stage lung cancer of various tumor locations were retrospectively evaluated for the study. Protonmore » and IMRT plans were designed following identical planning objective and constrains for each patient. Ventilation images were calculated from patients’ 4DCT using deformable image registration implemented by Velocity AI software based on Jacobian-metrics. Lung was delineated into two function level regions based on ventilation (low and high functional area). High functional region was defined as lung ventilation greater than 30%. Dose distribution and statistics in different lung function area was calculated for patients. Results: Variation in dosimetric statistics of different function lung region was observed between proton and IMRT plans. In all proton plans, high function lung regions receive lower maximum dose (100.2%–108.9%), compared with IMRT plans (106.4%–119.7%). Interestingly, three out of six proton plans gave higher mean dose by up to 2.2% than IMRT to high function lung region. Lower mean dose (lower by up to 14.1%) and maximum dose (lower by up to 9%) were observed in low function lung for proton plans. Conclusion: A systematic approach was developed to generate function lung ventilation imaging and use it to evaluate plans. This method hold great promise in function analysis of lung during planning. We are currently studying more subjects to evaluate this tool.« less

[Application of the computer-based respiratory sound analysis system based on Mel-frequency cepstral coefficient and dynamic time warping in healthy children].

PubMed

Yan, W Y; Li, L; Yang, Y G; Lin, X L; Wu, J Z

2016-08-01

We designed a computer-based respiratory sound analysis system to identify pediatric normal lung sound. To verify the validity of the computer-based respiratory sound analysis system. First we downloaded the standard lung sounds from the network database (website: http: //www.easyauscultation.com/lung-sounds-reference-guide) and recorded 3 samples of abnormal loud sound (rhonchi, wheeze and crackles) from three patients of The Department of Pediatrics, the First Affiliated Hospital of Xiamen University. We regarded such lung sounds as"reference lung sounds". The"test lung sounds"were recorded from 29 children form Kindergarten of Xiamen University. we recorded lung sound by portable electronic stethoscope and valid lung sounds were selected by manual identification. We introduced Mel-frequency cepstral coefficient (MFCC) to extract lung sound features and dynamic time warping (DTW) for signal classification. We had 39 standard lung sounds, recorded 58 test lung sounds. This computer-based respiratory sound analysis system was carried out in 58 lung sound recognition, correct identification of 52 times, error identification 6 times. Accuracy was 89.7%. Based on MFCC and DTW, our computer-based respiratory sound analysis system can effectively identify healthy lung sounds of children (accuracy can reach 89.7%), fully embodies the reliability of the lung sounds analysis system.

Polio

MedlinePlus

... severe they are. Treatment may include: Antibiotics for urinary tract infections Moist heat (heating pads, warm towels) to reduce ... abnormal buildup of fluid in the lungs) Shock Urinary tract infections Post-polio syndrome is a complication that develops ...

Chronic pulmonary interstitial fibrosis in a blue-fronted Amazon parrot (Amazona aestiva aestiva).

PubMed

Amann, Olga; Kik, Marja J L; Passon-Vastenburg, Maartje H A C; Westerhof, Ineke; Lumeij, Johannes T; Schoemaker, Nico J

2007-03-01

A 30-yr-old blue-fronted Amazon parrot (Amazon aestiva aestiva) was presented to the clinic with a history of sneezing more often during the last 2 mo. Physical examination revealed only a mild nasal discharge. Complete hematologic and plasma biochemical examination showed no abnormalities. Computerized tomography (CT) of the complete bird showed generalized lung alterations consistent with lung fibrosis. Two lung biopsies were taken. The results of the histologic examination of the biopsies confirmed the tentative CT diagnosis of pulmonary interstitial fibrosis. To our knowledge this is the first reported case of chronic pulmonary interstitial fibrosis diagnosed by means of a lung biopsy in an avian species. The histologic characteristics are discussed and compared with those of human idiopathic pulmonary fibrosis.

A case of systemic arterial supply to the right lower lobe of the lung: imaging findings and review of the literature.

PubMed

Mautone, Marcela; Naidoo, Parm

2014-03-01

Systemic arterialization of the lung without pulmonary sequestration is the rarest form of anomalous systemic arterial supply to the lung. This condition is characterised by an aberrant arterial branch arising from the aorta which supplies an area of lung parenchyma with normal bronchopulmonary anatomy. It is often diagnosed following investigation of an incidental cardiac murmur or based on abnormal imaging, as most patients are asymptomatic or minimally symptomatic. Thoracic computed tomography and computed tomography angiography are generally the most useful diagnostic tests. We present a case of a 22-year old female who was diagnosed with systemic arterial supply to a portion of otherwise normal right lower lobe following investigation of low volume haemoptysis.

Measurement and classification of heart and lung sounds by using LabView for educational use.

PubMed

Altrabsheh, B

2010-01-01

This study presents the design, development and implementation of a simple low-cost method of phonocardiography signal detection. Human heart and lung signals are detected by using a simple microphone through a personal computer; the signals are recorded and analysed using LabView software. Amplitude and frequency analyses are carried out for various phonocardiography pathological cases. Methods for automatic classification of normal and abnormal heart sounds, murmurs and lung sounds are presented. Various cases of heart and lung sound measurement are recorded and analysed. The measurements can be saved for further analysis. The method in this study can be used by doctors as a detection tool aid and may be useful for teaching purposes at medical and nursing schools.

Primary mesenchymal or mixed-cell-origin lung tumors in four dogs.

PubMed

Watson, A D; Young, K M; Dubielzig, R R; Biller, D S

1993-03-15

Primary lung tumors of mesenchymal or mixed cell origin were diagnosed in 4 dogs with clinical and radiographic abnormalities indicating an intrathoracic mass. Each dog had 1 large intrapulmonary lesion, and 1 dog also had nodules scattered throughout all lung lobes. Two dogs were euthanatized; 1 had a biphasic pulmonary blastoma; and the other had a pulmonary chondroblastic osteosarcoma with intrapulmonary metastases. The masses in the other 2 dogs were hamartomas (lipomatous in 1, microcystic in the other), which were resected. Both dogs survived more than 1 year after surgery. Primary lung tumors are uncommon in dogs and are generally malignant (adenocarcinomas or carcinomas). Tumors of connective tissue or mixed cell origin are rare, but the outcome is potentially good after surgical removal.

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

PubMed Central

Mora, Ana L.; Rojas, Mauricio

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with high mortality that is characterized by abnormal scarring of the lung parenchyma. There has been a recent attempt to define the age-associated changes predisposing individuals to develop IPF. Age-related perturbations that are increasingly found in epithelial cells and fibroblasts from IPF lungs compared with age-matched cells from normal lungs include defective autophagy, telomere attrition, altered proteostasis, and cell senescence. These divergent processes seem to converge in mitochondrial dysfunction and metabolic distress, which potentiate maladaptation to stress and susceptibility to age-related diseases such as IPF. Therapeutic approaches that target aging processes may be beneficial for halting the progression of disease and improving quality of life in IPF patients. PMID:28145905

Alveolar abnormalities

MedlinePlus

Albertine KH. Anatomy of the lungs. In: Broaddus VC, Mason RJ, Ernst JD, et al, eds. Murray and Nadel's Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 1. Hall JE. Respiratory insufficiency - pathophysiology, diagnosis, ...

Early Diagnosis of Respiratory Abnormalities in Asbestos-Exposed Workers by the Forced Oscillation Technique.

PubMed

de Sá, Paula Morisco; Castro, Hermano Albuquerque; Lopes, Agnaldo José; Melo, Pedro Lopes de

2016-01-01

The current reference test for the detection of respiratory abnormalities in asbestos-exposed workers is spirometry. However, spirometry has several shortcomings that greatly affect the efficacy of current asbestos control programs. The forced oscillation technique (FOT) represents the current state-of-the-art technique in the assessment of lung function. This method provides a detailed analysis of respiratory resistance and reactance at different oscillatory frequencies during tidal breathing. Here, we evaluate the FOT as an alternative method to standard spirometry for the early detection and quantification of respiratory abnormalities in asbestos-exposed workers. Seventy-two subjects were analyzed. The control group was composed of 33 subjects with a normal spirometric exam who had no history of smoking or pulmonary disease. Thirty-nine subjects exposed to asbestos were also studied, including 32 volunteers in radiological category 0/0 and 7 volunteers with radiological categories of 0/1 or 1/1. FOT data were interpreted using classical parameters as well as integer (InOr) and fractional-order (FrOr) modeling. The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC). Exposed workers presented increased obstruction (resistance p<0.001) and a reduced compliance (p<0.001), with a predominance of obstructive changes. The FOT parameter changes were correlated with the standard pulmonary function analysis methods (R = -0.52, p<0.001). Early respiratory abnormalities were identified with a high diagnostic accuracy (AUC = 0.987) using parameters obtained from the FrOr modeling. This accuracy was significantly better than those obtained with classical (p<0.001) and InOr (p<0.001) model parameters. The FOT improved our knowledge about the biomechanical abnormalities in workers exposed to asbestos. Additionally, a high diagnostic accuracy in the diagnosis of early respiratory abnormalities in asbestos-exposed workers was obtained. This makes the FOT particularly useful as a screening tool in the context of asbestos control and elimination. Moreover, it can facilitate epidemiological research and the longitudinal follow-up of asbestos exposure and asbestos-related diseases.

Thin-Section CT Features of Idiopathic Pulmonary Fibrosis Correlated with Micro-CT and Histologic Analysis.

PubMed

Mai, Cindy; Verleden, Stijn E; McDonough, John E; Willems, Stijn; De Wever, Walter; Coolen, Johan; Dubbeldam, Adriana; Van Raemdonck, Dirk E; Verbeken, Eric K; Verleden, Geert M; Hogg, James C; Vanaudenaerde, Bart M; Wuyts, Wim A; Verschakelen, Johny A

2017-04-01

Purpose To elucidate the underlying lung changes responsible for the computed tomographic (CT) features of idiopathic pulmonary fibrosis (IPF) and to gain insight into the way IPF proceeds through the lungs and progresses over time. Materials and Methods Micro-CT studies of tissue cores obtained from explant lungs were examined and were correlated 1:1 with a CT study obtained immediately before transplantation. Samples for histologic analysis were obtained from selected cores. Results In areas with no or minimal abnormalities on CT images, small areas of increased attenuation located in or near the interlobular septa can be seen on micro-CT studies. In more involved lung areas, the number of opacities increases and opacities enlarge and approach each other along the interlobular septa, causing a fine reticular pattern on CT images. Simultaneously, air-containing structures in and around these opacities arise, corresponding with small cysts on CT images. Honeycombing is caused by a progressive increase in the number and size of these cystic structures and tissue opacities that gradually extend toward the centrilobular region and finally replace the entire lobule. At histologic analysis, the small islands of increased attenuation very likely correspond with fibroblastic foci. Near these fibroblastic foci, an abnormal adjacency of alveolar walls was seen, suggesting alveolar collapse. In later stages, normal lung tissue is replaced by a large amount of young collagen, as seen in patients with advanced fibrosis. Conclusion Fibrosis and cyst formation in patients with IPF seem to start at the periphery of the pulmonary lobule and progressively extend toward the core of this anatomic lung unit. Evidence was found that alveolar collapse might already be present in an early stage when there is only little pulmonary fibrosis. © RSNA, 2016.

Thin-Section CT Features of Idiopathic Pulmonary Fibrosis Correlated with Micro-CT and Histologic Analysis

PubMed Central

Mai, Cindy; Verleden, Stijn E.; McDonough, John E.; Willems, Stijn; De Wever, Walter; Coolen, Johan; Dubbeldam, Adriana; Van Raemdonck, Dirk E.; Verbeken, Eric K.; Verleden, Geert M.; Hogg, James C.; Vanaudenaerde, Bart M.; Wuyts, Wim A.

2017-01-01

Purpose To elucidate the underlying lung changes responsible for the computed tomographic (CT) features of idiopathic pulmonary fibrosis (IPF) and to gain insight into the way IPF proceeds through the lungs and progresses over time. Materials and Methods Micro-CT studies of tissue cores obtained from explant lungs were examined and were correlated 1:1 with a CT study obtained immediately before transplantation. Samples for histologic analysis were obtained from selected cores. Results In areas with no or minimal abnormalities on CT images, small areas of increased attenuation located in or near the interlobular septa can be seen on micro-CT studies. In more involved lung areas, the number of opacities increases and opacities enlarge and approach each other along the interlobular septa, causing a fine reticular pattern on CT images. Simultaneously, air-containing structures in and around these opacities arise, corresponding with small cysts on CT images. Honeycombing is caused by a progressive increase in the number and size of these cystic structures and tissue opacities that gradually extend toward the centrilobular region and finally replace the entire lobule. At histologic analysis, the small islands of increased attenuation very likely correspond with fibroblastic foci. Near these fibroblastic foci, an abnormal adjacency of alveolar walls was seen, suggesting alveolar collapse. In later stages, normal lung tissue is replaced by a large amount of young collagen, as seen in patients with advanced fibrosis. Conclusion Fibrosis and cyst formation in patients with IPF seem to start at the periphery of the pulmonary lobule and progressively extend toward the core of this anatomic lung unit. Evidence was found that alveolar collapse might already be present in an early stage when there is only little pulmonary fibrosis. © RSNA, 2016 PMID:27715655

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

PubMed

Wielpütz, Mark O; von Stackelberg, Oyunbileg; Stahl, Mirjam; Jobst, Bertram J; Eichinger, Monika; Puderbach, Michael U; Nährlich, Lutz; Barth, Sandra; Schneider, Christian; Kopp, Matthias V; Ricklefs, Isabell; Buchholz, Michael; Tümmler, Burkhard; Dopfer, Christian; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich; Mall, Marcus A

2018-05-24

A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0-6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43-0.50, p < 0.01). Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

The number of lung transplants can be safely doubled using extended criteria donors; a single-center review.

PubMed

Meers, Caroline; Van Raemdonck, Dirk; Verleden, Geert M; Coosemans, Willy; Decaluwe, Herbert; De Leyn, Paul; Nafteux, Philippe; Lerut, Toni

2010-06-01

Relaxing the standard lung donor criteria may significantly increase the reported 15% organ yield but post-transplant recipient outcome should be carefully monitored. Charts from all consecutive deceased organ donors within our hospital network were reviewed over a 2-year period. Reasons for lung refusals and number of lungs transplanted were analysed. Hospital outcome including early recipient survival was compared between standard- and extended criteria donors. Out of 283 referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of these effective donors were declined for lung donation because of chest X-ray abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at our center, 23 from standard criteria donors versus 27 from extended criteria donors. There were no significant differences in hospital outcome and in early survival between lung recipients from both donor groups. Lung acceptance rate (34.1%) in our donor network is 10-20% higher than reported figures. The number of lung transplants in our center doubled by accepting extended criteria donors. This policy did not negatively influence our results after lung transplantation.

Microarray profiles reveal that circular RNA hsa_circ_0007385 functions as an oncogene in non-small cell lung cancer tumorigenesis.

PubMed

Jiang, Ming-Ming; Mai, Zhi-Tao; Wan, Shan-Zhi; Chi, Yu-Min; Zhang, Xin; Sun, Bao-Hua; Di, Qing-Guo

2018-04-01

Circular RNAs (circRNAs) are a novel class of non-protein-coding RNA. Emerging evidence indicates that circRNAs participate in the regulation of many pathophysiological processes. This study aims to explore the expression profiles and pathological effects of circRNAs in non-small cell lung cancer (NSCLC). Human circRNAs microarray analysis was performed to screen the expression profile of circRNAs in NSCLC tissue. Expressions of circRNA and miRNA in NSCLC tissues and cells were quantified by qRTPCR. Functional experiments were performed to investigate the biological functions of circRNA, including CCK-8 assay, colony formation assay, transwell assay and xenograft in vivo assay. Human circRNAs microarray revealed a total 957 abnormally expressed circRNAs (> twofold, P < 0.05) in NSCLC tissue compared with adjacent normal tissue. In further studies, hsa_circ_0007385 was significantly up regulated in NSCLC tissue and cells. In vitro experiments with hsa_circ_0007385 knockdown resulted in significant suppression of the proliferation, migration and invasion of NSCLC cells. In vivo xenograft assay using hsa_circ_0007385 knockdown, significantly reduced tumor growth. Bioinformatics analysis and luciferase reporter assay verified the potential target miR-181, suggesting a possible regulatory pathway for hsa_circ_0007385. In summary, results suggest hsa_circ_0007385 plays a role in NSCLC tumorigenesis, providing a potential therapeutic target for NSCLC.

Air Trapping on Chest CT Is Associated with Worse Ventilation Distribution in Infants with Cystic Fibrosis Diagnosed following Newborn Screening

PubMed Central

Hall, Graham L.; Logie, Karla M.; Parsons, Faith; Schulzke, Sven M.; Nolan, Gary; Murray, Conor; Ranganathan, Sarath; Robinson, Phil; Sly, Peter D.; Stick, Stephen M.

2011-01-01

Background In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF. Methods Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M1/M0 and M2/M0, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping. Results Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M2/M0 but not LCI or M1/M0. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes. Conclusion These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF. PMID:21886842

A non-aggregating Surfactant Protein C mutant is misdirected to early endosomes and disrupts phospholipid recycling

PubMed Central

Beers, Michael F.; Hawkins, Arie; Maguire, Jean Ann; Kotorashvili, Adam; Zhao, Ming; Newitt, Jennifer L.; Ding, Wenge; Russo, Scott; Guttentag, Susan; Gonzales, Linda; Mulugeta, Surafel

2011-01-01

Interstitial lung disease in both children and adults has been linked to mutations in the lung-specific Surfactant protein C gene (SFTPC). Among these, the missense mutation (isoleucine to threonine at codon 73 = hSP-CI73T) accounts for ~30% of all described SFTPC mutations. We reported previously that unlike the BRICHOS misfolding SFTPC mutants, expression of hSP-CI73T induces lung remodeling and alveolar lipoproteinosis without a substantial ER stress response or ER-mediated intrinsic apoptosis. We show here that, in contrast to its wild type counterpart that is directly routed to lysosomal-like organelles for processing, SP-CI73T is misdirected to the plasma membrane and subsequently internalized to the endocytic pathway via early endosomes, leading to the accumulation of abnormally processed proSP-C isoforms. Functionally, cells expressing hSP-CI73T demonstrated both impaired uptake and degradation of surfactant phospholipid, thus providing a molecular mechanism for the observed lipid accumulation in patients expressing hSP-CI73T through the disruption of normal phospholipid recycling. Our data provide evidence for a novel cellular mechanism for conformational protein associated diseases, and suggest a paradigm for mistargeted proteins involved in the disruption of the endosomal/lysosomal sorting machinery. PMID:21707890

[Effect of dust aerosol exposure on lung function and lung histopathology in rats].

PubMed

Lei, Fengfeng; Wang, Xuebin; Liu, Hua; Chen, Qizhang; Ma, Hui; Dong, Zhibao; Sang, Yingzhu

2015-08-25

To investigate the effect of dust aerosol exposure on lung function and lung histopathology in rats. According to random number table method, 120 Wistar male rats were divided into untreated control group, treated control group and experimental group, with 40 rats in each group. Experimental group were exposed to the wind tunnel simulation of sandstorm for 5 hours in every day; the untreated control group were put in the standard living environment next to the wind tunnel; the treated control group were exposed to the same wind tunnel simulation of sandstorm for 5 hours in every day, and the speed of wind was the same as the experimental group, but excluding dust. At different time points, the lung function and electron microscopy were performed in all rats. The level of Dynamic Compliance (Cdyn) ((0.227 ± 0.023), (0.198 ± 0.022) ml/cmH₂O, 1 cmH₂O=0.098 kPa) and forced vital capacity (FVC) ((6.24 ± 0.29), (5.59 ± 0.19) ml) were lower in the experimental group at 90 and 120 days, as compared to the untreated control group (Cdyn: (0.266 ± 0.014), (0.265 ± 0.018) ml/cmH2O; FVC: (7.15 ± 0.23), (7.17 ± 0.20) ml) and treated control group (Cdyn: (0.269 ± 0.015), (0.264 ± 0.019) ml/cmH2O; FVC: (7.14 ± 0.19), (7.15 ± 0.21) ml) (all P<0.05). At 120 days, The level of the forced expiratory flow after 50% of the FVC ((12.3 ± 2.2) ml/s) and peak expiratory flow ((25.79 ± 0.42) ml/s) were lower in the experimental group, as compared to the untreated control group ((15.9 ± 2.5), (27.99 ± 0.36) ml/s) and treated control group ((15.8 ± 2.1), (27.90 ± 0.38) ml/s) (all P<0.01). The FVC rate of 0.2 second in the experimental group was higher than that in the untreated control group and treated control group ( (85 ± 5)%, (73 ± 4)%, (73 ± 4)%, all P<0.05). The electron microscopy showed that the lung tissues had no obvious abnormalities at 30, 60, 90 and 120 days in untreated control group and treated control group. But in the experimental group, at 30 days, the endothelial cells of alveolar type I cells were swelled and the number of alveolar type II cells were increased; at 60 days, alveolar type II cells hyperplastic, basement membrane thinned and destructed; at 90 days, the number of alveolar type II cells decreased, Lamellar body evacuation; at 120 days, a lot of collagen fiber was formed in the alveolar septa. The strong sandstorm environmental exposure to a certain period of time can cause the decline of lung function and the damage of lung histopathology in rats. Exposure time was positively correlated with the damage of lung tissue.

Expression of pleiotrophin in small cell lung cancer.

PubMed

Wang, H Q; Wang, J

2015-01-01

Pleiotrophin (PTN) is a kind of heparin binding growth factor closely related to tumor progression. This study aimed to discuss the significance of the expression of PTN in benign and malignant lung cancer tissues, especially small cell lung cancer. Lung cancer samples were collected for study and lung tissue samples with benign lesions were taken as controls. The expression of PTN was detected using tissue chip combined with the immunohistochemical method, and the differences of small cell lung cancer with non-small cell lung cancer and benign lesion tissue were compared. It was found that PTN expression was mainly located in the cytoplasm and membrane of cells; PTN expression in the lung cancer group was higher than that in the control group (p < 0.01), and PTN expression in the small cell cancer group was higher than that in the squamous carcinoma group and glandular cancer group (p < 0.05). In addition, PTN expression quantity in patients with lung cancer were in close correlation with TNM staging, pathological type and tumor differentiation degree (p < 0.05). PTN was found to express abnormally high in lung cancer, especially small cell lung cancer tissue. PTN is most likely to be a new tumor marker for diagnosis and prognosis of lung cancer.

[Magnesium and bronchopulmonary dysplasia].

PubMed

Fridman, Elena; Linder, Nehama

2013-03-01

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that occurs in premature infants who have needed mechanical ventilation and oxygen therapy. BPD is defined as the presence of persistent respiratory symptoms, the need for supplemental oxygen to treat hypoxemia, and an abnormal chest radiograph at 36 weeks gestational age. Proinflammatory cytokines and altered angiogenic gene signaling impair prenatal and postnatal lung growth, resulting in BPD. Postnatal hyperoxia exposure further increases the production of cytotoxic free radicals, which cause lung injury and increase the levels of proinflammatory cytokines. Magnesium is the fourth most abundant metal in the body. It is commonly used for the treatment of preeclamsia, as well as for premature labor alleviation. Magnesium's role in BPD development is not clear. A significant association between high magnesium levels at birth and respiratory distress syndrome (RDS), pulmonary interstitial emphysema in the extremely low birth weight, respiratory failure, and later development BPD was found. Conversely, low magnesium intake is associated with lower lung functions, and hypomagnesemia was found in 16% of patients with acute pulmonary diseases. Magnesium is used for the treatment of asthmatic attacks. Magnesium deficiency in pregnant women is frequently seen due to low intake. Hypomagnesemia was also found among preterm neonates and respiratory distress syndrome (RDS). Experimental hypomagnesemia evokes an inflammatory response, and oxidative damage of tissues. These were accompanied by changes in gene expression mostly involved in regulation of cell cycle, apoptosis and remodeling, processes associated with BPD. It is rational to believe that hypomagnesemia can contribute to BPD pathogenesis.

Chronic obstructive pulmonary disease: quantitative and visual ventilation pattern analysis at xenon ventilation CT performed by using a dual-energy technique.

PubMed

Park, Eun-Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Hyun Ju; Lee, Chang Hyun; Park, Chang Min; Yoo, Chul-Gyu; Kim, Jong Hyo

2010-09-01

To evaluate the potential of xenon ventilation computed tomography (CT) in the quantitative and visual analysis of chronic obstructive pulmonary disease (COPD). This study was approved by the institutional review board. After informed consent was obtained, 32 patients with COPD underwent CT performed before the administration of xenon, two-phase xenon ventilation CT with wash-in (WI) and wash-out (WO) periods, and pulmonary function testing (PFT). For quantitative analysis, results of PFT were compared with attenuation parameters from prexenon images and xenon parameters from xenon-enhanced images in the following three areas at each phase: whole lung, lung with normal attenuation, and low-attenuating lung (LAL). For visual analysis, ventilation patterns were categorized according to the pattern of xenon attenuation in the area of structural abnormalities compared with that in the normal-looking background on a per-lobe basis: pattern A consisted of isoattenuation or high attenuation in the WI period and isoattenuation in the WO period; pattern B, isoattenuation or high attenuation in the WI period and high attenuation in the WO period; pattern C, low attenuation in both the WI and WO periods; and pattern D, low attenuation in the WI period and isoattenuation or high attenuation in the WO period. Among various attenuation and xenon parameters, xenon parameters of the LAL in the WO period showed the best inverse correlation with results of PFT (P < .0001). At visual analysis, while emphysema (which affected 99 lobes) commonly showed pattern A or B, airway diseases such as obstructive bronchiolitis (n = 5) and bronchiectasis (n = 2) and areas with a mucus plug (n = 1) or centrilobular nodules (n = 5) showed pattern D or C. WI and WO xenon ventilation CT is feasible for the simultaneous regional evaluation of structural and ventilation abnormalities both quantitatively and qualitatively in patients with COPD. (c) RSNA, 2010.

Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD.

PubMed

Jones, Joshua H; Zelt, Joel T; Hirai, Daniel M; Diniz, Camilla V; Zaza, Aida; O'Donnell, Denis E; Neder, J Alberto

2017-04-01

There is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV 1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation ([Formula: see text]E)/CO 2 output ([Formula: see text]CO 2 ) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake ([Formula: see text]O 2 ), higher [Formula: see text]E/[Formula: see text]CO 2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak [Formula: see text]O 2 and worse dyspnea were found in patients with higher [Formula: see text]E/[Formula: see text]CO 2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-[Formula: see text]O 2 exercise (p < 0.05). Higher [Formula: see text]E/[Formula: see text]CO 2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = -0.72) and blunted changes in PBF from rest to exercise (r = -0.69) (p < 0.01). Ventilation "wasted" in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (D L CO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

Achondroplasia

MedlinePlus

... Infants who receive the abnormal gene from both parents do not often live beyond a few months. ... problems from a small upper airway and from pressure on the area of the brain that controls breathing Lung problems from a small ribcage

Impact of switching from Caucasian to Indian reference equations for spirometry interpretation.

PubMed

Chhabra, S K; Madan, M

2018-03-01

In the absence of ethnically appropriate prediction equations, spirometry data in Indian subjects are often interpreted using equations for other ethnic populations. To evaluate the impact of switching from Caucasian (National Health and Nutrition Examination Survey III [NHANES III] and Global Lung Function Initiative [GLI]) equations to the recently published North Indian equations on spirometric interpretation, and to examine the suitability of GLI-Mixed equations for this population. Spirometry data on 12 323 North Indian patients were analysed using the North Indian equations as well as NHANES III, GLI-Caucasian and GLI-Mixed equations. Abnormalities and ventilatory patterns were categorised and agreement in interpretation was evaluated. The NHANES III and GLI-Caucasian equations and, to a lesser extent, the GLI-Mixed equations, predicted higher values and labelled more measurements as abnormal. In up to one third of the patients, these differed from Indian equations in the categorisation of ventilatory patterns, with more patients classified as having restrictive and mixed disease. The NHANES III and GLI-Caucasian equations substantially overdiagnose abnormalities and misclassify ventilatory patterns on spirometry in Indian patients. Such errors of interpretation, although less common with the GLI-Mixed equations, remain substantial and are clinically unacceptable. A switch to Indian equations will have a major impact on interpretation.

Bacterial Pneumonia in Patients with Cancer: Novel Risk Factors and Management.

PubMed

Wong, Justin L; Evans, Scott E

2017-06-01

Bacterial pneumonias exact unacceptable morbidity on patients with cancer. Although the risk is often most pronounced among patients with treatment-induced cytopenias, the numerous contributors to life-threatening pneumonias in cancer populations range from derangements of lung architecture and swallow function to complex immune defects associated with cytotoxic therapies and graft-versus-host disease. These structural and immunologic abnormalities often make the diagnosis of pneumonia challenging in patients with cancer and impact the composition and duration of therapy. This article addresses host factors that contribute to pneumonia susceptibility, summarizes diagnostic recommendations, and reviews current guidelines for management of bacterial pneumonia in patients with cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Interactive lung segmentation in abnormal human and animal chest CT scans

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

Kockelkorn, Thessa T. J. P., E-mail: thessa@isi.uu.nl; Viergever, Max A.; Schaefer-Prokop, Cornelia M.

2014-08-15

Purpose: Many medical image analysis systems require segmentation of the structures of interest as a first step. For scans with gross pathology, automatic segmentation methods may fail. The authors’ aim is to develop a versatile, fast, and reliable interactive system to segment anatomical structures. In this study, this system was used for segmenting lungs in challenging thoracic computed tomography (CT) scans. Methods: In volumetric thoracic CT scans, the chest is segmented and divided into 3D volumes of interest (VOIs), containing voxels with similar densities. These VOIs are automatically labeled as either lung tissue or nonlung tissue. The automatic labeling resultsmore » can be corrected using an interactive or a supervised interactive approach. When using the supervised interactive system, the user is shown the classification results per slice, whereupon he/she can adjust incorrect labels. The system is retrained continuously, taking the corrections and approvals of the user into account. In this way, the system learns to make a better distinction between lung tissue and nonlung tissue. When using the interactive framework without supervised learning, the user corrects all incorrectly labeled VOIs manually. Both interactive segmentation tools were tested on 32 volumetric CT scans of pigs, mice and humans, containing pulmonary abnormalities. Results: On average, supervised interactive lung segmentation took under 9 min of user interaction. Algorithm computing time was 2 min on average, but can easily be reduced. On average, 2.0% of all VOIs in a scan had to be relabeled. Lung segmentation using the interactive segmentation method took on average 13 min and involved relabeling 3.0% of all VOIs on average. The resulting segmentations correspond well to manual delineations of eight axial slices per scan, with an average Dice similarity coefficient of 0.933. Conclusions: The authors have developed two fast and reliable methods for interactive lung segmentation in challenging chest CT images. Both systems do not require prior knowledge of the scans under consideration and work on a variety of scans.« less

[Successful One-lung Ventilation with a Right-sided Double-lumen Tube in a Patient with a Right Upper Tracheal Bronchus, who Underwent Left Pneumonectomy for Left Hilar Lung Cancer].

PubMed

Kawagoe, Izumi; Kohchiyama, Tsukasa; Hayashida, Masakazu; Satoh, Daizoh; Suzuki, Kenji; Inada, Eiichi

2016-06-01

A 60-year-old male patient with left hilar lung cancer was scheduled to undergo left pneumonectomy or left sleeve lower lobectomy. Preoperative computer tomographic and bronchoscopic examinations revealed that the bronchus (B1) to the right apical segment (S1) was a tracheal bronchus (TB) originating from the trachea approximately 10 mm above the carina. Because the left main bronchus was to be dissected, a right-sided double-lumen tube (DLT) was selected to completely protect the right lung from spillage of secretions or cancer cells from the left lung. The right-sided DLT was placed so as to fit its lateral opening of the bronchial lumen to normal upper branches (B2, B3), while sacrificing ventilation of S1 with an abnormal branch (B1). However, one-lung ventilation (OLV) of the right lung could not be achieved, since a gas leakage from the opened tracheal lumen occurred, most probably due to intra-lobar micro-airway communications between S1 and S2/S3. The DLT was withdrawn until the blue bronchial cuff occluded the orifice of the TB (B1). Although the upper half of the blue bronchial cuff appeared above the tracheal carina, OLV through the two bronchial lumen openings could be achieved due to a specific, slanted doughnut shape of the blue bronchial cuff and the location of the abnormal branch (B1) approximate to the carina. Left pneumonectomy using successful OLV was completed safely without hypoxemia or hypercapnea. Our experience indicates that management of OLV for patients with a thoracheal bronchus needs special considerations of the exact location of the TB and intra-lobar micro-airway communications, in addition to types of scheduled surgical procedures.

The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis.

PubMed

Nguyen-Kim, Thi Dan Linh; Maurer, Britta; Suliman, Yossra A; Morsbach, Fabian; Distler, Oliver; Frauenfelder, Thomas

2018-04-01

To evaluate usability of slice-reduced sequential computed tomography (CT) compared to standard high-resolution CT (HRCT) in patients with systemic sclerosis (SSc) for qualitative and quantitative assessment of interstitial lung disease (ILD) with respect to (I) detection of lung parenchymal abnormalities, (II) qualitative and semiquantitative visual assessment, (III) quantification of ILD by histograms and (IV) accuracy for the 20%-cut off discrimination. From standard chest HRCT of 60 SSc patients sequential 9-slice-computed tomography (reduced HRCT) was retrospectively reconstructed. ILD was assessed by visual scoring and quantitative histogram parameters. Results from standard and reduced HRCT were compared using non-parametric tests and analysed by univariate linear regression analyses. With respect to the detection of parenchymal abnormalities, only the detection of intrapulmonary bronchiectasis was significantly lower in reduced HRCT compared to standard HRCT (P=0.039). No differences were found comparing visual scores for fibrosis severity and extension from standard and reduced HRCT (P=0.051-0.073). All scores correlated significantly (P<0.001) to histogram parameters derived from both, standard and reduced HRCT. Significant higher values of kurtosis and skewness for reduced HRCT were found (both P<0.001). In contrast to standard HRCT histogram parameters from reduced HRCT showed significant discrimination at cut-off 20% fibrosis (sensitivity 88% kurtosis and skewness; specificity 81% kurtosis and 86% skewness; cut-off kurtosis ≤26, cut-off skewness ≤4; both P<0.001). Reduced HRCT is a robust method to assess lung fibrosis in SSc with minimal radiation dose with no difference in scoring assessment of lung fibrosis severity and extension in comparison to standard HRCT. In contrast to standard HRCT histogram parameters derived from the approach of reduced HRCT could discriminate at a threshold of 20% lung fibrosis with high sensitivity and specificity. Hence it might be used to detect early disease progression of lung fibrosis in context of monitoring and treatment of SSc patients.

Heart Failure in a Preterm Infant. Case Report and Echocardiographic Clues for the Diagnostic Approach to Pulmonary Sequestration.

PubMed

Rodriguez-Gonzalez, Moises; Segado-Arenas, Antonio; Matamala-Morillo, Miguel A

2016-08-01

Pulmonary sequestration is an unusual cause of heart failure in infants. We report a preterm newborn with signs of congestive heart failure supposed secondary to a ductus arteriosus that was finally diagnosed as a coexistent extralobar pulmonary sequestration. In this case, Doppler echocardiography was essential for diagnosis, revealing an abnormal systemic arterial supply to the sequestered lung and abnormal venous drainage. © 2016, Wiley Periodicals, Inc.

The Feasibility and Impact of Routine Combined Limited Transthoracic Echocardiography and Lung Ultrasound on Diagnosis and Management of Patients Admitted to ICU: A Prospective Observational Study.

PubMed

Haji, Kavi; Haji, Darsim; Canty, David J; Royse, Alistair G; Tharmaraj, Dhaksha; Azraee, Meor; Hopkins, Lynda; Royse, Collin F

2018-02-01

Limited transthoracic echocardiography (TTE) and lung ultrasound increasingly is performed in the intensive care unit (ICU), though used in a goal-directed rather than routine manner. Prospective observational study. Tertiary ICU. Ninety-three critically ill participants within 24 hours of admission to ICU. A treating intensivist documented a clinical diagnosis and management plan before and after combined limited TTE and lung ultrasound. Ultrasound was performed by an independent intensivist and checked for accuracy offline by a second reviewer. Ultrasound images were interpretable in 99%, with good interobserver agreement. The hemodynamic diagnosis was altered in 66% of participants, including new (14%) or altered (25%) abnormal states or exclusion of clinically diagnosed abnormal state (27%). Valve pathology of at least moderate severity was diagnosed for mitral regurgitation (7%), aortic stenosis (1%), aortic stenosis and mitral regurgitation (1%), tricuspid regurgitation (3%), and 1 case of mitral regurgitation was excluded. Lung pathology diagnosis was changed in 58% of participants including consolidation (13%), interstitial syndrome (4%), and pleural effusion (23%), and exclusion of clinically diagnosed consolidation (6%), interstitial syndrome (3%), and pleural effusion (9%). Management changed in 65% of participants including increased (12%) or decreased (23%) fluid therapy, initiation (10%), changing (6%) or cessation (9%) of inotropic, vasoactive or diuretic drugs, non-invasive ventilation (3%), and pleural drainage (2%). Routine screening of patients with combined limited TTE and lung ultrasound on admission to ICU is feasible and frequently alters diagnosis and management. Copyright © 2018 Elsevier Inc. All rights reserved.

The forkhead box m1 transcription factor is essential for embryonic development of pulmonary vasculature.

PubMed

Kim, Il-Man; Ramakrishna, Sneha; Gusarova, Galina A; Yoder, Helena M; Costa, Robert H; Kalinichenko, Vladimir V

2005-06-10

Transgenic and gene knock-out studies demonstrated that the mouse Forkhead Box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) is essential for hepatocyte entry into mitosis during liver development, regeneration, and liver cancer. Targeted deletion of Foxm1 gene in mice produces an embryonic lethal phenotype due to severe abnormalities in the development of liver and heart. In this study, we show for the first time that Foxm1(-/-) lungs exhibit severe hypertrophy of arteriolar smooth muscle cells and defects in the formation of peripheral pulmonary capillaries as evidenced by significant reduction in platelet endothelial cell adhesion molecule 1 staining of the distal lung. Consistent with these findings, significant reduction in proliferation of the embryonic Foxm1(-/-) lung mesenchyme was found, yet proliferation levels were normal in the Foxm1-deficient epithelial cells. Severe abnormalities of the lung vasculature in Foxm1(-/-) embryos were associated with diminished expression of the transforming growth factor beta receptor II, a disintegrin and metalloprotease domain 17 (ADAM-17), vascular endothelial growth factor receptors, Polo-like kinase 1, Aurora B kinase, laminin alpha4 (Lama4), and the Forkhead Box f1 transcription factor. Cotransfection studies demonstrated that Foxm1 stimulates transcription of the Lama4 promoter, and this stimulation requires the Foxm1 binding sites located between -1174 and -1145 bp of the mouse Lama4 promoter. In summary, development of mouse lungs depends on the Foxm1 transcription factor, which regulates expression of genes essential for mesenchyme proliferation, extracellular matrix remodeling, and vasculogenesis.

The use of histology in 638 coronial post-mortem examinations of adults: an audit.

PubMed

Langlois, Neil E I

2006-10-01

An audit was performed to determine the effectiveness of histological sampling of forensic post-mortem cases based on a review of three years' data, which comprised 638 adult autopsy cases. During the study period organs and tissues that appeared macroscopically normal and abnormal were extensively sampled. Histology was regarded as in some way contributory (providing, altering or confirming a cause of death) 53% of the time. The use of histology provided the cause of death in 49 (24%) of the 203 cases not given a cause of death after the completion of the macroscopic examination. When an interim cause of death had been supplied following the completion of the gross examination it was changed in 4.8% of cases, but there were no changes of the manner of death. The majority of the histological diagnoses or discrepancies involved the lungs and the heart. All diagnoses relevant to determining the cause of death would have been made if samples had been taken only from the left ventricle, right ventricle, coronary arteries, lungs, kidneys and brain with any tissue or organ that appeared abnormal macroscopically. A macroscopically identified abnormality that appeared to have been responsible for death was not sampled in 20 cases; consequently, more attention will be paid to sampling macroscopically abnormal tissues. As a result of this audit histology sampling practice has been revised and will be re-audited in the future.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

Pulmonary function and respiratory symptoms in a population of airport workers.

PubMed

Tunnicliffe, W S; O'Hickey, S P; Fletcher, T J; Miles, J F; Burge, P S; Ayres, J G

1999-02-01

To assess the prevalence of respiratory symptoms and to measure spirometry in a sample of employees of Birmingham International Airport, United Kingdom, to examine whether occupational exposure to aircraft fuel or jet stream exhaust might be associated with respiratory symptoms or abnormalities of lung function. Cross sectional survey by questionnaire and on site measurement of lung function, skin prick tests, and exhaled carbon monoxide concentrations. Occupational exposure was assigned by job title, between group comparison were made by logistic regression analysis. 222/680 full time employees were studied (mean age 38.6 y, 63% male, 28% current smokers, 6% self reported asthma, 19% self reported hay fever). Upper and lower respiratory tract symptoms were common and 51% had one or more positive skin tests. There were no significant differences in lung function tests between exposure groups. Between group comparisons of respiratory symptoms were restricted to male members of the medium and high exposure groups. The adjusted odds ratio (OR) for cough with phlegm and runny nose were found to be significantly associated with high exposure (OR 3.5, 95% confidence interval (95% CI) 1.23 to 9.74 and 2.9, 1.32 to 6.40 respectively) when the measured confounding effects of age and smoking, and in the case of runny nose, self reported hay fever had been taken into account. There was no obvious association between high exposure and the presence of shortness of breath or wheeze, or for the symptoms of watering eyes or stuffy nose. These findings support an association in male airport workers, between high occupational exposures to aviation fuel or jet stream exhaust and excess upper and lower respiratory tract symptoms, in keeping with a respiratory irritant. It is more likely that these effects reflect exposure to exhaust rather than fuel, although the effects of an unmeasured agent cannot be discounted.

Pulmonary function and respiratory symptoms in a population of airport workers

PubMed Central

Tunnicliffe, W. S.; O'Hickey, S. P.; Fletcher, T. J.; Miles, J. F.; Burge, P. S.; Ayres, J. G.

1999-01-01

OBJECTIVES: To assess the prevalence of respiratory symptoms and to measure spirometry in a sample of employees of Birmingham International Airport, United Kingdom, to examine whether occupational exposure to aircraft fuel or jet stream exhaust might be associated with respiratory symptoms or abnormalities of lung function. METHODS: Cross sectional survey by questionnaire and on site measurement of lung function, skin prick tests, and exhaled carbon monoxide concentrations. Occupational exposure was assigned by job title, between group comparison were made by logistic regression analysis. RESULTS: 222/680 full time employees were studied (mean age 38.6 y, 63% male, 28% current smokers, 6% self reported asthma, 19% self reported hay fever). Upper and lower respiratory tract symptoms were common and 51% had one or more positive skin tests. There were no significant differences in lung function tests between exposure groups. Between group comparisons of respiratory symptoms were restricted to male members of the medium and high exposure groups. The adjusted odds ratio (OR) for cough with phlegm and runny nose were found to be significantly associated with high exposure (OR 3.5, 95% confidence interval (95% CI) 1.23 to 9.74 and 2.9, 1.32 to 6.40 respectively) when the measured confounding effects of age and smoking, and in the case of runny nose, self reported hay fever had been taken into account. There was no obvious association between high exposure and the presence of shortness of breath or wheeze, or for the symptoms of watering eyes or stuffy nose. CONCLUSIONS: These findings support an association in male airport workers, between high occupational exposures to aviation fuel or jet stream exhaust and excess upper and lower respiratory tract symptoms, in keeping with a respiratory irritant. It is more likely that these effects reflect exposure to exhaust rather than fuel, although the effects of an unmeasured agent cannot be discounted.   PMID:10448317

Thin-section computed tomography findings in 104 immunocompetent patients with adenovirus pneumonia.

PubMed

Park, Chan Kue; Kwon, Hoon; Park, Ji Young

2017-08-01

Background To date, there has been no computed tomography (CT) evaluation of adenovirus pneumonia in a large number of immunocompetent patients. Purpose To describe the thin-section CT findings of immunocompetent patients with adenovirus pneumonia. Material and Methods We prospectively enrolled 104 patients with adenovirus pneumonia from a military hospital. CT scans of each patient were retrospectively and independently assessed by two radiologists for the presence of abnormalities, laterality and zonal predominance of the parenchymal abnormalities, and dominant imaging patterns and their anatomic distributions. Results CT findings included consolidation (n = 92), ground-glass opacity (GGO; n = 82), septal thickening (n = 34), nodules (n = 46), bronchial wall thickening (n = 32), pleural effusion (n = 16), and lymphadenopathy (n = 3). Eighty-four patients (81%) exhibited unilateral parenchymal abnormalities and 57 (57%) exhibited lower lung zone abnormalities. The most frequently dominant CT pattern was consolidation with surrounding GGO (n = 50), with subpleural (70%) and peribronchovascular (94%) distributions. Consolidation-the second-most common pattern (n = 33)-also exhibited subpleural (79%) and peribronchovascular (97%) distributions. The dominant nodule pattern (n = 14) exhibited mixed (64%) and peribronchovascular (100%) distributions. A dominant GGO pattern was only observed in four patients; none had central distribution. Conclusion Although the manifestations of adenovirus pneumonia on CT are varied, we found the most frequent pattern was consolidation with or without surrounding GGO, with subpleural and peribronchovascular distributions. Parenchymal abnormalities were predominantly unilateral and located in the lower lung zone. If dominant consolidation findings are present in immunocompetent patients during the early stages, adenovirus pneumonia should be considered.

Genetics Home Reference: Farber lipogranulomatosis

MedlinePlus

... breakdown and use of fats in the body (lipid metabolism). In affected individuals, lipids accumulate abnormally in cells and tissues throughout the ... health problems beginning in infancy due to massive lipid deposits in the liver, spleen, lungs, and immune ...

Left-Sided Catamenial Pneumothorax with Thoracic Endometriosis and Bullae in the Alveolar Wall

PubMed Central

Takahashi, Ryo; Mizobuchi, Teruaki; Ebana, Hiroki; Yamanaka, Sumitaka

2016-01-01

Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions. PMID:27507105

Left-Sided Catamenial Pneumothorax with Thoracic Endometriosis and Bullae in the Alveolar Wall.

PubMed

Takahashi, Ryo; Kurihara, Masatoshi; Mizobuchi, Teruaki; Ebana, Hiroki; Yamanaka, Sumitaka

2017-04-20

Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions.

Splenogonadal fusion with limb deficiency and micrognathia.

PubMed

Moore, P J; Hawkins, E P; Galliani, C A; Guerry-Force, M L

1997-11-01

Splenogonadal fusion (SGF) is a rare abnormality with two known types. In the continuous type, the spleen is connected to the gonad, and there are often limb defects, micrognathia, or other congenital malformations such as ventricular septal defect, anal atresia, microgastria, spina bifida, craniosynostosis, thoracopagus, diaphragmatic hernia, hypoplastic lung and abnormal lung fissures, polymicrogyria, deficient coccyx, and bifid spine C6-T3. The discontinuous type is usually not associated with congenital defects, and the gonad that fused with an accessory spleen has no connection with the native spleen. The etiology of SGF is not known. Conceivably, a teratogenic insult occurring between 5 weeks' and 8 weeks' gestation could interfere with the normal development of the spleen, gonads, and limb buds. We describe a case of splenogonadal fusion in a stillborn black boy with associated micrognathia and limb deformities. Also, we review the possible teratogenic etiologies and embryonic basis of SGF.

[A new medical education using a lung sound auscultation simulator called "Mr. Lung"].

PubMed

Yoshii, Chiharu; Anzai, Takashi; Yatera, Kazuhiro; Kawajiri, Tatsunori; Nakashima, Yasuhide; Kido, Masamitsu

2002-09-01

We developed a lung sound auscultation simulator "Mr. Lung" in 2001. To improve the auscultation skills of lung sounds, we utilized this new device in our educational training facility. From June 2001 to March 2002, we used "Mr. Lung" for our small group training in which one hundred of the fifth year medical students were divided into small groups from which one group was taught every other week. The class consisted of ninety-minute training periods for auscultation of lung sounds. At first, we explained the classification of lung sounds, and then auscultation tests were performed. Namely, students listened to three cases of abnormal or adventitious lung sounds on "Mr. Lung" through their stethoscopes. Next they answered questions corresponding to the portion and quality of the sounds. Then, we explained the correct answers and how to differentiate lung sounds on "Mr. Lung". Additionally, at the beginning and the end of the lecture, five degrees of self-assessment for the auscultation of the lung sounds were performed. The ratio of correct answers for lung sounds were 36.9% for differences between bilateral lung sounds, 52.5% for coarse crackles, 34.1% for fine crackles, 69.2% for wheezes, 62.1% for rhonchi and 22.2% for stridor. Self-assessment scores were significantly higher after the class than before. The ratio of correct lung sound answers was surprisingly low among medical students. We believe repetitive auscultation of the simulator to be extremely helpful for medical education.

SURFACTANT DYSFUNCTION IN LUNG CONTUSION WITH AND WITHOUT SUPERIMPOSED GASTRIC ASPIRATION IN A RAT MODEL

PubMed Central

Raghavendran, Krishnan; Davidson, Bruce A.; Knight, Paul R.; Wang, Zhengdong; Helinski, Jadwiga; Chess, Patricia R.; Notter, Robert H.

2009-01-01

This study investigates surfactant dysfunction in rats with lung contusion (LC) induced by blunt chest trauma. Rats at 24 h postcontusion had a decreased percent content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL) and altered large-aggregate composition with decreased phosphatidylcholine (PC), increased lyso-PC, and increased protein compared with uninjured controls. The surface activity of large aggregates on a pulsating bubble surfactometer was also severely impaired at 24 h postcontusion. Decreases in large surfactant aggregate content and surface activity were improved, but still apparent, at 48 and 72 h postcontusion compared with uninjured control rats and returned to normal by 96 h postcontusion. The functional importance of surfactant abnormalities in LC injury was documented in pilot studies showing that exogenous surfactant replacement at 24 h postcontusion improved inflation/deflation lung volumes. Additional experiments investigated a clinically relevant combination of LC plus gastric aspiration (combined acid and small gastric food particles) and found reductions in large surfactant aggregates in BAL similar to those for LC. However, rats given LC + combined acid and small gastric food particles versus LC had more severe surfactant dysfunction based on decreases in surface activity and alterations in large aggregate composition. Combined data for all animal groups had strong statistical correlations between surfactant dysfunction (increased minimum surface tension, decreased large aggregates in BAL, decreased aggregate PC, and increased aggregate lyso-PC) and the severity of inflammatory lung injury (increased total protein, albumin, protein/phospholipid ratio, neutrophils, and erythrocytes in BAL plus increased whole lung myeloperoxidase activity). These results show that surfactant dysfunction is important in the pathophysiology of LC with or without concurrent gastric aspiration and provides a rationale for surfactant replacement therapy in these prevalent clinical conditions. PMID:18323743

Penconazole alters redox status, cholinergic function and lung's histoarchitecture of adult rats: Reversal effect of vitamin E.

PubMed

Chaâbane, Mariem; Elwej, Awatef; Ghorbel, Imen; Chelly, Sabrine; Mnif, Hela; Boudawara, Tahia; Ellouze Chaabouni, Semia; Zeghal, Najiba; Soudani, Nejla

2018-06-01

The present study pertains to the possible adverse effects of penconazole exposure on the lung of adult rats, and to the potential ability of vitamin E (Vit E) in mitigating the toxicity induced by this fungicide. Male Wistar rats were divided into four groups of six animals each: Group I (Controls): rats drank distilled water; Group II (PEN): rats received, by gavage, 50 mg/kg body weight (1/40 LD 50 ) of penconazole every 2 days during 10 days; Group III (Vit E): rats received daily 100 mg α-tocopherol acetate/kg body weight during 10 days by gavage; and Group IV (Vit E + PEN): rats received both vitamin E (100 mg α-tocopherol acetate/kg body weight) and penconazole (50 mg/kg body weight), being vitamin E given as a daily dosage and penconazole every 2 days, by gavage during 10 days. Results showed that penconazole induced oxidative stress in the lung demonstrated by an increase in malondialdehyde (+77%), hydrogen peroxide (+58%) and advanced oxidation protein product (+22%) levels, as compared to the controls. Furthermore, a decrease in the activities of catalase (-41%), superoxide dismutase (-45%), glutathione peroxidase (-23%) and acetylcholinesterase (-67%), and an increase in the levels of non-protein thiols (+17%), glutathione (+7%) and vitamin C (+44%) were registered. Abnormalities in lung histological sections such as alveolar edema, infiltration of inflammatory cells (leukocytes) and emphysema, were also observed following penconazole exposure. Vitamin E ameliorated the biochemical parameters, as well as the histological impairments induced by this fungicide. In conclusion, our study demonstrated that vitamin E, a natural antioxidant, was effective in alleviating penconazole-induced lung damage in Wistar rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cerebellar Ataxia, Seizures, Premature Death, and Cardiac Abnormalities in Mice with Targeted Disruption of the Cacna2d2 Gene

PubMed Central

Ivanov, Sergey V.; Ward, Jerrold M.; Tessarollo, Lino; McAreavey, Dorothea; Sachdev, Vandana; Fananapazir, Lameh; Banks, Melissa K.; Morris, Nicole; Djurickovic, Draginja; Devor-Henneman, Deborah E.; Wei, Ming-Hui; Alvord, Gregory W.; Gao, Boning; Richardson, James A.; Minna, John D.; Rogawski, Michael A.; Lerman, Michael I.

2004-01-01

CACNA2D2 is a putative tumor suppressor gene located in the human chromosome 3p21.3 region that shows frequent allelic imbalances in lung, breast, and other cancers. The α2δ-2 protein encoded by the gene is a regulatory subunit of voltage-dependent calcium channels and is expressed in brain, heart, and other tissues. Here we report that mice homozygous for targeted disruption of the Cacna2d2 gene exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities. The Cacna2d2tm1NCIF null phenotype has much in common with that of Cacna1a mutants, such as cerebellar neuro-degeneration associated with ataxia, seizures, and premature death. A tendency to bradycardia and limited response of null mutants to isoflurane implicate α2δ-2 in sympathetic regulation of cardiac function. In summary, our findings provide genetic evidence that the α2δ-2 subunit serves in vivo as a component of P/Q-type calcium channels, is indispensable for the central nervous system function, and may be involved in hereditary cerebellar ataxias and epileptic disorders in humans. PMID:15331424

Comparison between the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 short-term toxicity in adult albino rats.

PubMed

Elshama, Said Said; Osman, Hosam-Eldin Hussein; El-Kenawy, Ayman El-Meghawry; Youseef, Hamdi Mohamed

2016-02-17

Vitamin D3 has increased risk of toxicity due to its common use in multivitamin preparations. Vitamin K and vitamin A play an important role in vitamin D action. The goal of the current study was to compare the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 toxicity in rats by assessing serum calcium, renal function tests, cardiac enzymes, and related histopathological changes. Eighty adult albino rats were divided into four groups; each group consisted of 20 rats. The first group received water; the second received a toxic dose of vitamin D3; the third received a toxic dose of vitamin D3 with vitamin A; and the fourth received a toxic dose of vitamin D3 with vitamin K. Vitamin D3 toxicity led to significant abnormalities of cardiac enzymes, renal function tests, and serum calcium associated with histopathological changes in the kidney, heart, lung, adrenal gland, and aorta. Individual administration of vitamin A or vitamin K with a toxic dose of vitamin D improved the biochemical and histopathological abnormalities of hypervitaminosis D3. Vitamins A and K showed the same protective effects in the modulation of hypervitaminosis D3 short-term toxicity.

Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia

PubMed Central

Mourani, Peter M.; Abman, Steven H.

2015-01-01

Advances in the care of preterm infants have improved survival of infants born at earlier gestational ages. Yet, these infants remain at risk for the chronic lung disease of infancy, bronchopulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing pulmonary circulation to lung development, demonstrating that these infants are also at risk for pulmonary vascular disease (PVD), including pulmonary hypertension (PH) and pulmonary vascular abnormalities, which contributes significantly to morbidity and mortality. In the past few years, several epidemiological studies have delineated the incidence of PH in preterm infants and the impact on outcomes. However, these studies have also highlighted gaps in our understanding of PVD in BPD, including universally accepted definitions, approaches to diagnosis and treatment, and patient outcomes. Associated pulmonary vascular and cardiac abnormalities are increasingly recognized complications contributing to PH in these infants, but incidence of these lesions and degree of contribution to disease remains unknown. Therapeutic strategies for PVD in BPD are largely untested, but recent evidence presents the rationale for the approach to diagnosis and treatment of BPD infants with PH that can be evaluated in future studies. PMID:26593082

Cross sectional study on lung function of coke oven workers: a lung function surveillance system from 1978 to 1990

PubMed Central

Wu, J; Kreis, I; Griffiths, D; Darling, C

2002-01-01

Aims: To determine the association between lung function of coke oven workers and exposure to coke oven emissions. Methods: Lung function data and detailed work histories for workers in recovery coke ovens of a steelworks were extracted from a lung function surveillance system. Multiple regressions were employed to determine significant predictors for lung function indices. The first sets of lung function tests for 613 new starters were pooled to assess the selection bias. The last sets of lung function tests for 834 subjects with one or more year of coke oven history were pooled to assess determinants of lung function. Results: Selection bias associated with the recruitment process was not observed among the exposure groups. For subjects with a history of one or more years of coke oven work, each year of working in the most exposed "operation" position was associated with reductions in FEV1 of around 9 ml (p = 0.006, 95% CI: 3 ml to 16 ml) and in FVC of around 12 ml (p = 0.002, 95% CI: 4 ml to 19 ml). Negative effects of smoking on lung function were also observed. Conclusions: Exposure to coke oven emissions was found to be associated with lower FEV1 and FVC. Effects of work exposure on lung function are similar to those found in other studies. PMID:12468747

PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis

PubMed Central

Bueno, Marta; Lai, Yen-Chun; Romero, Yair; Brands, Judith; St. Croix, Claudette M.; Kamga, Christelle; Corey, Catherine; Herazo-Maya, Jose D.; Sembrat, John; Lee, Janet S.; Duncan, Steve R.; Rojas, Mauricio; Shiva, Sruti; Chu, Charleen T.; Mora, Ana L.

2014-01-01

Although aging is a known risk factor for idiopathic pulmonary fibrosis (IPF), the pathogenic mechanisms that underlie the effects of advancing age remain largely unexplained. Some age-related neurodegenerative diseases have an etiology that is related to mitochondrial dysfunction. Here, we found that alveolar type II cells (AECIIs) in the lungs of IPF patients exhibit marked accumulation of dysmorphic and dysfunctional mitochondria. These mitochondrial abnormalities in AECIIs of IPF lungs were associated with upregulation of ER stress markers and were recapitulated in normal mice with advancing age in response to stimulation of ER stress. We found that impaired mitochondria in IPF and aging lungs were associated with low expression of PTEN-induced putative kinase 1 (PINK1). Knockdown of PINK1 expression in lung epithelial cells resulted in mitochondria depolarization and expression of profibrotic factors. Moreover, young PINK1-deficient mice developed similarly dysmorphic, dysfunctional mitochondria in the AECIIs and were vulnerable to apoptosis and development of lung fibrosis. Our data indicate that PINK1 deficiency results in swollen, dysfunctional mitochondria and defective mitophagy, and promotes fibrosis in the aging lung. PMID:25562319

Axial segmentation of lungs CT scan images using canny method and morphological operation

NASA Astrophysics Data System (ADS)

Noviana, Rina; Febriani, Rasal, Isram; Lubis, Eva Utari Cintamurni

2017-08-01

Segmentation is a very important topic in digital image process. It is found simply in varied fields of image analysis, particularly within the medical imaging field. Axial segmentation of lungs CT scan is beneficial in designation of abnormalities and surgery planning. It will do to ascertain every section within the lungs. The results of the segmentation are accustomed discover the presence of nodules. The method which utilized in this analysis are image cropping, image binarization, Canny edge detection and morphological operation. Image cropping is done so as to separate the lungs areas, that is the region of interest. Binarization method generates a binary image that has 2 values with grey level, that is black and white (ROI), from another space of lungs CT scan image. Canny method used for the edge detection. Morphological operation is applied to smoothing the lungs edge. The segmentation methodology shows an honest result. It obtains an awfully smooth edge. Moreover, the image background can also be removed in order to get the main focus, the lungs.

Lung partitioning for x-ray CAD applications

NASA Astrophysics Data System (ADS)

Annangi, Pavan; Raja, Anand

2011-03-01

Partitioning the inside region of lung into homogeneous regions becomes a crucial step in any computer-aided diagnosis applications based on chest X-ray. The ribs, air pockets and clavicle occupy major space inside the lung as seen in the chest x-ray PA image. Segmenting the ribs and clavicle to partition the lung into homogeneous regions forms a crucial step in any CAD application to better classify abnormalities. In this paper we present two separate algorithms to segment ribs and the clavicle bone in a completely automated way. The posterior ribs are segmented based on Phase congruency features and the clavicle is segmented using Mean curvature features followed by Radon transform. Both the algorithms work on the premise that the presentation of each of these anatomical structures inside the left and right lung has a specific orientation range within which they are confined to. The search space for both the algorithms is limited to the region inside the lung, which is obtained by an automated lung segmentation algorithm that was previously developed in our group. Both the algorithms were tested on 100 images of normal and patients affected with Pneumoconiosis.

Advances in diagnostic interventional pulmonology

PubMed Central

Al-Zubaidi, Nassar; Soubani, Ayman O.

2015-01-01

The recent advances in diagnostic pulmonary procedures have revolutionized the evaluation of abnormal thoracic findings including lung nodules and masses, mediastinal lymphadenopathy, and pleural diseases. Bronchoscopies with endobronchial ultrasonography and electromagnetic navigation are examples of new technology that has significantly improved the specificity and sensitivity of these procedures in diagnosis and staging of lung cancer without the need for more invasive procedures. This report describes the different diagnostic pulmonary interventions providing a description of the procedures, their indications, diagnostic yield and drawback. PMID:26229756

Attenuation of Cigarette Smoke-Induced Airway Mucus Production by Hydrogen-Rich Saline in Rats

PubMed Central

Zhang, Jingxi; Dong, Yuchao; Xu, Wujian; Li, Qiang

2013-01-01

Background Over-production of mucus is an important pathophysiological feature in chronic airway disease such as chronic obstructive pulmonary disease (COPD) and asthma. Cigarette smoking (CS) is the leading cause of COPD. Oxidative stress plays a key role in CS-induced airway abnormal mucus production. Hydrogen protected cells and tissues against oxidative damage by scavenging hydroxyl radicals. In the present study we investigated the effect of hydrogen on CS-induced mucus production in rats. Methods Male Sprague-Dawley rats were divided into four groups: sham control, CS group, hydrogen-rich saline pretreatment group and hydrogen-rich saline control group. Lung morphology and tissue biochemical changes were determined by immunohistochemistry, Alcian Blue/periodic acid-Schiff staining, TUNEL, western blot and realtime RT-PCR. Results Hydrogen-rich saline pretreatment attenuated CS-induced mucus accumulation in the bronchiolar lumen, goblet cell hyperplasia, muc5ac over-expression and abnormal cell apoptosis in the airway epithelium as well as malondialdehyde increase in the BALF. The phosphorylation of EGFR at Tyr1068 and Nrf2 up-regulation expression in the rat lungs challenged by CS exposure were also abrogated by hydrogen-rich saline. Conclusion Hydrogen-rich saline pretreatment ameliorated CS-induced airway mucus production and airway epithelium damage in rats. The protective role of hydrogen on CS-exposed rat lungs was achieved at least partly by its free radical scavenging ability. This is the first report to demonstrate that intraperitoneal administration of hydrogen-rich saline protected rat airways against CS damage and it could be promising in treating abnormal airway mucus production in COPD. PMID:24376700

Noncystic Fibrosis Bronchiectasis: Regional Abnormalities and Response to Airway Clearance Therapy Using Pulmonary Functional Magnetic Resonance Imaging.

PubMed

Svenningsen, Sarah; Guo, Fumin; McCormack, David G; Parraga, Grace

2017-01-01

Evidence-based treatment and management for patients with bronchiectasis remain challenging. There is a need for regional disease measurements as focal distribution of disease is common. Our objective was to evaluate the ability of magnetic resonance imaging (MRI) to detect regional ventilation impairment and response to airway clearance therapy (ACT) in patients with noncystic fibrosis (CF) bronchiectasis, providing a new way to objectively and regionally evaluate response to therapy. Fifteen participants with non-CF bronchiectasis and 15 age-matched healthy volunteers provided written informed consent to an ethics board-approved Health Insurance Portability and Accountability Act-compliant protocol and underwent spirometry, plethysmography, computed tomography (CT), and hyperpolarized 3 He MRI. Bronchiectasis patients also completed a Six-Minute Walk Test, the St. George's Respiratory questionnaire, and Patient Evaluation Questionnaire (PEQ), and returned for a follow-up visit after 3 weeks of daily oscillatory positive expiratory pressure use. CT evidence of bronchiectasis was qualitatively reported by lobe, and MRI ventilation defect percent (VDP) was measured for the entire lung and individual lobes. CT evidence of bronchiectasis and abnormal VDP (14 ± 7%) was observed for all bronchiectasis patients and no healthy volunteers. There was CT evidence of bronchiectasis in all lobes for 3 patients and in 3 ± 1 lobes (range = 1-4) for 12 patients. VDP in lobes with CT evidence of bronchiectasis (19 ± 12%) was significantly higher than in lobes without CT evidence of bronchiectasis (8 ± 5%, P = .001). For patients, VDP in lung lobes with (P < .0001) and without CT evidence of bronchiectasis (P = .006) was higher than in healthy volunteers (3 ± 1%). For all patients, mean PEQ-ease-bringing-up-sputum (P = .048) and PEQ-patient-global-assessment (P = .01) were significantly improved post-oscillatory positive expiratory pressure. An improvement in regional VDP greater than the minimum clinical important difference was observed for 8 of the 14 patients evaluated. There was CT and MRI evidence of structure-function abnormalities in patients with bronchiectasis; in approximately half, there was evidence of ventilation improvements after airway clearance therapy. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Segmentation of ribs in digital chest radiographs

NASA Astrophysics Data System (ADS)

Cong, Lin; Guo, Wei; Li, Qiang

2016-03-01

Ribs and clavicles in posterior-anterior (PA) digital chest radiographs often overlap with lung abnormalities such as nodules, and cause missing of these abnormalities, it is therefore necessary to remove or reduce the ribs in chest radiographs. The purpose of this study was to develop a fully automated algorithm to segment ribs within lung area in digital radiography (DR) for removal of the ribs. The rib segmentation algorithm consists of three steps. Firstly, a radiograph was pre-processed for contrast adjustment and noise removal; second, generalized Hough transform was employed to localize the lower boundary of the ribs. In the third step, a novel bilateral dynamic programming algorithm was used to accurately segment the upper and lower boundaries of ribs simultaneously. The width of the ribs and the smoothness of the rib boundaries were incorporated in the cost function of the bilateral dynamic programming for obtaining consistent results for the upper and lower boundaries. Our database consisted of 93 DR images, including, respectively, 23 and 70 images acquired with a DR system from Shanghai United-Imaging Healthcare Co. and from GE Healthcare Co. The rib localization algorithm achieved a sensitivity of 98.2% with 0.1 false positives per image. The accuracy of the detected ribs was further evaluated subjectively in 3 levels: "1", good; "2", acceptable; "3", poor. The percentages of good, acceptable, and poor segmentation results were 91.1%, 7.2%, and 1.7%, respectively. Our algorithm can obtain good segmentation results for ribs in chest radiography and would be useful for rib reduction in our future study.

Pulmonary vasculature in COPD: The silent component.

PubMed

Blanco, Isabel; Piccari, Lucilla; Barberà, Joan Albert

2016-08-01

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction that results from an inflammatory process affecting the airways and lung parenchyma. Despite major abnormalities taking place in bronchial and alveolar structures, changes in pulmonary vessels also represent an important component of the disease. Alterations in vessel structure are highly prevalent and abnormalities in their function impair gas exchange and may result in pulmonary hypertension (PH), an important complication of the disease associated with reduced survival and worse clinical course. The prevalence of PH is high in COPD, particularly in advanced stages, although it remains of mild to moderate severity in the majority of cases. Endothelial dysfunction, with imbalance between vasodilator/vasoconstrictive mediators, is a key determinant of changes taking place in pulmonary vasculature in COPD. Cigarette smoke products may perturb endothelial cells and play a critical role in initiating vascular changes. The concurrence of inflammation, hypoxia and emphysema further contributes to vascular damage and to the development of PH. The use of drugs that target endothelium-dependent signalling pathways, currently employed in pulmonary arterial hypertension, is discouraged in COPD due to the lack of efficacy observed in randomized clinical trials and because there is compelling evidence indicating that these drugs may worsen pulmonary gas exchange. The subgroup of patients with severe PH should be ideally managed in centres with expertise in both PH and chronic lung diseases because alterations of pulmonary vasculature might resemble those observed in pulmonary arterial hypertension. Because this condition entails poor prognosis, it warrants specialist treatment. © 2016 Asian Pacific Society of Respirology.

Pulmonary Function and Respiratory Health of Military Personnel Before Southwest Asia Deployment.

PubMed

Skabelund, Andrew J; Rawlins, Frederic A; McCann, Edward T; Lospinoso, Joshua A; Burroughs, Lorraine; Gallup, Roger A; Morris, Michael J

2017-09-01

Significant concern exists regarding the respiratory health of military personnel deployed to Southwest Asia, given their exposures to numerous environmental hazards. Although the deployed military force is generally assumed to be fit, the pre-deployment respiratory health of these individuals is largely unknown. Soldiers deploying to Southwest Asia were recruited from the pre-deployment processing center at Fort Hood, Texas. Participants completed a general and respiratory health questionnaire and performed baseline spirometry. One thousand six hundred ninety-three pre-deployment evaluations were completed. The average age of the participants was 32.2 y, and 83.1% were male. More than one third of surveyed solders had a smoking history, 73% were overweight or obese, and 6.2% reported a history of asthma. Abnormal spirometry was found in 22.3% of participants. Soldiers with abnormal spirometry reported more asthma (10.1% vs 5.1%, P < .001), failed physical fitness tests (9.0% vs 4.6%, P = .02), and respiratory symptoms (32.8% vs 24.3%, P = .001). This is the first prospective pre-deployment evaluation of military personnel that delineates factors potentially associated with the development of pulmonary symptoms and/or disease. This study suggests that deploying soldiers are older, heavier, frequently smoke, and may have undiagnosed pre-deployment lung disease. Abnormal spirometry is common but may not represent underlying disease. Self-reported asthma, wheezing, and slower 2-mile run times were predictive of abnormal spirometry. Pre-deployment evaluation of military personnel identified numerous soldiers with active pulmonary symptoms and abnormal spirometry. When combined with questions regarding asthma history, wheezing and exercise intolerance, spirometry may identify individuals at risk for deployment-related respiratory complaints. Copyright © 2017 by Daedalus Enterprises.

Membrane-bound (MUC1) and secretory (MUC2, MUC3, and MUC4) mucin gene expression in human lung cancer.

PubMed

Nguyen, P L; Niehans, G A; Cherwitz, D L; Kim, Y S; Ho, S B

1996-01-01

Abnormalities of mucin-type glycoproteins have been described in lung cancers, but their molecular basis is unknown. In this study, mucin-core-peptide-specific antibodies and cDNA probes were used to determine the relative expression of mucin genes corresponding to one membrane-bound mucin (MUC1), two intestinal mucins (MUC2 and MUC3), and one tracheobronchial mucin (MUC4) in normal (nonneoplastic) lung, and in lung neoplasms. Normal lung tissues exhibited a distinct pattern of mucin gene expression, with high levels of MUC1 and MUC4 mRNA and low to absent levels of MUC2 and MUC3 mucin immunoreactivity and mRNA. In contrast, lung adenocarcinomas, especially well-differentiated cancers, exhibited increased MUC1, MUC3, and MUC4 mRNA levels. Lung squamous-cell, adenosquamous, and large-cell carcinomas were characterized by increased levels of MUC4 mucin only. We conclude that the expression of one membrane-bound and several secretory-type mucins is independently regulated and markedly altered in lung neoplasms. The frequent occurrence of increased MUC4 transcripts in a variety of non-small-cell lung cancers indicates the potential importance of this type of mucin in lung cancer biology.

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

PubMed

King, Paul T

2018-01-01

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

The Aurora kinase A inhibitor TC-A2317 disrupts mitotic progression and inhibits cancer cell proliferation

PubMed Central

Min, Yoo Hong; Kim, Wootae; Kim, Ja-Eun

2016-01-01

Mitotic progression is crucial for the maintenance of chromosomal stability. A proper progression is ensured by the activities of multiple kinases. One of these enzymes, the serine/threonine kinase Aurora A, is required for proper mitosis through the regulation of centrosome and spindle assembly. In this study, we functionally characterized a newly developed Aurora kinase A inhibitor, TC-A2317. In human lung cancer cells, TC-A2317 slowed proliferation by causing aberrant formation of centrosome and microtubule spindles and prolonging the duration of mitosis. Abnormal mitotic progression led to accumulation of cells containing micronuclei or multinuclei. Furthermore, TC-A2317–treated cells underwent apoptosis, autophagy or senescence depending on cell type. In addition, TC-A2317 inactivated the spindle assembly checkpoint triggered by paclitaxel, thereby exacerbating mitotic catastrophe. Consistent with this, the expression level of Aurora A in tumors was inversely correlated with survival in lung cancer patients. Collectively, these data suggest that inhibition of Aurora kinase A using TC-A2317 is a promising target for anti-cancer therapeutics. PMID:27713168

Signal transduction in the development of pulmonary arterial hypertension

PubMed Central

Malenfant, Simon; Neyron, Anne-Sophie; Paulin, Roxane; Potus, François; Meloche, Jolyane; Provencher, Steeve; Bonnet, Sébastien

2013-01-01

Pulmonary arterial hypertension (PAH) is a unique disease. Properly speaking, it is not a disease of the lung. It can be seen more as a microvascular disease occurring mainly in the lungs and affecting the heart. At the cellular level, the PAH paradigm is characterized by inflammation, vascular tone imbalance, pulmonary arterial smooth muscle cell proliferation and resistance to apoptosis and the presence of in situ thrombosis. At a clinical level, the aforementioned abnormal vascular properties alter physically the pulmonary circulation and ventilation, which greatly influence the right ventricle function as it highly correlates with disease severity. Consequently, right heart failure remains the principal cause of death within this cohort of patients. While current treatment modestly improve patients’ conditions, none of them are curative and, as of today, new therapies are lacking. However, the future holds potential new therapies that might have positive influence on the quality of life of the patient. This article will first review the clinical presentation of the disease and the different molecular pathways implicated in the pathobiology of PAH. The second part will review tomorrow's future putative therapies for PAH. PMID:24015329

Indoor air pollution and its association with poor lung function, microalbuminuria and variations in blood pressure among kitchen workers in India: a cross-sectional study.

PubMed

Singh, Amarnath; Kesavachandran, Chandrasekharan Nair; Kamal, Ritul; Bihari, Vipin; Ansari, Afzal; Azeez, Parappurath Abdul; Saxena, Prem Narain; Ks, Anil Kumar; Khan, Altaf Hussain

2017-04-04

The present study is an attempt to explore the association between kitchen indoor air pollutants and physiological profiles in kitchen workers with microalbuminuria (MAU) in north India (Lucknow) and south India (Coimbatore). The subjects comprised 145 control subjects, 233 kitchen workers from north India and 186 kitchen workers from south India. Information related to the personal and occupational history and health of the subjects at both locations were collected using a custom-made questionnaire. Worker lung function was measured using a spirometer. Blood pressure was monitored using a sphygmomanometer. Urinary MAU was measured using a urine analyzer. Indoor air monitoring in kitchens for particulate matter (PM), total volatile organic compounds (TVOC), carbon dioxide (CO 2 ) and carbon monoxide (CO) was conducted using indoor air quality monitors. The size and shape of PM in indoor air was assessed using a scanning electron microscope (SEM). Fourier transform infrared (FTIR) spectroscopy was used to detect organic or inorganic compounds in the air samples. Particulate matter concentrations (PM 2.5 and PM 1 ) were significantly higher in both north and south Indian kitchens than in non-kitchen areas. The concentrations of TVOC, CO and CO 2 were higher in the kitchens of north and south India than in the control locations (non-kitchen areas). Coarse, fine and ultrafine particles and several elements were also detected in kitchens in both locations by SEM and elemental analysis. The FTIR spectra of kitchen indoor air at both locations show the presence of organic chemicals. Significant declines in systolic blood pressure and lung function were observed in the kitchen workers with MAU at both locations compared to those of the control subjects. A higher prevalence of obstruction cases with MAU was observed among the workers in the southern region than in the controls (p < 0.01). Kitchen workers in south India have lower lung capacities and a greater risk of obstructive and restrictive abnormalities than their north Indian counterparts. The study showed that occupational exposure to multiple kitchen indoor air pollutants (ultrafine particles, PM 2.5 , PM 1 , TVOC, CO, CO 2 ) and FTIR-derived compounds can be associated with a decline in lung function (restrictive and obstructive patterns) in kitchen workers with microalbuminuria. Further studies in different geographical locations in India among kitchen workers on a wider scale are required to validate the present findings.

Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies

PubMed Central

Mirra, Virginia; Werner, Claudius; Santamaria, Francesca

2017-01-01

Primary ciliary dyskinesia (PCD) is an orphan disease (MIM 244400), autosomal recessive inherited, characterized by motile ciliary dysfunction. The estimated prevalence of PCD is 1:10,000 to 1:20,000 live-born children, but true prevalence could be even higher. PCD is characterized by chronic upper and lower respiratory tract disease, infertility/ectopic pregnancy, and situs anomalies, that occur in ≈50% of PCD patients (Kartagener syndrome), and these may be associated with congenital heart abnormalities. Most patients report a daily year-round wet cough or nose congestion starting in the first year of life. Daily wet cough, associated with recurrent infections exacerbations, results in the development of chronic suppurative lung disease, with localized-to-diffuse bronchiectasis. No diagnostic test is perfect for confirming PCD. Diagnosis can be challenging and relies on a combination of clinical data, nasal nitric oxide levels plus cilia ultrastructure and function analysis. Adjunctive tests include genetic analysis and repeated tests in ciliary culture specimens. There are currently 33 known genes associated with PCD and correlations between genotype and ultrastructural defects have been increasingly demonstrated. Comprehensive genetic testing may hopefully screen young infants before symptoms occur, thus improving survival. Recent surprising advances in PCD genetic designed a novel approach called “gene editing” to restore gene function and normalize ciliary motility, opening up new avenues for treating PCD. Currently, there are no data from randomized clinical trials to support any specific treatment, thus, management strategies are usually extrapolated from cystic fibrosis. The goal of treatment is to prevent exacerbations, slowing the progression of lung disease. The therapeutic mainstay includes airway clearance maneuvers mainly with nebulized hypertonic saline and chest physiotherapy, and prompt and aggressive administration of antibiotics. Standardized care at specialized centers using a multidisciplinary approach that imposes surveillance of lung function and of airway biofilm composition likely improves patients’ outcome. Pediatricians, neonatologists, pulmonologists, and ENT surgeons should maintain high awareness of PCD and refer patients to the specialized center before sustained irreversible lung damage develops. The recent creation of a network of PCD clinical centers, focusing on improving diagnosis and treatment, will hopefully help to improve care and knowledge of PCD patients. PMID:28649564

Drug-induced apnea.

PubMed

Boutroy, M J

1994-01-01

Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

The role of integrin α8β1 in fetal lung morphogenesis and injury

PubMed Central

Benjamin, John T.; Gaston, David C.; Halloran, Brian A.; Schnapp, Lynn M.; Zent, Roy; Prince, Lawrence S.

2009-01-01

Prenatal inflammation prevents normal lung morphogenesis and leads to bronchopulmonary dysplasia (BPD), a common complication of preterm birth. We previously demonstrated in a bacterial endotoxin mouse model of BPD that disrupting fibronectin localization in the fetal lung mesenchyme causes arrested saccular airway branching. In this study we show that expression of the fibronectin receptor, integrin α8β1, is decreased in the lung mesenchyme in the same inflammation model suggesting it is required for normal lung development. We verified a role for integrin α8β1 in lung development using integrin α8-null mice, which develop fusion of the medial and caudal lobes as well as abnormalities in airway division. We further show in vivo and vitro that α8-null fetal lung mesenchymal cells fail to form stable adhesions and have increased migration. Thus we propose that integrin α8β1 plays a critical role in lung morphogenesis by regulating mesenchymal cell adhesion and migration. Furthermore, our data suggests that disruption of the interactions between extracellular matrix and integrin α8β1 may contribute to the pathogenesis of BPD. PMID:19769957

Idiopathic pulmonary fibrosis fibroblasts become resistant to Fas ligand-dependent apoptosis via the alteration of decoy receptor 3.

PubMed

Im, Jintaek; Kim, Kyutae; Hergert, Polla; Nho, Richard Seonghun

2016-09-01

Idiopathic pulmonary fibrosis (IPF) is an irreversible lethal lung disease with an unknown etiology. IPF patients' lung fibroblasts express inappropriately high Akt activity, protecting them in response to an apoptosis-inducing type I collagen matrix. FasL, a ligand for Fas, is known to be increased in the lung tissues of patients with IPF, implicated with the progression of IPF. Expression of Decoy Receptor3 (DcR3), which binds to FasL, thereby subsequently suppressing the FasL-Fas-dependent apoptotic pathway, is frequently altered in various human disease. However, the role of DcR3 in IPF fibroblasts in regulating their viability has not been examined. We found that enhanced DcR3 expression exists in the majority of IPF fibroblasts on collagen matrices, resulting in the protection of IPF fibroblasts from FasL-induced apoptosis. Abnormally high Akt activity suppresses GSK-3β function, thereby accumulating the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) in the nucleus, increasing DcR3 expression in IPF fibroblasts. This alteration protects IPF cells from FasL-induced apoptosis on collagen. However, the inhibition of Akt or NFATc1 decreases DcR3 mRNA and protein levels, which sensitizes IPF fibroblasts to FasL-mediated apoptosis. Furthermore, enhanced DcR3 and NFATc1 expression is mainly present in myofibroblasts in the fibroblastic foci of lung tissues derived from IPF patients. Our results showed that when IPF cells interact with collagen matrix, aberrantly activated Akt increases DcR3 expression via GSK-3β-NFATc1 and protects IPF cells from the FasL-dependent apoptotic pathway. These findings suggest that the inhibition of DcR3 function may be an effective approach for sensitizing IPF fibroblasts in response to FasL, limiting the progression of lung fibrosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-01-09

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

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.

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

PubMed Central

Oh, Juliana J.; Koegel, Ashley; Phan, Diana T.; Razfar, Ali; Slamon, Dennis J.

2007-01-01

Summary Allele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour vs. adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected, instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC) whereas homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals. PMID:17606309

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

PubMed

Klar, Joakim; Blomstrand, Peter; Brunmark, Charlott; Badhai, Jitendra; Håkansson, Hanna Falk; Brange, Charlotte Sollie; Bergendal, Birgitta; Dahl, Niklas

2011-10-01

Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed. The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function. The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease. These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.

Chest X-Ray (Chest Radiography)

MedlinePlus

... may be necessary to clarify the results of a chest x-ray or to look for abnormalities not visible on the chest x-ray. top of page Additional Information and Resources RTAnswers.org Radiation Therapy for Lung Cancer top of page This page ...

Quantitative CT scans of lung parenchymal pathology in premature infants ages 0-6 years.

PubMed

Spielberg, David R; Walkup, Laura L; Stein, Jill M; Crotty, Eric J; Rattan, Mantosh S; Hossain, Md Monir; Brody, Alan S; Woods, Jason C

2018-03-01

Bronchopulmonary dysplasia (BPD) is a common, heterogeneous disease in premature infants. We hypothesized that quantitative CT techniques could assess lung parenchymal heterogeneity in BPD patients across a broad age range and demonstrate how pathologies change over time. A cross-sectional, retrospective study of children age 0-6 years with non-contrast chest CT scans was conducted. BPD subjects met NICHD/NHLBI diagnostic criteria for BPD and were excluded for congenital lung/airway abnormalities or other known/suspected pulmonary diagnoses; control subjects were not premature and had normal CT scan findings. Radiologic opacities, lucencies, and spatial heterogeneity were quantified via: 1) thresholding using CT-attenuation (HU); 2) manual segmentation; and 3) Ochiai reader-scoring system. Clinical outcomes included BPD severity by NICHD/NHLBI criteria, respiratory support at NICU discharge, wheezing, and respiratory exacerbations. Heterogeneity (standard deviation) of lung attenuation in BPD was significantly greater than in controls (difference 36.4 HU [26.1-46.7 HU], P < 0.001); the difference between the groups decreased 0.58 HU per month of age (0.08-1.07 HU per month, P = 0.02). BPD patients had greater amounts of opacities and lucencies than controls except with automated quantification of lucencies. Cross-sectionally, lucencies per Ochiai score and opacities per manual segmentation decreased with time. No approach measured a statistically significant relationship to BPD clinical severity. Opacities, lucencies, and overall heterogeneity of lungs via quantitative CT can distinguish BPD patients from healthy controls, and these abnormalities decrease with age across BPD patients. Defining BPD severity by clinical outcomes such as respiratory support at several time points (vs a single time point, per current guidelines) may be meaningful. © 2017 Wiley Periodicals, Inc.

Automatic lung segmentation using control feedback system: morphology and texture paradigm.

PubMed

Noor, Norliza M; Than, Joel C M; Rijal, Omar M; Kassim, Rosminah M; Yunus, Ashari; Zeki, Amir A; Anzidei, Michele; Saba, Luca; Suri, Jasjit S

2015-03-01

Interstitial Lung Disease (ILD) encompasses a wide array of diseases that share some common radiologic characteristics. When diagnosing such diseases, radiologists can be affected by heavy workload and fatigue thus decreasing diagnostic accuracy. Automatic segmentation is the first step in implementing a Computer Aided Diagnosis (CAD) that will help radiologists to improve diagnostic accuracy thereby reducing manual interpretation. Automatic segmentation proposed uses an initial thresholding and morphology based segmentation coupled with feedback that detects large deviations with a corrective segmentation. This feedback is analogous to a control system which allows detection of abnormal or severe lung disease and provides a feedback to an online segmentation improving the overall performance of the system. This feedback system encompasses a texture paradigm. In this study we studied 48 males and 48 female patients consisting of 15 normal and 81 abnormal patients. A senior radiologist chose the five levels needed for ILD diagnosis. The results of segmentation were displayed by showing the comparison of the automated and ground truth boundaries (courtesy of ImgTracer™ 1.0, AtheroPoint™ LLC, Roseville, CA, USA). The left lung's performance of segmentation was 96.52% for Jaccard Index and 98.21% for Dice Similarity, 0.61 mm for Polyline Distance Metric (PDM), -1.15% for Relative Area Error and 4.09% Area Overlap Error. The right lung's performance of segmentation was 97.24% for Jaccard Index, 98.58% for Dice Similarity, 0.61 mm for PDM, -0.03% for Relative Area Error and 3.53% for Area Overlap Error. The segmentation overall has an overall similarity of 98.4%. The segmentation proposed is an accurate and fully automated system.

Acute Lung Injury and Persistent Small Airway Disease in a Rabbit Model of Chlorine Inhalation

PubMed Central

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M.; Powell, Karen S.; Roberts, Andrew M.; Hoyle, Gary W.

2016-01-01

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure-volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. PMID:27913141

TU-G-BRA-02: Can We Extract Lung Function Directly From 4D-CT Without Deformable Image Registration?

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

Kipritidis, J; Woodruff, H; Counter, W

Purpose: Dynamic CT ventilation imaging (CT-VI) visualizes air volume changes in the lung by evaluating breathing-induced lung motion using deformable image registration (DIR). Dynamic CT-VI could enable functionally adaptive lung cancer radiation therapy, but its sensitivity to DIR parameters poses challenges for validation. We hypothesize that a direct metric using CT parameters derived from Hounsfield units (HU) alone can provide similar ventilation images without DIR. We compare the accuracy of Direct and Dynamic CT-VIs versus positron emission tomography (PET) images of inhaled {sup 68}Ga-labelled nanoparticles (‘Galligas’). Methods: 25 patients with lung cancer underwent Galligas 4D-PET/CT scans prior to radiation therapy.more » For each patient we produced three CT- VIs. (i) Our novel method, Direct CT-VI, models blood-gas exchange as the product of air and tissue density at each lung voxel based on time-averaged 4D-CT HU values. Dynamic CT-VIs were produced by evaluating: (ii) regional HU changes, and (iii) regional volume changes between the exhale and inhale 4D-CT phase images using a validated B-spline DIR method. We assessed the accuracy of each CT-VI by computing the voxel-wise Spearman correlation with free-breathing Galligas PET, and also performed a visual analysis. Results: Surprisingly, Direct CT-VIs exhibited better global correlation with Galligas PET than either of the dynamic CT-VIs. The (mean ± SD) correlations were (0.55 ± 0.16), (0.41 ± 0.22) and (0.29 ± 0.27) for Direct, Dynamic HU-based and Dynamic volume-based CT-VIs respectively. Visual comparison of Direct CT-VI to PET demonstrated similarity for emphysema defects and ventral-to-dorsal gradients, but inability to identify decreased ventilation distal to tumor-obstruction. Conclusion: Our data supports the hypothesis that Direct CT-VIs are as accurate as Dynamic CT-VIs in terms of global correlation with Galligas PET. Visual analysis, however, demonstrated that different CT-VI algorithms might have varying accuracy depending on the underlying cause of ventilation abnormality. This research was supported by a National Health and Medical Research Council (NHMRC) Australia Fellowship, an Cancer Institute New South Wales Early Career Fellowship 13-ECF-1/15 and NHMRC scholarship APP1038399. No commercial funding was received for this work.« less

Generalized Connective Tissue Disease in Crtap-/- Mouse

PubMed Central

Baldridge, Dustin; Lennington, Jennifer; Weis, MaryAnn; Homan, Erica P.; Jiang, Ming-Ming; Munivez, Elda; Keene, Douglas R.; Hogue, William R.; Pyott, Shawna; Byers, Peter H.; Krakow, Deborah; Cohn, Daniel H.; Eyre, David R.; Lee, Brendan; Morello, Roy

2010-01-01

Mutations in CRTAP (coding for cartilage-associated protein), LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1]) or PPIB (coding for Cyclophilin B [CYPB]) cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in α1(I) and α1(II) chains, there was also loss of 3Hyp at proline 986 in α2(V) chains. In contrast, at two of the known 3Hyp sites in α1(IV) chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V) collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin. PMID:20485499

Rapid Communication: Subclinical bovine respiratory disease - loci and pathogens associated with lung lesions in feedlot cattle.

PubMed

Kiser, J N; Lawrence, T E; Neupane, M; Seabury, C M; Taylor, J F; Womack, J E; Neibergs, H L

2017-06-01

Bovine respiratory disease (BRD) is an economically important disease of feedlot cattle that is caused by viral and bacterial pathogen members of the BRD complex. Many cases of subclinical BRD go untreated and are not detected until slaughter, when lung lesions are identified. The objectives of this study were to identify which BRD pathogens were associated with the presence of lung lesions at harvest and to identify genomic loci that were associated with susceptibility to lung lesions as defined by consolidation of the lung and/or the presence of fibrin tissue. Steers from a Colorado feedlot ( = 920) were tested for the presence of viral and bacterial pathogens using deep pharyngeal and mid-nasal swabs collected on entry into the study. Pathogen profiles were compared between cattle with or without lung consolidation (LC), fibrin tissue in the lung (FT), a combination of LC and FT in the same lung (lung lesions [LL]), and hyperinflated lungs (HIF) at harvest. Genotyping was conducted using the Illumina BovineHD BeadChip. Genomewide association analyses (GWAA) were conducted using EMMAX (efficient mixed-model association eXpedited), and pseudoheritabilities were estimated. The pathogen profile comparisons revealed that LC ( = 0.01, odds ratio [OR] = 3.37) and LL cattle ( = 0.04, OR = 4.58) were more likely to be infected with bovine herpes virus-1 and that HIF cattle were more likely to be infected with spp. ( = 0.04, OR = 4.33). Pseudoheritability estimates were 0.25 for LC, 0.00 for FT, 0.28 for LL, and 0.13 for HIF. Because pseudoheritability for FT was estimated to be 0, GWAA results for FT were not reported. There were 4 QTL that were moderately associated ( < 1 × 10) with only LC, 2 that were associated with only LL, and 1 that was associated with LC and LL. Loci associated with HIF included 12 that were moderately associated and 3 that were strongly associated (uncorrected P < 5 × 10-7). A 24-kb region surrounding significant lead SNP was investigated to identify positional candidate genes. Many positional candidate genes underlying or flanking the detected QTL have been associated with signal transduction, cell adhesion, or gap junctions, which have functional relevance to the maintenance of lung health. The identification of pathogens and QTL associated with the presence of lung abnormalities in cattle exhibiting subclinical BRD allows the identification of loci that may not be detected through manifestation of clinical disease alone.

Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

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

Tait, R.C.; Burnett, A.K.; Robertson, A.G.

1991-06-01

Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, asmore » measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.« less

Smoked marijuana as a cause of lung injury.

PubMed

Tashkin, D P

2005-06-01

In many societies, marijuana is the second most commonly smoked substance after tobacco. While delta9-tetrahydrocannabinol (THC) is unique to marijuana and nicotine to tobacco, the smoke of marijuana, like that of tobacco, consists of a toxic mixture of gases and particulates, many of which are known to be harmful to the lung. Although far fewer marijuana than tobacco cigarettes are generally smoked on a daily basis, the pulmonary consequences of marijuana smoking may be magnified by the greater deposition of smoke particulates in the lung due to the differing manner in which marijuana is smoked. Whereas THC causes modest short-term bronchodilation, regular marijuana smoking produces a number of long-term pulmonary consequences, including chronic cough and sputum, histopathologic evidence of widespread airway inflammation and injury and immunohistochemical evidence of dysregulated growth of respiratory epithelial cells, that may be precursors to lung cancer. The THC in marijuana could contribute to some of these injurious changes through its ability to augment oxidative stress, cause mitochondrial dysfunction, and inhibit apoptosis. On the other hand, physiologic, clinical or epidemiologic evidence that marijuana smoking may lead to chronic obstructive pulmonary disease or respiratory cancer is limited and inconsistent. Habitual use of marijuana is also associated with abnormalities in the structure and function of alveolar macrophages, including impairment in microbial phagocytosis and killing that is associated with defective production of immunostimulatory cytokines and nitric oxide, thereby potentially predisposing to pulmonary infection. In view of the growing interest in medicinal marijuana, further epidemiologic studies are needed to clarify the true risks of regular marijuana smoking on respiratory health.

From mice and men to earth and space: joint NASA-NCI workshop on lung cancer risk resulting from space and terrestrial radiation.

PubMed

Shay, Jerry W; Cucinotta, Francis A; Sulzman, Frank M; Coleman, C Norman; Minna, John D

2011-11-15

On June 27-28, 2011, scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA, available data suggest that lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space, the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high-energy protons from solar flares and not from gamma radiation. In contrast, the NCI is endeavoring to estimate the increased lung cancer risk from the potential widespread implementation of computed tomographic (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be X-rays from CT scans from the screening (which uses "low-dose" CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low-dose exposure to Earth's radiation. The workshop examined preclinical models, epidemiology, molecular markers, "omics" technology, radiobiology issues, and lung stem cells that relate to the development of lung cancer. ©2011 AACR

Chest CT scan findings in World Trade Center workers.

PubMed

de la Hoz, Rafael E; Weber, Jonathan; Xu, Dongming; Doucette, John T; Liu, Xiaoyu; Carson, Deborah A; Celedón, Juan C

2018-03-15

We examined the chest CT scans of 1,453 WTC responders using the International Classification of High-resolution CT for Occupational and Environmental Respiratory Diseases. Univariate and bivariate analyses of potential work-related pleural abnormalities were performed with pre-WTC and WTC-related occupational exposure data, spirometry, demographics and quantitative CT measurements. Logistic regression was used to evaluate occupational predictors of those abnormalities. Chest CT scans were performed first at a median of 6.8 years after 9/11/2001. Pleural abnormalities were the most frequent (21.1%) across all occupational groups In multivariable analyses, significant pre-WTC occupational asbestos exposure, and work as laborer/cleaner were predictive of pleural abnormalities, with prevalence being highest for the Polish subgroup (n = 237) of our population. Continued occupational lung disease surveillance is warranted in this cohort.

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

PubMed

Sonoda, Nao; Morimoto, Akiko; Tatsumi, Yukako; Asayama, Kei; Ohkubo, Takayoshi; Izawa, Satoshi; Ohno, Yuko

2018-05-01

To assess the impact of diabetes on restrictive and obstructive lung function impairment. This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) <80% predicted and forced expiratory volume in 1s (FEV 1 ) to FVC ratio (FEV 1 /FVC) <0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014. During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment. Copyright © 2017. Published by Elsevier Inc.

Proteasome function is not impaired in healthy aging of the lung.

PubMed

Caniard, Anne; Ballweg, Korbinian; Lukas, Christina; Yildirim, Ali Ö; Eickelberg, Oliver; Meiners, Silke

2015-10-01

Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age-related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase-like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging.

A novel sidestream ultrasonic flow sensor for multiple breath washout in children.

PubMed

Fuchs, Susanne I; Sturz, J; Junge, S; Ballmann, M; Gappa, M

2008-08-01

Inert gas multiple breath washout (MBW) for measuring Lung Clearance Index using mass spectrometry and 4% sulfur hexafluoride (SF(6)) as the tracer gas has been shown to be sensitive for detecting early Cystic Fibrosis (CF) lung disease. However, mass spectrometry requires bulky equipment and is expensive to buy and maintain. A novel sidestream ultrasonic device may overcome this problem. The aims of this study were to assess the feasibility and clinical validity of measuring lung volume (functional residual capacity, FRC) and the LCI using the sidestream ultrasonic flow sensor in children and adolescents with CF in relation to spirometry and plain chest radiographs. MBW using the sidestream ultrasonic device and conventional spirometry were performed in 26 patients with CF and 22 healthy controls. In the controls (4.7-17.7 years) LCI was similar to that reported using mass spectrometry (mean (SD) 6.7 (0.5)). LCI was elevated in 77% of the CF children (6.8-18.9 years), whereas spirometry was abnormal in only 38.5%, 61.5%, and 26.9% for FEV(1), MEF(25), and FEV(1)/FVC, respectively. This was more marked in children <10 years. LCI correlated with the Crispin-Norman score, whereas FEV(1) did not. Sidestream ultrasonic MBW is a valid and simple alternative to mass spectrometry for assessing ventilation homogeneity in children. (c) 2008 Wiley-Liss, Inc.

Comparative biology of cystic fibrosis animal models.

PubMed

Fisher, John T; Zhang, Yulong; Engelhardt, John F

2011-01-01

Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

Fully automated calculation of cardiothoracic ratio in digital chest radiographs

NASA Astrophysics Data System (ADS)

Cong, Lin; Jiang, Luan; Chen, Gang; Li, Qiang

2017-03-01

The calculation of Cardiothoracic Ratio (CTR) in digital chest radiographs would be useful for cardiac anomaly assessment and heart enlargement related disease indication. The purpose of this study was to develop and evaluate a fully automated scheme for calculation of CTR in digital chest radiographs. Our automated method consisted of three steps, i.e., lung region localization, lung segmentation, and CTR calculation. We manually annotated the lung boundary with 84 points in 100 digital chest radiographs, and calculated an average lung model for the subsequent work. Firstly, in order to localize the lung region, generalized Hough transform was employed to identify the upper, lower, and outer boundaries of lung by use of Sobel gradient information. The average lung model was aligned to the localized lung region to obtain the initial lung outline. Secondly, we separately applied dynamic programming method to detect the upper, lower, outer and inner boundaries of lungs, and then linked the four boundaries to segment the lungs. Based on the identified outer boundaries of left lung and right lung, we corrected the center and the declination of the original radiography. Finally, CTR was calculated as a ratio of the transverse diameter of the heart to the internal diameter of the chest, based on the segmented lungs. The preliminary results on 106 digital chest radiographs showed that the proposed method could obtain accurate segmentation of lung based on subjective observation, and achieved sensitivity of 88.9% (40 of 45 abnormalities), and specificity of 100% (i.e. 61 of 61 normal) for the identification of heart enlargements.

Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

NASA Astrophysics Data System (ADS)

Suzuki, H.; Mizuguchi, R.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

2015-03-01

Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, p<0.05). This paper demonstrates effectiveness of the proposed method in diagnosis and prognosis of early emphysema in CT screening for lung cancer.

[Henoch-Schönlein Purpura with lung abscess].

PubMed

Nakazawa, Junji; Watanabe, Atsushi; Nakajima, Tomohiro; Mishina, Taijiro; Miyajima, Masahiro; Higami, Tetsuya

2013-09-01

A 72-year-old man had underwent left lower lobectomy for squamous cell carcinoma in our hospital in 2008. Postoperative stage was I A (T1N0M0). In 2010, follow-up chest computed tomography (CT) images showed similar cavitary nodules in segments 2 and 8 of the right lung with positive uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) images. Physical examination, blood tests, and levels of serum tumor markers showed no abnormality. Transbronchial lung biopsy revealed the absence of malignant cells. Segment 8 of the right lower lobe with the nodule was partially resected, and pathological examination demonstrated lung abscess. He was discharged but was hospitalized in another hospital for purpuric rash, fever, and arthralgia. Microscopic albuminuria was noted, and renal biopsy revealed nephritis with immunoglobulin A( IgA)deposition. He was made a diagnosis of Henoch-Schönlein purpura. Oral steroid therapy( prednisolone 60 mg/d) was initiated, resulting in the improvement of symptoms and disapearance of the cavitary nodule in the right lung segment 2.

Preservation of normal lung regions in the adult respiratory distress syndrome

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

Maunder, R.J.; Shuman, W.P.; McHugh, J.W.

1986-05-09

In this report, the authors challenge the commonly held assumption that the adult respiratory distress syndrome (ARDS) is a homogeneous process associated with generalized and relatively uniform damage to the alveolar capillary membrane. They studied 13 patients with ARDS, comparing the pulmonary parenchymal changes seen by standard bedside chest roentgenograms with those seen by computed tomography of the chest. Three patients demonstrated generalized lung involvement by both radiologic techniques. In another eight patients, despite the appearance of generalized involvement on the standard chest x-ray film, the computed tomographic scans showed patchy infiltrates interspersed with areas of normal-appearing lung. Two patientsmore » showed patchy involvement by both techniques. The fact that ARDS spares some regions of lung parenchyma is useful knowledge in understanding the gas-exchange abnormalities of ARDS, the variable responsiveness to positive end-expiratory pressure, and the occurrence of oxygen toxicity. The problem of regional inhomogeneity should also be kept in mind when interpreting lung biopsy specimens or bronchoalveolar lavage fluid in patients with ARDS.« less

Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

PubMed Central

Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

2012-01-01

Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765