Lung最新文献

{"title":"Missing Nuts and Bolts: Translating Pulmonary Fibrosis from Preclinical Murine Models to Human Clinical Trials.","authors":"Isaac Kirubakaran Sundar, Scott M Matson","doi":"10.1007/s00408-024-00676-4","DOIUrl":"10.1007/s00408-024-00676-4","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Bronchial Epithelial Cell Transcriptome Changes in Response to Serum from Patients with Different Status of Inflammation.","authors":"Kokilavani Sivaraman, Bin Liu, Beatriz Martinez-Delgado, Julia Held, Manuela Büttner, Thomas Illig, Sonja Volland, Gema Gomez-Mariano, Nils Jedicke, Tetyana Yevsa, Tobias Welte, David S DeLuca, Sabine Wrenger, Beata Olejnicka, Sabina Janciauskiene","doi":"10.1007/s00408-024-00679-1","DOIUrl":"10.1007/s00408-024-00679-1","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the transcriptome of human bronchial epithelial cells (HBEC) in response to serum from patients with different degrees of inflammation.</p><p><strong>Methods: </strong>Serum from 19 COVID-19 patients obtained from the Hannover Unified Biobank was used. At the time of sampling, 5 patients had a WHO Clinical Progression Scale (WHO-CPS) score of 9 (severe illness). The remaining 14 patients had a WHO-CPS of below 9 (range 1-7), and lower illness. Multiplex immunoassay was used to assess serum inflammatory markers. The culture medium of HBEC was supplemented with 2% of the patient's serum, and the cells were cultured at 37 °C, 5% CO₂ for 18 h. Subsequently, cellular RNA was used for RNA-Seq.</p><p><strong>Results: </strong>Patients with scores below 9 had significantly lower albumin and serum levels of E-selectin, IL-8, and MCP-1 than patients with scores of 9. Principal component analysis based on 500 \"core genes\" of RNA-seq segregated cells into two subsets: exposed to serum from 4 (I) and 15 (II) patients. Cells from a subset (I) treated with serum from 4 patients with a score of 9 showed 5566 differentially expressed genes of which 2793 were up- and 2773 downregulated in comparison with cells of subset II treated with serum from 14 patients with scores between 1 and 7 and one with score = 9. In subset I cells, a higher expression of TLR4 and CXCL8 but a lower CDH1, ACE2, and HMOX1, and greater effects on genes involved in metabolic regulation, cytoskeletal organization, and kinase activity pathways were observed.</p><p><strong>Conclusion: </strong>This simple model could be useful to characterize patient serum and epithelial cell properties.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Exploration of the Altered Microbial Gut-Lung Axis in the Pathogenesis of Human Refractory Chronic Cough.","authors":"Simone Baldi, Alessio Fabbrizzi, Leandro Di Gloria, Marco Pallecchi, Giulia Nannini, Mario D'Ambrosio, Cristina Luceri, Gianluca Bartolucci, Matteo Ramazzotti, Giovanni Fontana, Claudia Mannini, Federico Lavorini, Amedeo Amedei","doi":"10.1007/s00408-024-00681-7","DOIUrl":"10.1007/s00408-024-00681-7","url":null,"abstract":"<p><strong>Purpose: </strong>Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut-lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM).</p><p><strong>Methods: </strong>16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances.</p><p><strong>Results: </strong>In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC.</p><p><strong>Conclusion: </strong>Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut-lung communication.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Time to First Cigarette Use and Urine Biomarkers of Tobacco Exposure in Adult Smokers.","authors":"Wenxue Lin","doi":"10.1007/s00408-024-00684-4","DOIUrl":"10.1007/s00408-024-00684-4","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of Extracorporeal Life Support (ECLS) in Acute Severe Asthma: A Narrative Review.","authors":"Nneoma Ekechukwu, Sachin Batra, Deborah Orsi, Marjan Rahmanian, Maneesha Bangar, Amira Mohamed","doi":"10.1007/s00408-023-00667-x","DOIUrl":"10.1007/s00408-023-00667-x","url":null,"abstract":"<p><strong>Background: </strong>In this narrative review we aimed to explore outcomes of extracorporeal life support (extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R)) as rescue therapy in patients with status asthmaticus requiring mechanical ventilation.</p><p><strong>Methods: </strong>Multiple databases were searched for studies fulfilling inclusion criteria. Articles reporting mortality and complications of ECMO and ECCO2R in mechanically ventilated patients with acute severe asthma (ASA) were included. Pooled estimates of mortality and complications were obtained by fitting Poisson's normal modeling.</p><p><strong>Results: </strong>Six retrospective studies fulfilled inclusion criteria thus yielding a pooled mortality rate of 17% (13-20%), pooled risk of bleeding of 22% (7-37%), mechanical complications in 26% (21-31%), infection in 8% (0-21%) and pneumothorax rate 4% (2-6%).</p><p><strong>Conclusion: </strong>Our review identified a variation between institutions in the initiation of ECMO and ECCO2R in patients with status asthmaticus and discrepancy in the severity of illness at the time of cannulation. Despite that, mortality in these studies was relatively low with some studies reporting no mortality which could be attributed to selection bias. While ECMO and ECCO2R use in severe asthma patients is associated with complication risks, further studies exploring the use of ECMO and ECCO2R with mechanical ventilation are required to identify patients with favorable risk benefit ratio.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Idiopathic Pulmonary Fibrosis and Prediction of Disease Severity via Machine Learning Analysis of Comprehensive Metabolic Panel and Complete Blood Count Data.","authors":"Alex N Mueller, Hunter A Miller, Matthew J Taylor, Sally A Suliman, Hermann B Frieboes","doi":"10.1007/s00408-024-00673-7","DOIUrl":"10.1007/s00408-024-00673-7","url":null,"abstract":"<p><strong>Background: </strong>Diagnosis of idiopathic pulmonary fibrosis (IPF) typically relies on high-resolution computed tomography imaging (HRCT) or histopathology, while monitoring disease severity is done via frequent pulmonary function testing (PFT). More reliable and convenient methods of diagnosing fibrotic interstitial lung disease (ILD) type and monitoring severity would allow for early identification and enhance current therapeutic interventions. This study tested the hypothesis that a machine learning (ML) ensemble analysis of comprehensive metabolic panel (CMP) and complete blood count (CBC) data can accurately distinguish IPF from connective tissue disease ILD (CTD-ILD) and predict disease severity as seen with PFT.</p><p><strong>Methods: </strong>Outpatient data with diagnosis of IPF or CTD-ILD (n = 103 visits by 53 patients) were analyzed via ML methodology to evaluate (1) IPF vs CTD-ILD diagnosis; (2) %predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) moderate or mild vs severe; (3) %predicted Forced Vital Capacity (FVC) moderate or mild vs severe; and (4) %predicted FVC mild vs moderate or severe.</p><p><strong>Results: </strong>ML methodology identified IPF from CTD-ILD with AUC_TEST = 0.893, while PFT was classified as DLCO moderate or mild vs severe with AUC_TEST = 0.749, FVC moderate or mild vs severe with AUC_TEST = 0.741, and FVC mild vs moderate or severe with AUC_TEST = 0.739. Key features included albumin, alanine transaminase, %lymphocytes, hemoglobin, %eosinophils, white blood cell count, %monocytes, and %neutrophils.</p><p><strong>Conclusion: </strong>Analysis of CMP and CBC data via proposed ML methodology offers the potential to distinguish IPF from CTD-ILD and predict severity on associated PFT with accuracy that meets or exceeds current clinical practice.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymptomatic Dysphagia and Aspiration in Patients with Idiopathic Bronchiectasis.","authors":"Tal Perluk, Eiman Abu Bandora, Ophir Freund, Tommy Jacob, Inbal Friedman Regev, Eyal Kleinhendler, Michal Shteinberg, Amir Bar-Shai, Yael Oestriecher-Kedem","doi":"10.1007/s00408-024-00683-5","DOIUrl":"10.1007/s00408-024-00683-5","url":null,"abstract":"<p><strong>Purpose: </strong>Although considered contributors to idiopathic bronchiectasis (IB), neither dysphagia nor silent aspiration have been systematically evaluated in IB patients. We aimed to explore the prevalence of asymptomatic dysphagia and silent aspiration in IB patients and to identify parameters predictive of their presence.</p><p><strong>Methods: </strong>This prospective cohort study included IB patients from our Pulmonary Institute without prior history of dysphagia and without prior dysphagia workup. Swallowing function was assessed by the Eating Assessment Tool (EAT-10) questionnaire and by the Fiberoptic Endoscopic Evaluation of Swallowing (FEES) test.</p><p><strong>Results: </strong>Forty-seven patients (31 females, mean age 67 ± 16 years) were recruited. An EAT-10 score ≥ 3 (risk for swallowing problems) was present in 21 patients (44.6%). Forty-two patients (89.3%) had at least one abnormal swallowing parameter in the FEES test. Six patients (12.7%) had a penetration aspiration score (PAS) in the FEES of at least 6, indicating aspiration. An EAT-10 score of 3 was found to be the ideal cutoff to predict aspiration in the FEES, with a good level of accuracy (area under the curve = 0.78, 95% CI 0.629-0.932, p = 0.03) and sensitivity of 83%. This cutoff also showed a trend towards a more severe disease using the FACED (forced expiratory volume, age, colonization with pseudomonas, extension of lung involvement, dyspnea) score (p = 0.05).</p><p><strong>Conclusion: </strong>Dysphagia is prevalent in IB and may be undiagnosed if not specifically sought. We recommend screening all patients with IB for dysphagia by the EAT-10 questionnaire and referring all those with a score of ≥ 3 to formal swallowing assessment.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysphagia as a Missing Link Between Post-surgical- and Opioid-Related Pneumonia.","authors":"Michael Frazure, Clinton L Greene, Kimberly E Iceman, Dena R Howland, Teresa Pitts","doi":"10.1007/s00408-024-00672-8","DOIUrl":"10.1007/s00408-024-00672-8","url":null,"abstract":"<p><strong>Purpose: </strong>Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk.</p><p><strong>Methods: </strong>Eight healthy adult cats were evaluated to determine changes in airway protection status and for evidence of dysphagia in two experiments. (1) In four female cats, airway protection status was tracked following routine abdominal surgery (spay surgery) plus low-dose opioid administration (buprenorphine 0.015 mg/kg, IM, q8-12 h; n = 5). (2) Using a cross-over design, four naive cats (2 male, 2 female) were treated with moderate-dose (0.02 mg/kg) or high-dose (0.04 mg/kg) buprenorphine (IM, q8-12 h; n = 5).</p><p><strong>Results: </strong>Airway protection was significantly affected in both experiments, but the most severe deficits occurred post-surgically as 75% of the animals exhibited silent aspiration.</p><p><strong>Conclusion: </strong>Oropharyngeal swallow is impaired by the partial mu-opioid receptor agonist buprenorphine, most remarkably in the postoperative setting. These findings have implications for the prevention and management of aspiration pneumonia in vulnerable populations.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways","authors":"Seung Min Baek, Mi Na Kim, Eun Gyul Kim, Yu Jin Lee, Chang Hyun Park, Min Jung Kim, Kyung Won Kim, Myung Hyun Sohn","doi":"10.1007/s00408-024-00682-6","DOIUrl":"https://doi.org/10.1007/s00408-024-00682-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140166990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Eosinophil Counts in Acute Exacerbations of Bronchiectasis: Unveiling a Distinct Clinical Phenotype.","authors":"Weixin Chen, Siyi Ran, Chenchang Li, Zhixin Li, Nili Wei, Jing Li, Naijian Li","doi":"10.1007/s00408-023-00668-w","DOIUrl":"10.1007/s00408-023-00668-w","url":null,"abstract":"<p><strong>Background: </strong>Non-cystic fibrosis bronchiectasis is a chronic respiratory disease characterized by bronchial dilation. However, the significance of elevated eosinophil counts in acute exacerbations of bronchiectasis remains unclear.</p><p><strong>Methods: </strong>This retrospective case-control study included 169 hospitalized patients with acute exacerbations of non-cystic fibrosis bronchiectasis. Based on blood eosinophil levels, patients were categorized into eosinophilic and non-eosinophilic bronchiectasis groups. Various clinical variables, including lung function, comorbidities and clinical features were collected for analysis. The study aimed to examine the differences between these groups and their clinical phenotypes.</p><p><strong>Results: </strong>Eosinophilic bronchiectasis (EB) was present in approximately 22% of all hospitalized patients with bronchiectasis, and it was more prevalent among male smokers (P < 0.01). EB exhibited greater severity of bronchiectasis, including worse airway obstruction, higher scores in the E-FACED (FACED combined with exacerbations) and bronchiectasis severity index (BSI), a high glucocorticoids medication possession ratio, and increased hospitalization cost (P < 0.05 or P < 0.01). Furthermore, we observed a significant positive correlation between blood eosinophil count and both sputum eosinophils (r = 0.49, P < 0.01) and serum total immunoglobulin E levels (r = 0.21, P < 0.05). Additional analysis revealed that patients with EB had a higher frequency of shortness of breath (P < 0.05), were more likely to have comorbid sinusitis (P < 0.01), and exhibited a greater number of lung segments affected by bronchiectasis (P < 0.01).</p><p><strong>Conclusions: </strong>These findings suggest that EB presents a distinct pattern of bronchiectasis features, confirming the notion that it is a specific phenotype.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}