Lung最新文献

{"title":"The Effects of Diabetes on Gas Transfer Capacity, Lung Volumes, Muscle Strength, and Cardio-pulmonary Responses During Exercise","authors":"Eldar Priel, Emir Ali, Danica Brister, Nermin Diab, Andy Freitag, Paul M. O’Byrne, Hertzel Gerstein, Kieran J. Killian, Imran Satia","doi":"10.1007/s00408-024-00744-9","DOIUrl":"https://doi.org/10.1007/s00408-024-00744-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known.</p><p>Research question</p><p>Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity?</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre. The impact of diabetes on physiological outcomes and maximum power output (MPO) was assessed using stepwise multiple additive linear regression models including age, height, weight, sex, muscle strength, and previous myocardial infarct as co-variates, and was also stratified based on BMI categories.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>40,776 subjects were included in the analysis; 1938 (5%, 66% male) had diabetes. Diabetics were older (59 vs. 53 years), heavier (88.3 vs.78.0 kg), and had a higher BMI (31 vs. 27 kg/m²). The presence of diabetes was independently associated with a reduction in FEV1 (− 130 ml), FVC (− 220 ml), DLCO (− 1.52 ml/min/mmHg), and VA (− 340ml) but not KCO. Patients with diabetes achieved a lower % predicted MPO[diabetic subjects 70% predicted (670 kpm/min ± 95% CI 284) vs. 80% in non-diabetics (786 kpm/min ± 342), <i>p</i> &lt; 0.001]. With the exception of KCO, these differences persisted across BMI categories and after adjusting for MI.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The presence of diabetes is independently associated with weaker muscles, lower ventilatory and gas transfer capacity and translates to a lower exercise capacity. These differences are independent of age, height, weight, sex, and previous MI.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200857","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":"Novel Therapeutic Target for ALI/ARDS: Forkhead Box Transcription Factors","authors":"Xi Zhu, Leyuan Meng, Liqin Xu, Yun Hua, Jian Feng","doi":"10.1007/s00408-024-00740-z","DOIUrl":"https://doi.org/10.1007/s00408-024-00740-z","url":null,"abstract":"<p>ALI/ARDS can be a pulmonary manifestation of a systemic inflammatory response or a result of overexpression of the body’s normal inflammatory response involving various effector cells, cytokines, and inflammatory mediators, which regulate the body’s immune response through different signalling pathways. Forkhead box transcription factors are evolutionarily conserved transcription factors that play a crucial role in various cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism, and DNA damage response. Transcription factors control protein synthesis by regulating gene transcription levels, resulting in diverse biological outcomes. The Fox family plays a role in activating or inhibiting the expression of various molecules related to ALI/ARDS through phosphorylation, acetylation/deacetylation, and control of multiple signalling pathways. An in-depth analysis of the integrated Fox family’s role in ALI/ARDS can aid in the development of potential diagnostic and therapeutic targets for the condition.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200858","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":"Utility of the 52-Gene Risk Score to Identify Patients with Idiopathic Pulmonary Fibrosis at Greater Risk of Mortality in the Era of Antifibrotic Therapy.","authors":"Julia F Söllner, Stefan Bentink, Christian Hesslinger, Thomas B Leonard, Megan L Neely, Nina M Patel, Thomas Schlange, Jamie L Todd, Richard Vinisko, Margaret L Salisbury","doi":"10.1007/s00408-024-00742-x","DOIUrl":"https://doi.org/10.1007/s00408-024-00742-x","url":null,"abstract":"<p><strong>Purpose: </strong>We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy.</p><p><strong>Methods: </strong>The 52-gene risk signature was implemented to classify patients as being at \"high risk\" or \"low risk\" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature.</p><p><strong>Results: </strong>The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort.</p><p><strong>Conclusions: </strong>These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145946","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":"Increased Pneumonia Risk Associated with Concomitant Use of Inhaled Corticosteroids and Benzodiazepines: A Pharmacovigilance Analysis.","authors":"Junlong Ma, Yaxin Liu, Yuanyuan Sun, Chengxian Guo, Guoping Yang","doi":"10.1007/s00408-024-00741-y","DOIUrl":"https://doi.org/10.1007/s00408-024-00741-y","url":null,"abstract":"<p><strong>Background: </strong>Inhaled corticosteroids (ICS) are effective in managing asthma and chronic obstructive pulmonary disease (COPD) but increase the risk of pneumonia. Benzodiazepines (BZD), commonly prescribed for comorbid psychiatric disorders in asthma or COPD patients, are also associated with pneumonia. This study investigates the risk of pneumonia associated with the concomitant use of ICS and BZD.</p><p><strong>Methods: </strong>Data from the FDA Adverse Event Reporting System from Q4 2013 to Q3 2023 were extracted. Reports involving asthma or COPD patients were included. Disproportionality analysis and logistic regression analysis were performed to assess the risk of pneumonia associated with the combined use of ICS and BZD. Additive and multiplicative models were used to further confirm the results. Additionally, subgroup analyses were conducted based on gender, age, and disease type.</p><p><strong>Results: </strong>A total of 238,411 reports were included. The combined use of ICS and BZD was associated with a higher reporting of pneumonia (ROR: 2.41, 95% CI 2.25-2.58). Using additive and multiplicative methods, the results remained significant. The strongest risk signals were observed in specific drug combinations, such as mometasone with clonazepam, budesonide with temazepam, and mometasone with zopiclone. Subgroup analyses showed higher pneumonia risks in females, patients over 60 years old, and those with asthma.</p><p><strong>Conclusion: </strong>Our findings identified a significantly elevated pneumonia risk with the combined use of ICS and BZD. These results highlighted the necessity for cautious co-prescription of ICS and BZD and suggested the need for more comprehensive clinical studies to assess this interaction.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080801","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":"Exhaled Volatile Organic Compounds Detection in Pneumonia Screening: A Comprehensive Meta-analysis.","authors":"Juan He, Ran Zhong, Linlu Xue, Yixuan Wang, Yang Chen, Zihui Xiong, Ziya Yang, Sitong Chen, Wenhua Liang, Jianxing He","doi":"10.1007/s00408-024-00737-8","DOIUrl":"https://doi.org/10.1007/s00408-024-00737-8","url":null,"abstract":"<p><strong>Background: </strong>Pneumonia is a common lower respiratory tract infection, and early diagnosis is crucial for timely treatment and improved prognosis. Traditional diagnostic methods for pneumonia, such as chest imaging and microbiological examinations, have certain limitations. Exhaled volatile organic compounds (VOCs) detection, as an emerging non-invasive diagnostic technique, has shown potential application value in pneumonia screening.</p><p><strong>Method: </strong>A systematic search was conducted on PubMed, Embase, Cochrane Library, and Web of Science, with the retrieval time up to March 2024. The inclusion criteria were diagnostic studies evaluating exhaled VOCs detection for the diagnosis of pneumonia, regardless of the trial design type. A meta-analysis was performed using a bivariate model for sensitivity and specificity.</p><p><strong>Results: </strong>A total of 14 diagnostic studies were included in this meta-analysis. The pooled results demonstrated that exhaled VOCs detection had a combined sensitivity of 0.94 (95% CI: 0.92-0.95) and a combined specificity of 0.83 (95% CI: 0.81-0.84) in pneumonia screening, with an area under the summary receiver operating characteristic (SROC) curve (AUC) of 0.96. The pooled diagnostic odds ratio (DOR) was 104.37 (95% CI: 27.93-390.03), and the pooled positive and negative likelihood ratios (LR) were 8.98 (95% CI: 3.88-20.80) and 0.11 (95% CI: 0.05-0.22), indicating a high diagnostic performance.</p><p><strong>Conclusion: </strong>This study highlights the potential of exhaled VOCs detection as an effective, non-invasive screening method for pneumonia, which could facilitate future diagnosis in pneumonia. Further high-quality, large-scale studies are required to confirm the clinical utility of exhaled VOCs detection in pneumonia screening.</p><p><strong>Study registration: </strong>PROSPERO, Review no. CRD42024520498.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046860","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":"Examination of Firefighting as an Occupational Exposure Criteria for Lung Cancer Screening.","authors":"Savan K Shah, Seungjun Kim, Arsalan A Khan, Vaishnavi Krishnan, Ann M Lally, Palmi N Shah, Gillian C Alex, Christopher W Seder, Michael J Liptay, Nicole M Geissen","doi":"10.1007/s00408-024-00736-9","DOIUrl":"https://doi.org/10.1007/s00408-024-00736-9","url":null,"abstract":"<p><strong>Purpose: </strong>Firefighting is known to be carcinogenic to humans. However, current lung cancer screening guidelines do not account for occupational exposure. We hypothesize that firefighting is an independent risk factor associated with the development of high-risk lung nodules on low-dose CT (LDCT).</p><p><strong>Methods: </strong>Members of a firefighter's union underwent LDCT at a single institution between April 2022 and June 2023 within a lung cancer screening program. Results were interpreted by designated chest radiologists and reported using the Lung-RADS scoring system. Demographic and radiographic data were recorded, and summary statistics are reported.</p><p><strong>Results: </strong>1347 individuals underwent lung cancer screening, with a median age of 51 years (IQR 42-58), including 56 (4.2%) females. Overall, 899 (66.7%) were never smokers, 345 (25.6%) were former smokers, and 103 (7.7%) were current smokers. There were 41 firefighters (3.0%) who had high-risk (Lung-RADS 3 or 4) nodules requiring intervention or surveillance, of which 21 (1.5%) were Lung-RADS 3 and 20 (1.5%) that were Lung-RADS 4. Of the firefighters with high-risk nodules, only 6 (14.6%) were eligible for LDCT based on current screening guidelines. There were 7 high-risk nodules (0.5%) that required procedural intervention, 6 (85.7%) of which were from the non-screening eligible cohort. There were also 20 never-smoking firefighters (57.1%) with high-risk nodules that were non-screening eligible.</p><p><strong>Conclusion: </strong>Firefighting, even in the absence of smoking history, may be associated with the development of high-risk lung nodules on LDCT. Carefully selected occupational exposures should be considered in the development of future lung cancer screening guidelines.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009000","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":"The Lymphatic Highway: How Lymphatics Drive Lung Health and Disease.","authors":"Xinyu Zhang, Xinqian Du, Ye Cui","doi":"10.1007/s00408-024-00739-6","DOIUrl":"https://doi.org/10.1007/s00408-024-00739-6","url":null,"abstract":"<p><p>The pulmonary lymphatic system has emerged as a critical regulator of lung homeostasis and a key contributor to the pathogenesis of respiratory diseases. As the primary conduit responsible for maintaining fluid balance and facilitating immune cell trafficking, the integrity of lymphatic vessels is essential for preserving normal pulmonary structure and function. Lymphatic abnormalities manifest across a broad spectrum of pulmonary disorders, underscoring their significance in respiratory health and disease. This review provides an overview of pulmonary lymphatic biology and delves into the involvement of lymphatics in four major lung diseases: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung transplant rejection. We examine how lymphatic abnormalities manifest in each of these conditions and investigate the mechanisms through which lymphatic remodeling and dysfunction contribute to disease progression. Furthermore, we explore the therapeutic potential of targeting the lymphatic system to ameliorate these debilitating respiratory conditions. Despite the current knowledge, several crucial questions remain unanswered, such as the spatial and temporal dynamics of lymphatic changes, the molecular crosstalk between lymphatics and the lung microenvironment, and the distinction between protective versus detrimental lymphatic phenotypes. Unraveling these mysteries holds the promise of identifying novel molecular regulators, characterizing lymphatic endothelial phenotypes, and uncovering bioactive mediators. By harnessing this knowledge, we can pave the way for the development of innovative disease-modifying therapies targeting the lymphatic highway in lung disorders.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009058","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":"Adam19 Deficiency Impacts Pulmonary Function: Human GWAS Follow-up in a Mouse Knockout Model.","authors":"Huiling Li, John S House, Cody E Nichols, Artiom Gruzdev, James M Ward, Jian-Liang Li, Annah B Wyss, Ezazul Haque, Matthew L Edin, Susan A Elmore, Beth W Mahler, Laura M Degraff, Min Shi, Darryl C Zeldin, Stephanie J London","doi":"10.1007/s00408-024-00738-7","DOIUrl":"10.1007/s00408-024-00738-7","url":null,"abstract":"<p><strong>Purpose: </strong>Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function.</p><p><strong>Methods: </strong>We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent.</p><p><strong>Results: </strong>Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV_0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways.</p><p><strong>Conclusion: </strong>Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996063","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":"Efficacy and Safety of Dexmedetomidine in the Prone Position in Elderly Patients with Pneumonia: A Prospective, Double-Blind, Randomized Controlled Study.","authors":"Huixing Zhang, Jingjing Tan, Hui Zhang, Guanghui An, Cheng Li, Lize Xiong","doi":"10.1007/s00408-024-00735-w","DOIUrl":"https://doi.org/10.1007/s00408-024-00735-w","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to identify a safe and effective method to assist older adults with pneumonia in tolerating the prone position for a longer duration.</p><p><strong>Methods: </strong>This was a randomized, controlled, double-blinded study performed at the Shanghai Fourth People's Hospital. Eighty patients with pneumonia aged ≥ 65 years were included. The patients were able to spontaneous breath in the prone position and were administered intravenous dexmedetomidine or an isotonic sodium chloride solution. The cumulative daily durations of prone positioning for all patients in the two groups were recorded. The primary outcome was the percentage of patients who completed ≥ 9 h/day in the prone position. The secondary outcomes included the incidence of complications in the prone position and patient outcomes.</p><p><strong>Results: </strong>Eighty patients were included (average age: 79.6 ± 8.9 years). The percentage of patients who completed ≥ 9 h/day in the prone position was significantly higher in the dexmedetomidine group than in the placebo group (P = 0.011). The percentage of patients who completed ≥ 12 h/day in the prone position was also significantly greater in the dexmedetomidine group than in the placebo group (P = 0.008). There were no significant differences in other variables between the two groups.</p><p><strong>Conclusions: </strong>The results of this study demonstrate that intravenous dexmedetomidine injection can significantly prolong the duration of spontaneous breathing in the prone position in elderly pneumonia patients without obvious adverse events. We provide a safe and effective method to help patients with pneumonia, especially those with delirium or cognitive impairment, who cannot tolerate the length of time needed for spontaneous breathing in the prone position to be effective.</p><p><strong>Trial registration: </strong>The study was registered with the Chinese Clinical Trial Center (registration number: ChiCRT2300067383) on 2023-01-05.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897763","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":"Pseudomonas aeruginosa Infection and Inflammation in Cystic Fibrosis: A Pilot Study With Lung Explants and a Novel Histopathology Scoring System","authors":"Sankalp Malhotra, Ching Yang, Kerri L. Nicholson, Daniel J. Wozniak, Don Hayes","doi":"10.1007/s00408-024-00733-y","DOIUrl":"https://doi.org/10.1007/s00408-024-00733-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p><i>Pseudomonas aeruginosa</i> is the predominant bacterial pathogen colonizing the cystic fibrosis (CF) lung. Mixed populations of nonmucoid and mucoid variants of <i>P. aeruginosa</i> have been isolated from the CF airway. While the association between mucoid variants and pulmonary function decline is well-established, their impact on inflammation and tissue damage in advanced CF lung disease remains unclear.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This pilot study utilized 1 non-CF and 3 CF lung explants to examine lobar distribution, inflammation, and histopathology related to nonmucoid and mucoid <i>P. aeruginosa</i> infection. To study tissue damage, we developed a novel lung histopathology scoring system, the first applied to human CF lung biopsies, which is comprised of five indicators: bronchiolar epithelial infiltrate, luminal inflammation, peribronchial/bronchiolar infiltrate, peribronchiolar fibrosis, and alveolar involvement.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Mucoid <i>P. aeruginosa</i> variants were distributed throughout the CF lung but associated with greater concentrations of proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-8, and IFN-γ, and one anti-inflammatory cytokine, IL-10, compared to nonmucoid variants. CF lung explants exhibited higher histopathology scores compared to a non-CF lung control. In mixed-variant infection, nonmucoid constituents associated with increased bronchiolar epithelial infiltration, one indicator of histopathology.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This pilot study suggests ongoing interplay between host and bacterial elements in late-stage CF pulmonary disease. Mucoid <i>P. aeruginosa</i> infection correlates with inflammation regardless of lung lobe, whereas nonmucoid <i>P. aeruginosa</i> is associated with increased inflammatory cell infiltration. The development of a novel lung histopathology scoring system lays the groundwork for future large-cohort investigations.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886301","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}