ERJ Open Research最新文献

{"title":"High-frequency percussive ventilation in acute respiratory failure.","authors":"Andrea Bruni, Giuseppe Neri, Gianmaria Cammarota, Vincenzo Bosco, Eugenio Biamonte, Letizia Troisi, Annalisa Boscolo, Paolo Navalesi, Federico Longhini, Eugenio Garofalo","doi":"10.1183/23120541.00401-2024","DOIUrl":"10.1183/23120541.00401-2024","url":null,"abstract":"<p><strong>Introduction: </strong>High-frequency percussive ventilation (HFPV) is a ventilation mode characterised by high-frequency breaths. This study investigated the impact of HFPV on gas exchange and clinical outcomes in acute respiratory failure (ARF) patients during spontaneous breathing, noninvasive ventilation (NIV) and invasive mechanical ventilation (iMV).</p><p><strong>Methods: </strong>This systematic review included randomised and nonrandomised studies up to August 2023. Inclusion criteria focused on adult ARF patients, HFPV application, comparisons with other ventilation modes, and outcomes related to oxygenation and clinical parameters. A pooled data analysis was performed comparing HFPV with iMV concerning gas exchange, pulmonary infection and mortality.</p><p><strong>Results: </strong>Of the 51 identified records, 29 met the inclusion criteria. HFPV was safely and effectively applied to ARF patients during spontaneous breathing or NIV, improving oxygenation. For patients who underwent iMV, HFPV significantly enhanced oxygenation and the arterial partial pressure of carbon dioxide, reduced pulmonary infection occurrence and improved survival. Barotrauma rates were not elevated with HFPV, and haemodynamic stability remained unaffected. HFPV was also utilised in patients undergoing extracorporeal membrane oxygenation, resulting in improved lung recruitment and oxygenation.</p><p><strong>Conclusion: </strong>HFPV had favourable effects on physiological and certain clinical outcomes in ARF patients. However, the overall evidence quality remains weak, necessitating large-scale randomised controlled trials for definitive conclusions.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of triple CFTR modulator therapy and azithromycin on ion channels and inflammation in cystic fibrosis.","authors":"Suhad Bani Melhim, Lisa E J Douglas, James A Reihill, Damian G Downey, S Lorraine Martin","doi":"10.1183/23120541.00502-2024","DOIUrl":"10.1183/23120541.00502-2024","url":null,"abstract":"<p><strong>Background: </strong>Inflammation in cystic fibrosis (CF) airways is difficult to treat with well-established regimens often including azithromycin (AZ) as an immunomodulatory drug. As AZ has been reported to require CF transmembrane conductance regulator (CFTR) to be able to reduce interleukin (IL)-8 and given the emergence of highly effective CFTR \"triple\" modulator therapy (elexacaftor/tezacaftor/ivacaftor; ETI), the aim of this study was to investigate the effect of AZ and ETI, singly and in combination, on ion channel activity and to assess the potential anti-inflammatory effects.</p><p><strong>Methods: </strong>Electrophysiological assessment of ETI and AZ was performed on three-dimensional cultures of primary CF human bronchial epithelial (HBE) cells using a Multi Trans-Epithelial Current Clamp. IL-8 from NuLi-1 (non-CF) and CuFi-1 (CF) cells treated with AZ was measured by ELISA. Inflammatory mediators from primary CF HBE cells exposed to tumour necrosis factor-α in the presence of AZ, ETI and their combination, were screened using the Proteome Profiler™ Human Cytokine Array Kit, with selected targets validated by ELISA.</p><p><strong>Results: </strong>AZ did not alter CFTR chloride efflux, nor did it have any synergistic/antagonistic effect in combination with ETI. AZ reduced IL-8 in NuLi-1 but not CuFi-1 cells. The Proteome Profiler™ screen identified several disease-relevant cytokines that were modulated by treatment. Subsequent analysis by ELISA showed IL-8, IL-6, CXCL1 and granulocyte-macrophage colony-stimulating factor to be significantly reduced by treatment with ETI, but not by AZ.</p><p><strong>Conclusions: </strong>Incorporating ETI into the standard of CF care provides an opportunity to re-evaluate therapeutic regimens to reduce treatment burden and safely discontinue chronic treatments such as AZ, without loss of clinical benefit. Identification of redundant treatments in the era of CFTR modulation may improve medication adherence and overcome potential adverse effects associated with the chronic use AZ and other drugs.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of hypercapnia and mortality in home mechanical ventilation: the population-based DISCOVERY study.","authors":"Andreas Palm, Magnus Ekström, Össur Emilsson, Karin Ersson, Mirjam Ljunggren, Josefin Sundh, Ludger Grote","doi":"10.1183/23120541.00461-2024","DOIUrl":"10.1183/23120541.00461-2024","url":null,"abstract":"<p><strong>Background: </strong>Studies on the survival of patients with home mechanical ventilation (HMV) are sparse. We aimed to analyse the impact of controlled hypercapnia on survival over 27 years among patients with HMV in Sweden.</p><p><strong>Study design and methods: </strong>Population-based cohort study of adult patients starting HMV in the Swedish Registry for Respiratory Failure (Swedevox) during 1996-2022 cross-linked with the National Cause of Death registry. Mortality risk factors were analysed using crude and multivariable Cox regression models, including adjustments for anthropometrics, comorbidities, the underlying diagnosis causing chronic hypercapnic respiratory failure (CRF) and the control of hypercapnia (<i>P</i> _aCO₂ ≤6.0 kPa) at follow-up.</p><p><strong>Results: </strong>We included 10 190 patients (50.1% women, age 62.9±14.5 years). Control of hypercapnia at follow-up after 1.3±0.9 years was associated with lower mortality, hazard ratio (HR) 0.74 (95% CI 0.68-0.80) and the association was strongest in those with pulmonary disease, restrictive thoracal disease (RTD), obesity hypoventilation syndrome (OHS) and amyotrophic lateral sclerosis (ALS). Predictors for increased mortality included age, Charlson Comorbidity Index, supplemental oxygen therapy and acute start of HMV therapy. Median survival varied between 0.8 years (95% CI 0.8-0.9 (n=1401)) for ALS and 7.6 years (95% CI 6.9-8.6 (n=1061)) for neuromuscular disease. Three-year survival decreased from 76% (95% CI 71-80) between 1996 and 1998 to 52% (95% CI 50-55) between 2017 and 2019. When adjusting for underlying diagnosis and age, the association between start year and decreased survival disappeared, HR 1.00 (95% CI 0.99-1.01).</p><p><strong>Conclusion: </strong>Controlling <i>P</i> _aCO₂ is a key treatment goal for survival in HMV therapy. Survival differed markedly between diagnosis and age groups, and survival rates have declined as the patient group has aged.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation of <i>Burkholderia cepacia</i> complex in adults with primary ciliary dyskinesia.","authors":"Giulia Spoletini, Connie Webster, Nicola Burke, Emma Farrell, Evie Robson, Miles Denton, Daniel Peckham","doi":"10.1183/23120541.00282-2024","DOIUrl":"10.1183/23120541.00282-2024","url":null,"abstract":"<p><p><b><i>Burkholderia cepacia</i> complex can be isolated in individuals with PCD. Extended microbiological analysis of respiratory samples can maximise the chances of isolation. Registry studies will help assessing the impact of these pathogens on long-term outcomes.</b> https://bit.ly/3xSHCD9.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Childhood lung function is associated with adolescent-onset and persistent asthma.","authors":"Hans Jacob L Koefoed, Anhar Ullah, Jenny Hallberg, Simon Kebede Merid, Maura M Kere, Lesley Lowe, Angela Simpson, Clare S Murray, Ulrike Gehring, Roel Vermeulen, Inger Kull, Anna Bergström, Judith M Vonk, Adnan Custovic, Erik Melén, Gerard H Koppelman","doi":"10.1183/23120541.00469-2024","DOIUrl":"10.1183/23120541.00469-2024","url":null,"abstract":"<p><strong>Background: </strong>Asthma is associated with impaired lung function; however, it is uncertain if a lower childhood lung function is associated with asthma onset and persistence during adolescence. The aims of the present study were to investigate the association between childhood lung function and onset and persistence of asthma during adolescence.</p><p><strong>Methods: </strong>In the population-based BAMSE (Sweden), PIAMA (Netherlands) and MAAS (UK) birth cohorts, we analysed the association of forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), FEV₁/FVC and forced expiratory volume at 75% of FVC at age 8 years with asthma onset and persistence in adolescence (age 12-16 years) using cohort-specific logistic regression analysis followed by meta-analysis.</p><p><strong>Results: </strong>In the BAMSE, PIAMA and MAAS cohorts, asthma incidence in adolescence was 6.1% (112/1824), 3.4% (36/1050) and 5.0% (39/779), respectively. Persistent asthma from childhood to adolescence was observed in 8.2%, 6.4% and 7.7% of all subjects within the respective cohorts. A higher FEV₁ % predicted and FEV₁/FVC at age 8 years was associated with a lower odds for adolescent-onset asthma: OR 0.98 (95% CI 0.97-1.00) and 0.97 (0.94-0.99). These associations remained significant also when restricting the analyses to subjects with no wheezing or asthma treatment in childhood. A higher FEV₁/FVC at age 8 years was associated with a lower odds for asthma persistence in adolescence (0.96 (0.93-0.99)). Sex by lung function interaction analysis was not significant.</p><p><strong>Conclusions: </strong>A higher lung function at school age was associated with a lower risk of adolescent-onset asthma, predominantly in males. This indicates that a lower lung function in childhood may precede and or potentially contribute to asthma incidence and persistence.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum metalloproteinase-7 as a biomarker of progressive pulmonary fibrosis.","authors":"Márcia Araújo, Marília Beltrão, Oksana Sokhatska, Natália Melo, Patrícia Caetano Mota, Helder Novais Bastos, André Terras, David Coelho, Luís Delgado, António Morais","doi":"10.1183/23120541.00553-2024","DOIUrl":"10.1183/23120541.00553-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Progressive pulmonary fibrosis (PPF) corresponds to any fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) that presents clinical, physiological and/or radiological evidence of disease progression similar to IPF. Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis and are associated with disease progression and reduced survival in IPF and other fibrotic ILDs. This study aimed to investigate the role of serum levels of MMP-1 and MMP-7 in patients with fibrotic non-IPF ILD as possible biomarkers of patients at risk of developing PPF.</p><p><strong>Methods: </strong>Newly diagnosed patients with fibrotic non-IPF ILD were included in this study. Serum levels of MMP-1 and MMP-7 were quantified at baseline and disease progression was monitored. PPF was defined according to the recent European Respiratory Society, American Thoracic Society, Japanese Respiratory Society and the Latin American Thoracic Society Clinical Practice Guidelines.</p><p><strong>Results: </strong>79 patients with fibrotic non-IPF ILDs were included and classified as having PPF or non-PPF. Significantly higher levels of MMP-7, but not MMP-1, were detected in the PPF group (p=0.01). MMP-7 was independently associated with PPF (adjusted OR 1.263, 95% CI 1.029-1.551; p=0.026) after adjustment for sex, age and smoking history. A cut-off value of 3.53 ng·mL^-1 for serum MMP-7 levels had a sensitivity of 61% and a specificity of 74% for predicting PPF in non-IPF ILDs.</p><p><strong>Conclusions: </strong>In patients with fibrotic non-IPF ILDs, serum MMP-7 levels were significantly greater in the subgroup of patients meeting the PPF criteria at follow-up. This can be considered and further investigated as a possible biomarker to identify fibrotic ILD patients at risk of PPF.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis Cohort.","authors":"Christian Leo-Hansen, Daniel Faurholt-Jepsen, Tavs Qvist, Christine Højte, Bibi U Nielsen, Thomas Bryrup, Esben H Henriksen, Terese Katzenstein, Marianne Skov, Inger H M Mathiesen, Majbritt Jeppesen, Søren Jensen-Fangel, Hanne V Olesen, Frederik Fouirnaies Buchvald, Kim Gjerum Nielsen, Espen Jimenez-Solem, Christian Ritz, Tacjana Pressler, Mette F Olsen","doi":"10.1183/23120541.00339-2024","DOIUrl":"10.1183/23120541.00339-2024","url":null,"abstract":"<p><strong>Background: </strong>People living with cystic fibrosis in Denmark had early, universal access to triple modulator treatment with elexacaftor/tezacaftor/ivacaftor. Close monitoring allowed us to assess the impact of treatment on lung function and progression of lung disease in an unselected nationwide cystic fibrosis population from 6 years of age.</p><p><strong>Methods: </strong>Data were analysed using linear mixed-effect models to assess changes in levels and annual rates of change (slopes) in percent predicted (pp) forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC (ppFEF_25-75%) between the 12 months pre-treatment and treatment periods. Subgroup analyses assessed the impact of elexacaftor/tezacaftor/ivacaftor among those with/without previous modulator treatment, normal/mild/moderate/severe lung disease at treatment initiation, children/adults and birth cohorts.</p><p><strong>Results: </strong>We included 392 people living with cystic fibrosis with a median (interquartile range) 12 (nine to 15) spirometry measurements per person. The mean (95% CI) improvement in ppFEV₁ was 13.0 (11.3-14.6) 12 months after initiation of elexacaftor/tezacaftor/ivacaftor treatment. The annual rate of change improved from -1.4 (-2.1 - -0.6) ppFEV₁ in the pre-treatment year to 2.7 (1.8-3.5) ppFEV₁ per year during treatment. Similarly, ppFVC increased by 8.0 (7.1-8.9) and FEF_25--75% by 19.5 (17.0-21.9).</p><p><strong>Conclusions: </strong>Using high-resolution data from a nationwide real-world setting, our study documents the impact of elexacaftor/tezacaftor/ivacaftor on lung function across subgroups based on age, disease severity and treatment history. These findings point towards a new period of consistent lung function improvement among people living with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated method of bronchus and artery dimension measurement in an adult bronchiectasis population.","authors":"Angelina L P Pieters, Qianting Lv, Jennifer J Meerburg, Tjeerd van der Veer, Eleni-Rosalina Andrinopoulou, Pierluigi Ciet, James D Chalmers, Michael R Loebinger, Charles S Haworth, J Stuart Elborn, Harm A W M Tiddens","doi":"10.1183/23120541.00231-2024","DOIUrl":"10.1183/23120541.00231-2024","url":null,"abstract":"<p><strong>Aim: </strong>Bronchiectasis (BE) is a disease defined by irreversible dilatation of the airway. Computed tomography (CT) plays an important role in the detection and quantification of BE. The aim of this study was three-fold: 1) to assess bronchus-artery (BA) dimensions using fully automated software in a cohort of BE disease patients; 2) to compare BA dimensions with semi-quantitative BEST-CT (Bronchiectasis Scoring Technique for CT) scores for BE and bronchial wall thickening; and 3) to explore the structure-function relationship between BA-method lumen dimensions and spirometry outcomes.</p><p><strong>Methods: </strong>Baseline CTs of BE patients who participated in a clinical trial were collected retrospectively. CTs were analysed manually with the BEST-CT scoring system and automatically using LungQ (v.2.1.0.1, Thirona, The Netherlands), which measures the following BA dimensions: diameters of bronchial outer wall (B_out), bronchial inner wall (B_in) and artery (A), and bronchial wall thickness (B_wt) and computes BA ratios (B_out/A and B_in/A) to assess bronchial widening. To assess bronchial wall thickness, we used the B_wt/A ratio and the ratio between the bronchus wall area (B_wa) and the area defined by the outer airway (B_oa) (B_wa/B_oa).</p><p><strong>Results: </strong>In total, 65 patients and 16 900 BA pairs were analysed by the automated BA method. The median (range) percentage of BA pairs defined as widened was 69 (55-84)% per CT using a cut-off value of 1.5 for B_out/A, and 53 (42-65)% of bronchial wall were thickened using a cut-off value of 0.14 for B_wt/A. BA dimensions were correlated with comparable outcomes for the BEST-CT scoring method with a correlation coefficient varying between 0.21 to 0.51. The major CT BA determinants of airflow obstruction were bronchial wall thickness (p=0.001) and a narrower bronchial inner diameter (p=0.003).</p><p><strong>Conclusion: </strong>The automated BA method, which is an accurate and sensitive tool, demonstrates a stronger correlation between visual and automated assessment and lung function when using a higher cut-off value to define bronchiectasis.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision disease management: prognostic biomarker for chronic lung damage in long COVID.","authors":"Adrian Oo, Justin Jang Hann Chu","doi":"10.1183/23120541.00647-2024","DOIUrl":"https://doi.org/10.1183/23120541.00647-2024","url":null,"abstract":"<p><p><b>Early detection of potential severe disease progression facilitates implementation of relevant precise disease management strategies. MMP-7 is a reliable prognostic biomarker for long COVID persistent lung damage that should be considered for clinical use.</b> https://bit.ly/3Ccxozg.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute exacerbations in patients with progressive pulmonary fibrosis.","authors":"Michael Kreuter, Elizabeth A Belloli, Elisabeth Bendstrup, Stefania Cerri, Kevin R Flaherty, Shane Shapera, Jin Woo Song, Heiko Mueller, Klaus B Rohr, Yasuhiro Kondoh","doi":"10.1183/23120541.00403-2024","DOIUrl":"https://doi.org/10.1183/23120541.00403-2024","url":null,"abstract":"<p><strong>Background: </strong>Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis.</p><p><strong>Methods: </strong>Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib or placebo. Associations between baseline characteristics and time to first acute exacerbation were assessed using pooled data from both treatment groups using Cox proportional hazard models, firstly univariable models and then a multivariable model using forward stepwise selection. The risk of death was estimated based on the Kaplan-Meier method.</p><p><strong>Results: </strong>Over a median follow-up of approximately 19 months, acute exacerbations were reported in 58 (8.7%) of 663 patients. In the risk factor analysis, the final model included diffusing capacity of the lung for carbon monoxide (<i>D</i> _LCO) % predicted, treatment and age. Lower <i>D</i> _LCO % predicted was associated with an increased risk of acute exacerbation with a hazard ratio (HR) of 1.56 (95% CI 1.21-2.02) per 10 units lower (p<0.001). Age ≥65 years was associated with a numerically increased risk (HR 1.55, 95% CI 0.87-2.77; p=0.14). Treatment with nintedanib conferred a numerically reduced risk <i>versus</i> placebo (HR 0.60, 95% CI 0.35-1.02; p=0.06). The estimated risks of death ≤30 days and ≤90 days after an acute exacerbation were 19.0% (95% CI 8.9-29.2) and 32.0% (95% CI 19.7-44.2).</p><p><strong>Conclusions: </strong>Acute exacerbations of progressive pulmonary fibrosis may have similar risk factors and prognostic impact as acute exacerbations of IPF.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"10 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}