ERJ Open Research最新文献

{"title":"Anxiety, depression, physical disease parameters and health-related quality of life in the BronchUK national bronchiectasis cohort.","authors":"Anthony De Soyza, Tess Saunders, Georgina Wild, Phil Mawson, Martin Kelly, Stuart Elborn, Adam T Hill, Tim Gatheral, Anita Sullivan, Charles Haworth, John R Hurst, Jeremy Brown, Mary Carroll, Vidya Navaratnam, Michael Loebinger, Gareth Davies, Henil Upadhyay, Judy Bradley, Paul P Walker, John Steer, Jamie Duckers, Jennifer Pollock, Megan Crichton, James D Chalmers, Richard McNally","doi":"10.1183/23120541.00348-2024","DOIUrl":"10.1183/23120541.00348-2024","url":null,"abstract":"<p><strong>Background: </strong>Bronchiectasis is associated with psychological comorbidity and poor quality of life (QoL), yet guidelines lack focus on psychological morbidity. Using data obtained from the BronchUK database (1341 patients), we examined the link between anxiety/depression and physical disease severity, QoL and long-term outcomes in bronchiectasis.</p><p><strong>Methods: </strong>Computed tomography-confirmed bronchiectasis patients enrolled in the BronchUK study with Hospital Anxiety and Depression Scale (HADS-A/D) data were studied. HADS-A/D scores ≥8 indicated anxiety/depression. QoL was measured by the St George's Respiratory Questionnaire and QoL-Bronchiectasis Questionnaire. Exacerbations during annual follow-up were analysed by negative binomial regression with time in study as an offset adjusted for age, body mass index, sex, <i>Pseudomonas</i> infection, diabetes and forced expiratory volume in 1 s (FEV₁). Cox regression determined probability of hospitalisation using time to first exacerbation.</p><p><strong>Results: </strong>1341 patients were included; 418 had anxiety (31%), 269 (20%) had depression and 201 (15%) had both conditions. HADS-A/D ≥8 was associated with worse QoL (p<0.0001) and clinical severity (<i>e.g.</i> Bronchiectasis Severity Index, FEV₁ and Medical Research Council dyspnoea score (all p<0.01). HADS-A/D ≥8 each was associated with exacerbation (rate ratio (RR) 1.42, 95% CI 1.32-1.52 for HADS-A; RR 1.45, 95% CI 1.34-1.56 for HADS-D, both p<0.0001) and hospitalisation risk (RR 1.58, 95% CI 1.29-1.92 for HADS-A; RR 1.76, 95% CI 1.43-2.17 for HADS-D, both p<0.001). HADS-A/D ≥8 each predicted future hospitalisation (HR 1.30, 95% CI 0.98-1.72, p=0.067 for HADS-A; HR 1.40 95% CI 1.04-1.88, p=0.027 for HADS-D).</p><p><strong>Interpretation: </strong>Anxiety and depression are common in bronchiectasis, correlate with disease severity and predict poor outcomes. Consideration of psychological comorbidities should be evaluated in routine bronchiectasis care.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157463","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":"Pneumonia-specific plasma metabolite profiles among patients hospitalised with infection in Southeast Asia.","authors":"Taylor D Coston, Lu Xia, Shelton W Wright, Viriya Hantrakun, Parinya Chamnan, Gumphol Wongsuvan, Rungnapa Phunpang, Adul Dulsuk, Ekkachai Thiansukhon, Ali Shojaie, Narisara Chantratita, Direk Limmathurotsakul, Sina A Gharib, T Eoin West","doi":"10.1183/23120541.00582-2024","DOIUrl":"10.1183/23120541.00582-2024","url":null,"abstract":"<p><strong>Background: </strong>Community-acquired pneumonia (CAP) is a major public health threat globally but is understudied in regions with the highest burden. The host immune response during infection may differ based on the site of infection. We hypothesised that analysis of the plasma metabolome in patients hospitalised with suspected infection could identify host response pathways specific to CAP.</p><p><strong>Methods: </strong>We analysed the plasma metabolomes of adults admitted to a tertiary care hospital in northeastern Thailand with suspected community-acquired infection. Multivariable linear regression was performed for differential metabolite analyses and the global test was used for pathway analysis comparing patients with CAP <i>versus</i> non-CAP infections and uninfected controls. The least absolute shrinkage and selection operator (LASSO) was used to identify a parsimonious metabolite prognostic signature that was tested on an internal validation set to predict mortality.</p><p><strong>Results: </strong>841 metabolites from 107 CAP patients and 152 non-CAP infected patients were analysed. 52 metabolites were differentially abundant between the CAP and non-CAP groups. CAP was characterised by increased metabolites involved in polyamine metabolism and decreased metabolites involved in lipid pathways. 13 pathways were differentially enriched between the CAP and non-CAP groups, consistent with individual metabolite analyses. 40 metabolites and four pathways were associated with CAP-specific mortality. A four-metabolite signature predicted 28-day mortality in CAP (area under the curve 0.79, 95% CI 0.62-0.97).</p><p><strong>Conclusion: </strong>In a rural tropical setting, CAP induced a distinct metabolomic state compared to non-CAP presentations of infection that may reflect the activation of select host immune responses.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157546","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":"Association of novel antihyperglycaemic drugs <i>versus</i> metformin with COPD exacerbations.","authors":"Yuya Kimura, Taisuke Jo, Norihiko Inoue, Maho Suzukawa, Hiroki Matsui, Yusuke Sasabuchi, Hideo Yasunaga","doi":"10.1183/23120541.00757-2024","DOIUrl":"10.1183/23120541.00757-2024","url":null,"abstract":"<p><strong>Background: </strong>Dipeptidyl peptidase-4 inhibitors (DPP-4 Is), glucagon-like peptidase 1 receptor agonists (GLP-1 RAs) and sodium glucose co-transporter-2 inhibitors (SGLT-2 Is) may contribute to better control of COPD due to their anti-inflammatory effects, like those observed with metformin. We aimed to investigate the association of these novel antihyperglycaemic drugs <i>versus</i> metformin with fewer COPD exacerbations in patients with type 2 diabetes (T2DM) comorbid with COPD.</p><p><strong>Methods: </strong>Using the national administrative database covering 99% of the medical facilities in Japan, we constructed three active comparators new-user cohorts comprising 36 317 patients with T2DM and COPD who initiated treatment with the novel antihyperglycaemic drugs and metformin between 2014 and 2022. Patients' backgrounds were balanced using overlap propensity score weighting. We calculated the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the initial occurrence of COPD exacerbation requiring systemic corticosteroids using a weighted Cox proportional hazards model.</p><p><strong>Results: </strong>DPP-4 Is were associated with a higher incidence of exacerbations requiring systemic corticosteroids (22.4 <i>versus</i> 20.4 per 100 person-years; HR 1.16, 95% CI 1.07-1.25) compared with metformin. In contrast, the incidence of such exacerbations in the GLP-1 RAs (30.1 <i>versus</i> 24.4 per 100 person-years; HR 1.07, 95% CI 0.87-1.32) and SGLT-2 Is (20.7 <i>versus</i> 21.8 per 100 person-years; HR 1.00, 95% CI 0.94-1.06) groups were comparable with that in the metformin group.</p><p><strong>Conclusions: </strong>While DPP-4 Is were associated with poorer control of COPD compared with metformin, GLP-1 RAs and SGLT-2 Is offered COPD control comparable with that of metformin.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157436","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 effect of acetazolamide on exercise haemodynamics in patients with pulmonary arterial and chronic thromboembolic pulmonary hypertension: a randomised controlled trial.","authors":"Arcangelo F Carta, Stéphanie Saxer, Laura Mayer, Simon R Schneider, Michael Furian, Esther I Schwarz, Erik R Swenson, Konrad E Bloch, Mona Lichtblau, Silvia Ulrich","doi":"10.1183/23120541.00782-2024","DOIUrl":"10.1183/23120541.00782-2024","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to investigate the acute effect of acetazolamide on pulmonary haemodynamics during exercise in patients with pulmonary vascular disease (PVD).</p><p><strong>Methods: </strong>Patients with PVD diagnosed as pulmonary arterial (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) underwent right-heart catheterisation with haemodynamic measurements at rest and during stepwise incremental cycling exercise 60 min after receiving intravenous acetazolamide (500 mg) or saline placebo in accordance with a double-blind, randomised-controlled, crossover design. The main outcomes were the difference between pulmonary vascular resistance (PVR) and its components mean pulmonary artery pressure (mPAP), cardiac output (CO) and pulmonary arterial wedge pressure (PAWP), during exercise, assessed by a mixed linear regression analysis.</p><p><strong>Results: </strong>A total of 24 patients (n=7 PAH, n=17 CTEPH; n=17 male) were included (mean±sd age 59±14 years). Treatment with acetazolamide compared with saline placebo showed the following average marginal effects during exercise: unchanged end-exercise power (mean difference -0.8 W, 95% CI -5.7-4.1 W; p=0.740), reduced mPAP (mean difference -1.7 mmHg, 95% CI -2.9- -0.5 mmHg; p=0.007), tendency to reduced CO (mean difference -0.3 L·min^-1, 95% CI -0.7-0.1 L·min^-1; p=0.097), unchanged PVR (mean difference -0.1 Wood units (WU), 95% CI -0.3-0.2 WU; p=0.694), unchanged PAWP (mean difference 0.0 mmHg, 95% CI -0.2-0.3 mmHg; p=0.783) and unchanged mPAP/CO slope (mean difference 0.1 WU, 95% CI -1.0-1.3 WU; p=0.839).</p><p><strong>Conclusion: </strong>Intravenous acetazolamide was well tolerated and resulted in a significant but small decrease in mPAP, while CO, PVR and the pressure-flow slope during exercise were unchanged.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157456","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":"Residual interstitial lung abnormalities post-COVID-19 infection appear independent of lung microbiota.","authors":"Sheridan G Mikhail, David N O'Dwyer","doi":"10.1183/23120541.01153-2024","DOIUrl":"10.1183/23120541.01153-2024","url":null,"abstract":"<p><p><b>The absence of distinct airway microbial signatures in COVID-19 RLA suggests maintenance of local homeostasis but going forward will require larger-scale integrated studies of host-related factors</b> https://bit.ly/3OqUtB3.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157560","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":"PROTEA study: a protocol for a randomised controlled trial evaluating the efficacy, immune effects and cost-effectiveness of oral bacterial lysate therapy to protect moderate-late preterm infants from respiratory tract infections and wheezing.","authors":"Inger C van Duuren, Hermelijn H Smits, Liesbeth Duijts, John Penders, Gerdien A Tramper-Stranders","doi":"10.1183/23120541.00591-2024","DOIUrl":"10.1183/23120541.00591-2024","url":null,"abstract":"<p><p>Infants, children and adults born moderate-late preterm (after 30-36 weeks of pregnancy) are at increased risk of respiratory infections, wheezing and lower lung function leading to increased medication use and hospitalisation. Risk factors frequently present in this population are, at least in part, associated with (lack of) exposure to microbes and subsequent perturbations in microbiome and immune system development. This manuscript presents the protocol of the double-blinded randomised placebo-controlled PROTEA trial, which will demonstrate whether treatment with immunomodulatory bacterial lysates (OM-85) can reduce lower respiratory tract infections and wheeze in the first year of life. The follow-up PROTEA-2 trial will identify possible carry-over effects of OM-85 treatment and investigate the clinical effect of continued treatment in the second year of life. Infants included are otherwise healthy infants born after 30-36 weeks of gestation, excluding those small for gestational age (<3rd percentile). They are recruited shortly after birth in 22 medical centres in the Netherlands. Participants will take OM-85 or placebo starting from 6-10 weeks of life till age 1 year (PROTEA study) or 2 years (PROTEA-2 study) and are closely monitored regarding respiratory health through e-applications. Biological samples, lung function measurements and detailed information on covariates will be collected at ages 2, 6, 12 and 24 months. Biological samples will aid in estimating the impact of bacterial lysate administration on immune cell composition, activation and maturation, vaccination responses, and microbiome diversity and maturation. Participant recruitment started in March 2022.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157555","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":"Impact of seropositivity and disease-modifying antirheumatic drugs on pulmonary tuberculosis risk in rheumatoid arthritis.","authors":"Hayoung Choi, Yeonghee Eun, Kyungdo Han, Jin-Hyung Jung, Wonyoung Jung, Hyungjin Kim, Dong Wook Shin, Hyun Lee","doi":"10.1183/23120541.00957-2024","DOIUrl":"10.1183/23120541.00957-2024","url":null,"abstract":"<p><strong>Background: </strong>It remains unclear whether active pulmonary tuberculosis risk is still high in rheumatoid arthritis patients in settings where tuberculosis infection screening is performed before the use of biologicals. Moreover, the impacts of seropositivity and disease-modifying antirheumatic drugs on active pulmonary tuberculosis risk should be elucidated.</p><p><strong>Methods: </strong>The incidence of active pulmonary tuberculosis was compared between patients with rheumatoid arthritis (n=59 577; 41 501 seropositive rheumatoid arthritis and 18 076 seronegative rheumatoid arthritis) and 1:5 age- and sex-matched controls without rheumatoid arthritis (n=297 885) enrolled between 2010 and 2017. The participants were followed until December 2019.</p><p><strong>Results: </strong>During a median follow-up duration of 4.4 years after a 1-year lag period (interquartile range 2.6-6.4 years; maximum 9 years), patients with rheumatoid arthritis showed a 3.2-fold (95% CI 2.91-3.55) higher active pulmonary tuberculosis risk than matched controls, even after adjusting for potential confounders. In an analysis of rheumatoid arthritis serological status, patients with seropositive rheumatoid arthritis and those with seronegative rheumatoid arthritis showed 3.20-fold (95% CI 2.86-3.58) and 2.54-fold (95% CI 2.13-3.04) increased risks, respectively, relative to matched controls. Furthermore, rheumatoid arthritis patients who were exposed to biological or targeted synthetic and disease-modifying antirheumatic drugs and those not exposed to the drugs showed 4.68-fold (95% CI 3.69-5.93) and 2.88-fold (95% CI 2.59-3.20) increased risks, respectively, relative to matched controls. In rheumatoid arthritis patients, active pulmonary tuberculosis risk factors included male sex, underweight and comorbidities such as diabetes mellitus.</p><p><strong>Conclusion: </strong>Rheumatoid arthritis patients are prone to active pulmonary tuberculosis development, with rates affected by seropositivity and disease-modifying antirheumatic drugs. Focused tuberculosis screenings may need to be carried out in rheumatoid arthritis patients based on our results.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157497","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 respiratory microbiome in patients with post-COVID-19 residual lung abnormalities resembles that of healthy individuals and is distinct from idiopathic pulmonary fibrosis.","authors":"David J F Smith, Nancy M Y Teng, Emma K Denneny, Puja Mehta, Stefan C Stanel, John F Blaikley, Rachel C Chambers, Nazia Chaudhuri, Ben Garfield, Justin L Garner, Peter M George, Poonam Ghai, Onn Min Kon, Yonghua Li, William D-C Man, Joanna C Porter, Valerie Quinn, Pilar Rivera-Ortega, Clare Ross, Leopoldo N Segal, Simone A Walker, Benjamin G Wu, Clare M Lloyd, Iain Stewart, R Gisli Jenkins, Philip L Molyneaux","doi":"10.1183/23120541.00826-2024","DOIUrl":"10.1183/23120541.00826-2024","url":null,"abstract":"<p><strong>Introduction: </strong>Up to 11% of patients are left with residual lung abnormalities following COVID-19 infection. It is unclear whether these changes resolve over time or progress to fibrosis. The airway microbiome is altered in interstitial lung disease, potentially contributing to pathogenesis and disease progression. We hypothesised that the airway microbiome in patients with post-COVID-19 residual lung abnormalities may be altered.</p><p><strong>Methods: </strong>The POST COVID-19 interstitial lung DiseasE (POSTCODE) study recruited subjects with post-COVID-19 residual lung abnormalities for bronchoscopy. 16S ribosomal RNA gene amplicon sequencing was performed on DNA extracted from bronchoalveolar lavage fluid and compared with that from patients with idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis and control subjects.</p><p><strong>Results: </strong>28 subjects with post-COVID-19 residual lung abnormalities were recruited an average of 11 months after infection. No significant associations were found between the lower airway microbiome or bacterial burden and disease severity or trajectory. There was no difference in bacterial burden between post-COVID-19 patients and interstitial lung disease or control subjects. Furthermore, no differences in microbial composition were observed between these patients and those with fibrotic hypersensitivity pneumonitis or controls. However, compared with idiopathic pulmonary fibrosis, there was an increased abundance of <i>Streptococcus</i> and higher α-diversity in subjects with post-COVID-19 residual lung abnormalities.</p><p><strong>Conclusions: </strong>The microbiome and bacterial burden in the lower airways of subjects with post-COVID-19 residual lung abnormalities do not differ from those of controls. The microbiome differs from idiopathic pulmonary fibrosis. This, and the absence of associations between microbial features and disease severity or clinical outcomes, suggests that the microbiome is unlikely to contribute to residual lung abnormalities in patients recovering from COVID-19 infection.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157510","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":"Phenotyping vasodilator responsiveness in idiopathic pulmonary arterial hypertension: any role for the cardiopulmonary exercise test?","authors":"Gayathiri Sivasubramaniam, Andrea Baccelli, Gulam Haji, Francesco Lo Giudice, Clare Weaver, Luke Howard, Rachel Davies","doi":"10.1183/23120541.00837-2024","DOIUrl":"10.1183/23120541.00837-2024","url":null,"abstract":"<p><p><b>Baseline PVR and <i>P</i> _ETCO₂ are independently associated with a positive acute vasoreactive response. Lower mean PAP and mean RAP, and higher RVEF, are seen when responders and non-responders are compared, independent of the degree of pulmonary vasculopathy.</b> https://bit.ly/3YlYKKI.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157502","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":"Deleterious effect of <i>Pseudomonas aeruginosa</i> on F508del-CFTR rescued by elexacaftor/tezacaftor/ivacaftor is clinical strain-dependent in patient-derived nasal cells.","authors":"Caterina Allegretta, Enza Montemitro, Maria Noemi Sgobba, Valeria Capurro, Emanuela Pesce, Fabiana Ciciriello, Gianfranco La Bella, Martina Rossito, Vanessa Tuccio, Fabio Arena, Tarini N A Gunawardena, Lorenzo Guerra, Nicoletta Pedemonte, Nazzareno Capitanio, Claudia Piccoli, Onofrio Laselva","doi":"10.1183/23120541.00970-2024","DOIUrl":"10.1183/23120541.00970-2024","url":null,"abstract":"<p><strong>Background: </strong>The triple cystic fibrosis transmembrane conductance regulator (CFTR) modulators combination elexacaftor/tezacaftor/ivacaftor (ETI) has been approved for people with cystic fibrosis (pwCF) bearing at least one <i>F508del</i> allele. Despite the development of CFTR modulators having dramatically improved respiratory outcomes in pwCF, clinical studies have showed variable responses to this drug formulation. Of note, airway inflammation and bacterial colonisation persist in the upper and lower respiratory tract even in ETI-treated patients.</p><p><strong>Methods: </strong>We first tested the clinical exoproducts (EXO) of <i>Pseudomonas aeruginosa</i> isolated from 15 CF patients in wild-type (WT) and F508del-CFTR CF bronchial epithelial (CFBE) cells. We were then prompted to evaluate the effects of EXO in <i>ex-vivo</i> patient-derived tissues. Therefore, we cultured primary nasal epithelial cells (HNECs) with EXO isolated from the corresponding pwCF to mimic the native status of CF airway.</p><p><strong>Results: </strong>We found that EXO variably decreased WT-, F508del- and ETI-dependent F508del-CFTR function and increased proinflammatory cytokines and reactive oxygen species (ROS) levels in a clinical strain-specific manner. Similarly, we observed a variable reduction of F508del-CFTR function in presence or absence of ETI and upregulation of proinflammatory cytokines and ROS levels. Interestingly, HNECs treated with EXO isolated from the corresponding donor and three different pwCF showed a variable reduction of ETI-dependent F508del-CFTR function mainly due to clinical strains with limited effect of patient background. Furthermore, we demonstrated that ETI pretreatment decreased the cytokines and ROS levels down to the levels of uninfected cells.</p><p><strong>Conclusion: </strong>These preclinical studies suggest that <i>in vitro</i> screening of patient-specific response to CFTR modulators under infection/inflammation conditions could prove to be a valuable tool to enhance the prediction of clinical response.</p>","PeriodicalId":11739,"journal":{"name":"ERJ Open Research","volume":"11 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12107384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157489","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}