ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2025-224631
Anja Maria Schaffer, Christine Rass, Sarah Schlagenhaufen, Florian Singer
{"title":"Effects of ambient air pollution exposure on lung function in cystic fibrosis: old stories or breaking news?","authors":"Anja Maria Schaffer, Christine Rass, Sarah Schlagenhaufen, Florian Singer","doi":"10.1136/thorax-2025-224631","DOIUrl":"10.1136/thorax-2025-224631","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"821-822"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2025-223325
Robert Lorenz Chua, Carmen Veith, Marc A Schneider, Katharina Jechow, Gelsomina Kaufhold, Said Alkildani, Michelle Wild, Alexander Sudy, Elizabeth Chang Xu, Michael Kreuter, Agnes Boots, Roland Eils, Nicolas C Kahn, Christian Conrad
{"title":"Transcriptomic signatures of IPF in ALI-cultured airway cells and their therapeutic implications.","authors":"Robert Lorenz Chua, Carmen Veith, Marc A Schneider, Katharina Jechow, Gelsomina Kaufhold, Said Alkildani, Michelle Wild, Alexander Sudy, Elizabeth Chang Xu, Michael Kreuter, Agnes Boots, Roland Eils, Nicolas C Kahn, Christian Conrad","doi":"10.1136/thorax-2025-223325","DOIUrl":"10.1136/thorax-2025-223325","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited treatment options. Most single-cell studies rely on end-stage explant lungs, leaving early disease mechanisms poorly understood. Profiling earlier stages may reveal distinct cellular phenotypes that could be pharmacologically targeted. Recent evidence also implicates airway epithelial cells in IPF disease development and progression.</p><p><strong>Methods: </strong>To investigate early-stage IPF mechanisms, we profiled the airway mucosa of newly diagnosed, treatment-naïve patients using single-cell RNA-sequencing of air-liquid interface cultures. We further assessed the transcriptional and functional responses of these cells to antifibrotic drugs (nintedanib and pirfenidone) and a Src kinase inhibitor (saracatinib).</p><p><strong>Results: </strong>Profiling of 129 986 transcriptomes identified primed fibroblasts (<i>PDGFRA</i> <sup>+</sup>, <i>SPP1</i> <sup>+</sup>), dysregulated basal cells (<i>TP63<sup>+</sup></i> , <i>KRT5<sup>+</sup></i> , <i>FN1<sup>+</sup></i> ), and proinflammatory airway epithelial cells (SAA, CXCL, CCL). Integrative analyses with explant-derived IPF atlases revealed different basal and fibroblast phenotypes spanning tissue regions and disease stages. In vitro, bronchial epithelial cells stimulated fibroblast proliferation and activation, and fibroblasts remained sensitive to TGF-β. While all three drugs attenuated many IPF signatures, saracatinib most effectively suppressed fibroblast activation and epithelial proliferation.</p><p><strong>Conclusions: </strong>This study defines epithelial-mesenchymal programmes of the airway mucosa at an early, diagnostic stage of IPF and demonstrates distinct drug responses at single-cell resolution. By linking airway-derived phenotypes to antifibrotic efficacy, our findings highlight the therapeutic potential of saracatinib and may inform future treatment strategies.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"859-870"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2025-222965
Steven L Taylor, Collin R Brooks, Lucy Pembrey, Sarah K Manning, Levi Elms, Harriet Mpairwe, Camila A Figueiredo, Aida Y Oviedo, Martha Chico, Jeroen Burmanje, Hajar Ali, Irene Nambuya, Pius Tumwesige, Steven Robertson, Charlotte E Rutter, Karin van Veldhoven, Susan M Ring, Mauricio L Barreto, Philip J Cooper, Álvaro A Cruz, Neil Pearce, Geraint B Rogers, Jeroen Douwes
{"title":"Airway microbiota in young people across four continents differ by country, asthma status and inflammatory phenotype.","authors":"Steven L Taylor, Collin R Brooks, Lucy Pembrey, Sarah K Manning, Levi Elms, Harriet Mpairwe, Camila A Figueiredo, Aida Y Oviedo, Martha Chico, Jeroen Burmanje, Hajar Ali, Irene Nambuya, Pius Tumwesige, Steven Robertson, Charlotte E Rutter, Karin van Veldhoven, Susan M Ring, Mauricio L Barreto, Philip J Cooper, Álvaro A Cruz, Neil Pearce, Geraint B Rogers, Jeroen Douwes","doi":"10.1136/thorax-2025-222965","DOIUrl":"10.1136/thorax-2025-222965","url":null,"abstract":"<p><strong>Background: </strong>Asthma is an umbrella diagnosis encompassing distinct pathophysiological mechanisms. While a global problem, our understanding of the interplay between respiratory microbiology and airway inflammation is largely from populations in high-income settings. As a result, treatment approaches align poorly with asthma characteristics in less studied populations.</p><p><strong>Objective: </strong>To identify conserved and geographically distinct relationships between airway inflammation and microbiota characteristics in young people with and without asthma.</p><p><strong>Methods: </strong>We conducted a cross-sectional study performing inflammatory phenotyping, microbiota analysis and enumeration of total bacteria, <i>Haemophilus influenzae</i> and <i>Moraxella catarrhalis</i> on 488 induced sputum samples from participants from Brazil (asthma: 68; non-asthma: 8), Ecuador (asthma: 89; non-asthma: 30), Uganda (asthma: 61; non-asthma: 8), New Zealand (asthma: 129; non-asthma: 58) and the UK (asthma: 25; non-asthma: 20). Microbiota characteristics were compared by country, asthma status and inflammatory characteristics, adjusting for age and sex.</p><p><strong>Results: </strong>Asthma inflammatory phenotypes and microbiology differed between countries, with Uganda characterised by higher neutrophils, microbial diversity and bacterial abundance. Comparison of airway inflammation with microbiota characteristics showed conserved relationships across centres, with airway neutrophil proportion explaining variance in microbiota Bray-Curtis dissimilarity (p<0.001) and being positively associated with bacterial abundance, including <i>H. influenzae</i> and <i>M. catarrhalis</i> load (all p<0.05). In contrast, eosinophil proportion was less strongly associated with microbiota dissimilarity (p=0.033) and only associated with <i>Streptococcus</i> abundance. Country-specific associations between airway inflammation and microbiology were evident.</p><p><strong>Conclusion: </strong>Both airway inflammation and microbiology varied geographically in young people with asthma. Associations between microbiota characteristics and neutrophilic phenotype were conserved.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"903-912"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2026-225025
Will Carroll, James Chapman, Francis J Gilchrist
{"title":"Making sense of azithromycin resistance patterns: what have we learnt and what should we do?","authors":"Will Carroll, James Chapman, Francis J Gilchrist","doi":"10.1136/thorax-2026-225025","DOIUrl":"10.1136/thorax-2026-225025","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"819-820"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2025-223863
Helen Strongman, Martina Sykorova, Yi Ting Nikki Yu, Aurélien Belot, Hema Mistry, Ellen Nolte, Sofia Helena Eriksson, Michelle A Miller, Krishnan Bhaskaran, Ian Edward Smith, Charlotte Warren-Gash
{"title":"Incidence and prevalence of obstructive sleep apnoea and narcolepsy in the UK: a population-based descriptive study.","authors":"Helen Strongman, Martina Sykorova, Yi Ting Nikki Yu, Aurélien Belot, Hema Mistry, Ellen Nolte, Sofia Helena Eriksson, Michelle A Miller, Krishnan Bhaskaran, Ian Edward Smith, Charlotte Warren-Gash","doi":"10.1136/thorax-2025-223863","DOIUrl":"10.1136/thorax-2025-223863","url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnoea (OSA) and narcolepsy are estimated to affect approximately 4.8% and 0.047% of the UK population, respectively. We do not know how many people have been diagnosed or how this varies over time and by demographic factors.</p><p><strong>Methods: </strong>We, therefore, conducted a historical population-based descriptive study estimating prevalence and incidence of diagnosed OSA and narcolepsy in England from 2000 to 2019 stratified by demographic factors, and compared estimates to Scotland, Wales and Northern Ireland. Data were from Clinical Practice Research Datalink (CPRD) primary care records linked to Hospital Episode Statistics (HES) admissions. The study population included people with ≥90 days follow-up between 1 January 2000 and 31 December 2019, no prior record of primary or central sleep apnoea, and aged ≥18 years (OSA only). Diagnoses were defined using the first coded record for each condition in CPRD or HES data. Annual prevalence was estimated at mid-year and directly age/sex-standardised to the national population. Incidence was estimated by dividing new diagnoses by total person-time at risk.</p><p><strong>Results: </strong>In England, 2019 adult standardised diagnosed OSA prevalence was 1.40% (95% CI 1.40% to 1.41%) representing approximately 622 528 people; standardised narcolepsy prevalence was 0.020% (95% CI 0.019% to 0.021%) representing approximately 11 307 people. Despite increases over time, diagnosed incidence and prevalence remained substantially lower than published estimates of symptomatic frequency. Rates varied by age, sex, ethnicity and UK nation for both conditions, and urban-rural living, area-based deprivation and practice size for OSA.</p><p><strong>Conclusion: </strong>Our results call for high-quality research to drive initiatives that increase diagnosis rates and address variation.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"871-884"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Significance of diffusing capacity of the lungs for carbon monoxide on chronic thromboembolic pulmonary hypertension.","authors":"Shun Minatsuki, Masaru Hatano, Kouta Funakoshi, Yu Taniguchi, Shiro Adachi, Takumi Inami, Kazuya Hosokawa, Jun Yamashita, Hitoshi Ogino, Ichizo Tsujino, Nobuhiro Yaoita, Nobutaka Ikeda, Nobuhiro Tanabe, Hiroto Shimokawahara, Kayoko Kubota, Ayako Shigeta, Koichiro Tatsumi, Koshin Horimoto, Yoshito Ogihara, Yoshihiro Dohi, Takahiro Hiraide, Takashi Kawakami, Hidekazu Ikemiyagi, Yuichi Tamura, Yoshihiro Fukumoto, Kohtaro Abe","doi":"10.1136/thorax-2025-223670","DOIUrl":"10.1136/thorax-2025-223670","url":null,"abstract":"<p><p>Reduced diffusing capacity of the lungs for carbon monoxide (DLco) reflects microvasculopathy in chronic thromboembolic pulmonary hypertension, yet its clinical value is uncertain. In a Japanese nationwide registry (2018-2023) we studied 1270 patients: 486 formed an event cohort and 299 a treatment cohort who underwent pulmonary endarterectomy or balloon pulmonary angioplasty. Lower baseline DLco was indicative of smaller postprocedural improvements in mean pulmonary artery pressure, pulmonary vascular resistance and cardiac index (all p≤0.023) and a higher risk of clinical events (HR 0.971, p=0.005). Outcomes deteriorated below 59.6%, indicating DLco may help stratify prognosis and treatment benefit.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"913-917"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2025-223943
Brian L Graham, Sanja Stanojevic
{"title":"Extreme value analysis has the potential to improve spirometry interpretation.","authors":"Brian L Graham, Sanja Stanojevic","doi":"10.1136/thorax-2025-223943","DOIUrl":"10.1136/thorax-2025-223943","url":null,"abstract":"<p><strong>Background: </strong>Spirometry is a measure of lung function used to make clinical decisions regarding the diagnosis and management of respiratory conditions. The goal of spirometry interpretation is to relate impairments in mechanical lung function to pulmonary pathology. In many circumstances, interpretation of measured spirometric values relies on comparisons with a 'healthy' reference population. Such inferences assume that spirometric values in healthy populations follow a Gaussian distribution with impaired values concentrated in the lower tail.</p><p><strong>Methods: </strong>We hypothesised that impairments in lung function mechanics generate spirometric values that follow a non-Gaussian distribution as predicted by extreme value analysis. We used a Gumbel distribution to model lung function impairment. We compared the Gaussian healthy distribution to the Gumbel impaired distribution to calculate the relative probability for impaired versus healthy values. The relative probability provides an objective measure of the likelihood that a particular spirometric value is within the healthy or impaired distribution.</p><p><strong>Results: </strong>The potential usefulness of the relative probability was demonstrated in simulated cases, providing an objective delineation of the zone of uncertainty in the transition from normal to impaired lung function.</p><p><strong>Conclusions: </strong>Considering the spirometric measures from people with lung function impairment as a separate distribution from people with healthy lung function provides a more analytic assessment of impairment. Applying extreme value analysis, the relative probability of a spirometric measurement being impaired versus healthy and a more precise definition of the zone of uncertainty potentially provides more objective discrimination of the intersection between the healthy and impaired lung function ranges.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"853-858"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2025-224006
Monica L Mullin, Priyam Verghese, Chuen R Khaw, Andrew Creamer, Amyn Bhamani, Ruth Prendecki, Jennifer L Dickson, Carolyn Horst, Sophie Tisi, Helen Hall, Kylie Gyertson, Esther Arthur-Darkwa, Laura Farrelly, John McCabe, Ricky Thakrar, Arjun Nair, Anand Devaraj, Neal Navani, Allan Hackshaw, Sam M Janes
{"title":"Upstaging of screen-detected lung cancers during diagnostic assessment.","authors":"Monica L Mullin, Priyam Verghese, Chuen R Khaw, Andrew Creamer, Amyn Bhamani, Ruth Prendecki, Jennifer L Dickson, Carolyn Horst, Sophie Tisi, Helen Hall, Kylie Gyertson, Esther Arthur-Darkwa, Laura Farrelly, John McCabe, Ricky Thakrar, Arjun Nair, Anand Devaraj, Neal Navani, Allan Hackshaw, Sam M Janes","doi":"10.1136/thorax-2025-224006","DOIUrl":"10.1136/thorax-2025-224006","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer is the leading cause of cancer-related death worldwide. Low-dose CT (LDCT) screening improves outcomes by detecting early-stage cancers as pulmonary nodules. As most are benign, diagnosing these nodules is challenging and often requires surveillance imaging. The aim of this study is to assess the frequency of cancer progression in a lung cancer screening study as measured by tumour stage (T-stage).</p><p><strong>Methods: </strong>SUMMIT is a prospective cohort study assessing implementation of lung cancer screening with LDCT in a high-risk population. Screen-detected lung cancers with clinical tumour stage cT1a-c at time of referral were included. Upstaging was defined as an increase in T-stage from referral to treatment. The date of death was obtained from the National Cancer Registration and Analysis Service. Cox proportional hazards analysis with adjustment for age, sex, Charlson Comorbidity Index and pack years was used to assess mortality between groups.</p><p><strong>Results: </strong>390 screen-detected cancers were stage cT1a-c at time of referral. Upstaging occurred more frequently in cT1a (n=48, 56%) compared with cT1b (n=83, 38%) or cT1c (n=34, 40%), p=0.01. The proportion of part-solid nodules was similar between groups (upstaged-N=47, 27%, vs not upstaged-N=45, 21%, p=0.19). 43% of tumours increased T-stage from referral to first treatment (n=165). In participants upstaged, time from referral to treatment was longer (upstaged: 84 days, 46-298 vs not upstaged: 72 days, 43-211, p=0.04). Adjusted overall survival analyses showed an association between upstaging and mortality (HR 1.68, 95% CI 1.13 to 2.51, p=0.01).</p><p><strong>Conclusion: </strong>Tumour upstaging occurred in nearly half of early-stage cases in a lung cancer screening population. Tumour upstaging was associated with longer time to treatment and poorer outcomes in this population.</p><p><strong>Trial registration number: </strong>NCT03934866.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"894-902"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2024-222710
Muhammad Saleem Khan, Benjamin Barratt, Bethan Davies, Nicholas J Simmonds, Frédéric B Piel
{"title":"Impact of air pollution on lung function in cystic fibrosis over a decade in London: a UK CF Registry study.","authors":"Muhammad Saleem Khan, Benjamin Barratt, Bethan Davies, Nicholas J Simmonds, Frédéric B Piel","doi":"10.1136/thorax-2024-222710","DOIUrl":"10.1136/thorax-2024-222710","url":null,"abstract":"<p><strong>Objective: </strong>Despite extensive research on the detrimental effects of air pollution on respiratory diseases like asthma and chronic obstructive pulmonary disease, the impact on people with cystic fibrosis (CF) remains understudied. Our study aimed to quantify the association between air pollution exposure and lung function decline in people with CF in London, UK.</p><p><strong>Methods: </strong>Using 10 years (2008-2017) of UK Cystic Fibrosis Registry data, we conducted a longitudinal cohort study to evaluate the association between air pollution and the rate of decline in percent predicted forced expiratory volume in 1 second (ppFEV<sub>1</sub>) among people with CF. Residential postcode exposure was based on high-resolution models of particulate matter with a diameter of less than 2.5 μm (PM<sub>2.5</sub>) and nitrogen dioxide (NO<sub>2</sub>) from the London Air Pollution Toolkit. We estimated the temporal decline in ppFEV<sub>1</sub> in high, medium and low exposure subgroups based on air pollutant concentration tertiles using linear mixed models with random intercepts.</p><p><strong>Results: </strong>We used 3333 ppFEV<sub>1</sub> measurements of 393 people with CF (122 children, 271 adults). Over 40% of these people with CF lived in postcodes falling into the most deprived national quintile. For PM<sub>2.5</sub>, the adjusted mean ppFEV<sub>1</sub> declined by 13.3% (95% CI -24.1% to -4.0%) over the study period in the high-exposure tertile compared with 8.5% (95% CI -11.7% to -6.4%) in the low-exposure tertile. Differences between the exposure groups were less consistent for NO<sub>2</sub>. Children and people with CF with severe genotypes seemed particularly vulnerable.</p><p><strong>Conclusions: </strong>This study provides novel evidence of the detrimental impact of air pollution on lung function in people with CF. Our findings highlight the importance of addressing air pollution as a modifiable risk factor to improve long-term outcomes of people with CF, and the need for national studies of the impact of environmental factors on CF in the UK.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"845-852"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ThoraxPub Date : 2026-08-14DOI: 10.1136/thorax-2025-224094
Ali F Aboklaish, W John Watkins, David Gallacher, Claudia Consoli, John Lowe, Julian R Marchesi, Sailesh Kotecha
{"title":"Assessment of macrolide resistance in the respiratory tract of preterm-born infants during treatment with azithromycin in the AZTEC clinical trial.","authors":"Ali F Aboklaish, W John Watkins, David Gallacher, Claudia Consoli, John Lowe, Julian R Marchesi, Sailesh Kotecha","doi":"10.1136/thorax-2025-224094","DOIUrl":"10.1136/thorax-2025-224094","url":null,"abstract":"<p><strong>Background: </strong>Our multicentre, double-blind, randomised, placebo-controlled Azithromycin therapy for prevention of chronic lung disease of prematurity trial assessed if early 10-day azithromycin treatment improved survival without development of chronic lung disease of prematurity when compared with placebo in 796 preterm-born infants. Since antibiotic resistance remains a significant global health priority, we had preplanned macrolide-resistance assessment in recruited infants. We, therefore, identified baseline macrolide-resistant genes in respiratory samples and determined if this was altered by azithromycin treatment. Furthermore, we assessed if macrolide-resistant bacteria isolated from respiratory samples were also resistant to other common antibiotic classes.</p><p><strong>Methods: </strong>Six common macrolide-resistant genes: <i>erm</i>(A), <i>erm</i>(B), <i>erm</i>(C), <i>erm</i>(F), <i>mef</i>(A/E) and <i>msr</i>(A) were identified by quantitative PCR (qPCR) from serial nasopharyngeal and endotracheal aspirates from recruited infants at baseline (pretreatment), day-5, day-10 and day-14 (post treatment). Azithromycin-resistant bacteria were assessed by culture in presence/absence of azithromycin and underlying resistance mechanisms were confirmed by qPCR. Resistance to other common antibiotics was also evaluated and molecular determinants were identified by whole genome sequencing.</p><p><strong>Results: </strong>From 1108 (n=541 azithromycin, n=567 placebo) respiratory aspirates from 348 preterm infants, the overall prevalence of macrolide-resistant genes was similar in the placebo (63.7%) and azithromycin (63.9%) groups, with only <i>erm</i>(C) gene increased by azithromycin. Azithromycin-resistant bacteria were resistant to multiple clinically used antibiotics, being associated with several different underlying resistance mechanisms. Coagulase-negative staphylococci (CoNS) were the most recovered macrolide-resistant bacteria.</p><p><strong>Conclusions: </strong>Macrolide-resistant genes were noticeably prevalent in the placebo group, with minimal increase with azithromycin treatment, suggesting that, regardless of the additional use of azithromycin, judicious use of antibiotics is required in preterm-born infants.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"838-844"},"PeriodicalIF":9.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}