Pub Date : 2026-03-04DOI: 10.1136/thorax-2025-223922
Ludovico Messineo,Molly Kim,Ali Azarbarzin,Daniel Vena,Madison Preuss,Neda Esmaeili,Atqiya Aishah,Natalie V Lawrence,Dillon C Gilbertson,David P White,Andrew Wellman,Scott A Sands
BACKGROUNDObstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity).METHODS11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between.RESULTSAs hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001).CONCLUSIONSAcetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA.TRIAL REGISTRATION NUMBERNCT05589792.
背景：阻塞性睡眠呼吸暂停（OSA）在快速眼动（REM）睡眠期间的发病机制与通气驱动下降和下游的颏舌肌张力低下有关。已知碳酸酐酶抑制剂乙酰唑胺可增加通气驱动并改善OSA严重程度。因此，我们测试了乙酰唑胺对rem期为主的OSA严重程度（呼吸暂停低通气指数（AHI）和缺氧负担，共同主要结局）和潜在生理机制（通气驱动、通气和咽肌活动）的影响。方法根据随机、交叉、双盲设计，11例基线多导睡眠图（REM AHI/非REM AHI≥2）以REM为主的OSA患者被分配给乙酰唑胺500 mg，连续3晚（第一晚剂量为一半）或安慰剂。每次干预后进行详细的生理多导睡眠图，记录膈肌和颏舌肌肌电图，中间有1周的洗脱期。与安慰剂相比，乙酰唑胺降低了35.5% （95% CI 23.1%至46.3%）的AHI和35.9% （95% CI 21.1%至48.4%）的缺氧负担（p<0.001），达到了主要终点。REM的机制分析显示，出乎意料的是，乙酰唑胺与安慰剂相比并没有减轻通气驱动的下降(前十分位数（+0.1(-1.0至1.3)L/min, p=0.8）。相反，乙酰唑胺降低了湿缩性（增加了通气：+1.4(1.2至1.8)L/min）并提高了肌肉反应性(通气vs通气坡度：+32(25至41)%通气/通气，p<0.001；颏舌肌与驱动斜率：+0.33（0.13至0.54)%max/(L/min), p=0.001）。结论头孢唑胺可适度改善REM睡眠呼吸暂停，对上气道生理有明显改善，但不能减轻REM睡眠呼吸暂停引起的通气驱动下降。试验注册号05589792。
{"title":"Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.","authors":"Ludovico Messineo,Molly Kim,Ali Azarbarzin,Daniel Vena,Madison Preuss,Neda Esmaeili,Atqiya Aishah,Natalie V Lawrence,Dillon C Gilbertson,David P White,Andrew Wellman,Scott A Sands","doi":"10.1136/thorax-2025-223922","DOIUrl":"https://doi.org/10.1136/thorax-2025-223922","url":null,"abstract":"BACKGROUNDObstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity).METHODS11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between.RESULTSAs hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001).CONCLUSIONSAcetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA.TRIAL REGISTRATION NUMBERNCT05589792.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"61 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350515","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}
Pub Date : 2026-03-03DOI: 10.1136/thorax-2025-224431
Laurence E Ruane,Paul Leong,James H Hull,Philip G Bardin
{"title":"Inducible laryngeal obstruction/vocal cord obstruction: still happening under our noses.","authors":"Laurence E Ruane,Paul Leong,James H Hull,Philip G Bardin","doi":"10.1136/thorax-2025-224431","DOIUrl":"https://doi.org/10.1136/thorax-2025-224431","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"40 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346403","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}
Pub Date : 2026-03-03DOI: 10.1136/thorax-2026-224743
Peer Ameen Shah,Sarah Diver,Chris E Brightling
{"title":"Global asthma and pest control: bugs and WASPs.","authors":"Peer Ameen Shah,Sarah Diver,Chris E Brightling","doi":"10.1136/thorax-2026-224743","DOIUrl":"https://doi.org/10.1136/thorax-2026-224743","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"19 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346401","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}
Pub Date : 2026-03-03DOI: 10.1136/thorax-2025-224461
William M Gardner,Pallavi P Balte,Christina M Eckhardt,Jack E Morris,Surya P Bhatt,David J Couper,Neal D Freedman,David R Jacobs,Ravi Kalhan,Laura R Loehr,Stephanie J London,Pamela L Lutsey,Joseph E Schwartz,Wendy White,Sachin Yende,Tiffany R Sanchez,Elizabeth C Oelsner
INTRODUCTIONSmoked tobacco is a leading risk factor for cardiopulmonary disease. Pipe and cigar use remains common among US adults, yet its risks remain insufficiently understood.METHODSWe analysed data from five pooled cohorts with adults enrolled from 1971 to 2011 with follow-up through 2018. Pipe/cigar use was defined by baseline self-report. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were measured by spirometry. All-cause mortality, coronary heart disease mortality and hospitalisation, respiratory-related mortality, and chronic obstructive pulmonary disease (COPD) mortality and hospitalisation were classified via adjudication or validated algorithms. Associations were estimated with linear mixed models and Fine-Gray subdistribution hazards models adjusted for sociodemographic and clinical factors.RESULTSAmong 22 823 participants (mean (SD) age 48.0 (15.7) years; 44.9% male sex; 70.5% white, 25.4% black, 2.4% Hispanic/Latino), 2621 (11.5%) reported ever pipe/cigar use, including 518 (2.3%) exclusive users without cigarette history. Compared with never tobacco users (n=9931), exclusive pipe/cigar use was associated with faster decline in FEV1 (3.36 mL/year; 95% CI 1.99 to 4.72), FVC (3.73 mL/year; 95% CI 2.05 to 5.42) and FEV1/FVC (0.031 per year; 95% CI 0.008 to 0.054). Exclusive users had higher all-cause mortality (adjusted HR (aHR) 1.24; 95% CI 1.08 to 1.41), COPD hospitalisation/mortality (aHR 2.02; 95% CI 1.41 to 2.90) and preserved ratio impaired spirometry (aHR 1.83; 95% CI 1.24 to 2.71).CONCLUSIONPipe and cigar use was associated with accelerated lung function decline and increased mortality and cardiopulmonary events, including among never cigarette users. These findings underscore the need for prevention and cessation efforts targeting non-cigarette tobacco.
吸烟是导致心肺疾病的主要危险因素。烟斗和雪茄的使用在美国成年人中仍然很普遍，但其风险仍然没有得到充分的了解。方法：我们分析了1971年至2011年纳入的5个成人队列的数据，随访至2018年。烟斗/雪茄使用由基线自我报告定义。肺活量法测定1 s用力呼气量（FEV1）、用力肺活量（FVC）及FEV1/FVC比值。全因死亡率、冠心病死亡率和住院率、呼吸相关死亡率和慢性阻塞性肺疾病（COPD）死亡率和住院率通过判定或经过验证的算法进行分类。用线性混合模型和细灰色亚分布风险模型对社会人口统计学和临床因素进行校正，估计相关性。结果22 823名参与者(平均（SD）年龄48.0（15.7）岁；44.9%为男性；70.5%白人，25.4%黑人，2.4%西班牙裔/拉丁裔)，2621人（11.5%）报告曾使用烟斗/雪茄，其中518人（2.3%）完全没有吸烟史。与从不吸烟的人（n=9931）相比，完全使用烟斗/雪茄与FEV1 （3.36 mL/年；95% CI 1.99至4.72）、FVC （3.73 mL/年；95% CI 2.05至5.42）和FEV1/FVC（0.031 /年；95% CI 0.008至0.054）下降更快相关。纯使用者的全因死亡率较高(调整HR (aHR) 1.24；95% CI 1.08 - 1.41)、COPD住院/死亡率（aHR 2.02; 95% CI 1.41 - 2.90）和肺活量测定保留率受损（aHR 1.83; 95% CI 1.24 - 2.71）。结论：烟斗和雪茄的使用与肺功能衰退加速、死亡率和心肺事件增加有关，包括从不吸烟的人群。这些发现强调需要针对非卷烟烟草进行预防和戒烟工作。
{"title":"Pipe and cigar use, lung function decline and clinical outcomes: an analysis of the NHLBI Pooled Cohorts Study.","authors":"William M Gardner,Pallavi P Balte,Christina M Eckhardt,Jack E Morris,Surya P Bhatt,David J Couper,Neal D Freedman,David R Jacobs,Ravi Kalhan,Laura R Loehr,Stephanie J London,Pamela L Lutsey,Joseph E Schwartz,Wendy White,Sachin Yende,Tiffany R Sanchez,Elizabeth C Oelsner","doi":"10.1136/thorax-2025-224461","DOIUrl":"https://doi.org/10.1136/thorax-2025-224461","url":null,"abstract":"INTRODUCTIONSmoked tobacco is a leading risk factor for cardiopulmonary disease. Pipe and cigar use remains common among US adults, yet its risks remain insufficiently understood.METHODSWe analysed data from five pooled cohorts with adults enrolled from 1971 to 2011 with follow-up through 2018. Pipe/cigar use was defined by baseline self-report. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were measured by spirometry. All-cause mortality, coronary heart disease mortality and hospitalisation, respiratory-related mortality, and chronic obstructive pulmonary disease (COPD) mortality and hospitalisation were classified via adjudication or validated algorithms. Associations were estimated with linear mixed models and Fine-Gray subdistribution hazards models adjusted for sociodemographic and clinical factors.RESULTSAmong 22 823 participants (mean (SD) age 48.0 (15.7) years; 44.9% male sex; 70.5% white, 25.4% black, 2.4% Hispanic/Latino), 2621 (11.5%) reported ever pipe/cigar use, including 518 (2.3%) exclusive users without cigarette history. Compared with never tobacco users (n=9931), exclusive pipe/cigar use was associated with faster decline in FEV1 (3.36 mL/year; 95% CI 1.99 to 4.72), FVC (3.73 mL/year; 95% CI 2.05 to 5.42) and FEV1/FVC (0.031 per year; 95% CI 0.008 to 0.054). Exclusive users had higher all-cause mortality (adjusted HR (aHR) 1.24; 95% CI 1.08 to 1.41), COPD hospitalisation/mortality (aHR 2.02; 95% CI 1.41 to 2.90) and preserved ratio impaired spirometry (aHR 1.83; 95% CI 1.24 to 2.71).CONCLUSIONPipe and cigar use was associated with accelerated lung function decline and increased mortality and cardiopulmonary events, including among never cigarette users. These findings underscore the need for prevention and cessation efforts targeting non-cigarette tobacco.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"249 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346402","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}
Pub Date : 2026-03-03DOI: 10.1136/thorax-2025-224611
Andrew S L Chan,Edmund M T Lau
{"title":"Customised interfaces for positive airway pressure therapy: precision engineering meets real-world complexity.","authors":"Andrew S L Chan,Edmund M T Lau","doi":"10.1136/thorax-2025-224611","DOIUrl":"https://doi.org/10.1136/thorax-2025-224611","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"42 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346404","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}
Pub Date : 2026-02-27DOI: 10.1136/thorax-2025-224666
Selinam Norgbe, David MacDonald
{"title":"Unraveling lung function trajectories and social determinants of health: the quest continues.","authors":"Selinam Norgbe, David MacDonald","doi":"10.1136/thorax-2025-224666","DOIUrl":"https://doi.org/10.1136/thorax-2025-224666","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318367","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}
Pub Date : 2026-02-26DOI: 10.1136/thorax-2025-223465
Michael G Crooks, Dominic L Sykes, Robert R Horne, Helena Cummings, Kay Roy, Alex Fynney, Andrew Whittamore, Shoaib Faruqi, Daryl Freeman, Jennifer K Quint, Katherine Hickman, Bev Bostock, Joanne King, Judith Dyson
{"title":"2024 BTS/NICE/SIGN asthma guidelines have the potential to improve UK asthma outcomes, but we must act now.","authors":"Michael G Crooks, Dominic L Sykes, Robert R Horne, Helena Cummings, Kay Roy, Alex Fynney, Andrew Whittamore, Shoaib Faruqi, Daryl Freeman, Jennifer K Quint, Katherine Hickman, Bev Bostock, Joanne King, Judith Dyson","doi":"10.1136/thorax-2025-223465","DOIUrl":"https://doi.org/10.1136/thorax-2025-223465","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147318347","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}
Pub Date : 2026-02-26DOI: 10.1136/thorax-2025-224612
António Araujo, Ana Rodrigues
{"title":"Rising burden of second primary lung cancers: from survivorship to secondary prevention.","authors":"António Araujo, Ana Rodrigues","doi":"10.1136/thorax-2025-224612","DOIUrl":"https://doi.org/10.1136/thorax-2025-224612","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310391","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}
Pub Date : 2026-02-26DOI: 10.1136/thorax-2025-224204
Vinayak Jain, Taha Khan, David Huard, Brent Brown, Adam Przebinda
{"title":"Large air embolus in the pulmonary artery.","authors":"Vinayak Jain, Taha Khan, David Huard, Brent Brown, Adam Przebinda","doi":"10.1136/thorax-2025-224204","DOIUrl":"https://doi.org/10.1136/thorax-2025-224204","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147310394","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}
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