Pub Date : 2025-10-08DOI: 10.1016/s2213-2600(25)00366-2
Priya Venkatesan
<h2>Section snippets</h2><section><section><h2>Early-life exposure to paracetamol versus ibuprofen</h2>Previous non-experimental studies suggest an association between paracetamol exposure in the first year of life and subsequent asthma and eczema developing in childhood; however, randomised trials are needed to establish whether a causal link truly exists. Stuart R Dalziel (University of Auckland, Auckland, New Zealand) presented 1-year results from the PIPPA Tamariki randomised <span><span>study</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> comparing the use of paracetamol versus ibuprofen in early life. The study included 3908 infants in New Zealand</section></section><section><section><h2>Astegolimab for COPD</h2>Triggers of exacerbations in chronic obstructive pulmonary disease (COPD) can release IL-33 that binds to the ST2 receptor and increase inflammation; therefore, targeting the IL-33/SL2 pathway is an area of therapeutic interest. Neil J Greening (University of Leicester, Leicester, UK) presented results from the phase 2b <span><span>ALIENTO trial</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> comparing astegolimab, a human IgG2 monoclonal antibody targeting ST2 and blocking IL-33 activity, versus placebo in current or former smokers aged 40–90 years</section></section><section><section><h2>Sotatercept for PAH</h2>Two studies were presented on sotatercept, a fusion protein that inhibits activin signalling, for the treatment of pulmonary arterial hypertension (PAH). In the first, Ioana R Preston (Tufts Medical Center, Boston, MA, USA) presented new safety data from the <span><span>SOTERIA</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> long-term follow-up study, the interim results for which were published <span><span>previously</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>. Chalmers commented “Sotatercept is a game changer in PAH supported by a series of impactful trials, [but] long-term safety of new therapies is</section></section><section><section><h2>Nerandomilast for IPF</h2>Justin M Oldham (University of Michigan, Ann Arbor, MI, USA) presented final data from the <span><span>FIBRONEER-IPF</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></pat
早期接触扑热息痛与布洛芬之前的非实验研究表明，在生命的第一年接触扑热息痛与随后在儿童时期发生哮喘和湿疹之间存在关联；然而，需要随机试验来确定因果关系是否真的存在。Stuart R Dalziel（新西兰奥克兰大学）介绍了PIPPA Tamariki随机研究1年的结果，比较了早期使用扑热息痛和布洛芬的情况。该研究包括新西兰的3908名婴儿，阿司哥利单抗治疗COPD慢性阻塞性肺疾病（COPD）恶化的触发因素可以释放与ST2受体结合的IL-33并增加炎症；因此，靶向IL-33/SL2通路是一个治疗领域。Neil J Greening （University of Leicester, Leicester， UK）发表了2b期ALIENTO试验的结果，比较了阿斯特戈利单抗（一种靶向ST2并阻断IL-33活性的人IgG2单克隆抗体）与安慰剂在40-90岁当前或曾经吸烟者中的疗效。首先，Ioana R Preston （Tufts Medical Center, Boston， MA， USA）介绍了SOTERIA长期随访研究的新安全性数据，该研究的中期结果已在之前发表。Chalmers评论道：“Sotatercept是一系列有影响力的试验支持的PAH的游戏规则改变者，[但是]新疗法的长期安全性是nerandomilast治疗IPF。justin M Oldham（密歇根大学，Ann Arbor， MI， USA）提交了磷酸二酯酶4B抑制剂nerandomilast治疗特发性肺纤维化（IPF）患者的FIBRONEER-IPF 3期试验的最终数据。1117名平均年龄约为70岁的患者被分配到12周的nerandomilast 9 mg每日2次，nerandomilast 18 mg每日2次或安慰剂组。77.7%的患者在入组时正在服用尼达尼布或吡非尼酮。先前发表的试验结果：高渗盐水和卡西汀治疗支气管扩张加重粘液活性药物，如高渗盐水和卡西汀，通常用于支气管扩张患者，以防止加重；然而，几乎没有证据表明它们的有效性。朱迪·M·布拉德利（英国贝尔法斯特女王大学威尔康-沃尔夫森实验医学研究所）评论说：“支气管扩张患者经常对服用似乎没有效果的药物感到沮丧。”布拉德利介绍了英国CLEAR试验的结果
{"title":"European Respiratory Society International Congress 2025","authors":"Priya Venkatesan","doi":"10.1016/s2213-2600(25)00366-2","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00366-2","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Early-life exposure to paracetamol versus ibuprofen</h2>Previous non-experimental studies suggest an association between paracetamol exposure in the first year of life and subsequent asthma and eczema developing in childhood; however, randomised trials are needed to establish whether a causal link truly exists. Stuart R Dalziel (University of Auckland, Auckland, New Zealand) presented 1-year results from the PIPPA Tamariki randomised <span><span>study</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> comparing the use of paracetamol versus ibuprofen in early life. The study included 3908 infants in New Zealand</section></section><section><section><h2>Astegolimab for COPD</h2>Triggers of exacerbations in chronic obstructive pulmonary disease (COPD) can release IL-33 that binds to the ST2 receptor and increase inflammation; therefore, targeting the IL-33/SL2 pathway is an area of therapeutic interest. Neil J Greening (University of Leicester, Leicester, UK) presented results from the phase 2b <span><span>ALIENTO trial</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> comparing astegolimab, a human IgG2 monoclonal antibody targeting ST2 and blocking IL-33 activity, versus placebo in current or former smokers aged 40–90 years</section></section><section><section><h2>Sotatercept for PAH</h2>Two studies were presented on sotatercept, a fusion protein that inhibits activin signalling, for the treatment of pulmonary arterial hypertension (PAH). In the first, Ioana R Preston (Tufts Medical Center, Boston, MA, USA) presented new safety data from the <span><span>SOTERIA</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> long-term follow-up study, the interim results for which were published <span><span>previously</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>. Chalmers commented “Sotatercept is a game changer in PAH supported by a series of impactful trials, [but] long-term safety of new therapies is</section></section><section><section><h2>Nerandomilast for IPF</h2>Justin M Oldham (University of Michigan, Ann Arbor, MI, USA) presented final data from the <span><span>FIBRONEER-IPF</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></pat","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"33 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247360","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 : 2025-09-30DOI: 10.1016/s2213-2600(25)00239-5
T M Maher, J G Goldin, J Hood, J Pitman, M de los Rios, B P Hobbs, A B Yu-Lin, I Buendia-Roldan, F Thien, J W Song, P C Perea, A Ramírez-Rivera, A DiFrancesco
<h3>Background</h3>The hedgehog (Hh) signalling pathway promotes fibrosis in idiopathic pulmonary fibrosis (IPF), an interstitial lung disease with a high mortality rate. Currently, there is no cure for IPF, and available anti-fibrotics only slow the rate of decline in lung function in IPF. We aimed to assess the safety and efficacy of taladegib (ENV-101), an Hh pathway inhibitor, in IPF in a phase 2a, proof-of-concept clinical trial.<h3>Methods</h3>ENV-IPF-101 was a randomised, double-blind, placebo-controlled, phase 2a trial conducted at 16 clinical sites in Australia, Canada, Malaysia, Mexico, and South Korea for patients with IPF older than 40 years who were not treated with concurrent IPF therapy. Patients were randomly assigned to taladegib 200 mg or placebo equivalent once daily, orally for 12 weeks, with a 6-week follow-up. The primary outcomes were safety in the intention-to-treat population and change from baseline in forced vital capacity (FVC) in the efficacy-evaluable population. Exploratory outcomes were measures of fibrosis on high-resolution CT (HRCT) in the efficacy-evaluable population. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT04968574</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>.<h3>Findings</h3>Between Aug 12, 2021, and July 28, 2023, 41 patients were randomly assigned to the taladegib group (n=21; three [14%] female and 18 [86%] male) or the placebo group (n=20; four [20%] female and 16 [80%] male). All treatment-emergent adverse events possibly or probably related to the study drug were grade 1 or 2, all except one were mild or moderate in severity, and none were serious adverse events. The most common treatment-emergent adverse events in the taladegib group were dysgeusia (12 [57%] of 21), muscle spasms (12 [57%] of 21), and alopecia (11 [52%] of 21); none of these events were reported in the placebo group, for which the most common adverse events reported were diarrhoea (four [20%] of 20), headache (three [15%] of 20), and dizziness (one [5%] of 20). Patients treated with taladegib had an improvement from baseline in FVC and across multiple HRCT-based measures of disease. Between-group differences in change from baseline to week 12 favoured taladegib for the efficacy measures of percent predicted FVC (3·95% [95% CI 0·31–7·60]; p=0·035; mean change from baseline of 1·9% in the taladegib group <em>vs</em> –1·3% for placebo), total lung capacity by HRCT (257·0 mL [95% CI 86·8–427·2]; p=0·0040; mean change from baseline of 206·67 mL in the taladegib group <em>vs</em> –55·58 mL in the placebo group), and percent quantita
hedgehog （Hh）信号通路促进特发性肺纤维化（IPF）的纤维化，IPF是一种高死亡率的间质性肺疾病。目前，还没有治愈IPF的方法，可用的抗纤维化药物只能减缓IPF患者肺功能下降的速度。我们的目的是在一项2a期概念验证临床试验中评估塔拉德吉（ENV-101）（一种Hh通路抑制剂）在IPF中的安全性和有效性。senv -IPF-101是一项随机、双盲、安慰剂对照的2a期临床试验，在澳大利亚、加拿大、马来西亚、墨西哥和韩国的16个临床点进行，针对年龄大于40岁且未同时接受IPF治疗的IPF患者。患者被随机分配到taladegib 200mg或安慰剂当量，每天一次，口服12周，随访6周。主要结果是意向治疗人群的安全性和可疗效评估人群中用力肺活量（FVC）与基线的变化。探索性结果是在可评估疗效的人群中通过高分辨率CT （HRCT）测量纤维化。本研究已在ClinicalTrials.gov注册，编号NCT04968574。在2021年8月12日至2023年7月28日期间，41名患者被随机分配到塔拉德吉组（n=21, 3名[14%]女性，18名[86%]男性）或安慰剂组（n=20, 4名[20%]女性，16名[80%]男性）。所有可能或可能与研究药物相关的治疗中出现的不良事件均为1级或2级，除一例外均为轻度或中度严重事件，没有一例为严重不良事件。taladegib组最常见的治疗不良事件是发音困难（21例中12例[57%]）、肌肉痉挛（21例中12例[57%]）和脱发（21例中11例[52%]）；在安慰剂组中没有这些事件的报告，最常见的不良事件是腹泻（20例中有4例[20%]）、头痛（20例中有3例[15%]）和头晕（20例中有1例[5%]）。接受塔拉德吉治疗的患者FVC和基于hrct的多种疾病测量均较基线有所改善。从基线到第12周的组间差异有利于塔拉德吉的疗效测量：预测FVC的百分比（3.95% [95% CI 0.31 - 7.60]; p= 0.035；塔拉德吉组较基线的平均变化为1.9%，安慰剂组为- 1.3%）、HRCT总肺活量（257·0 mL [95% CI 86·8-427·2];p= 0.0040；塔拉德吉组较基线的平均变化为206·67 mL，安慰剂组为-55·58 mL）和定量间质性肺疾病的百分比(p= 0.047；与基线相比，塔拉德吉组的平均变化为- 9.4%，安慰剂组为1.1%)。试验期间无死亡病例。塔拉德吉可接受的安全性和有效性分析支持在IPF患者（WHISTLE-PF）的2b期试验中进一步研究。FundingEndeavor共同参与。
{"title":"Taladegib for the treatment of idiopathic pulmonary fibrosis (ENV-IPF-101): a multicentre, randomised, double-blind, placebo-controlled, phase 2a trial","authors":"T M Maher, J G Goldin, J Hood, J Pitman, M de los Rios, B P Hobbs, A B Yu-Lin, I Buendia-Roldan, F Thien, J W Song, P C Perea, A Ramírez-Rivera, A DiFrancesco","doi":"10.1016/s2213-2600(25)00239-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00239-5","url":null,"abstract":"<h3>Background</h3>The hedgehog (Hh) signalling pathway promotes fibrosis in idiopathic pulmonary fibrosis (IPF), an interstitial lung disease with a high mortality rate. Currently, there is no cure for IPF, and available anti-fibrotics only slow the rate of decline in lung function in IPF. We aimed to assess the safety and efficacy of taladegib (ENV-101), an Hh pathway inhibitor, in IPF in a phase 2a, proof-of-concept clinical trial.<h3>Methods</h3>ENV-IPF-101 was a randomised, double-blind, placebo-controlled, phase 2a trial conducted at 16 clinical sites in Australia, Canada, Malaysia, Mexico, and South Korea for patients with IPF older than 40 years who were not treated with concurrent IPF therapy. Patients were randomly assigned to taladegib 200 mg or placebo equivalent once daily, orally for 12 weeks, with a 6-week follow-up. The primary outcomes were safety in the intention-to-treat population and change from baseline in forced vital capacity (FVC) in the efficacy-evaluable population. Exploratory outcomes were measures of fibrosis on high-resolution CT (HRCT) in the efficacy-evaluable population. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT04968574</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>Between Aug 12, 2021, and July 28, 2023, 41 patients were randomly assigned to the taladegib group (n=21; three [14%] female and 18 [86%] male) or the placebo group (n=20; four [20%] female and 16 [80%] male). All treatment-emergent adverse events possibly or probably related to the study drug were grade 1 or 2, all except one were mild or moderate in severity, and none were serious adverse events. The most common treatment-emergent adverse events in the taladegib group were dysgeusia (12 [57%] of 21), muscle spasms (12 [57%] of 21), and alopecia (11 [52%] of 21); none of these events were reported in the placebo group, for which the most common adverse events reported were diarrhoea (four [20%] of 20), headache (three [15%] of 20), and dizziness (one [5%] of 20). Patients treated with taladegib had an improvement from baseline in FVC and across multiple HRCT-based measures of disease. Between-group differences in change from baseline to week 12 favoured taladegib for the efficacy measures of percent predicted FVC (3·95% [95% CI 0·31–7·60]; p=0·035; mean change from baseline of 1·9% in the taladegib group <em>vs</em> –1·3% for placebo), total lung capacity by HRCT (257·0 mL [95% CI 86·8–427·2]; p=0·0040; mean change from baseline of 206·67 mL in the taladegib group <em>vs</em> –55·58 mL in the placebo group), and percent quantita","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"40 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188993","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 : 2025-09-30DOI: 10.1016/s2213-2600(25)00284-x
Paolo Spagnolo, Yet H Khor
No Abstract
没有抽象的
{"title":"Hedgehog signalling: on the way to curing idiopathic pulmonary fibrosis","authors":"Paolo Spagnolo, Yet H Khor","doi":"10.1016/s2213-2600(25)00284-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00284-x","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"5 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188994","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 : 2025-09-29DOI: 10.1016/s2213-2600(25)00325-x
Anna-Carin Olin
No Abstract
没有抽象的
{"title":"Inclusion of small airway dysfunction in asthma assessment and management: a place for impulse oscillometry?","authors":"Anna-Carin Olin","doi":"10.1016/s2213-2600(25)00325-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00325-x","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"94 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189052","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 : 2025-09-29DOI: 10.1016/s2213-2600(25)00299-1
Celeste Porsbjerg, Hitasha Rupani, John D Brannan, Shigeharu Ueki, Martijn C Nawijn, Jonas S Erjefält, Pascal Chanez, Gary P Anderson, Ian D Pavord
Remission is emerging as a feasible treatment goal in moderate-to-severe asthma, driven by the success of biologic therapies in controlling inflammation and reducing exacerbations. Yet current definitions of remission—focused on symptom control, lung function, and corticosteroid reduction—lack precision, can only be ascertained retrospectively, and do not reflect the underlying mechanisms and pathology that drive disease progression. This gap limits the clinical applicability of these definitions and might obscure opportunities for early, disease-modifying intervention. In this Series paper, we propose a refined framework for understanding and reaching remission, centred on distinguishing modifiable disease activity from irreversible remodelling and comorbidity-related factors that contribute to disease burden. We introduce the concept of at-risk asthma as a crucial phase characterised by high disease activity and immune dysregulation, in which timely intervention might prevent irreversible airway and extrapulmonary damage and support long-term disease modification. We examine how symptoms, lung function impairment, and exacerbations can arise from distinct and overlapping mechanisms, underscoring the need for careful attribution in clinical assessment. We also outline four key pathophysiological domains—airway hyper-responsiveness, immune hyper-responsiveness, immune remodelling, and structural remodelling—and describe their temporal evolution and implications for treatment responsiveness. Finally, we present a domain-based strategy for assessment and intervention, linking targeted therapies to underlying mechanisms. This approach supports more personalised treatment decisions and redefines remission, not simply as the absence of symptoms, but as stabilisation of disease biology. As the field advances towards earlier intervention and more tailored application of biologics in at-risk asthma, such a framework could be essential to improve long-term outcomes and prevent overtreatment of irreversible disease.
{"title":"Reframing remission in severe asthma: a conceptual framework for distinguishing disease activity versus damage","authors":"Celeste Porsbjerg, Hitasha Rupani, John D Brannan, Shigeharu Ueki, Martijn C Nawijn, Jonas S Erjefält, Pascal Chanez, Gary P Anderson, Ian D Pavord","doi":"10.1016/s2213-2600(25)00299-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00299-1","url":null,"abstract":"Remission is emerging as a feasible treatment goal in moderate-to-severe asthma, driven by the success of biologic therapies in controlling inflammation and reducing exacerbations. Yet current definitions of remission—focused on symptom control, lung function, and corticosteroid reduction—lack precision, can only be ascertained retrospectively, and do not reflect the underlying mechanisms and pathology that drive disease progression. This gap limits the clinical applicability of these definitions and might obscure opportunities for early, disease-modifying intervention. In this Series paper, we propose a refined framework for understanding and reaching remission, centred on distinguishing modifiable disease activity from irreversible remodelling and comorbidity-related factors that contribute to disease burden. We introduce the concept of at-risk asthma as a crucial phase characterised by high disease activity and immune dysregulation, in which timely intervention might prevent irreversible airway and extrapulmonary damage and support long-term disease modification. We examine how symptoms, lung function impairment, and exacerbations can arise from distinct and overlapping mechanisms, underscoring the need for careful attribution in clinical assessment. We also outline four key pathophysiological domains—airway hyper-responsiveness, immune hyper-responsiveness, immune remodelling, and structural remodelling—and describe their temporal evolution and implications for treatment responsiveness. Finally, we present a domain-based strategy for assessment and intervention, linking targeted therapies to underlying mechanisms. This approach supports more personalised treatment decisions and redefines remission, not simply as the absence of symptoms, but as stabilisation of disease biology. As the field advances towards earlier intervention and more tailored application of biologics in at-risk asthma, such a framework could be essential to improve long-term outcomes and prevent overtreatment of irreversible disease.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"37 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189053","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 : 2025-09-29DOI: 10.1016/s2213-2600(25)00256-5
Gerard H Koppelman, Maria Pino-Yanes, Erik Melén, Pippa Powell, Ken R Bracke, Juan C Celedón, Guy G Brusselle
Asthma is a common chronic airway disease affecting an estimated 260 million individuals of all ages worldwide, contributing to substantial morbidity, mortality, and economic burden. Asthma is heterogeneous in age at onset (childhood vs adult onset), clinical presentation, type of underlying airway inflammation (type 2 high vs type 2 low), prognosis, and treatment response. Asthma is caused by multiple genetic and environmental factors, and possibly their interaction, across the life course. Genetic studies have provided important insights into the pathogenesis, biology, and immunology of asthma, fostering drug discovery. The role of polygenic risk scores in aiding asthma diagnostics and delineating individuals at high risk of asthma development is becoming more evident. Four modifiable environmental, social, and lifestyle risk factors for asthma are responsible for nearly 30% of the global disability-adjusted life-years asthma burden: high BMI, occupational exposures, NO2 (as a proxy for traffic-related air pollution), and smoking. These modifiable risk factors offer substantial opportunities for primary prevention of asthma, at the individual and societal level. National, regional, and global strategies aligned with the UN Sustainable Development Goals are urgently needed to attenuate the predicted increase in asthma cases by 2050.
{"title":"Genetic and environmental risk factors for asthma: towards prevention","authors":"Gerard H Koppelman, Maria Pino-Yanes, Erik Melén, Pippa Powell, Ken R Bracke, Juan C Celedón, Guy G Brusselle","doi":"10.1016/s2213-2600(25)00256-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00256-5","url":null,"abstract":"Asthma is a common chronic airway disease affecting an estimated 260 million individuals of all ages worldwide, contributing to substantial morbidity, mortality, and economic burden. Asthma is heterogeneous in age at onset (childhood <em>vs</em> adult onset), clinical presentation, type of underlying airway inflammation (type 2 high <em>vs</em> type 2 low), prognosis, and treatment response. Asthma is caused by multiple genetic and environmental factors, and possibly their interaction, across the life course. Genetic studies have provided important insights into the pathogenesis, biology, and immunology of asthma, fostering drug discovery. The role of polygenic risk scores in aiding asthma diagnostics and delineating individuals at high risk of asthma development is becoming more evident. Four modifiable environmental, social, and lifestyle risk factors for asthma are responsible for nearly 30% of the global disability-adjusted life-years asthma burden: high BMI, occupational exposures, NO<sub>2</sub> (as a proxy for traffic-related air pollution), and smoking. These modifiable risk factors offer substantial opportunities for primary prevention of asthma, at the individual and societal level. National, regional, and global strategies aligned with the UN Sustainable Development Goals are urgently needed to attenuate the predicted increase in asthma cases by 2050.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"34 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189055","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 : 2025-09-29DOI: 10.1016/s2213-2600(25)00337-6
Peter Ranscombe
No Abstract
没有抽象的
{"title":"Guy Brusselle: using hypothesis-driven and hypothesis-free research to aid people with asthma","authors":"Peter Ranscombe","doi":"10.1016/s2213-2600(25)00337-6","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00337-6","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"116 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189062","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 : 2025-09-29DOI: 10.1016/s2213-2600(25)00283-8
Stanley P Galant, Pauline J M Kuks, Tessa M Kole, Monica Kraft, Salman Siddiqui, Leonardo M Fabbri, Bianca Beghé, Klaus F Rabe, Alberto Papi, Christopher E Brightling, Dave Singh, Janwillem W H Kocks, Laura Franzini, Judith M Vonk, Huib A M Kerstjens, Irene H Heijink, Simon D Pouwels, Dirk-Jan Slebos, Maarten van den Berge
<h3>Background</h3>Recent surveys suggest that asthma remains inadequately controlled in more than 50% of adults with asthma despite guideline-based standard therapy. Small airways are often under-recognised as major sites of airway obstruction and inflammation. This might be related to lack of assessment with current tools such as impulse oscillometry, and thus under-treatment might explain inadequate control. Small airway dysfunction, which is common in adults with well controlled asthma, might represent an important biomarker of future risk of exacerbations. We aimed to investigate whether small airway dysfunction is present in patients with well controlled asthma and, if so, whether it is a risk factor for future exacerbations in this population.<h3>Methods</h3>The observational Assessment of Small Airways Involvement in Asthma (ATLANTIS) study included 773 extensively characterised patients with asthma aged 18–65 years from 29 primary and specialty clinics in nine countries from June 30, 2014, to March 3, 2017. Patients were required to be diagnosed with asthma at least 6 months before inclusion based on evidence of airway hyper-responsiveness, bronchodilator reversibility, or peak expiratory flow variability. Patients were required to have stable asthma, defined as no asthma exacerbations and regular asthma treatment at a consistent dose for 8 weeks before baseline visits. The current analysis included patients with well controlled asthma, defined as an Asthma Control Questionnaire (ACQ-6) score of less than 0·75 at baseline. Small airway dysfunction was defined, based on deviation from predicted values of impulse oscillometry parameters, as a Z score of more than 1·645 for R5–R20 (resistance at 5 Hz minus resistance at 20 Hz) and AX (area of reactance) and a Z score of less than –1·645 for X5 (reactance at 5 Hz), with additional analyses exploring severe small airway dysfunction (Z score of 3 or –3). ATLANTIS is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT02123667</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>.<h3>Findings</h3>Of 773 patients, ACQ-6 assessments were available for 772 patients. Among these patients, 384 (50%) were classified as having well controlled asthma, and small airway dysfunction was present in 108 (36% [95% CI 30–41]) of 304 patients with impulse oscillometry data available for R5–R20, 89 (34% [28–42]) of 261 patients with data for AX, and 79 (26% [21–31]) of 303 patients with data for X5. In the multivariable analysis, we found that R5–R20-defined small airway dysfunction was associated with increased risk of future exacerbati
{"title":"Assessment of the role of small airway dysfunction in relation to exacerbation risk in patients with well controlled asthma (ATLANTIS): an observational study","authors":"Stanley P Galant, Pauline J M Kuks, Tessa M Kole, Monica Kraft, Salman Siddiqui, Leonardo M Fabbri, Bianca Beghé, Klaus F Rabe, Alberto Papi, Christopher E Brightling, Dave Singh, Janwillem W H Kocks, Laura Franzini, Judith M Vonk, Huib A M Kerstjens, Irene H Heijink, Simon D Pouwels, Dirk-Jan Slebos, Maarten van den Berge","doi":"10.1016/s2213-2600(25)00283-8","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00283-8","url":null,"abstract":"<h3>Background</h3>Recent surveys suggest that asthma remains inadequately controlled in more than 50% of adults with asthma despite guideline-based standard therapy. Small airways are often under-recognised as major sites of airway obstruction and inflammation. This might be related to lack of assessment with current tools such as impulse oscillometry, and thus under-treatment might explain inadequate control. Small airway dysfunction, which is common in adults with well controlled asthma, might represent an important biomarker of future risk of exacerbations. We aimed to investigate whether small airway dysfunction is present in patients with well controlled asthma and, if so, whether it is a risk factor for future exacerbations in this population.<h3>Methods</h3>The observational Assessment of Small Airways Involvement in Asthma (ATLANTIS) study included 773 extensively characterised patients with asthma aged 18–65 years from 29 primary and specialty clinics in nine countries from June 30, 2014, to March 3, 2017. Patients were required to be diagnosed with asthma at least 6 months before inclusion based on evidence of airway hyper-responsiveness, bronchodilator reversibility, or peak expiratory flow variability. Patients were required to have stable asthma, defined as no asthma exacerbations and regular asthma treatment at a consistent dose for 8 weeks before baseline visits. The current analysis included patients with well controlled asthma, defined as an Asthma Control Questionnaire (ACQ-6) score of less than 0·75 at baseline. Small airway dysfunction was defined, based on deviation from predicted values of impulse oscillometry parameters, as a Z score of more than 1·645 for R5–R20 (resistance at 5 Hz minus resistance at 20 Hz) and AX (area of reactance) and a Z score of less than –1·645 for X5 (reactance at 5 Hz), with additional analyses exploring severe small airway dysfunction (Z score of 3 or –3). ATLANTIS is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT02123667</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>Of 773 patients, ACQ-6 assessments were available for 772 patients. Among these patients, 384 (50%) were classified as having well controlled asthma, and small airway dysfunction was present in 108 (36% [95% CI 30–41]) of 304 patients with impulse oscillometry data available for R5–R20, 89 (34% [28–42]) of 261 patients with data for AX, and 79 (26% [21–31]) of 303 patients with data for X5. In the multivariable analysis, we found that R5–R20-defined small airway dysfunction was associated with increased risk of future exacerbati","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"75 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189424","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 : 2025-09-28DOI: 10.1016/s2213-2600(25)00290-5
Noemi Reguart, Lizza E L Hendriks
No Abstract
没有抽象的
{"title":"Rethinking immunotherapy in patients with SCLC with poor performance status","authors":"Noemi Reguart, Lizza E L Hendriks","doi":"10.1016/s2213-2600(25)00290-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00290-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"1 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183264","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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