Pulmonary Therapy最新文献

{"title":"Oscillation and Lung Expansion Therapy as Rescue Airway Clearance in Critically Ill Adults: A Case Series.","authors":"Nicole Boechler, Clare Smith, Kevin Huntley, Christina S Thornton","doi":"10.1007/s41030-026-00389-4","DOIUrl":"https://doi.org/10.1007/s41030-026-00389-4","url":null,"abstract":"<p><strong>Introduction: </strong>Retained airway secretions and lobar collapse are common in hospitalized adults with advanced lung disease. Conventional airway clearance depends on respiratory effort, requiring both an adequate inspiratory volume and sufficient expiratory airflow, and on cough strength, and therefore fails most often in the patients who need it most. Oscillation and lung expansion (OLE) therapy delivers continuous positive expiratory pressure (CPEP), continuous high-frequency oscillation (CHFO), and aerosolized medication in a single 10-min treatment, but reported experience is largely confined to postoperative prophylaxis and the home setting.</p><p><strong>Methods: </strong>We describe six consecutive adults (aged 18-77 years) treated with OLE (Volara system) at a Canadian tertiary center between March 2023 and April 2026, after conventional airway clearance had failed or after escalation to near-maximal noninvasive respiratory support. Feasibility (delivery of OLE as prescribed at the prevailing level of respiratory support) and tolerability (absence of adverse events or discontinuation for intolerance) were assessed retrospectively.</p><p><strong>Results: </strong>Diagnoses were cystic fibrosis exacerbation (n = 2), thoracic malignancy with lobar collapse from mucus plugging (n = 2), metapneumovirus pneumonia in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome (n = 1), and autoimmune pulmonary alveolar proteinosis with sepsis (n = 1). In each, the realistic alternatives were bronchoscopy, intubation, or palliation. All six demonstrated secretion clearance, radiographic re-expansion, or both. Supplemental oxygen requirements fell in five, two did not require the intensive care transfer or intubation that had been anticipated, and no adverse event was observed following OLE, including in one patient with a recently drained pneumothorax. One patient with metastatic malignancy died of her cancer during the same admission despite radiographic re-expansion.</p><p><strong>Conclusions: </strong>OLE was feasible and well tolerated when used as rescue airway clearance in high-acuity adults. These observations, while hypothesis-generating, require prospective, protocolized evaluation before OLE can be recommended for this indication.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149114430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced Pulmonary Drug Delivery Systems: A Narrative Review.","authors":"Dil Afrose, Melika Valizadeh, Shailesh B Kolekar, Mano J Mathew, Alexandr Ceasovschih, Alexandru Corlateanu, Pradeesh Sivapalan","doi":"10.1007/s41030-026-00387-6","DOIUrl":"10.1007/s41030-026-00387-6","url":null,"abstract":"<p><p>Pulmonary drug delivery systems have gained increasing attention as an effective strategy for the treatment of both respiratory and systemic diseases by enabling targeted, noninvasive, and efficient drug administration through the lungs, with advantages including rapid onset of action, lower drug doses, and reduced systemic adverse effects. Despite these advances, challenges related to formulation stability, aerosol performance, lung clearance mechanisms, and regulatory approval remain. This review explores advanced pulmonary drug delivery systems, with emphasis on the anatomical, physiological, pharmaceutical, and device-related factors that influence aerosol deposition and therapeutic performance. The review examines key mechanisms of particle deposition such as inertial impaction, gravitational sedimentation, Brownian diffusion, interception, and electrostatic interactions, and advanced pulmonary drug carrier systems, including liposomes, nanoparticles, large porous particles, dendrimers, polymeric micelles, biodegradable polymers, and lactose-based dry powder platforms, which enhance drug stability, controlled release, lung retention, and site-specific targeting. The review further summarizes advances in particle engineering technologies and common and advanced inhalation devices, including pressurized metered-dose inhalers, dry powder inhalers, nebulizers, soft mist inhalers, and smart inhaler platforms. Clinical applications of pulmonary drug delivery extend beyond asthma and chronic obstructive pulmonary disease (COPD) to include cystic fibrosis, pulmonary infections, and pulmonary arterial hypertension, while emerging applications in tuberculosis, diabetes, vaccination, gene therapy, and cancer continue to be investigated. Future directions include personalized pulmonary medicine, inhaled biologics and mRNA therapeutics, environmentally sustainable inhaler technologies, artificial intelligence-assisted formulation and device optimization, and evolving regulatory frameworks. Advancements in pulmonary drug delivery technologies may focus on improving drug targeting, optimizing therapeutic performance, and broadening their application in modern clinical practice.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness of Mepolizumab Initiation in Treating Asthma and Concurrent Chronic Obstructive Pulmonary Disease in the US.","authors":"Surya P Bhatt, Ravi Kalhan, Shibing Yang, Guillaume Germain, Rosirene Paczkowski, Stefanie Kolterer, Emmeline Burrows, Jihye Park, Jacob Klimek, Sophie Ma, François Laliberté, William W Busse","doi":"10.1007/s41030-026-00381-y","DOIUrl":"https://doi.org/10.1007/s41030-026-00381-y","url":null,"abstract":"<p><strong>Introduction: </strong>Mepolizumab reduces exacerbations in patients with asthma but real-world data on its effectiveness in asthma and concurrent chronic obstructive pulmonary disease (COPD) are limited. This study assessed the real-world impact of mepolizumab initiation in patients with asthma and concurrent COPD.</p><p><strong>Methods: </strong>Retrospective, longitudinal analysis from the US Komodo Research claims database (January 2016-June 2023). Eligible patients (aged ≥ 12 years; ≥ 2 mepolizumab claims) had ≥ 1 asthma claim and were categorized as asthma with concurrent COPD (≥ 1 COPD claim) or asthma only. Outcomes assessed in the 12 months post- versus 12 months pre-mepolizumab initiation included annualized exacerbation rates, oral corticosteroid (OCS) dispensing and burst rates, and asthma- and COPD-related healthcare resource utilization (HCRU), and healthcare costs.</p><p><strong>Results: </strong>A total of 2106 patients had asthma with concurrent COPD; 4674 asthma only. The annualized rate of exacerbations decreased by 50% post- versus pre-mepolizumab in patients with asthma and concurrent COPD {rate ratio [95% confidence interval (CI)]: 0.50 [0.48, 0.53]; P < 0.001}, and by 49% in patients with asthma only [0.51 (0.49, 0.53); P < 0.001]. The relative reduction [rate ratio (95% confidence interval)] in hospitalization-defined exacerbations was 52% [0.48 (0.42, 0.54); P < 0.001] and 41% [0.59 (0.52, 0.67); P < 0.001] in the asthma with concurrent COPD and asthma-only cohorts, respectively. Relative reductions of between 36 and 44% in OCS dispensing and bursts were observed across both cohorts (P < 0.001); relative reductions of 42-49% were observed across both cohorts in HCRU, including in hospitalizations and emergency room visits (P < 0.001). Mean total healthcare costs per patient per year in the asthma with concurrent COPD cohort were $11,770 (30,663) post- versus $23,771 (66,737) pre-mepolizumab initiation, corresponding to a cost difference (95% CI) of $-12,001 (-14,816, -9,186) (P < 0.001).</p><p><strong>Conclusion: </strong>In this analysis of a large US claims database, mepolizumab reduced exacerbations and overall disease burden in patients with asthma and concurrent COPD.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Global Initiative for Obstructive Sleep Apnea (GIFOSA): Rationale, Strategic Framework, and Call to Action.","authors":"Sy Duong-Quy, Naricha Chirakalwasan, Tayard Desudchit, Stanley Yung-Chuan Liu, Leow Leong Chai, Thien Thanh Dang-Vu, Hiroshi Kadotani, Sang-Ha Kim, Hyung Chae Yang, Rodolfo V Dizon, Ravi Gupta, Allen Widysanto, Rusdi Bin Abd Rashid, Yap Yoke Yeow, Jianchen Cui, Mohammed A Al-Abri, Mouhamad Ghyath Jamil, Hamza Dhafar, Babak Amra, Pei-Lin Lee, Kiong Fou Yoom, Glenn Roldan, Carlos Teixeira, Kouassi Boko Alexandre, Amine Benjelloun, Franck-Hardain Okemba-Okombi, Chan Sarin, Thai Nguyen-Duy, Dung Nguyen-Thi-Thu, Huong Le-Thi-Minh, Thuy Tran-Phan-Chung, Linh Pham-Van, Giap Vu-Van, Vinh Nguyen-Nhu, Bao Le-Khac, Nhung Nguyen-Viet, Franck Soyez, Véronique Bricout, Fannie Onen, Francis Martin, Ahmed BaHammam, Thomas Penzel, Timothy Craig, Clete Kushida","doi":"10.1007/s41030-026-00386-7","DOIUrl":"10.1007/s41030-026-00386-7","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is one of the most prevalent chronic sleep disorders worldwide, affecting an estimated nearly one billion adults globally, and is increasingly recognized as a major contributor to cardiometabolic disease, impaired quality of life, and escalating healthcare costs. Despite substantial advances in understanding OSA pathophysiology, diagnosis, and treatment, significant disparities persist in access to care, implementation of evidence-based practice, and long-term outcomes across regions and healthcare systems. The Global Initiative for Obstructive Sleep Apnea (GIFOSA) was established as an implementation-focused initiative to address these challenges through a coordinated, multidisciplinary framework that goes beyond existing regional and national efforts by integrating global coordination, action-oriented implementation strategies, practical tools, and policy engagement. This paper presents the conceptual foundations of GIFOSA and outlines its strategic pillars: strengthening clinical and scientific foundations, building workforce capacity, advancing person-centered management, and integrating OSA into population health and policy agendas. Central to its pragmatic structure is a focus on implementation feasibility, including context-sensitive care pathways, task-sharing approaches, and technology-enabled diagnostics and management strategies that can be adopted across resource levels. By emphasizing cross-disciplinary collaboration, technological innovation, and alignment with health systems and policy priorities, GIFOSA seeks to bridge the gap between knowledge and practice while promoting equitable access to diagnosis and treatment. The initiative further highlights the importance of prevention, digital health integration, and global research collaboration to support sustainable and measurable improvements in OSA care worldwide.Graphical Abstract is available with this article.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and Burdens in Refractory Chronic Cough: Patients' and Physicians' Perspectives.","authors":"Mandy Beadnell, José Canga Rodríguez, Ottilie Dotzenrod, Isadora Farrell, Mary Ellen McDonough, Wendi Smith, Thomas Carroll, Peter Dicpinigaitis, Bonnie Pobiner, Dasha Shamarina, Aarti Tarkar, Peter Kardos","doi":"10.1007/s41030-026-00384-9","DOIUrl":"https://doi.org/10.1007/s41030-026-00384-9","url":null,"abstract":"<p><p>Refractory chronic cough (RCC) is a disease identified in people with chronic cough that persists for > 8 weeks despite adequate treatment for known cough-related aetiologies. People with RCC can experience cough > 400 times/day, some of which may be sudden, intense coughing bouts, representing a substantial disease burden. To explore their experiences of living with the disease, nine adults with RCC (≥ 18 years old; USA = 4, UK and Germany = 5) were invited to one of two advice-seeking meetings, based on referral from the healthcare professional (HCP) who confirmed their RCC diagnosis. Sessions were conducted using a semi-structured discussion guide and were audio-recorded and transcribed. Content analysis was performed using Max Qualitative Data Analysis software. Three cough-specialist physicians were then asked to provide commentary on the lived experiences of these patients. The patient and cough-specialist perspectives highlight unmet needs throughout the RCC patient journey, particularly regarding diagnostic complexity and dissatisfaction with current treatments. The negative impact of daily symptoms on quality of life underscores the need for peer support initiatives. Variability in the diagnostic journey suggests that standard diagnostic checklists could support HCPs and reduce diagnostic delays or uncertainty. Improved recognition of patient-reported symptoms remains central to addressing symptom underestimation in clinical practice. Wearable symptom-monitoring devices may provide complementary objective data, although their correlation with patient-reported symptoms can be variable. Finally, broader dissemination of the experiences of people with RCC and their real-world treatment outcomes is needed to enhance HCP awareness and inform future therapeutic development. The first section of this article is authored by patients with RCC, who describe their experiences of living with RCC; the following section is written by the physicians, who discuss the management of RCC in the context of these experiences.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cough in Interstitial Lung Disease: Current Knowledge and Research Gaps.","authors":"Giacomo Giulianelli, Serena Bellani, Gioele Castelli, Giordano Fiorentù, Elisabetta Balestro, Surinder S Birring, Paolo Spagnolo","doi":"10.1007/s41030-026-00385-8","DOIUrl":"https://doi.org/10.1007/s41030-026-00385-8","url":null,"abstract":"<p><p>Chronic cough is one of the most frequent and burdensome symptoms in patients with interstitial lung disease (ILD), substantially impairing quality of life and, in idiopathic pulmonary fibrosis (IPF), being associated with disease progression. Despite its clinical relevance, the mechanisms underlying cough in ILD remain incompletely understood, and effective therapeutic options are limited. This narrative review summarizes current evidence on the epidemiology, pathophysiology, clinical assessment, and management of cough across the spectrum of ILD. Current data support the concept that ILD-related cough results from a complex interplay between cough reflex hypersensitivity, mechanical distortion of the fibrotic lung, airway and parenchymal inflammation, neural remodeling, and common comorbidities such as gastroesophageal reflux disease and obstructive sleep apnea. Disease-specific mechanisms are also discussed in connective tissue disease-associated ILD, sarcoidosis, and hypersensitivity pneumonitis. We review currently available qualitative and quantitative methods for cough assessment, including patient-reported outcome measures and objective cough monitoring technologies, highlighting their strengths and limitations in clinical practice and research. Finally, we examine established and emerging therapeutic approaches. While antifibrotic therapies have shown limited and inconsistent effects on cough, recent randomized clinical trials provide encouraging evidence for low-dose morphine and extended-release nalbuphine in IPF-associated chronic cough. Nonpharmacological interventions, particularly physiotherapy and speech and language therapy, also demonstrate meaningful benefits. Several novel therapeutic strategies targeting neural and inflammatory pathways are currently under investigation. A better understanding of the mechanisms driving cough in ILD, together with standardized assessment tools and adequately powered clinical trials, will be essential to develop effective, disease-specific treatments for this disabling symptom.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interstitial Lung Disease Induced by Monoclonal Antibodies for Psoriatic Arthritis, a Double Hit: A Case Report with a Literature and Clinical Trial Review.","authors":"Gioele Castelli, Giordano Fiorentù, Giuseppe Maggioni, Serena Bellani, Giacomo Giulianelli, Nicol Bernardinello, Elisabetta Cocconcelli, Federica Pezzuto, Roberta Polverosi, Fiorella Calabrese, Paolo Spagnolo, Elisabetta Balestro","doi":"10.1007/s41030-026-00378-7","DOIUrl":"10.1007/s41030-026-00378-7","url":null,"abstract":"<p><strong>Introduction: </strong>Monoclonal antibodies (mAb) play a central role in modern medicine; however, several of them have been associated with the development of drug-induced interstitial lung diseases (ILD). We present a case of a patient affected by psoriatic arthritis (PsA) treated with secukinumab, an anti-IL17 mAb, who developed a histological organising pneumonia pattern with microgranulomas. After resolution, the patient relapsed when exposed to guselkumab, an anti-IL23 mAb, with further histological confirmation. Treatment withdrawal and steroids resolved the ILD in both cases. To evaluate the risk of developing ILD in the context of those two drugs, we also performed a review of the literature and the clinical trials for the drugs in PsA.</p><p><strong>Methods: </strong>Papers presenting drug-induced ILD in patients treated with secukinumab and/or guselkumab in PubMed and Embase were searched and summarised. Respiratory-related adverse events reported in secukinumab and guselkumab clinical trials for PsA were summarised.</p><p><strong>Results: </strong>We summarised seven papers, finding a rare presentation (between 0.1% and 0.5%) of ILD in the treated population. The majority of the patients resolved the ILD after treatment withdrawal, with or without steroid treatment. In the clinical trials, respiratory-related adverse events were rarely reported, with only one case of ILD and one case of interstitial abnormalities at CT scan.</p><p><strong>Conclusions: </strong>This is the first case, to the best of our knowledge, that experienced a double hit from two different mAbs used for the treatment of PsA, secukinumab and guselkumab. Summarising the available literature and the reported adverse events for these two drugs, we also describe how, even in rare cases, mAbs in the context of PsA should raise suspicion of ILDs whenever the patient exhibits new respiratory symptoms.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"841-852"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating the Underreporting of COVID-19 Burden in Selected Countries in Asia, Africa, the Middle East, and Latin America in the Post-pandemic Era.","authors":"Carlos Fernando Mendoza, Julia Spinardi, Iustina Chirila, Claire Spencer, Moe Hein Kyaw, Ben Yarnoff","doi":"10.1007/s41030-026-00371-0","DOIUrl":"10.1007/s41030-026-00371-0","url":null,"abstract":"<p><strong>Introduction: </strong>The true number of coronavirus disease-19 (COVID-19) cases may be highly underestimated because of reduced efforts to track cases through testing in the postpandemic era. Earlier estimates of this underreporting have varied across regions, and countries in Asia, Africa, the Middle East, and Latin America have been notably impacted. This study investigates the true burden of COVID-19 cases in 2023 and 2024 across Asia, Africa, the Middle East, and Latin America.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of national public health surveillance data from 2022 to 2024 on COVID-19 cases, hospitalizations, and deaths in Asia, Africa, the Middle East, and Latin America. Using a method developed by the US Centers for Disease Control and Prevention to estimate the burden of COVID-19 and influenza, we estimated the number of cases for 2023 and 2024 by calculating the ratio of cases to hospitalization and cases to deaths, using 2022 as the baseline. We compared the estimated and reported number of cases each year to assess the level of underreporting.</p><p><strong>Results: </strong>The mean ratio of estimated cases to reported cases showed a high albeit variable level of underreporting in 2023 and 2024 across regions. In 2023, the levels of underreported cases were 1295%, 319%, 560%, and 3703% in Asia, the Middle East, Latin America, and Africa, respectively. The number of estimated underreported cases generally increased in 2024 to 2326%, 1415% and 16,664% in Asia, Latin America, and Africa, respectively, but in the Middle East decreased to 87% based on hospitalization data. The trend for death data was similar.</p><p><strong>Conclusions: </strong>The results highlight the high level of underreporting of COVID-19 cases, which has increased over time in many regions. Therefore, the true global burden of COVID-19 could be substantially higher than indicated by publicly available data. Continued COVID-19 surveillance is crucial for stabilizing public health measures such as prevention and target vaccination programs.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"905-915"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetic Architecture of Chronic Cough: From Sensory Hypersensitivity to Treatable Trait.","authors":"Ran Dong, Mengru Zhang, Alyn H Morice","doi":"10.1007/s41030-026-00382-x","DOIUrl":"10.1007/s41030-026-00382-x","url":null,"abstract":"<p><p>Chronic cough is a prevalent global clinical disorder with substantial quality-of-life impairment, and refractory cases remain a major unmet medical need. Cough hypersensitivity syndrome is the core pathological mechanism of chronic cough, and growing genetic evidence has confirmed that inherited susceptibility shapes cough hypersensitivity, clinical heterogeneity and therapeutic responsiveness, redefining chronic cough as a biologically mediated sensory-neural disorder rather than a non-specific secondary symptom of airway diseases. This review summarises genetic evidence for chronic cough from family-based studies, pharmacogenomics and genome-wide association studies (GWAS), revealing distinct genetic architectures of chronic dry cough and sputum production, with enrichment of sensory-neural pathway variants and key genetic loci such as replication factor C subunit 1 (RFC1) functional genomic analyses link genetic variation to vagal afferent excitability, and rare genetic neurological disorders further illuminate the neurogenic basis of cough hypersensitivity. Moreover, genetic insights identify tractable treatable traits and rationalise antitussive drug development, supporting genotype-guided patient stratification. We conclude that integrating genetic architecture into clinical phenotyping and translational research provides a critical framework for precision management of chronic cough, and future progress relies on harmonised deep phenotyping and multi-ancestry genetic studies.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"885-903"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Brensocatib in Participants of Asian Race with Non-cystic Fibrosis Bronchiectasis: A Subgroup Analysis of the ASPEN Trial.","authors":"Doreen Addrizzo-Harris, James D Chalmers, Stefano Aliberti, Pierre-Régis Burgel, Brian M Morrissey, Xiangmin Zhang, Chunpeng Fan, Melanie Lauterio, Sebastian Fucile, Dianne Griffis, Ariel Teper","doi":"10.1007/s41030-026-00375-w","DOIUrl":"10.1007/s41030-026-00375-w","url":null,"abstract":"<p><strong>Introduction: </strong>In the ASPEN trial, brensocatib, a dipeptidyl peptidase 1 inhibitor, significantly reduced the burden of pulmonary exacerbations versus placebo in participants with bronchiectasis. A prespecified subgroup analysis evaluated the efficacy and safety of brensocatib in participants of Asian race with bronchiectasis from ASPEN.</p><p><strong>Methods: </strong>Participants with confirmed bronchiectasis and a history of exacerbations in the 12 months before screening [adults (18-85 years), ≥ 2; adolescents (12- < 18 years), ≥ 1] received once-daily brensocatib (10 or 25 mg) or matching placebo for 52 weeks (adults, 1:1:1; adolescents, 2:2:1). Efficacy endpoints included annualized exacerbation rate, time to first exacerbation, and change at 52 weeks in post-bronchodilator (BD) forced expiratory volume (FEV) in 1 s (post-BD FEV₁) and Quality of Life-Bronchiectasis Respiratory Symptom Score (QOL-B RSS). Safety was monitored from enrollment through the end of study.</p><p><strong>Results: </strong>Overall, 191 participants were of Asian race (n = 63, brensocatib 10 mg; n = 64, brensocatib 25 mg; n = 64, placebo). Brensocatib 10 mg and brensocatib 25 mg significantly reduced the annualized exacerbation risk (both by ~ 60%; p = 0.0005 and p = 0.0012, respectively) and prolonged the time to first exacerbation (hazard reduced by ~ 55%; p = 0.0039 and 0.0082, respectively) versus placebo. Brensocatib 25 mg significantly reduced post-BD FEV₁ decline [least squares mean difference (95% CI): 69 (24-114) mL, p = 0.0029] and improved QOL-B RSS score [7.49 (2.48-12.50) points, p = 0.0034] versus placebo. The frequency of treatment-emergent adverse events was similar across treatment groups and consistent with the overall ASPEN results.</p><p><strong>Conclusions: </strong>In participants of Asian race, brensocatib 10 mg and 25 mg reduced the burden of pulmonary exacerbations, and the 25-mg dose reduced lung function decline and improved patient-reported symptoms versus placebo. The efficacy and safety of brensocatib in participants of Asian race were largely consistent with the overall ASPEN population, with select outcomes showing numerically greater benefit, although ASPEN was not powered to detect treatment differences in prespecified subgroup analyses.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT04594369.</p>","PeriodicalId":20919,"journal":{"name":"Pulmonary Therapy","volume":" ","pages":"917-936"},"PeriodicalIF":3.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}