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{"title":"Beyond pulmonary rehabilitation: can the PICk UP programme fill the gap? A randomised trial in COPD.","authors":"P Rebelo, D Brooks, J Cravo, M A Mendes, A C Oliveira, A S Rijo, M J Moura, A Marques","doi":"10.1016/j.pulmoe.2024.04.001","DOIUrl":"10.1016/j.pulmoe.2024.04.001","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Pulmonary rehabilitation (PR) is a fundamental intervention to manage COPD, however, maintaining its benefits is challenging. Engaging in physical activity might help to prolong PR benefits. This study assessed the efficacy and effectiveness of a personalised community-based physical activity programme to sustain physical activity and other health-related PR benefits, in people with COPD.</p><p><strong>Materials and methods: </strong>This was a multicentre, assessor blinded, randomised controlled trial. Following 12-weeks of PR, people with COPD were assigned to a six-months personalised community-based physical activity programme (experimental group), or to standard care (control group). Physical activity was assessed via: time spent in moderate to vigorous physical activities per day (primary outcome measure), steps/day and the brief physical activity assessment tool. Secondary outcomes included sedentary behaviour, functional status, peripheral muscle strength, balance, symptoms, emotional state, health-related quality of life, exacerbations and healthcare utilization. Assessments were performed immediately post-PR and after three- and six-months. Efficacy and effectiveness were evaluated using intention-to-treat and per-protocol analysis with linear mixed models.</p><p><strong>Results: </strong>Sixty-one participants (experimental group: <i>n</i> = 32; control group: <i>n</i> = 29), with balanced baseline characteristics between groups (69.6 ± 8.5 years old, 84 % male, FEV₁ 57.1 ± 16.7 %predicted) were included. Changes in all physical activity outcomes and in one-minute sit-to-stand were significantly different (<i>P</i> < 0.05) between groups at the six-month follow-up. In the remaining outcomes there were no differences between groups.</p><p><strong>Conclusions: </strong>The community-based physical activity programme resulted in better physical activity levels and sit-to-stand performance, six-months after completing PR, in COPD. No additional benefits were observed for other secondary outcomes.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":" ","pages":"2416827"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease burden, comorbidities and antecedents of chronic cough phenotypes in Australian adults.","authors":"S Suresh, J L Perret, E H Walters, M J Abramson, G Bowatte, C Lodge, A Lowe, B Erbas, P Thomas, G S Hamilton, A B Chang, S C Dharmage, D S Bui","doi":"10.1016/j.pulmoe.2023.08.003","DOIUrl":"10.1016/j.pulmoe.2023.08.003","url":null,"abstract":"<p><strong>Background and objectives: </strong>While adult chronic cough has high burden, its phenotypes, particularly those without aetiologically related underlying conditions, are understudied. We investigated the prevalence, lung function and comorbidities of adult chronic cough phenotypes.</p><p><strong>Methods: </strong>Data from 3608 participants aged 53 years from the Tasmanian Longitudinal Health Study (TAHS) were included. Chronic cough was defined as cough on most days for >3 months in a year. Chronic cough was classified into \"explained cough\" if there were any one of four major cough-associated conditions (asthma, COPD, gastroesophageal reflux disease or rhinosinusitis) or \"unexplained cough\" if none were present. Adjusted regression analyses investigated associations between these chronic cough phenotypes, lung function and non-respiratory comorbidities at 53 years.</p><p><strong>Results: </strong>The prevalence of chronic cough was 10% (95%CI 9.1,11.0%) with 46.4% being \"unexplained\". Participants with unexplained chronic cough had lower FEV₁/FVC (coefficient: -1.2% [95%CI:-2,3, -0.1]) and increased odds of comorbidities including obesity (OR=1.6 [95%CI: 1.2, 2.3]), depression (OR=1.4 [95%CI: 1.0, 2.1]), hypertension (OR=1.7 [95%CI: 1.2, 2.4]) and angina, heart attack or myocardial infarction to a lesser extent, compared to those without chronic cough. Participants with explained chronic cough also had lower lung function than both those with unexplained chronic cough and those without chronic cough.</p><p><strong>Conclusions: </strong>Chronic cough is prevalent in middle-age and a high proportion is unexplained. Unexplained cough contributes to poor lung function and increased comorbidities. Given unexplained chronic cough is not a symptom of major underlying respiratory conditions it should be targeted for better understanding in both clinical settings and research.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":" ","pages":"2416810"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of exhaled volatile organic compounds with serum biomarkers predicts respiratory infection severity.","authors":"Patricia Esteban, Santiago Letona-Gimenez, Maria Pilar Domingo, Elena Morte, Galadriel Pellejero-Sagastizabal, Maria Del Mar Encabo, Ariel Ramírez-Labrada, Rebeca Sanz-Pamplona, Julián Pardo, José Ramón Paño, Eva M Galvez","doi":"10.1080/25310429.2025.2477911","DOIUrl":"10.1080/25310429.2025.2477911","url":null,"abstract":"<p><strong>Objective: </strong>During respiratory infections, host-pathogen interaction alters metabolism, leading to changes in the composition of expired volatile organic compounds (VOCs) and soluble immunomodulators. This study aims to identify VOC and blood biomarker signatures to develop machine learning-based prognostic models capable of distinguishing infections with similar symptoms.</p><p><strong>Methods: </strong>Twenty-one VOCs and fifteen serum biomarkers were quantified in samples from 86 COVID-19 patients, 75 patients with non-COVID-19 respiratory infections, and 72 healthy donors. The populations were categorized into severity subgroups based on their oxygen support requirements. Descriptive and statistical analyses were conducted to assess group differentiation. Additionally, machine learning classifiers were developed to predict disease severity in both COVID-19 and non-COVID-19 patients.</p><p><strong>Results: </strong>VOC and biomarker profiles differed significantly among groups. Random Forest models demonstrated the best performance for severity prediction. The COVID-19 model achieved 93% accuracy, 100% sensitivity, and 89% specificity, identifying IL-6, IL-8, thrombomodulin, and toluene as key severity predictors. In non-COVID-19 patients, the model reached 89% accuracy, 100% sensitivity, and 67% specificity, with CXCL10 and methyl-isobutyl-ketone as key markers.</p><p><strong>Conclusion: </strong>VOCs and serum biomarkers differentiated HD, COVID-19, and non-COVID-19 patients, and enabled the development of high-performance severity prediction models. While promising, these findings require validation in larger independent cohorts.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":"31 1","pages":"2477911"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemic after pandemic: Dengue surpasses COVID-19 in number of deaths.","authors":"Nathália Mariana Santos Sansone, Luiz Felipe Azevedo Marques, Matheus Negri Boschiero, Lucas Silva Mello, Fernando Augusto Lima Marson","doi":"10.1080/25310429.2024.2448364","DOIUrl":"https://doi.org/10.1080/25310429.2024.2448364","url":null,"abstract":"","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":"31 1","pages":"2448364"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and use of home high flow nasal cannula in Portugal: Where are we?","authors":"Cristina Jácome, Mónica Duarte, João Carlos Winck, Salvador Díaz Lobato, Cátia Caneiras","doi":"10.1080/25310429.2024.2423556","DOIUrl":"https://doi.org/10.1080/25310429.2024.2423556","url":null,"abstract":"","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":"31 1","pages":"2423556"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographical variation in lung function: Results from the multicentric cross-sectional BOLD study.","authors":"Peter G J Burney, James Potts, Ben Knox-Brown, Gregory Erhabor, Hamid Hacene Cherkaski, Kevin Mortimer, Mahesh Padukudru Anand, David M Mannino, Joao Cardoso, Rana Ahmed, Asma Elsony, Cristina Barbara, Rune Nielsen, Eric Bateman, Stefanni Nonna M Paraguas, Li Cher Loh, Abdul Rashid, Emiel Fm Wouters, Frits Me Franssen, Hermínia Brites Dias, Thorarinn Gislason, Mohammed Al Ghobain, Mohammed El Biaze, Dhiraj Agarwal, Sanjay Juvekar, Fatima Rodrigues, Daniel O Obaseki, Parvaiz A Koul, Imed Harrabi, Asaad A Nafees, Terence Seemungal, Christer Janson, William M Vollmer, Andre Fs Amaral, A Sonia Buist","doi":"10.1080/25310429.2024.2430491","DOIUrl":"10.1080/25310429.2024.2430491","url":null,"abstract":"<p><p>Spirometry is used to determine what is \"unusual\" lung function compared with what is \"usual\" for healthy non-smokers. This study aimed to investigate regional variation in the forced vital capacity (FVC) and in the forced expiratory volume in one second to FVC ratio (FEV₁/FVC) using cross-sectional data from all 41 sites of the multinational Burden of Obstructive Lung Disease study. Participants (5,368 men; 9,649 women), aged ≥40 years, had performed spirometry, had never smoked and reported no respiratory symptoms or diagnoses. To identify regions with similar FVC, we conducted a principal component analysis (PCA) on FVC with age, age² and height², separately for men and women. We regressed FVC against age, age² and height², and FEV₁/FVC against age and height², for each sex and site, stratified by region. Mean age was 54 years (both sexes), and mean height was 1.69 m (men) and 1.61 m (women). The PCA suggested four regions: 1) Europe and richer countries; 2) the Near East; 3) Africa; and 4) the Far East. For the FVC, there was little variation in the coefficients for age, or age², but considerable variation in the constant (men: 2.97 L in the Far East to 4.08 L in Europe; women: 2.44 L in the Far East to 3.24 L in Europe) and the coefficient for height². Regional differences in the constant and coefficients for FEV₁/FVC were minimal (<1%). The relation of FVC with age, sex and height varies across and within regions. The same is not true for the FEV₁/FVC ratio.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":"31 1","pages":"2430491"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fractional exhaled nitric oxide in a respiratory healthy general population through the lifespan.","authors":"Christina Bal, Caspar Schiffers, Marie-Kathrin Breyer, Sylvia Hartl, Alvar Agusti, Ahmad Karimi, Wolfgang Pohl, Marco Idzko, Robab Breyer-Kohansal","doi":"10.1080/25310429.2024.2442662","DOIUrl":"10.1080/25310429.2024.2442662","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>The fractional exhaled fraction of nitric oxide (FeNO) is used in clinical practice for asthma diagnosis, phenotyping, and therapeutic management. Therefore, accurate thresholds are crucial. The normal FeNO values over lifespan in a respiratory healthy population and the factors related to them remain unclear.</p><p><strong>Materials and methods: </strong>We determined FeNO levels in 2,251 respiratory healthy, non-atopic, and non-smoking participants from the Lung, hEart, sociAl, boDy (LEAD) cohort, a general population, observational cohort study of participants aged 6-82 years in Austria.</p><p><strong>Results: </strong>The median FeNO value in the total study population was 13.0 [interquartile range: 9.0, 20.0] ppb, increases with age, and, except in young participants (<18 years: 9.0 [7.0, 12.0], ≥18 years: 15.0 [11.0, 22.0]), it was significantly lower in females versus males. Multiple regression analyses showed that body height and blood eosinophil counts were associated with higher FeNO levels, both in children/adolescents and adults. In children/adolescents, FeNO values were positively associated with total IgE levels, FEV1/FVC ratio, and urban living. In adults, FeNO was positively associated with age and negatively associated with the presence of cardiovascular and ischaemic vascular disease.</p><p><strong>Conclusions: </strong>We identified the normal FeNO ranges within a respiratory healthy population at different age ranges and associated factors. Collectively, they serve as a reference to frame FeNO values in clinical practice.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":"31 1","pages":"2442662"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application and internal validation of lung ultrasound score in COVID-19 setting: The ECOVITA observational study.","authors":"L Rinaldi, M Lugarà, V Simeon, F Perrotta, C Romano, C Iadevaia, C Sagnelli, L Monaco, C Altruda, M C Fascione, L Restivo, U Scognamiglio, N Laganà, R Nevola, G Oliva, M G Coppola, C Acierno, F Masini, E Pinotti, E Allegorico, S Tamburrini, G Vitiello, M Niosi, M L Burzo, G Franci, A Perrella, G Signoriello, V Frusci, S Mancarella, G Loche, G F Pellicano, M Berretta, G Calabria, L Pietropaolo, F G Numis, N Coppola, A Corcione, R Marfella, L E Adinolfi, A Bianco, F C Sasso, I de Sio","doi":"10.1016/j.pulmoe.2024.04.012","DOIUrl":"10.1016/j.pulmoe.2024.04.012","url":null,"abstract":"<p><strong>Background: </strong>The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support.</p><p><strong>Methods: </strong>In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: <b>Score 0:</b> normal A-lines. <b>Score 1:</b> multiple separated B-lines. <b>Score 2:</b> coalescent B-lines, alteration of pleural line. <b>Score 3:</b> consolidation area.</p><p><strong>Results: </strong>One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07-1.14; <i>p</i> < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity).</p><p><strong>Conclusions: </strong>The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":" ","pages":"2416842"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Legend score synthesizes Wells, PERC, Geneva, D-dimer and predicts acute pulmonary embolism prior to imaging tests.","authors":"Yunfeng Zhao, Yi Cheng, Hongwei Wang, He Du, Jinyuan Sun, Mei Xu, Yong Luo, Song Liu, Xuejun Guo, Wei Xiong","doi":"10.1016/j.pulmoe.2023.10.002","DOIUrl":"10.1016/j.pulmoe.2023.10.002","url":null,"abstract":"<p><strong>Introduction: </strong>The prediction rules of acute pulmonary embolism(PE) before imaging tests recommended by the commonly used guidelines have low diagnostic efficiency if not combined with D-dimer, therefore it is necessary to seek for a prediction rule with higher diagnostic efficiency.</p><p><strong>Methods: </strong>We designed a new score named Legend by synthesizing the scores of Wells, PERC, and Geneva, as well as D-dimer with patients in the development group(<i>n</i> = 2112), and then validated it in patients of validation group(<i>n</i> = 388). Diagnostic efficiency was also compared between Legend score and Wells+D-dimer (DD), PERC+DD, Geneva+DD, and YEARS+DD(YEAR algorithm).</p><p><strong>Results: </strong>The Legend score comprised active cancer, D-dimer≥1000 ng/mL, DVT symptoms and/or signs, previous venous thromboembolism (VTE) history, and surgery, trauma, or immobilization in the past month. The sensitivity, specificity, Youden index, and area under the curve(AUC) were 0.985, 0.744, 0.729, and (0.861[0.796-0.925], <i>P</i><0.001), respectively, for original Legend score, whereas were 0.982, 0.778, 0.760, and (0.871[0.823-0.920], <i>P</i><0.001), respectively, for simplified Legend score. The Kappa coefficient and P value of McNemar test were 0.988 and 1.000, respectively, between the original and simplified Legend scores. In the validation group, the sensitivity, specificity, Youden index, and C-index were 0.971, 0.749, 0.720, and (0.838[0.781-0.896], <i>P</i><0.001), respectively, for the original Legend score, whereas were 0.986, 0.715, 0.701, and (0.816[0.750-0.880], <i>P</i> = 0.001) respectively, for the simplified Legend score. The Kappa coefficient and P value of McNemar test between original Legend score and Wells+DD, PERC+DD, Geneva+DD, and YEARS+DD were (0.563, 0.001), (0.139, <0.001), (0.631, 0.006), and (0.732, 0.029), respectively. The Kappa coefficient and P value of McNemar test between simplified Legend score and aforementioned scores were (0.675, 0.009), (0.172, <0.001), (0.747, 0.001), and (0.883, 0.012), respectively.</p><p><strong>Discussion: </strong>In view of the fact the Legend score reserves the efficient predictors and eliminates the inefficient ones in Wells, PERC, and revised Geneva scores, and incorporates D-dimer into it, a more efficient, modified, and user-friendly one has replaced the original ones.</p><p><strong>Conclusions: </strong>The Legend score yields excellent diagnostic efficiency with good safety in the pretest prediction of acute PE prior to imaging tests. It also avoids more unnecessary imaging tests than Wells+DD, PERC+DD, Geneva+DD, or YEARS+DD.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":" ","pages":"2416828"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-1 antitrypsin deficiency and <i>Pi*S</i> and <i>Pi*Z SERPINA1</i> variants are associated with asthma exacerbations.","authors":"Elena Martín-González, José M Hernández-Pérez, José A Pérez Pérez, Javier Pérez-García, Esther Herrera-Luis, Ruperto González-Pérez, Orelvis González-González, Elena Mederos-Luis, Inmaculada Sánchez-Machín, Paloma Poza-Guedes, Olaia Sardón, Paula Corcuera, María J Cruz, Francisco J González-Barcala, Carlos Martínez-Rivera, Joaquim Mullol, Xavier Muñoz, José M Olaguibel, Vicente Plaza, Santiago Quirce, Antonio Valero, Joaquín Sastre, Javier Korta-Murua, Victoria Del Pozo, Fabián Lorenzo-Díaz, Jesús Villar, María Pino-Yanes, Mario A González-Carracedo","doi":"10.1016/j.pulmoe.2023.05.002","DOIUrl":"10.1016/j.pulmoe.2023.05.002","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Asthma is a chronic inflammatory disease of the airways. Asthma patients may experience potentially life-threatening episodic flare-ups, known as exacerbations, which may significantly contribute to the asthma burden. The <i>Pi*S</i> and <i>Pi*Z</i> variants of the <i>SERPINA1</i> gene, which usually involve alpha-1 antitrypsin (AAT) deficiency, had previously been associated with asthma. The link between AAT deficiency and asthma might be represented by the elastase/antielastase imbalance. However, their role in asthma exacerbations remains unknown. Our objective was to assess whether <i>SERPINA1</i> genetic variants and reduced AAT protein levels are associated with asthma exacerbations.</p><p><strong>Materials and methods: </strong>In the discovery analysis, <i>SERPINA1 Pi*S</i> and <i>Pi*Z</i> variants and serum AAT levels were analyzed in 369 subjects from La Palma (Canary Islands, Spain). As replication, genomic data from two studies focused on 525 Spaniards and publicly available data from UK Biobank, FinnGen, and GWAS Catalog (<i>Open Targets Genetics</i>) were analyzed. The associations between <i>SERPINA1 Pi*S</i> and <i>Pi*Z</i> variants and AAT deficiency with asthma exacerbations were analyzed with logistic regression models, including age, sex, and genotype principal components as covariates.</p><p><strong>Results: </strong>In the discovery, a significant association with asthma exacerbations was found for both <i>Pi*S</i> (odds ratio [OR]=2.38, 95% confidence interval [CI]= 1.40-4.04, <i>p</i>-value=0.001) and <i>Pi*Z</i> (OR=3.49, 95%CI=1.55-7.85, <i>p</i>-value=0.003)Likewise, AAT deficiency was associated with a higher risk for asthma exacerbations (OR=5.18, 95%CI=1.58-16.92, <i>p</i>-value=0.007) as well as AAT protein levels (OR= 0.72, 95%CI=0.57-0.91, <i>p</i>-value=0.005). The <i>Pi*Z</i> association with exacerbations was replicated in samples from Spaniards with two generations of Canary Islander origin (OR=3.79, <i>p</i>-value=0.028), and a significant association with asthma hospitalizations was found in the Finnish population (OR=1.12, <i>p</i>-value=0.007).</p><p><strong>Conclusions: </strong>AAT deficiency could be a potential therapeutic target for asthma exacerbations in specific populations.</p>","PeriodicalId":54237,"journal":{"name":"Pulmonology","volume":" ","pages":"2416870"},"PeriodicalIF":10.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9577634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}