Therapeutic Advances in Respiratory Disease最新文献

{"title":"The impact of quantitative platform on candidacy for bronchoscopic lung volume reduction: a multi-center retrospective cohort study.","authors":"Max Wayne, Suchitra Pilli, Hee Jae Choi, Nathaniel Moulton, Praveen Chenna, Allen Cole Burks, Alexander Chen","doi":"10.1177/17534666251314724","DOIUrl":"10.1177/17534666251314724","url":null,"abstract":"<p><strong>Background: </strong>Bronchoscopic lung volume reduction (BLVR) can be an effective treatment for highly selected patients with severe emphysema but only half of carefully selected patients derive clinical benefit. Two commercially available platforms exist to help determine candidacy for BLVR via quantitative analysis of computed tomography (CT) scans.</p><p><strong>Objectives: </strong>To determine if the two commercially available quantitative platforms identified the same patient population that may benefit from BLVR.</p><p><strong>Design: </strong>A multicenter, retrospective cohort study.</p><p><strong>Methods: </strong>Consecutive patients referred for BLVR between January 1, 2022 and March 31, 2023 at three medical centers in the United States with the same CT scan submitted for quantitative analysis to two commercially available platforms to determine BLVR candidacy were analyzed. The primary outcome of interest was whether quantitative analysis provided different recommendations for individual patients. The recommendation to proceed with BLVR was based on a prespecified algorithm using criteria established in clinical trials for each quantitative platform, respectively.</p><p><strong>Results: </strong>A total of 83 patients referred for BLVR across three centers were included; patients were a median 67 years old, had a median post bronchodilator FEV1 of 30% predicted (IQR: 25, 38), a median residual volume of 220% predicted (IQR: 185, 268), and 29 (34.9%) received endobronchial valves. A total of 26 patients (31.3%) received different recommendations from the two quantitative platforms.</p><p><strong>Conclusion: </strong>In this cohort of patients evaluated for BLVR across multiple medical centers, nearly a third of patients received different recommendations based on the platform utilized for valve assessment. This suggests that the selection process for BLVR may warrant refinement.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251314724"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elexacaftor/tezacaftor/ivacaftor and inflammation in children and adolescents with cystic fibrosis: a retrospective dual-center cohort study.","authors":"Angela Pepe, Cristina Fevola, Daniela Dolce, Silvia Campana, Novella Ravenni, Giovanni Taccetti, Donatello Salvatore, Vito Terlizzi","doi":"10.1177/17534666251314706","DOIUrl":"10.1177/17534666251314706","url":null,"abstract":"<p><strong>Background: </strong>Cystic fibrosis (CF) is characterized by chronic neutrophilic inflammation in the airways. Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has demonstrably improved clinical outcomes and quality of life in people with CF (pwCF), but its effects on systemic inflammatory parameters remain unclear.</p><p><strong>Objective: </strong>To evaluate the impact of ETI on systemic inflammation in children and adolescents with CF.</p><p><strong>Design: </strong>Retrospective, dual-center observational, propensity score-matching study of pediatric pwCF on ETI.</p><p><strong>Methods: </strong>PwCF aged ⩽ 18 years treated with ETI at two Italian reference centers were included in this study. Data on immunoglobulins (Ig) (A, G, and M), γ-globulin, leukocyte levels, percent predicted forced expiratory volume in the first second (ppFEV1), sweat chloride (SC) concentration, and sputum cultures were collected at baseline, 12, and 24 months of treatment. Laboratory data of a control group (pwCF, not in ETI therapy, same demographic characteristics as the study group) were also collected.</p><p><strong>Results: </strong>Sixty-six patients (30 males, median age: 12 years, F508del homozygous: 23) were included. Mean IgG levels (SD) significantly decreased (<i>p</i> = 0.001) from 1168.20 mg/dl (344.41) at baseline to 1093.05 mg/dl (258.73; 12 months) and 1092.87 mg/dl (232.42; 24 months). Similar reductions were observed for IgA and γ-globulin; IgM reduction was not statistically significant. Leukocyte levels also decreased significantly from 8.04 × 10³/µl (3.23 × 10³) at baseline to 6.61 × 10³/µl (1.74 × 10³) (12 months) and 6.45 × 10³/µl (1.70 × 10³; 24 months). As for the control group, no significant changes in the levels of Ig, leukocytes, and γ-globulin were detected throughout the study period (<i>p</i> > 0.05).The mean (SD) ppFEV1 and the overall mean (SD) SC concentration significantly decreased during the follow-up. Regarding cultures, 18 (27%) of the 27 patients positive (41%) for <i>Staphylococcus aureus</i> at baseline became negative during treatment. Three patients (4%) with persistently positive cultures for <i>Pseudomonas aeruginosa</i> during the first 12 months, became negative after 24 months. One patient (1.5%), with a baseline positive culture for <i>Pseudomonas Aeruginosa</i>, showed negative cultures after 12 months.</p><p><strong>Conclusion: </strong>ETI treatment improved respiratory outcomes and significantly reduced values of IgG, IgA, γ-globulin, and leukocytes, suggesting an effect on the systemic inflammatory response. Further research is warranted to elucidate the role of inflammatory parameters in monitoring response to therapy.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251314706"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel nomogram for predicting postoperative pneumonia risk in patients with localized bronchiectasis.","authors":"Cai Yongsheng, Ke Lihui, Hao Xuefeng, Qiao Anbang, Yang Xiaoxiao, Chen Wenhui, Li Weiqing, Yang Zeng, Wei Bo","doi":"10.1177/17534666251320471","DOIUrl":"10.1177/17534666251320471","url":null,"abstract":"<p><strong>Background: </strong>Pneumonia is one of the most common complications after lung resection. However, there are currently no reports of postoperative pneumonia in patients with bronchiectasis.</p><p><strong>Objectives: </strong>Our study aims to construct a new nomogram to predict the risk of postoperative pneumonia in patients with localized bronchiectasis.</p><p><strong>Design: </strong>The clinical data of patients with localized bronchiectasis from April 2012 to August 2022 were retrospectively analyzed.</p><p><strong>Methods: </strong>Independent risk factors were identified through simple linear regression and multiple linear regression analysis, and a new nomogram was constructed based on independent risk factors. The validity of the nomogram was evaluated using the consistency index (C-index), receiver operating characteristic curve, calibration chart, and decision curve analysis chart.</p><p><strong>Results: </strong>The new nomogram prediction model included five independent risk factors: tuberculosis history, smoking history, platelet-lymphocyte ratio (PLR), diffusing capacity of the lung for carbon monoxide, and controlled nutritional status score. The area under the curve of the prediction model is 0.870 (95% CI: 0.750-0.892), showing good discrimination ability, and the probability threshold was set at 0.2013. In addition, the calibration curve shows that the nomogram has good calibration. In the decision curve, the nomogram model showed good clinical net benefit.</p><p><strong>Conclusion: </strong>This study is the first to construct a nomogram prediction model for postoperative pneumonia of localized bronchiectasis, which can more accurately and directly assess the risk probability of postoperative pneumonia, and provide certain help for clinicians in prevention and treatment decisions.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251320471"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse effects of biologics used to treat asthma.","authors":"Andrea Sitek, Sergio E Chiarella, Thanai Pongdee","doi":"10.1177/17534666251319175","DOIUrl":"10.1177/17534666251319175","url":null,"abstract":"<p><p>In this review, we discuss the risks and adverse effects reported for the current Food and Drug Association (FDA)-approved biologics used in the management of asthma, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, and tezepelumab. Our review focuses on the risk of hypersensitivity reactions, infection, and malignancy. Where relevant, we have included information regarding the risk of cardiovascular disease and eosinophilia, and we have included specific information regarding vaccine use among patients receiving the above biologics. We also review currently available data regarding the use of biologics in the context of pregnancy. Our goal is to provide a comprehensive resource for providers utilizing these agents, so that they may adequately counsel patients about the risks of therapy and identify adverse events if they occur.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251319175"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between albumin corrected anion gap and in-hospital mortality in critically ill patients with chronic obstructive pulmonary disease.","authors":"Mohan Giri, Anju Puri, Lan Huang, Shuliang Guo","doi":"10.1177/17534666251315352","DOIUrl":"10.1177/17534666251315352","url":null,"abstract":"<p><strong>Background: </strong>The relationship between albumin-corrected anion gap (ACAG) and in-hospital mortality in critically ill patients with COPD remains unclear.</p><p><strong>Objective: </strong>This study investigated the association between ACAG levels and the risk of in-hospital mortality in critically ill patients with COPD.</p><p><strong>Design: </strong>A retrospective cohort study.</p><p><strong>Methods: </strong>This study uses data from the Medical Information Mart for Intensive Care (MIMIC-IV) database. The receiver operating characteristic (ROC) curve was used to determine the optimal threshold for ACAG, and participants were divided into two categories based on this threshold. The primary outcome was in-hospital mortality. We employed univariable and multivariable logistic regression analyses and Kaplan-Meier (KM) survival curves to assess the relationship between ACAG and the risk of in-hospital mortality. Moreover, subgroup analyses were conducted.</p><p><strong>Results: </strong>A total of 2121 patients (54.7% male) were enrolled in the study. The in-hospital mortality rate was 18.9%. In patients with elevated ACAG levels, the in-hospital mortality rate was significantly higher than in those with lower ACAG levels (27.7% vs 11.3%, <i>p</i> < 0.001). Multivariate logistic regression analysis indicated that even after mitigating for potential confounders, patients in the high ACAG group had significantly greater odds of in-hospital mortality across all models (Model I: OR = 3.000, 95% CI: 2.383-3.777, <i>p</i> < 0.001; Model II: OR = 3.021, 95% CI: 2.397-3.808, <i>p</i> < 0.001; Model III: OR = 1.916, 95% CI: 1.458-2.519, <i>p</i> < 0.001). Patients with elevated ACAG levels have more than twice the risk of in-hospital mortality compared to those with lower levels (hazard ratio (HR): 2.1277, 95% CI: 1.7490-2.5884).</p><p><strong>Conclusion: </strong>This study demonstrates that elevated ACAG levels are strongly associated with an increased risk of in-hospital mortality in critically ill COPD patients, suggesting that ACAG could serve as a potential predictor of adverse outcomes in this patient population.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251315352"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extrafine formulation of beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurized metered-dose inhaler in the treatment of asthma: a review.","authors":"Erminia Ridolo, Manlio Milanese, Alessandro Barone, Francesca Nicoletta, Martina Ottoni, Filippo Ferdinando Cosini, Giovanni Passalacqua, Carlo Lombardi","doi":"10.1177/17534666251332076","DOIUrl":"https://doi.org/10.1177/17534666251332076","url":null,"abstract":"<p><p>In the management of difficult-to-treat and severe asthma, the incorporation of a Long-Acting Muscarinic Antagonist (LAMA) into a regimen of Inhaled Corticosteroids plus Long-Acting β₂ agonists (ICS/LABA) represents a viable add-on therapeutic strategy. Historically, this approach required the use of separate inhalers; however, the recent advent of \"single-inhaler triple therapy\" (SITT) provided a valuable alternative. One such formulation is the extrafine combination of beclomethasone dipropionate (BDP), fluticasone furoate (FF), and glycopyrronium bromide (GB), which is delivered via a single pressurized metered-dose inhaler (pMDI). Clinical trials, including the TRIMARAN and TRIGGER studies, alongside subsequent post-hoc analyses, have elucidated the benefits of this SITT at both 87/5/9 μg and 172/5/9 μg dosing regimens administered daily. Findings indicated a significant improvement in respiratory function and a reduction in the frequency of exacerbations among patients with uncontrolled asthma. The BDP/FF/GB SITT confirmed efficacy and safety across various ethnic groups (including Caucasian, Japanese, and Chinese populations) and across different age cohorts (adults and adolescents), although it still remains unapproved for individuals under 18 years of age. The use of a single pMDI facilitates the deposition of extra- fine particles from all three active ingredients in the small airways enhancing therapeutic effectiveness. Moreover, the consolidation of medications into one device may improve patients' adherence by mitigating the risks associated with device mismanagement and ensuring optimal drug delivery. The cost-effectiveness analysis of the BDP/FF/GB SITT suggests favorable outcomes compared to traditional ICS/LABA and ICS/LABA plus tiotropium combinations. Additional data will be forthcoming from the ongoing real-life TRIMAXIMIZE observational study.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251332076"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatable traits in interstitial lung disease: a narrative review.","authors":"Megan Harrison, Chloe Lawler, Fiona Lake, Vidya Navaratnam, Caitlin Fermoyle, Yuben Moodley, Tamera J Corte","doi":"10.1177/17534666251335774","DOIUrl":"https://doi.org/10.1177/17534666251335774","url":null,"abstract":"<p><p>The interstitial lung diseases (ILDs) are a heterogeneous and complex group of diseases. The treatable trait (TT) model represents a shift in ILD management, away from traditional diagnostic labels towards a more individualised, trait-focused approach. This review explores the application of the TT paradigm to ILD, identifying key traits across the aetiological, pulmonary, extrapulmonary and behavioural domains. By addressing these traits, the TT model offers a framework to improve outcomes in ILD through multidisciplinary management with a precision medicine focus. Further research is necessary to evaluate the overall impact of this TT model on ILD care.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251335774"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifibrotic therapy combined with pulmonary vasodilator therapy may improve survival in patients with pulmonary fibrosis and pulmonary hypertension: a retrospective cohort study.","authors":"Christian Cardillo, Gerard J Criner, Shameek Gayen","doi":"10.1177/17534666251326743","DOIUrl":"10.1177/17534666251326743","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary fibrosis is a severe, progressive form of interstitial lung disease associated with increased morbidity and mortality. Pulmonary hypertension often accompanies severe pulmonary fibrosis and is also associated with worse outcomes. Antifibrotic therapy and pulmonary vasodilator therapy have demonstrated clinical benefits in pulmonary fibrosis and pulmonary hypertension, respectively. However, the benefit of combined antifibrotic and pulmonary vasodilator therapy in patients with both pulmonary fibrosis and pulmonary hypertension is less established.</p><p><strong>Objectives: </strong>We aimed to determine the effectiveness of a combination pulmonary vasodilator and antifibrotic therapy with regard to transplant-free survival and six-minute walk distance improvement in patients with pulmonary fibrosis and pulmonary hypertension.</p><p><strong>Design: </strong>This was a retrospective cohort study of patients with pulmonary fibrosis (idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, and other fibrotic interstitial lung disease) and pulmonary hypertension diagnosed via right heart catheterization. Patients received antifibrotic therapy with or without pulmonary vasodilator therapy.</p><p><strong>Methods: </strong>Patients who received combination antifibrotic therapy and pulmonary vasodilator therapy were compared to those prescribed antifibrotic therapy alone. Transplant-free survival and change in six-minute walk distance were compared between the two groups. Multivariable Cox regression was performed to determine predictors of transplant-free survival.</p><p><strong>Results: </strong>Patients who received antifibrotic and pulmonary vasodilator therapy had significantly improved transplant-free survival (log rank <i>p</i> = 0.001). Treatment with antifibrotic and pulmonary vasodilator therapy was significantly and independently associated with reduced risk of death or lung transplantation (HR 0.24, 95% CI 0.06-0.93, <i>p</i> = 0.04). These patients had worse pulmonary hemodynamics than those receiving antifibrotic therapy alone.</p><p><strong>Conclusion: </strong>We found a potential survival benefit when pulmonary vasodilator therapy was given in combination with antifibrotic therapy in patients with pulmonary fibrosis and pulmonary hypertension. This may be reflective of a pulmonary vascular phenotype among those with pulmonary fibrosis and pulmonary hypertension. Further trials are needed to better elucidate which patients benefit from combination therapy.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251326743"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting response to benralizumab in patients with COPD: a plain language summary of publication of the GALATHEA and TERRANOVA studies.","authors":"Gerard J Criner, Dave Singh, Alberto Papi, Maria Jison, Natalya Makulova, Vivian H Shih, Laura Brooks, Peter N Barker, Ubaldo J Martin","doi":"10.1177/17534666241312060","DOIUrl":"10.1177/17534666241312060","url":null,"abstract":"<p><p>Summary<b>What is this summary about?</b>● This is a plain language summary of two articles originally published in <i>The New England Journal of Medicine</i> and <i>The Lancet Respiratory Medicine</i>. These articles presented the results of GALATHEA and TERRANOVA, two clinical studies that took place across 41 countries. ○ GALATHEA and TERRANOVA measured how patients' COPD changed from before their first <b>benralizumab</b> (10, 30, or 100 mg) injection, to after 56 weeks of treatment. ○ In both studies, <b>benralizumab</b> was compared with <b>placebo</b>. ○ To see whether <b>benralizumab</b> treatment would benefit any particular patients included in these studies, researchers carried out an additional analysis following the main studies of GALATHEA and TERRANOVA.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666241312060"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the understanding and treatment of lung pathologies associated with alpha 1 antitrypsin deficiency.","authors":"Alice M Turner, Joachim H Ficker, Andrea Vianello, Christian F Clarenbach, Sabina Janciauskiene, Joanna Chorostowska-Wynimko, Jan Stolk, Noel Gerard McElvaney","doi":"10.1177/17534666251318841","DOIUrl":"10.1177/17534666251318841","url":null,"abstract":"<p><p>Alpha 1 antitrypsin deficiency (AATD) is a genetic disorder that alters the functionality and/or serum levels of alpha 1 antitrypsin (AAT). Dysfunctional forms of AAT, or low levels of serum AAT, predispose affected individuals to pulmonary complications. When AATD-associated lung disease develops, the most common pulmonary pathology is emphysema. The development of emphysema and decline in lung function varies by AATD genotype and is accelerated by risk factors, such as smoking. To improve the understanding and treatment of AATD, emerging knowledge and unresolved questions need to be discussed. Here we focus on developments in the areas of disease pathogenesis, biomarkers, and clinical endpoints for trials in AATD, as well as barriers to treatment. The clinical impact of AATD on lung function is highly variable and highlights the complexity of AATD pathogenesis, in which multiple underlying processes are involved. Reduced levels of functional AAT disrupt the protease-antiprotease homeostasis, leading to a loss of neutrophil elastase inhibition and the breakdown of elastin within the lung interstitium. Inflammatory processes also play a critical role in the development of AATD-associated lung disease, which is not yet fully understood. Biomarkers associated with the disease and its complications may have an important role in helping to address AATD underdiagnosis and evaluating response to treatment. To improve access to treatment, the problem of underdiagnosis needs to be addressed and the provision of therapeutic options needs to become uniform. Patients should also be empowered to play a key role in the self-management of the disease. Advancing our understanding of the disease will ultimately improve the life expectancy and quality of life for patients affected by AATD.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251318841"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}