Therapeutic Advances in Respiratory Disease最新文献

{"title":"Advances in acute COPD exacerbation: clarifying specific immune mechanisms of infectious and noninfectious factors.","authors":"Yadan Tu, Yong Chen, Xuanhan Li, Yigang Wang, Bangjiang Fang, Yi Ren, Chenghu Wang","doi":"10.1177/17534666241308408","DOIUrl":"10.1177/17534666241308408","url":null,"abstract":"<p><p>Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the main cause of hospitalization and death of patients with chronic obstructive pulmonary disease. This is largely due to bacterial resistance caused by clinical antibiotic abuse and the limited efficacy of current treatment strategies in managing noninfectious AECOPD, which presents a significant challenge for clinicians. Therefore, it is urgent for clinical treatment and prevention of AECOPD to fully understand the specific mechanism of AECOPD in the immune system and master the key differences between infectious factors and noninfectious factors. This article systematically discusses AECOPD triggered by various factors, including the activation of immune system, the recruitment and activation of inflammatory cells and the role of specific inflammatory responses, and through a comprehensive review of the literature, this article expounds the existing targeted diagnosis and treatment methods and technologies at different stages in order to provide new ideas and strategies for clinical prevention and treatment of AECOPD.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666241308408"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650928","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":"Early, integrated palliative care for people with chronic respiratory disease: lessons learnt from lung cancer.","authors":"Anne M Walker, Donald R Sullivan, Phan Nguyen, Anne E Holland, Natasha Smallwood","doi":"10.1177/17534666241305497","DOIUrl":"10.1177/17534666241305497","url":null,"abstract":"<p><p>Lung cancer and chronic non-malignant respiratory disease cause pervasive, multifactorial suffering for patients and informal carers alike. Palliative care aims to reduce suffering and improve quality of life for patients and their families. An established evidence base exists that has demonstrated the essential role of specialist palliative care for people with lung cancer. Emerging evidence supports similar benefits among people with chronic respiratory disease. Many lessons can be learnt from lung cancer care, particularly as the model of care delivery has transformed over recent decades due to major advances in the diagnostic pathway and the development of new treatments. This narrative review aims to summarize the evidence for specialist palliative care in lung cancer and chronic respiratory disease, by highlighting seven key lessons from lung cancer care that can inform the development of proactive, integrated models of palliative care among those with chronic respiratory disease. These seven lessons emphasize (1) managing challenging symptoms; (2) the efficacy of specialist palliative care; (3) the importance of providing specialist palliative care integrated with disease-directed care according to patients' needs not prognosis; (4) the need for new models of collaborative palliative care, (5) which are culturally appropriate and (6) able to evolve with changes in disease-directed care. Finally, we discuss (7) some of the critical research gaps that persist and reduce implementation in practice.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666241305497"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374274","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":"New era, new GOALs: cardiovascular screening and lipid management in cystic fibrosis.","authors":"Katherine A Despotes, Agathe S Ceppe, Jennifer L Goralski, Scott H Donaldson","doi":"10.1177/17534666251317200","DOIUrl":"10.1177/17534666251317200","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) risks are increasing in people with cystic fibrosis (pwCF). While cholesterol levels were historically low in pwCF, higher levels after initiating highly effective modulator therapy (HEMT) have been reported. Mechanisms are unclear and there is little guidance on screening.</p><p><strong>Objectives: </strong>To evaluate serum lipid changes at multiple timepoints after ivacaftor initiation, and to assess current screening practices for CVD risk factors among CF providers.</p><p><strong>Design: </strong>This was a post-hoc correlative analysis of prospectively collected clinical data and serum samples from the GOAL cohort study. Cross-sectional survey methodology was also employed.</p><p><strong>Methods: </strong>We evaluated serum lipids (total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) at baseline, 3- and 18 months after ivacaftor initiation using samples from the GOAL study biorepository. We also surveyed CF providers across the United States on their CVD risk screening practices.</p><p><strong>Results: </strong>Fifty GOAL participants' samples were analyzed. Using the repeated measures model, TC significantly varied by visit (<i>p</i> = 0.004), driven by a significant increase from baseline at 3 months (mean difference 9.4 mg/dL). This difference diminished by 18 months. BMI was a significant covariate for TC. No significant differences by visit were detected in LDL or HDL. Seventy-five respondents participated in the survey (response rate 5.6%; 41 adult providers, 18 pediatric providers, and 10 providers caring for both) with 67% reporting no lipid screening policy existed in their center. In the past year, 29% of adult providers prescribed lipid-lowering therapy, 54% started anti-hypertensive medications, and 48% initiated ischemic cardiac evaluations for pwCF.</p><p><strong>Conclusion: </strong>TC significantly increased within 3 months of initiating ivacaftor, but subsequently diminished toward baseline by 18 months. Lipid screening practices among CF providers were variable and providers are increasingly being confronted with managing CVD risk factors. Partnering with primary care providers is likely to become increasingly important in CF care models.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251317200"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075525","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":"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":"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":"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":"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":"Effect of pulmonary rehabilitation for patients with long COVID-19: a systematic review and meta-analysis of randomized controlled trials.","authors":"Shige Li, Bing Dai, Yusheng Hou, Liang Zhang, Jie Liu, Haijia Hou, Dandan Song, Shengchen Wang, Xiangrui Li, Hongwen Zhao, Wei Wang, Jian Kang, Wei Tan","doi":"10.1177/17534666251323482","DOIUrl":"10.1177/17534666251323482","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary rehabilitation (PR) has demonstrated efficacy in managing long COVID-19, underscoring the need to refine and tailor PR strategies for optimal patient outcomes.</p><p><strong>Objectives: </strong>To evaluate the impact of PR on patients with long COVID-19 and to compare the efficacy of different types and durations of PR interventions.</p><p><strong>Design: </strong>Systematic review and meta-analysis.</p><p><strong>Data sources and methods: </strong>We systematically searched randomized controlled trials (RCTs) of the effectiveness of PR in long COVID-19 patients published before April 2024. The primary outcomes were physical capacity assessed by the 6-minute walking test (6MWT), lung function measured by forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), health-related quality of life (HRQoL), and fatigue. Secondary outcomes were thirty-second sit-to-stand test (30STST), handgrip strength tests, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), dyspnea, depression, anxiety, perceived effort, and adverse events.</p><p><strong>Results: </strong>A total of 37 studies with 3363 patients were included. Compared to controls, PR improved physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, fatigue, dyspnea, and anxiety but did not reach statistical significance for depression. Subgroup analyses of PR duration indicated that programs of ⩽4 weeks improved 6MWT; those between 4 and 8 weeks significantly improved 6MWT, lung function (FEV1, FVC), HRQoL, and reduced fatigue; and programs over 8 weeks improved HRQoL and reduced fatigue. Exercise type analysis revealed that breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL; multicomponent exercises enhanced 6MWT performance and reduced fatigue; the combination of both types improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and reduced fatigue.</p><p><strong>Conclusion: </strong>PR improves physical capacity, lung function, and quality of life and alleviates dyspnea, fatigue, and anxiety in long COVID-19 patients. A 4- to 8-week PR program and a combination of both breath exercises and multicomponent training is most effective for managing long-term COVID-19 syndromes.</p><p><strong>Trial registration: </strong>PROSPERO ID: CRD42024455008.</p>","PeriodicalId":22884,"journal":{"name":"Therapeutic Advances in Respiratory Disease","volume":"19 ","pages":"17534666251323482"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626141","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":"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}