COPD: Journal of Chronic Obstructive Pulmonary Disease最新文献

{"title":"FBXL19 Targeted STK11 Degradation Enhances Cigarette Smoke-Induced Airway Epithelial Cell Cytotoxicity.","authors":"Xiuying Li, Sowmya P Lakshmi, Kiyoshi Uemasu, Zachary Lane, Rajan T Reddy, Divay Chandra, Chunbin Zou, Yu Jiang, Toru Nyunoya","doi":"10.1080/15412555.2024.2342797","DOIUrl":"10.1080/15412555.2024.2342797","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the effects of cigarette smoke (CS) on Serine/Threonine Kinase 11 (STK11) and to determine STK11's role in CS-induced airway epithelial cell cytotoxicity.<b>Methods:</b> STK11 expression levels in the lung tissues of smokers with or without COPD and mice exposed to CS or room air (RA) were determined by immunoblotting and RT-PCR. BEAS-2Bs-human bronchial airway epithelial cells were exposed to CS extract (CSE), and the changes in STK11 expression levels were determined by immunoblotting and RT-PCR. BEAS-2B cells were transfected with STK11-specific siRNA or STK11 expression plasmid, and the effects of CSE on airway epithelial cell cytotoxicity were measured. To determine the specific STK11 degradation-proteolytic pathway, BEAS-2Bs were treated with cycloheximide alone or combined with MG132 or leupeptin. Finally, to identify the F-box protein mediating the STK11 degradation, a screening assay was performed using transfection with a panel of FBXL E3 ligase subunits.<b>Results:</b> STK11 protein levels were significantly decreased in the lung tissues of smokers with COPD relative to smokers without COPD. STK11 protein levels were also significantly decreased in mouse lung tissues exposed to CS compared to RA. Exposure to CSE shortened the STK11 mRNA and protein half-life to 4 h in BEAS-2B cells. STK11 protein overexpression attenuated the CSE-induced cytotoxicity; in contrast, its knockdown augmented CSE-induced cytotoxicity. FBXL19 mediates CSE-induced STK11 protein degradation <i>via</i> the ubiquitin-proteasome pathway in cultured BEAS-2B cells. FBXL19 overexpression led to accelerated STK11 ubiquitination and degradation in a dose-dependent manner.<b>Conclusions:</b> Our results suggest that CSE enhances the degradation of STK11 protein in airway epithelial cells <i>via</i> the FBXL19-mediated ubiquitin-proteasomal pathway, leading to augmented cell death.HIGHLIGHTSLung tissues of COPD-smokers exhibited a decreased STK11 RNA and protein expression.STK11 overexpression attenuates CS-induced airway epithelial cell cytotoxicity.STK11 depletion augments CS-induced airway epithelial cell cytotoxicity.CS diminishes STK11 via FBXL19-mediated ubiquitin-proteasome degradation.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2342797"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship Between Chronic Obstructive Pulmonary Disease and Osteoporosis: A Scoping Review.","authors":"Ana Penedones, Diogo Mendes, Carlos Alves, Augusto Filipe, Tânia Oliveira, Francisco Batel-Marques","doi":"10.1080/15412555.2024.2356510","DOIUrl":"https://doi.org/10.1080/15412555.2024.2356510","url":null,"abstract":"<p><strong>Introduction: </strong>Potential associations between Chronic Obstructive Pulmonary Disease (COPD) and osteoporosis have been studied, but areas of uncertainty remain.</p><p><strong>Objective: </strong>This scoping review aimed to identify the published evidence on the epidemiological relationships between COPD and osteoporosis.</p><p><strong>Methods: </strong>Experimental and observational evidence evaluating relationships between COPD and osteoporosis on epidemiology, clinical manifestations, risk factors (RFs), therapeutic management and quality of life (QoL) was searched on PubMed and Embase (until May 2023). The studies were categorized according to their objectives and characteristics. Data were analyzed using descriptive statistics.</p><p><strong>Results: </strong>Ninety-nine studies were selected, namely 33 (33%) reporting epidemiologic measures, 11 (11%) clinical manifestations, 74 (75%) RFs (45 ones, of which body mass index [BMI; <i>n</i> = 22 studies], corticosteroids' use [<i>n</i> = 20], and COPD severity [<i>n</i> = 15] were the most studied), 7 (7%) therapeutic management, and 3 (3%) QoL. Twenty-seven (27.6%) studies evaluated ≥2 domains. Most studies followed a cross-sectional design (<i>n</i> = 37; 37.4%). Eighty-nine studies (90%) assessed patients with COPD at baseline and studied its relationship with osteoporosis.</p><p><strong>Conclusion: </strong>There are well-established features linking COPD and osteoporosis, including shared RFs, such as smoking, elderly, physical inactivity, or low BMI. Others deserve clarification, including the impact of COPD severity, or the use of inhaled corticosteroids on the incidence of osteoporosis and fractures, as well as the value of performing routine imaging tests, or prescribing anti-resorptive medications in COPD to prevent osteoporotic-related outcomes. QoL studies are also lacking. Investigating such issues is needed to propose clinical guidelines for managing osteoporosis in patients with COPD.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2356510"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbidity Patterns in Chronic Obstructive Pulmonary Disease and Their Associations with Service Utilization.","authors":"Yanran Duan, Hang Fu, Changying Chen, Yaojun Zhao, Shuai Jiang, Chengzeng Wang","doi":"10.1080/15412555.2024.2414793","DOIUrl":"10.1080/15412555.2024.2414793","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of combinations of comorbidities and their associations with inpatient service utilization and readmission among patients with chronic obstructive pulmonary disease (COPD) have not been extensively examined. To address this gap in knowledge, an observational prospective study was conducted using retrospective data.</p><p><strong>Aims: </strong>To identify patterns of comorbidities linked to length of hospital stay, daily expenses, and one-year readmission.</p><p><strong>Methods: </strong>The 30 most common comorbidities were identified in patients with secondary diagnoses using the association rule mining (ARM) method. Regression models were used to examine the relationships between combinations of comorbidities and service utilization, with adjustments for covariates.</p><p><strong>Results: </strong>The five most prevalent comorbidities were pulmonary heart disease (40.99%), ischemic heart disease (38.97%), heart failure (36.77%), hypertension (34.11%), and respiratory disorders (19.12%). Most combinations of comorbidities identified by ARM showed significant associations with an extended length of stay (>13 days), increased daily expenses (>930 CNY), and reduced readmission rates. Among these combinations, glycoprotein metabolism disorder had the strongest association with prolonged length of stay (adjusted odds ratio [aOR]): 1.89, 95% confidence interval [CI]: 1.82-1.95). Conversely, the combination of other brain diseases and respiratory failure was linked to higher daily expenses (aOR: 11.34, 95% CI: 10.58-12.15), and the presence of pulmonary heart disease was associated with elevated one-year readmission rates (aOR: 1.41, 95% CI: 1.37-1.46).</p><p><strong>Conclusion: </strong>Common combinations of comorbidities among inpatients with COPD were identified from an extensive collection of discharge medical records. Furthermore, the associations between comorbidities, inpatient service usage, and readmission rates were determined.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2414793"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Spirometry: Linking Wasted Ventilation to Exertional Dyspnea in the Initial Stages of COPD.","authors":"J Alberto Neder, Giles Santyr, Brandon Zanette, Miranda Kirby, Marina Pourafkari, Matthew D James, Sandra G Vincent, Carrie Ferguson, Chu-Yi Wang, Nicolle J Domnik, Devin B Phillips, Janos Porszasz, William W Stringer, Denis E O'Donnell","doi":"10.1080/15412555.2023.2301549","DOIUrl":"10.1080/15412555.2023.2301549","url":null,"abstract":"<p><p>Exertional dyspnea, a key complaint of patients with chronic obstructive pulmonary disease (COPD), ultimately reflects an increased inspiratory neural drive to breathe. In non-hypoxemic patients with largely preserved lung mechanics - as those in the initial stages of the disease - the heightened inspiratory neural drive is strongly associated with an exaggerated ventilatory response to metabolic demand. Several lines of evidence indicate that the so-called excess ventilation (high ventilation-CO₂ output relationship) primarily reflects poor gas exchange efficiency, namely increased physiological dead space. Pulmonary function tests estimating the extension of the wasted ventilation and selected cardiopulmonary exercise testing variables can, therefore, shed unique light on the genesis of patients' out-of-proportion dyspnea. After a succinct overview of the basis of gas exchange efficiency in health and inefficiency in COPD, we discuss how wasted ventilation translates into exertional dyspnea in individual patients. We then outline what is currently known about the structural basis of wasted ventilation in \"minor/trivial\" COPD vis-à-vis the contribution of emphysema versus a potential impairment in lung perfusion across non-emphysematous lung. After summarizing some unanswered questions on the field, we propose that functional imaging be amalgamated with pulmonary function tests beyond spirometry to improve our understanding of this deeply neglected cause of exertional dyspnea. Advances in the field will depend on our ability to develop robust platforms for deeply phenotyping (structurally and functionally), the dyspneic patients showing unordinary high wasted ventilation despite relatively preserved FEV₁.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2301549"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recognizing the Shades of Grey in the Diagnosis of COPD.","authors":"J Alberto Neder","doi":"10.1080/15412555.2024.2402706","DOIUrl":"https://doi.org/10.1080/15412555.2024.2402706","url":null,"abstract":"","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2402706"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Scoping Review of Factors Influencing Smoking Cessation in Patients with Chronic Obstructive Pulmonary Disease.","authors":"Tong Huimin, Tian Zheng, He Jingchun, Liu Dajun, Zhang Zhijun, Li Yuan, Zhang Nan, Wang Lan","doi":"10.1080/15412555.2024.2390988","DOIUrl":"10.1080/15412555.2024.2390988","url":null,"abstract":"<p><p>To provide a scoping review of studies on factors affecting smoking cessation in patients with chronic obstructive pulmonary disease (COPD), so as to provide a basis for healthcare professionals to intervene early in the process of cessation of smoking in patients with COPD, and to formulate personalized interventions for smoking cessation. Arksey and O'Malley's scoping review methodology as a framework, searched databases including CNKI, Wanfang Data, VIP, China Biomedical Database, PubMed, Web of Science, Embase, ProQuest, CINAHL, and Cochrane Library to collect literature on factors influencing smoking cessation among COPD patients. The literature was screened, data extracted, and summarized accordingly. A total of 28 papers were included. The socio-demographic related factors affecting smoking cessation in patients with COPD were age, educational level, residence, marital status, occupational status, economic status, race, and sex; tobacco related factors included smoking index, smoking duration (years), cumulative smoking (packs/year), smoking intensity (packs/day), and tobacco addiction; disease related factors included mMRC score, GOLD level, severity of airflow restrictions, symptom, activity limitation due to lung problems, history of deterioration in outpatient care, receipt of COPD medication, receipt of lung CT, receipt of pulmonary function tests, receipt of surgery, and comorbid comorbidities; psychologically related factors included mental health status, quit smoking health beliefs, smoking cessation self-efficacy, motivation to quit smoking, stress, and adverse emotions; environmental/Interpersonal network related factors-included environmental impacts, social support, family support, tobacco control policies, and satisfaction with cessation care; and behavior related factors included alcohol consumption, coffee consumption, eating, physical activity, and have a hobby. Healthcare professionals should avoid critical education of COPD patients in the process of smoking cessation management, pay attention to the adverse effects of medication side effects on patients, emphasize the improvement of patients' health beliefs and self-efficacy in smoking cessation, and help patients to establish a correct cognition of smoking cessation.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2390988"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic Cells Promote the Differentiation of ILCs into NCR^-ILC3s in the Lungs of Mice Exposed to Cigarette Smoke.","authors":"Caixia Liang, Ying Shen, Yifang Xu, Yi Liang, Shilin Qiu, Haijuan Tang, Xiaoning Zhong","doi":"10.1080/15412555.2024.2389909","DOIUrl":"https://doi.org/10.1080/15412555.2024.2389909","url":null,"abstract":"<p><p>The involvement of Group 3 innate lymphoid cells (ILC3s) and dendritic cells (DCs) in chronic lung inflammation has been increasingly regarded as the key to understand the inflammatory mechanisms of smoke-related chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the engagement of both remains unclear. Our study aimed to explore NCR^-ILC3 differentiation in the lungs of mice exposed to cigarette smoke (CS) and to further investigate whether DCs activated by CS exposure contribute to the differentiation of ILCs into NCR^-ILC3s. The study involved both <i>in vivo</i> and <i>in vitro</i> experiments. In the former, the frequencies of lung NCR^-ILC3s and NKp46^-IL-17A⁺ ILCs and the expression of DCs, CD40, CD86, IL-23, and IL-1β quantified by flow cytometry were compared between CS-exposed mice and air-exposed mice. In the latter, NKp46^-IL-17A⁺ ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45⁺Lin^-CD127⁺ ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45⁺Lin^-CD127⁺ ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCR^-ILC3s and NKp46^-IL-17A⁺ ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1β in CS-exposed mice; and in the frequency of NKp46^-IL-17A⁺ ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCR^-ILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCR^-ILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2389909"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impressions and Perceptions of a Smartphone and Smartwatch Self-Management Tool for Patients With COPD: A Qualitative Study.","authors":"Robert Wu, Maryann Calligan, Tanya Son, Harshmeet Rakhra, Eyal de Lara, Alex Mariakakis, Andrea S Gershon","doi":"10.1080/15412555.2023.2277158","DOIUrl":"10.1080/15412555.2023.2277158","url":null,"abstract":"<p><strong>Background: </strong>Patients with chronic obstructive pulmonary disease (COPD) often do not seek care until they experience an exacerbation. Improving self-management for these patients may increase health-related quality of life and reduce hospitalizations. Patients are willing to use wearable technology for real-time data reporting and perceive mobile technology as potentially helpful in COPD management, but there are many barriers to the uptake of these technologies.</p><p><strong>Objective: </strong>We aimed to understand patients' experiences using a wearable and mobile app and identify areas for improvement.</p><p><strong>Methods: </strong>We conducted semi-structured interviews as part of a larger prospective cohort study wherein patients used a wearable and app for 6 months. We asked which features patients found accessible, acceptable and useful.</p><p><strong>Results: </strong>We completed 26 interviews. We summarized our research findings into four main themes: (1) information, support and reassurance, (2) barriers to adoption, (3) impact on communication with health care providers, and (4) opportunities for improvement. Most patients found the feedback received through the app to be reassuring and useful. Some patients experienced technical difficulties with the app and found the wearable to be uncomfortable.</p><p><strong>Conclusions: </strong>Patients found a wearable device and mobile application to be acceptable and useful for the management of COPD. We identified barriers to adoption and opportunities for improvement to the design of our app. Further research is needed to understand what people with COPD and their healthcare providers want and will use in a mobile app and wearable for COPD management.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2277158"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Aspirin on Major COPD Outcomes: A Prevalent New-User Design Observational Study.","authors":"Charles Khouri, Sophie Dell'Aniello, Pierre Ernst, Samy Suissa","doi":"10.1080/15412555.2024.2317380","DOIUrl":"10.1080/15412555.2024.2317380","url":null,"abstract":"<p><p>Observational studies that have reported an association between aspirin use in chronic obstructive pulmonary disease (COPD) with reductions in mortality and COPD exacerbations were shown to be affected by time-related biases. We assessed this association using a prevalent new-user study design that avoids these biases. We used the United Kingdom's Clinical Practice Research Datalink (CPRD) to form a cohort of patients with COPD. Aspirin initiators were matched on time and propensity score with nonusers during 2002-2018. The outcomes were all-cause mortality and COPD exacerbation within a one-year follow-up. Hazard ratios (HR) and 95% confidence interval (CI) of each outcome associated with aspirin use compared to nonuse were estimated using an as-treated approach. The study cohort included 10,287 initiators of aspirin and 10,287 matched nonusers. The cumulative incidence of all-cause mortality at one year was 11.5% for aspirin users and 9.2% for nonusers. The HR of all-cause mortality associated with aspirin initiation was 1.22 (95% CI: 1.08-1.37), while for severe exacerbation it was 1.21 (95% CI 1.08-1.37), compared with nonuse. The HR of a first moderate or severe exacerbation with aspirin use was 0.90 (95% CI 0.85-0.95). These estimates did not vary by platelet count. This large population-based study, designed to emulate a trial, found aspirin use in patients with COPD associated with a higher risk of all-cause mortality and severe exacerbation, but a lower risk of moderate or severe exacerbation. Further research is warranted to assess this reduction in moderate or severe exacerbations, particularly in patients with cardiovascular risk factors.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2317380"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine-Learning Model Identifies Patients With Alpha-1 Antitrypsin Deficiency Using Claims Records.","authors":"Rajani Sharma, D Kyle Hogarth, Richard Colbaugh, Kristin Glass, Adel Mezine, Vassia Liakoni, Christopher Rudolf, Iris Himmelhan, Jimmy Hinson, Marie Sanchirico","doi":"10.1080/15412555.2024.2393348","DOIUrl":"https://doi.org/10.1080/15412555.2024.2393348","url":null,"abstract":"<p><p>Identifying patients with rare diseases like alpha-1 antitrypsin deficiency (AATD) is challenging. Machine-learning models may be trained to identify patients with rare diseases using large-scale, real-world databases, whereas electronic medical records have low numbers of confirmed cases and have limited use in training such models. We applied a machine-learning model to a large US claims database to identify undiagnosed symptomatic patients with AATD. Using deidentified data from the Komodo US claims database (April 26, 2016-January 31, 2023), a model was trained to identify symptomatic patients with high probability of AATD. Eighty claims records for high-probability candidates identified by the model were independently reviewed and validated by 2 clinical experts. The experts independently indicated that of the 80 high-probability candidate patients, 65 (81%) and 62 (78%) patients, respectively, should be tested for AATD. Feedback from this validation step informed model optimization. The optimized model was applied to claims data to identify symptomatic patients with probable AATD. Eleven and 14 \"features\" of the claims data were informative in distinguishing patients with AATD from patients with COPD without AATD and from unspecified chronic liver diseases. Moreover, patients with diagnosed AATD and COPD without AATD had unique cadences of similar medical events in their diagnostic journeys. Our work shows that a machine-learning model trained on a large US claims database can accurately identify symptomatic patients with AATD and provides useful insights into the diagnostic journey of patients with AATD.</p>","PeriodicalId":10704,"journal":{"name":"COPD: Journal of Chronic Obstructive Pulmonary Disease","volume":"21 1","pages":"2393348"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}