{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:09:47Z","timestamp":1792811387227,"version":"4.5.0"},"reference-count":121,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Although smoking is the main risk factor for chronic obstructive pulmonary disease (COPD), about one-third of patients have never smoked. This phenomenon supports the idea of a distinct phenotype of the disease in never-smokers, influenced by genetic, infectious, socioeconomic, environmental, and occupational factors. The paper is based on a narrative review of recent literature on the etiology, clinical features, evolution, and therapeutic strategies of COPD in never-smokers, mainly through the analysis of published studies over the last 3 years. COPD in never-smokers occurs predominantly in women, the elderly, and individuals from rural areas or with poor socioeconomic status. Key risk factors include exposure to occupational or environmental pollutants, air pollution, previous respiratory infections, particularly due to pulmonary tuberculosis, and genetic predisposition, mainly through alpha-1 antitrypsin deficiency (A1ATD). Clinically, COPD in never-smokers is characterized by chronic cough and dyspnea, with less severe pulmonary functional impairment, slow progression, and lower prevalence of emphysema compared to smokers. Imaging often highlights bronchiectasis or post-infectious sequelae, and biological markers indicate a significant eosinophilic component. Thus, COPD in never-smokers is a distinct clinical entity with multifactorial pathogenesis and distinct clinical-functional characteristics. Prompt recognition of this form of disease is essential for prevention and adaptation of therapeutic strategies. A personalized multidisciplinary approach can improve disease prognosis and the quality of life for these patients.<\/jats:p>","DOI":"10.3390\/life16010043","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:25:51Z","timestamp":1766989551000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Obstructive Pulmonary Disease in Never-Smokers\u2014A Distinct Entity Within the COPD Spectrum"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2471-3510","authenticated-orcid":false,"given":"Andreea-Nicoleta","family":"M\u0103l\u0103escu","sequence":"first","affiliation":[{"name":"Department of Cardio-Thoracic Pathology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Institute of Pneumology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin-Dumitru","family":"Mih\u0103l\u021ban","sequence":"additional","affiliation":[{"name":"Department of Cardio-Thoracic Pathology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Institute of Pneumology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6742-6334","authenticated-orcid":false,"given":"Ancu\u021ba-Alina","family":"Constantin","sequence":"additional","affiliation":[{"name":"Department of Cardio-Thoracic Pathology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Institute of Pneumology \u201cMarius Nasta\u201d, 050159 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"ref_1","unstructured":"(2025, March 28). Global Initiative for Chronic Obstructive Lung Disease\u2014GOLD [Internet]. 2025 GOLD Report. Available online: https:\/\/goldcopd.org\/2025-gold-report\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107284","DOI":"10.1016\/j.rmed.2023.107284","article-title":"Clinical characteristics of chronic obstructive pulmonary disease in never-smokers: A systematic review","volume":"214","year":"2023","journal-title":"Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.2147\/COPD.S427774","article-title":"COPD Risk Factor Profiles in General Population and Referred Patients: Potential Etiotypes","volume":"18","author":"Lee","year":"2023","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"161","DOI":"10.18332\/tid\/192745","article-title":"Prevalence, mortality and risk factors for self-reported COPD among smokers and never smokers, NHANES 1999\u20132018","volume":"22","author":"Li","year":"2024","journal-title":"Tob. Induc. Dis."},{"key":"ref_5","first-page":"174","article-title":"Clinical Characteristics of Non-Smoking Chronic Obstructive Pulmonary Disease Patients: Findings from the KOCOSS Cohort","volume":"19","author":"Choi","year":"2022","journal-title":"COPD J. Chronic Obstr. Pulm. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Park, H., Jo, S.M., Jin, K.N., Lee, H.J., Lee, H.W., Park, T.Y., Heo, E.Y., Kim, D.K., and Lee, J.-K. (2025). Distinct risks of exacerbation and lung function decline between never-smokers and ever-smokers with COPD. BMC Pulm. Med., 25.","DOI":"10.1186\/s12890-025-03604-1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7481","DOI":"10.1038\/s41598-024-58038-2","article-title":"Secondhand smoke increases the risk of developing chronic obstructive pulmonary disease","volume":"14","author":"Su","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8297","DOI":"10.1038\/s41467-023-44047-8","article-title":"Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors","volume":"14","author":"He","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"00532-2021","DOI":"10.1183\/23120541.00532-2021","article-title":"Predictors of chronic obstructive pulmonary disease in women who have never smoked: A cohort study","volume":"8","author":"Engel","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_10","first-page":"56","article-title":"COPD and Smoking Status\u2014It Does Matter: Characteristics and Prognosis of COPD According to Smoking Status","volume":"11","author":"Nielsen","year":"2023","journal-title":"Chronic Obstr. Pulm. Dis. J. COPD Found."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s12931-022-02144-0","article-title":"Prevalence, characteristics, and risk of exacerbation in young patients with chronic obstructive pulmonary disease","volume":"23","author":"Jo","year":"2022","journal-title":"Respir. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.2147\/COPD.S484664","article-title":"Analysis of COPD: Distinguishing Characteristics and Management of Smoking vs Never Smoking Patients","volume":"19","author":"Fekete","year":"2024","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2147\/COPD.S77662","article-title":"Risk factors for chronic obstructive pulmonary disease among never-smokers in Korea","volume":"10","author":"Lee","year":"2015","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2147\/COPD.S439307","article-title":"COPD in Never-Smokers: BOLD Australia Study","volume":"19","author":"Ivey","year":"2024","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S2213-2600(21)00506-3","article-title":"Chronic obstructive pulmonary disease in never-smokers: Risk factors, pathogenesis, and implications for prevention and treatment","volume":"10","author":"Yang","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.2147\/COPD.S523732","article-title":"Incidence and Risk Factors of Tuberculosis-Associated Chronic Obstructive Pulmonary Disease","volume":"20","author":"Joo","year":"2025","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.12771\/emj.2025.00059","article-title":"Pathophysiology, clinical manifestation, and treatment of tuberculosis-associated chronic obstructive pulmonary disease: A narrative review","volume":"48","author":"Choi","year":"2025","journal-title":"Ewha Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kotlyarov, S., and Oskin, D. (2025). The Role of Inflammation in the Pathogenesis of Comorbidity of Chronic Obstructive Pulmonary Disease and Pulmonary Tuberculosis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062378"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bezerra, F.S., Lanzetti, M., Nesi, R.T., Nagato, A.C., Silva, C.P.E., Kennedy-Feitosa, E., Melo, A.C., Cattani-Cavalieri, I., Porto, L.C., and Valenca, S.S. (2023). Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries. Antioxidants, 12.","DOI":"10.3390\/antiox12030548"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"bqab254","DOI":"10.1210\/endocr\/bqab254","article-title":"Sex and Gender Differences in Lung Cancer and Chronic Obstructive Lung Disease","volume":"163","author":"Siegfried","year":"2022","journal-title":"Endocrinology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13578-023-00998-5","article-title":"Sexual dimorphism in chronic respiratory diseases","volume":"13","author":"Reddy","year":"2023","journal-title":"Cell Biosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kayongo, A., Nyiro, B., Siddharthan, T., Kirenga, B., Checkley, W., Lutaakome Joloba, M., Ellner, J., and Salgame, P. (2023). Mechanisms of lung damage in tuberculosis: Implications for chronic obstructive pulmonary disease. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1146571"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Le, Y., Cao, W., Zhou, L., Fan, X., Liu, Q., Liu, F., Gai, X., Chang, C., Xiong, J., and Rao, Y. (2020). Infection of Mycobacterium tuberculosis Promotes Both M1\/M2 Polarization and MMP Production in Cigarette Smoke-Exposed Macrophages. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01902"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"284","DOI":"10.5152\/TurkThoracJ.2021.20147","article-title":"What are the Differences Between Smoker and Non-smoker COPD Cases? Is it a Different Phenotype?","volume":"22","author":"Polat","year":"2021","journal-title":"Turk. Thorac. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"230009","DOI":"10.1183\/16000617.0009-2023","article-title":"P4O2 consortium Identifying risk factors for COPD and adult-onset asthma: An umbrella review","volume":"32","author":"Holtjer","year":"2023","journal-title":"Eur. Respir. Rev. Off. J. Eur. Respir. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Gai, X., Chu, H., Qu, J., Li, L., and Sun, Y. (2024). Prevalence of non-smoking chronic obstructive pulmonary disease and its risk factors in China: A systematic review and meta-analysis. BMC Public Health, 24.","DOI":"10.1186\/s12889-024-20170-z"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2470954","DOI":"10.1080\/07853890.2025.2470954","article-title":"Childhood respiratory risk profiles associate with lung function and COPD among the old population","volume":"57","author":"Qin","year":"2025","journal-title":"Ann. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/crj.13479","article-title":"Risk factors for chronic obstructive pulmonary disease in never-smokers: A systematic review","volume":"16","author":"Golpe","year":"2022","journal-title":"Clin. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yeboah, K., Musa, L., and Bedu-Addo, K. (2024). Abnormal spirometric patterns and respiratory symptoms in HIV patients with no recent pulmonary infection in a periurban hospital in Ghana. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0273063"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e0213921","DOI":"10.1128\/spectrum.02139-21","article-title":"Sputum Microbiome and Chronic Obstructive Pulmonary Disease in a Rural Ugandan Cohort of Well-Controlled HIV Infection","volume":"11","author":"Kayongo","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1165\/rcmb.2021-0168OC","article-title":"Smoking and Human Immunodeficiency Virus 1 Infection Promote Retention of CD8+ T Cells in the Airway Mucosa","volume":"65","author":"Corleis","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Karado\u011fan, D., Dreger, B., Osaba, L., Ahmeto\u011flu, E., \u00d6zyurt, S., Y\u0131lmaz Kara, B., H\u00fcrsoy, N., Telatar, T.G., and \u015eahin, \u00dc. (2024). Clinical implications of the SERPINA1 variant, MPalermo, and alpha-1 antitrypsin deficiency in T\u00fcrkiye. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-03421-y"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/COPD.S340241","article-title":"The Clinical Course of Severe Alpha-1-Antitrypsin Deficiency in Patients Identified by Screening","volume":"17","author":"Hiller","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12931-023-02343-3","article-title":"Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function","volume":"24","author":"Kokturk","year":"2023","journal-title":"Respir. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.2147\/COPD.S531347","article-title":"Alpha-1 Antitrypsin Genotype Distribution in Patients with Emphysema","volume":"20","author":"Gegin","year":"2025","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Naeem, S., Wang, F., Mubarak, R., Shen, H., Li, X., Mommers, I., Hussain, S.R., Malik, S.S., Yu, C., and Hak, E. (2025). Mapping the Global distribution, risk factors, and temporal trends of COPD incidence and mortality (1990\u20132021): Ecological analysis. BMC Med., 23.","DOI":"10.1186\/s12916-025-04014-0"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1513\/AnnalsATS.202404-387OC","article-title":"Ambient Air Pollution and Chronic Obstructive Pulmonary Disease: The Multiethnic Cohort Study","volume":"22","author":"Park","year":"2025","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e001550","DOI":"10.1136\/bmjresp-2022-001550","article-title":"Prevalence, risk factors, and mortality of COPD in young people in the USA: Results from a population-based retrospective cohort","volume":"10","author":"Wang","year":"2023","journal-title":"BMJ Open Respir. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/15404153231210863","article-title":"Health and Demographic Factors for Chronic Obstructive Pulmonary Disease Among Hispanic Adults in the United States: Analysis of Behavioral Risk Factor Surveillance System Survey Data","volume":"22","author":"Workman","year":"2024","journal-title":"Hisp. Health Care Int. Off. J. Natl. Assoc. Hisp. Nurses"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1164\/rccm.202303-0444OC","article-title":"Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations","volume":"209","author":"Regan","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e002444","DOI":"10.1136\/bmjresp-2024-002444","article-title":"Low household income increases risks for chronic obstructive pulmonary disease in young population: A nationwide retrospective cohort study in South Korea","volume":"11","author":"Chung","year":"2024","journal-title":"BMJ Open Respir. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lee, H., Jung, J., and Yoon, H.-Y. (2025). Impact of socioeconomic status on chronic obstructive pulmonary disease prognosis: A national cohort study. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1584945"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"117978","DOI":"10.1016\/j.ecoenv.2025.117978","article-title":"The effect of long-term exposure to a mixture of air pollutants on chronic obstructive pulmonary disease","volume":"292","author":"Kim","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.ijheh.2019.03.009","article-title":"Association between chronic obstructive pulmonary disease and PM2.5 in Taiwanese nonsmokers","volume":"222","author":"Huang","year":"2019","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_45","first-page":"314","article-title":"Risk of Developing Chronic Obstructive Pulmonary Disease in Non-Smoking Adults Exposed to Particulate Matter 2.5 Compared to Those Without Exposure","volume":"44","author":"Notariza","year":"2024","journal-title":"J. Respirologi Indones."},{"key":"ref_46","first-page":"797","article-title":"Particulate matter in COPD pathogenesis: An overview","volume":"71","author":"Kaur","year":"2022","journal-title":"Inflamm. Res. Off. J. Eur. Histamine Res. Soc. Al"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103994","DOI":"10.1016\/j.ebiom.2022.103994","article-title":"Air pollution and risk of chronic obstructed pulmonary disease: The modifying effect of genetic susceptibility and lifestyle","volume":"79","author":"Wang","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zheng, J., Liu, S., Peng, J., Peng, H., Wang, Z., Deng, Z., Li, C., Li, N., Tang, L., and Xu, J. (2022). Traffic-related air pollution is a risk factor in the development of chronic obstructive pulmonary disease. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.1036192"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"119240","DOI":"10.1016\/j.envres.2024.119240","article-title":"Associations of long-term exposure to air pollution and greenness with incidence of chronic obstructive pulmonary disease in Northern Europe: The Life-GAP project","volume":"257","author":"Xu","year":"2024","journal-title":"Environ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cioboata, R., Balteanu, M.A., Mitroi, D.M., Vrabie, S.C., Vlasceanu, S.G., Andrei, G.M., Riza, A.L., Streata, I., Zlatian, O.M., and Olteanu, M. (2025). Beyond Smoking: Emerging Drivers of COPD and Their Clinical Implications in Low- and Middle-Income Countries: A Narrative Review. J. Clin. Med., 14.","DOI":"10.3390\/jcm14134633"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ortiz-Quintero, B., Mart\u00ednez-Espinosa, I., and P\u00e9rez-Padilla, R. (2022). Mechanisms of Lung Damage and Development of COPD Due to Household Biomass-Smoke Exposure: Inflammation, Oxidative Stress, MicroRNAs, and Gene Polymorphisms. Cells, 12.","DOI":"10.3390\/cells12010067"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Elonheimo, H.M., Mattila, T., Andersen, H.R., Bocca, B., Ruggieri, F., Haverinen, E., and Tolonen, H. (2022). Environmental Substances Associated with Chronic Obstructive Pulmonary Disease-A Scoping Review. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19073945"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1136\/thoraxjnl-2020-216523","article-title":"Lifetime occupational exposures and chronic obstructive pulmonary disease risk in the UK Biobank cohort","volume":"77","author":"Jarvis","year":"2022","journal-title":"Thorax"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.arbres.2023.10.014","article-title":"Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population","volume":"60","author":"Loeb","year":"2024","journal-title":"Arch. Bronconeumol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Loeb, E., Zock, J.-P., Miravitlles, M., Rodr\u00edguez, E., Kromhout, H., Vermeulen, R., Soler-Catalu\u00f1a, J.J., Soriano, J.B., Garc\u00eda-R\u00edo, F., and de Lucas, P. (2024). Occupational Exposures, Chronic Obstructive Pulmonary Disease and Tomographic Findings in the Spanish Population. Toxics, 12.","DOI":"10.3390\/toxics12100689"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"356","DOI":"10.21037\/jtd-23-646","article-title":"Effects of occupational exposure to dust, gas, vapor and fumes on chronic bronchitis and lung function","volume":"16","author":"Zheng","year":"2024","journal-title":"J. Thorac. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2147\/COPD.S403158","article-title":"Secondhand Smoke Exposure and the Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis","volume":"18","author":"Chen","year":"2023","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_58","first-page":"11","article-title":"Nonsmoker COPD represents a clinically Distinct Phenotype: A Prospective Observational Study","volume":"71","author":"Rani","year":"2023","journal-title":"J. Assoc. Physicians India"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zeng, Y., Spruit, M.A., Deng, Q., Franssen, F.M.E., and Chen, P. (2023). Differences of Clinical Characteristics and Drug Prescriptions between Men and Women with COPD in China. Toxics, 11.","DOI":"10.3390\/toxics11020102"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1164\/rccm.202109-2171OC","article-title":"Impaired Ventilatory Efficiency, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study","volume":"205","author":"Phillips","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Alishapour, E., Nayeri, M.A., Bahrami, R., Haghshenas, A., and Mehrabi, S. (2025). Validity and reliability of the persian version of the dyspnea-12 questionnaire in assessing dyspnea among COPD patients. BMC Res. Notes, 18.","DOI":"10.1186\/s13104-025-07290-4"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"254","DOI":"10.21037\/jtd-24-1267","article-title":"The impact of smoking on respiratory rehabilitation efficacy and correlation analysis in patients with chronic obstructive pulmonary disease: A retrospective study","volume":"17","author":"Li","year":"2025","journal-title":"J. Thorac. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"00697-2023","DOI":"10.1183\/23120541.00697-2023","article-title":"Chronic cough associated with COPD exacerbation, pneumonia and death in the general population","volume":"10","author":"Landt","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"00887-2024","DOI":"10.1183\/23120541.00887-2024","article-title":"Prevalence and risk factors of chronic cough in an adult community-dwelling Portuguese population","volume":"11","author":"Caires","year":"2025","journal-title":"ERJ Open Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e001462","DOI":"10.1136\/bmjresp-2022-001462","article-title":"CT airway remodelling and chronic cough","volume":"10","author":"Abozid","year":"2023","journal-title":"BMJ Open Respir. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"106921","DOI":"10.1016\/j.rmed.2022.106921","article-title":"on behalf of the NOVELTY study investigators. Frequent productive cough: Symptom burden and future exacerbation risk among patients with asthma and\/or COPD in the NOVELTY study","volume":"200","author":"Hughes","year":"2022","journal-title":"Respir. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5455\/msm.2025.37.32-36","article-title":"Clinical and Paraclinical Characteristics and Predictive Factors of Chronic Obstructive Pulmonary Exacerbation","volume":"37","author":"Thuy","year":"2025","journal-title":"Mater. Socio-Medica"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"00574-2021","DOI":"10.1183\/23120541.00574-2021","article-title":"The impact of personal and outdoor temperature exposure during cold and warm seasons on lung function and respiratory symptoms in COPD","volume":"8","author":"Scheerens","year":"2022","journal-title":"ERJ Open Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6047","DOI":"10.21037\/jtd-23-1031","article-title":"Clinical implications of wheezing in patients with chronic obstructive pulmonary disease","volume":"15","author":"Seo","year":"2023","journal-title":"J. Thorac. Dis."},{"key":"ref_70","first-page":"165","article-title":"Treatable Traits in Misdiagnosed Chronic Obstructive Pulmonary Disease: Data from the Akershus Cardiac Examination 1950 Study","volume":"9","author":"Caspersen","year":"2022","journal-title":"Chronic Obstr. Pulm. Dis."},{"key":"ref_71","first-page":"01052","article-title":"Symptom burden and its associations with clinical characteristics in patients with COPD: A clustering approach","volume":"10","author":"Deng","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/jocn.16234","article-title":"Symptom clusters, associated factors and health-related quality of life in patients with chronic obstructive pulmonary disease: A structural equation modelling analysis","volume":"32","author":"Fei","year":"2023","journal-title":"J. Clin. Nurs."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41533-025-00419-9","article-title":"Prevalence, diagnostic accuracy, and healthcare utilization patterns in patients with COPD in primary healthcare: A population-based study","volume":"35","author":"Vila","year":"2025","journal-title":"npj Prim. Care Respir. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2147\/COPD.S346456","article-title":"Different Smoking Statuses on Survival and Emphysema in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease","volume":"17","author":"Ding","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2147\/COPD.S436242","article-title":"Quantitative Assessment Characteristics of Small Pulmonary Vessel Remodelling in Populations at High Risk for COPD and Smokers Using Low-Dose CT","volume":"19","author":"Pu","year":"2024","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3348\/jksr.2022.0130","article-title":"Quantitative CT Analysis Based on Smoking Habits and Chronic Obstructive Pulmonary Disease in Patients with Normal Chest CT","volume":"84","author":"Byon","year":"2023","journal-title":"J. Korean Soc. Radiol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Xu, J., Zeng, Q., Li, S., Su, Q., and Fan, H. (2024). Inflammation mechanism and research progress of COPD. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1404615"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"742","DOI":"10.3892\/mmr.2021.12382","article-title":"Alteration of immune profiles is associated with pulmonary function and symptoms in patients with chronic obstructive pulmonary disease","volume":"24","author":"Li","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Lan, C.-C., Yang, M.-C., Su, W.-L., Huang, K.-L., Lin, C.-C., Huang, Y.-C., Huang, C.-Y., Chen, H.-Y., Wu, C.-W., and Lee, C. (2025). Unraveling the Immune Landscape of Chronic Obstructive Pulmonary Disease: Insights into Inflammatory Cell Subtypes, Pathogenesis, and Treatment Strategies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073365"},{"key":"ref_80","first-page":"e56212","article-title":"Neutrophil-to-Lymphocyte Ratio and Blood Eosinophil Levels As Inflammatory Indicators in Smoker and Non-smoker Young Adult Patients with Chronic Obstructive Pulmonary Disease at a Tertiary Care Hospital","volume":"16","author":"Waseem","year":"2024","journal-title":"Cureus"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"128","DOI":"10.4103\/lungindia.lungindia_261_24","article-title":"Bronchodilator reversibility and eosinophilic biomarkers in chronic obstructive pulmonary disease patients","volume":"42","author":"Ameet","year":"2025","journal-title":"Lung India"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Liu, Y., Ma, G., Mou, Y., Liu, X., Qiu, W., Zheng, Y., Zhu, H., and Ge, H. (2022). The Combined Value of Type2 Inflammatory Markers in Chronic Obstructive Pulmonary Disease. J. Clin. Med., 11.","DOI":"10.3390\/jcm11102791"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"20406223231190480","DOI":"10.1177\/20406223231190480","article-title":"Fractional nitric oxide measurement in exhaled air (FeNO): Perspectives in the management of respiratory diseases","volume":"14","author":"Ragnoli","year":"2023","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Ambrosino, P., Fuschillo, S., Accardo, M., Mosella, M., Molino, A., Spedicato, G.A., Motta, A., and Maniscalco, M. (2022). Fractional Exhaled Nitric Oxide (FeNO) in Patients with Stable Chronic Obstructive Pulmonary Disease: Short-Term Variability and Potential Clinical Implications. J. Pers. Med., 12.","DOI":"10.3390\/jpm12111906"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4046\/trd.2023.0175","article-title":"Lack of Association between Inhaled Corticosteroid Use Based on the Exhaled Nitric Oxide and Acute Exacerbation of Chronic Obstructive Pulmonary Disease","volume":"87","author":"Kim","year":"2024","journal-title":"Tuberc. Respir. Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"101736","DOI":"10.1016\/j.cegh.2024.101736","article-title":"Blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) for steroid stewardship in chronic obstructive pulmonary disorder (COPD): A systematic review","volume":"29","author":"Dhawan","year":"2024","journal-title":"Clin. Epidemiol. Glob. Health"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ellingsen, J., Janson, C., Br\u00f6ms, K., H\u00e5rdstedt, M., H\u00f6gman, M., Lisspers, K., Palm, A., St\u00e4llberg, B., and Malinovschi, A. (2024). CRP, Fibrinogen, White Blood Cells, and Blood Cell Indices as Prognostic Biomarkers of Future COPD Exacerbation Frequency: The TIE Cohort Study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13133855"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.2147\/COPD.S312560","article-title":"Update on Asthma-COPD Overlap (ACO): A Narrative Review","volume":"16","author":"Mekov","year":"2021","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"00437-2020","DOI":"10.1183\/23120541.00437-2020","article-title":"Targeted therapy in eosinophilic chronic obstructive pulmonary disease","volume":"7","author":"Fieldes","year":"2021","journal-title":"ERJ Open Res."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Fouka, E., Papaioannou, A.I., Hillas, G., and Steiropoulos, P. (2022). Asthma-COPD Overlap Syndrome: Recent Insights and Unanswered Questions. J. Pers. Med., 12.","DOI":"10.3390\/jpm12050708"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Meteran, H., Sivapalan, P., and St\u00e6hr Jensen, J.-U. (2021). Treatment Response Biomarkers in Asthma and COPD. Diagnostics, 11.","DOI":"10.3390\/diagnostics11091668"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3904\/kjim.2024.386","article-title":"Stability, variability, and treatment implications of the blood eosinophil count in Korean patients with chronic obstructive pulmonary disease","volume":"40","author":"Lee","year":"2025","journal-title":"Korean J. Intern. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3904\/kjim.2024.034","article-title":"Blood eosinophil count and treatment patterns of chronic obstructive pulmonary disease patients in South Korea using real-world data","volume":"40","author":"Rhee","year":"2025","journal-title":"Korean J. Intern. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e066354","DOI":"10.1136\/bmjopen-2022-066354","article-title":"Multicentre double-blind randomised controlled trial of systematic corticosteroid therapy in patients with acute exacerbations of chronic obstructive pulmonary disease admitted to hospital with higher eosinophil levels: The ECHO protocol","volume":"13","author":"Liang","year":"2023","journal-title":"BMJ Open"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"776","DOI":"10.3855\/jidc.20466","article-title":"Utility of neutrophil to lymphocyte ratio in the prediction of inflammation and COPD mortality","volume":"19","author":"Zecevic","year":"2025","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Hu, H.-S., Wang, Z., Jian, L.-Y., Zhao, L.-M., and Liu, X.-D. (2023). Optimizing inhaled corticosteroid use in patients with chronic obstructive pulmonary disease: Assessing blood eosinophils, neutrophil-to-lymphocyte ratio, and mortality outcomes in US adults. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1230766"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Alwafi, H., Naser, A.Y., Ashoor, D.S., Alsharif, A., Aldhahir, A.M., Alghamdi, S.M., Alqarni, A.A., Alsaleh, N., Samkari, J.A., and Alsanosi, S.M. (2024). Prevalence and predictors of polypharmacy and comorbidities among patients with chronic obstructive pulmonary disease: A cross-sectional retrospective study in a tertiary hospital in Saudi Arabia. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-03274-5"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Wang, G., Ma, A., Zhang, L., Guo, J., Liu, Q., Petersen, F., Wang, Z., and Yu, X. (2022). Acute exacerbations of chronic obstructive pulmonary disease in a cohort of Chinese never smokers goes along with decreased risks of recurrent acute exacerbation, emphysema and comorbidity of lung cancer as well as decreased levels of circulating eosinophils and basophils. Front. Med., 9.","DOI":"10.3389\/fmed.2022.907893"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e001798","DOI":"10.1136\/bmjresp-2023-001798","article-title":"Comorbidities and mortality among patients with chronic obstructive pulmonary disease","volume":"10","author":"Skajaa","year":"2023","journal-title":"BMJ Open Respir. Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Li, N., Li, X., Liu, M., Wang, Y., and Wang, J. (2023). Sex differences in comorbidities and mortality risk among patients with chronic obstructive pulmonary disease: A study based on NHANES data. BMC Pulm. Med., 23.","DOI":"10.1186\/s12890-023-02771-3"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Jurevi\u010dien\u0117, E., Burneikait\u0117, G., Dambrauskas, L., Kasiulevi\u010dius, V., Kaz\u0117nait\u0117, E., Navickas, R., Puronait\u0117, R., Smailyt\u0117, G., Visockien\u0117, \u017d., and Danila, E. (2022). Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) Comorbidities in Lithuanian National Database: A Cluster Analysis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19020970"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/s13019-022-02042-y","article-title":"Preoperative inhalation therapy for patients with chronic obstructive pulmonary disease undergoing lung surgery: A retrospective study","volume":"17","author":"Machino","year":"2022","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Pagano, L., Dennis, S., Wootton, S., Chan, A.S.L., Zwar, N., Mahadev, S., Pallavicini, D., and McKeough, Z. (2023). The effects of an innovative GP-physiotherapist partnership in improving COPD management in primary care. BMC Prim. Care, 24.","DOI":"10.1186\/s12875-023-02097-3"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Xu, G., Luo, Q., Sun, M., Huang, L., Liu, J., Yang, C., Huang, Q., Xiong, C., Yang, Z., and Yang, S. (2024). Effectiveness and safety of acupuncture as an adjunctive therapy for chronic obstructive pulmonary disease: A randomised controlled trial. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04630-y"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"103146","DOI":"10.1016\/j.ctim.2025.103146","article-title":"Effect of acupuncture on patients with chronic obstructive pulmonary disease: A multicenter randomized controlled trial","volume":"89","author":"Li","year":"2025","journal-title":"Complement. Ther. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"00668-2024","DOI":"10.1183\/23120541.00668-2024","article-title":"Effectiveness of a long-term acupuncture treatment in patients with COPD: A randomised controlled trial","volume":"11","author":"Suzuki","year":"2025","journal-title":"ERJ Open Res."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Kayo, T., Suzuki, M., Mitsuma, T., and Fukuda, F. (2024). The effect of acupuncture on exercise capacity in patients with COPD is mediated by improvements of dyspnea and leg fatigue: A causal mediation analysis using data from a randomized controlled trial. BMC Complement. Med. Ther., 24.","DOI":"10.1186\/s12906-024-04353-0"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4103\/jalh.jalh_60_24","article-title":"Phenotypic Differences between Patients with Smoking Chronic Obstructive Pulmonary Disease and Non-smoking Chronic Obstructive Pulmonary Disease","volume":"5","author":"Nagar","year":"2025","journal-title":"J. Adv. Lung Health"},{"key":"ref_109","first-page":"2454","article-title":"Comparative study of smoking and non-smoking chronic obstructive pulmonary disease","volume":"60","author":"Verma","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"14799731241235213","DOI":"10.1177\/14799731241235213","article-title":"The Fagerstr\u00f6m Test for Nicotine Dependence, as a prognostic factor, in current smokers with and without COPD: A cross-sectional study in northern Greece","volume":"21","author":"Papadopoulou","year":"2024","journal-title":"Chron. Respir. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Sun, S., Wang, Y., Hou, H., Chen, L., Niu, Y., Shao, Y., and Zhang, X. (2025). Analysis of chronic disease comorbidity patterns in middle-aged and elderly smokers in China: The China Health and Retirement Longitudinal Study. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0319026"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"520","DOI":"10.4149\/BLL_2023_080","article-title":"Obesity, Charlson comorbidity index, and neutrophil-to-lymphocyte ratio in chronic obstructive pulmonary disease: Relationship to disease severity","volume":"124","author":"Uzunlar","year":"2023","journal-title":"Bratisl. Med. J."},{"key":"ref_113","first-page":"1358","article-title":"Symptom profile in obese COPD (Chronic Obstructive Pulmonary Disease) patients compared with non-obese patients: Retrospective evaluation in the French overseas department of Reunion Island (period 2015\u20132020)","volume":"60","author":"Omarjee","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2478\/pneum-2025-0015","article-title":"Comparing triggers and comorbidities of acute exacerbations in COPD: Smokers versus non-smokers","volume":"73","author":"Sontakke","year":"2025","journal-title":"Pneumologia"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.2147\/COPD.S458356","article-title":"Impact of Smoking and Chronic Obstructive Pulmonary Disease on All-Cause, Respiratory, and Cardio-Cerebrovascular Mortality","volume":"19","author":"Kang","year":"2024","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.amjms.2025.07.001","article-title":"COPET study findings regarding the clinical relevance of biomass exposure as an etiotype in COPD","volume":"370","author":"Yazar","year":"2025","journal-title":"Am. J. Med. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1164\/rccm.202407-1379CI","article-title":"Current Smoker: A Clinical COPD Phenotype Affecting Disease Progression and Response to Therapy","volume":"211","author":"Celli","year":"2025","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1007\/s12325-021-01855-y","article-title":"Efficacy and Safety of Umeclidinium\/Vilanterol in Current and Former Smokers with COPD: A Prespecified Analysis of The EMAX Trial","volume":"38","author":"Bjermer","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"107040","DOI":"10.1016\/j.rmed.2022.107040","article-title":"Single-inhaler triple therapy fluticasone furoate\/umeclidinium\/vilanterol versus dual therapy in current and former smokers with COPD: IMPACT trial post hoc analysis","volume":"205","author":"Bardsley","year":"2022","journal-title":"Respir. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.2147\/COPD.S546528","article-title":"Decreased Sputum Type-2 Gene Expression in COPD Current Smokers","volume":"20","author":"Southworth","year":"2025","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.amjmed.2021.09.006","article-title":"The Use of Inhaled Corticosteroids for Patients with COPD Who Continue to Smoke Cigarettes: An Evaluation of Current Practice","volume":"135","author":"Adcock","year":"2022","journal-title":"Am. J. Med."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/1\/43\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:38:27Z","timestamp":1766990307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/1\/43"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":121,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["life16010043"],"URL":"https:\/\/doi.org\/10.3390\/life16010043","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]}}}