Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease

Abstract Background Aging has been established as an independent risk factor for chronic obstructive pulmonary disease (COPD). Biological age (BA), a novel metric for gauging the extent of aging, has rarely been investigated in the context of acute exacerbation of COPD (AECOPD). Our study aimed to e...

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Main Authors: Yujiao Wang, Ting Mu, Yufen Fu, Yuxin Wang, Guoping Li
Format: Article
Language:English
Published: BMC 2025-08-01
Series:BMC Pulmonary Medicine
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Online Access:https://doi.org/10.1186/s12890-025-03841-4
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author Yujiao Wang
Ting Mu
Yufen Fu
Yuxin Wang
Guoping Li
author_facet Yujiao Wang
Ting Mu
Yufen Fu
Yuxin Wang
Guoping Li
author_sort Yujiao Wang
collection DOAJ
description Abstract Background Aging has been established as an independent risk factor for chronic obstructive pulmonary disease (COPD). Biological age (BA), a novel metric for gauging the extent of aging, has rarely been investigated in the context of acute exacerbation of COPD (AECOPD). Our study aimed to elucidate the association between BA and AECOPD, thereby highlighting the potential of BA as a predictive tool in clinical practice. Methods The dataset encompasses patients hospitalized at Chengdu Third People's Hospital between 2018 and 2022. The AECOPD patients enrolled in this study were hospitalized due to rapidly worsening symptoms, including cough, sputum production, and dyspnea, whereas the COPD patients were clinically stable. BA and biological age acceleration were ascertained through the Klemera-Doubale method (KDM). A multivariable logistic regression analysis was conducted to evaluate the correlation between BA, biological age acceleration, and the incidence of AECOPD, complemented by subgroup analyses to explore the dose‒response dynamics between biological age acceleration and the risk of AECOPD. The dataset was partitioned into training and validation sets at a 7:3 ratio, and LASSO regression was applied to refine the model's variable composition. To assess the ability of different variables to discriminate current disease status, we developed the initial model and three subsequent models, with the following variables added in the new model: Chronological age (CA), BA, and biological age acceleration. The models were subsequently evaluated within both datasets. Results The study cohort comprised 2,511 patients, through an analysis of the transect data, with 59.1% experiencing acute exacerbations. Both BA (79.14 ± 9.49 years) and biological age acceleration (1.04 ± 2.82 years) emerged as independent risk factors for AECOPD (P < 0.001). In Model 3, each year increment in BA and biological age acceleration corresponded to a 1.04-fold (95% CI = 1.027–1.048, P < 0.001) and 1.18-fold (95% CI = 1.14–1.224, P < 0.001) increase in exacerbation risk, respectively. The biological age of patients with stable COPD was significantly lower than the actual age (-0.36 ± 2.56 years), which suggests a significant inter-individual heterogeneity in the biological aging process of COPD patients. Subgroup analysis confirmed a pronounced dose‒response relationship between biological age acceleration and AECOPD risk(Q4 vs. Q1: OR = 2.7, 95% CI = 2.172–3.518). LASSO regression pinpointed BMI, Diabetes, Hypertensive heart disease, Cor pulmonale, Stroke, and Hyperlipidemia as critical variables within the model. The internal validation process revealed AUC values of 0.735 (95% CI = 0.7–0.77), 0.742 (95% CI = 0.707–0.777), 0.753 (95% CI = 0.719–0.787), and 0.766 (95% CI = 0.733–0.8) for the respective models. The HL test confirmed the models' good fit (P = 0.128, P = 0.121, P = 0.272, P = 0.795), with Model 4 exhibiting the most precise calibration against the diagonal reference. Decision curve analysis (DCA) indicated that all the models provided a net benefit in disease outcome discrimination, with Model 4 yielding the most significant advantage. Conclusions The acceleration of aging portends an increased propensity for acute exacerbations, and a distinct dose–response relationship is observable between biological age acceleration and exacerbation events. BA and biological age acceleration outperform chronological age in discerning the likelihood of acute exacerbations, underscoring their enhanced ability to predict this critical health outcome.
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spelling doaj-art-c6a77b4b37f243d6adeb5b3155d9fafb2025-08-24T11:05:56ZengBMCBMC Pulmonary Medicine1471-24662025-08-0125111310.1186/s12890-025-03841-4Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary diseaseYujiao Wang0Ting Mu1Yufen Fu2Yuxin Wang3Guoping Li4Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Southwest Medical UniversityDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Southwest Medical UniversityDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Southwest Medical UniversityDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Southwest Medical UniversityDepartment of Respiratory and Critical Care Medicine, Affiliated Hospital of Southwest Medical UniversityAbstract Background Aging has been established as an independent risk factor for chronic obstructive pulmonary disease (COPD). Biological age (BA), a novel metric for gauging the extent of aging, has rarely been investigated in the context of acute exacerbation of COPD (AECOPD). Our study aimed to elucidate the association between BA and AECOPD, thereby highlighting the potential of BA as a predictive tool in clinical practice. Methods The dataset encompasses patients hospitalized at Chengdu Third People's Hospital between 2018 and 2022. The AECOPD patients enrolled in this study were hospitalized due to rapidly worsening symptoms, including cough, sputum production, and dyspnea, whereas the COPD patients were clinically stable. BA and biological age acceleration were ascertained through the Klemera-Doubale method (KDM). A multivariable logistic regression analysis was conducted to evaluate the correlation between BA, biological age acceleration, and the incidence of AECOPD, complemented by subgroup analyses to explore the dose‒response dynamics between biological age acceleration and the risk of AECOPD. The dataset was partitioned into training and validation sets at a 7:3 ratio, and LASSO regression was applied to refine the model's variable composition. To assess the ability of different variables to discriminate current disease status, we developed the initial model and three subsequent models, with the following variables added in the new model: Chronological age (CA), BA, and biological age acceleration. The models were subsequently evaluated within both datasets. Results The study cohort comprised 2,511 patients, through an analysis of the transect data, with 59.1% experiencing acute exacerbations. Both BA (79.14 ± 9.49 years) and biological age acceleration (1.04 ± 2.82 years) emerged as independent risk factors for AECOPD (P < 0.001). In Model 3, each year increment in BA and biological age acceleration corresponded to a 1.04-fold (95% CI = 1.027–1.048, P < 0.001) and 1.18-fold (95% CI = 1.14–1.224, P < 0.001) increase in exacerbation risk, respectively. The biological age of patients with stable COPD was significantly lower than the actual age (-0.36 ± 2.56 years), which suggests a significant inter-individual heterogeneity in the biological aging process of COPD patients. Subgroup analysis confirmed a pronounced dose‒response relationship between biological age acceleration and AECOPD risk(Q4 vs. Q1: OR = 2.7, 95% CI = 2.172–3.518). LASSO regression pinpointed BMI, Diabetes, Hypertensive heart disease, Cor pulmonale, Stroke, and Hyperlipidemia as critical variables within the model. The internal validation process revealed AUC values of 0.735 (95% CI = 0.7–0.77), 0.742 (95% CI = 0.707–0.777), 0.753 (95% CI = 0.719–0.787), and 0.766 (95% CI = 0.733–0.8) for the respective models. The HL test confirmed the models' good fit (P = 0.128, P = 0.121, P = 0.272, P = 0.795), with Model 4 exhibiting the most precise calibration against the diagonal reference. Decision curve analysis (DCA) indicated that all the models provided a net benefit in disease outcome discrimination, with Model 4 yielding the most significant advantage. Conclusions The acceleration of aging portends an increased propensity for acute exacerbations, and a distinct dose–response relationship is observable between biological age acceleration and exacerbation events. BA and biological age acceleration outperform chronological age in discerning the likelihood of acute exacerbations, underscoring their enhanced ability to predict this critical health outcome.https://doi.org/10.1186/s12890-025-03841-4AgingBiological age (BA)Biological age accelerationChronological age (CA)Chronic obstructive pulmonary disease (COPD)Acute exacerbation of COPD (AECOPD)
spellingShingle Yujiao Wang
Ting Mu
Yufen Fu
Yuxin Wang
Guoping Li
Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease
BMC Pulmonary Medicine
Aging
Biological age (BA)
Biological age acceleration
Chronological age (CA)
Chronic obstructive pulmonary disease (COPD)
Acute exacerbation of COPD (AECOPD)
title Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease
title_full Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease
title_fullStr Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease
title_full_unstemmed Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease
title_short Modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease
title_sort modelling of biological age in stable and acute exacerbations of chronic obstructive pulmonary disease
topic Aging
Biological age (BA)
Biological age acceleration
Chronological age (CA)
Chronic obstructive pulmonary disease (COPD)
Acute exacerbation of COPD (AECOPD)
url https://doi.org/10.1186/s12890-025-03841-4
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