Abstract
Spirometry provides limited insight into small airway dysfunction in COPD, and evaluation of physiologic parameters such as the expiratory time constant (Tc) may offer complementary information for risk assessment. This retrospective cohort study included 1479 patients with COPD from two tertiary hospitals who underwent baseline chest computed tomography and post-bronchodilator spirometry between 2014 and 2023, with at least five years of follow-up. The Tc was computed from volume-time curves via standardized image analysis. The primary outcome was moderate-to-severe exacerbation. Subgroup analyses were conducted based on symptom severity, airflow limitation, emphysema extent, and airway wall thickness. A prolonged Tc was independently associated with an increased risk of moderate-to-severe exacerbations (adjusted hazard ratio, 1.188; 95% confidence interval, 1.028–1.373). This association was particularly evident in dyspneic patients and was more pronounced among those without a prior history of frequent exacerbations. Consistent patterns of association were observed across subgroups characterized by increased airway wall thickness, preserved diffusing capacity, and lower emphysema burden, corresponding to airway-predominant features. A threshold of 1.14 s was identified, above which the risk of exacerbation was significantly elevated. The Tc may improve individualized risk stratification by identifying patients with COPD who are at increased risk of exacerbations, even in the absence of prior exacerbation history or before the development of advanced parenchymal destruction.
Data availability
The datasets generated and/or analysed during the current study are not publicly available to maintain patient confidentiality and comply with ethical guidelines but are available from the corresponding author on reasonable request.
Abbreviations
- AE-COPD:
-
Acute exacerbation of chronic obstructive pulmonary disease
- ATS:
-
American thoracic society
- BMI:
-
Body mass index
- CCI:
-
Charlson comorbidity index
- CI:
-
Confidence interval
- COPD:
-
Chronic obstructive pulmonary disease
- CT:
-
Computed tomography
- DLCO:
-
Diffusing capacity of the lung for carbon monoxide
- Tc:
-
Expiratory time constant
- FEF25–75:
-
Forced expiratory flow at 25% to 75% of forced vital capacity
- FEV1 :
-
Forced expiratory volume in 1 s
- FVC:
-
Forced vital capacity
- HU:
-
Hounsfield unit
- ICS:
-
Inhaled corticosteroid
- IPTW:
-
Inverse probability of treatment weighting
- IQR:
-
Interquartile range
- LAA:
-
Low attenuation area
- LAMA:
-
Long-acting muscarinic antagonist
- mMRC:
-
Modified medical research council
- NLR:
-
Neutrophil-to-lymphocyte ratio
- Pi10:
-
Square root of airway wall area for a theoretical airway with internal perimeter of 10 mm
- SD:
-
Standard deviation
- STROBE:
-
Strengthening the reporting of observational studies in epidemiology
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Funding
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : RS-2021-KH114109).
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Study concept and design: H.W.L.Acquisition of data: E.T.J., D.H.K., H.W.L.Analysis and interpretation of data: E.T.J., D.H.K., H.W.L.Drafting the manuscript: E.T.J., D.H.K.Critical revision of the manuscript and important intellectual content: H.P., J.K.L., E.Y.H., C.H.L., D.K.K., H.W.L.Study supervision: H.W.L.
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The study was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board of the Seoul Metropolitan Government-Seoul National University (SMG-SNU) Boramae Medical Center (IRB no. 20-2023-11). The requirement for written informed consent was waived due to the retrospective nature of the study.
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Jeon, ET., Kim, D.H., Park, H. et al. Prolonged expiratory time constant and risk of moderate-to-severe exacerbations in stable COPD. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39987-2
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DOI: https://doi.org/10.1038/s41598-026-39987-2
