Impact of bronchodilator responsiveness on lung age in patients with respiratory diseases and/or symptoms: implications for clinical practice from a cross-sectional study

BACKGROUND: Lung age (LA) that expresses lung function as a form of biological age and facilitates clinical interpretation. Bronchodilator responsiveness (BDR) is important for assessing airway reversibility, but its influence on LA remains unclear. This study aimed to evaluate the impact of BDR on LA and to explore its clinical implications. METHODS: In this cross-sectional study, we analyzed participants with respiratory disease and/or symptoms who underwent spirometry and BDR testing between January 2023 and December 2024. LA was calculated using a reference equation established from healthy, non-smoking Chinese adults. Participants were categorized into three groups: normal [the difference between lung age and age (DeltaLA) ≤0], normally high [DeltaLA >0 and ≤ upper limit of normal for DeltaLA (DeltaLAULN)], and abnormally high (DeltaLA > DeltaLAULN). A random forest model was used to identify predictors of post-LA improvement. Nonlinear regression was employed to evaluate associations between DeltaLA and spirometric parameters. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of difference between ULN and LA (ULNLA) and spirometric measurements to predict a post-bronchodilator forced expiratory volume in one second to forced vital capacity (FEV₁/FVC) ratio <0.7. RESULTS: Nine thousand three hundred and sixteen participants (mean age 58.6±12.9 years; 69.7% male) were included. After bronchodilator, LA significantly improved and 34.03% of those in normally high LA improved to normal group (all P<0.001); 21.83% of participants in the abnormally high LA group had a significant BDR, compared with 3.68% and 4.02% in the normal and normally high LA groups, respectively (P<0.001). DeltaLA was correlated with FEV₁, forced expiratory flow at 50% of FVC (FEF50%), forced expiratory flow at 75% of FVC (FEF75%), and FVC (r=-0.80 to -0.46, all P<0.001). The ability of ULNLA to predict a post-bronchodilator FEV₁/FVC ratio <0.7 was comparable to FEV₁ (area under the curve: 0.84 vs. 0.85). CONCLUSIONS: Pre-bronchodilator LA alone may result in misclassification, whereas post-bronchodilator LA provides a more accurate evaluation. ULNLA demonstrates predictive ability of airflow limitation is comparable to FEV1% predicted.