Differences in baseline characteristics were compared between patient groups treated with and without the perioperative use of a bronchodilator using χ2 tests for categorical variables and t-tests for continuous variables. The primary outcome was the change in FEV1 following perioperative bronchodilator treatment. We compared quantitative changes in pulmonary function, including absolute values of FVC and FEV1, and the percentages of predicted values (% pred) for FEV1 and FVC at each time point in patient groups treated with and without a perioperative bronchodilator using linear mixed models with random intercepts and random slopes37. We estimated differences in the changes of pulmonary function from preoperative values (with 95% CI) between participants treated with and those treated without a perioperative bronchodilator. To control for potential confounding factors, we adjusted analyses for age, sex, body mass index [underweight (< 18.5 kg/m2), normal (18.5–22.9 kg/m2), overweight (23–24.9 kg/m2), or obese (≥ 25 kg/m2)], smoking status (never, past, or current), surgical extent (limited resection, lobectomy, bilobectomy, or pneumonectomy), VATS, and preoperative baseline FEV1 (mL). We also performed the same analysis using IPTW of preoperative baseline FEV138. To evaluate if changes in pulmonary function correlated with the type of bronchodilator used, we conducted additional analyses after separating patients into mono and dual bronchodilator groups. In addition, we performed stratified analyses to evaluate if the association of perioperative use of bronchodilator with change in FEV1 at 4 months after surgery differed in pre-specified subgroups defined by age (< 65 vs. ≥ 65 years), sex, obesity (no vs. yes), smoking (never vs. ever), and adjuvant therapy (no vs. yes). We also performed sensitivity analyses in patients who received lobectomy (N = 194). We considered a P-value < 0.05 as statistically significant. All analyses were performed using STATA version 15 (StataCorp LP, College Station, TX, USA).

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