The risk factors for future exacerbations in COPD patients without exacerbation history: an observational study

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated lung function decline, reduced physical activity, and increased mortality. Although prior exacerbations predict future events, patients without an exacerbation history may still be at substantial risk. This study aimed to identify clinical risk factors for future exacerbations in this population. A total of 2,475 COPD patients without an exacerbation in the preceding year were enrolled from the RealDTC study (Registration Date: January 14, 2017). Baseline demographic and clinical data were collected, and patients were followed for three years. They were categorized into exacerbation and non-exacerbation groups based on whether an exacerbation occurred during follow-up. During follow-up, 38.3% experienced at least one exacerbation. These patients were older; had lower BMI, FEV1%pred, and FEV1/FVC; and had higher CAT and mMRC scores. They also showed poorer treatment adherence and lower use of LABA+LAMA or LABA+LAMA + ICS therapy. Multivariate analysis identified female sex, high CAT score, and non-adherence as independent risk factors, whereas high BMI, high educational level, using LABA+LAMA, adherence to GOLD2023, and using LABA+LAMA + ICS were protective. Among female patients, high CAT score and biofuel exposure were independent risk factors whereas low educational level, and low BMI remained protective.A further subgroup multivariate analysis comparing exacerbations within the first year of follow-up with no exacerbations after the first year confirmed that high educational level, BMI 20–25 and 25–30, LABA+LAMA therapy, adherence to GOLD 2023 and good treatment adherence were independent protective factors against early exacerbations. COPD patients without prior exacerbations still face a considerable risk of future events. High symptom burden, low BMI, female sex, and absence of dual or triple inhaled therapy are key predictors. In women, biofuel exposure and low educational merit particular attention.