BMI is associated with FEV1 decline in chronic obstructive pulmonary disease: a meta-analysis of clinical trials

Background: There is considerable heterogeneity in the rate of lung function decline in chronic obstructive pulmonary disease (COPD), the determinants of which are largely unknown. Observational studies in COPD indicate that low body mass index (BMI) is associated with worse outcomes, and overweight/obesity has a protective effect - the socalled "obesity paradox". We aimed to determine the relationship between BMI and the rate of FEV1 decline in data from published clinical trials in COPD. Methods: We performed a systematic review of the literature, and identified 5 randomized controlled trials reporting the association between BMI and FEV1 decline. Four of these were included in the meta-analyses. We analyzed BMI in 4 categories: BMI-I (< 18.5 or < 20 kg/m(2)), BMI-II (18.5 or 20 to < 25kg/m(2)), BMI-III (25 to < 29 or < 30 kg/m(2)) and BMI-IV (>= 29 or >= 30 kg/m(2)). We then performed a meta-regression of all the estimates against the BMI category. Results: The estimated rate of FEV1 decline decreased with increasing BMI. Meta-regression of the estimates showed that BMI was significantly associated with the rate of FEV1 decline (linear trend p = 1.21 x 10(-5)). Conclusions: These novel findings support the obesity paradox in COPD: compared to normal BMI, low BMI is a risk factor for accelerated lung function decline, whilst high BMI has a protective effect. The relationship may be due to common but as-of-yet unknown causative factors; further investigation into which may reveal novel endotypes or targets for therapeutic intervention.