Body Composition Phenotypes Defined by Adiposity and Muscularity and Their Clinical Outcomes in COPD: A Multicenter Prospective Cohort Study

Background The prognostic value of body mass index (BMI) in chronic obstructive pulmonary disease (COPD) remains inconsistent. The clinical implications of phenotyping based on adiposity and muscularity have not been well established. Methods In this prospective multicenter cohort study, patients with spirometry-confirmed COPD (October 2021–December 2023) underwent bioelectrical impedance analysis. Low fat-free mass index (FFMI) was defined as <17.4 kg/m² (men) and <15.0 kg/m² (women); high fat mass index (FMI) as ≥5.9 kg/m² (men) and ≥7.0 kg/m² (women). Participants were classified into four phenotypes: lean-robust (low FMI, high FFMI), wasting (low FMI, low FFMI), sarcopenic obesity (high FMI, low FFMI), and obese-robust (high FMI, high FFMI). The primary outcome was severe acute exacerbation; the secondary outcome was three-year all-cause mortality. Cox proportional hazards models were applied. Results Among 648 participants (mean age 73.2 years; 88.6% male), 6.9% were underweight, 29.9% overweight and 4.9% obese by BMI. Compared with normal weight, underweight was associated with higher risk of severe exacerbation (HR 2.05, 95% CI: 1.27–3.32) and mortality (HR 2.94, 95% CI: 1.50–5.77), whereas overweight showed lower mortality risk (HR 0.24, 95% CI 0.09–0.61). Based on adiposity–muscularity phenotyping, 21.9% were lean-robust, 28.4% wasting, 20.1% sarcopenic obesity, and 29.6% obese-robust. Using lean-robust as reference, wasting and sarcopenic obesity were associated with increased risks of severe exacerbation (HR 1.96, 95% CI:1.26-3.06; HR 1.81, 95% CI:1.12-2.94) and mortality (HR 12.6, 95% CI: 3.01-53.2; HR 15.2, 95% CI: 3.57-64.61). The obese-robust demonstrated comparable risks of severe exacerbation and mortality to the lean-robust group. Conclusion BMI alone inadequately stratifies prognosis in COPD. Phenotyping based on adiposity and muscularity identifies high-risk subgroups more precisely. The apparent obesity paradox may reflect preserved muscularity rather than adiposity itself, underscoring the importance of body composition assessment in clinical practice.