Cardiorespiratory Fitness, Inflammation, and Risk of Chronic Obstructive Pulmonary Disease in Middle-Aged Men

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by chronic lung inflammation. The relationship between cardiorespiratory fitness (CRF) and COPD has not been well characterized. We aimed to evaluate the independent and joint associations of inflammation (high-sensitivity C-reactive protein [hsCRP]) and CRF with COPD risk in a cohort of White men. Methods: Among 2274 men aged 42-61 yr at baseline, serum hsCRP level was measured using an immunometric assay and CRF was assessed using a respiratory gas exchange analyzer. The level of hsCRP was categorized as normal and high (≤3 and >3 mg/L, respectively) and CRF as low and high. We corrected for within-person variability in exposures using repeat measurements taken several years apart. Results: A total of 116 COPD cases occurred during a median follow-up of 26.0 yr. The age-adjusted regression dilution ratio of hsCRP and CRF was 0.57 (95% CI, 0.50-0.64) and 0.58 (95% CI, 0.53-0.64), respectively. Comparing high versus normal hsCRP levels, the multivariable-adjusted HR for COPD was 1.79 (95% CI, 1.20-2.68). The COPD risk decreased linearly with increasing CRF. The multivariable-adjusted HR for COPD per 1-SD increase in CRF was 0.75 (95% CI, 0.60-0.95). Compared with men with normal hsCRP-low CRF, high hsCRP-low CRF was associated with an increased COPD risk, 1.80 (95% CI, 1.12-2.89), with no evidence of an association for high hsCRP-high CRF and COPD risk, 1.35 (95% CI, 0.68-2.69). Conclusions: Both hsCRP and CRF are associated with COPD risk in middle-aged men. However, high CRF levels attenuate the increased COPD risk related to high hsCRP levels.