Cardiorespiratory fitness, inflammation, and the incident risk of pneumonia

Introduction: Both inflammation and cardiorespiratory fitness (CRF) are associated with the risk of respiratory infections. To clarify the hypothesis that CRF attenuates the incident risk of pneumonia due to inflammation, we conducted a prospective study examining the independent and joint associations of inflammation and CRF on the risk of pneumonia in a population sample of 2041 middle-aged men. Methods: Cardiorespiratory fitness was directly measured as peak oxygen uptake (V^· o_2peak) during progressive exercise testing to volitional fatigue, and categorized into tertiles. Inflammation was defined by high-sensitivity C-reactive protein (hsCRP). Pneumonia cases were identified by internal medicine physicians using the International Classification of Diseases codes in clinical practice. Results: During a median follow-up of 27 yr, 432 pneumonia cases were recorded. High hsCRP and CRF were associated with a higher risk (HR = 1.38; 95% CI, 1.02-1.88) and a lower risk of pneumonia (HR = 0.55; CI, 0.39-0.76) after adjusting for potential confounders, respectively. Compared with normal hsCRP-Fit, moderate to high hsCRP-Unfit had an increased risk of pneumonia (HR = 1.63; CI, 1.21-2.20), but moderate to high hsCRP-Fit was not associated with an increased risk of pneumonia (HR = 1.25; CI, 0.93-1.68). Conclusions: High CRF attenuates the increased risk of pneumonia due to inflammation. These findings have potential implications for the prevention of respiratory infection characterized by systemic inflammation, such as coronavirus disease-2019 (COVID-19).