Association of Physical Activity with Asthma and Chronic Obstructive Pulmonary Disease and Mediation of Frailty: Mendelian Randomization Analyses

Background: The existence of an association between physical activity (PA) and asthma and chronic obstructive pulmonary disease (COPD) has been confirmed in observational studies. Therefore, it is necessary to reveal whether there is a risk-effect relationship between physical activity and asthma and COPD through Mendelian randomization (MR) analysis. Materials and Methods: Univariate Mendelian randomization (UVMR) analyses were performed to examine the associations between moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA), accelerometer-assessed physical activity (AA), and strenuous exercise or other exercise (SSOE) with asthma and COPD. The methods of analysis were dominated by Inverse Variance-Weighted (IVW), Weighted median (WM), and MR-Egger methods. In addition, multivariate Mendelian randomization (MVMR) analyses were performed to correct the effects of four types of physical activity on asthma and COPD. Finally, potential mediating effect relationships were identified through mediation analyses. Results: The results of Univariate Mendelian randomization analysis showed that SSOE could reduce the risk of asthma and COPD (asthma: OR=0.15,95% CI=0.04-0.58, P=0.006; COPD: OR=0.05, 95% CI=0.01-0.33, P=0.002). The results of the Multivariate Mendelian randomization analysis showed that SSOE was still able to reduce the risk of asthma and COPD after adjusting for the effects of different types of physical activity(asthma: 95% CI=-2.77--0.31, P=0.014; COPD: 95% CI=-4.00--0.50, P=0.012). Mediation analyses showed that frailty intervened in the causal relationship between physical activity and asthma and chronic Conclusion: SSOE is a protective factor for asthma and COPD in the European population, while frailty plays a mediating role.