Association of frailty with respiratory tract infections: Evidence from cross-sectional analysis and mendelian randomization

BACKGROUND: Respiratory tract infections (RTI) remain a challenge to global health, particularly in the frail populations. However, an understanding of the causal relationship between frailty and RTI is limited. METHODS: Two complementary approaches were used. First, we conducted a cross-sectional analysis to examine the association between frailty index (FI) and RTI, using data from the NHANES 2013-2014. We then introduced Mendelian randomization (MR) using genome-wide association study summary statistics to determine the causality between frailty index, low grip strength, walking pace, light physical activity, and upper (URTI) or lower RTI (LRTI). The primary method of inverse variance weighting and complementary MR methods were used to verify causality. Sensitivity analysis was conducted to confirm the robustness of the primary results. RESULTS: A total of 2249 participants were enrolled in the cross-sectional study. Weighted multivariable-adjusted logistic regression analysis showed that the frailty index was positively associated with RTI after adjusting for covariates (Continuous FI, odds ratio [OR] = 4.95; 95 % confidence interval [CI], 1.69-14.50, P = 0.004; Categorical FI, OR = 1.51 [95 % CI, 1.11-2.06, P = 0.009]). Restricted cubic spline analysis showed a significant increase in the prevalence of RTI when FI was >0.24. The results of the MR analysis supported a causal relationship between the frailty index and LRTI (OR = 1.939 [95 % CI, 1.180-3.186, P = 0.009]). Sensitivity analysis further confirmed the robustness of these findings. CONCLUSION: Our study identified a potential association between the FI and RTI at both phenotypic and genetic levels. The results revealed a causal relationship between the FI and LRTI.