The relationship between respiratory symptoms and frailty: findings from observational and Mendelian randomization analyses

Introduction

As ageing accelerates, frailty increasingly impacts public health. Cough, sputum, wheezing and dyspnea are common respiratory symptoms, and the relationship to frailty is unclear. We aimed to analyze the relationship between respiratory symptoms and frailty.

Methods

Cross-sectional and Mendelian randomization (MR) studies were used. Cross-sectional data involved 14,021 participants from the National Health and Nutrition Examination Survey (NHANES). Logistic and linear regression were used to analyze the relationship between respiratory symptoms (cough, sputum, wheezing, dyspnea) and frailty. We adjusted for multiple variables and used propensity score matching (PSM). Mediation analysis was used to explore the role of inflammatory markers and age in the relationship between the two. We analyzed the relationship using a two-sample MR approach with data from genome-wide association studies (GWAS) to enhance causal inference.

Results

Observational studies have shown that cough (OR 1.74, 95 CI% 1.44, 2.09), sputum (OR 1.87, 95 CI% 1.57, 2.22), wheezing (OR 2.01, 95 CI% 1.68, 2.40), and dyspnea (OR 2.60, 95 CI% 2.28, 2.97) are associated with an elevated risk of frailty. The PSM results were stable. Mediation analyses indicated that elevated inflammatory markers and advancing age were mediators between respiratory symptoms and frailty. The results of the MR study showed that sputum and wheezing were associated with an elevated frailty index; and in the study of FI on respiratory symptoms, all respiratory symptoms were elevated with elevated FI.

Conclusions

Our study identified a potential association between frailty and respiratory symptoms. Inflammation and ageing may be essential factors mediating this association.