The interaction and mediation role of intrinsic capacity in the association between asthma and all-cause mortality

Asthma and intrinsic capacity (IC) decline were individually examined with mortality, yet the complex interplay between them remains largely unknown. This study aimed to examine the potential roles of IC decline in the association between asthma and all-cause mortality. We conducted a prospective cohort study using data from UK Biobank, where IC decline was defined as a decline in any domain of psychological, sensory, vitality, and locomotion. Cox proportional hazard models were used to examine the associations between asthma, IC decline, and all-cause mortality. The relative excess risk due to additive interaction (RERI) was calculated. Mediation analysis was performed to explore the mediating effect of IC decline. And a four-way decomposition method was utilized to quantify both the interaction and mediation role of IC decline. Among 439,973 participants, 51,558 (11.7%) had asthma, 290,964 (66.1%) experienced IC decline, and 37,204 deaths occurred during 5.92 million person-years follow-up. Significant multiplicative and additive interactions were observed between asthma and any IC domain decline on all-cause mortality (Multiplicative: HR = 1.14, 95% CI: 1.06-1.24; Additive: RERI = 0.20, 95% CI: 0.11-0.29). The proportion of the association between asthma and all-cause mortality mediated by decline in all four domains was 28.14% (95% CI: 23.84-34.92%). The results of four-way decomposition were similar. Asthma was associated with increased all-cause mortality, and this association may be partially accounted for by both the interaction and mediation effects of IC decline. These findings underscore the importance of comprehensive interventions that address both asthma management and preservation of IC function to enhance health outcomes in middle-late life.