Timing and burden of documented multimorbidity and risk of subsequent COPD diagnosis: a UK biobank cohort study

This study aimed to examine the associations of the documented timing and burden of multimorbidity with subsequent chronic obstructive pulmonary disease (COPD) diagnosis and to assess whether these associations differed by specific disease pairs, sex, and smoking status. We analysed 484,537 adults (aged 40–69) from the prospective UK Biobank cohort, recruited between 2006 and 2010 across 22 assessment centers in England, Scotland, and Wales. Multimorbidity was defined as ≥ 2 of 15 ageing-related conditions. Cause-specific Cox and Fine-Gray competing risk models were used to estimate the associations of documented multimorbidity timing and burden, assessed at landmark ages 50, 60, and 70 years, with subsequent COPD diagnosis. A central sensitivity analysis reconstructed multimorbidity using 11 non-respiratory conditions and excluded COPD cases with preceding asthma, bronchiectasis, obstructive sleep apnoea, or lung cancer. The prevalence of multimorbidity increased with age, and 28,240 subsequent COPD diagnoses were identified. Adjusted for covariates, multimorbidity at age 50 was associated with more than twice the hazard of subsequent COPD diagnosis (cause-specific hazard ratio [HR]: 2.33, 95% CI 2.24–2.43; incidence 5.72/1000 person-years). At the age-60 landmark, multimorbidity documented before age 50 (HR 2.28, 95% CI 2.15–2.41) and between ages 50 and 60 (HR 2.19, 95% CI 2.10–2.27) showed broadly similar associations. At the age-70 landmark, the HRs were 2.31 (95% CI 2.07–2.57) for multimorbidity documented before age 50, 1.95 (95% CI 1.82–2.10) for ages 50–60, and 2.21 (95% CI 2.11–2.33) for ages 60–70, indicating that timing associations varied across landmark ages. Multimorbidity burden demonstrated a clearer gradient: at age 50, incidence reached 17.98/1000 person-years for individuals with ≥ 5 conditions (HR 6.30, 95% CI 5.19–7.65), with larger estimates also observed at ages 60 (HR 5.02) and 70 (HR 3.97). Disease-pair analyses identified large estimates for bronchiectasis combined with asthma (HR 7.08, 95% CI 6.43–7.79) or obstructive sleep apnoea (HR 5.08, 95% CI 3.84–6.72). Associations remained evident in Fine-Gray analyses and across sex and smoking strata. In the restrictive non-respiratory sensitivity analysis, the age-50 estimate was attenuated to HR 1.62 (95% CI 1.52–1.74), while a graded association with burden persisted. Documented multimorbidity and greater cumulative burden were associated with subsequent COPD diagnosis. Associations across documented timing categories varied across landmark ages. Multimorbidity may serve as a clinical risk marker, but the value of multimorbidity-guided respiratory screening requires prospective evaluation.