The association of comorbidity clusters with long-term survival and incidence of exacerbation in a COPD cohort. The HUNT Study, Norway

Background: COPD is a heterogeneous disease often viewed as part of a multimorbidity complex. Different clusters of comorbidities in COPD have been described but have not been related to long-term outcomes. This study aims to examine how such clusters are associated with severe exacerbations and mortality in COPD. Methods: Participants with COPD were recruited from the second and third survey of the HUNT Study and followed until April 2020. Ten objectively identified comorbidities were clustered using self-organizing maps. Severe exacerbations were assessed using hospital registry data. All-cause mortality was collected from registries. Multivariable Cox regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for the association between comorbidity clusters and all-cause mortality, and Poisson regression was used to calculate incidence rate ratios (IRR) with 95% CI for the cumulative number of severe exacerbations for each cluster. Results: A total of 82% of patients had >1 comorbidities. Five clusters were identified, including less comorbidity, psychological, cardiovascular, metabolic and cachectic clusters. Using the less comorbidity cluster as reference, the psychological and cachectic clusters were associated with all-cause mortality; HR 1.23 (1.04-1.45) and HR 1.83 (1.52-2.20). The same clusters also had an increased risk of severe exacerbations, with an unadjusted IRR of 1.24 (1.04-1.48) and 1.50 (1.23-1.83), correspondingly. Conclusions: With 25 years follow-up, individuals in the psychological and cachectic clusters had increased mortality and increased risk of severe exacerbations requiring hospitalizations.