Treatment Burden Among Adults with Chronic Obstructive Pulmonary Disease and Comorbidities: A Mixed-Methods Systematic Review of Direct and Indirect Evidence

Background: Chronic obstructive pulmonary disease (COPD) commonly coexists with other chronic conditions, which may add to treatment burden. This mixed-methods systematic review synthesized direct and indirect evidence on treatment burden in adults with COPD and comorbidities and identified instruments used to measure it. Methods: We followed Joanna Briggs Institute mixed-methods methodology and PRISMA 2020. Five databases were searched from inception to 6 August 2026, with supplementary grey-literature, citation and PubMed searches. Eligible studies included adults with COPD and at least one comorbidity and reported treatment burden directly (validated patient-reported instruments or qualitative accounts) or indirectly (regimen complexity or clinical control analyzed in relation to comorbidity); the indirect criterion was refined during full-text screening. A convergent segregated narrative synthesis was performed. Results: Nine studies from five countries were included. One study measured patient-reported treatment burden with a validated instrument and one explored it qualitatively; two developed or validated a burden instrument, three assessed regimen complexity or medication counts, and two assessed clinical control. Most were cross-sectional. Greater comorbidity was generally associated with more complex medication regimens and poorer clinical control. In the only study measuring it directly, comorbidity and regimen complexity were associated with higher treatment burden, and social support and self-efficacy with lower burden. Qualitatively, behavior-change tasks were most burdensome. In one prospective cohort, higher regimen complexity was associated with lower medication discontinuation but more re-exacerbations and readmissions. Conclusion: Direct evidence on treatment burden in adults with COPD and comorbidities is scarce, and most available evidence relies on indirect indicators. Observed associations are compatible with comorbidity adding to treatment workload but cannot establish causality; because the search omitted regimen-complexity and clinical-control terms, some indirect evidence may have been missed. Prospective studies using validated patient-reported treatment-burden measures in people with COPD and multimorbidity are needed to guide multidisciplinary care.