Associations of SP-D and MFAP4 with patient-reported outcomes in a primary care COPD cohort: results from PROTECCT-M

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with substantial morbidity, mortality, and variable disease trajectories. While patient-reported outcomes (PROMs) are central to understanding symptom burden and quality of life, there is growing interest in identifying biomarkers that may aid in phenotyping patients and predicting outcomes. Surfactant protein D (SP-D) and microfibril-associated glycoprotein 4 (MFAP4) have emerged as potential biomarkers linked to pulmonary inflammation, extracellular matrix remodeling, and comorbidities. This study describes baseline characteristics of a primary care COPD cohort and examines associations between SP-D, MFAP4, and PROMs. The PROTECCT-M study is a population-based cohort from general practices on Funen, Denmark. Eligible participants were ≥ 40 years with a GP-confirmed COPD diagnosis. Baseline data (2012–2016) included spirometry, clinical characteristics, blood sampling for SP-D and MFAP4, and two PROMs: the Clinical COPD Questionnaire (CCQ) and the SF-12 physical component score (PCS). Descriptive analyses characterized the cohort, and multivariable linear regression models estimated associations between biomarkers and PROMs, adjusting for demographic, socioeconomic, and health-related covariates. Of 625 enrolled patients, 434 were included in the final analyses. Women were younger and more often lived alone compared with men. Median SP-D levels were higher among men and current smokers, while MFAP4 was slightly higher among former or never smokers. Boxplots showed no clear crude associations between biomarker quartiles and CCQ, while PCS showed a weak inverse trend with increasing MFAP4 levels. In adjusted analyses, neither SP-D nor MFAP4 was associated with CCQ scores. MFAP4 showed a statistically significant association with PCS: each 10-unit increase corresponded to a − 0.9 (95% CI: −1.6 to − 0.3) decrease in PCS. SP-D showed no significant association with PCS. In this general practice COPD cohort, SP-D and MFAP4 showed limited associations with patient-reported health status. Only MFAP4 demonstrated a modest association with poorer physical quality of life. While these biomarkers may still hold prognostic potential, their explanatory value for baseline PROMs in primary care appears limited, underscoring the continued clinical importance of PROMs. ClinicalTrials.gov Identifier: NCT01698151 .