The clinical utility of elevated monocyte count in patients with fibrotic interstitial lung disease

Rationale: Higher peripheral blood monocyte count has been associated with disease progression and mortality in patients with fibrotic interstitial lung disease (fILD), but with uncertainty regarding the strength of this association and the potential impact of confounding. This study aimed to characterise the associations of clinically ascertained peripheral blood monocyte count with survival and lung function decline in patients with fILD. Methods: Patients with fILD enrolled in the prospective Canadian Registry for Pulmonary Fibrosis (CARE-PF) with baseline complete blood count were included. Monocyte counts were analysed continuously and dichotomised ≥0.6 versus <0.6×10⁹ cells·L^-1 and ≥0.95 versus <0.95×10⁹ cells·L^-1. Cox proportional hazards models, unadjusted and adjusted for age, sex, lung function, smoking and treatment, evaluated associations of monocytes with transplant-free survival. Survival analysis was repeated using the prospective PROFILE cohort. Unadjusted and adjusted linear mixed models evaluated association of monocyte count with annual decline in forced vital capacity (FVC) % predicted. Results: In 1489 patients with fILD, higher monocyte count was associated with reduced transplant-free survival in unadjusted models, but not after adjustment for relevant confounders (continuous model, HR 0.79, 95% CI 0.54-1.17; p=0.24; dichotomised at 0.6 cells·L^-1, HR 0.89, 95% CI 0.72-1.10; p=0.29; and dichotomised at 0.95 cells·L^-1, HR 0.93, 95% CI 0.68-1.26; p=0.62). Findings were consistent in the PROFILE external replication cohort. Monocyte count was not associated with FVC % decline in the full cohort or within fILD subtypes. Conclusions: Peripheral blood monocyte count was not associated with transplant-free survival or lung function decline in this multicentre cohort study, indicating that it is not a reliable biomarker in fILD.