Role of serum surfactant protein-D as a prognostic predictor in fibrotic hypersensitivity pneumonitis

Background: Serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) are candidate diagnostic and activity markers for fibrotic hypersensitivity pneumonitis (HP), although their correlation with prognosis remains unclear. We aimed to evaluate the prognostic usefulness of serum KL-6 and SP-D in patients with fibrotic HP.

Methods: This was a retrospective medical record review of 185 patients with fibrotic HP at a single center from 2005 to 2019. The baseline and minimum serum KL-6 and SP-D levels over two years were recorded. The contribution of KL-6 and SP-D levels to the incidence of progressive fibrosing interstitial lung disease (PF-ILD) and mortality were evaluated using multivariate analysis.

Results: The respective baseline and minimum levels were 1441 and 808 U/ml for KL-6 and 254 and 132 ng/mL for SP-D. A high minimum SP-D level was significantly associated with a high incidence of PF-ILD by logistic regression, independent of baseline forced vital capacity and honeycombing. Similarly, a high minimum SP-D level was significantly associated with high mortality by Cox proportional hazard model analysis. The stratified minimum SP-D levels of <100, 100-200, and >200 revealed significantly distinct groups in the entire cohort, with PF-ILD incidence rates of 28%, 48%, and 74% and median survival times of 120, 74, and 45 months, respectively.

Conclusions: High minimum SP-D levels over two years were correlated with an unfavorable prognosis in our cohort. Patient with consistently high SP-D levels during the clinical course may have a poor prognosis and be a candidate for early treatment intensification.