Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cystic lung disease of unknown etiology that affects young to middle-aged smokers of both sexes. Its natural course is highly variable and difficult to predict in an individual patient. When the disease progresses, it usually manifests as airway obstruction, that is, a decline in forced expiratory volume in one second (FEV1). Previous work conducted in a large prospective cohort had shown a more favorable overall survival than previously reported (greater than 90% at ten years), while distinguishing two markedly different FEV1 trajectories: the majority of patients maintain a normal and stable FEV1, whereas approximately one-fifth exhibit an initially lower FEV1 that declines over time, with a poorer prognosis. However, the clinical features collected at diagnosis do not reliably distinguish these two profiles, hence the value of identifying prognostic blood biomarkers.
To address this question, the authors measured serum concentrations of thirty mediators at diagnosis using multiplexed immunoassays. Nine patients with FEV1 decline and an available blood sample collected at diagnosis were matched to sixteen patients whose FEV1 remained stable over a median follow-up of 3.6 years. Logistic regression models adjusted for the matching variables—age, sex, and daily tobacco consumption—were used to compare concentrations between the two groups, limiting the influence of demographic characteristics and smoking.
Two mediators stood out significantly. TNF-α (tumor necrosis factor alpha) reached a median concentration of 137 pg/mL in the declining-FEV1 group versus 60 pg/mL in the stable group (p = 0.032), while MMP-7 (matrix metalloproteinase 7) levels were 16,344 pg/mL and 11,555 pg/mL, respectively (p = 0.047). A negative correlation was observed between FEV1 and MMP-7 levels (rho = −0.65, p = 0.001), but not with TNF-α (rho = −0.33, p = 0.14). The authors place these observations in the context of lung tissue degradation and remodeling by histiocytic lesions, a process in which metalloproteinases are involved, and emphasize that MMP-7 has already been validated as a blood marker of progression in idiopathic pulmonary fibrosis.
The authors acknowledge the limitations of this work, in particular the small sample size, which precluded multivariate analyses and the study of the individual rate of decline, as well as the lack of serial sampling during follow-up. They conclude that TNF-α and MMP-7 constitute candidate prognostic blood biomarkers for PLCH, easily measured in clinical practice, whose value will need to be confirmed in larger cohorts.