Determinants of survival in pulmonary Langerhans' cell granulomatosis (histiocytosis X). Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord

Abstract

The course of pulmonary Langerhans' cell granulomatosis (pulmonary LCG) is variable, difficult to predict and ranges from spontaneous remission to progressive respiratory insufficiency and death. To identify the determinants of survival, we performed a survival analysis on 45 patients with pulmonary LCG. The patients were aged 28 +/- 10 yrs (mean +/- SD) (range 12-62 yrs), 32 males and 13 females, almost exclusively current smokers (96%), and 78% presented symptoms at the time of diagnosis. Diagnosis was made by lung biopsy in 25 patients (56%) and by bronchoalveolar lavage (BAL) analysis in 20 patients (44%). The patients were followed for a median period of 6 yrs (range 1-29 yrs) after the diagnosis. During the period of observation, 33 (73%) patients survived (median follow-up period = 5.8 yrs; range, 1-29 yrs) and 12 (27%) died or underwent lung transplantation (median follow-up period = 8.4 yrs; range 1.4 - 16.1 yrs). The median survival was approximately 13 years. A univariate analysis demonstrated that diminished survival was significantly associated with: an older age at diagnosis (p = 0.0001); a lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio at diagnosis (p = 0.005); a higher residual volume/total lung volume (RV/TLC) ratio at diagnosis (p = 0.02); and steroid therapy during follow-up (p = 0.03). Additional predictive information on mortality was: age > 26 yrs (sensitivity 83%, specificity 64%); FEV1/FVC ratio < 0.66 (sensitivity 75%, specificity 86%); and a RV/TLC ratio > 0.33 (sensitivity 75%, specificity 63%). In multivariate Cox analysis, the combination of factors which gave the best prognostic value was FEV1/FVC ratio and age (p < 0.01). The present findings suggest that adverse prognosis factors at diagnosis in pulmonary Langerhans' cell granulomatosis include older age, lower FEV1/FVC ratio and higher RV/TLC ratio, with additional predictive information on mortality if aged > 26 yrs, FEV1/FVC ratio < 0.66, and RV/TLC ratio > 0.33.