The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study

BACKGROUND: The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. METHODS: In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV(1) and/or FVC and/or DL(CO), compared with baseline values. At each visit, smoking status was recorded based on the patients’ self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. RESULTS: The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV(1) and DL(CO), and 9% for FVC). In the multivariate analysis, smoking status and PaO(2) at inclusion were the only factors associated with the risk of lung function deterioration. The patients’ smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. CONCLUSIONS: Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. TRIAL REGISTRATION: ClinicalTrials.gov: No: NCT01225601. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-015-0249-2) contains supplementary material, which is available to authorized users.