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

Abstract

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 FEV1 and/or FVC and/or DLCO, 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 FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 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 .

Figures

Figure 1

The estimated cumulative incidence of lung function deterioration during the study. The overall lung function corresponds to a decrease of at least 15% in FEV1, FVC, and/or DLCO. FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; DLCO = diffusion capacity for carbon monoxide.

Figure 2

Detailed changes in the smoking statuses of the patients during the study. The patients’ smoking statuses were recorded at each scheduled visit based on their self-reports and urinary cotinine concentrations (except in patients using nicotine replacement therapy). Each line represents a patient. Periods of current smoking are displayed in black, periods of smoking cessation in grey, and periods of loss to follow-up in white.

Figure 3

Variations in the lung HRCT scores at the different scheduled visits of the study. The data are expressed as the means ± SEMs of the lung HRCT nodular and cystic scores. The lung HRCT was available at inclusion for 56 patients. The maximal values for the HRCT nodular and cystic scores are 18 and 24, respectively.