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

Abstract

BackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionsSerial 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 registrationClinicalTrials.gov: No: NCT01225601.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0249-2) contains supplementary material, which is available to authorized users.

Pulmonary Langerhans cell histiocytosis: analysis of 14 patients and literature review

“…Previous study found that lung function deteriorated in 60% of the patients and improved in 20% (16). Serial lung function assessment is necessary for the follow-up of PLCH patients to identify their disease progression (28). However, in the current study, PFTs data during follow-up are not achieved, so a larger follow-up study is needed to prove the findings in the previous study (16).…”

How I manage pulmonary Langerhans cell histiocytosis

“…Obstructive, restrictive and mixed patterns have been described. In the early stages, pulmonary function testing may be normal in ∼10% of patients [13]. The most common abnormality is a reduction of DLCO, which is observed in 80-90% of cases and is primarily a reflection of pulmonary vascular dysfunction [13,14,23].…”

“…At clinical presentation [13,14], PLCH is diagnosed by three main symptoms. 1) Respiratory symptoms (cough and dyspnoea on exertion), which occur in approximately two-thirds of all such cases.…”

“…Over the last decade, significant progress has been made in expanding our knowledge of the natural history of PLCH, which has allowed more standardised management of patients in clinical practice [13,15,16]. Here, we first describe several clinical situations in which pulmonary physicians may be faced with decisions related to PLCH.…”

“…PLCH is mainly observed in young patients of both sexes, with a peak incidence at age 20-40 years, and females possibly develop PLCH at slightly older ages. It occurs almost exclusively in smokers (90-100% patients are current or ex-smokers in the largest series) [13,14].…”