title: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov: No: NCT01225601 .
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence de l'histiocytose Langerhansienne, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475, Paris Cedex 10, France. abdellatif.tazi@sls.aphp.fr.|Univ Paris Diderot, Sorbonne Paris Cité, U1153 CRESS, Biostatistics and Clinical Epidemiology research team, Paris, France. abdellatif.tazi@sls.aphp.fr.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Tazi
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Radiologie, Hôpital Saint-Louis, Paris, France. constancedemm@gmail.com.
authors.forename: Constance
authors.initials: C
authors.lastname: de Margerie
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Avicenne, Bobigny, France. jean-marc.naccache@tnn.aphp.fr.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Naccache
authors.affiliation: Service de Pneumologie et Immuno-allergologie, Centre de compétence des maladies pulmonaires rares, Hôpital Calmette, Lille, France. stephanie.fry@CHRU-LILLE.FR.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Fry
authors.affiliation: Département de Pneumologie, Hôpital Charles Nicolle, Rouen, France. stephane.dominique@chu-rouen.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dominique
authors.affiliation: IRSET UMR 1085, Université de Rennes 1; Service de Pneumologie, Hôpital Pontchaillou, Rennes, France. Stephane.JOUNEAU@chu-rennes.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jouneau
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence de l'histiocytose Langerhansienne, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475, Paris Cedex 10, France. gwenael.lorillon@sls.aphp.fr.
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Lorillon
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence de l'histiocytose Langerhansienne, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475, Paris Cedex 10, France. emmanuelle.bugnet@sls.aphp.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bugnet
authors.affiliation: Département de Pneumologie, Hôpital Arnaud de Villeneuve, Montpellier, France. r-chiron@chu-montpellier.fr.
authors.forename: Raphael
authors.initials: R
authors.lastname: Chiron
authors.affiliation: Service de Pneumologie et Immuno-allergologie, Centre de compétence des maladies pulmonaires rares, Hôpital Calmette, Lille, France. Benoit.WALLAERT@CHRU-LILLE.FR.|Université Lille 2, Lille, France. Benoit.WALLAERT@CHRU-LILLE.FR.
authors.forename: Benoit
authors.initials: B
authors.lastname: Wallaert
authors.affiliation: Université Paris 13, Sorbonne Paris Cité; Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Avicenne, Bobigny, France. dominique.valeyre@avc.aphp.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, U1153 CRESS, Biostatistics and Clinical Epidemiology research team, Paris, France. sylvie.chevret@paris7.jussieu.fr.|Assistance Publique-Hôpitaux de Paris; Hôpital Saint-Louis, Service de Biostatistique et Information Médicale, Paris, France. sylvie.chevret@paris7.jussieu.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
mesh_terms: D000328:Adult; D018450:Disease Progression; D015150:Echocardiography, Doppler; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects; D014057:Tomography, X-Ray Computed