title: Physiologic Determinants of Exercise Capacity in Pulmonary Langerhans Cell Histiocytosis: A Multidimensional Analysis.
abstract: BACKGROUND
  Reduced exercise capacity severely impacts quality of life in pulmonary Langerhans cell histiocytosis. Ascertaining mechanisms that impair exercise capacity is necessary to identify targets for symptomatic treatments.
  
  
  METHODS
  Dyspnea, pulmonary function tests and cardiopulmonary exercise test were analysed in 62 study participants. Data were compared between subjects with impaired and normal aerobic capacity (V'O2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included V'O2 peak as the dependent variable and principal components as covariates.
  
  
  RESULTS
  V'O2 peak was reduced in 44 subjects (71%). Subjects with impaired aerobic capacity presented: (i) decreased FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA and increased AaDO2, (ii) increased ventilatory equivalents at ventilatory threshold, VD/VT peak, AaDO2 peak and PaCO2 peak and decreased ventilatory reserve and PaO2 peak. There was no difference between groups in dyspnea scores. Principal component analysis extracted 4 principal components interpreted as follows: PC1: gas exchange; PC2: "pseudorestriction"; PC3: exercise-induced hyperpnea; PC4: air trapping. Multivariate analysis explained 65% of V'O2 peak. The 4 principal components were independently associated with V'O2 peak (βcoefficients: PC1: 9.3 [4.6; 14], PC2: 7.5 [3; 11.9], PC3: -5.3 [-9.6;-1.], PC4: -9.8 [-14,9;-4.7]).
  
  
  CONCLUSIONS
  Impaired exercise capacity is frequent in pulmonary Langerhans cell histiocytosis. It is mainly caused by pulmonary changes but is not associated with increased dyspnea intensity. Therefore, treating the lung represents a relevant approach for improving exercise capacity, even in patients experiencing mild dyspnea.
authors.affiliation: Service de Pneumologie et ImmunoAllergologie, Centre de Compétence des Maladies Pulmonaires Rares, CHU Lille, Univ. Lille, Lille, France.|Service de Pneumologie et Réanimation médicale, APHP-Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Paris, France.|UMRS 1158 Neurophysiologie respiratoire expérimentale et clinique, Sorbonne Universités, UPMC Univ Paris 06, INSERM, Paris, France.
authors.forename: Camille
authors.identifier: http://orcid.org/0000-0001-6455-6823
authors.initials: C
authors.lastname: Rolland-Debord
authors.affiliation: Service de Pneumologie et ImmunoAllergologie, Centre de Compétence des Maladies Pulmonaires Rares, CHU Lille, Univ. Lille, Lille, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fry
authors.affiliation: Pôle de Santé Publique, Pharmacie et Pharmacologie, CHU Lille, Univ. Lille, Lille, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Giovannelli
authors.affiliation: Service de Biostatistiques, CHU Lille, Univ. Lille, Lille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Langlois
authors.affiliation: Service de Radiologie, CHU Lille, Univ. Lille, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bricout
authors.affiliation: Université Joseph-Fourrier, Faculté de médecine, La Tronche, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Aguilaniu
authors.affiliation: UMRS 1158 Neurophysiologie respiratoire expérimentale et clinique, Sorbonne Universités, UPMC Univ Paris 06, INSERM, Paris, France.|Service d'Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée, APHP-Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Paris, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Bellocq
authors.affiliation: Service de Pneumologie et ImmunoAllergologie, Centre de Compétence des Maladies Pulmonaires Rares, CHU Lille, Univ. Lille, Lille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Rouzic
authors.affiliation: Clinique Pneumologique, Hôpital Charles Nicolle, Université de Rouen, Centre Hospitalier Universitaire de Rouen, Rouen, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Dominique
authors.affiliation: Service de Pneumologie, Centre Hospitalier Régional de la citadelle, Liège, Belgique.
authors.forename: Alain
authors.initials: A
authors.lastname: Delobbe
authors.affiliation: Service de Pneumologie et Réanimation, Centre Hospitalier Universitaire d'Amiens, Université de Picardie Jules Verne, Amiens, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: François
authors.affiliation: Service de Pneumologie, Centre de Référence de l'Histiocytose Langerhansienne, APHP - Hôpital Saint-Louis, Université Paris-Diderot, Sorbonne Paris Cité; INSERM UMR 1153 CRESS, Equipe de Recherche en Biostatistiques et Epidémiologie Clinique, Paris, France.
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Tazi
authors.affiliation: Service de Pneumologie et ImmunoAllergologie, Centre de Compétence des Maladies Pulmonaires Rares, CHU Lille, Univ. Lille, Lille, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Wallaert
authors.affiliation: Service de Pneumologie et ImmunoAllergologie, Centre de Compétence des Maladies Pulmonaires Rares, CHU Lille, Univ. Lille, Lille, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Chenivesse
mesh_terms: D000328:Adult; D015308:Anaerobic Threshold; D004417:Dyspnea / Q000209:etiology / Q000503:physiopathology*; D017079:Exercise Tolerance; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests