Date Published: January 10, 2017
Publisher: Public Library of Science
Author(s): Camille Rolland-Debord, Stephanie Fry, Jonathan Giovannelli, Carole Langlois, Nicolas Bricout, Bernard Aguilaniu, Agnes Bellocq, Olivier Le Rouzic, Stephane Dominique, Alain Delobbe, Geraldine François, Abdellatif Tazi, Benoit Wallaert, Cecile Chenivesse, Stelios Loukides.
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.
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.
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]).
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.
Langerhans cell histiocytosis is a rare systemic disease characterized by proliferation of Langerhans cells that infiltrate the tissues. In adults, this disorder affects a limited number of organs, predominantly the lungs, skin and bone . Pulmonary Langerhans cell histiocytosis (PLCH) is mostly observed in genetically predisposed young adult smokers . The most common symptoms are cough, breathlessness and fatigue. Chest computed tomography (CT) scan typically shows bilateral micronodular interstitial syndrome, excavated nodules and cysts predominantly located in the upper and middle areas of the lung . Pulmonary hypertension is present in 10% of cases  due to infiltration of pulmonary capillaries by Langerhans cells  or complicating the interstitial lung disease. Pulmonary function tests (PFT) show various abnormalities including reduction of the diffusing capacity of the lung for carbon monoxide (DLCO), decreased vital capacity (VC), increased residual volume (RV) and airway obstruction .
This study provides a revisited analysis of physiologic determinants of exercise capacity in PLCH including the largest population studied until now and a more comprehensive set of measurements on exercise endorsed by a principal component analysis. The main results of this study can be summarized as follows: (i) impaired exercise capacity is common among patients with moderate PLCH, (ii) it is caused by multifactorial alteration of lung function including alteration of gas exchange, air trapping, pseudorestriction and exercise-induced hyperventilation (iii) it is not associated with increased dyspnea intensity.
In conclusion, exercise limitation is frequent in PLCH and is mainly caused by multifactorial pulmonary changes including alteration of gas exchange, air trapping, “pseudorestriction” and hyperpnea but does not appear to be associated with increased dyspnea. This suggests that treating the lung represents an approach for improving exercise, even in patients experiencing mild dyspnea. In particular, our results suggest assessing the effect of therapies targeting air trapping such as bronchodilators on aerobic capacity.