Physiologic Determinants of Exercise Capacity in Pulmonary Langerhans Cell Histiocytosis: A Multidimensional Analysis

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’O 2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included V’O 2 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 FEV 1 , FVC, FEV 1 /FVC, DL CO and DL CO /VA and increased AaDO 2 , (ii) increased ventilatory equivalents at ventilatory threshold, V D /V T peak, AaDO 2 peak and PaCO 2 peak and decreased ventilatory reserve and PaO 2 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]). Conclusion 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.