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 (ßcoefficients 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.