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

Abstract

BackgroundReduced 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.MethodsDyspnea, 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.ResultsV’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]).ConclusionImpaired 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.

New insights in lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis

“…A correlation between V′O 2 peak and resting dead space/tidal volume ratio (VD/VT), RV and resting alveolar-to-arterial oxygen tension difference, and DLCO have also been observed [125]. Recently, ROLLAND-DEBORD et al [126] collected data on dyspnoea, PFT and CPET in 62 patients. 44 subjects (71%) showed exercise limitation (V′O 2 peak <84%).…”

“…No difference was found in dyspnoea score between patients with impaired and normal aerobic capacity. Despite possible biases related to the retrospective design of the study, multidimensional analysis showed that the reduction of aerobic exercise capacity in patients with PLCH has a multifactorial origin, which includes gas exchange, air trapping, ventilatory abnormalities and hyperpnoea [126].…”

How I manage pulmonary Langerhans cell histiocytosis

“…Blood gas levels at rest remain normal for a long time, but exertion may cause alveolar arterial oxygen gradient elevation and hypoxaemia [25,26]. 6MWT distance may be impaired in patients with advanced disease [16].…”

Avaliação dos mecanismos determinantes de limitação ao esforço e da capacidade de exercício em pacientes com histiocitose pulmonar de células de Langerhans

“…O teste cardiopulmonar de exercício (TCPE) avalia respostas dinâmicas cardiovasculares, respiratórias e metabólicas no esforço em ambiente monitorizado. É útil para confirmação e mensuração da limitação ao esforço e possibilita a identificação dos múltiplos fatores contribuintes para a redução da tolerância durante o exercício (69,70) . (66,71) .…”

“…A redução da capacidade de exercício em pacientes com HPCL foi demonstrada em poucos estudos prévios. Os mecanismos de limitação ao exercício aventados nesses pacientes são alterações cardiovasculares (incluindo HP), ventilatórias, HD e distúrbios de troca gasosa que podem ocorrer de maneira isolada ou associada (24,70) . ouro -nem mesmo triagem através de ecocardiograma (24) .…”