Mechanisms of Exercise Limitation and Prevalence of Pulmonary Hypertension in Pulmonary Langerhans Cell Histiocytosis

Background: Pulmonary Langerhans cell histiocytosis (PLCH) determines reduced exercise capacity. The speculated mechanisms of exercise impairment in PLCH are ventilatory and cardiocirculatory limitations, including pulmonary hypertension (PH).

Research question: What are the mechanisms of exercise limitation, the exercise capacity, and the prevalence of dynamic hyperinflation (DH) and PH in PLCH?

Study design and methods: In a cross-sectional study, patients with PLCH underwent an incremental treadmill cardiopulmonary exercise test with an evaluation of DH, pulmonary function tests, and transthoracic echocardiography. Those patients with lung diffusing capacity for carbon monoxide (Dlco) < 40% predicted and/or transthoracic echocardiogram with tricuspid regurgitation velocity > 2.5 m/s and/or with indirect PH signs underwent right heart catheterization.

Results: Thirty-five patients were included (68% women; mean age, 47 ± 11 years). Ventilatory and cardiocirculatory limitations, impairment suggestive of PH, and impaired gas exchange occurred in 88%, 67%, 29%, and 88% of patients, respectively. The limitation was multifactorial in 71%, exercise capacity was reduced in 71%, and DH occurred in 68% of patients. FEV₁ and Dlco were 64 ± 22% predicted and 56 ± 21% predicted. Reduction in Dlco, an obstructive pattern, and air trapping occurred in 80%, 77%, and 37% of patients. FEV₁ and Dlco were good predictors of exercise capacity. The prevalence of PH was 41%, predominantly with a precapillary pattern, and mean pulmonary artery pressure correlated best with FEV₁ and tricuspid regurgitation velocity.

Interpretation: PH is frequent and exercise impairment is common and multifactorial in PLCH. The most prevalent mechanisms are ventilatory, cardiocirculatory, and suggestive of PH limitations.

Clinical trial registration: ClinicalTrials.gov; No.: NCT02665546; URL: www.clinicaltrials.gov.