Chest
Volume 158, Issue 6, December 2020, Pages 2440-2448
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Diffuse Lung Disease: Original Research
Mechanisms of Exercise Limitation and Prevalence of Pulmonary Hypertension in Pulmonary Langerhans Cell Histiocytosis

Data were partially presented orally at the European Respiratory Society Conference in Milan, Italy, in 2017 and in Madrid, Spain, in 2019.
https://doi.org/10.1016/j.chest.2020.05.609Get rights and content

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

Section snippets

Study Population

Patients with a diagnosis of PLCH assessed according to lung biopsy or the presence of a typical chest CT scan (evaluated by two radiologist experts) with a history of smoking13 were invited to participate in this cross-sectional study. The protocol was approved by the local research ethics committee, registered at www.clinicaltrials.gov,14 and had financial support from the São Paulo Research Foundation (FAPESP-2015/06604-0). All patients signed the informed consent form. Patients were

Results

Of the 38 patients with PCLH followed up at our center from February 2016 to August 2018, three patients were not included because of death (n = 1), lung transplantation (n = 1), and refusal to participate in the study (n = 1) (Fig 1). Thus, 35 patients were enrolled, and 68% were women. Clinical and functional data are described in Table 1. The mean age of the patients was 47 ± 11 years, 92% were current or ex-smokers, one patient was a marijuana user, and one patient had a history of cocaine

Discussion

To our knowledge, this study is the first that thoroughly evaluated the potential mechanisms of exercise limitation and the prevalence of DH and PH in patients with PLCH of various severities. The main findings of this study are as follows: (1) ventilatory and cardiocirculatory limitations, including those suggestive of PH, were the most common mechanisms of exercise limitation in PLCH; (2) multifactorial impairment occurred in 71% of those with reduced exercise capacity; (3) exercise

Interpretation

This study highlights that the majority of patients with PLCH present with reduced exercise capacity, secondary to multiple mechanisms of limitation, predominantly ventilatory and cardiocirculatory, and associated with functional impairment. Furthermore, DH and PH were common in PLCH and correlated with functional abnormalities. Future studies are necessary to define the role of different interventions over the potential mechanisms of impairment to improve exercise tolerance in PLCH.

Acknowledgments

Author contributions: B. G. B. is the guarantor of the paper and contributed to the study design, data collection, data analysis, writing, and manuscript review. G. I. H. contributed to the study design, data collection, data analysis, writing, and manuscript review; J. B. S. and C. S. G. F. contributed to the data collection and manuscript review; A. L. P. d. A., J. M. S., R. A. K., and C. R. R. C. contributed to the study design, writing, and manuscript review; C. J. C. d. S. F. contributed

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    FUNDING/SUPPORT: The study protocol had financial support from the São Paulo Research Foundation [FAPESP-2015/06604-0].

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