Evaluation of Exercise Capacity and Mechanisms of Exercise Limitation in Patients With Pulmonary Langerhans Cell Histiocytosis
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Maximal O2 uptake capacity (VO2 max)
Study Overview
Brief Summary
Pulmonary Langerhans Histiocytosis Cells (PLCH) is characterized by infiltration of Langerhans cells and formation of loose granulomas with lymphocytic infiltrate and formation of nodular and cystic lesions on chest CT, and is often associated with smoking. Functionally, there may be obstructive and / or restrictive defect, with reduced carbon monoxide diffusing capacity. Dyspnea and lower exercise tolerance are common in PLCH, but exercise capacity in this disease is poorly understood and has not been compared to controls. Besides, the mechanisms involved in limiting exercise are poorly understood and cover multiple factors such as change in gas exchange, pulmonary hypertension (PH), dynamic hyperinflation, physical deconditioning and left heart failure. The involvement of pulmonary circulation in PLCH has unknown prevalence, but contributes to the symptoms. In the PH classification, PLCH belongs to the group 5, of multifactorial etiology. The definition of the presence and contribution of dyspnea mechanisms in different severities of PLCH is important to understanding the disease and individualization of treatment. The objective of the study is to evaluate the exercise capacity of patients with HCLP, and determinate mechanisms of dyspnea and lower exercise tolerance beyond its impact on quality of life.
Detailed Description
Langerhans cells are antigen-presenting cells of monocyte-macrophage lineage present in various epithelium like airways. Langerhans cell histiocytosis (LCH), also called histiocytosis X or pulmonary eosinophilic granulomatosis, are characterized by proliferation and infiltration of Langerhans cells in the affected organs, including skin, lung, bones, pituitary gland, liver, lymph nodes and thyroid gland.
Several clinical presentations have been described. In the pediatric population, clonal neoplastic processes are responsible for acute disseminated forms (Letterer-Siwe syndrome) or multifocal forms (Syndrome Hand-Schuller-Christian),and both have an unfavorable prognosis.
In adults, LCH may affect one or several organs in a multisystemic disease. The pulmonary form is usually sporadic and occurs almost exclusively in smokers, with smoking history of at least 20 pack-years. It is believed that, unlike systemic forms, exposure to tobacco antigens generates a polyclonal response with recruitment and accumulation of Langerhans cells throughout the interstitium of small airways.
LCH is a rare condition. The prevalence of 3.4% found in a series of 502 surgical lung biopsies may be underestimated, because many patients may improve spontaneously or may be asymptomatic and diagnosis is defined based on radiological findings. The main clinical features are cough, dyspnea and respiratory failure. The mean age of diagnosis is between 20 and 40 years. Men and women are equally affected, which probably reflects the characteristics of smoking habits nowadays.
In the study of Vassallo and colleagues, median survival was 12.5 years between diagnosis and death in patients with LCH, which is lower than that described in general population. Among the predictors of poor prognosis In this study the predictors of worse prognosis include an obstructive pattern, air trapping and reduction in carbon monoxide diffusing capacity (DLCO) in pulmonary function tests.
Study Design
- Study Type
- Observational
- Observational Model
- Other
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •proven diagnosis of pulmonary Langerhans cell histiocytosis based on histopathological or clinical and radiological findings;
Exclusion Criteria
- •lung transplantation
- •cognitive or musculoskeletal disorders that preclude exercise test;
- •severe or decompensated heart disease.
Outcomes
Primary Outcomes
Maximal O2 uptake capacity (VO2 max)
Time Frame: Baseline
Maximal O2 uptake capacity (VO2 max) during a cardiopulmonary exercise test (mL/kg/min)
Secondary Outcomes
- Six-minute walk distance(Baseline)
- Velocity measurement of tricuspid regurgitant jet(Baseline)
- Residual volume(Baseline)
- Ejection fraction(Baseline)
- Diffusing capacity for carbon monoxide(Baseline)
- Residual volume/total lung capacity ratio(baseline)
- Baseline Dyspnea Index(Baseline)
- Short Form Health Survey (SF-36)(Baseline)
- Inspiratory capacity(Baseline)
- Forced expiratory volume in the first 1 second (FEV1)(baseline)
- Six-minute walk test desaturation(Baseline)
- Diameter of the cardiac chambers(Baseline)
Investigators
Bruno Guedes Baldi
phD
InCor Heart Institute