Clinical Trial: Evaluation of Exercise Capacity and Exercise Limitation in Patients With Pulmonary Langerhans Cell Histiocytosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Evaluation of Exercise Capacity and Mechanisms of Exercise Limitation in Patients With Pulmonary Langerhans Cell Histiocytosis

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 Summary:

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. Am
Sponsor: InCor Heart Institute

Current Primary Outcome: Maximal O2 uptake capacity (VO2 max) [ Time Frame: Baseline ]

Maximal O2 uptake capacity (VO2 max) during a cardiopulmonary exercise test (mL/kg/min)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Six-minute walk distance [ Time Frame: Baseline ]
    Distance during a six-minute walk test in meters
  • Short Form Health Survey (SF-36) [ Time Frame: Baseline ]
    SF-36 questionnaire to evaluate quality of life
  • Diffusing capacity for carbon monoxide [ Time Frame: Baseline ]
    Diffusing capacity for carbon monoxide (mL/min/mmHg)
  • Inspiratory capacity [ Time Frame: Baseline ]
    Serial measurement of inspiratory capacity during incremental cardiopulmonary exercise test (L)
  • Forced expiratory volume in the first 1 second (FEV1) [ Time Frame: baseline ]
    FEV1 (Pulmonary lung function - spirometry) - L
  • Velocity measurement of tricuspid regurgitant jet [ Time Frame: Baseline ]
    Velocity measurement of tricuspid regurgitant jet evaluated by transthoracic echocardiography (m/s)
  • Residual volume/total lung capacity ratio [ Time Frame: baseline ]
    Residual volume/total lung capacity ratio evaluated in pulmonary lung function - plethysmography
  • Residual volume [ Time Frame: Baseline ]
    Residual volume evaluated in pulmonary lung function - plethysmography (L)
  • Baseline Dyspnea Index [ Time Frame: Baseline ]
    Baseline Dyspnea Index
  • Six-minute walk test desaturation [ Time Frame: Baseline ]
    Desaturation during a six-minute walk test (%)
  • Ejection fraction [ Time Frame: Baseline ]
    Ejection fraction evaluated by transthoracic echocardiography (%)
  • Diameter of the cardiac chambers [ Time Frame: Baseline ]
    Diameter of the cardiac chambers evaluated by transthoracic echocardiography (cm)


Original Secondary Outcome: Same as current

Information By: InCor Heart Institute

Dates:
Date Received: January 14, 2016
Date Started: March 2016
Date Completion: December 2017
Last Updated: August 29, 2016
Last Verified: August 2016