Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

Blood and Lymph Conditions

Neoplasms

Nervous System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Asthma

Sclerosis

Lung Diseases

Fibrosis

Pulmonary Fibrosis

Cystic Fibrosis

Sarcoidosis

Alpha 1-Antitrypsin Deficiency

Tuberous Sclerosis

Sarcoidosis, Pulmonary

Respiratory Tract Diseases

Hypersensitivity

Pancreatic Diseases

Gastrointestinal Diseases

Genetic Diseases, Inborn

Infant, Newborn, Diseases

Lung Diseases, Interstitial

Lymphoproliferative Disorders

Lymphatic Diseases

Hypersensitivity, Delayed

Hamartoma

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Alpha-1 Antitrypsin Deficiency

Tuberous Sclerosis Complex

Vasodilator Agents

Respiratory System Agents

All Drugs and Chemicals

Nitric Oxide

Alpha 1-Antitrypsin

Protein C Inhibitor

Subjects with pulmonary disease or possible pulmonary disease and Relatives

Tatyana Worthy, R.N.

Joel Moss, M.D.

Tatyana Worthy, B.S.

This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease.

The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers.

Optional CT Sub-study

The standard CT scan will be compared to the low dose radiation CT scan for the 150 subjects enrolled in the sub-study to assess the variation between the two techniques. Specifically, the quantitative computer aided detection of lung CT abnormalities from LAM can be compared to assess whether low radiation dose CT exams is an alternative to conventional CT to monitor disease

status.

This optional sub-study will be offered to up to 100 adult subjects with lung disease and up to 50 children age 9 and older with CF. Children will not be enrolled in the optional CT sub-study unless they have had a standard CT scan for medical purposes to use in comparison. One additional low dose radiation CT scan of the chest may be done as part of this sub-study when these subjects have their next annual CT scan.

This study is designed to evaluate genetic mechanisms of lung disease by surveying polymorphic genes involved in respiratory function and examining gene expression in the lung cells of individuals with pulmonary disease (e.g., alpha 1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis, history of infection, and genetic mutations consistent with lung pathology). Emphasis will be on defining the distribution of allelic variants of nitric oxide synthase, alpha 1-antitrypsin, and the cystic fibrosis transmembrane conductance regulator genes in patients and in age- and sex-matched healthy individuals in a control population.

Role of Genetic Factors in the Development of Lung Disease

Role of Genetic Factors in the Pathogenesis of Lung Disease

.This is a new requirement and the sharing of IPD is not discussed in the protocol.

distribution of genetic variants of nitric oxide synthases and other candidate genes involved in pulmonary function

The secondary scan can also be used to obtain a detailed assessment of AML-like tumors and lymphangioleiomyomas in the abdomen or pelvis region when they are detected in the standard chest-abdomen-pelvis CT scan. The enhanced resolution is expected to help classify the tumors without the need for invasive biopsy, for example, by detecting traces of fatty tissue in the tumor to confirm the identity of AML.

Suburban Hospital

National Heart, Lung, and Blood Institute (NHLBI)

Necrosis

Platelet Aggregation Inhibitors

Pentoxifylline

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Protective Agents

Radiation-Protective Agents

Antioxidants

Sarcoidosis is a disease most commonly affecting the lungs, but it can also involve lymph nodes, skin, liver, spleen, eyes, bones, and glands. The cause of the disease is unknown. When it occurs it can produce an inflammatory reaction leading to irreversible organ damage and disability.

In sarcoidosis granulomas can form in various organs (primarily lung) which can lead to its dysfunction. Granuloma is formed by clusters of inflammatory cells. The formation of these granulomas is influenced by the release of a substance called TNF-alpha (tumor necrosis factor alpha) which is found in some white blood cells. A drug known as pentoxifylline (POF) is known to markedly reduce the release of TNF-alpha.

The standard medical treatment for sarcoidosis is steroid therapy. However, steroid therapy is associated with significant side effects and often must be stopped. Unfortunately, some of these patients can relapse when the steroid therapy is discontinued. Because of this, researchers are interested in finding alternative therapies for the treatment of sarcoidosis.

This study will evaluate the effectiveness of giving POF to patients with sarcoidosis currently taking steroids. Researchers will compare the results between patients taking steroids with pentoxifylline and those patients taking steroids alone.

Corticosteroids are currently the mainstay of therapy for active pulmonary sarcoidosis and are used to prevent relapses in many patients with stable disease. The pulmonary manifestations of sarcoidosis are heterogenous and not all patients require corticosteroid therapy. Corticosteroids often produce undesirable side effects and, therefore, other therapies that can reduce or replace corticosteroid use are being sought. As tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the formation of granulomata (the pathological hallmark of the disease), drugs that inhibit its production/release may prove effective in the treatment of this disease. Pentoxifylline (POF), a xanthine derivative used for many years in the treatment of peripheral vascular disease, is known to inhibit TNF-alpha release by human peripheral blood mononuclear cells and alveolar macrophages from patients with active sarcoidosis. To evaluate whether this drug is beneficial in the treatment of sarcoidosis, we propose to conduct a randomized, double-blind, placebo-controlled trial with POF in patients with pulmonary sarcoidosis on corticosteroid therapy. The primary objective of this study is to determine whether POF treatment can be beneficial as an adjunct to corticosteroid therapy in patients with pulmonary sarcoidosis. The role of TNF-alpha and other cytokines (released from alveolar macrophages) in explaining treatment responses defined by whether or not a patient improved will be assessed by testing whether the effect of treatment on the probability of improvement varies with cytokine levels.

Treatment of Pulmonary Sarcoidosis With Pentoxifylline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Role of Genetic Factors in the Development of Lung Disease	NCT00001532	Cystic Fibrosis Pulmonary Fibro... Tuberous Sclero... Asthma Pulmonary Sarco...		2 Years - 90 Years	National Institutes of Health Clinical Center (CC)
Treatment of Pulmonary Sarcoidosis With Pentoxifylline	NCT00001877	Pulmonary Sarco...	Pentoxifylline	-	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for pulmonary sarcoidosis