Background:

- Lymphangioleiomyomatosis (LAM) is a rare type of lung disease that occurs almost exclusively in women. In LAM, muscle tissue grows in the lungs and starts to block the flow of air. It is a progressive disease, and in severe cases may require a lung transplant. One possible treatment to improve breathing in people with LAM is inhaled albuterol. Albuterol can be given in a metered dose inhaler (MDI) or with a nebulizer. Researchers want to compare these methods to see which method best improves lung function in women with LAM.

Objectives:

- To see whether a nebulizer or MDI can better improve lung function in women with LAM.

Eligibility:

- Women at least 18 years of age who have impaired lung function because of LAM.

Design:

• Participants will be screened with a physical exam and medical history. No lab tests will be needed for this study.
• Participants will have a 3-day overnight stay at the National Institutes of Health. Those who are using long-acting inhalers will have to stop taking these drugs 1 week before the study.
• Participants will receive either the nebulizer or two or four puffs of the inhaler. Four puffs of albuterol is a higher dose than is normally prescribed, and is being tested on this study.
• Participants will have each treatment around the same time of day on each of the 3 days. Before and after taking the albuterol, participants will have lung function tests.

We have reported that approximately one third of patients with lymphangioleiomyomatosis (LAM) who have airflow obstruction respond to bronchodilators such as albuterol, a Beta2-adenergic receptor agonist, with an increase in forced expiratory flow in one second (FEV1) of 12% and 200 ml above baseline values. Others however, have questioned these findings, reporting instead, a low rate of response of only six percent. Contrasting with our study, in this study albuterol was administered with a metered dose inhaler whereas in ours it was given by nebulizer. We propose to measure changes in lung function after administration of albuterol, respectively by metered inhaler and nebulizer, for 3 consecutive days in 100 LAM subjects. Our hypothesis is that albuterol administered by nebulization will produce a greater increase in FEV1 than two puffs of inhaled albuterol. If this hypothesis is confirmed, then we may recommend that patients with LAM and airflow obstruction use as a method of drug administration a nebulizer, rather than a metered dose inhaler.

• INCLUSION CRITERIA:
• Diagnosis of LAM either by tissue biopsy, evidence of lung and other organ involvement (renal angiomyolipomas, chylous effusions, lymphangioleiomyomas), high serum levels of vascular endothelial growth factor D (VGEF-D)(1) or a diagnosis of TSC associated with cystic lung lesions.
• Age 18 years or over
• Evidence of airflow obstruction: FEV1/VC ratio < fifth percentile of predicted normal and an FEV(1) <80% predicted of the normal values.

EXCLUSION CRITERIA:

Subjects will be excluded from the study if they meet one or more of the following criteria:

• History of hypersensitivity to albuterol or any of its components.
• Moderate or large pleural effusions (chest x-ray and or CT scan procedure completed under Protocol 95-H-0186)
• History of seizures other than during infancy
• Inability to withhold bronchodilators for 24 hours
• Cognitive Impairment
• Age less than 18 years
• Male sex
• Status-post lung or kidney transplantation
• Pregnant or breast feeding (women of childbearing potential will undergo a blood or urine pregnancy test under Protocol 95-H-0186).
• Treatment with monoaminoxidase inhibitors, tricyclic antidepressants or Beta-adrenergic receptor antagonists or long acting anticholinergic bronchodilators who are unable to be discontinued for at least seven days before enrollment.
• Patients with URI, uncontrolled hyperthyroidism or severe gastro-esophageal reflux. Major systemic diseases (i.e., malignancy; myocardial infarction or unstable angina; type 1 diabetes, severe hypertension; liver cirrhosis).