Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Bronchodilator Effects of Nebulized Versus Inhaled Albuterol in Subjects With Lymphangioleiomyomatosis

Conditions
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Lymphangioleiomyomatosis

Intervention / Treatment
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* Drug: albuterol inhaler
* Drug: albuterol nebulizer
* Procedure: PFT


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Nebullizer | Drug: albuterol nebulizer<br>* Albuterol administered by nebulization will produce a greater increase in FEV1<br>Procedure: PFT<br>* Breathing Test<br>|
| Active Comparator: 2<br>Inhaler | Drug: albuterol inhaler<br>* 2 puffs of Metered Dose inhaler for Bronchodilation<br>Procedure: PFT<br>* Breathing Test<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Greater improvement in lung function with nebulized albuterol. | Greater improvement in lung function with nebulized albuterol. | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Albuterol, Bronchodilator, Nebulizer, Metered Dose Inhaler