Nebulized or Inhaled Albuterol for Lymphangioleiomyomatosis

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).