Reversible airflow obstruction in lymphangioleiomyomatosis.
BACKGROUND
We previously reported that approximately one-fourth of patients with lymphangioleiomyomatosis (LAM) may respond to therapy with bronchodilators. However, the validity of those observations has been questioned. The aims of the present study were to determine the prevalence of reversible airflow obstruction in patients with LAM and to identify associated clinical and physiologic parameters.


METHODS
First, the clinical and physiologic characteristics of 235 patients were analyzed to determine the frequency of the response to albuterol during a total of 2,307 visits. Second, we prospectively evaluated the response to albuterol (2.5 mg) and ipratropium (500 mug) in 130 patients, and correlated their responses with their clinical and physiologic characteristics.


RESULTS
In the retrospective study, 51% of the patients responded at least once to bronchodilators; of these, 12% responded >/= 50% of the time. A higher frequency of positive bronchodilator responses was associated with greater rates of decline in FEV(1) and diffusing capacity of the lung for carbon monoxide (Dlco). In the prospective study, 39 patients (30%) responded to bronchodilators, including 12 to ipratropium, 9 to albuterol, and 18 to both. The prevalence of asthma and smoking in the 39 responders was not different from that seen in the 91 nonresponders. Patients who responded to ipratropium, albuterol, or both had significantly (p < 0.02) lower FEV(1) and Dlco, and a greater rate of FEV(1) decline (p = 0.044) and Dlco decline (p = 0.039) than patients who did not respond to these bronchodilators. After adjusting for FEV(1)/FVC ratio, Dlco decline also was greater in responders than in nonresponders (p = 0.009).


CONCLUSIONS
Patients with LAM may have partially reversible airflow obstruction. A positive response to bronchodilators is associated with an accelerated rate of decline in pulmonary function.
Taveira-DaSilva
Angelo M
AM
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Electronic address: dasilvaa@nhlbi.nih.gov.
Steagall
Wendy K
WK
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Rabel
Antoinette
A
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Hathaway
Olanda
O
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Harari
Sergio
S
Unità di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, Milan, Italy.
Cassandro
Roberto
R
Unità di Pneumologia e Terapia Semi-Intensiva Respiratoria, Servizio di Fisiopatologia Respiratoria ed Emodinamica Polmonare, Ospedale San Giuseppe, Milan, Italy.
Stylianou
Mario
M
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Moss
Joel
J
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use; D001213:Asian; D001993:Bronchodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006630:Hispanic or Latino; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology / Q000627:therapeutic use; D018192:Lymphangioleiomyomatosis / Q000188:drug therapy* / Q000208:ethnology / Q000503:physiopathology; D008875:Middle Aged; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology; D012189:Retrospective Studies; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects / Q000502:physiology; D044465:White People
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D009241:Ipratropium; D000420:Albuterol