Chest
Volume 136, Issue 6, December 2009, Pages 1596-1603
Journal home page for Chest

Original Research
Lymphangioleiomyomatosis
Reversible Airflow Obstruction in Lymphangioleiomyomatosis

https://doi.org/10.1378/chest.09-0624Get rights and content

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 μg) 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 FEV1 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 FEV1 and Dlco, and a greater rate of FEV1 decline (p = 0.044) and Dlco decline (p = 0.039) than patients who did not respond to these bronchodilators. After adjusting for FEV1/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.

Section snippets

Study Populations

For the retrospective analysis, the population comprised 235 patients with LAM who had at least five visits to the National Institutes of Health (NIH) [National Heart, Lung, and Blood Institute Protocol 95-H-0186]. For the prospective study, the population consisted of 106 patients participating in the same protocol at NIH (Bethesda, MD) and 24 patients who were followed up at the Ospedale San Giuseppe (Milan, Italy). Physiologic data from 21 of the 106 NIH patients participating in the

Retrospective Study

Age and pulmonary function data of the population are listed in Table 1. Of the study population, 211 were white, 13 were African American, 9 were Asian, and 2 were Hispanic. The number of visits per patient was 9.8 ± 0.3 (range, 5 to 22), for a total of 2,307 visits. The response to a β-adrenergic bronchodilator was tested at all visits.

Bronchodilator Response, Severity of Lung Disease, and Decline in Lung Function

Twenty-eight patients (12%) responded to albuterol at ≥ 50% of the visits, 93 patients (40%) responded < 50% of the time, and 114 patients (48%) never

Discussion

Our retrospective analysis showed that a greater frequency of a positive bronchodilator response to β-adrenergic bronchodilators was associated with worse lung function and a greater rate of decline in FEV1 and Dlco. Although patients with worse lung function were more likely to be treated with bronchodilators, we found no evidence that the use of these agents changed the rate of decline in lung function.

The prospective study confirmed that responders to bronchodilators have greater rates of FEV

Acknowledgments

Author contributions: Drs. Taveira-DaSilva and Moss were responsible for writing the manuscript, with assistance from Drs. Steagall and Stylianou. Drs. Steagall and Stylianou carried out most of the data analysis for the retrospective study. Ms. Hathaway and Ms. Rabel collected and organized the demographic data for both the retrospective and the prospective studies. Drs. Harari and Cassandro performed the studies and organized the data for the Italian patients. Dr. Stylianou wrote the

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Funding/Support: This study was funded in part by the Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).

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