Chest
Volume 126, Issue 6, December 2004, Pages 1867-1874
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Clinical Investigations
PULMONARY FUNCTION TRAITS
Decline in Lung Function in Patients With Lymphangioleiomyomatosis Treated With or Without Progesterone

https://doi.org/10.1378/chest.126.6.1867Get rights and content

Study objective:

Lymphangioleiomyomatosis (LAM), a disease affecting women and causing cystic lung lesions, and, in some instances, leading to respiratory failure and death, appears to be exacerbated by estrogens. Hence, hormonal therapy with progesterone is frequently employed; however, efficacy has not been demonstrated. Our aim was to determine whether progesterone administration slowed the decline in lung function in LAM.

Design:

Retrospective study.

Setting:

National Institutes of Health, Bethesda, MD.

Design and subjects:

The study population comprised 348 patients with LAM participating in a longitudinal research protocol. Declines in diffusion capacity of the lung for carbon monoxide (Dlco) and FEV1 were measured in 275 patients observed for approximately 4 years. The declines in Dlco and FEV1 of patients treated with progesterone, po (n = 67) or IM (n = 72), were compared with those of untreated patients (n = 136).

Measurements and results:

Overall yearly rates of decline in Dlco and FEV1 were 2.4 ≤ 0.4% predicted (0.69 ≤ 0.07 mL/min/mm Hg) and 1.7 ≤ 0.4% predicted (75 ≤ 9 mL), respectively (mean ≤ SEM). The most significant predictors of functional decline were initial lung function and age. After adjusting for initial FEV1, age, and duration of disease, patients treated with IM progesterone tended to have lower rates of decline in FEV1 than patients treated po (1.9 ≤ 0.6% predicted vs 3.2 ≤ 0.8% predicted, respectively; p = 0.081). However, there was no significant difference in rates of decline in FEV1 between patients treated with IM progesterone and untreated patients (1.9 ≤ 0.6% predicted vs 0.8 ≤ 0.5% predicted, respectively; p = 0.520), and patients treated with po progesterone and untreated patients (3.2 ≤ 0.8% predicted vs 0.8 ≤ 0.5% predicted, respectively; p = 0.064). After adjusting for initial Dlco, rates of decline in Dlco were significantly higher in patients treated with po progesterone (3.6 ≤ 0.7% predicted, p = 0.002) and IM progesterone (2.8 ≤ 0.5% predicted, p = 0.022) than in untreated patients (1.6 ≤ 0.6% predicted).

Conclusions:

Within the limitations of a retrospective study, our data suggest that progesterone therapy does not slow the decline in lung function in LAM.

Section snippets

Study Population

The study population consisted of 348 patients with LAM referred to the National Institutes of Health since 1996 for participation in a longitudinal study (National Heart, Lung, and Blood Institute [NHLBI] protocol 95-H-0186) approved by the NHLBI Institutional Review Board. In addition to self-referral or referral through individual physicians, subjects were informed of the study by the LAM Foundation and the Tuberous Sclerosis Alliance. All subjects gave informed consent before enrollment.

Patient Characteristics

The mean age of the 275 patients at the time of the first test was 42.3 ≤ 0.6 years (range, 19 to 77 years). Sixteen patients were Asian, 9 patients were African American, 2 patients were African, and the rest (248) were white. Twelve patients were smokers (10 ≤ 5 pack-years), 25 patients were ex-smokers (20 ≤ 2 pack-years), and the rest were nonsmokers. Mean age at the time of diagnosis was 41.0 ≤ 0.6 years. However, based on the history of LAM-related symptoms (pneumothorax, chylous

Discussion

We report here a retrospective analysis of the decline in lung function in a large population of patients with LAM, focusing on patients who were treated with progesterone by the po or IM route vs those who did not receive hormonal therapy. To quantify the decline in lung function, we selected the Dlco and FEV1 because these tests correlate well with disease severity defined by CT scans and LAM histology scores.101124 Initial Dlco and FEV1 and age were the most important predictors of rates of

ACKNOWLEDGMENT

We thank Dr. Martha Vaughan for discussions and critical review, and Xiaoling Chen for assistance in compilation and analysis of the data. We also thank the LAM Foundation and the Tuberous Sclerosis Alliance for their assistance in recruiting patients. This study would not have been possible without the cooperation of patients with LAM, who, in many cases, traveled great distances to participate in our clinical research protocols.

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      Citation Excerpt :

      Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease which affects women almost exclusively, in either a sporadic form or in association with tuberous sclerosis complex (TSC) [1–6]. LAM is a progressive lung disease, with a mean loss of forced expiratory volume in 1 s (FEV1) of 70–140 mL per year [3,7]. Progression of the disease, although typically gradual, can be life threatening, necessitating referral for lung transplantation.

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    Supported by the NHLBI, Division of Intramural Research.

    Ms. Xiaoling Chen was supported in part by a grant from the LAM Foundation.

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