Chest
Volume 144, Issue 2, August 2013, Pages 578-585
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Original Research
Diffuse Lung Disease
Lymphangioleiomyomatosis Screening in Women With Tuberous Sclerosis

https://doi.org/10.1378/chest.12-2813Get rights and content

Background

Lymphangioleiomyomatosis (LAM) occurs in at least 40% of women with tuberous sclerosis complex (TSC), as diagnosed based on chest CT scan findings. Early identification may inform lifestyle choices and treatment decisions. Here we report LAM prevalence in a large TSC clinic and propose an approach to CT scan screening for LAM in women with TSC.

Methods

We retrospectively reviewed initial chest CT scans of all female patients with TSC aged ≥ 15 years seen at our center over a 12-year period. Each CT image slice was manually scored for the presence or absence of characteristic thin-walled cysts, and the diagnosis of LAM was made if the sum of the cysts on all slices exceeded three cysts.

Results

Of 133 female patients with TSC, 101 had chest CT scans available for review. Forty-eight (47.5%) met criteria for TSC-LAM on the initial CT scan. The risk of LAM was age dependent, rising by about 8% per year. The prevalence of LAM was 27% in subjects < 21 years of age and 81% in subjects > 40 years of age. Among asymptomatic subjects with LAM, 84% had cysts present in the single image at the level of the carina. Most subjects with LAM eventually developed pulmonary symptoms (63%), and 12.5% died from LAM.

Conclusions

These results suggest that most women with TSC ultimately develop cystic changes consistent with LAM and that most cases can be identified from a single CT imaging slice at the level of the carina. TSC-LAM was associated with appreciable morbidity and mortality in this referral population. An age-based approach using limited CT scanning methods may facilitate screening and subsequent treatment decisions with decreased radiation exposure in this at-risk population.

Section snippets

Materials and Methods

We performed a retrospective review of chest CT scans for all female patients with TSC aged ≥ 15 years seen at the Tuberous Sclerosis Clinic at Cincinnati Children's Hospital Medical Center from 1999 to 2011. This study was approved by the institutional review board at Cincinnati Children's Hospital Medical Center and The University of Cincinnati (#2010-0776). The diagnosis of TSC was established using clinical criteria, by genetic analysis, or both. The initial conventional, volumetric, or

Study Subjects

We identified 133 female patients with TSC aged ≥ 15 years seen in our TSC clinic from 1999 to 2011, 82.7% of whom had undergone a chest CT scan (Fig 1). A subset of subjects were excluded from further analysis because the scans were not available for review (n = 3) or because inadequate quality precluded accurate interpretation (motion artifact, n = 4; spinal rods, n = 2). Of the 101 female subjects with CT scans of acceptable quality available for review, 48 (47.5%) had TSC-LAM based on the

Discussion

The long-term goal of this line of investigation is to develop strategies for safe and effective screening for TSC-LAM in this at-risk population. We identified age as a critical clinical risk factor for development of cystic lung disease in women with TSC, with marked increase in probability of LAM observed after age 30 years. As cystic lung disease prevalence was 81% in TSC subjects > 40 years of age, our data suggest that LAM may be nearly inevitable in women with TSC. Furthermore, we

Acknowledgments

Author Contributions: Dr Young is responsible for the overall study inception, execution, and data interpretation.

Dr Cudzilo: contributed to case ascertainment and chart review, CT scan review and scoring, study design, data analysis, and drafting of the manuscript.

Dr Szczesniak: contributed to study design, statistical analyses, data analysis, and drafting of the manuscript.

Dr Brody: contributed to CT scan review and scoring, study design, data analysis, and drafting of the manuscript.

Dr

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    Drs Cudzilo and Szczesniak contributed equally to this manuscript.

    Funding/Support: This study was supported by the Department of Defense [Grant W81XWH-10-1-0885 to Drs McCormack and Young].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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