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Lung Cysts, Spontaneous Pneumothorax, and Genetic Associations in 89 Families with Birt-Hogg-Dubé Syndrome

¹ Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; ² Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; ³ Basic Research Program, SAIC–Frederick, Inc., NCI–Frederick, Frederick, Maryland; and ⁴ Molecular Imaging Program, ⁵ Biostatistics and Data Management Section, and ⁶ Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland

Correspondence and requests for reprints should be addressed to Jorge R. Toro, M.D., Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Executive Plaza South, Room 7012, Rockville, MD 20892-7231. E-mail: torojo{at}exchange.nih.gov

Rationale: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to fibrofolliculomas, kidney neoplasms, lung cysts, and spontaneous pneumothorax.

Objectives: We evaluated 198 patients from 89 families with BHDS to characterize the risk factors for pneumothorax and genotype–pulmonary associations.

Methods: Helical computed tomography scans of the chest were used to screen for pulmonary abnormalities. BHD mutation data were used for genotype–pulmonary associations. We examined the relationship of pneumothorax with categorical parameters (sex, smoking history, and lung cysts) and continuous parameters (number of cysts, lung cyst volume, and largest cyst diameter and volume). Logistic regression analyses were used to identify the risk factors associated with pneumothorax.

Measurements and Main Results: Twenty-four percent (48/198) of patients with BHDS had a history of pneumothorax. The presence of lung cysts was significantly associated with pneumothorax (p = 0.006). Total lung cyst volume, largest cyst diameter and volume, and every parameter related to the number of lung cysts were significantly associated (p < 0.0001) with pneumothorax. A logistic regression analysis showed that only the total number of cysts in the right parenchymal lower lobe and the total number of cysts located on the pleural surface in the right middle lobe were needed to classify a patient as to whether or not he or she was likely to have a pneumothorax. Exon location of the BHD mutation was associated with the numbers of cysts (p = 0.0002).

Conclusions: This study indicates that patients with BHDS have a significant association between lung cysts and spontaneous pneumothorax.

Key Words: Birt-Hogg-Dubé • syndrome • familial spontaneous pneumothorax • lung cysts • fibrofolliculomas • renal neoplasms

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to skin lesions (fibrofolliculomas), kidney cancer, lung cysts, and spontaneous pneumothorax. Germline mutation in the BHD gene predisposes to BHDS. What This Study Adds to the Field Patients with BHDS have a significant association between lung cysts and spontaneous pneumothorax.

 

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