title: Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubé syndrome.
abstract: BACKGROUND
  Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to fibrofolliculomas, kidney neoplasms, lung cysts, and spontaneous pneumothorax.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892-7231, USA. torojo@exchange.nih.gov
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Toro
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Pautler
authors.forename: Laveta
authors.initials: L
authors.lastname: Stewart
authors.forename: Gladys M
authors.initials: GM
authors.lastname: Glenn
authors.forename: Michael
authors.initials: M
authors.lastname: Weinreich
authors.forename: Ousmane
authors.initials: O
authors.lastname: Toure
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Wei
authors.forename: Laura S
authors.initials: LS
authors.lastname: Schmidt
authors.forename: Lewis
authors.initials: L
authors.lastname: Davis
authors.forename: Berton
authors.initials: B
authors.lastname: Zbar
authors.forename: Peter
authors.initials: P
authors.lastname: Choyke
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Dao M
authors.initials: DM
authors.lastname: Nguyen
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
mesh_terms: D001994:Bronchogenic Cyst / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D011030:Pneumothorax / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors; D012871:Skin Diseases / Q000453:epidemiology / Q000235:genetics*; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C476078:FLCN protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins