title: Genetic and morphologic determinants of pneumothorax in lymphangioleiomyomatosis.
abstract: Lymphangioleiomyomatosis, a multisystem disease affecting women, is characterized by proliferation of abnormal smooth muscle-like cells in the lungs, leading to cystic destruction of the parenchyma and recurrent pneumothoraces. Clinical characteristics of lymphangioleiomyomatosis patients were analyzed to determine the relationship of pneumothoraces to disease progression. Patients were genotyped for polymorphisms in genes of extracellular matrix proteins collagen, elastin, and matrix metalloproteinase-1 to assess their association with pneumothoraces. Clinical data and polymorphisms in the genes for types I and III collagen, elastin, and matrix metalloproteinase-1 were compared with the prevalence of pneumothorax. Of 227 patients, 57% reported having had at least one pneumothorax. Cyst size on high-resolution computed tomography scans was associated with pneumothorax; patients with a history of pneumothorax were more likely to have larger cysts than patients who had no pneumothoraces. In patients with mild disease, those with a history of pneumothorax had a faster rate of decline in forced expiratory volume in 1 s (FEV(1); P = 0.001, adjusted for age) than those without. Genotype frequencies differed between patients with and without pneumothorax for polymorphisms in the types I and III collagen and matrix metalloproteinase-1 genes. Larger cysts may predispose lymphangioleiomyomatosis patients to pneumothorax, which, in early stages of disease, correlates with a more rapid rate of decline in FEV(1). Polymorphisms in types I and III collagen and matrix metalloproteinase-1 genes may cause differences in lung extracellular matrix that result in greater susceptibility to pneumothorax.
authors.affiliation: Pulmonary Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Bethesda, Maryland 20892-1590, USA.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Steagall
authors.forename: Connie G
authors.initials: CG
authors.lastname: Glasgow
authors.forename: Olanda M
authors.initials: OM
authors.lastname: Hathaway
authors.forename: Nilo A
authors.initials: NA
authors.lastname: Avila
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Taveira-Dasilva
authors.forename: Antoinette
authors.initials: A
authors.lastname: Rabel
authors.forename: Mario P
authors.initials: MP
authors.lastname: Stylianou
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Lin
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Chen
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D018192:Lymphangioleiomyomatosis / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D018700:Pleurodesis; D011030:Pneumothorax / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D011374:Progesterone / Q000494:pharmacology; D011795:Surveys and Questionnaires; D014057:Tomography, X-Ray Computed; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D011374:Progesterone