Search

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 (FEV1; 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 FEV1. 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. [ABSTRACT FROM AUTHOR]

Surfactant protein B (SP-B) is an essential component of surfactant that promotes adsorption and spreading of surfactant phospholipids and stabilizes the phospholipid monolayer. SP-B is essential for respiratory function in newborn humans and mice; adult mice with levels of SP-B below 25% of wild-type develop fatal respiratory distress syndrome. A potential regulatory function of the C/A(-18) single nucleotide polymorphism (SNP) in the promoter of the SP-B gene was examined. Transcriptional analysis and ELISA on bronchoalveolar lavage fluid revealed that the presence of the C allele correlated with more SP-B promoter activity and protein. There was approximately threefold difference in amounts of SP-B in bronchoalveolar lavage fluid from CA(-18) and AA(-18) individuals. By EMSA, Sp1 bound more tightly to the C allele sequence than to the A allele sequence, perhaps accounting for the differences in transcription. Genotyping of a normal volunteer population showed ~31% of the population were AA homozygotes, suggesting that these individuals produce less SP-B. Differences in amounts of SP-B resulting from the promoter SNP could affect the clinical presentation of pulmonary disease. [ABSTRACT FROM AUTHOR]