Association of elevated plasminogen activator inhibitor 1 levels with diminished lung function in patients with asthma

Background: We previously reported that plasminogen activator inhibitor 1 (PAI-1) was upregulated in human asthmatic airways and promotes airway fibrosis in an allergen-challenged murine model of asthma. Objectives: To examine whether elevated plasma levels of PAI-1 are associated with poor lung function in asthmatic patients. Methods: Five hundred nineteen adults were eligible for the study, and ultimately 353 adults were enrolled and completed the baseline protocol between January 24, 2004, and July 30, 2005. Of these, 231 adults with asthma from the Chicago Initiative to Raise Asthma Health Equity study were randomly selected and the plasma levels of PAI-1 were measured by enzyme-linked immunosorbent assay. Asthma burden, medication, smoking status, and body mass index (BMI) were obtained by history and spirometry was performed. A multivariate regression analysis was performed to evaluate the association of PAI-1 levels and lung function and the potential determinant variables that were associated with PAI-1. Results: We found associations between PAI-1 and BMI (β = 0.606, P = .002), smoking (β = 7.526, P = .001), and African American race (β = -9.061, P = .01). Obese patients showed a significant increase in PAI-1, and current smokers demonstrated higher levels of PAI-1 compared with nonsmokers. When we evaluated the associations between lung function parameters and PAI-1, we found that PAI-1 was negatively associated with forced vital capacity (FVC) (β = -0.098, P = .011) but not with forced expiratory volume in 1 second (FEV ₁) or the FEV ₁/FVC ratio. There was a negative association between BMI and FVC, and PAI-1 may mediate some of this association. Conclusions: This study suggests a significant association between PAI-1 and lung function in patients with asthma. The effect of obesity on FVC may in part be mediated by PAI-1.