PAI-1, early life infections and asthma risk, exacerbations, and reduced lung function
Rajesh K, Cho S, Min J, Kang J, Chan W, Kim D, Oh S, Torgerson D, del Mar Del-Pino-Yanes M, Hu D, Sen S, Huntsman S, Eng C, Farber HJ, Rodriguez-Santana W, Serebrisky D, Thyne S, Borrell L, Williams KL, Seibold M, Gonzalez Burchard E, Avila PC. PAI-1, early life infections and asthma risk, exacerbations, and reduced lung function. J Allergy Clin Immunol 2016; 137(2 Suppl):AB178.
J Allergy Clin Immunol
RATIONALE: Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if PAI-1 genetic variants and early life lower respiratory infections jointly affect asthma risk.
METHODS:We included Latino children aged 8-21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of aPAI-1 gain of function polymorphism and Respiratory Syncytial Virus(RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function.
RESULTS: RSV infection (9.9, 95%CI 4.9-20.2) and other LRI (9.1, 95%CI 7.2–11.5) were independently associated with asthma, but PAI-1genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3-50.2) and genotype-LRI (OR 11.7,95% CI 8.8-16.4). A joint effect of genotype-RSV resulted in a 3.1-foldincreased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted, FVC % predicted,and FEV1/FVC % predicted were further reduced in the genotype-RSV group (β -7.2, 95% CI -10.3 - -4.2; β -5.7, 95% CI -8.7 - -2.7; and β -1.9, 95% CI -3.7 - -0.2 respectively).
CONCLUSIONS: A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population.