585
PAI-1, Early Life Infections and Asthma Risk, Exacerbations, and Reduced Lung Function
Sunday, March 6, 2016: 3:00 PM
Room 502B (Convention Center)
Rajesh Kumar, MD, MS, FAAAAI, , , , , , , , , , , , , , , , , , , , , ,
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 a PAI-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-1 genotype 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-fold increased 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.