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Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

ABSTRACT: BACKGROUND:Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk. METHODS:We included Latino children, adolescents, and young adults 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 bronchiolitis / 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 (OR 9.9, 95%CI 4.9-20.2) and other LRI (OR 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 and FEV1/FVC % predicted were further reduced in the genotype-LRI group (? -2.1, 95% CI -4.0 to -0.2; ? -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (? -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted. 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.

SUBMITTER: Cho SH

PROVIDER: S-EPMC4996454 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

Cho Seong H SH Min Jin-Young JY Kim Dong Young DY Oh Sam S SS Torgerson Dara R DR Pino-Yanes Maria M Hu Donglei D Sen Saunak S Huntsman Scott S Eng Celeste C Farber Harold J HJ Rodriguez-Cintron William W Rodriguez-Santana Jose R JR Serebrisky Denise D Thyne Shannon M SM Borrell Luisa N LN Williams L Keoki LK DuPont William W Seibold Max A MA Burchard Esteban G EG Avila Pedro C PC Kumar Rajesh R

PloS one 20160824 8

<h4>Background</h4>Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.<h4>Methods</h4>We included Latino children, adolescents, and young adults 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 clini ...[more]

PMID: 27556405

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Project description:Changes in dietary patterns may partly explain the epidemic of asthma in industrialized countries. The objective of this study was to examine the relationship between dietary patterns and lung function and asthma exacerbations in Puerto Rican children. This is a case-control study of 678 Puerto Rican children (ages 6-14 years) in San Juan (Puerto Rico). All participants completed a respiratory health questionnaire and a 75-item food frequency questionnaire. Food items were aggregated into 7 groups: fruits, vegetables, grains, protein, dairy, fats, and sweets. Logistic regression was used to evaluate consumption frequency of each group and asthma. Based on the results, a dietary score was created [range from -2 (unhealthy diet: high consumption of dairy and sweets, low consumption of vegetables and grains) to 2 (healthy diet: high consumption of vegetables and grains and low consumption of dairy and sweet)]. Multivariable linear or logistic regression was used to assess the relationship between dietary score and lung function or asthma exacerbations. After adjustment for covariates, a healthier diet (each 1-point increment in dietary score) was associated with significantly higher %predicted forced expiratory volume in the first second (FEV1) and %predicted forced vital capacity (FVC) in control subjects. Dietary pattern alone was not associated with asthma exacerbations, but children with an unhealthy diet and vitamin D insufficiency (plasma 25(OH)D <30?ng/mL) had higher odds of ?1 severe asthma exacerbation [odds ratio (OR)?=?3.4, 95% confidence interval (CI)?=?1.5-7.5] or ?1 hospitalization due to asthma (OR?=?3.9, 95% CI?=?1.6-9.8, OR?=?3.4, 95% CI?=?1.5-7.5) than children who ate a healthy diet and were vitamin D sufficient. A healthy diet, with frequent consumption of vegetables and grains and low consumption of dairy products and sweets, was associated with higher lung function (as measured by FEV1 and FVC). Vitamin D insufficiency, together with an unhealthy diet, may have detrimental effects on asthma exacerbations in children.

Project description:RationaleAllergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.ObjectivesTo test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma.MethodsIn the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression.Measurements and main resultsRVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84).ConclusionsIn children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).

Dataset Information

Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

Publications

Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function.

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