27 research outputs found
Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life
Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model.
Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age.
Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels.
Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma
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Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans
Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk.
Objectives—We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis.
Methods: We selected 3186 SNPs for replication based on the p-values from the EVE Consortium meta-analysis. These SNPs were genotyped in ethnically diverse replication samples from nine different studies, totaling to 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study and the resulting test statistics were combined in a meta-analysis.
Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined OR = 1.18; 95% CI 1.10 – 1.25) and rs9570077 (combined OR =1.20 95% CI 1.12–1.29) on chromosome 13q21. We could not replicate any additional associations in the African American or Latino individuals.
Conclusions: This extended replication study identified two additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latino individuals highlights the difficulty in replicating associations in admixed populations
ADRB2 Gly16Arg polymorphism, asthma control and lung function decline
Arg/Arg homozygous for the Gly16Arg polymorphism in ADRB2 have a reduced response to short acting \u3b22-agonists but no effect has been associated with long-acting \u3b22-agonists (LABA). We selected 604 subjects from the European Community Respiratory Health Study with current asthma to evaluate if asthma control and lung function decline were associated with Gly16Arg polymorphism and test if LABA or inhaled corticosteroids (ICS) use modified these effects. There was an increased risk of non-controlled asthma OR=1.33 (1.01-1.75, p=0.046) for each Arg allele. Among nonusers of ICS, the risk of non-controlled asthma among Arg/Arg vs. Gly/Gly subjects was OR=2.73 (1.28-5.82, p=0.009). No increased risk of non-controlled asthma associated to the Arg allele was observed among ICS and/or LABA users. For each Arg allele a decrease of 7.7\u2005mL\ub7year(-1) (SE 2.5) in FEV1 decline was found (p-trend=0.003), irrespective of ICS or LABA use. Arg/Arg subjects vs. Gly/Gly subjects had an increased risk of bronchial hyperresponsiveness with an OR of 2.51 (1.12-5.63, p=0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and bronchial hyperresponsiveness. Absence of genotypic effects on asthma control among ICS users may be due to reversed ADRB2 desensitization
ADRB2 Gly16Arg polymorphism, asthma control and lung function decline.
Arg/Arg homozygous for the Gly16Arg polymorphism in ADRB2 have a reduced response to short acting β2-agonists but no effect has been associated with long-acting β2-agonists (LABA). We selected 604 subjects from the European Community Respiratory Health Study with current asthma to evaluate if asthma control and lung function decline were associated with Gly16Arg polymorphism and test if LABA or inhaled corticosteroids (ICS) use modified these effects. There was an increased risk of non-controlled asthma OR=1.33 (1.01-1.75, p=0.046) for each Arg allele. Among nonusers of ICS, the risk of non-controlled asthma among Arg/Arg vs. Gly/Gly subjects was OR=2.73 (1.28-5.82, p=0.009). No increased risk of non-controlled asthma associated to the Arg allele was observed among ICS and/or LABA users. For each Arg allele a decrease of 7.7 mL·year(-1) (SE 2.5) in FEV1 decline was found (p-trend=0.003), irrespective of ICS or LABA use. Arg/Arg subjects vs. Gly/Gly subjects had an increased risk of bronchial hyperresponsiveness with an OR of 2.51 (1.12-5.63, p=0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and bronchial hyperresponsiveness. Absence of genotypic effects on asthma control among ICS users may be due to reversed ADRB2 desensitization
ADRB2 Gly16Arg polymorphism, asthma control and lung function decline
Arg/Arg homozygotes for the Gly16Arg polymorphism in the
beta(2)-adrenoreceptor gene (ADRB2) have a reduced response to
short-acting beta(2)-agonists but no effect has been associated with
long-acting beta(2)-agonists (LABAs).
We selected 604 subjects with current asthma from the European Community
Respiratory Health Study to evaluate whether asthma control and lung
function decline were associated with Gly16Arg polymorphism, and to test
whether LABA or inhaled corticosteroid (ICS) use modified these effects.
There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI
1.01-1.75; p=0.046) for each Arg allele. Among nonusers of ICS, the odds
ratio of noncontrolled asthma among Arg/Arg versus Gly/Gly subjects was
2.73 (95% CI 1.28-5.82; p=0.009). No increased risk of noncontrolled
asthma associated with the Arg allele was observed among ICS and/or LABA
users. For each Arg allele, a mean+/-SE decrease in decline in forced
expiratory volume in 1 s of 7.7+/-2.5 mL.yr(-1) was found (p-value for
trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an
increased risk of bronchial hyperresponsiveness (BHR) versus Gly/Gly
subjects, with an odds ratio of 2.51 (95% CI 1.12-5.63; p=0.025) if
they did not use ICS.
The Arg allele was associated with poorer asthma control, a steeper lung
function decline and BHR. Absence of genotypic effects on asthma control
among ICS users may be due to reversed beta(2)-adrenoreceptor
desensitisation
ADRB2 Gly16Arg polymorphism, asthma control and lung function decline.
Arg/Arg homozygous for the Gly16Arg polymorphism in ADRB2 have a reduced response to short acting β2-agonists but no effect has been associated with long-acting β2-agonists (LABA). We selected 604 subjects from the European Community Respiratory Health Study with current asthma to evaluate if asthma control and lung function decline were associated with Gly16Arg polymorphism and test if LABA or inhaled corticosteroids (ICS) use modified these effects. There was an increased risk of non-controlled asthma OR=1.33 (1.01-1.75, p=0.046) for each Arg allele. Among nonusers of ICS, the risk of non-controlled asthma among Arg/Arg vs. Gly/Gly subjects was OR=2.73 (1.28-5.82, p=0.009). No increased risk of non-controlled asthma associated to the Arg allele was observed among ICS and/or LABA users. For each Arg allele a decrease of 7.7 mL·year(-1) (SE 2.5) in FEV1 decline was found (p-trend=0.003), irrespective of ICS or LABA use. Arg/Arg subjects vs. Gly/Gly subjects had an increased risk of bronchial hyperresponsiveness with an OR of 2.51 (1.12-5.63, p=0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and bronchial hyperresponsiveness. Absence of genotypic effects on asthma control among ICS users may be due to reversed ADRB2 desensitization