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β2-adrenergic receptor haplotype linked to intubation and mechanical ventilation in children with asthma
Christopher L Carroll1, Kathleen A Sala, Aaron R Zucker
1Department of Pediatrics, Connecticut Children's Medical Center, 282 Washington Street, Hartford, CT 06106, USA. ccarrol@ccmckids.org
Insights
Genetic factors, specifically the Arg16Gly-Gln27Gln haplotype of the beta-2 adrenergic receptor (ADRβ2), significantly increase the risk of intubation in children with severe asthma exacerbations.
Area of Science:
- Pediatric Pulmonology
- Medical Genetics
- Asthma Research
Background:
- Asthma exacerbations can lead to respiratory failure in children, necessitating intubation and mechanical ventilation.
- While clinical factors are known, genetic predispositions to severe asthma requiring ventilation are not well understood.
- The beta-2 adrenergic receptor (ADRβ2) plays a role in bronchodilation and asthma management.
Purpose of the Study:
- To investigate the association between genetic polymorphisms of the ADRβ2 and the need for intubation and mechanical ventilation in children with severe asthma.
- To identify specific ADRβ2 genetic variants that may predict a more severe asthma phenotype.
Main Methods:
- Genotyping of the ADRβ2 gene was performed on 104 children admitted to the ICU for severe asthma exacerbations.
- The ADRβ2 genotype, specifically at amino acid positions 16 and 27, was analyzed.
- Associations between ADRβ2 haplotypes and intubation for respiratory failure were statistically evaluated.
Main Results:
- The Arg16Gly-Gln27Gln haplotype of the ADRβ2 was significantly associated with a higher likelihood of intubation (OR = 4.2; p = .036).
- No association was found between intubation and clinical factors like age, obesity, race/ethnicity, or NHLBI asthma classification.
- Children with the identified haplotype showed a trend towards longer ICU stays, though not statistically significant.
Conclusions:
- The Arg16Gly-Gln27Gln ADRβ2 haplotype is a significant genetic risk factor for intubation in pediatric severe asthma exacerbations.
- Genetic variations in the ADRβ2 may contribute to the development of a severe asthma phenotype requiring mechanical ventilation.
- These findings highlight the potential role of pharmacogenetics in managing severe pediatric asthma.
Background And Aims:
Children with asthma and respiratory failure comprise a small but significant subset of children with acute asthma. In addition to clinical and historical factors that have been associated with respiratory failure, there may also be genetic factors that predispose some asthmatic children to intubation and mechanical ventilation. However, this has not previously been assessed in this population. We hypothesized that genetic polymorphisms of the β(2)-adrenergic receptor (ADRβ(2)) are associated with intubation and mechanical ventilation in children with asthma.
Materials And Methods:
We performed genotyping of the ADRβ(2) in a pooled cohort of 104 children admitted to the intensive care unit (ICU) with a severe asthma exacerbation between 2002 and 2008. Genotype of the ADRβ(2) was compared with intubation for respiratory failure.
Results:
At amino acid position 16, 33% (n = 34) of children were homozygous for the glycine allele (Gly16Gly), 15% (n = 16) were homozygous for the arginine allele (Arg16Arg), and 52% (n = 54) were heterozygous (Arg16Gly). At amino acid position 27, 54% (n = 56) of children were homozygous for the glutamine allele (Gln27Gln), 8% (n = 8) were homozygous for the glutamic acid allele (Glu27Glu), and 38% (n = 40) were heterozygous (Gln27Glu). The haplotypes at these positions were Arg16Gly-Gln27Gln (29%, n = 30), Arg16Gly-Gln27Glu (22%, n = 23), Gly16Gly-Gln27Glu (16%, n = 17), Arg16Arg-Gln27Gln (16%, n = 17), Gly16Gly-Gln27Gln (9%, n = 9), and Gly16Gly-Glu27Glu (8%, n = 8). Twelve children in this cohort were intubated for respiratory failure. Intubation was not associated with age, obesity, race/ethnicity, or NHBLI asthma classification. However, children with the Arg16Gly-Gln27Gln haplotype were significantly more likely to be intubated and mechanical ventilated (OR = 4.2; 95% CI = 1.2-14.5; p = .036) than children with other haplotypes of the ADRβ(2). When examining the subset of intubated children, those with the Arg16Gly-Gln27Gln haplotype trended towards longer ICU length of stay (329 ± 270 vs. 124 ± 57 hours; p = .09), but this was not statistically significant.
Conclusions:
Children with the Arg16Gly-Gln27Gln haplotype of the ADRβ(2) were four times more likely to be intubated and mechanically ventilated during severe asthma exacerbations. Genetic factors may influence the development of a more severe asthma phenotype during acute exacerbations.
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