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β 2-adrenergic receptor haplotype linked to intubation and mechanical ventilation in children with asthma

机译：β2-肾上腺素能受体单倍型与哮喘儿童气管插管和机械通气相关

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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 β2-adrenergic receptor (ADRβ2) are associated with intubation and mechanical ventilation in children with asthma. Materials and methods. We performed genotyping of the ADRβ2 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 ADRβ2 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 1.214.5; p = .036) than children with other haplotypes of the ADRβ2. 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 ADRβ2 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.
机译：背景和目标。哮喘和呼吸衰竭的儿童占急性哮喘儿童的一小部分，但占很大比例。除了与呼吸衰竭相关的临床和历史因素外，还可能有遗传因素使一些哮喘儿童易患气管插管和机械通气。但是，这尚未在此人群中进行评估。我们假设β2-肾上腺素能受体（ADRβ2）的遗传多态性与哮喘儿童的插管和机械通气有关。材料和方法。我们对2002年至2008年间入选重症监护病房（ICU）并重度哮喘加重的104名儿童的ADRβ2基因型进行了基因分型。将ADRβ2的基因型与插管法进行了呼吸衰竭比较。结果。在第16个氨基酸位置，有33（n = 34）个儿童的甘氨酸等位基因（Gly16Gly）是纯合子，有15％（n = 16）的精氨酸等位基因（Arg16Arg）是纯合子，有52％（n = 54）是儿童。杂合的（Arg16Gly）。在第27位氨基酸处，谷氨酰胺等位基因（Gln27Gln）的纯合子为54％（n = 56），谷氨酸等位基因（Glu27Glu）的纯合子为8％（n = 8），38％（n = 40）为纯合子。 ）是杂合子（Gln27Glu）。这些位置的单倍型为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）和Gly16Gly-Glu27Glu（8％，n ＝ 8）。该队列中的十二名儿童因呼吸衰竭而插管。插管与年龄，肥胖，种族/民族或NHBLI哮喘分类无关。但是，具有Arg16Gly-Gln27Gln单倍型的儿童比具有其他ADRβ2单倍型的儿童插管和机械通气的可能性更高（OR = 4.2; 95％CI 1.214.5; p = .036）。在检查插管儿童的子集时，具有Arg16Gly-Gln27Gln单倍型的儿童倾向于ICU的住院时间更长（329±270 vs. 124±57小时; p = .09），但这在统计学上并不显着。结论。在严重哮喘加重期间，具有ADRβ2的Arg16Gly-Gln27Gln单倍型的儿童进行插管和机械通气的可能性高出四倍。遗传因素可能会影响急性发作期间更严重的哮喘表型的发展。

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