摘要
背景和目的：哮喘和呼吸衰竭在儿童中的发病率较低，但在急性哮喘儿童中较常见。除了临床因素和病史因素与呼吸衰竭相关外，某些遗传因素也能预测哮喘患儿的气管插管和机械通气，但之前未在该人群中进行研究。我们认为，β2肾上腺素受体（ADRβ2）遗传多态性与哮喘患儿的气管插管和机械通气相关。
材料与方法：对2002年～2008年因严重哮喘加重而在重症监护室（ICU）治疗的104名患者进行ADRβ2基因分型检测。同时，无气管插管与因呼吸衰竭而气管插管的患儿比较ADRβ2 基因型。
结果：在16位氨基酸，33%（n = 34）的儿童甘氨酸等位基因为纯合子（Gly16Gly），15%（n = 16）的患儿精氨酸等位基因为纯合子（Arg16Arg），52%的患儿（n = 54）为杂合子（Arg16Gly）。在27位氨基酸，54%的患儿（n = 56）谷氨酰胺等位基因为纯合子（Gln27Gln），8%（n = 8）的患儿谷氨酸等位基因为纯合子（Glu27Glu），38%的患儿（n = 40）为杂合子（Gln27Glu）。这些位点的单倍体为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）。12名儿童因为呼吸衰竭进行气管插管。气管插管与年龄、肥胖、种族以及NHBLI哮喘分类无关。然而，ADRβ2的Arg16Gly-Gln27Gln单倍体患儿更有可能出现气管插管和机械通气（OR = 4.2; 95% CI = 1.2-14.5; P=0.036）。对气管插管患儿亚群进行分析后显示，Arg16Gly-Gln27Gln单倍体患儿的ICU住院时间更长（329 ± 270 h vs. 124 ± 57 h；P=0.09），但无统计学显著性。
结论：ADRβ2的Arg16Gly-Gln27Gln单倍体哮喘患儿，在哮喘严重加重时，出现气管插管和机械通气的可能性是其他患儿的4倍。遗传因素能影响哮喘急性加重时更为严重的哮喘表型的出现。
(林江涛 审校)
J Asthma. 2012 Aug;49(6):563-8.
β(2)-Adrenergic Receptor Haplotype Linked to Intubation and Mechanical Ventilation in Children with Asthma.
Carroll CL, Sala KA, Zucker AR, Schramm CM.
Source
Department of Pediatrics, Connecticut Children’s Medical Center , Hartford, CT , USA.
Abstract
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.
J Asthma. 2012 Aug;49(6):563-8.
背景和目的：哮喘和呼吸衰竭在儿童中的发病率较低，但在急性哮喘儿童中较常见。除了临床因素和病史因素与呼吸衰竭相关外，某些遗传因素也能预测哮喘患儿的气管插管和机械通气，但之前未在该人群中进行研究。我们认为，β2肾上腺素受体（ADRβ2）遗传多态性与哮喘患儿的气管插管和机械通气相关。
材料与方法：对2002年～2008年因严重哮喘加重而在重症监护室（ICU）治疗的104名患者进行ADRβ2基因分型检测。同时，无气管插管与因呼吸衰竭而气管插管的患儿比较ADRβ2 基因型。
结果：在16位氨基酸，33%（n = 34）的儿童甘氨酸等位基因为纯合子（Gly16Gly），15%（n = 16）的患儿精氨酸等位基因为纯合子（Arg16Arg），52%的患儿（n = 54）为杂合子（Arg16Gly）。在27位氨基酸，54%的患儿（n = 56）谷氨酰胺等位基因为纯合子（Gln27Gln），8%（n = 8）的患儿谷氨酸等位基因为纯合子（Glu27Glu），38%的患儿（n = 40）为杂合子（Gln27Glu）。这些位点的单倍体为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）。12名儿童因为呼吸衰竭进行气管插管。气管插管与年龄、肥胖、种族以及NHBLI哮喘分类无关。然而，ADRβ2的Arg16Gly-Gln27Gln单倍体患儿更有可能出现气管插管和机械通气（OR = 4.2; 95% CI = 1.2-14.5; P=0.036）。对气管插管患儿亚群进行分析后显示，Arg16Gly-Gln27Gln单倍体患儿的ICU住院时间更长（329 ± 270 h vs. 124 ± 57 h；P=0.09），但无统计学显著性。
结论：ADRβ2的Arg16Gly-Gln27Gln单倍体哮喘患儿，在哮喘严重加重时，出现气管插管和机械通气的可能性是其他患儿的4倍。遗传因素能影响哮喘急性加重时更为严重的哮喘表型的出现。
(林江涛 审校)
J Asthma. 2012 Aug;49(6):563-8.
β(2)-Adrenergic Receptor Haplotype Linked to Intubation and Mechanical Ventilation in Children with Asthma.
Carroll CL, Sala KA, Zucker AR, Schramm CM.
Source
Department of Pediatrics, Connecticut Children’s Medical Center , Hartford, CT , USA.
Abstract
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.
J Asthma. 2012 Aug;49(6):563-8.
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