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ABSTRACT: Status asthmaticus is a frequent cause of admission to a pediatric intensive care unit. Prompt assessment and aggressive treatment are critical. First-line or conventional treatment includes supplemental oxygen, aerosolized albuterol, and corticosteroids. There are several second-line treatments available; however, few comparative studies have been performed and in the absence of good evidence-based treatments, the use of these therapies is highly variable and dependent on local practice and provider preference. In this article the pathophysiology and treatment of status asthmaticus is discussed, and the literature regarding second-line treatments is critically assessed to apply an evidence basis to the treatment of this severe disease.
Critical care clinics 04/2013; 29(2):153-66. · 1.72 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Journal of Asthma 08/2012; 49(6):563-8. · 1.52 Impact Factor
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ABSTRACT: During severe exacerbations, asthmatic children vary significantly in their response to high-dose continuous β(2) -adrenergic receptor (ADRβ(2) ) agonist therapy. Genetic polymorphisms have been identified within the ADRβ(2) that may be functionally relevant, but few studies have been performed in this population. Our hypothesis was that genotypic differences are associated with magnitude of response to ADRβ(2) agonist treatment during severe asthma exacerbations in children.
Children aged 2-18 years admitted to the ICU (intensive care unit) with a severe asthma exacerbation between 2006 and 2008 were eligible. Genotyping of the ADRβ(2) was performed.
Eighty-nine children consented and were enrolled. Despite similar clinical asthma scores on admission, children with the Gly(16) Gly genotype at amino acid position 16 had significantly shorter ICU length of stay (LOS) and hospital LOS, compared to children with Arg(16) Arg and Arg(16) Gly genotypes. Children with either the Gln(27) Glu or Glu(27) Glu genotype at amino acid position 27 also had significantly shorter ICU LOS and hospital LOS compared to children with the Gln(27) Gln genotype. The Arg(16) Gly-Gln(27) Gln haplotype was associated with the longest ICU LOS, but this was not statistically different from other haplotypes.
In this cohort of children with severe asthma exacerbations, ADRβ(2) polymorphisms were associated with responses to therapy. Knowledge of the genetic profile of children with asthma may allow for targeted therapy during acute exacerbations.
Pediatric Pulmonology 09/2011; 47(3):233-9. · 2.53 Impact Factor
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ABSTRACT: Asthma exacerbations are one of the most common causes of hospitalization in children and account for approximately 10,000 intensive care unit (ICU) admissions per year in the United States. Despite the prevalence of this disease in children, the factors associated with the development of these severe exacerbations are largely unknown.
A retrospective case-control study was conducted involving all eligible children admitted to the hospital with asthma for a 1-year period. Potential associated factors and outcomes of children admitted to the ICU with a severe exacerbation (cases) were compared to those of children with acute asthma admitted to the ward (controls).
A total of 188 children were hospitalized with asthma during the study period, 57 (30%) of whom required admission to the ICU. There were no differences in age, gender, or race between cases and controls. Children admitted to the ICU were significantly more likely to have an allergy or irritant-triggered exacerbation than children admitted to the ward (OR 3.9; 95% CI 1.9-8.2; p = .0003). Additionally, children in the ICU had a significantly shorter duration of illness before being admitted to the hospital compared to those admitted to the ward (1.7 ± 2.3 vs. 3.4 ± 4.8 days; p = .002).
In this retrospective review, severe asthma exacerbations in children are associated with a more rapid onset of symptoms and are more likely to be associated with allergens or irritants, supporting the importance of atopy in this population.
Journal of Asthma 06/2011; 48(6):558-64. · 1.52 Impact Factor
