Aaron R. Zucker

Childhood obesity increases duration of therapy during severe asthma exacerbations

Objectives: Childhood obesity contributes to a wide array of medical conditions, including asthma. There is also increasing evidence in adult patients admitted to the intensive care unit (ICU) that obesity contributes to increased morbidity and to a prolonged length of stay. We hypothesized that obesity is associated with the need for increased duration of therapy in children admitted to the ICU with status asthmaticus. Design: Retrospective cohort study. Setting: A tertiary pediatric ICU in a university-affiliated childrens hospital. Patients: We retrospectively examined data from all children older than 2 yrs admitted to the ICU with status asthmaticus between April 1997 and June 2004. Children were classified as normal weight (<95% weight-for-age percentile) or obese (>95% weight-for-age). Interventions: None. Measurements and Main Results: Of the 209 children admitted to the ICU with asthma, 45 (22%) were obese. Compared with children of normal weight, the obese children were older (9.7 ± 4.4 vs. 8.0 ± 4.3 yrs, p = .02), more likely to be female (60% vs. 37%, p < .01), and more likely to have been admitted to the ICU previously (40% vs. 20%, p = .01). The obese children also had a statistically significant difference in race (more likely to be Hispanic) and in baseline asthma classification (more likely to have persistent asthma). Despite similar severity of illness at ICU admission, obese children had a significantly longer ICU length of stay (116 ± 125 hrs vs. 69 ± 57 hrs, p = .02) and hospital length of stay (9.8 ± 7.0 vs. 6.5 ± 3.4 days, p < .01). Obese children also received longer courses of supplemental oxygen, continuous albuterol, and intravenous steroids. Conclusions: Childhood obesity significantly affects the health of children with asthma. Obese children with status asthmaticus recovered more slowly from an acute exacerbation, even after adjustment for baseline asthma severity and admission severity of illness.

Endotracheal intubation and pediatric status asthmaticus: Site of original care affects treatment*

Objectives: Status asthmaticus is a common cause of admission to a pediatric intensive care unit (PICU). Children unresponsive to medical therapies may require endotracheal intubation; however, this treatment carries significant risk, and thresholds for intubation vary. Our hypothesis was that children who sought care at community hospitals received less aggressive treatment and more frequent intubation than children who sought care at a childrens hospital. Design: Retrospective cohort study. Setting: A university-affiliated childrens hospital PICU. Patients: We retrospectively examined data from all children older than 2 yrs admitted to the PICU with status asthmaticus between April 1997 and July 2005. Interventions: None. Measurements and Main Results: Of the 251 children admitted to the PICU with status asthmaticus, 130 initially presented to the emergency department of a childrens hospital and 116 presented to the emergency department of a community hospital. Despite similar illness severity, children presenting to a community hospital were significantly more likely to be intubated than those presenting to a childrens hospital (17% vs. 5%; p = .004). In addition, those children intubated at community hospitals were intubated sooner after presentation (2.4 ± 5.2 vs. 7.5 ± 5.8 hrs; p = .009), had shorter durations of intubation (71 ± 73 vs. 151 ± 81 hrs; p = .02), and had shorter PICU length of stays (129 ± 82 vs. 230 ± 84 hrs; p = .01). Conclusions: Children with status asthmaticus are more likely to be intubated, and intubated sooner, at a community hospital. The shorter duration of intubation suggests that some children may not have been intubated had they presented to a childrens hospital or received more aggressive therapy at their community hospital.

Severe Exacerbations in Children with Mild Asthma: Characterizing a Pediatric Phenotype

Background: NHLBI guidelines classify asthma in children as intermittent, mild persistent, moderate persistent, and severe persistent asthma based on baseline symptoms and pulmonary function. However, this may not capture the spectrum of asthma in children, since even mild baseline disease can have significant effects on quality of life. Our objective was to describe a population of children with mild asthma admitted to the ICU with severe exacerbations. Methods: We examined data from all children with asthma who were admitted to the ICU with an acute exacerbation between April 1997, and December 2006. Children were defined as having mild asthma if their disease was classified as intermittent or mild persistent according to NHLBI criteria. Results: Of the 298 children admitted to the ICU with asthma, 164 (55%) were classified as having mild baseline asthma. Compared with children with more severe baseline asthma, mild asthmatic children were younger and less likely to have been previously admitted to the hospital for asthma. Other demographics, including admission severity of illness, gender, and prevalence of overweight, were similar in the two groups. There were no differences between the groups in ICU length of stay, hospital length of stay or types of therapies received. Thirteen children with mild asthma were intubated, although less frequently than those with more severe disease. Conclusions: Children with mild asthma have severe exacerbations. This suggests that chronic asthma severity does not necessarily predict asthma phenotypes during acute exacerbations.

β2-Adrenergic Receptor Haplotype Linked to Intubation and Mechanical Ventilation in Children with 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 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 = 1.2–14.5; 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.

Pulmonary Mechanics Following Albuterol Therapy in Mechanically Ventilated Infants with Bronchiolitis

Background and aims. Bronchiolitis is a common cause of critical illness in infants. Inhaled β2-agonist bronchodilators are frequently used as part of treatment, despite unproven effectiveness. The purpose of this study was to describe the physiologic response to these medications in infants intubated and mechanically ventilated for bronchiolitis. Materials and methods. We conducted a prospective trial of albuterol treatment in infants intubated and mechanically ventilated for bronchiolitis. Before and for 30 minutes following inhaled albuterol treatment, sequential assessments of pulmonary mechanics were determined using the interrupter technique on repeated consecutive breaths. Results: Fifty-four infants were enrolled. The median age was 44 days (25–75%; interquartile range (IQR) 29–74 days), mean hospital length of stay (LOS) was 18.3 ± 13.3 days, mean ICU LOS was 11.3 ± 6.4 days, and mean duration of mechanical ventilation was 8.5 ± 3.5 days. Fifty percent (n = 27) of the infants were male, 81% (n = 44) had public insurance, 80% (n = 41) were Caucasian, and 39% (n = 21) were Hispanic. Fourteen of the 54 (26%) had reduction in respiratory system resistance (Rrs) that was more than 30% below baseline, and were defined as responders to albuterol. Response to albuterol was not associated with demographic factors or hospitalization outcomes such as LOS or duration of mechanical ventilation. However, increased Rrs, prematurity, and non-Hispanic ethnicity were associated with increased LOS. Conclusions. In this population of mechanically ventilated infants with bronchiolitis, relatively few had a reduction in pulmonary resistance in response to inhaled albuterol therapy. This response was not associated with improvements in outcomes.