Implementation of the asthma CPM was associated with improved compliance with CAC-3 and with a delayed, yet significant and sustained decrease in hospital asthma readmission rates, validating CAC-3 as a quality measure. Due to high baseline compliance, CAC-1 and CAC-2 are of questionable value as quality measures.

Inhaled irritants activate transient receptor potential ankyrin-1 (TRPA1), resulting in cough, bronchoconstriction, and inflammation/edema. TRPA1 is also implicated in the pathogenesis of asthma. Our hypothesis was that particulate materials activate TRPA1 via a mechanism distinct from chemical agonists and that, in a cohort of children with asthma living in a location prone to high levels of air pollution, expression of uniquely sensitive forms of TRPA1 may correlate with reduced asthma control. Variant forms of TRPA1 were constructed by mutating residues in known functional elements and corresponding to single-nucleotide polymorphisms in functional domains. TRPA1 activity was studied in transfected HEK-293 cells using allyl-isothiocynate, a model soluble electrophilic agonist; 3,5-ditert butylphenol, a soluble nonelectrophilic agonist and a component of diesel exhaust particles; and insoluble coal fly ash (CFA) particles. The N-terminal variants R3C and R58T exhibited greater, but not additive, activity with all three agonists. The ankyrin repeat domain-4 single nucleotide polymorphisms E179K and K186N exhibited decreased response to CFA. The predicted N-linked glycosylation site residues N747A and N753A exhibited decreased responses to CFA, which were not attributable to differences in cellular localization. The pore-loop residue R919Q was comparable to wild-type, whereas N954T was inactive to soluble agonists but not CFA. These data identify roles for ankyrin domain-4, cell surface N-linked glycans, and selected pore-loop domain residues in the activation of TRPA1 by insoluble particles. Furthermore, the R3C and R58T polymorphisms correlated with reduced asthma control for some children, which suggest that TRPA1 activity may modulate asthma, particularly among individuals living in locations prone to high levels of air pollution.

BACKGROUND AND OBJECTIVES: Gaps exist in inpatient asthma care. Our aims were to assess the impact of an evidence-based care process model (EB-CPM) 5 years after implementation at Primary Children's Hospital (PCH), a tertiary care facility, and after its dissemination to 7 community hospitals.METHODS: Participants included asthmatics 2 to 17 years admitted at 8 hospitals between 2003 and 2013. The EB-CPM was implemented at PCH between January 2008 and March 2009, then disseminated to 7 community hospitals between January and June 2011. We measured compliance using a composite score (CS) for 8 quality measures. Outcomes were compared between preimplementation and postimplementation periods. Confounding was addressed through multivariable regression analyses.RESULTS: At PCH, the CS increased and remained at .90% for 5 years after implementation. We observed sustained reductions in asthma readmissions (P = .026) and length of stay (P , .001), a trend toward reduced costs (P = .094), and no change in hospital resource use, ICU transfers, or deaths. The CS also increased at the 7 community hospitals, reaching 80% to 90% and persisting .2 years after dissemination, with a slight but not significant readmission reduction (P = .119), a significant reduction in length of stay (P , .001) and cost (P = .053), a slight increase in hospital resource use (P = .032), and no change in ICU transfers or deaths.CONCLUSIONS: Our intervention resulted in sustained, long-term improvement in asthma care and outcomes at the tertiary care hospital and successful dissemination to community hospitals.

Objective To determine the relationship between allelic variations in genes involved in fluticasone propionate (FP) metabolism and asthma control among children with asthma managed with inhaled FP. Study design The relationship between variability in asthma control scores and genetic variation in drug metabolism was assessed by genotyping nine single nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, and CYP3A7. Genotype information was compared with asthma control scores (0 = well-controlled to 15 = poorly-controlled), determined by using a questionnaire modified from the National Heart Lung and Blood Institute Expert Panel 3 guidelines. Results Our study cohort was comprised of 734 children with asthma (mean age 8.8 ± 4.3 years), who were predominantly male (61%) and non-Hispanic Whites (53%); 413 children (56%) were receiving inhaled glucocorticoids daily, of which FP was prescribed most frequently (65%). Among the children receiving daily FP, SNPs in the genes CYP3A5 and CYP3A7 were not associated with asthma control scores. In contrast, asthma control scores were significantly improved among 20 (7%) children with the CYP3A4*22 allele (median 3, range 0-6), as compared with the 201 patients without the CYP3A4*22 allele (median 4, range 0-15) (P=0.02). The presence of CYP3A4*22 was associated with improved asthma control scores by 2.1 points (95% CI: 0.5-3.8). Conclusions The presence of CYP3A4*22, which is associated with decreased hepatic CYP3A4 expression and activity, was accompanied by improved asthma control among FP treated children. Decreased CYP3A4 activity may improve asthma control with inhaled FP.

Neighborhood-level ADI measure is associated with asthma hospitalization outcomes. However, insurance coverage modifies this relationship and needs to be considered when using the ADI to identify and address health care disparities.