Single Nucleotide Polymorphisms (SNPs) in PRKG1 & SPATA13-AS1 are associated with bronchodilator response: a pilot study during acute asthma exacerbations in African American children.

OBJECTIVE: Inhaled bronchodilators are the first-line treatment for asthma exacerbations, but individual bronchodilator response (BDR) varies by race and ethnicity. Studies have examined BDR's genetic underpinnings, but many did not include children or were not conducted during an asthma exacerbation. This pilot study tested single-nucleotide polymorphisms' (SNPs') association with pediatric African American BDR during an acute asthma exacerbation. METHODS: This was a study of pediatric asthma patients in the age group 2-18 years treated in the emergency department for an asthma exacerbation. We measured BDR before and after inhaled bronchodilator treatments using both the Pediatric Asthma Severity Score (PASS) and asthma severity score. We collected genomic DNA and examined whether 21 candidate SNPs from a review of the literature were associated with BDR using crude odds ratios (OR) and adjusted analysis. RESULTS: The final sample population was 53 children, with an average age of 7.2 years. The average initial PASS score (scale of ascending severity from 0 to 6) was 2.5. After adjusting for BMI, age category, gender and smoke exposure, rs912142 was associated with decreased odds of having low BDR (OR, 0.20; 95% confidence interval (CI), 0.02-0.92), and rs7081864 and rs7903366 were associated with decreased odds of having high BDR (OR, 0.097; 95% CI, 0.009-0.62). CONCLUSIONS: We found three SNPs significantly associated with pediatric African American BDR that provide information regarding a child's potential response to emergency asthma exacerbation treatment. Once validated in larger studies, such information could guide pharmacogenomic evidence-based emergency asthma treatment to improve patient outcomes.

Methods and implementation of a pediatric asthma pharmacogenomic study in the emergency department setting.

OBJECTIVES: The emergency department (ED) is a challenging setting to conduct pharmacogenomic studies and integrate that data into fast-paced and potentially life-saving treatment decisions. Therefore, our objective is to present the methods and feasibility of a pilot pharmacogenomic study set in the ED that measured pediatric bronchodilator response (BDR) during acute asthma exacerbations. METHODS: This is an exploratory pilot study that collected buccal swabs for DNA and measured BDR during ED encounters for pediatric asthma exacerbations. We evaluated the study's feasibility with a qualitative analysis of ED provider surveys and quantitatively by the proportion of eligible patients enrolled. RESULTS: We enrolled 59 out of 90 patients (65%) that were identified and considered eligible during a 5-month period (target enrollment 60 patients over 12 months). The median patient age was 7 years (interquartile range 4-9 years), 61% (N = 36) were male, and 92% (N = 54) were African American. Quality DNA collection was successful for all 59 patients. The ED provider survey response rate was 100%. Most ED providers reported that the study did not impact their workflow (98% of physicians, 88% of nurses, and 90% of respiratory therapists). ED providers did report difficulties with spirometry in the younger age group. CONCLUSIONS: Pharmacogenomic studies can be conducted in the ED setting, and enroll a younger patient population with a high proportion of minority participants. By disseminating this study's methods and feasibility analysis, we aim to increase interest in pharmacogenomic studies set in the ED and aimed toward future ED-based pharmacogenomic decision-making.

Ondansetron Prescription Is Associated With Reduced Return Visits to the Pediatric Emergency Department for Children With Gastroenteritis.

STUDY OBJECTIVE: We determine whether an ondansetron prescription for pediatric patients with vomiting or gastroenteritis is associated with decreased return visits to the emergency department (ED), and whether alternate diagnoses are more frequent on return visits in patients prescribed ondansetron. METHODS: This is a retrospective cohort study of patients 6 months to 18 years of age, presenting to a pediatric ED or its affiliated urgent care centers between 2012 and 2017 with an International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, 10th Revision diagnosis of gastroenteritis, gastritis, vomiting, or vomiting with diarrhea. Multivariate logistic regression analysis was used to measure the association between an ondansetron prescription and the odds of 72-hour return visits. Rates of alternate diagnoses on return visits (appendicitis, intussusception, intracranial mass, meningitis, and diabetic ketoacidosis) were compared between patients who were prescribed ondansetron for home use and those who were not. RESULTS: A total of 82,139 patients were studied, with a median age of 4 years. An ondansetron prescription was given to 13.4% of patients on discharge. The 72-hour return visit rate was 4.7%. Patients receiving an ondansetron prescription had decreased odds of 72-hour return visits (adjusted odds ratio 0.84; 95% confidence interval 0.75 to 0.93). The subgroup of patients specifically receiving a diagnosis of gastroenteritis had decreased odds of 72-hour return visits (adjusted odds ratio 0.82; 95% confidence interval 0.72 to 0.95). There was no significant difference between groups in the diagnosis of appendicitis on return visit (odds ratio 0.97; 95% confidence interval 0.37 to 2.18). CONCLUSION: An ondansetron prescription is associated with reduced 72-hour ED return visit rates for children with vomiting or acute gastroenteritis and is not associated with masking alternate diagnoses.