Fellows journal Club
Article: Wechsler, Michael E et al. “Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.” The New England Journal of Medicine vol. 381,13 (2019): 1227-1239.
Fellow: Claire Seguin, MD, MA, Children’s Mercy Hospital, Kansas City
Summary: Wechsler et al. performed two separate prospective, randomized, double-blind, four-way crossover clinical trials comparing step-up dosing of inhaled corticosteroid (ICS) with or without long-acting beta-agonist (LABA) in black children aged 5-12 years old (study 1) and adolescents and adults aged >12 years old (study 2) all with poorly controlled asthma. The primary outcomes of exacerbations, control days and percent predicted FEV1 were hierarchically evaluated in this order to assign treatment superiority. In children, increasing ICS x4 without LABA and increasing ICS x2 with LABA led to equivalent response (p=0.99). Both of these regimens led to superior response compared to increasing ICS x2 alone. In contrast, more adults and adolescents had superior responses with ICS x1 with added LABA as compared to increasing ICS x2.5 or x5 or increasing ICS x2.5 with LABA. Every person in the study had at least one grandparent who identified as black, and there were no associations between percentage of African ancestry assessed by genomic markers and treatment responses.
Key Strengths: One major strength of this article is its study design as a double-blind, randomized trial that compared treatment responses for individual children and adolescents/adults. The study included black Americans, a population that is both disproportionally affected by asthma and under-represented in previous clinical trials that heavily inform guidelines and practice.
Limitations/Flaws: Environmental and social inequities are known to impact asthma outcomes of black Americans, yet these factors were not considered. The study used dry powder inhalers which, while approved to age 5, are not ideal for younger children because of the inhalation force needed for consistent delivery of medications. While not necessarily a limitation, salmeterol was used in this study, while formoterol has been most extensively studied for single-inhaler and controller therapies. Finally, the study narrowly (by 4 patients) missed the target sample size to achieve its intended power.
Takeaway Message: Black children with uncontrolled asthma had similar response to increasing ICS x4 and increasing ICS x2 with added LABA, a result not seen in studies of black adults or white adults or children. This study highlights the importance of clinical study participation that is inclusive of the population of patients for whom medications and guidelines are used.
Practice Impact: As we begin to implement the updated National Heart Lung and Blood Institute’s EPR-4 guidelines (1), we should keep in mind that much of the supporting data is from predominantly white study populations and continue to advocate for follow-up research with study populations representative of our patients.
1 Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, Dixon AE, Elward KS, Hartert T, Krishnan JA, Lemanske RF Jr, Ouellette DR, Pace WD, Schatz M, Skolnik NS, Stout JW, Teach SJ, Umscheid CA, Walsh CG. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. Erratum in: J Allergy Clin Immunol. 2021 Apr;147(4):1528-1530. PMID: 33280709; PMCID: PMC7924476.
Fellow: Claire Seguin, MD, MA, Children’s Mercy Hospital, Kansas City
Summary: Wechsler et al. performed two separate prospective, randomized, double-blind, four-way crossover clinical trials comparing step-up dosing of inhaled corticosteroid (ICS) with or without long-acting beta-agonist (LABA) in black children aged 5-12 years old (study 1) and adolescents and adults aged >12 years old (study 2) all with poorly controlled asthma. The primary outcomes of exacerbations, control days and percent predicted FEV1 were hierarchically evaluated in this order to assign treatment superiority. In children, increasing ICS x4 without LABA and increasing ICS x2 with LABA led to equivalent response (p=0.99). Both of these regimens led to superior response compared to increasing ICS x2 alone. In contrast, more adults and adolescents had superior responses with ICS x1 with added LABA as compared to increasing ICS x2.5 or x5 or increasing ICS x2.5 with LABA. Every person in the study had at least one grandparent who identified as black, and there were no associations between percentage of African ancestry assessed by genomic markers and treatment responses.
Key Strengths: One major strength of this article is its study design as a double-blind, randomized trial that compared treatment responses for individual children and adolescents/adults. The study included black Americans, a population that is both disproportionally affected by asthma and under-represented in previous clinical trials that heavily inform guidelines and practice.
Limitations/Flaws: Environmental and social inequities are known to impact asthma outcomes of black Americans, yet these factors were not considered. The study used dry powder inhalers which, while approved to age 5, are not ideal for younger children because of the inhalation force needed for consistent delivery of medications. While not necessarily a limitation, salmeterol was used in this study, while formoterol has been most extensively studied for single-inhaler and controller therapies. Finally, the study narrowly (by 4 patients) missed the target sample size to achieve its intended power.
Takeaway Message: Black children with uncontrolled asthma had similar response to increasing ICS x4 and increasing ICS x2 with added LABA, a result not seen in studies of black adults or white adults or children. This study highlights the importance of clinical study participation that is inclusive of the population of patients for whom medications and guidelines are used.
Practice Impact: As we begin to implement the updated National Heart Lung and Blood Institute’s EPR-4 guidelines (1), we should keep in mind that much of the supporting data is from predominantly white study populations and continue to advocate for follow-up research with study populations representative of our patients.
1 Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, Dixon AE, Elward KS, Hartert T, Krishnan JA, Lemanske RF Jr, Ouellette DR, Pace WD, Schatz M, Skolnik NS, Stout JW, Teach SJ, Umscheid CA, Walsh CG. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270. doi: 10.1016/j.jaci.2020.10.003. Erratum in: J Allergy Clin Immunol. 2021 Apr;147(4):1528-1530. PMID: 33280709; PMCID: PMC7924476.
Fellow: Claire Seguin, MD, MA, Children’s Mercy Hospital, Kansas City
Current Research: My focus during fellowship has been implementation of evidence-based asthma care and behavioral health. I am working to improve consistency of asthma guideline use across pediatric disciplines and studying barriers to guideline adherence in different settings. I am also conducting an educational QI project to provide residents with skills to de-escalate agitated families and patients.
Future Plans: I am looking forward to practicing and teaching as an academic hospitalist and participating in evidence-based medicine implementation.
Fun Fact: I love throwing dinner parties that celebrate different cultures and help me to learn about cooking techniques and other traditions.
Current Research: My focus during fellowship has been implementation of evidence-based asthma care and behavioral health. I am working to improve consistency of asthma guideline use across pediatric disciplines and studying barriers to guideline adherence in different settings. I am also conducting an educational QI project to provide residents with skills to de-escalate agitated families and patients.
Future Plans: I am looking forward to practicing and teaching as an academic hospitalist and participating in evidence-based medicine implementation.
Fun Fact: I love throwing dinner parties that celebrate different cultures and help me to learn about cooking techniques and other traditions.
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