Kevin R. Murphy’s research while affiliated with Boys Town and other places

Background: In patients with asthma, bronchoconstriction and airway inflammation both contribute to airway narrowing and airflow limitations, which lead to symptoms and exacerbations. Short-acting beta 2-agonist (SABA)-only rescue therapy addresses only bronchoconstriction and is associated with increased morbidity and mortality. Current asthma management guidelines recommend concomitant treatment of symptoms and inflammation with a fast-acting bronchodilator and inhaled corticosteroid (ICS) as rescue therapy for patients 12 years of age. However, there is an education and outreach gap for the wider adoption of anti-inflammatory rescue therapy in clinical practice.Objective: AstraZeneca has developed an education program for health-care practitioners (HCPs) based on a Knowledge-to-Action Framework, with the aim of increasing HCPs’ understanding of key disease-state concepts related to evidence-basedmanagement of asthma.Methods: A multichannel, evidence-based education program was presented at medical conferences across the United States between December 2022 and December 2023. Before and after each event, attendees were asked to complete a survey that rated their agreement with six disease-state concepts on a five-point Likert scale. These concepts related to the role of airway inflammation, fluctuations in inflammation, SABA and ICS therapy, and the risk of exacerbations.Postevent responses to the survey were assessed relative to pre-event responses and longitudinally over 12 months by using calculated odds ratios and 95% confidence intervals. Acceptance and/or understanding of a concept was defined as a rating of “agree” or “strongly agree” from at least 80% of respondents.Results: The proportion of respondents who agreed or strongly agreed with each concept was significantly higher postevent versus pre-event (p < 0.001). The 80% acceptance and/or understanding threshold was surpassed for all concepts after the event.Conclusion: The medical education program improved understanding and/or acceptance of key disease-state concepts related to asthma management among participating HCPs. Effective communication of disease management concepts may lead to improved patient health outcomes through more rapid acceptance of guideline-recommended medical therapies.

Background Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab. Methods This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12–52, and mean change from baseline in ppFEV1 to Week 12. Results At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥10%. During the Week 12–52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52–60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥5%. Conclusion Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12. Trial Registration NCT02948959.