Is the assessment of asthma treatment efficacy sufficiently comprehensive?

The goal of asthma guideline therapy is to achieve disease control, by minimizing impairment and decreasing the risk of exacerbations and adverse effects of the disease and its treatment. The primary objective of most clinical trials of biologics for severe asthma is a reduction in exacerbation rate. Recently, studies with patients at the lower guideline steps have also selected exacerbation reduction as a primary objective. These trials in patients with milder disease frequently demonstrate statistically significantly fewer exacerbations, but their power calculations reflect larger sample size and smaller effect size. Exacerbations have a precise consensus definition, although a minimal clinically important difference has not been established. Reduction of exacerbations in severe asthma is commonly 10-fold greater than in mild disease. Further, reduction in exacerbations is not always associated with reduced impairment. If superior control is the objective, both domains should demonstrate consistent and parallel improvement. The disconnect may reflect the need for alternative tools for measurement of impairment or, possibly, different therapeutic mechanisms of action. Determining response to biologics or discussion of disease remission requires assessing symptoms that may occur daily rather than focusing on exacerbations that occur once or twice a year for patients at the highest steps of care according to the guidelines.

Type 2 Inflammation and Asthma in Children: A Narrative Review.

Increased understanding of the underlying pathophysiology has highlighted the heterogeneity of asthma and identified that most children with asthma have type 2 inflammation with elevated biomarkers, such as blood eosinophils and/or fractional exhaled nitric oxide. Although in the past most of these children may have been categorized as having allergic asthma, identifying the type 2 inflammatory phenotype provides a mechanism to explain both allergic and non-allergic triggers in pediatric patients with asthma. Most children achieve control with low to medium doses of inhaled corticosteroids. However, in a small but significant proportion of children, asthma remains uncontrolled despite maximum conventional treatment, with an increased risk of severe exacerbations. In this review, we focus on the role of type 2 inflammation and allergic processes in children with asthma, together with evidence of the efficacy of available treatment options for those who experience severe symptoms.

Reducing asthma attacks in disadvantaged school children with asthma: study protocol for a type 2 hybrid implementation-effectiveness trial (Better Asthma Control for Kids, BACK).

BACKGROUND: Asthma is a leading cause of children's hospitalizations, emergency department visits, and missed school days. Our school-based asthma intervention has reduced asthma exacerbations for children experiencing health disparities in the Denver Metropolitan Area, due partly to addressing care coordination for asthma and social determinants of health (SDOH), such as access to healthcare and medications. Limited dissemination of school-based asthma programs has occurred in other metropolitan and rural areas of Colorado. We formed and engaged community advisory boards in socioeconomically diverse regions of Colorado to develop two implementation strategy packages for delivering our school-based asthma intervention - now termed "Better Asthma Control for Kids (BACK)" - with tailoring to regional priorities, needs and resources. METHODS: In this proposed type 2 hybrid implementation-effectiveness trial, where the primary goal is equitable reach to families to reduce asthma disparities, we will compare two different packages of implementation strategies to deliver BACK across four Colorado regions. The two implementation packages to be compared are: 1) standard set of implementation strategies including Tailor and Adapt to context, Facilitation and Training termed, BACK-Standard (BACK-S); 2) BACK-S plus an enhanced implementation strategy, that incorporates network weaving with community partners and consumer engagement with school families, termed BACK-Enhanced (BACK-E). Our evaluation will be guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, including its Pragmatic Robust Implementation Sustainability Model (PRISM) determinants of implementation outcomes. Our central hypothesis is that our BACK-E implementation strategy will have significantly greater reach to eligible children/families than BACK-S (primary outcome) and that both BACK-E and BACK-S groups will have significantly reduced asthma exacerbation rates ("attacks") and improved asthma control as compared to usual care. DISCUSSION: We expect both the BACK-S and BACK-E strategy packages will accelerate dissemination of our BACK program across the state - the comparative impact of BACK-S vs. BACK-E on reach and other RE-AIM outcomes may inform strategy selection for scaling BACK and other effective school-based programs to address chronic illness disparities. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT06003569, registered on August 22, 2023, https://classic. CLINICALTRIALS: gov/ct2/show/NCT06003569 .

Lebrikizumab in Uncontrolled Asthma: Reanalysis in a Well-Defined Type 2 Population.

BACKGROUND: LAVOLTA (L)I, LII, and ACOUSTICS were randomized, placebo-controlled, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting IL-13 in patients with uncontrolled asthma. Failure to demonstrate efficacy may have been related to patient selection in those trials. OBJECTIVE: To assess the efficacy in a well-defined subpopulation of patients with elevated blood eosinophil counts and a minimum number of prior asthma exacerbations. We performed an additional analysis in a subpopulation of patients with elevated FeNO and prior exacerbations. METHODS: Adult (LI and LII) and adolescent patients (aged 12-17 years weighing ≥40 kg, ACOUSTICS) with uncontrolled asthma received lebrikizumab (125 mg, n = 832; or 37.5 mg, n = 829) or placebo (n = 833) subcutaneously every 4 weeks. Post hoc analysis of the annualized adjusted exacerbation rate (AER) was performed in a subpopulation of patients with baseline blood eosinophils of 300 cells/µL or greater and history of one or more exacerbations. In this subpopulation, there were 227 patients in the placebo group, 222 in the lebrikizumab 37.5-mg group, and 217 in the lebrikizumab 125-mg group. We summarized safety in patients who received at least one dose of lebrikizumab using adverse events. RESULTS: Lebrikizumab significantly reduced AER compared with placebo in adults (AER reduction: 125 mg [38%]; and 37.5 mg [41%]) and adolescents (AER reduction:125 mg [59%]; 37.5 mg [64%]) with baseline blood eosinophils of 300 cells/µL or greater and one or more exacerbations. Most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. CONCLUSION: Lebrikizumab significantly reduced asthma exacerbations in a subpopulation of patients with elevated blood eosinophils, elevated FeNO, and a history of asthma exacerbation.

Understanding Core Community Needs for School-Based Asthma Programming: A Qualitative Assessment in Colorado Communities.

Objectives: Asthma is one of the most prevalent chronic conditions affecting approximately 8.5% of children in Colorado. Our school-based asthma program (SBAP) has effectively improved asthma control and reduced asthma disparities among children but has been largely limited to the Denver area. We interviewed community stakeholders in 5 regions of Colorado to understand community needs for broader dissemination of SBAPs. Methods: In-depth, semistructured key informant interviews were conducted with school nurses, parents, pediatric healthcare providers, public health professionals, and community resource organization representatives. Inductive and deductive analyses were informed by the practical, robust, implementation, and sustainability model, an implementation science framework. Results: Participants (n=52) identified 6 types of needs for successful future implementation of our SBAP: (1) buy-in from stakeholders; (2) asthma prioritization; (3) improved relationships, communication, and coordination among school nurses, healthcare providers, and community organizations that address social determinants of health (SDOH) and children/families; (4) resources to address healthcare and SDOH needs and awareness of existing resources; (5) asthma education for children/families, school staff, and community members; and (6) improved coordination for School Asthma Care Plan completion. These needs mapped to a 3-tiered, progressive structure of foundational, relational, and functional needs for implementation success. Conclusion: These 6 types of needs illuminate factors that will allow this SBAP to work well and program delivery approaches and implementation strategies that may need modification to be successful. Next steps should include tailoring implementation strategies to variations in local context to support fit, effectiveness, and sustainment.

Developing a Social Determinants of Health Needs Assessment for Colorado Kids (SNACK) Tool for a School-Based Asthma Program: Findings from a Pilot Study.

Background: School-based asthma programs effectively address poorly controlled asthma and asthma disparities, especially when coupled with screening for and addressing social determinants of health (SDOH) needs. Existing screening tools are tailored to clinical settings; therefore, we sought to develop a community-based SDOH screening tool. Design/Methods: We used a four-phase iterative design process to develop and pilot a community-based screening tool. We used a modified Delphi process to identify screening tool domains, identified validated items for inclusion, and developed an appropriate tool layout for populations with limited health/general literacy. Community advisory boards reviewed and refined a draft tool. Next, we conducted a qualitative pilot test of acceptability to parents and feasibility for staff in a community health center. Results: Six domains are included in our SDOH screening tool: health care access, transportation, food insecurity, public benefits, housing, and utilities. In the pilot test, 41 screenings were completed, and 36 parents (16.7% Spanish speaking) provided feedback. Most families understood the purpose of the screening; felt that the questions were clear, appropriate, and quick to complete; and liked the pictures. The clinic's care coordinator expressed a preference for the pilot tool compared to their existing screening tool and recommended improvements to encourage honest reporting by patients. Conclusion: This community-based screening tool addresses key SDOH needs that impact asthma and is acceptable to families. The next steps are to implement the tool in school-based asthma programs to support improvements in asthma outcomes and disparities by identifying and addressing families' unmet SDOH needs.