Asthma remains one of the most important challenges to pediatric public health in the US, affecting millions of children, causing significant morbidity, mortality, and source of tremendous financial burden. Prevention of asthma is a pressing, unmet need of utmost priority. The vast majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization (IgE antibody production), which remains the pivotal risk factor for developing persistent, progressive asthma throughout life. It has recently been shown that aeroallergen sensitization precedes viral wheezing and is the pivotal causal pathway and essential susceptibility factor in the persistence and progression of the disease. Most aeroallergen sensitization begins around the age of 2-3 years and escalates during school age. The progression appears to be dependent on exposures to offending allergens-- the greatest increase in development and impairment from asthma is seen in those with a tendency toward Type 2 inflammation who are sensitized and exposed to high levels of offending allergens. In addition to its role in mediating allergen-induced responses, IgE signals impair innate anti-viral immune responses which could lead to increased viral infections and thus potentially further enhance the cascade of progression to asthma. Omalizumab (anti-IgE) markedly reduces asthma exacerbations during the viral season and anti- IgE treated children have demonstrated restored IFN-? response to rhinovirus. This suggests that anti-IgE prevents IgE driven responses to offending allergen exposure in those with a Type 2 phenotype AND attenuates viral infections in this Type 2 phenotype. Thus, utilizing anti-IgE in young children has the potential to prevent the development of established asthma in susceptible children by blocking all IgE allergen-antibody interactions (including responses to subclinical exposures) AND by reducing the response to viral exposure which may lead to asthma. We hypothesize that blockade of IgE in young children (age 2-3) at high risk for development of asthma will prevent progression to established asthma. We will test this hypothesis by examining the effect of anti-IgE on the development of asthma in a double-blind, randomized, placebo- controlled parallel trial of anti-IgE vs placebo in 250 children aged 2-3 years old at high risk of developing asthma, who will be followed for 2 years after 2 years of therapy is discontinued. Primary outcome will be the proportion of participants with current, active asthma as defined in the NIAID URECA birth cohort, between the two treatment groups at the end of Year 4, the final 12 months of the trial off study medication. Secondary outcomes will include occurrence of wheezing episodes, exacerbations requiring steroids, and new and persistent allergen-specific IgE sensitizations after IgE therapy. If confirmed, anti-IgE therapy would be the first intervention to change the natural history of childhood asthma. This trial will not only allow us to expand our understanding of asthma immunopathogenesis, but will also create opportunities to identify IgE mediated and other novel approaches impacting our understanding towards preventing the disease.
Asthma remains one of the most important challenges to pediatric public health in the United States affecting millions of children, and continues to increase in prevalence, causing significant morbidity, mortality, and tremendous financial burden. Prevention of asthma is a pressing, unmet need of utmost priority. This protocol is aimed at the prevention of progression from allergic wheezing to asthma and will address the hypothesis that treatment of high-risk children with allergic sensitization and wheeze with omalizumab (anti-IgE), an intervention directed towards IgE, will alter disease progression as reflected by a reduced current, active diagnosis of asthma 2 years after the completion of therapy.
| Lai, Peggy S; Kolde, Raivo; Franzosa, Eric A et al. (2018) The classroom microbiome and asthma morbidity in children attending 3 inner-city schools. J Allergy Clin Immunol 141:2311-2313 |
| Lai, Peggy S; Massoud, Amir H; Xia, Mingcan et al. (2018) Gene-environment interaction between an IL4R variant and school endotoxin exposure contributes to asthma symptoms in inner-city children. J Allergy Clin Immunol 141:794-796.e3 |
| Naja, Ahmad Salaheddine; Permaul, Perdita; Phipatanakul, Wanda (2018) Taming Asthma in School-Aged Children: A Comprehensive Review. J Allergy Clin Immunol Pract 6:726-735 |
| Esty, Brittany; Phipatanakul, Wanda (2018) School exposure and asthma. Ann Allergy Asthma Immunol 120:482-487 |
| Louisias, Margee; Wright, Lakiea; Phipatanakul, Wanda (2018) Asthma in the melting pot. Ann Allergy Asthma Immunol : |
| Gaffin, Jonathan M; Hauptman, Marissa; Petty, Carter R et al. (2018) Nitrogen dioxide exposure in school classrooms of inner-city children with asthma. J Allergy Clin Immunol 141:2249-2255.e2 |
| Kantor, David B; Phipatanakul, Wanda; Hirschhorn, Joel N (2017) Reply. J Allergy Clin Immunol 139:1717-1718 |
| Gaffin, Jonathan M; Phipatanakul, Wanda (2017) The Calculated Risk of Childhood Asthma From Severe Bronchiolitis. J Allergy Clin Immunol Pract 5:97-98 |
| Louisias, Margee; Phipatanakul, Wanda (2017) Managing Asthma in Low-Income, Underrepresented Minority, and Other Disadvantaged Pediatric Populations: Closing the Gap. Curr Allergy Asthma Rep 17:68 |
| Dilley, Meredith A; Sheehan, William J; Petty, Carter R et al. (2017) Comparison of treatment modalities for inpatient asthma exacerbations among US pediatric hospitals. J Allergy Clin Immunol Pract 5:855-857.e1 |
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