TY - JOUR
T1 - Preventing asthma in high risk kids (PARK) with omalizumab
T2 - Design, rationale, methods, lessons learned and adaptation
AU - PARK Study Team
AU - Phipatanakul, Wanda
AU - Mauger, David T.
AU - Guilbert, Theresa W.
AU - Bacharier, Leonard B.
AU - Durrani, Sandy
AU - Jackson, Daniel J.
AU - Martinez, Fernando D.
AU - Fitzpatrick, Anne M.
AU - Cunningham, Amparito
AU - Kunselman, Susan
AU - Wheatley, Lisa M.
AU - Bauer, Cindy
AU - Davis, Carla M.
AU - Geng, Bob
AU - Kloepfer, Kirsten M.
AU - Lapin, Craig
AU - Liu, Andrew H.
AU - Pongracic, Jacqueline A.
AU - Teach, Stephen J.
AU - Chmiel, James
AU - Gaffin, Jonathan M.
AU - Greenhawt, Matthew
AU - Gupta, Meera R.
AU - Lai, Peggy S.
AU - Lemanske, Robert F.
AU - Morgan, Wayne J.
AU - Sheehan, William J.
AU - Stokes, Jeffrey
AU - Thorne, Peter S.
AU - Oettgen, Hans C.
AU - Israel, Elliot
AU - Bartnikas, Lisa
AU - Kantor, David
AU - Permaul, Perdita
AU - Akar-Ghibril, Nicole
AU - Haktanir-Abul, Mehtap
AU - Gunnalaugsson, Sigfus
AU - Esty, Brittany
AU - Crestani, Elena
AU - Maciag, Michelle
AU - Hauptman, Marissa
AU - Baxi, Sachin N.
AU - Burke-Roberts, Elizabeth
AU - Louisias, Margee
AU - Banzon, Tina
AU - Habiballah, Saddiq
AU - Nguyen, Alan
AU - Simoneau, Tregony
AU - Makhija, Melanie
AU - Robison, Rachel
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/1
Y1 - 2021/1
N2 - Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma – viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2–3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.
AB - Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma – viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2–3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.
KW - Allergies
KW - Anti-IgE
KW - Asthma
KW - Atopic march
KW - Omalizumab
KW - Prevention
UR - http://www.scopus.com/inward/record.url?scp=85098122859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098122859&partnerID=8YFLogxK
U2 - 10.1016/j.cct.2020.106228
DO - 10.1016/j.cct.2020.106228
M3 - Article
C2 - 33242697
AN - SCOPUS:85098122859
SN - 1551-7144
VL - 100
JO - Contemporary Clinical Trials
JF - Contemporary Clinical Trials
M1 - 106228
ER -