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The Precision Interventions for Severe and Exacerbation Prone Asthma (PrecISE) Network seeks to define the biology of severe and exacerbation prone endotypes.

PrecISE Network

Conventional asthma therapies are often ineffective for patients with severe and exacerbation-prone asthma, conditions accounting for up to half of the morbidity, mortality and economic burden of asthma. The Pediatric Translational Research group at the Herman B Wells Center and others have identified subsets of these patients (endotypes) for whom there are treatable mechanisms contributing to airflow obstruction. The investigators in the Precision Interventions for Severe and Exacerbation Prone Asthma (PrecISE) Network have collaborated for nearly two decades to define the biology of severe and exacerbation prone endotypes.

The group has also developed biomarkers that will likely predict response to therapy targeted specifically to each endotype. Many of these biomarker/endotype pairs are studied by the PrecISE consortium. The investigators are focused on treating three of these that their data suggests will overlap minimally with one another and will be safe, effective and cost-saving. These are 1) urinary bromotyrosine to identify the 70% of eosinophilic patients for whom ant-IL5 will be effective; 2) serum superoxide dismutase activity to identify patients who will respond to oral Coenzyme Q; and 3) serum dehydroepiandrosterone (DHEA) sulfate to identify patients who will respond to oral DHEA. The research group proposes to use an adaptive trial design to test and improve the predictive and response biomarkers for all three endotypes. These studies fit into the framework of a sequential multiple assignment randomized trial (SMART) or equivalent, where each patient will start an initial treatment based on the baseline biomarker profile, followed by re- assignment of non-responders to other treatments at each subsequent stage.

The key objectives are summarized by three Aims.

  • Precision treatment Aim 1. Test the hypothesis that Anti-Interleukin 5 (Mepolizumab) will decrease eosinophil activation as measured by urine bromotyrosine (BrTyr) in the Th2-high severe asthmatic patient and consequently improve lung function and asthma control.
  • Precision treatment Aim 2. Test the hypothesis that CoQ supplementation will restore the antioxidant capacity and reducing-oxidizing balance in severe asthmatic patients with decreased serum SOD activity, and will consequently improve lung function and asthma control.
  • Precision treatment Aim 3. Test the hypothesis that DHEA supplementation will improve FEV1, asthma control and DHEAS levels in older women and younger male adolescents with SA and EPA.

To accomplish these Aims, the Pediatric Translational Research group plans to participate in the PrecISE network, enrolling 100 subjects with severe and/or exacerbation prone asthma. These will include both children (12-18) and adults, reflecting the group’s longstanding Pediatric/adult collaboration. The Pediatric Translational Research team has research infrastructures at three sites that have already collaborated for over a decade and has extensive experience with NIH and industry-based trials.

PrecISE Network logo

The major goal of this network is to conduct sequential, adaptive, phase II/proof of concept clinical trials with precision interventions in stratified patient populations. 

Visit the PrecISE website for more information


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    J Allergy Clin Immunol. 2022 Feb;149(2):488-516.e9. doi: 10.1016/j.jaci.2021.10.035. Epub 2021 Nov 29.
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  • Interleukin-5 receptor alpha (CD125) expression on human blood and lung neutrophils.
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  • Innate immune cell dysregulation drives inflammation and disease in aspirin-exacerbated respiratory disease.
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  • Asthma Risk Among Individuals With Androgen Receptor Deficiency.
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  • PrecISE: Precision Medicine in Severe Asthma: An adaptive platform trial with biomarker ascertainment.
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    PMID: 33667479 
  • Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory in Adults with Moderate-to-Severe Asthma.
    Denlinger LC, Phillips BR, Sorkness RL, Bleecker ER, Castro M, DeBoer MD, Fitzpatrick AM, Hastie AT, Gaffin JM, Moore WC, Peters MC, Peters SP, Phipatanakul W, Cardet JC, Erzurum SC, Fahy JV, Fajt ML, Gaston B, Levy BD, Meyers DA, Ross K, Teague WG, Wenzel SE, Woodruff PG, Zein J, Jarjour NN, Mauger DT, Israel E.
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  • The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations.
    Ivanova A, Israel E, LaVange LM, Peters MC, Denlinger LC, Moore WC, Bacharier LB, Marquis MA, Gotman NM, Kosorok MR, Tomlinson C, Mauger DT, Georas SN, Wright RJ, Noel P, Rosner GL, Akuthota P, Billheimer D, Bleecker ER, Cardet JC, Castro M, DiMango EA, Erzurum SC, Fahy JV, Fajt ML, Gaston BM, Holguin F, Jain S, Kenyon NJ, Krishnan JA, Kraft M, Kumar R, Liu MC, Ly NP, Moy JN, Phipatanakul W, Ross K, Smith LJ, Szefler SJ, Teague WG, Wechsler ME, Wenzel SE, White SR.
    J Biopharm Stat. 2020 Nov 1;30(6):1026-1037. doi: 10.1080/10543406.2020.1821705. Epub 2020 Sep 17.
    PMID: 32941098
  • Sex, androgens and regulation of pulmonary AR, TMPRSS2 and ACE2.
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