Asthma research addressing the mechanisms of severity of symptoms, asthma control, exacerbations, and response to therapy can be optimized with a multidisciplinary network. The Madison center has been a part of the Asthma Clinical Research Network (ACRN) and the Childhood Asthma Research and Education (CARE) Network since their inceptions in 1993 and 1999, respectively. Our center has extensive experience in clinical trials, skilled study personnel, and an integrated infrastructure that will allow us to conduct asthma protocols in both adult and pediatric participants.. In addition, the Madison center is experienced in performing several physiologic studies. The Madison center has an excellent history of subject recruitment and retention and has considerable experience in creating, and fostering a spirit of collaboration. We have access to adequate recruitment populations for pediatric, adult, and severe adult asthma subjects. UW received one of the CTSAs, permitting the establishment of the UW Institute for Clinical and Translational Research (ICTR), which collaborates with numerous member sites across Wisconsin. The application describes four novel protocols that address all of the clinical research areas deemed essential in the RFA. The first main trial, termed PITSA, is a therapeutic trial in adults with severe asthma to determine if asthma control can be improved using a combination regimen directed at reducing both eosinophilic and neutrophilic inflammation and will determine if the phenotypic profile of sputum inflammatory granulocytes predicts response to the treatment. The second main trial, termed LISA, answers an important question in preschool children by comparing the relative superiority of two asthma controllers on multiple risk and impairment domains of asthma control to address an important need in high-risk toddlers with recurrent wheezing and how atopy affects response to therapy. VIVA is a proof of concept and will evaluate the contribution of vitamin D levels to asthma control and the ability to modulate control through vitamin D supplementation. VISA is an overarching (age, severity, and environment) protocol that will prospectively evaluate an important determinant of asthma control and exacerbations: viral respiratory tract infections.
The proposed studies focus on the evaluation and characterization of asthma phenotypes (airway inflammatory biomarkers in severe asthma), therapeutic response parameters in children (e.g., atopy), epidemiologic and mechanistic factors undertying asthma exacerbations in both children and adults (viral respiratory infections), and potential novel therapies (Vitamin D). All are highly relevant to human asthma.
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| Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T et al. (2018) Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations. N Engl J Med 378:891-901 |
| Lima, John J; Castro, Mario; King, Tonya S et al. (2018) Association of free vitamin D3 concentrations and asthma treatment failures in the VIDA Trial. Ann Allergy Asthma Immunol 121:444-450.e1 |
| Sorkness, Christine A; King, Tonya S; Dyer, Anne-Marie et al. (2018) Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era. Contemp Clin Trials 77:98-103 |
| Cardet, Juan Carlos; Louisias, Margee; King, Tonya S et al. (2018) Income is an independent risk factor for worse asthma outcomes. J Allergy Clin Immunol 141:754-760.e3 |
| Morris, Claudia R; Mauger, David T; Suh, Jung H et al. (2018) Glutathione and arginine levels: Predictors for acetaminophen-associated asthma exacerbation? J Allergy Clin Immunol 142:308-311.e9 |
| Durack, Juliana; Lynch, Susan V; Nariya, Snehal et al. (2017) Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment. J Allergy Clin Immunol 140:63-75 |
| Nyenhuis, Sharmilee M; Krishnan, Jerry A; Berry, Alalia et al. (2017) Race is associated with differences in airway inflammation in patients with asthma. J Allergy Clin Immunol 140:257-265.e11 |
| Lemanske Jr, Robert F (2016) Asthma in Childhood: Expression, Exacerbation, and Progression. J Allergy Clin Immunol Pract 4:36-7 |
| Denlinger, Loren C; King, Tonya S; Cardet, Juan Carlos et al. (2016) Vitamin D Supplementation and the Risk of Colds in Patients with Asthma. Am J Respir Crit Care Med 193:634-41 |
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