This Asthma Clinical Research Network (ACRN) grant application involves three investigators who have extensive experience in multicenter asthma investigation. The areas of research expertise that will be brought to the ACRN include adult and pediatric investigation, allergy and immunology, pulmonology, pharmacology, chronobiology, steroid and beta-2 agonist receptor knowledge, airway inflammation, morphometrics, infection, physiology, and patient care. The two research protocols are potentially of great importance to the understanding of asthma pathophysiology and patient care. Protocol 1 will determine the link between chronic infection (Mycoplasma pneumoniae and Chlamydia pneumoniae) and chronic asthma. In a pilot study, we have shown that approximately 50% of patients with asthma exhibit evidence of M. pneumoniae or C. pneumoniae in their airways, and respond to treatment with a macrolide antibiotic. However, evaluation and extension of these observations in large multi-center trials are critical, if we are to potentially identify a new asthma phenotype, and thus affect therapy of asthma. Therefore, we propose to evaluate these patients with both a macrolide antibiotic and an inhaled corticosteroid (ICS) in subjects (+) and (-) for these bacteria. As we have been interested in corticosteroid responsiveness for many years, Protocol 2 will evaluate biomarkers to predict ICS responders (good, marginal, and poor) as well as determining why these different responses occur. This protocol is an extension of our own work, and work through ACRN with Denver as the lead center. Additive therapy, long-acting beta-2 agonists and anti-lgE, will be studied to determine if either or both improve responses to ICS. The ability to predict who will and will not respond to corticosteroids and additive therapy will greatly improve our ability to treat asthma effectively.
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| 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 |
| Peters, Stephen P; Bleecker, Eugene R; Kunselman, Susan J et al. (2013) Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol 132:1068-1074.e1 |
| Calhoun, William J; Ameredes, Bill T; King, Tonya S et al. (2012) Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. JAMA 308:987-97 |
| Sutherland, E Rand; Goleva, Elena; King, Tonya S et al. (2012) Cluster analysis of obesity and asthma phenotypes. PLoS One 7:e36631 |
| McGrath, Kelly Wong; Icitovic, Nikolina; Boushey, Homer A et al. (2012) A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. Am J Respir Crit Care Med 185:612-9 |
| Szefler, Stanley J; Chinchilli, Vernon M; Israel, Elliot et al. (2012) Key observations from the NHLBI Asthma Clinical Research Network. Thorax 67:450-5 |
| Sutherland, E Rand; Goleva, Elena; Jackson, Leisa P et al. (2010) Vitamin D levels, lung function, and steroid response in adult asthma. Am J Respir Crit Care Med 181:699-704 |
| Peters, Stephen P; Kunselman, Susan J; Icitovic, Nikolina et al. (2010) Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med 363:1715-26 |
| Sutherland, E Rand; King, Tonya S; Icitovic, Nikolina et al. (2010) A trial of clarithromycin for the treatment of suboptimally controlled asthma. J Allergy Clin Immunol 126:747-53 |
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