Viral respiratory tract infections are an important cause of asthma exacerbations. Rhinoviruses (RV) are the most common type detected in these patients. We have evidence that RV infect the lower airway, and stimulate the generation of proinflammatory mediators leading to recruitment of neutrophils which then cause airway injury including epithelial damage and increased mucus secretion. These changes result in airway obstruction, hyper-responsiveness and increased asthma symptoms. Since asthma exacerbations develop only in a subset of asthma patients who suffer a viral respiratory tract infection, host susceptibility factors including decreased generation of antiviral factors or increased release of proinflammatory mediators have been suspected to play a role in the pathogenesis of these attacks. We therefore, hypothesize that virus-induced asthma exacerbation (VIAX) with RV infections are the result of enhanced neutrophil recruitment and activation in the lower airway with subsequent intraluminal airway obstruction and airway parenchymal uncoupling. We further propose that this enhanced neutrophilic inflammatory response is seen in a subset of asthma patients with altered antiviral responses and increased generation of proinflammatory responses to RV. To test this hypothesis we will determine the physiological consequences of VIAX on lung function including intraluminal bronchial obstruction and airway-parenchymal uncoupling. We will also use radiological imaging with CT scans, 3He-MRI, and 18FDG PET to determine the functional and structural changes in the lung during VIAX and to determine the relationship of these changes to observed pulmonary physiology. Finally we will determine the mechanisms of lower airway inflammation associated with the VIAX by analysis of sputum and bronchial lavage cells and mucosal biopsies, determine the relationship of these virus-induced effects to airflow obstruction and lung structure, and begin to determine the genetic host susceptibility factors that may regulate these processes. From these observations, we will be able to better define the mechanisms of VIAX and hopefully help develop improved treatment.
| Mummy, David G; Kruger, Stanley J; Zha, Wei et al. (2018) Ventilation defect percent in helium-3 magnetic resonance imaging as a biomarker of severe outcomes in asthma. J Allergy Clin Immunol 141:1140-1141.e4 |
| Shim, Sung Shine; Schiebler, Mark L; Evans, Michael D et al. (2018) Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients. J Allergy Clin Immunol 142:1773-1780.e9 |
| Hahn, Andrew D; Cadman, Robert V; Sorkness, Ronald L et al. (2016) Redistribution of inhaled hyperpolarized 3He gas during breath-hold differs by asthma severity. J Appl Physiol (1985) 120:526-36 |
| Schwantes, Elizabeth A; Denlinger, Loren C; Evans, Michael D et al. (2015) Severity of virus-induced asthma symptoms is inversely related to resolution IFN-? expression. J Allergy Clin Immunol 135:1656-9 |
| Kruger, Stanley J; Niles, David J; Dardzinski, Bernard et al. (2014) Hyperpolarized Helium-3 MRI of exercise-induced bronchoconstriction during challenge and therapy. J Magn Reson Imaging 39:1230-7 |
| Manthei, D M; Schwantes, E A; Mathur, S K et al. (2014) Nasal lavage VEGF and TNF-? levels during a natural cold predict asthma exacerbations. Clin Exp Allergy 44:1484-93 |
| Denlinger, Loren C; Sorkness, Ron L; Lee, Wai-Ming et al. (2011) Lower airway rhinovirus burden and the seasonal risk of asthma exacerbation. Am J Respir Crit Care Med 184:1007-14 |
| Bochkov, Yury A; Palmenberg, Ann C; Lee, Wai-Ming et al. (2011) Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nat Med 17:627-32 |
| Johansson, Mats W; Mosher, Deane F (2011) Activation of beta1 integrins on blood eosinophils by P-selectin. Am J Respir Cell Mol Biol 45:889-97 |
| Peterson, Eric T; Gordon, Jeremy W; Erickson, Matthew G et al. (2011) Dynamic nuclear polarization system output volume reduction using inert fluids. J Magn Reson Imaging 33:1003-8 |
Showing the most recent 10 out of 14 publications
