The long-term objective of this proposal is to determine the mechanism by which exercise produces airway obstruction in asthmatics. The attraction of studying this aspect of asthma is that exercise is a potent, naturally occurring stimulus that is potentially operational in the everyday life of all people with this illness. Thus, if one could unravel the manner in which exercise produces airway obstruction, it may be possible to gain great insights into the pathophysiology of asthma in general and ultimately into mechanisms for its control. The proposed studies are designed to: (1) to examine, in greater depth, the role of the bronchial microvasculature in the development of EIA; (2) to determine if mediators of immediate hypersensitivity are released with thermal challenges and if they play a role in producing the obstructive response; (3) to further explore the mechanism for the refractory period; and (4) to examine the relationship between the airway obstruction produced by ultrasonic aerosols and thermal challenges. To achieve the first goal, a group of asthmatics will perform standard isocapnic hyperventilation stimulus-response curves while breathing cold, room, body condition, and hot dry air. On other occasion they will undergo bronchoscopy with insertion of a thermal probe and will repeat the above challenges, in all particulars while airstream temperatures are recorded continuously from the mouth to the peripheral airways during hyperpnea and recovery. These data will permit a systemation evaluation of the variables that are believed to be important in the pathogenesis of EIA. In the second set of studies a blinded multicenter trial will be undertaken in which multiple mediators will be measured in blood and bronchoalveolar fluid with exercise and compared with antigen. The third goal will be obtained by determining if repetitive exercise slows the rate of airway rewarming and if this phenomenon can be offset by increasing the end-challenge thermal gradient. To see if the release of catecholamines plays a part in this response, the study will be repeated using isocapnic hypercapnic hyperventilation. This stimulus produces the same thermal effects exercise, but does so without an increase in circulating catecholamines.
The final aim will be accomplished by having asthmatics undergo an exercise bronchoprovocation while airstream temperatures are recorded. Surface osmolarities will be calculated from these data. On another day the subjects will inhale sufficient quantities of 3% saline to produce the same degree of obstruction and the changes in osmolarity with this challenge will be compared with that induced with exercise.
| Yeh, Karen H; Skowronski, Mary E; Coreno, Albert J et al. (2011) Impact of obesity on the severity and therapeutic responsiveness of acute episodes of asthma. J Asthma 48:546-52 |
| Nicolacakis, Katina; Skowronski, Mary E; Coreno, Albert J et al. (2008) Observations on the physiological interactions between obesity and asthma. J Appl Physiol 105:1533-41 |
| McFadden Jr, E R (2008) Asthma-obesity relationship: association or causality? Curr Allergy Asthma Rep 8:85-6 |
| Stern, Thomas; Garg, Asha; Dawson, Neal et al. (2007) Validating a guidelines based asthma decision support system: step one. J Asthma 44:635-8 |
| McFadden, E R (2007) Exhaled nitric oxide in asthma: ""everything we have always wanted"" or ""not quite ready for prime time?"". Curr Allergy Asthma Rep 7:237-8 |
| El-Ekiaby, Amr; Brianas, Lori; Skowronski, Mary E et al. (2006) Impact of race on the severity of acute episodes of asthma and adrenergic responsiveness. Am J Respir Crit Care Med 174:508-13 |
| West, Erin; Skowronski, Mary; Ms, Albert Coreno et al. (2005) The effects of hyperpnea on exhaled nitric oxide synthesis in normal subjects. Chest 128:3316-21 |
| Kotaru, Chakradhar; Coreno, Albert; Skowronski, Mary et al. (2005) Morphometric changes after thermal and methacholine bronchoprovocations. J Appl Physiol 98:1028-36 |
| Coreno, Albert; Skowronski, Mary; West, Erin et al. (2005) Bronchoprotective effects of single doses of salmeterol combined with montelukast in thermally induced bronchospasm. Chest 127:1572-8 |
| McFadden Jr, E R (2003) Acute severe asthma. Am J Respir Crit Care Med 168:740-59 |
Showing the most recent 10 out of 49 publications
