This investigation focuses on the physiologic and pathologic effects of thermal stimuli in normal man and in patients with airway disease. We propose to: (1) characterize the pulmonary mechanical effects of cold exposure in health and in subjects with asthma, rhinitis, and chronic bronchitis; (2) determine the mechanisms by which skin cooling produces bronchial narrowing; (3) evaluate whether cold interacts with other stimuli to alter upper and/or lower airway function; (4) ascertain if reductions in ambient temperatures change the manner in which inspired air is conditioned; and (5) further explore when, and how nasal obstruction develops with cold air. In the first set of studies, we will have participants inhale frigid air at resting ventilations in association with cooling of the skin of the thorax and the head while we monitor upper and lower airway caliber. The subjects will then return while the effects of each thermal stimulus is studied separately. The second set of experiments is designed to examine whether skin cooling produces airway constriction through somatic afferent-vagal efferent reflexes and if pretreatment with beta2-agonists will provide effective prophylaxis. The third proposed trials will examine if skin and airway cooling each enhance the response to this constrictor stimuli such as antigen, SO2 and methacholine. The protocols in the fourth section involve the measurement of intra-airway temperatures and test the hypothesis that cold exposure alters the conditioning of inspired air, respiratory heat exchange and the blood flow to the mucosa of the mouth and nose. The final trials will describe the spectrum of responses that exist to nasal cold exposure and will determine if they bear any relationship to bronchial hyperreactivity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044920-09
Application #
2883231
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1991-04-01
Project End
2001-02-28
Budget Start
1999-03-01
Budget End
2001-02-28
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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McFadden Jr, E R; Nelson, J A; Skowronski, M E et al. (1999) Thermally induced asthma and airway drying. Am J Respir Crit Care Med 160:221-6
Sompradeekul, S; Hejal, R; McLane, M et al. (1998) Lack of interaction of hyperpnoea with methacholine and histamine in asthma. Clin Sci (Lond) 95:611-9
Skowronski, M E; Ciufo, R; Nelson, J A et al. (1998) Effects of skin cooling on airway reactivity in asthma. Clin Sci (Lond) 94:525-9
McDonald, J S; Nelson, J; Lenner, K A et al. (1997) Effects of the combination of skin cooling and hyperpnea of frigid air in asthmatic and normal subjects. J Appl Physiol 82:453-9
Gilbert, I A; Lenner, K A; Nelson, J A et al. (1994) Inhaled furosemide attenuates hyperpnea-induced obstruction and intra-airway thermal gradients. J Appl Physiol 76:409-15
Gilbert, I A; McFadden Jr, E R (1992) Airway cooling and rewarming. The second reaction sequence in exercise-induced asthma. J Clin Invest 90:699-704
Gilbert, I A; Regnard, J; Lenner, K A et al. (1991) Intrathoracic airstream temperatures during acute expansions of thoracic blood volume. Clin Sci (Lond) 81:655-61