This investigation focuses on the effects of thermal stimuli on airway mechanics and ventilatory patterns in normal man and in patients with airway disease. We propose to: characterize the pulmonary mechanical and ventilatory responses to cold exposure in normal man and in patients with chronic bronchitis, asthma, and rhinitis; determine the mechanism by which cold exposure produces respiratory effects; determine whether cold interacts positively with other constrictor stimuli; explore whether cold alters ventilatory patterns and/or airway temperatures, and so changes the manner in which air is heated and humidified; and examine how cold exposure influences the mucosal blood supply in the upper airways. In the first set of studies we will have the participants sit in a cold room (-10oC) while we monitor pulmonary mechanics and minute ventilation. The next task will be to isolate the stimuli. Using the same subjects, we will apply cold first to the body and then the airways. In both situations stimulus- response curves will be generated. In another set of experiments, we will see if cold applied to the skin amplifies the effects of cold applied to the airways during resting breathing and when ventilation is increased. We will also see if cold on the skin and in the airways influences the responses to other constrictor agents and if cold response increases airway reactivity. The second major set of experiments is designed to determine if cold exposure alters airway temperatures directly or by changing the pattern or level of ventilation. We plan to use a specially designed thermal probe to measure intraairway temperatures in our subjects before, during and after exposure of their skin and airways to cold air. A subset of these experiments will also be performed to determine if exposure to cold increases nasal resistance causing a shift from nasal to oral breathing. In these studies we will also determine how the pattern of breathing (nose vs mouth) influences heat and water exchange in the upper and lower airways in a distributed fashion in temperate and frigid environments. The final studies will provide data on the direct and reflex effects of cold exposure on increased blood flow in the upper airways. We will also determine how fluctuations n blood flow influence local and global respiratory heat exchange. These data are to be collected using a specially designed sensor that measures the conductivity of heat as an index of tissue perfusion.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044920-02
Application #
3363734
Study Section
Pathology A Study Section (PTHA)
Project Start
1991-04-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
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