Hyperpnea (HP) has important effects on lung function. It stimulates bronchospasm in asthmatics during exercise or hyperventilation, and may reduce parenchymal compliance through inactivation of surfactant in animals. We became intrigued with this effect on parenchymal lung mechanics when we observed that peripheral resistance (Rp) rises and peripheral compliance falls following simulated local HP in a wedged airway segment with high-flow cold,dry air. This led to the hypothesis that HP affects parenchymal lung.function in humans by the following mechanisms: 1) increased Rp due to direct inflammatory mediator release; and 2) direct effects on surfactant function. The current project is designed to explore the physiological and biochemical effects of HP in humans, both normal and asthmatic. Specifically, we will look for changes in parenchymal lung mechanics by measuring lung elastic recoil, compliance and hysteresis, and relate these changes to airway function. We will also relate these whole-lung parameters to changes in Rp, and immediately lavage the stimulated airway and segment to assess the changes in mediators and surfactant that may develop following HP. Beta-agonists and exogenous surfactant will then be given to directly perturbate the system in order to establish mechanism. Finally, we will determine the effects of PEEP and alterations in lung volume on parenchymal mechanics, and the interdependence of the parenchyma and airways.
| Kaminsky, D A; Bates, J H; Irvin, C G (2000) Effects of cool, dry air stimulation on peripheral lung mechanics in asthma. Am J Respir Crit Care Med 162:179-86 |
| Kaminsky, D A; Mitchell, J; Carroll, N et al. (1999) Nitrotyrosine formation in the airways and lung parenchyma of patients with asthma. J Allergy Clin Immunol 104:747-54 |
| Kaminsky, D A (1998) Paradigm shift in mechanical ventilatory support for acute respiratory distress syndrome: do no harm. Coron Artery Dis 9:527-33 |
| Kaminsky, D A; Wenzel, S E; Carcano, C et al. (1997) Hyperpnea-induced changes in parenchymal lung mechanics in normal subjects and in asthmatics. Am J Respir Crit Care Med 155:1260-6 |
