No abstract

Prospective follow-up information obtained between 1976 and 1981 on mortality among 2539 individuals showed that pulmonary function impairment is a risk factor for short-term mortality, even when risk factors such as age, sex, and smoking are considered. Predicted risk curves for impaired individuals (those with forced expiratory volume in one second less than 68% of forced vital capacity) are consistently higher among all race-sex categories over all ages. Survival analysis using the proportional hazards model shows a steeper decline in estimated survival among individuals with poor pulmonary function compared to those with good pulmonary function, adjusted for age, race, and smoking effects. These observations are consistent with the concept that impairment of pulmonary function is a risk factor for morbidity and mortality from several nonrespiratory as well as respiratory diseases and that it acts by contributing to various pathogenic mechanisms in different organ systems.

Epithelium in airways, like endothelium in blood vessels, may regulate responses of adjacent smooth muscle. To study the intact trachea from guinea pigs we developed an in vitro preparation that permits independent stimulation from either the inner epithelial surface or the outer serosal surface. The whole guinea pig trachea was excised, cannulated, and perfused at a constant flow with Krebs-Henseleit (KH) solution that was in direct contact with the inner epithelial-lined surface. The outer serosal surface of the trachea was immersed in a separate system (bath) containing KH solution. Tracheal responses were assessed by measuring the pressure drop between the tracheal inlet and the outlet under conditions of constant flow. When the trachea was precontracted with carbachol or KCl, hyperosmolar stimuli (KCl, mannitol, urea, or NaCl) produced concentration-dependent relaxation when applied to the inner epithelial surface. Relaxation was not produced when the hyperosmolar stimulus was applied to the serosal surface and was markedly reduced or abolished when the epithelial surface had been physically damaged or removed. These results indicate that hyperosmotic stimuli induce epithelial-dependent relaxation of trachea. A defect in this mechanism may be partially responsible for the bronchoconstriction seen in asthmatic subjects after exercise.

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466-471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

To determine whether collateral ventilation (defined as the ventilation of alveolar structures through passages or channels that bypass the normal airways) changes with age or emphysema, we compared the mechanics of collateral ventilation in seven young normal subjects, three old normal subjects and five patients with emphysema. In supine normal subjects at the end of a quiet expiration, resistance to airflow was greater through collateral channels than through bronchi and bronchioles. In emphysema, airways resistance could exceed collateral resistance, causing air to flow preferentially through collateral pathways. We conclude that high collateral resistance minimizes collateral airflow in supine normal subjects. When peripheral airways become obstructed or obliterated in emphysema, collateral channels may provide for more even distribution of ventilation.