The proposed project is a longitudinal study of the relationship between the rate of decline of pulmonary function and measurements of cortisol concentration and excretion in a sample of middle-aged and older men. This study will test the hypothesis, suggested by preliminary data of the investigators, that persons whose plasma cortisol concentrations are relatively low, albeit within the normal range, are predisposed to excessively rapid deterioration of pulmonary function during aging. All subjects currently participating in the Normative Aging Study will be recruited for the proposed study at the time of their next scheduled examination. Twenty-four hour urinary excretion of free cortisol, morning serum cortisol concentration, and pre- and post-bronchodilator spirometric indices will be measured. For the 700 subjects who will be recruited during years 1 and 2 of the study, these measurements will be repeated when subjects return for their next triennial examination in years 4 and 5 of the study. Respiratory illness and smoking questionnaire data, total and differential leukocyte counts, and methacholine inhalation challenge test data will also be available at both time points.
The specific aims of the study will be to examine: (1) the cross-sectional relationship between level of pulmonary function and both morning serum cortisol concentration and 24-hour urinary free cortisol excretion; (2) the relationship between the rate of decline of pulmonary function during the follow-up interval and these measurements of cortisol concentration and excretion; (3) whether these relationships are modified by smoking history, blood total leukocyte count, methacholine airway responsiveness, or other characteristics; and (4) the stability over time of serum cortisol concentration and urinary cortisol excretion in this aging population. It is hoped that this study will provide important insights into the pathogenesis of chronic obstructive pulmonary disease with potential implications for prevention and early therapeutic intervention.
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