Impaired adrenergic- and corticotropic-axis outflow during exercise in chronic obstructive pulmonary disease

Abstract

Exercise stimulates coordinated release of the sympathoadrenal hormones adrenocorticotropic hormone (ACTH), cortisol, norepinephrine (NE), and epinephrine (Epi). The study hypothesis was that chronic obstructive pulmonary disease (COPD) is marked by heightened sympathoadrenal outflow at comparable relative workloads. The location of the study was at a clinical research unit. Eight healthy men and 9 men with stable COPD (forced expiratory volume at 1 second <75% predicted) were studied. Volunteers rested (baseline) or exercised at individual submaximal (35% ± 5%) or maximal oxygen consumption. Blood was sampled every 2 minutes for 40 minutes concurrently. Two-way analysis of covariance was applied to examine group (healthy/COPD) and exercise (3 levels) effects on ACTH, cortisol, NE, and Epi release and regularity (estimable by approximate entropy). The timing of peak hormone concentrations was Epi, 14 minutes; NE, 16 minutes; ACTH, 22 minutes; and cortisol, 34 minutes in both cohorts. Type of exercise regimen influenced all 4 hormones (each P < .001), and subject group (control vs COPD) affected cortisol (P < .001) and Epi (P = .048) responses. Exercise regimen and group together controlled ACTH, cortisol, and Epi (each P < .001), but not NE, responses. In particular, endocrine responses were attenuated in COPD compared with control subjects. Approximate entropy analysis also identified loss of maximal exercise-induced ACTH-secretory regularity in COPD patients (P = .042). These outcomes demonstrate impaired rather than augmented exercise-associated sympathocorticotropic-axis outflow in patients with COPD even when outcomes are normalized to maximal oxygen consumption, suggesting that factors other than fitness are at work.

Figure 1

Mean (± SEM) time-concentration profiles in normal untrained men (N = 8) and patients with COPD (N = 9) studied at rest (baseline) and during submaximal (35 ± 5% of VO₂ max) or maximal exercise. Blood was sampled at 2-min intervals for 40 minutes for measurements of ACTH (top left), cortisol (top right), Epi (bottom left) and NE (bottom right).

Figure 2

Mean (Panel A) and peak (Panel B) plasma concentrations of ACTH, cortisol, Epi and NE assessed by two-way ANCOVA. Means with unshared (unique) alphabetic superscripts (such as A vs C, but not A vs AB) are significantly different by Tukey’s honestly significantly different multiple-comparison test (P < 0.05). Open and hatched bars denote control and COPD, respectively.

Figure 2

Mean (Panel A) and peak (Panel B) plasma concentrations of ACTH, cortisol, Epi and NE assessed by two-way ANCOVA. Means with unshared (unique) alphabetic superscripts (such as A vs C, but not A vs AB) are significantly different by Tukey’s honestly significantly different multiple-comparison test (P < 0.05). Open and hatched bars denote control and COPD, respectively.

Figure 3

ApEn (approximate entropy) estimates of ACTH, cortisol, Epi and NE secretory irregularity, a quantifiable measure of altered feedback/feedforward strength. Higher ApEn defines greater irregularity (greater process randomness). Data are presented otherwise as defined in Figure 2.

Figure 4

Cross-ApEn estimates of joint (pairwise) asynchrony between ACTH and cortisol (feedforward), cortisol and ACTH (feedback) and analogously for NE-ACTH and ACTH-NE. Higher cross-ApEn quantifies greater synchrony (less pattern coordination). See data presentation format in Figure 2.