Hypothalamic dysfunction

Abbreviations: ACTH = corticotropin; NA = nocturnal asthma; NL = control subject; NNA = nonnocturnal asthma

Patients with nocturnal asthma (NA) have increased airway inflammation at night, a phenomenon not seen in patients with non-NA (NNA). We hypothesized that alterations in hypothalamic-pituitary-adrenal axis function may be of importance in the pathogenesis of NA.

MATERIALS AND METHODS

Subjects with NA (four subjects), NNA (six subjects), and healthy control subjects (NL; six subjects) maintained a mini-constant-sleep-wake routine for 8 days. On day 8, serum samples were drawn every 2 h over a 24-h period (12 samples per subject) and were analyzed for circadian differences in corticotropin (ACTH) and cortisol levels. Between-group comparisons were made at each time point during the hours of sleep (ie, 10:00 PM to 6:00 AM) using repeated-measures analysis of variance.

RESULTS

During sleep, there was a linear increase in both ACTH and cortisol levels in all three groups (p < 0.004).

ACTH

Mean ([+ or -] SEM) ACTH levels in NA subjects were the highest at 4:00 AM (28.5 [+ or -] 3.9 pg/mL). Mean ACTH levels at 4:00 AM in NNA subjects (14.3 [+ or -] 3.2 pg/mL; p = 0.01, NA vs NNA group)and NL subjects, (16.0 [+ or -] 3.8 pg/mL; p = 0.03, NA vs NL) were similar, lower than NA subjects. ACTH levels of NNA subjects did not differ from those of NLs (p = 0.74).

Cortisol

Although NA subjects had the highest mean cortisol levels at 4:00 AM (17.1 [+ or -] 3.7 [micro]g/dL), they were not significantly greater than the levels of NNA subjects (13.3 [+ or -] 2.2 [micro]g/dL; p = 0.31). The cortisol levels of NA subjects were higher than those of NLs (7.4 [+ or -] 2.5 [micro]g/dL; p = 0.01), but those of NNA subjects were not (p = 0.08).

ACTH/Cortisol Correlation

Within-group correlations between ACTH and cortisol levels were (in ascending order) as follows: NA group, r = 0.71 and p = 0.0005; NNA group, r = 0.74 and p = 0.0001; and NL group, r = 0.82 and p = 0.0001.

CONCLUSIONS

Although subjects with NA demonstrate significantly increased ACTH levels at night, these were not accompanied by a commensurate cortisol response. The adrenal response to ACTH may be blunted in NA subjects, permitting increased airway inflammation in these subjects.

* From the National Jewish Medical and Research Center, Denver, CO.

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Correspondence to: R.J. Martin, MD, FCCP, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO 80206; e-mail: martinr@njc.org

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