Severe/Fatal Asthma*

Sally Wenzel Chest 2003;123;405S-410S DOI 10.1378/chest.123.3_suppl.405S-a

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finity and decreased steroid responsiveness at night. J Allergy Clin Immunol 1999; 103:66 71 Kraft M, Hamid Q, Chrousos GP, et al. Decreased steroid responsiveness at night in nocturnal asthma: Is the macrophage responsible? Am J Respir Crit Care Med 2001; 163:12191225 Jarjour NN, Lacouture PG, Busse WW. Theophylline inhibits the late asthmatic response to nighttime antigen challenge in patients with mild atopic asthma. Ann Allergy Asthma Immunol 1998; 81:231236 Selby C, Engleman HM, Fitzpatrick MF, et al. Inhaled salmeterol or oral theophylline in nocturnal asthma? Am J Respir Crit Care Med 1997; 155:104 108 Kraft M, Wenzel SE, Bettinger CM, et al. The effect of salmeterol on nocturnal symptoms, airway function, and inflammation in asthma. Chest 1997; 111:1249 1254 Wiegand L, Mende CN, Zaidel G, et al. Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma. Chest 1999; 115:15251532

ACTH
Mean ( SEM) ACTH levels in NA subjects were the highest at 4:00 am (28.5 3.9 pg/mL). Mean ACTH levels at 4:00 am in NNA subjects (14.3 3.2 pg/mL; p 0.01, NA vs NNA group) and NL subjects, (16.0 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 3.7 g/dL), they were not significantly greater than the levels of NNA subjects (13.3 2.2 g/dL; p 0.31). The cortisol levels of NA subjects were higher than those of NLs (7.4 2.5 g/dL; p 0.01), but those of NNA subjects were not (p 0.08).

Hypothalamic-Pituitary-Adrenal Axis Dysfunction During Sleep in Nocturnal Asthma*

E. Rand Sutherland, MD, FCCP; Monica Kraft, MD, FCCP; M.D. Rex, BS; Misoo C. Ellison, PhD; and Richard J. Martin, MD, FCCP

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
(CHEST 2003; 123:405S) Abbreviations: ACTH corticotropin; NA nocturnal asthma; NL control subject; NNA nonnocturnal asthma with nocturnal asthma (NA) have P atients inflammation at night, a phenomenonincreased airway not seen 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.

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.

Severe/Fatal Asthma*
Sally Wenzel, MD, FCCP

Materials and Methods

Subjects with NA (four subjects), NNA (six subjects), and healthy control subjects (NL; six subjects) maintained a miniconstant-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).
*From the National Jewish Medical and Research Center, Denver, CO. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org). 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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Severe asthma is poorly understood clinically, physiologically, and pathologically. While milder forms of asthma are generally easily treated, more severe forms often remain refractory to the best current medical care. Although some patients with severe asthma have had severe disease for most of their lives, there appears to be a second group that develops severe disease in adulthood. Additionally, it is not clear which genetic and environmental elements may be the most important in the development of severe disease. Physiologically, these patients often have airtrapping and may have loss of elastic recoil, as well. The pathology demonstrates a heterogeneity of findings, including continued eosinophilic inflammation, structural changes, distal disease, and, in at least one third of patients, a different pathology. Treatment remains problematic and likely will remain so until a better understanding of this disease develops. (CHEST 2003; 123:405S 410S)
CHEST / 123 / 3 / MARCH, 2003 SUPPLEMENT

405S

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Severe/Fatal Asthma* Sally Wenzel Chest 2003;123; 405S-410S DOI 10.1378/chest.123.3_suppl.405S-a This information is current as of April 21, 2009
Updated Information & Services Updated Information and services, including high-resolution figures, can be found at: http://www.chestjournal.org/content/123/3_suppl/405S.2 .full.html This article cites 42 articles, 25 of which can be accessed free at: http://www.chestjournal.org/content/123/3_suppl/40 5S.2.full.html#ref-list-1 This article has been cited by 3 HighWire-hosted articles: http://www.chestjournal.org/content/123/3_suppl/40 5S.2.full.html#related-urls Freely available online through CHEST open access option Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestjournal.org/site/misc/reprints.xhtml Information about ordering reprints can be found online: http://www.chestjournal.org/site/misc/reprints.xhtml Receive free email alerts when new articles cit this article. sign up in the box at the top right corner of the online article. Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online article figure for directions.

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