IS LOW ENDOGENOUS CORTISOL A RISK FACTOR FOR ASTHMA?

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To the Editor:

In their paper, Clark and colleagues (1) suggest that low cortisol may relate to pulmonary emphysema. Previous findings in male veterans reported associations of cortisol with low FEV₁ or longitudinal change in lung function (2), but were not confirmed by Clark and colleagues. Asthma was an exclusion criteria for both previous reports. The relationships of endogenous cortisol with inflammatory obstructive diseases, such as emphysema or asthma, have not been studied thoroughly until now.

We measured serum cortisol in a population of 349 policemen 33 to 62 years of age (3) (mean ± SD: 13.2 ± 0.4 µg/100 ml) at the time of the examination of the subject, i.e., between 8:00 A.M. and 4:30 P.M. The analysis was conducted in 270 men, after exclusion of men who were working night shifts, sleeping less than six hours per night or taking sleeping pills. Cortisol was, as expected, related to the hour of blood sampling (p < 0.01, with a nonlinear relation due to postprandial peak) and to pulse rate, an indicator of stress (p < 0.01). Prior to analysis, cortisol level was adjusted by multiple regression analysis for the time of sampling (using a qualitative variable by half hour) and pulse rate (quantitative variable).

Eighteen men (7%) reported a history of asthma (assessed by asking "Have you ever had attacks of shortness of breath at rest with wheezing?" or "Have you ever had asthma attacks?") and 11 (4%), of whom 4 were asthmatics, reported nocturnal wheezing. Four asthmatics were under steroid treatment (any type). As expected, they had lower cortisol levels than other men (p < 0.01). The proportion of asthmatics under reported steroid treatment in that working population was similar to the general population of Paris (4). They have been excluded from the analysis.

As in Clark and coworkers' study, FEV₁ (age and height adjusted) was not related to cortisol level (r = 0.04) or to smoking on the day of examination. Men who reported a history of asthma had lower cortisol than nonasthmatics (11.4 versus 13.2 µg/100 ml; p = 0.06). The subjects with asthma (A) and nocturnal wheezing (NW) had cortisol level decreased by 24% compared with those without any of these two traits. The subjects with asthma alone or nocturnal wheezing alone were in an intermediate position (13.3, 12.7, 11.9, and 10.1 µg/100 ml for ANW, ANW+, A+NW, and A+NW+, respectively; p [trend] = 0.04). Cortisol circadian variations may explain the occurrence of nocturnal symptoms among asthmatics, but the importance of this mechanism is unclear (5). Delineation of asthmatic or COPD patients who may derive greater benefit from steroid treatment is of clinical importance. Results suggest that subjects with the lowest basal values within the normal range of endogenous serum cortisol may be at risk for nocturnal symptoms of asthma. More studies on the relationships of endogenous cortisol in various respiratory inflammatory conditions should be conducted. Studies in both men and women are warranted, as competition between cortisol and progesterone for steroid receptor has been proposed to explain variations in asthma symptomatology during pregnancy (6).

Epidemiology and StatisticsINSERM U472, Villejuif, France

ANNE GUIOCHON-MANTEL

Hormones and ReproductionINSERM U135, Kremlin-Bicêtre, France

Françoise Neukirch

EpidemiologyINSERM U408, Paris, France

1. Clark, K. D., N. Wardrobe-Wong, and P. D. Snashall. 1999. Endogenous cortisol and lung damage in a predominantly smoking population. Am. J. Respir. Crit. Care Med. 159: 755-759 [Abstract/Free Full Text].

2. Sparrow, D., G. T. O'Connor, B. Rosner, D. DeMolles, and S. T. Weiss. 1993. A longitudinal study of plasma cortisol concentration and pulmonary function decline in men: The Normative Aging Study. Am. Rev. Respir. Dis. 147: 1345-1348 [Medline].

3. Oryszczyn, M. P., I. Annesi, F. Neukirch, M. F. Dore, and F. Kauffmann. 1995. Longitudinal observations of serum IgE and skin prick test response. Am. J. Respir. Crit. Care Med. 151: 663-668 [Abstract].

4. Bousquet, J., J. Knani, C. Henry, et al . 1996. Undertreatment in a nonselected population of adult patients with asthma. Allergy Clin. Immunol. 98: 514-521 [Medline].

5. Barnes, P., G. Fitzgerald, M. Brown, and C. Dollery. 1980. Nocturnal asthma and changes in circulating epinephrine, histamine, and cortisol. N. Engl. J. Med. 303: 263-267 [Medline].

6. Schatz, M., K. Harden, A. Forsythe, et al . 1988. The course of asthma during pregnancy, post partum and with successive pregnancies: a prospective analysis. J. Allergy Clin. Immunol. 81: 509-517 [Medline].