Studies of Adrenocortical Function in Continuous Asthma.

Asthma has been defined (Ciba Guest Symposium, 1959) as a condition with widespread narrowing of the bronchial airways, which changes its severity over short periods of time either spontaneously or under treatment. The clinical features are abnormal breathlesness, which may be paroxysmal or persistent, wheezing, and in most cases relief by bronchodilator drugs, including corticosteroids. This definition describes a disorder of function which may be measured by any simple test of airways obstruction (Scadding, 1963). Asthmatics may be divided into two groups depending on whether the narrowing of the airways is intermittent or continuous. Intermittent asthma is characterized by recurrent attacks of bronchospasm with periods of remission when there is no clinical evidence of asthma and ventilatory tests are normal. In continuous asthma, there is a continuously or intermittently audible wheeze, usually with breathlessness on exertion, and invariably there is evidence of expiratory obstruction on ventilatory testing. While the dyspnoea and wheezing may vary considerably and at times may not be noticed by the patient, the two groups can usually be distinguished by a careful history, and a ventilatory defect will persist despite the absence of symptoms (Engstr6m, Escardo, Karlberg, and Kraepelin, 1959; Strang, 1961). The classification of asthma as 'intermittent' and 'continuous' is based on clinical observation and implies no aetiological significance in itself, but Ogilvie (1962) has shown that, in terms of clinical course and prognosis, this classification accords closely with the aetiological classification of 'extrinsic' and 'intrinsic' asthma. Extrinsic asthma is thought to follow exposure to an inhalant or some other allergen to which the patient is specifically sensitive. Since many asthmatics do not fall into this group, they have been called the 'mixed, unidentified, and bacterial' or intrinsic group by Rackemann and Edwards (1952). Rackemann (1958) followed 272 patients with intrinsic asthma for a long period: usually infection was the major factor in the initiation and continuation of symptoms, but it was not the only cause since many other factors seemed to be involved. Fifty-nine of his patients became 'cleared' of asthma (21.7%), but six of these relapsed, and in his view these six patients (and, by implication, the 213 whose symptoms did not regress completely) 'show that a basic mechanism of some kind is still operative'. The idea of a basic mechanism is borne in upon anyone concerned with asthmatic patients, and it is possible that this mechanism could be endocrine in nature. This possibility is reinforced by the favourable response to corticosteroid treatment seen in the majority of asthmatic patients, although it must be recognized that some patients fail to respond to corticosteroid hormones; similarly, some respond to corticotrophin whereas others seem resistant. While infection and emotional influences may account for unexpected and refractory behaviour in many asthmatics, the continuation of symptoms can be seen in the absence of such factors. We have tried to find out if the adrenal cortex is fundamentally concerned in continuous asthma. This is not a new concept, but most other workers have estimated the urinary and, occasionally, plasma steroids, and no consistent abnormality has been demonstrated. In recent years methods of investigation have been developed for the specific assay of plasma cortisol itself and for the measurement of actual cortisol production rates. In the present investigation these techniques have been applied to the study of adrenocortical function in continuous asthmatics and they will give a more accurate assessment of the functional state of the adrenal cortex than could be obtained by the earlier methods.