Airway response to salbutamol: effect of regular salbutamol inhalations in normal, atopic, and asthmatic subjects.

Abstract

This study was designed to determine whether resistance to the airway effects of the beta-agonist, salbutamol, would develop in three groups of subjects while taking large doses of inhaled salbutamol. Six normal non-atopic, six atopic non-asthmatic, and eight atopic asthmatic subjects were studied by an identical technique. The development of resistance was assessed from salbutamol dose-response studies in which the airway response was measured as specific airway conductance (sGaw). Further evidence was sought in the atopic and asthmatic subjects by measuring the airway response to a standard histamine inhalation challenge and the protective effect of 100 f4g salbutamol on this challenge, and by six-hourly peak flow recordings. Subjects were assessed before and during four weeks in which they took inhaled salbutamol regularly in doses increasing to 500 /g qid in week 4. Normal subjects showed a progressive reduction in the bronchodilator (sGaw) response to salbutamol during the four weeks, indicating the progressive development of resistance. The atopic subjects, both asthmatic and non-asthmatic, showed no reduction in the response to salbutamol during the four weeks, nor any change in the response to histamine challenge or in regular peak flow readings. These results demonstrate that asthmatic patients do not develop bronchial beta-adrenoceptor resistance easily and suggests that they and atopic non-asthmatic subjects are less susceptible to its development than normal subjects.

In vitro responsiveness of human asthmatic bronchus to carbachol, histamine, beta‐adrenoceptor agonists and theophylline.

“…However, recent findings suggest that, in contrast to ,-adrenoceptors in leukocytes from asthmatics, 3-adrenoceptors in asthmatic airways do not become significantly desensitized after regular exposure to long acting ,-adrenoceptor agonists (Harvey & Tattersfield, 1982;Tashkin et al, 1982). Reduced responsiveness to ,-adrenoceptor agonists in bronchi from asthmatic subjects 1 and 2, who had received little or no P-adrenoceptor agonist therapy, appears to have resulted from a reduction in the number of functional airways 13-adrenoceptors associated with the disease state.…”

“…However, controversy remains as to whether the reduced 3-adrenoceptor responsiveness and the reduced 3-adrenoceptor density observed in lymphocytes harvested from asthma sufferers, were directly related to therapy with 3-adrenoceptor agonists (Galant et al, 1978a,b; Morris, 1980) and/or to the disease state (Parker & Smith, 1973;Brooks et al, 1979). Furthermore, studies in lymphocytes may not always reflect the status of 3-adrenoceptors in the lung (Harvey & Tattersfield, 1982;Tashkin et al, 1982;Hasegawa & Townley, 1983). Clearly, an in vitro study of 3-adrenoceptor function, as well as of responsiveness to airway spasmogens such as carbachol and histamine in asthmatic airways is desirable.…”

Regular nebulised terbutaline in chronic obstructive airways disease: dose‐response studies fail to detect tolerance.

“…Firstly, we employed a different technique. Secondly, we studied a very different group of patients who may have been less susceptible to the development of tolerance although it has been suggested that asthmatics and atopic non-asthmatics may be less prone to the development of tolerance than non atopic subjects (Harvey & Tattersfield, 1982); few of our subjects were atopic. Thirdly, corticosteroids may have masked the development of tolerance (Ellul-Micallef & Fenech, 1975;Parker et al, 1973).…”

“…However concerns remain over side effects (Harvey et al, 1981) and the possible development of tolerance. The question of tolerance to P2-adrenoceptor agonists has been extensively studied with clear evidence of tolerance as regards heart rate (Barnes and Pride, 1983), metabolic responses (Harvey & Tattersfield, 1982;Jenne etal., 1977), tremor (Prior & Cochrane, 1982) and bronchodilator effects in normal subjects (Larsson et al, 1977), but the majority of studies have failed to detect evidence of bronchodilator tolerance in asthma (Larsson et al, 1977;Nelson et al, 1983;Tattersfield, 1985).…”

The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine

“…One proposed mechanism of this desensitization is uncoupling of P-adrenoceptors from adenylate cyclase and internalisation of the agonistreceptor complex by the cell (Harden, Cotton, Waldo, Lutton & Perkins, 1980). Furthermore, resistance can occur to the bronchodilator effects of 1-stimulants in vivo (Holgate, Baldwin & Tattersfield, 1977), although this is not demonstrable in subjects with asthma or atopy (Harvey & Tattersfield, 1982), nor is the phenomenon necessarily related to the tolerance seen at the cellular level (Paterson, Woolcock & Shenfield, 1980). In human lung fragments, we failed to observe any tolerance to the antianaphylactic effect of salbutamol, even when the tissue was exposed to drug for up to 19 h before challenge.…”