Dose related effects of salbutamol and ipratropium bromide on airway calibre and reactivity in subjects with asthma.

Abstract

The relationship between change in airway calibre and change in airway reactivity after administration of bronchodilator drugs has been investigated by comparing the effect of increasing doses ofinhaled salbutamol and ipratropium bromide on the forced expiratory volume in one second (FEV,), specific airways conductance (sGaw), and the dose of histamine causing a 20% fall in FEV, (PD20) in six subjects with mild asthma. On each of 10 occasions measurements were made of baseline FEV,, sGaw, and PD20 after 15 minutes' rest, and followed one hour later, when the FEV, had returned to baseline, by a single nebulised dose of salbutamol (placebo, 5, 30, 200 and 1000 pg) or ipratropium (placebo, 5, 30, 200 and 1000 jig) given in random order. Measurements of FEV,, sGaw, and PD20 were repeated 15 minutes after salbutamol and 40 minutes after ipratropium. Salbutamol and ipratropium caused a similar dose related increase in FEV, and sGaw, with a mean increase after the highest doses of0-76 and 0-69 litres for FEV1 and 1-15 and 0-96 s-kPa-1 for sGaw. Salbutamol also caused a dose related increase in PD20 to a maximum of 2-87 (95% confidence interval 2-18-3-55) doubling doses of histamine after the 1000 pg dose, but ipratropium bromide caused no significant change in PD20 (maximum increase 0-24 doubling doses, 95% confidence interval -0-73 to 1 22).Thus bronchodilatation after salbutamol was associated with a significantly greater change in airway reactivity than a similar amount of bronchodilatation after ipratropium bromide. This study shows that the relation between change in airway reactivity and bronchodilatation is different for two drugs with different mechanisms of action, suggesting that change in airway calibre is not a major determinant of change in airway reactivity with bronchodilator drugs.Several studies have confirmed an association between increased airway reactivity and diminished airway calibre in subjects with airflow obstruction'" but the cause of the association is not clear. There are reasons to expect that an increase in airway reactivity would lead to increased airflow obstruction, and vice versa that an increase in airflow obstruction would increase airway reactivity, by a combination of mechanisms.9' Alternatively, both airflow obstruction and increased airway reactivity may occur as a result of a common underlying disease process.Bronchodilator drugs such as ,B agonists, antimuscarinic agents, and methylxanthines have been shown to cause a decrease in airway reactivity in conjunction

Salmeterol in exercise-induced bronchoconstriction in asthmatic children: comparison of two doses

“…Several studies have evaluated the protection of beta 2 -adrenoceptor agents against different bronchoconstrictive challenges. Whilst a dose-response effect has been demonstrated for chemical stimuli [17,[25][26][27], contradictory results have been obtained with exercise [28,29]. In the present study, 25 and 50 µg doses of salmeterol provided the same protection against EIA at 1 h. After 12 h, although no statistical difference emerged between the two dosages in the mean of the percentage drops in FEV1, only SLM 50 was more protective than placebo.…”

Sustained protection against distilled water provocation by a single dose of salmeterol in patients with asthma

“…A larger concentration of a β 2 -agonist may be required to prevent contraction to a potent stimulus as a provocation test, as compared with the concentration of the drug to produce relaxation of the relatively modest level of bronchospasm at baseline [31]. Several studies showed a relationship between bronchodilator dose and the degree of inhibition of provocation [32]. A greater concentration of salmeterol may be required to prevent contraction to UNDW provocation than is required to produce relaxation.…”

The interaction of α‐human atrial natriuretic peptide (ANP) with salbutamol, sodium nitroprusside and isosorbide dinitrate in human bronchial smooth muscle

“…These findings suggest that 'functional antagonism' might not simply be the mechanism by which bronchodilators exert a pre-protective effect. It has been proposed (Persson et al, 1982), that &2-agonists, for example, have effects on cells other than airway smooth muscle and that this may contribute to their protective effects in human asthmatic subjects (Britton et al, 1988).…”