Comparison of the effects of inhaled ipratropium bromide and salbutamol on the bronchoconstrictor

A double blind, placebo controlled compa-rison was made of the effects of nebulised ipratropium bromide (0O05 and 0-5 mg) and salbutamol (0-25 and 2-5 mg) on lung function and the airway response to hyperventilation in eight normal subjects. Both agents at both doses caused similar baseline bronchodilatation, confirming the presence of resting bronchomotor tone. The overall mean increases as percentages of control were 33% in specific airway conductance (sGaw), 10% in maximal flow after expiration of 50% of vital capacity, and 3-7% in FEV1. Hypocapnia (mean end tidal carbon dioxide tension 2-2 kPa) was produced by three minutes of voluntary hyperventilation and resulted in a mean fall in sGaw of 0-49 s1 kPa-' (20%). After inhalation of 0-25 mg salbutamol hypocapnic hyperventilation still produced a mean fall in sGaw of 0 55 s 1 kPa-1, whereas salbutamol 2 5 mg reduced this response to 0-15 s 1 kPa-' (6%). After both doses of ipratropium the decrease in sGaw caused by hyperventilation was similar to the control. This suggests that bronchoconstriction in response to hypocapnic hyperventilation in normal subjects is not mediated via a cholinergic reflex. Hypocapnic hyperventilation in normal subjects has been shown to cause bronchoconstriction, -3 unlike isocapnic hyperventilation.3 The constrictor response to hypocapnia may be due to a reflex action or to a direct action on airway smooth muscle. It has been reported that pretreatment with a ,B agonist blocked the response whereas atropine pretreatment did not,4 suggesting a non-cholinergic mechanism for this effect of hypocapnia. Consistent with this hypothesis, more severe hypocapnia produced by unilateral pulmonary artery occlusion5 caused a shift of ventilation towards the normally perfused lung; this effect could be inhibited by a ,B agonist or by 6% carbon dioxide but vagotomy had no effect. In contrast, Newhouse et al' and Sterling2 found that atropine pretreatment did reduce hypocapnia induced bronchoconstriction, Address for reprint requests: Dr J P Jamison, Department of Physiology, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL. Accepted 23 March 1987 indicating that cholinergic mechanisms might have a role in the response. This study is a further investigation into the mechanism of the bronchoconstrictor response to hypocapnia in normal subjects with the use of the cholinergic antagonist N-isopropyl atropine (the quaternary derivative of atropine)-that is, ipratropium bromide.6 Voluntary hyperventilation was carried out in a manner shown previously in this laboratory to cause bronchoconstriction that is entirely dependent on hypocapnia.3 Since one explanation for the blockade of the airway response to hyperventilation by atropine in previous studies may have been airway dilatation after drug administration, a control for this was provided by giving salbutamol in a dose that caused a degree of bronchodilatation similar to that of ipratropium. Since hypocapnia may occur in severe asthma,7 the findings of this study may be relevant to the treatment of severe asthma or asthmatic attacks triggered by hypocapnic hyperventilation. 809 group.bmj.com on June 21, 2017 Published by http://thorax.bmj.com/ Downloaded from