Stable Asthma in Adults

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A very large number of studies have compared the bronchodilator potential of various anticholinergic agents with that of adrenergic agents in patients with asthma. (There are at present no definitive publications of the effects of tiotropium in asthma, nor is this agent approved in the United States for the treatment of asthma.) While many of these studies are flawed by the fact that they used recommended doses rather than optimal doses, they provide useful information about the comparative actions of these bronchodilators (25). Figure 4, which is typical of most such studies, illustrates many of these points. Ipratropium bromide is slow to reach peak effect, typically 30 to 60 minutes, compared with about 15 minutes for short-acting adrenergic agents. Their peak effect is almost invariably less than that of agents such as albuterol but their duration of action is slightly longer. (Tiotropium bromide is even slower to reach peak effect than ipratropium and is thus not appropriate for occasional use to relieve bronchoconstriction.)

Neither ipratropium nor tiotropium, the only anticholinergic agents available by inhalation in the United States, is indicated for the treatment of asthma by the Food and Drug Administration (FDA). Among asthmatic patients, however, there is substantial variation in responsiveness, and although some patients respond very little to anticholinergic agents, others respond almost as well to them as to adrenergic agents. Ipratropium, either alone or in fixed combination with an adrenergic agent (below), is approved for asthma in some other countries.

It has been difficult to identify subgroups of asthmatic patients who are likely to have the greatest response to anticholinergic therapy. The broncho-dilating effect of ipratropium may increase with age, in contrast to the decline in response to albuterol (26). Individuals with intrinsic asthma and those

SALBUTAMOL -

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TIME (minutes)

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200 Mg Salbutamol

Figure 4 Increase in FEV1 of 25 patients with asthma after inhalation of 200 mg salbutamol by metered dose inhaler (MDI) or 40 mg ipratropium by MDI on separate days. All patients received an additional dose of salbutamol at 480 minutes. Asterisks denote significant differences (p < 0.05). Source: From Ref. 25.

30 60 90 120 180 240 300 360

TIME (minutes)

420 480

200 Mg Salbutamol

Figure 4 Increase in FEV1 of 25 patients with asthma after inhalation of 200 mg salbutamol by metered dose inhaler (MDI) or 40 mg ipratropium by MDI on separate days. All patients received an additional dose of salbutamol at 480 minutes. Asterisks denote significant differences (p < 0.05). Source: From Ref. 25.

with longer duration of asthma may also respond better than individuals with extrinsic asthma (27), although these factors appear to be poor predictors of response. An individual trial remains the best way to identify responsiveness (28).

Recently, attention has focused on the role postnasal drip may play in promoting asthma. Ipratropium nasal spray is commercially available, and effective at reducing rhinorrhea (29), thus, in these patients, it may reduce asthma symptoms.

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