To study the relative contributions of parasympathetic and sympathetic mechanisms in airway obstruction in patients with emphysema, we gave supramaximal doses of anticholinergic and adrenergic agents in sequence and in combination. Serial doses of one agent were administered to achieve a plateau of bronchodilatation; after that the other agent was administered. The plateau achieved with the anticholinergic agent (atropine methonitrate) was significantly higher than that achieved with the adrenergic agent (salbutamol). When the adrenergic agent was given first, additional bronchodilatation was achieved with subsequent use of the anticholinergic agent. When the anticholinergic agent was given first, no additional bronchodilatation was achieved with subsequent administration of the adrenergic agent. When both agents were given simultaneously, the degree of bronchodilatation was virtually identical to that obtained with the anticholinergic agent alone. Tests sensitive to small-airway and large-airway function and lung volumes gave essentially the same results. Thus, all achievable bronchodilatation was obtained with the anticholinergic agent alone. These results suggest that the two classes of agents produce bronchodilatation through a common cholinergic pathway in emphysema, and support the concept that parasympathetic activity is the dominant reversible component of airway obstruction in this disease.

The anticholinergic, antimuscarinic compounds are potent and hitherto neglected bronchodilators. Although atropine itself has drawbacks, principally related to its rapid absorption and consequent systemic side effects, its quaternary ammonium congeners, atropine methonitrate and ipratropium bromide, are poorly absorbed. When given by inhalation, they are as effective bronchodilators as atropine is, but longer acting and much less prone to side effects. They act predominantly at a site that is different from adrenergic agents and thus afford an alternative, complementary approach to the treatment of airways obstruction. In stable asthmatic subjects, ipratropium is almost as potent a bronchodilator as beta 2-adrenergic agents are. In patients with chronic bronchitis and emphysema, it is more potent than beta 2-adrenergic agents are. In both conditions, its combination with other bronchodilators adds significantly to the level and duration of bronchodilatation. It may also be occasionally useful in counteracting bronchospasm caused by specific stimuli, such as cold air and exercise, and particularly that caused by inadvertent beta-adrenergic blockade. By inhalation, ipratropium is relatively free of side effects, even in doses as much as 20 times those that produce maximal bronchodilatation. It does not significantly affect mucus production, viscosity, or clearance, problems for which atropine is suspect. Nor does it produce tremor and tachycardia, as do adrenergic agents. It can also probably be safely used in patients with glaucoma and bladder neck obstruction, unlike atropine. Ipratropium will probably find its major application in the long-term management of chronic bronchitis and emphysema, and in asthmatic patients who are poorly controlled by, or who experience troublesome side effects from, adrenergic agents.

We performed a dose-response study of ipratropium bromide as a nebulized solution in patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind crossover format. Five doses from 0.05 to 0.6 mg of ipratropium bromide as a nebulized solution, the standard dose of ipratropium bromide by metered-dose inhaler, 40 micrograms, and placebo were given in random order on separate days. End points were the maximal increase in FEV1 and FVC, and the area under the FEV1 and FVC curves in the 8 h after administration of each of the seven treatments. Forty-two patients completed all seven study days. By each of the above end points for FEV1, 0.4 and 0.6 mg of nebulized ipratropium bromide achieved significantly more bronchodilatation than did each of the other treatments. These two doses were not significantly different from each other, suggesting that the optimal dose in this patient population is 0.4 mg. After this dosage, the FEV1 increased by 440 +/- 194 (mean +/- 1 SD) ml at peak effect between 1 and 2 h, and significant bronchodilatation persisted for 6.5 h. Ipratropium bromide by metered-dose inhaler (40 micrograms) was equivalent to approximately 0.1 mg by nebulized solution and achieved only 63 to 73% of the bronchodilatation achieved by optimal doses of the nebulized solution. In terms of FVC, all treatments with ipratropium were significantly better than with placebo. The area under the FVC curve was significantly greater after 0.4 and 0.6 mg of nebulized solution than after other treatments. No significant adverse experiences occurred with any of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

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Magnesium sulfate, 1.2 g over 20 minutes after beta-agonist administration, is safe and modestly efficacious in the treatment of acute exacerbations of chronic obstructive pulmonary disease, and its bronchodilator effect is greater than that of a beta-agonist given alone and lasts beyond the period of magnesium sulfate administration.

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Oxygen therapy improves submaximal exercise tolerance in hypoxemic patients with chronic obstructive pulmonary disease (COPD). This study compared the standard nasal cannula, reservoir nasal cannula, and a demand flow device in 15 male hypoxemic patients with COPD. On six separate occasions each subject used, in a randomized order, all three systems while completing incremental cycle ergometry and a test circuit composed of tasks that simulate activities of daily living. Oxygen flow required during exercise was 1.8 +/- 0.9 and 2.8 +/- 0.7 L/min for reservoir nasal cannula and standard nasal cannula use, respectively (p < 0.0001). The effect of the three oxygen delivery systems on oxygen saturation (Spo2) during the last 30 s of exercise varied with type of activity. Only during demand flow device use while undressing and dressing was the subjects' Spo2 (90 +/- 3%) significantly lower (p = 0.019). There was a trend toward lower Spo2 with the demand flow device (p = 0.103) during arm work above shoulder level. Although not statistically significant, reservoir nasal cannula use resulted in consistently lower tidal volume and minute ventilation during test circuit activities. Exercise tolerance was not significantly different between the three oxygen delivery systems.