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Studies concerning the ability of an inhaled beta2-agonist to produce dose-related bronchodilatation are conflicting. In five asthmatic, five bronchitic, and five normal subjects, specific airway conductance (Gaw/VL), flow-volume curves, and single-breath nitrogen washout were recorded after noncummulative inhalation of 0.65 mg, 1.30 mg, 1.95 mg, and, in some subjects, 2.60 mg of metaproterenol sulfate. Bronchodilatation appeared to be dose-related and was best assessed by using Gaw/VL; in all but one subject with chronic bronchitis, there was a significant linear relationship between log dose and precent change in Gaw/VL. Measurements of flow rate could demonstrate significant log dose-responses in eight subjects, maximum midexpiratory flow being the most sensitive measurement of flow rate, followed in order by forced expiratory volume in one second, flow at 50 percent of forced vital capacity, peak expiratory flow rate, and flow at 75 percent of forced vital capacity. No log dose-respone curve could be observed by using the single-breath nitrogen-washout technique. This demonstration of significant log dose-responses to inhaled metaproterenol is consistent with the response to drugs acting upon receptors and suggests that patients may benefit from increasing doses of bronchodilators.

In 15 asthmatic subjects, flow volume loops were recorded before and after quantitative nebulization of increasing concentration of histamine and allergen, until a threshold response (-delta FEV110%) was obtained. Nine subjects with reproducible threshold doses to these two agents were included in the study. After pretreatment with 10 mg of intravenously administered chlorpheniramine, the threshold dose of histamine increased fourfold in eight subjects and eightfold in one subject, whereas the threshold doses to allergen doubled in seven and remained unaffected in two. One of these two subjects required 15 mg chlorpheniramine intravenously for comparable protection. In three subjects, the threshold dose to inhaled acetylcholine was determined with a similar procedure and found reproducible. Pretreatment with 10 to 15 mg chlorpheniramine increased this threshold dose two to four times, similarly to the effect produced by 0.4 mg of subcutaneously administered atropine. However, 0.4 mg atropine sc. did not alter the airway responses to allergen. The results suggest that intravenously administered chlorpheniramine provided it has a dose ratio of at least four against inhaled histamine, can prevent attacks of allergen-induced asthma. The effect is probably mediated through the H1 rather than the acetylcholine receptor.