Methods of testing nonspecific bronchial hyperresponsiveness.

Many methods of testing nonspecific bronchial responsiveness have been devised, since Curry first demonstrated the heightened bronchial responsiveness of asthmatics to histamine. The preferred rou1e of administration of bronchoconstrictors at the presem Lime is by inhalation, rather than systemically, in order to minimize unacceptable side effects. The agents inhaled have included irritants, cholinergic drugs, numerous mediators and more recently isocapnic hyperventilation of cold air, this latter requiring a rather complicated apparatus. It is no1 critical which method of inducing bronchoconsLriction is used since, in general, they produce comparable responses. For instance, the responses to histamine and methacholine and those to methacholine and isocapnic hyperventilation of cold air correlate well with each other [1, 2). Nevertheless, the best validated methods, most used in clinical work and epidemiological surveys, involve the inhalation of histamine or methacholine aerosols. Since higher doses of histamine may produce flushing or headaches, methacholine may be preferrable. Jet nebulizers have mainly been used to generate aerosols for challenge, but ultrasonic nebulizers are now used also. The particle sizes from most commercially available nebulizers are suitable for bronchial provocation [3]. However, the outputs of the jet nebulizers vary considerably, both between nebulizers of the same type and between different types of nebulizer and are critically dependent on the driving pressure or flow rate [3]. The output of the ultrasonic nebulizers is approximately ten times that of the jet nebulizers. Thus, to calculate the dose of bronchoconstrictor inhaled, the output of the nebulizer used must be determined [4]. The depth of inspiration and the breath holding time also influence the site of deposition and the subsequent bronchial response [3], and should therfore, be standardized. Recently, different delivery systems have been compared. Despite large differences in nebulizcr outputs, responses similar in degree and reproducibility have been reported when the method of CocKcRoFr et al. [5] (two minutes tidal breathing from a continuously running Wright's nebulizer) was compared with the method of Ctw et al. [6] (standardized dose of aerosol produced from a DeVilbiss No. 646 nebulizer attached to a breath actuated dosimeter) [7, 8]. Similarly, a rapidly increasing dose regime, given from a hand-operated DeVilbiss No. 40 nebulizer (Y an method), was found to give comparable responses to histamine, in terms of sensitivity and