Comparison of Isocapnic Hyperventilation and Histamine or Methacholine Inhalation for the Assessment of Airway Responsiveness

Several stimuli have been used to evaluate the degree of airway hyperresponsiveness in asthma. Each of these has possible advantages and disadvantages when compared to the other methods. The most widely used involves the inhalation of chemical bronchoconstrictors, most commonly histamine or methacholine. This paper contrasts these inhalation tests with airway challenges using isocapnic hyperventilation of dry air. Isocapnic hyperventilation uses a naturally occurring stimulus to provoke bronchoconstriction rather than a chemical stimulus and can be administered in a dose-response fashion. Therefore, isocapnic hyperventilation may be particularly useful in epidemiologic surveys. The maximal dose administered, however, is determined by the level of a subject's maximal voluntary ventilation; also the equipment needed to administer the challenge is relatively complex when compared to other methods. By contrast, histamine and methacholine inhalation tests require simple, inexpensive equipment and can be inhaled at high concentrations, which means that airway responsiveness can be measured even in many nonasthmatic subjects. However, at high inhaled concentrations, histamine has many more systemic side effects than methacholine. Once the factors known to influence the measurements of airway responsiveness are controlled, the measurements made with one method correlate well with all other methods. Therefore, the method chosen will often depend on the requirements of the study or clinical laboratory.