Comparing methods for assessing bronchial responsiveness in children: single step cold air challenge, multiple step cold air challenge, and histamine provocation.
Cold air challenge (CACh) can be applied by either a single step (SSCACh) or a multiple step (MSCACh) protocol. The interrelationship of the responses of the different protocols has not yet been studied. Furthermore, there is contradictory information on the correlation of cold air challenge responses to the outcome of pharmacological provocations. A single and a multiple step cold air challenge and a histamine provocation were performed in random order on three consecutive days on 28 children and adolescents with bronchial asthma, who were currently symptom- and medication-free. Single step cold air challenge consisted of a 4 min isocapnic hyperventilation of dry, -10 degrees C air; the subjects's response was quantified by the induced change in forced expiratory volume in one second (FEV1). Multiple step cold air challenge consisted of a series of 3 min, cold dry air hyperventilation steps from 20 to 80% of maximal voluntary ventilation (MVV); response was expressed as the provocative dose causing a 10% fall in FEV1 (PD10). Histamine provocation consisted of a series of 2 min inhalations of stepwise increasing histamine concentrations from 0.03 to 8.0 mg.mL-1; response was expressed as the provocative concentration of histamine causing a 20% fall in FEV1 (PC20). Change in FEV1 (delta FEV1) (SSCACh) correlated closely with PD10 (MSCACh); scatter around the regression line was minimal. With one exception, both types of CACh identified the same subjects as hyper- and normoresponsive. delta FEV1 (SSCACh) correlated significantly to PC20 (histamine), but scatter around the regression line was substantial. The correlation of PD10 (MSCACh) to PC20 (histamine) failed to reach statistical significance. These results indicate that the stimulus applied and the bronchoconstrictor mechanism activated, and not the challenge protocol, determine the outcome of a cold air challenge. In clinical practice, a brief single step cold air challenge can substitute for a more time-consuming multiple step cold air challenge. As nonpharmacological challenges seem to measure a different type of bronchial responsiveness, neither a single step nor a multiple step cold air challenge can substitute for a pharmacological provocation.