Spirometric Response to Bronchodilator and Eucapnic Voluntary Hyperpnea in Adults With Asthma

The spirometric response to fast-acting bronchodilator is used clinically to diagnose asthma and in clinical research to verify its presence. However, bronchodilator responsiveness does not correlate with airway hyper-responsiveness measured with the direct-acting stimulus of methacholine, demonstrating that bronchodilator responsiveness is a problematic method for diagnosing asthma. The relationship between bronchodilator responsiveness and airway hyper-responsiveness assessed with indirect-acting stimuli is not known.

Retrospectively, the spirometric responses to inhaled bronchodilator and a eucapnic voluntary hyperpnea challenge (EVH) were compared in 39 non-smoking adult subjects with asthma (26 male, 13 female; mean ± SD age 26.9 ± 7.8 y; mean ± SD body mass index 26.3 ± 4.7 kg/m²). All subjects met one or both of 2 criteria: ≥ 12% and 200 mL increase in FEV₁ after inhaled bronchodilator, and ≥ 10% decrease in FEV₁ after an EVH challenge.

Overall, FEV₁ increased by 9.9 ± 7.9% after bronchodilator (3.93 ± 0.97 to 4.28 ± 0.91 L, P < .001) and decreased by 23.9 ± 15.0% after the EVH challenge (3.89 ± 0.89 to 2.96 ± 0.88 L, P < .001). However, the change in FEV₁ after bronchodilator did not correlate with the change after EVH challenge (r = 0.062, P = .71). Significant bronchodilator responsiveness predicted a positive response to EVH challenge in 9 of 33 subjects (sensitivity 27%). Following EVH, the change in FEV₁ strongly correlated with the change in FVC (FEV₁ percent change vs FVC percent change, r = 0.831, P < .001; FEV₁ ΔL vs FVC ΔL, r = 0.799, P < .001).

These results extend previous findings that demonstrate a lack of association between bronchodilator responsiveness and methacholine responsiveness. Given the poor concordance between the spirometric response to fast-acting bronchodilator and the EVH challenge, these findings suggest that the airway response to inhaled β₂-agonist must be interpreted with caution and in the context of its determinants and limitations.