Detection of excessive bronchoconstriction in asthma

Airway hyperresponsiveness is easily assessed by measuring the concentration or dose of an inhaled agonist that produces a defined response, e.g., PC₂₀ or PD₂₀. However, this measure does not assess excessive bronchoconstriction. We report the results of analyzing bronchial dose- response curves by measuring percent fall in vital capacity (ΔFVC%) as the response rather than the PC₂₀. In our analysis, ΔFVC% was measured at the PC₂₀, and therefore it was the dependent variable, whereas the concentration of agonist was the independent variable, in contrast to the usual bronchoprovocation tests in which the response is the independent variable and the dose is the dependent variable. We reasoned that a dose- dependent increase in gas trapping with histamine would detect excessive bronchoconstriction as a decrease in FVC; in contrast, PC₂₀ measures only the ease of bronchoconstriction. In 10 patients with mild asthma the reproducibility of ΔFVC% when FEV₁ fell by 20%, i.e., at the PC₂₀ concentration of histamine, taken from a greater than 6-s FVC on an otherwise standard histamine challenge test was comparable to that of PC₂₀. In 10 healthy asymptomatic subjects there were only trivial falls (0.3%) in FVC to as much as 16 mg/ml histamine. In a retrospective study of 146 patients with mild asthma, the ΔFVC% was normally distributed (13.2 ± 5.5 SD%) and did not correlate with the number of β₂-agonist prescriptions or the PC₂₀, but it did correlate with the number of prescriptions written per month for oral prednisone (r = 0.55, p < 0.02). We conclude that ΔFVC% when FEV₁ falls by 20% is a safe method of detecting excessive bronchoconstriction, and it reveals that different asthmatics react in fundamentally different ways to the same agonist. This may be useful in detecting the asthmatic at risk for serious disease.