Dose-response slope of forced oscillation and forced expiratory parameters in bronchial challenge testing

Abstract

In population studies, the provocative dose (PD) of bronchoconstrictor causing a significant decrement in lung function cannot be calculated for most subjects. Dose-response curves for carbachol were examined to determine whether this relationship can be summarized by means of a continuous index likely to be calculable for all subjects, namely the two-point dose response slope (DRS) of mean resistance (R(m)) and resistance at 10 Hz (R10) measured by the forced oscillation technique (FOT). Five doses of carbachol (320 μg each) were inhaled by 71 patients referred for investigation of asthma (n=16), chronic cough (n=15), nasal polyposis (n=8), chronic rhinitis (n=8), dyspnoea (n=8), urticaria (n=5), post-anaphylactic shock (n=4) and miscellaneous conditions (n=7). FOT resistance and forced expiratory volume in one second (FEV1) were measured in close succession. The PD of carbachol leading to a fall in FEV1 ≥20% (PD20) or a rise in R(m) or R10 ≥47% (PD(47,R(m)) and PD(47,R10) were calculated by interpolation. DRS for FEV1 (DRS(FEV1)), R(m) (DRSR(m)) and R10 (DRS(R10)) were obtained as the percentage change at last dose divided by the total dose of carbachol. The sensitivity (Se) and specificity (Sp) of DRS(R(m)), DRS10 Δ%R(m) and Δ%R10 in detecting spirometric bronchial hyperresponsiveness (BHR, fall in FEV1 ≥20%) were assessed by receiver operating characteristic (ROC) curves. There were 23 (32%) 'spirometric' reactors. PD20 correlated strongly with DRS(FEV1) (r=-0.962; p=0.0001); PD(47,R(m)) correlated significantly with DRS(R(m)) (r=-0.648; p= 0.0001) and PD(47,R10) with DRS(R10) (r=-0.552; p=0.0001). DRS(FEV1) correlated significantly with both DRS(R(m)) (r=0.700; p=0.0001) and DRS(R10) (r=0.784; p=0.0001). The Se and Sp of the various FOT indices to correctly detect spirometric BHR were as follows: DRS(R(m)): Se=91.3%, Sp=81.2%; DRS(R10): Se=91.3%, Sp=95.8%; Δ%R(m): Se=86.9%, Sp=52.1%; and Δ%R10: Se=91.3%, Sp=58.3%. Dose-response slopes of indices of forced oscillation technique resistance, especially the dose-response slope of resistance at 10Hz are proposed as simple quantitative indices of bronchial responsiveness which can be calculated for all subjects and that may be useful in occupational epidemiology.