Interrupter resistance to measure dose-response to salbutamol in wheezy preschool children

Using a non-invasive lung function technique (interrupter resistance, Rint), we aimed to determine whether a dose-response to salbutamol could be detected in wheezy preschool children and if so, which dose of salbutamol should be administered to routinely evaluate bronchial reversibility.

Wheezy children (3 to <7 years) were enrolled in a prospective multicenter study. Rint was measured at baseline, and after random assignment to a first dose (100 or 200 μg) and a second dose (cumulative dose: 400, 600, or 800 μg) of salbutamol. Data were analyzed using mixed modeling approach with an inhibitory maximal effect (I_max ) model, to account for a sparse sampling design. Simulations were performed to predict the percentage of children with significant Rint reversibility at several doses.

Final results were available in 99 children out of 106 children included. The model adequately fitted the data, showing satisfactory goodness-of-fit plots and a low residual error of 8%. Children with uncontrolled symptoms had lower I_max (ie, showed less reversibility) compared to children with totally/partly controlled symptoms (0.23 vs. 0.31, P < 0.001). Dose to reach 50% of I_max (D₅₀ ) was 51 μg. According to simulations, 88.1% of children with significant reversibility at dose 800 μg would already show significant reversibility at 400 μg.

Interrupter resistance was able to measure a dose-response curve to salbutamol in wheezy preschool children, which was similar to that of older patients. Young children require a high dose of salbutamol to correctly assess airway bronchodilator response, especially these with poor symptom control.