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

Pediatr Pulmonol. 2018 Sep;53(9):1252-1259. doi: 10.1002/ppul.24116. Epub 2018 Jul 3.


Aim: 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.

Method: 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 (Imax ) model, to account for a sparse sampling design. Simulations were performed to predict the percentage of children with significant Rint reversibility at several doses.

Results: 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 Imax (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 Imax (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.

Conclusion: 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.

Keywords: asthma & early wheeze; bronchodilation; pharmacodynamic; pulmonary function testing.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Resistance*
  • Albuterol / administration & dosage*
  • Albuterol / pharmacology
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / pharmacology
  • Child
  • Child, Preschool
  • Computer Simulation
  • Female
  • Hospitalization
  • Humans
  • Male
  • Prospective Studies
  • Respiratory Function Tests*
  • Respiratory Sounds*


  • Bronchodilator Agents
  • Albuterol