Application of a Shortened Inhaled Adenosine-5′-Monophosphate Challenge in Young Children Using the Forced Oscillation Technique

Abstract

Adenosine-5'-monophosphate (AMP) is an indirect challenge agent thought to reflect allergic airway inflammation. The forced oscillation technique (FOT) is ideal for use in young children and is suitable for inhaled challenge studies in patients who are in this age group. We assessed the agreement between a shortened and a standard AMP challenge and the repeatability of the shortened AMP challenge using FOT as a primary outcome variable. Eighteen children completed a shortened and a standard AMP challenge, and 20 children completed repeated shortened AMP challenges. The children inhaled nebulized AMP tidally for 2 min, following which the presence of wheeze and pulse oximetric saturation (Spo(2)) was recorded prior to FOT measurement. Testing continued until the maximum dose was reached or until wheeze, a decrease in Spo(2) to < 90%, or an increase in respiratory resistance at 8 Hz of 2.0 hPa/s/L or 30% was noted. Concordance was assessed as a binary response, and agreement in provocation concentrations (PCs) causing a response was assessed with intraclass correlations. There was a high degree of concordance between the shortened and standard AMP protocols (94%) and repeated shortened AMP protocols (100%). The mean log(10) PCs displayed a high degree of agreement for both AMP protocols, with intraclass correlation coefficients of 0.94 (95% confidence interval, 0.85 to 0.98) and 0.94 (95% confidence interval, 0.82 to 0.98), respectively. We demonstrated that a shortened AMP challenge that can be applied to young children is comparable to the standard AMP challenge and is highly repeatable. Further studies in young children to assess the clinical role of a shortened AMP challenge using FOT are required.