Changes in Airway Reactivity with Age in Normal Infants and Young Children

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Abstract
We have previously demonstrated that normal healthy infants exhibit airway reactivity to inhaled methacholine. The purpose of this study was to evaluate the changes in airway reactivity with age in infants and young children. We tested 24 healthy term subjects 4 to 24 months of age (mean 13 months) with history negative for lower respiratory illnesses and wheezing. Airway function was assessed by maximal expiratory flow at FRC (.ovrhdot.VmaxFRC), generated by rapid chest compression. After baseline measurements, each subject inhaled increasing concentrations of methacholine (Mch), beginning with 0.075 mg/ml, until .ovrhdot.VmaxFRC decreased 30% or Mch = 2.5 mg/ml. Sensitivity to Mch was defined as the threshold concentration (TC) required to decrease .ovrhdot.VmaxFRC 2 SD from control, and the Mch required to decrease .ovrhdot.VmaxFRC 30% (PC-30). Airway reactivity was defined as the slope between TC and PC-30 (SPC-30). We found significant regressions for TC, PC-30, and log SPC-30 versus age. TC and PC-30 increased with increasing age (r = 0.51, p < 0.02; r = 0.63, p < 0.001, respectively), indicating decreasing sensitivity to Mch with increasing age. Log SPC-30 became less steep with increasing age (r = -0.59, p < 0.01), reflecting decreasing reactivity to Mch with increasing age. Of these infants, 10 had their Mch challenge repeated a mean of 8 months (range 4 to 11.5) following their initial test, with no lower respiratory illnesses in the interim. For these 10 infants, paired t tests demonstrated that PC-30 increased (1.00 to 2.14 mg/ml, p < 0.05) and log SPC-30 decreased (1.98 to 1.23, p < 0.02), indicative of decreasing sensitivity and reactivity with increasing age. We conclude that both cross-sectional and longitudinal data demonstrate a decrease in airway reactivity to Mch with increasing age in infants and young children.