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We compared the responses of cystic fibrosis (CF) (N = 14) and normal (N = 14) infants with inhaled methacholine. Airway function was assessed by forced expiratory flows at functional residual capacity (Vmax FRC) generated by the rapid compression technique, and methacholine responsiveness was quantitated as (1) TC: the threshold concentration to decrease Vmax FRC by 2 SD from baseline; (2) PC50: the provocative concentration to decrease Vmax FRC by 30%; and (3) SPC30; the slope of the dose-response curve between TC and PC30. There were no significant differences in age between CF and normal infants (16 +/- 8 versus 17 +/- 5 months, p greater than 0.3); however, the CF infants were shorter (74 +/- 10 versus 81 +/- 5 cm, p less than 0.05), had lower absolute Vmax FRC (241 +/- 103 versus 374 +/- 113 ml/s, p less than 0.001), and tended to have lower percentage of predicted flow values (87 +/- 13 versus 111 +/- 34%, p less than 0.10). Comparison of the indices of airway responsiveness revealed no difference in logTC; however, the CF infants had smaller, more negative values for logPC30 (-0.76 +/- 0.52 versus -0.22 +/- 0.53, p less than 0.02) and steeper slopes to their dose-response curves (logSPC30, 2.42 +/- 0.45 versus 1.88 +/- 0.74, p less than 0.025). Indices of airway responsiveness correlated significantly with baseline Vmax FRC (% of predicted). After the influence of baseline flow upon airway responsiveness was accounted for by multiple linear regression analysis, there was a tendency for CF infants to be more responsive than control infants.(ABSTRACT TRUNCATED AT 250 WORDS)

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 (VmaxFRC), generated by rapid chest compression. After baseline measurements, each subject inhaled increasing concentrations of methacholine (Mch), beginning with 0.075 mg/ml, until VmaxFRC decreased 30% or Mch = 2.5 mg/ml. Sensitivity to Mch was defined as the threshold concentration (TC) required to decrease VmaxFRC 2 SD from control, and the Mch required to decrease 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 less than 0.02; r = 0.63, p less than 0.001, respectively), indicating decreasing sensitivity to Mch with increasing age. Log SPC-30 became less steep with increasing age (r = -0.59, p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

The weighted-spirometer method for noninvasive determination of static total respiratory system compliance (Crs) was adapted for use in infants. Ten normal newborns and 5 infants with bronchopulmonary dysplasia (BPD) were studied. The newborns had a mean Crs of 3.8 ml/cm H2O. Their mean specific Crs was 1.13 ml/cm H2O/kg body weight and 0.075 ml/cm H2O/cm body length. These Crs values were similar to those reported by other investigators who used the Hering-Breuer airway occlusion technique. The infants with BPD, who were of the same weight, height, and postconception age as the normal newborns, had significantly (p less than 0.05) lower mean specific Crs (0.60 ml/cm H2O/kg body weight and 0.047 ml/cm H2O/cm body length) relative to the normal newborns. These data suggest that intrinsic changes in lung elastic characteristics may contribute to the reduced lung compliance of infants with BPD. The weighted-spirometer method for measuring Crs is a potential tool for the noninvasive study of the elastic properties of the respiratory system during infancy in health and disease.

Response to the inhaled bronchodilator, metaproterenol, was evaluated in 28 outpatient infants and young children with cystic fibrosis (CF) (mean age, 16 months) and in 22 normal control children (mean age, 13 months). Lung function was assessed from partial expiratory flow volume curves generated by the rapid compression technique and was quantitated by the maximal expiratory flow at functional residual capacity (VmaxFRC). For the normal control group there was no significant change in VmaxFRC after the aerosol of either normal saline or metaproterenol. At baseline, the group of infants with CF had significantly lower values of VmaxFRC than did the normal control infants (202 versus 273 ml/s, p less than 0.05). The CF group demonstrated no significant change from baseline VmaxFRC after the aerosol of normal saline. However, after metaproterenol the CF group had a significant increase (p less than 0.001) in VmaxFRC, which eliminated the difference in VmaxFRC between the CF and normal control groups (267 versus 276 ml/s). We conclude that infants and young children with CF have increased bronchomotor tone and that bronchoconstriction represents a significant component of the airway obstruction present in patients with CF at this age.

Pulmonary function tests were performed on a total of 125 healthy infants younger than 25 postconception (pc) months of age. Maximal expiratory flow at functional residual capacity (VmaxFRC) was measured from partial expiratory flow-volume curves, and functional residual capacity (FRC) was measured by the helium dilution technique. There was a highly significant (p less than 0.01) linear regression for both VmaxFRC and FRC with increasing body length. The highest size-corrected flows (VmaxFRC/FRC) were obtained in the healthy premature (2.7 FRC/s, n = 6) and full-term (2.5 FRC/s, n = 5) infants, and there was a relatively constant value between 13 and 25 pc months of age (1.2 FRC/s), which was similar to those reported in older children and adults. In an age-matched group of infants 10 to 16 pc months of age, females had both higher absolute flows (126 versus 102 ml/s, p less than 0.03) and size-corrected flows (1.4 versus 1.0 FRC/s, p less than 0.001) than did males. These physiologic data support the concepts that neonates have proportionately larger airways relative to their lung volume at FRC, infants have size-corrected flows similar to those in older children and adults, and female infants have proportionately larger airways relative to their lung size than do male infants.

Total respiratory system compliance (Crs) was assessed by the weighted spirometer method in 11 asymptomatic infants (mean age, 11.1 months) with cystic fibrosis (CF) who had normal chest radiographs. In addition to Crs, functional residual capacity (FRC), respiratory rate (RR), and mixing index (MI) were measured. There was no significant difference in FRC between normal controls (n = 36) and CF infants (190 +/- 69 versus 186 +/- 63 ml; p less than 0.8), although the CF group had a higher RR (32 +/- 7 versus 37 +/- 7 BPM; p less than 0.05) and a lower MI (45 +/- 7 versus 40 +/- 8%; p less than 0.05), reflecting an abnormal distribution of ventilation. The lower Crs (9.0 +/- 3.4 versus 5.7 +/- 2.8 ml/cm H2O; p less than 0.01) and the lower specific compliance, Crs/FRC (0.049 +/- 0.013 versus 0.029 +/- 0.007 1/cm H2O; p less than 0.0001), in the CF group were the parameters that best distinguished the normal control and CF infants. We conclude that the measurement of Crs represents a noninvasive method for detecting early pulmonary function abnormalities in CF infants.