ASTHMA: PATHOPHYSIOLOGY |
Bronchodilator Responsiveness in Normal Infants and Young Children
Indianapolis, IN
Purpose of the Study. To evaluate the baseline airway responsiveness to a bronchodilator, albuterol, in normal infants and young children using changes in maximal expiratory flow rates.
Study Population. In 2 major children’s hospitals, healthy infants <3 years old were recruited for the study. Exclusion criteria included preterm (<36 weeks’ gestation) birth, congenital malformations, or 2 or more episodes of recurrent wheezing with lower respiratory tract infections. Infants who had chronic respiratory conditions were also excluded. At the time of the study, they had to be free of any respiratory tract symptoms and have not had a cold for the previous 2 weeks.
Methods. Questions were asked about prenatal and postnatal smoke exposure. Infant pulmonary function testing was performed at each institution using technologies well-established at each institution (Columbus Children’s Hospital, Columbus, Ohio, and James Whitcomb Riley Hospital for Children, Indianapolis, Indiana). Maximal expiratory flow-volume curves were obtained at baseline. Measurements included forced vital capacity, forced expiratory flow at 25, 50, 75, 85, and between 25 and 75% of the expired forced vital capacity (FEF25%, FEF50%, FEF75%, FEF85%, and FEF25–75%). The forced expired volume in 0.5 second, FEV0.5, was also measured. Albuterol was given using a metered-dose inhaler and spacer. Adequate drug delivery was assumed when the resting heart rate increased by 10%. Repeated doses of albuterol were given until the heart rate increased until a maximum of 8 puffs over 8 minutes. Measurements of pulmonary function began 10 minutes after the first dose of albuterol. A second group of infants received placebo. Response to albuterol was either a percent change in FEF75 >2 standard deviations from the mean response seen in the placebo group or by visual inspection of the flow-volume curves.
Results. There were 28 in the albuterol group and 13 in the placebo group. There were no significant differences between the groups in any parameter except for a greater percentage of smoking parents in the albuterol group. An average of 4.2 puffs of albuterol were given to the "albuterol" group. Albuterol caused significant increased in FEF75%, FEF85%, FEV0.5%, and FEF25–75%. The changes versus placebo were FEF75% 10.6 versus –3.1%, FEF85% 12.9 versus 0.46%, and FEV0.5 2.2 versus –1.5%. Using the method of standard deviation, 6 of 28 infants responded to albuterol. All of the responders were <1 year old. There were a total of 16 infants in the albuterol group, 6 of 16 responded to albuterol. There were no significant differences in baseline measures of pulmonary function between albuterol responders and nonresponders. Responders were significantly younger and had a higher percentage of mothers who smoke during pregnancy—4 of the 6 compared to 5 of 22 nonresponders. Albuterol responders also had a higher percentage of smoking parents. Five of 6 of the albuterol responders had parents who smoked as compared with 10 of the 22 nonresponders. When all the infants born to mothers who smoked were evaluated, the mean increase in FEF75% with albuterol was 19.8% compared with 6.3% of infants born to nonsmoking mothers.
Conclusions. Normal healthy infants who have no respiratory symptoms have baseline airway tone that can be reversed with albuterol using measurements from a forced expiratory maneuver. Also, young infants and those exposed to maternal smoking during pregnancy had greater increases in forced expiratory flow after albuterol.
Reviewer’s Comments. The technology exists to measure airflow in infants and young children. In this article, the authors evaluate normal children and have verified the findings of a few previous studies. Cigarette smoke exposure can increase airway responsiveness in infants. The concern is that this is seen in infants who at the time of the study had no lower respiratory tract symptoms. One of the concerns is what will happen prospectively to these infants. Will they declare themselves with more severe lower respiratory tract illness in the future? Are they at risk? Did parental behavior change, did they stop smoking when shown this data?? Perhaps more reasons to discourage smoking.
REFERENCES
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Goldstein AB, Castile RG, Davis SD, et al.
Am J Respir Crit Care Med.2001; 164
:447
–454
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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