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We previously reported a randomised controlled trial of β2 agonist in wheezing infants.1 Within this paper we reported no measurable physiological response to 400 μg salbutamol. Pulmonary function tests were performed after the completion of a symptom diary study and prior to enrolment in a study of inhaled corticosteroid.2 Raw values of maximum flow at functional residual capacity (V′maxFRC) and bronchodilator response were reported as there were no suitable standard values for V′maxFRC available, either from our laboratory or internationally.
Subsequently, collaboration between centres in the UK and USA has produced enough data to allow calculation of standard deviation scores (Z scores) for V′maxFRC.3 We have now reanalysed our data in the light of this new information.
Of 29 subjects, seven had abnormal baseline V′maxFRC Z scores (⩽ −2). In comparison with subjects with normal baseline V′maxFRC (Z score > −2) these patients showed a significantly greater response to salbutamol (see table 1). Six of seven subjects showed a significant change in V′maxFRC (>12.5% or >2× group coefficient of variation) compared to 3/22 in the normal group (see fig 1). This suggests that patients with identifiable obstruction at the time of testing are more likely to respond to inhaled salbutamol.
The evidence for efficacy of bronchodilators in early life is lacking. Although many intervention studies have been performed, the majority have suboptimal methodology or insensitive outcome measures.4 Infant pulmonary function studies are usually performed at a time the child is asymptomatic due to concerns of sedating ill patients, reducing the opportunity to measure a response. Due to the protocol design of our study, subjects could only have pulmonary function measured during a two week period1,2 and thus, although not acutely unwell on the day of testing, may have had a recent exacerbation or upper respiratory tract infection with persisting changes of airway obstruction. This may have allowed us to measure this response, although this was not apparent without the use of an appropriate reference standard.
Post hoc subgroup analysis of this kind should always be interpreted with caution. An alternative explanation for these findings could be regression towards the mean, with those with worst baseline function becoming more “normal”. While this data involves only small numbers and no control group, it does indicate a possible benefit of salbutamol in infants with demonstrable airway obstruction at the time of testing, and invites further studies using appropriate techniques and reference standards.
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