Airway responsiveness in wheezy infants: evidence for functional beta adrenergic receptors.

Abstract

The effect of nebulised salbutamol on the bronchial response to nebulised histamine was studied in five wheezy infants aged 3-12 months. The response to doubling concentrations of up to 8 g/l of histamine was assessed by the change in maximum flow at FRC (VmaxFRc), measured by flow-volume curves produced during forced expiration with a pressure jacket. The concentration of histamine required to provoke a 30% fall in VmaxFRc (PC30) was measured. All of the infants responded to low concentrations of histamine during control tests before and after nebulised saline (mean PC30 1 07 and 0-51 g/l). On a separate day there was a similar response to histamine before salbutamol (PC30 0 57 g/l), but after salbutamol the response was completely abolished up to the maximum concentration of histamine in all subjects (PC30 > 8 g/1). Thus wheezy infants have highly effective P2 adrenoceptors in intrathoracic airways.Wheezing disorders of infancy, although common, are difficult to treat.1 Physiological studies carried out on wheezy infants have failed to show any useful response to nebulised f adrenergic agents in terms of reduction in the overall respiratory resistance or work of breathing.2`Since, however, in infants more than 50% of total airway resistance is contributed by the upper airways, a change in intrathoracic airway calibre may well be masked in this type of study. In a recent study of airway responsiveness to salbutamol in wheezy infants we used a pressure jacket to produce partial expiratory flow-volume (PEFV) curves. From these curves we determined forced expiratory flow at FRC (VmaxFRc) as an index of intrathoracic airway function. In common with others5 -7we found a significant fall in VmaXFRc after nebulised salbutamol. Although negative, this observation supports the concept that ,B receptors are present in the infant airway in sufficient density to be recognisable by gross physiological measurements. A possible explanation for this paradoxical response to a "bronchodilator" drug is that a reduction in smooth muscle tone, without a commensurate fall in airway resistance, renders the airways more compliant and therefore less able to support high flow rates.8

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

“…Double-blind placebo-controlled studies have demonstrated significant bronchodilatory effects [95][96][97][98] and protective effects against bronchoconstrictor agents [99,100] in infants and preschool children treated with rapidly acting inhaled b 2 -agonist. Thus, infants possess functional b 2 -receptors from birth, and stimulation of these receptors can produce the same effects as in older children, although paradoxical responses to inhaled b 2 -agonists have been reported in infants [50,101]. Oral administration of b 2 -agonist is also effective but is limited by systemic side-effects [102].…”

Bronchodilator responsiveness testing using raised volume forced expiration in recurrently wheezing infants

“…The majority of infants we tested had a history of significant past wheezing illnesses, but none were symptomatic at the time of testing. Previous studies of bronchodilators in infants have evaluated: a) acutely wheezing infants 2,9,10,11 ; b) infants immediately prior to discharge following an admission with a wheezing illness 1 ; c) recurrently wheezy infants who were asymptomatic at the time of testing, 3,4,7 as in this study. We chose the latter of these three groups as the study population for this initial study since they had a small risk on administration of chloral hydrate compared to acutely wheezing infants.…”

“…Others have found no evidence of bronchodilator responsiveness using forced expiratory techniques in infants. 1,3 However, there is evidence that bronchodilators protect against induced bronchoconstriction 4 and also hasten its recovery. 5 There is debate as to what should be considered a significant response to bronchodilators; some suggest that it is more appropriate to take a fixed volume (of 180 ml in adults) rather than a percentage change.…”

“…Others have demonstrated a decrease in forced expiratory flows in the acute phase of the disease. 2 There are also studies showing that inhaled bronchodilators have no detectable bronchodilator effect, but offer protection against induced bronchoconstriction in recurrently wheezy but asymptomatic infants 3,4 and speed recovery from histamine-induced bronchoconstriction in wheezy 5 and healthy 6 infants. Estimates of gas trapping have been shown to improve in response to bronchodilators in recurrently wheezy infants.…”

Medicines used in respiratory diseases only seen in children

“…A 2002 Cochrane review sought to determine the effectiveness of b 2 -agonists for infants (,2 yrs) with ''recurrent or persistent wheeze'' [164]. Eight studies meeting the Cochrane criteria were identified [165][166][167][168][169][170][171][172]. Five studies had clinical end-points, and three assessed changes in lung function.…”