ORIGINALEffect of inhaled fluticasone on lung function in infants with recurrent wheezing: a randomised controlled trial
Introduction
Recurrent wheezing (RW) is a common health problem during infancy and probably one of the most frequent causes of medical consultation and admissions during the first two years of age. Several infants with RW are treated with regular inhaled corticosteroids (ICS) at the clinical setting even though there is controversy about their effect on symptoms and lung function in infants with recurrent asthma-like symptoms. It has been reported that inhaled fluticasone delivered to wheezy infants using pressurised metered dose inhalers (pMDI) plus holding chambers is useful to control respiratory symptoms and to improve lung function1., 2., 3., 4., 5., 6., 7.. However, other randomised controlled trials have not found clinical or functional benefit when treating infants with RW with pMDI fluticasone 8 or p MDI beclomethasone 9. Regardless of discrepancies on the beneficial effects of ICS in infants with RW, those medications are being increasingly prescribed to infants with repeated asthma symptoms in the clinical practice. Recently the use of ICS in those young patients has been supported by evidence-based recommendations10., 11..
Although ICS have been reported to be useful for the treatment of infants with asthma-like symptoms, the few trials which have considered lung function as endpoint reported contradicting results on the effect of ICS on lung function in wheezy infants12. The latter is likely to be the result of large methodological differences between studies regarding case definitions, age of patients, formulation of pMDI ICS, doses and delivery systems (jet nebulisers or pMDI plus spacers), aerosol quality (particle size distribution) and importantly, in the techniques employed for measuring lung function in infants.
A recent spirometric-like technique, the raised volume rapid thoracic-abdominal compression (RVRTAC), which performs measurements in a more physiological range13 and has a very low variability14, may offer significant advantages over other methods to assess the functional effect of ICS in infants with RW. This technique measures forced volumes (FVC and FEVt) and expiratory flows (FEF50 %, FEF75 %, FEF25-75 %) from a lung volume quite close to total lung capacity which makes it, as occurs with spirometry in older children, suitable to assess changes of lower airway calibre determined by treatments or diseases.
This randomised, double-blind and placebo-controlled study was undertaken to determine the effect of once-daily inhalation of 375 μg of fluticasone propionate, inhaled during 12 weeks, on forced expiratory flows measured by the RVRTAC technique in infants with recurrent wheezing at risk of asthma.
Section snippets
Subjects
Fifty infants with three or more troublesome episodes of physician diagnosed wheezing and at least one direct relative (parent or sibling) with physician-diagnosed asthma were recruited from our outpatient clinic at the Department of Pediatric Respiratory Medicine, Hospital El Pino in Santiago de Chile. Subjects were excluded if they had a birth-weight less than 2.5 kilograms, oxygen requirement in the neonatal period, cystic fibrosis, cardio-pulmonary malformations, neurological impairment, or
Results
Of the 50 infants who entered the study, six subjects were withdrawn: five patients because parents were unwilling to continue with the trial (three in fluticasone group and two in placebo group), and one from the placebo group because of receiving oral corticosteroids prescribed for a wheezing exacerbation soon after randomisation.
Therefore, we are reporting the results of lung function measurements in the 44 infants (21 in the fluticasone group and 23 in placebo group) who completed the study.
Parental Assessment
Wheezing and cough in the four weeks prior to entering the study were reported by parents in almost all infants in both groups (22/23 in fluticasone group and 22/24 in the placebo group). At discharge from the study, the proportion of mothers who reported their children were “definitely better than when they entered the study” was significantly greater for the fl uticasone (95.2 %) than for the placebo group (30.4 %),p < 0.001).
Discussion
This study found that once-daily inhalation of 375 μg fluticasone during 3 months caused a modest yet significant increase of forced expiratory flows (FEF50, FEF75 and FEF25–75) measured by the RVRTAC technique in infants with RW at risk of asthma, without significant changes in FVC and FEV0.5. This finding would suggest an underlying airway inflammatory defect as responsible for the bronchial narrowing in these infants, which could be better detected by measures of forced expiratory flow than
Conclusions
This randomised, double-blind, placebo-controlled study in infants with RW at risk of asthma demonstrated that treatment with once-daily inhaled 375 μg of fluticasone during 3 months improves forced expiratory flows (FEF50 %, FEF75 % and FEF25 %-75 %) and controlled symptoms without altering plasma cortisol levels. A clinical improvement reported by parents also occurred in one third of infants from the placebo group. The spirometry-like technique is a useful and objective tool to assess the
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2012, Kendig and Chernick's Disorders of the Respiratory Tract in ChildrenInhaled steroids for young children with recurrent wheezing: friend or foe?
2009, Allergologia et ImmunopathologiaPredicting the outcome of respiratory disease in wheezing infants using tidal flow-volume loop shape
2020, Allergologia et ImmunopathologiaCitation Excerpt :A simple and non-invasive method to evaluate the respiratory system at this age is needed. Some of the available studies that have assessed the response of wheezing disorders to inhaled corticosteroids14 are mainly based on thoraco-abdominal compression techniques on sedated children; however, this approach is not practical in daily medical practice. While the tPEF/tE ratio has been used to detect airway obstruction together with respiratory rate (RR),6,12,15 with a degree of success, the association of this parameter with a small airway caliber could not be demonstrated,16,17 possibly because parametric measurements exclude some valuable information expressed by the whole expiratory limb.