ORIGINAL
Effect of inhaled fluticasone on lung function in infants with recurrent wheezing: a randomised controlled trial

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Abstract

Background

Inhaled corticosteroids are used to treat infants with troublesome asthma-like symptoms but their effect on the lung function of these young patients is controversial.

Material and Methods

Forty-four infants with recurrent wheezing (more than 3 episodes) and family history of asthma completed this randomised, parallel, double-blind, controlled trial to compare the effect on lung function (main endpoint) of once-daily inhaled fluticasone (375 μg) versus placebo for 3 months. Pulmonary function was measured while infants were asymptomatic, using the raised volume rapid thoracic compression technique (spirometry-like), and values were converted to z-scores.

Results

The fluticasone group showed a significant increase in forced flows, (p < 0.001), a lower number of physician diagnosed wheezing episodes (p < 0.002), and a significant decrease in the parent-reported number of wheezing episodes per month (p < 0.03), as compared to placebo. One third of parents in the placebo group reported a clinical improvement in their infants. There was no significant difference in morning plasma cortisol between groups at entry or discharge.

Conclusions

We conclude that once-daily treatment with 375 μg fluticasone increased forced flows and controlled symptoms in infants with recurrent wheezing without altering plasma cortisol levels. The spirometry-like technique is a useful tool to objectively assess the efficacy of anti-asthma medications in infants with repeated troublesome asthma-like symptoms.

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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