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Inicio Allergologia et Immunopathologia Inhaled steroids for young children with recurrent wheezing: friend or foe?
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Vol. 37. Núm. 2.
Páginas 55-56 (abril 2009)
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Vol. 37. Núm. 2.
Páginas 55-56 (abril 2009)
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Inhaled steroids for young children with recurrent wheezing: friend or foe?
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Dirceu Solé
Full Professor and Head of Division of Allergy, Clinical Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil
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Wheezing and cough are common respiratory symptoms in children and may be the clinical expression of several localised problems of the respiratory tract. The incidence of wheezing is high during the first year of life, mainly in developing countries, reaching up to 80 % in a cohort of infants living in a poor urban region1. A recent study which used a standard written questionnaire showed that almost 50 % of unselected 1-year-old children interviewed during routine clinical evaluation have experienced at least one episode of wheezing and half of them have had three or more episodes; they were defined as recurrent wheezers2.

Recurrent wheezing (RW) is reported to be associated with an increase in nocturnal respiratory symptoms, visits to emergency department, severity of symptoms and hospitalisations for respiratory distress. Furthermore, population-based birth cohort studies have demonstrated that infants with RW have higher risk of developing persistent asthma later in childhood or in adolescence, and those who were atopic are particularly more likely to continue wheezing3,4.

During the first two years of life the diagnosis of asthma is not an easy task. Frequently, it is possible only through long-term follow-up, consideration of the extensive differential diagnosis and by observing the child's response to bronchodilator and/or anti-inflammatory treatment5. Nevertheless, it has been proposed that children with RW must be considered as having asthma, and anti-inflammatory treatment be promptly initiated5,6.

Inhaled corticosteroids (ICS) are pointed out as the first line treatment for children with persistent asthma. Nevertheless, the treatment with ICS for children with RW is still controversial. They are recommended for those with persistent/severe symptoms6. The main reasons for using these agents are to decrease or remit airway inflammation and to prevent the development of irreversible airway obstruction, inducing a possible potential disease-modifying effect6.

Clinical effects of ICS are variable according to the drug studied. They depend on the amount of drug that reaches the lungs and also on the inhalation technique, the type of inhaler used, the solvent, the propellant, the size of delivered particles, if a spacer is used or not, and the dose utilised7.

Fluticasone propionate (FP) is one the most used ICS for the treatment of children with RW8–16. Notwithstanding it is administered in combination with spacers, the results observed with the treatment of children with RW are quite variable. Increase in percentage of symptom-free days8–10,12, decrease in symptoms score9,14,15, reduction in the number of exacerbations8,10,12, decrease in the use of rescue medication (inhaled beta 2 agonists8,10,12 or oral corticosteroids8,16) were the main clinical outcomes observed. Improvement of lung function was verified by some 10,12, but not by others9,13,15.

The administered doses of FP, the type of spacer, the length of the treatment, the type of patient treated (virus-induced RW or children with RW and high-risk of asthma), and the outcomes established: clinical and/or lung function measurements are some factors that would interfere with the disparities observed in results.

The dose of FP utilized in these studies has varied between 200 mcg and 750 mcg, once or twice daily, administered by pressurised metered dose-inhaler plus spacer. Patients with high-risk of asthma, in general respond better to the treatment with inhaled FP10,12. Another factor which can interfere in the results is the lung function measurement technique applied. Several methods are available for use in infants and young children17. It is well known that the measurement of forced flows is the most sensitive parameter to detect changes during the drug administration17.

This issue of Allergologia et Immunopathologia features the study of Mallol et al which evaluates the once a day 375 mcg FP treatment, administered by pressurised metered dose-inhaler plus spacer to RW children with high-risk of asthma during three months18. At the end of the study they observed an improvement of clinical data: a reduction in the number of wheezing episodes reported by parents and diagnosed by a physician. A significant increase in forced flows was also observed and measured by the raised volume rapid thoracic compression technique (spirometry-like). These results might reinforce the anti-inflammatory action of FP to reduce the airway obstruction secondary to mucosa inflammation often present in these children. No interferences of the cortisol levels after the treatment were reported.

Considering that at least one third of children with RW would undergo asthma, inhaled FP would be prescribed for children with moderate to severe RW and followed for at least three months, with this scheme maintained for those who experienced clinical improvement. Although the incidence of adverse effects due to ICS is low, patients must be closely followed-up to detect them early.

Apart from the good results reported by some authors, the long-term studies with ICS have demonstrated that, besides the control of symptoms, there is no evidence to support a subsequent disease-modifying effect of ICS i.e. there is no long-lasting effect on the natural history of wheezing/asthma in children12,13,19.

References
[1.]
J. Mallol, R. Andrade, F. Auger, J. Rodríguez, R. Alvarado, L. Figueroa.
Wheezing during the first year of life in infants from low-income population: a descriptive study.
Allergol Immunopathol (Madr), 33 (2005), pp. 257-263
[2.]
H.J. Chong Neto, N.A. Rosário, D. Solé, J. Mallol.
Prevalence of recurrent wheezing in infants.
J Pediatr (Rio J), 83 (2007), pp. 357-362
[3.]
S. Illi, M.E. von, S. Lau, B. Niggemann, C. Gruber, U. Wahn.
Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study.
[4.]
E. Piippo-Savolainen, M. Korppi.
Wheezy babies-wheezy adults? Review on long-term outcome until adulthood after early childhood wheezing.
Acta Paediatr, 97 (2008), pp. 5-11
[5.]
National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Im munol 2007;120(5 Suppl):S94-138. Erratum in: J Allergy Clin Immunol. 2008;121:1330.
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Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report.
[7.]
Inhalation devices.
CMAJ, 173 (2005), pp. S39-S45
[8.]
H. Bisgaard, D. Allen, J. Milanowski, I. Kalev, L. Willits, P. Davies.
Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1 to 3 years with recurrent wheezing.
Pediatrics, 113 (2004), pp. e87-e94
[9.]
W. Hofhius, E.C. van der Wiel, E.M. Nieuwhof, W.C.J. Hop, M.J. Affourtit, F.J. Smit, et al.
Efficacy of fluticasone propionate on lung function and symptoms in wheezy infants.
Am J Respir Crit Care Med, 171 (2005), pp. 328-333
[10.]
A.M. Tepper, C.D. Kofman, G.A. Szuklman, S.M. Vidaurreta, A.F. Maffey.
Fluticasone improves pulmonary function in children under 2 years old with risk factors for asthma.
Am J Respir Crit Care Med, 1771 (2005), pp. 587-590
[11.]
H. Bisgaard, M.N. Hermansen, L. Loland, L.B. Halkjaer, F. Buchvald.
Intermittent inhaled corticosteroids in infants with episodic wheezing.
N Engl J Med, 354 (2006), pp. 1998-2005
[12.]
T.W. Guilbert, W.J. Morgan, R.S. Zeiger, D.T. Mauger, S.J. Boehmer, S.J. Szefler, et al.
Long-term inhaled corticosteroids in preschool children at high risk for asthma.
N Engl J Med, 354 (2006), pp. 1985-1997
[13.]
C.S. Murray, A. Woodcock, S.J. Langley, J. Morris, A. Custovic.
Secondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy Infants (IFWIN): double-blind, randomized, controlled study.
[14.]
S. Schokker, E.M. Kooi, T.W. de Vries, P.L. Brand, P.G. Mulder, E.J. Duiverman, et al.
Inhaled corticosteroids for recurrent respiratory symptoms in preschool children in general practice: randomized controlled trial.
Pulm Pharmacol Ther, 21 (2008), pp. 88-97
[15.]
E.M. Kooi, S. Schokker, M. Boezen, T.W. de Vries, A.A. Vaessen-Verbene, T. van der Molen, et al.
Fluticasone or montelukast for preschool children with asthma-like symptoms: randomized controlled trial.
Pulm Pharmacol Ther, 21 (2008), pp. 798-804
[16.]
F.M. Ducharme, C. Lemire, F.J. Noya, G.M. Davies, N. Alos, H. Leblond, et al.
Preemptive use of high-dose fluticasone for virus-induced wheezing in young children.
N Engl J Med, 360 (2009), pp. 339-353
[17.]
G.L. Larsen, J.K.B. Kang, T. Guilbert, W. Morgan.
Assessing respiratory function in young children: developmental considerations.
J Allergy Clin Immunol, 115 (2005), pp. 657-666
[18.]
J. Mallol, V. Aguirre, L. Barrueto, G. Wandalsen, R. Tepper.
Effect of inhaled fluticasone on lung function in infants with recurrent wheezing: a randomised controlled trial.
Allergol et Immunopathol, 37 (2009), pp. 57-62
[19.]
C.S. Murray.
Can inhaled corticosteroids influence the natural history of asthma?.
Curr Opin Allergy Clin Immunol, 8 (2008), pp. 77-81
Copyright © 2009. Sociedad Española de Inmunología Clínica y Alergología Pediátrica y Elsevier España, S.L.
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