The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial
BMJ 2009; 338 doi: https://doi.org/10.1136/bmj.b897 (Published 31 March 2009) Cite this as: BMJ 2009;338:b897
- Marieke J J Ermers, junior research fellow1,
- Maroeska M Rovers, epidemiologist 2,
- Job B van Woensel, paediatrician, intensive care specialist3,
- Jan L L Kimpen, professor of paediatric infectious diseases1,
- Louis J Bont, paediatrician, infectious diseases specialist1
- on behalf of the RSV Corticosteroid Study Group
- 1Department of Paediatric Infectious Diseases, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, PO Box 85090, 3508 AB Utrecht, Netherlands
- 2Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Netherlands
- 3Department of Paediatric Intensive Care, Emma Children’s Hospital, Academic Medical Centre, Amsterdam, Netherlands
- Correspondence to: L J Bont l.bont{at}umcutrecht.nl
- Accepted 19 November 2008
Abstract
Objective To determine whether early initiated anti-inflammatory therapy with prolonged high dose inhaled glucocorticoids influences the occurrence and severity of recurrent wheeze after respiratory syncytial virus related lower respiratory tract infections.
Design Randomised double blind placebo controlled trial.
Setting Paediatric departments of 19 Dutch clinical centres.
Participants 243 previously healthy infants (126 boys, 117 girls) aged less than 13 months and admitted to hospital with respiratory syncytial virus infection.
Interventions 200 μg extra fine hydrofluoroalkane (HFA) beclometasone dipropionate twice daily or matched placebo administered by a pressurised metered dose inhaler and a spacer during the first three months after hospital admission.
Main outcome measure The primary outcome was the number of days with wheeze in the year after the three month intervention period.
Results Of the 243 eligible infants, 119 were randomised to receive beclometasone and 124 to receive placebo. No significant difference was found in the number of days with wheeze between the two groups (total days, 1761/33 568 in the beclometasone group v 2301/36 556 in the placebo group, P=0.31) and the proportion of infants with wheeze did not differ between the groups (61% in the beclometasone group v 62% in the placebo group, P=0.90). In the predefined subgroup of infants who did not need mechanical ventilation (n=221), beclometasone reduced the number of days with wheeze by 32% (relative reduction in total days, 1315/30 405 in the beclometasone group v 2120/33 149 in the placebo group, P=0.046). This reduction was most pronounced during the first six months of the follow-up year after intervention. The proportion of infants with wheeze did not differ between the groups (59% in the beclometasone group v 60% in the placebo group, P=0.89).
Conclusions Early initiated high dose extra fine HFA beclometasone to infants during the first three months after hospital admission for respiratory syncytial virus infection has no major effect on recurrent wheeze. The general use of such treatment during lower respiratory tract infection with respiratory syncytial virus should not be advocated.
Trial registration Current Controlled Trials ISRCTN12352714.
Footnotes
We thank the asthma nurses and students for their help with this project. Extra fine HFA beclometasone dipropionate (Qvar) was provided by 3M, Teva Pharma (Haarlem, the Netherlands) and the Aerochamber was kindly provided by Trudell International Europe (Nottingham, United Kingdom). In addition to the authors, the following paediatricians participated in the Respiratory Syncytial Virus Corticosteroid Study Group: M ten Berge-Kuipers, St Antonius Hospital, Nieuwegein; J de Bie, Hofpoort Hospital, Woerden; D Blom, Academic Medical Centre, Amsterdam; R Bruinsma, Gelre Hospital, Apeldoorn; F Brus, Rijnstate Hospital, Arnhem; M Colombijn, Beatrix Hospital, Gorinchem; G van Enk, Gelderse Vallei Hospital, Ede; K van der Ent, University Medical Centre, Utrecht; R van Gent, Maxima Medical Centre, Veldhoven; M Hoetjer, Meander Medical Centre, Amersfoort; A van der Kaaden, Hospital Hilversum, Hilversum; E van Leer, Groene Hart Hospital, Gouda; R de Moor, Twee Steden Hospital, Tilburg; A Nieuwenhuis, Jeroen Bosch Hospital, ‘s-Hertogenbosch; M Pekelharing, Diakonessen Hospital, Utrecht; C Smeets, St Elisabeth Hospital, Tilburg; E de Vries, Jeroen Bosch Hospital, ‘s-Hertogenbosch; A van Wermeskerken, Flevoziekenhuis, Almere; D van der Zwet-Fandri, Mesos Medical Centre, Utrecht.
Contributors: All authors conceived and designed the study, interpreted the results, and wrote the manuscript. MJJE recruited patients. MJJE and MMR analysed the data. LJB obtained the funding and was responsible for overall supervision of the study.
Funding: This study was supported by a grant from the Dutch Asthma Foundation (No 3.2.03.22). No financial support was obtained from pharmaceutical companies. The study drugs and inhalers were provided unconditionally by the manufacturers.
Competing interests: None declared.
Ethical approval: This study was done in accordance with the principles of the Declaration of Helsinki and was approved by the ethics review committee of the University Medical Centre Utrecht and the ethics review committees of the participating centres.
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