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. 2002;2002(3):CD002873.
doi: 10.1002/14651858.CD002873.

Short acting beta agonists for recurrent wheeze in children under 2 years of age

R Chavasse  1 , P Seddon, A Bara, M McKean
Affiliations

Short acting beta agonists for recurrent wheeze in children under 2 years of age

R Chavasse et al. Cochrane Database Syst Rev. 2002.

Abstract

Background: Wheeze is a common symptom in infancy and is a common cause for both primary care consultations and hospital admission. Beta2-adrenoceptor agonists (b2-agonists) are the most frequently used as bronchodilator but their efficacy is questionable.

Objectives: To determine the effectiveness of b2-agonist for the treatment of infants with recurrent and persistent wheeze.

Search strategy: Relevant trials were identified using the Cochrane Airways Group database (CENTRAL), Medline and Pubmed. The database search used the following terms: Wheeze or asthma and Infant or Child and Short acting beta-agonist or Salbutamol (variants), Albuterol, Terbutaline (variants), Orciprenaline, Fenoterol

Selection criteria: Randomised controlled trials comparing the effect of b2-agonist against placebo in children under 2 years of age who had had two or more previous episodes of wheeze, not related to another form of chronic lung disease.

Data collection and analysis: Eight studies met the criteria for inclusion in this meta-analysis. The studies investigated patients in three settings: at home (3 studies), in hospital (2 studies) and in the pulmonary function laboratory (3 studies). The main outcome measure was change in respiratory rate except for community based studies where symptom scores were used.

Main results: The studies were markedly heterogeneous and between study comparisons were limited. Improvement in respiratory rate, symptom score and oxygen saturation were noted in one study in the emergency department following two salbutamol nebulisers but this had no impact on hospital admission. There was a reduction in bronchial reactivity following salbutamol. There was no significant benefit from taking regular inhaled salbutamol on symptom scores recorded at home.

Reviewer's conclusions: There is no clear benefit of using b2-agonists in the management of recurrent wheeze in the first two years of life although there is conflicting evidence. At present, further studies should only be performed if the patient group can be clearly defined and there is a suitable outcome parameter capable of measuring a response.

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Conflict of interest statement

The authors who have been involved in this review have done so without any known conflict of interest. RC and PS were the co‐investigators of one of the primary studies (Chavasse 1999a) however neither are paid consultants of any related pharmaceutical company.

Figures

1.1
1.1. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 1 Respiratory Rate.
1.2
1.2. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 2 Symptom Score.
1.3
1.3. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 3 Oxygen Saturation.
1.4
1.4. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 4 Hospital Admission.
1.5
1.5. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 5 Non‐Responders.
1.6
1.6. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 6 Functional Residual Capacity (TGV ml/kg).
1.7
1.7. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 7 Conductance (Gaw L/s/H2O/kg).
1.8
1.8. Analysis
Comparison 1 Salbutamol versus Placebo. Parallel Group Studies, Outcome 8 Specific Conductance % change (sGaw).
2.1
2.1. Analysis
Comparison 2 Salbutamol versus Placebo. Crossover Studies, Outcome 1 Symptom Score.
2.2
2.2. Analysis
Comparison 2 Salbutamol versus Placebo. Crossover Studies, Outcome 2 Symptom Free Days.
2.3
2.3. Analysis
Comparison 2 Salbutamol versus Placebo. Crossover Studies, Outcome 3 Additional Treatment Given per Day.
2.4
2.4. Analysis
Comparison 2 Salbutamol versus Placebo. Crossover Studies, Outcome 4 Parent identification of benefit from inhaler.
2.5
2.5. Analysis
Comparison 2 Salbutamol versus Placebo. Crossover Studies, Outcome 5 V'maxFRC (ml/s).
2.6
2.6. Analysis
Comparison 2 Salbutamol versus Placebo. Crossover Studies, Outcome 6 Histamine Responsiveness (PC30 g/dl).
See this image and copyright information in PMC

References

References to studies included in this review

Bentur 1992 {published data only}
    1. Bentur L, Canny GJ, Shields MD, Kerem E, Schuh S, Reisman MD, et al. Controlled trial of nebulised albuterol in children younger than 2 years of age with acute asthma. Pediatrics 1992;89(1):133‐7. - PubMed
Chavasse 1999a {published data only}
    1. Chavasse RJ, Bastian‐Lee Y, Richter H, Hilliard T, Seddon P. Inhaled salbutamol for wheezy infants: A randomised controlled trial. Archives of Disease in Childhood 2000;82:370‐5. - PMC - PubMed
Clarke 1993 {published data only}
    1. Clarke JR, Aston H, Silverman M. Delivery of salbutamol by metered dose inhaler and valved spacer to wheezy infants: effect on bronchial responsiveness. Archives of Disease in Childhood 1993;69:125‐9. - PMC - PubMed
Fox 1996 {published data only}
    1. Fox GF, Marsh MJ, Milner AD. Treatment of recurrent acute wheezing episodes in infancy with oral salbutamol and prednisolone. European Journal of Pediatrics 1996;155:512‐6. - PubMed
Kraemer 1991 {published data only}
    1. Kraemer R, Frey U, Sommer W, Russi E. Short‐term effect on albuterol, delivered via a new auxilliary device, in wheezy infants. American Review of Respiratory Disease 1991;144:347‐51. - PubMed
Kraemer 1997 {published data only}
    1. Kraemer R, Graf Bigler U, Casaulta Aebischer C, Weder M, Birrer P. Clinical and physiological improvement after inhalation of low‐dose beclomethasone dipripionate and salbutamol in wheezy infants. Respiration 1997;64:342‐9. - PubMed
Prahl 1986 {published data only}
    1. Prahl P, Petersen NT, Hornsleth A. Beta2‐agonists for the treatment of wheezy bronchitis. Annals of Allergy 1986;57:439‐41. - PubMed
Prendiville 1987a {published data only}
    1. Prendiville A, Green S, Silverman M. Airway responsiveness in wheezy infants: evidence for functional B adrenergic receptors. Thorax 1987;42:100‐4. - PMC - PubMed

References to studies excluded from this review

Bentur 1990 {published data only}
    1. Bentur L, Kerem E, Canny G, Reisman J, Schuh S, Stein R, et al. Response of acute asthma to beta2 agonist in children less than two years of age. Annals of Allergy 1990;65:122‐6. - PubMed
Bremont 1992 {published data only}
    1. Bremont F, Moisan V, Dutau G. Continuous subcutaneous infusion of B2‐agonists in infantile asthma. Pediatric Pulmonology 1992;12:81‐3. - PubMed
Closa 1998 {published data only}
    1. Closa RM, Ceballos JM, Gomez‐Papi A, Galiana AS, Gutierrez C, Marti‐Henneber C. Efficacy of bronchodilators administered by nebulizers versus spacer devices in infants with acute wheezing. Pediatric Pulmonology 1998;26:344‐8. - PubMed
Connor 1989 {published data only}
    1. Connor WT, Dolovich MB, Frame RA, Newhouse MT. Reliable salbutamol administration in 6‐ to 36‐month‐old children by means of a metered dose inhaler and aerochamber with mask. Pediatric Pulmonology 1989;6:263‐7. - PubMed
Daugbjerg 1993 {published data only}
    1. Daugbjerg P, Brenoe E, Forchammer H, Glazowski MJ, Kaas Ibsen K, Knabe N, et al. A comparison between nebulised terbutaline, nebulised corticosteroid and systemic corticosteroid for acute wheezing in children up to 18 months of age. Acta Paediatrica 1993;82:547‐51. - PubMed
De La Luz 1999 {published data only}
    1. Luz Valencia Chavez M, Manotas R. Inhaled versus nebulised salbutamol in the management of acute asthma exacerbation in preschool children. A randomised controlled trial [Salbutamol inhalado o nebulizado en el tratamiento de la exacerbacion aguda del asma en el preescolar. Estudio comparativo aleatorizado]. Iateria 1999;12(3):130‐4.
Hayden 1998(b) {published data only}
    1. Hayden MJ, Petak F, Hantos Z, Hall G, Sly PD. Using low‐frequency oscillation to detect bronchodilator responsiveness in infants. American Journal of Respiratory and Critical Care Medicine 1998;157:574‐579. - PubMed
Hayden 1998a {published data only}
    1. Hayden MJ, Wildhaber JH, LeSouef PN. Bronchodilator responsiveness testing using raised volume forced expiration in recurrently wheezing infants. Pediatric Pulmonology 1998;26:35‐41. - PubMed
Henderson 1993 {published data only}
    1. Henderson AJW, Young S, Stick SM, Landau LI, Lesouef PN. Effect of salbutamol on histamine induced bronchoconstriction in healthy infants. Thorax 1993;48:317‐23. - PMC - PubMed
Hickey 1994 {published data only}
    1. Hickey RW, Gochman RF, Chande V, Davis HW. Albuterol delivered via metered‐dose inhaler with spacer for outpatient treatment of young children with wheezing. Arichives of Pediatrics and Adolescent Medicine 1994;148:189‐94. - PubMed
Holmgren 1992 {published data only}
    1. Holmgren D, Bjure J, Engstrom I, Sixt R, Sten G, Wennergren G. Transcutaneous blood gas monitoring during salbutamol inhalations in young children with acute asthmatic symptoms. Pediatric Pulmonology 1992;14:75‐9. - PubMed
Jackson 1999 {published data only}
    1. Jackson AC, Tennhoff W, Kraemer R, Frey U. Airway and tissue resistance in wheezy infants: Effects of albuterol. American Journal of Respiratory and Critical Care Medicine 1999;160:557‐63. - PubMed
Lenney 1978 {published data only}
    1. Lenney W, Milner AD. At what age do bronchodilator drugs work?. Archives of Disease in Childhood 1978;53:532‐5. - PMC - PubMed
Mallol 1987a {published data only}
    1. Mallol J, Barrueto L, Girardi G, Toro O. Bronchodilator effect of fenoterol and ipratropium bromide in infants with acute wheezing: Use of MDI with a spacer device. Pediatric Pulmonology 1987;3:352‐6. - PubMed
Mallol 1987b {published data only}
    1. Mallol J, Barrueto L, Girardi G, Munoz R, Puppo H, Ulloa V, et al. Use of nebulised bronchodilators in infants: analysis of four forms of therapy. Pediatric Pulmonology 1987;3:298‐303. - PubMed
Naspitz 1992 {published data only}
    1. Naspitz CK, Sole D. Treatment of acute wheezing and dyspnea attacks in children under 2 years old: Inhalation of fenoterol plus ipratropium bromide versus fenoterol. Journal of Asthma 1992;29(4):253‐8. - PubMed
O'Callaghan 1986 {published data only}
    1. O'Callaghan C, Milner AD, Swarbrick A. Paradoxical deterioration in lung function after nebulised salbutamol in wheezy infants. The Lancet 1986;2(8521‐2):1424‐5. - PubMed
O'Callaghan 1988 {published data only}
    1. O'Callaghan C, Milner AD, Swarbrick A. Nebulised salbutamol does have a protective effect on airways in children under 1 year old. Archives of Disease in Childhood 1988;63:479‐83. - PMC - PubMed
Orlowski 1991 {published data only}
    1. Orlowski L, Zychowicz C, Migdal M, Gutkowski P. Effect of salbutamol on specific airway resistance in infants with a history of wheezing. Pediatric Pulmonology 1991;10:191‐4. - PubMed
Ploin 2000 {published data only}
    1. Ploin D, Chapuis FR, Stamm D, Robert J, David L, Chatelain PG, et al. High‐dose albuterol by metered dose inhaler plus a spacer device versus nebulization in preschool children with recurrent wheezing: A double‐blind randomized equivalence trial. Pediatrics 2000;106(2):311‐7. - PubMed
Prendiville 1987b {published data only}
    1. Prendiville A, Green S, Silverman M. Paradoxical response to nebulised salbutamol in wheezy infants, assessed by partial expiratory flow‐volume curves. Thorax 1987;42:86‐91. - PMC - PubMed
Prendiville 1987c {published data only}
    1. Prendiville A, Rose A, Maxwell DL, Silverman M. Hypoxaemia in wheezy infants after bronchodilator treatment. Archives of Disease in Childhood 1987;62:997‐1000. - PMC - PubMed
Radford 1975 {published data only}
    1. Radford M. Effect of salbutamol in infants with wheezy bronchitis. Archives of Disease in Childhood 1975;50:535‐8. - PMC - PubMed
Rubilar 2000 {published data only}
    1. Rubilar L, Castro‐Rodriguez JA, Girardi G. Randomised trial of salbutamol via metered‐dose inhaler with spacer versus nebulizer for acute wheezing in children less than 2 years of age. Pediatric Pulmonology 2000;29:264‐9. - PubMed
Rutter 1975 {published data only}
    1. Rutter N, Milner AD, Hillier EJ. Effect of bronchodilators on respiratory resistance in infants and young children with bronchiolitis and wheezy bronchitis. Archives of Disease in Childhood 1975;50:719‐22. - PMC - PubMed
Schweich 1992 {published data only}
    1. Sweich PJ, Hurt TL, Walkley EI, Mullen N, Archibald LF. The use of nebulised albuterol in wheezing infants. Pediatric Emergency Care 1992;8(4):184‐8. - PubMed
Seidenberg 1991 {published data only}
    1. Seidenberg J, Mir Y, Hardt H. Hypoxaemia after nebulised salbutamol in wheezy infants: The importance of aerosol acidity. Archives of Disease in Childhood 1991;66:672‐5. - PMC - PubMed
Spier 1985 {published data only}
    1. Spier S, Lapierre JG, Lamarre A. Response to salbutamol during a 1st or 2nd episode of wheezing in infancy. American Review of Respiratory Disease 1985;101:A259.
Tal 1983 {published data only}
    1. Tal A, Baviliski C, Yohai D, Bearman JE, Gorodischer R, Moses SW. Dexamethasone and salbutamol in the treatment of acute wheezing in infants. Pediatrics 1983;71(1):13‐8. - PubMed

Additional references

BTS 1997
    1. British Thoracic Society. Asthma in children under five years of age. Thorax 1997;52 Suppl (1):9‐10,18‐21.
Chavasse 1999b
    1. Chavasse R, Bastian‐Lee Y, Seddon P. Preferences of bronchodilator to treat infant wheeze: A regional survey. European Respiratory Journal. 1999; Vol. 14 Suppl (30):178.
Clough 1993
    1. Clough J. Bronchodilators in infancy. Thorax 1993;48(4):308. - PMC - PubMed
Everard 1999
    1. Everard M, Kurian M. Anti‐cholinergic drugs for wheeze in children under the age of two years (Cochrane review). Cochrane Database of Systematic Reviews 1999, Issue 2. - PubMed
Jadad 1996
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomised controlled trials: Is blinding necessary?. Controlled Clinical Trials 1995;17(1):1‐12. - PubMed
Kellner 1999
    1. Kellner JD, Ohlsson A, Gadomski AM, Wang EEL. Bronchodilators for bronchiolitis (Cochrane review). The Cochrane Library 1999, Issue 2. - PubMed
Martinez 1995
    1. Martinez FD, Wright AL, Taussig L, Holberg CJ, Halonen M, Morgan W. Asthma and wheezing in the first six years of life. New England Journal of Medicine 1995;332(3):133‐8. - PubMed
NIH 1997
    1. Anonymous. Guidelines for the diagnosis and management of asthma. Expert Panel Report 2. NIH Publication 97‐4051 1997.
Pavon 1999
    1. Pavon D, Castro‐Rodriguez JA, Rubilar L, Girardi G. Relation between pulse oximetry and clinical score in children with acute wheezing less than 24 months of age. Pediatric Pulmonology 1999;27:423‐7. - PubMed
Silverman 1995
    1. Silverman M, Wilson N. Wheezing disorders in infancy. In: Silverman M editor(s). Childhood asthma and other wheezing disorders. 1. London: Chapman & Hall Medical, 1995:375‐400. [ISBN 0‐412‐56900‐0]
Strachan 1995
    1. Strachan DP. Epidemiology. Childhood asthma and other wheezing disorders. 1. London: Chapman & Hall, 1995:7‐31. [ISBN 0 412 56900 0]
Tager 1993
    1. Tager IB, Hanrahan JP, Tosteson TD. Lung function, pre‐ and postnatal smoke exposure, and wheezing in the first year of life. American Review of Respiratory Disease 1993;147:811‐7. - PubMed
Yung 1996
    1. Yung M, South M, Byrt T. Evaluation of an asthma severity score. Journal of Pediatrics and Child Health 1996;32:261‐4. - PubMed

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