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Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma

  1. Christopher J Cates1,*,
  2. Emma J Welsh1,
  3. Brian H Rowe2,3

Editorial Group: Cochrane Airways Group

Published Online: 13 SEP 2013

Assessed as up-to-date: 14 FEB 2013

DOI: 10.1002/14651858.CD000052.pub3


How to Cite

Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD000052. DOI: 10.1002/14651858.CD000052.pub3.

Author Information

  1. 1

    St George's, University of London, Population Health Research Institute, London, UK

  2. 2

    University of Alberta, Department of Emergency Medicine, Edmonton, AB, Canada

  3. 3

    University of Alberta, School of Public Heath, Edmonton, Canada

*Christopher J Cates, Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK. ccates@sgul.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 13 SEP 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 
Summary of findings for the main comparison. Multiple treatment of beta₂-agonist via spacer (chamber) compared to nebuliser for children with acute asthma

Multiple treatment of beta₂-agonist via spacer (chamber) compared to nebuliser for children with acute asthma

Patient or population: children with acute asthma
Settings: Community or Emergency Department
Intervention: Multiple treatments with beta₂-agonist via spacer (chamber)
Comparison: Multiple treatments with beta₂-agonist via nebuliser

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

NebuliserMultiple treatment of beta2-agonist via spacer (chamber)

Hospital admission 110 per 100078 per 1000
(52 to 119)
RR 0.71
(0.47 to 1.08)
757
(9 studies)
⊕⊕⊝⊝
low1,2
Large increases in the proportion of children admitted to hospital on spacer in comparison to nebuliser are ruled out by this 95% confidence interval.

Duration in emergency department (minutes)The mean duration in emergency department (minutes) in the control groups was
103 minutes
The mean duration in emergency department (minutes) in the intervention groups was
33 minutes shorter
(43 minutes shorter to 24 minutes shorter)
396
(3 studies)
⊕⊕⊕⊝
moderate1
There was a consistent direction of shortening of time in ED in all 3 studies, and although the size of this effect varied between studies (I² = 66%), we felt that the mean difference was important in all studies.

Final rise in FEV₁ (% predicted) The mean final rise in FEV₁ (% predicted) in the control groups was
27% predicted at baseline
The mean final rise in FEV₁ (% predicted) in the intervention groups was
0.92% higher
(4.96% lower to 6.79% higher)
48
(2 studies)
⊕⊕⊝⊝
low1,2

Rise in pulse rate (% baseline) The mean rise in pulse rate (% baseline) in the control groups was
7% rise from baseline
The mean rise in pulse rate (% baseline) in the intervention groups was
5.62% lower
(7.52% to 3.72% lower)
670
(9 studies)
⊕⊕⊕⊝
moderate1

Number of participants developing tremor 142 per 100091 per 1000
(62 to 135)
RR 0.64
(0.44 to 0.95)
254
(4 studies)
⊕⊕⊕⊝
moderate1

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Mostly open label studies
2 Wide confidence intervals

 Summary of findings 2 Multiple treatment of beta₂-agonist via spacer (chamber) compared to nebuliser for adults with acute asthma

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of the condition and intervention

Exacerbations of asthma are common and account for a considerable number of physician encounters, both in hospital and in primary care. In exacerbations the airways become narrowed due to mucosal oedema, hypersecretion and bronchospasm. Depending on the severity of the attack, treatment with inhaled beta₂-agonists is often required in addition to other agents such as corticosteroids. The use of beta₂-agonists is intended to relieve the bronchospasm. This is accomplished most effectively when the drug is delivered to the peripheral airways. This is made more difficult in acute asthma since the narrowed airways and faster respiratory rate result in increased drug deposition in the throat and large airways. Consequently, it is less effective and may cause more side effects.

Two different delivery methods have been employed to overcome this problem: wet nebulisations and metered-dose inhalers (MDIs) with a holding chamber (spacer). Nebulisation creates a mist of beta₂-agonist diluted in saline which is inhaled through a mask by tidal breathing. Nebulisation can be accomplished with room air or supplemental oxygen, and requires a supply of compressed gas or a power source. More recently, beta₂-agonists delivered via MDIs through a spacer have been used in acute asthma. The drug is released into the spacer by pressing the MDI after it has been shaken and inserted into the spacer (also called 'actuation'). The drug in the spacer is then emptied by the person using either tidal breathing (normal breathing in and out) or a single deep breath.

 

Why it is important to do this review

Whilst nebulisers have historically been used in exacerbations of asthma, a meta-analysis of trials in adults with asthma or chronic obstructive pulmonary disease (COPD) suggested that metered-dose inhalers with a spacer are as effective (Turner 1997).There has been considerable controversy regarding the merits of each delivery method, but current guidelines have now moved towards the use of spacers in acute asthma, particularly in children (BTS/SIGN 2011). In addition, cost and infection control considerations may be important additional determinants of which system is employed. For example, in the community the cost of nebulisers exceeds a spacer and MDI. In hospital emergency departments, the cost calculations are more complex since disposable nebuliser masks are often driven by piped oxygen; costs may depend on whether or not all patients are sent home with a new spacer. Nebulisers also represent a potential source of cross-infection, and require regular maintenance. As a result of these controversies, this systematic review has been updated to assess all the available evidence from randomised controlled trials comparing the two delivery methods in adults and children with acute asthma.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

To assess the effects of holding chambers (spacers) compared to nebulisers for the delivery of beta₂-agonists for acute asthma.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Only randomised controlled trials were considered for this review.

 

Types of participants

Adults and children (but not infants) with acute asthma presenting for medical assistance in the community setting or hospital emergency department. Studies describing people who had already been admitted to hospital have been included in this update. Studies of children with a mean age of two years or more were included, as it is difficult to diagnose asthma under this age. Studies of people with asthma and chronic obstructive pulmonary diease (COPD) were included as long as separate results could be obtained for the asthma patients.

 

Types of interventions

Any beta₂-agonist given by any nebuliser versus the same beta₂-agonist given by metered-dose inhaler with any spacer. The dose of drug and method of administration must have been recorded. Co-interventions and contamination (cross-over) may have occurred, but these must have been recorded.

 

Types of outcome measures

 

Primary outcomes

  1. Admission to hospital.
  2. Duration of hospital stay for inpatients.

 

Secondary outcomes

  1. Duration in the emergency department.
  2. Change in respiratory rate.
  3. Blood gases.
  4. Pulse rate.
  5. Tremor.
  6. Symptom score.
  7. Lung function.
  8. Use of steroids.
  9. Relapse rates.

 

Search methods for identification of studies

 

Electronic searches

We identified trials using the Cochrane Airways Group Specialised Register, which is maintained by the Trials Search Co-ordinator for the Group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, and handsearching of respiratory journals and meeting abstracts (see Appendix 1 for further details). All records in the Specialised Register coded as 'asthma' were searched using the following terms:

(spacer* OR "holding chamber*" or holding-chamber* OR volumatic OR nebuhaler* OR aerochamber* OR fisonair OR extension* OR "spacing device*" OR inspirease OR babyhaler* or MDI or turbuhaler) AND (nebuli*)

The most recent search of the Register was carried out in February 2013.

 

Searching other resources

We searched the bibliographies of all included papers and reviews for further references. We contacted authors of included studies for identification of any unpublished or missed trials.

 

Data collection and analysis

 

Selection of studies

One review author (CJC) originally checked abstracts identified by the above search and obtained the full text of publications of possibly relevant studies, including translation when required. Trials identified for potential inclusion were independently assessed by one review author (CJC) and William Griffiths, a student at St George's University of Londonfor the present update.

 

Data extraction and management

CJC extracted data and JAC checked them. They contacted trial authors by letter asking for clarification of allocation concealment, devices used, location of the participants and outcomes where these were not clear in the original publication.

 

Assessment of risk of bias in included studies

Two people (CJC, and William Griffiths or EW) independently assessed risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreements by discussion. We assessed the risk of bias according to the following domains.

  1. Random sequence generation.
  2. Allocation concealment.
  3. Blinding of participants and personnel.
  4. Blinding of outcome assessment.
  5. Incomplete outcome data.
  6. Selective outcome reporting.
  7. Other bias.

We graded each potential source of bias as high, low or unclear, and provided a quote from the study report together with a justification for our judgement in the 'Risk of bias' tables. We summarised the risk of bias judgements across different studies for each of the domains listed. We considered blinding separately for different key outcomes where necessary (e.g. for unblinded outcome assessment, risk of bias for all-cause mortality may be very different than for a participant-reported pain scale).

 

Assessment of heterogeneity

Heterogeneity was originally measured using the Chi² test and latterly the I² statistics for more recent updates. Where heterogeneity was found, we explored sources of heterogeneity and pooled results using a random-effects model, or did not pool across subgroups.

 

Data synthesis

We calculated a weighted treatment effect across trials using the Cochrane statistical package, Review Manager (RevMan; initially version 4, now 5.2). Results are expressed as risk ratios (RR) and a 95% confidence interval (CI) for dichotomous outcomes and mean differences (MD) and a 95% CI for continuous outcomes. We used a fixed-effect model for continuous outcomes, but also checked results using a random-effects model.

We have now separated the results for adults and children in each outcome, in view of the significant heterogeneity identified in the pooled analyses. Furthermore it can be argued that adults and children may differ in their ability to use the devices, their degree of airways reversibility and in their sensitivity to side effects from inhaled beta₂-agonists.

We have not pooled the single-treatment trials because of concerns over confounding due to uncertainty about the relative dose delivered and the wide range of dose-ratios used (from 1:1 to 1:13, with the larger doses administered via nebuliser).

 

Sensitivity analysis

We performed sensitivity analyses on the basis of methodological quality. The results were originally re-analysed using only studies of the lowest risk of bias. Sensitivity analyses were performed to check on the effect of estimating standard deviations and the data re-analysed without any estimated results. In addition, we generated a funnel plot of hospital admissions to check for publication bias. In view of the temporary discontinuation of Volumatic spacers in some countries, we also separated the trials that used Volumatic from other types of spacer in an additional post hoc subgroup analysis.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of studies

 

Results of the search

There were 35 included studies previously identified by literature searches conducted up to 2008. For this review update, our literature search covered the period 2008 to 2013 (see Figure 1 for details). We have included four new trials (Dhuper 2008; Direkwatanachai 2008; Ferrés 1989; Yasmin 2012), and have excluded three (Fayaz 2009; Hart 2009; Kaashmiri 2010).

 FigureFigure 1. Study flow diagram

 

Included studies

See Characteristics of included studies tables for full details.

There are now 1203 children (in 15 trials) and 613 adults (in 10 trials) who were randomised to spacer or nebuliser using multiple-treatment protocols. There are also 487 children (in six trials) and 88 adults (in two trials) who were randomised to a single-treatment regimen. In addition there are six trials incorporating 207 children and 28 adults studied after hospital admission.  Table 1 gives details of the location and design of each study, as well as the type of spacer used.

The studies come from all over the world. Only two were carried out in the community (Chong-Neto 2005; Morrone 1990); six trials have been conducted in an inpatient setting (Ba 1989; Burrows 2004; Coker 1995; Dewar 1999; Morley 1988; Parkin 1995), and all others were conducted in hospital emergency departments (although Direkwatanachai 2008 also recruited children from outpatients, and Yasmin 2012 only reports that the trial was carried out in the Department of Paediatrics). The single pre-hospital study comparing nebulisation to metered-dose inhaler (MDI) (Campbell 1995) was excluded, as there was no randomisation. Different beta₂-agonists, spacers and nebulisers were represented in the studies.

The dosage ratio between delivery methods varied from 1:1 to 1:13, with the larger doses administered via nebuliser. The median dose administered via nebuliser was four times that administered via spacer, a dosage ratio of 1:4 (interquartile range (IQR) 1:2 to 1:8).

Many recent studies used multiple treatments at 10- to 30-minute intervals (Batra 1997; Chong-Neto 2005; Chou 1995; Colacone 1993; Direkwatanachai 2008; Duarte 2002; Idris 1993; Jamalvi 2006; Leversha 2000; Ploin 2000; Rao 2002; Rodrigo 1993; Rodrigo 1998; Sannier 2007; Valencia 1999; Vivek 2003; Yasmin 2012). Most studies used commercially-available spacers (Aerochamber, Babyhaler, InspirEase, Lite Aire, Nebuhaler and Volumatic), but two studies from Brazil and one from Bangladesh (Chong-Neto 2005; Duarte 2002; Yasmin 2012) used home-made spacers in the form of a 500 mL mineral water plastic bottle. Duarte 2002 coated the bottle with detergent to avoid electrostatic charge, whilst Chong-Neto 2005 included 10 children treated with aerochamber and 10 children using a 500 mL water bottle glued onto the MDI with Araldite. The studies using salbutamol all used the racemic form of the drug.

 

Excluded studies

See Characteristics of excluded studies tables for full details.

 

Risk of bias in included studies

Overall, the methodological quality of the included studies was variable, with sequence generation and allocation concealment not described in many studies (see Characteristics of included studies). Many studies did not comment on withdrawals and dropouts, and also did not report whether intention-to-treat analysis was employed, but in short-term trials of acute treatment we would not expect large numbers of dropouts. The hospital admission rate reported in one study has been amended using an intention-to-treat analysis (Colacone 1993).

In general the sample size of many individual studies was small, (range 18 to 196 participants in the emergency-room studies, and 28 to 61 for inpatients). Whilst eight of the 13 studies in adults used a double-blind, double-dummy design (Colacone 1993; Dhuper 2008; Idris 1993; Rodrigo 1993; Rodrigo 1998; Rao 2002; Salzman 1989; Turner 1988) only six of the 26 studies in children were double-blind (Ba 1989; Chong-Neto 2005; Kerem 1993; Leversha 2000; Ploin 2000; Robertson 1998); see Figure 2.

 FigureFigure 2. Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

A funnel plot of hospital admissions did not suggest publication bias in relation to the primary outcome of this review, since the smaller studies showed equal spread of results on both sides of the overall risk ratio (Figure 3).

 FigureFigure 3. Funnel plot of comparison: 1 Spacer (chamber) versus Nebuliser (Multiple treatment studies), outcome: 1.1 Hospital admission.

 

'Summary of findings' Tables

The assessments of risks of bias have been incorporated in two 'Summary of findings' tables, which are presented separately for children ( Summary of findings for the main comparison) and adults ( Summary of findings 2) for the 2013 update of this review.

 

Effects of interventions

See:  Summary of findings for the main comparison Multiple treatment of beta₂-agonist via spacer (chamber) compared to nebuliser for children with acute asthma;  Summary of findings 2 Multiple treatment of beta₂-agonist via spacer (chamber) compared to nebuliser for adults with acute asthma

 

Spacer versus nebuliser multiple treatments

 
Primary outcome: Hospital admission

Hospital admission rates did not differ significantly on the basis of delivery method in adults (risk ratio (RR) 0.94; 95% confidence interval (CI) 0.61 to 1.43, 9 trials, n = 582;  Analysis 1.1) or in children (RR 0.71; 95% CI 0.47 to 1.08, 9 trials, n = 757; Figure 4). No significant heterogeneity was observed.

 FigureFigure 4. Forest plot of comparison: 1 Spacer (chamber) versus Nebuliser (Multiple treatment studies), outcome: 1.1 Hospital admission.

 
Subgroup analysis by type of spacer

In the light of the decision to temporarily withdraw Volumatic spacers from the UK market in 2005, we carried out a post hoc sensitivity analysis according to whether Volumatic spacers were used in each study. The type of spacer used is documented in  Table 1 and this shows that the majority of adults and children studied used other types of spacer. No significant differences were found between the results from trials using Volumatic (166 adults and 163 children) and those using other types of spacer (366 adults and 515 children). There were no significant differences between the results for Volumatic and other spacer types in either adults or children (see  Analysis 4.1). No studies included a direct comparison between Volumatic and other types of spacer.

 
Secondary outcome: Treatment failure

Three studies in children did not report admissions but did report data on poor outcomes (Batra 1997; Leversha 2000; Yasmin 2012). When these are pooled together with the data on hospital admissions, the risk ratio in children of admission or poor outcome is not significantly different between spacer and nebuliser (RR 1.00; 95% CI 0.75 to 1.33, 12 trials, n = 937;  Analysis 1.2). The definition of treatment failure varied across studies, and we included these data post hoc.

 
Secondary outcome: Time spent in emergency department

Time spent in the emergency department (ED) showed significant heterogeneity when the results from adults and children were pooled in the original version of this review, (Chi² = 8.2, df = 2, P < 0.02). However, no significant heterogeneity was demonstrated when adults and children were analysed separately at that time. The results for adults and children have therefore been shown in separate subgroups in the analyses in Figure 5.

 FigureFigure 5. Forest plot of comparison: 1 Spacer (chamber) versus Nebuliser (Multiple treatment studies), outcome: 1.3 Duration in emergency department (minutes). [mins].

Duration in the ED in children was significantly shorter with the spacer (mean difference (MD) -33 minutes; 95% CI -43 to -24 minutes, I² = 66%, 3 studies, n = 398;  Analysis 1.3). This finding is based on three studies (Chou 1995; Duarte 2002; Sannier 2007), containing 396 participants, in which the median duration in ED on nebulised treatment was 103 minutes. The studies in children were open-label and did not use a double-dummy design, whereas the studies in adults were double-dummy so adults would have received both nebuliser and spacer. This is likely to have had a bearing on these results as nebulisation is much more time-consuming than use of MDI and spacer (Duarte 2002). In adults the duration of the ED visit was similar in both groups (MD 2 minutes; 95% CI -23 to 27 minutes;  Analysis 1.2). Results in children and adults are shown using a random-effects model.

 
Secondary outcome: Lung function

No significant differences were demonstrated between the two delivery methods in terms of peak flow and forced expiratory volume (FEV₁) at 30 minutes and at the end of the study in either adults or children. More specifically, in the four studies in adults that included analysis of changes in lung function in the most severely affected participants (e.g. FEV₁ < 30% predicted), there was no statistically significant difference between the two delivery methods (MD -1.6% predicted; 95% CI -7.69 to 4.49%). The only study (Maldano-Alanis 1997) which found a significant difference in FEV₁ between the nebuliser and spacer groups used a low dose of salbutamol via the spacer (200 mcg), and showed a significant decline in FEV₁ in this group three to six hours after the treatment was administered. This trial could not be included in the analysis as no standard deviations were reported and the authors did not respond to requests for further information. Maldano-Alanis 1997 did not contribute to the primary outcome of hospital admission.

 
Secondary outcome: Pulse rate

Pulse rate after treatment (expressed as % change from baseline), was significantly lower when a spacer was used in children (MD -5.41 %; 95% CI -8.34 to -2.48, I² = 53%, random-effects). In adults, no significant difference was found between methods (MD -1.23 %; 95% CI -4.06 to 1.60, random-effects). These results were similar for fixed- and random-effects models. There was a significant difference between the pulse changes in adults and children (test for subgroup differences: Chi² = 4.03, df = 1 (P = 0.04), I² = 75.2%, random-effects, see Figure 6).

 FigureFigure 6. Forest plot of comparison: 1 Spacer (chamber) versus Nebuliser (Multiple treatment studies), outcome: 1.9 Rise in pulse rate (% baseline) [%].

 
Secondary outcome: Oxygen saturation

There were no data available in adults for the outcome oxygen saturation. Oxygen saturation in children was not significantly different between groups at the end of the studies (MD -0.19%; 95% CI -0.61% to 0.24%, 6 studies, 476 children;  Analysis 1.10). One study (Duarte 2002), however, reported that 25% of children treated with oxygen-driven nebuliser suffered desaturation at some point during treatment compared to 9% of those treated with MDI and spacer (P = 0.006).

 
Secondary outcome: Adverse events (tremor)

Development of tremor was more common with nebuliser treatment in the four studies that reported this in children (RR 0.64; 95% CI 0.44 to 0.95, random-effects), but the test for interaction between adults and children was not significant.

 
Other secondary outcomes

No significant differences were demonstrated between the two delivery methods for the other measured outcomes: change in respiratory rate and the number of participants given steroids.

We have made no attempt to combine the findings for symptom score as the scales used were highly variable and the standard deviation of results were rarely reported.

 

Spacer versus nebuliser single treatments

We did not pool results from single-treatment studies because of concern over confounding by the variable amounts of beta₂-agonists delivered to the airways from the different delivery methods.

Blood gas results were reported in two studies (Kerem 1993; Lin 1995). The participant numbers were small but both show less deterioration in gases with a spacer. One study (Lin 1995) also measured lung function 15 minutes after the start of treatment and found a significantly greater rise in peak expiratory flow (PEF) at this time with the spacer (MD 10.1% predicted; 95% CI 15.7 to 4.4%); this study is of low methodological quality, so this information should be interpreted with caution. More recently, Hussein 2002 reported similar changes in oxygen saturation in a single-treatment study in 60 children. The author has not responded to a request for further details.

 

Spacer versus nebuliser Inpatient studies

Individual patient data have been provided by the authors of Burrows 2004 on children who were aged two years or more and these have been incorporated into the 2013 update.

Primary outcome: Duration of hospital admission

The primary outcome of duration of admission was available from four studies (Burrows 2004; Dewar 1999; Morley 1988; Parkin 1995) but the results in Dewar 1999 were skewed and presented as medians so are not suitable for combination with the other two studies in children. The duration of admission did not show a significant difference between delivery methods in a single study in adults (MD -0.60 days; 95% CI -3.23 to 2.03) or in the two studies in children (MD 0.33 days; 95% CI -0.10 to 0.76), see  Analysis 3.1.

Secondary outcomes: Respiratory rate, heart rate and oxygen saturation

It was possible to combine the data provided by Burrows 2004 with the results from Dewar 1999 for three of the secondary outcomes (including 76 children).

There were no significant differences found in these children between spacers and nebulisers in respiratory rate (MD -0.91; 95% CI -3.20 to 1.38,  Analysis 3.9), heart rate (MD 1.06; 95% CI -5.48 to 7.61,  Analysis 3.10) or oxygen saturation at discharge (MD 0.12; 95% CI -0.42 to 0.66,  Analysis 3.11).

The results from the individual studies have been outlined below.

Ba 1989 was a single-dose comparison in children, and did not measure the primary outcome (time to discharge). The design was double-blind with double dummy. Continuous intravenous aminophylline was given to all children in both groups. There was a significant difference between groups in baseline lung function, spacer baseline FEV₁ 38.2 (SD 7.9)% predicted and nebuliser 49.8 (SD 14)% predicted. Results are only presented as change from baseline, and this will favour the spacer group. There was no significant difference in FEV₁ between groups over three hours, and the significant advantage for the spacer in change in forced vital capacity (FVC) is probably due to baseline difference. The paper reported significantly more children treated with spacer increased their pulse rate at 10 minutes compared to the nebuliser group, but this data could not be used as the number of participants with increased pulse reported in the spacer group (17) was greater than the group total (14).

Coker 1995 was a single-dose comparison in children, and did not measure the primary outcome (time to discharge). There was no blinding and participants were allocated by alternation. No co-interventions were reported and no significant differences in respiratory score or PEF were found between groups over six hours.

Dewar 1999 compared multiple treatments in children, given up to one-hourly by each delivery method. Allocation was concealed with sequential pre-sealed envelopes and all children received oral steroids on admission and repeated on subsequent mornings for three to five days according to their recovery. No blinding was reported. Data for duration of stay were noted to be skewed by small numbers of lengthy inpatient stays so medians were used which did not show a significant difference between groups, (36.5 hours for the spacer group and 40 hours for the nebuliser group). Although readmission rates were lower in the spacer group, this group were also given a written asthma plan and this may have confounded the results for readmission and symptoms after discharge. Children requiring immediate intravenous treatment were excluded from the study, and five children were withdrawn due to deterioration requiring intravenous treatment (three in the spacer group and two in the nebuliser group). The authors calculated a significant cost benefit for the spacer group in terms of drug costs, GBP 5.43 per participant in the spacer group and GBP 20.25 in the nebuliser group (P < 0.001).

Morley 1988 was the only inpatient study in adults, and used multiple treatments. Allocation was by alternation and no blinding was described. Intravenous aminophylline and methylprednisolone were given at standard doses. Mean duration of hospitalisation was not significantly different between groups, 5.8 days in the spacer group and 6.4 days in the nebuliser group, mean difference of -0.6 days (95% CI -3.2 to 2.0). No significant differences were found in lung function between groups.

Parkin 1995 compared multiple treatments in younger children (aged one to five years), but gave both salbutamol and ipratropium by spacer or nebuliser. The research nurse only was blinded and all children received intravenous or oral steroids. There was no significant difference in hours to discharge (spacer 53 hours and nebuliser 46 hours), hours to the change of treatments to four-hourly intervals or total number of inhaled doses received. Nine participants in the spacer group crossed over to nebuliser treatment, but their results were analysed by original group assignment (intention-to-treat analysis).

Burrows 2004 studied 29 children aged one to six years old with moderate to severe asthma according to British Thoracic Society (BTS) guidelines, who were hospitalised between September 2003 and February 2004. No significant differences were reported in any outcomes except for cost (which was GBP 7.68 per participant in the nebuliser group and GBP 5.96 per participant in the spacer group). The length of stay was 16.5 hours in the nebuliser group and 26.5 hours in the MDI and spacer group, with change in respiratory rate of -5.4 and -6.3, change in pulse of 2.9 and 4.6, and change in oxygen saturation of 0.53 and 1.07 for nebuliser and spacer, respectively. The authors of Burrows 2004 have provided individual patient data for the children aged 2 years or more from this study and this has been added to duration of hospital admission from Parkin 1995. There was no significant difference in duration of admission (MD 0.33 days; 95% CI -0.10 to 0.76) and shown in  Analysis 3.1. Similarly the individual patient data from this study have been combined with results from Dewar 1999 as outlined in the secondary outcomes above.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Summary of main results

Overall, we found no significant advantage of wet nebuliser over metered-dose inhaler (MDI) with spacer administration of beta₂-agonists in the treatment of acute asthma when treatments are repeated and titrated to the response of the participant for our primary outcome of hospital admissions. Thus the major take-home message from this review is that nebulisers have not been shown to be superior to spacers in preventing hospital admissions. Importantly we found that children had shorter emergency department (ED) visits when short-acting beta₂-agonists were administered via spacer rather than nebuliser. The entire confidence interval indicated a patient-important benefit - we think parents would be happy to spend between 23 to 43 minutes less in the ED if their child was having an asthma attack, potentially saving health services time and money. It is not possible to say whether there is a time benefit in adults; this may be partly because all the adult trials contributing to this outcome were double-blind and double-dummy. Since both groups received both nebuliser and spacer this may have confounded any possible time saving from using the spacer. In addition hypoxia was reduced, and pulse rates and risk of tremor were lowered compared to participants receiving the same beta₂-agonist via wet nebulisation.

In clinical practice the dose of beta₂-agonist delivered to the airways varies depending on the type of nebuliser or spacer used and the characteristics of the individual's airways at that time (Lipworth 1997). Uncertainty over the dose of beta₂-agonists required through any delivery method was overcome in many of the studies (613 adults and 1203 children) by repeating treatments at short intervals. For example, one respule (via nebuliser) or four to six puffs (via spacer) every 10 to 30 minutes until the person responded to treatment (see  Table 1 for a list of trials using multiple treatments). This approach reduced confounding by different dosages of drug delivered.

 

Overall completeness and applicability of evidence

People with life-threatening asthma exacerbations were excluded from the studies (for example those who were considered for ventilation). We do not know how this patient group would respond to treatment using spacers, or indeed whether they would be able to use a spacer under these circumstances.

Only two small studies were carried out in a community setting (Chong-Neto 2005; Morrone 1990) and this review did not compare people being randomised to receive either nebuliser or spacer at home for delivery of beta₂-agonists when their symptoms get worse. While we do not have evidence in these populations, it is logical to conclude that provided people are proficient at using their spacer (or can clearly instruct their child to use their spacer correctly) there is no advantage in buying an expensive home nebuliser when a spacer is cheaper and more portable. However, our confidence in this statement is low as the evidence in this review comes form an ED setting where treatment can be supervised by health professionals.

Few authors reported specifically on numbers of people presenting who were excluded from each study, and intention-to-treat analysis was not usually reported. Thus it is not entirely clear how these results apply to all people who present with an exacerbation.

Analysis of the data regarding lung function tests in many papers was complicated by a lack of standardised reporting. In addition, data regarding standard deviation related to the changes that were measured were not always reported. Peak flow and forced expiratory volume (FEV₁) were the most commonly reported measurements and these were both included in the outcome tables. These concerns are not enough to overturn our confidence in the patient-important outcome of reduced time in the ED in children.

 

Quality of the evidence

Sequence generation and allocation concealment were unclear in many of the included studies, and only eight studies in adults and six studies in children used a double-bind (double-dummy) design (see Figure 2). Performance and assessment bias might therefore have reduced the size of true differences between the two delivery methods.

 

Agreements and disagreements with other studies or reviews

 
Use of oral or parenteral steroids

Successful response to beta₂-agonists does not diminish the necessity to consider oral steroids in acute attacks of asthma. A previous meta-analysis demonstrated that steroids clearly reduce relapses when given to patients following discharge, and reduce hospitalisation when used early in the course of emergency treatment (Rowe 2007).

 
Dosage of beta₂ agonist

The studies included in this review used nominal dosage ratios between nebuliser and spacer that varied from 1:1 to 1:13 (lower dose in the spacer). One of the included studies plotted a log dose-response curve (Colacone 1993); the equivalent dose ratio found in this study was 1:6 with the lower dose in the spacer. In adults, no additional benefit was found using six puffs of salbutamol (100 mcg each) given at 10-minute intervals through a Volumatic spacer, when compared with four puffs at 10-minute intervals (Rodrigo 1996). A comparison in children between doses of 0.5 mg/kg and 1.5 mg/kg given at 20-minute intervals via nebuliser showed significantly greater improvement in lung function at the higher dose (Schuh 1989).

Experimental evidence suggests that the beta₂-agonist should be released (actuated) into the spacer in individual puffs that can be inhaled by tidal breathing or single breaths (Gleeson 1988; Newman 1984). Some of the early studies mentioned difficulty with the valve movement with some spacers; however, this did not appear to be a problem in more recent studies. Some children may co-operate more with either spacer or nebuliser, so this may be an important factor in the choice of delivery method.

 
Type of spacer

Two studies compared different types of spacer; Chong-Neto 2005 studied 10 children with aerochamber and 10 with a home-made spacer constructed from a 500 mL mineral water bottle. The study failed to identify differences between the types of spacer other than lower pulse rates with the Aerochamber than with the home-made spacer. Williams 1996 included 20 children treated with an Aerochamber and 22 children treated with an ACE spacer (both around 150 mL) and found no significant differences between the groups in respiratory rate and lung function.

Overall comparisons between types of spacer are confounded by all the other differences between the designs of each trial. In view of the discontinuation of Volumatic spacers in the UK in 2005, additional details to allow identification of type of spacer used have been added in  Table 1. This indicates that the findings of this review for the primary outcome of hospital admission are unchanged in children when trials using Volumatic spacers are excluded, but the confidence intervals widen for adults as fewer data contribute to the outcome. We found no significant subgroup differences for any outcome between the trials using Volumatic or other spacers.

 
Cost of treatment

Cost considerations may dictate which delivery system is used in different settings. In many parts of the world nebulisation is not available in peripheral hospitals and clinics for economic reasons (Rao 2002). Several recent studies have now included a calculation of costs of drug treatment (Burrows 2004; Chong-Neto 2005; Dewar 1999; Dhuper 2008; Duarte 2002) and found a cost advantage for spacer delivery.

Total costs in a hospital setting are more complex to calculate; however, when patients return to the community the cost of a home nebuliser and respules is considerably more than an MDI and spacer (and the nebuliser requires regular maintenance). A before-after ED study (Newman 2002) assessed the consequences of changing the acute asthma treatment algorithm from nebulised to MDI/spacer albuterol (salbutamol). Admission rates did not rise following the change in delivery method and duration of stay in the ED fell significantly from 175 minutes to 164 minutes. There were also reductions in charges that did not reach significance. Lower relapse rates following the change to MDI/spacer delivery were confounded by other changes, such as an asthma bag containing a spacer, peak-flow meter, instructional handout and canister of inhaled corticosteroid given to the patients at discharge. This makes data on relapse rates difficult to interpret, although significant reductions were seen following the combined interventions. As expected, the total dose of albuterol given to patients was lower with MDI/spacer delivery.

 
Changing Practice

Current guidelines recommend MDI/spacer delivery of beta₂-agonists in acute asthma (BTS/SIGN 2011; GINA 2012). However, implementing research findings is not an easy process, and Powell 2001 found that successfully changing hospital practice from nebulisers to spacers required a structured strategy to overcome the 'nebuliser culture' both in hospital medical and nursing staff, as well as parents and families of children with asthma. Osmond 2007 carried out a survey of the use of nebulisers and spacers in Canadian paediatric EDs, and found that 21% of emergency physicians used MDI and spacer; the largest perceived barriers amongst non-users included safety and costs, and the lack of a physician champion for change.

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 

Implications for practice

  1. For adults seen and assessed for acute asthma, this review found no significant differences between the two delivery methods. Consequently, the choice of delivery method should reflect patient preference, practice situations and formal economic evaluation
  2. In children, no outcomes were significantly worse with the spacers, and the available evidence suggests that in most cases nebulisers could be replaced with spacers to deliver beta₂-agonists in acute asthma. Moreover, other observed benefits (time spent in emergency department, oxygenation and side effects) may favour the groups treated with metered-dose inhaler (MDI) and spacer.
  3. The experimental method adopted in many of the studies was to give repeated treatments at short intervals (e.g. one respule via a nebuliser or four puffs of a MDI via a spacer every 10 to 15 minutes). The number of treatments required was adjusted to the individual patient's response, overcoming the uncertainty of dosage delivery from different devices. Tidal breathing is easier for adults and children using a spacer for acute asthma, but each puff should be inhaled from the spacer before the next puff is delivered into the spacer. Current evidence is therefore based upon titrated treatment regimens and this should be considered when implementing any change in practice.
  4. The studies excluded people with life-threatening asthma; therefore, the results of this meta-analysis should not be extrapolated to this patient population.

 
Implications for research

  1. Further studies are required to confirm whether these findings, largely from hospital emergency departments, can be replicated in the community setting.
  2. Further studies in children and adults with more severe asthma are required to confirm whether spacers are as efficacious as nebulisers in this group.
  3. In order to avoid confounding due to differences in the dose of drug delivered to the airways, future studies should use multiple treatments at short intervals titrated against individual patient response.
  4. Implementation of change to continue to overcome the 'nebuliser culture' needs further work.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Partial funding from the NHS Executive, North Thames and Eastern Regions supported this review. The reviewers would like to acknowledge Jacqueline Crilly (JAC), co-author of the 2003, 2006 and 2008 updates of this review. In addition, the reviewers would like to acknowledge the assistance provided by the Cochrane Airways Review Group staff (Steve Milan, Anna Bara, Jane Dennis, Toby Lasserson, Liz Stovold) in identifying the trials from the register, obtaining copies of the papers, and translating a paper from Spanish. We would like to acknowledge Robert Chapman for his assistance with the methodological assessment of the trials in the original version of this review, Janet Reynolds from the Watford Postgraduate Medical Centre Library for help with obtaining reprints and Mr and Mrs Clement for their assistance in translation of papers from Spanish and Portuguese. We also thank Kirsty Olsen for copy editing an update of this review and William Griffiths (St George's, University of London) for help with 'Risk of bias' assessments and data extraction for the 2013 update.

We would like to thank the following authors for responding to correspondence and supplying additional data for the review: Tom Burrows, Professor Gerard Canny, Dr Chong Neto, Dr Katherine Chou, Dr Mahmut Coker, Dr. Jeroni Ferrés, Dr Yung-Zen Lin, Dr Nelson Morrone, Dr Dominique Ploin, Dr C Robertson, Dr Ivan Solarte, Dr Gary Salzman, Joan Turner, Dr P Vivek.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
Download statistical data

 
Comparison 1. Spacer (chamber) versus nebuliser (multiple-treatment studies)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hospital admission18Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Adults
9582Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.61, 1.43]

    1.2 Children
9757Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.47, 1.08]

 2 Hospital admission or poor response to treatment21Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Adults
9582Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.61, 1.43]

    2.2 Children
12937Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.75, 1.33]

 3 Duration in emergency department (minutes).5Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 Adults
2132Mean Difference (IV, Random, 95% CI)1.75 [-23.45, 26.95]

    3.2 Children
3396Mean Difference (IV, Random, 95% CI)-33.48 [-43.32, -23.65]

 4 Final rise in FEV₁ (% predicted)8Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Adults
6307Mean Difference (IV, Fixed, 95% CI)0.96 [-2.54, 4.46]

    4.2 Children
248Mean Difference (IV, Fixed, 95% CI)0.92 [-4.96, 6.79]

 5 30 minute rise in FEV₁ (% predicted)3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    5.1 Adults
3200Mean Difference (IV, Fixed, 95% CI)-0.20 [-3.18, 2.78]

 6 Severe asthmatics final rise in FEV₁ (% predicted)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    6.1 Adults
494Mean Difference (IV, Fixed, 95% CI)1.60 [-4.49, 7.69]

 7 Final rise in peak flow (% predicted)6Mean Difference (IV, Fixed, 95% CI)Subtotals only

    7.1 Adults
3139Mean Difference (IV, Fixed, 95% CI)-0.49 [-4.60, 3.63]

    7.2 Children
3166Mean Difference (IV, Fixed, 95% CI)-2.99 [-8.88, 2.91]

 8 30 minute rise in peak flow (% predicted)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    8.1 Adults
2147Mean Difference (IV, Fixed, 95% CI)0.92 [-2.68, 4.51]

 9 Rise in pulse rate (% baseline)16Mean Difference (IV, Random, 95% CI)Subtotals only

    9.1 Adults
7376Mean Difference (IV, Random, 95% CI)-1.23 [-4.06, 1.60]

    9.2 Children
9670Mean Difference (IV, Random, 95% CI)-5.41 [-8.34, -2.48]

 10 % Oxygen saturation (change from baseline)6Mean Difference (IV, Fixed, 95% CI)Subtotals only

   10.1 Adults
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.2 Children
6476Mean Difference (IV, Fixed, 95% CI)-0.19 [-0.61, 0.24]

 11 Number of participants developing tremor8Risk Ratio (IV, Random, 95% CI)Subtotals only

    11.1 Adults
4234Risk Ratio (IV, Random, 95% CI)0.82 [0.28, 2.37]

    11.2 Children
4254Risk Ratio (IV, Random, 95% CI)0.64 [0.44, 0.95]

 12 Number of participants given steroids4Risk Ratio (M-H, Random, 95% CI)Subtotals only

    12.1 Adults
288Risk Ratio (M-H, Random, 95% CI)0.71 [0.08, 6.02]

    12.2 Children
2297Risk Ratio (M-H, Random, 95% CI)1.12 [0.95, 1.32]

 13 Rise in respiratory rate (breaths per minute)13Mean Difference (IV, Random, 95% CI)Subtotals only

    13.1 Adults
5257Mean Difference (IV, Random, 95% CI)0.28 [-2.29, 2.84]

    13.2 Children
8686Mean Difference (IV, Random, 95% CI)-0.94 [-2.84, 0.97]

 
Comparison 2. Spacer (chamber) versus nebuliser (single-treatment studies)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hospital admission5Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Adults
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Children
4Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Final peak flow (% predicted)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   2.1 Adults
0Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 30 minute rise in FEV₁ (% predicted)2Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 Adults
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 15 minute rise in FEV₁ (% predicted)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 30 minute rise in peak flow (% predicted)3Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 Adults
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Children
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 15 minute rise in peak flow (% predicted)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Rise in pulse rate (% baseline)3Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 Adults
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Children
2Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Number of participants developing tremor1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    8.1 Children
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Number of participants with deterioration in blood gases2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    9.1 Children
2Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Rise in respiratory rate2Mean Difference (IV, Fixed, 95% CI)Totals not selected

    10.1 Adults
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Spacer (chamber) versus nebuliser (inpatient studies)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Duration of hospital admission (days)3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    1.1 Adults
118Mean Difference (IV, Fixed, 95% CI)-0.60 [-3.23, 2.03]

    1.2 Children
275Mean Difference (IV, Fixed, 95% CI)0.33 [-0.10, 0.76]

 2 Number of hours until reached 4-hourly dosing regimen1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   2.1 Adults
0Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Total number of inhaled doses received1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   3.1 Adults
0Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Number of participants returning to normal PEFR and respiratory score levels (end of study)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

   4.1 Adults
0Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Children
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Number of symptom-free participants 14 days post-discharge1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

   5.1 Adults
0Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Children
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Readmissions in the subsequent 12 months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

   6.1 Adults
0Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Children
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Clinical asthma score (end of trial)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   7.1 Adults
0Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Maximum percentage decrease in respiratory score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   8.1 Adults
0Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Respiratory rate at discharge2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   9.1 Adults
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Children
275Mean Difference (IV, Fixed, 95% CI)-0.91 [-3.20, 1.38]

 10 Heart rate at discharge2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   10.1 Adults
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.2 Children
276Mean Difference (IV, Fixed, 95% CI)1.06 [-5.48, 7.61]

 11 Oxygen saturations at discharge2Mean Difference (IV, Fixed, 95% CI)Subtotals only

   11.1 Adults
00Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    11.2 Children
276Mean Difference (IV, Fixed, 95% CI)0.12 [-0.42, 0.66]

 12 30 minute rise in FEV₁2Std. Mean Difference (IV, Fixed, 95% CI)Totals not selected

    12.1 Adults
1Std. Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    12.2 Children
1Std. Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 13 Final rise in FEV₁2Std. Mean Difference (IV, Fixed, 95% CI)Totals not selected

    13.1 Adults
1Std. Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    13.2 Children
1Std. Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 14 Final rise in peak flow (% change from baseline)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

   14.1 Adults
0Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    14.2 Children
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. Spacer (chamber) versus nebuliser (multiple-treatment studies with Volumatic subgroups)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Hospital admission16Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Adults with other spacers
6366Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.55, 2.84]

    1.2 Adults with Volumatic
2166Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.51, 1.38]

    1.3 Children with other spacers
6515Risk Ratio (M-H, Fixed, 95% CI)0.61 [0.39, 0.96]

    1.4 Children with Volumatic
2163Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.05, 6.11]

 2 Hospital admission or poor response to treatment19Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Adults with other spacers
6366Risk Ratio (M-H, Fixed, 95% CI)1.25 [0.55, 2.84]

    2.2 Adults with Volumatic
2166Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.51, 1.38]

    2.3 Children with other spacers
8635Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.55, 1.16]

    2.4 Children with Volumatic
3223Risk Ratio (M-H, Fixed, 95% CI)1.29 [0.79, 2.13]

 3 Duration in emergency department (minutes).4Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 Adults with other spacers
135Mean Difference (IV, Random, 95% CI)-9.0 [-42.91, 24.91]

    3.2 Adults with Volumatic
197Mean Difference (IV, Random, 95% CI)15.00 [-22.65, 52.65]

    3.3 Children with other spacers
2348Mean Difference (IV, Random, 95% CI)-29.89 [-40.47, -19.32]

 4 Final rise in FEV₁ (% predicted)7Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Adults with other spacers
3168Mean Difference (IV, Fixed, 95% CI)0.30 [-4.70, 5.30]

    4.2 Adults with Volumatic
2119Mean Difference (IV, Fixed, 95% CI)1.20 [-4.13, 6.53]

    4.3 Children with other spacers
130Mean Difference (IV, Fixed, 95% CI)0.0 [-6.17, 6.17]

    4.4 Children with Volumatic
118Mean Difference (IV, Fixed, 95% CI)9.8 [-9.41, 29.01]

 5 30 minute rise in FEV₁ (% predicted)2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    5.1 Adults with other spacers
153Mean Difference (IV, Fixed, 95% CI)-3.80 [-8.51, 0.91]

    5.2 Adults with Volumatic
197Mean Difference (IV, Fixed, 95% CI)1.5 [-3.07, 6.07]

 6 Severe asthmatics final rise in FEV₁ (% predicted)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    6.1 Adults with other spacers
355Mean Difference (IV, Fixed, 95% CI)0.86 [-6.77, 8.48]

    6.2 Adults with Volumatic
139Mean Difference (IV, Fixed, 95% CI)2.90 [-7.21, 13.01]

 7 Final rise in peak flow (% predicted)5Mean Difference (IV, Fixed, 95% CI)Subtotals only

    7.1 Adults with Volumatic
2119Mean Difference (IV, Fixed, 95% CI)-0.39 [-4.77, 3.98]

    7.2 Children with other spacers
2148Mean Difference (IV, Fixed, 95% CI)-3.75 [-9.95, 2.45]

    7.3 Children with Volumatic
118Mean Difference (IV, Fixed, 95% CI)4.10 [-14.81, 23.01]

 8 30 minute rise in peak flow (% predicted)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 Adults with Volumatic
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Rise in pulse rate (% baseline)13Mean Difference (IV, Fixed, 95% CI)Subtotals only

    9.1 Adults with other spacers
3168Mean Difference (IV, Fixed, 95% CI)-2.28 [-7.81, 3.24]

    9.2 Adults with Volumatic
3188Mean Difference (IV, Fixed, 95% CI)-0.16 [-3.89, 3.58]

    9.3 Children with other spacers
5464Mean Difference (IV, Fixed, 95% CI)-6.80 [-9.14, -4.45]

    9.4 Children with Volumatic
278Mean Difference (IV, Fixed, 95% CI)-6.73 [-11.24, -2.23]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Appendix 1. Sources and search methods for the Cochrane Airways Group Specialised Register (CAGR)

 

Electronic searches: core databases


DatabaseFrequency of search

CENTRAL (the Cochrane Library)Monthly

MEDLINE (Ovid)Weekly

EMBASE (Ovid)Weekly

PsycINFO (Ovid)Monthly

CINAHL (EBSCO)Monthly

AMED (EBSCO)Monthly



 

 

Hand-searches: core respiratory conference abstracts


ConferenceYears searched

American Academy of Allergy, Asthma and Immunology (AAAAI)2001 onwards

American Thoracic Society (ATS)2001 onwards

Asia Pacific Society of Respirology (APSR)2004 onwards

British Thoracic Society Winter Meeting (BTS)2000 onwards

Chest Meeting2003 onwards

European Respiratory Society (ERS)1992, 1994, 2000 onwards

International Primary Care Respiratory Group Congress (IPCRG)2002 onwards

Thoracic Society of Australia and New Zealand (TSANZ)1999 onwards



 

 

MEDLINE search strategy used to identify trials for the CAGR

 

Asthma search

1. exp Asthma/

2. asthma$.mp.

3. (antiasthma$ or anti-asthma$).mp.

4. Respiratory Sounds/

5. wheez$.mp.

6. Bronchial Spasm/

7. bronchospas$.mp.

8. (bronch$ adj3 spasm$).mp.

9. bronchoconstrict$.mp.

10. exp Bronchoconstriction/

11. (bronch$ adj3 constrict$).mp.

12. Bronchial Hyperreactivity/

13. Respiratory Hypersensitivity/

14. ((bronchial$ or respiratory or airway$ or lung$) adj3 (hypersensitiv$ or hyperreactiv$ or allerg$ or insufficiency)).mp.

15. ((dust or mite$) adj3 (allerg$ or hypersensitiv$)).mp.

16. or/1-15

 

Filter to identify RCTs

1. exp "clinical trial [publication type]"/

2. (randomised or randomised).ab,ti.

3. placebo.ab,ti.

4. dt.fs.

5. randomly.ab,ti.

6. trial.ab,ti.

7. groups.ab,ti.

8. or/1-7

9. Animals/

10. Humans/

11. 9 not (9 and 10)

12. 8 not 11

The MEDLINE strategy and RCT filter are adapted to identify trials in other electronic databases.

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Last assessed as up-to-date: 14 February 2013.


DateEventDescription

30 June 2014AmendedThe studies excluded life-threatening asthma, and this was added to the abstract.



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Protocol first published: Issue 2, 1996
Review first published: Issue 3, 1996


DateEventDescription

9 May 2014AmendedAmended a sentence in the conclusion to make it clearer that "in most cases nebulisers could be replaced with spacers to deliver beta₂-agonists in acute asthma" after receiving a suggestion from Andrés Infante Llanos. Thanks Andrés.

4 November 2013AmendedTypos corrected. Changed LABA to SABA in the discussion and expanded an occurence of LABA to beta2-agonists.

14 February 2013New search has been performedLiterature search run

14 February 2013New citation required and conclusions have changedFour further new studies including 58 adults and 295 children have been added (Dhuper 2008; Direkwatanachai 2008; Ferrés 1989 (single treatment); Yasmin 2012). Also individual patient data has been incorporated from Burrows 2004 for children over 2 years of age treated as inpatients.

Two 'Summary of findings' Tables have been added. We also completed a new 'Risk of bias' assessment using the Review Manager 5 tool. Conclusions have been changed to emphasise the use of repeated treatments titrated to the participant's response in the trials.

28 July 2008New search has been performedConverted to new review format and two new studies added (Jamalvi 2006 and Sannier 2007). No change in conclusions.

4 January 2006New search has been performedFor the 2006 update of this review five new trials have been added: Burrows 2004 including 29 paediatric in-patients, Chong-Neto 2005 included 30 children given multiple treatments, Hussein 2002 including 60 children given a single treatment, Rao 2002 including 50 adults given multiple treatments and Vivek 2003 including 120 patients aged 10-50 (and therefore classified as adult) given multiple treatments.
An additional table has been added with details of the holding chambers used in each study, and new comparisons added according to type of chamber. This was done because Volumatic spacers were no longer being manufactured (but they have now been reintroduced).

29 July 2003New search has been performedOne trial was added to the review in 1997 (Williams 1996). Four further trials were added to the review in 1999 (Batra 1997; Maldano-Alanis 1997; Robertson 1998; Rodrigo 1998), but the conclusions of the review remained unchanged. For the 2001 update a further four studies were added (Leversha 2000; Ploin 2000; Rodriguez 1999; Valencia 1999) and reduced the confidence intervals around the results.
One open trial in children has been added for the 2003 update (Duarte 2002) including a further 196 children studied in an emergency room setting in Brazil.
In addition the 2003 update has expanded the review to include trials on in-patients and five new trials have been added including 184 children and 28 adults (Ba 1989, Coker 1995, Dewar 1999, Morley 1988 and Parkin 1995). The results of the in-patient trials are in keeping with the findings in the emergency room and community setting, that holding chambers can be as effective as nebulisers for delivery of beta-agonists in acute asthma.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

CJC had the initial idea for the review and wrote the protocol and review in conjunction with BHR. The data extraction and analysis were performed by CJC and the methodological quality was independently assessed by Robert Chapman for the original papers. Anna Bara independently assessed trials for inclusion, and extracted trial data for the 1997,1999 and 2001 updates. JAC and CJC assessed trials for inclusion and extracted data for the 2003 and 2006 update (to include trials on inpatients). CJC and BHR have updated the review to include further trials in 1997, 1999 and 2001. CJC, JAC and BHR have carried out the 2003, 2006, 2008 updates, and CJC and BHR carried out the 2013 update with help from William Griffiths, who independently assessed risks of bias and outcome data. EJW drafted the summary of findings table, contributed to discussion during the 2013 update and commented critically on the paper.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

The authors have no financial interest in any of the devices used to deliver beta₂-agonists in acute asthma and no involvement with the primary studies.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Internal sources

  • NHS Executive, North Thames, UK.
  • NHS Executive Eastern Region, UK.
  • Department of Emergency Medicine, University of Alberta, Edmonton, Canada.
  • St George's University of London, UK.

 

External sources

  • Garfield Weston Foundation, UK.
  • Canadian Institutes of Health Research (CIHR), Ottawa, Canada.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

We have now included studies on people who had been admitted to hospital, and we have used the Review Manager 5 'Risk of bias' tool and I² statistics (which were not available when the original protocol was written).

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. Additional references
  23. References to other published versions of this review
Ba 1989 {published data only}
  • Ba M, Spier S, Lapierre G, Lamarre A. Wet nebulizer versus spacer and metered dose inhaler via tidal breathing. Journal of Asthma 1989;26:355-8. [MEDLINE: 192630]
Batra 1997 {published data only}
  • Batra V, Sethi G, Sachdev H. Comparative efficacy of jet nebuliser and metered dose inhaler with spacer device in the treatment of acute asthma. Indian Pediatrics 1997;34:497-503.
Burrows 2004 {published and unpublished data}
  • Burrows T, Connett GJ. The relative benefits and acceptability of metered dose inhalers and nebulisers to treat acute asthma in preschool children [Abstract]. Thorax 2004;59(Suppl II):ii20. [: CN-00517341]
Chong-Neto 2005 {published data only}
  • Alves Cardozo C. Cost of treatment of acute asthma in children using different inhaler devices [Dissertation]. Pontifícia Universidade Católica do Paraná (Brazil) 2005:88p.
  • Chong-Neto HJ, Chong-Silva DC, Marani DM, Kuroda F, Olandowisky M, Noronha L, et al. Different inhaled devices in acute asthma attacks: a randomized, double-blinded, placebo controlled study. Jornal de Pediatria 2005;81:298-304.
Chou 1995 {published and unpublished data}
  • Chou KJ, Cunningham SJ, Crain EF. Metered-dose inhalers with spacers versus nebulizers for pediatric asthma. Archives of Pediatrics and Adolescent Medicine 1995;149:201-5.
Coker 1995 {published data only}
  • Coker M, Tanac R. Comparison of three methods of inhaling salbutamol in acute childhood asthma. Turkish Journal of Medical Sciences 1995;23:293-7.
Colacone 1993 {published data only}
Dewar 1999 {published data only}
  • Dewar AL, Stewar A, Cogswell JJ, Connett GL. A randomised controlled trial to assess the relative benefits of large volume spacers and nebulisers to treat acute asthma in hospital. Archives of Disease in Childhood 1999;80:421-3.
Dhuper 2008 {published data only}
  • Dhuper S, Chandra A, Ahmed A, Bista S, Moghekar A, Verma R, et al. Bronchodilator administration between MDI's with a disposable spacer and nebulizer used for acute asthma treatment: a comparison of efficacy and cost analysis [Abstract]. American Thoracic Society International Conference; 2008 May 16-21; Toronto. 2008.
  • Dhuper S, Chandra A, Ahmed A, Bista S, Moghekar A, Verma R, et al. Efficacy and cost comparisons of bronchodilatator administration between metered dose inhalers with disposable spacers and nebulizers for acute asthma in an inner-city adult population. Journal of Emergency Medicine 2011; Vol. 40, issue 3:247-255.
Direkwatanachai 2008 {published data only}
  • Direkwatanachai C, Teeratakulpisarn J, Suntornlohanakul S, Trakultivakorn M, Ngamphaiboon J, Wongpitoon N, et al. Comparison of salbutamol efficacy in children--via the metered-dose inhaler (MDI) with Volumatic spacer and via the dry powder inhaler, Easyhaler, with the nebulizer--in mild to moderate asthma exacerbation: a multicenter, randomized study. Asia-Pacific Journal of Allergy and Immunology 2011;29:25-33.
  • Sirikul C, Chumpakdee K, Vangveeravong M. A comparative study of efficacy of salbutamol via metered dose inhaler (MDI) with volumatic spacer and via dry powder inhaler (DPI) Easyhaler to nebulization in mild to moderate severity acute asthma exacerbation in children [Abstract]. Journal of Allergy and Clinical Immunology 2008;121(2 Suppl 1):S156.
  • Vangveeravong M. A comparative study of efficacy of salbutamol via metered dose inhaler with volumatic spacer and via dry powder inhaler, easyhaler, to nebulization in mild to moderate severity acute asthma exacerbation in childhood. Journal of the Medical Association of Thailand 2008;91(Suppl 3):S115-23.
Duarte 2002 {published data only}
  • Duarte M, Camargos P. Efficacy and safety of a home-made non-valved spacer for bronchodilator therapy in acute asthma. Acta Paediatrica 2002;91:909-13.
Ferrés 1989 {published data only}
  • Ferrés J, Querol J, Guasch, E. Beta2-adrenergic stimulants: Nebulizer versus holding chambers for the treatment of pediatric acute asthma. Anales Españoles de Pediatría 1989;31(2):175.
Freelander 1984 {published data only}
  • Freelander M, Van Asperen PP. Nebuhaler versus nebuliser in children with acute asthma. BMJ 1984;288:1873-4.
Hussein 2002 {published data only}
  • Hussein ZM, Bader-Eldin OMK, Galal AA, Abd-Allah SA. Metered dose inhaler with spacer versus nebulizer in children with acute bronchial asthma. European Respiratory Society Annual Congress; 2002 Sep 14-18; Sweden. 2002.
Idris 1993 {published data only}
  • Idris AH, McDermott MF, Raucci JC, Morrabel A, McGorray S, Hendeles L. Emergency department treatment of severe asthma. Metered-dose inhaler plus holding chamber is equivalent in effectiveness to nebulizer. Chest 1993;103:665-72.
Jamalvi 2006 {published data only}
  • Jamalvi SW, Raza SJ, Naz F, Shamim S, Jamalvi SM. Management of acute asthma in children using metered dose inhaler and small volume nebulizer. Journal of the Pakistan Medical Association 2006; Vol. 56, issue 12:595-9.
Kerem 1993 {published and unpublished data}
  • Kerem E, Levison H, Schuh S, OBrodovich H, Reisman J, Bentur L, et al. Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. Journal of Pediatrics 1993;123:313-7.
Leversha 2000 {published data only}
  • Leversha AM, Campanella SG, Aickin RP, Asher MI. Costs and effectiveness of spacer versus nebulizer in young children with moderate and severe asthma. Journal of Pediatrics 2000;136(4):497-502.
Lin 1995 {published and unpublished data}
  • Lin Y-Z, Hsieh K-H. Metered dose inhaler and nebuliser in acute asthma. Archives of Disease in Childhood 1995;72:214-8.
Maldano-Alanis 1997 {published data only}
  • Maldano-Alanis M, Linares-Zapien F, Rio-Navarro B, Sienna-Monge J. Comparison between salbutamol administered through metered dose inhalers with spacers vs nebulisers in children with acute asthma. Boletin Medico del Hospital Infantil de Mexico 1997;54:374-8.
Morley 1988 {published data only}
  • Morley TF, Marozsan E, Zappasodi SJ, Gordon R, Griesback R, Giudice JC. Comparison of beta-adrenergic agents delivered by nebulizer vs metered dose inhaler with InspirEase in hospitalised asthmatic patients. Chest 1988;94(6):1205-10.
Morrone 1990 {published and unpublished data}
  • Morrone N, Freire JA, Pereira CA, Ferreira AK. Bronchodilation induced by fenoterol in asthmatic patients: comparison of jet nebulization and spacer device. Revista Paulista de Medicina 1990;108:83-7.
Parkin 1995 {published data only}
  • Parkin PC, Saunders NR, Diamond SA, Winders PM, Macarthur C. Randomised trial spacer v nebuliser for acute asthma. Archives of Disease in Childhood 1995;72:239-40.
Pendergast 1989 {published data only}
  • Pendergast J, Hopkins J, Timms B, Van Asperen PP. Comparative efficacy of terbutaline administered by Nebuhaler and by nebulizer in young children with acute asthma. Medical Journal of Australia 1989;151:406-8.
Ploin 2000 {published and unpublished data}
  • Ploin D, Chapuis FR, Stamm D, Robert J, David L, Chatelain PG, et al. High dose aerosolised salbutamol via chamber and nebuliser in wheezy infants and young children [Fortes doses de salbutamol par aérosol doseur et chambre d'inhalation chez les nourrissons et les jeunes enfants siffleurs]. Revue Francaise D' Allergologie Immunologie Clinique 2001;41:155-64.
  • 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 nebulisation in pre-school children with recurrent wheezing: a double-blind, randomised equivalence trial. Pediatrics 2000;106(2):311-7.
Raimondi 1997 {published data only}
  • Raimondi AC, Schottlender J, Lombardi D, Molfino N. Treatment of acute severe asthma with inhaled albuterol delivered by jet nebulizer, metered dose inhaler with spacer or dry powder. Chest 1997;112(1):24-8.
Rao 2002 {published data only}
  • Rao NA, Rizvi N. The efficacy of salbutamol delivered by inhaler plus spacer device and nebulizer in acute asthma: a comparative study. Journal-College of Physicians and Surgeons of Pakistan 2002;12(10):579-82.
Robertson 1998 {published data only}
  • Robertson C, Norden M, Fitzgerald D, Connor F, Van Asperen PP, Cooper PJ, et al. Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler. Journal of Paediatrics and Child Health 1998;34:142-6.
Rodrigo 1993 {published data only}
  • Rodrigo G, Rodrigo C. Comparison of salbutamol delivered by nebulizer or metered-dose inhaler with a pear-shaped spacer in acute asthma. Current Therapeutic Research, Clinical and Experimental 1993;54:797-808.
Rodrigo 1998 {published data only}
Rodriguez 1999 {unpublished data only}
  • Rodriguez IS, Buitrago JR, Garcia RL. Nebulizer versus inhaler plus holding chamber for acute asthma in adults. Data on file 1999.
Salzman 1989 {published data only}
  • Salzman GA, Steele MT, Pribble JP, Elenbaas RM, Pyszczynski DR. Aerosolized metaproterenol in the treatment of asthmatics with severe airflow obstruction. Comparison of two delivery methods. Chest 1989;95:1017-20.
Sannier 2007 {published data only}
  • Sannier N, Timsit S, Cojocaru B, Leis A, Wille C, Garel D, et al. Metered-dose inhaler with spacer versus nebulization for severe and potentially severe acute asthma treatment in the pediatric emergency department. [French]. Revue Francaise d Allergologie et d Immunologie Clinique 2007; Vol. 47, issue 2:64-71.
Turner 1988 {published and unpublished data}
  • Turner JR, Corkery KJ, Eckman D, Gelb AM, Lipavsky A, Sheppard D. Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction. Chest 1988;93:476-81.
Valencia 1999 {published data only}
  • Valencia ML, Manotas R. Inhaled versus nebulised salbutamol in the management of acute asthma exacerbation in pre-school children. A randomised comparative trial [Salbutamol inhalado o nebulizado en el tratamiento de la exacerbacion aguda del asma en el preescolar. Estudio comparativo aleatorizado]. Iatreia 1999;12(3):130-4.
Vazquez 1992 {published data only}
  • Vazquez Cordero C, Corera Sanchez M, Molinuevo Alvaro J. Comparison of treatment of acute asthma attacks in children with salbutamol dispensed by the Volumatic dispenser or by a nebulizer. Anales Espanoles de Pediatria 1992;36:359-62.
Vivek 2003 {published and unpublished data}
  • Vivek P, Joshi M. A randomised controlled trial comparing the efficacy of inhalation therapy by spacer device v nebulizer in acute exacerbation of asthma. Thorax 2003;58(Suppl 3):iii44.
Williams 1996 {published data only}
Yasmin 2012 {published data only}
  • Yasmin S, Mollah AH, Basak R, Islam KT, Chowdhury YS. Efficacy of salbutamol by nebulizer versus metered dose. Mymensingh Medical Journal 2012; Vol. 21, issue 1:66-71.

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. Additional references
  23. References to other published versions of this review
Beasley 1985 {published data only}
  • Beasley CRW, O'Donnell TV. Pear shaped spacer Nebuhaler compared with nebulised solution for terbutaline administration in acute severe asthma. New Zealand Medical Journal 1985;98:854-5. [MEDLINE: 191150]
Benton 1989 {published data only}
  • Benton G, Thomas RC, Nickerson BG, McQuitty JC, Okikawa J. Experience with a metered dose inhaler with spacer in pediatric emergency department. Annals of Disease in Childhood 1989;43:678-81.
Berenberg 1985 {published data only}
  • Berenberg MJ, Baigelmann W, Cupples LA, Pearce L. Comparison of metered-dose inhaler attached to an aerochamber with an updraft nebuliser for the administration of metaproterenol in hospitalised patients. Journal of Asthma 1985;22:87-92.
Campbell 1995 {published data only}
  • Campbell IA, Colman SB, Mao JH, Prescott RJ, Weston CFM. An open, prospective comparison of beta 2 agonists given via nebuliser, Nebuhaler, or pressurised inhaler by ambulance crew as emergency treatment. Thorax 1995;50:79-80. [MEDLINE: 19920]
Deerojanawong 2005 {published data only}
  • Deerojanawong J, Manuyakorn W, Prapphal N, Harnruthakorn C, Sritippayawan S, Samransamruajkit R. Randomized controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer vs. jet nebulizer in young children with wheezing. Pediatric Pulmonology 2005;39(5):466-72.
  • Wiparat, M. A prospective randomized controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer versus jet nebulizer for young children with acute wheezing [Dissertation]. Chulalongkorn Univerisity. Bangkok. (Thailand). Graduate School. 2002.
Fayaz 2009 {published data only}
  • Fayaz M, Sultan A, Rai M E. Comparison between efficacy of mdi+spacer and nebuliser in the management of acute asthma in children. Journal of Ayub Medical College Abbottabad 2009;21(1):32-4.
Fuglsang 1986 {published data only}
Hart 2009 {published data only}
  • Hart M, Abmas E, Boehm R, Hernandez G, Millard M. Comparison of valved-holding chamber (VHC)-facemask/mouthpiece with small volume nebulizer-facemask (SVN-F for bronchodilator delivery [Abstract]. European Respiratory Society Annual Congress; 2009 Sep 12-16; Vienna. 2009.
Hodder 1988 {published data only}
  • Hodder RV, Calcutt LE, Leech JA. Metered dose inhaler with spacer is superior to wet nebulisation for emergency room treatment of acute severe asthma. Chest 1988;94 Suppl:53.
Jasper 1987 {published data only}
Kaashmiri 2010 {published data only}
  • Kaashmiri M, Shepard J, Goodman B, Lincourt WR, Trivedi R, Ellsworth A, et al. Repeat dosing of albuterol via metered-dose inhaler in infants with acute obstructive airway disease: A randomized controlled safety trial. Paediatric Emergency Care 2010;26(3):197-202.
Levitt 1995 {published data only}
  • Levitt MA, Gambrioli EF, Fink JB. Comparative trial of continuous nebulization versus metered-dose inhaler in the treatment of acute bronchospasm. Annals of Emergency Medicine 1995;26:273-7.
Madsen 1982 {published data only}
  • Madsen EB, Bundgaard A, Hidinger K. Cummulative dose-response study comparing terbutaline pressurised aerosol administered via a pear-shaped spacer and terbutaline in a nebulized solution. European Journal of Clinical Pharmacology 1982;23:27-30.
Maguire 1991 {published data only}
Mandelberg 1997 {published data only}
Mandelberg 2000 {published data only}
  • Mandelberg A, Tsehori S, Houri S, Gilad E, Morag B, Priel IE. Is nebulized aerosol treatment necessary in a pediatric emergency department? Comparison with a metal spacer device for metered-dose inhaler. Chest 2000;117(5):1309-13.
Morgan 1982 {published data only}
  • Morgan MDL, Singh BV, Frame MH, Williams SJ. Terbutaline aerosol given through pear spacer in acute severe asthma. BMJ 1982;285:849-50.
Newman 2002 {published data only}
  • Newman KB, Milne S, Hamilton C, Hall K. A comparison of albuterol administered by metered-dose inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency department with acute asthma. Chest 2002;121:1036-41.
Rubilar 2000 {published data only}
  • Rubilar L, Castro-Rodriguez JA, Girardi G. Randomized 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.
Shaikh 2001 {published data only}
  • Shaikh GP, Pednekar S, Paidhungat AJ, Nabar ST, Iyenger V, Khatri DP. A study of pulmonary functions, metabolic parameters and electro-cardiogram after salbutamol for bronchial asthma using two delivery systems. Indian Practitioner 2001;54(9):619-23.
Shim 1984 {published data only}
Summer 1989 {published data only}
  • Summer W, Elston R, Tharpe L, Nelson S, Haponik EF. Aerosol bronchodilator delivery methods. Relative impact on pulmonary function and cost of respiratory care. Archives of Internal Medicine 1989;149:618-23. [MEDLINE: 19920]
Tarala 1980 {published data only}
  • Tarala RA, Madsen BW, Paterson JW. Comparative efficacy of salbutamol by pressurized aerosol and wet nebulizer in acute asthma. British Journal of Clinical Pharmacology 1980;10:393-7.
Vilarinho 2003 {published data only}
  • Vilarinho LC, Cardeal Mendes CM, De Freitas Souza LS. Metered-dose inhalers with home-made spacers versus nebulizers to treat moderate wheezing attacks in children. Jornal de Pediatria 2003;79(5):403-12. [PUBMED: 14557840]
Wildhaber 1999 {published data only}
  • Wildhaber JH, Dore ND, Wilson JM, Devadson SG, LeSouef PN. Inhalation therapy in asthma: nebulizer or pressurised metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children. Journal of Pediatrics 1999;135(1):28-33.

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. Additional references
  23. References to other published versions of this review
BTS/SIGN 2011
  • British Guideline on the Management of Asthma.  A national clinical guideline.  May 2008.  Revised May 2011. British Thoracic Society www.brit-thoracic.org.uk and Scottish Intercollegiate Guidelines Network www.sign.ac.uk.
GINA 2012
  • Global Initiative for Asthma (GINA). The Global Strategy for Asthma Management and Prevention. www.ginasthma.org/ (accessed 1st June 2013) 2012.
Gleeson 1988
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Lipworth 1997
  • Lipworth BJ, Clark DJ. Effects of airway calibre on lung delivery of nebulised salbutamol. Thorax 1997;52(12):1036-9.
Newman 1984
Osmond 2007
  • Osmond MH, Gazarian M, Henry RL, Clifford TJ, Tetzlaff J. Barriers to metered-dose inhaler/spacer use in Canadian pediatric emergency departments: a national survey. Academic Emergency Medicine 2007;14(11):1106-13.
Powell 2001
Rodrigo 1996
Rowe 2007
Schuh 1989
  • Schuh S, Parkin P, Rajan A, Canny G, Healy R, Reider M, et al. High- versus low-dose, frequently administered, nebulised albuterol in children with acute severe asthma. Pediatrics 1989;83:513-8.
Turner 1997
  • Turner MO, Patel A, Ginsburg S, Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. Archives of Internal Medicine 1997;157:1736-44.

References to other published versions of this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. Additional references
  23. References to other published versions of this review
Cates 2004
  • Cates CJ, Bara A, Crilly JA, Rowe BH. Holding chambers versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/14651858.CD000052]
Cates 2006
  • Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD000052.pub2]