Commercial versus home‐made spacers in delivering bronchodilator therapy for acute therapy in children
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The aim of this review is to determine the efficacy of the commercially produced spacers versus home‐made spacers in delivering bronchodilator therapy to children with acute asthma attacks.
Background
Asthma is a major cause of childhood morbidity (Anderson 1989) and disability (Newacheck 2000), with acute exacerbations of the disease being a common reason for emergency department (ED) visits and hospital admissions (Akinbami 2002). The main drugs used in the management of acute asthma are nebulised beta‐agonists, and oral or parenteral corticosteroids. Ipratropium bromide (Plotnick 2000), inhaled glucocorticosteroids (Edmonds 2000; Edmonds 2003), and intravenous magnesium (Rowe 2000) may confer benefit in acute asthma. Antibiotics, inhaled mucolytics, aminophylline, sedation and antihistamines have no established role in the treatment of exacerbations. Although rapid‐acting inhaled beta 2‐agonists are generally administered by nebulization, equivalent (Cates 2003) or even greater bronchodilatation (Rodríguez 2004) with a more rapid onset, fewer side effects, and less time in the emergency department can be achieved using an metered‐dose inhaler (MDI) with spacer.
Effective use of MDI requires synchronization of inhalation with actuation of the device. Since synchronization is difficult in children, spacer devices are used to overcome this problem of co‐ordination. Spacers have further advantages in that they improve efficacy (increase lung deposition and decrease oropharyngeal deposition) and reduce side effects from inhaled drugs (Amirav 1997; Singhal 2001). For this reason, inhaled therapy using a MDI with attached spacer has been increasingly recognized as the optimal method for delivering rapid acting beta 2‐agonists for acute asthma attacks. A wide variety of commercially produced spacers are available; these differ in shape, size, material out of which they are constructed, and the presence of valves (Zar 2002). However, high cost and lack of availability of commercial produced spacers have limited their use in developing countries.
As an alternative, rapid acting beta 2‐agonists via MDI has been delivered attached to home‐made spacers for treating children with acute asthma (Singhal 2001; Zar 1999; Zar 2002). A wide variety of home‐made spacers have been developed, including plastic cold‐drink bottles, plastic mineral water bottles, polystyrene cups, plastic zip‐up bags, and paper spacers. In spite of the wide use of these home‐made spacers in developing countries, there are only a few studies comparing its use for delivery of rapid acting beta 2‐agonists via MDI versus the same bronchodilator therapy with commercially produced spacers for treating acute asthma attacks in children under 18 years of age.
Although several studies have concluded that rapid acting 2‐agonists via MDI given attached to home‐made spacers produce similar bronchodilation than the same bronchodilator therapy delivered with commercially produced spacers for treating acute asthma attacks in children, some of these studies may have had type II errors because of inadequate sample sizes. As a consequence, a systematic review of published trials will be useful and important.
Objectives
The aim of this review is to determine the efficacy of the commercially produced spacers versus home‐made spacers in delivering bronchodilator therapy to children with acute asthma attacks.
Methods
Criteria for considering studies for this review
Types of studies
All randomised, controlled clinical trials will be included in the analysis.
Types of participants
Children under 18 years with acute exacerbation of asthma presenting to an ED or equivalent care setting.
Types of interventions
Intervention: Rapid acting beta‐2 agonists via MDI given attached to home‐made spacers. Combination treatment with anti‐cholinergic agents will be permitted.
Controls: The same bronchodilator therapy delivered with commercially produced spacers. Combination treatment with anti‐cholinergic agents will be permitted.
Types of outcome measures
The review will address the following variables, as available from the primary trials:
Primary outcome
Hospital discharge
Secondary outcomes
Changes from baseline for physiologic variables, such as peak expiratory flow rate, FEV1% and oxygenation parameters; including timing of assessment for all parameters.
Differences in outcomes related to morbidity, such as hospital and ICU admission data, emergency department length of stay, and clinical scores.
Complications, such as dysrhythmia, desaturation, tremor, nausea.
Symptomatology, such as dyspnea, accessory muscle use.
Number of additional bronchodilator treatments required upon completion of the intervention protocol.
Physical signs, such as wheezing, accessory muscle use.
Search methods for identification of studies
In order to identify potentially relevant trials we will search the electronic databases MEDLINE (from January 1966 to July 2005), EMBASE (from January 1974 to July 2005), Cochrane Airways Group Specialised Register (from January 1966 to July 2005), and LILACS (from January 1982 to July 2005).
Searches of the databases will be completed based on the following MeSHterms and text words:
Asthma/ OR Bronchial Spasm/ OR Albuterol/administration and dosage OR Administration, Inhalation OR Bronchodilator Agents/administration and dosage OR Bronchodilator Agents/therapeutic use OR Anti‐Asthmatic Agents/therapeutic use, AND Inhalation Spacers/ OR Aerosols/ OR Nebulizers and Vaporizers/ OR Respiratory Therapy/ OR home‐made spacer* OR improvised spacer device* OR Indigenous spacer* OR plastic bottle* OR polystyrene cup* OR plastic zip‐up bag* OR paper spacer* OR alternative spacer device* OR Metered Dose Inhalers/economics.
To identify potentially relevant trials we will use the Cochrane highly sensitive search filter for controlled trials (Robinson 2002). We will include citations in any language. An advanced search of the Cochrane Central Register of Controlled Trials (CENTRAL) (first quarter 2005) will be completed using the above search strategy to identify any additional trials. Hand searching of 20 relevant respiratory journals, and proceedings of the American Thoracic Society and the European Respiratory Society will be completed. We also will review the bibliographies of the randomised trials identified, contact the authors and known experts in the field, and approach pharmaceutical companies that manufacture inhalation spacers to identify additional published or unpublished data.
Data collection and analysis
I. Trial Selection
In Phase I, on the basis of Title, Abstract, and MeSH Headings, two reviewers (CRM, MPS) will independently examine citations generated from the computerized search. Trials will be designated as RCT, possible RCT, non‐RCT. All potentially relevant articles will be retrieved (RCTs and possible RCTs).
In Phase II, copies of the full text of articles will be reviewed independently by the same two reviewers (CRM, MPS). Decisions on inclusion will be based on the population, intervention, outcome, and trial design criteria described above. Disagreement will be resolved by consensus. Checklist instruments to guide the selection process will be pilot‐tested using a small sample of abstracts or trials.
II. Trial Quality Assessment
The methodological quality assessment will be performed using two methods and independently by two reviewers (CRM, MPS). First, using the Cochrane approach to assessment of allocation concealment, all trials will be scored and entered using the following principles:
Grade A: Adequate concealment
Grade B: Uncertain
Grade C: Clearly inadequate concealment
Inter‐rater reliability will be measured by using simple agreement and kappa weighted statistics. The methodological quality of the eligible RCTs will be assessed with a modified version of a 5 point scoring instrument, proposed by Jadad (1995) summarized as follows:
1 Was the trial described as randomized (1=yes; 0=no)?;
2 Was the trial described as double‐blind (1=yes; 0=no)?;
3 Was there a description of withdrawals and dropouts (1=yes; 0=no)?;
4 Was the method of randomisation well described and appropriate (1=yes;0=no);
5 Was the method of blinding well described and appropriate (1=yes; 0=no)?;
6 Deduct 1 point if methods for randomization or blinding were inappropriate.
Data collection:
Data from the trials will be extracted, independently, by two reviewers (CRM, MPS) to eliminate transcription errors onto a specially designed form, and entered into RevMan 4.2.8 by one reviewer (CRM) and checked by a second using the double data entry facility.
If possible confirmation and supplementation of the published findings will be make by communication with the principal study investigator of each trial. Information about randomised patients excluded from the published analyses will be seek and if available will be incorporated into the analyses.
Data analysis:
Cochrane Review Manager 4.2 software (Cochrane Review Manager, Cochrane Collaboration, Oxford, UK: 2005) and RevMan Analyses 1.0.2, its companion, will be used to compile and analyze the data. For binary outcomes, a random effects relative risk (RR) and their 95% confidence intervals (CI) will be calculated for each study. The number of patients needed to treat (NNT) to prevent the adverse outcome of interest will be calculated.
For continuous outcomes the weighted mean difference (WMD) (for variables using the same unit of measure), or the standardised mean differences (SMD) (for variables using different units of measure) and 95% CI will be calculated. We will test for heterogeneity by using the DerSimonian and Laird Q statistic. We will also measure heterogeneity by using the I2 test (Higgins 2003). Values of 50%, and 75% will be regarded as showing moderate and high heterogeneity, respectively.
Publication bias will be evaluated by means of formal statistical analysis, and by preparing funnel plots (Egger 1997). Otherwise, a P value of less than 0.05 using a two‐tailed test will be used to indicate significance.
The following sub‐groups will be examined in an attempt to examine group effects:
1. Severity of asthma attack at presentation (mild, moderate or severe);
2. Valved commercially produced spacers, versus those not‐valved;
3. Children under 5 years, versus children 5 ‐ 18 years;
4. Plastic home‐made spacer, versus those made of a different material.
5. Patients receiving systemic corticosteroids, versus those not on systemic corticosteroids
6. Patients receiving anti‐cholinergics, versus those not on anti‐cholinergics.
If significant heterogeneity exists, sensitivity analyses will be performed in an attempt to explain the findings using the following domains:
a. If there are sufficient trials in each category, sensitivity analyses will be performed to assess the effect of shortcomings with respect to individual methodological aspects of the trials, especially allocation concealment;
b. Random effects vs fixed effects modeling;
c. Timing of assessment.
