Are Metered-Dose Inhalers with Holding Chambers Better Than Nebulizers for Treating Acute Asthma?

JOHN EPLING, M.D., and MIN HO CHANG, State University of New York Upstate Medical University, Syracuse, New York

The Cochrane Abstract below is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. John Epling, M.D., and Min Ho Chang present a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract.

Clinical Scenario

A 15-year-old boy with an acute asthma exacerbation is brought to the emergency department.

Clinical Question

Is a metered-dose inhaler (MDI) with a holding chamber more effective than a nebulizer for delivering beta₂ agonists to treat acute asthma exacerbations?

Evidence-Based Answer

In the emergency room, MDIs with holding chambers are as effective as nebulizers for delivering beta₂ agonists to treat acute asthma in adults and children older than age two. There might be slightly less beta₂ agonist­induced tachycardia in children when MDIs with holding chambers are used.

Cochrane Abstract Background. In acute asthma, inhaled beta2 agonists are often administered to relieve bronchospasm by wet nebulization, but some researchers have argued that metered-dose inhalers with a holding chamber (spacer) can be equally effective. In the community setting, nebulizers are more expensive, require a power source, and need regular maintenance. Objectives. There is controversy as to whether wet nebulizers are better than metered-dose inhalers with holding chambers to deliver beta2-agonist medications for acute asthma. Comparisons of hospital and home use are also of interest. The objective of this review1 was to assess the effects of holding chambers compared with nebulizers for the delivery of beta2 agonists for acute asthma. Search Strategy. The authors searched the Cochrane Airways Group trials register and the Cochrane Controlled Trials Register. Selection Criteria. Randomized trials in adults and children (from two years of age) with asthma, where holding-chamber beta2-agonist delivery was compared with wet nebulization. Data Collection and Analysis. Two reviewers independently applied study-inclusion criteria, extracted the data, and assessed trial quality. Missing data were obtained from the authors or estimated. Primary Results. This review was updated in 2001 to include four new trials and has now analyzed 880 children and 444 adults who were included in 21 trials. Method of delivery of beta2 agonists did not appear to affect hospital admission rates. In adults, the relative risk of admission for holding chamber versus nebulizer use was 0.88 (95 percent confidence interval [CI], 0.56 to 1.38). The relative risk for children was 0.65 (95 percent CI, 0.4 to 1.06). One study in children found a significantly shorter length of stay in the emergency department when the holding chamber was used, with a weighted mean difference of -0.62 hours (95 percent CI, -0.84 to -0.40 hours). Adults' length of stay in the emergency department was similar for the two delivery methods. Peak flow and forced expiratory volume were also similar for the two delivery methods. In children, pulse rate was lower with use of holding chambers (weighted mean difference -7.8 percent baseline [95 percent CI, -10.2 to -5.3]). Reviewers' Conclusions. Metered-dose inhalers with holding chambers produced outcomes that were at least equivalent to those of nebulizer delivery. In children with acute asthma, holding chambers might have some advantages compared with nebulizers. These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in The Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (www.cochrane.org).

Cochrane Critique

Did the authors address a focused clinical question? Yes.

Were the criteria used to select articles for inclusion appropriate? Yes. However, only one community-based study was found; the rest were emergency-department studies.

Is it likely that important relevant articles were missed? No. Funnel-plot testing did not reveal any publication bias.

Was the validity of the individual articles appraised? Yes.

Were the assessments of studies reproducible? Yes. The kappa values for the Jadad quality-rating questions ranged from 0.8 to 1.0 (strong agreement), with the exception of the "method of blinding" question, which had a kappa value of 0.5 (moderate agreement).

Were the results similar from study to study? Yes. However, studies of adults and children were separated for the analysis to improve homogeneity.

How precise were the results? All results fell within reasonably narrow confidence intervals.

Reading the Numbers When a group of studies measures a change in a continuous variable (such as blood-pressure readings, cholesterol levels, or pain scores), the most accessible way to analyze the change over all the studies is to use a weighted mean difference (WMD). "Difference" refers to the difference in outcomes between the intervention and control groups at the end of the study and ideally is measured with the usual units for this outcome (e.g., mm Hg for blood pressure). The studies are weighted according to their sample sizes, and the mean refers to the average of these differences across the included studies. A WMD can be calculated if the studies use the same units of measurement for a given outcome and if the mean, sample size, and standard deviation for each of the studies are known. Using WMD in a meta-analysis has the advantage of expressing outcomes in measurement units that clinicians can readily understand and is therefore the Cochrane Collaboration's preferred method of reporting outcomes for continuous variables.2

Can the results be applied to patient care? Yes.

Do the conclusions make biologic and clinical sense? Yes.

Are the benefits worth the harms and cost? Probably, but a formal cost analysis is needed.

Practice Pointers

In 1999, more than 10 million people reported an asthma episode that occurred during the previous year, almost 2 million people visited an emergency department for an asthma episode, and almost 478,000 patients were hospitalized.³ Costs of treatment and indirect effects are estimated to total $12.7 billion annually.⁴ Standard therapy for acute asthma includes beta₂ agonists, oxygen, and corticosteroid therapy.

Nebulization generally has been the preferred method of beta₂-agonist delivery because of its ease of use, but since the introduction of holding chambers, this practice has been re-evaluated. MDIs with holding chambers generally are a less-expensive method of beta₂-agonist delivery in emergency departments and are certainly less expensive in outpatient settings, where air-compressor machinery is needed for nebulization. The National Heart, Lung, and Blood Institute guidelines on asthma diagnosis and management state that MDIs with holding chambers can produce bronchodilation equivalent to that achieved with nebulizers. However, they note that the effectiveness can be limited by the patient's age and agitation level, and by the severity of the exacerbation. In addition, more research is necessary to determine whether MDIs with holding chambers produce similar results in outpatient settings where there is not a respiratory therapist to supervise the administration of the medication.

This review shows that in adult patients who used nebulizers or MDIs with holding chambers, there were no significant differences in hospital admission rate, peak flow, or forced expiratory volume. The findings in children were similar to those in adults. In children, MDIs with holding chambers have the added advantages of decreasing the time spent in the emergency department and limiting the beta₂ agonist­induced rise in pulse rate. The data in this review are from studies of patients who were treated in hospital emergency departments and who were not in imminent respiratory failure; one study done in a community setting was of poor quality and was not used in the analysis.

MDIs with holding chambers are an effective alternative to nebulizers for treating asthma exacerbations in emergency departments when respiratory failure is not imminent. Further formal cost-effectiveness analysis, taking into account equipment costs and infection-control issues, is necessary to determine whether MDIs with holding chambers should be routinely recommended.

REFERENCES

1. Cates CJ, Rowe B, Bara A. Holding chambers versus nebulizers for beta-agonist treatment of acute asthma (Cochrane Review). Cochrane Database Syst Rev 2002;2:CD000052.
2. Statistical methods available in Review Manager and CDSR. In: Cochrane reviewers' handbook 4.1.5. Accessed November 2002, from www.cochrane.org/software/Documentation/Handbook/ handbook.pdf.
3. Mannino DM, Homa DM, Akinbami LJ, Moorman JE, Gwynn C, Redd SC. Surveillance for asthma--United States, 1980-1999. MMWR Surveill Summ 2002;51:1-13.
4. Trends in asthma morbidity and mortality. Accessed November 2002, from www.lungusa.org/data/asthma/ASTHMA1.pdf.

John Epling, M.D., is clinical assistant professor of family medicine and a fellow in evidence-based practice, policy, and education at the State University of New York (SUNY) Upstate Medical University's Center for Evidence-Based Practice, Syracuse, N.Y. He completed his family-medicine residency at the Medical University of South Carolina, Charleston.

Min Ho Chang is a second-year medical student and research assistant at SUNY Upstate Medical University's Center for Evidence-Based Practice.

Address correspondence to John Epling, M.D., Center for Evidence-Based Practice, Department of Family Medicine, SUNY Upstate Medical University, 475 Irving Ave., Suite 200, Syracuse, NY 13210 (e-mail: eplingj@upstate.edu). Reprints are not available from the authors.