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Clinical Investigations: ASTHMA |

Effect of Air Filtration Systems on Asthma*: A Systematic Review of Randomized Trials FREE TO VIEW

Ellen McDonald, RN; Deborah Cook, MD, FCCP; Toni Newman, BA; Lauren Griffith, MS Biostatistics; Gerard Cox, MD; Gordon Guyatt, MD, FCCP
Author and Funding Information

*From the Departments of Clinical Epidemiology and Biostatistics (Ms. McDonald, Ms. Newman, Ms. Griffith, and Drs. Cook and Guyatt) and Medicine (Dr. Cox), McMaster University, Hamilton, ON, Canada.

Correspondence to: Ellen McDonald, RN, Critical Care Research Office, St. Joseph’s Hospital, 50 Charlton Ave, East Hamilton, ON, Canada; e-mail: emcdonal@mcmaster.ca



Chest. 2002;122(5):1535-1542. doi:10.1378/chest.122.5.1535
Text Size: A A A
Published online

Study objectives: To systematically review the evidence of randomized trials evaluating the effects of residential air filtration systems on patients with asthma.

Data sources: We searched for published and unpublished studies using MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Collaboration. We reviewed all reference lists for additional articles of relevance, and contacted experts in the field and air filter manufacturers.

Study selection: We identified 10 relevant randomized controlled trials that examined the influence of a residential air filtration system on patients with asthma.

Data extraction: In duplicate and independently, we abstracted data on the methodologic quality, population, intervention, and outcomes.

Data synthesis: Five of 10 studies enrolled adults only. One study included children only. The sample size ranged from 9 to 45 participants in each study, for a total of 216 patients across all studies. Two studies reported a statistically significant decrease in airway responsiveness associated with air filter utilization. Air filters were associated with significantly lower total symptom scores (weighted mean difference of 0.47; 95% confidence interval [CI], 0.69 to 0.25) on a 10-point scale, and lower sleep disturbance score (weighted mean difference of 0.93; 95% CI, 1.44 to 0.42); however, heterogeneity of results weakens the inferences from these trials. Air filtration systems were not associated with any differences in medication use or morning peak expiratory flow values. None of these trials employed validated scales to measure clinical symptoms or quality of life.

Conclusions: Among patients with allergies and asthma, use of air filters is associated with fewer symptoms. Rigorous sufficiently powered randomized clinical trials are needed to more precisely define the influence of air filtration on health-related quality of life and symptom control for asthmatic patients.

Figures in this Article

Asthma is a prevalent and disabling disease worldwide.12 The prevalence of asthma has markedly increased over the past 2 decades in adults and in children.34 Habbick et al5 estimated a lifetime prevalence of asthma among children in two Canadian cities to be 19%.

The cornerstone of asthma management is administration of anti-inflammatory medications and bronchodilators.6In addition, there are adjunctive therapies that may contribute to the overall control of asthma. Some of these therapies, despite showing early promise, have not always proved effective. A Cochrane Collaboration systematic review has shown that limited asthma education is unlikely to improve health outcomes in adults.7However, interactive education is more effective in changing the behavior of clinicians and patients than passive education.8Alternative interventions also demonstrated to be ineffective include chiropractic manipulation.9

Public concern has been raised recently about environmental influences on asthma control. The National Institutes of Health guidelines for the diagnosis and management of asthma address indoor and outdoor air quality.10The Canadian Asthma Consensus Conference panel concluded that indoor irritants, particularly tobacco smoke, represent a greater health risk than outdoor air pollutants.11Among several environmental interventions, indoor air filters appear to be effective in reducing some airborne irritants. The high-efficiency particulate air (HEPA) filter has higher efficiencies for both larger and smaller particles than other filters, with a minimal particle removal efficiency of 99.97% for particles of > 0.3 μm in diameter.12The HEPA filter has been associated with reduced airborne levels of cat allergen in a case-control study of 50 homes with a cat and 50 homes without a cat.13Other observational studies have shown that HEPA filters reduce the burden of particles from mold spores14and cigarette smoke.15

In 1992, a narrative review recommended that patients with severe allergies or asthma should use an air-filtering vacuum cleaner and an air cleaner with a HEPA filter.12 However, the influence of air filtration on patient-centered outcomes has not been established.11 Evidence about the use of residential air cleaners was graded as level 3C by the 1999 Canadian Asthma Consensus Conference, indicating “poor evidence to support a recommendation for or against use.”16 Subsequently, investigators have suggested that future research should address the influence of improving air quality on asthma control.5 The objective of this systematic review is to critically appraise and summarize the current randomized trial evidence about the effect of residential air filters on signs and symptoms of asthma, and to inform patients, clinicians, and researchers of our findings.

Data Sources

We searched the computerized databases MEDLINE and Cumulative Index to Nursing and Allied Health Literature from 1976 to 2000 using the following text words and key words: “asthma,” “quality of life,” “air filter,” “indoor air quality,” and “randomized controlled trials.” We also searched the Cochrane Collaboration Controlled Trials Registry. To identify additional potentially relevant studies, we corresponded with experts in the field of asthma research, manufacturers of air filtration systems, and the authors of the primary studies included in this review. We also reviewed the citation lists or bibliographies of all the relevant studies and reviews, and retrieved any article that looked relevant to this systematic review. We had no language restrictions.

Study Selection

Using criteria determined a priori, two of the authors (E.M., T.N.) independently reviewed the first literature search to identify primary research studies that addressed the question posed. Based on title and abstract, all citations identified as potentially relevant by either reviewer were then retrieved for full review.

To be included in the systematic review, the studies needed to meet the following criteria: (1) design, randomized controlled trials; (2) population, children or adults with a diagnosis of asthma; (3) intervention, use of a residential air filtration system; and (4) patient-oriented outcomes, as reported in each study such as asthma signs and symptoms, physiologic, laboratory, and other end points (ie, measurement and documentation of particulate). We did not consider observational studies, surveys, asthma classification documents, and practice guidelines for this review. We excluded studies of patients with poor asthma control following hospitalization.

Data Extraction: Validity Assessment and Clinical Characteristics

In duplicate, independently, we abstracted data to describe the methodologic quality and clinical characteristics of these trials.17 Methodologic features we report include the method of treatment allocation, masking of treatment allocation (concealment), blinding of the patients, clinicians and outcome assessors, whether cointerventions were described, the proportion of patients who were excluded after randomization, and intention-to-treat analysis. We also report source of funding. Clinical characteristics we report include the population, sample size, duration of exposure, and outcomes. Differences between abstractors were resolved by consensus.

Data Synthesis

Symptoms and medication use were originally reported in different units in each trial, precluding combining these data as reported. To address this issue, we transformed and standardized those data to allow for comparison across the trials.18To combine individual symptom results from each study, we created a total symptom score that included nighttime symptoms when available. Second, we combined nasal symptom scores using the same methodology. Third, we created a nocturnal symptom score by combining symptoms experienced at night, such as awakening and sleep disturbance. We then created a total medication score by combining maintenance and “as-needed” medications among studies reporting total medication use. As reported in some studies, we also generated a combined symptom and medication outcome score. The symptom scores were indexed on a 10-point scale. Peak expiratory flow (PEF) values were analyzed as reported using morning values in milliliters per minute. For statistical synthesis, we used both random-effects and fixed-effects models.19 The random-effects model assumes that the studies included in the review are a random sample of a population of studies addressing the clinical question. The random-effect model takes into account both within-study variability and variability in results beyond what is attributable to within-study variability. The fixed-effects model assumes that there is a single true value underlying all the study results, and that the observed estimates of effect differ from each other only because of random error. The fixed-effects model only takes into account within-study variability.

Study Selection

Our search strategies identified 10 randomized trials evaluating the effect of air filtration systems in patients with asthma.2029 Four of 10 authors of the original studies responded to our request for further studies or additional information. Agreement on studies to be included was 100%.

Validity Assessment

The validity of included trials is summarized in Table 1 . Eight of the 10 trials used a crossover design.2026,29 Masking of treatment allocation (eg, concealment of treatment allocation prior to randomization) was not documented in any trial. After randomization, patients were blinded to whether their air filter was active or not in 9 of 10 studies.,2024,2629 Blinding of health-care workers was conducted in two trials.24,29 Blinding of outcome assessors occurred in all 10 trials. Of the 216 total patients enrolled in these 10 studies, 26 patients were unavailable for follow-up. Intention-to-treat analysis was reported in two trials.25,27

Clinical Characteristics

Five of 10 trials enrolled exclusively adults,22,24,2628 while 1 trial enrolled exclusively children29 (Table 2 ). The sample size ranged from 9 to 45 participants in each study, for a total of 216 patients across all studies.

Outcomes

Multiple outcome measures were used to determine the effectiveness of air filters in each study (Table 2). Five studies reported lung function.23,2527,29 All but one study used a subjective measure of symptoms.27 However, none of these trials employed validated scales to measure clinical symptoms or quality of life. Five studies reported allergen levels.22,2528

Air filtration systems were not associated with any differences in medication use or symptom/medication scores (Table 3 ). We found no improvement in morning PEF values whether the fixed- or random-effects model was used for data pooling (Fig 1 ).

Two trials showed that air filters were associated with significantly fewer symptoms.20,22Two studies reported a statistically significant decrease in airway responsiveness associated with air filter exposure.23,29

We present the meta-analysis of study results in Table 3. There was a trend toward lower total symptom scores as shown by a weighted mean difference of 0.76 (95% confidence interval [CI], 2.17 to 0.65; p = 0.29) on a 10-point scale using the random-effects model. Using the fixed-effects model, the symptom improvement was statistically significant (weighted mean difference of 0.47; 95% CI, 0.69 to 0.25; p < 0.01). However, the magnitude of this apparent benefit on symptoms differed across studies (p value for heterogeneity < 0.01). These results are graphically depicted in Figure 2 . The most conservative estimate of the effect of HEPA filters on symptoms is shown by the random-effects model and the associated wide CI. Air filters were not associated with any improvement in nasal symptoms. We also found a trend toward less sleep disturbance associated with air filters, as shown by a weighted mean difference of 1.08 (95% CI, 2.78 to 0.62; p = 0.21) using a random-effects model, or 0.93 (95% CI, 1.44 to 0.42; p < 0.01) using a fixed-effects model. However, these study results were also heterogenous, weakening the inferences we can draw from this meta-analysis (p value for heterogeneity < 0.01).

In this systematic review of 10 randomized clinical trials among adults and children with asthma and allergy symptoms, we found a small but statistically significant difference in total symptoms and sleep disturbance associated with use of domestic air filters. We did not identify any benefit conferred by air filters with respect to nasal symptoms, medication use, or PEF values.

We adhered to rigorous systematic review methods17,30and transparent reporting31in this review. Jadad and colleagues32 previously summarized the clinical, methodologic, and reporting aspects of systematic reviews and meta-analyses on the treatment of asthma, highlighting how serious methodologic flaws limited their usefulness. Strengths of this systematic review include a focused clinical question, a comprehensive search for published and unpublished research, explicit selection criteria, validity assessments conducted in duplicate independently, and reporting of the heterogeneity of study results.

In critically appraising review articles, it is important to distinguish between the quality of the review methods and the quality of the studies included in the review. Accordingly, we evaluated and reported the randomized trial methodology in detail,17 thereby allowing readers to make their own inferences about the primary evidence. None of the studies explicitly reported on concealment of treatment allocation. Few studies reported strategies to maintain the blinding of participants, caregivers, clinicians, and outcome assessors; however, eight studies used sham air filters in the control period (Table 2).

Of the 10 randomized trials included in this systematic review, 9 trials evaluated asthma symptoms, but none included a validated generic or disease-specific quality-of-life instrument. At the time that many of these trials were conducted, few such instruments were available. Some simple symptom measures used in these trials may be insensitive to detect clinically important improvements due to environmental modifications. This hypothesis is supported by the observation that a reduction in airborne particulate matter associated with air filters did not always correlate with an improvement in symptoms.24 Currently available valid and reliable disease-specific quality-of-life or symptom tools in this field include the Asthma Quality of Life Questionnaire,3334 the Living With Asthma Quality of Life Questionnaire,35and the Asthma Control Questionnaire36for adults, and the Pediatric Asthma Quality of Life Questionnaire37 for children.

The dearth of randomized trials evaluating the effect of air filters in children merits comment. Only one study enrolled exclusively children,29 despite the high and growing prevalence of asthma in this population.5 The Seattle-King County Healthy Homes Project, which surveyed low-income urban caregivers of children with asthma, found that 12% used a vacuum with a HEPA quality filter.38However, the random-effects model meta-analysis in this review that gives smaller studies proportionally greater weight in the pooled estimate, and results in more conservative interpretation of the effect of HEPA filters, suggests no overall benefit in terms of symptoms and sleep disturbance. These findings, and the fact that disease-specific outcomes were not measured, precludes making guidelines or policy recommendations about the use of air filters.39 However, the epidemiologic trend of increased asthma and allergy symptoms, the growing importance of patient empowerment through symptom control, and the need to measure outcomes that are important to patients suggest that further large rigorous randomized trials of environmental interventions such as air filters are warranted.

Abbreviations: CI = confidence interval; HEPA = high-efficiency particulate air; PEF = peak expiratory flow

This work was funded by the Hamilton Community Foundation and the Father Sean O’Sullivan Research Center, St. Joseph’s Hospital.

Table Graphic Jump Location
Table 1. Methodologic Quality of Randomized Trials of Air Filtration Systems*
* 

RCT = randomized clinical trial; NR = not reported.

 

Two patients enrolled twice.

Table Graphic Jump Location
Table 2. Clinical Characteristics of Randomized Trials of Air Filtration Systems*
* 

PD20 = provocative dose of methacholine causing a 20% fall in FEV1; RAST = radiollergosorbent test.

Table Graphic Jump Location
Table 2A. Continued
Table Graphic Jump Location
Table 3. Meta-analysis of Randomized Trials of Air Filtration Systems
* 

A negative difference indicates a better outcome for the active filter group in all cases except PEF.

 

Overall meta-analysis results difference.

 

Significant differences among study results.

§ 

Weighted mean differences are reported in effect size units.

Figure Jump LinkFigure 1. Weighted mean difference for morning PEF. This figure shows the results of four randomized trials of domiciliary air filtration systems with respect to morning PEF values. The pooled analysis using both the fixed- and random-effects analysis show no benefit of air filtration on PEF values.Grahic Jump Location
Figure Jump LinkFigure 2. Weighted mean difference for total symptoms. This figure shows the results of four randomized trials of domiciliary air filtration systems with respect to total asthma symptoms. Overall, a modest improvement in symptoms is shown by the pooled data. The fixed-effects analysis shows a significant reduction in symptoms, while the random-effects analysis shows a trend toward improvement.Grahic Jump Location
. Centers for Disease Control and Prevention (1996) Asthma mortality and hospitalization among children and young adults: United States, 1980–1993.MMWR Morb Mortal Wkly Rep45,350-353. [PubMed]
 
Sears, MR Epidemiological trends in asthma.Can Respir J1996;3,261-268
 
Burney, PGJ, China, S, Rona, RJ Has the prevalence of asthma increased in children? Evidence from the National Study of Health and Growth 1973–1986.BMJ1990;300,1306-1310. [PubMed] [CrossRef]
 
Ninan, TK, Russell, G Respiratory symptoms and atopy in Aberdeen school-children: evidence from two surveys 25 years apart.BMJ1992;304,857-858. [PubMed]
 
Habbick, BR, Pizzichini, MMM, Taylor, B, et al Prevalence of asthma, rhinitis, and eczema among children in 2 Canadian cities: the International Study of Asthma and Allergies in Children.Can Med Assoc J1999;160,1824-1828
 
Haahtela, T, Jarvinen, M, Kava, T, et al Comparison of a β2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma.N Engl J Med1991;325,388-392. [PubMed]
 
Gibson, PG, Coughlan, J, Wilson, AJ, et al The effects of limited (information only) patient education programs on the health outcomes of adults with asthma. Cochrane Collaboration. Cochrane Library. Issue 3. 1998; Update Software. Oxford, UK:.
 
Davis, DA, Thompson, MA, Oxman, A, et al Changing physician performance: a systematic review of the effect of continuing medical education strategies.JAMA1995;274,700-705. [PubMed]
 
Balon, J, Aker, PD, Crowther, ER, et al A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma.N Engl J Med1998;339,1013-1020. [PubMed]
 
National Asthma Education and Prevention Program.. Expert panel report 2: guidelines for the diagnosis and management of asthma. 1998; National Institutes of Health. Bethesda, MD: publication No. 97–4051.
 
Ernst, P, Fitzgerald, JM, Spier, S Canadian Asthma Consensus Conference summary of recommendations.Can Respir J1996;3,89-100
 
Evans, R Environmental control and immunotherapy for allergic disease.J Allergy Clin Immunol1992;90,462-468. [PubMed]
 
Custovic, A, Simpson, A, Pahdi, H, et al Distribution, aerodynamic characteristics, and removal of the major cat allergen Fel d 1 in British homes.Thorax1998;53,33-38. [PubMed]
 
Maloney, MJ, Wray, BB, DuRant, RH, et al Effect of an electronic air cleaner and negative ionizer on the population of indoor mold spores.Ann Allergy1987;59,192-194. [PubMed]
 
US Environmental Protection Agency.. Residential air- cleaning devices: a summary of available information. 1990; Office of Air and Radiation, US Environmental Protection Agency. Washington, DC:.
 
Boulet, LP, Becker, A, Berube, D, et al 1998 revision of the Canadian Asthma Consensus Guidelines: Asthma Consensus Editorial Committee.Can Respir J1999;6,231-232. [PubMed]
 
Guyatt, GH, Sackett, DL, Cook, DJ Users’ guides to the medical literature: II. How to use an article about therapy or prevention; A. Are the results of the study valid? Evidence-Based Medicine Working Group.JAMA1993;270,2598-2601. [PubMed]
 
Fleiss, JL The statistical basis of meta-analysis.Stat Methods Med Res1993;2,121-145. [PubMed]
 
DerSimonian, R, Laird, N Meta-analysis in clinical trials.Control Clin Trials1986;7,177-188. [PubMed]
 
Zwemer, RJ, Karibo, J Use of laminar control device as adjunct to standard environmental control measures in symptomatic asthmatic children.Ann Allergy1973;31,284-290. [PubMed]
 
Villaveces, JW, Rosengreen, H, Evans, J Use of a laminar air flow portable filter in asthmatic children.Ann Allergy1977;38,400-404. [PubMed]
 
Kooistra, JB, Pasch, PE, Reed, CE The effects of air cleaners on hay fever symptoms in air-conditioned homes.J Allergy Clin Immunol1978;61,315-319. [PubMed]
 
Verral, B, Muir, DCF, Wilson, W, et al Laminar flow air cleaner bed attachment: a controlled trial.Ann Allergy1988;61,117-122. [PubMed]
 
Reisman, RE, Mauriello, PM, Davis, GB, et al A double-blind study of the effectiveness of a high efficiency particulate air (HEPA) filter in the treatment of patients with perennial allergic rhinitis and asthma.J Allergy Clin Immunol1990;85,1050-1057. [PubMed]
 
Antonicelli, M, Bilo, MB, Pucci, S, et al Efficacy of an air-cleaning device equipped with a high efficiency particulate air filter in house dust mite respiratory allergy.Allergy1991;46,594-600. [PubMed]
 
Warburton, CJ, Niven, RM, Pickering, CAC, et al Domiciliary air filtration units, symptoms and lung function in atopic asthmatics.Respir Med1994;88,771-776. [PubMed]
 
van der Heide, S, Kauffman, HF, Dubois, AEJ, et al Allergen reduction in houses of allergic asthmatic patients: effects of air-cleaners and allergen-impermeable mattress covers.Eur Respir J1997;10,1217-1223. [PubMed]
 
Wood, RA, Johnson, EF, Van Natta, ML, et al A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy.Am J Respir Crit Care Med1998;158,115-120. [PubMed]
 
van der Heide, S, van Aalderen, WMC, Kaufman, AF, et al Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens:J Allergy Clin Immunol1999;104(2 pt 1),447-451
 
Cook, DJ, Sackett, DL, Spitzer, WO Methodologic guidelines for systematic reviews of randomized control trials in health care from the Potsdam consultation on meta-analysis.J Clin Epidemiol1995;48,167-171. [PubMed]
 
Moher, D, Cook, DJ, Eastwood, S, et al Improving the quality of reports of meta-analyses of randomised controlled trials: the QUORUM statement. Quality of Reporting of Meta-analyses.Lancet1999;354,1896-1900. [PubMed]
 
Jadad, AR, Moher, D, Browman, GP, et al Systematic reviews and meta-analyses on treatment of asthma: critical evaluation.BMJ2000;320,537-540. [PubMed]
 
Juniper, EF, Guyatt, GH, Epstein, RS, et al Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials.Thorax1992;47,76-83. [PubMed]
 
Juniper, EF, Buist, S, Cox, FM, et al Validation of a standardized version of the Asthma Quality of Life Questionnaire.Chest1999;115,1265-1270. [PubMed]
 
van der Molen, T, Postma, DS, Schreurs, AJM, et al Discriminative aspects of two generic and two asthma-specific instruments: relation with symptoms, bronchodilator use and lung function in patients in patients with mild asthma.Qual Life Res1997;6,353-361. [PubMed]
 
Juniper, EF, O’Byrne, PM, Guyatt, GH, et al Development and validation of a questionnaire to measure asthma control.Eur Respir J1999;14,902-907. [PubMed]
 
Juniper, EF, Guyatt, GH, Feeney, DH, et al Measuring quality of life in children with asthma.Qual Life Res1996;5,35-46. [PubMed]
 
Krieger, JW, Song, L, Takaro, TK, et al Asthma and the home environment of low-income urban children: preliminary findings from the Seattle-King County Healthy Homes Project.J Urban Health2000;77,50-67. [PubMed]
 
Bero, LA, Jadad, AR How consumers and policymaker use systematic reviews for decision making.Ann Intern Med1997;127,37-42. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Weighted mean difference for morning PEF. This figure shows the results of four randomized trials of domiciliary air filtration systems with respect to morning PEF values. The pooled analysis using both the fixed- and random-effects analysis show no benefit of air filtration on PEF values.Grahic Jump Location
Figure Jump LinkFigure 2. Weighted mean difference for total symptoms. This figure shows the results of four randomized trials of domiciliary air filtration systems with respect to total asthma symptoms. Overall, a modest improvement in symptoms is shown by the pooled data. The fixed-effects analysis shows a significant reduction in symptoms, while the random-effects analysis shows a trend toward improvement.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Methodologic Quality of Randomized Trials of Air Filtration Systems*
* 

RCT = randomized clinical trial; NR = not reported.

 

Two patients enrolled twice.

Table Graphic Jump Location
Table 2. Clinical Characteristics of Randomized Trials of Air Filtration Systems*
* 

PD20 = provocative dose of methacholine causing a 20% fall in FEV1; RAST = radiollergosorbent test.

Table Graphic Jump Location
Table 2A. Continued
Table Graphic Jump Location
Table 3. Meta-analysis of Randomized Trials of Air Filtration Systems
* 

A negative difference indicates a better outcome for the active filter group in all cases except PEF.

 

Overall meta-analysis results difference.

 

Significant differences among study results.

§ 

Weighted mean differences are reported in effect size units.

References

. Centers for Disease Control and Prevention (1996) Asthma mortality and hospitalization among children and young adults: United States, 1980–1993.MMWR Morb Mortal Wkly Rep45,350-353. [PubMed]
 
Sears, MR Epidemiological trends in asthma.Can Respir J1996;3,261-268
 
Burney, PGJ, China, S, Rona, RJ Has the prevalence of asthma increased in children? Evidence from the National Study of Health and Growth 1973–1986.BMJ1990;300,1306-1310. [PubMed] [CrossRef]
 
Ninan, TK, Russell, G Respiratory symptoms and atopy in Aberdeen school-children: evidence from two surveys 25 years apart.BMJ1992;304,857-858. [PubMed]
 
Habbick, BR, Pizzichini, MMM, Taylor, B, et al Prevalence of asthma, rhinitis, and eczema among children in 2 Canadian cities: the International Study of Asthma and Allergies in Children.Can Med Assoc J1999;160,1824-1828
 
Haahtela, T, Jarvinen, M, Kava, T, et al Comparison of a β2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma.N Engl J Med1991;325,388-392. [PubMed]
 
Gibson, PG, Coughlan, J, Wilson, AJ, et al The effects of limited (information only) patient education programs on the health outcomes of adults with asthma. Cochrane Collaboration. Cochrane Library. Issue 3. 1998; Update Software. Oxford, UK:.
 
Davis, DA, Thompson, MA, Oxman, A, et al Changing physician performance: a systematic review of the effect of continuing medical education strategies.JAMA1995;274,700-705. [PubMed]
 
Balon, J, Aker, PD, Crowther, ER, et al A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma.N Engl J Med1998;339,1013-1020. [PubMed]
 
National Asthma Education and Prevention Program.. Expert panel report 2: guidelines for the diagnosis and management of asthma. 1998; National Institutes of Health. Bethesda, MD: publication No. 97–4051.
 
Ernst, P, Fitzgerald, JM, Spier, S Canadian Asthma Consensus Conference summary of recommendations.Can Respir J1996;3,89-100
 
Evans, R Environmental control and immunotherapy for allergic disease.J Allergy Clin Immunol1992;90,462-468. [PubMed]
 
Custovic, A, Simpson, A, Pahdi, H, et al Distribution, aerodynamic characteristics, and removal of the major cat allergen Fel d 1 in British homes.Thorax1998;53,33-38. [PubMed]
 
Maloney, MJ, Wray, BB, DuRant, RH, et al Effect of an electronic air cleaner and negative ionizer on the population of indoor mold spores.Ann Allergy1987;59,192-194. [PubMed]
 
US Environmental Protection Agency.. Residential air- cleaning devices: a summary of available information. 1990; Office of Air and Radiation, US Environmental Protection Agency. Washington, DC:.
 
Boulet, LP, Becker, A, Berube, D, et al 1998 revision of the Canadian Asthma Consensus Guidelines: Asthma Consensus Editorial Committee.Can Respir J1999;6,231-232. [PubMed]
 
Guyatt, GH, Sackett, DL, Cook, DJ Users’ guides to the medical literature: II. How to use an article about therapy or prevention; A. Are the results of the study valid? Evidence-Based Medicine Working Group.JAMA1993;270,2598-2601. [PubMed]
 
Fleiss, JL The statistical basis of meta-analysis.Stat Methods Med Res1993;2,121-145. [PubMed]
 
DerSimonian, R, Laird, N Meta-analysis in clinical trials.Control Clin Trials1986;7,177-188. [PubMed]
 
Zwemer, RJ, Karibo, J Use of laminar control device as adjunct to standard environmental control measures in symptomatic asthmatic children.Ann Allergy1973;31,284-290. [PubMed]
 
Villaveces, JW, Rosengreen, H, Evans, J Use of a laminar air flow portable filter in asthmatic children.Ann Allergy1977;38,400-404. [PubMed]
 
Kooistra, JB, Pasch, PE, Reed, CE The effects of air cleaners on hay fever symptoms in air-conditioned homes.J Allergy Clin Immunol1978;61,315-319. [PubMed]
 
Verral, B, Muir, DCF, Wilson, W, et al Laminar flow air cleaner bed attachment: a controlled trial.Ann Allergy1988;61,117-122. [PubMed]
 
Reisman, RE, Mauriello, PM, Davis, GB, et al A double-blind study of the effectiveness of a high efficiency particulate air (HEPA) filter in the treatment of patients with perennial allergic rhinitis and asthma.J Allergy Clin Immunol1990;85,1050-1057. [PubMed]
 
Antonicelli, M, Bilo, MB, Pucci, S, et al Efficacy of an air-cleaning device equipped with a high efficiency particulate air filter in house dust mite respiratory allergy.Allergy1991;46,594-600. [PubMed]
 
Warburton, CJ, Niven, RM, Pickering, CAC, et al Domiciliary air filtration units, symptoms and lung function in atopic asthmatics.Respir Med1994;88,771-776. [PubMed]
 
van der Heide, S, Kauffman, HF, Dubois, AEJ, et al Allergen reduction in houses of allergic asthmatic patients: effects of air-cleaners and allergen-impermeable mattress covers.Eur Respir J1997;10,1217-1223. [PubMed]
 
Wood, RA, Johnson, EF, Van Natta, ML, et al A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy.Am J Respir Crit Care Med1998;158,115-120. [PubMed]
 
van der Heide, S, van Aalderen, WMC, Kaufman, AF, et al Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens:J Allergy Clin Immunol1999;104(2 pt 1),447-451
 
Cook, DJ, Sackett, DL, Spitzer, WO Methodologic guidelines for systematic reviews of randomized control trials in health care from the Potsdam consultation on meta-analysis.J Clin Epidemiol1995;48,167-171. [PubMed]
 
Moher, D, Cook, DJ, Eastwood, S, et al Improving the quality of reports of meta-analyses of randomised controlled trials: the QUORUM statement. Quality of Reporting of Meta-analyses.Lancet1999;354,1896-1900. [PubMed]
 
Jadad, AR, Moher, D, Browman, GP, et al Systematic reviews and meta-analyses on treatment of asthma: critical evaluation.BMJ2000;320,537-540. [PubMed]
 
Juniper, EF, Guyatt, GH, Epstein, RS, et al Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials.Thorax1992;47,76-83. [PubMed]
 
Juniper, EF, Buist, S, Cox, FM, et al Validation of a standardized version of the Asthma Quality of Life Questionnaire.Chest1999;115,1265-1270. [PubMed]
 
van der Molen, T, Postma, DS, Schreurs, AJM, et al Discriminative aspects of two generic and two asthma-specific instruments: relation with symptoms, bronchodilator use and lung function in patients in patients with mild asthma.Qual Life Res1997;6,353-361. [PubMed]
 
Juniper, EF, O’Byrne, PM, Guyatt, GH, et al Development and validation of a questionnaire to measure asthma control.Eur Respir J1999;14,902-907. [PubMed]
 
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