Canadian asthma consensus report, 1999

The first Canadian guidelines on the best approach to management of asthma in children and adults in an ambulatory care setting were established in 1989 by a panel of Canadian and international specialists on asthma under the leadership of Dr. Frederick E. Hargreave.1 In 1995, the Asthma Committee of the Canadian Thoracic Society organized a meeting to review the guidelines and incorporate the recent recommendations of the Canadian Association of Emergency Physicians on acute asthma2 into the revised document.3

In light of recent research, a group of respirologists, pediatricians, immunoallergists, emergency and family physicians met at Niagara-on-the-Lake, Ont., from 28 to 31 May 1998, to review and revise the 1995 recommendations.3

All recognized the importance of adapting treatment to the individual and the situation at hand; however, we provide these evidence-based recommendations as a guide to clinicians. Recommendations are made for both adults and children. There may be some duplication of information across the various sections, but this will allow a more comprehensive reading of each section and emphasize the most important messages.

Goals

The goals of participants in the conference were to:

• review and discuss recent developments in the treatment of asthma

• review and revise the 1995 evidence-based Canadian guidelines3 on asthma for children and adults

• develop strategies to implement the asthma guidelines at the regional level

• determine what key studies are required to increase the level of evidence supporting the recommendations.

Levels of evidence

Recommendations are based on a critical review of the scientific literature by small groups before the meeting and are categorized into 5 levels according to the strength of the supporting evidence (Table 1).4

These 5 levels do not describe the quality or credibility of the evidence; rather, they indicate its nature. In general, a randomized, controlled trial has the greatest credibility (level I evidence); however, it may have defects that diminish its value, and these should be noted. Evidence based on too few observations to give a statistically significant result is classified as level II. Generally, level III studies carry less credibility than level I or level II studies, but credibility is increased when consistent results are obtained from several level III studies carried out at different times and in different places.

Decisions must often be made in the absence of published evidence. In these situations, it is necessary to rely on the opinion of experts based on their knowledge and clinical experience. Distinction is made between the published opinion of authorities (level IV) and the opinion of those who have contributed to these guidelines (level V). Nevertheless, because of the exhaustive consensus-building process used in the preparation of these guidelines, this level V evidence has achieved a level of credibility that is at least equivalent to level IV evidence.

General principles of management of asthma

Asthma is characterized by paroxysmal or persistent symptoms such as dyspnea, chest tightness, wheezing, sputum production and cough, associated with variable airflow limitation and a variable degree of hyperresponsiveness of airways to endogenous or exogenous stimuli.

Inflammation and its resultant effects on airway structure are considered to be the main mechanisms leading to the development and maintenance of asthma; therefore, the main thrust of asthma therapy is to limit exposure to triggering factors and to reduce the inflammatory process using anti-inflammatory agents. If needed, therapies to maintain optimal airway calibre and to control symptoms may be added to ensure acceptable asthma control and to improve quality of life. This requires individual assessment of the need for therapeutic intervention and establishment of the risks and benefits of various therapeutic choices (environmental measures, education and pharmacotherapy).

Environmental control, particularly avoidance of relevant allergens and respiratory irritants, and proper patient education are essential to achieve adequate control of asthma. A list of the most common environmental measures is included in the section on environment.

Conference participants agreed to retain the concept of the asthma continuum adopted at the last Canadian Asthma Consensus Conference,3 reflecting a dynamic therapeutic approach that allows drug therapy to be adapted to the severity of the underlying illness and facilitates adjustment of the intensity of therapy to the degree of control achieved.

They also agreed that the concept of "control" of asthma should be differentiated from "severity" of asthma.5

Asthma management: a continuum

We propose the following algorithm for the management of asthma:

A. When asthma is suspected from symptoms and clinical presentation, confirm diagnosis by objective measures of variable airflow obstruction and assess severity

• Spirometry (the preferred method): A 12% (preferably 15%) or greater improvement in FEV₁ (i.e., at least 180 mL) from the baseline 15 minutes after use of an inhaled short-acting β₂-agonist, a 20% (250 mL) or greater improvement after 10-14 days of ingested prednisone when symptoms are stable or 20% (250 mL) or greater "spontaneous variability" is considered significant.

• Serial measures of PEF: > 20% change after administration of a bronchodilator or over time.

• Methacholine challenge: Provocative concentration of methacholine giving a 20% reduction in FEV₁ (PC₂₀) < 8 mg/mL (Juniper method6).

B. Rapidly achieve best asthma control

• If symptoms are infrequent and expiratory flows are normal, an inhaled short-acting β₂-agonist should be used on demand.

• If a rescue β₂-agonist is needed more than 3 times a week or if lung function is abnormal, an inhaled glucocorticosteroid equivalent to 400-1000 μg/d of beclomethasone dipropionate is the preferred next step (200-1000 μg/d in children).

• If symptoms are frequent and expiratory flows are < 60% of predicted value, initial therapy with prednisone should be considered.

C. Maintain acceptable asthma control (Table 2 and Fig. 1)

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Fig. 1: Continuum of asthma management. Severity of asthma is ideally assessed by medication required to maintain asthma control. Environmental control and education should be instituted for all asthma patients. Very mild asthma is treated with short-acting β₂-agonists, taken as needed. If β₂-agonists are needed more than 3 times/week (excluding 1 dose/day before exercise), then inhaled glucocorticosteroids should be added at the minimum daily dose required to control the asthma. If asthma is not adequately controlled by moderate doses (500-1000 μg/d of beclomethasone or equivalent), additional therapy (including long-acting β₂-agonists, leukotriene antagonists or, less often, other medications) should be considered. Severe asthma may require additional treatment with prednisone.

• Determine minimal medication needs to keep best results, then write an action plan (Appendix).

D. Ensure regular follow-up

• Regularly review asthma control, medication needs and the action plan.

• Reassess environmental control and compliance with treatment.

• Assess the need for additional investigation, education or referral.

General principles of drug therapy

Medications used to treat asthma are generally divided into 2 main categories: relievers and controllers.

Relievers are best represented by the inhaled short-acting β₂-agonists. These quick-acting bronchodilators are used to relieve acute intercurrent asthma symptoms, only on demand and at the minimum required dose and frequency. Inhaled ipratropium bromide is less effective, but is occasionally used as a reliever medication in patients intolerant of short-acting β₂-agonists.

Controllers (or preventers) include anti-inflammatory medications, such as inhaled (and oral) glucocorticosteroids, leukotriene-receptor antagonists, and anti-allergic or inhaled nonsteroidal agents, such as cromoglycate and nedocromil. These agents are generally taken regularly to control asthma and prevent exacerbations. Inhaled glucocorticosteroids are the most effective agents in this category.

The controller group also includes some bronchodilators that are taken regularly in addition to inhaled glucocorticosteroids to help achieve and maintain asthma control. These include the long-acting inhaled β₂-agonists salmeterol and formoterol, which are the first choice in this category, as well as theophylline and ipratropium. The β₂-agonists and ipratropium are considered of no significant benefit in reducing airway inflammation. There is some evidence that theophylline may have immunomodulatory effects, but the clinical significance of this remains to be demonstrated.

Asthma drugs are preferably inhaled, because this route minimizes systemic absorption and, thus, improves the ratio of the therapeutic benefit to the potential side-effects. The patient must have repeated instruction on how to use the inhaled medication. The recently developed oral leukotriene-receptor antagonists have good safety and tolerance profiles and are taken orally, which may help certain patients comply with treatment.

Asthma medications should be used at the minimum dose and frequency required to maintain acceptable asthma control; they should not be used as a substitute for proper control of the environment. Asthma medications are considered to be safe over many years when used appropriately.

The participants in the asthma consensus conference have reviewed the role of each category of medication. In the following sections they describe briefly the mode of action, pharmacologic and clinical profile, mode of administration and potential side-effects of these drugs.

Competing interests: The authors have received consultancy fees, travel assistance to attend meetings, speaker fees and honoraria from various manufacturers of asthma medications.

Sponsoring organizations: The Canadian Association of Emergency Physicians; Canadian Pediatric Society; The Canadian Society of Allergy and Clinical Immunology; Canadian Thoracic Society; College of Family Physicians of Canada; Family Physician Asthma Group of Canada; The Lung Association

Supporters: The Lung Association; 3M Pharmaceuticals; Astra Pharma Inc.; Boehringer Ingelheim Canada, Ltd.; Glaxo Wellcome Canada Inc.; Merck Frosst Canada Inc.; Novartis Pharma Canada Inc; Zeneca Pharma Inc.

Appendix 1

Members of the Canadian Asthma Consensus Group: John C. Acres, MD, Moncton, NB; Tony R. Bai, MD, Vancouver, BC; Meyer S. Balter, MD, Toronto, Ont.; Allan Becker, MD, Winnipeg, Man.; Denis Berubé, MD, Montréal, Que.; Robert Beveridge, MD, Saint John, NB; Jacques Bouchard, MD, La Malbaie, Que.; Louis-Philippe Boulet, MD, Sainte-Foy, Que.; Dennis M. Bowie, MD, Halifax, NS; William W. Busse, MD, Madison, Wisc.; André Cartier, MD, Montréal, Que.; Andrew J. Cave, MD, Edmonton, Alta.; Moira Chan-Yeung, MD, Vancouver, BC; Kenneth R. Chapman, MD, Toronto, Ont.; Victor Chernick, MD, Winnipeg, Man.; Donald W. Cockcroft, MD, Saskatoon, Sask.; Johanne Côté, MD, Sainte-Foy, Que.; Robert L. Cowie, MD, Calgary, Alta.; Anna Day, MD, Toronto, Ont.; Mervyn M. Dean, MD, Corner Brook, Nfld.; Myrna Dolovich, PEng, Hamilton, Ont.; Denis Drouin, MD, Québec, Que.; Francine Ducharme, MD, Montréal, Que.; Nigel J. Duiguid, MD, St. John's, Nfld.; Anthony D. D'Urzo, MD, Toronto, Ont.; Gordon H. Dyck, MD, Steinback, Man.; Pierre Ernst, MD, Montréal, Que.; Alexander C. Ferguson, MD, Vancouver, BC; J. Mark Fitzgerald, MD, Vancouver, BC; Anton F. Grunfeld, MD, Vancouver, BC; Frederick E. Hargreave, MD, Hamilton, Ont.; Richard V. Hodder, MD, Ottawa, Ont.; John Hoey, MD, Ottawa, Ont.; Daniel Hughes, MD, Halifax, NS; Robert H. Hyland, MD, Toronto, Ont.; Robert Jin, MD, Ottawa, Ont.; Alan Kaplan, MD, Richmond Hill, Ont.; John Kolbe, MD, Auckland, NZ; Thomas Kovesi, MD, Ottawa, Ont.; Brent L. Kvern, MD, Winnipeg, Man.; Eric S. Leith, MD, Oakville, Ont.; Alex Leung, MD, Kamloops, BC; Ian B. MacLusky, MD, Toronto, Ont.; Carina M. Majaesic, MD, Edmonton, Alta.; S.F. Paul Man, MD, Edmonton, Alta.; Francisco J.D. Noya, MD, Montréal, Que.; Paul O'Byrne, MB, Hamilton, Ont.; J. Grahame Owen, MD, Oakville, Ont.; Sharon D. Peters, MD, St. John's, Nfld.; Georges B. Rivard, MD, Sainte-Foy, Que.; Michel-Y. Rouleau, MD, Québec, Que.; Robert Schellenberg, MD, Vancouver, BC; Malcolm R. Sears, MB, Hamilton, Ont.; Estelle R. Simons, MD, Winnipeg, Man.; Arthur Slutsky, MD, Toronto, Ont.; Sheldon Spier, MD, Calgary, Alta.; Robert L. Thivierge, MD, Montréal, Que.; John H. Toogood, MD, London, Ont.; Michel Turgeon, MD, Sainte-Foy, Que.; David W. Warren, MD, London, Ont.; Sally E. Wenzel, MD, Denver, Colo.; Barry Zimmerman, MD, Toronto, Ont.