Clinical Evidence Concise
A Publication of BMJ Publishing Group
Am Fam Physician. 2004 Jul 1;70(1):143-146.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been systematically reviewed by an AAFP-approved source. The practice recommendations in this activity are available at http://www.clinicalevidence.com/ceweb/conditions/rdc/1501/1501.jsp.
What are the effects of treatments for chronic asthma?
Adding Long-Acting Inhaled Beta2Agonists in People with Mild, Persistent Asthma that Is Poorly Controlled by Inhaled Corticosteroids. One systematic review and three additional randomized controlled trials (RCTs) have found that adding regular doses of long-acting inhaled beta2 agonists improves lung function and symptoms and reduces rescue medication compared with increasing the dose of inhaled corticosteroids. However, one further RCT found that increasing inhaled corticosteroid dose reduced exacerbations compared with adding long-acting inhaled beta2 agonists. We found insufficient evidence about effects of adding long-acting inhaled beta2 agonists on mortality.
Adding Long-Acting Inhaled Beta2Agonists to Inhaled Corticosteroids in Poorly Controlled Mild to Moderate, Persistent Asthma (for Symptom Control). RCTs have found that, in people with asthma that is poorly controlled with inhaled corticosteroids, adding regular long-acting inhaled beta2 agonists improves symptoms and lung function compared with adding placebo or a leukotriene antagonist. We found insufficient evidence about effects of adding long-acting inhaled beta2 agonists on mortality.
Low-Dose, Inhaled Corticosteroids in Mild, Persistent Asthma. Systematic reviews and RCTs have found that, in people with mild, persistent asthma, low doses of inhaled corticosteroids improve symptoms and lung function compared with placebo or regular inhaled beta2 agonists.
Short-Acting Inhaled Beta2Agonists as Needed for Symptom Relief (as Effective as Regular Use) in Adults with Mild to Moderate, Persistent Asthma. One systematic review and one subsequent RCT found no significant difference between regular and as-needed short-acting inhaled beta2 agonists for clinically important outcomes.
LIKELY TO BE BENEFICIAL
Adding Leukotriene Antagonists in People with Mild to Moderate, Persistent Asthma (Likely to Be Better than Adding No Treatment, But No Clear Evidence of Benefit Over Adding Inhaled Corticosteroids). RCTs in people taking beta2 agonists alone have found that leukotriene antagonists reduce asthma symptoms and beta2 agonist use compared with placebo. One systematic review and three out of nine subsequent RCTs have found that adding leukotriene antagonists increases exacerbations, reduces lung function, and is less effective for symptom control compared with inhaled corticosteroids. The other six RCTs found no significant difference between adding leukotriene antagonists and adding corticosteroids. Two RCTs have found that an inhaled corticosteroid plus a long-acting beta2 agonist improved symptoms, lung function, and exacerbations compared with a leukotriene antagonist at 12 weeks.
Adding Theophylline in People with Mild to Moderate, Persistent Asthma Poorly Controlled by Inhaled Corticosteroids. One RCT has found that adding theophylline improves peak expiratory flow rate compared with continuing low-dose corticosteroids plus placebo after six months in people with mild to moderate, persistent asthma that was poorly controlled with inhaled corticosteroids alone. One small RCT found no significant difference in lung function or symptoms between theophylline and formoterol (a long-acting beta2 agonist) or between theophylline and zafirlukast (a leukotriene antagonist) after three months.
Adding Leukotriene Antagonists Plus Inhaled Corticosteroids in People with Mild to Moderate, Persistent Asthma. One systematic review in people taking inhaled corticosteroids found no significant difference between leukotriene antagonists and placebo for exacerbation rates at four to 16 weeks. However, one subsequent RCT in people taking a stable dose of budesonide found that adding montelukast increased asthma-free days and decreased nocturnal waking compared with placebo at 16 weeks. One RCT in people taking inhaled corticosteroids found no significant difference between adding montelukast and doubling budesonide in peak expiratory flow rate, daytime symptoms, nocturnal wakening, days with asthma exacerbations, and quality of life.
What are the effects of treatments for acute asthma?
Inhaled Corticosteroids for Acute Asthma (Better than Placebo). One systematic review has found that inhaled corticosteroids given in the emergency department reduce hospital admission rates in adults compared with placebo. One systematic review and one subsequent RCT found no significant difference in relapse rates following emergency department discharge between oral and inhaled steroids at seven to 10 days. One systematic review found no significant difference in relapse rates between inhaled plus oral corticosteroids and oral corticosteroids alone up to 24 days.
Inhaled Plus Oral Corticosteroids for Acute Asthma (as Effective as Oral Corticosteroid Alone). One systematic review found no significant difference in relapse rates for inhaled plus oral corticosteroid compared with oral corticosteroids up to 24 days.
Ipratropium Bromide Added to Beta2Agonists for Acute Exacerbations. Two systematic reviews and one subsequent RCT have found that ipratropium bromide plus salbutamol improves lung function compared with salbutamol alone and is likely to reduce hospital admission in people with severe acute asthma.
Short Courses of Systemic Corticosteroids for Acute Exacerbations. Two systematic reviews and one subsequent RCT have found that early treatment with systemic corticosteroids reduces admission and relapse rates compared with placebo in people with acute asthma. One systematic review and one small subsequent RCT found no significant difference between oral and inhaled steroids after emergency department discharge in relapse rates at seven to 10 days in adults with acute asthma.
Spacer Devices for Delivering Inhaled Medications from Pressurized Metered-Dose Inhalers in Acute Asthma (as Good as Nebulizers). One systematic review in people with acute, but not life-threatening exacerbations of asthma, found no significant difference between beta2 agonists delivered by spacer device compared with nebulizers in rates of hospital admission, time spent in the emergency department, peak expiratory flow rate, or forced expiratory volume in one second.
LIKELY TO BE BENEFICIAL
Education About Acute Asthma. One systematic review and one subsequent RCT provided evidence that education to facilitate self management of asthma in adults reduced hospital admission, unscheduled visits to the doctor, and days off work compared with usual care. One subsequent RCT provided insufficient evidence about effects of asthma education on quality of life or social functioning at six months.
Magnesium Sulphate for People with Severe Acute Asthma. We found limited evidence from one systematic review and two subsequent RCTs that intravenous magnesium improved lung function compared with placebo in people with severe acute asthma. One systematic review and three subsequent RCTs found no significant difference between intravenous magnesium sulphate and placebo for hospital admission rates.
Mechanical Ventilation for People with Severe Acute Asthma. We found no RCTs comparing mechanical ventilation with or without inhaled beta2 agonists versus no mechanical ventilation in people with severe acute asthma. Evidence from cohort studies support its use, although observational studies suggest that ventilation is associated with a high level of morbidity. (Highly likely to be effective. RCTs unlikely to be conducted.)
Oxygen Supplementation for Acute Asthma. We found no systematic review or RCTs of oxygen in acute asthma. However, consensus opinion and pathophysiology suggest that its role is vital in acute asthma. (Highly likely to be effective. RCTs unlikely to be conducted.)
Specialist Care for Acute Exacerbations (More Effective than Generalist Care). One systematic review found limited evidence that specialist care improved outcomes in people with acute asthma compared with generalist care.
UNLIKELY TO BE BENEFICIAL
Continuous Nebulized Short-Acting Beta2Agonists for Acute Asthma (No More Effective than Intermittent Nebulized Short-Acting Beta2Agonists). One systematic review and one subsequent RCT found no significant difference in admission rate between continuous and intermittent nebulized short-acting beta2 agonists for hospital admission rates in adults. The subsequent RCT also found no significant difference between continuous and intermittent nebulized short-acting beta2 agonists in lung function.
Helium–Oxygen Mixture for Acute Asthma. One systematic review found no significant difference between helium–oxygen mixture and air or oxygen in pulmonary function tests at 60 minutes for adults and children.
Intravenous Short-Acting Beta2Agonists for Acute Asthma (No More Effective than Nebulized Short-Acting Beta2Agonists). One systematic review found that intravenous delivery of short-acting beta2 agonists was no more effective than nebulized delivery in improving peak expiratory flow rate at 60 minutes.
Asthma is characterized by variable airflow obstruction and airway hyperresponsiveness. Symptoms include dyspnea, cough, chest tightness, and wheezing. The normal diurnal variation of peak expiratory flow rate is increased in people with asthma. Chronic asthma is defined here as asthma requiring maintenance treatment. Asthma is classified differently in the United States and United Kingdom. Where necessary, the text specifies the system of classification used.1,2
Acute asthma is defined here as an exacerbation of underlying asthma requiring urgent treatment.
Reported prevalence of asthma is increasing world-wide. About 10 percent of people have suffered an attack of asthma.3–5 Epidemiologic studies also have found marked variations in prevalence in different countries.6,7
Most people with asthma are atopic. Exposure to certain stimuli initiates inflammation and structural changes in airways causing airway hyperresponsiveness and variable airflow obstruction, which in turn cause most asthma symptoms. There are a large number of such stimuli; the more important include environmental allergens, occupational sensitizing agents, and respiratory viral infections.8,9
Chronic Asthma. In people with mild asthma, prognosis is good and progression to severe disease is rare. However, as a group, people with asthma lose lung function faster than those without asthma, although less quickly than people without asthma who smoke.10 People with chronic asthma can improve with treatment. However, some people (possibly up to 5 percent) have severe disease that responds poorly to treatment. These people are most at risk of morbidity and death from asthma.
Acute Asthma. About 10 to 20 percent of people presenting to the emergency department with asthma are admitted to the hospital. Of these, fewer than 10 percent receive mechanical ventilation.11,12 Those who are ventilated are at 19-fold increased risk of ventilation for a subsequent episode.13 It is unusual for people to die unless they have suffered respiratory arrest before reaching the hospital.14 One prospective study of 939 people discharged from emergency care found that 17 percent (95 percent; confidence interval 14 to 20 percent) relapsed by two weeks.15
J. Mark FitzGerald has received honoraria for lectures and research funds from GlaxoSmithKline, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Byk Canada, Schering Canada, and 3M.
The authors acknowledge previous contributorsof this chapter: Chris Cates, Paul O'Byrne, and Bazian Ltd.
SEARCH DATE: May 2003
Adapted with permission from FitzGerald JM, Dennis RJ, Solarte I. Asthma. Clin Evid Concise 2004;11:371–4.
Editor's Note: Salbutamol is called albuterol in the United States.
1. National Heart, Blood and Lung Institute. National Asthma Education and Prevention Program. Expert Panel Report 2. Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 97-4051; July 1997:20.
2. British Thoracic Society Guidelines. Thorax. 1997;52:S1-S2
3. Kaur B, Anderson HR, Austin J, et al. Prevalence of asthma symptoms, diagnosis, and treatment in 12–14 year old children across Great Britain (international study of asthma and allergies in childhood, ISAAC UK). BMJ. 1998;316:118-24
4. Woolcock AJ, Peat JK. Evidence for an increase in asthma world-wide. Ciba Found Symp. 1997;206:122-34
5. Holgate ST. The epidemic of allergy and asthma. Nature. 1999;402:B2-B4
6. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee.Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet. 1998;351:1225-32
7. Burney P, Chinn DJ, Luczynska C, et al. Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey. Eur Respir J. 1996;9:687-95
8. Duff AL, Platts-Mills TA. Allergens and asthma. Pediatr Clin North Am. 1992;39:1277-91
9. Chan-Yeung M, Malo JL. Occupational asthma. N Engl J Med. 1995;333:107-12
10. Lange P, Parner J, Vestbo J, et al. A 15-year follow-up study of ventilatory function in adults with asthma. N Engl J Med. 1998;339:1194-200
11. FitzGerald JM, Grunfeld A. Acute life-threatening asthma. In: FitzGerald JM, Ernst PP, Boulet LP, et al, eds. Evidence based asthma management. Decker: Hamilton, Ontario, 2000:233–44.
12. Nahum A, Tuxen DT. Management of asthma in the intensive care unit. In: FitzGerald JM, Ernst PP, Boulet LP, et al, eds. Evidence based asthma management. Decker: Hamilton, Ontario, 2000:245–61.
13. Turner MT, Noertjojo K, Vedal S, et al. Risk factors for near-fatal asthma: a case control study in patients hospitalised with acute asthma. Am J Respir Crit Care Med. 1998;157:1804-9
14. Molfino NA, Nannimi A, Martelli AN, et al. Respiratory arrest in near fatal asthma. N Engl J Med. 1991;324:285-8
15. Emmerman CL, Woodruff PG, Cydulka RK, et al. Prospective multi-center study of relapse following treatment for acute asthma among adults presenting to the emergency department. Chest. 1999;115:919-27
This is one in a series of chapters excerpted from Clinical Evidence Concise, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence Concise is published in print twice a year and is updated monthly online. Each topic is revised every eight months, and subscribers should view the most up-to-date version at http://www.clinicalevidence.com. If you are interested in contributing to Clinical Evidence, please contact Claire Folkes (firstname.lastname@example.org). This series is part of the AFP’s CME. See “Clinical Quiz” on page 25.
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