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Diagnosis and management of adult asthma
ADULT ASTHMA
Diagnosis and management of adult asthma
What’s new ?
Matthew Masoli
• Addition of a long-acting β-agonist has been shown to be more effective than doubling the dose of inhaled corticosteroid in unstable asthma
• Recent studies have shown a relatively flat dose–response curve for inhaled corticosteroids
Richard Beasley
and lowest peak flow rates vary by more than 15% diurnally. This period of monitoring is useful in confirming the diagnosis of asthma, determining its severity and establishing a guided selfmanagement plan (see below). Bronchodilator responsiveness is determined by measuring the forced expiratory volume in 1 second (FEV1) or peak flow before and after administration of a bronchodilator during the clinical consultation. The diagnosis of asthma is confirmed in individuals in whom FEV1 or peak flow improves by more than 15%. Absence
Diagnosis Clinical diagnosis of asthma is usually based on an accurate history, supported by physical examination and confirmed by the demonstration of reversible airflow obstruction on repeated measures of lung function. History The characteristic symptoms of asthma are any combination of wheezing, chest tightness, cough, sputum and breathlessness, which are episodic and occur in response to a wide range of clinical situations and provoking factors (Figure 1). In diagnosis, an attempt is made to determine whether these symptoms occur in response to such circumstances. The following points should be noted. • In some individuals, not all symptoms are present, or some symptoms may predominate. • The presence and frequency of some symptoms (e.g. nocturnal wakening) may help in determining the severity of the asthma. • Some provoking factors may help in identifying risk factors for the development of asthma (e.g. occupational asthma).
Clinical situations and provoking factors in asthma • • • • • • • •
Examination Physical examination may not be helpful in the diagnosis of asthma because airflow obstruction may not be present at the time of the consultation. Widespread rhonchi on auscultation of the chest should be sought; if these are not found, the patient is asked to perform a forced expiratory manoeuvre, which may provoke audible wheeze. Signs of differential diagnoses (e.g. bronchiectasis) and other allergic disorders (e.g. eczema, rhinoconjunctivitis) should also be sought.
Night or early morning Exercise or cold air Viral respiratory tract infection Allergens (e.g. house dust mite, cat fur) Nonspecific irritants (e.g. cigarette smoke, perfumes) Drugs (e.g. β-blockers, aspirin) Emotion or stress Occupational exposure
1
Peak expiratory flow (litres/minute)
Characteristic pattern of peak flow in asthma
Objective assessment Objective assessment of variable airflow obstruction is crucial in confirming the diagnosis of asthma. Three approaches are used. Home peak flow monitoring involves repeated measurement of peak flow (best of three hard blows) at different times of the day and night (Figure 2). In asthmatic individuals, the highest
600 500 400 300 200 100 0 a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. 1 2 3 4 5 6 7 8
Day The peak flow record of an untreated asthmatic patient shows characteristic diurnal variability
Matthew Masoli is a Medical Research Fellow at the Medical Research Institute of New Zealand, Wellington, New Zealand.
Source: Clark T J H, ed. Bronchodilator therapy: the basis of asthma and chronic obstructive airways disease management. Auckland: Adis Press, 1994.
Richard Beasley is Director of the Medical Research Institute of New Zealand, Wellington, New Zealand and Visiting Professor at the University of Southampton, UK.
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of such an improvement does not necessarily mean that the patient does not have asthma – he or she may not have airflow obstruction at the time of the test, may have taken a β-agonist before the test, or may have more fixed airflow obstruction. In these individuals, the diagnosis is clarified by home peak flow monitoring. Response to corticosteroid therapy – in some patients with relatively fixed airflow obstruction in whom asthma is still suspected, improvement in lung function (FEV1 or peak flow) following a trial of oral or inhaled corticosteroid therapy may be useful in confirming the diagnosis.
diagnosis is difficult. Although airways inflammation represents the underlying disease process in asthma (Figure 3), measurement of biological markers of this (e.g. eosinophil cationic protein) are not recommended because they are poor predictors of asthma and its severity. Differential diagnosis Because asthma is so common, it is easy to miss other disorders that may present in a similar manner. Consideration of differential diagnoses is therefore worthwhile; depending on the presentation, these include: • chronic obstructive pulmonary disease (COPD) • left ventricular failure • drug use (e.g. angiotensin-converting enzyme inhibitors may cause cough) • pulmonary embolism • laryngeal causes of airways obstruction • Churg–Strauss syndrome • bronchiectasis with airflow obstruction • hyperventilation syndrome. These conditions should be considered particularly in patients who do not respond as expected to a standard management regimen.
Investigations Chest radiography, full blood count (for eosinophil level) and skin-prick tests for common allergens may be useful, but are not essential in all patients with asthma. They can be undertaken as a routine screen in those with moderate or severe asthma, or in severe asthma for a specific reason (e.g. to exclude an alternative diagnosis, to identify sensitization to specific allergens). Measurement of nonspecific bronchial responsiveness (e.g. methacholine challenge tests, exercise tests) is not recommended in the routine diagnosis of asthma because it is neither sensitive nor specific for the condition, but is occasionally useful when
b
a
3 Characteristic appearance of the bronchial mucosa on fibre-optic bronchoscopy in a a healthy individual and b a patient with asthma. Note the presence of chronic and acute inflammatory changes in the asthma biopsy, including extensive inflammatory cell infiltration, thickened basement membrane and loss of the ciliated respiratory epithelium.
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Stepwise management of asthma in adults Step 5: Continuous or frequent use of oral corticosteroids Use daily corticosteroid tablet at lowest dose providing adequate control Maintain high-dose inhaled corticosteroid, 2000 µg/day1 Consider other treatments to minimize use of corticosteroid tablets Refer patient for specialist care Step 4: Persistent poor control Consider trials of the following • Increase inhaled corticosteroid, up to 2000 µg/day1 • Add a fourth drug (e.g. leukotriene receptor antagonist, theophylline, β2-agonist tablet) Step 3: Add-on therapy Add long-acting β2-agonist Assess control of asthma by the following means • Good response to long-acting β2-agonist – continue • Benefit from long-acting β2-agonist but control remains inadequate – continue, and increase inhaled corticosteroid to 800 µg/day1 (if patient not already on this dose) • No response to long-acting β2-agonist – stop, and increase inhaled corticosteroid to 800 µg/day1; if control remains inadequate, institute trial of other therapies (e.g. leukotriene receptor antagonist, theophylline) Step 2: Regular preventer therapy Add inhaled corticosteroid, 200–800 µg/day1 Start at a dose appropriate to the severity of disease (in many patients, 400 µg/day) Step 1: Mild, intermittent asthma Use inhaled short-acting β2-agonist as required 1 Beclomethasone dipropionate or equivalent Source: British Guideline on Asthma Management
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Inhaled short-acting β-agonists All patients with asthma should be prescribed an inhaled shortacting β-agonist for use as required for relief of symptoms, rather than according to a regular, scheduled regimen. With as-required regimens, frequency of use and the resulting response can be used as a guide to changes in the severity of asthma.
Management Aims The aims of management of asthma are control of symptoms (including nocturnal symptoms and exercise-induced asthma), prevention of exacerbations and achievement of the best possible pulmonary function with minimal side-effects. It is not appropriate to define a fixed level of lung function or symptom control – this depends on the severity of the asthma, and the aims and preferences of the patient and doctor.
Inhaled corticosteroids Regular inhaled corticosteroid is the most effective antiinflammatory disease-modifying treatment available for the long-term management of asthma. Long-term use leads to improved lung function, reduced symptoms (e.g. nocturnal wakening), reduced frequency of severe exacerbations leading to hospital or ICU admission, and reduced risk of mortality.2,3 Recommended regimens are beclomethasone dipropionate (BDP), 200–2000 µg/day, budesonide, 200–2000 µg/day, or fluticasone, 100–1000 µg/day. Current evidence indicates that, in mild-to-moderate disease, most therapeutic benefit is obtained with BDP or budesonide doses of about 400 µg/day or fluticasone about 200 µg/day; maximum effect is achieved with about 1000 µg/day of BDP or budesonide, or 500 µg/day of fluticasone (Figure 5).4 There is significant individual variability, however, and these findings do not exclude the possibility that higher doses may be beneficial in severe asthma.
Stepwise approach Management of adult asthma is outlined in Figure 4.1 It is recommended that treatment is started at the step most appropriate for the initial severity of the patient’s asthma. The stepwise approach involves ‘stepping-up’ treatment as necessary to achieve control and ‘stepping-down’ when control has been maintained for a prolonged period of time. In patients in whom control is not achieved, the diagnosis of asthma and risk factors should be reviewed, compliance and inhaler technique should be checked, and complications such as allergic bronchopulmonary aspergillosis should be considered. If no reason for the poor response to therapy is identified, additional drug therapy can be initiated.
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It is recommended that inhaled corticosteroids are introduced in patients who have symptoms and/or require β-agonist therapy on most days.1 It has been suggested that inhaled corticosteroids should be started at a high dose and then titrated down, but this approach is not supported by clinical studies,5 which indicate that the best approach is to start treatment with the dose most likely to be required, based on the severity of the patient’s asthma. Inhaled corticosteroid therapy is then titrated to the lowest dose at which asthma control is maintained. Most patients are prescribed inhaled corticosteroids twice daily, but a once-daily (evening) regimen is an acceptable alternative in those with mild asthma, and may improve compliance.
Dose–response relationship for inhaled corticosteroids in the treatment of adult asthma Fluticasone dose (µg/day) 0
200
300
400
500
100
% of maximum effect
80
Inhaled long-acting β-agonists Inhaled long-acting β-agonists have a duration of bronchodilator action of more than 12 hours.6 They are recommended in patients with asthma that is not adequately controlled by regular inhaled corticosteroid. Addition of a long-acting β-agonist to inhaled corticosteroid at a dose of about 500–1000 µg/day BDP or equivalent achieves a better therapeutic response than increasing the dose of inhaled corticosteroid.7 Salmeterol, 50 µg, and formoterol, 6 µg, are recommended for use twice daily, with a short-acting β-agonist continued as required. Long-acting β-agonists are not recommended as sole therapy – they must be given in conjunction with regular inhaled corticosteroid. Use of fixed combination inhalers delivering both a long-acting β-agonist and a corticosteroid ensures that the β-agonist is not given as monotherapy and is likely to improve compliance with inhaled corticosteroid therapy.
60
40
Peak expiratory flow (morning) β-agonist use Night wakenings Major exacerbations
20
0 0
200
400
600
800
1000
Budesonide (µg/day)
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Other therapies Oral theophylline8 and oral leukotriene receptor antagonists9 are additional therapies that can be used when asthma is not controlled by inhaled corticosteroid therapy. In some older patients with coexisting chronic bronchitis, an inhaled anticholinergic agent (e.g. ipratropium, oxitropium) may be taken in addition or as an alternative to a short-acting β-agonist, as inhaled bronchodilator therapy.10 Monoclonal anti-IgE antibodies are novel agents that will soon be available, primarily for patients with severe asthma; however, their use is likely to be limited by their high cost.11
The risk of a fatal attack is increased more than tenfold in patients who have been admitted to hospital for asthma in the previous year;14 5-year mortality may be as high as 20% in those who have been admitted to an ICU for asthma, particularly if they required mechanical ventilation.15 Monitoring asthma control Patients can be taught to recognize changes in the severity of acute asthma by identifying key symptoms and using objective measures of airflow obstruction such as peak flow rate. Unstable asthma is identified by the development of nocturnal symptoms and/or a peak flow rate of 80% or less of the predicted or previous best
Reducing exposure to provoking factors Reducing exposure to inhaled allergens from house dust mites and cats has been proposed as a means of reducing the severity of asthma,12 though recent evidence has not confirmed the efficacy of such an approach.13 Patients who smoke should stop. The possibility of occupational asthma should be considered, particularly in those who first develop asthma in adult life.
High-risk asthma patients • • • • • • • • •
Assessment of risk A priority in management is recognition of patients who are at increased risk of asthma attacks leading to hospital admission or a fatal outcome. Clinical characteristics associated with such an increased risk have been identified (Figure 6). High-risk asthma patients are most practically identified as those who: • request repeat prescriptions of two or more β-agonist inhalers per month • frequently visit their general practitioner or hospital emergency department with severe asthma • have recently been admitted to hospital.
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Previous life-threatening attack (greatest risk factor) Adolescents Disadvantaged racial groups Psychological or psychosocial problems Three or more asthma medications prescribed Requirement for two or more β-agonist inhalers per month Frequent visits to general practitioner with unstable asthma One or more visits to hospital emergency department Recent hospital admission
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achieved. Severe asthma is identified by frequent requirement for inhaled β-agonist therapy (2–3-hourly) and a reduction in peak flow to less than 60% best despite β-agonist therapy.
Figures 7 and 8 show a prototype self-management plan based on the guidelines discussed above. Steps 1 and 2 guide overall long-term management. The instruction to vary the dose of inhaled corticosteroid in a stepwise manner according to changes in severity is not based on strong evidence, but is a practical means of encouraging compliance with the treatment of chronic persistent asthma. Steps 3 and 4 guide the treatment of severe asthma; intensive treatment is started by the patient to prevent the development of a life-threatening attack. Recommendations for acute severe and chronic persistent asthma can thus be combined in one system (Figure 9).
Guided self-management Incorporating guidelines for long-term treatment into a simple, practical regimen that can be undertaken by the patient is a challenge in the management of asthma. Guided self-management plans have been developed in which patients make changes to their treatment in response to changes in the severity of their asthma, and in accordance with a predetermined plan.16
Adult asthma self-management plan: what to do and when Step
Peak flow
Symptoms
Action
1
80–100% best
Intermittent/few
Continue regular inhaled corticosteroids; consider reduction if patient is well for several months; inhaled β-agonist for relief of symptoms
2
60–80% best
Waking at night with asthma; symptoms of a ‘cold’
Start inhaled corticosteroid or increase the dose
3
40–60% best
Increasing breathlessness; using β-agonist 2–3-hourly
Start oral corticosteroid and call a doctor
4
< 40% best
Severe attack of asthma; poor response to β-agonist
Call emergency doctor or ambulance urgently
At all stages, take inhaled β-agonist for relief of symptoms The peak flow levels at each stage may need to be varied; an alternative is > 85%, 70–85%, 50–70%, < 50% best
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Few symptoms
Use of β-agonist 2–3 hourly Increasing breathlessness Poor response to β-agonist Difficulty talking
500
100
Increase in peak flow after β-agonist therapy
400
80
300
60
200
40
% of best
Waking at night Symptoms of cold
Peak expiratory flow (litres/minute)
Use of a self-management plan in a patient with deteriorating asthma
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100 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Time (days)
Well controlled Inhaled corticosteroid twice daily Inhaled β-agonist as required
Unstable asthma Inhaled corticosteroid four times daily Inhaled β-agonist as required
Severe asthma Prednisolone, 30–40 mg daily p.o. Inhaled β-agonist as required Contact doctor
Lifethreatening Gradual response attack Continue course Contact of prednisolone emergency Inhaled corticosteroid medical four times daily service Inhaled β-agonist as required Admit to hospital
Stable asthma Wean off prednisolone Inhaled corticosteroid twice daily Inhaled β-agonist as required
In this example, an asthma attack develops over 1 week. The patient recognizes stages of worsening asthma by the development of key symptoms and decreases in peak expiratory flow from previous best values, and institutes changes in management according to predetermined written guidelines. 8
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treatment. Am J Respir Crit Care Med 1998; 158: 121–5. 6 Rabe K F, Jörres R, Nowak D et al. Comparison of the effects of salmeterol and formoterol on airway tone and responsiveness over 24 hours in bronchial asthma. Am Rev Respir Dis 1993; 147: 1436–41. 7 Shrewsbury S, Pyke S, Brotton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000; 320: 1368–73. 8 Evans D J, Taylor D A, Zetterstrom O et al. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med 1997; 337: 1412–18. 9 Drazen J M, Israel E, O’Byrne P M. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med 1999; 340: 197–206. 10 Campbell S. For COPD a combination of ipratropium bromide and albuterol sulphate is more effective than albuterol base. Arch Intern Med 1999; 159: 156–60. 11 Milgrom H, Fick R B Jr, Su J Q et al. Treatment of allergic asthma with monoclonal anti-IgE antibody: rhuMAb-E25 Study Group. N Engl J Med 1999; 341: 1966–73. 12 Custovic A, Simpson A, Chapman M D et al. Allergen avoidance in the treatment of asthma and atopic disorders. Thorax 1998; 53: 63–72. 13 Woodcock A, Forster L, Matthews E et al. Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. N Engl J Med 2003; 349: 225–36. 14 Rea H H, Scragg R, Jackson R et al. A case-control study of death from asthma. Thorax 1986; 41: 833–9. 15 Marquette C H, Saulnier F, Leroy O et al. Long-term prognosis of near-fatal asthma: a 6 year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis 1992; 146: 76–81. 16 Fishwick D, D’Souza W, Beasley R. The asthma self-management plan system of care: what does it mean, how is it done, does it work, what models are available, what do patients want and who needs it? Patient Educ Couns 1997; 32: S21–33. 17 Gibson P G, Coughlan J, Wilson A J et al. Self-management education and regular general practitioner review for adults with asthma. Cochrane Database Sys Rev 2002; 2. 18 Lahdensuo A, Haahtela T, Herrala J et al. Randomised comparison of guided self-management and traditional treatment of asthma over one year. BMJ 1996; 312: 748–52. 19 Abramson M J, Bailey M J, Couper F J et al. Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med 2001; 163: 12–18.
Basic principles of self-management in high-risk patients with asthma • Objective assessment of asthma severity and educated interpretation of key symptoms and peak flow recordings • Regular inhaled corticosteroids and intermittent β-agonists for long-term treatment of asthma; systemic corticosteroids, high-dose inhaled β-agonists, oxygen therapy and medical review for acute severe exacerbations • Integration of self-assessment and self-management with written guidelines for both long-term treatment of asthma and treatment of acute severe asthma • Specialist review
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No single plan is suitable for every individual. Features that may be varied include the amount of detail provided, the number of stages, the specific drug treatment recommended at each stage, the level (or range of levels) of peak flow (pre-bronchodilator or post-bronchodilator) at which the patient is advised to modify therapy or seek medical assistance, and the optimal frequency of peak flow monitoring (routinely or only during exacerbations). It has been suggested that, in patients who have suffered a nearfatal attack, each stage is set at a higher level, particularly for self-referral to hospital. In such patients, more aggressive selfmanagement has been proposed, involving self-administration of oxygen and nebulized β-agonist at home during life-threatening attacks. A recent Cochrane meta-analysis has confirmed that this self-management system is effective in terms of reducing asthma morbidity and the need for acute medical services.17,18 It has also been shown to reduce the risk of death from asthma.19 Patient education is also important. Provision of information on the nature of the disease, how to use treatments, and selfmonitoring and assessment skills enables patients to self-manage their disease more effectively.
REFERENCES 1 British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on asthma management: a national clinical guideline. Thorax 2003; 58: (Suppl. 1): i1–94. 2 Barnes P J. Inhaled glucocorticoids for asthma. N Engl J Med 1995; 332: 868–75. 3 Suissa S, Ernst P, Benayoun S et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343: 332–6. 4 Holt S, Suder A, Weatherall M et al. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis. BMJ 2001; 323: 1–8. 5 Van der Molen T, Meyboom-De Jong B, Mulder H et al. Starting with a higher dose of inhaled corticosteroids in primary care asthma
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FURTHER READING Asthma. In: Gibson J G, Geddes D M, Costabel U et al., eds. Respiratory medicine. 3rd ed. Philadelphia: Saunders, 2003: 1202–444. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on asthma management: a national clinical guideline. Thorax 2003; 58: (Suppl. 1): i1–94. Holgate S T, Boushey H A, Fabbri L M, eds. Difficult asthma. London: Dunitz, 1999. O’Byrne P M, Thomson N C, eds. Manual of asthma management. 2nd ed. London: Saunders, 2001.
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Diagnosis and management of adult asthma
What’s new ?
Matthew Masoli
• Addition of a long-acting β-agonist has been shown to be more effective than doubling the dose of inhaled corticosteroid in unstable asthma
• Recent studies have shown a relatively flat dose–response curve for inhaled corticosteroids
Richard Beasley
and lowest peak flow rates vary by more than 15% diurnally. This period of monitoring is useful in confirming the diagnosis of asthma, determining its severity and establishing a guided selfmanagement plan (see below). Bronchodilator responsiveness is determined by measuring the forced expiratory volume in 1 second (FEV1) or peak flow before and after administration of a bronchodilator during the clinical consultation. The diagnosis of asthma is confirmed in individuals in whom FEV1 or peak flow improves by more than 15%. Absence
Diagnosis Clinical diagnosis of asthma is usually based on an accurate history, supported by physical examination and confirmed by the demonstration of reversible airflow obstruction on repeated measures of lung function. History The characteristic symptoms of asthma are any combination of wheezing, chest tightness, cough, sputum and breathlessness, which are episodic and occur in response to a wide range of clinical situations and provoking factors (Figure 1). In diagnosis, an attempt is made to determine whether these symptoms occur in response to such circumstances. The following points should be noted. • In some individuals, not all symptoms are present, or some symptoms may predominate. • The presence and frequency of some symptoms (e.g. nocturnal wakening) may help in determining the severity of the asthma. • Some provoking factors may help in identifying risk factors for the development of asthma (e.g. occupational asthma).
Clinical situations and provoking factors in asthma • • • • • • • •
Examination Physical examination may not be helpful in the diagnosis of asthma because airflow obstruction may not be present at the time of the consultation. Widespread rhonchi on auscultation of the chest should be sought; if these are not found, the patient is asked to perform a forced expiratory manoeuvre, which may provoke audible wheeze. Signs of differential diagnoses (e.g. bronchiectasis) and other allergic disorders (e.g. eczema, rhinoconjunctivitis) should also be sought.
Night or early morning Exercise or cold air Viral respiratory tract infection Allergens (e.g. house dust mite, cat fur) Nonspecific irritants (e.g. cigarette smoke, perfumes) Drugs (e.g. β-blockers, aspirin) Emotion or stress Occupational exposure
1
Peak expiratory flow (litres/minute)
Characteristic pattern of peak flow in asthma
Objective assessment Objective assessment of variable airflow obstruction is crucial in confirming the diagnosis of asthma. Three approaches are used. Home peak flow monitoring involves repeated measurement of peak flow (best of three hard blows) at different times of the day and night (Figure 2). In asthmatic individuals, the highest
600 500 400 300 200 100 0 a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. a.m. p.m. 1 2 3 4 5 6 7 8
Day The peak flow record of an untreated asthmatic patient shows characteristic diurnal variability
Matthew Masoli is a Medical Research Fellow at the Medical Research Institute of New Zealand, Wellington, New Zealand.
Source: Clark T J H, ed. Bronchodilator therapy: the basis of asthma and chronic obstructive airways disease management. Auckland: Adis Press, 1994.
Richard Beasley is Director of the Medical Research Institute of New Zealand, Wellington, New Zealand and Visiting Professor at the University of Southampton, UK.
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of such an improvement does not necessarily mean that the patient does not have asthma – he or she may not have airflow obstruction at the time of the test, may have taken a β-agonist before the test, or may have more fixed airflow obstruction. In these individuals, the diagnosis is clarified by home peak flow monitoring. Response to corticosteroid therapy – in some patients with relatively fixed airflow obstruction in whom asthma is still suspected, improvement in lung function (FEV1 or peak flow) following a trial of oral or inhaled corticosteroid therapy may be useful in confirming the diagnosis.
diagnosis is difficult. Although airways inflammation represents the underlying disease process in asthma (Figure 3), measurement of biological markers of this (e.g. eosinophil cationic protein) are not recommended because they are poor predictors of asthma and its severity. Differential diagnosis Because asthma is so common, it is easy to miss other disorders that may present in a similar manner. Consideration of differential diagnoses is therefore worthwhile; depending on the presentation, these include: • chronic obstructive pulmonary disease (COPD) • left ventricular failure • drug use (e.g. angiotensin-converting enzyme inhibitors may cause cough) • pulmonary embolism • laryngeal causes of airways obstruction • Churg–Strauss syndrome • bronchiectasis with airflow obstruction • hyperventilation syndrome. These conditions should be considered particularly in patients who do not respond as expected to a standard management regimen.
Investigations Chest radiography, full blood count (for eosinophil level) and skin-prick tests for common allergens may be useful, but are not essential in all patients with asthma. They can be undertaken as a routine screen in those with moderate or severe asthma, or in severe asthma for a specific reason (e.g. to exclude an alternative diagnosis, to identify sensitization to specific allergens). Measurement of nonspecific bronchial responsiveness (e.g. methacholine challenge tests, exercise tests) is not recommended in the routine diagnosis of asthma because it is neither sensitive nor specific for the condition, but is occasionally useful when
b
a
3 Characteristic appearance of the bronchial mucosa on fibre-optic bronchoscopy in a a healthy individual and b a patient with asthma. Note the presence of chronic and acute inflammatory changes in the asthma biopsy, including extensive inflammatory cell infiltration, thickened basement membrane and loss of the ciliated respiratory epithelium.
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Stepwise management of asthma in adults Step 5: Continuous or frequent use of oral corticosteroids Use daily corticosteroid tablet at lowest dose providing adequate control Maintain high-dose inhaled corticosteroid, 2000 µg/day1 Consider other treatments to minimize use of corticosteroid tablets Refer patient for specialist care Step 4: Persistent poor control Consider trials of the following • Increase inhaled corticosteroid, up to 2000 µg/day1 • Add a fourth drug (e.g. leukotriene receptor antagonist, theophylline, β2-agonist tablet) Step 3: Add-on therapy Add long-acting β2-agonist Assess control of asthma by the following means • Good response to long-acting β2-agonist – continue • Benefit from long-acting β2-agonist but control remains inadequate – continue, and increase inhaled corticosteroid to 800 µg/day1 (if patient not already on this dose) • No response to long-acting β2-agonist – stop, and increase inhaled corticosteroid to 800 µg/day1; if control remains inadequate, institute trial of other therapies (e.g. leukotriene receptor antagonist, theophylline) Step 2: Regular preventer therapy Add inhaled corticosteroid, 200–800 µg/day1 Start at a dose appropriate to the severity of disease (in many patients, 400 µg/day) Step 1: Mild, intermittent asthma Use inhaled short-acting β2-agonist as required 1 Beclomethasone dipropionate or equivalent Source: British Guideline on Asthma Management
4
Inhaled short-acting β-agonists All patients with asthma should be prescribed an inhaled shortacting β-agonist for use as required for relief of symptoms, rather than according to a regular, scheduled regimen. With as-required regimens, frequency of use and the resulting response can be used as a guide to changes in the severity of asthma.
Management Aims The aims of management of asthma are control of symptoms (including nocturnal symptoms and exercise-induced asthma), prevention of exacerbations and achievement of the best possible pulmonary function with minimal side-effects. It is not appropriate to define a fixed level of lung function or symptom control – this depends on the severity of the asthma, and the aims and preferences of the patient and doctor.
Inhaled corticosteroids Regular inhaled corticosteroid is the most effective antiinflammatory disease-modifying treatment available for the long-term management of asthma. Long-term use leads to improved lung function, reduced symptoms (e.g. nocturnal wakening), reduced frequency of severe exacerbations leading to hospital or ICU admission, and reduced risk of mortality.2,3 Recommended regimens are beclomethasone dipropionate (BDP), 200–2000 µg/day, budesonide, 200–2000 µg/day, or fluticasone, 100–1000 µg/day. Current evidence indicates that, in mild-to-moderate disease, most therapeutic benefit is obtained with BDP or budesonide doses of about 400 µg/day or fluticasone about 200 µg/day; maximum effect is achieved with about 1000 µg/day of BDP or budesonide, or 500 µg/day of fluticasone (Figure 5).4 There is significant individual variability, however, and these findings do not exclude the possibility that higher doses may be beneficial in severe asthma.
Stepwise approach Management of adult asthma is outlined in Figure 4.1 It is recommended that treatment is started at the step most appropriate for the initial severity of the patient’s asthma. The stepwise approach involves ‘stepping-up’ treatment as necessary to achieve control and ‘stepping-down’ when control has been maintained for a prolonged period of time. In patients in whom control is not achieved, the diagnosis of asthma and risk factors should be reviewed, compliance and inhaler technique should be checked, and complications such as allergic bronchopulmonary aspergillosis should be considered. If no reason for the poor response to therapy is identified, additional drug therapy can be initiated.
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It is recommended that inhaled corticosteroids are introduced in patients who have symptoms and/or require β-agonist therapy on most days.1 It has been suggested that inhaled corticosteroids should be started at a high dose and then titrated down, but this approach is not supported by clinical studies,5 which indicate that the best approach is to start treatment with the dose most likely to be required, based on the severity of the patient’s asthma. Inhaled corticosteroid therapy is then titrated to the lowest dose at which asthma control is maintained. Most patients are prescribed inhaled corticosteroids twice daily, but a once-daily (evening) regimen is an acceptable alternative in those with mild asthma, and may improve compliance.
Dose–response relationship for inhaled corticosteroids in the treatment of adult asthma Fluticasone dose (µg/day) 0
200
300
400
500
100
% of maximum effect
80
Inhaled long-acting β-agonists Inhaled long-acting β-agonists have a duration of bronchodilator action of more than 12 hours.6 They are recommended in patients with asthma that is not adequately controlled by regular inhaled corticosteroid. Addition of a long-acting β-agonist to inhaled corticosteroid at a dose of about 500–1000 µg/day BDP or equivalent achieves a better therapeutic response than increasing the dose of inhaled corticosteroid.7 Salmeterol, 50 µg, and formoterol, 6 µg, are recommended for use twice daily, with a short-acting β-agonist continued as required. Long-acting β-agonists are not recommended as sole therapy – they must be given in conjunction with regular inhaled corticosteroid. Use of fixed combination inhalers delivering both a long-acting β-agonist and a corticosteroid ensures that the β-agonist is not given as monotherapy and is likely to improve compliance with inhaled corticosteroid therapy.
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40
Peak expiratory flow (morning) β-agonist use Night wakenings Major exacerbations
20
0 0
200
400
600
800
1000
Budesonide (µg/day)
5
Other therapies Oral theophylline8 and oral leukotriene receptor antagonists9 are additional therapies that can be used when asthma is not controlled by inhaled corticosteroid therapy. In some older patients with coexisting chronic bronchitis, an inhaled anticholinergic agent (e.g. ipratropium, oxitropium) may be taken in addition or as an alternative to a short-acting β-agonist, as inhaled bronchodilator therapy.10 Monoclonal anti-IgE antibodies are novel agents that will soon be available, primarily for patients with severe asthma; however, their use is likely to be limited by their high cost.11
The risk of a fatal attack is increased more than tenfold in patients who have been admitted to hospital for asthma in the previous year;14 5-year mortality may be as high as 20% in those who have been admitted to an ICU for asthma, particularly if they required mechanical ventilation.15 Monitoring asthma control Patients can be taught to recognize changes in the severity of acute asthma by identifying key symptoms and using objective measures of airflow obstruction such as peak flow rate. Unstable asthma is identified by the development of nocturnal symptoms and/or a peak flow rate of 80% or less of the predicted or previous best
Reducing exposure to provoking factors Reducing exposure to inhaled allergens from house dust mites and cats has been proposed as a means of reducing the severity of asthma,12 though recent evidence has not confirmed the efficacy of such an approach.13 Patients who smoke should stop. The possibility of occupational asthma should be considered, particularly in those who first develop asthma in adult life.
High-risk asthma patients • • • • • • • • •
Assessment of risk A priority in management is recognition of patients who are at increased risk of asthma attacks leading to hospital admission or a fatal outcome. Clinical characteristics associated with such an increased risk have been identified (Figure 6). High-risk asthma patients are most practically identified as those who: • request repeat prescriptions of two or more β-agonist inhalers per month • frequently visit their general practitioner or hospital emergency department with severe asthma • have recently been admitted to hospital.
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Previous life-threatening attack (greatest risk factor) Adolescents Disadvantaged racial groups Psychological or psychosocial problems Three or more asthma medications prescribed Requirement for two or more β-agonist inhalers per month Frequent visits to general practitioner with unstable asthma One or more visits to hospital emergency department Recent hospital admission
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achieved. Severe asthma is identified by frequent requirement for inhaled β-agonist therapy (2–3-hourly) and a reduction in peak flow to less than 60% best despite β-agonist therapy.
Figures 7 and 8 show a prototype self-management plan based on the guidelines discussed above. Steps 1 and 2 guide overall long-term management. The instruction to vary the dose of inhaled corticosteroid in a stepwise manner according to changes in severity is not based on strong evidence, but is a practical means of encouraging compliance with the treatment of chronic persistent asthma. Steps 3 and 4 guide the treatment of severe asthma; intensive treatment is started by the patient to prevent the development of a life-threatening attack. Recommendations for acute severe and chronic persistent asthma can thus be combined in one system (Figure 9).
Guided self-management Incorporating guidelines for long-term treatment into a simple, practical regimen that can be undertaken by the patient is a challenge in the management of asthma. Guided self-management plans have been developed in which patients make changes to their treatment in response to changes in the severity of their asthma, and in accordance with a predetermined plan.16
Adult asthma self-management plan: what to do and when Step
Peak flow
Symptoms
Action
1
80–100% best
Intermittent/few
Continue regular inhaled corticosteroids; consider reduction if patient is well for several months; inhaled β-agonist for relief of symptoms
2
60–80% best
Waking at night with asthma; symptoms of a ‘cold’
Start inhaled corticosteroid or increase the dose
3
40–60% best
Increasing breathlessness; using β-agonist 2–3-hourly
Start oral corticosteroid and call a doctor
4
< 40% best
Severe attack of asthma; poor response to β-agonist
Call emergency doctor or ambulance urgently
At all stages, take inhaled β-agonist for relief of symptoms The peak flow levels at each stage may need to be varied; an alternative is > 85%, 70–85%, 50–70%, < 50% best
7
Few symptoms
Use of β-agonist 2–3 hourly Increasing breathlessness Poor response to β-agonist Difficulty talking
500
100
Increase in peak flow after β-agonist therapy
400
80
300
60
200
40
% of best
Waking at night Symptoms of cold
Peak expiratory flow (litres/minute)
Use of a self-management plan in a patient with deteriorating asthma
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100 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Time (days)
Well controlled Inhaled corticosteroid twice daily Inhaled β-agonist as required
Unstable asthma Inhaled corticosteroid four times daily Inhaled β-agonist as required
Severe asthma Prednisolone, 30–40 mg daily p.o. Inhaled β-agonist as required Contact doctor
Lifethreatening Gradual response attack Continue course Contact of prednisolone emergency Inhaled corticosteroid medical four times daily service Inhaled β-agonist as required Admit to hospital
Stable asthma Wean off prednisolone Inhaled corticosteroid twice daily Inhaled β-agonist as required
In this example, an asthma attack develops over 1 week. The patient recognizes stages of worsening asthma by the development of key symptoms and decreases in peak expiratory flow from previous best values, and institutes changes in management according to predetermined written guidelines. 8
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treatment. Am J Respir Crit Care Med 1998; 158: 121–5. 6 Rabe K F, Jörres R, Nowak D et al. Comparison of the effects of salmeterol and formoterol on airway tone and responsiveness over 24 hours in bronchial asthma. Am Rev Respir Dis 1993; 147: 1436–41. 7 Shrewsbury S, Pyke S, Brotton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000; 320: 1368–73. 8 Evans D J, Taylor D A, Zetterstrom O et al. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med 1997; 337: 1412–18. 9 Drazen J M, Israel E, O’Byrne P M. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med 1999; 340: 197–206. 10 Campbell S. For COPD a combination of ipratropium bromide and albuterol sulphate is more effective than albuterol base. Arch Intern Med 1999; 159: 156–60. 11 Milgrom H, Fick R B Jr, Su J Q et al. Treatment of allergic asthma with monoclonal anti-IgE antibody: rhuMAb-E25 Study Group. N Engl J Med 1999; 341: 1966–73. 12 Custovic A, Simpson A, Chapman M D et al. Allergen avoidance in the treatment of asthma and atopic disorders. Thorax 1998; 53: 63–72. 13 Woodcock A, Forster L, Matthews E et al. Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. N Engl J Med 2003; 349: 225–36. 14 Rea H H, Scragg R, Jackson R et al. A case-control study of death from asthma. Thorax 1986; 41: 833–9. 15 Marquette C H, Saulnier F, Leroy O et al. Long-term prognosis of near-fatal asthma: a 6 year follow-up study of 145 asthmatic patients who underwent mechanical ventilation for a near-fatal attack of asthma. Am Rev Respir Dis 1992; 146: 76–81. 16 Fishwick D, D’Souza W, Beasley R. The asthma self-management plan system of care: what does it mean, how is it done, does it work, what models are available, what do patients want and who needs it? Patient Educ Couns 1997; 32: S21–33. 17 Gibson P G, Coughlan J, Wilson A J et al. Self-management education and regular general practitioner review for adults with asthma. Cochrane Database Sys Rev 2002; 2. 18 Lahdensuo A, Haahtela T, Herrala J et al. Randomised comparison of guided self-management and traditional treatment of asthma over one year. BMJ 1996; 312: 748–52. 19 Abramson M J, Bailey M J, Couper F J et al. Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med 2001; 163: 12–18.
Basic principles of self-management in high-risk patients with asthma • Objective assessment of asthma severity and educated interpretation of key symptoms and peak flow recordings • Regular inhaled corticosteroids and intermittent β-agonists for long-term treatment of asthma; systemic corticosteroids, high-dose inhaled β-agonists, oxygen therapy and medical review for acute severe exacerbations • Integration of self-assessment and self-management with written guidelines for both long-term treatment of asthma and treatment of acute severe asthma • Specialist review
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No single plan is suitable for every individual. Features that may be varied include the amount of detail provided, the number of stages, the specific drug treatment recommended at each stage, the level (or range of levels) of peak flow (pre-bronchodilator or post-bronchodilator) at which the patient is advised to modify therapy or seek medical assistance, and the optimal frequency of peak flow monitoring (routinely or only during exacerbations). It has been suggested that, in patients who have suffered a nearfatal attack, each stage is set at a higher level, particularly for self-referral to hospital. In such patients, more aggressive selfmanagement has been proposed, involving self-administration of oxygen and nebulized β-agonist at home during life-threatening attacks. A recent Cochrane meta-analysis has confirmed that this self-management system is effective in terms of reducing asthma morbidity and the need for acute medical services.17,18 It has also been shown to reduce the risk of death from asthma.19 Patient education is also important. Provision of information on the nature of the disease, how to use treatments, and selfmonitoring and assessment skills enables patients to self-manage their disease more effectively.
REFERENCES 1 British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on asthma management: a national clinical guideline. Thorax 2003; 58: (Suppl. 1): i1–94. 2 Barnes P J. Inhaled glucocorticoids for asthma. N Engl J Med 1995; 332: 868–75. 3 Suissa S, Ernst P, Benayoun S et al. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343: 332–6. 4 Holt S, Suder A, Weatherall M et al. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis. BMJ 2001; 323: 1–8. 5 Van der Molen T, Meyboom-De Jong B, Mulder H et al. Starting with a higher dose of inhaled corticosteroids in primary care asthma
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FURTHER READING Asthma. In: Gibson J G, Geddes D M, Costabel U et al., eds. Respiratory medicine. 3rd ed. Philadelphia: Saunders, 2003: 1202–444. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on asthma management: a national clinical guideline. Thorax 2003; 58: (Suppl. 1): i1–94. Holgate S T, Boushey H A, Fabbri L M, eds. Difficult asthma. London: Dunitz, 1999. O’Byrne P M, Thomson N C, eds. Manual of asthma management. 2nd ed. London: Saunders, 2001.
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