Treating asthma to control symptoms
ASTHMA MEDICATIONS
Categories of asthma medications
When compared with medications used for other chronic diseases, most of the medications used for treatment of asthma have very favorable therapeutic ratios (Appendix Chapter 5). The pharmacological options for long-term treatment of asthma fall into the following three main categories.
• Controller medications: these are used for regular maintenance treatment. They reduce airway inflammation, control symptoms, and reduce future risks such as exacerbations and decline in lung function.
• Reliever (rescue) medications: these are provided to all patients for as-needed relief of breakthrough symptoms, including during worsening asthma or exacerbations. They are also recommended for short-term prevention of exercise-induced bronchoconstriction. Reducing and, ideally, eliminating the need for reliever treatment is both an important goal in asthma management and a measure of the success of asthma treatment.
• Add-on therapies for patients with severe asthma (Box 3-14, p.70): these may be considered when patients have persistent symptoms and/or exacerbations despite optimized treatment with high dose controller medications (usually a high dose ICS and a LABA) and treatment of modifiable risk factors (see Box 3-8, p.50).
Initial controller treatment
For the best outcomes, regular daily controller treatment should be initiated as soon as possible after the diagnosis of asthma is made, as the evidence suggests that:
• Early initiation of low dose ICS in patients with asthma leads to a greater improvement in lung function than if symptoms have been present for more than 2–4 years.146,147 One study showed that after this time, higher ICS doses were required, and lower lung function was achieved.148
• Patients not taking ICS who experience a severe exacerbation have a greater long-term decline in lung function than those who have already started ICS.92
• For patients with occupational asthma, early removal from exposure to the sensitizing agent and early treatment increase the probability of recovery.30
Recommended options for initial controller treatment in adults and adolescents, based on evidence (where available) and consensus, are listed in Box 3-4. The patient’s response should be reviewed, and treatment stepped down once good control is achieved. Recommendations for a stepwise approach to ongoing treatment are found in Box 3-5 (p.43).
Stepwise approach for adjusting asthma treatment in adults, adolescents and children 6–11 years old Once asthma treatment has been commenced (Box 3-4), ongoing treatment decisions are based on a cycle of assessment, adjustment of treatment, and review of the response. Controller medication is adjusted up or down in a stepwise approach (Box 3-5) to achieve good symptom control and minimize future risk of exacerbations, fixed airflow limitation and medication side-effects. Once good asthma control has been maintained for 2–3 months, treatment may be stepped down in order to find the patient’s minimum effective treatment (Box 3-7, p.49).
If a patient has persisting symptoms and/or exacerbations despite 2–3 months of controller treatment, assess and correct the following common problems before considering any step up in treatment:
• Incorrect inhaler technique
• Poor adherence
• Persistent exposure at home/work to agents such as allergens, tobacco smoke, indoor or outdoor air pollution, or to medications such as beta-blockers or (in some patients) non-steroidal anti-inflammatory drugs (NSAIDs)
• Comorbidities that may contribute to respiratory symptoms and poor quality of life
• Incorrect diagnosis.
Box 3-4. Recommended options for initial controller treatment in adults and adolescents
Presenting symptoms Preferred initial controller Asthma symptoms or need for SABA less than twice a month; no
waking due to asthma in last month; and no risk factors for
exacerbations (Box 2-2B, p17), including no exacerbations in the last year
No controller (Evidence D)*
Infrequent asthma symptoms, but the patient has one or more risk factors for exacerbations (Box 2-2B); e.g. low lung function, or exacerbation requiring OCS in the last year, or has ever been in intensive care for asthma
Low dose ICS** (Evidence D)*
Asthma symptoms or need for SABA between twice a month and twice a week, or patient wakes due to asthma once or more a month
Low dose ICS** (Evidence B)
Asthma symptoms or need for SABA more than twice a week Low dose ICS** (Evidence A)
Other less effective options are LTRA or theophylline
Troublesome asthma symptoms most days; or waking due to asthma once a week or more, especially if any risk factors exist (Box 2-2B)
Medium/high dose ICS† (Evidence A), or Low dose ICS/LABA†# (Evidence A) Initial asthma presentation is with severely uncontrolled asthma, or
with an acute exacerbation
Short course of oral corticosteroids AND Start regular controller treatment; options are
• High-dose ICS (Evidence A), or
• Moderate-dose ICS/LABA# (Evidence D) Before starting initial controller treatment
• Record evidence for the diagnosis of asthma, if possible
• Record the patient’s level of symptom control and risk factors, including lung function (Box 2-2, p17)
• Consider factors influencing choice of treatment (Box 3-3, p27)
• Ensure that the patient can use the inhaler correctly
• Schedule an appointment for a follow-up visit After starting initial controller treatment
• Review patient’s response (Box 2-2) after 2–3 months, or earlier depending on clinical urgency
• See Box 3-5 for recommendations for ongoing treatment and other key management issues
• Step down treatment once good control has been maintained for 3 months (Box 3-7, p.49).
ICS: inhaled corticosteroids; LABA: long-acting beta2-agonist; LTRA: leukotriene receptor antagonist; OCS: oral corticosteroids; SABA: short-acting beta2-agonist .
This table is based on evidence from available studies and consensus, including considerations of cost.
* These recommendations reflect the evidence for chronic airway inflammation in asthma even when symptoms are infrequent, the known benefit of low dose ICS in reducing serious exacerbations in broad asthma populations, and the lack of large studies comparing the effect of ICS and as-needed SABA alone on exacerbations in these populations.
**Corresponds to starting at Step 2 in Box 3-5.
† Corresponds to starting at Step 3 in Box 3-5.
# Not recommended for initial treatment in children 6–11 years.
Box 3-5. Stepwise approach to control symptoms and minimize future risk
ICS: inhaled corticosteroids; LABA: long-acting beta2-agonist; med: medium dose; OCS: oral corticosteroids. See Box 3-6 (p.44) for low, medium and high doses of ICS for adults, adolescents and children 6–11 years. See Chapter 3 Part D (p.65) for management of exercise-induced
bronchoconstriction.
* Not for children <12 years.
** For children 6–11 years, the preferred Step 3 treatment is medium dose ICS.
# Low dose ICS/formoterol is the reliever medication for patients prescribed low dose budesonide/formoterol or low dose beclometasone/formoterol maintenance and reliever therapy.
Tiotropium by mist inhaler is an add-on treatment for patients with a history of exacerbations; it is not indicated in children <12 years.
Comment [A3]: Box 3-5: Step 5 updated to include examples of tiotropium, omalizumab and mepolizumab. Age for tiotropium changed from 18 to 12. Symbols changed.
Deleted:
Deleted: ; anti-IgE: anti-immunoglobulin E therapy
Deleted: * Deleted: *
Deleted: theophylline is not recommended, and
Deleted: **
Deleted: # Deleted: soft-Deleted: 18
Box 3-6. Low, medium and high daily doses of inhaled corticosteroids Adults and adolescents (12 years and older)
Drug Daily dose (mcg)
Low Medium High
Beclometasone dipropionate (CFC)* 200–500 >500–1000 >1000 Beclometasone dipropionate (HFA) 100–200 >200–400 >400
Budesonide (DPI) 200–400 >400–800 >800
Ciclesonide (HFA) 80–160 >160–320 >320
Fluticasone furoate (DPI) 100 n.a. 200
Fluticasone propionate(DPI) 100–250 >250–500 >500 Fluticasone propionate (HFA) 100–250 >250–500 >500
Mometasone furoate 110–220 >220–440 >440
Triamcinolone acetonide 400–1000 >1000–2000 >2000 Children 6–11 years (for children 5 years and younger, see Box 6-6, p.110)
Beclometasone dipropionate (CFC)* 100–200 >200–400 >400 Beclometasone dipropionate (HFA) 50-100 >100-200 >200
Budesonide (DPI) 100–200 >200–400 >400
Budesonide (nebules) 250–500 >500–1000 >1000
Ciclesonide 80 >80-160 >160
Fluticasone furoate (DPI) n.a. n.a. n.a.
Fluticasone propionate (DPI) 100–200 >200–400 >400 Fluticasone propionate (HFA) 100–200 >200–500 >500
Mometasone furoate 110 ≥220–<440 ≥440
Triamcinolone acetonide 400–800 >800–1200 >1200
CFC: chlorofluorocarbon propellant; DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant; n.a. not applicable *Beclometasone dipropionate CFC is included for comparison with older literature.
Box 3-6 is not a table of equivalence, but of estimated clinical comparability. Categories of ‘low’, ‘medium’, and ‘high’
doses are based on published information and available studies, including direct comparisons where available. Doses may be country-specific depending on labelling requirements. Most of the clinical benefit from ICS is seen at low doses, and clear evidence of dose-response relationships is seldom available within the dose ranges evaluated for regulatory purposes. ‘High’ doses are arbitrary, but for most ICS are those that, with prolonged use, are associated with increased risk of systemic side-effects.
For new preparations, manufacturer’s information should be reviewed carefully; products containing the same molecule may not be clinically equivalent. For more detailed discussion see Raissy et al.95
In clinical practice, the choice of medication, device and dose should be based on assessment of symptom control, risk factors, patient preference, and practical issues (cost, ability to use the device, and adherence) (Box 3-3, p27). It is important to monitor the response to treatment and any side-effects, and to adjust the dose accordingly (Box 3-5, p31).
Once good symptom control has been maintained for 3 months, the ICS dose should be carefully titrated to the minimum dose, taken regularly, that will maintain good symptom control and minimize exacerbation risk, while reducing the potential for side-effects (Box 3-7). Patients who are being considered for a high daily dose of ICS (except for short periods) should be referred for expert assessment and advice, where possible (Box 3-14, p55).
More detail about asthma medications is provided in Appendix Chapter 5 (adults: Part A; children 6–11 years: Part B).