Reliever = bronchodilator
Preventer = anti-inflammatory
Symptom controller = long-acting β2-agonist (LABA)
It is useful to teach patients the concept of the ‘preventer’ and the ‘reliever’ for their asthma treatment. The pharmacological treatment of asthma is summarised in TABLE 82.3.
Table 82.3Pharmacological treatment of asthma5 ||Download (.pdf) Table 82.3 Pharmacological treatment of asthma5
| || || ||Vehicle of administration |
|Generic types ||Examples ||Nebulising solution ||Oral ||Aerosol (metered dose inhalation) ||Dry powder (inhalation) ||Injection |
|1 β2-adrenoceptor agonists ||Salbutamol ||Ventolin ||✓ ||✓ ||✓ ||✓ ||✓ |
|Salmeterol ||Serevent || || ||✓ ||✓ || |
|Terbutaline ||Bricanyl ||✓ ||✓ || ||✓ ||✓ |
|Eformoterol ||Foradile, Oxis || || || ||✓ || |
|Indacaterol ||Onbrez || || || || || |
|Adrenaline || || || || || ||✓ |
|2 Anticholinergics ||Ipratropium bromide ||Atrovent ||✓ || ||✓ || || |
|3 Methylxanthines ||Theophylline ||Nuelin || ||✓ || || || |
|Aminophylline || || || || || ||✓ |
|Mast cell stabilisers |
| ||Sodium cromoglycate ||Intal ||✓ || || |
|✓ || |
| ||Nedocromil sodium ||Tilade || || ||✓ || || |
|Corticosteroids—for inhalation |
| ||Beclomethasone ||QVAR || || ||✓ ||✓ || |
| ||Budesonide ||Pulmicort ||✓ || ||✓ ||✓ || |
| ||Ciclesonide ||Alvesco || || ||✓ || || |
| ||Fluticasone ||Flixotide ||✓ || ||✓ ||✓ || |
|Combination reliever (LABA) + preventer (ICS)—fixed combination MDI |
|Salmeterol + fluticasone (Seretide) || || || ||✓ ||✓ || |
|Eformoterol + fluticasone (Flutiform) || || || ||✓ || || |
|Eformoterol + budesonide (Symbicort) || || || ||✓ ||✓ || |
|Vilanterol + fluticasone (Breo ellipta) || || || || ||✓ || |
|Leucotriene antagonists |
‘Preventer’ drugs: anti-inflammatory agents
These medications are directed towards the underlying abnormalities—bronchial hyper-reactivity and associated airway inflammation. Treatment with a ‘preventer’ is recommended if asthma episodes are >3/week or those who use SABA >3 times a week.
oropharyngeal candidiasis, dysphonia (hoarse voice)—less risk with once daily ciclesonide
bronchial irritation: cough
adrenal suppression (doses of 2000 mcg/daily; sometimes as low as 800 mcg)
Note: Rinse mouth with water and spit out after using inhaled steroids.
ICSs have a flat dose–response curve so it may not be necessary to prescribe above ICS doses considered high—beclomethasone or budesonide 1000 mcg/day or fluticasone 500 mcg/day. For newly diagnosed patients with mild-to-moderate asthma ‘start low and step up prn’ (e.g. 250–400 mcg/day).6 Step down the dose when safe to do so.
Note: Most adults and older adolescents with asthma should be on long-term inhaled corticosteroid therapy.1
Prednisolone is used mainly for exacerbations. It is given with the usual inhaled corticosteroids and bronchodilators.
these are minimal if drug is used for short periods
long-term use has significant side effects: osteoporosis, glucose intolerance, adrenal suppression, thinning of skin and easy bruising
Note: Short-term oral corticosteroids can be ceased abruptly.
These are sodium cromoglycate (SCG) and nedocromil sodium. SCG is available as dry capsules for inhalation, metered dose aerosols and a nebuliser solution. They are often inhaled via a spacer in children. Adverse effects are uncommon; local irritation may be caused by the dry powder. Systemic effects do not occur.
Nedocromil is used for frequent episodic asthma in children over 2 years of age for the prevention of exercise-induced asthma and the treatment of mild-to-moderate asthma in some adults. The initial dose is 2 inhalations qid. Adverse effects are uncommon.
These drugs, which include montelukast and zafirlukast, are very useful for seasonal asthma and aspirin-sensitive asthma and reduce the need for inhaled steroids or offer an alternative for those who cannot tolerate ICSs or have trouble using an inhaler. Favourable evidence is based on a small number of trials only, mostly in children but some adults benefit.9 Montelukast is taken as a 5 or 10 mg chewable tablet once daily.
Indications for preventive therapy10
Guidelines for introducing preventive asthma therapy in adults and children include any of the following:
requirement of β2-agonist >2 days per week or >1 canister every 3 months (excluding pre-exercise)
symptoms (non-exercise) >2 times per week between attacks
any symptoms during the night or on waking
spirometry showing reversible airflow obstruction during asymptomatic phases
asthma significantly interfering with physical activity despite appropriate pre-treatment
asthma attacks ≥twice per month
infrequent asthma attacks but severe or life-threatening
‘Reliever’ drugs or bronchodilators
The three groups of bronchodilators are:
These drugs stimulate the β2 adrenoreceptors and thus relax bronchial smooth muscle. Inhalation is the preferred route of delivery; the vehicles of administration include metered dose inhalation, a dry powder, and nebulisation where the solution is converted to a mist of small droplets by a flow of oxygen or air through the solution.
Oral administration of β2-agonists is not required. The inhaled drugs produce measurable bronchodilation in 1–2 minutes and peak effects by 10–20 minutes. The traditional agents such as salbutamol and terbutaline are short-acting preparations. The new longer-acting agents (LABA) include salmeterol, eformoterol and vilanterol.
These are to be used in combination with an ICS, not as monotherapy.11
These oral drugs may have complementary value to the inhaled agents but tend to be limited by side effects and efficacy.
Anti-IgE monoclonal antibodies
These newer agents (e.g. omalizumab) bind IgE without activating mast cells. They are directed for use in patients >12 years of age with moderate to severe allergic eosinophilic asthma who have been treated by ICS and who have raised serum IgE levels. They are given by SC injection.
Antibiotic use for chronic asthma12
Antibiotics are not recommended apart from clinical evidence of super-respiratory infection. However, a recent Australian study concluded that ‘adults with persistent symptomatic asthma experience fewer exacerbations and improved quality of life when treated with oral azithromycin (500 mg tds) for several weeks’. Its clinical use remains uncertain.
Current treatment supports the initial treatment (summarised in TABLE 82.2) of a SABA with low to moderate doses of ICS with estimated equivalent doses shown in the table.
Initiate therapy sufficient to achieve best lung function promptly.
Wean inhaled corticosteroids to the minimum dose needed to maintain adequate asthma control.
This term is reserved for those medications that are taken prior to known trigger factors, particularly for exercise-induced asthma.
Exercise-induced asthma (options)
β2-agonist inhaler (puffer): two puffs 5 minutes immediately before exercise last 1–2 hours. LABA such as salmeterol and eformoterol are more effective if used with ICS.
SCG or nedocromil, two puffs
Combination β2-agonist + SCG (5–10 minutes beforehand)
Montelukast 10 mg (less in children ≥2 years) oral daily or 1–2 hours beforehand
Paediatricians often recommend a non-drug warm-up program as an alternative to medication.
The three-step asthma control plan13,14
The National Asthma Council of Australia has developed the following follow-up plan, summarised in FIGURE 82.3.
Asthma: ongoing management steps
Source: Reprinted with permission from NPS Medicine Wise
Step 1: Assess asthma symptom control and identify the patient’s risk factors.
Assess asthma symptom control over the previous 4 weeks.
Assess the patient’s risk factors.
Exclude factors contributing to poor control before intensifying preventer treatment:
– check adherence
– check inhaler technique
– check inhaler device is appropriate
– consider that symptoms may be due to alternative or comorbid diagnoses
Step 2: Treat and adjust to achieve good control.
All patients should have a reliever inhaler for as-needed use.
Most patients can achieve well-controlled asthma with low-dose ICS.
Trial low-dose ICS before ICS/LABA fixed combination therapy15
Reserve ICS/LABA as a later option. This combination is too readily used in Australia.
Where appropriate, step down treatment.
Schedule follow-up visit.
Step 3: Review response and monitor to maintain control.
A general management plan for chronic asthma is summarised in FIGURE 82.4.
Stepped approach to adjusting asthma medication in adults14
Source: Reprinted with permission from NPS Medicine Wise
Correct use of the asthma MDI (puffer)
faulty inhaler technique occurs in at least one-third of users?
in faulty technique, up to 90% of the medication sticks to the mouth and does not reach the lungs?
it is the inhalation effort—not the pressure from the aerosol—that gets the medication to the lungs?
it is important to instruct patients properly and check their technique regularly?
The open-mouth technique and the closed-mouth technique are the main methods, and both are effective but the closed-mouth technique is preferred. Both techniques are suitable for most adults. Most children from the age of 7 can learn to use puffers quite well.
The closed-mouth technique
Using the metered dose inhaler: the closed-mouth technique
Instructions for patients:
Remove the cap. Shake the puffer vigorously for 1–2 seconds. Hold it upright (canister on top).
Place the mouthpiece between your teeth (do not bite it) and close your lips around it.
Breathe out slowly and gently to a comfortable level.
Tilt your head back slightly with your chin up.
Just as you then start to breathe in (slowly) through your mouth, press the puffer firmly, once. Breathe in as far as you can over 3–5 seconds. (Do not breathe in through your nose.)
Remove the puffer from your mouth and hold your breath for about 10 seconds; then breathe out gently.
Breathe normally and then repeat the inhalation if you need to.
The usual dose of standard MDI is one or two puffs (adult) every 3–4 hours for an attack (four puffs in children).
If you do not get adequate relief from your normal dose, contact your doctor.
It is quite safe to increase the dose, such as to 4–6 puffs.
If you are using your inhaler very often, it usually means your other asthma medication is not being used properly. Discuss this with your doctor.
The Autohaler is a breath-activated MDI which can improve lung deposition in patients with poor inhaler technique.
The Turbuhaler is a dry powder delivery system that is widely used as an alternative to the MDI. It is a breath-activated device.
Other dry powder devices are the Accuhaler and Diskhaler.
Spacers versus nebulisers
Both MDIs via a spacer and dry powder inhalers are at least as effective as a nebuliser for treating acute exacerbations in both adults and children.16 They are considerably cheaper and more readily available than an electrically powered device.
Summary of devices
Breath-activated MDIs: Autohaler
Breath-activated dry powder inhalers: Accuhaler, Aerolizer, Diskhaler, Rotahaler, Spinhaler, Turbuhaler
Large-volume spacer: Nebuhaler, Volumatic
Small-volume spacer: Aerochamber, Breath-A-Tech