PULMONOLOGY

add-on treatment in children whose asthma is insufficiently controlled by low doses of inhaled glucocorticosteroids, leukotriene modifiers provide moderate clinical improvements, including a significant reduction in exacerbations.

Not all patients respond, so if no benefit is evident after four weeks, the leukotriene modifiers should be withdrawn.

Leukotriene receptor antagonists are safe and effective for treatment of asthma in young children, from as early as six months of age. In pre-school children, LTRAs have been proposed as alternative first-line therapy to ICSs for episodic or mild persistent asthma, particularly in children who have difficulty in utilising inhalation treatment, with poor compliance, or with exerciseinduced bronchospasm( EIB). Their routine use as monotherapy in asthma in adults is not advised.

Another potential role for leukotriene modifiers is in those patients with co-morbid asthma and allergic rhinitis, as their anti-inflammatory action extends from the nasal mucosa to the bronchial tree. This is in line with the concept of the‘ united air way’ disease in which asthma and allergic rhinitis are regarded as manifestations of a single disorder, and treating one disease may affect the control of the other.

Side effects

Leukotriene modifiers are generally very well tolerated. Headaches and gastrointestinal upset are the most commonly encountered side effects. Skin rashes or flu like symptoms are much less common. Post marketing surveillance has shown agitation, irritability, anxiousness, insomnia and nightmares in a small proportion of patients.

3.1.3 Long-acting β2 agonists( LABAs)

Salmeterol and formoterol are LABAs currently available in

SA and are administered twice daily. LABAs can be added to low to medium doses of inhaled corticosteroids instead of increasing the dose of inhaled corticosteroid further. They are useful for control of nocturnal symptoms and exercise-induced asthma. Studies have reported improvements in peak flow and lung function with the addition of a LABA. However, the effect on symptoms, need for rescue medication and frequency of exacerbations has been less consistent. LABAs as monotherapy have been associated with an increase in asthma-related mortality so they must always be taken together with an inhaled corticosteroid. Combination products( i. e. those containing an inhaled corticosteroid and a LABA in the same device) are preferable to administration via separate inhalers.

Fixed combination inhalers ensure that the LABA is always accompanied by an ICS. Combination products available in South Africa are fluticasone / salmeterol and budesonide / formoterol. Newer inhaled steroid / LABA combinations include fluticasone furoate / vilanterol and mometasone furoate / formaterol will soon be available in SA.

LABAs have been inadequately studied in children under four years of age, so are currently not recommended in this age group. Some patients may not respond to LABAs. LABAs are generally well tolerated. Side effects are similar in type and frequency to those of shortacting bronchodilators( SABAs), and include muscle tremor, headache and palpitations. Both salmeterol and formoterol have sustained bronchodilator activity, but differ in the time of onset of action. The time of onset of salmeterol is delayed but formoterol has a rapid onset of bronchodilation( within 10- 15 minutes of administration)

similar to that of short-acting B2 agonists. In addition, formoterol has a wider dose range, whereas salmeterol has an upper dose limit of 50ug bd. Formoterol / ICS combinations are thus suitable to be used for both control and relief of asthma symptoms.

3.1.4 Slow-release( SR) Theophyllines

Theophylline can be used in the treatment of asthma mainly as a bronchodilator( 10-20 mg / kg / day), though it may also have anti-inflammatory effects at lower doses( 5-10 mg / kg / day).

The anti-inflammatory effects of theophylline are small( less than that of lowdose ICSs) and side effects are common.

Theophylline may be used as alternative, adjunctive therapy with ICSs in children older than five years old and in adults. They should not be used as monotherapy.

Most formulations of SR theophyllines have a 12 hour and some a 24 hour duration of action. They are administered orally. There is no role for oral short-acting theophyllines in chronic asthma.

Their disadvantages include a narrow therapeutic range, drug interactions and frequent side effects( nausea, vomiting, abdominal pain, gastro-oesophageal reflux, palpitations, insomnia, irritability and seizures). More serious side effects such as arrhythmias and gastric bleeding may occur. These side effects are mainly seen at doses > 10 mg / kg / day. The risk of adverse effects is reduced if treatment is initiated with daily doses around 5 mg / kg / day and then gradually increased to 10 mg / kg / day. Severe overdosing with theophylline can be fatal.

Monitoring of serum theophylline concentration is essential. Long-term treatment with theophylline is not generally recommended in young children because of its adverse effects.

clinical improvement happens rapidly

The Specialist Forum | Vol. 17 No. 4

May 2017 | 15