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Not all patients respond , so if no benefit is evident after four weeks , the leukotriene modifiers should be withdrawn .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