title: Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?
abstract: There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤ 2,000 μg · day(-1) fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting β(2)-agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous β(2)-agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.
authors: Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. a.bush@rbht.nhs.uk
authors: A
authors: A
authors: Bush
authors: S
authors: S
authors: Pedersen
authors: G
authors: G
authors: Hedlin
authors: E
authors: E
authors: Baraldi
authors: A
authors: A
authors: Barbato
authors: F
authors: F
authors: de Benedictis
authors: K C
authors: KC
authors: Lødrup Carlsen
authors: J
authors: J
authors: de Jongste
authors: G
authors: G
authors: Piacentini
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D004351:Drug Resistance; D019317:Evidence-Based Medicine / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D018927:Anti-Asthmatic Agents; D000935:Antifungal Agents; D007166:Immunosuppressive Agents