Table 3

Acute treatment of asthma attacks

Attack phenotypic characteristic	Agent	Strategy	Patient group/phenotype (all with asthma △)	Efficacy for treatment of attacks	Mechanism for treatment effect
Airway obstruction	β₂-agonists	Increasing dose	Adults	Recommended as part of acute treatment Increasing β₂-agonist use described prior to hospital attendance with severe exacerbation56 Effectiveness of SABA ↓ during exacerbation	β-adrenergic receptor stimulation → smooth muscle relaxation → bronchodilation Loss of effectiveness of SABA during attack: Subgroup of patients (<33%) with poor PEFR response to salbutamol described with ↑ airway obstruction, ↑ symptom duration and ↑ healthcare utilisation124 ↓ β₂-agonist FEV₁ response during exacerbations—during viral exacerbations β₂-adrenoceptor function is impaired58
	Short-acting anticholinergics	Systematic review: inhaled anticholinergics + β₂-agonists in emergency management of asthma125	Adults	Recommended in acute severe asthma Risk of admission ↓ 28%	Decreased cholinergic tone →smooth muscle relaxation →bronchodilation
	Magnesium	Systematic review: intravenous magnesium sulfate in acute asthma126	Adults	Recommended in acute severe asthma with poor initial response to inhaled bronchodilators odds of admission ↓ 27% (significant study heterogeneity/threshold for magnesium unclear)	Smooth muscle relaxation → bronchodilation
Airway inflammation	Inhaled steroids	Doubling dose: Based on symptom score, PEFR <80%127 Based on symptom score, morning PEFR ↓ ≥15%128	Age ≥13 years Attack within ≤12/12 Age ≥16 years Attack within ≤12/12	No effect on requirement for OCS No effect on requirement for OCS	No treatment effect observed
		Quadrupling dose during deteriorations in asthma control84	Adults Attack within ≤12/12	Chance of exacerbation over 12-month period (hazard rate) ↓ 20%	Unknown
		Quintupling ICS dose for 7 days at the early signs of loss of asthma control129	5–11 year old children	No effect	No treatment effect observed
		Systematic review130 : pre-emptive high-dose ICS in viral wheeze/asthma episodes (vs placebo)	Children ≤6 years with intermittent asthma/viral triggered wheeze n=422	Exacerbation rate↓ 35%	Reduction in (likely) virally triggered exacerbations Mechanism unclear
		Pooled RCT data131: inhaled budesonide/formoterol (SMART) versus fixed ICS strategy (assumption SMART group ↑ ICS dose during attack via ↑ reliever use)	Child and adult patients step 2–4 treatment ≥1 attack in last 12/12 Suboptimal control during run-in. n=12 507	↓ 36% in ‘cold-related’ exacerbations with SMART versus other strategies	Reduction in (likely) virally triggered exacerbations Mechanism unclear
		Meta-analysis132: systemic corticosteroids versus systemic corticosteroids + ICS for acute asthma treatment in ED	Child and adult patients admitted to ED with acute asthma 25 studies, n=2733	Odds of admission ↓ 27%	Unknown
	Oral steroids	Cochrane review133: early ED treatment of acute asthma with systemic corticosteroids	Child and adult patients, n=863	Odds of admission ↓ 60%	Unknown
	Oral steroids	Cochrane review: steroids to prevent relapse post-attack134	6 trials, n=374	Odds of relapse in week post-exacerbation ↓ 62%	Unknown
Airway infection	Antibiotics	Cochrane review135: antibiotics for exacerbations of asthma	6 studies (3 adult and 3 children aged 1–18 years), n=681	No effect (significant heterogeneity in study design/patient selection)	No treatment effect observed
Airway infection	Inhaled IFN-β treatment	14-day treatment with inhaled IFN-β within 24 hours of developing cold symptoms136	Adults Previous viral attack and ≥1 viral attack in last 24 months, n=147	No effect on 1⁰ outcome (ACQ). Morning PEFR ↑ in treatment group and both measures ↑ in severe asthma subgroup	? Due to impaired IFN expression in severe asthma35

ACQ, Asthma Control Questionnaire; ED, emergency department; ICS, inhaled corticosteroid; IFN-β, interferon β; OCS, oral corticosteroid; PEFR, peak expiratory flow rate; RCT, randomised controlled trial; SABA, short-acting β-agonist; SMART, steroid in maintenance and reliever therapy.