Severe asthma

Key points

• Not all patients with “difficult-to-control” asthma have “severe asthma”. Many of them have either an incorrect diagnosis, or mild-moderate asthma with unrecognised aggravating factors, or are non-compliant with prescribed therapy.

• For a diagnosis of severe asthma, it is necessary to confirm the diagnosis of asthma, to evaluate and treat endogenous and exogenous aggravating factors, and to closely follow the patient for ≥6 months.

• Severe asthma is a heterogeneous condition with different phenotypes. Defining clinical phenotypes is necessary to improve understanding of underlying mechanisms, to help guide current treatment and to provide clues for novel therapeutic interventions.

• Despite intensive multi-drug treatment with high-dose inhaled and oral corticosteroids, many patients with severe asthma remain uncontrolled. There is an urgent need for new, more-effective treatments.

Educational aims

• To help the reader distinguish between “difficult-to-control”, “refractory” and “severe” asthma.

• To discuss the initial approach to and assessment of a patient with difficult-to-control asthma.

• To inform the reader how to recognise different clinical phenotypes of severe asthma.

• To outline management strategies and discuss treatment modalities.

Summary “Severe asthma” refers to asthma that remains difficult to control despite intensive multidrug therapy, extensive assessment and management of comorbidity, and long-term observation by an asthma specialist.

The three main clinical phenotypes of severe asthma include asthma with frequent severe exacerbations, asthma with chronic airflow limitation, and steroid-resistant asthma.

Many patients with severe asthma are oral-steroid dependent. Classical steroid-sparing drugs (gold, methotrexate, cyclosporin) are only weakly effective and have unacceptable side-effects. Monoclonal antibodies against immunoglobulin (Ig)E and tumour necrosis factor (TNF)-α have shown clinical benefit in subgroups of patients with severe asthma, and large studies are under way to confirm these promising findings.