Key learning points
- A small percentage of patients with asthma may remain symptomatic despite intensive treatment
- Patients with severe asthma should be referred to a specialist centre for systematic assessment to confirm their diagnosis, optimise their management and characterise their phenotype
- Where appropriate, targeted asthma therapy can improve symptom control of severe asthma, as well as decrease reliance on oral corticosteroids and reduce unscheduled healthcare use
Asthma is the commonest long-term respiratory condition, affecting approximately 350 million people worldwide.1 Usually, symptom control can be attained by titration of inhaled therapies, with or without additional asthma controllers, according to guidelines.2 Approximately 5% of patients however, require high-dose inhaled corticosteroid/long-acting beta-agonist inhalers, plus another asthma controller (with or without maintenance oral corticosteroid therapy) to achieve disease control – or they may remain symptomatic even with intensive treatment.3
Despite the array of treatments available, approximately 1,000 deaths each day are attributed to asthma globally.1 Personal and population-level costs appear to be rising, with the annual cost of asthma in the USA estimated at $81.9 billion.4
Justin, a 40-year-old man, was referred to the severe asthma clinic. He had a history of nasal polyposis and recurrent sinusitis. There was no childhood history of asthma or atopy. He had never been a smoker and did not drink alcohol or describe any relevant occupational exposures.
Justin had been diagnosed with asthma at the age of 32. Initially, his predominant symptom was a nocturnal cough, although over the subsequent eight years he became short of breath on exertion. He had required six hospital admissions in the year before referral and noted that his peak expiratory flow rate varied between 240 and 260 L/min. Due to recurrent exacerbations, he described taking oral corticosteroids ‘almost constantly’ in the preceding two-year period.
On referral, Justin was taking budesonide/formoterol 200/6 two puffs four times a day, salbutamol, aminophylline, loratadine, omeprazole, calcium and nasal budesonide. Maintenance prednisolone (10–20mg daily) had been initiated. His weight had increased from 96 to 100kg (body mass index 31.9kg/m2). He had developed type 2 diabetes mellitus, treated with oral hypoglycaemics, and obstructive sleep apnoea, which was managed with continuous positive airways pressure.
On referral, Justin’s blood eosinophil count was 400 cells/µL (normal range: 100–500 cells/µL) and serum IgE was 140 IU/ml (normal range: 3–150 IU/ml), with no evidence of sensitisation to a perennial aeroallergen. Aspergillus serology was negative. His FEV1 was 1.7L and FVC 3.07 (respectively 51.5% and 75.0% predicted).
Aminophylline was stopped due to lack of efficacy. Justin was commenced on treatment with an anti-IL5 monoclonal antibody.
Two years after starting anti-IL5 treatment, Justin’s prednisolone dose has been successfully weaned to 5mg daily. His weight has decreased by 12kg. Severe exacerbations have been avoided. Symptom control and spirometry figures have been maintained despite the significant reduction in oral corticosteroid dose. Treatment for his type 2 diabetes and obstructive sleep apnoea was being maintained.
Asthma has long been associated with eosinophilia.5 Eosinophilic asthma is an important phenotype which may present in adulthood and is often associated with other clinical features such as nasal polyposis and corticosteroid-responsiveness.6
In centres with access to sputum cytology, a cut-off point of 3% is commonly used to define sputum eosinophilia. The majority of centres however rely on the blood eosinophil count in order to identify patients with eosinophilic asthma. Eosinophils have a circulating half-life of approximately 18 hours.7 The blood eosinophil count can fluctuate greatly over time, increasing during exacerbations and being suppressed by corticosteroid therapy. The identification of a high eosinophil count can therefore require repeated measurements and blood eosinophilia may only be revealed during exacerbations or if asthma therapy is de-escalated.
Until recent years, if a patient with eosinophilic asthma remained symptomatic despite maximal conventional asthma management, therapeutic options were limited, and maintenance oral corticosteroid therapy would often be added. Long-term oral corticosteroid treatment is associated with numerous adverse effects including increased risk of severe infections, peptic ulcers, diabetes mellitus and bone fractures.8
Targeted anti-eosinophil therapies aim to reduce the exacerbation frequency and minimise the cumulative exposure to oral corticosteroids for this patient group.
Patients with severe asthma should be referred to a specialist centre and undergo a systematic assessment under the care of a multidisciplinary team in order to confirm their diagnosis, optimise their management and characterise their phenotype. Where appropriate, targeted asthma therapy should be offered, which can improve symptom control, decrease reliance on oral corticosteroids with their associated co-morbidities and reduce unscheduled healthcare use.
Claire McBrien, respiratory registrar/clinical research fellow and Professor Andrew Menzies-Gow, consultant respiratory physician
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