ArticlesAsthma exacerbations and sputum eosinophil counts: a randomised controlled trial
Introduction
Asthma is characterised by variable airflow obstruction, airway hyper-responsiveness, and chronic airway inflammation, which is generally eosinophilic.1 It is a common disease that can cause much morbidity and mortality.2, 3 Although bronchodilators and moderate doses of regular inhaled steroids provide good control for most individuals with asthma, some develop severe exacerbations that are difficult to prevent and can lead to time off work, admission to hospital, and life-threatening attacks. Management decisions in asthma have traditionally been based on assessment of symptoms, airway function, and use of rescue β2 agonists.4 These features do not relate closely to the underlying eosinophilic airway inflammation5 and, consequently, clinicians cannot always predict the nature and extent of lower airway inflammation in patients with symptomatic asthma.6
Eosinophils are thought to have an important proinflammatory role in the pathogenesis of asthma. Eosinophils and their mediators are consistently identified in asthmatic but not healthy lungs, and suppression of eosinophil infiltration in clinical disease by glucocorticoids is usually associated with an amelioration of symptoms and disordered airway function.1 Although use of antibodies to interleukin 5 do not lend support to a role for eosinophils in development of early or late responses to allergen challenge,7 eosinophils are probably associated with asthma exacerbations.8 Furthermore, sputum eosinophilia develops several weeks before the onset of an exacerbation.8, 9 We therefore postulated that a management strategy that controls lower airway eosinophilic inflammation and symptoms would result in fewer exacerbations than would a traditional approach. Development of non-invasive techniques to assess airway inflammation has made it feasible to investigate such an approach to management of asthma.10
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Patients
We invited all patients aged 18–75 years who had a diagnosis of asthma and were thought to need continued hospital follow-up to participate. All patients were attending one of three specialist clinics at Glenfield Hospital, Leicester, UK, between March and October, 2000. We excluded patients if they were current smokers, had a smoking history of more than 15 pack years, or if they had clinically important comorbidity. We also excluded patients who were considered by their physician to comply
Results
We recruited 82 patients, of whom 74 were allocated to a management group; eight patients withdrew during the runin period and a further six patients withdrew during followup, leaving 34 patients in each group who completed the study (figure 1). No patient withdrew because of poor asthma control. The two treatment groups were matched at baseline for demographic and clinical features and similar numbers of patients in each group received an oral corticosteroid trial (table).
Sputum induction was
Discussion
Severe exacerbations of asthma needing courses of oral corticosteroids or admission are the most serious manifestation of this disease. They lead to asthma deaths, patient morbidity, and a high cost to the health service in terms of doctor consultations, drug use, and hospital beds.24 Our results show that a strategy directed at maintenance of a normal airway eosinophilic count caused a large reduction in the number of severe exacerbations in a group of patients with moderate to severe asthma
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