Elsevier

The Lancet

Volume 360, Issue 9347, 30 November 2002, Pages 1715-1721
The Lancet

Articles
Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial

https://doi.org/10.1016/S0140-6736(02)11679-5Get rights and content

Summary

Background

Treatment decisions in asthma are based on assessments of symptoms and simple measures of lung function, which do not relate closely to underlying eosinophilic airway inflammation. We aimed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a standard management strategy.

Methods

We recruited 74 patients with moderate to severe asthma from hospital clinics and randomly allocated them to management either by standard British Thoracic Society asthma guidelines (BTS management group) or by normalisation of the induced sputum eosinophil count and reduction of symptoms (sputum management group). We assessed patients nine times over 12 months. The results were used to manage those in the sputum management group, but were not disclosed in the BTS group. The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation, measured by induced sputum eosinophil count. Analyses were by intention to treat.

Findings

The sputum eosinophil count was 63% (95% CI 24–100) lower over 12 months in the sputum management group than in the BTS management group (p=0·002). Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group (35 vs 109; p=0·01) and significantly fewer patients were admitted to hospital with asthma (one vs six, p=0·047). The average daily dose of inhaled or oral corticosteroids did not differ between the two groups.

Interpretation

A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment.

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

Section snippets

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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