Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations

Abstract

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils ≤2%; symptoms and spirometry were used to identify clinical control, exacerbations and other treatments. Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS, thus removing bias. First, the minimum treatment to maintain control was identified in 107 patients (Phase 1) and then this treatment was continued (Phase 2) for the remaining of the 2 yrs. The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation. The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed. The duration and number of exacerbations in Phase 1 were similar in both groups. In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS (62.7%) and 47 (37.3%) in the SS groups. The majority of the 126 exacerbations (101; 80.1%) were mild. The majority of the 102 exacerbations, where sputum examination was performed before any treatment (n = 70), were noneosinophilic. In the SS patients, the time to the first exacerbation was longer (by 213 days) especially in those considered to need treatment with a long acting β 2-agonist (by 490 days), the relative risk ratio was lower (by 49%), and the number of exacerbations needing prednisone was reduced (5 versus 15). This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone >250 μg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.