Importantly, the value of measuring airway inflammation in sputum extends beyond these relatively short-term studies on corticosteroid responsiveness. Corticosteroid reduction studies16–17 have shown that sputum eosinophilia develops well before the onset of an exacerbation, suggesting that targeted therapy in asthma aimed at normalizing the sputum eosinophil count could lead to a reduction in asthma exacerbations. Indeed, there is now strong evidence from two independent studies11,18 supporting the importance of monitoring airway inflammation by sputum induction to reduce asthma exacerbations. In a randomized placebo-controlled trial,11 74 subjects with asthma were assigned to either a management strategy aimed at normalizing their sputum eosinophil count or standard clinical care. Patients in the sputum management group had significantly fewer severe asthma exacerbations than patients in the control group (35 exacerbations vs 109 exacerbations, p = 0.01) [Fig 2]
, and significantly fewer patients were admitted to hospital with asthma (one patient vs six patients, p = 0.047). The reduction in exacerbations was achieved without an increase in the total corticosteroid dose in the sputum guidelines group, as monitoring airway inflammation in the sputum guidelines group identified a group of patients with noneosinophilic asthma whose sputum eosinophil counts remained within the normal range; and in these subjects the dose of corticosteroids was reduced without evidence of deterioration in control subjects. In a second study,18 of 117 asthmatics entered into a 2-year follow-up multicenter, randomized, parallel-group effectiveness study, treatment directed at normalizing the sputum eosinophil count also led to a reduction in exacerbations (79 exacerbations vs 47 exacerbations, p = 0.04) and increased the time to first exacerbation by 213 days. This benefit was not at the expense of increased therapy in the intervention group. In this study, the inflammatory phenotype of the exacerbations were characterized; and in the sputum guidelines group, eosinophilic, but not noneosinophilic exacerbations were reduced. Interestingly, noneosinophilic exacerbations were more common (56%). The reduction in exacerbations was more apparent in those with severe disease. This suggests that it is probably most appropriate to apply this technique to the management of difficult-to-treat or refractory asthma, but that its use may not be generalizable to a primary care population.