LEICESTER, UK—Strategies for asthma management typically involve periodic assessment of symptoms and lung function to tailor pharmacotherapy. A recent study has demonstrated that monitoring sputum eosinophilia, a marker of the underlying airway inflammation, allows medication to be adjusted more efficiently than is possible with traditional approaches. Management employing sputum monitoring was significantly better in preventing asthma exacerbations and hospitalizations, as well as in reducing sputum eosinophil counts.[1]

Principal investigator Ian D. Pavord, DM, FRCP, remarked, “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 patients with moderate to severe asthma. “Such an effect has implications for management of asthma in that it strongly supports the view that airway inflammation should be monitored regularly for the best treatment of this group of patients,” emphasized Dr. Pavord, Consultant Physician at Glenfield Hospital in Leicester.

Dr. Pavord and colleagues recruited patients with moderate to severe asthma to participate in the study. After a two-week run-in period during which baseline data were gathered, patients were randomized to conventional management under a modified version of the British Thoracic Society (BTS) guidelines or to sputum management for 12 months. All patients made monthly office visits for the first four months and once every two months thereafter. Thirty-four patients in each group remained in the study through follow-up.

Each patient in the BTS management group was treated based on traditional measurements of symptoms, peak expiratory flow, and ß2-agonist use. The progression of drug therapy was as follows:
• ß2-Agonists only as required.
• ß2-Agonist with the addition of a low-dose inhaled corticosteroid.
• Low-dose inhaled corticosteroid with a long-acting ß2-agonist.
• High-dose inhaled corticosteroid with the addition of a leukotriene antagonist, theophylline, nebulized bronchodilators, or oral prednisolone.
Treatment was considered inadequate and medications were increased if:
• An asthma exacerbation had occurred since the last visit.
• Average day or night symptom scores were 0.5 points greater than at baseline.
• Rescue ß2-agonist use was more than 0.5 puffs per day higher than at baseline.
• Peak expiratory flow was less than 80% of baseline personal best on two or more consecutive days.

If control was stable for at least two months, medication levels were reduced.

Each patient in the sputum management group was given the minimum dose of an inhaled or oral corticosteroid that could maintain a sputum eosinophil count of 3%. If a patient’s sputum eosinophil count was less than 1%, the corticosteroid dose was reduced without regard to asthma control. Eosinophil counts above 3% prompted an increase in anti-inflammatory treatment, and no change was indicated with counts of 1% to 3%. Bronchodilators were used for symptomatic relief; their dosages were adjusted based on the BTS protocol.

Sputum induction was successful in 87% of attempts. When a patient could not produce sputum, exhaled nitric oxide was employed as a surrogate marker for inflammation, with a goal of less than 8 ppb.

SPUTUM MANAGEMENT REDUCES INFLAMMATION, EXACERBATIONS

During the 12 months of treatment, the sputum management group had 63% lower average sputum eosinophil counts and 48% lower mean nitric oxide measurements than did the conventional management group. Furthermore, reduction in methacholine responsiveness was significantly better in the sputum group at both six months and 12 months.

More important, the incidence of severe exacerbations was significantly reduced among the sputum patients compared with the BTS patients (35 vs 109 exacerbations, respectively). Furthermore, significantly fewer patients in the sputum group were admitted to a hospital for asthma exacerbations (one, vs six patients in the BTS group).

Those undergoing sputum management also received fewer rescue courses of oral corticosteroids than did the BTS patients (24 vs 73 courses). In addition, fewer patients in the sputum group required nebulized bronchodilators (four vs 11).

CORTICOSTEROID DOSAGE REDUCED IN PATIENTS WITH NONEOSINOPHILIC INFLAMMATION

During the study, normal (below 1.9%) sputum eosinophil counts were consistently obtained from 13 patients in the sputum group and 11 of those receiving BTS management. A significant treatment difference was noted within this subgroup: Those managed with sputum monitoring had an average final decrease in inhaled corticosteroid dosage of 961 µg/d per patient, whereas the average dosage increased by 464 µg/d per patient among those managed according to the BTS protocol. “Thus, monitoring of airway inflammation allowed treatment to be targeted and used more efficiently,” the authors observe. Additionally, these findings provide further support “for the presence of an asthma phenotype that is noneosinophilic and resistant to corticosteroids,” they point out. Therefore, sputum eosinophil counts could prove valuable in identifying those asthma patients unlikely to benefit from a course of corticosteroids.

—Mimi Zucker, PhD

Reference
1. Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;360:1715-1721.

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