POTENTIAL MASKING EFFECTS OF SALMETEROL ON AIRWAY INFLAMMATION IN ASTHMA

We hypothesized that regular use of long-acting P-agonists could delay recognition of (''mask'') increasing airway inflammation. We studied steroid-sparing and ''masking'' effects of salmeterol versus placebo i n 13 asthmatic individuals requiring greater than or equal to 1,500 mu g inhaled corticosteroid daily. Corticosteroid doses were reduced wee kly until criteria were met for an exacerbation or the corticosteroid was fully withdrawn. Subjects were restabilized on their original dose of inhaled corticosteroid for 4 wk before crossover to the alternativ e treatment. Subjects maintained symptom and peak expiratory flow (PEF ) diaries, and underwent weekly spirometric, methacholine challenge, s putum eosinophil, and serum eosinophil cationic protein (ECP) measurem ents. Mean corticosteroid dose was reduced by 87% during salmeterol tr eatment, versus 69% with placebo (p = 0.04). Sputum eosinophils increa sed before exacerbation despite stable symptoms, FEV1, and PEF. In the week before clinical exacerbation, sputum eosinophil counts were high er in the salmeterol-treatment arm (19.9 +/- 29.8% [mean +/- SD], vers us placebo 9.3 +/- 77.6%; p = 0.006). Five subjects showed > 10% sputu m eosinophilia before exacerbation during salmeterol treatment, as com pared with two receiving placebo. In this model, salmeterol controlled symptoms and lung function until inflammation became significantly mo re advanced. We conclude that the bronchodilating and symptom-relievin g effects of salmeterol can mask increasing inflammation and delay awa reness of worsening asthma.