Analysis of induced sputum before and after withdrawal of treatment with inhaled corticosteroids in asthmatic patients

Abstract

To assess whether sputum eosinophilia predicts the recurrence of asthma symptoms after withdrawal of therapy in moderate stable asthmatics on low-dose inhaled corticosteroids. Randomized, double-blind, placebo-controlled study involving 30 subjects with stable asthma, asymptomatic, with low PEF variability measured over two run-in weeks, on treatment with low-dose inhaled beclomethasone dipropionate (BDP, 250 microgram b.i.d. in the last 3 months). At the end of the run-in, all patients underwent a methacholine challenge test and sputum induction (T1). They then stopped therapy and received either placebo (20 subjects, study group) or BDP at the same dose as in the previous 3 months (10 subjects, control group). They continued to monitor PEF and symptom score for 3 months, or until asthma symptoms recurred (diurnal and nocturnal symptom score >/=2 on two consecutive days). At the end of the study (T2), i.e., either within 5 days from the beginning of asthma symptoms or after 3 months in subjects without recurrence of asthma symptoms, all subjects repeated the methacholine challenge test and sputum induction. In the placebo-treated group, sputum eosinophils at T1 were significantly higher in subjects who subsequently developed recurrence of asthma symptoms (n = 7) after cessation of treatment than in subjects who remained asymptomatic for 3 months (8.2% [0-56.6] vs 0.9% [0-11], P < 0.05). At the time of recurrence of asthma symptoms, sputum eosinophil percentages significantly increased (from 8.2% [0-56.6] to 16.6% [5.8-73.6], P < 0.05). The positive predictive value of sputum eosinophils for the recurrence of asthma symptoms was 71%, while the negative predicting value was 84%. In the BDP-treated control group, none of the subjects experienced recurrence of asthma symptoms, and sputum eosinophil percentages measured at the beginning (T1) and at the end (T2) of the study were similar. Sputum eosinophil percentages may vary over a wide range in asthmatic subjects, although regularly treated and apparently well controlled. However, high sputum eosinophil percentages are related to early recurrence of asthma symptoms after cessation of inhaled corticosteroids.