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Mild Exacerbations and Eosinophilic Inflammation in Patients With Stable, Well-Controlled Asthma After 1 Year of Follow-up^*

^* From the Hospital de la Santa Creu i Sant Pau, Barcelona, Catalunya, Spain.

Correspondence to: Joaquin Sanchis, MD, PhD, Departament de Pneumologia, Hospital de la Santa Creu i de Sant Pau, C/Sant Antoni Maria Claret, 167 08025-Barcelona, Spain; e-mail: jsanchis{at}hsp.santpau.es

Objectives: To determine the time to exacerbation and probability of a mild exacerbation of asthma, and the impact of eosinophilic inflammation on these parameters in patients with stable, well-controlled asthma.

Patients and methods: A cohort of 31 patients with stable, well-controlled asthma receiving inhaled steroid treatment regularly were followed up for 1 year or until a mild exacerbation occurred. Mild exacerbation was defined as symptoms of asthma lasting > 48 h with a fall in peak expiratory flow > 20%. FEV₁, provocative concentration of methacholine causing a 20% fall in FEV₁, eosinophil count, and eosinophilic cationic protein (ECP) levels in blood and in sputum were measured at the first visit and every 2 months.

Results: At baseline, the mean (SD) eosinophil count was 0.39 x 10⁹/L (0.21 x 10⁹/L) in blood and 13% (14%) in sputum; ECP was 30 µg/L (28 µg/L) in blood and 75 µg/L (85 µg/L) in sputum. Thirteen subjects experienced a mild exacerbation during the 1-year follow-up period. The mean time to mild exacerbation was 293 days (95% confidence interval [CI], 248 to 337 days), and the cumulative probability of not experiencing a mild exacerbation in 1 year was 49% (95% CI, 39 to 59%). An increased risk of mild exacerbation was associated with blood eosinophil count > 0.4 x 10⁹/L (relative risk 4.5; 95% CI of relative risk, 1.8 to 38.0), blood ECP > 20 µg/L (relative risk, 2.1; 95% CI of relative risk, 1.0 to 9.2), and sputum ECP > 40 µg/L (relative risk, 2.5; 95% CI of relative risk, 1.2 to 11.2), but was unassociated with other variables.

Conclusions: Patient with stable, well-controlled asthma are at risk of mild exacerbation during 1 year of follow-up despite regular inhaled steroid treatment. Eosinophilic inflammation expressed as eosinophil count and ECP is associated with higher risk of mild exacerbation.

Key Words: asthma • eosinophilic cationic protein • eosinophils • exacerbation • risk factors

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