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Asymptomatic Worsening of Airway Inflammation during Low-Dose Allergen Exposure in Asthma

Protection by Inhaled Steroids

Departments of Pulmonology and Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands

Correspondence and requests for reprints should be addressed to Josephine de Kluijver, Lung Function Laboratory, C2-P-62 Leiden University Medical Center, P.O. Box 9600, NL-2300 RC, Leiden, The Netherlands. E-mail: j.de_kluijver{at}lumc.nl

Asthma is a chronic inflammatory disease that persists even during adequate therapy and asymptomatic episodes. We questioned whether "silent" chronic allergen exposure can induce and maintain airway inflammation and whether this still occurs during regular treatment with inhaled steroids. Twenty-six patients with house dust mite allergy and mild asthma (dual responders) participated in a parallel, double-blind study. All patients inhaled a low-dose of allergen on 10 subsequent working days (Days 1–5, 8–12). They were treated with 400 µg budesonide once daily (n = 13) or placebo (n = 13) from Days -3 to 19. At baseline (Day -6) and on Days 5, 12, and 19 we measured the provocative concentration of methacholine causing a 20% fall in FEV₁ (PC₂₀), and percent eosinophils, interleukin (IL)-5/interferon- messenger RNA ratio (in sputum cells by real-time reverse transcription-polymerase chain reaction [RT-PCR]), and eosinophilic cationic protein (ECP) in induced sputum. Symptoms, peak expiratory flow (PEF), FEV₁, and exhaled nitric oxide (NO) were recorded repeatedly during the study. In the placebo group, repeated low-dose allergen exposure resulted in a significant increase in sputum eosinophils (p = 0.043), ECP (p = 0.011), IL-5/IFN- messenger RNA ratio (p = 0.04), and in exhaled NO (p = 0.001), without worsening of symptoms, PEF, or baseline FEV₁ (p > 0.07). In the budesonide group, the changes in PC₂₀, sputum ECP, and exhaled NO were significantly different as compared with the placebo group (p < 0.03). We conclude that repeated low-dose allergen exposure in asthma can lead to airway inflammation without worsening of symptoms, which can be prevented by inhaled steroid treatment. This suggests that antiinflammatory therapy is beneficial during allergen exposure, even during asymptomatic episodes.

Key Words: asthma • airway hyperresponsiveness • induced sputum • eosinophils • inhaled steroids

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