Asymptomatic worsening of airway inflammation during low-dose allergen exposure in asthma: protection by inhaled steroids.
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 micro g 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 FEV(1) (PC(20)), and percent eosinophils, interleukin (IL)-5/interferon-gamma 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), FEV(1), 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-gamma messenger RNA ratio (p = 0.04), and in exhaled NO (p = 0.001), without worsening of symptoms, PEF, or baseline FEV(1) (p > 0.07). In the budesonide group, the changes in PC(20), 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.
de Kluijver
Josephine
J
Department of Pulmonology, Lung Function Laboratory, C2-P-62 Leiden University Medical Center, PO Box 9600, NL-2300 RC Leiden, The Netherlands. j.de_kluijver@lumc.nl
Evertse
Christine E
CE
Schrumpf
Jasmijn A
JA
van der Veen
Hilly
H
Zwinderman
Aeilko H
AH
Hiemstra
Pieter S
PS
Rabe
Klaus F
KF
Sterk
Peter J
PJ
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001249:Asthma / Q000150:complications / Q000188:drug therapy*; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000150:complications / Q000517:prevention & control*; D008297:Male; D012129:Respiratory Function Tests; D012140:Respiratory Tract Diseases / Q000139:chemically induced* / Q000150:complications / Q000517:prevention & control*; D012720:Severity of Illness Index
D000485:Allergens; D000893:Anti-Inflammatory Agents; D019819:Budesonide