Increase in airway neutrophils after oral but not inhaled corticosteroid therapy in mild asthma.
BACKGROUND
Neutrophils, in addition to eosinophils, are prominent in the airways of patients with severe asthma who are usually on long-term oral and inhaled corticosteroid treatment. We determined whether inhaled or oral corticosteroid therapy can induce airway neutrophilia.


METHODS
We performed two separate placebo-controlled studies in which patients with mild asthma were treated with either prednisolone (30mg per day for 7 days; n = 9) or placebo tablets (n = 8), or with either inhaled budesonide (800 microg twice daily for 4 weeks; n = 6) or inhaled placebo (n = 6). Fiberoptic bronchoscopy was performed before treatment and at day 7 of oral treatment, and at day 28 of inhaled therapy. Bronchial sections were immunostained with an antibody to major basic protein for eosinophils, and with an antibody to neutrophil elastase for neutrophils. Induced sputum was obtained in the prednisolone study.


RESULTS
Neutrophils in airway submucosa increased after prednisolone from median 76 to 140/mm2 (P = 0.05); this change was higher than that after placebo (P = 0.04). Eosinophils decreased from 24 to 9/mm2 (P = 0.03), but this was not significantly different from placebo. Eosinophils and neutrophils, and levels of IL-8 and myeloperoxidase in induced sputum did not change after prednisolone. There was no change in neutrophil counts after budesonide, but the reduction in eosinophils was greater than placebo (P = 0.05). Budesonide improved bronchial responsiveness, but prednisolone did not.


CONCLUSIONS
Corticosteroid therapy by the oral but not inhaled route can induce neutrophil recruitment into the airways of patients with mild asthma. This could explain the increase in airway neutrophils observed in severe asthmatics treated with oral corticosteroids.
Nguyen
Lan Tien
LT
Department of Thoracic Medicine, Imperial College and Royal Brompton Hospital, National Heart and Lung Institute, London SW36LY, UK.
Lim
Sam
S
Oates
Timothy
T
Chung
Kian Fan
KF
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D019819:Budesonide / Q000008:administration & dosage*; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D011239:Prednisolone / Q000008:administration & dosage*; D013183:Sputum / Q000737:chemistry
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D019819:Budesonide; D011239:Prednisolone