Rhinovirus-induced airway inflammation in asthma: effect of treatment with inhaled corticosteroids before and during experimental infection.
Asthma exacerbations are frequently linked to rhinovirus infections. However, the associated inflammatory pathways are poorly understood, and treatment of exacerbations is often unsatisfactory. In the present study we investigated whether antiinflammatory treatment with inhaled corticosteroids prevents any rhinovirus-induced worsening of lower airway inflammation. To that end, we selected 25 atopic patients with mild asthma who underwent experimental rhinovirus 16 (RV16) infection, while receiving double-blind, placebo-controlled treatment with the inhaled corticosteroid budesonide (800 microg twice a day) throughout the study period, starting 2 wk before infection. We assessed inflammatory cell numbers in the bronchial mucosa as obtained by bronchial biopsies 2 d before and 6 d after RV16 infection, and analyzed those in relation to cold symptoms, changes in blood leukocyte counts, airway obstruction, and airway hyperresponsiveness. RV16 colds induced an increase in CD3(+) cells in the lamina propria (p = 0.03) and tended to decrease the numbers of epithelial eosinophils (p = 0.06) in both groups analyzed as a whole. The T cell accumulation was positively associated with cold symptoms. Budesonide pretreatment improved airway hyperresponsiveness (p = 0.02) and eosinophilic airways inflammation (p = 0.04). Yet it did not significantly affect the RV16-associated changes in the numbers of any of the inflammatory cell types. We conclude that RV16 infection by itself induces only subtle worsening of airway inflammation in asthma, which is not improved (or worsened) by inhaled corticosteroids. The latter finding is in keeping with the limited protection of inhaled corticosteroids against acute asthma exacerbations.
Grünberg
K
K
Department of Pulmonology, Department of Medical Decision Making, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Sharon
R F
RF
Sont
J K
JK
In 't Veen
J C
JC
Van Schadewijk
W A
WA
De Klerk
E P
EP
Dick
C R
CR
Van Krieken
J H
JH
Sterk
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001249:Asthma / Q000145:classification / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001706:Biopsy; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019819:Budesonide / Q000008:administration & dosage* / Q000494:pharmacology; D003139:Common Cold / Q000145:classification / Q000188:drug therapy* / Q000821:virology*; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D012229:Rhinovirus / Q000187:drug effects*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D019819:Budesonide