title: Are rhinovirus-induced airway responses in asthma aggravated by chronic allergen exposure?
abstract: Airway inflammation in asthma may represent a favorable environment for respiratory viral infections, augmenting virus-induced exacerbations in asthma. We postulated that repeated low-dose allergen exposure preceding experimental rhinovirus 16 (RV16) infection increases the severity of RV-induced airway obstruction and inflammation. Thirty-six house dust mite-allergic patients with mild to moderate asthma participated in a three-arm, parallel, placebo-controlled, double-blind study. Patients inhaled a low dose of house dust mite allergen for 10 subsequent working days (Days 1-5 and 8-12) and/or were subsequently infected with RV16 (Days 15 and 16). Allergen exposure resulted in a significant fall in FEV1 (p < 0.001) and provocative concentration of histamine causing a 20% fall in FEV1 (p < 0.001) and an increase in exhaled nitric oxide (p < 0.001) and percentage of sputum eosinophils (p < 0.001). RV16 infection led to a fall in FEV1 (p = 0.02) and increases in the percentage of sputum neutrophils (p = 0.01), sputum interleukin-8 (p = 0.04), and neutrophil elastase (p = 0.04). Successive allergen exposure and RV16 infection had no synergistic or additive effect on any of the clinical or inflammatory outcomes. In conclusion, repeated low-dose allergen exposure and RV16 infection induce distinct inflammatory profiles within the airways in asthma without apparent interaction between these two environmental triggers. This suggests that preceding allergen exposure, at the used dose and duration, is not a determinant of the severity of RV-induced exacerbations in patients with mild to moderate asthma.
authors.affiliation: Lung Function Laboratory, Department of Pulmonology, Leiden University Medical Center, P.O. Box 9600, NL-2300 RC Leiden, The Netherlands.
authors.forename: Josephine
authors.initials: J
authors.lastname: de Kluijver
authors.forename: Christine E
authors.initials: CE
authors.lastname: Evertse
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Sont
authors.forename: Jasmijn A
authors.initials: JA
authors.lastname: Schrumpf
authors.forename: Christel J G
authors.initials: CJ
authors.lastname: van Zeijl-van der Ham
authors.forename: Claire R
authors.initials: CR
authors.lastname: Dick
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000502:physiology*; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000502:physiology*; D001249:Asthma / Q000209:etiology* / Q000821:virology; D002908:Chronic Disease; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010850:Picornaviridae Infections / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012229:Rhinovirus / Q000502:physiology*; D012720:Severity of Illness Index
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides