title: Experimental rhinovirus 16 infection. Effects on cell differentials and soluble markers in sputum in asthmatic subjects.
abstract: Asthma exacerbations are often associated with respiratory virus infections, particularly with rhinovirus. In the present study we investigated the effect of experimental rhinovirus 16 (RV16) infection on airway inflammation as assessed by analysis of hypertonic saline-induced sputum. Twenty-seven nonsmoking atopic, mildly asthmatic subjects participated in a placebo-controlled parallel study. RV16 (n = 19) or its diluent (n = 8) was nasally administered. Sputum inductions were performed at entry and on Days 2 and 9 after inoculation, and airway responsiveness to histamine (PC20) was measured on Days 4 and 11. Cell differentials and levels of albumin, eosinophil cationic protein (ECP), IL-8, and IL-6 were determined. The cellular origin of IL-8 was investigated by intracellular staining. RV infection was confirmed by culture and/or by antibody titer rise in each of the RV16-treated subjects. There were no significant changes in the sputum differentials of nonsquamous cells (MANOVA, p > or = 0.40). In the RV16 group, there was a significant increase in the levels of ECP, IL-8, and IL-6 at Day 2 after infection (p < 0.05), whereas the albumin levels did not change (p = 0.82). The levels of IL-8 and IL-6 remained elevated for as long as 9 d after infection (p < 0.05). The increase in the percentage of IL-8 positive cells at Day 2 after infection could be attributed to the increase in IL-8 positive neutrophils (p < 0.02). There was a significant decrease in PC20 at Day 4 (p = 0.02), which was no longer significant at Day 11 (p = 0.19). The decrease in PC20 correlated significantly with the increase in ECP in the first week (r = -0.60) and with the change in the percentage eosinophils in the second week after inoculation (r = -0.58). We conclude that experimental RV16 infection in atopic asthmatic subjects increases airway hyperresponsiveness in conjunction with augmented airway inflammation, as reflected by an increase in ECP, IL-8, and IL-6 in sputum. Our results suggest that the RV16-enhanced airway hyperresponsiveness is associated with eosinophilic inflammation.
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Grünberg
authors.forename: H H
authors.initials: HH
authors.lastname: Smits
authors.forename: M C
authors.initials: MC
authors.lastname: Timmers
authors.forename: E P
authors.initials: EP
authors.lastname: de Klerk
authors.forename: R J
authors.initials: RJ
authors.lastname: Dolhain
authors.forename: E C
authors.initials: EC
authors.lastname: Dick
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006632:Histamine; D006801:Humans; D008297:Male; D010850:Picornaviridae Infections / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D010919:Placebos; D012129:Respiratory Function Tests / Q000379:methods; D012229:Rhinovirus; D012995:Solubility; D013183:Sputum / Q000737:chemistry* / Q000166:cytology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D010919:Placebos; D006632:Histamine