Am. J. Respir. Crit. Care Med., Volume 156, Number 2, August 1997, 609-616

Experimental Rhinovirus 16 Infection
Effects on Cell Differentials and Soluble Markers in Sputum in Asthmatic Subjects

KATRIEN GRÜNBERG, HERMELIJN H. SMITS, MIEKE C. TIMMERS, ERIK P. A. de KLERK, RADBOUD J. E. M. DOLHAIN, ELLIOT C. DICK, PIETER S. HIEMSTRA, and PETER J. STERK

Department of Pulmonology, Department of Virology, Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands; Department of Preventive Medicine, University of Wisconsin, Madison, Wisconsin

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  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.

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