Effects of allergic inflammation of the nasal mucosa on the severity of rhinovirus 16 cold.

BACKGROUND: Despite the strong association of asthma exacerbations with rhinovirus (RV) infection, inoculation of asthmatic subjects with RV only causes small changes in lower airway function, suggesting that RV infection is not itself sufficient to provoke asthma exacerbations. OBJECTIVE: Our purpose was to test whether allergic inflammation increases the airway response to RV infection. METHODS: We compared the severity of RV type 16-induced colds in 2 groups of 10 subjects with allergic rhinitis. One group received 3 nasal challenges with allergen and the other received challenges with placebo over the week before nasal inoculation with RV type 16 (4000 tissue culture infective dose 50% per subject). Subjects kept symptom diaries and were assessed with spirometry, methacholine challenge, nasal lavage, and sputum induction on days 2, 4, 7, 10, 15, and 30 after inoculation. RESULTS: The 2 groups developed equal rates of infection (90%), similar cold symptoms (Jackson score median [interquartile range], 11 [6-33] vs 20.5 [6-42] for allergen and placebo groups respectively, P =.54), and similar changes in cellular profile and in IL-6 and IL-8 concentrations in nasal lavage fluid and induced sputum after RV inoculation. The incubation period was significantly longer in the allergen group (2.5 [1-5.5] vs 1 [1-1] day, P =.03) and the duration of cold symptoms was shorter (5 [4-7] vs 8.5 [6-10] days, P =.008). We also found an inverse correlation between the percent of eosinophils in nasal lavage fluid before inoculation and the severity of cold symptoms (r = -0.58, P =. 008). CONCLUSION: In subjects with allergic rhinitis, augmented nasal allergic inflammation before inoculation with RV type 16 does not worsen the severity of cold symptoms but delays their onset and shortens their duration.

Effect of clarithromycin on experimental rhinovirus-16 colds: a randomized, double-blind, controlled trial.

PURPOSE: Macrolide antibiotics are frequently prescribed to patients with symptoms of a common cold. Despite their lack of proven antiviral activity, macrolide antibiotics may have anti-inflammatory actions, such as inhibition of mucus secretion and production of interleukins 6 and 8 by epithelial cells. Because the symptoms of rhinovirus colds are attributed to the inflammatory response to infection, we studied the effects of treatment with clarithromycin on the symptomatic and inflammatory response to nasal inoculation with rhinovirus. SUBJECTS AND METHODS: We performed a prospective, double-blind, controlled trial in 24 healthy subjects who were seronegative for antibodies to rhinovirus-16. Subjects were randomly assigned to receive either clarithromycin (500 mg) or trimethoprim-sulfamethoxazole (800/160 mg, as a control antibiotic) twice a day for 8 days, beginning 24 hours before inoculation with rhinovirus-16. RESULTS: All 12 subjects in each group were infected and developed symptomatic colds. The groups did not differ in the intensity of cold symptoms (median [25th to 75th percentile] score in the clarithromycin group of 25 [5 to 33] versus 21 [11 to 26] in the trimethoprim-sulfamethoxazole group, P = 0.86), weight of nasal secretions (25 g [8 to 56 g] versus 12 g [5 to 28 g], P = 0.27), or decline in nasal peak flow during the 8 days following viral inoculation. In both groups, similar and significant increases from baseline were observed in the numbers of total cells and neutrophils, and in the concentrations of interleukins 6 and 8, in nasal lavage fluid during the cold. The changes that we observed did not differ from those in an untreated historical control group. CONCLUSIONS: We conclude that clarithromycin treatment has little or no effect on the severity of cold symptoms or the intensity of neutrophilic nasal inflammation in experimental rhinovirus-16 colds.