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Abstract
Introduction and Objectives The majority of acute exacerbations of COPD are associated with viral infection and rhinoviruses are the most frequently detected species. Exacerbations represent a major unmet health need and mechanisms are poorly understood. The association between nitrative stress and virus induced exacerbations of COPD are unclear. To investigate this we used an experimental rhinovirus challenge study.
Methods Experimental rhinovirus challenge was performed in COPD (GOLD stage II) subjects (COPD, n=9), and non-obstructed control smokers (Smk, n=10) and non-smokers (NS, n=11). Rhinovirus infection was confirmed with quantitative PCR performed on nasal lavage and sputum samples collected at baseline and days 3, 5, 9, 12, 15, 21 and 42 post virus inoculation. Nitrite concentration was measured in sputum supernatant using the Griess assay, as a marker of total nitrative stress.
Results At baseline the geometric mean (95% CI) nitrite levels were similar between the groups studied (NS 5.13 (3.27 to 8.05); Smk 2.82 (1.37 to 5.80) and COPD 4.17 (3.04 to 5.72); p=0.281). Nitrite levels were significantly higher in COPD subjects on day 15 when compared to both control groups (geometric mean (95% CI) NS 7.94 (7.59 to 8.31); Smk 7.59 (4.41 to 13.04) and COPD 20.98 (13.92 to 31.36); p=0.008). (Abstract S50 figure 1). At every time point sampled there was a significant increase in nitrite concentration from baseline in COPD subjects, but not controls. The area under the curve for nitrite concentration over the time course for NS, Smk and COPD subjects was 18, 43 and 76 respectively (p<0.05).
Time course of sputum supernatant nitrite levels in COPD subjects and non-obstructed non-smoking (NS) and smoking (Smk) controls. Data presented mean +/-SEM. (* One-way ANOVA p<0.05).
Conclusions Rhinovirus infection is associated with increased nitrative stress in COPD subjects compared to smoking and non-smoking controls. This may play a role in COPD exacerbations.