Rhinovirus-Induced Exacerbations of Asthma and COPD

Hershenson, Marc B.

In contrast to the study showing temperature restriction, subsequent studies showed that many RV strains replicate at body temperature. [4, 10] . For that matter, the temperature of the lower airways may decrease to 33-35 ∘ C during periods of increased minute ventilation (i.e., exercise) or cold temperature [11] . However, it was the advent of PCR for the detection of respiratory viruses which really changed the understanding of exacerbations. PCR-based studies examining the prevalence of virus identification among various cohorts of patients with chronic airways disease consistently show a higher prevalence of viral infection during exacerbations. Outpatient children who are sick with asthma exacerbations show anywhere from 62-81% positivity for viral infection versus only 12-41% of children who are well [12, 13] . Picornaviruses (primarily RV) were detected in 65% of cases, coronaviruses in 17%, influenza and parainfluenza viruses in 9%, and RSV in 5% [12] . Similar studies have been performed in hospitalized children, adult outpatients, and hospitalized adults [14] [15] [16] [17] [18] [19] [20] [21] . Adults seem to show a slightly lower prevalence of viral infection during exacerbations. Finally, 22 to 64% of patients with COPD exacerbations have virus identified by PCR versus 12 to 19% of nonexacerbating subjects [22] [23] [24] [25] [26] . Across all of these studies, RV makes up approximately 50% of the viruses isolated ( Table 2 ). The prevalence of rhinovirus may be even higher depending on the time of year. A recent study detected on RV in 82% of all children admitted to an emergency room for acute asthma between January and July [27] . Together, these studies suggest that viral infections cause exacerbation of asthma and COPD. Additional information that viruses indeed cause attacks of chronic airways disease comes from an analysis of emergency department presentations for asthma and COPD over the course of a calendar year. Exacerbations of asthma in children peak after school return from summer vacation (in North America, the first week of September), consistent with an infectious cause [28] . This "epidemic" of asthma exacerbations in children is primarily associated with fall rhinovirus It is now clear that rhinovirus can indeed infect the lower airways. Following experimental infection, RV has been detected in the lower airways by immunostaining, PCR, and in situ hybridization for positive-strand viral RNA [29] [30] [31] [32] . A study from the University of Wisconsin [30] was highly instructive. These investigators infected adult control and asthmatic subjects with RV16 and then stained biopsy tissue for RV16 capsid protein by immunohistochemistry. RV staining was clearly seen in the cytoplasm of cells in the epithelium ( Figure 1 ). However, staining was patchy and in some samples only 1 or 2 cells were positive. Other investigators have similarly noted that RV infects relatively few cells in the airway [33, 34] . Researchers from Imperial College, London [31] performed in situ hybridization of biopsies from experimentally infected patients and found positive-strand viral RNA in the epithelium. Interestingly, there was also sparse staining of cells in the subepithelial layer (there was insufficient detail to determine cell type).