An impact of activated Epstein–Barr Virus and HHV-6 on the course and control of bronchial asthma in children of the Amur Region

Abstract

The role of viral infection in bronchial asthma (BA) is well-known being reflected particularly in GINA. An effect of pneumotropic intracellular persistent herpesviruses on the course of BA is of particular interest. The most common viruses of this group are cytomegalovirus (CMV), EpsteinBarr virus (EBV), and human herpesvirus 6 (HHV-6). The CMV role has been discussed in our previous publications allowing us to focus here on EBV and HHV-6. We examined 167 children with BA that was diagnosed and clinically assessed in accordance with the current national clinical guidelines. Patients with controlled asthma (70 patients), partially controlled and uncontrolled asthma (97 patients) were stratified into several groups. The detection of EBV and HHV-6 DNA was carried out in throat swabs by PCR; the level of total and virus-specific IgA, IgM, IgG, IgE as well as serum level of IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-8 and TNF was assessed by enzyme linked immunosorbent assay; lymphocyte subpopulations were analyzed by flow cytometry. The dose of topic GCS was taken into account with reference to the fluticosone equivalent; the function of external respiration was studied by spirometry. It was revealed that EBV DNA was found in 14.2% of cases, whereas HHV-6 in 19.0% of cases, but 14.4% and 52.4% of patients, respectively, shed no pathogen-linked DNA. At the same time, patients with uncontrolled BA are significantly more likely to shed the pathogen DNA, so that EBV is released in 17.1% vs 4.5% of patients with controlled BA, HHV-6 in 19.5% vs 13.6%. On the contrary, children with controlled BA were significantly more often (63.6% vs 51.2%) negative for viral DNA shedding. Moreover, virus shedding was paralleled with higher levels of IL-5: it was as high as 0.91 pg/ml and 0.29 pg/ml for EBV and HHV-6, respectively; those shedding DNA of both pathogens vs no shedding had IL-5 at level of 0.25 pg/ml vs 0.11 pg/ml. Similar pattern was observed for higher total IgE: 184.5 IU for EBV, 113.1 IU for HHV-6, and 371.7 IU shedding both viruses vs 95.2 IU in without DNA pathogen shedding; lower level of FEV1: EBV 96.6%, HHV-6 98.8%, and 106.2% in patients shedding both viruses vs 109.8% in patients not shedding the pathogen DNA. Patients shedding EBV DNA require higher doses of topic GCS to achieve disease control: EBV 325.0 mg, HHV-6 186.4 mg; shedding both viruses 328.1 mg of topic GCS vs 198.6 mg in patients without pathogen DNA shedding. Thus, activation of both EBV and HHV-6 worsens BA control and aggravates its course, but EBV persistence has a more pronounced effect on the course and control of the disease.