Impact of respiratory viruses on the course of chronic obstructive pulmonary disease: Towards optimizing treatment

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The paper analyzes the currently available data on the impact of respiratory viruses (RVs) on the exacerbations and clinical phenotype of chronic obstructive pulmonary disease (COPD), as well as on the molecular mechanisms of this impact. It emphasizes the role of acute respiratory viral infections (ARVI), primarily rhinovirus infections (RVI) as the most important triggers of COPD exacerbations and the causes of their severe and long-term course. Particular attention is given to ARVI-induced secondary bacterial infections that worsen COPD exacerbations. The mechanisms of how RVs potentiate chronic inflammation and remodeling of the airway, which are caused by tobacco smoke, are depicted. There are arguments that there is a much greater correlation of the acute episodes showing the more severe respiratory symptoms of COPD with ARVI than can be found by molecular methods for RV verification. The body’s genetic and/or acquired excessive response to viral invasion does not reflect the efficacy of antiviral defense and is an endogenous damaging factor in this situation. The role of RVs in the formation of the clinical phenotypes of COPD with frequent exacerbations remains debatable. The need for a search and more active practical introduction of means to prevent virus-induced COPD exacerbations appears obvious. In this regard, the authors identify chemical and mechanical polyvalent bacterial lysates for oral and sublingual administration. In addition to nonspecific stimulation of antiviral defense, these medicines induce antigen-specific mucosal and systemic reactions against bacterial pathogens. The role of ARVI pathogens in COPD exacerbations deserves a greater practical attention focused towards optimizing the treatment of this social disease.


  1. Yach D., Hawkes C., Gould C.L., Hofman K.J. The global burden of chronic diseases: overcoming impediments to prevention and control. JAMA 2004; 291: 2616—2622.
  2. Bousquet J., Khaltaev N. (ed.) Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach. Geneva: World Health Organization; 2007.
  3. Landis S.H., Muellerova H., Mannino D.M. et al. Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012—2013. Int J COPD 2014; 9: 597—611.
  4. Central Intelligence Agency. The World Factbook 2013—14. Washington, DC: Central Intelligence Agency; 2014.
  5. Федеральная служба государственной статистики. Численность населения Российской Федерации по полу и возрасту на 1 января 2012 года.
  6. Mathers C.D., Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3: e442.
  7. Frickmann H., Jungblut S., Hirche T.O. et al. The influence of virus infections on the course of COPD. Eur J Microbiol Immunol (Bp) 2012; 2 (3): 176—185.
  8. Калюжин О.В. Острые респираторные вирусные инфекции: современные вызовы, противовирусный ответ, иммунопрофилактика и иммунотерапия. М: Медицинское информационное агентство 2014.
  9. Чучалин А.Г., Айсанов З.Р., Авдеев С.Н. и др. Федеральные клинические рекомендации по диагностике и лечению хронической обструктивной болезни легких. Рус мед журн 2014; 5: 331—347.
  10. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease (Updated 2014). Global Initiative for Chronic Obstructive Lung Disease, Inc 2014.
  11. Глобальная стратегия диагностики, лечения и профилактики хронической обструктивной болезни легких (пересмотр 2011 г.). Пер. с англ. Под ред. А.С. Белевского. М: Российское респираторное общество 2012.
  12. Anthonisen N.R. OM-85 BV for COPD. Am J Respir Crit Care Med 1997; 156: 1713—1714.
  13. Collet J.P., Shapiro S., Ernst P. et al. Effect of an immunostimulating agent on acute exacerbations and hospitalizations in COPD patients. Am J Respir Crit Care Med 1997; 156: 1719—1724.
  14. Li J., Zheng J.P., Yuan J.P. et al. Protective effect of a bacterial extract against acute exacerbation in patients with chronic bronchitis accompanied by chronic obstructive pulmonary disease. Chin Med J 2004; 117: 828—834.
  15. Singanayagam A., Joshi P.V., Mallia P., Johnston S.L. Viruses exacerbating chronic pulmonary disease: the role of immune modulation. BMC Medicine 2012; 10: 27.
  16. Mohan A., Chandra S., Agarwal D. et al. Prevalence of viral infection detected by PCR and RT-PCR in patients with acute exacerbation of COPD: A systematic review. Respirology 2010; 15: 536—542.
  17. Wu X., Chen D., Gu X. et al. Prevalence and risk of viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease: a meta-analysis. Mol Biol Reports 2014; 41 (7): 4743—4751.
  18. Garcia-Aymerich J., Gomez F.P., Benet M. et al. Identification and prospective validation of clinically relevant chronic pulmonary disease (COPD) subtypes. Thorax 2011; 66 (5): 430—437.
  19. Hurst J.R., Vestbo J., Anzueto A. et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010; 363 (12): 1128—1138.
  20. Tashkin D.P. Frequent exacerbations of chronic obstructive pulmonary disease — a distinct phenotype? N Engl J Med 2010; 363 (12): 1183—1184.
  21. Kherad O., Bridevaux P.-O., Kaiser L. et al. Is Acute Exacerbation of COPD (AECOPD) Related to Viral Infection Associated with Subsequent Mortality or Exacerbation Rate? Open Respir Med J 2014; 8: 18—21.
  22. Wedzicha J.A., Donaldson G.C. Natural history of successive COPD exacerbations. Thorax 2012; 67 (11): 935—936.
  23. Seemungal T., Harper-Owen R., Bhowmik A. et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164 (9): 1618—1623.
  24. Ezzeldin N., Shalaby A., Saad-Hussein A., Ezzeldin H. Association of TNF-α —308G/A, SP-B 1580 C/T, IL-13 —1055 C/T gene polymorphisms and latent adenoviral infection with chronic obstructive pulmonary disease in an Egyptian population. Arch Med Sci 2012; 8 (2): 286—295.
  25. Bardin P.G., Sanderson G., Robinson B.S. et al. Experimental rhinovirus infection in volunteers. Eur Respir J 1996; 9: 2250—2255.
  26. Mallia P., Footitt J., Sotero R. et al. Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012; 186 (11): 1117—1124.
  27. Hutchinson A.F., Ghimire A.K., Thompson M.A. et al. A community-based, time-matched, case-control study of respiratory viruses and exacerbations of COPD. Respir Med 2007; 101: 2472—2481.
  28. Short K.R., Habets M.N., Hermans P.W., Diavatopoulos D.A. Interactions between Streptococcus pneumoniae and influenza virus: a mutually beneficial relationship? Future Microbiol 2012; 7 (5): 609—624.
  29. Nishikawa T., Shimizu K., Tanaka T. et al. Bacterial neuraminidase rescues influenza virus replication from inhibition by a neuraminidase inhibitor. PLoS One 2012; 7 (9): e45371.
  30. Bosch A.A.T.M., Biesbroek G., Trzcinski K. et al. Viral and bacterial interactions in the upper respiratory tract. PLoS Pathog 2013; 9 (1): e1003057.
  31. Ghoneim H.E., Thomas P.G., McCullers J.A. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol 2013; 191 (3): 1250—1259.
  32. Gavala M., Bertics P.J., Gern J.E. Rhinoviruses, allergic inflammation, and asthma. Immunol Rev 2011; 242 (1): 69—90.
  33. Калюжин О.В. Острые респираторные вирусные инфекции: современные вызовы, новый взгляд на место индукторов интерферонов в профилактике и терапии. Леч врач 2013; 9: 78—84.
  34. Shahangian A., Chow E.K., Tian X. et al. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice. J Clin Invest 2009; 119 (7): 1910—1920.
  35. Li W., Moltedo B., Moran T.M. Type I interferon induction during influenza virus infection increases susceptibility to secondary Streptococcus pneumoniae infection by negative regulation of γδ T cells. J Virol 2012; 86 (22): 12304—12312.
  36. Eltom S., Dale N., Raemdonck K.R.G. et al. Respiratory Infections Cause the Release of Extracellular Vesicles: Implications in Exacerbation of Asthma/COPD. PLoS One 2014; 9 (6): e101087.
  37. Lommatzsch M., Cicko S., Müller T. et al. Extracellular adenosine triphosphate and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010; 181: 928—934.
  38. Yerkovich S.T., Hales B.J., Carroll M.L. et al. Reduced rhinovirus-specific antibodies are associated with acute exacerbations of chronic obstructive pulmonary disease requiring hospitalization. BMC Pulm Med 2012; 12: 37.
  39. Zhang Y., Zhou B. Functions of thymic stromal lymphopoietin in immunity and disease. Immunol Res 2012; 52 (3): 211—223.
  40. Calvén J., Yudina Y., Hallgren O. et al. Viral stimuli trigger exaggerated thymic stromal lymphopoietin expression by chronic obstructive pulmonary disease epithelium: role of endosomal TLR3 and cytosolic RIG-I-like helicases. J Innate Immun 2012; 4 (1): 86—99.
  41. Lee H.-C., Headley M.B., Loo Y.-M. et al. Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection. J Allergy Clin Immunol 2012; 130: 1187—1196.
  42. Brandelius A., Persson I.M., Calvén J. et al. Selective inhibition by simvastatin of IRF3 phosphorylation and TSLP production in dsRNA-challenged bronchial epithelial cells from COPD donors. Br J Pharmacol 2013; 168 (2): 363—374.
  43. Blamoun A.I., Batty G.N., Debari V.A. et al. Statins may reduce episodes of exacerbation and the requirement for intubation in patients with COPD: evidence from a retrospective cohort study. Int J Clin Pract 2008; 62: 1373—1378.
  44. Hirota T., Takahashi A., Kubo M. et al. Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. Nat Genet 2011; 43: 893—896 10.1038/ng.887.
  45. Baines K.J., Hsu A.C.-Y., Tooze M. et al. Novel immune genes associated with excessive inflammatory and antiviral responses to rhinovirus in COPD. Respir Res 2013; 14 (1): 15.
  46. Miller E.K., Hernandez J.Z., Wimmenauer V. et al. A mechanistic role for type III IFN-λ1 in asthma exacerbations mediated by human rhinoviruses. Am J Respir Crit Care Med 2012; 185 (5): 508—516.
  47. Van Ly D., Faiz A., Jenkins C. et al. Characterising the mechanism of airway smooth muscle b2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells. PLoS ONE 2013; 8 (2): e56058.
  48. Kuo C., Lim S., King N.J.C. et al. Rhinovirus infection induces expression of airway remodelling factors in vitro and in vivo. Respirology 2011; 16: 367—377.
  49. Foronjy R.F., Dabo A.J., Taggart C.C. et al. Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice. PLoS One 2014; 9 (2): e90567.
  50. Караулов А.В., Калюжин О.В. Иммунотерапия инфекционных болезней: проблемы и перспективы. Тер арх 2013; 11: 100—108.
  51. Караулов А.В., Калюжин О.В. Иммунотропные препараты: принципы применения и клиническая эффективность. М.: МЦФЭР; 2007.
  52. Козлов И.Г. Критический взгляд на рынок иммуномодуляторов в России. Росс вестн перинат педиатр 2009; 4: 94—99.
  53. Braido F., Tarantini F., Ghiglione V. et al. Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections. Int J Chron Obstruct Pulmon Dis 2007; 2 (3): 335—345.
  54. Sprenkle M.D., Niewoehner D.E., MacDonald R. et al. Clinical efficacy of OM-85 BV in COPD and chronic bronchitis: a systematic review. COPD 2005; 2: 167—175.
  55. Steurer-Stey C., Bachmann L.M., Steurer J., Tramèr M.R. Oral purified bacterial extracts in chronic bronchitis and COPD: systematic review. Chest 2004; 126: 1645—1655.
  56. Cazzola M., Anapurapu S., Page C.P. Polyvalent mechanical bacterial lysate for the prevention of recurrent respiratory infections: a meta-analysis. Pulm Pharmacol Ther 2012; 25 (1): 62—68.
  57. Macchi A., Vecchia L.D. Open comparative, randomized controlled clinical study of a new immunostimulating bacterial lysate in the prophylaxis of upper respiratory tract infections. Arzneim Forsch 2005; 55: 276—281.
  58. RossiS., Tazza R. Efficacy and safety of a new immunostimulating bacterial lysate in the prophylaxis of acute lower respiratory tract infections. Arzneim. Forsch 2004; 54: 50—56.

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