Update on Rhinovirus and Coronavirus Infections

ABSTRACT

Rhinoviruses and coronaviruses cause significant morbidity in immunocompetent people of all ages and in patients with underlying chronic medical or immunosuppressed conditions. Newer diagnostic tests, such as polymerase chain reaction (PCR), have expanded our understanding of these respiratory viruses in clinical infections. These sensitive diagnostic tests have been used to describe new members of these virus families, such as human rhinovirus C (HRVC) and human coronavirus NL-63 (HCoV-NL63). The epidemiology of these newly described viruses will help us develop better intervention strategies.

KEYWORDS

Rhinovirus - coronavirus - asthma - COPD - otitis media - sinusitis - croup

REFERENCES

• 1 Greenberg S B. Respiratory consequences of rhinovirus infection.  Arch Intern Med. 2003;  163 (3) 278-284
• 2 Wat D. The common cold: a review of the literature.  Eur J Intern Med. 2004;  15 (2) 79-88
• 3 Larson H E, Reed S E, Tyrrell D A. Isolation of rhinoviruses and coronaviruses from 38 colds in adults.  J Med Virol. 1980;  5 (3) 221-229
• 4 Gwaltney Jr J M, Winther B, Patrie J T, Hendley J O. Combined antiviral-antimediator treatment for the common cold.  J Infect Dis. 2002;  186 (2) 147-154
• 5 Gwaltney Jr J M, Phillips C D, Miller R D, Riker D K. Computed tomographic study of the common cold.  N Engl J Med. 1994;  330 (1) 25-30
• 6 Whimbey E, Champlin R E, Couch R B et al.. Community respiratory virus infections among hospitalized adult bone marrow transplant recipients.  Clin Infect Dis. 1996;  22 (5) 778-782
• 7 Greenberg S B, Allen M, Wilson J, Atmar R L. Respiratory viral infections in adults with and without chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2000;  162 (1) 167-173
• 8 El-Sahly H M, Atmar R L, Glezen W P, Greenberg S B. Spectrum of clinical illness in hospitalized patients with “common cold” virus infections.  Clin Infect Dis. 2000;  31 (1) 96-100
• 9 Wedzicha J A. Role of viruses in exacerbations of chronic obstructive pulmonary disease.  Proc Am Thorac Soc. 2004;  1 (2) 115-120
• 10 Johnston S L, Pattemore P K, Sanderson G et al.. Community study of role of viral infections in exacerbations of asthma in 9–11 year old children.  BMJ. 1995;  310 (6989) 1225-1229
• 11 Hiatt P W, Grace S C, Kozinetz C A et al.. Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis.  Pediatrics. 1999;  103 (3) 619-626
• 12 Chonmaitree T, Howie V M, Truant A L. Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media.  Pediatrics. 1986;  77 (5) 698-702
• 13 Pitkäranta A, Virolainen A, Jero J, Arruda E, Hayden F G. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction.  Pediatrics. 1998;  102 (2 Pt 1) 291-295
• 14 Arden K E, Mackay I M. Newly identified human rhinoviruses: molecular methods heat up the cold viruses.  Rev Med Virol. 2010;  20 (3) 156-176
• 15 Greenberg S B. Rhinovirus and coronavirus infections.  Semin Respir Crit Care Med. 2007;  28 (2) 182-192
• 16 Hayden F G. Rhinovirus and the lower respiratory tract.  Rev Med Virol. 2004;  14 (1) 17-31
• 17 Greve J M, Davis G, Meyer A M et al.. The major human rhinovirus receptor is ICAM-1.  Cell. 1989;  56 (5) 839-847
• 18 Marlovits T C, Abrahamsberg C, Blaas D. Soluble LDL minireceptors. Minimal structure requirements for recognition of minor group human rhinovirus.  J Biol Chem. 1998;  273 (50) 33835-33840
• 19 Uncapher C R, DeWitt C M, Colonno R J. The major and minor group receptor families contain all but one human rhinovirus serotype.  Virology. 1991;  180 (2) 814-817
• 20 ICTV official taxonomy: updates since the 8th report. http://talk.ictvonline.org/media/p/1201.aspx Accessed August 30, 2009
• 21 Miller E K, Khuri-Bulos N, Williams J V et al.. Human rhinovirus C associated with wheezing in hospitalised children in the Middle East.  J Clin Virol. 2009;  46 (1) 85-89
• 22 Loens K, Goossens H, de Laat C et al.. Detection of rhinoviruses by tissue culture and two independent amplification techniques, nucleic acid sequence-based amplification and reverse transcription-PCR, in children with acute respiratory infections during a winter season.  J Clin Microbiol. 2006;  44 (1) 166-171
• 23 Briese T, Renwick N, Venter M et al.. Global distribution of novel rhinovirus genotype.  Emerg Infect Dis. 2008;  14 (6) 944-947
• 24 Lau S K, Yip C C, Lin A W et al.. Clinical and molecular epidemiology of human rhinovirus C in children and adults in Hong Kong reveals a possible distinct human rhinovirus C subgroup.  J Infect Dis. 2009;  200 (7) 1096-1103
• 25 Yeager C L, Ashmun R A, Williams R K et al.. Human aminopeptidase N is a receptor for human coronavirus 229E.  Nature. 1992;  357 (6377) 420-422
• 26 Hofmann H, Pyrc K, van der Hoek L, Geier M, Berkhout B, Pöhlmann S. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry.  Proc Natl Acad Sci U S A. 2005;  102 (22) 7988-7993
• 27 van der Hoek L, Pyrc K, Berkhout B. Human coronavirus NL63, a new respiratory virus.  FEMS Microbiol Rev. 2006;  30 (5) 760-773
• 28 Wevers B A, van der Hoek L. Recently discovered human coronaviruses.  Clin Lab Med. 2009;  29 (4) 715-724
• 29 Williams R K, Jiang G S, Holmes K V. Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins.  Proc Natl Acad Sci U S A. 1991;  88 (13) 5533-5536
• 30 Lai M M, Holmes K V. Coronaviridae: the viruses and their replication. In: Knipe D M, Howley P M, eds. Fundamental Virology. Philadelphia, PA: Lippincott, Williams & Wilkins; 2001: 641-664
• 31 Johnston S L. Overview of virus-induced airway disease.  Proc Am Thorac Soc. 2005;  2 (2) 150-156
• 32 Jarjour N N, Gern J E, Kelly E A, Swenson C A, Dick C R, Busse W W. The effect of an experimental rhinovirus 16 infection on bronchial lavage neutrophils.  J Allergy Clin Immunol. 2000;  105 (6 Pt 1) 1169-1177
• 33 Johnston S L, Papi A, Bates P J, Mastronarde J G, Monick M M, Hunninghake G W. Low grade rhinovirus infection induces a prolonged release of IL-8 in pulmonary epithelium.  J Immunol. 1998;  160 (12) 6172-6181
• 34 Laza-Stanca V, Stanciu L A, Message S D, Edwards M R, Gern J E, Johnston S L. Rhinovirus replication in human macrophages induces NF-kappaB-dependent tumor necrosis factor alpha production.  J Virol. 2006;  80 (16) 8248-8258
• 35 Griego S D, Weston C B, Adams J L, Tal-Singer R, Dillon S B. Role of p38 mitogen-activated protein kinase in rhinovirus-induced cytokine production by bronchial epithelial cells.  J Immunol. 2000;  165 (9) 5211-5220
• 36 Blau D M, Holmes K V. Human coronavirus HCoV-229E enters susceptible cells via the endocytic pathway.  Adv Exp Med Biol. 2001;  494 193-198
• 37 Pyrc K, Jebbink M F, Berkhout B, van der Hoek L. Genome structure and transcriptional regulation of human coronavirus NL63.  Virol J. 2004;  1 7
• 38 Callow K A, Parry H F, Sergeant M, Tyrrell D A. The time course of the immune response to experimental coronavirus infection of man.  Epidemiol Infect. 1990;  105 (2) 435-446
• 39 Schmidt O W, Kenny G E. Immunogenicity and antigenicity of human coronaviruses 229E and OC43.  Infect Immun. 1981;  32 (3) 1000-1006
• 40 Arruda E, Pitkäranta A, Witek Jr T J, Doyle C A, Hayden F G. Frequency and natural history of rhinovirus infections in adults during autumn.  J Clin Microbiol. 1997;  35 (11) 2864-2868
• 41 Mäkelä M J, Puhakka T, Ruuskanen O et al.. Viruses and bacteria in the etiology of the common cold.  J Clin Microbiol. 1998;  36 (2) 539-542
• 42 Gonzales R, Malone D C, Maselli J H, Sande M A. Excessive antibiotic use for acute respiratory infections in the United States.  Clin Infect Dis. 2001;  33 (6) 757-762
• 43 Hendley J O, Gwaltney Jr J M. Mechanisms of transmission of rhinovirus infections.  Epidemiol Rev. 1988;  10 243-258
• 44 Lee W-M, Kiesner C, Pappas T et al.. A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants.  PLoS ONE. 2007;  2 (10) e966
• 45 Kiang D, Kalra I, Yagi S et al.. Assay for 5′ noncoding region analysis of all human rhinovirus prototype strains.  J Clin Microbiol. 2008;  46 (11) 3736-3745
• 46 Tapparel C, Junier T, Gerlach D et al.. New respiratory enterovirus and recombinant rhinoviruses among circulating picornaviruses.  Emerg Infect Dis. 2009;  15 (5) 719-726
• 47 McErlean P, Shackleton L A, Andrewes E et al.. Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C).  PloS One. 2008;  3 (4) e1847
• 48 Miller E K, Khuri-Bulos N, Williams J V et al.. Human rhinovirus C associated with wheezing in hospitalised children in the Middle East.  J Clin Virol. 2009;  46 (1) 85-89
• 49 Lau S KP, Yip C CY, Tsoi H-W et al.. Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children.  J Clin Microbiol. 2007;  45 (11) 3655-3664
• 50 Renwick N, Schweiger B, Kapoor V et al.. A recently identified rhinovirus genotype is associated with severe respiratory-tract infection in children in Germany.  J Infect Dis. 2007;  196 (12) 1754-1760
• 51 Savolainen-Kopra C, Blomqvist S, Kilpi T, Roivainen M, Hovi T. Novel species of human rhinoviruses in acute otitis media.  Pediatr Infect Dis J. 2009;  28 (1) 59-61
• 52 Linsuwanon P, Payungporn S, Samransamruajkit R et al.. High prevalence of human rhinovirus C infection in Thai children with acute lower respiratory tract disease.  J Infect. 2009;  59 (2) 115-121
• 53 Tapparel C, L'Huillier A G, Rougemont A L, Beghetti M, Barazzone-Argiroffo C, Kaiser L. Pneumonia and pericarditis in a child with HRV-C infection: a case report.  J Clin Virol. 2009;  45 (2) 157-160
• 54 Khetsuriani N, Lu X, Teague W G, Kazerouni N, Anderson L J, Erdman D D. Novel human rhinoviruses and exacerbation of asthma in children.  Emerg Infect Dis. 2008;  14 (11) 1793-1796
• 55 Kneider M, Bergström T, Gustafsson C et al.. Sequence analysis of human rhinovirus aspirated from the nasopharynx of patients with relapsing-remitting MS.  Mult Scler. 2009;  15 (4) 437-442
• 56 Miller E K, Edwards K M, Weinberg G A New Vaccine Surveillance Network et al. A novel group of rhinoviruses is associated with asthma hospitalizations.  J Allergy Clin Immunol. 2009;  123 (1) 98-104, e1
• 57 Alper C M, Winther B, Mandel E M, Hendley J O, Doyle W J. Rate of concurrent otitis media in upper respiratory tract infections with specific viruses.  Arch Otolaryngol Head Neck Surg. 2009;  135 (1) 17-21
• 58 Urquhart G ED, Grist N R. Virological studies of sudden, unexplained infant deaths in Glasgow 1967-70.  J Clin Pathol. 1972;  25 (5) 443-446
• 59 Xatzipsalti M, Kyrana S, Tsolia M et al.. Rhinovirus viremia in children with respiratory infections.  Am J Respir Crit Care Med. 2005;  172 (8) 1037-1040
• 60 Jartti T, Lehtinen P, Vuorinen T, Koskenvuo M, Ruuskanen O. Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children.  J Med Virol. 2004;  72 (4) 695-699
• 61 Winther B, Hayden F G, Hendley J O. Picornavirus infections in children diagnosed by RT-PCR during longitudinal surveillance with weekly sampling: association with symptomatic illness and effect of season.  J Med Virol. 2006;  78 (5) 644-650
• 62 Cate T R, Couch R B, Johnson K M. Studies with rhinoviruses in volunteers: production of illness, effect of naturally acquired antibody, and demonstration of a protective effect not associated with serum antibody.  J Clin Invest. 1964;  43 56-67
• 63 van Elden L J, Sachs A P, van Loon A M et al.. Enhanced severity of virus associated lower respiratory tract disease in asthma patients may not be associated with delayed viral clearance and increased viral load in the upper respiratory tract.  J Clin Virol. 2008;  41 (2) 116-121
• 64 Hendley J O, Gwaltney Jr J M. Viral titers in nasal lining fluid compared to viral titers in nasal washes during experimental rhinovirus infection.  J Clin Virol. 2004;  30 (4) 326-328
• 65 Rosenbaum M J, De Berry P, Sullivan E J, Pierce W E, Mueller R E, Peckinpaugh R O. Epidemiology of the common cold in military recruits with emphasis on infections by rhinovirus types 1A, 2, and two unclassified rhinoviruses.  Am J Epidemiol. 1971;  93 (3) 183-193
• 66 Dick E C, Blumer C R, Evans A S. Epidemiology of infections with rhinovirus types 43 and 55 in a group of university of Wisconsin student families.  Am J Epidemiol. 1967;  86 (2) 386-400
• 67 Arden K E, Mackay I M. Human rhinoviruses: coming in from the cold.  Genome Med. 2009;  1 (4) 44
• 68 Piralla A, Rovida F, Campanini G et al.. Clinical severity and molecular typing of human rhinovirus C strains during a fall outbreak affecting hospitalized patients.  J Clin Virol. 2009;  45 (4) 311-317
• 69 Huang T, Wang W, Bessaud M et al.. Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection.  PLoS ONE. 2009;  4 (7) e6355
• 70 Dominguez S R, Briese T, Palacios G et al.. Multiplex MassTag-PCR for respiratory pathogens in pediatric nasopharyngeal washes negative by conventional diagnostic testing shows a high prevalence of viruses belonging to a newly recognized rhinovirus clade.  J Clin Virol. 2008;  43 (2) 219-222
• 71 Savolainen C, Mulders M N, Hovi T. Phylogenetic analysis of rhinovirus isolates collected during successive epidemic seasons.  Virus Res. 2002;  85 (1) 41-46
• 72 Tyrrell D A, Bynoe M L. Cultivation of viruses from a high proportion of patients with colds.  Lancet. 1966;  1 (7428) 76-77
• 73 Hamre D, Procknow J J. A new virus isolated from the human respiratory tract.  Proc Soc Exp Biol Med. 1966;  121 (1) 190-193
• 74 McIntosh K, Dees J H, Becker W B, Kapikian A Z, Chanock R M. Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease.  Proc Natl Acad Sci U S A. 1967;  57 (4) 933-940
• 75 McIntosh K, Kapikian A Z, Turner H C, Hartley J W, Parrott R H, Chanock R M. Seroepidemiologic studies of coronavirus infection in adults and children.  Am J Epidemiol. 1970;  91 (6) 585-592
• 76 Monto A S. Medical reviews: coronaviruses.  Yale J Biol Med. 1974;  47 (4) 234-251
• 77 McIntosh K, Ellis E F, Hoffman L S, Lybass T G, Eller J J, Fulginiti V A. Association of viral and bacterial respiratory infection with exacerbations of wheezing in young asthmatic children.  Chest. 1973;  63 (Suppl) 43S
• 78 Monto A S. Epidemiology of respiratory viruses in persons with and without asthma and COPD.  Am J Respir Crit Care Med. 1995;  151 (5) 1653-1657 discussion 1657-1658
• 79 Falsey A R, McCann R M, Hall W J et al.. The “common cold” in frail older persons: impact of rhinovirus and coronavirus in a senior daycare center.  J Am Geriatr Soc. 1997;  45 (6) 706-711
• 80 Falsey A R, Walsh E E, Hayden F G. Rhinovirus and coronavirus infection-associated hospitalizations among older adults.  J Infect Dis. 2002;  185 (9) 1338-1341
• 81 Peiris J S, Lai S T, Poon L L SARS study group et al. Coronavirus as a possible cause of severe acute respiratory syndrome.  Lancet. 2003;  361 (9366) 1319-1325
• 82 van der Hoek L, Pyrc K, Jebbink M F et al.. Identification of a new human coronavirus.  Nat Med. 2004;  10 (4) 368-373
• 83 Fouchier R A, Hartwig N G, Bestebroer T M et al.. A previously undescribed coronavirus associated with respiratory disease in humans.  Proc Natl Acad Sci U S A. 2004;  101 (16) 6212-6216
• 84 Esper F, Weibel C, Ferguson D, Landry M L, Kahn J S. Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children.  J Infect Dis. 2005;  191 (4) 492-498
• 85 Woo P C, Lau S K, Chu C M et al.. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia.  J Virol. 2005;  79 (2) 884-895
• 86 Esper F, Weibel C, Ferguson D, Landry M L, Kahn J S. Coronavirus HKU1 infection in the United States.  Emerg Infect Dis. 2006;  12 (5) 775-779
• 87 Talbot H K, Shepherd B E, Crowe Jr J E et al.. The pediatric burden of human coronaviruses evaluated for twenty years.  Pediatr Infect Dis J. 2009;  28 (8) 682-687
• 88 Gerna G, Campanini G, Rovida F et al.. Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients.  J Med Virol. 2006;  78 (7) 938-949
• 89 Garbino J, Crespo S, Aubert J D et al.. A prospective hospital-based study of the clinical impact of non-severe acute respiratory syndrome (Non-SARS)-related human coronavirus infection.  Clin Infect Dis. 2006;  43 (8) 1009-1015
• 90 Sung R Y, Chan P K, Tsen T et al.. Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays.  J Med Virol. 2009;  81 (1) 153-159
• 91 Kim S R, Ki C S, Lee N Y. Rapid detection and identification of 12 respiratory viruses using a dual priming oligonucleotide system-based multiplex PCR assay.  J Virol Methods. 2009;  156 (1–2) 111-116
• 92 Yoo S J, Kuak E Y, Shin B M. Detection of 12 respiratory viruses with two-set multiplex reverse transcriptase-PCR assay using a dual priming oligonucleotide system.  Korean J Lab Med. 2007;  27 (6) 420-427
• 93 Vijgen L, Keyaerts E, Lemey P et al.. Circulation of genetically distinct contemporary human coronavirus OC43 strains.  Virology. 2005;  337 (1) 85-92
• 94 Dagher H, Donninger H, Hutchinson P, Ghildyal R, Bardin P. Rhinovirus detection: comparison of real-time and conventional PCR.  J Virol Methods. 2004;  117 (2) 113-121
• 95 van Kraaij M G, van Elden L J, van Loon A M et al.. Frequent detection of respiratory viruses in adult recipients of stem cell transplants with the use of real-time polymerase chain reaction, compared with viral culture.  Clin Infect Dis. 2005;  40 (5) 662-669
• 96 Vuorinen T, Vainionpää R, Hyypiä T. Five years' experience of reverse-transcriptase polymerase chain reaction in daily diagnosis of enterovirus and rhinovirus infections.  Clin Infect Dis. 2003;  37 (3) 452-455
• 97 Loens K, Goossens H, de Laat C et al.. Detection of rhinoviruses by tissue culture and two independent amplification techniques, nucleic acid sequence-based amplification and reverse transcription-PCR, in children with acute respiratory infections during a winter season.  J Clin Microbiol. 2006;  44 (1) 166-171
• 98 Lee B E, Robinson J L, Khurana V, Pang X L, Preiksaitis J K, Fox J D. Enhanced identification of viral and atypical bacterial pathogens in lower respiratory tract samples with nucleic acid amplification tests.  J Med Virol. 2006;  78 (5) 702-710
• 99 van de Pol A C, Wolfs T F, Jansen N J, van Loon A M, Rossen J W. Diagnostic value of real-time polymerase chain reaction to detect viruses in young children admitted to the paediatric intensive care unit with lower respiratory tract infection.  Crit Care. 2006;  10 (2) R61
• 100 Beckham J D, Cadena A, Lin J et al.. Respiratory viral infections in patients with chronic, obstructive pulmonary disease.  J Infect. 2005;  50 (4) 322-330
• 101 Schmidt O W. Antigenic characterization of human coronaviruses 229E and OC43 by enzyme-linked immunosorbent assay.  J Clin Microbiol. 1984;  20 (2) 175-180
• 102 Kahn J S, McIntosh K. History and recent advances in coronavirus discovery.  Pediatr Infect Dis J. 2005;  24 (11, Suppl) S223-S227 discussion S226
• 103 Johnston S L, Pattemore P K, Sanderson G et al.. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.  BMJ. 1995;  310 (6989) 1225-1229
• 104 Atmar R L, Guy E, Guntupalli K K et al.. Respiratory tract viral infections in inner-city asthmatic adults.  Arch Intern Med. 1998;  158 (22) 2453-2459
• 105 Nicholson K G, Kent J, Ireland D C. Respiratory viruses and exacerbations of asthma in adults.  BMJ. 1993;  307 (6910) 982-986
• 106 Miller E K, Edwards K M, Weinberg G A et al.. A novel group of rhinoviruses is associated with asthma hospitalizations.  J Allergy Clin Immunol. 2009;  123 (1) 98-104.e1
• 107 Khetsuriani N, Lu X, Teague W G, Kazerouni N, Anderson L J, Erdman D D. Novel human rhinoviruses and exacerbation of asthma in children.  Emerg Infect Dis. 2008;  14 (11) 1793-1796
• 108 Xiang Z, Gonzalez R, Xie Z et al.. Human rhinovirus group C infection in children with lower respiratory tract infection.  Emerg Infect Dis. 2008;  14 (10) 1665-1667
• 109 Wark P A, Johnston S L, Moric I, Simpson J L, Hensley M J, Gibson P G. Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma.  Eur Respir J. 2002;  19 (1) 68-75
• 110 Corne J M, Marshall C, Smith S et al.. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study.  Lancet. 2002;  359 (9309) 831-834
• 111 Grünberg K, Timmers M C, de Klerk E P, Dick E C, Sterk P J. Experimental rhinovirus 16 infection causes variable airway obstruction in subjects with atopic asthma.  Am J Respir Crit Care Med. 1999;  160 (4) 1375-1380
• 112 Calhoun W J, Dick E C, Schwartz L B, Busse W W. A common cold virus, rhinovirus 16, potentiates airway inflammation after segmental antigen bronchoprovocation in allergic subjects.  J Clin Invest. 1994;  94 (6) 2200-2208
• 113 Fraenkel D J, Bardin P G, Sanderson G, Lampe F, Johnston S L, Holgate S T. Lower airways inflammation during rhinovirus colds in normal and in asthmatic subjects.  Am J Respir Crit Care Med. 1995;  151 (3 Pt 1) 879-886
• 114 Papadopoulos N G, Bates P J, Bardin P G et al.. Rhinoviruses infect the lower airways.  J Infect Dis. 2000;  181 (6) 1875-1884
• 115 Gern J E, Galagan D M, Jarjour N N, Dick E C, Busse W W. Detection of rhinovirus RNA in lower airway cells during experimentally induced infection.  Am J Respir Crit Care Med. 1997;  155 (3) 1159-1161
• 116 Zhu Z, Tang W, Gwaltney Jr J M, Wu Y, Elias J A. Rhinovirus stimulation of interleukin-8 in vivo and in vitro: role of NF-kappaB.  Am J Physiol. 1997;  273 (4 Pt 1) L814-L824
• 117 Gern J E, Vrtis R, Grindle K A, Swenson C, Busse W W. Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection.  Am J Respir Crit Care Med. 2000;  162 (6) 2226-2231
• 118 Zhu Z, Tang W, Ray A et al.. Rhinovirus stimulation of interleukin-6 in vivo and in vitro: evidence for nuclear factor kappa B-dependent transcriptional activation.  J Clin Invest. 1996;  97 (2) 421-430
• 119 Wark P A, Johnston S L, Bucchieri F et al.. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.  J Exp Med. 2005;  201 (6) 937-947
• 120 Cheung D, Dick E C, Timmers M C, de Klerk E P, Spaan W J, Sterk P J. Rhinovirus inhalation causes long-lasting excessive airway narrowing in response to methacholine in asthmatic subjects in vivo.  Am J Respir Crit Care Med. 1995;  152 (5 Pt 1) 1490-1496
• 121 Smart J M, Horak E, Kemp A S, Robertson C F, Tang M L. Polyclonal and allergen-induced cytokine responses in adults with asthma: resolution of asthma is associated with normalization of IFN-gamma responses.  J Allergy Clin Immunol. 2002;  110 (3) 450-456
• 122 Papadopoulos N G, Stanciu L A, Papi A, Holgate S T, Johnston S L. A defective type 1 response to rhinovirus in atopic asthma.  Thorax. 2002;  57 (4) 328-332
• 123 Sheppard P, Kindsvogel W, Xu W et al.. IL-28, IL-29 and their class II cytokine receptor IL-28R.  Nat Immunol. 2003;  4 (1) 63-68
• 124 Contoli M, Message S D, Laza-Stanca V et al.. Role of deficient type III interferon-lambda production in asthma exacerbations.  Nat Med. 2006;  12 (9) 1023-1026
• 125 Piotrowska Z, Vázquez M, Shapiro E D et al.. Rhinoviruses are a major cause of wheezing and hospitalization in children less than 2 years of age.  Pediatr Infect Dis J. 2009;  28 (1) 25-29
• 126 Chung J Y, Han T H, Kim S W, Kim C K, Hwang E S. Detection of viruses identified recently in children with acute wheezing.  J Med Virol. 2007;  79 (8) 1238-1243
• 127 Jackson D J, Gangnon R E, Evans M D et al.. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children.  Am J Respir Crit Care Med. 2008;  178 (7) 667-672
• 128 Lemanske Jr R F, Jackson D J, Gangnon R E et al.. Rhinovirus illnesses during infancy predict subsequent childhood wheezing.  J Allergy Clin Immunol. 2005;  116 (3) 571-577
• 129 Gern J E. Rhinovirus and the initiation of asthma.  Curr Opin Allergy Clin Immunol. 2009;  9 (1) 73-78
• 130 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
• 131 Smith C B, Golden C A, Kanner R E, Renzetti Jr A D. Association of viral and Mycoplasma pneumoniae infections with acute respiratory illness in patients with chronic obstructive pulmonary diseases.  Am Rev Respir Dis. 1980;  121 (2) 225-232
• 132 Rohde G, Wiethege A, Borg I et al.. Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study.  Thorax. 2003;  58 (1) 37-42
• 133 Ko F W, Ip M, Chan P K et al.. Viral etiology of acute exacerbations of COPD in Hong Kong.  Chest. 2007;  132 (3) 900-908
• 134 Kherad O, Kaiser L, Bridevaux P O et al.. Upper respiratory infection, biomarkers, and COPD exacerbations.  Chest. 2010;  138 (4) 896-904
• 135 Keatings V M, Collins P D, Scott D M, Barnes P J. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma.  Am J Respir Crit Care Med. 1996;  153 (2) 530-534
• 136 Ishizuka S, Yamaya M, Suzuki T et al.. Effects of rhinovirus infection on the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells.  J Infect Dis. 2003;  188 (12) 1928-1939
• 137 Sajjan U S, Jia Y, Newcomb D C et al.. H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ICAM-1 and TLR3 expression.  FASEB J. 2006;  20 (12) 2121-2123
• 138 Nokso-Koivisto J, Räty R, Blomqvist S et al.. Presence of specific viruses in the middle ear fluids and respiratory secretions of young children with acute otitis media.  J Med Virol. 2004;  72 (2) 241-248
• 139 Heikkinen T, Chonmaitree T. Importance of respiratory viruses in acute otitis media.  Clin Microbiol Rev. 2003;  16 (2) 230-241
• 140 Chantzi F M, Papadopoulos N G, Bairamis T et al.. Human rhinoviruses in otitis media with effusion.  Pediatr Allergy Immunol. 2006;  17 (7) 514-518
• 141 Pitkäranta A, Roivainen M, Blomgren K et al.. Presence of viral and bacterial pathogens in the nasopharynx of otitis-prone children: a prospective study.  Int J Pediatr Otorhinolaryngol. 2006;  70 (4) 647-654
• 142 Alper C M, Winther B, Mandel E M, Hendley J O, Doyle W J. Rate of concurrent otitis media in upper respiratory tract infections with specific viruses.  Arch Otolaryngol Head Neck Surg. 2009;  135 (1) 17-21
• 143 Chonmaitree T, Revai K, Grady J J et al.. Viral upper respiratory tract infection and otitis media complication in young children.  Clin Infect Dis. 2008;  46 (6) 815-823
• 144 Rihkanen H, Carpén O, Roivainen M, Vaheri A, Pitkäranta A. Rhinovirus in adenoid tissue.  Int J Pediatr Otorhinolaryngol. 2004;  68 (7) 903-908
• 145 Elkhatieb A, Hipskind G, Woerner D, Hayden F G. Middle ear abnormalities during natural rhinovirus colds in adults.  J Infect Dis. 1993;  168 (3) 618-621
• 146 McBride T P, Doyle W J, Hayden F G, Gwaltney Jr J M. Alterations of the eustachian tube, middle ear, and nose in rhinovirus infection.  Arch Otolaryngol Head Neck Surg. 1989;  115 (9) 1054-1059
• 147 Bulut Y, Güven M, Otlu B et al.. Acute otitis media and respiratory viruses.  Eur J Pediatr. 2007;  166 (3) 223-228
• 148 Sung B S, Chonmaitree T, Broemeling L D et al.. Association of rhinovirus infection with poor bacteriologic outcome of bacterial-viral otitis media.  Clin Infect Dis. 1993;  17 (1) 38-42
• 149 Turner B W, Cail W S, Hendley J O et al.. Physiologic abnormalities in the paranasal sinuses during experimental rhinovirus colds.  J Allergy Clin Immunol. 1992;  90 (3 Pt 2) 474-478
• 150 Gwaltney Jr J M, Phillips C D, Miller R D, Riker D K. Computed tomographic study of the common cold.  N Engl J Med. 1994;  330 (1) 25-30
• 151 Gwaltney Jr J M. Acute community-acquired sinusitis.  Clin Infect Dis. 1996;  23 (6) 1209-1223 quiz 1224-1225
• 152 Pitkäranta A, Arruda E, Malmberg H, Hayden F G. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR.  J Clin Microbiol. 1997;  35 (7) 1791-1793
• 153 Gwaltney Jr J M, Hendley J O, Phillips C D, Bass C R, Mygind N, Winther B. Nose blowing propels nasal fluid into the paranasal sinuses.  Clin Infect Dis. 2000;  30 (2) 387-391
• 154 Marcos M A, Esperatti M, Torres A. Viral pneumonia.  Curr Opin Infect Dis. 2009;  22 (2) 143-147
• 155 Nascimento-Carvalho C M, Ribeiro C T, Cardoso M R et al.. The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country.  Pediatr Infect Dis J. 2008;  27 (10) 939-941
• 156 Cilla G, Oñate E, Perez-Yarza E G, Montes M, Vicente D, Perez-Trallero E. Viruses in community-acquired pneumonia in children aged less than 3 years old: High rate of viral coinfection.  J Med Virol. 2008;  80 (10) 1843-1849
• 157 Hamano-Hasegawa K, Morozumi M, Nakayama E Acute Respiratory Diseases Study Group et al. Comprehensive detection of causative pathogens using real-time PCR to diagnose pediatric community-acquired pneumonia.  J Infect Chemother. 2008;  14 (6) 424-432
• 158 Louie J K, Roy-Burman A, Guardia-Labar L et al.. Rhinovirus associated with severe lower respiratory tract infections in children.  Pediatr Infect Dis J. 2009;  28 (4) 337-339
• 159 Lahti E, Peltola V, Waris M et al.. Induced sputum in the diagnosis of childhood community-acquired pneumonia.  Thorax. 2009;  64 (3) 252-257
• 160 Berkley J A, Munywoki P, Ngama M et al.. Viral etiology of severe pneumonia among Kenyan infants and children.  JAMA. 2010;  303 (20) 2051-2057
• 161 Camps Serra M, Cervera C, Pumarola T et al.. Virological diagnosis in community-acquired pneumonia in immunocompromised patients.  Eur Respir J. 2008;  31 (3) 618-624
• 162 Templeton K E, Scheltinga S A, van den Eeden W C, Graffelman A W, van den Broek P J, Claas E C. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction.  Clin Infect Dis. 2005;  41 (3) 345-351
• 163 Ko F W, Ip M, Chan P K, Ng S S, Chau S S, Hui D S. A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia.  Respir Med. 2008;  102 (8) 1109-1116
• 164 Jennings L C, Anderson T P, Beynon K A et al.. Incidence and characteristics of viral community-acquired pneumonia in adults.  Thorax. 2008;  63 (1) 42-48
• 165 Johnstone J, Majumdar S R, Fox J D, Marrie T J. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation.  Chest. 2008;  134 (6) 1141-1148
• 166 Diederen B M, Van Der Eerden M M, Vlaspolder F, Boersma W G, Kluytmans J A, Peeters M F. Detection of respiratory viruses and Legionella spp. by real-time polymerase chain reaction in patients with community acquired pneumonia.  Scand J Infect Dis. 2009;  41 (1) 45-50
• 167 Lieberman D, Shimoni A, Shemer-Avni Y, Keren-Naos A, Shtainberg R, Lieberman D. Respiratory viruses in adults with community-acquired pneumonia.  Chest. 2010;  138 (4) 811-816
• 168 Stempel H E, Martin E T, Kuypers J, Englund J A, Zerr D M. Multiple viral respiratory pathogens in children with bronchiolitis.  Acta Paediatr. 2009;  98 (1) 123-126
• 169 Gaunt E R, Hardie A, Claas E C, Simmonds P, Templeton K E. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR.  J Clin Microbiol. 2010;  48 (8) 2940-2947
• 170 Ebihara T, Endo R, Ma X, Ishiguro N, Kikuta H. Detection of human coronavirus NL63 in young children with bronchiolitis.  J Med Virol. 2005;  75 (3) 463-465
• 171 Midulla F, Scagnolari C, Bonci E et al.. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants.  Arch Dis Child. 2010;  95 (1) 35-41
• 172 Freymuth F, Vabret A, Dina J et al.. Bronchiolitis viruses [in French].  Arch Pediatr. 2010;  17 (8) 1192-1201
• 173 Collinson J, Nicholson K G, Cancio E et al.. Effects of upper respiratory tract infections in patients with cystic fibrosis.  Thorax. 1996;  51 (11) 1115-1122
• 174 Smyth A R, Smyth R L, Tong C Y, Hart C A, Heaf D P. Effect of respiratory virus infections including rhinovirus on clinical status in cystic fibrosis.  Arch Dis Child. 1995;  73 (2) 117-120
• 175 Olesen H V, Nielsen L P, Schiotz P O. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic.  Pediatr Pulmonol. 2006;  41 (12) 1197-1204
• 176 Wat D, Gelder C, Hibbitts S et al.. The role of respiratory viruses in cystic fibrosis.  J Cyst Fibros. 2008;  7 (4) 320-328
• 177 de Almeida M B, Zerbinati R M, Tateno A F et al.. Rhinovirus C and respiratory exacerbations in children with cystic fibrosis.  Emerg Infect Dis. 2010;  16 (6) 996-999
• 178 Garbino J, Gerbase M W, Wunderli W et al.. Respiratory viruses and severe lower respiratory tract complications in hospitalized patients.  Chest. 2004;  125 (3) 1033-1039
• 179 Whimbey E, Champlin R E, Couch R B et al.. Community respiratory virus infections among hospitalized adult bone marrow transplant recipients.  Clin Infect Dis. 1996;  22 (5) 778-782
• 180 Ison M G, Hayden F G, Kaiser L, Corey L, Boeckh M. Rhinovirus infections in hematopoietic stem cell transplant recipients with pneumonia.  Clin Infect Dis. 2003;  36 (9) 1139-1143
• 181 Hassan I A, Chopra R, Swindell R, Mutton K J. Respiratory viral infections after bone marrow/peripheral stem-cell transplantation: the Christie hospital experience.  Bone Marrow Transplant. 2003;  32 (1) 73-77
• 182 Ljungman P, Ward K N, Crooks B N et al.. Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.  Bone Marrow Transplant. 2001;  28 (5) 479-484
• 183 Ghosh S, Champlin R, Couch R et al.. Rhinovirus infections in myelosuppressed adult blood and marrow transplant recipients.  Clin Infect Dis. 1999;  29 (3) 528-532
• 184 Milano F, Campbell A P, Guthrie K A et al.. Human rhinovirus and coronavirus detection among allogeneic hematopoietic stem cell transplantation recipients.  Blood. 2010;  115 (10) 2088-2094
• 185 Eccles R. Efficacy and safety of over-the-counter analgesics in the treatment of common cold and flu.  J Clin Pharm Ther. 2006;  31 (4) 309-319
• 186 Singh M. Heated, humidified air for the common cold.  Cochrane Database Syst Rev. 2004;  (2) CD001728
• 187 Rotbart H A. Antiviral therapy for enteroviruses and rhinoviruses.  Antivir Chem Chemother. 2000;  11 (4) 261-271
• 188 Samo T C, Greenberg S B, Couch R B et al.. Efficacy and tolerance of intranasally applied recombinant leukocyte A interferon in normal volunteers.  J Infect Dis. 1983;  148 (3) 535-542
• 189 Hayden F G, Gwaltney Jr J M. Intranasal interferon-alpha 2 treatment of experimental rhinoviral colds.  J Infect Dis. 1984;  150 (2) 174-180
• 190 Higgins P G, Phillpotts R J, Scott G M, Wallace J, Bernhardt L L, Tyrrell D A. Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers.  Antimicrob Agents Chemother. 1983;  24 (5) 713-715
• 191 Sasaki T, Yamaya M, Yasuda H et al.. The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured human tracheal epithelial cells.  Eur J Pharmacol. 2005;  509 (2–3) 201-210
• 192 Hayden F G, Herrington D T, Coats T L Pleconaril Respiratory Infection Study Group et al. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials.  Clin Infect Dis. 2003;  36 (12) 1523-1532
• 193 Patick A K, Brothers M A, Maldonado F et al.. In vitro antiviral activity and single-dose pharmacokinetics in humans of a novel, orally bioavailable inhibitor of human rhinovirus 3C protease.  Antimicrob Agents Chemother. 2005;  49 (6) 2267-2275
• 194 Hayden F G, Turner R B, Gwaltney J M et al.. Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers.  Antimicrob Agents Chemother. 2003;  47 (12) 3907-3916
• 195 Schoop R, Klein P, Suter A, Johnston S L. Echinacea in the prevention of induced rhinovirus colds: a meta-analysis.  Clin Ther. 2006;  28 (2) 174-183
• 196 Sperber S J, Shah L P, Gilbert R D, Ritchey T W, Monto A S. Echinacea purpurea for prevention of experimental rhinovirus colds.  Clin Infect Dis. 2004;  38 (10) 1367-1371
• 197 Turner R B. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds.  Clin Infect Dis. 2001;  33 (11) 1865-1870
• 198 Kurugöl Z, Akilli M, Bayram N, Koturoglu G. The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children.  Acta Paediatr. 2006;  95 (10) 1175-1181
• 199 Turner R B, Hendley J O. Virucidal hand treatments for prevention of rhinovirus infection.  J Antimicrob Chemother. 2005;  56 (5) 805-807
• 200 Turner R B, Biedermann K A, Morgan J M, Keswick B, Ertel K D, Barker M F. Efficacy of organic acids in hand cleansers for prevention of rhinovirus infections.  Antimicrob Agents Chemother. 2004;  48 (7) 2595-2598
• 201 Sung J Y, Lee H J, Eun B W et al.. Role of human coronavirus NL63 in hospitalized children with croup.  Pediatr Infect Dis J. 2010;  29 (9) 822-826
• 202 Xiang Z, Gonzalez R, Xie Z et al.. Human rhinovirus C infections mirror those of human rhinovirus A in children with community-acquired pneumonia.  J Clin Virol. 2010;  49 (2) 94-99
• 203 Fairchok M P, Martin E T, Chambers S et al.. Epidemiology of viral respiratory tract infections in a prospective cohort of infants and toddlers attending daycare.  J Clin Virol. 2010;  49 (1) 16-20
• 204 Franz A, Adams O, Willems R et al.. Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection.  J Clin Virol. 2010;  48 (4) 239-245
• 205 Arden K E, Chang A B, Lambert S B, Nissen M D, Sloots T P, Mackay I M. Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital.  J Med Virol. 2010;  82 (8) 1458-1461