Chapter 2 : Respiratory Infections

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Respiratory Infections, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819439/9781555819422.ch2-1.gif /docserver/preview/fulltext/10.1128/9781555819439/9781555819422.ch2-2.gif


Respiratory viral infections have a major impact on health. Acute respiratory illnesses, largely caused by viruses, are the most common illness experienced by otherwise healthy adults and children. Data from the United States, collected in the 1992 National Health Interview Survey, suggest that such illnesses are experienced at a rate of 85.6 illnesses per 100 persons per year and account for 54% of all acute conditions exclusive of injuries (1). A total of 44% of these illnesses require medical attention and result in 287 days of restricted activity, 94.4 days lost from work, and 182 days lost from school per 100 persons per year. The morbidity of acute respiratory disease in the family setting is significant. The Tecumseh study, a family-based surveillance study of respiratory illness, estimated that approximately one-quarter of respiratory illnesses result in consultation with a physician (2). Illness rates for all acute respiratory conditions are highest in young children, and children below the age of 9 have been estimated to experience between five and nine respiratory illnesses per year (3).

Citation: Treanor J. 2017. Respiratory Infections, p 9-29. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch2
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Many of the viruses that affect the respiratory tract exhibit a seasonal variation in prevalence. In this figure, numbers of virus isolates from children seen in private pediatric practices in Rochester, NY, are plotted by month of isolation. Data represent the 6-year average from 1990 to 1995 and are expressed as the percentage of all isolates of that virus that occurred in the given month.

Citation: Treanor J. 2017. Respiratory Infections, p 9-29. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch2
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Posteroanterior roentgenogram of the neck of a child with viral croup that shows the characteristic narrowing of the air shadow of the trachea in the subglottic area. (Courtesy of Dr. Carolyn B. Hall, University of Rochester)

Citation: Treanor J. 2017. Respiratory Infections, p 9-29. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch2
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Lateral neck films of the neck in a child with epiglottitis demonstrates the characteristic thickening of the epiglottis in this disease and may be helpful in distinguishing this illness from croup or retropharyngeal abscess. (Courtesy of Dr. Caren B. Hall, University of Rochester)

Citation: Treanor J. 2017. Respiratory Infections, p 9-29. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch2
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Pathophysiology of croup. Both mechanical obstruction of airflow and ventilation-perfusion mismatching due to parenchymal infection of the lung are responsible for the hypoxia and respiratory distress of croup. (Modified from Hall, Reference , with permission)

Citation: Treanor J. 2017. Respiratory Infections, p 9-29. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch2
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

The CXR in bronchiolitis characteristically shows hyperinflation due to obstruction to airflow. A variety of other findings may be present, including interstitial infiltrates or lobar consolidation. (Courtesy of Dr. Caren B. Hall, University of Rochester)

Citation: Treanor J. 2017. Respiratory Infections, p 9-29. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch2
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6

Pathophysiology of bronchiolitis. Viral infection of the lower respiratory tract results in inflammation and increased mucus production. Both airway obstruction and ventilation-perfusion mismatching are responsible for the clinical findings of hypoxia, hyperinflation, and hypoventilation. If uncorrected, these defects can lead to apnea or sudden death. (Modified from Wohl and Chernick, Reference , with permission)

Citation: Treanor J. 2017. Respiratory Infections, p 9-29. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch2
Permissions and Reprints Request Permissions
Download as Powerpoint


1. National Center for Health Statistics . 1994. Current estimates from the National Health Interview survey, 1992. DHHS Publication No (PHS) 94-1517 Department of Health and Human Services, Hyattsville, MD.
2. Monto AS, Sullivan KM . 1993. Acute respiratory illness in the community. Frequency of illness and the agents involved. Epidemiol Infect 110 : 145 160.[PubMed]
3. Lambert SB, Allen KM, Druce JD, Birch CJ, Mackay IM, Carlin JB, Carapetis JR, Sloots TP, Nissen MD, Nolan TM . 2007. Community epidemiology of human metapneumovirus, human coronavirus NL63, and other respiratory viruses in healthy preschool-aged children using parent-collected specimens. Pediatrics 120 : e929 e937.[PubMed]
4. Berman S . 1991. Epidemiology of acute respiratory infections in children of developing countries. Rev Infect Dis 13( Suppl 6) : S454 S462.[PubMed]
5. Legend A, Briand S, Shindo N, Brooks WA, de Jong MD, Farrar J, , et al . 2013. Addressing the public health burden of respiratory viruses: the Battle against Respiratory Viruses (BRaVe) Initiative. Future Virology. 8: 953 968.
6. Falsey AR, McCann RM, Hall WJ, Criddle MM, Formica MA, Wycoff D, Kolassa JE . 1997. The “common cold” in frail older persons: impact of rhinovirus and coronavirus in a senior daycare center. J Am Geriatr Soc 45 : 706 711.[PubMed]
7. Gwaltney JM Jr, Hendley JO, Simon G, Jordan WS Jr . 1966. Rhinovirus infections in an industrial population. I. The occurrence of illness. N Engl J Med 275 : 1261 1268.[PubMed]
8. Arruda E, Pitkäranta A, Witek TJJ Jr, Doyle CA, Hayden FG . 1997. Frequency and natural history of rhinovirus infections in adults during autumn. J Clin Microbiol 35 : 2864 2868.[PubMed]
9. Thompson M, Vodicka TA, Blair PS, Buckley DI, Heneghan C, Hay AD TARGET Programme Team . 2013. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ 347 : f7027.[PubMed]
10. Elkhatieb A, Hipskind G, Woerner D, Hayden FG . 1993. Middle ear abnormalities during natural rhinovirus colds in adults. J Infect Dis 168 : 618 621.[PubMed]
11. Buchman CA, Doyle WJ, Skoner DP, Post JC, Alper CM, Seroky JT, Anderson K, Preston RA, Hayden FG, Fireman P, Ehrlich GD . 1995. Influenza A virus—induced acute otitis media. J Infect Dis 172 : 1348 1351.[PubMed]
12. Dingle JH, Badger GF, Jordan WS Jr . 1964. Illness in the Home: Study of 25,000 Illnesses in a Group of Cleveland Families. Press of Case Western University, Cleveland.
13. Henderson FW, Collier AM, Sanyal MA, Watkins JM, Fairclough DL, Clyde WA Jr, Denny FW . 1982. A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion. N Engl J Med 306 : 1377 1383.[PubMed]
14. Pitkäranta A, Virolainen A, Jero J, Arruda E, Hayden FG . 1998. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 102 : 291 295.[PubMed]
15. Gwaltney JM Jr, Phillips CD, Miller RD, Riker DK . 1994. Computed tomographic study of the common cold. N Engl J Med 330 : 25 30.[PubMed]
16. Turner BW, Cail WS, Hendley JO, Hayden FG, Doyle WJ, Sorrentino JV, Gwaltney JM Jr . 1992. Physiologic abnormalities in the paranasal sinuses during experimental rhinovirus colds. J Allergy Clin Immunol 90 : 474 478.[PubMed]
17. Friedlander SL, Busse WW . 2005. The role of rhinovirus in asthma exacerbations. J Allergy Clin Immunol 116 : 267 273.[PubMed]
18. Wilkinson TM, Hurst JR, Perera WR, Wilks M, Donaldson GC, Wedzicha JA . 2006. Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD. Chest 129 : 317 324.[PubMed]
19. Mallia P, Johnston SL . 2006. How viral infections cause exacerbation of airway diseases. Chest 130 : 1203 1210.[PubMed]
20. Arruda E, Boyle TR, Winther B, Pevear DC, Gwaltney JM Jr, Hayden FG . 1995. Localization of human rhinovirus replication in the upper respiratory tract by in situ hybridization. J Infect Dis 171 : 1329 1333.[PubMed]
21. Rautiainen M, Nuutinen J, Kiukaanniemi H, Collan Y . 1992. Ultrastructural changes in human nasal cilia caused by the common cold and recovery of ciliated epithelium. Ann Otol Rhinol Laryngol 101 : 982 987.[PubMed]
22. Fraenkel DJ, Bardin PG, Sanderson G, Lampe F, Johnston SL, Holgate ST . 1994. Immunohistochemical analysis of nasal biopsies during rhinovirus experimental colds. Am J Respir Crit Care Med 150 : 1130 1136.[PubMed]
23. Turner RB, Wecker MT, Pohl G, Witek TJ, McNally E, St George R, Winther B, Hayden FG . 1999. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial. JAMA 281 : 1797 1804.[PubMed]
24. Mosser AG, Vrtis R, Burchell L, Lee WM, Dick CR, Weisshaar E, Bock D, Swenson CA, Cornwell RD, Meyer KC, Jarjour NN, Busse WW, Gern JE . 2005. Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues. Am J Respir Crit Care Med 171 : 645 651.[PubMed]
25. Igarashi Y, Skoner DP, Doyle WJ, White MV, Fireman P, Kaliner MA . 1993. Analysis of nasal secretions during experimental rhinovirus upper respiratory infections. J Allergy Clin Immunol 92 : 722 731.[PubMed]
26. Naclerio RM, Proud D, Lichtenstein LM, Kagey-Sobotka A, Hendley JO, Sorrentino J, Gwaltney JM . 1988. Kinins are generated during experimental rhinovirus colds. J Infect Dis 157 : 133 142.[PubMed]
27. Proud D, Reynolds CJ, Lacapra S, Kagey-Sobotka A, Lichtenstein LM, Naclerio RM . 1988. Nasal provocation with bradykinin induces symptoms of rhinitis and a sore throat. Am Rev Respir Dis 137 : 613 616.[PubMed]
28. Gaffey MJ, Gwaltney JM Jr, Sastre A, Dressler WE, Sorrentino JV, Hayden FG . 1987. Intranasally and orally administered antihistamine treatment of experimental rhinovirus colds. Am Rev Respir Dis 136 : 556 560.[PubMed]
29. Doyle WJ, Casselbrant ML, Li-Korotky HS, Doyle AP, Lo CY, Turner R, Cohen S . 2010. The interleukin 6 -174 C/C genotype predicts greater rhinovirus illness. J Infect Dis 201 : 199 206.[PubMed]
30. Rees GL, Eccles R . 1994. Sore throat following nasal and oropharyngeal bradykinin challenge. Acta Otolaryngol 114 : 311 314.[PubMed]
31. Okamoto Y, Kudo K, Ishikawa K, Ito E, Togawa K, Saito I, Moro I, Patel JA, Ogra PL . 1993. Presence of respiratory syncytial virus genomic sequences in middle ear fluid and its relationship to expression of cytokines and cell adhesion molecules. J Infect Dis 168 : 1277 1281.[PubMed]
32. Gwaltney JM Jr, Druce HM . 1997. Efficacy of brompheniramine maleate for the treatment of rhinovirus colds. Clin Infect Dis 25 : 1188 1194.[PubMed]
33. Turner RB, Sperber SJ, Sorrentino JV, O'Connor RR, Rogers J, Batouli AR, Gwaltney JM Jr . 1997. Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold. Clin Infect Dis 25 : 824 830.[PubMed]
34. Taverner D, Danz C, Economos D . 1999. The effects of oral pseudoephedrine on nasal patency in the common cold: a double-blind single-dose placebo-controlled trial. Clin Otolaryngol Allied Sci 24 : 47 51.[PubMed]
35. Jawad SS, Eccles R . 1998. Effect of pseudoephedrine on nasal airflow in patients with nasal congestion associated with common cold. Rhinology 36 : 73 76.[PubMed]
36. Sperber SJ, Hendley JO, Hayden FG, Riker DK, Sorrentino JV, Gwaltney JM Jr . 1992. Effects of naproxen on experimental rhinovirus colds. A randomized, double-blind, controlled trial. Ann Intern Med 117 : 37 41.[PubMed]
37. Doyle WJ, Riker DK, McBride TP, Hayden FG, Hendley JO, Swarts JD, Gwaltney JM . 1993. Therapeutic effects of an anticholinergic-sympathomimetic combination in induced rhinovirus colds. Ann Otol Rhinol Laryngol 102 : 521 527.[PubMed]
38. Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E, Morgenstern LB, Wilterdink JL, Horwitz RI . 2000. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 343 : 1826 1832.[PubMed]
39. Yoon BW, Bae HJ, Hong KS, Lee SM, Park BJ, Yu KH, Han MK, Lee YS, Chung DK, Park JM, Jeong SW, Lee BC, Cho KH, Kim JS, Lee SH, Yoo KM Acute Brain Bleeding Analysis (ABBA) Study Investigators . 2007. Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke. Neurology 68 : 146 149.[PubMed]
40. Diamond L, Dockhorn RJ, Grossman J, Kisicki JC, Posner M, Zinny MA, Koker P, Korts D, Wecker MT . 1995. A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold. J Allergy Clin Immunol 95 : 1139 1146.[PubMed]
41. Barrett B, Brown R, Rakel D, Mundt M, Bone K, Barlow S, Ewers T . 2010. Echinacea for treating the common cold: a randomized trial. Ann Intern Med 153 : 769 777.[PubMed]
42. Karsch-Völk M, Barrett B, Linde K . 2015. Echinacea for preventing and treating the common cold. JAMA 313 : 618 619.[PubMed]
43. Science M, Johnstone J, Roth DE, Guyatt G, Loeb M . 2012. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 184 : E551 E561.[PubMed]
44. Huovinen P, Lahtonen R, Ziegler T, Meurman O, Hakkarainen K, Miettinen A, Arstila P, Eskola J, Saikku P . 1989. Pharyngitis in adults: the presence and coexistence of viruses and bacterial organisms. Ann Intern Med 110 : 612 616.[PubMed]
45. Luzuriaga K, Sullivan JL . 2010. Infectious mononucleosis. N Engl J Med 362 : 1993 2000.[PubMed]
46. Attia M, Zaoutis T, Eppes S, Klein J, Meier F . 1999. Multivariate predictive models for group A beta-hemolytic streptococcal pharyngitis in children. Acad Emerg Med 6 : 8 13.[PubMed]
47. Centor RM, Atkinson TP, Ratliff AE, Xiao L, Crabb DM, Estrada CA, Faircloth MB, Oestreich L, Hatchett J, Khalife W, Waites KB . 2015. The clinical presentation of Fusobacterium-positive and streptococcal-positive pharyngitis in a university health clinic: a cross-sectional study. Ann Intern Med 162 : 241 247.[PubMed]
48. Lean WL, Arnup S, Danchin M, Steer AC . 2014. Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis. Pediatrics 134 : 771 781.[PubMed]
49. Spink A, Glasziou PP, Del Mar CB . 2013. Antibiotics for sore throat. Cochrane Database of Systematic Reviews ID CD000023.
50. McIsaac WJ, Kellner JD, Aufricht P, Vanjaka A, Low DE . 2004. Empirical validation of guidelines for the management of pharyngitis in children and adults. JAMA 291 : 1587 1595.[PubMed]
51. Foy HM, Cooney MK, Maletzky AJ, Grayston JT . 1973. Incidence and etiology of pneumonia, croup and bronchiolitis in preschool children belonging to a prepaid medical care group over a four-year period. Am J Epidemiol 97 : 80 92.[PubMed]
52. Denny FW, Murphy TF, Clyde WAJ Jr, Collier AM, Henderson FW . 1983. Croup: an 11-year study in a pediatric practice. Pediatrics 71 : 871 876.[PubMed]
53. van der Hoek L, Sure K, Ihorst G, Stang A, Pyrc K, Jebbink MF, Petersen G, Forster J, Berkhout B, Uberla K . 2005. Croup is associated with the novel coronavirus NL63. PLoS Med 2 : e240.[PubMed]
54. Ross LA, Mason WH, Lanson J, Deakers TW, Newth CJL . 1992. Laryngotracheobronchitis as a complication of measles during an urban epidemic. J Pediatr 121 : 511 515.[PubMed]
55. Kim HW, Brandt CD, Arrobio JO, Murphy B, Chanock RM, Parrott RH . 1979. Influenza A and B virus infection in infants and young children during the years 1957–1976. Am J Epidemiol 109 : 464 479.[PubMed]
56. Mayo-Smith MF, Spinale JW, Donskey CJ, Yukawa M, Li RH, Schiffman FJ . 1995. Acute epiglottitis. An 18-year experience in Rhode Island. Chest 108 : 1640 1647.[PubMed]
57. Hall CB, Geiman JM, Breese BB, Douglas RG Jr . 1977. Parainfluenza viral infections in children: correlation of shedding with clinical manifestations. J Pediatr 91 : 194 198.[PubMed]
58. Hall CB, McBride JT, . 2000. Acute Laryngotracheobronchitis, p 663 669. In Mandell GL, Bennet JE, Dolin R (ed), Principles and Practice of Infectious Diseases. Churchill Livingstone, Philadelphia.
59. Lang SA, Duncan PG, Shephard DA, Ha HC . 1990. Pulmonary oedema associated with airway obstruction. Can J Anaesth 37 : 210 218.[PubMed]
60. Super DM, Cartelli NA, Brooks LJ, Lembo RM, Kumar ML . 1989. A prospective randomized double-blind study to evaluate the effect of dexamethasone in acute laryngotracheitis. J Pediatr 115 : 323 329.[PubMed]
61. Geelhoed GC, Macdonald WB . 1995. Oral dexamethasone in the treatment of croup: 0.15 mg/kg versus 0.3 mg/kg versus 0.6 mg/kg. Pediatr Pulmonol 20 : 362 368.[PubMed]
62. Husby S, Agertoft L, Mortensen S, Pedersen S . 1993. Treatment of croup with nebulised steroid (budesonide): a double blind, placebo controlled study. Arch Dis Child 68 : 352 355.[PubMed]
63. Klassen TP, Feldman ME, Watters LK, Sutcliffe T, Rowe PC . 1994. Nebulized budesonide for children with mild-to-moderate croup. N Engl J Med 331 : 285 289.[PubMed]
64. Johnson DW, Jacobson S, Edney PC, Hadfield P, Mundy ME, Schuh S . 1998. A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. N Engl J Med 339 : 498 503.[PubMed]
65. Bjornson CL, Klassen TP, Williamson J, Brant R, Mitton C, Plint A, Bulloch B, Evered L, Johnson DW Pediatric Emergency Research Canada Network . 2004. A randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J Med 351 : 1306 1313.[PubMed]
66. Skolnik NS . 1989. Treatment of croup. A critical review. Am J Dis Child 143 : 1045 1049.[PubMed]
67. Fogel JM, Berg IJ, Gerber MA, Sherter CB . 1982. Racemic epinephrine in the treatment of croup: nebulization alone versus nebulization with intermittent positive pressure breathing. J Pediatr 101 : 1028 1031.[PubMed]
68. Westley CR, Cotton EK, Brooks JG . 1978. Nebulized racemic epidnephrine by IPPB for the treatment of croup. Am J Dis Child 132 : 484 487.[PubMed]
69. Cherry JD . 2008. Clinical practice. Croup. N Engl J Med 358 : 384 391.[PubMed]
70. Pitluk JD, Uman H, Safranek S . 2011. Clinical inquiries. What's best for croup? J Fam Pract 60 : 680 681.[PubMed]
71. Wohl MEB, Chernick V . 1978. State of the art: bronchiolitis. Am Rev Respir Dis 118 : 759 781.[PubMed]
72. Hall CB, Hall WJ, Speers DM . 1979. Clinical and physiological manifestations of bronchiolitis and pneumonia. Outcome of respiratory syncytial virus. Am J Dis Child 133 : 798 802.[PubMed]
73. Khamapirad T, Glezen WP . 1987. Clinical and radiographic assessment of acute lower respiratory tract disease in infants and children. Semin Respir Infect 2 : 130 144.[PubMed]
74. Friis B, Eiken M, Hornsleth A, Jensen A . 1990. Chest X-ray appearances in pneumonia and bronchiolitis. Correlation to virological diagnosis and secretory bacterial findings. Acta Paediatr Scand 79 : 219 225.[PubMed]
75. Dawson KP, Long A, Kennedy J, Mogridge N . 1990. The chest radiograph in acute bronchiolitis. J Paediatr Child Health 26 : 209 211.[PubMed]
76. Gozal D, Colin AA, Jaffe M, Hochberg Z . 1990. Water, electrolyte, and endocrine homeostasis in infants with bronchiolitis. Pediatr Res 27 : 204 209.[PubMed]
77. van Steensel-Moll HA, Hazelzet JA, van der Voort E, Neijens HJ, Hackeng WHL . 1990. Excessive secretion of antidiuretic hormone in infections with respiratory syncytial virus. Arch Dis Child 65 : 1237 1239.[PubMed]
78. Pahl E, Gidding SS . 1988. Echocardiographic assessment of cardiac function during respiratory syncytial virus infection. Pediatrics 81 : 830 834.[PubMed]
79. Parrott RH, Kim HW, Arrobio JO, Hodes DS, Murphy BR, Brandt CD, Camargo E, Chanock RM . 1973. Epidemiology of respiratory syncytial virus infection in Washington, D.C. II. Infection and disease with respect to age, immunologic status, race and sex. Am J Epidemiol 98 : 289 300.[PubMed]
80. Kim HW, Arrobio JO, Brandt CD, Jeffries BC, Pyles G, Reid JL, Chanock RM, Parrott RH . 1973. Epidemiology of respiratory syncytial virus infection in Washington, D.C. I. Importance of the virus in different respiratory tract disease syndromes and temporal distribution of infection. Am J Epidemiol 98 : 216 225.[PubMed]
81. Henderson FW, Clyde WA Jr, Collier AM, Denny FW, Senior RJ, Sheaffer CI, Conley WG III, Christian RM . 1979. The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr 95 : 183 190.[PubMed]
82. Glezen WP, Taber LH, Frank AL, Kasel JA . 1986. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 140 : 543 546.[PubMed]
83. MacDonald NE, Hall CB, Suffin SC, Alexson C, Harris PJ, Manning JA . 1982. Respiratory syncytial viral infection in infants with congenital heart disease. N Engl J Med 307 : 397 400.[PubMed]
84. Hall CB, Powell KR, MacDonald NE, Gala CL, Menegus ME, Suffin SC, Cohen HJ . 1986. Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med 315 : 77 81.[PubMed]
85. Lebel MH, Gauthier M, Lacroix J, Rousseau E, Buithieu M . 1989. Respiratory failure and mechanical ventilation in severe bronchiolitis. Arch Dis Child 64 : 1431 1437.[PubMed]
86. McConnochie KM, Roghmann KJ . 1986. Parental smoking, presence of older siblings, and family history of asthma increase risk of bronchiolitis. Am J Dis Child 140 : 806 812.[PubMed]
87. Wright AL, Taussig LM, Ray CG, Harrison HR, Holberg CJ . 1989. The Tucson Children's Respiratory Study. II. Lower respiratory tract illness in the first year of life. Am J Epidemiol 129 : 1232 1246.[PubMed]
88. García CG, Bhore R, Soriano-Fallas A, Trost M, Chason R, Ramilo O, Mejias A . 2010. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics 126 : e1453 e1460.[PubMed]
89. Hasegawa K, Jartti T, Mansbach JM, Laham FR, Jewell AM, Espinola JA, Piedra PA, Camargo CA Jr . 2015. Respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the United States and Finland. J Infect Dis 211 : 1550 1559.[PubMed]
90. van den Hoogen BG, de Jong JC, Groen J, Kuiken T, de Groot R, Fouchier RA, Osterhaus AD . 2001. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med 7 : 719 724.[PubMed]
91. Williams JV, Harris PA, Tollefson SJ, Halburnt-Rush LL, Pingsterhaus JM, Edwards KM, Wright PF, Crowe JE Jr . 2004. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med 350 : 443 450.[PubMed]
92. Edwards KM, Zhu Y, Griffin MR, Weinberg GA, Hall CB, Szilagyi PG, Staat MA, Iwane M, Prill MM, Williams JV New Vaccine Surveillance Network . 2013. Burden of human metapneumovirus infection in young children. N Engl J Med 368 : 633 643.[PubMed]
93. Chidekel AS, Bazzy AR, Rosen CL . 1994. Rhinovirus infection associated with severe lower respiratory tract illness and worsening lung disease in infants with bronchopulmonary dysplasia. Pediatr Pulmonol 18 : 261 263.[PubMed]
94. Becroft DMO . 1971. Bronchiolitis obliterans, bronchiectasis, and other sequelae of adenovirus type 21 infection in young children. J Clin Pathol 24 : 72 82.[PubMed]
95. Esper F, Weibel C, Ferguson D, Landry ML, Kahn JS . 2005. Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children. J Infect Dis 191 : 492 498.[PubMed]
96. Midulla F, Scagnolari C, Bonci E, Pierangeli A, Antonelli G, De Angelis D, Berardi R, Moretti C . 2010. Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants. Arch Dis Child 95 : 35 41.[PubMed]
97. Waner JL, Whitehurst NJ, Todd SJ, Shalaby H, Wall LV . 1990. Comparison of directigen RSV with viral isolation and direct immunofluorescence for the identification of respiratory syncytial virus. J Clin Microbiol 28 : 480 483.[PubMed]
98. Barnes SD, Leclair JM, Forman MS, Townsend TR, Laughlin GM, Charache P . 1989. Comparison of nasal brush and nasopharyngeal aspirate techniques in obtaining specimens for detection of respiratory syncytial viral antigen by immunofluorescence. Pediatr Infect Dis J 8 : 598 601.[PubMed]
99. Aherne W, Bird T, Court SDM, Gardner PS, McQuillin J . 1970. Pathological changes in virus infections of the lower respiratory tract in children. J Clin Pathol 23 : 7 18.[PubMed]
100. LeSouëf PN, Geelhoed GC, Turner DJ, Morgan SE, Landau LI . 1989. Response of normal infants to inhaled histamine. Am Rev Respir Dis 139 : 62 66.[PubMed]
101. van Schaik SM, Welliver RC, Kimpen JLL . 2000. Novel pathways in the pathogenesis of respiratory syncytial virus disease. Pediatr Pulmonol 30 : 131 138.[PubMed]
102. Larsen GL, Colasurdo GN . 1999. Neural control mechanisms within airways: disruption by respiratory syncytial virus. J Pediatr 135 : 21 27.[PubMed]
103. Miyairi I, DeVincenzo JP . 2008. Human genetic factors and respiratory syncytial virus disease severity. Clin Microbiol Rev 21 : 686 703.[PubMed]
104. Stein RT, Sherrill D, Morgan WJ, Holberg CJ, Halonen M, Taussig LM, Wright AL, Martinez FD . 1999. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 354 : 541 545.[PubMed]
105. Poorisrisak P, Halkjaer LB, Thomsen SF, Stensballe LG, Kyvik KO, Skytthe A, Schioetz PO, Bisgaard H . 2010. Causal direction between respiratory syncytial virus bronchiolitis and asthma studied in monozygotic twins. Chest 138 : 338 344.[PubMed]
106. Miller EK, Williams JV, Gebretsadik T, Carroll KN, Dupont WD, Mohamed YA, Morin LL, Heil L, Minton PA, Woodward K, Liu Z, Hartert TV . 2011. Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness. J Allergy Clin Immunol 127 : 883 891.[PubMed]
107. Carroll KN, Gebretsadik T, Minton P, Woodward K, Liu Z, Miller EK, Williams JV, Dupont WD, Hartert TV . 2012. Influence of maternal asthma on the cause and severity of infant acute respiratory tract infections. J Allergy Clin Immunol 129 : 1236 1242.[PubMed]
108. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, Phelan KJ, Zorc JJ, Stanko-Lopp D, Brown MA, Nathanson I, Rosenblum E, Sayles S III, Hernandez-Cancio S American Academy of Pediatrics . 2014. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 134 : e1474 e1502.[PubMed]
109. Wu S, Baker C, Lang ME, Schrager SM, Liley FF, Papa C, Mira V, Balkian A, Mason WH . 2014. Nebulized hypertonic saline for bronchiolitis: a randomized clinical trial. JAMA Pediatr 168 : 657 663.[PubMed]
110. Sinha IP, McBride AK, Smith R, Fernandes RM . 2015. CPAP and high-flow nasal cannula oxygen in bronchiolitis. Chest 148 : 810 823.[PubMed]
111. Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S, Price D, Moloney S, Kimberley A, Woolfield N, Cadzow S, Fiumara F, Wilson P, Mego S, VandeVelde D, Sanders S, O'Rourke P, Francis P . 2003. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med 349 : 27 35.[PubMed]
112. Corneli HM, Zorc JJ, Mahajan P, Shaw KN, Holubkov R, Reeves SD, Ruddy RM, Malik B, Nelson KA, Bregstein JS, Brown KM, Denenberg MN, Lillis KA, Cimpello LB, Tsung JW, Borgialli DA, Baskin MN, Teshome G, Goldstein MA, Monroe D, Dean JM, Kuppermann N Bronchiolitis Study Group of the Pediatric Emergency Care Applied Research Network (PECARN) . 2007. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med 357 : 331 339.[PubMed]
113. Pinto LA, Pitrez PM, Luisi F, de Mello PP, Gerhardt M, Ferlini R, Barbosa DC, Daros I, Jones MH, Stein RT, Marostica PJ . 2012. Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes: a randomized, double-blinded, and placebo-controlled clinical trial. J Pediatr 161 : 1104 1108.[PubMed]
114. IMpactRSVStudyGroup . 1998. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102 : 531537.
115. American Academy of Pediatrics Committee on Infectious DiseasesAmerican Academy of Pediatrics Bronchiolitis Guidelines Committee . 2014. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 134 : 415420.[PubMed]
116. Fulginiti VA, Eller JJ, Sieber OF, Joyner JW, Minamitani M, Meiklejohn G . 1969. Respiratory virus immunization. I. A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and an alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol 89 : 435 448.[PubMed]
117. Sherry MK, Klainer AS, Wolff M, Gerhard H . 1988. Herpetic tracheobronchitis. Ann Intern Med 109 : 229 233.[PubMed]
118. Gonzales R, Sande MA . 2000. Uncomplicated acute bronchitis. Ann Intern Med 133 : 981 991.[PubMed]
119. Wenzel RP, Fowler AA III . 2006. Clinical practice. Acute bronchitis. N Engl J Med 355 : 2125 2130.[PubMed]
120. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, Likos AM, Posey DL, Klimov A, Lindstrom SE, Balish A, Medina MJ, Wallis TR, Guarner J, Paddock CD, Shieh WJ, Zaki SR, Sejvar JJ, Shay DK, Harper SA, Cox NJ, Fukuda K, Uyeki TM Influenza Special Investigations Team . 2005. Influenza-associated deaths among children in the United States, 2003–2004. N Engl J Med 353 : 2559 2567.[PubMed]
121. Louie JK, Acosta M, Samuel MC, Schechter R, Vugia DJ, Harriman K, Matyas BT California Pandemic (H1N1) Working Group . 2011. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis 52 : 301 312.[PubMed]
122. Kwong JC, Campitelli MA, Rosella LC . 2011. Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: a cohort study. Clin Infect Dis 53 : 413 421.[PubMed]
123. Siston AM, Rasmussen SA, Honein MA, Fry AM, Seib K, Callaghan WM, Louie J, Doyle TJ, Crockett M, Lynfield R, Moore Z, Wiedeman C, Anand M, Tabony L, Nielsen CF, Waller K, Page S, Thompson JM, Avery C, Springs CB, Jones T, Williams JL, Newsome K, Finelli L, Jamieson DJ Pandemic H1N1 Influenza in Pregnancy Working Group . 2010. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 303 : 1517 1525.[PubMed]
124. Louie JK, Acosta M, Jamieson DJ, Honein MA California Pandemic (H1N1) Working Group . 2010. Severe 2009 H1N1 influenza in pregnant and postpartum women in California. N Engl J Med 362 : 27 35.[PubMed]
125. Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR . 1998. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 148 : 1094 1102.[PubMed]
126. Louria DB, Blumenfeld HL, Ellis JT, Kilbourne ED, Rogers DE . 1959. Studies on influenza in the pandemic of 1957–1958. II. Pulmonary complications of influenza. J Clin Invest 38 : 213 265.[PubMed]
127. Schwarzmann SW, Adler JL, Sullivan RJ Jr, Marine WM . 1971. Bacterial pneumonia during the Hong Kong influenza epidemic of 1968–1969. Arch Intern Med 127 : 1037 1041.[PubMed]
128. Ruuskanen O, Lahti E, Jennings LC, Murdoch DR . 2011. Viral pneumonia. Lancet 377 : 1264 1275.[PubMed]
129. Gadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF, Hill AT, Templeton KE . 2016. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis 62 : 817 823.[PubMed]
130. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L CDC EPIC Study Team . 2015. Community-acquired pneumonia requiring hospitalization among US adults. N Engl J Med 373 : 415 427.[PubMed]
131. Karhu J, Ala-Kokko TI, Vuorinen T, Ohtonen P, Syrjälä H . 2014. Lower respiratory tract virus findings in mechanically ventilated patients with severe community-acquired pneumonia. Clin Infect Dis 59 : 62 70.[PubMed]
132. Sangil A, Calbo E, Robles A, Benet S, Viladot ME, Pascual V, Cuchí E, Pérez J, Barreiro B, Sánchez B, Torres J, Canales L, De Marcos JA, Garau J . 2012. Aetiology of community-acquired pneumonia among adults in an H1N1 pandemic year: the role of respiratory viruses. Eur J Clin Microbiol Infect Dis 31 : 2765 2772.[PubMed]
133. Choi SH, Hong SB, Ko GB, Lee Y, Park HJ, Park SY, Moon SM, Cho OH, Park KH, Chong YP, Kim SH, Huh JW, Sung H, Do KH, Lee SO, Kim MN, Jeong JY, Lim CM, Kim YS, Woo JH, Koh Y . 2012. Viral infection in patients with severe pneumonia requiring intensive care unit admission. Am J Respir Crit Care Med 186 : 325 332.[PubMed]
134. Garbino J, Soccal PM, Aubert J-D, Rochat T, Meylan P, Thomas Y, Tapparel C, Bridevaux PO, Kaiser L . 2009. Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in adults. Thorax 64 : 399 404.[PubMed]
135. Klinger JR, Sanchez MP, Curtin LA, Durkin M, Matyas B . 1998. Multiple cases of life-threatening adenovirus pneumonia in a mental health care center. Am J Respir Crit Care Med 157 : 645 649.[PubMed]
136. Louie JK, Kajon AE, Holodniy M, Guardia-LaBar L, Lee B, Petru AM, Hacker JK, Schnurr DP . 2008. Severe pneumonia due to adenovirus serotype 14: a new respiratory threat? Clin Infect Dis 46 : 421 425.[PubMed]
137. Hall WJ, Hall CB, Speers DM . 1978. Respiratory syncytial virus infection in adults: clinical, virologic, and serial pulmonary function studies. Ann Intern Med 88 : 203 205.[PubMed]
138. Zaroukian MH, Leader I . 1988. Community-acquired pneumonia and infection with respiratory syncytial virus. Ann Intern Med 109 : 515 516.[PubMed]
139. Falsey AR . 1998. Respiratory syncytial virus infection in older persons. Vaccine 16 : 1775 1778.[PubMed]
140. Han LL, Alexander JP, Anderson LJ . 1999. Respiratory syncytial virus pneumonia among the elderly: an assessment of disease burden. J Infect Dis 179 : 25 30.[PubMed]
141. Marx A, Gary HE Jr, Marston BJ, Erdman DD, Breiman RF, Török TJ, Plouffe JF, File TM Jr, Anderson LJ . 1999. Parainfluenza virus infection among adults hospitalized for lower respiratory tract infection. Clin Infect Dis 29 : 134 140.[PubMed]
142. Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki SR, Ksiazek TG, Rollin PE, Nichol S, Umland ET, Moolenaar RL, Reef SE, Nolte KB, Gallaher MM, Butler JC, Breiman RF The Hantavirus Study Group . 1994. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. N Engl J Med 330 : 949 955.[PubMed]
143. Butler JC, Peters CJ . 1994. Hantaviruses and hantavirus pulmonary syndrome. Clin Infect Dis 19 : 387 394.[PubMed]
144. Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK, Yuen KY SARS study group . 2003. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361 : 1319 1325.[PubMed]
145. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA . 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367 : 1814 1820.[PubMed]
146. Drosten C, Seilmaier M, Corman VM, Hartmann W, Scheible G, Sack S, Guggemos W, Kallies R, Muth D, Junglen S, Müller MA, Haas W, Guberina H, Röhnisch T, Schmid-Wendtner M, Aldabbagh S, Dittmer U, Gold H, Graf P, Bonin F, Rambaut A, Wendtner CM . 2013. Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect Dis 13 : 745 751.[PubMed]
147. Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, Flemban H, Al-Nassir WN, Balkhy HH, Al-Hakeem RF, Makhdoom HQ, Zumla AI, Memish ZA . 2013. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis 13 : 752 761.[PubMed]
148. Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, Walmsley SL, Mazzulli T, Avendano M, Derkach P, Ephtimios IE, Kitai I, Mederski BD, Shadowitz SB, Gold WL, Hawryluck LA, Rea E, Chenkin JS, Cescon DW, Poutanen SM, Detsky AS . 2003. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 289 : 2801 2809.[PubMed]
149. Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, Ahuja A, Yung MY, Leung CB, To KF, Lui SF, Szeto CC, Chung S, Sung JJ . 2003. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 348 : 1986 1994.[PubMed]
150. Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, Stockmann C, Anderson EJ, Grijalva CG, Self WH, Zhu Y, Patel A, Hymas W, Chappell JD, Kaufman RA, Kan JH, Dansie D, Lenny N, Hillyard DR, Haynes LM, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Finelli L CDC EPIC Study Team . 2015. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med 372 : 835 845.[PubMed]
151. García-García MLMDP, Calvo C, Pozo F, Villadangos PAMD, Pérez-Breña P, Casas I . 2012. Spectrum of respiratory viruses in children with community-acquired pneumonia. Pediatr Infect Dis J 31 : 808 813.[PubMed]
152. Frost HM, Robinson CC, Dominguez SR . 2014. Epidemiology and clinical presentation of parainfluenza type 4 in children: a 3-year comparative study to parainfluenza types 1–3. J Infect Dis 209 : 695 702.[PubMed]
153. Sugaya N, Nerome K, Ishida M, Nerome R, Nagae M, Takeuchi Y, Osano M .