Bronchiolitis

http://emedicine.medscape.com/article/304649-overview

Medscape Reference Reference

News Reference Education MEDLINE

Bronchiolitis
Author: John Udeani, MD, FAAEM; Chief Editor: Zab Mosenifar, MD more... Updated: Jun 9, 2011

Background
Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused by a viral infection. Although it may occur in persons of any age, severe symptoms are usually only evident in young infants; the larger airways of older children and adults better accommodate mucosal edema. Bronchiolitis usually affects children younger than 2 years, with a peak in infants aged 3-6 months. Acute bronchiolitis is the most common cause of lower respiratory tract infection in the first year of life. It is generally a self-limiting condition and is most commonly associated with respiratory syncytial virus. Bronchiolar injury and the consequent interplay between inflammatory and mesenchymal cells can lead to diverse pathological and clinical syndromes. Bronchioles are small airways, less than 2 mm in diameter, and lack cartilage and submucosal glands. The terminal bronchiole, a 16th generation airway, is the final conducting airway that terminates in the respiratory bronchioles. The acinus (ie, the gas exchange unit of the lung) consists of respiratory bronchioles, the alveolar duct, and alveoli. The bronchiolar lining consists of surfactant-secreting Clara cells and neuroendocrine cells, which are the source of bioactive products such as somatostatin, endothelin, and serotonin. Wilhelm Lange first described obliterative bronchiolitis (OB) in 1901 by reporting 2 cases of interstitial bronchiolar disorder. In 1985,[1] bronchiolitis obliterans-organizing pneumonia (BOOP) was described as a separate condition with different clinical, radiographic, and prognostic features than OB. BOOP is a histopathologic lesion, not a specific diagnosis. Its pathologic hallmark is proliferative bronchiolitis or bronchiolitis obliterans in association with organizing pneumonia. BOOP and OB are beyond the scope of this article and are not discussed further.

Pathophysiology
Bronchiolitis is very contagious. The virus that causes it is spread from person to person by direct contact with nasal secretions, airborne droplets, and fomites. The effects of bronchiolar injury include the following: Increased mucus secretion Bronchial obstruction and constriction Alveolar cell death, mucus debris, viral invasion Air trapping Atelectasis Reduced ventilation that leads to ventilation/perfusion mismatch Labored breathing Ninety percent of cases are caused by respiratory syncytial virus (RSV). Other causes of bronchiolitis are addressed in Causes. Complex immunologic mechanisms play a role in the pathogenesis of RSV bronchiolitis. Type 1 allergic reactions mediated by immunoglobulin E may account for some clinically significant bronchiolitis. Infants that are

1 of 7

06/10/2012 13:35

Bronchiolitis

http://emedicine.medscape.com/article/304649-overview

breastfed with colostrum rich in immunoglobulin A appear relatively protected from bronchiolitis.

Epidemiology
Frequency
United States Approximately 1 in 9 infants contracts bronchiolitis in the first year of life, usually during the fall and winter months. In one study, an estimated 1.65 million hospitalizations for bronchiolitis occurred among children younger than 5 years from 1980-1996, accounting for 7 million inpatient days. Children younger than 6 months accounted for 57% of these hospital visits; those younger than 1 year accounted for 81%. International According to the World Health Organization bulletin, an estimated 150 million new cases occur annually; 11-20 million (7-13%) of these cases are severe enough to require hospital admission. Worldwide, 95% of all cases occur in developing countries. Descriptive epidemiologic data from a population-based cohort (Georgia Air Basin, Canada) reported by Koehoorn et al indicated that from 1999-2002, bronchiolitis was associated with 12,474 inpatient and outpatient physician contacts during the first year of life. This equates to 134.2 cases per 1000 person-years. In total, 1588 bronchiolitis cases resulted in hospitalization, which is 17.1 cases per 1000 person-years.[4]
[3] [2]

Mortality/Morbidity
Acute respiratory tract infection in children younger than 5 years is still the leading cause of childhood mortality in the world. In 2000, acute respiratory tract infection accounted for an estimated 1.9 million deaths worldwide; 70% of these deaths occurred in Africa and Southeast Asia.

Race
Race and low socioeconomic status may adversely affect outcome in patients with acute bronchiolitis. In one study,
[5]

RSV bronchiolitis seemed to be more severe in white children than in black children. The reason for this

finding is unknown. A study by La Via et al[6] demonstrated that although more minority children than white children were hospitalized with RSV infection, nothing indicated that the infections in minority children were more or less severe than those in white children.

Sex
The incidence of bronchiolitis is slightly higher in boys. The exact etiology is unclear.

Age
Age was found to be a significant factor in the severity of infection. The younger the person, the more severe the infection tended to be, as measured by the lowest oxygen saturation. Infants younger than 6 months are most severely affected, owing to smaller, more easily obstructed airways and a decreased ability to clear secretions. Intrauterine cigarette-smoke exposure may impair in utero airway development or alter the elastic properties of the lung tissue. Second-hand cigarette smoke (eg, by a parent or family member) in the postnatal period compounds the severity of RSV bronchiolitis in infants.

Contributor Information and Disclosures

Author John Udeani, MD, FAAEM Assistant Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science, University of California, Los Angeles, David Geffen School of Medicine John Udeani, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians Disclosure: Nothing to disclose.

2 of 7

06/10/2012 13:35

Bronchiolitis

http://emedicine.medscape.com/article/304649-overview

Coauthor(s) Charles I Ojielo, MD Assistant Professor of Medicine, Rush Medical College; Consulting Staff, Resident Education Coordinator, Department of Pulmonary and Critical Care Medicine, John H Stroger Hospital of Cook County/Rush University Medical Center Charles I Ojielo, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and American Thoracic Society Disclosure: Nothing to disclose. Specialty Editor Board Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Professor of Genomics and Personalized Medicine Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi Disclosure: See below for list of all activities None None Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Om Prakash Sharma, MD, FRCP, FCCP, DTM&H Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine Disclosure: Nothing to disclose. Timothy D Rice, MD Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians Disclosure: Nothing to disclose. Chief Editor Zab Mosenifar, MD Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society Disclosure: Nothing to disclose.

References
1. Epler GR, Colby TV, McLoud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med. Jan 17 1985;312(3):152-8. [Medline]. 2. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA. Oct 20 1999;282(15):1440-6. [Medline]. 3. Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H. Global estimate of the incidence of clinical pneumonia

3 of 7

06/10/2012 13:35

Bronchiolitis

http://emedicine.medscape.com/article/304649-overview

among children under five years of age. Bull World Health Organ. Dec 2004;82(12):895-903. [Medline]. 4. [Best Evidence] Koehoorn M, Karr CJ, Demers PA, Lencar C, Tamburic L, Brauer M. Descriptive epidemiological features of bronchiolitis in a population-based cohort. Pediatrics. Dec 2008;122(6):1196-203. [Medline]. 5. Bradley JP, Bacharier LB, Bonfiglio J, et al. Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy. Pediatrics. Jan 2005;115(1):e7-14. [Medline]. 6. La Via WV, Grant SW, Stutman HR, Marks MI. Clinical profile of pediatric patients hospitalized with respiratory syncytial virus infection. Clin Pediatr (Phila). Aug 1993;32(8):450-4. [Medline]. 7. Saijo M, Ishii T, Kokubo M, Murono K, Takimoto M, Fujita K. White blood cell count, C-reactive protein and erythrocyte sedimentation rate in respiratory syncytial virus infection of the lower respiratory tract. Acta Paediatr Jpn. Dec 1996;38(6):596-600. [Medline]. 8. Vieira RA, Diniz EM, Vaz FA. Clinical and laboratory study of newborns with lower respiratory tract infection due to respiratory viruses. J Matern Fetal Neonatal Med. May 2003;13(5):341-50. [Medline]. 9. Kuppermann N, Bank DE, Walton EA, Senac MO Jr, McCaslin I. Risks for bacteremia and urinary tract infections in young febrile children with bronchiolitis. Arch Pediatr Adolesc Med. Dec 1997;151(12):1207-14. [Medline]. 10. Liebelt EL, Qi K, Harvey K. Diagnostic testing for serious bacterial infections in infants aged 90 days or younger with bronchiolitis. Arch Pediatr Adolesc Med. May 1999;153(5):525-30. [Medline]. 11. Antonow JA, Hansen K, McKinstry CA, Byington CL. Sepsis evaluations in hospitalized infants with bronchiolitis. Pediatr Infect Dis J. Mar 1998;17(3):231-6. [Medline]. 12. Bloomfield P, Dalton D, Karleka A, Kesson A, Duncan G, Isaacs D. Bacteraemia and antibiotic use in respiratory syncytial virus infections. Arch Dis Child. Apr 2004;89(4):363-7. [Medline]. 13. Dawson KP, Long A, Kennedy J, Mogridge N. The chest radiograph in acute bronchiolitis. J Paediatr Child Health. Aug 1990;26(4):209-11. [Medline]. 14. Shaw KN, Bell LM, Sherman NH. Outpatient assessment of infants with bronchiolitis. Am J Dis Child. Feb 1991;145(2):151-5. [Medline]. 15. Friis B, Eiken M, Hornsleth A, Jensen A. Chest X-ray appearances in pneumonia and bronchiolitis. Correlation to virological diagnosis and secretory bacterial findings. Acta Paediatr Scand. Feb 1990;79(2):219-25. [Medline]. 16. [Best Evidence] Ralston S, Roohi M. A randomized, controlled trial of nasal phenylephrine in infants hospitalized for bronchiolitis. J Pediatr. Dec 2008;153(6):795-8. [Medline]. 17. [Guideline] American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. Oct 2006;118(4):1774-93. [Medline]. 18. [Guideline] Brown KK. Chronic cough due to nonbronchiectatic suppurative airway disease (bronchiolitis): ACCP evidence-based clinical practice guidelines. Chest. Jan 2006;129(1 Suppl):132S-137S. [Medline]. 19. [Best Evidence] Amirav I, Luder AS, Kruger N, et al. A double-blind, placebo-controlled, randomized trial of montelukast for acute bronchiolitis. Pediatrics. Dec 2008;122(6):e1249-55. [Medline]. 20. Menon K, Sutcliffe T, Klassen TP. A randomized trial comparing the efficacy of epinephrine with salbutamol in the treatment of acute bronchiolitis. J Pediatr. Jun 1995;126(6):1004-7. [Medline]. 21. Wainwright C, Altamirano L, Cheney M, et al. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med. Jul 3 2003;349(1):27-35. [Medline]. 22. Hartling L, Fernandes RM, Bialy L, et al. Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysis. BMJ. Apr 6 2011;342:d1714. [Medline]. [Full Text]. 23. Corneli HM, Zorc JJ, Mahajan P, et al. A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis. N Engl J Med. Jul 26 2007;357(4):331-9. [Medline]. 24. Adcock PM, Sanders CL, Marshall GS. Standardizing the care of bronchiolitis. Arch Pediatr Adolesc Med. Aug 1998;152(8):739-44. [Medline].

4 of 7

06/10/2012 13:35

Bronchiolitis

http://emedicine.medscape.com/article/304649-overview

25. American Thoracic Society (ATS) and the European Respiratory Society (ERS). American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. Feb 2000;161(2 Pt 1):646-64. [Medline]. 26. Becroft DM. Bronchiolitis obliterans, bronchiectasis, and other sequelae of adenovirus type 21 infection in young children. J Clin Pathol. Feb 1971;24(1):72-82. [Medline]. 27. Bordley WC, Viswanathan M, King VJ, et al. Diagnosis and testing in bronchiolitis: a systematic review. Arch Pediatr Adolesc Med. Feb 2004;158(2):119-26. [Medline]. 28. Brand PL, Vaessen-Verberne AA. Differences in management of bronchiolitis between hospitals in The Netherlands. Dutch Paediatric Respiratory Society. Eur J Pediatr. May 2000;159(5):343-7. [Medline]. 29. Brooks AM, McBride JT, McConnochie KM, Aviram M, Long C, Hall CB. Predicting deterioration in previously healthy infants hospitalized with respiratory syncytial virus infection. Pediatrics. Sep 1999;104(3 Pt 1):463-7. [Medline]. 30. Brown L, Shaw T, Wittlake WA. Does leucocytosis identify bacterial infections in febrile neonates presenting to the emergency department?. Emerg Med J. Apr 2005;22(4):256-9. [Medline]. 31. Byington CL, Castillo H, Gerber K, et al. The effect of rapid respiratory viral diagnostic testing on antibiotic use in a children's hospital. Arch Pediatr Adolesc Med. Dec 2002;156(12):1230-4. [Medline]. 32. Byington CL, Enriquez FR, Hoff C, et al. Serious bacterial infections in febrile infants 1 to 90 days old with and without viral infections. Pediatrics. Jun 2004;113(6):1662-6. [Medline]. 33. Cade A, Brownlee KG, Conway SP, et al. Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis. Arch Dis Child. Feb 2000;82(2):126-30. [Medline]. 34. Carlsen KH, Orstavik I, Halvorsen K. Viral infections of the respiratory tract in hospitalized children. A study from Oslo during a 90 months' period. Acta Paediatr Scand. Jan 1983;72(1):53-8. [Medline]. 35. Castro M, Schechtman KB, Halstead J, Bloomberg G. Risk factors for asthma morbidity and mortality in a large metropolitan city. J Asthma. Dec 2001;38(8):625-35. [Medline]. 36. Christakis DA, Cowan CA, Garrison MM, Molteni R, Marcuse E, Zerr DM. Variation in inpatient diagnostic testing and management of bronchiolitis. Pediatrics. Apr 2005;115(4):878-84. [Medline]. 37. Colby TV. Bronchiolitis. Pathologic considerations. Am J Clin Pathol. Jan 1998;109(1):101-9. [Medline]. 38. De Boeck K. Respiratory Syncytial virus: Clinical Aspects and epidemiology. Monaldi Arch Chest Dis. 1996;51:210-213. 39. Downham MA, Scott R, Sims DG, Webb JK, Gardner PS. Breast-feeding protects against respiratory syncytial virus infections. Br Med J. Jul 31 1976;2(6030):274-6. [Medline]. 40. Duttweiler L, Nadal D, Frey B. Pulmonary and systemic bacterial co-infections in severe RSV bronchiolitis. Arch Dis Child. Dec 2004;89(12):1155-7. [Medline]. 41. Edelson PJ. Respiratory syncytial virus pneumonia. In: Pediatric Emergency Casebook. 3. New York, NY: World Health Communications; 1985:1-15. 42. Fernandez JA, Tapia L, Palomino MA, Larranaga C, Pena M, Jaramillo H. Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection. Eur Cytokine Netw. Jan-Mar 2005;16(1):35-40. [Medline]. 43. Field CM, Connolly JH, Murtagh G, Slattery CM, Turkington EE. Antibiotic treatment of epidemic bronchiolitis--a double-blind trial. Br Med J. Jan 8 1966;1(5479):83-5. [Medline]. 44. Flores G, Horwitz RI. Efficacy of beta2-agonists in bronchiolitis: a reappraisal and meta-analysis. Pediatrics. Aug 1997;100(2 Pt 1):233-9. [Medline]. 45. Fox GF, Everard ML, Marsh MJ, Milner AD. Randomised controlled trial of budesonide for the prevention of post-bronchiolitis wheezing. Arch Dis Child. Apr 1999;80(4):343-7. [Medline]. 46. Gurkan F, Kiral A, Dagli E, Karakoc F. The effect of passive smoking on the development of respiratory syncytial virus bronchiolitis. Eur J Epidemiol. May 2000;16(5):465-8. [Medline].

5 of 7

06/10/2012 13:35

Bronchiolitis

http://emedicine.medscape.com/article/304649-overview

47. Hall CB. Respiratory syncytial virus. In: Feigen RD, Cherry JC, eds. Textbook of Pediatric Infectious Disease. Philadelphia, Pa: WB Saunders; 1992:1653-75. 48. Hall CB, Powell KR, Schnabel KC, Gala CL, Pincus PH. Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection. J Pediatr. Aug 1988;113(2):266-71. [Medline]. 49. Henderson FW, Clyde WA Jr, Collier AM, et al. The etiologic and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr. Aug 1979;95(2):183-90. [Medline]. 50. Kellner JD, Ohlsson A, Gadomski AM, Wang EE. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2000;CD001266. [Medline]. 51. King VJ, Viswanathan M, Bordley WC, et al. Pharmacologic treatment of bronchiolitis in infants and children: a systematic review. Arch Pediatr Adolesc Med. Feb 2004;158(2):127-37. [Medline]. 52. Kini NM, Robbins JM, Kirschbaum MS, Frisbee SJ, Kotagal UR. Inpatient care for uncomplicated bronchiolitis: comparison with Milliman and Robertson guidelines. Arch Pediatr Adolesc Med. Dec 2001;155(12):1323-7. [Medline]. 53. Kou M, Mayer TA. Pediatric Asthma and Bronchiolitis. In: Tintinalli J, Kelen G, Stspczynski J. Emergency Medicine: A Comprehensive Study Guide. 5 ed. New York, NY: McGraw-Hill; 1999:821-4. 54. Lanari M, Giovannini M, Giuffre L, et al. Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity. Pediatr Pulmonol. Jun 2002;33(6):458-65. [Medline]. 55. Law BJ, Wang EE, MacDonald N, et al. Does ribavirin impact on the hospital course of children with respiratory syncytial virus (RSV) infection? An analysis using the pediatric investigators collaborative network on infections in Canada (PICNIC) RSV database. Pediatrics. Mar 1997;99(3):E7. [Medline]. 56. Leer JA Jr, Green JL, Heimlich EM, et al. Corticosteroid treatment in bronchiolitis. A controlled, collaborative study in 297 infants and children. Am J Dis Child. May 1969;117(5):495-503. [Medline]. 57. Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections. Pediatrics. Jun 2004;113(6):1728-34. [Medline]. 58. Lugo RA, Nahata MC. Pathogenesis and treatment of bronchiolitis. Clin Pharm. Feb 1993;12(2):95-116. [Medline]. 59. Mallory MD, Shay DK, Garrett J, Bordley WC. Bronchiolitis management preferences and the influence of pulse oximetry and respiratory rate on the decision to admit. Pediatrics. Jan 2003;111(1):e45-51. [Medline]. 60. Meissner HC. Uncertainty in the management of viral lower respiratory tract disease. Pediatrics. Oct 2001;108(4):1000-3. [Medline]. 61. Njoku DB, Kliegman RM. Atypical extrapulmonary presentations of severe respiratory syncytial virus infection requiring intensive care. Clin Pediatr (Phila). Aug 1993;32(8):455-60. [Medline]. 62. Numa AH, Williams GD, Dakin CJ. The effect of nebulized epinephrine on respiratory mechanics and gas exchange in bronchiolitis. Am J Respir Crit Care Med. Jul 1 2001;164(1):86-91. [Medline]. 63. Panitch HB, Callahan CW Jr, Schidlow DV. Bronchiolitis in children. Clin Chest Med. Dec 1993;14(4):715-31. [Medline]. 64. Perlstein PH, Kotagal UR, Bolling C, et al. Evaluation of an evidence-based guideline for bronchiolitis. Pediatrics. Dec 1999;104(6):1334-41. [Medline]. 65. Perlstein PH, Kotagal UR, Schoettker PJ, et al. Sustaining the implementation of an evidence-based guideline for bronchiolitis. Arch Pediatr Adolesc Med. Oct 2000;154(10):1001-7. [Medline]. 66. Plint AC, Johnson DW, Wiebe N, et al. Practice variation among pediatric emergency departments in the treatment of bronchiolitis. Acad Emerg Med. Apr 2004;11(4):353-60. [Medline]. 67. Prendiville A, Green S, Silverman M. Ipratropium bromide and airways function in wheezy infants. Arch Dis Child. Apr 1987;62(4):397-400. [Medline]. 68. Purcell K, Fergie J. Concurrent serious bacterial infections in 2396 infants and children hospitalized with respiratory syncytial virus lower respiratory tract infections. Arch Pediatr Adolesc Med. Apr 2002;156(4):322-4. [Medline].
th

6 of 7

06/10/2012 13:35

Bronchiolitis

http://emedicine.medscape.com/article/304649-overview

69. Ryu JH, Myers JL, Swensen SJ. Bronchiolar disorders. Am J Respir Crit Care Med. Dec 1 2003;168(11):1277-92. [Medline]. 70. S Simila, O Linna, P Lanning, E Heikkinen and M Ala-Houhala. Chronic lung damage caused by adenovirus type 7: a ten-year follow-up study.Chest. 1981 Aug;80(2):127-31. Chest. Aug 1981;80(2):127-31. 71. Sanchez I, De Koster J, Powell RE, Wolstein R, Chernick V. Effect of racemic epinephrine and salbutamol on clinical score and pulmonary mechanics in infants with bronchiolitis. J Pediatr. Jan 1993;122(1):145-51. [Medline]. 72. Schroeder AR, Marmor AK, Pantell RH, Newman TB. Impact of pulse oximetry and oxygen therapy on length of stay in bronchiolitis hospitalizations. Arch Pediatr Adolesc Med. Jun 2004;158(6):527-30. [Medline]. 73. Singh SP, Barrett EG, Kalra R, et al. Prenatal cigarette smoke decreases lung cAMP and increases airway hyperresponsiveness. Am J Respir Crit Care Med. Aug 1 2003;168(3):342-7. [Medline]. 74. Smith RA. Background and mechanism of action of ribavirin. In: Smith RA, Knight V, Smith JA. Clinical Applications of Ribavirin. Vol 1. Orlando, Fla: Academic Press; 1984:1-18. 75. Swingler GH, Hussey GD, Zwarenstein M. Duration of illness in ambulatory children diagnosed with bronchiolitis. Arch Pediatr Adolesc Med. Oct 2000;154(10):997-1000. [Medline]. 76. Titus MO, Wright SW. Prevalence of serious bacterial infections in febrile infants with respiratory syncytial virus infection. Pediatrics. Aug 2003;112(2):282-4. [Medline]. 77. Todd J, Bertoch D, Dolan S. Use of a large national database for comparative evaluation of the effect of a bronchiolitis/viral pneumonia clinical care guideline on patient outcome and resource utilization. Arch Pediatr Adolesc Med. Nov 2002;156(11):1086-90. [Medline]. 78. van Woensel JB, van Aalderen WM, de Weerd W, et al. Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus. Thorax. May 2003;58(5):383-7. [Medline]. 79. Wainwright C, Altamirano L, Cheney M, et al. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med. Jul 3 2003;349(1):27-35. [Medline]. 80. Welliver RC, Wong DT, Sun M, Middleton E Jr, Vaughan RS, Ogra PL. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med. Oct 8 1981;305(15):841-6. [Medline]. 81. Wennergren G, Kristjnsson S. Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases. Eur Respir J. Dec 2001;18(6):1044-58. [Medline]. 82. Williams BG, Gouws E, Boschi-Pinto C, Bryce J, Dye C. Estimates of world-wide distribution of child deaths from acute respiratory infections. Lancet Infect Dis. Jan 2002;2(1):25-32. [Medline]. 83. Wohl ME, Chernick V. Treatment of acute bronchiolitis. N Engl J Med. Jul 3 2003;349(1):82-3. [Medline]. Medscape Reference 2011 WebMD, LLC

7 of 7

06/10/2012 13:35