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  • 1. The n e w e ng l a n d j o u r na l of m e dic i n e clinical practice Croup James D. Cherry, M.D., M.Sc. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. Crouplike symptoms develop in a previously healthy 2-year-old girl at 11 p.m. She is seen in an emergency department 2 hours later with a barking cough and, when upset, inspiratory stridor. Her temperature is 36.1°C, respiratory rate 20 breaths per minute, heart rate 151 beats per minute, and oxygen saturation 94% while she is breathing ambient air. She has mild sternal retractions but no cyanosis. How should she be evaluated and treated? The Cl inic a l Probl e mFrom the Division of Infectious Diseases, Before the 20th century, all crouplike illnesses were thought to be diphtheria.1 To-Mattel Children’s Hospital UCLA, and the day, the word “croup” is used to refer to a number of respiratory illnesses that areDepartment of Pediatrics, David GeffenSchool of Medicine at UCLA — both in characterized by varying degrees of inspiratory stridor, barking cough, and hoarse-Los Angeles. Address reprint requests to ness due to obstruction in the region of the larynx.1-4Dr. Cherry at the Dept. of Pediatrics, DavidGeffen School of Medicine at UCLA,10833 Le Conte Ave., MDCC 22-442, Los CLASSIFICATIONAngeles, CA 90095-1752, or at jcherry@ The terminology for croup illnesses has evolved over time, but unfortunately, classifications have been imprecise.1-7 For example, the term “laryngotracheobronchi-N Engl J Med 2008;358:384-91. tis” is often used to describe either spasmodic croup or laryngotracheitis. A classifica-Copyright © 2008 Massachusetts Medical Society. tion scheme with definitions and clinical features is presented in Table 1. The vast majority of cases of croup are either laryngotracheitis or spasmodic croup.8 EPIDEMIOLOGIC FEATURES Croup (laryngotracheitis and spasmodic croup) is an illness of infants and children younger than 6 years of age,9,10 with a peak incidence between 7 and 36 months of age. During the second year of life, about 5% of children have croup. The incidence in boys is about 1.5 times that in girls. In a 14-year study of hospitalizations for croup in Ontario, Canada, between 1988 and 2002, a biennial midautumn peak and an annual summer trough were observed.10 PATHOLOGICAL FEATURES AND PATHOGENESIS In acute laryngotracheitis, there is erythema and swelling of the lateral walls of the trachea, just below the vocal cords.11,12 Histologically, the involved area is edema- tous, with cellular infiltration in the lamina propria, submucosa, and adventitia. The infiltrate contains histiocytes, lymphocytes, plasma cells, and neutrophils.13,14 In bacterial croup — laryngotracheobronchitis and laryngotracheobronchopneumo- nitis — the tracheal wall is infiltrated with inflammatory cells, and in addition, ulceration, pseudomembranes, and microabscesses are present.2,15 There is thick pus within the lumen of the trachea and the lower air passages.2,16 In spasmodic croup, there is noninflammatory edema in the subglottic region.11384 n engl j med 358;4 january 24, 2008 The New England Journal of Medicine Downloaded from at UC SHARED JOURNAL COLLECTION on September 21, 2011. For personal use only. No other uses without permission. Copyright © 2008 Massachusetts Medical Society. All rights reserved.
  • 2. clinical pr actice Table 1. Classification, Definition, and Clinical Features of Croup Illnesses. Definition and LTB and LTBP (Including Characteristic Spasmodic Croup Acute Laryngotracheitis Bacterial Tracheitis)* Laryngeal Diphtheria Definition Sudden nighttime onset of in- Inflammation of the larynx Inflammation of the larynx, Infection involving the larynx spiratory stridor; associat- and trachea trachea, and bronchi or and other areas of the ed with mild upper respi- lung; usually similar in on- airway due to Corynebac­ ratory tract infection, with- set to laryngotracheitis, but terium diphtheriae, re- out inflammation with more severe illness sulting in progressive airway obstruction Typical age at 3 mo to 3 yr 3 mo to 3 yr 3 mo to 3 yr All ages occurrence Individual and Possible family history of Possible family history of Possible family history of Lack of immunization or in- family his- croup; possible previous croup croup adequate immunization tory attack Prodrome Minimal coryza Usually coryza Usually coryza Usually pharyngitis Onset (time to Sudden, always at night; the Moderately rapid but variable; Usually gradually progressive Slow, progressing over a pe- full-blown characteristic presentation onset mimics that of a over a period of 12 hr to riod of 2 to 3 days disease) is that of a child who at cold, with nasal irrita- 7 days bedtime was thought to be tion, cough, and coryza; well or perhaps to have mild fever occurs within the cold symptoms but who first 24 hr; within 12 to awakened suddenly with 48 hr, signs of obstructed croupy cough and stridor upper airway and symp- toms occur Symptoms on Hoarseness and barking Hoarseness and barking Hoarseness and barking Hoarseness and barking presenta- cough, no dysphagia, cough, no dysphagia, cough; no dysphagia; in- cough; usually dyspha- tion minimal-to-moderate in- minimal-to-severe inspi- spiratory stridor, usually gia; minimal-to-severe in- spiratory stridor; nontoxic ratory stridor; usually severe; typically toxic pre- spiratory stridor; usually presentation minimally toxic presenta- sentation nontoxic presentation tion Signs on pre- No fever; no pharyngitis; nor- Fever, generally 37.8 to Fever, generally 37.8 to Fever, generally 37.8 to sentation mal epiglottis 40.5°C; usually minimal 40.5°C; usually minimal 38.5°C; membranous pharyngitis; normal epi- pharyngitis; normal epi- pharyngitis; epiglottis glottis glottis usually normal but may contain membrane Radiographic Subglottic narrowing on pos- Subglottic narrowing on Subglottic narrowing on pos- Not useful findings terior–anterior view posterior–anterior view terior–anterior view, irreg- ular soft-tissue densities in trachea on lateral view, bilateral pneumonia White-cell Normal Mildly elevated, with >70% Usually elevated or abnormal- Usually elevated, with in- count polymorphonuclear cells ly low, with >70% neutro- creased percentage of phils and increased per- band forms centage of band forms Microbiologic Etiologic agents similar to Most commonly caused by Although may be caused by a C. diphtheriae (identified on findings those in laryngotracheitis parainfluenza virus 1 virus (e.g., parainfluenza smear and culture of (responsible for frequent virus 1, 2, or 3 or influenza membrane) fall outbreaks); many oth- virus A or B), in most in- er viruses also implicated, stances the illness is due including other parain- to secondary bacterial in- fluenza viruses and in- fection, particularly from fluenza viruses (influen- Staphylococcus aureus; other za virus A and parainflu- bacteria include group A enza virus 3 often cause streptococci, Streptococcus severe cases), respiratory pneumoniae, Haemophilus syncytial virus, measles influenzae, and Moraxella virus, adenoviruses, and catarrhalis rhinoviruses * LTB denotes laryngotracheobronchitis, and LTBP laryngotracheobronchopneumonitis. n engl j med 358;4 january 24, 2008 385 The New England Journal of MedicineDownloaded from at UC SHARED JOURNAL COLLECTION on September 21, 2011. For personal use only. No other uses without permission. Copyright © 2008 Massachusetts Medical Society. All rights reserved.
  • 3. The n e w e ng l a n d j o u r na l of m e dic i n e the child than the degree of inspiratory diffi- Table 2. Assessment of the Severity of Croup.* culty would suggest. A lateral neck radiograph Level of Severity† Characteristics will confirm the diagnosis of epiglottitis but is Mild Occasional barking cough; no audible stridor at rest, and rarely necessary, since the clinical findings noted either mild or no suprasternal or intercostal indrawing above are often diagnostic. (retractions of the skin of the chest wall) Both foreign-body and angioneurotic edema Moderate Frequent barking cough, easily audible stridor at rest, and can cause upper-airway obstruction. They usually suprasternal and sternal retractions at rest, but little or no agitation occur suddenly, without fever or other signs and Severe Frequent barking cough, prominent inspiratory and, occa- symptoms of infection. sionally, expiratory stridor, marked sternal retractions, Laryngotracheobronchitis and laryngotracheo- and agitation and distress bronchopneumonia can be differentiated from Impending respi- Barking cough (often not prominent), audible stridor at spasmodic croup and laryngotracheitis by signs ratory failure rest (occasionally hard to hear), sternal retractions of lower-airway involvement (crackles, air trap- (may not be marked), lethargy or decreased level of consciousness, and often dusky appearance in the ab- ping, wheezing, and pneumonia seen on a radio- sence of supplemental oxygen graph).2,6,15,21,22 A bacterial cause should be sus- pected in these cases and also in cases of* Adapted from the Alberta Medical Association.4 laryngotracheitis when symptoms and signs per-† Corresponding Westley scores for level of severity would be 0 to 2 for mild croup, 3 to 5 for moderate croup, 6 to 11 for severe croup, and 12 to 17 for sist or worsen despite treatment with corticoste- impending respiratory failure.8 roids and epinephrine. In both laryngotracheo- bronchitis and laryngotracheobronchopneumonia, a lateral neck radiograph may reveal soft densi- Host factors appear to be important in patho- ties indicating purulent exudate within the tra- genesis, since parainfluenza virus infections (par- chea. Laryngeal diphtheria should be considered ticularly type 3) are common in infants and in unimmunized patients with possible exposure. young children,17 yet croup develops in only a Laboratory studies are rarely useful in the small percentage of those exposed.18 A number evaluation of routine croup. If clinical findings of studies have indicated that allergic factors suggest laryngotracheobronchitis or laryngotra- play a role in recurrent croup.5,19,20 It is possible cheobronchopneumonia, white-cell and differen- that primary infection with parainfluenza virus tial counts and posterior–anterior and lateral chest type 3 (which may go unrecognized) leads to and neck radiographs are indicated. In these sensitization to the parainfluenza virus group cases, intubation is commonly required, and a rather than to type 3 alone,5 setting the stage for tracheal bacterial culture should be obtained at spasmodic croup due to parainfluenza virus types the time of intubation. Also useful in cases of 1 and 2. laryngotracheobronchitis or laryngotracheobron- chopneumonia, as well as in severe cases of laryn- S t r ategie s a nd E v idence gotracheitis, is a specimen (from nasal wash or tracheal secretions) for the direct identification Evaluation of influenza virus, which can help guide deci- Differential Diagnosis sions about the use of antiviral therapy. Since the croup illnesses discussed above and presented in Table 1 differ in severity as well as Assessment of Severity in their treatment, the differential diagnosis is im- A variety of scoring systems have been developed portant. Correct diagnosis of other acute obstruc- to evaluate the severity of croup.8,23,24 The most tive illnesses in the region of the larynx (e.g., commonly used scoring system has been that of epiglottitis, foreign body, angioneurotic edema of Westley et al.,24 which evaluates the severity of the epiglottis) is also essential and lifesaving.2,6 croup by assessing five factors: level of conscious- Epiglottitis rather than croup is suggested by ness, cyanosis, stridor, air entry, and retractions. the absence of a croupy cough (which sounds This system has been extremely valuable in treat- similar to a barking seal or sea lion); the sitting ment trials but has little use in the routine clini- posture of the child, with the chin pushed for- cal setting.8 However, a clinically useful severity- ward and a reluctance or refusal to lie down; and assessment table has been developed by an Alberta greater apprehension and anxiety on the part of Clinical Practice Guideline Working Group4 (Ta-386 n engl j med 358;4 january 24, 2008 The New England Journal of MedicineDownloaded from at UC SHARED JOURNAL COLLECTION on September 21, 2011. For personal use only. No other uses without permission. Copyright © 2008 Massachusetts Medical Society. All rights reserved.
  • 4. clinical pr actice ble 2). Based on this classification scheme, 85% strated significant improvement in patients treat- of children seen in 21 general emergency depart- ed with corticosteroids as compared with con- ments in Alberta, Canada, had mild croup, and trols. For example, in a meta-analysis of 37 trials, less than 1% had severe croup.8 patients who were given corticosteroids had sig- nificantly lower croup scores at 6 hours, a de- TREATMENT crease in return visits, and a decrease in time During the past 50 years, there has been consid- spent in emergency rooms or hospitals.30 erable controversy regarding many therapies for Trials of corticosteroids in croup have in- croup, including the role of humidified air and volved a variety of drugs, dosages, and routes of the optimal type (warm vs. cold) and the roles of administration.30-33 The regimens studied most corticosteroids and racemic epinephrine.2 How- frequently have been single-dose dexamethasone ever, the marked success of corticosteroids in the (0.6 mg per kilogram of body weight given outpatient management of croup and the effec- orally or intramuscularly) and nebulized budeso- tiveness of nebulized epinephrine in more severe nide (2 mg in 4 ml of water); some studies have cases have led to the resolution of many of the involved additional doses (up to four doses of controversies. dexamethasone or nebulized budesonide given over a period of 2 days). No studies have directly Acute Laryngotracheitis and Spasmodic Croup compared the outcomes of single-dose therapy Humidified Air with the outcomes of 2-day treatment schedules. During much of the 20th century, treatment with The 1992 recommendation by the Canadian humidified air (mist therapy) was the corner- Paediatric Society to use dexamethasone for treat- stone of the management of croup.1,2 More re- ment was followed by a marked decrease in cently, however, the effectiveness of mist therapy hospitalizations for croup in Ontario, providing has been questioned.4,8,25 In a recent trial26 com- further support for the use of corticoste- paring the effects of high humidity (100%), low roids.10,34,35 Similar findings were noted in Perth, humidity (40%), and blow-by humidity (in which Australia.36 a plastic hose is held near the child’s nose and A potential concern with corticosteroids, how- mouth) in children with mild croup, there were ever, is their immunosuppressive effects, which no significant differences in the croup-score re- might predispose the patient to infectious com- sponses among the three groups; each group had plications.2,5-7 Trials have not been powered to significant improvement (about 33%) over base- assess these risks, but such complications would line in the croup score 60 minutes after adminis- be expected to be rare with standard (single- tration. In two other small trials, control subjects dose) therapy. who received nebulized saline also had improve- Epinephrine ment in their croup scores over the baseline val- Nebulized epinephrine has been extensively stud- ues.23,24 Since none of these studies included an ied for the treatment of croup.2,5,8,23-25,37-42 Early untreated control group, it is not possible to controlled trials demonstrated that the adminis- know whether the improvements were due to the tration of 2.25% racemic epinephrine (0.5 ml in moist air. A recent Cochrane Collaboration re- 2.5 ml of saline) by intermittent positive-pressure view of data from three other studies concluded breathing resulted in a significant reduction in that there was no evidence that inhalation of hu- the croup-severity score,24,37 but this benefit last- midified air in children with mild-to-moderate ed for less than 2 hours. Subsequent trials showed croup resulted in a substantial improvement in that the administration of racemic epinephrine the croup score.27 by nebulization alone was as effective as its ad- Corticosteroid Therapy ministration by intermittent positive-pressure Corticosteroid therapy is now routinely recom- breathing.41 Later trials also showed that nebu- mended by all experts.4,5,8,10,25 In a cotton-rat lized l-epinephrine diluted in 5 ml of saline at a laryngotracheitis model,18 corticosteroids reduced ratio of 1:1000 was as effective as racemic epi- the degree of inflammation and cell damage; al- nephrine in the treatment of croup.42 In severe though the viral load was increased, the duration croup, repeated treatments with epinephrine have of shedding was not prolonged. Meta-analyses of been used and have often decreased the need for randomized trials28-30 have consistently demon- intubation. n engl j med 358;4 january 24, 2008 387 The New England Journal of MedicineDownloaded from at UC SHARED JOURNAL COLLECTION on September 21, 2011. For personal use only. No other uses without permission. Copyright © 2008 Massachusetts Medical Society. All rights reserved.
  • 5. The n e w e ng l a n d j o u r na l of m e dic i n e Other Treatments Guidel ine s Children with moderate or severe croup and hypoxia (oxygen saturation while breathing The American Academy of Pediatrics has no ambient air, <92%) should receive oxygen.4 guidelines for the management of croup. The In- This is best administered with the blow-by tech- fectious Diseases and Immunization Committee nique. of the Canadian Paediatric Society published a A helium–oxygen mixture (heliox) has been brief statement in 1992, recommending cortico- shown in a small study to improve croup-sever- steroid therapy for children admitted to the hos- ity scores in hospitalized children with croup.43 pital with croup.34 The Alberta Medical Associa- However, this treatment was no better — and tion published a guideline for the diagnosis and was more expensive — than treatment with ra- management of croup in 2004, which was up- cemic epinephrine. dated in 2007.4 An algorithm for the manage- Antitussive and decongestant agents have not ment of croup in the outpatient setting is shown been studied in children with croup, and their in Figure 1. use is not indicated.4 Since laryngotracheitis and spasmodic croup are viral illnesses, there is no C onclusions reason to treat them with antibiotics unless clini- a nd R ec om mendat ions cal manifestations or laboratory values suggest secondary bacterial infection. In severe croup due Croup — both spasmodic croup and laryngotra- to infection with influenza A or B virus, treatment cheitis — is a common illness of early childhood with neuraminidase inhibitors should be consid- that is frightening for both patients and their ered, although there are no data demonstrating parents. For children such as the one described the efficacy of such treatment in reducing the se- in the vignette, the standard of care is short- verity of croup.44 Since influenza immunization course corticosteroid therapy. This is most prac- is now routinely recommended for children, the tically accomplished by the administration of a occurrence of croup due to influenza viruses will single dose of oral dexamethasone (0.6 mg per probably become less common. kilogram).4,8,49 I would not recommend addition- al corticosteroid doses in children who do not Laryngotracheobronchitis have a response to this therapy, given the lack of and Laryngotracheobronchopneumonitis data showing the efficacy of repeated doses and Since most children with laryngotracheobronchi- the potential risks associated with longer-term tis or laryngotracheobronchopneumonia have bac- therapy. Depending on the severity of symptoms, terial disease, antibiotics should be administered children who do not have a response to dexa- after appropriate cultures have been obtained. methasone should be evaluated in an emergency Treatment should be directed against Staphylococ­ room or admitted to the hospital; further testing cus aureus, Streptococcus pyogenes, Streptococcus pneu­ may be useful in such cases, including chest ra- moniae, Haemophilus influenzae, and Moraxella catar­ diography for possible laryngotracheobronchitis rhalis. Most cases of laryngotracheobronchitis or or laryngotracheobronchopneumonia, as well as laryngotracheobronchopneumonia in children re- rapid influenza testing in the appropriate sea- quire the placement of a mechanical airway and son. Children with severe symptoms should be treatment in an intensive care unit. treated with nebulized epinephrine (0.5 ml of 2.25% racemic epinephrine in 4.5 ml of normal A r e a s of Uncer ta in t y saline or l-epinephrine diluted in 5 ml of normal saline at a ratio of 1:1000). If treatment is given Efforts are warranted to improve the use of cor- in an outpatient setting, it should be followed by ticosteroids in the treatment of croup. In prac- at least 2 hours of observation for a return of tice, many children continue to receive prolonged obstructive symptoms before discharge. Nebu- courses of corticosteroids for croup rather than lized epinephrine treatments may need to be re- single-dose therapy. I and others have observed peated many times in children with severe laryn- viral, bacterial, and fungal complications in as- gotracheitis, but in many cases, this will prevent sociation with corticosteroid treatment2,5-7,45-48; the need for endotracheal intubation. in all cases, these complications occurred in chil- If the evaluation suggests laryngotracheo- dren who had received multiple doses. bronchitis or laryngotracheobronchopneumonia388 n engl j med 358;4 january 24, 2008 The New England Journal of MedicineDownloaded from at UC SHARED JOURNAL COLLECTION on September 21, 2011. For personal use only. No other uses without permission. Copyright © 2008 Massachusetts Medical Society. All rights reserved.
  • 6. clinical pr actice Mild Moderate Severe Give oral or intramuscular Give oral or intramuscular Minimize situations that may dexamethasone, 0.6 mg/kg dexamethasone, 0.6 mg/kg cause distress in child, such Discuss with parents likely course Minimize situations that may as separation from parents of illness and when to seek cause distress in child, such and unnecessary examination additional care if further as separation from parents Provide “blow-by” oxygen if respiratory distress occurs and unnecessary examination cyanosis is present Observe for improvement Give oral or intramuscular for 1–4 hr dexamethasone, 0.6 mg/kg Administer epinephrine by nebulization, either racemic Discharge home epinephrine 2.25%, 0.5 ml in 2.5 ml of saline, or L-epineph- If patient improves — If no or minimal improve- rine, 1:1000 dilution in 5 ml as evidenced by no ment after 4 hr, consider of saline stridor at rest and no hospitalization chest-wall indrawing — then discuss with parents likely course of illness and when to If good response to If poor response, repeat seek additional care epinephrine, observe nebulized epinephrine; for 2 hr if poor response to second treatment, admit child for ICU care and probable workup for LTB, Discharge home LTBP, and secondary bacterial infection If only mild symptoms If severe respiratory persist (i.e., croupy distress recurs, repeat cough) and there is nebulized epinephrine no recurrence of stridor at rest or of chest-wall indrawing, then discuss with parents when to seek additional care Discharge home If good response, If poor response to observe for 2 hr; if second treatment with only mild symptoms nebulized epinephrine, persist and there is admit child for ICU care no recurrence of stridor and probable workup at rest or of chest-wall for LTB, LTBP, and indrawing, then discuss secondary bacterial with parents when infection to seek additional care Discharge home Figure 1. Management of Croup in Outpatients. ICM AUTHOR: Cherry Treatment guidelines are based on the severity of croup at the time of initial assessment. ICU1st RETAKE denotes intensive care unit, LTB laryngo- 2nd REG F FIGURE: 1 of 1 tracheobronchitis, and LTBP laryngotracheobronchopneumonitis. 3rd CASE Revised EMail Line 4-C SIZE ARTIST: ts H/T H/T n engl j med Enon 358;4 january 24, 2008 Combo 39p6 389 AUTHOR, PLEASE NOTE: The New England Journal of Medicine Figure has been redrawn and type has been reset.Downloaded from at UC SHARED JOURNAL COLLECTION on September 21, 2011. For personal use only. No other uses without permission. Please check carefully. Copyright © 2008 Massachusetts Medical Society. All rights reserved.
  • 7. The n e w e ng l a n d j o u r na l of m e dic i n e (i.e., an increased or low white-cell count with enza viruses, treatment with neuramidase in- an increase in band forms, or radiographs show- hibitors is appropriate.44 ing pneumonia or soft densities within the tra- Dr. Cherry reports receiving consulting and lecture fees from chea), treatment with antibiotics (e.g., vancomy- Sanofi Pasteur and consulting fees from GlaxoSmithKline and cin and cefotaxime) should be instituted, and in MedImmune. No other potential conflict of interest relevant to most instances, endotracheal intubation should this article was reported. I thank Candice Bjornson and David Johnson, who supplied be performed. In cases of severe croup occurring the case vignette, and Paul Krogstad, who offered helpful com- during documented epidemics caused by influ- ments. References 1. Cherry JD. Croup. In: Kiple KF, ed. autopsies in eight cases. Arch Otolaryn- halation for treating croup. Cochrane Data- The Cambridge world history of human gol 1941;33:926-60. base Syst Rev 2006;3:CD002870. disease. New York: Cambridge University 14. Richards L. A further study of the pa- 28. Kairys SW, Olmstead EN, O’Connor Press, 1993:654-7. thology of acute laryngo-tracheobronchi- GT. Steroid treatment of laryngotrache- 2. Idem. Croup (laryngitis, laryngotrache- tis in children. Ann Otol Rhinol Laryngol itis: a meta-analysis of the evidence from itis, spasmodic croup, laryngotracheo- 1938;47:326-41. randomized trials. Pediatrics 1989;83: bronchitis, bacterial tracheitis, and laryn- 15. Hopkins A, Lahiri T, Salerno R, Heath 683-93. gotracheobronchopneumonitis). In: Feigin B. Changing epidemiology of life-threat- 29. Ausejo M, Saenz A, Pham B, et al. The RD, Cherry JD, Demmler GJ, Kaplan S, ening upper airway infections: the re- effectiveness of glucocorticoids in treat- eds. Textbook of pediatric infectious dis- emergence of bacterial tracheitis. Pediat- ing croup: meta-analysis. BMJ 1999;319: eases. 5th ed. Philadelphia: W.B. Saun- rics 2006;118:1418-21. 595-600. ders, 2004:252-66. 16. Kasian GF, Bingham WT, Steinberg J, 30. Russell K, Wiebe N, Saenz A, et al. 3. Davison FW. Acute obstructive laryn- et al. Bacterial tracheitis in children. Glucocorticoids for croup. Cochrane Data- gitis in children. Penn Med J 1950;53:250- CMAJ 1989;140:46-50. base Syst Rev 2003;4:CD001955. 4. 17. Hall CB. Parainfluenza viruses. In: 31. Çetinkaya F, Tüfekçi BS, Kutluk G. 4. Guideline for the diagnosis and man- Feigin RD, Cherry JD, Demmler GJ, Ka- A comparison of nebulized budesonide, agement of croup. Alberta, ON, Canada: plan S, eds. Textbook of pediatric infec- and intramuscular, and oral dexametha- Alberta Medical Association, 2007. (Ac- tious diseases. 5th ed. Philadelphia: W.B. sone for treatment of croup. Int J Pediatr cessed December 28, 2007, at http://www. Saunders, 2004:2270-83. Otorhinolaryngol 2004;68:453-6. 18. Ottolini MG, Porter DD, Blanco JC, 32. Sparrow A, Geelhoed G. Prednisolone B072F5EF-1728-4BED-A88A-68A99341B98A/ Prince GA. A cotton rat model of human versus dexamethasone in croup: a ran- 0/croup_guideline.pdf.) parainfluenza 3 laryngotracheitis: virus domized equivalence trial. Arch Dis Child 5. Cherry JD. State of the evidence for growth, pathology, and therapy. J Infect 2006;91:580-3. standard-of-care treatments for croup: are Dis 2002;186:1713-7. 33. Geelhoed GC. Budesonide offers no we where we need to be? Pediatr Infect 19. Welliver RC, Sun M, Rinaldo D. De- advantage when added to oral dexametha- Dis J 2005;24:Suppl:S198-S202. fective regulation of immune response in sone in the treatment of croup. Pediatr 6. Idem. Acute epiglottitis, laryngitis and croup due to parainfluenza virus. Pediatr Emerg Care 2005;21:359-62. croup. In: Remington JS, Swartz MN, eds. Res 1985;19:716-20. 34. Canadian Paediatric Society. Steroid Current clinical topics in infectious dis- 20. Welliver RC. 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  • 8. clinical pr actice CB. Racemic epinephrine in the treatment 44. Prevention and control of influenza: a complication of combined steroid and of croup: nebulization alone versus nebu- recommendations of the Advisory Com- antibiotic usage in croup. Int J Pediatr lization with intermittent positive pres- mittee on Immunization Practices (ACIP). Otorhinolaryngol 1992;23:171-5. sure breathing. J Pediatr 1982;101:1028- MMWR Recomm Rep 2006;55:RR-10:1-42. 48. Myers C, Corbelli R, Schrenzel J, Ger- 31. [Erratum, MMWR Morb Mortal Wkly Rep vaix A. Multiple pulmonary abscesses 42. Waisman Y, Klein BL, Boenning DA, 2006;55:800.] caused by Legionella pneumophila infection et al. Prospective randomized double- 45. Super DM, Cartelli NA, Brooks LJ, in an infant with croup. Pediatr Infect Dis blind study comparing L-epinephrine and Lembo RM, Kumar ML. A prospective ran- J 2006;25:753-4. racemic epinephrine aerosols in the treat- domized double-blind study to evaluate 49. Bjornson CL, Klassen TP, Williamson J, ment of laryngotracheitis (croup). Pediat- the effect of dexamethasone in acute la- et al. A randomized trial of a single dose rics 1992;89:302-6. ryngotracheitis. J Pediatr 1989;115:323-9. of oral dexamethasone for mild croup. 43. Weber JE, Chudnofsky CR, Younger 46. Johnson DW, Schuh S, Koren G, Jaffee N Engl J Med 2004;351:1306-13. JG, et al. A randomized comparison of DM. Outpatient treatment of croup with Copyright © 2008 Massachusetts Medical Society. helium-oxygen mixture (Heliox) and race- nebulized dexamethasone. Arch Pediatr mic epinephrine for the treatment of mod- Adolesc Med 1996;150:349-55. erate to severe croup. Pediatrics 2001; 47. Burton DM, Seid AB, Kearns DB, 107(6):E96. Pransky SM. Candida laryngotracheitis: images in clinical medicine The Journal welcomes consideration of new submissions for Images in Clinical Medicine. Instructions for authors and procedures for submissions can be found on the Journal’s Web site at At the discretion of the editor, images that are accepted for publication may appear in the print version of the Journal, the electronic version, or both. n engl j med 358;4 january 24, 2008 391 The New England Journal of MedicineDownloaded from at UC SHARED JOURNAL COLLECTION on September 21, 2011. For personal use only. No other uses without permission. Copyright © 2008 Massachusetts Medical Society. All rights reserved.