diagnosis and management of bronchiolitis

DOI: 10.1542/peds.2006-2223 2006;118;1774Pediatrics

Subcommittee on Diagnosis and Management of BronchiolitisDiagnosis and Management of Bronchiolitis

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CLINICAL PRACTICE GUIDELINE

Diagnosis and Management ofBronchiolitisSubcommittee on Diagnosis and Management of Bronchiolitis

Endorsed by the American Academy of Family Physicians, the American College of Chest Physicians, and the American Thoracic Society.

ABSTRACTBronchiolitis is a disorder most commonly caused in infants by viral lower respi-ratory tract infection. It is the most common lower respiratory infection in this agegroup. It is characterized by acute inflammation, edema, and necrosis of epithelialcells lining small airways, increased mucus production, and bronchospasm.

The American Academy of Pediatrics convened a committee composed ofprimary care physicians and specialists in the fields of pulmonology, infectiousdisease, emergency medicine, epidemiology, and medical informatics. The com-mittee partnered with the Agency for Healthcare Research and Quality and the RTIInternational-University of North Carolina Evidence-Based Practice Center todevelop a comprehensive review of the evidence-based literature related to thediagnosis, management, and prevention of bronchiolitis. The resulting evidencereport and other sources of data were used to formulate clinical practice guidelinerecommendations.

This guideline addresses the diagnosis of bronchiolitis as well as various ther-apeutic interventions including bronchodilators, corticosteroids, antiviral and an-tibacterial agents, hydration, chest physiotherapy, and oxygen. Recommendationsare made for prevention of respiratory syncytial virus infection with palivizumaband the control of nosocomial spread of infection. Decisions were made on thebasis of a systematic grading of the quality of evidence and strength of recommen-dation. The clinical practice guideline underwent comprehensive peer reviewbefore it was approved by the American Academy of Pediatrics.

This clinical practice guideline is not intended as a sole source of guidance in themanagement of children with bronchiolitis. Rather, it is intended to assist clini-cians in decision-making. It is not intended to replace clinical judgment or estab-lish a protocol for the care of all children with this condition. These recommen-dations may not provide the only appropriate approach to the management ofchildren with bronchiolitis.

INTRODUCTIONTHIS GUIDELINE EXAMINES the published evidence on diagnosis and acute manage-ment of the child with bronchiolitis in both outpatient and hospital settings,including the roles of supportive therapy, oxygen, bronchodilators, antiinflamma-tory agents, antibacterial agents, and antiviral agents and make recommendationsto influence clinician behavior on the basis of the evidence. Methods of prevention

www.pediatrics.org/cgi/doi/10.1542/peds.2006-2223

doi:10.1542/peds.2006-2223

All clinical practice guidelines from theAmerican Academy of Pediatricsautomatically expire 5 years afterpublication unless reafrmed, revised, orretired at or before that time.

The recommendations in this guidelinedo not indicate an exclusive course oftreatment or serve as a standard of care.Variations, taking into account individualcircumstances, may be appropriate.

KeyWordbronchiolitis

AbbreviationsCAMcomplementary and alternativemedicineLRTIlower respiratory tract infectionAHRQAgency for Healthcare Researchand QualityRSVrespiratory syncytial virusAAPAmerican Academy of PediatricsAAFPAmerican Academy of FamilyPhysiciansRCTrandomized, controlled trialCLDchronic neonatal lung diseaseSBIserious bacterial infectionUTIurinary tract infectionAOMacute otitis mediaSpO2oxyhemoglobin saturationLRTDlower respiratory tract disease

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Organizational Principles to Guide andDene the Child Health Care System and/orImprove the Health of All Children

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are reviewed, as is the potential role of complementaryand alternative medicine (CAM).

The goal of this guideline is to provide an evidence-based approach to the diagnosis, management, and pre-vention of bronchiolitis in children from 1 month to 2years of age. The guideline is intended for pediatricians,family physicians, emergency medicine specialists, hos-pitalists, nurse practitioners, and physician assistantswho care for these children. The guideline does notapply to children with immunodeficiencies includingHIV, organ or bone marrow transplants, or congenitalimmunodeficiencies. Children with underlying respira-tory illnesses such as chronic neonatal lung disease(CLD; also known as bronchopulmonary dysplasia) andthose with significant congenital heart disease are ex-cluded from the sections on management unless other-wise noted but are included in the discussion of preven-tion. This guideline will not address long-term sequelaeof bronchiolitis, such as recurrent wheezing, which is afield with distinct literature of its own.

Bronchiolitis is a disorder most commonly caused ininfants by viral lower respiratory tract infection (LRTI).It is the most common lower respiratory infection in thisage group. It is characterized by acute inflammation,edema and necrosis of epithelial cells lining small air-ways, increased mucus production, and bronchospasm.Signs and symptoms are typically rhinitis, tachypnea,wheezing, cough, crackles, use of accessory muscles,and/or nasal flaring.1 Many viruses cause the same con-stellation of symptoms and signs. The most commonetiology is the respiratory syncytial virus (RSV), with thehighest incidence of RSV infection occurring betweenDecember and March.2 Ninety percent of children areinfected with RSV in the first 2 years of life,3 and up to40% of them will have lower respiratory infection.4,5

Infection with RSV does not grant permanent or long-term immunity. Reinfections are common and may beexperienced throughout life.6 Other viruses identified ascausing bronchiolitis are human metapneumovirus, in-fluenza, adenovirus, and parainfluenza. RSV infectionleads to more than 90 000 hospitalizations annually.Mortality resulting from RSV has decreased from 4500deaths annually in 1985 in the United States2,6 to anestimated 510 RSV-associated deaths in 19976 and 390in 1999.7 The cost of hospitalization for bronchiolitis inchildren less than 1 year old is estimated to be more than$700 million per year.8

Several studies have shown a wide variation in howbronchiolitis is diagnosed and treated. Studies in theUnited States,9 Canada,10 and the Netherlands11 showedvariations that correlated more with hospital or individ-ual preferences than with patient severity. In addition,length of hospitalization in some countries averagestwice that of others.12 This variable pattern suggests alack of consensus among clinicians as to best practices.

In addition to morbidity and mortality during the

acute illness, infants hospitalized with bronchiolitis aremore likely to have respiratory problems as older chil-dren, especially recurrent wheezing, compared withthose who did not have severe disease.1315 Severe dis-ease is characterized by persistently increased respiratoryeffort, apnea, or the need for intravenous hydration,supplemental oxygen, or mechanical ventilation. It isunclear whether severe viral illness early in life predis-poses children to develop recurrent wheezing or if in-fants who experience severe bronchiolitis have an un-derlying predisposition to recurrent wheezing.

METHODSTo develop the clinical practice guideline on the diagno-sis and management of bronchiolitis, the AmericanAcademy of Pediatrics (AAP) convened the Subcommit-tee on Diagnosis and Management of Bronchiolitis withthe support of the American Academy of Family Physi-cians (AAFP), the American Thoracic Society, the Amer-ican College of Chest Physicians, and the European Re-spiratory Society. The subcommittee was chaired by aprimary care pediatrician with expertise in clinical pul-monology and included experts in the fields of generalpediatrics, pulmonology, infectious disease, emergencymedicine, epidemiology, and medical informatics. Allpanel members reviewed the AAP Policy on Conflict ofInterest and Voluntary Disclosure and were given anopportunity to declare any potential conflicts.

The AAP and AAFP partnered with the AHRQ and theRTI International-University of North Carolina Evi-dence-Based Practice Center (EPC) to develop an evi-dence report, which served as a major source of infor-mation for these practice guideline recommendations.1

Specific clinical questions addressed in the AHRQ evi-dence report were the (1) effectiveness of diagnostictools for diagnosing bronchiolitis in infants and children,(2) efficacy of pharmaceutical therapies for treatment ofbronchiolitis, (3) role of prophylaxis in prevention ofbronchiolitis, and (4) cost-effectiveness of prophylaxisfor management of bronchiolitis. EPC project staffsearched Medline, the Cochrane Collaboration, and theHealth Economics Database. Additional articles wereidentified by review of reference lists of relevant articlesand ongoing studies recommended by a technical expertadvisory group. To answer the question on diagnosis,both prospective studies and randomized, controlled tri-als (RCTs) were used. For questions related to treatmentand prophylaxis in the AHRQ report, only RCTs wereconsidered. For the cost-effectiveness of prophylaxis,studies that used economic analysis were reviewed. Forall studies, key inclusion criteria included outcomes thatwere both clinically relevant and able to be abstracted.Initially, 744 abstracts were identified for possible inclu-sion, of which 83 were retained for systematic review.Results of the literature review were presented in evi-dence tables and published in the final evidence report.1

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An additional literature search of Medline and theCochrane Database of Systematic Reviews was per-formed in July 2004 by using search terms submitted bythe members of the Subcommittee on the Diagnosis andManagement of Bronchiolitis. The methodologic qualityof the research was appraised by an epidemiologist be-fore consideration by the subcommittee.

The evidence-based approach to guideline develop-ment requires that the evidence in support of a policy beidentified, appraised, and summarized and that an ex-plicit link between evidence and recommendations bedefined. Evidence-based recommendations reflect thequality of evidence and the balance of benefit and harmthat is anticipated when the recommendation is fol-lowed. The AAP policy statement Classifying Recom-mendations for Clinical Practice Guidelines16 was fol-lowed in designating levels of recommendation (Fig 1;Table 1).

A draft version of this clinical practice guideline un-derwent extensive peer review by committees and sec-tions within the AAP, American Thoracic Society, Euro-pean Respiratory Society, American College of ChestPhysicians, and AAFP, outside organizations, and otherindividuals identified by the subcommittee as experts inthe field. Members of the subcommittee were invited todistribute the draft to other representatives and commit-tees within their specialty organizations. The resultingcomments were reviewed by the subcommittee and,when appropriate, incorporated into the guideline.

This clinical practice guideline is not intended as asole source of guidance in the management of childrenwith bronchiolitis. Rather, it is intended to assist clini-cians in decision-making. It is not intended to replaceclinical judgment or establish a protocol for the care of

all children with this condition. These recommendationsmay not provide the only appropriate approach to themanagement of children with bronchiolitis.

All AAP guidelines are reviewed every 5 years.Definitions used in the guideline are:

Bronchiolitis: a disorder most commonly caused ininfants by viral LRTI; it is the most common lowerrespiratory infection in this age group and is charac-terized by acute inflammation, edema and necrosis ofepithelial cells lining small airways, increased mucusproduction, and bronchospasm.

CLD, also known as bronchopulmonary dysplasia: aninfant less than 32 weeks gestation evaluated at 36weeks postmenstrual age or one of more than 32weeks gestation evaluated at more than 28 days butless than 56 days of age who has been receiving sup-plemental oxygen for more than 28 days.17

Routine: a set of customary and often-performed pro-cedures such as might be found in a routine admissionorder set for children with bronchiolitis.

Severe disease: signs and symptoms associated withpoor feeding and respiratory distress characterized bytachypnea, nasal flaring, and hypoxemia.

Hemodynamically significant congenital heart disease:children with congenital heart disease who are receiv-ing medication to control congestive heart failure,have moderate to severe pulmonary hypertension, orhave cyanotic heart disease.

RECOMMENDATION 1aClinicians should diagnose bronchiolitis and assess disease se-verity on the basis of history and physical examination. Clini-cians should not routinely order laboratory and radiologicstudies for diagnosis (recommendation: evidence level B; diag-nostic studies with minor limitations and observational studieswith consistent findings; preponderance of benefits over harmsand cost).

RECOMMENDATION 1bClinicians should assess risk factors for severe disease such asage less than 12 weeks, a history of prematurity, underlyingcardiopulmonary disease, or immunodeficiency when makingdecisions about evaluation and management of children withbronchiolitis (recommendation: evidence level B; observationalstudies with consistent findings; preponderance of benefits overharms).

The 2 goals in the history and physical examination ofinfants presenting with cough and/or wheeze, particu-larly in the winter season, are the differentiation ofinfants with probable bronchiolitis from those withother disorders and the estimation of the severity ofillness. Most clinicians recognize bronchiolitis as a con-stellation of clinical symptoms and signs including a viralupper respiratory prodrome followed by increased respi-

FIGURE 1Integrating evidence quality appraisal with an assessment of the anticipated balancebetween benets and harms if a policy is carried out leads to designation of a policy as astrong recommendation, recommendation, option, or no recommendation.

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ratory effort and wheezing in children less than 2 yearsof age. Clinical signs and symptoms of bronchiolitis con-sist of rhinorrhea, cough, wheezing, tachypnea, and in-creased respiratory effort manifested as grunting, nasalflaring, and intercostal and/or subcostal retractions.

Respiratory rate in otherwise healthy childrenchanges considerably over the first year of life, decreas-ing from a mean of approximately 50 breaths per minutein term newborns to approximately 40 breaths perminute at 6 months of age and 30 breaths per minute at12 months.1820 Counting respiratory rate over the courseof 1 minute may be more accurate than measurementsextrapolated to 1 minute but observed for shorter peri-ods.21 The absence of tachypnea correlates with the lackof LRTIs or pneumonia (viral or bacterial) in infants.22,23

The course of bronchiolitis is variable and dynamic,ranging from transient events such as apnea or mucusplugging to progressive respiratory distress from lowerairway obstruction. Important issues to assess includethe impact of respiratory symptoms on feeding and hy-dration and the response, if any, to therapy. The abilityof the family to care for the child and return for furthercare should be assessed. History of underlying conditionssuch as prematurity, cardiac or pulmonary disease, im-munodeficiency, or previous episodes of wheezingshould be identified.

The physical examination reflects the variability inthe disease state and may require serial observationsover time to fully assess the childs status. Upper airwayobstruction may contribute to work of breathing. Nasalsuctioning and positioning of the child may affect theassessment. Physical examination findings of importance

include respiratory rate, increased work of breathing asevidenced by accessory muscle use or retractions, andauscultatory findings such as wheezes or crackles.

The evidence relating the presence of specific findingsin the assessment of bronchiolitis to clinical outcomes islimited. Most studies are retrospective and lack valid andunbiased measurement of baseline and outcome vari-ables. Most studies designed to identify the risk of severeadverse outcomes such as requirement for intensive careor mechanical ventilation have focused on inpa-tients.2426 These events are relatively rare among allchildren with bronchiolitis and limit the power of thesestudies to detect clinically important risk factors associ-ated with disease progression.

Several studies have associated premature birth (lessthan 37 weeks) and young age of the child (less than612 weeks) with an increased risk of severe disease.2628

Young infants with bronchiolitis may develop apnea,which has been associated with an increased risk forprolonged hospitalization, admission to intensive care,and mechanical ventilation.26 Other underlying condi-tions that have been associated with an increased risk ofprogression to severe disease or mortality include hemo-dynamically significant congenital heart disease,26,29

chronic lung disease (bronchopulmonary dysplasia, cys-tic fibrosis, congenital anomaly),26 and the presence ofan immunocompromised state.26,30

Findings on physical examination have been less con-sistently associated with outcomes of bronchiolitis.Tachypnea, defined as a respiratory rate of 70 or morebreaths per minute, has been associated with increasedrisk for severe disease in some studies24,27,31 but not oth-

TABLE 1 Guideline Denitions for Evidence-Based Statements

Statement Denition Implication

Strong recommendation A strong recommendation in favor of a particular action is madewhen the anticipated benets of the recommendedintervention clearly exceed the harms (as a strongrecommendation against an action is made when theanticipated harms clearly exceed the benets) and thequality of the supporting evidence is excellent. In someclearly identied circumstances, strong recommendationsmay be made when high-quality evidence is impossible toobtain and the anticipated benets strongly outweigh theharms.

Clinicians should follow a strong recommendationunless a clear and compelling rationale for analternative approach is present.

Recommendation A recommendation in favor of a particular action is made whenthe anticipated benets exceed the harms but the quality ofevidence is not as strong. Again, in some clearly identiedcircumstances, recommendations may be made when high-quality evidence is impossible to obtain but the anticipatedbenets outweigh the harms.

Clinicians would be prudent to follow arecommendation but should remain alert to newinformation and sensitive to patient preferences.

Option Options dene courses that may be taken when either thequality of evidence is suspect or carefully performed studieshave shown little clear advantage to one approach overanother.

Clinicians should consider the option in theirdecision-making, and patient preference mayhave a substantial role.

No recommendation No recommendation indicates that there is a lack of pertinentpublished evidence and that the anticipated balance ofbenets and harms is presently unclear.

Clinicians should be alert to new publishedevidence that claries the balance of benetversus harm.


ers.32 An AHRQ report1 found 43 of 52 treatment trialsthat used clinical scores, all of which included measuresof respiratory rate, respiratory effort, severity of wheez-ing, and oxygenation. The lack of uniformity of scoringsystems made comparison between studies difficult.1 Themost widely used clinical score, the Respiratory DistressAssessment Instrument,33 is reliable with respect to scor-ing but has not been validated for clinical predictivevalue in bronchiolitis. None of the other clinical scoresused in the various studies have been assessed for reli-ability and validity. Studies that have assessed otherphysical examination findings have not found clinicallyuseful associations with outcomes.27,32 The substantialtemporal variability in physical findings as well as po-tential differences in response to therapy may accountfor this lack of association. Repeated observation over aperiod of time rather than a single examination mayprovide a more valid overall assessment.

Pulse oximetry has been rapidly adopted into clinicalassessment of children with bronchiolitis on the basis ofdata suggesting that it can reliably detect hypoxemia thatis not suspected on physical examination.27,34 Few stud-ies have assessed the effectiveness of pulse oximetry topredict clinical outcomes. Among inpatients, perceivedneed for supplemental oxygen that is based on pulseoximetry has been associated with higher risk of pro-longed hospitalization, ICU admission, and mechanicalventilation.24,26,35 Among outpatients, available evidencediffers on whether mild reductions in pulse oximetry(less than 95% on room air) predict progression of dis-ease or need for a return visit for care.27,32

Radiography may be useful when the hospitalizedchild does not improve at the expected rate, if the se-verity of disease requires further evaluation, or if an-other diagnosis is suspected. Although many infantswith bronchiolitis have abnormalities that show on chestradiographs, data are insufficient to demonstrate thatchest radiograph abnormalities correlate well with dis-ease severity.16 Two studies suggest that the presence ofconsolidation and atelectasis on a chest radiograph isassociated with increased risk for severe disease.26,27 Onestudy showed no correlation between chest radiographfindings and baseline severity of disease.36 In prospectivestudies including 1 randomized trial, children with sus-pected LRTI who received radiographs were more likelyto receive antibiotics without any difference in time torecovery.37,38 Current evidence does not support routineradiography in children with bronchiolitis.

The clinical utility of diagnostic testing in infants withsuspected bronchiolitis is not well supported by evi-dence.3941 The occurrence of serious bacterial infections(SBIs; eg, urinary tract infections [UTIs], sepsis, menin-gitis) is very low.42,43 The use of complete blood countshas not been shown to be useful in either diagnosingbronchiolitis or guiding its therapy.1

Virologic tests for RSV, if obtained during peak RSV

season, demonstrate a high predictive value. However,the knowledge gained from such testing rarely altersmanagement decisions or outcomes for the vast majorityof children with clinically diagnosed bronchiolitis.1 Viro-logic testing may be useful when cohorting of patients isfeasible.

Evidence Prole 1a: Diagnosis

Aggregate evidence quality: B; diagnostic studies withminor limitations and observational studies with con-sistent findings

Benefit: cost saving, limitation of radiation and bloodtests

Harm: risk of misdiagnosis

Benefits-harms assessment: preponderance of benefitover harm

Policy level: recommendation

Evidence Prole 1b: Risk Factors

Aggregate evidence quality: B; observational studieswith consistent findings

Benefit: improved care of patients with risk factors forsevere disease

Harm: increased costs, increased radiation and bloodtesting



RECOMMENDATION 2aBronchodilators should not be used routinely in the manage-ment of bronchiolitis (recommendation: evidence level B; RCTswith limitations; preponderance of harm of use over benefit).

RECOMMENDATION 2bA carefully monitored trial of -adrenergic or -adrenergicmedication is an option. Inhaled bronchodilators should becontinued only if there is a documented positive clinical re-sponse to the trial using an objective means of evaluation(option: evidence level B; RCTs with limitations and expertopinion; balance of benefit and harm).

The use of bronchodilator agents continues to be con-troversial. RCTs have failed to demonstrate a consistentbenefit from -adrenergic or -adrenergic agents. Sev-eral studies and reviews have evaluated the use of bron-chodilator medications for viral bronchiolitis. A Co-chrane systematic review44 found 8 RCTs involving 394children.33,4550 Some of the studies included infants whohad a history of previous wheezing. Several used agentsother than albuterol/salbutamol or epinephrine/adrena-line (eg, ipratropium and metaproterenol). Overall, re-sults of the meta-analysis indicated that, at most, 1 in 4


children treated with bronchodilators might have a tran-sient improvement in clinical score of unclear clinicalsignificance. This needs to be weighed against the po-tential adverse effects and cost of these agents and thefact that most children treated with bronchodilators willnot benefit from their use. Studies assessing the impactof bronchodilators on long-term outcomes have foundno impact on the overall course of the illness.1,44,51

Albuterol/SalbutamolSome outpatient studies have demonstrated modest im-provement in oxygen saturation and/or clinical scores.Schweich et al52 and Schuh et al53 evaluated clinicalscores and oxygen saturation after 2 treatments of neb-ulized albuterol. Each study showed improvement in theclinical score and oxygen saturation shortly after com-pletion of the treatment. Neither measured outcomesover time. Klassen et al47 evaluated clinical score andoxygen saturation 30 and 60 minutes after a single sal-butamol treatment. Clinical score, but not oxygen satu-ration, was significantly improved at 30 minutes, but nodifference was demonstrated 60 minutes after a treat-ment. Gadomski et al54 showed no difference betweenthose in groups on albuterol or placebo after 2 nebulizedtreatments given 30 minutes apart.

Studies of inpatients have not shown a clinical changethat would justify recommending albuterol for routinecare. Dobson et al55 conducted a randomized clinical trialin infants who were hospitalized with moderately severeviral bronchiolitis and failed to demonstrate clinical im-provement resulting in enhanced recovery or an atten-uation of the severity of illness. Two meta-analyses1,56

could not directly compare inpatient studies of albuterolbecause of widely differing methodology. Overall, thestudies reviewed did not show the use of albuterol ininfants with bronchiolitis to be beneficial in shorteningduration of illness or length of hospital stay.

Epinephrine/AdrenalineThe AHRQ evidence report1 notes that the reviewedstudies show that nebulized epinephrine has some po-tential for being efficacious. In contrast, a later multi-center controlled trial by Wainwright et al51 concludedthat epinephrine did not impact the overall course of theillness as measured by hospital length of stay. Analysis ofoutpatient studies favors nebulized epinephrine overplacebo in terms of clinical score, oxygen saturation, andrespiratory rate at 60 minutes57 and heart rate at 90minutes.58 However, the differences were small, and itcould not be established that they are clinically signifi-cant in altering the course of the illness. One study59

found significant improvement in airway resistance (butno change in oxygen need), suggesting that a trial of thisagent may be reasonable for such infants.

Several studies have compared epinephrine to albu-terol (salbutamol) or epinephrine to placebo. Racemic

epinephrine has demonstrated slightly better clinical ef-fect than albuterol. It is possible that the improvement isrelated to the effect of the medication.60 Hartling et al61

performed a meta-analysis of studies comparing epi-nephrine to albuterol and also participated in the Co-chrane review of epinephrine.62 The Cochrane reportconcluded: There is insufficient evidence to support theuse of epinephrine for the treatment of bronchiolitisamong inpatients. There is some evidence to suggest thatepinephrine may be favorable to salbutamol (albuterol)and placebo among outpatients.

Although there is no evidence from RCTs to justifyroutine use of bronchodilators, clinical experience sug-gests that, in selected infants, there is an improvement inthe clinical condition after bronchodilator administra-tion.47,52,53,57,58 It may be reasonable to administer a neb-ulized bronchodilator and evaluate clinical response. In-dividuals and institutions should assess the patient anddocument pretherapy and posttherapy changes using anobjective means of evaluation. Some of the documenta-tion tools that have been used can be found in articles byAlario et al,45 Bierman and Pierson,63 Gadomski et al,54

Lowell et al,33 Wainwright et al,51 Schuh et al,64 andGorelick et al.65 In addition, a documentation tool hasbeen developed by Cincinnati Childrens Hospital (Cin-cinnati, OH).66

Extrapolation from the studies discussed above sug-gests that epinephrine may be the preferred bronchodi-lator for this trial in the emergency department and inhospitalized patients. In the event that there is docu-mented clinical improvement, there is justification forcontinuing the nebulized bronchodilator treatments. Inthe absence of a clinical response, the treatment shouldnot be continued.

Because of a lack of studies, short duration of action,and potential adverse effects, epinephrine is usually notused in the home setting. Therefore, it would be moreappropriate that a bronchodilator trial in the office orclinic setting use albuterol/salbutamol rather than race-mic epinephrine. Parameters to measure its effectivenessinclude improvements in wheezing, respiratory rate, re-spiratory effort, and oxygen saturation.

Anticholinergic agents such as ipratropium have notbeen shown to alter the course of viral bronchiolitis.Although a minority of individual patients may show apositive clinical response to anticholinergic agents, stud-ies have shown that the groups as a whole showed nosignificant improvement. At this point there is no justi-fication for using anticholinergic agents, either alone orin combination with -adrenergic agents, for viral bron-chiolitis.6769

Evidence Prole 2a: Routine Use of Bronchodilators

Aggregate evidence quality: B; RCTs with limitations

Benefit: short-term improvement in clinical symptoms


Harm: adverse effects, cost of medications, cost toadminister

Benefits-harms assessment: preponderance of harmover benefit


Evidence Prole 2b: Trial of Bronchodilators


Benefit: some patients with significant symptomaticimprovement

Harm: adverse effects, cost of medications, cost toadminister

Benefits-harms assessment: preponderance of benefitover harm in select patients

Policy level: option

RECOMMENDATION 3Corticosteroid medications should not be used routinely in themanagement of bronchiolitis (recommendation: evidence levelB; based on RCTs with limitations and a preponderance of riskover benefit).

Reports indicate that up to 60% of infants admitted tothe hospital for bronchiolitis receive corticosteroid ther-apy.9,12,70 Systematic review and meta-analyses of RCTsinvolving close to 1200 children with viral bronchiolitishave not shown sufficient evidence to support the use ofsteroids in this illness.1,71,72

A Cochrane database review on the use of glucocor-ticoids for acute bronchiolitis71 included 13 stud-ies.37,50,64,7382 The 1198 patients showed a pooled de-crease in length of stay of 0.38 days. However, thisdecrease was not statistically significant. The review con-cluded: No benefits were found in either LOS [length ofstay] or clinical score in infants and young childrentreated with systemic glucocorticoids as compared withplacebo. There were no differences in these outcomesbetween treatment groups; either in the pooled analysisor in any of the sub analyses. Among the three studiesevaluating hospital admission rates following the initialhospital visit there was no difference between treatmentgroups. There were no differences found in respiratoryrate, hemoglobin oxygen saturation, or hospital revisitor readmission rates. Subgroup analyses were signifi-cantly limited by the low number of studies in eachcomparison. Specific data on the harm of corticosteroidtherapy in this patient population are lacking. Availableevidence suggests that corticosteroid therapy is not ofbenefit in this patient group.71

The 2 available studies that evaluated inhaled corti-costeroids in bronchiolitis83,84 showed no benefit in thecourse of the acute disease. Because the safety of high-dose inhaled corticosteroids in infants is still not clear,

their use should be avoided unless there is a clear like-lihood of benefit.

There are insufficient data to make a recommenda-tion regarding the use of leukotriene modifiers in bron-chiolitis. Until additional randomized clinical trials arecompleted, no conclusions can be drawn.

Evidence Prole 3: Corticosteroids

Aggregate evidence quality: B; randomized clinical tri-als with limitations

Benefit: possibility that corticosteroid may be of somebenefit

Harm: exposure to unnecessary medication



RECOMMENDATION 4Ribavirin should not be used routinely in children with bron-chiolitis (recommendation: evidence level B; RCTs with limita-tions and observational studies; preponderance of harm overbenefit).

The indications for specific antiviral therapy for bron-chiolitis are controversial. A recent review of 11 ran-domized clinical trials of ribavirin therapy for RSV LRTIs,including bronchiolitis, summarized the reported out-comes.85 Nine of the studies measured the effect of riba-virin in the acute phase of illness.8694 Two evaluated theeffect on long-term wheezing and/or pulmonary func-tion.95,96 Three additional studies were identified withsimilar results. Two of these evaluated effectiveness inthe acute phase97,98 and one on subsequent respiratorystatus.99

Each of the 11 studies that addressed the acute treat-ment effects of ribavirin included a small sample sizeranging from 26 to 53 patients and cumulatively totaling375 subjects. Study designs and outcomes measuredwere varied and inconsistent. Seven of the trials dem-onstrated some improvement in outcome attributed toribavirin therapy, and 4 did not. Of those showing ben-efit, 4 documented improved objective outcomes (eg,better oxygenation, shorter length of stay), and 3 re-ported improvement in subjective findings such as respi-ratory scores or subjective clinical assessment. The qual-ity of the studies was highly variable.

Of the studies that focused on long-term pulmonaryfunction, one was an RCT assessing the number of sub-sequent wheezing episodes and LRTIs over a 1-yearperiod.96 Two others were follow-up studies of previousrandomized trials and measured subsequent pulmonaryfunction as well as wheezing episodes.95,99 The firststudy96 found fewer episodes of wheezing and infectionsin the ribavirin-treated patients, and the latter 2 stud-ies95,99 found no significant differences between groups.


No randomized studies of other antiviral therapies ofbronchiolitis were identified.

Specific antiviral therapy for RSV bronchiolitis re-mains controversial because of the marginal benefit, ifany, for most patients. In addition, cumbersome deliveryrequirements,100 potential health risks for caregivers,101

and high cost102 serve as disincentives for use in themajority of patients. Nevertheless, ribavirin may be con-sidered for use in highly selected situations involvingdocumented RSV bronchiolitis with severe disease or inthose who are at risk for severe disease (eg, immuno-compromised and/or hemodynamically significant car-diopulmonary disease).

Evidence Prole 4: Ribavirin

Aggregate evidence quality: B; RCTs with limitationsand observational studies

Benefit: some improvement in outcome

Harm: cost, delivery method, potential health risks tocaregivers



RECOMMENDATION 5Antibacterial medications should be used only in children withbronchiolitis who have specific indications of the coexistence ofa bacterial infection. When present, bacterial infection shouldbe treated in the same manner as in the absence of bronchiolitis(recommendation: evidence level B; RCTs and observationalstudies; preponderance of benefit over harm).

Children with bronchiolitis frequently receive anti-bacterial therapy because of fever,103 young age,104 or theconcern over secondary bacterial infection.105 EarlyRCTs106,107 showed no benefit from antibacterial treat-ment of bronchiolitis. However, concern remains re-garding the possibility of bacterial infections in younginfants with bronchiolitis; thus, antibacterial agents con-tinue to be used.

Several retrospective studies41,108113 identified lowrates of SBI (0%3.7%) in patients with bronchiolitisand/or infections with RSV. When SBI was present, itwas more likely to be a UTI than bacteremia or menin-gitis. In a study of 2396 infants with RSV bronchiolitis,69% of the 39 patients with SBI had a UTI.110

Three prospective studies of SBI in patients withbronchiolitis and/or RSV infections also demonstratedlow rates of SBI (1%12%).42,43,114 One large study offebrile infants less than 60 days of age43 with bronchi-olitis and/or RSV infections demonstrated that the over-all risk of SBI in infants less than 28 days of age, al-though significant, was not different between RSV-positive and RSV-negative groups (10.1% and 14.2%,respectively). All SBIs in children between 29 and 60

days of age with RSV-positive bronchiolitis were UTIs.The rate of UTIs in RSV-positive patients between 28 and60 days old was significantly lower than those who wereRSV-negative (5.5% vs 11.7%).

Approximately 25% of hospitalized infants withbronchiolitis will have radiographic evidence of atelec-tasis or infiltrates, often misinterpreted as possible bac-terial infection.115 Bacterial pneumonia in infants withbronchiolitis without consolidation is unusual.116

Although acute otitis media (AOM) in bronchioliticinfants may be caused by RSV alone, there are no clinicalfeatures that permit viral AOM to be differentiated frombacterial. Two studies address the frequency of AOM inpatients with bronchiolitis. Andrade et al117 prospectivelyidentified AOM in 62% of 42 patients who presentedwith bronchiolitis. AOM was present in 50% on entry tothe study and developed in an additional 12% within 10days. Bacterial pathogens were isolated from 94% ofmiddle-ear aspirates, with Streptococcus pneumoniae, Hae-mophilus influenzae, and Moraxella catarrhalis being themost frequent isolates. A subsequent report118 followed150 children hospitalized for bronchiolitis for the devel-opment of AOM. Seventy-nine (53%) developed AOM,two thirds within the first 2 days of hospitalization.Tympanocentesis was performed on 64 children withAOM, and 33 middle-ear aspirates yielded pathogens. Hinfluenzae, S pneumoniae, and M catarrhalis were the onesmost commonly found. AOM did not influence the clin-ical course or laboratory findings of bronchiolitis. Whenfound, AOM should be managed according to the AAP/AAFP guidelines for diagnosis and management ofAOM.119

Evidence Prole 5: Antibacterial Therapy

Aggregate evidence quality: B; RCTs and observationalstudies with consistent results

Benefit: appropriate treatment of bacterial infections,decreased exposure to unnecessary medications andtheir adverse effects when a bacterial infection is notpresent, decreased risk of development of resistantbacteria

Harm: potential to not treat patient with bacterialinfection



RECOMMENDATION 6aClinicians should assess hydration and ability to take fluidsorally (strong recommendation: evidence level X; validatingstudies cannot be performed; clear preponderance of benefitover harm).


RECOMMENDATION 6bChest physiotherapy should not be used routinely in the man-agement of bronchiolitis (recommendation: evidence level B;RCTs with limitations; preponderance of harm over benefit).

The level of respiratory distress caused by bronchioli-tis guides the indications for use of other treatments.

Intravenous FluidsInfants with mild respiratory distress may require onlyobservation, particularly if feeding remains unaffected.When the respiratory rate exceeds 60 to 70 breaths perminute, feeding may be compromised, particularly ifnasal secretions are copious. Infants with respiratorydifficulty may develop nasal flaring, increased intercostalor sternal retractions, and prolonged expiratory wheez-ing and be at increased risk of aspiration of food into thelungs.120 Children who have difficulty feeding safely be-cause of respiratory distress should be given intravenousfluids. The possibility of fluid retention related to pro-duction of antidiuretic hormone has been reported inpatients with bronchiolitis.121,122 Clinicians should adjustfluid management accordingly.

Airway ClearanceBronchiolitis is associated with airway edema andsloughing of the respiratory epithelium into airways,which results in generalized hyperinflation of the lungs.Lobar atelectasis is not characteristic of this disease, al-though it can be seen on occasion. A Cochrane review123

found 3 RCTs that evaluated chest physiotherapy inhospitalized patients with bronchiolitis.124126 No clinicalbenefit was found using vibration and percussion tech-niques. Suctioning of the nares may provide temporaryrelief of nasal congestion. There is no evidence to sup-port routine deep suctioning of the lower pharynx orlarynx.

Evidence Prole 6a: Fluids

Aggregate evidence quality: evidence level X; validat-ing studies cannot be performed

Benefit: prevention of dehydration

Harm: overhydration, especially if syndrome of inap-propriate secretion of antidiuretic hormone (SIADH)is present

Benefits-harms assessment: clear preponderance ofbenefit over harm

Policy level: strong recommendation

Evidence Prole 6b: Chest Physiotherapy


Benefit: clearance of secretions, prevention of atelec-tasis

Harm: stress to infant during procedure, cost of ad-ministering chest physiotherapy



RECOMMENDATION 7aSupplemental oxygen is indicated if oxyhemoglobin saturation(SpO2) falls persistently below 90% in previously healthy in-fants. If the SpO2 does persistently fall below 90%, adequatesupplemental oxygen should be used to maintain SpO2 at orabove 90%. Oxygen may be discontinued if SpO2 is at or above90% and the infant is feeding well and has minimal respira-tory distress (option: evidence level D; expert opinion andreasoning from first principles; some benefit over harm).

RECOMMENDATION 7bAs the childs clinical course improves, continuous measure-ment of SpO2 is not routinely needed (option: evidence level D;expert opinion; balance of benefit and harm).

RECOMMENDATION 7cInfants with a known history of hemodynamically significantheart or lung disease and premature infants require closemonitoring as the oxygen is being weaned (strong recommen-dation: evidence level B; observational studies with consistentfindings; preponderance of benefit over harm).

Healthy infants have an SpO2 greater than 95% onroom air, although transient decreases to an SpO2 of lessthan 89% occur.127,128 In bronchiolitis, airway edema andsloughing of respiratory epithelial cells cause mismatch-ing of ventilation and perfusion and subsequent reduc-tions in oxygenation (PaO2 and SpO2).

In the clinical setting, pulse oximeters are convenient,safe tools to measure oxygenation status. Clinicians or-dering pulse oximetry should understand that the shapeof the oxyhemoglobin dissociation curve dictates thatwhen SpO2 is above 90%, large increases in PaO2 areassociated with small increases in SpO2. In contrast,when SpO2 is below 90%, a small decrease in PaO2 isassociated with large decreases in SpO2 (Fig 2). Thisraises the question of whether there is a single value forSpO2 that can serve as a decision point to hospitalize orinitiate supplemental oxygen in infants with bronchioli-tis.

In studies that examined treatment for bronchiolitisin hospitalized infants, some investigators started sup-plemental oxygen when SpO2 fell below 90%, and oth-ers started oxygen before the SpO2 reached 90%.98,129

Although data are lacking to codify a single value ofSpO2 to be used as a cutoff point for initiating or discon-tinuing supplemental oxygen, these studies and the re-lationship between PaO2 and SpO2 support the positionthat otherwise healthy infants with bronchiolitis whohave SpO2 at or above 90% at sea level while breathing


room air likely gain little benefit from increasing PaO2with supplemental oxygen, particularly in the absence ofrespiratory distress and feeding difficulties. Because sev-eral factors including fever, acidosis, and some hemoglo-binopathies shift the oxyhemoglobin dissociation curveso that large decreases in PaO2 begin to occur at an SpO2of more than 90%, clinicians should consider maintain-ing a higher SpO2 in children with these risk factors.130,131

Although widely used pulse oximeters have someshortcomings, under normal circumstances the accuracyof SpO2 may vary slightly (most oximeters are accurateto 2%). More importantly, poorly placed probes andmotion artifact will lead to inaccurate measurementsand false readings and alarms.132 Before instituting O2therapy, the accuracy of the initial reading should beverified by repositioning the probe and repeating themeasurement. The infants nose and, if necessary, oralairway should be suctioned. If SpO2 remains below 90%,O2 should be administered. The infants clinical work ofbreathing should also be assessed and may be consideredas a factor in a decision to use oxygen supplementation.

Premature or low birth weight infants and infantswith bronchopulmonary dysplasia or hemodynamicallysignificant congenital heart disease merit special atten-tion because they are at risk to develop severe illnessthat requires hospitalization, often in the ICU.7,29,133135

These infants often have abnormal baseline oxygenationcoupled with an inability to cope with the pulmonaryinflammation seen in bronchiolitis. This can result inmore severe and prolonged hypoxia compared with nor-

mal infants, and clinicians should take this into accountwhen developing strategies for using and weaning sup-plemental oxygen.

Evidence Prole 7a: Supplemental Oxygen

Aggregate evidence quality: D; expert opinion andreasoning from first principles

Benefit: use of supplemental oxygen only when ben-eficial, shorter hospitalization

Harm: inadequate oxygenation

Benefits-harms assessment: some benefit over harm


Evidence Prole 7b: Measurement of SpO2

Aggregate evidence quality: D; expert opinion

Benefit: shorter hospitalization

Harm: inadequate oxygenation between measure-ments



Evidence Prole 7c: High-Risk Infants


Benefit: improved care of high-risk infants

Harm: longer hospitalization, use of oxygen when notbeneficial


Policy level: Strong recommendation

RECOMMENDATION 8aClinicians may administer palivizumab prophylaxis to selectedinfants and children with CLD or a history of prematurity (lessthan 35 weeks gestation) or with congenital heart disease(recommendation: evidence level A; RCT; preponderance ofbenefit over harm).

RECOMMENDATION 8bWhen given, prophylaxis with palivizumab should be given in5 monthly doses, usually beginning in November or December,at a dose of 15 mg/kg per dose administered intramuscularly(recommendation: evidence level C; observational studies andexpert opinion; preponderance of benefit over cost).

The 2006 Report of the Committee on Infectious Dis-ease (Red Book) included the following recommendationsfor the use of palivizumab136:

Palivizumab prophylaxis should be considered for in-fants and children younger than 24 months of agewith chronic lung disease of prematurity who have

FIGURE 2Oxyhemoglobin dissociation curve showing percent saturation of hemoglobin at variouspartial pressures of oxygen. Note that the position of the curve and the afnity of hemo-globin for oxygen changes with changing physiologic conditions. (Reproduced withpermission from the educational website www.anaesthesiauk.com.)


required medical therapy (supplemental oxygen,bronchodilator or diuretic or corticosteroid therapy)for CLD within 6 months before the start of the RSVseason. Patients with more severe CLD who continueto require medical therapy may benefit from prophy-laxis during a second RSV season. Data are limitedregarding the effectiveness of palivizumab during thesecond year of life. Individual patients may benefitfrom decisions made in consultation with neonatolo-gists, pediatric intensivists, pulmonologists, or infec-tious disease specialists.

Infants born at 32 weeks of gestation or earlier maybenefit from RSV prophylaxis, even if they do nothave CLD. For these infants, major risk factors toconsider include their gestational age and chronologicage at the start of the RSV season. Infants born at 28weeks of gestation or earlier may benefit from pro-phylaxis during their first RSV season, whenever thatoccurs during the first 12 months of life. Infants bornat 29 to 32 weeks of gestation may benefit most fromprophylaxis up to 6 months of age. For the purpose ofthis recommendation, 32 weeks gestation refers to aninfant born on or before the 32nd week of gestation(ie, 32 weeks, 0 days). Once a child qualifies for initi-ation of prophylaxis at the start of the RSV season,administration should continue throughout the sea-son and not stop at the point an infant reaches either6 months or 12 months of age.

Although palivizumab has been shown to decrease thelikelihood of hospitalization in infants born between32 and 35 weeks of gestation (ie, between 32 weeks, 1day and 35 weeks, 0 days), the cost of administeringprophylaxis to this large group of infants must beconsidered carefully. Therefore, most experts recom-mend that prophylaxis should be reserved for infantsin this group who are at greatest risk of severe infec-tion and who are younger than 6 months of age at thestart of the RSV season. Epidemiologic data suggestthat RSV infection is more likely to lead to hospital-ization for these infants when the following risk factorare present: child care attendance, school-aged sib-lings, exposure to environmental air pollutants, con-genital abnormalities of the airways, or severe neuro-muscular disease. However, no single risk factorcauses a very large increase in the rate of hospitaliza-tion, and the risk is additive as the number of riskfactors for an individual infant increases. Therefore,prophylaxis should be considered for infants between32 and 35 weeks of gestation only if 2 or more of theserisk factors are present. Passive household exposure totobacco smoke has not been associated with an in-creased risk of RSV hospitalization on a consistentbasis. Furthermore, exposure to tobacco smoke is arisk factor that can be controlled by the family of aninfant at increased risk of severe RSV disease, and

preventive measures will be far less costly than palivi-zumab prophylaxis. High-risk infants never should beexposed to tobacco smoke. In contrast to the well-documented beneficial effect of breastfeeding againstmany viral illnesses, existing data are conflicting re-garding the specific protective effect of breastfeedingagainst RSV infection. High-risk infants should be keptaway from crowds and from situations in which ex-posure to infected individuals cannot be controlled.Participation in group child care should be restrictedduring the RSV season for high-risk infants wheneverfeasible. Parents should be instructed on the impor-tance of careful hand hygiene. In addition, all high-risk infants and their contacts should be immunizedagainst influenza beginning at 6 months of age.

In the Northern hemisphere and particularly withinthe United States, RSV circulates predominantly be-tween November and March. The inevitability of theRSV season is predictable, but the severity of the sea-son, the time of onset, the peak of activity, and the endof the season cannot be predicted precisely. There canbe substantial variation in timing of community out-breaks of RSV disease from year to year in the samecommunity and between communities in the sameyear, even in the same region. These variations, how-ever, occur within the overall pattern of RSV out-breaks, usually beginning in November or December,peaking in January or February, and ending by theend of March or sometime in April. Communities inthe southern United States tend to experience theearliest onset of RSV activity, and Midwestern statestend to experience the latest. The duration of theseason for western and northeast regions typicallyoccurs between that noted in the South and the Mid-west. In recent years, the national median duration ofthe RSV season has been 15 weeks and even in theSouth, with a seasonal duration of 16 weeks, therange is 13 to 20 weeks. Results from clinical trialsindicate that palivizumab trough serum concentra-tions 30 days after the fifth dose will be well abovethe protective concentration for most infants. If thefirst dose is administered in November, 5 monthlydoses of palivizumab will provide substantially morethan 20 weeks of protective serum antibody concen-trations for most of the RSV season, even with varia-tion in season onset and end. Changes from this rec-ommendation of 5 monthly doses require carefulconsideration of the benefits and costs.

Children who are 24 months of age or younger withhemodynamically significant cyanotic and acyanoticcongenital heart disease will benefit from palivizumabprophylaxis. Decisions regarding prophylaxis withpalivizumab in children with congenital heart diseaseshould be made on the basis of the degree of physio-logic cardiovascular compromise. Children younger


than 24 months of age with congenital heart diseasewho are most likely to benefit from immunoprophy-laxis include: Infants who are receiving medication to controlcongestive heart failure

Infants with moderate to severe pulmonary hyper-tension

Infants with cyanotic heart disease

Results from 2 blinded, randomized, placebo-con-trolled trials with palivizumab involving 2789 infantsand children with prematurity, CLD, or congenital heartdisease demonstrated a reduction in RSV hospitalizationrates of 39% to 78% in different groups.137,138 Resultsfrom postlicensure observational studies suggest thatmonthly immunoprophylaxis may reduce hospitaliza-tion rates to an even greater extent than that describedin the prelicensure clinical trials.139 Palivizumab is noteffective in the treatment of RSV disease and is notapproved for this indication.

Several economic analyses of RSV immunoprophy-laxis have been published.140147 The primary benefit ofimmunoprophylaxis with palivizumab is a decrease inthe rate of RSV-associated hospitalization. None of the 5clinical RCTs have demonstrated a significant decrease inrate of mortality attributable to RSV infection in infantswho receive prophylaxis. Most of the economic analysesfail to demonstrate overall savings in health care dollarsbecause of the high cost if all at-risk children were toreceive prophylaxis. Estimates of cost per hospitalizationprevented have been inconsistent because of consider-able variation in the baseline rate of hospitalization at-tributable to RSV in different high-risk groups. Otherconsiderations that will influence results include theeffect of prophylaxis on outpatient costs and a resolutionof the question of whether prevention of RSV infectionin infancy decreases wheezing and lower respiratorytract problems later in childhood.

Evidence Prole 8a: Palivizumab Prophylaxis

Aggregate evidence quality: A; RCTs

Benefit: prevention of morbidity and mortality inhigh-risk infants

Harm: cost



Evidence Prole 8b: Five-Dose Regimen

Aggregate evidence quality: C; observational studiesand expert opinion

Benefit: decreased cost resulting from using minimalnumber of needed doses

Harm: risk of illness from RSV outside the usual sea-son



RECOMMENDATION 9aHand decontamination is the most important step in preventingnosocomial spread of RSV. Hands should be decontaminatedbefore and after direct contact with patients, after contact withinanimate objects in the direct vicinity of the patient, and afterremoving gloves (strong recommendation: evidence level B;observational studies with consistent results; strong preponder-ance of benefit over harm).

RECOMMENDATION 9bAlcohol-based rubs are preferred for hand decontamination.An alternative is hand-washing with antimicrobial soap (rec-ommendation: evidence level B; observational studies with con-sistent results; preponderance of benefit over harm).

RECOMMENDATION 9cClinicians should educate personnel and family members onhand sanitation (recommendation: evidence level C; observa-tional studies; preponderance of benefit over harm).

Efforts should be made to decrease the spread of RSVand other causative agents of bronchiolitis in medicalsettings, especially in the hospital. RSV RNA has beenidentified in air samples as much as 22 feet from thepatients bedside.148 Secretions from infected patients canbe found on beds, crib railings, tabletops, and toys. Or-ganisms on fomites may remain viable and contagiousfor several hours.149

It has been shown that RSV as well as many otherviruses can be carried and spread to others on the handsof caregivers.150 Frequent hand-washing by health careworkers has been shown to reduce RSVs nosocomialspread.150 The Centers for Disease Control and Preven-tion published an extensive review of the hand-hygieneliterature and made recommendations as to indicationsfor hand-washing and hand antisepsis.151 Among therecommendations are that hands should be decontami-nated before and after direct contact with patients, aftercontact with inanimate objects in the direct vicinity ofthe patient, and after removing gloves. If hands are notvisibly soiled, an alcohol-based rub is preferred. An al-ternative is to wash hands with an antimicrobial soap.The guideline also describes the appropriate techniquefor using these products.

Other methods that have been shown to be effectivein controlling the spread of RSV are education of per-sonnel and family members; surveillance for the onset ofRSV season; use of gloves, with frequent changes toavoid the spread of organisms on the gloves; and wear-ing gowns for direct contact with the patient. It has not


been clearly shown that wearing masks offers additionalbenefit to the above-listed measures.149 Isolation and/orcohorting of RSV-positive patients, including assignmentof personnel to care only for these patients, is effec-tive152,153 but may not be feasible. Strict hand decontam-ination and education of staff and families about preven-tion of spread of organisms is essential regardless ofwhether isolation is used.

Programs that implement the above-mentioned prin-ciples have been shown to decrease the nosocomialspread of RSV. Johns Hopkins Hospital (Baltimore, MD)instituted a program of pediatric droplet precaution forall children less than 2 years old with respiratory symp-toms during RSV season until the child is shown to nothave RSV. Nosocomial transmission of RSV decreased byapproximately 50%. Before intervention, a patient was2.6 times more likely to have nosocomially transmittedRSV than after the intervention.154 A similar program atChildrens Hospital of Philadelphia (Philadelphia, PA)resulted in a decrease of nosocomial RSV infections of39%.155

Evidence Prole 9a: Hand Decontamination


Benefit: decreased spread of infection

Harm: time

Benefits-harms assessment: strong preponderance ofbenefit over harm


Evidence Prole 9b: Alcohol-Based Rubs



Harm: irritative effect of alcohol-based rubs



Evidence Prole 9c: Education

Aggregate evidence quality: C; observational studies


Harm: time, cost of gloves and gowns if used, barriersto parental contact with patient



RECOMMENDATION 10aInfants should not be exposed to passive smoking (strong rec-ommendation: evidence level B; observational studies with con-sistent results; strong preponderance of benefit over harm).

RECOMMENDATION 10bBreastfeeding is recommended to decrease a childs risk ofhaving lower respiratory tract disease (LRTD) (recommenda-tion: evidence level C; observational studies; preponderance ofbenefit over harm).

Tobacco SmokePassive smoking increases the risk of having an RSVinfection with a reported odds ratio of 3.87.156 Therehave been numerous studies on the effect of passivesmoking on respiratory illness in infants and children. Ina systematic review of passive smoking and lower respira-tory illness in infants and children, Strachan and Cook157

showed a pooled odds ratio of 1.57 if either parent smokedand an odds ratio of 1.72 if the mother smoked. Stocks andDezateux158 reviewed 20 studies of pulmonary function ininfants. These studies showed a significant decrease in pul-monary function in infants of mothers who smoked duringand after pregnancy. Forced expiratory flowwas decreasedby approximately 20%. Other measures of pulmonaryfunction were likewise abnormal.

Paternal smoking also has an effect. The prevalence ofupper respiratory tract illness increased from 81.6% to95.2% in infants under 1 year of age in householdswhere only the father smoked.159

BreastfeedingBreast milk has been shown to have immune factors toRSV including immunoglobulin G and A antibodies160

and interferon-.161 Breast milk has also been shown tohave neutralizing activity against RSV.162 In one studythe relative risk of hospital admission with RSV was 2.2in children who were not being breastfed.163 In anotherstudy, 8 (7%) of 115 children hospitalized with RSVwere breastfed, and 46 (27%) of 167 controls werebreastfed.164

A meta-analysis of the relationship of breastfeedingand hospitalization for LRTD in early infancy165 exam-ined 33 studies, all of which showed a protective asso-ciation between breastfeeding and the risk of hospital-ization for LRTD. Nine studies met all inclusion criteriafor analysis. The conclusion was that infants who werenot breastfed had almost a threefold greater risk of beinghospitalized for LRTD than those exclusively breastfedfor 4 months (risk ratio: 0.28).

Evidence Prole 10a: Secondhand Smoke


Benefit: decreased risk of LRTI


Harm: none

Benefits-harms assessment: strong preponderance ofbenefit over harm


Evidence Prole 10b: Breastfeeding

Aggregate evidence quality: C; observational studies

Benefit: improved immunity, decreased risk of LRTI,improved nutrition

Harm: implied inadequacy of mothers who cannot orprefer to not breastfeed



RECOMMENDATION 11Clinicians should inquire about use of CAM (option: evidencelevel D; expert opinion; some benefit over harm).

No recommendations for CAM for treatment of bron-chiolitis are made because of limited data. Cliniciansnow recognize that an increasing number of parents/caregivers are using various forms of nonconventionaltreatment for their children. Treatments that have beenused specifically for bronchiolitis include homeopathy,herbal remedies, osteopathic manipulation, and appliedkinesiology. Substantially more data are available re-garding the use of homeopathic and herbal remedies forthe treatment of bronchitis and the common cold.Whether these therapies would prevent the developmentof bronchiolitis is unknown. A single recent trial indicatedthat an herbal preparation containing Echinacea, propolis,and vitamin C prevented the development of upper respi-ratory infections in children between the ages of 1 and 5years.166 Bronchiolitis was not specifically studied.

To date, there are no studies that conclusively show abeneficial effect of alternative therapies used for thetreatment of bronchiolitis. Recent interest in the use ofCAM has led to research efforts to investigate its efficacy.It is difficult to design and conduct studies on certainforms of CAM because of the unique nature of thetreatment. Any study conducted will need to show proofof effectiveness of a specific therapy when comparedwith the natural history of the disease. Conclusions re-garding CAM cannot be made until research evidence isavailable. However, because of the widespread use ofCAM, clinicians should ask parents what alternativeforms of treatment they are using and be ready to discusspotential benefits or risks.

Evidence Prole 11: Asking About CAM

Aggregate evidence quality: D; expert opinion

Benefit: improved parent-physician communication,

awareness of other, possibly harmful treatments beingused

Harm: time required for discussion, lack of knowledgeabout CAM by many pediatricians



FUTURE RESEARCHThe AHRQ evidence report1 points out that outcomesmeasured in future studies of bronchiolitis should beclinically relevant and of interest to parents, clinicians,and health systems. Among the recommended outcomesare rates of hospitalization, need for more intensive ser-vices in the hospital, costs of care, and parental satisfac-tion with treatment.1 One of the difficulties with thebronchiolitis literature is the absence of validated clinicalscoring scales that are objective, replicable, and can beeasily be performed in the hospital, emergency depart-ment, and outpatient settings. Studies should also be ofsufficient size to be able to draw meaningful conclusionsfor the above-mentioned outcomes. Because bronchioli-tis is a self-limited disease, large numbers of patientswould need to be enrolled to observe small changes inoutcome. This would necessitate large multicenter studyprotocols. Currently, such multicentered studies are be-ing conducted in the United States and Canada on theuse of corticosteroids in the emergency department.

Future research should include:

development of rapid, cost-effective tests for virusesother than RSV that may also play a role in bronchi-olitis;

studies to determine if there are selected patients whomay benefit from bronchodilators or corticosteroids;

clinical studies of the target SpO2 for the most efficientuse of oxygen and oxygen monitoring;

development of new therapies including new antiviralmedications;

continued research into the development of an RSVvaccine; and

continued development of immunoprophylaxis thatwould require fewer doses and decreased cost.

SUMMARYThis clinical practice guideline provides evidence-basedrecommendations on the diagnosis and management ofbronchiolitis in infants less than 2 years of age. It em-phasizes using only diagnostic and management modal-ities that have been shown to affect clinical outcomes.

Bronchiolitis is a clinical diagnosis that does not re-quire diagnostic testing. Many of the commonly usedmanagement modalities have not been shown to beeffective in improving the clinical course of the illness.This includes the routine use of bronchodilators, corti-


costeroids, ribavirin, antibiotics, chest radiography, chestphysiotherapy, and complementary and alternativetherapies. Options for the appropriate use of oxygen andoxygen monitoring have been presented. Specific pre-vention with palivizumab and general prevention, par-ticularly the use of hand decontamination to preventnosocomial spread, were also discussed.

CONCLUSIONS

1a. Clinicians should diagnose bronchiolitis and assessdisease severity on the basis of history and physicalexamination. Clinicians should not routinely orderlaboratory and radiologic studies for diagnosis (rec-ommendation).

1b. Clinicians should assess risk factors for severe dis-ease such as age less than 12 weeks, a history ofprematurity, underlying cardiopulmonary disease,or immunodeficiency when making decisions aboutevaluation and management of children with bron-chiolitis (recommendation).

2a. Bronchodilators should not be used routinely in themanagement of bronchiolitis (recommendation).

2b. A carefully monitored trial of -adrenergic or -ad-renergic medication is an option. Inhaled broncho-dilators should be continued only if there is a doc-umented positive clinical response to the trial usingan objective means of evaluation (option).

3. Corticosteroid medications should not be used rou-tinely in the management of bronchiolitis (recom-mendation).

4. Ribavirin should not be used routinely in childrenwith bronchiolitis (recommendation).

5. Antibacterial medications should only be used in chil-dren with bronchiolitis who have specific indicationsof the coexistence of a bacterial infection. Whenpresent, bacterial infection should be treated in thesame manner as in the absence of bronchiolitis (rec-ommendation).

6a. Clinicians should assess hydration and ability to takefluids orally (strong recommendation).

6b. Chest physiotherapy should not be used routinely inthe management of bronchiolitis (recommenda-tion).

7a. Supplemental oxygen is indicated if SpO2 falls per-sistently below 90% in previously healthy infants. Ifthe SpO2 does persistently fall below 90%, adequatesupplemental oxygen should be used to maintain anSpO2 at or above 90%. Oxygen may be discontinuedif SpO2 is at or above 90% and the infant is feedingwell and has minimal respiratory distress (option).

7b. As the childs clinical course improves, continuousmeasurement of SpO2 is not routinely needed (op-tion).

7c. Infants with a known history of hemodynamicallysignificant heart or lung disease and premature in-fants require close monitoring as oxygen is beingweaned (strong recommendation).

8a. Clinicians may administer palivizumab prophylaxisfor selected infants and children with CLD or a his-tory of prematurity (less than 35 weeks gestation)or with congenital heart disease (recommendation).

8b. When given, prophylaxis with palivizumab shouldbe given in 5 monthly doses, usually beginning inNovember or December, at a dose of 15 mg/kg perdose administered intramuscularly (recommenda-tion).

9a. Hand decontamination is the most important step inpreventing nosocomial spread of RSV. Hands shouldbe decontaminated before and after direct contactwith patients, after contact with inanimate objects inthe direct vicinity of the patient, and after removinggloves (strong recommendation).

9b. Alcohol-based rubs are preferred for hand decon-tamination. An alternative is hand-washing withantimicrobial soap (recommendation).

9c. Clinicians should educate personnel and familymembers on hand sanitation (recommendation).

10a. Infants should not be exposed to passive smoking(strong recommendation).

10b. Breastfeeding is recommended to decrease a childsrisk of having LRTD (recommendation).

11. Clinicians should inquire about use of CAM(option).

SUBCOMMITTEE ON THE DIAGNOSIS ANDMANAGEMENT OF

BRONCHIOLITIS, 20042006

Allan S. Lieberthal, MD, ChairpersonHoward Bauchner, MDCaroline B. Hall, MDDavid W. Johnson, MDUma Kotagal, MDMichael J. Light, MD (on the AstraZeneca and

MedImmune speakers bureaus; research grant fromMedImmune)

Wilbert Mason, MD (on the MedImmune speakersbureau)

H. Cody Meissner, MDKieran J. Phelan, MDJoseph J. Zorc, MD


LIASONS

Mark A. Brown, MD (on the GlaxoSmithKline,AstraZeneca, and MedImmune speakers bureaus)American Thoracic Society

Richard D. Clover, MD (continuing medical educationpresenter for institutions that received unrestrictededucational grants from Sanofi Pasteur and Merck)American Academy of Family Physicians

Ian T. Nathanson, MDAmerican College of Chest Physicians

Matti Korppi, MDEuropean Respiratory Society

CONSULTANTS

Richard N. Shiffman, MDDanette Stanko-Lopp, MA, MPH

STAFF

Caryn Davidson, MA

REFERENCES1. Agency for Healthcare Research and Quality. Management of

Bronchiolitis in Infants and Children. Evidence Report/Tech-nology Assessment No. 69. Rockville, MD: Agency for Health-care Research and Quality; 2003. AHRQ Publication No. 03-E014

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