pediatrics 2014 ralston peds.2014 2742

CLINICAL PRACTICE GUIDELINE

Clinical Practice Guideline: The Diagnosis, Management,and Prevention of Bronchiolitis

abstractThis guideline is a revision of the clinical practice guideline, Diagnosisand Management of Bronchiolitis, published by the American Academyof Pediatrics in 2006. The guideline applies to children from 1 through23 months of age. Other exclusions are noted. Each key action state-ment indicates level of evidence, benefit-harm relationship, and levelof recommendation. Key action statements are as follows: Pediatrics2014;134:e1474e1502

DIAGNOSIS

1a. Clinicians should diagnose bronchiolitis and assess disease se-verity on the basis of history and physical examination (EvidenceQuality: B; Recommendation Strength: Strong Recommendation).

1b. Clinicians should assess risk factors for severe disease, such asage less than 12 weeks, a history of prematurity, underlying car-diopulmonary disease, or immunodeficiency, when making decisionsabout evaluation and management of children with bronchiolitis(Evidence Quality: B; Recommendation Strength: Moderate Rec-ommendation).

1c. When clinicians diagnose bronchiolitis on the basis of history andphysical examination, radiographic or laboratory studies shouldnot be obtained routinely (Evidence Quality: B; RecommendationStrength: Moderate Recommendation).

TREATMENT

2. Clinicians should not administer albuterol (or salbutamol) to in-fants and children with a diagnosis of bronchiolitis (Evidence Qual-ity: B; Recommendation Strength: Strong Recommendation).

3. Clinicians should not administer epinephrine to infants and childrenwith a diagnosis of bronchiolitis (Evidence Quality: B; Recommen-dation Strength: Strong Recommendation).

4a. Nebulized hypertonic saline should not be administered to in-fants with a diagnosis of bronchiolitis in the emergency depart-ment (Evidence Quality: B; Recommendation Strength: ModerateRecommendation).

4b. Clinicians may administer nebulized hypertonic saline to infantsand children hospitalized for bronchiolitis (Evidence Quality: B;Recommendation Strength: Weak Recommendation [based on ran-domized controlled trials with inconsistent findings]).

Shawn L. Ralston, MD, FAAP, Allan S. Lieberthal, MD, FAAP,H. Cody Meissner, MD, FAAP, Brian K. Alverson, MD, FAAP, Jill E.Baley, MD, FAAP, Anne M. Gadomski, MD, MPH, FAAP,David W. Johnson, MD, FAAP, Michael J. Light, MD, FAAP,Nizar F. Maraqa, MD, FAAP, Eneida A. Mendonca, MD, PhD,FAAP, FACMI, Kieran J. Phelan, MD, MSc, Joseph J. Zorc, MD,MSCE, FAAP, Danette Stanko-Lopp, MA, MPH, Mark A.Brown, MD, Ian Nathanson, MD, FAAP, ElizabethRosenblum, MD, Stephen Sayles III, MD, FACEP, and SinsiHernandez-Cancio, JD

KEY WORDSbronchiolitis, infants, children, respiratory syncytial virus,evidence-based, guideline

ABBREVIATIONSAAPAmerican Academy of PediatricsAOMacute otitis mediaCIconfidence intervalEDemergency departmentKASKey Action StatementLOSlength of stayMDmean differencePCRpolymerase chain reactionRSVrespiratory syncytial virusSBIserious bacterial infection

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authors havefiled conflict of interest statements with the American Academy ofPediatrics. Any conflicts have been resolved through a processapproved by the Board of Directors. The American Academy ofPediatrics has neither solicited nor accepted any commercialinvolvement in the development of the content of this publication.

The recommendations in this report do not indicate an exclusivecourse of treatment or serve as a standard ofmedical care. Variations,taking into account individual circumstances, may be appropriate.

All clinical practice guidelines from the American Academy ofPediatrics automatically expire 5 years after publication unlessreaffirmed, revised, or retired at or before that time.

Dedicated to the memory of Dr Caroline Breese Hall.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-2742

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5. Clinicians should not administersystemic corticosteroids to infantswith a diagnosis of bronchiolitis inany setting (Evidence Quality: A; Rec-ommendation Strength: Strong Rec-ommendation).

6a. Clinicians may choose not to ad-minister supplemental oxygen ifthe oxyhemoglobin saturation ex-ceeds 90% in infants and childrenwith a diagnosis of bronchiolitis(Evidence Quality: D; Recommen-dation Strength: Weak Recommen-dation [based on low level evidenceand reasoning from first princi-ples]).

6b. Clinicians may choose not to usecontinuous pulse oximetry for in-fants and children with a diagnosisof bronchiolitis (Evidence Quality:D; Recommendation Strength: WeakRecommendation [based on low-level evidence and reasoning fromfirst principles]).

7. Clinicians should not use chestphysiotherapy for infants and chil-dren with a diagnosis of bron-chiolitis (Evidence Quality: B;Recommendation Strength: Mod-erate Recommendation).

8. Clinicians should not administerantibacterial medications to in-fants and children with a diagno-sis of bronchiolitis unless thereis a concomitant bacterial infec-tion, or a strong suspicion of one(Evidence Quality: B; Recommen-dation Strength: Strong Recom-mendation).

9. Clinicians should administer naso-gastric or intravenous fluids forinfants with a diagnosis of bron-chiolitis who cannot maintain hy-dration orally (Evidence Quality: X;Recommendation Strength: StrongRecommendation).

PREVENTION

10a. Clinicians should not administerpalivizumab to otherwise healthyinfants with a gestational age of

29 weeks, 0 days or greater(Evidence Quality: B; Recom-mendation Strength: StrongRecommendation).

10b. Clinicians should administerpalivizumab during the firstyear of life to infants with he-modynamically significant heartdisease or chronic lung diseaseof prematurity defined as pre-term infants21%oxygen for at least the first28 days of life (Evidence Quality:B; Recommendation Strength:Moderate Recommendation).

10c. Clinicians should administera maximum 5 monthly doses(15 mg/kg/dose) of palivizumabduring the respiratory syncytialvirus season to infants whoqualify for palivizumab in thefirst year of life (Evidence Quality:B; Recommendation Strength:Moderate Recommendation).

11a. All people should disinfect handsbefore and after direct contactwith patients, after contact withinanimate objects in the directvicinity of the patient, and afterremoving gloves (Evidence Qual-ity: B; Recommendation Strength:Strong Recommendation).

11b. All people should use alcohol-based rubs for hand decontam-ination when caring for childrenwith bronchiolitis. When alcohol-based rubs are not available,individuals should wash theirhands with soap and water(Evidence Quality: B; Recom-mendation Strength: StrongRecommendation).

12a. Clinicians should inquire aboutthe exposure of the infant orchild to tobacco smoke whenassessing infants and chil-dren for bronchiolitis (EvidenceQuality: C; RecommendationStrength: Moderate Recom-mendation).

12b. Clinicians should counsel care-givers about exposing the in-fant or child to environmentaltobacco smoke and smokingcessation when assessing achild for bronchiolitis (EvidenceQuality: B; RecommendationStrength: Strong).

13. Clinicians should encourage ex-clusive breastfeeding for at least6 months to decrease the mor-bidity of respiratory infections.(Evidence Quality: B; Recommen-dation Strength: Moderate Rec-ommendation).

14. Clinicians and nurses should ed-ucate personnel and family mem-bers on evidence-based diagnosis,treatment, and prevention in bron-chiolitis. (Evidence Quality: C; obser-vational studies; RecommendationStrength: Moderate Recommenda-tion).

INTRODUCTION

In October 2006, the American Acad-emy of Pediatrics (AAP) published theclinical practice guideline Diagnosisand Management of Bronchiolitis.1

The guideline offered recommendationsranked according to level of evidenceand the benefit-harm relationship. Sincecompletion of the original evidence re-view in July 2004, a significant body ofliterature on bronchiolitis has beenpublished. This update of the 2006 AAPbronchiolitis guideline evaluates pub-lished evidence, including that used inthe 2006 guideline as well as evidencepublished since 2004. Key action state-ments (KASs) based on that evidenceare provided.

The goal of this guideline is to providean evidence-based approach to the di-agnosis, management, and preventionof bronchiolitis in children from 1 monththrough 23 months of age. The guidelineis intended for pediatricians, familyphysicians, emergency medicine spe-cialists, hospitalists, nurse practitioners,

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and physician assistants who care forthese children. The guideline does notapply to children with immunodeficien-cies, including those with HIV infectionor recipients of solid organ or hema-topoietic stem cell transplants. Childrenwith underlying respiratory illnesses,such as recurrent wheezing, chronicneonatal lung disease (also known asbronchopulmonary dysplasia), neuro-muscular disease, or cystic fibrosis andthose with hemodynamically significantcongenital heart disease are excludedfrom the sections on management un-less otherwise noted but are included inthe discussion of prevention. This guide-line will not address long-term sequelaeof bronchiolitis, such as recurrentwheezing or risk of asthma, which isa field with a large and distinct lit-erature.

Bronchiolitis is a disorder commonlycaused by viral lower respiratory tractinfection in infants. Bronchiolitis ischaracterized by acute inflammation,edema, and necrosis of epithelial cellslining small airways, and increasedmucus production. Signs and symp-toms typically begin with rhinitis andcough, which may progress to tachy-pnea, wheezing, rales, use of accessorymuscles, and/or nasal flaring.2

Many viruses that infect the respiratorysystem cause a similar constellation ofsigns and symptoms. The most com-mon etiology of bronchiolitis is re-spiratory syncytial virus (RSV), with thehighest incidence of infection occurringbetween December and March in NorthAmerica; however, regional variationsoccur3 (Fig 1).4 Ninety percent of chil-dren are infected with RSV in the first2 years of life,5 and up to 40% willexperience lower respiratory tract in-fection during the initial infection.6,7

Infection with RSV does not grant per-manent or long-term immunity, withreinfections common throughout life.8

Other viruses that cause bronchiolitisinclude human rhinovirus, human meta-

pneumovirus, influenza, adenovirus,coronavirus, human, and parainflu-enza viruses. In a study of inpatientsand outpatients with bronchiolitis,9

76% of patients had RSV, 39% hadhuman rhinovirus, 10% had influenza,2% had coronavirus, 3% had humanmetapneumovirus, and 1% had para-influenza viruses (some patients hadcoinfections, so the total is greater than100%).

Bronchiolitis is themost common causeof hospitalization among infants duringthe first 12 months of life. Approximately100 000 bronchiolitis admissions occurannually in the United States at anestimated cost of $1.73 billion.10 Oneprospective, population-based studysponsored by the Centers for DiseaseControl and Prevention reported the

average RSV hospitalization rate was5.2 per 1000 children younger than 24months of age during the 5-year pe-riod between 2000 and 2005.11 Thehighest age-specific rate of RSV hos-pitalization occurred among infantsbetween 30 days and 60 days of age(25.9 per 1000 children). For preterminfants (

preterm infants is similar to that ofterm infants.12,13

METHODS

In June 2013, the AAP convened a newsubcommittee to review and revise the2006 bronchiolitis guideline. The sub-committee included primary care physi-cians, including general pediatricians,a family physician, and pediatric sub-specialists, including hospitalists, pul-monologists, emergency physicians, aneonatologist, and pediatric infectiousdisease physicians. The subcommit-tee also included an epidemiologisttrained in systematic reviews, a guide-line methodologist/informatician, and aparent representative. All panel mem-bers reviewed the AAP Policy on Conflictof Interest and Voluntary Disclosure andwere given an opportunity to declare anypotential conflicts. Any conflicts can befound in the author listing at the end ofthis guideline. All funding was providedby the AAP, with travel assistance fromthe American Academy of Family Phy-sicians, the American College of ChestPhysicians, the American ThoracicSociety, and the American Collegeof Emergency Physicians for theirliaisons.

The evidence search and review includedelectronic database searches in TheCochrane Library, Medline via Ovid,and CINAHL via EBSCO. The searchstrategy is shown in the Appendix. Re-lated article searches were conductedin PubMed. The bibliographies of arti-cles identified by database searcheswere also reviewed by 1 of 4 membersof the committee, and references iden-tified in this manner were added tothe review. Articles included in the2003 evidence report on bronchiolitisin preparation of the AAP 2006 guide-line2 also were reviewed. In addition,the committee reviewed articles pub-lished after completion of the sys-tematic review for these updatedguidelines. The current literature re-

view encompasses the period from2004 through May 2014.

The evidence-based approach to guide-line development requires that the evi-dence in support of a policy be identified,appraised, and summarized and that anexplicit link between evidence and rec-ommendations be defined. Evidence-based recommendations reflect thequality of evidence and the balance ofbenefit and harm that is anticipatedwhen the recommendation is followed.The AAP policy statement Classify-ing Recommendations for ClinicalPractice14 was followed in designat-ing levels of recommendation (Fig 2;Table 1).

A draft version of this clinical practiceguideline underwent extensive peerreview by committees, councils, andsections within AAP; the AmericanThoracic Society, American College ofChest Physicians, American Academy

of Family Physicians, and AmericanCollege of Emergency Physicians; otheroutside organizations; and other in-dividuals identified by the subcom-mittee as experts in the field. Theresulting comments were reviewedby the subcommittee and, when ap-propriate, incorporated into the guide-line.

This clinical practice guideline is notintended as a sole source of guidancein the management of children withbronchiolitis. Rather, it is intended toassist clinicians in decision-making.It is not intended to replace clinicaljudgment or establish a protocol forthe care of all children with bronchi-olitis. These recommendations may notprovide the only appropriate approachto the management of children withbronchiolitis.

All AAP guidelines are reviewed every5 years.

FIGURE 2Integrating evidence quality appraisal with an assessment of the anticipated balance between benefitsand harms leads to designation of a policy as a strong recommendation, moderate recommendation,or weak recommendation.





DIAGNOSIS

Key Action Statement 1a

Clinicians should diagnose bronchi-olitis and assess disease severityon the basis of history and physicalexamination (Evidence Quality: B;Recommendation Strength: StrongRecommendation).

Action Statement Profile KAS 1a

Key Action Statement 1b

Clinicians should assess risk fac-tors for severe disease, such asage

be made. Most clinicians recognizebronchiolitis as a constellation of clin-ical signs and symptoms occurring inchildren younger than 2 years, includ-ing a viral upper respiratory tractprodrome followed by increased re-spiratory effort and wheezing. Clinicalsigns and symptoms of bronchiolitisconsist of rhinorrhea, cough, tachypnea,wheezing, rales, and increased respi-ratory effort manifested as grunting,nasal flaring, and intercostal and/orsubcostal retractions.

The course of bronchiolitis is variableand dynamic, ranging from transientevents, such as apnea, to progressiverespiratory distress from lower airwayobstruction. Important issues to assessin the history include the effects of re-spiratory symptoms on mental status,feeding, and hydration. The clinicianshould assess the ability of the familyto care for the child and to return forfurther evaluation if needed. Historyof underlying conditions, such as pre-maturity, cardiac disease, chronicpulmonary disease, immunodeficiency,or episodes of previous wheezing, shouldbe identified. Underlying conditions thatmay be associated with an increasedrisk of progression to severe diseaseor mortality include hemodynamicallysignificant congenital heart disease,chronic lung disease (bronchopulmonarydysplasia), congenital anomalies,1517

in utero smoke exposure,18 and thepresence of an immunocompromisingstate.19,20 In addition, genetic abnormal-ities have been associated with moresevere presentation with bronchiolitis.21

Assessment of a child with bronchiolitis,including the physical examination, canbe complicated by variability in the dis-ease state and may require serialobservations over time to fully assess thechilds status. Upper airway obstructioncontributes to work of breathing. Suc-tioning and positioning may decreasethe work of breathing and improve thequality of the examination. Respiratory

rate in otherwise healthy childrenchanges considerably over the firstyear of life.2225 In hospitalized children,the 50th percentile for respiratory ratedecreased from 41 at 0 to 3 months ofage to 31 at 12 to 18 months of age.26

Counting respiratory rate over thecourse of 1 minute is more accuratethan shorter observations.27 The pres-ence of a normal respiratory ratesuggests that risk of significant viralor bacterial lower respiratory tractinfection or pneumonia in an infant islow (negative likelihood ratio approxi-mately 0.5),2729 but the presence oftachypnea does not distinguish be-tween viral and bacterial disease.30,31

The evidence relating the presence ofspecific findings in the assessment ofbronchiolitis to clinical outcomes islimited. Most studies addressing thisissue have enrolled children whenpresenting to hospital settings, in-cluding a large, prospective, multicen-ter study that assessed a variety ofoutcomes from the emergency de-partment (ED) and varied inpatientsettings.18,32,33 Severe adverse events,such as ICU admission and need formechanical ventilation, are uncommonamong children with bronchiolitis andlimit the power of these studiesto detect clinically important risk fac-tors associated with disease pro-gression.16,34,35 Tachypnea, defined asa respiratory rate 70 per minute, hasbeen associated with increased risk ofsevere disease in some studies3537 butnot others.38 Many scoring systemshave been developed in an attempt toobjectively quantify respiratory dis-tress, although none has achievedwidespread acceptance and few havedemonstrated any predictive validity,likely because of the substantial tem-poral variability in physical findings ininfants with bronchiolitis.39

Pulse oximetry has been rapidly adoptedinto clinical assessment of childrenwith bronchiolitis on the basis of data

suggesting that it reliably detects hyp-oxemia not suspected on physicalexamination36,40; however, few studieshave assessed the effectiveness ofpulse oximetry to predict clinical out-comes. Among inpatients, perceivedneed for supplemental oxygen on thebasis of pulse oximetry has been as-sociated with prolonged hospitaliza-tion, ICU admission, and mechanicalventilation.16,34,41 Among outpatients,available evidence differs on whethermild reductions in pulse oximetry (1 month for full-terminfants or 48 weeks postconceptionalage for preterm infants, and absenceof any previous apneic event at pre-sentation to the hospital.44 Anotherlarge multicenter study found no asso-ciation between the specific viral agentand risk of apnea in bronchiolitis.42

The literature on viral testing for bron-chiolitis has expanded in recent yearswith the availability of sensitive poly-merase chain reaction (PCR) assays.Large studies of infants hospitalized forbronchiolitis have consistently foundthat 60% to 75% have positive test resultsfor RSV, and have noted coinfectionsin up to one-third of infants.32,33,45

In the event an infant receivingmonthly prophylaxis is hospitalizedwith bronchiolitis, testing should beperformed to determine if RSV is theetiologic agent. If a breakthrough RSVinfection is determined to be presentbased on antigen detection or other





assay, monthly palivizumab prophylaxisshould be discontinued because of thevery low likelihood of a second RSVinfection in the same year. Apart fromthis setting, routine virologic testing isnot recommended.

Infants with non-RSV bronchiolitis, inparticular human rhinovirus, appear tohave a shorter courses and may rep-resent a different phenotype associatedwith repeated wheezing.32 PCR assayresults should be interpreted cautiously,given that the assay may detect pro-longed viral shedding from an unrelatedprevious illness, particularly with rhi-novirus. In contrast, RSV detected byPCR assay almost always is associatedwith disease. At the individual patientlevel, the value of identifying a spe-cific viral etiology causing bronchi-olitis has not been demonstrated.33

Current evidence does not supportroutine chest radiography in childrenwith bronchiolitis. Although manyinfants with bronchiolitis have abnor-malities on chest radiography, dataare insufficient to demonstrate thatchest radiography correlates well withdisease severity. Atelectasis on chestradiography was associated with in-creased risk of severe disease in 1outpatient study.16 Further studies, in-cluding 1 randomized trial, suggestchildren with suspected lower respi-ratory tract infection who had radiog-raphy performed were more likely toreceive antibiotics without any differ-ence in outcomes.46,47 Initial radiographyshould be reserved for cases in whichrespiratory effort is severe enough towarrant ICU admission or where signsof an airway complication (such aspneumothorax) are present.

TREATMENT

ALBUTEROL

Key Action Statement 2

Clinicians should not administeralbuterol (or salbutamol) to infants

and children with a diagnosis ofbronchiolitis (Evidence Quality: B;Recommendation Strength: StrongRecommendation).

Action Statement Profile KAS 2

Although several studies and reviewshave evaluated the use of bronchodi-lator medications for viral bronchiolitis,most randomized controlled trials havefailed to demonstrate a consistent ben-efit from - or -adrenergic agents.Several meta-analyses and systematicreviews4853 have shown that broncho-dilators may improve clinical symptomscores, but they do not affect diseaseresolution, need for hospitalization, orlength of stay (LOS). Because clinicalscores may vary from one observer tothe next39,54 and do not correlate withmore objective measures, such as pul-monary function tests,55 clinical scoresare not validated measures of the effi-cacy of bronchodilators. Although tran-sient improvements in clinical scorehave been observed, most infantstreated with bronchodilators will notbenefit from their use.

A recently updated Cochrane system-atic review assessing the impact ofbronchodilators on oxygen saturation,the primary outcomemeasure, reported30 randomized controlled trials in-volving 1992 infants in 12 countries.56

Some studies included in this reviewevaluated agents other than albuterol/salbutamol (eg, ipratropium and meta-proterenol) but did not include epi-nephrine. Small sample sizes, lack ofstandardized methods for outcomeevaluation (eg, timing of assessments),and lack of standardized intervention(various bronchodilators, drug dosages,routes of administration, and nebuliza-tion delivery systems) limit the in-terpretation of these studies. Becauseof variable study designs as well as theinclusion of infants who had a history ofprevious wheezing in some studies,there was considerable heterogeneityin the studies. Sensitivity analysis (ie,including only studies at low risk ofbias) significantly reduced heterogene-ity measures for oximetry while havinglittle effect on the overall effect size ofoximetry (mean difference [MD] 0.38,95% confidence interval [CI] 0.75 to0.00). Those studies showing benefit5759

are methodologically weaker than otherstudies and include older children withrecurrent wheezing. Results of theCochrane review indicated no benefit inthe clinical course of infants withbronchiolitis who received bronchodi-lators. The potential adverse effects(tachycardia and tremors) and cost ofthese agents outweigh any potentialbenefits.

In the previous iteration of this guideline,a trial of -agonists was included asan option. However, given the greaterstrength of the evidence demonstrat-ing no benefit, and that there is nowell-established way to determine anobjective method of response tobronchodilators in bronchiolitis, thisoption has been removed. Although itis true that a small subset of children

Aggregateevidencequality

B

Benefits Avoid adverse effects, avoidongoing use of ineffectivemedication, lower costs

Risk, harm, cost Missing transient benefit ofdrug

Benefit-harmassessment

Benefits outweigh harms

Value judgments Overall ineffectivenessoutweighs possibletransient benefit

Intentionalvagueness

None

Role of patientpreferences

None

Exclusions NoneStrength Strong recommendationDifferences ofopinion

None

Notes This guideline no longerrecommends a trial ofalbuterol, as was consideredin the 2006 AAP bronchiolitisguideline

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with bronchiolitis may have reversibleairway obstruction resulting fromsmooth muscle constriction, attemptsto define a subgroup of respondershave not been successful to date. Ifa clinical trial of bronchodilators isundertaken, clinicians should note that thevariability of the disease process, the hostsairway, and the clinical assessments, par-ticularly scoring, would limit the cliniciansability to observe a clinically relevant re-sponse to bronchodilators.

Chavasse et al60 reviewed the availableliterature on use of -agonists for chil-dren younger than 2 years with re-current wheezing. At the time of thatreview, there were 3 studies in theoutpatient setting, 2 in the ED, and 3in the pulmonary function laboratorysetting. This review concluded therewere no clear benefits from the useof -agonists in this population. Theauthors noted some conflicting evi-dence, but further study was recom-mended only if the population could beclearly defined and meaningful out-come measures could be identified.

The population of children with bron-chiolitis studied in most trials ofbronchodilators limits the ability tomake recommendations for all clinicalscenarios. Children with severe diseaseor with respiratory failure were gen-erally excluded from these trials, andthis evidence cannot be generalized tothese situations. Studies using pulmo-nary function tests show no effect ofalbuterol among infants hospitalizedwith bronchiolitis.56,61 One study ina critical care setting showed a smalldecrease in inspiratory resistance af-ter albuterol in one group and leval-buterol in another group, but therapywas accompanied by clinically signifi-cant tachycardia.62 This small clinicalchange occurring with significant ad-verse effects does not justify recom-mending albuterol for routine care.

EPINEPHRINE


Clinicians should not administerepinephrine to infants and childrenwith a diagnosis of bronchiolitis(Evidence Quality: B; Recommenda-tion Strength: Strong Recommen-dation).


Epinephrine is an adrenergic agentwith both - and -receptor agonistactivity that has been used to treatupper and lower respiratory tract ill-nesses both as a systemic agent anddirectly into the respiratory tract,where it is typically administered asa nebulized solution. Nebulized epi-nephrine has been administered inthe racemic form and as the purifiedL-enantiomer, which is commerciallyavailable in the United States for in-travenous use. Studies in other dis-eases, such as croup, have found nodifference in efficacy on the basis ofpreparation,63 although the compari-son has not been specifically studiedfor bronchiolitis. Most studies havecompared L-epinephrine to placebo oralbuterol. A recent Cochrane meta-

analysis by Hartling et al64 systemati-cally evaluated the evidence on thistopic and found no evidence for utilityin the inpatient setting. Two large,multicenter randomized trials com-paring nebulized epinephrine to pla-cebo65 or albuterol66 in the hospitalsetting found no improvement in LOSor other inpatient outcomes. A recent,large multicenter trial found a similarlack of efficacy compared with pla-cebo and further demonstrated lon-ger LOS when epinephrine was usedon a fixed schedule compared with anas-needed schedule.67 This evidencesuggests epinephrine should not beused in children hospitalized for bron-chiolitis, except potentially as a rescueagent in severe disease, although for-mal study is needed before a recom-mendation for the use of epinephrinein this setting.

The role of epinephrine in the out-patient setting remains controver-sial. A major addition to the evidencebase came from the Canadian Bron-chiolitis Epinephrine Steroid Trial.68

This multicenter randomized trialenrolled 800 patients with bron-chiolitis from 8 EDs and comparedhospitalization rates over a 7-dayperiod. This study had 4 arms: neb-ulized epinephrine plus oral dexa-methasone, nebulized epinephrineplus oral placebo, nebulized placeboplus oral dexamethasone, and neb-ulized placebo plus oral placebo. Thegroup of patients who received epi-nephrine concomitantly with corti-costeroids had a lower likelihoodof hospitalization by day 7 than thedouble placebo group, although thiseffect was no longer statistically sig-nificant after adjusting for multiplecomparisons.

The systematic review by Hartlinget al64 concluded that epinephrinereduced hospitalizations comparedwith placebo on the day of the ED visitbut not overall. Given that epinephrine


B

Benefits Avoiding adverse effects, lowercosts, avoiding ongoing useof ineffective medication

Risk, harm, cost Missing transient benefit ofdrug



Value judgments The overall ineffectivenessoutweighs possible transientbenefit


None


None

Exclusions Rescue treatment of rapidlydeteriorating patients

Strength Strong recommendationDifferences of

opinionNone





has a transient effect and home ad-ministration is not routine practice,discharging an infant after observinga response in a monitored settingraises concerns for subsequent pro-gression of illness. Studies have notfound a difference in revisit rates,although the numbers of revisits aresmall and may not be adequatelypowered for this outcome. In summary,the current state of evidence does notsupport a routine role for epineph-rine for bronchiolitis in outpatients,although further data may help tobetter define this question.

HYPERTONIC SALINE


Nebulized hypertonic saline shouldnot be administered to infants witha diagnosis of bronchiolitis in theemergency department (EvidenceQuality: B; Recommendation Strength:Moderate Recommendation).



Clinicians may administer nebulizedhypertonic saline to infants andchildren hospitalized for bron-chiolitis (Evidence Quality: B; Rec-ommendation Strength: Weak

Recommendation [based on ran-domized controlled trials withinconsistent findings]).

Action Statement Profile KAS 4b

Nebulized hypertonic saline is an in-creasingly studied therapy for acuteviral bronchiolitis. Physiologic evidencesuggests that hypertonic saline in-creases mucociliary clearance in bothnormal and diseased lungs.6971 Becausethe pathology in bronchiolitis involvesairway inflammation and resultantmucus plugging, improved mucocili-ary clearance should be beneficial, al-though there is only indirect evidenceto support such an assertion. A morespecific theoretical mechanism of ac-tion has been proposed on the basis ofthe concept of rehydration of the air-way surface liquid, although again,evidence remains indirect.72

A 2013 Cochrane review73 included 11trials involving 1090 infants with mild tomoderate disease in both inpatient andemergency settings. There were 6 studiesinvolving 500 inpatients providing data

for the analysis of LOS with an aggregate1-day decrease reported, a result largelydriven by the inclusion of 3 studies withrelatively long mean length of stay of 5 to6 days. The analysis of effect on clinicalscores included 7 studies involving 640patients in both inpatient and outpatientsettings and demonstrated incrementalpositive effect with each day posttreat-ment from day 1 to day 3 (0.88 MD onday 1, 1.32 MD on day 2, and 1.51 MDon day 3). Finally, Zhang et al73 found noeffect on hospitalization rates in thepooled analysis of 1 outpatient and 3 EDstudies including 380 total patients.

Several randomized trials published afterthe Cochrane review period further in-formed the current guideline recommen-dation. Four trials evaluated admissionrates from the ED, 3 using 3% saline and 1using 7% saline.7476 A single trial76 dem-onstrated a difference in admission ratesfrom the ED favoring hypertonic saline,although the other 4 studies were con-cordant with the studies included in theCochrane review. However, contrary to thestudies included in the Cochrane review,none of the more recent trials reportedimprovement in LOS and, when added tothe older studies for an updated meta-analysis, they significantly attenuate thesummary estimate of the effect on LOS.76,77

Most of the trials included in the Cochranereview occurred in settings with typicalLOS of more than 3 days in their usualcare arms. Hence, the significant decreasein LOS noted by Zhang et al73 may not begeneralizable to the United States wherethe average LOS is 2.4 days.10 One otherongoing clinical trial performed in theUnited States, unpublished except in ab-stract form, further supports the obser-vation that hypertonic saline does notdecrease LOS in settings where expectedstays are less than 3 days.78

The preponderance of the evidence sug-gests that 3% saline is safe and effective atimproving symptoms of mild to moderatebronchiolitis after 24 hours of use andreducing hospital LOS in settings in which


B

Benefits Avoiding adverse effects, suchas wheezing and excesssecretions, cost

Risk, harm, cost NoneBenefit-harmassessment


Value judgments NoneIntentionalvagueness

None


None

Exclusions NoneStrength Moderate recommendationDifferences ofopinion

None


B

Benefits May shorten hospital stay if LOSis >72 h

Risk, harm, cost Adverse effects such aswheezing and excesssecretions; cost


Benefits outweigh harms forlonger hospital stays

Value judgments Anticipating an individualchilds LOS is difficult. MostUS hospitals report anaverage LOS of 72 h


This weak recommendation isbased on an average LOS anddoes not address theindividual patient.


None

Exclusions NoneStrength WeakDifferences ofopinion

None



the duration of stay typically exceeds 3days. It has not been shown to be effectiveat reducing hospitalization in emergencysettings or in areas where the lengthof usage is brief. It has not beenstudied in intensive care settings,and most trials have included onlypatients with mild to moderate dis-ease. Most studies have used a 3%saline concentration, and most havecombined it with bronchodilatorswith each dose; however, there isretrospective evidence that the rateof adverse events is similar withoutbronchodilators,79 as well as pro-spective evidence extrapolated from2 trials without bronchodilators.79,80

A single study was performed in theambulatory outpatient setting81; how-ever, future studies in the United Statesshould focus on sustained usage onthe basis of pattern of effects dis-cerned in the available literature.

CORTICOSTEROIDS


Clinicians should not administersystemic corticosteroids to infantswith a diagnosis of bronchiolitis inany setting (Evidence Quality: A;Recommendation Strength: StrongRecommendation).


Although there is good evidence ofbenefit from corticosteroids in other

respiratory diseases, such as asthmaand croup,8284 the evidence on corti-costeroid use in bronchiolitis is nega-tive. The most recent Cochranesystematic review shows that cortico-steroids do not significantly reduceoutpatient admissions when comparedwith placebo (pooled risk ratio, 0.92;95% CI, 0.78 to 1.08; and risk ratio, 0.86;95% CI, 0.7 to 1.06, respectively) anddo not reduce LOS for inpatients (MD0.18 days; 95% CI 0.39 to 0.04).85 Noother comparisons showed relevantdifferences for either primary or sec-ondary outcomes. This review con-tained 17 trials with 2596 participantsand included 2 large ED-based ran-domized trials, neither of which showedreductions in hospital admissions withtreatment with corticosteroids as com-pared with placebo.69,86

One of these large trials, the CanadianBronchiolitis Epinephrine Steroid Trial,however, did show a reduction in hos-pitalizations 7 days after treatment withcombined nebulized epinephrine andoral dexamethasone as compared withplacebo.69 Although an unadjusted ana-lysis showed a relative risk for hospi-talization of 0.65 (95% CI 0.45 to 0.95;P = .02) for combination therapy ascompared with placebo, adjustmentfor multiple comparison rendered theresult insignificant (P = .07). Theseresults have generated considerablecontroversy.87 Although there is nostandard recognized rationale for whycombination epinephrine and dexa-methasone would be synergistic ininfants with bronchiolitis, evidence inadults and children older than 6years with asthma shows that addinginhaled long-acting agonists tomoderate/high doses of inhaled cor-ticosteroids allows reduction of thecorticosteroid dose by, on average,60%.88 Basic science studies focusedon understanding the interaction be-tween agonists and corticosteroidshave shown potential mechanisms for

why simultaneous administration ofthese drugs could be synergistic.8992

However, other bronchiolitis trials ofcorticosteroids administered by us-ing fixed simultaneous bronchodila-tor regimens have not consistentlyshown benefit9397; hence, a recommen-dation regarding the benefit of com-bined dexamethasone and epinephrinetherapy is premature.

The systematic review of cortico-steroids in children with bronchiolitiscited previously did not find any dif-ferences in short-term adverse eventsas compared with placebo.86 However,corticosteroid therapy may prolongviral shedding in patients with bron-chiolitis.17

In summary, a comprehensive sys-tematic review and large multicenterrandomized trials provide clear evi-dence that corticosteroids alone donot provide significant benefit tochildren with bronchiolitis. Evidencefor potential benefit of combinedcorticosteroid and agents with both- and -agonist activity is at besttentative, and additional large trialsare needed to clarify whether thistherapy is effective.

Further, although there is no evidenceof short-term adverse effects fromcorticosteroid therapy, other thanprolonged viral shedding, in infantsand children with bronchiolitis, thereis inadequate evidence to be certainof safety.

OXYGEN


Clinicians may choose not to ad-minister supplemental oxygen if theoxyhemoglobin saturation exceeds90% in infants and children with adiagnosis of bronchiolitis (EvidenceQuality: D; Recommendation Strength:Weak Recommendation [based onlow-level evidence and reasoningfrom first principles]).

Aggregateevidence quality

A

Benefits No clinical benefit, avoidingadverse effects

Risk, harm, cost NoneBenefit-harm

assessmentBenefits outweigh harms

Value judgments NoneIntentional

vaguenessNone


None

Exclusions NoneStrength Strong recommendationDifferences of

opinionNone







Clinicians may choose not to usecontinuous pulse oximetry for in-fants and children with a diagnosisof bronchiolitis (Evidence Quality:C; Recommendation Strength: WeakRecommendation [based on lower-level evidence]).


Although oxygen saturation is a poorpredictor of respiratory distress, it is

associated closely with a perceivedneed for hospitalization in infants withbronchiolitis.98,99 Additionally, oxygensaturation has been implicated asa primary determinant of LOS inbronchiolitis.40,100,101

Physiologic data based on the oxyhe-moglobin dissociation curve (Fig 3)demonstrate that small increases inarterial partial pressure of oxygen areassociated with marked improvementin pulse oxygen saturation when thelatter is less than 90%; with pulse oxy-gen saturation readings greater than90% it takes very large elevations inarterial partial pressure of oxygen toaffect further increases. In infants andchildren with bronchiolitis, no data existto suggest such increases result in anyclinically significant difference in physi-ologic function, patient symptoms, orclinical outcomes. Although it is wellunderstood that acidosis, temperature,and 2,3-diphosphoglutarate influencethe oxyhemoglobin dissociation curve,there has never been research todemonstrate how those influencespractically affect infants with hypox-emia. The risk of hypoxemia must beweighed against the risk of hospitali-zation when making any decisionsabout site of care. One study of hospi-talized children with bronchiolitis, forexample, noted a 10% adverse error ornear-miss rate for harm-causing inter-ventions.103 There are no studies on theeffect of short-term, brief periods ofhypoxemia such as may be seen inbronchiolitis. Transient hypoxemia iscommon in healthy infants.104 Travel ofhealthy children even to moderate alti-tudes of 1300 m results in transientsleep desaturation to an average of84% with no known adverse con-sequences.105 Although children withchronic hypoxemia do incur devel-opmental and behavioral problems,children who suffer intermittent hyp-oxemia from diseases such as asthma

do not have impaired intellectual abil-ities or behavioral disturbance.106108

Supplemental oxygen provided for in-fants not requiring additional re-spiratory support is best initiated withnasal prongs, although exact mea-surement of fraction of inspired oxy-gen is unreliable with this method.109

Pulse oximetry is a convenient methodto assess the percentage of hemo-globin bound by oxygen in children.Pulse oximetry has been erroneouslyused in bronchiolitis as a proxy forrespiratory distress. Accuracy of pulseoximetry is poor, especially in the 76%to 90% range.110 Further, it has beenwell demonstrated that oxygen satu-ration has much less impact on re-spiratory drive than carbon dioxideconcentrations in the blood.111 Thereis very poor correlation between re-spiratory distress and oxygen satu-rations among infants with lowerrespiratory tract infections.112 Otherthan cyanosis, no published clinicalsign, model, or score accurately iden-tifies hypoxemic children.113

Among children admitted for bronchi-olitis, continuous pulse oximetry mea-surement is not well studied andpotentially problematic for children whodo not require oxygen. Transient desa-turation is a normal phenomenon inhealthy infants. In 1 study of 64 healthyinfants between 2 weeks and 6 monthsof age, 60% of these infants exhibiteda transient oxygen desaturation below90%, to values as low as 83%.105 A ret-rospective study of the role of continu-ous measurement of oxygenation ininfants hospitalized with bronchiolitisfound that 1 in 4 patients incur unnec-essarily prolonged hospitalization asa result of a perceived need for oxygenoutside of other symptoms40 and noevidence of benefit was found.

Pulse oximetry is prone to errors ofmeasurement. Families of infants hospi-talized with continuous pulse oximetersare exposed to frequent alarms that

Benefits Decreased hospitalizations,decreased LOS

Risk, harm, cost Hypoxemia, physiologic stress,prolonged LOS, increasedhospitalizations, increasedLOS, cost



Value judgments Oxyhemoglobin saturation>89% is adequate tooxygenate tissues; the riskof hypoxemia withoxyhemoglobin saturation>89% is minimal


None


Limited

Exclusions Children with acidosis or feverStrength Weak recommendation (based

on low-level evidence/reasoning from firstprinciples)

Differences ofopinion

None


C

Benefits Shorter LOS, decreased alarmfatigue, decreased cost

Risk, harm, cost Delayed detection of hypoxemia,delay in appropriate weaningof oxygen




None


Limited

Exclusions NoneStrength Weak recommendation (based

on lower level of evidence)Differences ofopinion

None



may negatively affect sleep. Alarm fa-tigue is recognized by The JointCommission as a contributor towardin-hospital morbidity and mortality.114

One adult study demonstrated verypoor documentation of hypoxemia al-erts by pulse oximetry, an indicatorof alarm fatigue.115 Pulse oximetryprobes can fall off easily, leading toinaccurate measurements and alarms.116

False reliance on pulse oximetry maylead to less careful monitoring of re-spiratory status. In one study, contin-uous pulse oximetry was associatedwith increased risk of minor adverseevents in infants admitted to a gen-eral ward.117 The pulse oximetrymonitored patients were found tohave less-effective surveillance of theirseverity of illness when controlling forother variables.

There are a number of new approachesto oxygen delivery in bronchiolitis, 2of which are home oxygen and high-frequency nasal cannula. There isemerging evidence for the role of homeoxygen in reducing LOS or admissionrate for infants with bronchiolitis, in-

cluding 2 randomized trials.118,119 Mostof the studies have been performed inareas of higher altitude, where pro-longed hypoxemia is a prime deter-minant of LOS in the hospital.120,121

Readmission rates may be moderatelyhigher in patients discharged withhome oxygen; however, overall hospitaluse may be reduced,122 although not inall settings.123 Concerns have beenraised that home pulse oximetry maycomplicate care or confuse families.124

Communication with follow-up physi-cians is important, because primarycare physicians may have difficulty de-termining safe pulse oximetry levelsfor discontinuation of oxygen.125 Addi-tionally, there may be an increaseddemand for follow-up outpatient visitsassociated with home oxygen use.124

Use of humidified, heated, high-flownasal cannula to deliver air-oxygenmixtures provides assistance to in-fants with bronchiolitis through mul-tiple proposed mechanisms.126 Thereis evidence that high-flow nasal can-nula improves physiologic measuresof respiratory effort and can generate

continuous positive airway pressurein bronchiolitis.127130 Clinical evidencesuggests it reduces work of breath-ing131,132 and may decrease need forintubation,133136 although studies aregenerally retrospective and small. Thetherapy has been studied in the ED136,137

and the general inpatient setting,134,138

as well as the ICU. The largest and mostrigorous retrospective study to datewas from Australia,138 which showeda decline in intubation rate in the sub-group of infants with bronchiolitis (n =330) from 37% to 7% after the intro-duction of high-flow nasal cannula,while the national registry intubationrate remained at 28%. A single pilotfor a randomized trial has been pub-lished to date.139 Although promising,the absence of any completed ran-domized trial of the efficacy of high-flownasal cannula in bronchiolitis precludesspecific recommendations on it use atpresent. Pneumothorax is a reportedcomplication.

CHEST PHYSIOTHERAPY


Clinicians should not use chest phys-iotherapy for infants and childrenwith a diagnosis of bronchiolitis (Evi-dence Quality: B; RecommendationStrength: Moderate Recommendation).


FIGURE 3Oxyhemoglobin dissociation curve showing percent saturation of hemoglobin at various partialpressures of oxygen (reproduced with permission from the educational Web site www.anaesthesiauk.com).102


B

Benefits Decreased stress fromtherapy, reduced cost




None


None

Exclusions NoneStrength Moderate recommendationDifferences ofopinion

None




www.anaesthesiauk.comwww.anaesthesiauk.comhttp://pediatrics.aappublications.org/

Airway edema, sloughing of respiratoryepithelium into airways, and general-ized hyperinflation of the lungs, coupledwith poorly developed collateral venti-lation, put infants with bronchiolitis atrisk for atelectasis. Although lobar at-electasis is not characteristic of thisdisease, chest radiographs may showevidence of subsegmental atelectasis,prompting clinicians to consider or-dering chest physiotherapy to promoteairway clearance. A Cochrane Review140

found 9 randomized controlled trialsthat evaluated chest physiotherapy inhospitalized patients with bronchiolitis.No clinical benefit was found by usingvibration or percussion (5 trials)141144

or passive expiratory techniques (4 tri-als).145148 Since that review, a study149

of the passive expiratory techniquefound a small, but significant reductionin duration of oxygen therapy, but noother benefits.

Suctioning of the nasopharynx to re-move secretions is a frequent practicein infants with bronchiolitis. Althoughsuctioning the nares may providetemporary relief of nasal congestionor upper airway obstruction, a retro-spective study reported that deepsuctioning150 was associated withlonger LOS in hospitalized infants 2to 12 months of age. The same studyalso noted that lapses of greaterthan 4 hours in noninvasive, externalnasal suctioning were also associ-ated with longer LOS. Currently, thereare insufficient data to make a rec-ommendation about suctioning, butit appears that routine use of deepsuctioning151,153 may not be beneficial.

ANTIBACTERIALS


Clinicians should not administerantibacterial medications to infantsand children with a diagnosis ofbronchiolitis unless there is a con-comitant bacterial infection, or astrong suspicion of one. (Evidence

Quality: B; Recommendation Strength:Strong Recommendation).


Infants with bronchiolitis frequently re-ceive antibacterial therapy because offever,152 young age,153 and concern forsecondary bacterial infection.154 Earlyrandomized controlled trials155,156

showed no benefit from routine anti-bacterial therapy for children withbronchiolitis. Nonetheless, antibiotictherapy continues to be overused inyoung infants with bronchiolitis becauseof concern for an undetected bacterialinfection. Studies have shown that febrileinfants without an identifiable source offever have a risk of bacteremia that maybe as high as 7%. However, a child witha distinct viral syndrome, such asbronchiolitis, has a lower risk (muchless than 1%) of bacterial infection of thecerebrospinal fluid or blood.157

Ralston et al158 conducted a systematicreview of serious bacterial infections(SBIs) occurring in hospitalized febrileinfants between 30 and 90 days of agewith bronchiolitis. Instances of bacter-emia or meningitis were extremely rare.

Enteritis was not evaluated. Urinary tractinfection occurred at a rate of approxi-mately 1%, but asymptomatic bacteri-uria may have explained this finding. Theauthors concluded routine screening forSBI among hospitalized febrile infantswith bronchiolitis between 30 and 90days of age is not justified. Limited datasuggest the risk of bacterial infection inhospitalized infants with bronchiolitisyounger than 30 days of age is similar tothe risk in older infants. An abnormalwhite blood cell count is not useful forpredicting a concurrent SBI in infantsand young children hospitalized with RSVlower respiratory tract infection.159 Sev-eral retrospective studies support thisconclusion.160166 Four prospective stud-ies of SBI in patients with bronchiolitisand/or RSV infections also demonstratedlow rates of SBI.167171

Approximately 25% of hospitalized in-fants with bronchiolitis have radio-graphic evidence of atelectasis, and itmay be difficult to distinguish betweenatelectasis and bacterial infiltrate orconsolidation.169 Bacterial pneumoniain infants with bronchiolitis withoutconsolidation is unusual.170 Antibiotictherapy may be justified in some chil-dren with bronchiolitis who requireintubation and mechanical ventilationfor respiratory failure.172,173

Although acute otitis media (AOM) ininfants with bronchiolitis may be at-tributable to viruses, clinical featuresgenerally do not permit differentiation ofviral AOM from those with a bacterialcomponent.174 Two studies address thefrequency of AOM in patients withbronchiolitis. Andrade et al175 pro-spectively identified AOM in 62% of 42patients who presented with bronchi-olitis. AOM was present in 50% on entryto the study and developed in an addi-tional 12% within 10 days. A subsequentreport176 followed 150 children hospi-talized for bronchiolitis for the de-velopment of AOM. Seventy-nine (53%)developed AOM, two-thirds within the


B

Benefits Fewer adverse effects, lessresistance toantibacterial agents,lower cost




Strong suspicion is notspecifically definedand requires clinicianjudgment. An evaluationfor the source of possibleserious bacterial infectionshould be completedbefore antibiotic use


None

Exclusions NoneStrength Strong recommendationDifferences ofopinion

None



first 2 days of hospitalization. AOM didnot influence the clinical course orlaboratory findings of bronchiolitis. Thecurrent AAP guideline on AOM177 rec-ommends that a diagnosis of AOMshould include bulging of the tympanicmembrane. This is based on bulgingbeing the best indicator for the pres-ence of bacteria in multiple tympano-centesis studies and on 2 articlescomparing antibiotic to placebo ther-apy that used a bulging tympanicmembrane as a necessary part of thediagnosis.178,179 New studies are neededto determine the incidence of AOM inbronchiolitis by using the new criterionof bulging of the tympanic membrane.Refer to the AOM guideline180 for rec-ommendations regarding the manage-ment of AOM.

NUTRITION AND HYDRATION


Clinicians should administer naso-gastric or intravenous fluids forinfants with a diagnosis of bron-chiolitis who cannot maintain hy-dration orally (Evidence Quality: X;Recommendation Strength: StrongRecommendation).


The level of respiratory distressattributable to bronchiolitis guidesthe indications for fluid replacement.Conversely, food intake in the previous24 hours may be a predictor of oxygensaturation among infants with bron-

chiolitis. One study found that food in-take at less than 50% of normal for theprevious 24 hours is associated witha pulse oximetry value of

infants with a gestational age of 29weeks, 0 days or greater (EvidenceQuality: B; Recommendation Strength:Strong Recommendation).



Clinicians should administer pal-ivizumab during the first year oflife to infants with hemodynami-cally significant heart disease orchronic lung disease of prema-turity defined as preterm infants21% oxygen for at leastthe first 28 days of life (EvidenceQuality: B; Recommendation Strength:Moderate Recommendation).


Key Action Statement 10c

Clinicians should administer a max-imum 5 monthly doses (15 mg/kg/dose) of palivizumab during theRSV season to infants who qualifyfor palivizumab in the first yearof life (Evidence Quality: B, Recom-mendation Strength: ModerateRecommendation).

Action Statement Profile KAS 10c

Detailed evidence to support the policystatement on palivizumab and thispalivizumab section can be found in thetechnical report on palivizumab.192

Palivizumab was licensed by the USFood and Drug Administration in June1998 largely on the basis of results of 1clinical trial.193 The results of a secondclinical trial among children with con-genital heart disease were reported inDecember 2003.194 No other prospec-tive, randomized, placebo-controlledtrials have been conducted in anysubgroup. Since licensure of pal-ivizumab, new peer-reviewed pub-lications provide greater insight intothe epidemiology of disease caused byRSV.195197 As a result of new data, theBronchiolitis Guideline Committee andthe Committee on Infectious Diseaseshave updated recommendations foruse of prophylaxis.

PREMATURITY

Monthly palivizumab prophylaxis shouldbe restricted to infants born before 29weeks, 0 days gestation, except forinfants who qualify on the basis ofcongenital heart disease or chroniclung disease of prematurity. Datashow that infants born at or after 29weeks, 0 days gestation have an RSVhospitalization rate similar to the rateof full-term infants.11,198 Infants witha gestational age of 28 weeks, 6 daysor less who will be younger than 12months at the start of the RSV sea-son should receive a maximum of 5

monthly doses of palivizumab or untilthe end of the RSV season, whichevercomes first. Depending on the monthof birth, fewer than 5 monthly doses

Aggregate evidencequality

B

Benefits Reduced pain ofinjections, reduceduse of a medicationthat has shownminimal benefit,reduced adverseeffects, reducedvisits to health careprovider with lessexposure to illness

Risk, harm, cost Minimal increase in riskof RSV hospitalization

Benefit-harm assessment Benefits outweighharms

Value judgments NoneIntentional vagueness NoneRole of patientpreferences

Parents may choose tonot acceptpalivizumab

Exclusions Infants with chroniclung disease ofprematurity andhemodynamicallysignificant cardiacdisease (as describedin KAS 10b)

Strength RecommendationDifferences of opinion NoneNotes This KAS is harmonized

with the AAP policystatement onpalivizumab

Aggregate evidence quality BBenefits Reduced risk of RSV

hospitalizationRisk, harm, cost Injection pain;

increased risk ofillness fromincreased visits toclinician office orclinic; cost; sideeffects frompalivizumab


Value judgments NoneIntentional vagueness NoneRole of patient preferences Parents may choose

to not acceptpalivizumab

Exclusions NoneStrength Moderate

recommendationDifferences of opinion NoneNotes This KAS is

harmonized withthe AAP policystatement onpalivizumab191,192

Aggregate evidence quality BBenefits Reduced risk of hospitalization; reduced admission to ICURisk, harm, cost Injection pain; increased risk of illness from increased visits to clinician

office or clinic; cost; adverse effects of palivizumabBenefit-harm assessment Benefits outweigh harmsValue judgments NoneIntentional vagueness NoneRole of patient preferences NoneExclusions Fewer doses should be used if the bronchiolitis season ends before the

completion of 5 doses; if the child is hospitalized with a breakthrough RSV,monthly prophylaxis should be discontinued

Strength Moderate recommendationDifferences of opinion NoneNotes This KAS is harmonized with the AAP policy statement on palivizumab191,192



will provide protection for most in-fants for the duration of the season.

CONGENITAL HEART DISEASE

Despite the large number of subjectsenrolled, little benefit from pal-ivizumab prophylaxis was found inthe industry-sponsored cardiac studyamong infants in the cyanotic group(7.9% in control group versus 5.6% inpalivizumab group, or 23 fewer hos-pitalizations per1000 children; P =.285).197 In the acyanotic group (11.8%vs 5.0%), there were 68 fewer RSVhospitalizations per 1000 prophylaxisrecipients (P = .003).197,199,200

CHRONIC LUNG DISEASE OFPREMATURITY

Palivizumab prophylaxis should beadministered to infants and childrenyounger than 12 months who developchronic lung disease of prematurity,defined as a requirement for 28 daysof more than 21% oxygen beginningat birth. If a child meets these cri-teria and is in the first 24 months oflife and continues to require sup-plemental oxygen, diuretic therapy,or chronic corticosteroid therapywithin 6 months of the start of theRSV season, monthly prophylaxis shouldbe administered for the remainder ofthe season.

NUMBER OF DOSES

Community outbreaks of RSV diseaseusually begin in November or December,peak in January or February, and end bylate March or, at times, in April.4 Figure 1shows the 20112012 bronchiolitis sea-son, which is typical of most years.Because 5 monthly doses will providemore than 24 weeks of protective se-rum palivizumab concentration, admin-istration of more than 5 monthly dosesis not recommended within the conti-nental United States. For infants whoqualify for 5 monthly doses, initiation ofprophylaxis in November and continua-

tion for a total of 5 doses will provideprotection into April.201 If prophylaxis isinitiated in October, the fifth and finaldose should be administered in Febru-ary, and protection will last into Marchfor most children.

SECOND YEAR OF LIFE

Because of the low risk of RSV hospi-talization in the second year of life,palivizumab prophylaxis is not recom-mended for children in the second yearof life with the following exception.Children who satisfy the definition ofchronic lung disease of infancy andcontinue to require supplemental oxy-gen, chronic corticosteroid therapy,or diuretic therapy within 6 monthsof the onset of the second RSV sea-son may be considered for a secondseason of prophylaxis.

OTHER CONDITIONS

Insufficient data are available to rec-ommend routine use of prophylaxis inchildren with Down syndrome, cysticfibrosis, pulmonary abnormality, neu-romuscular disease, or immune com-promise.

Down Syndrome

Routine use of prophylaxis for childrenin the first year of life with Downsyndrome is not recommended unlessthe child qualifies because of cardiacdisease or prematurity.202

Cystic Fibrosis

Routine use of palivizumab prophylaxisin patients with cystic fibrosis is notrecommended.203,204 Available studiesindicate the incidence of RSV hospital-ization in children with cystic fibrosisis low and unlikely to be different fromchildren without cystic fibrosis. No ev-idence suggests a benefit from pal-ivizumab prophylaxis in patients withcystic fibrosis. A randomized clinicaltrial involving 186 children with cystic

fibrosis from 40 centers reported 1subject in each group was hospitalizedbecause of RSV infection. Although thisstudy was not powered for efficacy, noclinically meaningful differences inoutcome were reported.205 A survey ofcystic fibrosis center directors pub-lished in 2009 noted that palivizumabprophylaxis is not the standard of carefor patients with cystic fibrosis.206 Ifa neonate is diagnosed with cystic fi-brosis by newborn screening, RSVprophylaxis should not be adminis-tered if no other indications are pres-ent. A patient with cystic fibrosis withclinical evidence of chronic lung dis-ease in the first year of life may beconsidered for prophylaxis.

Neuromuscular Disease andPulmonary Abnormality

The risk of RSV hospitalization is notwell defined in children with pulmonaryabnormalities or neuromuscular dis-ease that impairs ability to clearsecretions from the lower airway be-cause of ineffective cough, recurrentgastroesophageal tract reflux, pulmo-nary malformations, tracheoesophagealfistula, upper airway conditions, orconditions requiring tracheostomy. Nodata on the relative risk of RSV hospi-talization are available for this cohort.Selected infants with disease or con-genital anomaly that impairs theirability to clear secretions from thelower airway because of ineffectivecough may be considered for pro-phylaxis during the first year of life.

Immunocompromised Children

Population-based data are not avail-able on the incidence or severity of RSVhospitalization in children who un-dergo solid organ or hematopoieticstem cell transplantation, receivechemotherapy, or are immunocom-promised because of other conditions.Prophylaxis may be considered forhematopoietic stem cell transplant





patients who undergo transplantationand are profoundly immunosup-pressed during the RSV season.207

MISCELLANEOUS ISSUES

Prophylaxis is not recommended forprevention of nosocomial RSV diseasein the NICU or hospital setting.208,209

No evidence suggests palivizumab isa cost-effective measure to preventrecurrent wheezing in children. Pro-phylaxis should not be administeredto reduce recurrent wheezing in lateryears.210,211

Monthly prophylaxis in Alaska Nativechildren who qualify should be de-termined by locally generated dataregarding season onset and end.

Continuation of monthly prophylaxisfor an infant or young child who ex-periences breakthrough RSV hospital-ization is not recommended.

HAND HYGIENE


All people should disinfect handsbefore and after direct contactwith patients, after contact withinanimate objects in the direct vi-cinity of the patient, and after re-moving gloves (Evidence Quality: B;Recommendation Strength: StrongRecommendation).



All people should use alcohol-basedrubs for hand decontamination whencaring for children with bronchioli-tis. When alcohol-based rubs arenot available, individuals shouldwash their hands with soap andwater (Evidence Quality: B; Recom-mendation Strength: Strong Rec-ommendation).


Efforts should be made to decrease thespread of RSV and other causativeagents of bronchiolitis in medicalsettings, especially in the hospital.Secretions from infected patients canbe found on beds, crib railings, ta-bletops, and toys.12 RSV, as well asmany other viruses, can survive betteron hard surfaces than on poroussurfaces or hands. It can remain in-fectious on counter tops for 6 hours,on gowns or paper tissues for 20to 30 minutes, and on skin for up to20 minutes.212

It has been shown that RSV can be carriedand spread to others on the hands of

caregivers.213 Studies have shown thathealth care workers have acquired in-fection by performing activities such asfeeding, diaper change, and playingwith the RSV-infected infant. Caregiverswho had contact only with surfacescontaminated with the infants secre-tions or touched inanimate objects inpatients rooms also acquired RSV. Inthese studies, health care workerscontaminated their hands (or gloves)with RSV and inoculated their oral orconjunctival mucosa.214 Frequent handwashing by health care workers hasbeen shown to reduce the spread ofRSV in the health care setting.215

The Centers for Disease Control andPrevention published an extensive re-view of the hand-hygiene literature andmade recommendations as to indica-tions for hand washing and handantisepsis.216 Among the recom-mendations are that hands should bedisinfected before and after directcontact with every patient, after con-tact with inanimate objects in the di-rect vicinity of the patient, and beforeputting on and after removing gloves.If hands are not visibly soiled, analcohol-based rub is preferred. Inguidelines published in 2009, theWorld Health Organization also rec-ommended alcohol-based hand-rubsas the standard for hand hygiene inhealth care.217 Specifically, systematicreviews show them to remove organ-isms more effectively, require lesstime, and irritate skin less often thanhand washing with soap or other anti-septic agents and water. The availabilityof bedside alcohol-based solutions in-creased compliance with hand hygieneamong health care workers.214

When caring for hospitalized childrenwith clinically diagnosed bronchioli-tis, strict adherence to hand de-contamination and use of personalprotective equipment (ie, gloves andgowns) can reduce the risk of cross-infection in the health care setting.215

Aggregate evidence quality BBenefits Decreased

transmissionof disease

Risk, harm, cost Possible handirritation


Value judgments NoneIntentional vagueness NoneRole of patient preferences NoneExclusions NoneStrength Strong

recommendationDifferences of opinion None

Aggregate evidence quality BBenefits Less hand irritationRisk, harm, cost If there is visible

dirt on thehands, handwashing isnecessary;alcohol-basedrubs are noteffective forClostridiumdifficile, presenta fire hazard,and have a slightincreased cost


Value judgments NoneIntentional vagueness NoneRole of patient preferences NoneExclusions NoneStrength Strong




Other methods of infection control inviral bronchiolitis include education ofpersonnel and family members, surveil-lance for the onset of RSV season, andwearing masks when anticipating expo-sure to aerosolized secretions whileperforming patient care activities. Pro-grams that implement the aforemen-tioned principles, in conjunction witheffective hand decontamination andcohorting of patients, have been shownto reduce the spread of RSV in thehealth care setting by 39% to 50%.218,219

TOBACCO SMOKE


Clinicians should inquire about theexposure of the infant or child totobacco smoke when assessinginfants and children for bron-chiolitis (Evidence Quality: C; Rec-ommendation Strength: ModerateRecommendation).



Clinicians should counsel care-givers about exposing the infant or

child to environmental tobaccosmoke and smoking cessationwhen assessing a child for bron-chiolitis (Evidence Quality: B; Rec-ommendation Strength: StrongRecommendation).


Tobacco smoke exposure increases therisk and severity of bronchiolitis. Stra-chan and Cook220 first delineated theeffects of environmental tobacco smokeon rates of lower respiratory tract dis-ease in infants in a meta-analysis in-cluding 40 studies. In a more recentsystematic review, Jones et al221 founda pooled odds ratio of 2.51 (95% CI 1.96to 3.21) for tobacco smoke exposureand bronchiolitis hospitalization amongthe 7 studies specific to the condition.Other investigators have consistentlyreported tobacco smoke exposureincreases both severity of illness andrisk of hospitalization for bronchioli-

tis.222225 The AAP issued a technicalreport on the risks of secondhandsmoke in 2009. The report makes rec-ommendations regarding effective waysto eliminate or reduce secondhandsmoke exposure, including education ofparents.226

Despite our knowledge of this impor-tant risk factor, there is evidence tosuggest health care providers identifyfewer than half of children exposed totobacco smoke in the outpatient, in-patient, or ED settings.227229 Further-more, there is evidence thatcounseling parents in these settings iswell received and has a measurableimpact. Rosen et al230 performed ameta-analysis of the effects of inter-ventions in pediatric settings on pa-rental cessation and found a pooledrisk ratio of 1.3 for cessation amongthe 18 studies reviewed.

In contrast to many of the otherrecommendations, protecting chil-dren from tobacco exposure isa recommendation that is primarilyimplemented outside of the clinicalsetting. As such, it is critical thatparents are fully educated about theimportance of not allowing smokingin the home and that smoke lingerson clothes and in the environmentfor prolonged periods.231 It shouldbe provided in plain language andin a respectful, culturally effectivemanner that is family centered, en-gages parents as partners in theirchilds health, and factors in theirliteracy, health literacy, and primarylanguage needs.

BREASTFEEDING


Clinicians should encourage exclusivebreastfeeding for at least 6 monthsto decrease the morbidity of respi-ratory infections (Evidence Quality:Grade B; Recommendation Strength:Moderate Recommendation).

Aggregate evidence quality CBenefits Can identify infants

and children atrisk whosefamily maybenefit fromcounseling,predicting risk ofsevere disease

Risk, harm, cost Time to inquireBenefit-harm assessment Benefits outweigh

harmsValue judgments NoneIntentional vagueness NoneRole of patient preferences Parent may choose

to deny tobaccouse even thoughthey are, in fact,users



Aggregate evidence quality BBenefits Reinforces the

detrimentaleffects ofsmoking,potential todecreasesmoking

Risk, harm, cost Time to counselBenefit-harm assessment Benefits outweigh

harmsValue judgments NoneIntentional vagueness NoneRole of patient preferences Parents may choose

to ignorecounseling


recommendationDifferences of opinion NoneNotes Counseling for

tobacco smokepreventionshould begin inthe prenatalperiod andcontinue infamily-centeredcare and at allwell-infant visits






In 2012, the AAP presented a generalpolicy on breastfeeding.232 The policystatement was based on the provenbenefits of breastfeeding for at least 6months. Respiratory infections wereshown to be significantly less commonin breastfed children. A primary re-source was a meta-analysis from theAgency for Healthcare Research andQuality that showed an overall 72%reduction in the risk of hospitalizationsecondary to respiratory diseases ininfants who were exclusively breastfedfor 4 or more months compared withthose who were formula fed.233

The clinical evidence also supportsdecreased incidence and severity ofillness in breastfed infants with bron-chiolitis. Dornelles et al234 concludedthat the duration of exclusive breast-feeding was inversely related to thelength of oxygen use and the length ofhospital stay in previously healthyinfants with acute bronchiolitis. Ina large prospective study in Australia,Oddy et al235 showed that breastfeedingfor less than 6 months was associated

with an increased risk for 2 or moremedical visits and hospital admissionfor wheezing lower respiratory illness.In Japan, Nishimura et al236 lookedat 3 groups of RSV-positive infantsdefined as full, partial, or token breast-feeding. There were no significantdifferences in the hospitalization rateamong the 3 groups; however, therewere significant differences in theduration of hospitalization and therate of requiring oxygen therapy, bothfavoring breastfeeding.

FAMILY EDUCATION


Clinicians and nurses should edu-cate personnel and family mem-bers on evidence-based diagnosis,treatment, and prevention inbronchiolitis (Evidence Quality: C;observational studies; Recommen-dation Strength; Moderate Recom-mendation).


Shared decision-making with parentsabout diagnosis and treatment ofbronchiolitis is a key tenet of patient-centered care. Despite the absence ofeffective therapies for viral bronchi-olitis, caregiver education by cliniciansmay have a significant impact on carepatterns in the disease. Children withbronchiolitis typically suffer fromsymptoms for 2 to 3 weeks, andparents often seek care in multiplesettings during that time period.237

Given that children with RSV gener-ally shed virus for 1 to 2 weeks andfrom 30% to 70% of family membersmay become ill,238,239 education aboutprevention of transmission of diseaseis key. Restriction of visitors to new-borns during the respiratory virusseason should be considered. Con-sistent evidence suggests that pa-rental education is helpful in thepromotion of judicious use of anti-biotics and that clinicians may mis-interpret parental expectations abouttherapy unless the subject is openlydiscussed.240242

FUTURE RESEARCH NEEDS

Better algorithms for predictingthe course of illness

Impact of clinical score on patientoutcomes

Evaluating different ethnic groupsand varying response to treat-ments

Does epinephrine alone reduce ad-mission in outpatient settings?

Additional studies on epinephrinein combination with dexametha-sone or other corticosteroids

Hypertonic saline studies in theoutpatient setting and in in hospi-tals with shorter LOS

More studies on nasogastric hy-dration

More studies on tonicity of intrave-nous fluids

Aggregate evidence quality BBenefits May reduce the risk

of bronchiolitisand otherillnesses;multiple benefitsof breastfeedingunrelated tobronchiolitis

Risk, harm, cost NoneBenefit-harm assessment Benefits outweigh

risksValue judgments NoneIntentional vagueness NoneRole of patient preferences Parents may choose

to feed formularather thanbreastfeed


recommendationNotes Education on

breastfeedingshould begin inthe prenatalperiod

Aggregate evidence quality CBenefits Decreased

transmission ofdisease, benefitsof breastfeeding,promotion ofjudicious use ofantibiotics, risksof infant lungdamageattributable totobacco smoke

Risk, harm, cost Time to educateproperly


Value judgments NoneIntentional vagueness Personnel is not

specificallydefined butshould includeall people whoenter a patientsroom

Role of patient preferences NoneExclusions NoneStrength Moderate




Incidence of true AOM in bron-chiolitis by using 2013 guidelinedefinition

More studies on deep suction-ing and nasopharyngeal suction-ing

Strategies for monitoring oxygensaturation

Use of home oxygen Appropriate cutoff for use of oxy-

gen in high altitude

Oxygen delivered by high-flow na-sal cannula

RSV vaccine and antiviral agents Use of palivizumab in special

populations, such as cystic fib-rosis, neuromuscular diseases,Down syndrome, immune defi-ciency

Emphasis on parent satisfaction/patient-centered outcomes in allresearch (ie, not LOS as the onlymeasure)

SUBCOMMITTEE ON BRONCHIOLITIS(OVERSIGHT BY THE COUNCIL ONQUALITY IMPROVEMENT AND PATIENTSAFETY, 20132014)Shawn L. Ralston, MD, FAAP: Chair, PediatricHospitalist (no financial conflicts; publishedresearch related to bronchiolitis)Allan S. Lieberthal, MD, FAAP: Chair, GeneralPediatrician with Expertise in Pulmonology (noconflicts)Brian K. Alverson, MD, FAAP: Pediatric Hos-pitalist, AAP Section on Hospital MedicineRepresentative (no conflicts)Jill E. Baley, MD, FAAP: Neonatal-PerinatalMedicine, AAP Committee on Fetus and New-born Representative (no conflicts)Anne M. Gadomski, MD, MPH, FAAP: GeneralPediatrician and Research Scientist (no financialconflicts; published research related to bronchi-olitis including Cochrane review of bronchodilators)David W. Johnson, MD, FAAP: Pediatric Emer-gency Medicine Physician (no financial conflicts;published research related to bronchiolitis)Michael J. Light, MD, FAAP: Pediatric Pulmo-nologist, AAP Section on Pediatric PulmonologyRepresentative (no conflicts)Nizar F. Maraqa, MD, FAAP: Pediatric In-fectious Disease Physician, AAP Section on In-fectious Diseases Representative (no conflicts)H. Cody Meissner, MD, FAAP: Pediatric In-fectious Disease Physician, AAP Committee on

Infectious Diseases Representative (no con-flicts)Eneida A. Mendonca, MD, PhD, FAAP, FACMI:Informatician/Academic Pediatric IntensiveCare Physician, Partnership for Policy Imple-mentation Representative (no conflicts)Kieran J. Phelan, MD, MSc: General Pedia-trician (no conflicts)Joseph J. Zorc, MD, MSCE, FAAP: PediatricEmergency Physician, AAP Section on EmergencyMedicine Representative (no financial conflicts;published research related to bronchiolitis)Danette Stanko-Lopp, MA, MPH: Methodolo-gist, Epidemiologist (no conflicts)Mark A. Brown, MD: Pediatric Pulmonologist,American Thoracic Society Liaison (no conflicts)Ian Nathanson, MD, FAAP: Pediatric Pulmo-nologist, American College of Chest PhysiciansLiaison (no conflicts)Elizabeth Rosenblum, MD: Academic FamilyPhysician, American Academy of Family Physi-cians liaison (no conflicts).Stephen Sayles, III, MD, FACEP: EmergencyMedicine Physician, American College ofEmergency Physicians Liaison (no conflicts)Sinsi Hernndez-Cancio, JD: Parent/ConsumerRepresentative (no conflicts)

STAFFCaryn Davidson, MALinda Walsh, MAB

REFERENCES

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2. Agency for Healthcare Research andQuality. Management of Bronchiolitis inInfants and Children. Evidence Report/Technology Assessment No. 69. Rockville,MD: Agency for Healthcare Research andQuality; 2003. AHRQ Publication No. 03-E014

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