Discussion: Diagnosis and Management of Respiratory, Cardiovascular, and Genetic Disorders

CLINICAL PRACTICE GUIDELINE

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

abstract This guideline is a revision of the clinical practice guideline, “Diagnosis and Management of Bronchiolitis,” published by the American Academy of Pediatrics in 2006. The guideline applies to children from 1 through 23 months of age. Other exclusions are noted. Each key action state- ment indicates level of evidence, benefit-harm relationship, and level of recommendation. Key action statements are as follows: Pediatrics 2014;134:e1474–e1502

DIAGNOSIS

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

1b. Clinicians should assess risk factors for severe disease, such as age less than 12 weeks, a history of prematurity, underlying car- diopulmonary disease, or immunodeficiency, when making decisions about 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 and physical examination, radiographic or laboratory studies should not be obtained routinely (Evidence Quality: B; Recommendation Strength: 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 children with 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: Moderate Recommendation).

4b. Clinicians may administer nebulized hypertonic saline to infants and 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, Elizabeth Rosenblum, MD, Stephen Sayles III, MD, FACEP, and Sinsi Hernandez-Cancio, JD

KEY WORDS bronchiolitis, infants, children, respiratory syncytial virus, evidence-based, guideline

ABBREVIATIONS AAP—American Academy of Pediatrics AOM—acute otitis media CI—confidence interval ED—emergency department KAS—Key Action Statement LOS—length of stay MD—mean difference PCR—polymerase chain reaction RSV—respiratory syncytial virus SBI—serious bacterial infection

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

The recommendations in this report do not indicate an exclusive course 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 of Pediatrics automatically expire 5 years after publication unless reaffirmed, 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

doi:10.1542/peds.2014-2742

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2014 by the American Academy of Pediatrics

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5. Clinicians should not administer systemic corticosteroids to infants with a diagnosis of bronchiolitis in any setting (Evidence Quality: A; Rec- ommendation Strength: Strong Rec- ommendation).

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

6b. Clinicians may choose not to use continuous pulse oximetry for in- fants and children with a diagnosis of bronchiolitis (Evidence Quality: D; Recommendation Strength: Weak Recommendation [based on low- level evidence and reasoning from first principles]).

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

8. Clinicians should not administer antibacterial medications to in- fants and children with a diagno- sis of bronchiolitis unless there is 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 for infants with a diagnosis of bron- chiolitis who cannot maintain hy- dration orally (Evidence Quality: X; Recommendation Strength: Strong Recommendation).

PREVENTION

10a. Clinicians should not administer palivizumab to otherwise healthy infants with a gestational age of

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

10b. Clinicians should administer palivizumab during the first year of life to infants with he- modynamically significant heart disease or chronic lung disease of prematurity defined as pre- term infants<32 weeks 0 days’ gestation who require >21% oxygen for at least the first 28 days of life (Evidence Quality: B; Recommendation Strength: Moderate Recommendation).

10c. Clinicians should administer a maximum 5 monthly doses (15 mg/kg/dose) of palivizumab during the respiratory syncytial virus season to infants who qualify for palivizumab in the first year of life (Evidence Quality: B; Recommendation Strength: Moderate Recommendation).

11a. All people should disinfect hands before and after direct contact with patients, after contact with inanimate objects in the direct vicinity of the patient, and after removing gloves (Evidence Qual- ity: B; Recommendation Strength: Strong Recommendation).

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

12a. Clinicians should inquire about the exposure of the infant or child to tobacco smoke when assessing infants and chil- dren for bronchiolitis (Evidence Quality: C; Recommendation Strength: Moderate Recom- mendation).

12b. Clinicians should counsel care- givers about exposing the in- fant or child to environmental tobacco smoke and smoking cessation when assessing a child for bronchiolitis (Evidence Quality: B; Recommendation Strength: Strong).

13. Clinicians should encourage ex- clusive breastfeeding for at least 6 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; Recommendation Strength: Moderate Recommenda- tion).

INTRODUCTION

In October 2006, the American Acad- emy of Pediatrics (AAP) published the clinical practice guideline “Diagnosis and Management of Bronchiolitis.”1

The guideline offered recommendations ranked according to level of evidence and the benefit-harm relationship. Since completion of the original evidence re- view in July 2004, a significant body of literature on bronchiolitis has been published. This update of the 2006 AAP bronchiolitis guideline evaluates pub- lished evidence, including that used in the 2006 guideline as well as evidence published since 2004. Key action state- ments (KASs) based on that evidence are provided.

The goal of this guideline is to provide an evidence-based approach to the di- agnosis, management, and prevention of bronchiolitis in children from 1 month through 23 months of age. The guideline is intended for pediatricians, family physicians, emergency medicine spe- cialists, hospitalists, nurse practitioners,

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and physician assistants who care for these children. The guideline does not apply to children with immunodeficien- cies, including those with HIV infection or recipients of solid organ or hema- topoietic stem cell transplants. Children with underlying respiratory illnesses, such as recurrent wheezing, chronic neonatal lung disease (also known as bronchopulmonary dysplasia), neuro- muscular disease, or cystic fibrosis and those with hemodynamically significant congenital heart disease are excluded from the sections on management un- less otherwise noted but are included in the discussion of prevention. This guide- line will not address long-term sequelae of bronchiolitis, such as recurrent wheezing or risk of asthma, which is a field with a large and distinct lit- erature.

Bronchiolitis is a disorder commonly caused by viral lower respiratory tract infection in infants. Bronchiolitis is characterized by acute inflammation, edema, and necrosis of epithelial cells lining small airways, and increased mucus production. Signs and symp- toms typically begin with rhinitis and cough, which may progress to tachy- pnea, wheezing, rales, use of accessory muscles, and/or nasal flaring.2

Many viruses that infect the respiratory system cause a similar constellation of signs and symptoms. The most com- mon etiology of bronchiolitis is re- spiratory syncytial virus (RSV), with the highest incidence of infection occurring between December and March in North America; however, regional variations occur3 (Fig 1).4 Ninety percent of chil- dren are infected with RSV in the first 2 years of life,5 and up to 40% will experience lower respiratory tract in- fection during the initial infection.6,7

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

Other viruses that cause bronchiolitis include human rhinovirus, human meta-

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

76% of patients had RSV, 39% had human rhinovirus, 10% had influenza, 2% had coronavirus, 3% had human metapneumovirus, and 1% had para- influenza viruses (some patients had coinfections, so the total is greater than 100%).

Bronchiolitis is themost common cause of hospitalization among infants during the first 12 months of life. Approximately 100 000 bronchiolitis admissions occur annually in the United States at an estimated cost of $1.73 billion.10 One prospective, population-based study sponsored by the Centers for Disease Control and Prevention reported the

average RSV hospitalization rate was 5.2 per 1000 children younger than 24 months of age during the 5-year pe- riod between 2000 and 2005.11 The highest age-specific rate of RSV hos- pitalization occurred among infants between 30 days and 60 days of age (25.9 per 1000 children). For preterm infants (<37 weeks’ gestation), the RSV hospitalization rate was 4.6 per 1000 children, a number similar to the RSV hospitalization rate for term infants of 5.2 per 1000. Infants born at <30 weeks’ gestation had the highest hospitalization rate at 18.7 children per 1000, although the small number of infants born before 30 weeks’ gestation make this number unreliable. Other studies indicate the RSV hospitalization rate in extremely

FIGURE 1 RSV season by US regions. Centers for Disease Control and Prevention. RSV activity—United States, July 2011–Jan 2013. MMWR Morb Mortal Wkly Rep. 2013;62(8):141–144.

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preterm infants is similar to that of term infants.12,13

METHODS

In June 2013, the AAP convened a new subcommittee to review and revise the 2006 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, a neonatologist, and pediatric infectious disease physicians. The subcommit- tee also included an epidemiologist trained in systematic reviews, a guide- line methodologist/informatician, and a parent representative. All panel mem- bers reviewed the AAP Policy on Conflict of Interest and Voluntary Disclosure and were given an opportunity to declare any potential conflicts. Any conflicts can be found in the author listing at the end of this guideline. All funding was provided by the AAP, with travel assistance from the American Academy of Family Phy- sicians, the American College of Chest Physicians, the American Thoracic Society, and the American College of Emergency Physicians for their liaisons.

The evidence search and review included electronic database searches in The Cochrane Library, Medline via Ovid, and CINAHL via EBSCO. The search strategy is shown in the Appendix. Re- lated article searches were conducted in PubMed. The bibliographies of arti- cles identified by database searches were also reviewed by 1 of 4 members of the committee, and references iden- tified in this manner were added to the review. Articles included in the 2003 evidence report on bronchiolitis in 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 updated guidelines. The current literature re-

view encompasses the period from 2004 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 an explicit link between evidence and rec- ommendations be defined. Evidence- based recommendations reflect the quality of evidence and the balance of benefit and harm that is anticipated when the recommendation is followed. The AAP policy statement “Classify- ing Recommendations for Clinical Practice”14 was followed in designat- ing levels of recommendation (Fig 2; Table 1).

A draft version of this clinical practice guideline underwent extensive peer review by committees, councils, and sections within AAP; the American Thoracic Society, American College of Chest Physicians, American Academy

of Family Physicians, and American College of Emergency Physicians; other outside organizations; and other in- dividuals identified by the subcom- mittee as experts in the field. The resulting comments were reviewed by the subcommittee and, when ap- propriate, incorporated into the guide- line.

This clinical practice guideline is not intended as a sole source of guidance in the management of children with bronchiolitis. Rather, it is intended to assist clinicians in decision-making. It is not intended to replace clinical judgment or establish a protocol for the care of all children with bronchi- olitis. These recommendations may not provide the only appropriate approach to the management of children with bronchiolitis.

All AAP guidelines are reviewed every 5 years.

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

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DIAGNOSIS

Key Action Statement 1a

Clinicians should diagnose bronchi- olitis and assess disease severity on the basis of history and physical examination (Evidence Quality: B; Recommendation Strength: Strong Recommendation).

Action Statement Profile KAS 1a

Key Action Statement 1b

Clinicians should assess risk fac- tors for severe disease, such as age <12 weeks, a history of pre- maturity, underlying cardiopulmo- nary disease, or immunodeficiency, when making decisions about eval-

uation and management of children with bronchiolitis (Evidence Quality: B; Recommendation Strength: Mod- erate Recommendation).

Action Statement Profile KAS 1b

Key Action Statement 1c

When clinicians diagnose bronchi- olitis on the basis of history and physical examination, radiographic or laboratory studies should not be obtained routinely (Evidence Qual- ity: B; Recommendation Strength: Moderate Recommendation).

Action Statement Profile KAS 1b

The main goals in the history and physical examination of infants pre- senting with wheeze or other lower respiratory tract symptoms, particularly in the winter season, is to differentiate infants with probable viral bronchiolitis from those with other disorders. In ad- dition, an estimate of disease severity (increased respiratory rate, retractions, decreased oxygen saturation) should

TABLE 1 Guideline Definitions for Evidence-Based Statements

Statement Definition Implication

Strong recommendation A particular action is favored because anticipated benefits clearly exceed harms (or vice versa), and quality of evidence is excellent or unobtainable.

Clinicians should follow a strong recommendation unless a clear and compelling rationale for an alternative approach is present.

Moderate recommendation A particular action is favored because anticipated benefits clearly exceed harms (or vice versa), and the quality of evidence is good but not excellent (or is unobtainable).

Clinicians would be prudent to follow a moderate recommendation but should remain alert to new information and sensitive to patient preferences.

Weak recommendation (based on low-quality evidence

A particular action is favored because anticipated benefits clearly exceed harms (or vice versa), but the quality of evidence is weak.

Clinicians would be prudent to follow a weak recommendation but should remain alert to new information and very sensitive to patient preferences.

Weak recommendation (based on balance of benefits and harms)

Weak recommendation is provided when the aggregate database shows evidence of both benefit and harm that appear similar in magnitude for any available courses of action

Clinicians should consider the options in their decision making, but patient preference may have a substantial role.

Aggregate evidence quality

B

Benefits Inexpensive, noninvasive, accurate

Risk, harm, cost Missing other diagnoses

Benefit-harm assessment

Benefits outweigh harms

Value judgments None Intentional vagueness None Role of patient preferences

None

Exclusions None Strength Strong recommendation Differences of opinion None

Aggregate evidence quality

B

Benefits Improved ability to predict course of illness, appropriate disposition

Risk, harm, cost Possible unnecessary hospitalization parental anxiety

Benefit-harm assessment

Benefits outweigh harms

Value judgments None Intentional vagueness

“Assess” is not defined

Role of patient preferences

None

Exclusions None Strength Moderate recommendation Differences of opinion

None

Aggregate evidence quality

B

Benefits Decreased radiation exposure, noninvasive (less procedure-associated discomfort), decreased antibiotic use, cost savings, time saving

Risk, harm, cost Misdiagnosis, missed diagnosis of comorbid condition

Benefit-harm assessment

Benefits outweigh harms

Value judgments None Intentional vagueness

None

Role of patient preferences

None

Exclusions Infants and children with unexpected worsening disease

Strength Moderate recommendation Differences of opinion

None

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be made. Most clinicians recognize bronchiolitis as a constellation of clin- ical signs and symptoms occurring in children younger than 2 years, includ- ing a viral upper respiratory tract prodrome followed by increased re- spiratory effort and wheezing. Clinical signs and symptoms of bronchiolitis consist of rhinorrhea, cough, tachypnea, wheezing, rales, and increased respi- ratory effort manifested as grunting, nasal flaring, and intercostal and/or subcostal retractions.

The course of bronchiolitis is variable and dynamic, ranging from transient events, such as apnea, to progressive respiratory distress from lower airway obstruction. Important issues to assess in the history include the effects of re- spiratory symptoms on mental status, feeding, and hydration. The clinician should assess the ability of the family to care for the child and to return for further evaluation if needed. History of underlying conditions, such as pre- maturity, cardiac disease, chronic pulmonary disease, immunodeficiency, or episodes of previous wheezing, should be identified. Underlying conditions that may be associated with an increased risk of progression to severe disease or mortality include hemodynamically significant congenital heart disease, chronic lung disease (bronchopulmonary dysplasia), congenital anomalies,15–17

in utero smoke exposure,18 and the presence of an immunocompromising state.19,20 In addition, genetic abnormal- ities have been associated with more severe presentation with bronchiolitis.21

Assessment of a child with bronchiolitis, including the physical examination, can be complicated by variability in the dis- ease state and may require serial observations over time to fully assess the child’s status. Upper airway obstruction contributes to work of breathing. Suc- tioning and positioning may decrease the work of breathing and improve the quality of the examination. Respiratory

rate in otherwise healthy children changes considerably over the first year of life.22–25 In hospitalized children, the 50th percentile for respiratory rate decreased from 41 at 0 to 3 months of age to 31 at 12 to 18 months of age.26

Counting respiratory rate over the course of 1 minute is more accurate than shorter observations.27 The pres- ence of a normal respiratory rate suggests that risk of significant viral or bacterial lower respiratory tract infection or pneumonia in an infant is low (negative likelihood ratio approxi- mately 0.5),27–29 but the presence of tachypnea does not distinguish be- tween viral and bacterial disease.30,31

The evidence relating the presence of specific findings in the assessment of bronchiolitis to clinical outcomes is limited. Most studies addressing this issue have enrolled children when presenting to hospital settings, in- cluding a large, prospective, multicen- ter study that assessed a variety of outcomes from the emergency de- partment (ED) and varied inpatient settings.18,32,33 Severe adverse events, such as ICU admission and need for mechanical ventilation, are uncommon among children with bronchiolitis and limit the power of these studies to detect clinically important risk fac- tors associated with disease pro- gression.16,34,35 Tachypnea, defined as a respiratory rate ≥70 per minute, has been associated with increased risk of severe disease in some studies35–37 but not others.38 Many scoring systems have been developed in an attempt to objectively quantify respiratory dis- tress, although none has achieved widespread acceptance and few have demonstrated any predictive validity, likely because of the substantial tem- poral variability in physical findings in infants with bronchiolitis.39

Pulse oximetry has been rapidly adopted into clinical assessment of children with bronchiolitis on the basis of data

suggesting that it reliably detects hyp- oxemia not suspected on physical examination36,40; however, few studies have assessed the effectiveness of pulse oximetry to predict clinical out- comes. Among inpatients, perceived need for supplemental oxygen on the basis of pulse oximetry has been as- sociated with prolonged hospitaliza- tion, ICU admission, and mechanical ventilation.16,34,41 Among outpatients, available evidence differs on whether mild reductions in pulse oximetry (<95% on room air) predict progression of disease or need for a return obser- vational visit.38

Apnea has been reported to occur with a wide range of prevalence estimates and viral etiologies.42,43 Retrospective, hospital-based studies have included a high proportion of infants with risk factors, such as prematurity or neuro- muscular disease, that may have biased the prevalence estimates. One large study found no apnea events for infants assessed as low risk by using several risk factors: age >1 month for full-term infants or 48 weeks’ postconceptional age for preterm infants, and absence of any previous apneic event at pre- sentation to the hospital.44 Another large multicenter study found no asso- ciation between the specific viral agent and risk of apnea in bronchiolitis.42

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

In the event an infant receiving monthly prophylaxis is hospitalized with bronchiolitis, testing should be performed to determine if RSV is the etiologic agent. If a breakthrough RSV infection is determined to be present based on antigen detection or other

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assay, monthly palivizumab prophylaxis should be discontinued because of the very low likelihood of a second RSV infection in the same year. Apart from this setting, routine virologic testing is not recommended.

Infants with non-RSV bronchiolitis, in particular human rhinovirus, appear to have a shorter courses and may rep- resent a different phenotype associated with repeated wheezing.32 PCR assay results should be interpreted cautiously, given that the assay may detect pro- longed viral shedding from an unrelated previous illness, particularly with rhi- novirus. In contrast, RSV detected by PCR assay almost always is associated with disease. At the individual patient level, the value of identifying a spe- cific viral etiology causing bronchi- olitis has not been demonstrated.33

Current evidence does not support routine chest radiography in children with bronchiolitis. Although many infants with bronchiolitis have abnor- malities on chest radiography, data are insufficient to demonstrate that chest radiography correlates well with disease severity. Atelectasis on chest radiography was associated with in- creased risk of severe disease in 1 outpatient study.16 Further studies, in- cluding 1 randomized trial, suggest children with suspected lower respi- ratory tract infection who had radiog- raphy performed were more likely to receive antibiotics without any differ- ence in outcomes.46,47 Initial radiography should be reserved for cases in which respiratory effort is severe enough to warrant ICU admission or where signs of an airway complication (such as pneumothorax) are present.

TREATMENT

ALBUTEROL

Key Action Statement 2

Clinicians should not administer albuterol (or salbutamol) to infants

and children with a diagnosis of bronchiolitis (Evidence Quality: B; Recommendation Strength: Strong Recommendation).

Action Statement Profile KAS 2

Although several studies and reviews have evaluated the use of bronchodi- lator medications for viral bronchiolitis, most randomized controlled trials have failed to demonstrate a consistent ben- efit from α- or β-adrenergic agents. Several meta-analyses and systematic reviews48–53 have shown that broncho- dilators may improve clinical symptom scores, but they do not affect disease resolution, need for hospitalization, or length of stay (LOS). Because clinical scores may vary from one observer to the next39,54 and do not correlate with more objective measures, such as pul- monary function tests,55 clinical scores are not validated measures of the effi- cacy of bronchodilators. Although tran- sient improvements in clinical score have been observed, most infants treated with bronchodilators will not benefit from their use.

A recently updated Cochrane system- atic review assessing the impact of bronchodilators on oxygen saturation, the primary outcomemeasure, reported 30 randomized controlled trials in- volving 1992 infants in 12 countries.56

Some studies included in this review evaluated agents other than albuterol/ salbutamol (eg, ipratropium and meta- proterenol) but did not include epi- nephrine. Small sample sizes, lack of standardized methods for outcome evaluation (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. Because of variable study designs as well as the inclusion of infants who had a history of previous wheezing in some studies, there was considerable heterogeneity in the studies. Sensitivity analysis (ie, including only studies at low risk of bias) significantly reduced heterogene- ity measures for oximetry while having little effect on the overall effect size of oximetry (mean difference [MD] –0.38, 95% confidence interval [CI] –0.75 to 0.00). Those studies showing benefit57–59

are methodologically weaker than other studies and include older children with recurrent wheezing. Results of the Cochrane review indicated no benefit in the clinical course of infants with bronchiolitis who received bronchodi- lators. The potential adverse effects (tachycardia and tremors) and cost of these agents outweigh any potential benefits.

In the previous iteration of this guideline, a trial of β-agonists was included as an option. However, given the greater strength of the evidence demonstrat- ing no benefit, and that there is no well-established way to determine an “objective method of response” to bronchodilators in bronchiolitis, this option has been removed. Although it is true that a small subset of children

Aggregate evidence quality

B

Benefits Avoid adverse effects, avoid ongoing use of ineffective medication, lower costs

Risk, harm, cost Missing transient benefit of drug

Benefit-harm assessment

Benefits outweigh harms

Value judgments Overall ineffectiveness outweighs possible transient benefit

Intentional vagueness

None

Role of patient preferences

None

Exclusions None Strength Strong recommendation Differences of opinion

None

Notes This guideline no longer recommends a trial of albuterol, as was considered in the 2006 AAP bronchiolitis guideline

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with bronchiolitis may have reversible airway obstruction resulting from smooth muscle constriction, attempts to define a subgroup of responders have not been successful to date. If a clinical trial of bronchodilators is undertaken, clinicians should note that the variability of the disease process, the host’s airway, and the clinical assessments, par- ticularly scoring, would limit the clinician’s ability to observe a clinically relevant re- sponse to bronchodilators.

Chavasse et al60 reviewed the available literature on use of β-agonists for chil- dren younger than 2 years with re- current wheezing. At the time of that review, there were 3 studies in the outpatient setting, 2 in the ED, and 3 in the pulmonary function laboratory setting. This review concluded there were no clear benefits from the use of β-agonists in this population. The authors noted some conflicting evi- dence, but further study was recom- mended only if the population could be clearly defined and meaningful out- come measures could be identified.

The population of children with bron- chiolitis studied in most trials of bronchodilators limits the ability to make recommendations for all clinical scenarios. Children with severe disease or with respiratory failure were gen- erally excluded from these trials, and this evidence cannot be generalized to these situations. Studies using pulmo- nary function tests show no effect of albuterol among infants hospitalized with bronchiolitis.56,61 One study in a critical care setting showed a small decrease in inspiratory resistance af- ter albuterol in one group and leval- buterol in another group, but therapy was accompanied by clinically signifi- cant tachycardia.62 This small clinical change occurring with significant ad- verse effects does not justify recom- mending albuterol for routine care.

EPINEPHRINE

Key Action Statement 3

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

Action Statement Profile KAS 3

Epinephrine is an adrenergic agent with both β- and α-receptor agonist activity that has been used to treat upper and lower respiratory tract ill- nesses both as a systemic agent and directly into the respiratory tract, where it is typically administered as a nebulized solution. Nebulized epi- nephrine has been administered in the racemic form and as the purified L-enantiomer, which is commercially available in the United States for in- travenous use. Studies in other dis- eases, such as croup, have found no difference in efficacy on the basis of preparation,63 although the compari- son has not been specifically studied for bronchiolitis. Most studies have compared L-epinephrine to placebo or albuterol. A recent Cochrane meta-

analysis by Hartling et al64 systemati- cally evaluated the evidence on this topic and found no evidence for utility in the inpatient setting. Two large, multicenter randomized trials com- paring nebulized epinephrine to pla- cebo65 or albuterol66 in the hospital setting found no improvement in LOS or other inpatient outcomes. A recent, large multicenter trial found a similar lack of efficacy compared with pla- cebo and further demonstrated lon- ger LOS when epinephrine was used on a fixed schedule compared with an as-needed schedule.67 This evidence suggests epinephrine should not be used in children hospitalized for bron- chiolitis, except potentially as a rescue agent in severe disease, although for- mal study is needed before a recom- mendation for the use of epinephrine in this setting.

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

This multicenter randomized trial enrolled 800 patients with bron- chiolitis from 8 EDs and compared hospitalization rates over a 7-day period. This study had 4 arms: neb- ulized epinephrine plus oral dexa- methasone, nebulized epinephrine plus oral placebo, nebulized placebo plus oral dexamethasone, and neb- ulized placebo plus oral placebo. The group of patients who received epi- nephrine concomitantly with corti- costeroids had a lower likelihood of hospitalization by day 7 than the double placebo group, although this effect was no longer statistically sig- nificant after adjusting for multiple comparisons.

The systematic review by Hartling et al64 concluded that epinephrine reduced hospitalizations compared with placebo on the day of the ED visit but not overall. Given that epinephrine

Aggregate evidence quality

B

Benefits Avoiding adverse effects, lower costs, avoiding ongoing use of ineffective medication

Risk, harm, cost Missing transient benefit of drug

Benefit-harm assessment

Benefits outweigh harms

Value judgments The overall ineffectiveness outweighs possible transient benefit

Intentional vagueness

None

Role of patient preferences

None

Exclusions Rescue treatment of rapidly deteriorating patients

Strength Strong recommendation Differences of

opinion None

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has a transient effect and home ad- ministration is not routine practice, discharging an infant after observing a response in a monitored setting raises concerns for subsequent pro- gression of illness. Studies have not found a difference in revisit rates, although the numbers of revisits are small and may not be adequately powered for this outcome. In summary, the current state of evidence does not support a routine role for epineph- rine for bronchiolitis in outpatients, although further data may help to better define this question.

HYPERTONIC SALINE

Key Action Statement 4a

Nebulized hypertonic saline should not be administered to infants with a diagnosis of bronchiolitis in the emergency department (Evidence Quality: B; Recommendation Strength: Moderate Recommendation).

Action Statement Profile KAS 4a

Key Action Statement 4b

Clinicians may administer nebulized hypertonic saline to infants and children hospitalized for bron- chiolitis (Evidence Quality: B; Rec- ommendation Strength: Weak

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

Action Statement Profile KAS 4b

Nebulized hypertonic saline is an in- creasingly studied therapy for acute viral bronchiolitis. Physiologic evidence suggests that hypertonic saline in- creases mucociliary clearance in both normal and diseased lungs.69–71 Because the pathology in bronchiolitis involves airway inflammation and resultant mucus plugging, improved mucocili- ary clearance should be beneficial, al- though there is only indirect evidence to support such an assertion. A more specific theoretical mechanism of ac- tion has been proposed on the basis of the concept of rehydration of the air- way surface liquid, although again, evidence remains indirect.72

A 2013 Cochrane review73 included 11 trials involving 1090 infants with mild to moderate disease in both inpatient and emergency settings. There were 6 studies involving 500 inpatients providing data

for the analysis of LOS with an aggregate 1-day decrease reported, a result largely driven by the inclusion of 3 studies with relatively long mean length of stay of 5 to 6 days. The analysis of effect on clinical scores included 7 studies involving 640 patients in both inpatient and outpatient settings and demonstrated incremental positive effect with each day posttreat- ment from day 1 to day 3 (–0.88 MD on day 1, –1.32 MD on day 2, and –1.51 MD on day 3). Finally, Zhang et al73 found no effect on hospitalization rates in the pooled analysis of 1 outpatient and 3 ED studies including 380 total patients.

Several randomized trials published after the Cochrane review period further in- formed the current guideline recommen- dation. Four trials evaluated admission rates from the ED, 3 using 3% saline and 1 using 7% saline.74–76 A single trial76 dem- onstrated a difference in admission rates from the ED favoring hypertonic saline, although the other 4 studies were con- cordant with the studies included in the Cochrane review. However, contrary to the studies included in the Cochrane review, none of the more recent trials reported improvement in LOS and, when added to the older studies for an updated meta- analysis, they significantly attenuate the summary estimate of the effect on LOS.76,77

Most of the trials included in the Cochrane review occurred in settings with typical LOS of more than 3 days in their usual care arms. Hence, the significant decrease in LOS noted by Zhang et al73 may not be generalizable to the United States where the average LOS is 2.4 days.10 One other ongoing clinical trial performed in the United States, unpublished except in ab- stract form, further supports the obser- vation that hypertonic saline does not decrease LOS in settings where expected stays are less than 3 days.78

The preponderance of the evidence sug- gests that 3% saline is safe and effective at improving symptoms of mild to moderate bronchiolitis after 24 hours of use and reducing hospital LOS in settings in which

Aggregate evidence quality

B

Benefits Avoiding adverse effects, such as wheezing and excess secretions, cost

Risk, harm, cost None Benefit-harm assessment

Benefits outweigh harms

Value judgments None Intentional vagueness

None

Role of patient preferences

None

Exclusions None Strength Moderate recommendation Differences of opinion

None

Aggregate evidence quality

B

Benefits May shorten hospital stay if LOS is >72 h

Risk, harm, cost Adverse effects such as wheezing and excess secretions; cost

Benefit-harm assessment

Benefits outweigh harms for longer hospital stays

Value judgments Anticipating an individual child’s LOS is difficult. Most US hospitals report an average LOS of <72 h for patients with bronchiolitis. This weak recommendation applies only if the average length of stay is >72 h

Intentional vagueness

This weak recommendation is based on an average LOS and does not address the individual patient.

Role of patient preferences

None

Exclusions None Strength Weak Differences of opinion

None

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the duration of stay typically exceeds 3 days. It has not been shown to be effective at reducing hospitalization in emergency settings or in areas where the length of usage is brief. It has not been studied in intensive care settings, and most trials have included only patients with mild to moderate dis- ease. Most studies have used a 3% saline concentration, and most have combined it with bronchodilators with each dose; however, there is retrospective evidence that the rate of adverse events is similar without bronchodilators,79 as well as pro- spective evidence extrapolated from 2 trials without bronchodilators.79,80

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

CORTICOSTEROIDS

Key Action Statement 5

Clinicians should not administer systemic corticosteroids to infants with a diagnosis of bronchiolitis in any setting (Evidence Quality: A; Recommendation Strength: Strong Recommendation).

Action Statement Profile KAS 5

Although there is good evidence of benefit from corticosteroids in other

respiratory diseases, such as asthma and croup,82–84 the evidence on corti- costeroid use in bronchiolitis is nega- tive. The most recent Cochrane systematic review shows that cortico- steroids do not significantly reduce outpatient admissions when compared with 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) and do not reduce LOS for inpatients (MD –0.18 days; 95% CI –0.39 to 0.04).85 No other comparisons showed relevant differences for either primary or sec- ondary outcomes. This review con- tained 17 trials with 2596 participants and included 2 large ED-based ran- domized trials, neither of which showed reductions in hospital admissions with treatment with corticosteroids as com- pared with placebo.69,86

One of these large trials, the Canadian Bronchiolitis Epinephrine Steroid Trial, however, did show a reduction in hos- pitalizations 7 days after treatment with combined nebulized epinephrine and oral dexamethasone as compared with placebo.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 as compared with placebo, adjustment for multiple comparison rendered the result insignificant (P = .07). These results have generated considerable controversy.87 Although there is no standard recognized rationale for why combination epinephrine and dexa- methasone would be synergistic in infants with bronchiolitis, evidence in adults and children older than 6 years with asthma shows that adding inhaled long-acting β agonists to moderate/high doses of inhaled cor- ticosteroids allows reduction of the corticosteroid dose by, on average, 60%.88 Basic science studies focused on understanding the interaction be- tween β agonists and corticosteroids have shown potential mechanisms for

why simultaneous administration of these drugs could be synergistic.89–92

However, other bronchiolitis trials of corticosteroids administered by us- ing fixed simultaneous bronchodila- tor regimens have not consistently shown benefit93–97; hence, a recommen- dation regarding the benefit of com- bined dexamethasone and epinephrine therapy is premature.

The systematic review of cortico- steroids in children with bronchiolitis cited previously did not find any dif- ferences in short-term adverse events as compared with placebo.86 However, corticosteroid therapy may prolong viral shedding in patients with bron- chiolitis.17

In summary, a comprehensive sys- tematic review and large multicenter randomized trials provide clear evi- dence that corticosteroids alone do not provide significant benefit to children with bronchiolitis. Evidence for potential benefit of combined corticosteroid and agents with both α- and β-agonist activity is at best tentative, and additional large trials are needed to clarify whether this therapy is effective.

Further, although there is no evidence of short-term adverse effects from corticosteroid therapy, other than prolonged viral shedding, in infants and children with bronchiolitis, there is inadequate evidence to be certain of safety.

OXYGEN

Key Action Statement 6a

Clinicians may choose not to ad- minister supplemental oxygen if the oxyhemoglobin saturation exceeds 90% in infants and children with a diagnosis of bronchiolitis (Evidence Quality: D; Recommendation Strength: Weak Recommendation [based on low-level evidence and reasoning from first principles]).

Aggregate evidence quality

A

Benefits No clinical benefit, avoiding adverse effects

Risk, harm, cost None Benefit-harm

assessment Benefits outweigh harms

Value judgments None Intentional

vagueness None

Role of patient preferences

None

Exclusions None Strength Strong recommendation Differences of

opinion None

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Action Statement Profile KAS 6a

Key Action Statement 6b

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

Action Statement Profile KAS 6b

Although oxygen saturation is a poor predictor of respiratory distress, it is

associated closely with a perceived need for hospitalization in infants with bronchiolitis.98,99 Additionally, oxygen saturation has been implicated as a primary determinant of LOS in bronchiolitis.40,100,101

Physiologic data based on the oxyhe- moglobin dissociation curve (Fig 3) demonstrate that small increases in arterial partial pressure of oxygen are associated with marked improvement in pulse oxygen saturation when the latter is less than 90%; with pulse oxy- gen saturation readings greater than 90% it takes very large elevations in arterial partial pressure of oxygen to affect further increases. In infants and children with bronchiolitis, no data exist to suggest such increases result in any clinically significant difference in physi- ologic function, patient symptoms, or clinical outcomes. Although it is well understood that acidosis, temperature, and 2,3-diphosphoglutarate influence the oxyhemoglobin dissociation curve, there has never been research to demonstrate how those influences practically affect infants with hypox- emia. The risk of hypoxemia must be weighed against the risk of hospitali- zation when making any decisions about site of care. One study of hospi- talized children with bronchiolitis, for example, noted a 10% adverse error or near-miss rate for harm-causing inter- ventions.103 There are no studies on the effect of short-term, brief periods of hypoxemia such as may be seen in bronchiolitis. Transient hypoxemia is common in healthy infants.104 Travel of healthy children even to moderate alti- tudes of 1300 m results in transient sleep desaturation to an average of 84% with no known adverse con- sequences.105 Although children with chronic 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.106–108

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

Pulse oximetry is a convenient method to assess the percentage of hemo- globin bound by oxygen in children. Pulse oximetry has been erroneously used in bronchiolitis as a proxy for respiratory distress. Accuracy of pulse oximetry is poor, especially in the 76% to 90% range.110 Further, it has been well demonstrated that oxygen satu- ration has much less impact on re- spiratory drive than carbon dioxide concentrations in the blood.111 There is very poor correlation between re- spiratory distress and oxygen satu- rations among infants with lower respiratory tract infections.112 Other than cyanosis, no published clinical sign, model, or score accurately iden- tifies hypoxemic children.113

Among children admitted for bronchi- olitis, continuous pulse oximetry mea- surement is not well studied and potentially problematic for children who do not require oxygen. Transient desa- turation is a normal phenomenon in healthy infants. In 1 study of 64 healthy infants between 2 weeks and 6 months of age, 60% of these infants exhibited a transient oxygen desaturation below 90%, to values as low as 83%.105 A ret- rospective study of the role of continu- ous measurement of oxygenation in infants hospitalized with bronchiolitis found that 1 in 4 patients incur unnec- essarily prolonged hospitalization as a result of a perceived need for oxygen outside of other symptoms40 and no evidence of benefit was found.

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

Benefits Decreased hospitalizations, decreased LOS

Risk, harm, cost Hypoxemia, physiologic stress, prolonged LOS, increased hospitalizations, increased LOS, cost

Benefit-harm assessment

Benefits outweigh harms

Value judgments Oxyhemoglobin saturation >89% is adequate to oxygenate tissues; the risk of hypoxemia with oxyhemoglobin saturation >89% is minimal

Intentional vagueness

None

Role of patient preferences

Limited

Exclusions Children with acidosis or fever Strength Weak recommendation (based

on low-level evidence/ reasoning from first principles)

Differences of opinion

None

Aggregate evidence quality

C

Benefits Shorter LOS, decreased alarm fatigue, decreased cost

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

Benefit-harm assessment

Benefits outweigh harms

Value judgments None Intentional vagueness

None

Role of patient preferences

Limited

Exclusions None Strength Weak recommendation (based

on lower level of evidence) Differences of opinion

None

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may negatively affect sleep. Alarm fa- tigue is recognized by The Joint Commission as a contributor toward in-hospital morbidity and mortality.114

One adult study demonstrated very poor documentation of hypoxemia al- erts by pulse oximetry, an indicator of alarm fatigue.115 Pulse oximetry probes can fall off easily, leading to inaccurate measurements and alarms.116

False reliance on pulse oximetry may lead to less careful monitoring of re- spiratory status. In one study, contin- uous pulse oximetry was associated with increased risk of minor adverse events in infants admitted to a gen- eral ward.117 The pulse oximetry– monitored patients were found to have less-effective surveillance of their severity of illness when controlling for other variables.

There are a number of new approaches to oxygen delivery in bronchiolitis, 2 of which are home oxygen and high- frequency nasal cannula. There is emerging evidence for the role of home oxygen in reducing LOS or admission rate for infants with bronchiolitis, in-

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

Readmission rates may be moderately higher in patients discharged with home oxygen; however, overall hospital use may be reduced,122 although not in all settings.123 Concerns have been raised that home pulse oximetry may complicate care or confuse families.124

Communication with follow-up physi- cians is important, because primary care physicians may have difficulty de- termining safe pulse oximetry levels for discontinuation of oxygen.125 Addi- tionally, there may be an increased demand for follow-up outpatient visits associated with home oxygen use.124

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

continuous positive airway pressure in bronchiolitis.127–130 Clinical evidence suggests it reduces work of breath- ing131,132 and may decrease need for intubation,133–136 although studies are generally retrospective and small. The therapy has been studied in the ED136,137

and the general inpatient setting,134,138

as well as the ICU. The largest and most rigorous retrospective study to date was from Australia,138 which showed a 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 intubation rate remained at 28%. A single pilot for 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-flow nasal cannula in bronchiolitis precludes specific recommendations on it use at present. Pneumothorax is a reported complication.

CHEST PHYSIOTHERAPY

Key Action Statement 7

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

Action Statement Profile KAS 7

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

Aggregate evidence quality

B

Benefits Decreased stress from therapy, reduced cost

Risk, harm, cost None Benefit-harm assessment

Benefits outweigh harms

Value judgments None Intentional vagueness

None

Role of patient preferences

None

Exclusions None Strength Moderate recommendation Differences of opinion

None

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Airway edema, sloughing of respiratory epithelium into airways, and general- ized hyperinflation of the lungs, coupled with poorly developed collateral venti- lation, put infants with bronchiolitis at risk for atelectasis. Although lobar at- electasis is not characteristic of this disease, chest radiographs may show evidence of subsegmental atelectasis, prompting clinicians to consider or- dering chest physiotherapy to promote airway clearance. A Cochrane Review140

found 9 randomized controlled trials that evaluated chest physiotherapy in hospitalized patients with bronchiolitis. No clinical benefit was found by using vibration or percussion (5 trials)141–144

or passive expiratory techniques (4 tri- als).145–148 Since that review, a study149

of the passive expiratory technique found a small, but significant reduction in duration of oxygen therapy, but no other benefits.

Suctioning of the nasopharynx to re- move secretions is a frequent practice in infants with bronchiolitis. Although suctioning the nares may provide temporary relief of nasal congestion or upper airway obstruction, a retro- spective study reported that deep suctioning150 was associated with longer LOS in hospitalized infants 2 to 12 months of age. The same study also noted that lapses of greater than 4 hours in noninvasive, external nasal suctioning were also associ- ated with longer LOS. Currently, there are insufficient data to make a rec- ommendation about suctioning, but it appears that routine use of “deep” suctioning151,153 may not be beneficial.

ANTIBACTERIALS

Key Action Statement 8

Clinicians should not administer antibacterial medications to infants and children with a diagnosis of bronchiolitis unless there is a con- comitant bacterial infection, or a strong suspicion of one. (Evidence

Quality: B; Recommendation Strength: Strong Recommendation).

Action Statement Profile KAS 8

Infants with bronchiolitis frequently re- ceive antibacterial therapy because of fever,152 young age,153 and concern for secondary bacterial infection.154 Early randomized controlled trials155,156

showed no benefit from routine anti- bacterial therapy for children with bronchiolitis. Nonetheless, antibiotic therapy continues to be overused in young infants with bronchiolitis because of concern for an undetected bacterial infection. Studies have shown that febrile infants without an identifiable source of fever have a risk of bacteremia that may be as high as 7%. However, a child with a distinct viral syndrome, such as bronchiolitis, has a lower risk (much less than 1%) of bacterial infection of the cerebrospinal fluid or blood.157

Ralston et al158 conducted a systematic review of serious bacterial infections (SBIs) occurring in hospitalized febrile infants between 30 and 90 days of age with bronchiolitis. Instances of bacter- emia or meningitis were extremely rare.

Enteritis was not evaluated. Urinary tract infection occurred at a rate of approxi- mately 1%, but asymptomatic bacteri- uria may have explained this finding. The authors concluded routine screening for SBI among hospitalized febrile infants with bronchiolitis between 30 and 90 days of age is not justified. Limited data suggest the risk of bacterial infection in hospitalized infants with bronchiolitis younger than 30 days of age is similar to the risk in older infants. An abnormal white blood cell count is not useful for predicting a concurrent SBI in infants and young children hospitalized with RSV lower respiratory tract infection.159 Sev- eral retrospective studies support this conclusion.160–166 Four prospective stud- ies of SBI in patients with bronchiolitis and/or RSV infections also demonstrated low rates of SBI.167–171

Approximately 25% of hospitalized in- fants with bronchiolitis have radio- graphic evidence of atelectasis, and it may be difficult to distinguish between atelectasis and bacterial infiltrate or consolidation.169 Bacterial pneumonia in infants with bronchiolitis without consolidation is unusual.170 Antibiotic therapy may be justified in some chil- dren with bronchiolitis who require intubation and mechanical ventilation for respiratory failure.172,173

Although acute otitis media (AOM) in infants with bronchiolitis may be at- tributable to viruses, clinical features generally do not permit differentiation of viral AOM from those with a bacterial component.174 Two studies address the frequency of AOM in patients with bronchiolitis. Andrade et al175 pro- spectively identified AOM in 62% of 42 patients who presented with bronchi- olitis. AOM was present in 50% on entry to the study and developed in an addi- tional 12% within 10 days. A subsequent report176 followed 150 children hospi- talized for bronchiolitis for the de- velopment of AOM. Seventy-nine (53%) developed AOM, two-thirds within the

Aggregate evidence quality

B

Benefits Fewer adverse effects, less resistance to antibacterial agents, lower cost

Risk, harm, cost None Benefit-harm assessment

Benefits outweigh harms

Value judgments None Intentional vagueness

Strong suspicion is not specifically defined and requires clinician judgment. An evaluation for the source of possible serious bacterial infection should be completed before antibiotic use

Role of patient preferences

None

Exclusions None Strength Strong recommendation Differences of opinion

None

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first 2 days of hospitalization. AOM did not influence the clinical course or laboratory findings of bronchiolitis. The current AAP guideline on AOM177 rec- ommends that a diagnosis of AOM should include bulging of the tympanic membrane. This is based on bulging being the best indicator for the pres- ence of bacteria in multiple tympano- centesis studies and on 2 articles comparing antibiotic to placebo ther- apy that used a bulging tympanic membrane as a necessary part of the diagnosis.178,179 New studies are needed to determine the incidence of AOM in bronchiolitis by using the new criterion of bulging of the tympanic membrane. Refer to the AOM guideline180 for rec- ommendations regarding the manage- ment of AOM.

NUTRITION AND HYDRATION

Key Action Statement 9

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

Action Statement Profile KAS 9

The level of respiratory distress attributable to bronchiolitis guides the indications for fluid replacement. Conversely, food intake in the previous 24 hours may be a predictor of oxygen saturation among infants with bron-

chiolitis. One study found that food in- take at less than 50% of normal for the previous 24 hours is associated with a pulse oximetry value of <95%.180

Infants with mild respiratory distress may require only observation, particu- larly if feeding remains unaffected. When the respiratory rate exceeds 60 to 70 breaths per minute, feeding may be compromised, particularly if nasal secretions are copious. There is limited evidence to suggest coordination of breathing with swallowing may be impaired among infants with bron- chiolitis.181 These infants may develop increased nasal flaring, retractions, and prolonged expiratory wheezing when fed and may be at increased risk of aspiration.182

One study estimated that one-third of infants hospitalized for bronchiolitis require fluid replacement.183 One case series184 and 2 randomized trials,185,186 examined the compara- tive efficacy and safety of the in- travenous and nasogastric routes for fluid replacement. A pilot trial in Israel that included 51 infants younger than 6 months demon- strated no significant differences in the duration of oxygen needed or time to full oral feeds between

infants receiving intravenous 5% dextrose in normal saline solution or nasogastric breast milk or for- mula.187 Infants in the intravenous group had a shorter LOS (100 vs 120 hours) but it was not statistically

significant. In a larger open ran- domized trial including infants be- tween 2 and 12 months of age and conducted in Australia and New Zealand, there were no significant differences in rates of admission to ICUs, need for ventilatory support, and adverse events between 381 infants assigned to nasogastric hy- dration and 378 infants assigned to intravenous hydration.188 There was a difference of 4 hours in mean LOS between the intravenous group (82.2 hours) and the nasogastric group (86.2 hours) that was not statisti- cally significant. The nasogastric route had a higher success rate of insertion than the intravenous route. Parental satisfaction scores did not differ between the in- travenous and nasogastric groups. These studies suggest that infants who have difficulty feeding safely because of respiratory distress can receive either intravenous or naso- gastric fluid replacement; however, more evidence is needed to increase the strength of this recommendation.

The possibility of fluid retention re- lated to production of antidiuretic hormone has been raised in patients with bronchiolitis.187–189 Therefore, receipt of hypotonic fluid replace- ment and maintenance fluids may increase the risk of iatrogenic hypo- natremia in these infants. A recent meta-analysis demonstrated that among hospitalized children requiring main- tenance fluids, the use of hypotonic fluids was associated with significant hyponatremia compared with iso- tonic fluids in older children.190 Use of isotonic fluids, in general, appears to be safer.

PREVENTION

Key Action Statement 10a

Clinicians should not administer palivizumab to otherwise healthy

Aggregate evidence quality X Benefits Maintaining hydration Risk, harm, cost Risk of infection, risk of aspiration with nasogastric tube, discomfort,

hyponatremia, intravenous infiltration, overhydration Benefit-harm assessment Benefits outweigh harms Value judgments None Intentional vagueness None Role of patient preferences Shared decision as to which mode is used Exclusions None Strength Strong recommendation Differences of opinion None

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

Action Statement Profile KAS 10a

Key Action Statement 10b

Clinicians should administer pal- ivizumab during the first year of life to infants with hemodynami- cally significant heart disease or chronic lung disease of prema- turity defined as preterm infants <32 weeks, 0 days’ gestation who require >21% oxygen for at least the first 28 days of life (Evidence Quality: B; Recommendation Strength: Moderate Recommendation).

Action Statement Profile KAS 10b

Key Action Statement 10c

Clinicians should administer a max- imum 5 monthly doses (15 mg/kg/ dose) of palivizumab during the RSV season to infants who qualify for palivizumab in the first year of life (Evidence Quality: B, Recom- mendation Strength: Moderate Recommendation).

Action Statement Profile KAS 10c

Detailed evidence to support the policy statement on palivizumab and this palivizumab section can be found in the technical report on palivizumab.192

Palivizumab was licensed by the US Food and Drug Administration in June 1998 largely on the basis of results of 1 clinical trial.193 The results of a second clinical trial among children with con- genital heart disease were reported in December 2003.194 No other prospec- tive, randomized, placebo-controlled trials have been conducted in any subgroup. Since licensure of pal- ivizumab, new peer-reviewed pub- lications provide greater insight into the epidemiology of disease caused by RSV.195–197 As a result of new data, the Bronchiolitis Guideline Committee and the Committee on Infectious Diseases have updated recommendations for use of prophylaxis.

PREMATURITY

Monthly palivizumab prophylaxis should be restricted to infants born before 29 weeks, 0 days’ gestation, except for infants who qualify on the basis of congenital heart disease or chronic lung disease of prematurity. Data show that infants born at or after 29 weeks, 0 days’ gestation have an RSV hospitalization rate similar to the rate of full-term infants.11,198 Infants with a gestational age of 28 weeks, 6 days or less who will be younger than 12 months at the start of the RSV sea- son should receive a maximum of 5

monthly doses of palivizumab or until the end of the RSV season, whichever comes first. Depending on the month of birth, fewer than 5 monthly doses

Aggregate evidence quality

B

Benefits Reduced pain of injections, reduced use of a medication that has shown minimal benefit, reduced adverse effects, reduced visits to health care provider with less exposure to illness

Risk, harm, cost Minimal increase in risk of RSV hospitalization

Benefit-harm assessment Benefits outweigh harms

Value judgments None Intentional vagueness None Role of patient preferences

Parents may choose to not accept palivizumab

Exclusions Infants with chronic lung disease of prematurity and hemodynamically significant cardiac disease (as described in KAS 10b)

Strength Recommendation Differences of opinion None Notes This KAS is harmonized

with the AAP policy statement on palivizumab

Aggregate evidence quality B Benefits Reduced risk of RSV

hospitalization Risk, harm, cost Injection pain;

increased risk of illness from increased visits to clinician office or clinic; cost; side effects from palivizumab

Benefit-harm assessment Benefits outweigh harms

Value judgments None Intentional vagueness None Role of patient preferences Parents may choose

to not accept palivizumab

Exclusions None Strength Moderate

recommendation Differences of opinion None Notes This KAS is

harmonized with the AAP policy statement on palivizumab191,192

Aggregate evidence quality B Benefits Reduced risk of hospitalization; reduced admission to ICU Risk, harm, cost Injection pain; increased risk of illness from increased visits to clinician

office or clinic; cost; adverse effects of palivizumab Benefit-harm assessment Benefits outweigh harms Value judgments None Intentional vagueness None Role of patient preferences None Exclusions 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 recommendation Differences of opinion None Notes This KAS is harmonized with the AAP policy statement on palivizumab191,192

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

CONGENITAL HEART DISEASE

Despite the large number of subjects enrolled, little benefit from pal- ivizumab prophylaxis was found in the industry-sponsored cardiac study among infants in the cyanotic group (7.9% in control group versus 5.6% in palivizumab group, or 23 fewer hos- pitalizations per1000 children; P = .285).197 In the acyanotic group (11.8% vs 5.0%), there were 68 fewer RSV hospitalizations per 1000 prophylaxis recipients (P = .003).197,199,200

CHRONIC LUNG DISEASE OF PREMATURITY

Palivizumab prophylaxis should be administered to infants and children younger than 12 months who develop chronic lung disease of prematurity, defined as a requirement for 28 days of more than 21% oxygen beginning at birth. If a child meets these cri- teria and is in the first 24 months of life and continues to require sup- plemental oxygen, diuretic therapy, or chronic corticosteroid therapy within 6 months of the start of the RSV season, monthly prophylaxis should be administered for the remainder of the season.

NUMBER OF DOSES

Community outbreaks of RSV disease usually begin in November or December, peak in January or February, and end by late March or, at times, in April.4 Figure 1 shows the 2011–2012 bronchiolitis sea- son, which is typical of most years. Because 5 monthly doses will provide more than 24 weeks of protective se- rum palivizumab concentration, admin- istration of more than 5 monthly doses is not recommended within the conti- nental United States. For infants who qualify for 5 monthly doses, initiation of prophylaxis in November and continua-

tion for a total of 5 doses will provide protection into April.201 If prophylaxis is initiated in October, the fifth and final dose should be administered in Febru- ary, and protection will last into March for 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 year of life with the following exception. Children who satisfy the definition of chronic lung disease of infancy and continue to require supplemental oxy- gen, chronic corticosteroid therapy, or diuretic therapy within 6 months of the onset of the second RSV sea- son may be considered for a second season of prophylaxis.

OTHER CONDITIONS

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

Down Syndrome

Routine use of prophylaxis for children in the first year of life with Down syndrome is not recommended unless the child qualifies because of cardiac disease or prematurity.202

Cystic Fibrosis

Routine use of palivizumab prophylaxis in patients with cystic fibrosis is not recommended.203,204 Available studies indicate the incidence of RSV hospital- ization in children with cystic fibrosis is low and unlikely to be different from children without cystic fibrosis. No ev- idence suggests a benefit from pal- ivizumab prophylaxis in patients with cystic fibrosis. A randomized clinical trial involving 186 children with cystic

fibrosis from 40 centers reported 1 subject in each group was hospitalized because of RSV infection. Although this study was not powered for efficacy, no clinically meaningful differences in outcome were reported.205 A survey of cystic fibrosis center directors pub- lished in 2009 noted that palivizumab prophylaxis is not the standard of care for patients with cystic fibrosis.206 If a neonate is diagnosed with cystic fi- brosis by newborn screening, RSV prophylaxis should not be adminis- tered if no other indications are pres- ent. A patient with cystic fibrosis with clinical evidence of chronic lung dis- ease in the first year of life may be considered for prophylaxis.

Neuromuscular Disease and Pulmonary Abnormality

The risk of RSV hospitalization is not well defined in children with pulmonary abnormalities or neuromuscular dis- ease that impairs ability to clear secretions from the lower airway be- cause of ineffective cough, recurrent gastroesophageal tract reflux, pulmo- nary malformations, tracheoesophageal fistula, upper airway conditions, or conditions requiring tracheostomy. No data on the relative risk of RSV hospi- talization are available for this cohort. Selected infants with disease or con- genital anomaly that impairs their ability to clear secretions from the lower airway because of ineffective cough 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 RSV hospitalization in children who un- dergo solid organ or hematopoietic stem cell transplantation, receive chemotherapy, or are immunocom- promised because of other conditions. Prophylaxis may be considered for hematopoietic stem cell transplant

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

MISCELLANEOUS ISSUES

Prophylaxis is not recommended for prevention of nosocomial RSV disease in the NICU or hospital setting.208,209

No evidence suggests palivizumab is a cost-effective measure to prevent recurrent wheezing in children. Pro- phylaxis should not be administered to reduce recurrent wheezing in later years.210,211

Monthly prophylaxis in Alaska Native children who qualify should be de- termined by locally generated data regarding season onset and end.

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

HAND HYGIENE

Key Action Statement 11a

All people should disinfect hands before and after direct contact with patients, after contact with inanimate objects in the direct vi- cinity of the patient, and after re- moving gloves (Evidence Quality: B; Recommendation Strength: Strong Recommendation).

Action Statement Profile KAS 11a

Key Action Statement 11b

All people should use alcohol-based rubs for hand decontamination when caring for children with bronchioli- tis. When alcohol-based rubs are not available, individuals should wash their hands with soap and water (Evidence Quality: B; Recom- mendation Strength: Strong Rec- ommendation).

Action Statement Profile KAS 11b

Efforts should be made to decrease the spread of RSV and other causative agents of bronchiolitis in medical settings, especially in the hospital. Secretions from infected patients can be found on beds, crib railings, ta- bletops, and toys.12 RSV, as well as many other viruses, can survive better on hard surfaces than on porous surfaces or hands. It can remain in- fectious on counter tops for ≥6 hours, on gowns or paper tissues for 20 to 30 minutes, and on skin for up to 20 minutes.212

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

caregivers.213 Studies have shown that health care workers have acquired in- fection by performing activities such as feeding, diaper change, and playing with the RSV-infected infant. Caregivers who had contact only with surfaces contaminated with the infants’ secre- tions or touched inanimate objects in patients’ rooms also acquired RSV. In these studies, health care workers contaminated their hands (or gloves) with RSV and inoculated their oral or conjunctival mucosa.214 Frequent hand washing by health care workers has been shown to reduce the spread of RSV in the health care setting.215

The Centers for Disease Control and Prevention published an extensive re- view of the hand-hygiene literature and made recommendations as to indica- tions for hand washing and hand antisepsis.216 Among the recom- mendations are that hands should be disinfected before and after direct contact with every patient, after con- tact with inanimate objects in the di- rect vicinity of the patient, and before putting on and after removing gloves. If hands are not visibly soiled, an alcohol-based rub is preferred. In guidelines published in 2009, the World Health Organization also rec- ommended alcohol-based hand-rubs as the standard for hand hygiene in health care.217 Specifically, systematic reviews show them to remove organ- isms more effectively, require less time, and irritate skin less often than hand washing with soap or other anti- septic agents and water. The availability of bedside alcohol-based solutions in- creased compliance with hand hygiene among health care workers.214

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

Aggregate evidence quality B Benefits Decreased

transmission of disease

Risk, harm, cost Possible hand irritation

Benefit-harm assessment Benefits outweigh harms

Value judgments None Intentional vagueness None Role of patient preferences None Exclusions None Strength Strong

recommendation Differences of opinion None

Aggregate evidence quality B Benefits Less hand irritation Risk, harm, cost If there is visible

dirt on the hands, hand washing is necessary; alcohol-based rubs are not effective for Clostridium difficile, present a fire hazard, and have a slight increased cost

Benefit-harm assessment Benefits outweigh harms

Value judgments None Intentional vagueness None Role of patient preferences None Exclusions None Strength Strong

recommendation Differences of opinion None

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Other methods of infection control in viral bronchiolitis include education of personnel and family members, surveil- lance for the onset of RSV season, and wearing masks when anticipating expo- sure to aerosolized secretions while performing patient care activities. Pro- grams that implement the aforemen- tioned principles, in conjunction with effective hand decontamination and cohorting of patients, have been shown to reduce the spread of RSV in the health care setting by 39% to 50%.218,219

TOBACCO SMOKE

Key Action Statement 12a

Clinicians should inquire about the exposure of the infant or child to tobacco smoke when assessing infants and children for bron- chiolitis (Evidence Quality: C; Rec- ommendation Strength: Moderate Recommendation).

Action Statement Profile KAS 12a

Key Action Statement 12b

Clinicians should counsel care- givers about exposing the infant or

child to environmental tobacco smoke and smoking cessation when assessing a child for bron- chiolitis (Evidence Quality: B; Rec- ommendation Strength: Strong Recommendation).

Action Statement Profile KAS 12b

Tobacco smoke exposure increases the risk and severity of bronchiolitis. Stra- chan and Cook220 first delineated the effects of environmental tobacco smoke on rates of lower respiratory tract dis- ease in infants in a meta-analysis in- cluding 40 studies. In a more recent systematic review, Jones et al221 found a pooled odds ratio of 2.51 (95% CI 1.96 to 3.21) for tobacco smoke exposure and bronchiolitis hospitalization among the 7 studies specific to the condition. Other investigators have consistently reported tobacco smoke exposure increases both severity of illness and risk of hospitalization for bronchioli-

tis.222–225 The AAP issued a technical report on the risks of secondhand smoke in 2009. The report makes rec- ommendations regarding effective ways to eliminate or reduce secondhand smoke exposure, including education of parents.226

Despite our knowledge of this impor- tant risk factor, there is evidence to suggest health care providers identify fewer than half of children exposed to tobacco smoke in the outpatient, in- patient, or ED settings.227–229 Further- more, there is evidence that counseling parents in these settings is well received and has a measurable impact. Rosen et al230 performed a meta-analysis of the effects of inter- ventions in pediatric settings on pa- rental cessation and found a pooled risk ratio of 1.3 for cessation among the 18 studies reviewed.

In contrast to many of the other recommendations, protecting chil- dren from tobacco exposure is a recommendation that is primarily implemented outside of the clinical setting. As such, it is critical that parents are fully educated about the importance of not allowing smoking in the home and that smoke lingers on clothes and in the environment for prolonged periods.231 It should be provided in plain language and in a respectful, culturally effective manner that is family centered, en- gages parents as partners in their child’s health, and factors in their literacy, health literacy, and primary language needs.

BREASTFEEDING

Key Action Statement 13

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

Aggregate evidence quality C Benefits Can identify infants

and children at risk whose family may benefit from counseling, predicting risk of severe disease

Risk, harm, cost Time to inquire Benefit-harm assessment Benefits outweigh

harms Value judgments None Intentional vagueness None Role of patient preferences Parent may choose

to deny tobacco use even though they are, in fact, users

Exclusions None Strength Moderate

recommendation Differences of opinion None

Aggregate evidence quality B Benefits Reinforces the

detrimental effects of smoking, potential to decrease smoking

Risk, harm, cost Time to counsel Benefit-harm assessment Benefits outweigh

harms Value judgments None Intentional vagueness None Role of patient preferences Parents may choose

to ignore counseling

Exclusions None Strength Moderate

recommendation Differences of opinion None Notes Counseling for

tobacco smoke prevention should begin in the prenatal period and continue in family-centered care and at all well-infant visits

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Action Statement Profile KAS 13

In 2012, the AAP presented a general policy on breastfeeding.232 The policy statement was based on the proven benefits of breastfeeding for at least 6 months. Respiratory infections were shown to be significantly less common in breastfed children. A primary re- source was a meta-analysis from the Agency for Healthcare Research and Quality that showed an overall 72% reduction in the risk of hospitalization secondary to respiratory diseases in infants who were exclusively breastfed for 4 or more months compared with those who were formula fed.233

The clinical evidence also supports decreased incidence and severity of illness in breastfed infants with bron- chiolitis. Dornelles et al234 concluded that the duration of exclusive breast- feeding was inversely related to the length of oxygen use and the length of hospital stay in previously healthy infants with acute bronchiolitis. In a large prospective study in Australia, Oddy et al235 showed that breastfeeding for less than 6 months was associated

with an increased risk for 2 or more medical visits and hospital admission for wheezing lower respiratory illness. In Japan, Nishimura et al236 looked at 3 groups of RSV-positive infants defined as full, partial, or token breast- feeding. There were no significant differences in the hospitalization rate among the 3 groups; however, there were significant differences in the duration of hospitalization and the rate of requiring oxygen therapy, both favoring breastfeeding.

FAMILY EDUCATION

Key Action Statement 14

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

Action Statement Profile KAS 14

Shared decision-making with parents about diagnosis and treatment of bronchiolitis is a key tenet of patient- centered care. Despite the absence of effective therapies for viral bronchi- olitis, caregiver education by clinicians may have a significant impact on care patterns in the disease. Children with bronchiolitis typically suffer from symptoms for 2 to 3 weeks, and parents often seek care in multiple settings during that time period.237

Given that children with RSV gener- ally shed virus for 1 to 2 weeks and from 30% to 70% of family members may become ill,238,239 education about prevention of transmission of disease is key. Restriction of visitors to new- borns during the respiratory virus season should be considered. Con- sistent evidence suggests that pa- rental education is helpful in the promotion of judicious use of anti- biotics and that clinicians may mis- interpret parental expectations about therapy unless the subject is openly discussed.240–242

FUTURE RESEARCH NEEDS

� Better algorithms for predicting the course of illness

� Impact of clinical score on patient outcomes

� Evaluating different ethnic groups and varying response to treat- ments

� Does epinephrine alone reduce ad- mission in outpatient settings?

� Additional studies on epinephrine in combination with dexametha- sone or other corticosteroids

� Hypertonic saline studies in the outpatient 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 B Benefits May reduce the risk

of bronchiolitis and other illnesses; multiple benefits of breastfeeding unrelated to bronchiolitis

Risk, harm, cost None Benefit-harm assessment Benefits outweigh

risks Value judgments None Intentional vagueness None Role of patient preferences Parents may choose

to feed formula rather than breastfeed

Exclusions None Strength Moderate

recommendation Notes Education on

breastfeeding should begin in the prenatal period

Aggregate evidence quality C Benefits Decreased

transmission of disease, benefits of breastfeeding, promotion of judicious use of antibiotics, risks of infant lung damage attributable to tobacco smoke

Risk, harm, cost Time to educate properly

Benefit-harm assessment Benefits outweigh harms

Value judgments None Intentional vagueness Personnel is not

specifically defined but should include all people who enter a patient’s room

Role of patient preferences None Exclusions None Strength Moderate

recommendation Differences of opinion None

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� Incidence of true AOM in bron- chiolitis by using 2013 guideline definition

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

� Strategies for monitoring oxygen saturation

� 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 all research (ie, not LOS as the only measure)

SUBCOMMITTEE ON BRONCHIOLITIS (OVERSIGHT BY THE COUNCIL ON QUALITY IMPROVEMENT AND PATIENT SAFETY, 2013–2014) Shawn L. Ralston, MD, FAAP: Chair, Pediatric Hospitalist (no financial conflicts; published research related to bronchiolitis) Allan S. Lieberthal, MD, FAAP: Chair, General Pediatrician with Expertise in Pulmonology (no conflicts) Brian K. Alverson, MD, FAAP: Pediatric Hos- pitalist, AAP Section on Hospital Medicine Representative (no conflicts) Jill E. Baley, MD, FAAP: Neonatal-Perinatal Medicine, AAP Committee on Fetus and New- born Representative (no conflicts) Anne M. Gadomski, MD, MPH, FAAP: General Pediatrician and Research Scientist (no financial conflicts; 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 Pulmonology Representative (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 Intensive Care 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: Pediatric Emergency Physician, AAP Section on Emergency Medicine 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 Physicians Liaison (no conflicts) Elizabeth Rosenblum, MD: Academic Family Physician, American Academy of Family Physi- cians liaison (no conflicts). Stephen Sayles, III, MD, FACEP: Emergency Medicine Physician, American College of Emergency Physicians Liaison (no conflicts) Sinsi Hernández-Cancio, JD: Parent/Consumer Representative (no conflicts)

STAFF Caryn Davidson, MA Linda Walsh, MAB

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APPENDIX 1 SEARCH TERMS BY TOPIC

Introduction

MedLine

((“bronchiolitis”[MeSH]) OR (“respira- tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields])

1. and exp Natural History/

2. and exp Epidemiology/

3. and (exp economics/ or exp “costs and cost analysis”/ or exp “cost allocation”/ or exp cost-benefit analysis/ or exp “cost control”/ or exp “cost of illness”/ or exp “cost sharing”/ or exp health care costs/ or exp health expenditures/)

4. and exp Risk Factors/

Limit to English Language AND Humans AND (“all infant (birth to 23 months)” or “newborn infant (birth to 1 month)” or “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”) AND (“natural history” OR (MM “Epidemiology”) OR (MM “Costs and Cost Analysis”) OR (MM “Risk Factors”))

The Cochrane Library

Bronchiolitis AND (epidemiology OR risk factor OR cost)

Diagnosis/Severity

MedLine

exp BRONCHIOLITIS/di [Diagnosis] OR exp Bronchiolitis, Viral/di [Diagnosis]

limit to English Language AND (“all infant (birth to 23 months)” or “new- born infant (birth to 1 month)” or “infant (1 to 23 months)”)

CINAHL

(MH “Bronchiolitis/DI”)

The Cochrane Library

Bronchiolitis AND Diagnosis

*Upper Respiratory Infection Symp- toms

MedLine

(exp Bronchiolitis/ OR exp Bronchioli- tis, Viral/) AND exp *Respiratory Tract Infections/

Limit to English Language

Limit to “all infant (birth to 23 months)” OR “newborn infant (birth to 1 month)” OR “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”) AND (MM “Re- spiratory Tract Infections+”)

The Cochrane Library

Bronchiolitis AND Respiratory Infection

Inhalation Therapies

*Bronchodilators & Corticosteroids

MedLine

((“bronchiolitis”[MeSH]) OR (“respira- tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields])

AND (exp Receptors, Adrenergic, β-2/ OR exp Receptors, Adrenergic, β/ OR exp Receptors, Adrenergic, β-1/ OR β adrenergic*.mp. OR exp ALBUTEROL/ OR levalbuterol.mp. OR exp EPINEPH- RINE/ OR exp Cholinergic Antagonists/ OR exp IPRATROPIUM/ OR exp Anti-In- flammatory Agents/ OR ics.mp. OR in- haled corticosteroid*.mp. OR exp Adrenal Cortex Hormones/ OR exp Leu- kotriene Antagonists/ OR montelukast. mp. OR exp Bronchodilator Agents/)

Limit to English Language AND (“all infant (birth to 23 months)” or “new- born infant (birth to 1 month)” or “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”) AND (MM “Bronchodilator Agents”)

The Cochrane Library

Bronchiolitis AND (bronchodilator OR epinephrine OR albuterol OR salbuta- mol OR corticosteroid OR steroid)

*Hypertonic Saline

MedLine

((“bronchiolitis”[MeSH]) OR (“respira- tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields])

AND (exp Saline Solution, Hypertonic/ OR (aerosolized saline.mp. OR (exp AEROSOLS/ AND exp Sodium Chloride/)) OR (exp Sodium Chloride/ AND exp “Nebulizers and Vaporizers”/) OR neb- ulized saline.mp.)

Limit to English Language

Limit to “all infant (birth to 23 months)” OR “newborn infant (birth to 1 month)” OR “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”) AND (MM “Sa- line Solution, Hypertonic”)

The Cochrane Library

Bronchiolitis AND Hypertonic Saline

Oxygen

MedLine

((“bronchiolitis”[MeSH]) OR (“respira- tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields])

1. AND (exp Oxygen Inhalation Therapy/ OR supplemental oxygen.mp. OR ox- ygen saturation.mp. OR *Oxygen/ad, st [Administration & Dosage, Stand- ards] OR oxygen treatment.mp.)

2. AND (exp OXIMETRY/ OR oxi- meters.mp.) AND (exp “Reproduc- ibility of Results”/ OR reliability. mp. OR function.mp. OR technical specifications.mp.) OR (percuta- neous measurement*.mp. OR exp Blood Gas Analysis/)

Limit to English Language

Limit to “all infant (birth to 23 months)” OR “newborn infant (birth to 1 month)” OR “infant (1 to 23 months)”)

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CINAHL

(MM “Bronchiolitis+”) AND

((MM “Oxygen Therapy”) OR (MM “Ox- ygen+”) OR (MM “Oxygen Saturation”) OR (MM “Oximetry+”) OR (MM “Pulse Oximetry”) OR (MM “Blood Gas Moni- toring, Transcutaneous”))

The Cochrane Library

Bronchiolitis AND (oxygen OR oximetry)

Chest Physiotherapy and Suctioning

MedLine

((“bronchiolitis”[MeSH]) OR (“respira- tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields])

1. AND (Chest physiotherapy.mp. OR (exp Physical Therapy Techniques/ AND exp Thorax/))

2. AND (Nasal Suction.mp. OR (exp Suction/))

Limit to English Language

Limit to “all infant (birth to 23 months)” OR “newborn infant (birth to 1 month)” OR “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”)

1. AND ((MH “Chest Physiotherapy (Saba CCC)”) OR (MH “Chest Phys- ical Therapy+”) OR (MH “Chest Physiotherapy (Iowa NIC)”))

2. AND (MH “Suctioning, Nasopharyn- geal”)

The Cochrane Library

Bronchiolitis AND (chest physiotherapy OR suction*)

Hydration

MedLine

((“bronchiolitis”[MeSH]) OR (“respi- ratory syncytial viruses”[MeSH])

NOT “bronchiolitis obliterans”[All Fields])

AND (exp Fluid Therapy/ AND (exp infusions, intravenous OR exp admin- istration, oral))

Limit to English Language

Limit to (“all infant (birth to 23 months)” or “newborn infant (birth to 1 month)” or “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”) AND

((MM “Fluid Therapy+”) OR (MM “Hy- dration Control (Saba CCC)”) OR (MM “Hydration (Iowa NOC)”))

The Cochrane Library

Bronchiolitis AND (hydrat* OR fluid*)

SBI and Antibacterials

MedLine

((“bronchiolitis”[MeSH]) OR (“respira- tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields])

AND

(exp Bacterial Infections/ OR exp Bac- terial Pneumonia/ OR exp Otitis Media/ OR exp Meningitis/ OR exp *Anti-bac- terial Agents/ OR exp Sepsis/ OR exp Urinary Tract Infections/ OR exp Bac- teremia/ OR exp Tracheitis OR serious bacterial infection.mp.)

Limit to English Language

Limit to (“all infant (birth to 23 months)” or “newborn infant (birth to 1 month)” or “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”) AND

((MM “Pneumonia, Bacterial+”) OR (MM “Bacterial Infections+”) OR (MM “Otitis Media+”) OR (MM “Meningitis, Bacterial+”) OR (MM “Antiinfective Agents+”) OR (MM “Sepsis+”) OR (MM

“Urinary Tract Infections+”) OR (MM “Bacteremia”))

The Cochrane Library

Bronchiolitis AND (serious bacterial infection OR sepsis OR otitis media OR meningitis OR urinary tract infection or bacteremia OR pneumonia OR anti- bacterial OR antimicrobial OR antibi- otic)

Hand Hygiene, Tobacco, Breastfeeding, Parent Education

MedLine

((“bronchiolitis”[MeSH]) OR (“respira- tory syncytial viruses”[MeSH]) NOT “bronchiolitis obliterans”[All Fields])

1. AND (exp Hand Disinfection/ OR hand decontamination.mp. OR handwashing.mp.)

2. AND exp Tobacco/

3. AND (exp Breast Feeding/ OR exp Milk, Human/ OR exp Bottle Feeding/)

Limit to English Language

Limit to (“all infant (birth to 23 months)” or “newborn infant (birth to 1 month)” or “infant (1 to 23 months)”)

CINAHL

(MM “Bronchiolitis+”)

1. AND (MH “Handwashing+”)

2. AND (MH “Tobacco+”)

3. AND (MH “Breast Feeding+” OR MH “Milk, Human+” OR MH “Bottle Feeding+”)

The Cochrane Library

Bronchiolitis

1. AND (Breast Feeding OR breast- feeding)

2. AND tobacco

3. AND (hand hygiene OR handwash- ing OR hand decontamination)

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DOI: 10.1542/peds.2014-2742 ; originally published online October 27, 2014;Pediatrics

Hernandez-Cancio A. Brown, Ian Nathanson, Elizabeth Rosenblum, Stephen Sayles III and Sinsi

Eneida A. Mendonca, Kieran J. Phelan, Joseph J. Zorc, Danette Stanko-Lopp, Mark Baley, Anne M. Gadomski, David W. Johnson, Michael J. Light, Nizar F. Maraqa,

Shawn L. Ralston, Allan S. Lieberthal, H. Cody Meissner, Brian K. Alverson, Jill E. Bronchiolitis

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

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Eneida A. Mendonca, Kieran J. Phelan, Joseph J. Zorc, Danette Stanko-Lopp, Mark Baley, Anne M. Gadomski, David W. Johnson, Michael J. Light, Nizar F. Maraqa,

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