DOI: 10.1542/peds.2013-3250; originally published online December 16, 2013; 2014;133;e213Pediatrics

David N. CornfieldBronchiolitis: Doing Less and Still Getting Better

  

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of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2014 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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Bronchiolitis: Doing Less and Still Getting Better

Infection with respiratory syncytial virus (RSV) is among the universalexperiences of childhood. Worldwide, by 1 year of life, half of all childrenhave been infected with RSV and by 2 years of age, virtually all childrenhave been infected with RSV.1 Unlike many viral infections, it is theprevalence, as opposed to the severity, of infection that motivates ourcollective focus on the optimal treatment course for infants with RSV.Although acknowledging that in some small subset of high-riskinfants, preventive strategies are justified,2,3 the focus of this com-mentary concerns a randomized, controlled trial of treatment withnebulized hypertonic saline in infants with acute bronchiolitis pub-lished in this issue of Pediatrics.4

In general, bronchiolitis results primarily from RSV infection and causesa few days of congestive symptoms before resolving spontaneously.Despite suggestions that RSV infection increases the longitudinal riskfor developing asthma, there is little direct evidence in support of suchan association.5 In fact, there is substantial evidence indicating thatinfants with underlying airways reactivity, as demonstrated by neo-natal pulmonary function before acquiring a viral infection, are morelikely to be more symptomatic from RSV infection than infants withnormal pulmonary function.6,7

Taken together, these observations beg the question of whether, asopposed to how, to treat infants with bronchiolitis. Certainly some in-fants with bronchiolitis are hypoxemic, dehydrated, or at risk for re-spiratory collapse. Providing supplemental oxygen for trulyhypoxemic infants (oxygen saturations ,90%) or intravenous fluidsfor infants unable to feed or drink owing to tachypnea or increase inwork of breathing is without controversy. Such children representan important, but relatively small percentage of children with bron-chiolitis.8

However, in the overwhelming majority of children with bronchiolitis,symptoms of fever, cough, wheeze, and nasal congestion are modestand readily managed conservatively, absent hospitalization. The ill-ness is generally self-limited. Supportive care can be provided in thehome.

The article entitled “7% Hypertonic saline in acute bronchiolitis: arandomized controlled trial” by Jacobs et al4 explicitly addresses thepropriety of treating bronchiolitic infants with hypertonic saline. How-ever, the article also implicitly addresses the notion of whether to treatinfants with bronchiolitis. Relative to the treatment tested in the piecewritten by Jacobs et al,4 the conclusions seem both important andclear. Nebulized delivery of 7% saline did not confer a measurableadvantage over 0.9% saline delivered via nebulizer. The findings sup-port previous reports wherein 3% saline conferred no benefit relativeto 0.9% saline.9 Perhaps these reports, taken together, might allow forthe collective realization that hypertonic saline confers no objectiveand reproducible benefit in the context of bronchiolitis. Notwithstanding

AUTHOR: David N. Cornfield, MD

Divisions of Pediatric Pulmonary Medicine and Critical CareMedicine, Department of Pediatrics, Center for Excellence inPulmonary Biology, Stanford University School of Medicine,Stanford, California

KEY WORDSbronchiolitis, hypertonic saline, hypoxia

ABBREVIATIONRSV—respiratory syncytial virus

Opinions in these commentaries are those of the author and notnecessarily those of the American Academy of Pediatrics or itsCommittees.

www.pediatrics.org/cgi/doi/10.1542/peds.2013-3250

doi:10.1542/peds.2013-3250

Accepted for publication Oct 9, 2013

Address correspondence to David N. Cornfield, MD, Center forExcellence in Pulmonary Biology, 770 Welch Rd, Suite 350,Stanford, CA 94304. E-mail: cornfield@stanford.edu

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

Copyright © 2014 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The author has indicated he has nofinancial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The author has indicated hehas no potential conflicts of interest to disclose.

COMPANION PAPER: A companion to this article can be found onpage e8, online at www.pediatrics.org/cgi/doi/10.1542/peds.2013-1646.

PEDIATRICS Volume 133, Number 1, January 2014 e213

COMMENTARY

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the relatively consistent message be-tween studies, that there is no substan-tial benefit with nebulized hypertonicsaline, there is substantial likelihoodthat further investigations will be un-dertaken to identify the exact circum-stances wherein nebulized salinemight confer a previously unknownclinical benefit. After all, each of thetrials includes some imperfection. Inthe present article, investigators usedepinephrine in both treatment andcontrol arms, leaving open the sug-gestion that nebulized epinephrinemight somehow counter the beneficialeffects of hypertonic saline. Althoughthis aspect of the study seems com-pletely reasonable, doubtless it can

be used to mitigate the study’s conclu-sions.

As opposed to devoting time, effort,and resources to identify a strategywherein a questionable therapeutic in-tervention (hypertonic saline) mightbe optimized to allow for detection ofa marginal therapeutic benefit, mightwe do better by considering the un-stated implications of this trial, espe-cially in light of similar efforts to“treat” bronchiolitis? Present data sug-gest that rather than treating bron-chiolitis, patients with bronchiolitisought to be supported. Perhaps thetime has arrived to recognize the limitsof our putative interventions, especiallythose with uncertain or difficult to mea-

sure benefit, and focus effort on doingmore even while doing less. In the con-text of bronchiolitis, perhaps the mostimportant message of the article isthat a self-limited illness might be bestmanaged with limited treatments.

Might we do better, collectively, by rec-ognizing that a negative clinical trial canbe as instructive as a positive trial? Asdemonstrated by this article, it seemslikely that hypertonic saline confers littleor no therapeutic benefit. In that case,hypertonic saline can be placed in thesame category as b-agonist therapy,oral albuterol syrup, systemic steroids,and racemic epinephrine as treat-ment strategies for bronchiolitis thatought not to be routinely applied.

REFERENCES

1. Shay DK, Holman RC, Newman RD, Liu LL, StoutJW, Anderson LJ. Bronchiolitis-associatedhospitalizations among US children, 1980-1996. JAMA. 1999;282(15):1440–1446

2. The PREVENT Study Group. Reduction ofrespiratory syncytial virus hospitaliza-tion among premature infants andinfants with bronchopulmonary dyspla-sia using respiratory syncytial virus im-mune globulin prophylaxis. Pediatrics.1997;99(1):93–99

3. Palivizumab, a humanized respiratory syn-cytial virus monoclonal antibody, reduceshospitalization from respiratory syncytialvirus infection in high-risk infants. The

IMpact-RSV Study Group. Pediatrics. 1998;102(3 pt 1):531–537

4. Jacobs JD, Foster M, Wan J, Pershad J. 7%Hypertonic saline in acute bronchiolitis:a randomized controlled trial. Pediatrics.2014;133(1). Available at: www.pediatrics.org/cgi/content/full/133/1/e8

5. Jackson DJ, Lemanske RF Jr. The role ofrespiratory virus infections in childhoodasthma inception. Immunol Allergy Clin NorthAm. 2010;30(4):513–522, vi

6. Turner SW, Young S, Landau LI, Le Souëf PN.Reduced lung function both before bron-chiolitis and at 11 years. Arch Dis Child.2002;87(5):417–420

7. Drysdale SB, Wilson T, Alcazar M, et al. Lungfunction prior to viral lower respiratorytract infections in prematurely born infants.

Thorax. 2011;66(6):468–473

8. Hasegawa K, Tsugawa Y, Brown DF, Mansbach

JM, Camargo CA Jr. Trends in bronchiolitishospitalizations in the United States, 2000-2009. Pediatrics. 2013;132(1):28–36

9. Grewal S, Ali S, McConnell DW, VandermeerB, Klassen TP. A randomized trial of nebu-lized 3% hypertonic saline with epinephrinein the treatment of acute bronchiolitis in theemergency department. Arch Pediatr Ado-lesc Med. 2009;163(11):1007–1012

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DOI: 10.1542/peds.2013-3250; originally published online December 16, 2013; 2014;133;e213Pediatrics

David N. CornfieldBronchiolitis: Doing Less and Still Getting Better

  

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