Viral or bacterial coinfection with RSV bronchiolitis

Rehder KJ, et al. Detection of multiple respiratory viruses associated with mortality and severity of illness in children. Pediatr Crit Care Med. 2015 Sep;16(7):e201-6.

Although prior studies have demonstrated association between viral codetection and diagnosis of viral pneumonia (23), hospitalization rates (12, 15), and the severity of illness (14), this is the first study to demonstrate both an increased severity of illness and mortality in children presenting to the hospital with isolation of viral copathogens. This finding is of particular import as some studies have demonstrated no worsening in clinical outcomes in the presence of multiple respiratory viruses (20–22). Increased mortality was associated with viral codetection for this entire cohort, as well as patients with normal immune function, and for children without any previously existing comorbidities. The association between viral codetection and moderate or severe illness also persisted in multivariable analysis.

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Hendaus MA, Jomha FA, Alhammadi AH. Virus-induced secondary bacterial infection: a concise review. Ther Clin Risk Manag. 2015 Aug 24;11:1265-71.

Respiratory diseases are a very common source of morbidity and mortality among children. Health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. The reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. The aim of this review is to update the current evidence on the virus-induced bacterial infection. We present several clinical as well in vitro studies that support the correlation between virus and secondary bacterial infections. In addition, we discuss the pathophysiology and prevention modes of the virus-bacterium coexistence. A search of the PubMed and MEDLINE databases was carried out for published articles covering bacterial infections associated with respiratory viruses. This review should provide clinicians with a comprehensive idea of the range of bacterial and viral coinfections or secondary infections that could present with viral respiratory illness.

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Use of heated humidified high-flow nasal cannula for bronchiolitis

Sinha IP, McBride AK, Smith R, Fernandes RM. Continuous positive airway pressure and high flow nasal cannula oxygen in bronchiolitis. Chest. 2015 Apr 2.

“CPAP and HFNC are conceptually attractive modalities for infants with severe
bronchiolitis, and they may improve physiological and clinical outcomes associated
with respiratory distress and failure. Both deliver high concentrations of warmed,
humidified oxygen, precisely and accurately. PEEP generated by CPAP devices may
also help overcome airway resistance and atelectasis, and HFNC may also generate
significant distending pressure but the current evidence around this is conflicting.
Observational studies suggest that CPAP and HFNC may reduce the need for
intensive care, but there is no evidence from RCTs that this is the case. High quality
RCTs, using standardized methodology, should be conducted to identify whether
HFNC and CPAP do in fact confer benefits on important clinical outcomes for infants
with bronchiolitis.”

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Haq I, Gopalakaje S, Fenton AC, et al. The evidence for high flow nasal cannula devices in infants. Paediatr Respir Rev. 2014 Jun;15(2):124-34.

High flow nasal cannula (HFNC) devices deliver an adjustable mixture of heated and humidified oxygen and air at a variable flow rate. Over recent years HFNC devices have become a frequently used method of non-invasive respiratory support in infants and preterm neonates that is generally popular amongst clinicians and nursing staff due to ease of use and being well tolerated by patients. Despite this rapid adoption relatively little is known about the exact mechanisms of action of HFNC however and only recently have data from randomised controlled trials started to become available. We describe the features of a modern HFNC device and discuss current knowledge about the mechanisms of action and results of clinical studies in preterm neonates and infants with bronchiolitis. We also highlight future areas of research that are likely to increase our understanding, inform best clinical practice and strengthen the evidence base for the use of HFNC.

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EBM Review: 7% hypertonic saline in acute bronchiolitis: a randomized controlled trial

Jacobs JD, Foster M, Wan J, Pershad J. 7% hypertonic saline in acute bronchiolitis: a randomized controlled trial. Pediatrics. 2014 Jan;133(1):e8-13.

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BACKGROUND: Research suggests that hypertonic saline (HS) may improve mucous flow in infants with acute bronchiolitis. Data suggest a trend favoring reduced length of hospital stay and improved pulmonary scores with increasing concentration of nebulized solution to 3% and 5% saline as compared with 0.9% saline mixed with epinephrine. To our knowledge, 7% HS has not been previously investigated.

METHODS: We conducted a prospective, double-blind, randomized controlled trial in 101 infants presenting with moderate to severe acute bronchiolitis. Subjects received either 7% saline or 0.9% saline, both with epinephrine. Our primary outcome was a change in bronchiolitis severity score (BSS), obtained before and after treatment, and at the time of disposition from the emergency department (ED). Secondary outcomes measured were hospitalization rate, proportion of admitted patients discharged at 23 hours, and ED and inpatient length of stay.

RESULTS: At baseline, study groups were similar in demographic and clinical characteristics. The decrease in mean BSS was not statistically significant between groups (2.6 vs 2.4 for HS and control groups, respectively). The difference between the groups in proportion of admitted patients (42% in HS versus 49% in normal saline), ED or inpatient length of stay, and proportion of admitted patients discharged at 23 hours was not statistically significant.

CONCLUSIONS: In moderate to severe acute bronchiolitis, inhalation of 7% HS with epinephrine does not appear to confer any clinically significant decrease in BSS when compared with 0.9% saline with epinephrine.

Reviewed by:

Natalie Metzig, MD Natalie Metzig, MD

Tiffany Vinet, MD Tiffany Bell Vinet, MD

Main points

  • Assess effectiveness of hypertonic saline 7% on lowering clinical severity of illness, admission rate or length of stay
  • Previous data suggest these are lower with 3% and 5% hypertonic saline, no studies evaluating 7%
  • Prospective, double-blind, randomized controlled trial
  • 101 infants with moderate to severe acute bronchiolitis being treated in ED were included in study
  • Given HTS 7% w/ epinephrine (52) or 0.9% saline with epinephrine (49)
  • Primary outcome was bronchiolitis severity score (BSS) before and after treatment
  • Secondary outcomes were hospitalization rate, proportion of admitted patients d/c’ed at 23 hours, and length of ED and inpatient stays
  • Decrease in mean BSS was not statistically significant between groups
  • Proportion of admitted patients, ED or inpatient length of stay, and proportion discharged at 23 hours was not statistically significant between groups


  • Bronchiolitis is the most common lower respiratory infection of infants and young children
  • Annual inpatient disease burden exceeds cost of any respiratory disease in US in children < 2 yo
  • Many treatments have been investigated, and only few have been shown to be effective
  • Mainstay of treatment is supportive care with oxygen as needed and hydration
  • Currently, corticosteroids and bronchodilators not recommended
  • Some evidence epinephrine may be more efficacious compared to bronchodilators
  • Nebulized HTS shown promise
  • All studies to date on 3% HTS have shown it to be safe and reduced length of hospital stay and improve clinical severity score


  • BSS is an objective tool that has been previously validated and used modified BSS
    • Modified BSS has been used in this institution since 2006
    • Assessed correlation before beginning study and correlation was high
  • 2 groups were similar in all clinical and historical characteristics
    • Difference in proportion who received albuterol or supplemental O2 was not statistically significant
  • Randomized controlled trial, double-blind study

Limitations and Future Studies

  • Use of 7% HS with racemic epinephrine ONLY
    • Study results can only be interpreted as HTS does not show significant effect when used with racemic epinephrine
    • Does interaction play a role in outcome of study?
    • Would it work alone? Would it work with another medication such as albuterol?
  • Frequency of treatment 
    • Q6H therapy from admission, throughout stay (what if Q4H?)
  • Severity of illness
    • (most were moderately ill, excluded most severely ill patients)
    • Would need a large-scale study to capture severely ill patients
    • Possibly separate trials based on severity
    • Can use data from this study to determine appropriate sample size for additional studies
  • Natural history of the disease
    • Average patient was on day 3 of illness.
    • Would it help to treat sooner? Were they getting better on their own?
    • Future study could look at patients on day 1 or 2 of illness.

Clinical Significance

  • Not much changed.
    • Supportive care is still primary management (airway management and rehydration as needed)
    • No evidence 7% is better when used with racemic epinephrine,
    • You can continue with 3-5% if use Hypertonic Saline as deemed fit.

Final Summary

  • Mainstay of bronchiolitis management is supportive care
  • Some evidence that 3%-5% hypertonic saline nebs may decrease BSS and hospital length of stay
  • Research on 7% HTS is limited. This study suggests no significant improvement of patients received 7% HTS compared to normal saline when used with epinephrine.
  • Further research into Hypertonic Saline nebs is needed in the future.