Predicting Deterioration in Previously Healthy Infants Hospitalized With Respiratory Syncytial Virus Infection

Brooks, Ann; McBride, John T.; McConnochie, Kenneth M.; Aviram, Micah; Long, Christine; Hall, Caroline Breese

doi:10.1542/peds.104.3.463

Cited by 69 publications

(59 citation statements)

References 10 publications

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“…Length of hospital stay was significantly shorter in the 3% hypertonic saline group, which is consistent with previous reports [16,[21][22][23][24][25][26]. The use of corticosteroids and antibiotics during hospitalization was similar in both groups, so these are unlikely to account for such difference.…”

Section: Discussionsupporting

confidence: 90%

“…Although several factors have been associated with an increased risk of severe disease, most infants with acute bronchiolitis admitted to the PICU are reported to be previously healthy and not considered of high risk [22,23]. The rate of patients with high risk factors admitted to the intensive care unit in our sample was 6.5% in the group receiving physiological saline and 3.1% in the group with 3% hypertonic saline, similar to that described in other series.…”

Section: Discussionsupporting

confidence: 85%

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Effect of Nebulized 3% Hypertonic Saline on Intensive Care Unit Admission Rates of Infants with Moderate Acute Bronchiolitis

González¹,

Campoy²

2016

J Clin Res Bioeth

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Objectives: To investigate whether the use of nebulized 3% hypertonic saline in infants hospitalized for acute bronchiolitis reduces their rate of pediatric intensive care unit (PICU) admission, the mean length of PICU stay and total hospital stay.Methods: Cross-sectional study including 626 infants hospitalized for moderate acute bronchiolitis comparing a group receiving nebulized 3% hypertonic saline (HS group) between September 2011 and May 2014 (n=320), with a historic control group treated with normal saline (NS group) between September 2007 and May 2010 (n=306) independently of the concomitant use of bronchodilators.Results: Overall hospital stay including days at PICU, was significantly reduced in HS group (4 days (0-46) vs 5 days (1-73); p<0.0001). However, we did not find a significant reduction in PICU admission rate in the HS group (p=0.115), neither in the length of stay (LOS) in PICU (5 days (1-30) vs 6 days (1-26); p=0.402). Half as many admission were observed in patients with risk factors of severe disease in HS group (6.5% of those with risk factors vs 3.1% of those without risk factors), although this failure to find a difference (p=0.136). Conclusions:Treatment with nebulized 3% hypertonic saline was not accompanied by a reduction in PICU admission. There was no difference in PICU length of stay in infants with acute bronchiolitis, and admission rates in infants with risk factors for serious bronchiolitis; it was also associated with a significantly shorter mean hospital stay.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 85%

Effect of Nebulized 3% Hypertonic Saline on Intensive Care Unit Admission Rates of Infants with Moderate Acute Bronchiolitis

González¹,

Campoy²

2016

J Clin Res Bioeth

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“…Hypoxemia is a primary indicator of disease in children with RSV (42). We previously hypothesized that hypoxemia could result from impaired AFC in RSV infection (4), and in this study we found that infection of mice with RSV resulted in mild hypoxemia in conscious mice on Day 2, when compared with matched preinfection Sm O 2 values.…”

Section: Effect Of Leflunomide On Hypoxemia In Rsv Infectionmentioning

confidence: 48%

Leflunomide Prevents Alveolar Fluid Clearance Inhibition by Respiratory Syncytial Virus

Davis

Lazarowski

Hickman-Davis

et al. 2006

Am J Respir Crit Care Med

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Rationale: Previously, we demonstrated that intranasal infection of BALB/c mice with respiratory syncytial virus (RSV) resulted in an early 40% reduction in alveolar fluid clearance (AFC), an effect mediated via P2Y purinergic receptors. Objectives: To confirm that RSV-induced inhibition of AFC is mediated by uridine triphosphate (UTP), and to demonstrate that inhibition of de novo pyrimidine synthesis with leflunomide prevents increased UTP release after RSV infection, and thereby also prevents inhibition of AFC by RSV. Methods: BALB/c mice were infected intranasally with RSV strain A2. AFC was measured in anesthetized, ventilated mice by instillation of 5% bovine serum albumin into the dependent lung. Some mice were pretreated with leflunomide or 6-mercaptopurine. Measurements and Main Results: RSV-mediated inhibition of AFC is associated temporally with a 20-nM increase in UTP and ATP content of bronchoalveolar lavage fluid, hypoxemia, and altered nasal potential difference. RSV-mediated nucleotide release, AFC inhibition, and physiologic sequelae thereof can be prevented by pretreatment of mice with the de novo pyrimidine synthesis inhibitor leflunomide, which is not toxic to the mice, and which does not affect RSV replication in the lungs. In contrast, pretreatment of mice with 6-mercaptopurine, an inhibitor of de novo purine synthesis, has no beneficial effect on AFC or other indicators of disease progression. Finally, RSV-mediated inhibition of AFC is prevented by volumeregulated anion channel inhibitors. Conclusion: Pyrimidine synthesis or release pathways may provide novel therapeutic targets to counter the pathophysiologic sequelae of impaired AFC in RSV disease.Keywords: ion transport; paramyxovirus infections; pneumonia, viral; pulmonary edemaThe dominant ion transport process of the alveolar epithelium is active movement of Na ϩ ions from the airspace lining fluid to the interstitium (1). This creates an osmotic gradient, causing water to follow passively. This process of alveolar fluid clearance (AFC) is crucial to efficient gas exchange. Importantly, patients with acute lung injury with intact AFC have lower morbidity and mortality than those with compromised AFC (2).Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants and children worldwide (3), but its pathogenesis remains poorly understood. Previously, we demonstrated that infection of BALB/c mice with RSV results in reduced AFC at early time points after infection, and inferred that RSV-mediated inhibition of AFC 2 d after infection was mediated by uridine triphosphate (UTP), acting on P2Y receptors (P2YRs) on lung epithelial cells (4). The aim of the current study was to confirm the central role of UTP in mediating the inhibitory effects of RSV on AFC, and to demonstrate that pharmacologic inhibition of de novo pyrimidine synthesis with leflunomide prevents increased UTP release after RSV infection, and thereby also prevents inhibition of AFC by RSV. Furthermore, we demonstrated that blockag...

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“…By applying a threshold to a single clinical parameter, Brooks et al [55] built a model to predict whether an infant admitted to the general pediatric ward with RSV infection will be transferred to the ICU. In theory, this capability could support development of alternative care strategies, such as early use of NIPPV, for treating infants with RSV infection who present initially with milder symptoms.…”

Section: Predicting Icu Admissionmentioning

confidence: 99%

A systematic review of predictive modeling for bronchiolitis

Luo

Nkoy

Gesteland

et al. 2014

International Journal of Medical Informatics

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Purpose: Bronchiolitis is the most common cause of illness leading to hospitalization in young children. At present, many bronchiolitis management decisions are made subjectively, leading to significant practice variation among hospitals and physicians caring for children with bronchiolitis. To standardize care for bronchiolitis, researchers have proposed various models to predict the disease course to help determine a proper management plan. This paper reviews the existing state of the art of predictive modeling for bronchiolitis. Predictive modeling for respiratory syncytial virus (RSV) infection is covered whenever appropriate, as RSV accounts for about 70% of bronchiolitis cases.Methods: A systematic review was conducted through a PubMed search up to April 25, 2014. The literature on predictive modeling for bronchiolitis was retrieved using a comprehensive search query, which was developed through an iterative process.Search results were limited to human subjects, the English language, and children (birth-18 years). Results:The literature search returned 2,312 references in total. After manual review, 168 of these references were determined to be relevant and are discussed in this paper. We identify several limitations and open problems in predictive modeling for bronchiolitis, and provide some preliminary thoughts on how to address them, with the hope to stimulate future research in this domain. Conclusions:Many problems remain open in predictive modeling for bronchiolitis. Future studies will need to address them to achieve optimal predictive models.

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Predicting Deterioration in Previously Healthy Infants Hospitalized With Respiratory Syncytial Virus Infection

Cited by 69 publications

References 10 publications

Effect of Nebulized 3% Hypertonic Saline on Intensive Care Unit Admission Rates of Infants with Moderate Acute Bronchiolitis

Effect of Nebulized 3% Hypertonic Saline on Intensive Care Unit Admission Rates of Infants with Moderate Acute Bronchiolitis

Leflunomide Prevents Alveolar Fluid Clearance Inhibition by Respiratory Syncytial Virus

A systematic review of predictive modeling for bronchiolitis

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