Vital sign predictors of severe influenza among children in an emergent care setting

Suchitra Rao, Angela Moss, Molly Lamb, Bruce L Innis, Edwin J Asturias, Suchitra Rao, Angela Moss, Molly Lamb, Bruce L Innis, Edwin J Asturias

Abstract

Background: Decisions regarding the evaluation of children with influenza infection rely on the likelihood of severe disease. The role of early vital signs as predictors of severe influenza infection in children is not well known. Our objectives were to determine the value of vital signs in predicting hospitalization/recurrent emergency department (ED) visits due to influenza infection in children.

Methods: We conducted a prospective study of children aged 6 months to 8 years of age with influenza like illness evaluated at an ED/UC from 2016-2018. All children underwent influenza testing by PCR. We collected heart rate, respiratory rate and temperature, and converted heart rate (HR) and respiratory rate (RR) to z-scores by age. HR z scores were further adjusted for temperature. Our primary outcome was hospitalization/recurrent ED visits within 72 hours. Vital sign predictors with p< 0.2 and other clinical covariates were entered into a multivariable logistic regression model to determine odds ratios (OR) and 95% CI; model performance was assessed using the Brier score and discriminative ability with the C statistic.

Results: Among 1478 children, 411 (27.8%) were positive for influenza, of which 42 (10.2%) were hospitalized or had a recurrent ED visit. In multivariable analyses, adjusting for age, high-risk medical condition and school/daycare attendance, higher adjusted respiratory rate (OR 2.09, 95%CI 1.21-3.61, p = 0.0085) was a significant predictor of influenza hospitalization/recurrent ED visits.

Conclusions: Higher respiratory rate adjusted for age was the most useful vital sign predictor of severity among young children with PCR-confirmed influenza.

Trial registration: ClinicalTrials.gov NCT02979626.

Conflict of interest statement

Bruce Innis was employed by the GlaxoSmithKline Biologicals SA group of companies at the time of study conception and planning. Edwin Asturias received research support from the GSK group of companies and receives research support from Pfizer. Suchitra Rao received funding support from the GSK group of companies and Biofire. Molly Lamb received funding support from the GSK group of companies and Biofire. This does not alter our adherence to PLOS ONE policies on sharing data and materials All other authors have no conflicts of interest to disclose.

Figures

Fig 1. Odds of hospitalization and recurrent…
Fig 1. Odds of hospitalization and recurrent ED visits among children with PCR-confirmed influenza using vital sign data as clinical predictors, model adjusted for age, high risk co-morbidities, school or daycare attendance.

References

    1. Grohskopf LA, Alyanak E, Broder KR, Walter EB, Fry AM, Jernigan DB. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2019–20 Influenza Season. MMWR Recomm Rep. 2019;68(3):1–21. doi: 10.15585/mmwr.rr6803a1
    1. Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, et al.. Influenza-associated hospitalizations in the United States. Jama. 2004;292(11):1333–40. doi: 10.1001/jama.292.11.1333
    1. Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng PY, Steiner C, et al.. Hospitalizations associated with influenza and respiratory syncytial virus in the United States, 1993–2008. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2012;54(10):1427–36.
    1. Dawood FS, Fiore A, Kamimoto L, Nowell M, Reingold A, Gershman K, et al.. Influenza-associated pneumonia in children hospitalized with laboratory-confirmed influenza, 2003–2008. The Pediatric infectious disease journal. 2010;29(7):585–90. doi: 10.1097/inf.0b013e3181d411c5
    1. Coffin SE, Leckerman K, Keren R, Hall M, Localio R, Zaoutis TE. Oseltamivir shortens hospital stays of critically ill children hospitalized with seasonal influenza: a retrospective cohort study. The Pediatric infectious disease journal. 2011;30(11):962–6. doi: 10.1097/INF.0b013e318232ede9
    1. Launes C, Garcia-Garcia JJ, Jordan I, Martinez-Planas A, Selva L, Munoz-Almagro C. 2009 Influenza A H1N1 infections: delays in starting treatment with oseltamivir were associated with a more severe disease. Pediatr Infect Dis J. 2011;30(7):622–5. doi: 10.1097/INF.0b013e3182093397
    1. Eriksson CO, Graham DA, Uyeki TM, Randolph AG. Risk factors for mechanical ventilation in U.S. children hospitalized with seasonal influenza and 2009 pandemic influenza A*. Pediatr Crit Care Med. 2012;13(6):625–31. doi: 10.1097/PCC.0b013e318260114e
    1. Call SA, Vollenweider MA, Hornung CA, Simel DL, McKinney WP. Does this patient have influenza? Jama. 2005;293(8):987–97. doi: 10.1001/jama.293.8.987
    1. Ebell MH, White LL, Casault T. A systematic review of the history and physical examination to diagnose influenza. J Am Board Fam Pract. 2004;17(1):1–5. doi: 10.3122/jabfm.17.1.1
    1. Stein J, Louie J, Flanders S, Maselli J, Hacker JK, Drew WL, et al.. Performance characteristics of clinical diagnosis, a clinical decision rule, and a rapid influenza test in the detection of influenza infection in a community sample of adults. Ann Emerg Med. 2005;46(5):412–9. doi: 10.1016/j.annemergmed.2005.05.020
    1. Hsu J, Santesso N, Mustafa R, Brozek J, Chen YL, Hopkins JP, et al.. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med. 2012;156(7):512–24. doi: 10.7326/0003-4819-156-7-201204030-00411
    1. Louie JK, Yang S, Samuel MC, Uyeki TM, Schechter R. Neuraminidase inhibitors for critically ill children with influenza. Pediatrics. 2013;132(6):e1539–45. doi: 10.1542/peds.2013-2149
    1. Ison MG. Optimizing antiviral therapy for influenza: understanding the evidence. Expert Rev Anti Infect Ther. 2015;13(4):417–25. doi: 10.1586/14787210.2015.1018183
    1. Singanayagam A, Singanayagam A, Wood V, Chalmers JD. Factors associated with severe illness in pandemic 2009 influenza a (H1N1) infection: implications for triage in primary and secondary care. The Journal of infection. 2011;63(4):243–51. doi: 10.1016/j.jinf.2011.07.014
    1. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E, et al.. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. The New England journal of medicine. 2009;361(7):680–9. doi: 10.1056/NEJMoa0904252
    1. Heinonen S, Peltola V, Silvennoinen H, Vahlberg T, Heikkinen T. Signs and symptoms predicting influenza in children: a matched case-control analysis of prospectively collected clinical data. European journal of clinical microbiology & infectious diseases: official publication of the European Society of Clinical Microbiology. 2012;31(7):1569–74.
    1. Ma HY, Wu JL, Lu CY, Chen JM, Lee PI, Chang LY, et al.. Risk factors associated with severe influenza virus infections in hospitalized children during the 2013 to 2014 season. Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi. 2015. doi: 10.1016/j.jmii.2015.05.015
    1. Rao S YE, Moss A, Lamb MM, Schuind A, Bekkat-Berkani B, Innis BL, et al.. Evaluation of a new Clinical Endpoint for Moderate-to-severe Influenza Disease in Children: A Prospective Cohort Study. Journal of the Pediatric Infectious Diseases Society (in press). 2019;(in press).
    1. Budd ABL, Grohskopf L, Campbell A, Dugan V, Wentworth DE, Brammer L. Manual for the Surveillance of Vaccine-Preventable Diseases.
    1. Grohskopf LA, Sokolow LZ, Broder KR, Walter EB, Bresee JS, Fry AM, et al.. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2017–18 Influenza Season. MMWR Recomm Rep. 2017;66(2):1–20. doi: 10.15585/mmwr.rr6602a1
    1. Bonafide CP, Brady PW, Keren R, Conway PH, Marsolo K, Daymont C. Development of heart and respiratory rate percentile curves for hospitalized children. Pediatrics. 2013;131(4):e1150–7. doi: 10.1542/peds.2012-2443
    1. Daymont C, Bonafide CP, Brady PW. Heart rates in hospitalized children by age and body temperature. Pediatrics. 2015;135(5):e1173–81. doi: 10.1542/peds.2014-3738
    1. Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, et al.. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology. 2010;21(1):128–38. doi: 10.1097/EDE.0b013e3181c30fb2
    1. Reed C, Madhi SA, Klugman KP, Kuwanda L, Ortiz JR, Finelli L, et al.. Development of the Respiratory Index of Severity in Children (RISC) score among young children with respiratory infections in South Africa. PloS one. 2012;7(1):e27793. doi: 10.1371/journal.pone.0027793
    1. Alshahrani M, Alsubaie A, Alshamsy A, Alkhliwi B, Alshammari H, Alshammari M, et al.. Can the emergency department triage category and clinical presentation predict hospitalization of H1N1 patients? Open Access Emerg Med. 2019;11:221–8. doi: 10.2147/OAEM.S204110
    1. Echevarria-Zuno S, Mejia-Arangure JM, Mar-Obeso AJ, Grajales-Muniz C, Robles-Perez E, Gonzalez-Leon M, et al.. Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis. Lancet. 2009;374(9707):2072–9. doi: 10.1016/S0140-6736(09)61638-X
    1. Palafox M, Guiscafre H, Reyes H, Munoz O, Martinez H. Diagnostic value of tachypnoea in pneumonia defined radiologically. Arch Dis Child. 2000;82(1):41–5. doi: 10.1136/adc.82.1.41
    1. Royston P, Altman DG, Sauerbrei W. Dichotomizing continuous predictors in multiple regression: a bad idea. Stat Med. 2006;25(1):127–41. doi: 10.1002/sim.2331
    1. Naggara O, Raymond J, Guilbert F, Roy D, Weill A, Altman DG. Analysis by categorizing or dichotomizing continuous variables is inadvisable: an example from the natural history of unruptured aneurysms. AJNR Am J Neuroradiol. 2011;32(3):437–40. doi: 10.3174/ajnr.A2425
    1. Spruijt B, Vergouwe Y, Nijman RG, Thompson M, Oostenbrink R. Vital signs should be maintained as continuous variables when predicting bacterial infections in febrile children. J Clin Epidemiol. 2013;66(4):453–7. doi: 10.1016/j.jclinepi.2012.09.014
    1. Vasoo S, Singh K, Trenholme GM. Predicting need for hospitalization of patients with pandemic (H1N1) 2009, Chicago, Illinois, USA. Emerg Infect Dis. 2010;16(10):1594–7. doi: 10.3201/eid1610.091889
    1. Dalziel SR, Thompson JM, Macias CG, Fernandes RM, Johnson DW, Waisman Y, et al.. Predictors of severe H1N1 infection in children presenting within Pediatric Emergency Research Networks (PERN): retrospective case-control study. BMJ. 2013;347:f4836. doi: 10.1136/bmj.f4836
    1. Crocker ME, Hossen S, Goodman D, Simkovich SM, Kirby M, Thompson LM, et al.. Effects of high altitude on respiratory rate and oxygen saturation reference values in healthy infants and children younger than 2 years in four countries: a cross-sectional study. Lancet Glob Health. 2020;8(3):e362–e73. doi: 10.1016/S2214-109X(19)30543-1
    1. Yaron M, Niermeyer S, Lindgren KN, Honigman B, Strain JD, Cairns CB. Physiologic response to moderate altitude exposure among infants and young children. High Alt Med Biol. 2003;4(1):53–9. doi: 10.1089/152702903321488988
    1. Ucros S, Granados CM, Castro-Rodriguez JA, Hill CM. Oxygen Saturation in Childhood at High Altitude: A Systematic Review. High Alt Med Biol. 2020;21(2):114–25. doi: 10.1089/ham.2019.0077
    1. Darville T, Yamauchi T. Respiratory syncytial virus. Pediatr Rev. 1998;19(2):55–61. doi: 10.1542/pir.19-2-55
    1. Pereira JM, Moreno RP, Matos R, Rhodes A, Martin-Loeches I, Cecconi M, et al.. Severity assessment tools in ICU patients with 2009 influenza A (H1N1) pneumonia. Clin Microbiol Infect. 2012;18(10):1040–8. doi: 10.1111/j.1469-0691.2011.03736.x
    1. Kappen TH, van Loon K, Kappen MA, van Wolfswinkel L, Vergouwe Y, van Klei WA, et al.. Barriers and facilitators perceived by physicians when using prediction models in practice. Journal of clinical epidemiology. 2016;70:136–45. doi: 10.1016/j.jclinepi.2015.09.008
    1. van Smeden M, de Groot JA, Moons KG, Collins GS, Altman DG, Eijkemans MJ, et al.. No rationale for 1 variable per 10 events criterion for binary logistic regression analysis. BMC Med Res Methodol. 2016;16(1):163. doi: 10.1186/s12874-016-0267-3
    1. Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165(6):710–8. doi: 10.1093/aje/kwk052
    1. Iyriboz Y, Powers S, Morrow J, Ayers D, Landry G. Accuracy of pulse oximeters in estimating heart rate at rest and during exercise. Br J Sports Med. 1991;25(3):162–4. doi: 10.1136/bjsm.25.3.162
    1. Alwadhi V, Sarin E, Kumar P, Saboth P, Khera A, Gupta S, et al.. Measuring accuracy of plethysmography based respiratory rate measurement using pulse oximeter at a tertiary hospital in India. Pneumonia (Nathan). 2020;12:4. doi: 10.1186/s41479-020-00067-2

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