Derivation and validation of age and temperature specific reference values and centile charts to predict lower respiratory tract infection in children with fever: prospective observational study
BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e4224 (Published 03 July 2012) Cite this as: BMJ 2012;345:e4224
- R G Nijman, PhD student 1,
- M Thompson, senior clinical scientist and general practitioner 2,
- M van Veen, resident in paediatrics1,
- R Perera, university lecturer in statistics 2,
- H A Moll, professor of paediatrics1,
- R Oostenbrink, paediatrician1
- 1Department of General Paediatrics, Erasmus MC-Sophia Children’s Hospital, 3015 GJ Rotterdam, Netherlands
- 2Department of Primary Care Health Sciences, Oxford University, Oxford, UK
- Correspondence to: R Oostenbrink r.oostenbrink{at}erasmusmc.nl
- Accepted 14 May 2012
Abstract
Objectives To develop reference values and centile charts for respiratory rate based on age and body temperature, and to determine how well these reference values can predict the presence of lower respiratory tract infections (LRTI) in children with fever.
Design Prospective observational study.
Participants Febrile children aged at least 1 month to just under 16 years (derivation population, n=1555; validation population, n=671) selected from patients attending paediatric emergency departments or assessment units in hospitals.
Setting One hospital in the Netherlands in 2006 and 2008 (derivation population); one hospital in the Netherlands in 2003-05 and one hospital in the United Kingdom in 2005-06 (validation population).
Intervention We used the derivation population to produce respiratory rate centile charts, and calculated 50th, 75th, 90th, and 97th centiles of respiratory rate at a specific body temperature. Multivariable regression analysis explored associations between respiratory rate, age, and temperature; results were validated in the validation population by calculating diagnostic performance measures, z scores, and corresponding centiles of children with diagnoses of pneumonic LRTI (as confirmed by chest radiograph), non-pneumonic LRTI, and non-LRTI.
Main outcome measure Age, respiratory rate (breaths/min) and body temperature (°C), presence of LRTI.
Results Respiratory rate increased overall by 2.2 breaths/min per 1°C rise (standard error 0.2) after accounting for age and temperature in the model. We observed no interactions between age, temperature, and respiratory rates. Age and temperature dependent cut-off values at the 97th centile were more useful for ruling in LRTI (specificity 0.94 (95% confidence interval 0.92 to 0.96), positive likelihood ratio 3.66 (2.34 to 5.73)) than existing respiratory rate thresholds such as Advanced Pediatrics Life Support values (0.53 (0.48 to 0.57), 1.59 (1.41 to 1.80)). However, centile cut-offs could not discriminate between pneumonic LRTI and non-pneumonic LRTI.
Conclusions Age specific and temperature dependent centile charts describe new reference values for respiratory rate in children with fever. Cut-off values at the 97th centile were more useful in detecting the presence of LRTI than existing respiratory rate thresholds.
Footnotes
Contributors: All authors contributed substantially to the writing of the manuscript. RN developed the protocol, was responsible for the data analysis, and was the main author of the paper. MT developed the protocol and was responsible for data acquisition and critical revision of the manuscript. RP contributed to protocol development, statistical analysis, and revision of the manuscript. MV was responsible for data acquisition and protocol development. HM and RO supervised the protocol development, data analysis, and writing of the manuscript. All authors read and approved the final manuscript. All authors had full access to all of the data in the study and can take full responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: The study was received no funding.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; RN is supported by ZonMW, a Dutch organisation for health research and development, and Erasmus MC Doelmatigheid; RO is supported by an unrestricted grant of Europe Container Terminals BV and by a fellowship grant of the European Society of Pediatric Infectious Diseases in 2010; MT is supported by a National Institute for Health Research (NIHR) programme grant (MaDOx), and the MaDOx programme presents independent research commissioned by NIHR under its Programme Grant for Applied Research funding stream (RP-PG-0407-10347).
Ethical approval: Ethical approval obtained from local Erasmus MC-Sophia Children’s Hospital ethics committee and Coventry local research ethics committee 04/Q2802/115.
Patient consent: Erasmus MC-Sophia’s Children’s Hospital ethics committee waived the requirement of informed consent for the development population. Informed consent was required and given for the two validation populations.
Data sharing: No additional data available.
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