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

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.