Published ahead of print on October 17, 2008, doi:10.1164/rccm.200805-700OC Am. J. Respir. Crit. Care Med., Volume 178, Number 12, December 2008, 1262-1270 A more recent version of this article appeared on December 15, 2008
Submitted on May 8, 2008 Cross-sectional and Longitudinal Spirometry in Children and Adolescents: Interpretative StrategiesPhilip H Quanjer1*,1 Sophia's Children's Hospital, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands, 2 Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands, 3 Department of Physiology, University of Tartu, Tartu, Estonia, 4 Department of Pediatrics, Division of Respiratory Medicine, Radboud University Medical Centre, Nijmegen, Netherlands, 5 Hankinson Consulting, Valdosta, Georgia, United States, 6 Centre for Environmental Health Research, National Institute for Public Health and the Environment, Bilthoven, Netherlands, 7 Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands, 8 Biometry and Data Management, ZKS (CCT - Center of Clinical Trials), University Medical Center, Freiburg, Germany, 9 Klinik fur Kinder- und Jugendmedizin, Zentrum fur Kinder und Frauen Kinderklinik Stadtisches Klinikum, Karlsruhe, Germany * To whom correspondence should be addressed. E-mail: pquanjer{at}xs4all.nl.
Rationale: Single and serial spirometric data are commonly compared to predicted values to assess pulmonary function and normal lung growth. Objectives: Do reference equations adequately describe pulmonary function in a population and in growing individuals? Measurements and Main Results: We applied 5 sets of reference equations with appropriate age ranges to cross-sectional data of FEV1, FVC and FEV1/FVC from the USA, Estonia and the Netherlands (1487 boys, 1340 girls, 6-18 yr), and to serial measurements in Dutch (6-19 yr, 430 girls, 769 boys) and in German and Austrian children (6-13 yr, 1305 girls, 1303 boys). Compared with reference equations from Polgar and Zapletal cross-sectional FEV1 and FVC declined between ages 6-12, then increased leading to a spurious change of up to 25% predicted; this pattern was most pronounced in boys. In cross-sectional data this trend was much weaker when using reference equations from Hankinson, Quanjer and Stanojevic, and these equations provided a good fit from age 12 upward. In longitudinal data, i.e. within individuals, the trend was more pronounced for FEV1 in boys than in girls. No set of equations provided satisfactory lower limits of normal, Hankinson and Stanojevic performing best. Conclusion: Spirometric reference equations that use only height are unsuitable. Those that incorporate height and age demonstrate some discrepancy with longitudinal data. Failure to take these spurious trends into account leads to significant errors in estimating the natural course of respiratory disease, in allocating patients to treatment groups or in assessing long-term effects of drug intervention in schoolchildren and adolescents. Key words: spirometry • reference values • cross-sectional studies • longitudinal studies • growth
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