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Standard deviation scores of maximal expiratory flow in infants

Lung function testing in infants and toddlers with respiratory disease has developed into a very valuable tool for clinical and research purposes for the very young. Obviously, with the growing awareness that early interventions may contribute to improved long-term outcome in various respiratory disorders, there is a need for objective endpoints to evaluate treatment strategies (1, 2). One of the key issues in evaluating outcome is the availability of valid reference data, especially for maximal flow at functional residual capacity (maxFRC). However, much of the original published normative data for maxFRC had limited external validity, because equipment, techniques, and procedures were not standardized and comparable at that time. With the publication of sex-specific prediction equations for maxFRC in infants by Hoo and colleagues in AJRCCM (3), a major step forward has been made in tackling this issue. The data from this multicenter collaborative study are unique because they are based on a representative population of healthy control subjects, and are the first to detect and describe sex-specific lung function data. Because of its sample size, reliable standard deviation scores can be calculated, which improves expression of lung function parameters considerably. Using these data, differences between study results and between research groups can be quantified, and multicenter studies have become a more attractive option.

However, the accessibility, and hence the widespread use of these reference equations, is currently limited because of their mathematical complexity (due to log-transformation and standard deviation score calculation). We therefore suggest that when publishing such data, authors should provide the necessary software for automatic calculation of Z-scores, and that manufacturers should incorporate such algorithms into the current generation of infant lung function equipment. Indeed, efforts should be made by the ATS/ERS to facilitate provision and/or distribution of such software required to stimulate international standardized procedures in the diagnosis and treatment of respiratory disorders, possibly by encouraging authors to deposit appropriate material in the electronic repository or on a website.

Peter Merkus^a and Monika Gappa^b

^a Erasmus Medical Center Rotterdam, The Netherlands
^b Medizinische Hochschule Hannover, Germany

REFERENCES

1. Gappa M, Ranganathan SC, Stocks J. Lung function testing in infants with cystic fibrosis: lessons from the past and future directions. Pediatr Pulmonol 2001;32:228–245.[CrossRef][Medline]
2. Sly PD, Tepper R, Henschen M, Gappa M, Stocks J. Tidal forced expirations. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society. Eur Respir J 2000;16:741–748.[Abstract]
3. Hoo AF, Dezateux C, Hanrahan JP, Cole TJ, Tepper RS, Stocks J. Sex-specific prediction equations for Vmax(FRC) in infancy: a multicenter collaborative study. Am J Respir Crit Care Med 2002;165:1084–1092.[Abstract/Free Full Text]

We thank Drs. Merkus and Gappa for highlighting the fact that when publishing prediction equations for lung function, they should be available in a suitable format for subsequent routine clinical or research use. We agree with their suggestions and have now developed some add-in macros to be used in Microsoft Excel to automatically calculate the standard deviation (SD) scores for maximal expiratory flow at functional residual capacity (maxFRC) for any infant, together with the expected, and range of expected, values (based on ± 2 SD scores). These scores can be calculated based on either the infant's height or age plus height SD scores, and can be used for interpretation of results either from individual infants or from an entire dataset. This program and instructions on how to install and use the Vmax.xla file can now be downloaded from the online supplement associated with our publication (1) at http://ajrccm.atsjournals.org/ or from section B/Respiratory epidemiology/key papers, at http://www.ich.ucl.ac.uk/ich/html/academicunits/portex/rmp/research1_resp_function.html

The reference dataset comprised 654 measurements of maxFRC from 459 healthy infants. Data were obtained within the first 20 months of life from three centers (London, Indianapolis, and Boston), over a height range of 40–90 cm (1). To facilitate automatic calculations of height SD score when using the macro based on age and height SD score, a selected portion of the Child Growth Foundation reference data (2) (pertaining to the growth charts from 0–20 months of age) has been incorporated into this program.

Similar prediction equations were obtained whether or not data from preterm infants studied shortly after birth (n = 92) were included in this dataset. These equations therefore seem appropriate for calculating an SD score for preterm infants up to 8 weeks corrected postnatal age. However, they may not be appropriate for older preterm infants, since significant reductions in maxFRC SD score have been observed in such infants by 1 year of age, even in the absence of any neonatal or subsequent respiratory disease (3). Wherever possible, users should ascertain whether these equations and the derived score are applicable to their own laboratory, equipment, and local population by undertaking measurements in a group of healthy infants to check whether mean (SD) of the maxFRC SD score from such infants approaches 0 (1). Appropriate use of SD scores, which indicate a "normal" range (± 2 SD score) for maxFRC during infancy, should improve interpretation of both clinical and research studies.

Ah-Fong Hoo, Janet Stocks, Huiqi Pan and Tim J. Cole

Institute of Child Health and Great Ormond Street Hospital NHS Trust London, United Kingdom

REFERENCES

1. Hoo A-F, Dezateux C, Hanrahan JP, Cole TJ, Tepper RS, Stocks J. Sex-specific prediction equations for V'maxFRC in infancy: a multi-center collaborative study. Am J Respir Crit Care Med 2002;165:1084–1092.
2. Freeman JV, Cole TJ, Chinn S, Jones PRM, White EM, Preece MA. Cross sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 1995;73:17–24.[Abstract]
3. Hoo A-F, Dezateux C, Henschen M, Costeloe K, Stocks J. The development of airway function in infancy following preterm delivery. J Pediatr 2002;141:652–658.[CrossRef][Medline]

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