Reference percentiles for FEV(1) and BMI in European children and adults with cystic fibrosis

Abstract

Background: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV(1) and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV(1) and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents.

Methods: 34859 FEV(1) and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV(1) and with the WHO 2007 normative values for BMI.

Results: FEV(1) and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV(1) were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany).

Conclusion: The CF specific percentile approach applied to FEV(1) and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

Figure 1

Cystic fibrosis specific FEV₁percentiles according to age and sex, in males (a) and females (b). The grey zone shows the 95% confidence interval for the median percentile; and the dashed lines correspond to reference values obtained in US patients.

Figure 2

Cystic fibrosis specific BMI percentiles according to age, in male (a) and female (b) patients. The grey zone shows the 95% confidence interval for the median percentile. The dashed line shows the normative median from the WHO 2007 definition.

Figure 3

Age and country cystic fibrosis specific FEV₁(a) and BMI (b) percentile distributions in European cystic fibrosis patients. Boxes extend from the first to the last quartile,with the median as a thick line, and whiskers over the whole range. Notches correspond with the 95% Bonferroni adjusted (12 comparisons) confidence intervals for the country median, a star indicating that the expected median percentile (50%) is not within the confidence interval. Definitions: Infants: 2 to 6 years old; Children: 6 to 13 years old; Teenagers: 13 to 20 years old; Adults: over 20 years old.