Improvements in Lung Function and Height among Cohorts of 6-Year-Olds with Cystic Fibrosis from 1994 to 2012

Abstract

To characterize spirometry and height changes in cohorts of 6-year-old children with cystic fibrosis (CF). Global Lung Initiative forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and the Centers for Disease Control and Prevention height-for-age (HFA) z-scores were generated for 6-year-old children from the Cystic Fibrosis Foundation Patient Registry each year between 1994 and 2012. Z-score mean differences were analyzed by the t test, and time trends of means were analyzed by least squares regression for all children and for subgroups of sex, F508del mutation genotype, Medicaid insurance, and prenatal/newborn screening identification. Z-score distributions were compared using the 2-sample Kolmogorov-Smirnov test. A total of 11 670 children with CF were studied, of whom 50.5% were males, 50.2% had the F508del/F508del genotype, and 46.6% were insured by Medicaid. Mean HFA, FEV1, and FVC z-scores increased significantly over the period in the entire cohort and in all subgroups (P < .001), but FEV1/FVC z-scores were below normal and did not change significantly. In 2012, children identified by screening had significantly higher mean HFA (P = .002), FEV1 (P < .001), and FVC (P < .001) z-scores compared with children not screened, with 90% of FVC and 71.4% of FEV1z-scores greater than predicted by the normal distribution. FEV1/FVC z-scores were not different between the children who were and were not screened. Consistent, significant increases in HFA, FEV1, and FVC occurred between 1994 and 2012, but FEV1/FVC, a measure of airway obstruction, did not change appreciably during this period. FVC and FEV1z-score distributions suggest that normative equation reference populations underpredict lung volumes of children with CF, but the reasons for this remain unclear.