Lung function is abnormal in 3-month-old infants with cystic fibrosis diagnosed by newborn screening.

BACKGROUND: Long-term benefits of newborn screening (NBS) for cystic fibrosis (CF) have been established with respect to nutritional status, but effects on pulmonary health remain unclear. HYPOTHESIS: With early diagnosis and commencement of standardised treatment, lung function at ∼3 months of age is normal in NBS infants with CF. METHODS: Lung clearance index (LCI) and functional residual capacity (FRC) using multiple breath washout (MBW), plethysmographic (pleth) FRC and forced expirations from raised lung volumes were measured in 71 infants with CF (participants in the London CF Collaboration) and 54 contemporaneous healthy controls age ∼3 months. RESULTS: Compared with controls, and after adjustment for body size and age, LCI, FRC(MBW) and FRC(pleth) were significantly higher in infants with CF (mean difference (95% CI): 0.5 (0.1 to 0.9), p=0.02; 0.4 (0.1 to 0.7), p=0.02 and 0.9 (0.4 to 1.3), p<0.001, z-scores, respectively), while forced expiratory volume (FEV(0.5)) and flows (FEF(25-75)) were significantly lower (-0.9 (-1.3 to -0.6), p<0.001 and -0.7 (-1.1 to -0.2), p=0.004, z-scores, respectively). 21% (15/70) of infants with CF had an elevated LCI (>1.96 z-scores) and 25% (17/68) an abnormally low FEV(0.5) (below -1.96 z-scores). While only eight infants with CF had abnormalities of LCI and FEV(0.5), using both techniques identified abnormalities in 35% (24/68). Hyperinflation (FRC(pleth) >1.96 z-scores) was identified in 18% (10/56) of infants with CF and was significantly correlated with diminished FEF(25-75) (r=-0.43, p<0.001) but not with LCI or FEV(0.5). CONCLUSION: Despite early diagnosis of CF by NBS and protocol-driven treatment in specialist centres, abnormal lung function, with increased ventilation inhomogeneity and hyperinflation and diminished airway function, is evident in many infants with CF diagnosed through NBS by 3 months of age.

Nutritional status and pulmonary outcome in children and young people with cystic fibrosis.

BACKGROUND: Nutrition is closely related to mortality and pulmonary and respiratory muscle function in cystic fibrosis (CF) patients. We initially validated results from a bioelectrical impedance device against dual energy x-ray absorptiometry (DEXA). We then determined whether fat free mass assessed by a portable impedance device rather than body mass index (BMI) better correlated with pulmonary function, respiratory muscle strength and exercise capacity in CF patients. METHODS: Eighteen young people and adults (median age 19, range 12-39 years) with CF had dual energy X-ray absorptiometry and direct segmental multi-frequency impedance analysis. Body composition, pulmonary function, respiratory muscle function and exercise tolerance using the impedance device were measured in 29 young people with CF with median age 15 (range 12-19) years. MAIN FINDINGS: There was a significant correlation between impedance and absorptiometry results (r2 = 0.947). Fat free mass correlated with the forced vital capacity z-score (r = 0.442, p = 0.016), maximal inspiratory pressure (r = 0.451, p = 0.014) and exercise tolerance (r = 0. 707, p < 0.001). BMI z-scores did not significantly correlate with pulmonary or respiratory muscle function. Subjects with a fat free mass z-score of ≤2 had a lower forced expiratory volume in 1 s z-score (p = 0.007), lower forced vital capacity z-score (p = 0.001), higher residual volume z-score (p = 0.042), lower maximal inspiratory pressure (p = 0.039), more days of intravenous antibiotics per year (p = 0.016) and a higher rate of chronic infections (p = 0.006). PRINCIPAL CONCLUSIONS: Fat-free mass measured by impedance correlated better with pulmonary and respiratory muscle function and exercise capacity than BMI.