The Thanh Diem Nguyen

Rationale Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants. Objective To assess changes in pulmonary function during the first year of life in CF NBS infants. Methods Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRC_pleth)) and forced expired volume (FEV_0.5) were measured at 3 months and 1 year of age. Main results Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV_0.5 improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p0.5 was only 0.52 (0.89 to 0.15) z-scores less than in controls. LCI and FRC_pleth remained stable throughout the first year of life, being on average 0.8 z-scores higher in infants with CF. Pulmonary function at 1 year was predicted by that at 3 months. Among the 45 CF infants with entirely normal LCI and FEV_0.5 at 3 months, 80% remained so at 1 year, while 74% of those with early abnormalities remained abnormal at 1 year. Conclusions This is the first study reporting improvements in FEV_0.5 over time in stable NBS CF infants treated with standard therapy. Milder changes in lung function occurred by 1 year than previously reported. Lung function at 3 months predicts a high-risk group, who should be considered for intensification of treatment and enrolment into RCTs.

Rationale: With increasing use of infant pulmonary function tests (IPFTs) in both clinical and research studies, appropriate interpretation of results is essential.Objectives: To investigate the potential bias associated with “normalising” IPF by expressing results as a ratio of body size and to develop reference ranges for tidal breathing parameters, passive respiratory mechanics (compliance [C_rs] and resistance [R_rs]) and plethysmographic functional residual capacity (FRC_p) for white infants during the first 2 years of life.Methods: IPFTs were measured using the Jaeger BabyBody system and standardized protocols. Reference equations, adjusted for body size, age, and sex where appropriate, were created using multilevel modeling.Results: The ratio of lung function to body length changes markedly with growth, thereby precluding its use for any outcome. While the ratio of tidal volume and C_rs to body weight remained relatively constant with growth, this was not the case for FRC_p. Even in healthy infants, a strong inverse relationship was observed between lung function/body weight and weight z‐score which could distort interpretation of results in growth‐restricted infants with lung disease, such as cystic fibrosis. Reference equations were derived from 153 healthy white infants on 232 test occasions (median age 35.5 weeks [range: 2.6–104.7]). Crown‐heel length was the strongest predictor of IPF.Conclusions: When reporting IPF, use of size‐corrected ratios should be discouraged, with interpretation instead based on appropriate reference equations. The current equations are applicable to white infants and young children up to 2 years of age, studied using the same commercially available equipment. The extent to which these equations are applicable to infants and young children of other ethnic backgrounds or who are tested with different equipment needs to be established. Pediatr Pulmonol. 2013; 48:370–380.