Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year.

BACKGROUND: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. METHODS: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. RESULTS: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. CONCLUSIONS: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes.

[Real-world effectiveness of ivacaftor in children with cystic fibrosis and the G551D mutation]. / Efectividad de ivacaftor en vida real en niños con fibrosis quística y mutación G551D.

INTRODUCTION: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has been shown to improve the nutritional status and lung function of cystic fibrosis patients with the G551D mutation in clinical trials. The objective of this study was to describe the real-world progress of children receiving ivacaftor. METHODS: We describe the real-world progress of four children with cystic fibrosis and the F508del/G551D genotype comparing data during ivacaftor treatment with baseline and with the year before commencing treatment. RESULTS: Our sample comprised 4 children aged between 6 and 14 years and including one with a recent diagnosis of CF and other with persistent Mycobacterium abscessus (M. abscessus) and recurrent allergic bronchopulmonary aspergillosis. The baseline FEV1 was 58.5% to 81.8% of the predicted value, and ivacaftor was taken for a mean 24 months (range, 12-30 months). All patients experienced a significant and sustained improvement in lung function. Compared to baseline, the weight z-score improved by 1.53 points, and the BMI z-score by 1.6 points. Compared to the year before starting ivacaftor, the frequency of Pseudomonas aeruginosa (P. aeruginosa) isolates decreased (-0.4/patient/year), as did the number of respiratory exacerbations (-1.8/patient/year). The weight-adjusted dose of lipase per kilogram decreased progressively in all patients. In 1 patient, a previously persistent M. abscessus infection and recurrent allergic bronchopulmonary aspergillosis resolved during treatment. CONCLUSIONS: Children with cystic fibrosis and the F508del/G551D genotype receiving treatment with ivacaftor experienced a real-world improvement in lung function, nutritional status, respiratory exacerbations, isolation of P. aeruginosa, and dose of pancreatic enzymes.

Randomized controlled trial of fluticasone in preschool children with intermittent wheeze.

Preschool children with intermittent wheeze are often prescribed inhaled corticosteroids, although there is no proven benefit. Measurement of airway resistance by the interrupter technique can be used to objectively assess response to treatment. If lung function improves, treatment may be justified. Children with intermittent wheeze aged 2 to