Novel end points for clinical trials in young children with cystic fibrosis.

Cystic fibrosis (CF) lung disease commences early in the disease progression and is the most common cause of mortality. While new CF disease-modifying agents are currently undergoing clinical trial evaluation, the implementation of such trials in young children is limited by the lack of age-appropriate clinical trial end points. Advances in infant and preschool lung function testing, imaging of the chest and the development of biochemical biomarkers have led to increased possibility of quantifying mild lung disease in young children with CF and objectively monitoring disease progression over the course of an intervention.

Risk factors for bronchiectasis in children with cystic fibrosis.

Background: Bronchiectasis develops early in the course of cystic fibrosis, being detectable in infants as young as 10 weeks of age, and is persistent and progressive. We sought to determine risk factors for the onset of bronchiectasis, using data collected by the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) intensive surveillance program.

Methods: We examined data from 127 consecutive infants who received a diagnosis of cystic fibrosis after newborn screening.

Assessment of early bronchiectasis in young children with cystic fibrosis is dependent on lung volume.

Objective: The aim of this study was to determine whether assessment of early CT scan-detected bronchiectasis in young children with cystic fibrosis (CF) depends on lung volume.

Methods: This study, approved by the hospital ethics committee, included 40 young children with CF from a newborn screened population contributing paired volume-controlled inspiratory and expiratory volumetric chest CT scans acquired under general anesthesia while clinically stable. Bronchiectasis was assessed with a semiquantitative CT scan score in inspiration and expiration, and the sensitivity of the expiratory CT scan to detect bronchiectasis was compared with the inspiratory CT scan by sensitivity and intraclass correlation coefficient analysis and Bland-Altman plots.

Distribution of early structural lung changes due to cystic fibrosis detected with chest computed tomography.

Objective: To examine the distribution of early structural lung changes in clinically stable infants and young children with cystic fibrosis using chest computed tomography (CT).

Study Design: This cross-sectional study included 62 children aged 1-6 years with volume-controlled volumetric chest CT scans performed under general anesthesia as part of an early surveillance program. Each lobe was scored for presence and extent of bronchiectasis, mucus plugging, and air trapping using a semiquantitative score.

Progression of early structural lung disease in young children with cystic fibrosis assessed using CT.

Background: Cross-sectional studies implicate neutrophilic inflammation and pulmonary infection as risk factors for early structural lung disease in infants and young children with cystic fibrosis (CF). However, the longitudinal progression in a newborn screened population has not been investigated.

Aim: To determine whether early CF structural lung disease persists and progresses over 1 year and to identify factors associated with radiological persistence and progression.

Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening.

Background: In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.

Methods: Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed.

Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis.

We aimed to determine whether myeloperoxidase (MPO) is the main peroxidase present in the airways of children with cystic fibrosis (CF) and to assess which oxidants it produces and whether they are associated with clinical features of CF. Children with CF (n=54) and without CF (n=16) underwent bronchoscopy and bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. BAL fluid was analyzed for MPO, halogenated tyrosines as markers of hypohalous acids, thiocyanate, and protein carbonyls.

Bronchiectasis in an asymptomatic infant with cystic fibrosis diagnosed following newborn screening.

Many countries have introduced newborn screening for cystic fibrosis to facilitate diagnosis prior to the development of lung disease. Although most infants with cystic fibrosis are asymptomatic from a respiratory point of view at diagnosis, structural lung disease has been detected by computed tomography. We present a case of an asymptomatic infant with cystic fibrosis diagnosed following newborn screening who had endobronchial infection with Pseudomonas aeruginosa and radiological evidence of bronchiectasis at 3 months of age.

Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

Rationale: The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis.

Objectives: To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS.