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.

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. Methods: Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol. Measurements and Main Results: Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 × 10³ cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease. Conclusions: These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.

Rationale: Better understanding of evolution of lung function in infants with cystic fibrosis (CF) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aimed at limiting lung damage and the role of lung function as outcomes in such studies. Objectives: To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation. Methods: Infants diagnosed after newborn screening or clinical presentation were recruited prospectively. FVC, forced expiratory volume in 0.5 seconds (FEV0.5), and forced expiratory flows at 75% of exhaled vital capacity (FEF75) were measured using the raised-volume technique, and z-scores were calculated from published reference equations. Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing. Measurements and Main Results: Thirty-seven infants had at least two successful repeat lung function measurements. Mean (SD) z-scores for FVC were −0.8 (1.0), −0.9 (1.1), and −1.7 (1.2) when measured at the first visit, 1-year visit, or 2-year visit, respectively. Mean (SD) z-scores for FEV0.5 were −1.4 (1.2), −2.4 (1.1), and −4.3 (1.6), respectively. In those infants in whom free neutrophil elastase was detected, FVC z-scores were 0.81 lower (P = 0.003), and FEV0.5 z-scores 0.96 lower (P = 0.001), respectively. Significantly greater decline in FEV0.5 z-scores occurred in those infected with Staphylococcus aureus (P = 0.018) or Pseudomonas aeruginosa (P = 0.021). Conclusions: In infants with CF, pulmonary inflammation is associated with lower lung function, whereas pulmonary infection is associated with a greater rate of decline in lung function. Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF.

BACKGROUND Reported wheeze is the cornerstone of asthma diagnosis. AIMS To determine what parents understand by wheeze. METHODS Two studies were undertaken: (1) Parents of clinic attendees with reported wheeze (n=160) were asked by questionnaire what they understood by “wheeze” and how they knew their child was wheezy. Responses were compared to definitions of wheeze in 12 epidemiology studies and their response options. (2) The extent of agreement of parents' reports (n=139) of acute wheezing in their children and clinicians' findings of “wheeze” and “asthma” was examined. RESULTS (1) “Sound” and “difficulty in breathing” were perceived central to “wheeze”. “What you hear” was not selected by 23% (95% confidence interval (CI) 16–30%). “Whistling” was mentioned by 11% (CI 6–15%) but featured in 11 of 12 epidemiology questionnaires. (2) There was les than 50% agreement between parents' and clinicians' reports of wheeze and asthma. CONCLUSIONS Conceptual understandings of “wheeze” for parents of children with reported wheeze are different from epidemiology definitions. Parents' reports of acute wheeze and clinicians' findings also differ.

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. Methods 143 children aged 0.2–6.5 years with CF from a newborn screened population contributed 444 limited slice annual chest CT scans for analysis that were scored for bronchiectasis and air trapping and analysed as paired scans 1 year apart. Logistic and linear regression models, using generalised estimating equations to account for multiple measures, determined associations between persistence and progression over 1 year and age, sex, severe cystic fibrosis transmembrane regulator (CFTR) genotype, pancreatic sufficiency, current respiratory symptoms, and neutrophilic inflammation and infection measured by bronchoalveolar lavage. Results Once detected, bronchiectasis persisted in 98/133 paired scans (74%) and air trapping in 178/220 (81%). The extent of bronchiectasis increased in 139/227 (63%) of paired scans and air trapping in 121/264 (47%). Radiological progression of bronchiectasis and air trapping was associated with severe CFTR genotype, worsening neutrophilic inflammation and pulmonary infection. Discussion CT-detected structural lung disease identified in infants and young children with CF persists and progresses over 1 year in most cases, with deteriorating structural lung disease associated with worsening inflammation and pulmonary infection. Early intervention is required to prevent or arrest the progression of structural lung disease in young children with CF.