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.

Rationale: Progressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies. Objectives: To measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation. Methods: Infants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied. Forced vital capacity, FEV_0.5, and forced expiratory flows at 75% of exhaled vital capacity (FEF₇₅) were measured using the raised-volume rapid thoracoabdominal compression technique. Forty-eight hours later, infants with CF had bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. Measurements and Main Results: In the CF group, the deficit in FEV_0.5 z score increased by −0.77 (95% confidence interval, −1.14 to −0.41; P < 0.001) with each year of age. The mean FEV_0.5 z score did not differ between infants with CF and healthy control subjects less than 6 months of age (−0.06 and 0.02, respectively; P = 0.87). However, the mean FEV_0.5 z score was lower by 1.15 in infants with CF who were older than 6 months of age compared with healthy infants (P < 0.001). FVC and FEF₇₅ followed a similar pattern. Pulmonary infection and inflammation in BAL samples did not explain the lung function results. Conclusions: Lung function, measured by forced expiration, is normal in infants with CF at the time of diagnosis by newborn screening but is diminished in older infants. These findings suggest that in CF the optimal timing of therapeutic interventions aimed at preserving lung function may be within the first 6 months of life.

Rationale: In cystic fibrosis (CF), lung disease is the predominant cause of morbidity and mortality. Little is known about the spectrum of structural abnormalities on CT scans from patients with CF with severe advanced lung disease (SALD). No specific CT scoring system for SALD is available. Objectives: To design a quantitative CT scoring system for SALD, to determine the spectrum of structural abnormalities in patients with SALD and to correlate the SALD system with an existing scoring system for mild CF lung disease and pulmonary function tests (PFTs). Methods: 57 patients with CF contributed one CT made during screening for lung transplantation. For the SALD system, lung tissue was divided into four components: infection/inflammation (including bronchiectasis, airway wall thickening, mucus and consolidations), air trapping/hypoperfusion, bulla/cysts and normal/hyperperfused tissue. The volume proportion of the components was estimated on a 0–100% scale; mean volumes for the whole lung were computed. Scores were correlated with Brody-II scores and PFTs. Results: The SALD system identified a wide spectrum of structural abnormalities ranging from predominantly infection/inflammation to predominantly air trapping/hypoperfusion. SALD infection/inflammation scores correlated with Brody-II scores (r_s = 0.36–0.64) and SALD normal/hyperperfusion scores correlated with forced expiratory volume in 1 s (FEV₁; r_s = 0.37). Reproducibility for both systems was good. Conclusions: A CT scoring system was developed to characterise the structural abnormalities in patients with SALD. A wide spectrum was observed in SALD, ranging from predominantly air trapping to predominantly infection/inflammation-related changes. This spectrum may have clinical implications for patients with SALD.