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Background: Chest computerized tomography (CT) scores are associated with the frequency of future pulmonary exacerbations in people with cystic fibrosis (CF). However, cut-off values to identify children with mild lung disease with different risks for frequent future pulmonary exacerbations have not been identified., Methods: Chest CT scans were assessed using the Brody score for participants of the Pulmozyme Early Intervention Trial (PEIT) and Wisconsin Randomized Clinical Trial of CF Newborn Screening (WI RCT). We determined the area under the receiver operating characteristic (ROC) curve for Brody scores and forced expiratory volume in 1 s (FEV 1 ) to compare with the frequency of pulmonary exacerbations up to 10 years later., Results: There were 60 participants in the PEIT with mean (SD) age 10.6 (1.7) years at the time of the CT and 81 participants in the WI RCT with mean age 11.5 (3.0) years. The Brody score cut-off that best identified children at-risk for ≥0.3 annual pulmonary exacerbations was 3.6 in the PEIT and 2.1 in the WI RCT. There were no statistical differences between ROC curves for the Brody CT score and FEV 1 % predicted in either study (P ≥ 0.4)., Conclusions: CT score cut-off values that identify children with CF with mild lung disease at different risks for frequent pulmonary exacerbations over an extended follow up period are similar in separate cohorts. Brody scores and FEV 1 % predicted have similar abilities to identify these children, suggesting that FEV 1 % predicted alone may be adequate for predicting future frequency of pulmonary exacerbations., (© 2018 Wiley Periodicals, Inc.)

Rationale: People with CF treated with IV antibiotics for a pulmonary exacerbation (PEx) frequently fail to recover to baseline FEV 1 . The long-term impact of these events has not been studied., Objectives: To determine if a patient's spirometric recovery after a PEx is associated with time to next PEx within 1 year, the spirometric recovery after the next PEx, and/or the number of PEx episodes in the next 3 years., Methods: We used data from the CF Foundation Patient Registry from 2004 to 2011. We randomly selected one PEx per patient that met inclusion/exclusion criteria. Patients were defined as Non-Responders if their best FEV 1 (in liters) recorded in the 3 months after the PEx was <90% of the best FEV 1 (in liters) in the 6 months before the PEx. We compared Responders and Non-Responders using multivariable regression models., Results: We randomly chose 13 954 PEx episodes that met inclusion/exclusion criteria. A total of 2 762 (19.8%) patients were classified as Non-Responders. Non-Responders had a shorter median time to the next PEx, 235 (95%CI 218, 252) days, versus >365 days for Responders. Thirty-four percent of Non-Responders at the initial PEx were also Non-Reponders at the next PEx, versus 20% of Responders at the initial PEx. Non-Responders had more PEx episodes over the next 3 years, 4.99 (95%CI 4.84, 5.13), than Responders, 3.46 (95%CI 3.41, 3.51)., Conclusions: Poor recovery after a PEx is associated with a shorter time to the next PEx, increased risk of poor recovery at a second PEx, and more frequent subsequent PEx treatments., (© 2017 Wiley Periodicals, Inc.)

Rationale: Abnormalities on chest computed tomography (CT) in children with cystic fibrosis (CF) have been shown to correlate with short-term measures of lung disease. Chest CT scores offer promise as a potential surrogate end point in CF; however, there is limited information available on the ability of chest CT scores to predict future morbidity., Objectives: Determine whether chest CT scores are associated with the rate of pulmonary exacerbations over the next 10 years., Methods: Ten years of follow-up data were obtained from the CF Foundation Patient Registry for 60 children enrolled in the Pulmozyme Early Intervention Trial and who had chest CT scans at baseline., Measurements and Main Results: Multivariable Poisson regression was used to compare Brody CT scores and the number of pulmonary exacerbations in the following 10 years. At the time of the chest CT, the mean (SD) age was 10.6 (1.7) years. A 1-point increase in the Brody CT score was associated with an increase in the mean (95% confidence interval) rate of pulmonary exacerbations of 1.39 (1.15, 1.67) (P < 0.001). Brody CT scores were more strongly associated with the number of pulmonary exacerbations than FEV1 % predicted at the time of the chest CT (P = 0.037 by chi-square test)., Conclusions: There is a significant association between Brody CT scores and the rate of pulmonary exacerbations up to 10 years later. This association is stronger than for FEV1 obtained at the time of the CT, suggesting that chest CT scores offer improved ability to predict future outcomes.

Rationale: Previous studies of risk factors for progression of lung disease in cystic fibrosis (CF) have suffered from limitations that preclude a comprehensive understanding of the determinants of CF lung disease throughout childhood. The epidemiologic component of the 27-year Wisconsin Randomized Clinical Trial of CF Neonatal Screening Project (WI RCT) afforded us a unique opportunity to evaluate the significance of potential intrinsic and extrinsic risk factors for lung disease in children with CF., Objectives: Describe the most important intrinsic and extrinsic risk factors for progression of lung disease in children with CF., Methods: Variables hypothesized at the onset of the WI RCT study to be determinants of the progression of lung disease and potential risk factors previously identified in the WI RCT study were assessed with multivariable generalized estimating equation models for repeated measures of chest radiograph scores and pulmonary function tests in the WI RCT cohort., Measurements and Main Results: Combining all patients in the WI RCT, 132 subjects were observed for a mean of 16 years and contributed 1,579 chest radiographs, and 1,792 pulmonary function tests. The significant determinants of lung disease include genotype, poor growth, hospitalizations, meconium ileus, and infection with mucoid Pseudomonas aeruginosa. The previously described negative effect of female sex was not seen., Conclusions: Modifiable extrinsic risk factors are the major determinants of progression of lung disease in children with CF. Better interventions to prevent or treat these risk factors may lead to improvements in lung health for children with CF.

Progression of lung disease is a major event in children with cystic fibrosis (CF), but regional differences in its evolution are unclear. We hypothesized that regional differences occur beginning in early childhood. We examined this issue by evaluating 132 patients followed in the Wisconsin Neonatal Screening Project between 1985 and 2010. We scored chest X-rays obtained every 1-2 years with the Wisconsin chest X-ray system, in which we divided the lungs into quadrants, and gave special attention to ratings for bronchiectasis (BX) and nodular/branching opacities. We compared the upper and lower quadrant scores, and upper right and left quadrant scores, as patients aged using a multivariable generalized estimation equation (GEE) model. We did a confirmatory analysis for a subset of 81 patients with chest computerized tomography (CT) images obtained in 2000 and scored using the Brody scoring system. The chest X-ray analysis shows that the upper quadrants have higher BX (P<0.001) and nodular/branching opacities (P<0.001) scores than the lower quadrants. CT analysis likewise reveals that the upper quadrants have more BX (P=0.02). Patients positive for mucoid PA showed significantly higher BX scores than patients with non-mucoid PA (P=0.001). Chest X-ray scoring also revealed that the upper right quadrant has more BX (P<0.001) than the upper left quadrant, and CT analysis was again confirmatory (P<0.001). We conclude that pediatric patients with CF develop more severe lung disease in the upper lobes than the lower lobes in association with mucoid PA infections and also have more severe lung disease on the right side than on the left side in the upper quadrants. A variety of potential explanations such as aspiration episodes may be clinically relevant and provide insights regarding therapies., (Copyright © 2011 Wiley Periodicals, Inc.)

Rationale: Chest CT scans detect structural abnormalities in children with cystic fibrosis (CF), even when pulmonary function tests (PFTs) are normal. The use of chest CT is limited in clinical practice, because of concerns over expense, increased resource utilization, and radiation exposure. Quantitative chest radiography scores are useful in detecting mild lung disease, but whether they are sensitive to the presence of CT scan abnormalities has not been evaluated., Objective: To determine in a cross-sectional study if quantitative chest radiography is a more sensitive marker of chest CT abnormalities than other lung disease surrogates., Methods: Brody chest CT scores were calculated for 81 children enrolled in the Wisconsin CF Neonatal Screening Project. We determined the sensitivity for Wisconsin (WCXR) and Brasfield (BCXR) chest radiography scores, PFTs, positive cultures for P. aeruginosa (PA), and parental report of symptoms to detect a Brody score worse than the median score for study participants., Measurements and Main Results: The mean FEV(1) for the study population was 91% predicted. Abnormal WCXR and BCXR scores had the highest sensitivity to detect a chest CT score worse than the median; abnormal PFTs, parental report of symptoms, and the presence of PA had much lower sensitivity (P < 0.001)., Conclusions: In this cross sectional study, quantitative chest radiography has excellent sensitivity to detect an abnormal chest CT and may have a role in monitoring lung disease progression in children with CF., (Copyright © 2011 Wiley Periodicals, Inc.)

Rationale: Most children with cystic fibrosis (CF) experience a slow decline in spirometry, although some children continue to be at risk for more significant lung disease progression. Chest computed tomography (CT) scans have been shown to be more sensitive to changes in lung disease than spirometry and may provide a means for predicting future lung disease progression., Objectives: We hypothesized that Brody chest CT scan scores obtained in 2000 in a prospectively monitored cohort of children with CF would be associated with the most recent measures of lung disease severity., Methods: Brody chest CT scan scores were calculated for 81 children enrolled in the Wisconsin CF Neonatal Screening Project. Multivariable linear regression was used to determine associations between Brody scores and the most recent (age 21 yr or June 30, 2010, whichever was later) measures of CF lung disease., Measurements and Main Results: The mean observation time after the chest CT scan was 7.5 years. Brody chest CT scan scores were significantly associated with the most recent measures of spirometry (P < 0.001) and Wisconsin and Brasfield chest radiograph scores (P < 0.001). The strength of this association was much stronger than spirometry obtained near the time of the chest CT scan (P < 0.01) but not chest radiograph scores., Conclusions: Chest CT scan scores are associated with future lung disease severity, and quantitative chest imaging(chest CT scan and chest radiograph scores) is more strongly associated with future lung disease severity than measures of spirometry. These findings may help clinicians identify patients at risk of future lung disease progression.

The proportion of insufficient sweat tests after positive newborn screening for cystic fibrosis was determined. Infants ≤ 3 months old had a mean (± standard deviation) rate of 7.2% (± 7.6) (range, 0% to 40%). Collection methods did not affect the rates. The high and variable rates indicate a need for quality improvement., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: Chronic pulmonary infection with Pseudomonas aeruginosa (PA) is responsible for significant morbidity and mortality in cystic fibrosis (CF). Because of the limited studies evaluating early exposure and the progression of genetic variability of PA, our goal was to assess PA in young children with CF followed in two clinic types., Methods: A total of 39 infants with CF diagnosed through newborn screening were randomly assigned to either a segregated (PA-free) or mixed (PA-positive) clinic at two different CF centers, one of which replaced an older, mixed clinic where nosocomial acquisition was suspected. Oropharyngeal (OP) swab cultures were examined with subsequent genotyping to characterize the strains of PA isolated., Results: We found that 13/21 segregated clinic patients and 14/18 mixed clinic patients showed positive PA, with median acquisition ages of 3.3 and 2.2 years, respectively (P = 0.57). The median time to PA acquisition, however, was significantly longer in the new clinic with proper hygiene precautions compared to an old site (5.0 years vs. 1.7 years, P < 0.001). The majority of subjects isolated a single genotype of PA or AP-PCR types during the study period with eight subjects clearing the isolate after only one positive culture. The development of chronic colonization yielded the predominance of a single major genotype or AP-PCR type., Conclusions: Segregation of infants and young children with CF in PA-negative or PA-positive clinics did not alter the time to first PA isolation in this randomized assessment of facilities with hygienic precautions. During the early infection period where PA is first isolated in young children with CF, patients cleared different PA strains until a predominant strain established permanent colonization.

Background: With the rapid implementation of cystic fibrosis (CF) newborn screening (NBS), quality improvement (QI) has become essential to identify and prevent errors. Using Process Failure Modes and Effects Analysis (PFMEA), we adapted this method to determine if it could be applied to discover and rank high priority QI opportunities., Methods: Site visits to three programmes were conducted, and PFMEA exercises were accomplished in Colorado, Massachusetts and Wisconsin with 23 experienced professionals. During each of these comprehensive sessions, participants identified and ranked potential failures based on severity, occurrence and detection to calculate risk priority number (RPN) values., Results: A total of 96 failure modes were generated and ranked in a list of the 20 riskiest problems that show no significant discordances by site, although there were differences by profession of the rater, particularly nurses., Conclusions: Our results illustrate that the PFMEA method applies well to CF NBS and that steps requiring communication and information transfer are perceived to be the highest risks. The number of identified failures makes and their potential impact demonstrate considerable overall risk and a need for ongoing QI., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: A comparison of the longitudinal progression of lung disease in cystic fibrosis patients identified through newborn screening (NBS) in cohorts located in two different countries has never been performed and was the primary objective of this study., Methods: The study included 56 patients in Brittany diagnosed through NBS between 1989 and 1994 and 69 similar patients in Wisconsin between 1985 and 1994. The onset and progression of lung disease was radiographically quantified using the Wisconsin Chest X-ray (WCXR) scoring system. A single pediatric pulmonologist blinded to all identifiers scored the films., Results: Generalized estimating equation analyses adjusted for age, genotype, sex, pancreatic insufficiency, and meconium ileus showed worse WCXR scores in Brittany patients compared to Wisconsin patients (average score difference=4.48; p<0.001). Percent predicted FEV1 was also worse among Brittany patients (p<0.001)., Conclusions: The finding of milder radiographically-quantified lung disease using the WCXR scoring system, as well as better FEV1 values, may be explained by variations in nutrition, environmental exposures, or healthcare delivery.

Purpose: To correlate the severity of bronchiectasis in children with cystic fibrosis with clinical and microbiologic variables in order to clarify risk factors for the development of irreversible lung disease., Materials and Methods: After institutional review board approval and parental informed consents were obtained, a HIPAA-compliant longitudinal epidemiologic evaluation was performed in patients with cystic fibrosis who were enrolled in the Wisconsin trial of newborn screening from 1985 to 2009. Thin-section chest computed tomography (CT) was used in a prospective cross-sectional design to study patients ranging in age from 6.6 to 17.6 years (mean, 11.5 years). Thin-section CT scores were determined objectively on coded images by multiple raters in a standardized fashion. Microbiologic data were obtained by means of culture of respiratory secretions by using methods for differentiation of Pseudomonas aeruginosa (PA) as either nonmucoid or mucoid., Results: Eighty-three percent of patients (68 of 82) showed bronchiectasis of varying severity. Of 12 potential risk factors, only respiratory infection with mucoid PA correlated significantly with bronchiectasis (P = .041)., Conclusion: The severity of bronchiectasis in children with cystic fibrosis is significantly related to respiratory infection with mucoid PA; attempts to prevent bronchiectasis should include reducing exposure to and early eradication of PA.

Objectives: To ensure that each newborn receives an equitable test of the highest possible sensitivity, we recognized the necessity to reassess immunoreactive trypsinogen and DNA issues in cystic fibrosis newborn screening algorithms. Our objectives included clarification of various factors that influence immunoreactive trypsinogen concentrations and resolution of long-standing questions about variations in immunoreactive trypsinogen levels among newborns., Methods: Immunoreactive trypsinogen data on 660443 newborns who were born between July 1, 1994, and June 30, 2004, were abstracted from the Wisconsin State Laboratory of Hygiene databases and deidentified for analysis. Using a compiled data set, we analyzed various demographic characteristics to determine their role, if any, in immunoreactive trypsinogen variation. Specifically, season of birth, reagent lot, and birth weight were examined. Sensitivities of the most common cystic fibrosis newborn screening protocols, namely immunoreactive trypsinogen/immunoreactive trypsinogen and immunoreactive trypsinogen/DNA, were also investigated., Results: Mean and 95th percentile immunoreactive trypsinogen levels were shown to vary by both season and reagent lot number and affect sensitivity of the assay. Low birth weight infants had significantly higher immunoreactive trypsinogen values than normal birth weight infants. Sensitivities were also found to vary on the basis of the algorithm used, with the highest sensitivity of 96.2% calculated for an immunoreactive trypsinogen/DNA protocol with 23 cystic fibrosis transmembrane conductance regulator mutation analyses compared with 80.2% with the immunoreactive trypsinogen/immunoreactive trypsinogen method used in 9 states., Conclusions: Floating, rather than fixed, cutoff values for the initial immunoreactive trypsinogen portion of any cystic fibrosis newborn screening protocol are generally necessary on the basis of the seasonal and reagent lot variations observed. Because of its lower sensitivity, immunoreactive trypsinogen/immunoreactive trypsinogen does not optimize detection of patients with cystic fibrosis.

Introduction: Computerized tomography (CT) scanning shows promise as an outcome surrogate for cystic fibrosis (CF) lung disease progression. The scoring system used to convert the CT image to numeric data is an essential determinant of the performance of CT scanning., Methods: Three radiologists independently scored 16 high-resolution CT scans performed on children in the Wisconsin CF Neonatal Screening Project. The test scans were selected to provide a broad range of disease severity. The scoring system provided subscores for the presence and severity of 5 findings of CF lung disease. The sum of the subscores provided a total score. The CT scans were then read again by each of the radiologists at least 11 months later. Using Mixed Effects Linear Model Analysis, the sources of error (scan-to-scan variation, interrater variance, and intrarater variance) were calculated., Results: For the total score, the scan-to-scan variation was 14.48, interrater variance was 0.28, and intrarater variance was 0.45, with an overall reproducibility of 95%. The square root of scan-to-scan variance, a measure of sensitivity, was 3.81. Evaluation of the subscores showed higher reproducibility for bronchiectasis and hyperinflation (95% and 88%, respectively). The bronchiectasis score was more sensitive than the air-trapping score (1.46 vs. 0.89)., Discussion: This system was developed to provide a reproducible method that could be used to evaluate the lobar location, severity, and extent of a broad spectrum of CT features of CF lung disease, especially in children. This study demonstrates that the overall score is both sensitive to variation in the severity of lung disease and reproducible.

Background: Although there are more than 1000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, most of them are uncommon and only limited information exists regarding genotype-pulmonary phenotype relationships., Methods: We determined and classified the CFTR mutations using denaturing high-performance liquid chromatography and developed new, quantitative methods to categorize pulmonary phenotypes., Results: Two novel alleles were discovered, namely G1047R and 1525-2A-->G, which were accompanied by F508del and G551D mutations, respectively. Assessment of numerous options revealed that CF pulmonary phenotype categorization in children cannot be accomplished with clinical or pulmonary function data but is facilitated by longitudinal quantitative chest radiology. It was most useful to categorize pulmonary disease status by evaluating the typical pattern of abnormalities in patients homozygous for the F508del mutation, and then compare patients with minor mutations to this typical CF pulmonary phenotype. By this method, both patients with novel mutations have pulmonary phenotypes typical of F508del homozygotes. However, patients with class IV mutations (e.g., R347P) or with pancreatic sufficiency showed serial chest radiographs that were atypically mild., Conclusions: Longitudinal quantitative chest radiography provides a new strategy for CF pulmonary phenotype categorization that should be useful for genotype-phenotype delineation in individual patients and in both epidemiologic studies and clinical trials involving groups of children with CF.

Objective: To generate and examine evidence in support of diagnosing cystic fibrosis (CF) early through newborn screening (NBS)., Study Design: Using a randomized controlled trial with unique unblinding/surveillance, we evaluated patients with CF receiving similar treatment after assignment to an early diagnosis (screened) group or to a control group. Outcomes studied at diagnosis and longitudinally included measures of nutritional status and lung disease., Results: Assessment of patients with CF without meconium ileus who had pancreatic insufficiency revealed marked differences in age and condition at diagnosis--screened patients had significantly better length/height, weight, and head circumference. Follow-up evaluation for 16 years showed that height and weight differences persisted long term. Although screened patients had better chest x-ray scores at diagnosis, our trial suggests that the effects of confounders such as Pseudomonas aeruginosa infections led to deterioration of their scores after 10 years, but there were no significant differences between the 2 CF/pancreatic insufficiency subgroups., Conclusions: Early diagnosis of CF and aggressive nutritional management can prevent malnutrition and growth failure. Although CF NBS provides a potential opportunity for better pulmonary outcomes, it appears that other factors can predominate over time in pulmonary prognosis. Overall, the Wisconsin trial is positive and provides enough evidence for routine CF NBS.

Context: Although Pseudomonas aeruginosa is the most common virulent respiratory pathogen in cystic fibrosis (CF), the longitudinal development of P aeruginosa infection and its effect on antibody responses and lung disease progression in children with CF remain unclear., Objective: To prospectively examine the epidemiology of P aeruginosa infection and its impact on CF pulmonary morbidity., Design, Setting, and Patients: We prospectively evaluated 56 CF patients at 2 CF centers in Madison and Milwaukee, Wis, from birth up to age 16 years between April 15, 1985, and April 15, 2004, with diagnoses made through the Wisconsin CF Neonatal Screening Project., Main Outcome Measures: Timing of nonmucoid P aeruginosa and mucoid P aeruginosa acquisition was assessed by first positive result. Longitudinal development from no P aeruginosa to nonmucoid P aeruginosa and from nonmucoid P aeruginosa to mucoid P aeruginosa was examined. Outcome measurements included antibody titers, respiratory symptoms, quantitative chest radiography, and pulmonary function tests., Results: Sixteen patients (29%) acquired nonmucoid P aeruginosa in the first 6 months of life. The age-specific prevalence of mucoid P aeruginosa increased markedly from age 4 to 16 years. Nonmucoid and mucoid P aeruginosa were acquired at median ages of 1.0 and 13.0 years, respectively. In contrast with the short transition time from no P aeruginosa to nonmucoid P aeruginosa, the transition time from nonmucoid to mucoid P aeruginosa was relatively long (median, 10.9 years) and could be slightly extended by brief/low anti-P aeruginosa antibiotic treatment. Antibody titers increased with both transitions, but the deterioration in cough scores, chest radiograph scores, and pulmonary function correlated best with transition from nonmucoid to mucoid P aeruginosa., Conclusions: Early prevention and detection of nonmucoid and mucoid P aeruginosa are critical because of early acquisition and prevalence. There is a window of opportunity for suppression and possible eradication (by aggressive anti-P aeruginosa treatment) of initial nonmucoid P aeruginosa. Mucoid P aeruginosa plays a much greater role in CF lung disease progression than nonmucoid P aeruginosa. Antibody titers, cough scores, and chest radiographs are early signs of nonmucoid P aeruginosa and especially mucoid P aeruginosa stages.

Although meconium ileus (MI) is the earliest manifestation of cystic fibrosis (CF), and is associated with poorer growth, the longitudinal pulmonary progression of CF children with MI is not clear. To test the hypothesis that MI is associated with worse pulmonary outcomes, we prospectively compared from diagnosis to 12 years of age 32 CF children with MI to 50 CF children without MI who were diagnosed during early infancy through neonatal screening. Pulmonary outcome measures included respiratory symptoms, respiratory infections, pathogens, antibiotic usage, hospitalizations, quantitative chest radiology, spirometry, and lung volume determinations. Obstructive lung disease was defined as percent predicted spirometry values below the lower limits of normal. Longitudinal analyses revealed no significant differences in cough, wheezing, respiratory infections, prevalence of and median times to acquisition of Pseudomonas aeruginosa or Staphylococcus aureus, antibiotic usage, and chest radiograph scores between the two groups. However, MI children showed significantly worse forced expiratory volume in 1 sec (FEV(1)), forced vital capacity (FVC), forced expiratory flow between 25-75% of FVC (FEF(25-75)), % predicted FEV(1), % predicted FEF(25-75), and total lung capacity (TLC). These differences were particularly apparent beginning at age 8-10 years. MI children also had higher rates of and shorter median times to obstructive lung disease. Subgroup analyses showed MI children treated surgically and those treated medically had similar pulmonary outcomes. In conclusion, MI children have worse lung function and more obstructive lung disease than those without MI. Such abnormalities are accompanied by reduced lung volume. MI is a distinct CF phenotype with more severe pulmonary dysfunction.

Although early diagnosis of cystic fibrosis (CF) can lead to nutritional benefits, there has been uncertainty about pulmonary outcomes. Using a randomized controlled trial with unique unblinding/surveillance, we evaluated patients with CF who received similar treatment after being assigned to an early diagnosis (screened) group or to a standard diagnosis (control) group. When the youngest patient was 7 years of age, we compared outcomes using pulmonary function data and quantitative chest radiology. In the screened group (56 patients), diagnosis was made at a younger age of 12.4 weeks, compared with the diagnosis in control group (47 control patients) at the age of 95.8 weeks, but included a significantly greater proportion of patients with deltaF508 genotypes and pancreatic insufficiency. The first chest radiograph showed significantly fewer abnormalities in the screened group; but, over time, the two groups converged, and after 10 years of age the screened patients showed worse chest X-ray scores associated with earlier acquisition of Pseudomonas aeruginosa. No differences were detected in any measure of pulmonary dysfunction, which was generally mild in each group. Although CF neonatal screening provides a potential opportunity for better pulmonary outcomes, it appears that respiratory infections and pancreatic status are the dominant factors in pulmonary prognosis.

Children with cystic fibrosis (CF) develop bronchopulmonary disease at variable ages. Determining the epidemiology of chronic lung disease and quantifying its severity, however, have been difficult in infants and young children. As part of the Wisconsin CF Neonatal Screening Project, we were presented with an ideal opportunity to assess longitudinally the evolution of symptoms, signs, and quantitative measures of CF respiratory disease. After newborn screening test results led to early recognition, 64 patients diagnosed at a median age of 6.71 weeks were enrolled and studied systematically at a median age of 11.3 years to obtain clinical information, chest radiographs, and pulmonary function tests. Our observations revealed that a frequent cough by history is evident by 10.5 months of age in half the patients. Quantitative chest radiology (CXR scoring) demonstrated that potentially irreversible abnormalities are present in half the children by 2 years. The severity of Wisconsin and Brasfield CXR scores increased in association with respiratory infections. Longitudinal progression of Wisconsin CXR scores was related to age (P < 0.001), pancreatic insufficiency (P = 0.005), and respiratory secretion cultures positive for Staphylococus aureas (P = 0.039). In contrast, serial spirometry showed limited sensitivity, as did lung volume determinations; neither was satisfactory as repeated measures with acceptable quality control until after 7 years of age. Time to event analyses revealed that half the patients had % predicted FEF(25-75) and FEV(1)/FVC values greater than 80% until 10.7 and 9.9 years, respectively. We conclude that of the methods evaluated, quantitative chest radiology is currently the best procedure for frequent assessment of bronchopulmonary disease in CF, and that radiographic progression is evident in approximately 85% of patients by 5 years of age. Our results also suggest that bronchiectasis and other radiographic evidence of chronic infection are apparent prior to airways obstruction in young CF patients., (Copyright 2003 Wiley-Liss, Inc.)