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Biomedical subjects

Alan S Brody

Publications and source records attributed to Alan S Brody.

At least 19 recordsLinked to original sources
PubMed2006

Reproducibility of a scoring system for computed tomography scanning in 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.

Adolescent↗
PubMed2005

Computed tomography correlates with pulmonary exacerbations in children with cystic fibrosis.

RATIONALE: High-resolution computed tomography (HRCT) has been suggested as a potential outcome surrogate for cystic fibrosis (CF) lung disease. An important attribute of a valid outcome surrogate is that the surrogate reflects true clinical outcomes. OBJECTIVES: We performed this study to validate HRCT, a proposed surrogate outcome measure for CF lung disease, against a true clinical outcome, the number of respiratory tract exacerbations occurring in 2 yr, and to assess the correlation of CT scores and pulmonary function tests (PFTs) with this clinical outcome. METHODS: CTs and PFTs were performed on 6- to 10-yr-old children at the beginning and end of a 2-yr study during which the number of exacerbations were recorded. Spearman correlations and Poisson models were used to assess the correlation of the number of exacerbations with baseline values and changes in PFTs and CT scores. MEASUREMENTS AND MAIN RESULTS: Nine of 61 subjects had a total of 22 respiratory tract exacerbations. At baseline, PFTs and four CT scores showed significant correlation with number of exacerbations, but no variable by itself predicted exacerbations with high accuracy. For change over the 2-yr period, three CT scores showed significant correlation with exacerbations, whereas no PFTs showed significant correlation. CONCLUSION: This is the first study showing correlation between CT and a true clinical outcome. Change in CT scores correlates moderately well with the number of exacerbation. Poor correlation between change in FEV1 and exacerbations suggests that HRCT may be a more appropriate outcome surrogate for longitudinal studies of young children.

Anti-Bacterial Agents↗
PubMed2005

Computed tomography in the evaluation of cystic fibrosis lung disease.

The first report of computed tomography (CT) scanning to monitor cystic fibrosis (CF)-related lung disease was published in 1986. Further publications followed, but in general there was little interest in this technique until recently. Two factors in particular have led to this increased interest. First is an increasing realization that pulmonary function tests, long the mainstay of CF evaluation, often underestimate the presence and severity of mild and moderate lung disease. Second is the need for more sensitive outcome measures to assess new therapies. This had led to new interest and a series of important publications. The goal of this article is to present the current status of CT scanning in CF.

Cystic Fibrosis↗
PubMed2005

Imaging considerations: interstitial lung disease in children.

This article provides a guide for the technique and interpretation of high-resolution chest CT of diffuse lung disease in children. Specific causes of diffuse lung disease in infants and children are reviewed as a guide to the interpretation of these images. New information, particularly the identification of surfactant protein mutations, is included. The idiopathic interstitial pneumonia classification, which is frequently applied to pediatric lung biopsy specimens, is also discussed.

Child↗
PubMed2005

Identifying children with pneumonia in the emergency department.

Emergency physicians need to clinically differentiate children with and without radiographic evidence of pneumonia. In this prospective cohort study of 510 patients 2 to 59 months of age presenting with symptoms of lower respiratory tract infection, 100% were evaluated with chest radiography and 44 (8.6%) had pneumonia on chest radiography. With use of multivariate analysis, the adjusted odds ratio (AOR) and 95% confidence intervals (CI) of the clinical findings significantly associated with focal infiltrates were age older than 12 months (AOR 1.4, CI 1.1-1.9), RR 50 or greater (AOR 3.5, CI 1.6-7.5), oxygen saturation 96% or less (AOR 4.6, CI 2.3-9.2), and nasal flaring (AOR 2.2 CI 1.2-4.0) in patients 12 months of age or younger. The combination of age older than 12 months, RR 50 or greater, oxygen saturation 96% or less, and in children under age 12 months, nasal flaring, can be used in determining which young children with lower respiratory tract infection symptoms have radiographic pneumonia.

Age Distribution↗
PubMed2004

High-resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests.

OBJECTIVE: To assess pulmonary abnormalities detected by high-resolution computed tomography (HRCT) in young children with cystic fibrosis (CF) and mild to moderate lung disease. STUDY DESIGN: High-resolution computed tomography was performed in 60 children, 6 to 10 years old, with mild to moderate lung disease (forced expiratory volume in 1 minute [FEV(1)], 52-137; mean, 102; SD, 15% predicted). HRCTs were scored by using a system that evaluates each lobe for severity and extent of CF lung disease. Findings of CF lung disease were tabulated in all subjects and in a subgroup with normal pulmonary function tests. HRCT scores were correlated with FEV(1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of expired vital capacity (FEF(25-75)) in 57 patients. RESULTS: Bronchiectasis was present in 35% of subjects, mucous plugging in 15%, and air trapping in 63%. No abnormality was detected in 25%. In 37 subjects with FEV(1), FVC, and FEF(25-75) >85% predicted, bronchiectasis was present in 30%. In 17% of these subjects, bronchiectasis was seen in > or =4 lobes. Correlations between HRCT scores and FEV(1) were significant and showed fair to moderate correlation (r=0.36-0.46). CONCLUSIONS: High-resolution computed tomography demonstrated a broad range of pulmonary abnormalities in young patients with CF with mild to moderate lung disease. In this study, abnormalities, including bronchiectasis, were common in young children with CF and normal pulmonary function tests.

Bronchiectasis↗
PubMed2004

Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial.

STUDY OBJECTIVES: The primary objective was to determine the safety and tolerability of repeated doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) [tgAAVCF], an adeno-associated virus (AAV) vector encoding the complete human CFTR cDNA. Secondary objectives included evaluation of pulmonary function assessed by spirometry, lung abnormalities by high-resolution CT (HRCT), airway cytokines, vector shedding, serum neutralizing antibody to AAV serotype 2 (AAV2), and gene transfer and expression in a subset of subjects undergoing bronchoscopy with bronchial brushings. DESIGN: Randomized, double-blind, placebo-controlled, phase II trial. SETTING: Eight cystic fibrosis (CF) centers in the United States. SUBJECTS: CF patients with mild lung disease, defined as FEV(1) > or =60% predicted. INTERVENTIONS: Subjects were randomized to inhale three aerosolized doses of 1 x 10(13) deoxyribonuclease-resistant particles of tgAAVCF or matching placebo at 30-day intervals using the Pari LC Plus nebulizer (PARI; Richmond, VA). MEASUREMENTS AND RESULTS: Of 42 subjects randomized, 20 subjects received at least one dose of tgAAVCF and 17 subjects received placebo. No difference in the pattern of adverse events or laboratory abnormalities was noted between the two treatment groups. Improvements in induced-sputum interleukin-8 (p = 0.03) and FEV(1) (p = 0.04) were observed at day 14 and day 30, respectively, in the group receiving tgAAVCF when compared to those receiving placebo. No significant differences in HRCT scans were noted. Vector shedding in sputum was observed at low levels up to 90 days after the third dose of vector. All subjects receiving tgAAVCF exhibited an increase (by at least fourfold) in serum AAV2-neutralizing antibodies and detectable levels in BAL fluid from five of six treated subjects undergoing BAL. Gene transfer but not gene expression was detected in a subset of six tgAAVCF subjects who underwent bronchoscopy. CONCLUSIONS: Repeat doses of aerosolized tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease.

Administration, Inhalation↗
PubMed2003

Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference.

Because of the difficulties of recognizing allergic bronchopulmonary aspergillosis (ABPA) in the context of cystic fibrosis (because of overlapping clinical, radiographic, microbiologic, and immunologic features), advances in our understanding of the pathogenesis of allergic aspergillosis, new possibilities in therapy, and the need for agreed-upon definitions, an international consensus conference was convened. Areas addressed included fungal biology, immunopathogenesis, insights from animal models, diagnostic criteria, epidemiology, the use of new immunologic and genetic techniques in diagnosis, imaging modalities, pharmacology, and treatment approaches. Evidence from the existing literature was graded, and the consensus views were synthesized into this document and recirculated for affirmation. Virulence factors in Aspergillus that could aggravate these diseases, and particularly immunogenetic factors that could predispose persons to ABPA, were identified. New information has come from transgenic animals and recombinant fungal and host molecules. Diagnostic criteria that could provide a framework for monitoring were adopted, and helpful imaging features were identified. New possibilities in therapy produced plans for managing diverse clinical presentations.

Animals↗
PubMed2003

Utility of simple radiation dose measurements in the evaluation of different CT scanners used for high-resolution CT.

In recent years radiation risk from CT scanning has become an important area of investigation. Many authors have suggested that radiation dose can be decreased without loss of diagnostic information. This dose reduction has primarily been achieved through a decrease in tube current. An area that has received little attention has been variations in dose from different CT scanners. To evaluate this aspect of radiation exposure, we measured the radiation dose of 4 different CT scanners. We found that the radiation dose for the same CT technique can vary by as much as a factor of 3 when 1 mm slices are used. CT dose variation was greatest for thin slices, making these observations particularly important for high-resolution CT. Our measurement technique used standard quality assurance equipment available in most radiology departments. Use of these measurements to assess the radiation dose from different CT scanners is an easily performed technique that may allow a decrease in radiation exposure in departments by choosing the most appropriate intra departmental CT scanner for specific indications.

Humans↗
PubMed2003

Clinical predictors for the selective use of chest radiographs in pediatric blunt trauma evaluations.

BACKGROUND: Chest radiographs continue to be a routine part of the evaluation of children sustaining blunt trauma. This study sought to determine those clinical markers associated with an abnormal chest radiograph in nonintubated, pediatric, blunt trauma victims. METHODS: A retrospective case-control study was performed for severely injured pediatric trauma patients presenting to our emergency department between January 1, 1996, and December 31, 1997. Abnormal chest radiographs were identified through the trauma registry and four controls were matched to each case. Radiographs were reevaluated by our study radiologist. Variables associated with an abnormal chest radiograph were grouped to develop a set of clinical markers that could predict an abnormal chest radiograph with a high degree of sensitivity. RESULTS: An initial chest radiograph was obtained in 457 of 587 trauma patients. Thirty study patients with an abnormal radiograph that met inclusion criteria were analyzed with 133 controls. The presence of either an abnormal respiratory rate for age, chest tenderness, or back abrasions had a sensitivity of 1.0 (95% confidence interval, 0.86-1.0) and a specificity of 0.38 (95% confidence interval, 0.30-0.47). CONCLUSION: In pediatric trauma patients, the presence of chest tenderness, back abrasions, or an abnormal respiratory rate identified all abnormal chest radiographs.

Case-Control Studies↗
PubMed2002

High-resolution CT of pediatric lung disease.

High-resolution CT in children remains a technically challenging procedure, both to perform optimally and to interpret correctly. Although much remains to be learned about its optimal application, it is apparent that often confusing or nonspecific chest radiographs are clarified and a much clearer understanding is being gained about the diagnosis and evolution of both common and unusual pediatric lung diseases. As new therapies become available for these disorders, and CT becomes faster and easier to perform, it will become increasingly used not only for more accurate diagnosis but also for better evaluation of effects of therapy.

Adolescent↗
PubMed2002

"Missing" sternal ossification center: potential mimicker of disease in young children.

PURPOSE: To evaluate the frequency of "missing" sternal ossification center (asynchronous non-ossification) in young children. MATERIALS AND METHODS: Lateral chest radiographs obtained in 229 children (mean age, 3.7 years) were retrospectively evaluated for sternal ossification. Four superior sternal segments were considered normal if they were ossified to a similar degree. A segment was considered asynchronous if decreased ossification, as compared with the remaining sternal segments, was demonstrated or if ossification was absent. Asynchronous ossification of inferior sternal segment 5 was recorded separately. Logistic regression analysis was applied to determine if there was a statistically significant relationship (P <.05) between age or sex and pattern of sternal ossification (normal vs asynchronous). RESULTS: Of the 916 superior four sternal segments (four segments in each of 229 patients) evaluated, 32 (3.5%) showed asynchronously decreased or absent ossification. Locations of these 32 segments follow: segment 1, two (0.2%) instances; segment 2, 14 (1.5%) instances; segment 3, two (0.2%) instances; and segment 4, 14 (1.5%) instances. Inferior segment 5 was not ossified in 73 (31.9%) patients. There was a statistically significant relationship between decreased age and increased likelihood of occurrence of asynchronous ossification of one of the sternal ossification centers 1-4 (P >.003) and of occurrence of asynchronous ossification at sternal segment 2 (P <.018). CONCLUSION: Missing sternal ossification centers occur most commonly at segments 2 and 4. Such asynchronous non-ossifications become less common in older children.

Child↗