Jong, P.A. de

Optimisation of volume-doubling time cutoff for fast-growing lung nodules in CT lung cancer screening reduces false-positive referrals (Article)

2013-03-19T00:00:00Z

Objective: To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals. Methods: Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50-500 mm3), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference. Results: Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days. Conclusion: All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT ≤232 days. Lowering the VDT cutoff may reduce false-positive referrals. Key Points: • Lung nodules are common in CT lung cancer screening, most being benign • Short-term follow-up CT can identify fast-growing intermediate-size lung nodules • Most fast-growing nodules on short-term follow-up CT still prove to be benign • A new volume-doubling time (VDT) cut-off is proposed for lung screening • The optimised VDT cutoff may decrease false-positive case referrals for lung cancer

Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans (Article)

2011-10-26T00:00:00Z

Context: Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional individuals with COPD at an early stage. Objective: To determine whether low-dose lung cancer screening CT scans can be used to identify participants with COPD. Design, Setting, and Patients: Single-center prospective cross-sectional study within an ongoing lung cancer screening trial. Prebronchodilator pulmonary function testing with inspiratory and expiratory CT on the same day was obtained from 1140 male participants between July 2007 and September 2008. Computed tomographic emphysema was defined as percentage of voxels less than -950 Hounsfield units (HU), and CT air trapping was defined as the expiratory:inspiratory ratio of mean lung density. Chronic obstructive pulmonary disease was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 70%. Logistic regression was used to develop a diagnostic prediction model for airflow limitation. Main Outcome Measures: Diagnostic accuracy of COPD diagnosis using pulmonary function tests as the reference standard. Results: Four hundred thirty-seven participants (38%) had COPD according to lung function testing. A diagnostic model with CT emphysema, CT air trapping, body mass index, pack-years, and smoking status corrected for overoptimism (internal validation) yielded an area under the receiver operating characteristic curve of 0.83 (95% CI, 0.81-0.86). Using the point of optimal accuracy, the model identified 274 participants with COPD with 85 false-positives, a sensitivity of 63% (95% CI, 58%-67%), specificity of 88% (95% CI, 85%-90%), positive predictive value of 76% (95% CI, 72%-81%); and negative predictive value of 79% (95% CI, 76%-82%). The diagnostic model showed an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.86-0.88) for participants with symptoms and 0.78 (95% CI, 0.76-0.80) for those without symptoms. Conclusion: Among men who are current and former heavy smokers, low-dose inspiratory and expiratory CT scans obtained for lung cancer screening can identify participants with COPD, with a sensitivity of 63% and a specificity of 88%.

Screening for lung cancer with digital chest radiography: Sensitivity and number of secondary work-up CT examinations (Article)

2010-05-01T00:00:00Z

Purpose: To estimate the performance of digital chest radiography for detection of lung cancer. Materials and Methods: The study had ethics committee approval, and a nested case-control design was used and included 55 patients with lung cancer detected at computed tomography (CT) and confirmed with histologic examination and a sample of 72 of 4873 control subjects without nodules at CT. All patients underwent direct-detector digital chest radiography in two projections within 2 months of the screening CT. Four radiologists with varying experience identified and localized potential cancers on chest radiographs by using a confidence scale of level 1 (no lesion) to 5 (definite lesion). Localization receiver operating characteristic (ROC) analysis was performed. On the basis of the assumption that suspicious lesions seen at chest radiography would lead to further work-up with CT, the number of work-up CT examinations per detected cancer (CT examinations per cancer) was calculated at various confidence levels for the screening population (cancer rate in study population, 1.3%). Results: Tumor size ranged from 6.8 to 50.7 mm (median, 11.8 mm). Areas under the localization ROC curve ranged from 0.52 to 0.69. Detection rates substantially varied with the observers' experience and confidence level: At a confidence level of 5, detection rates ranged from 18% at one CT examination per cancer to 53% at 13 CT examinations per cancer. At a confidence level of 2 or higher, detection rates ranged from 94% at 62 CT examinations per cancer to 78% at 44 CT examinations per cancer. Conclusion: A detection rate of 94% for lung tumors with a diameter of 6.8-50.7 mm found at CT screening was achievable with chest radiography only at the expense of a high false-positive rate and an excessive number of work-up CT examinations. Detection performance is strongly observer dependent.

Structural lung changes, lung function, and non-invasive inflammatory markers in cystic fibrosis (Article)

2010-05-01T00:00:00Z

Cystic fibrosis (CF) lung disease is characterized by chronic airway inflammation and recurrent infections, resulting in (ir)reversible structural lung changes and a progressive decline in lung function. The objective of this study was to investigate the relationship between non-invasive inflammatory markers (IM) in exhaled breath condensate (EBC), lung function indices and structural lung changes, visualized by high resolution computed tomography (HRCT) scans in CF. In 34 CF patients, lung function indices (forced expiratory volume in 1 s, forced vital capacity [FVC], residual volume, and total lung capacity [TLC]) and non-invasive IM (exhaled nitric oxide, and condensate acidity, nitrate, nitrite, 8-isoprostane, hydrogen peroxide, interferon-gamma) were assessed. HRCT scans were scored in a standardized and validated way, a composite score and component scores were calculated. In general, the correlations between non-invasive IM and structural lung changes, and between IM and lung function were low (correlation coefficients <0.40). Patients with positive sputum Pseudomonas cultures had higher EBC nitrite levels and higher parenchymal HRCT subscores than patients with Pseudomonas-negative cultures (p < 0.05). Multiple linear regression models demonstrated that FVC was significantly predicted by hydrogen peroxide in EBC, and the scores of bronchiectasis and mosaic perfusion (Pearson correlation coefficient R = 0.78, p < 0.001). TLC was significantly predicted by 8-isoprostane, nitrate, hydrogen peroxide in EBC, and the mucous plugging subscore (R = 0.92, p < 0.01). Static and dynamic lung function indices in this CF group were predicted by the combination of non-invasive IM in EBC and structural lung changes on HRCT imaging. Future longitudinal studies should reveal whether non-invasive monitoring of airway inflammation in CF adds to better follow-up of patients.

The spectrum of structural abnormalities on CT scans from patients with CF with severe advanced lung disease (Article)

2009-10-01T00:00:00Z

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 (rs = 0.36-0.64) and SALD normal/hyperperfusion scores correlated with forced expiratory volume in 1 s (FEV1; rs = 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.

Tracheomalacia in adults with cystic fibrosis: Determination of prevalence and severity with dynamic cine CT (Article)

2009-08-01T00:00:00Z

Purpose: To determine the prevalence and severity of tracheomalacia in adults with cystic fibrosis (CF) by using dynamic cine multidetector computed tomography (CT) and to correlate these findings with pulmonary function test (PFT) results and the severity of parenchymal lung disease. Materials and Methods: In this institutional review board-approved HIPAA-compliant study, 40 patients with CF (22 men, 18 women; mean age, 28 years ± 8 [standard deviation]; age range, 18-54 years) prospectively underwent PFTs, standard thin-section CT, and two dynamic cine multidetector CT acquisitions. Ten control subjects underwent dynamic cine multidetector CT. After standard thin-section CT was completed, dynamic cine multidetector CT was performed during a forced expiratory maneuver and during coughing. Dynamic cine multidetector CT images in nine patients were excluded. Maximal inspiratory, dynamic expiratory, and end-expiratory tracheal luminal areas were compared (Student t test) and correlated (Spearman rank) with PFT results and severity of parenchymal lung disease. Results: Mean predicted forced expiratory volume in 1 second (FEV1) was 70.6% ± 20.7, and mean Bhalla CT score was 41.8% ± 13.6. In patients with CF, dynamic cine mean tracheal cross-sectional area reduction was 51.7% ± 18.4 (range, 9%-89%) for forced expiratory maneuvers and 68.8% ± 11.7 (range, 18%-88%) for coughing (P = .001). Tracheomalacia was demonstrated in 24 (69%) patients and no control subjects during forced expiratory maneuvers (P = .001) and in 10 (29%) patients and one (10%) control subject during coughing. For end-expiration images, mean tracheal luminal reduction was 16.1% ± 14.0% (range, 0.0%-53.0%), with one patient demonstrating tracheal luminal reduction of more than 50%. There was no correlation between tracheal cross-sectional luminal reduction and either predicted FEV1or CT Bhalla score. Conclusion: Tracheomalacia depicted at dynamic cine multidetector CT is a highly prevalent finding in adults with CF.

Structural and functional lung disease in primary ciliary dyskinesia (Article)

2008-08-01T00:00:00Z

Background: High-resolution CT (HRCT) scan data on primary ciliary dyskinesia (PCD) related lung disease are scarce. Study objectives: We evaluated the lung disease in children and adults with PCD by a modified Brody composite HRCT scan score to assess the prevalence of the structural abnormalities; to evaluate the correlation among HRCT scan scores, spirometry findings, and clinical data; and to compare the PCD scores with those of age-matched and sex-matched cystic fibrosis (CF) patients. Patients and methods: Twenty PCD patients (age range, 4.6 to 27.5 years) underwent HRCT scanning, spirometry, and deep throat or sputum culture. A modified Brody score was used to assess bronchiectasis, mucous plugging, peribronchial thickening, parenchyma abnormalities, and mosaic perfusion. Results: The total HRCT scan score was 6% of the maximal score (range, 0.5 to 25.5). Subscores were as follows: bronchiectasis, 5.6%; mucous plugging, 5.6%; peribronchial thickening, 8.3%; parenchyma, 3%; and mosaic perfusion, 0%. The prevalence of lung changes were as follows: bronchiectasis, 80%; peribronchial thickening, 80%; mucous plugging, 75%; parenchyma, 65%; and mosaic perfusion, 45%. Sixteen of 19 PCD patients had positive culture findings, and the most common pathogen found was Haemophilus influenzae (84%). The total HRCT scan score was significantly related to age (p = 0.006), FEV1(p = 0.02), and FVC (p = 0.02). The bronchiectasis subscore was significantly related to FEV1(p = 0.04) and FVC (p = 0.03). In CF patients, the total HRCT scan score was significantly higher than that in PCD patients (p = 0.02). Conclusions: PCD patients show significantly lower pulmonary HRCT scan scores than CF patients. The PCD total and bronchiectasis scores correlate with spirometry findings. The PCD HRCT scan score might be used for longitudinal assessment and/or represent an outcome surrogate in future studies. Copyright

Estimation of the radiation dose from CT in cystic fibrosis (Article)

2008-05-01T00:00:00Z

Imaging and clinical trials in cystic fibrosis (Article)

2007-08-01T00:00:00Z

Lung function parameters have been used in most therapeutic studies to date. Thanks to improvements in cystic fibrosis (CF) therapy, these parameters have become a less sensitive endpoint in clinical studies. Computed tomography (CT) in CF can identify highly relevant structural lung changes, such as bronchiectasis and air trapping. CT scoring systems have been developed to quantify in a systematic fashion these structural changes on CT scans. Clinical studies have been conducted using CT scores as an outcome parameter. These studies suggest strongly that CT scoring ismore sensitive than pulmonary function tests for the detection of relevant disease progression in CF. Bronchiectasis, which is progressive and irreversible in CF, is probably the most relevant structural change on CT scans that can be scored reliably. CT measurement of airway wall thickening is possible. Airway wall thickening is related to inflammation; thus, this endpoint is of significance for interventional studies that include antiinflammatory drugs.

Cystic fibrosis-specific computed tomography scoring (Article)

2007-08-01T00:00:00Z

This article presents a review and discussion of the current knowledge regarding cystic fibrosis (CF)-specific scoring of chest computed tomography (CT) scans. First, the basic principles of CT scoring systems in CF are described. Second, between- and within-observer variability of a composite CT score and of component CT scores are reviewed, and issues regarding training of CT scan readers discussed. Third, arguments regarding whether CT scoring systems are ready to be used in clinical studies as a surrogate endpoint are summarized. The between- and within-observer variability of the present CT composite scoring systems is low enough to be useful for clinical studies, although the variability for some of the component scores is larger than for others. Scoring systems fulfill the requirements for surrogate endpoints for CF lung disease, but this role could be further strengthened by including CT scans in large trials and demonstrating the correlation with true endpoints. The conclusion presented is that, given the experience of the variety of published scoring systems, it is important to develop a consensus CT scoring system for future studies in CF. Such a scoring system should evaluate all lung lobes individually and include all relevant CT findings in CF. Development of reference images for the components of this system will be important in reducing the variability between observers and to train new readers.

Monitoring of Cystic Fibrosis Lung Disease Using Computed Tomography (Doctoral Thesis)

2005-12-14T00:00:00Z

For clinical management of cystic fibrosis (CF) lung disease to be effective, onset and worsening of lung abnormalities should be closely monitored. Pulmonary function tests (PFTs) are currently the gold standard to monitor CF lung disease. Lung structure can be more sensitively monitored using computed tomography (CT) rather than chest radiography. Firstly, we compared in two pediatric cohorts the sensitivities of CT and PFTs to detect onset and worsening of CF lung disease. We showed that five published CT scoring systems are comparable and have good intra- and interobserver agreement. Secondly, we showed that CT scoring systems and quantitative CT-measurements of airway wall thickening and bronchiectasis are more sensitive to detect the start and worsening of CF lung disease than are PFTs. Bronchiectasis-score worsened most in children and the worsening remained undetected by the PFTs and the quantitative measurements. Quantitative CT-measurements of air! way wall thickening worsened significantly, whereas PFTs and airway wall thickness measured by scoring remained unchanged. Thirdly, we developed a computational model to study radiation risks associated with CT scanning in CF. Risks from lifelong biennial CT scanning in CF were found to be acceptably low given the currently reduced life expectancy. Finally we provided normal CT-values of lung parenchyma and airway wall and lumen that can be used to study lung growth aberrations due to CF. Our data support routine CT scanning to monitor CF lung disease. In addition, bronchiectasis-score and quantitatively measured airway wall thickening may be useful surrogate endpoints for clinical trials in CF.

Changes in airway dimensions on computed tomography scans of children with cystic fibrosis. (Article)

2005-07-15T00:00:00Z

RATIONALE: In cystic fibrosis (CF), chronic bacterial infection and inflammation lead to progressive airway wall thickening and lumen dilatation. Objectives: To quantify airway wall thickening and lumen dilatation in children with CF over a 2-year interval. METHODS: Children with CF (n = 23) who had two computed tomography (CT) scans (CT(cf1) and CT(cf2)) combined with pulmonary function tests (PFTs), with a 2-year interval between measurements, were compared with control subjects (n = 21) who had one CT (CT(controls)). On cross-sectional cut airway-artery pairs, airway wall area (WA), airway lumen area (LA) and perimeter, and arterial area (AA) were quantified. LA/AA (= marker of bronchiectasis), airway wall thickness (AWT), and WA/AA (= markers of wall thickness) were calculated. CT scans were scored using four different scoring systems. PFTs were expressed as percent predicted. RESULTS: Airway WA-to-AA ratio was 1.45 (p < 0.001) and airway LA-to-AA ratio was 1.92 times higher (p < 0.001) in children with CF compared with age-matched control subjects. LA/AA and WA/AA remained unchanged from CT(cf1) to CT(cf2) and did not increase with age. AWT as a function of airway size increased from CT(cf1) to CT(cf2) by 2% (0.03 mm; p = 0.02). The change in AWT was inversely related to the change in forced expiratory flow between 25 and 75% of expiratory VC (p = 0.002). CONCLUSIONS: In CF, quantitative measurements of airways on CT scans show an increased ratio between airway LA and AA and progressive airway wall thickening. Scoring systems show progression of bronchiectasis but unchanged AWT. PFTs remained stable.

Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements. (Article)

2004-05-01T00:00:00Z

PURPOSE: To retrospectively compare thin-section computed tomographic (CT) scores obtained with five scoring systems for assessment of pulmonary disease in children with cystic fibrosis and to determine additional value of bronchial and arterial dimension measurements. MATERIALS AND METHODS: Scores obtained with five thin-section CT scoring systems were compared. A score of 0 indicated the absence of abnormalities; a higher score meant that more structural abnormalities were seen. Three observers assigned scores and then reassigned scores after intervals varying from 1-2 weeks to 1-2 months at review of thin-section CT scans obtained in 25 children with cystic fibrosis. Interobserver and intraobserver reliability was calculated with intraclass correlation coefficients. Quantitative measurements of bronchial and arterial dimensions were obtained. Thin-section CT scores were correlated (Spearman correlation) with bronchial and arterial dimensions and with results of pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV(1)). RESULTS: Scores with all five scoring systems were reproducible, with intraclass correlation coefficients of 0.74 and higher (P <.05), and showed significant correlations with FEV(1) (R = -0.73 to -0.69, P <.01). Ratio of bronchial diameter to accompanying pulmonary arterial diameter was correlated with thin-section CT scores but not with FEV(1). Ratio of bronchial wall thickness to accompanying pulmonary arterial diameter was not correlated with thin-section CT scores or PFT results. CONCLUSION: Thin-section CT scores were reproducible and were correlated with PFT results. Measurements of bronchial dimensions were not significantly related to scores or PFT results.

Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis (Article)

2004-01-01T00:00:00Z

For effective clinical management of cystic fibrosis (CF) lung disease it is important to closely monitor the start and progression of lung damage. The aim of this study was to investigate the ability of high-resolution computed tomography (HRCT) scoring systems and pulmonary function tests (PFT) to detect changes in lung disease. CF children (n=48) had two HRCT scans in combination with two PFT 2 yrs apart. Their scans were scored using five scoring systems (Castile, Brody, Helbich, Santamaria and Bhalla). "Sensitivity" was defined as the ability to detect disease progression. In this group of children, HRCT scores worsened. PFT remained unchanged or improved. Of the HRCT parameters, mucous plugging and the severity, extent and peripheral extension of bronchiectasis worsened significantly. Relationships between changes in HRCT scores and PFT were weak. Substantial structural lung damage was evident in some children who had normal lung function. These data show that high-resolution computed tomography is more sensitive than pulmonary function tests in the detection of early and progressive lung disease, and suggest that high-resolution computed tomography may be useful in the follow up of cystic fibrosis children and as an outcome measure in studies that aim to reduce lung damage.

Estimation of lung growth using computed tomography (Article)

2003-01-01T00:00:00Z

Anatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed tomography (CT). Therefore, the gas volume per gram of lung tissue was estimated from measurements of lung density obtained from CT scans performed on children throughout the growth period. CT scans were performed on 17 males and 18 females, ranging in age from 15 days-17.6 yrs. CT-measured lung weight was correlated with predicted post mortem values and CT measured gas volume with predicted values of functional residual capacity. The median value for lung expansion was 1.86 mL x g(-1) at 15 days, decreased to 0.79 mL x g(-1) by 2 yrs and then increased steadily to 5.07 mL x g(-1) at 17 yrs. Computed tomography scans can be used to estimate lung weight, gas volume and expansion of normal lungs during the growth period. The increase in the lung expansion after the age of 2 yrs suggests progressive alveolar expansion with increasing lung volume.