In vivo polarisation sensitive optical coherence tomography for fibrosis assessment in interstitial lung disease: a prospective, exploratory, observational study.

INTRODUCTION: Endobronchial polarisation sensitive optical coherence tomography (EB-PS-OCT) is a bronchoscopic imaging technique exceeding resolution of high-resolution CT (HRCT) by 50-fold. It detects collagen birefringence, enabling identification and quantification of fibrosis. STUDY AIM: To assess pulmonary fibrosis in interstitial lung diseases (ILD) patients with in vivo EB-PS-OCT using histology as reference standard. PRIMARY OBJECTIVE: Visualisation and quantification of pulmonary fibrosis by EB-PS-OCT. SECONDARY OBJECTIVES: Comparison of EB-PS-OCT and HRCT detected fibrosis with histology, identification of ILD histological features in EB-PS-OCT images and comparison of ex vivo PS-OCT results with histology. METHODS: Observational prospective exploratory study. Patients with ILD scheduled for transbronchial cryobiopsy or surgical lung biopsy underwent in vivo EB-PS-OCT imaging prior to tissue acquisition. Asthma patients were included as non-fibrotic controls. Per imaged lung segment, fibrosis was automatically quantified assessing the birefringent area in EB-PS-OCT images. Fibrotic extent in corresponding HRCT areas and biopsies were compared with EB-PS-OCT detected fibrosis. Microscopic ILD features were identified on EB-PS-OCT images and matched with biopsies from the same segment. RESULTS: 19 patients were included (16 ILD; 3 asthma). In 49 in vivo imaged airway segments the parenchymal birefringent area was successfully quantified and ranged from 2.54% (no to minimal fibrosis) to 21.01% (extensive fibrosis). Increased EB-PS-OCT detected birefringent area corresponded to increased histologically confirmed fibrosis, with better predictive value than HRCT. Microscopic ILD features were identified on both in vivo and ex vivo PS-OCT images. CONCLUSIONS: EB-PS-OCT enables pulmonary fibrosis quantification, thereby has potential to serve as an add-on bronchoscopic imaging technique to diagnose and detect (early) fibrosis in ILD.

Assisted versus Manual Interpretation of Low-Dose CT Scans for Lung Cancer Screening: Impact on Lung-RADS Agreement.

Purpose To compare the inter- and intraobserver agreement and reading times achieved when assigning Lung Imaging Reporting and Data System (Lung-RADS) categories to baseline and follow-up lung cancer screening studies by using a dedicated CT lung screening viewer with integrated nodule detection and volumetric support with those achieved by using a standard picture archiving and communication system (PACS)-like viewer. Materials and Methods Data were obtained from the National Lung Screening Trial (NLST). By using data recorded by NLST radiologists, scans were assigned to Lung-RADS categories. For each Lung-RADS category (1 or 2, 3, 4A, and 4B), 40 CT scans (20 baseline scans and 20 follow-up scans) were randomly selected for 160 participants (median age, 61 years; interquartile range, 58-66 years; 61 women) in total. Seven blinded observers independently read all CT scans twice in a randomized order with a 2-week washout period: once by using the standard PACS-like viewer and once by using the dedicated viewer. Observers were asked to assign a Lung-RADS category to each scan and indicate the risk-dominant nodule. Inter- and intraobserver agreement was analyzed by using Fleiss κ values and Cohen weighted κ values, respectively. Reading times were compared by using a Wilcoxon signed rank test. Results The interobserver agreement was moderate for the standard viewer and substantial for the dedicated viewer, with Fleiss κ values of 0.58 (95% CI: 0.55, 0.60) and 0.66 (95% CI: 0.64, 0.68), respectively. The intraobserver agreement was substantial, with a mean Cohen weighted κ value of 0.67. The median reading time was significantly reduced from 160 seconds with the standard viewer to 86 seconds with the dedicated viewer (P < .001). Conclusion Lung-RADS interobserver agreement increased from moderate to substantial when using the dedicated CT lung screening viewer. The median reading time was substantially reduced when scans were read by using the dedicated CT lung screening viewer. Keywords: CT, Thorax, Lung, Computer Applications-Detection/Diagnosis, Observer Performance, Technology Assessment Supplemental material is available for this article. © RSNA, 2021.

CT-Detected Subsolid Nodules: A Predictor of Lung Cancer Development at Another Location?

The purpose of this case-cohort study was to investigate whether the frequency and computed tomography (CT) features of pulmonary nodules posed a risk for the future development of lung cancer (LC) at a different location. Patients scanned between 2004 and 2012 at two Dutch academic hospitals were cross-linked with the Dutch Cancer Registry. All patients who were diagnosed with LC by 2014 and a random selection of LC-free patients were considered. LC patients who were determined to be LC-free at the time of the scan and all LC-free patients with an adequate scan were included. The nodule count and types (solid, part-solid, ground-glass, and perifissural) were recorded per scan. Age, sex, and other CT measures were included to control for confounding factors. The cohort included 163 LC patients and 1178 LC-free patients. Cox regression revealed that the number of ground-glass nodules and part-solid nodules present were positively correlated to future LC risk. The area under the receiver operating curve of parsimonious models with and without nodule type information were 0.827 and 0.802, respectively. The presence of subsolid nodules in a clinical setting may be a risk factor for future LC development in another pulmonary location in a dose-dependent manner. Replication of the results in screening cohorts is required for maximum utility of these findings.

Cystic Primary Lung Cancer: Evolution of Computed Tomography Imaging Morphology Over Time.

PURPOSE: Primary lung cancers associated with cystic airspaces are increasingly being recognized; however, there is a paucity of data on their natural history. We aimed to evaluate the prevalence, pathologic, and imaging characteristics of cystic lung cancer in a regional thoracic surgery center with a focus on the evolution of computed tomography morphology over time. MATERIALS AND METHODS: Consecutive patients referred for potential surgical management of primary lung cancer between January 2016 and December 2018 were included. Clinical, imaging, and pathologic data were collected at the time of diagnosis and at the time of the oldest computed tomography showing the target lesion. Descriptive analysis was carried out. RESULTS: A total of 441 cancers in 431 patients (185 males, 246 females), median age 69.6 years (interquartile range: 62.6 to 75.3 y), were assessed. Overall, 41/441 (9.3%) primary lung cancers were cystic at the time of diagnosis. The remaining showed solid (67%), part-solid (22%), and ground-glass (2%) morphologies. Histopathology of the cystic lung cancers at diagnosis included 31/41 (76%) adenocarcinomas, 8/41 (20%) squamous cell carcinomas, 1/41 (2%) adenosquamous carcinoma, and 1/41 (2%) unspecified non-small cell lung carcinoma. Overall, 8/34 (24%) cystic cancers at the time of diagnosis developed from different morphologic subtype precursor lesions, while 8/34 (24%) cystic precursor lesions also transitioned into part-solid or solid cancers at the time of diagnosis. CONCLUSIONS: This study demonstrates that cystic airspaces within lung cancers are not uncommon, and may be seen transiently as cancers evolve. Increased awareness of the spectrum of cystic lung cancer morphology is important to improve diagnostic accuracy and lung cancer management.

Microsimulation modeling of extended annual CT screening among lung cancer cases in the National Lung Screening Trial.

PURPOSE: To microsimulate the effects of three additional annual CT screening rounds on lung cancer (LC) survival in the National Lung Screening Trial (NLST). METHODS: We used multiple imputation to model the effect of additional screening in the full NLST cohort on the time to LC diagnosis and on LC death in those participants who were diagnosed with LC by the end of NLST. Nodule growth models were derived from a Dutch in-vivo study. Microsimulations were repeated 500 times. The method was validated by simulating three rounds of CT screening in the original chest radiography (CXR) cohort. The times up to which the simulations remained within the 95 % confidence bands of the CT cohort's original results were used to estimate the validity of the results in the CT cohort with three additional simulated screening rounds. RESULTS: Validation of the simulation approach on the CXR cohort resulted in a LC mortality reduction which remained well within the 95 % confidence intervals of the original CT cohort up to 6.5 years after the start of simulations. Simulating additional CT screening in the CT cohort led to LCs being diagnosed earlier than originally, resulting in a relative risk reduction in LC mortality of 11 % (95 % confidence bands, 7 %-14 %) at 6.5 years. This is equivalent to preventing 71 % (48 %-94 %) more LC deaths than the original CT cohort achieved in comparison to the original CXR cohort. CONCLUSION: Three additional annual CT screening rounds in the NLST may have led to substantial further LC mortality reduction.

Chronic Lung Allograft Dysfunction: Review of CT and Pathologic Findings.

Chronic lung allograft dysfunction (CLAD) is the most common cause of mortality in lung transplant recipients after the 1st year of transplantation. CLAD has traditionally been classified into two distinct obstructive and restrictive forms: bronchiolitis obliterans syndrome and restrictive allograft syndrome. However, CLAD may manifest with a spectrum of imaging and pathologic findings and a combination of obstructive and restrictive physiologic abnormalities. Although the initial CT manifestations of CLAD may be nonspecific, the progression of findings at follow-up should signal the possibility of CLAD and may be present on imaging studies prior to the development of functional abnormalities of the lung allograft. This review encompasses the evolution of CT findings in CLAD, with emphasis on the underlying pathogenesis and pathologic condition, to enhance understanding of imaging findings. The purpose of this article is to familiarize the radiologist with the initial and follow-up CT findings of the obstructive, restrictive, and mixed forms of CLAD, for which early diagnosis and treatment may result in improved survival. Supplemental material is available for this article. © RSNA, 2021.

Observer variability for Lung-RADS categorisation of lung cancer screening CTs: impact on patient management.

OBJECTIVES: Lung-RADS represents a categorical system published by the American College of Radiology to standardise management in lung cancer screening. The purpose of the study was to quantify how well readers agree in assigning Lung-RADS categories to screening CTs; secondary goals were to assess causes of disagreement and evaluate its impact on patient management. METHODS: For the observer study, 80 baseline and 80 follow-up scans were randomly selected from the NLST trial covering all Lung-RADS categories in an equal distribution. Agreement of seven observers was analysed using Cohen's kappa statistics. Discrepancies were correlated with patient management, test performance and diagnosis of malignancy within the scan year. RESULTS: Pairwise interobserver agreement was substantial (mean kappa 0.67, 95% CI 0.58-0.77). Lung-RADS category disagreement was seen in approximately one-third (29%, 971) of 3360 reading pairs, resulting in different patient management in 8% (278/3360). Out of the 91 reading pairs that referred to scans with a tumour diagnosis within 1 year, discrepancies in only two would have resulted in a substantial management change. CONCLUSIONS: Assignment of lung cancer screening CT scans to Lung-RADS categories achieves substantial interobserver agreement. Impact of disagreement on categorisation of malignant nodules was low. KEY POINTS: • Lung-RADS categorisation of low-dose lung screening CTs achieved substantial interobserver agreement. • Major cause for disagreement was assigning a different nodule as risk-dominant. • Disagreement led to a different follow-up time in 8% of reading pairs.

Primary lung cancer in patients with previous malignancies: a nationwide study.

Overall survival of patients with cancer continues to increase and so they receive more frequent CT imaging, making oncological patients a growing population that effectively receives lung cancer screening in the course of daily practice. However, it is currently uncertain how early lung cancer detection in this subgroup of patients should be optimally managed. We describe the relationship between primary lung cancer and prior malignancies in a nationwide cohort, in an attempt to identify possible areas of improvement in nodule management. We found that a substantial number of subjects with lung cancer suffered from a prior malignancy; however, with the exception of otorhinolaryngeal malignancies, they did not show a high absolute risk for lung cancer. Future research should provide more data on how to handle this subgroup of patients in clinical and screening setting.

Cyst-related primary lung malignancies: an important and relatively unknown imaging appearance of (early) lung cancer.

It is well known that lung cancer can manifest itself in imaging as solid and subsolid nodules or masses. However, in this era of increased computed tomography use another morphological computed tomography appearance of lung cancer is increasingly being recognised, presenting as a malignancy in relation to cystic airspaces. Despite the fact that it seems to be a relatively common finding in daily practice, literature on this entity is scarce and presumably the overall awareness is limited. This can lead to misinterpretation and delay in diagnosis and, therefore, increased awareness is urgently needed. This review aims to illustrate the imaging appearances of cyst-related primary lung malignancies, demonstrate its mimickers and potential pitfalls, and discuss the clinical implications based on the available literature and our own experience in four different hospitals.

Brock malignancy risk calculator for pulmonary nodules: validation outside a lung cancer screening population.

OBJECTIVE: To assess the performance of the Brock malignancy risk model for pulmonary nodules detected in routine clinical setting. METHODS: In two academic centres in the Netherlands, we established a list of patients aged ≥40 years who received a chest CT scan between 2004 and 2012, resulting in 16 850 and 23 454 eligible subjects. Subsequent diagnosis of lung cancer until the end of 2014 was established through linking with the National Cancer Registry. A nested case-control study was performed (ratio 1:3). Two observers used semiautomated software to annotate the nodules. The Brock model was separately validated on each data set using ROC analysis and compared with a solely size-based model. RESULTS: After the annotation process the final analysis included 177 malignant and 695 benign nodules for centre A, and 264 malignant and 710 benign nodules for centre B. The full Brock model resulted in areas under the curve (AUCs) of 0.90 and 0.91, while the size-only model yielded significantly lower AUCs of 0.88 and 0.87, respectively (p<0.001). At 10% malignancy risk, the threshold suggested by the British Thoracic Society, sensitivity of the full model was 75% and 81%, specificity was 85% and 84%, positive predictive values were 14% and 10% at negative predictive value (NPV) of 99%. The optimal threshold was 6% for centre A and 8% for centre B, with NPVs >99%. DISCUSSION: The Brock model shows high predictive discrimination of potentially malignant and benign nodules when validated in an unselected, heterogeneous clinical population. The high NPV may be used to decrease the number of nodule follow-up examinations.

In vivo growth of 60 non-screening detected lung cancers: a computed tomography study.

Current pulmonary nodule management guidelines are based on nodule volume doubling time, which assumes exponential growth behaviour. However, this is a theory that has never been validated in vivo in the routine-care target population. This study evaluates growth patterns of untreated solid and subsolid lung cancers of various histologies in a non-screening setting.Growth behaviour of pathology-proven lung cancers from two academic centres that were imaged at least three times before diagnosis (n=60) was analysed using dedicated software. Random-intercept random-slope mixed-models analysis was applied to test which growth pattern most accurately described lung cancer growth. Individual growth curves were plotted per pathology subgroup and nodule type.We confirmed that growth in both subsolid and solid lung cancers is best explained by an exponential model. However, subsolid lesions generally progress slower than solid ones. Baseline lesion volume was not related to growth, indicating that smaller lesions do not grow slower compared to larger ones.By showing that lung cancer conforms to exponential growth we provide the first experimental basis in the routine-care setting for the assumption made in volume doubling time analysis.

Incidental perifissural nodules on routine chest computed tomography: lung cancer or not?

OBJECTIVES: Perifissural nodules (PFNs) are a common finding on chest CT, and are thought to represent non-malignant lesions. However, data outside a lung cancer-screening setting are currently lacking. METHODS: In a nested case-control design, out of a total cohort of 16,850 patients ≥ 40 years of age who underwent routine chest CT (2004-2012), 186 eligible subjects with incident lung cancer and 511 controls without were investigated. All non-calcified nodules ≥ 4 mm were semi-automatically annotated. Lung cancer location and subject characteristics were recorded. RESULTS: Cases (56 % male) had a median age of 64 years (IQR 59-70). Controls (60 % male) were slightly younger (p<0.01), median age of 61 years (IQR 51-70). A total of 262/1,278 (21 %) unique non-calcified nodules represented a PFN. None of these were traced to a lung malignancy over a median follow-up of around 4.5 years. PFNs were most often located in the lower lung zones (72 %, p<0.001). Median diameter was 4.6 mm (range: 4.0-8.1), volume 51 mm3 (range: 32-278). Some showed growth rates < 400 days. CONCLUSIONS: Our data show that incidental PFNs do not represent lung cancer in a routine care, heterogeneous population. This confirms prior screening-based results. KEY POINTS: • One-fifth of non-calcified nodules represented a perifissural nodule in our non-screening population. • PFNs fairly often show larger size, and can show interval growth. • When morphologically resembling a PFN, nodules are nearly certainly not a malignancy. • The assumed benign aetiology of PFNs seems valid outside the screening setting.

Malignancy estimation of Lung-RADS criteria for subsolid nodules on CT: accuracy of low and high risk spectrum when using NLST nodules.

PURPOSE: Lung-RADS proposes malignancy probabilities for categories 2 (<1%) and 4B (>15%). The purpose of this study was to quantify and compare malignancy rates for Lung-RADS 2 and 4B subsolid nodules (SSNs) on a nodule base. METHODS: We identified all baseline SSNs eligible for Lung-RADS 2 and 4B in the National Lung Screening Trial (NLST) database. Solid cores and nodule locations were annotated using in-house software. Malignant SSNs were identified by an experienced radiologist using NLST information. Malignancy rates and percentages of persistence were calculated. RESULTS: Of the Lung-RADS 2SSNs, 94.3% (1790/1897) could be located on chest CTs. Likewise, 95.1% (331/348) of part-solid nodules ≥6 mm in diameter could be located. Of these, 120 had a solid core ≥8 mm, corresponding to category 4B. Category 2 SSNs showed a malignancy rate of 2.5%, exceeding slightly the proposed rate of <1%. Category 4B SSNs showed a malignancy rate of 23.9%. In both categories one third of benign lesions were transient. CONCLUSION: Malignancy probabilities for Lung-RADS 2 and 4B generally match malignancy rates in SSNs. An option to include also category 2 SSNs for upgrade to 4X designed for suspicious nodules might be useful in the future. Integration of short-term follow-up to confirm persistence would prevent unnecessary invasive work-up in 4B SSNs. KEY POINTS: • Malignancy probabilities for Lung-RADS 2/4B generally match malignancy risks in SSNs. • Transient rate between low-risk Lung-RADS 2 and high-risk 4B lesions were similar. • Upgrade of highly suspicious Lung-RADS 2 SSNs to Lung-RADS 4X might be useful. • Up to one third of the benign high-risk Lung-RADS 4B lesions were transient. • Short-term follow-up confirming persistence would avoid unnecessary invasive work-up of 4B lesions.

Lung-RADS Category 4X: Does It Improve Prediction of Malignancy in Subsolid Nodules?

Purpose To evaluate the added value of Lung CT Screening Reporting and Data System (Lung-RADS) assessment category 4X over categories 3, 4A, and 4B for differentiating between benign and malignant subsolid nodules (SSNs). Materials and Methods SSNs on all baseline computed tomographic (CT) scans from the National Lung Cancer Trial that would have been classified as Lung-RADS category 3 or higher were identified, resulting in 374 SSNs for analysis. An experienced screening radiologist volumetrically segmented all solid cores and located all malignant SSNs visible on baseline scans. Six experienced chest radiologists independently determined which nodules to upgrade to category 4X, a recently introduced category for lesions that demonstrate additional features or imaging findings that increase the suspicion of malignancy. Malignancy rates of purely size-based categories and category 4X were compared. Furthermore, the false-positive rates of category 4X lesions were calculated and observer variability was assessed by using Fleiss κ statistics. Results The observers upgraded 15%-24% of the SSNs to category 4X. The malignancy rate for 4X nodules varied from 46% to 57% per observer and was substantially higher than the malignancy rates of categories 3, 4A, and 4B SSNs without observer intervention (9%, 19%, and 23%, respectively). On average, the false-positive rate for category 4X nodules was 7% for category 3 SSNs, 7% for category 4A SSNs, and 19% for category 4B SSNs. Of the falsely upgraded benign lesions, on average 27% were transient. The agreement among the observers was moderate, with an average κ value of 0.535 (95% confidence interval: 0.509, 0.561). Conclusion The inclusion of a 4X assessment category for lesions suspicious for malignancy in a nodule management tool is of added value and results in high malignancy rates in the hands of experienced radiologists. Proof of the transient character of category 4X lesions at short-term follow-up could avoid unnecessary invasive management. © RSNA, 2017.

Subsolid pulmonary nodule morphology and associated patient characteristics in a routine clinical population.

OBJECTIVES: To determine the presence and morphology of subsolid pulmonary nodules (SSNs) in a non-screening setting and relate them to clinical and patient characteristics. METHODS: A total of 16,890 reports of clinically obtained chest CT (06/2011 to 11/2014, single-centre) were searched describing an SSN. Subjects with a visually confirmed SSN and at least two thin-slice CTs were included. Nodule volumes were measured. Progression was defined as volume increase exceeding the software interscan variation. Nodule morphology, location, and patient characteristics were evaluated. RESULTS: Fifteen transient and 74 persistent SSNs were included (median follow-up 19.6 [8.3-36.8] months). Subjects with an SSN were slightly older than those without (62 vs. 58 years; p = 0.01), but no gender predilection was found. SSNs were mostly located in the upper lobes. Women showed significantly more often persistent lesions than men (94 % vs. 69 %; p = 0.002). Part-solid lesions were larger (1638 vs. 383 mm3; p < 0.001) and more often progressive (68 % vs. 38 %; p = 0.02), compared to pure ground-glass nodules. Progressive SSNs were rare under the age of 50 years. Logistic regression analysis did not identify additional nodule parameters of future progression, apart from part-solid nature. CONCLUSIONS: This study confirms previously reported characteristics of SSNs and associated factors in a European, routine clinical population. KEY POINTS: • SSNs in women are significantly more often persistent compared to men. • SSN persistence is not associated with age or prior malignancy. • The majority of (persistent) SSNs are located in the upper lung lobes. • A part-solid nature is associated with future nodule growth. • Progressive solitary SSNs are rare under the age of 50 years.

Follow-up of CT-derived airway wall thickness: Correcting for changes in inspiration level improves reliability.

OBJECTIVES: Airway wall thickness (AWT) is affected by changes in lung volume. This study evaluated whether correcting AWT on computed tomography (CT) for differences in inspiration level improves measurement agreement, reliability, and power to detect changes over time. METHODS: Participants of the Dutch-Belgian lung cancer screening trial who underwent 3-month repeat CT for an indeterminate pulmonary nodule were included. AWT on CT was calculated by the square root of the wall area at a theoretical airway with an internal perimeter of 10mm (Pi10). The scan with the highest lung volume was labelled as the reference scan and the scan with the lowest lung volume was labelled as the comparison scan. Pi10 derived from the comparison scan was corrected by multiplying it with the ratio of CT lung volume of the comparison scan to CT lung volume on the reference scan. Agreement of uncorrected and corrected Pi10 was studied with the Bland-Altman method, reliability with intra-class correlation coefficients (ICC), and power to detect changes over time was calculated. RESULTS: 315 male participants were included. Limit of agreement and reliability for Pi10 was -0.61 to 0.57mm (ICC=0.87), which improved to -0.38 to 0.37mm (ICC=0.94) after correction for inspiration level. To detect a 15% change over 3 months, 71 subjects are needed for Pi10 and 26 subjects for Pi10 adjusted for inspiration level. CONCLUSIONS: Correcting Pi10 for differences in inspiration level improves reliability, agreement, and power to detect changes over time.

Fleischner recommendations for the management of subsolid pulmonary nodules: high awareness but limited conformance - a survey study.

OBJECTIVES: The aim of this study was to assess awareness and conformance to the Fleischner society recommendations for the management of subsolid pulmonary nodules (SSN) in clinical practice. METHODS: An online questionnaire with four imaging cases was sent to 1579 associates from the European Respiratory Society and 757 from the European Society of Thoracic Imaging. Each respondent was asked to choose from several options which one they thought was the indicated management for the nodule presented. Awareness and conformance to the Fleischner recommendations (FR) were assessed and correlated to respondents characteristics. RESULTS: In total, 119 radiologists (response rate 16.0 %) and 243 pulmonologists (response rate 16.5 %) were included. Awareness of the FR was higher in radiologists than in pulmonologists (93 % vs. 70 %, p < 0.001), as was implementation in daily practice (66 % vs. 47 %, p < 0.001). Radiologists conformed to FR in rates of 31, 69, 68, and 82 %, and pulmonologists in 12, 43, 70, and 75 % for cases 1 to 4, respectively. Overmanagement was common. Conformance in SSN management was associated with awareness, working in an academic practice, larger practice size, teaching residents, and higher SSN exposure. CONCLUSIONS: Although awareness of the Fleischner recommendations for SSN management is widespread, management choices in clinical practice show large heterogeneity. KEY POINTS: • Guideline awareness among clinicians is widespread, but conformance shows large heterogeneity. • Awareness and conformance is significantly higher among radiologists than pulmonologists. • Overmanagement is common, which may lead to avoidable financial and physical burden.

Emphysema Is Common in Lungs of Cystic Fibrosis Lung Transplantation Patients: A Histopathological and Computed Tomography Study.

BACKGROUND: Lung disease in cystic fibrosis (CF) involves excessive inflammation, repetitive infections and development of bronchiectasis. Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy. The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs. METHODS: In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology specimens. Also, emphysema was automatically quantified on pre-transplantation computed tomography (CT) using the percentage of voxels below -950 Houndfield Units and was visually scored on CT. The relation between emphysema extent, pre-transplantation lung function and age was determined. RESULTS: All CF patients showed emphysema on histological examination: 3/20 (15%) showed mild, 15/20 (75%) moderate and 2/20 (10%) severe emphysema, defined as 0-20% emphysema, 20-50% emphysema and >50% emphysema in residual lung tissue, respectively. Visually upper lobe bullous emphysema was identified in 13/20 and more diffuse non-bullous emphysema in 18/20. Histology showed a significant correlation to quantified CT emphysema (p = 0.03) and visual emphysema score (p = 0.001). CT and visual emphysema extent were positively correlated with age (p = 0.045 and p = 0.04, respectively). CONCLUSIONS: In conclusion, this study both pathologically and radiologically confirms that emphysema is common in end-stage CF lungs, and is age related. Emphysema might become an increasingly important disease component in the aging CF population.

Contribution of CT quantified emphysema, air trapping and airway wall thickness on pulmonary function in male smokers with and without COPD.

Emphysema, airway wall thickening and air trapping are associated with chronic obstructive pulmonary disease (COPD). All three can be quantified by computed tomography (CT) of the chest. The goal of the current study is to determine the relative contribution of CT derived parameters on spirometry, lung volume and lung diffusion testing. Emphysema, airway wall thickening and air trapping were quantified automatically on CT in 1,138 male smokers with and without COPD. Emphysema was quantified by the percentage of voxels below -950 Hounsfield Units (HU), airway wall thickness by the square root of wall area for a theoretical airway with 10 mm lumen perimeter (Pi10) and air trapping by the ratio of mean lung density at expiration and inspiration (E/I-ratio). Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were obtained. Standardized regression coefficients (ß) were used to analyze the relative contribution of CT changes to pulmonary function measures. The independent contribution of the three CT measures differed per lung function parameter. For the FEV1 airway wall thickness was the most contributing structural lung change (ß = -0.46), while for the FEV1/FVC this was emphysema (ß = -0.55). For the residual volume (RV) air trapping was most contributing (ß = -0.35). Lung diffusion capacity was most influenced by emphysema (ß = -0.42). In a cohort of smokers with and without COPD the effect of different CT changes varies per lung function measure and therefore emphysema, airway wall thickness and air trapping need to be taken in account.