Publications by authors named "Hester A Gietema"

45 Publications

Implementation of Bronchoscopic Lung Volume Reduction Using One-Way Endobronchial Valves: A Retrospective Single-Centre Cohort Study.

Respiration 2021 Dec 22:1-9. Epub 2021 Dec 22.

Department of Respiratory Medicine and Allergology, COPD Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: Bronchoscopic lung volume reduction (BLVR) using 1-way endobronchial valves (EBV) has become a guideline treatment in patients with advanced emphysema. Evidence from this minimally invasive treatment derives mainly from well-designed controlled trials conducted in high-volume specialized intervention centres. Little is known about real-life outcome data in hospitals setting up this novel treatment and which favourable conditions are required for a continuous successful program.

Objectives: In this study, we aim to evaluate the eligibility rate for BLVR and whether the implementation of BLVR in our academic hospital is feasible and yields clinically significant outcomes.

Method: A retrospective evaluation of patients treated with EBV between January 2016 and August 2019 was conducted. COPD assessment test (CAT), forced expiratory volume in 1 s (FEV1), residual volume (RV), and 6-min walking test (6MWT) were measured at baseline and 3 months after intervention. Paired sample t tests were performed to compare means before and after intervention.

Results: Of 350 subjects screened, 283 (81%) were not suitable for intervention mostly due to lack of a target lobe. The remaining 67 subjects (19%) underwent bronchoscopic assessment, and if suitable, valves were placed in the same session. In total, 55 subjects (16%) were treated with EBV of which 10 did not have complete follow-up: 6 subjects had their valves removed because of severe pneumothorax (n = 2) or lack of benefit (n = 4) and the remaining 4 had missing follow-up data. Finally, 45 patients had complete follow-up at 3 months and showed an average change ± SD in CAT -4 ± 6 points, FEV1 +190 ± 140 mL, RV -770 ± 790 mL, and +37 ± 65 m on the 6MWT (all p < 0.001). After 1-year follow-up, 34 (76%) subjects had their EBV in situ.

Conclusion: Implementing BLVR with EBV is feasible and effective. Only 16% of screened patients were eligible, indicating that this intervention is only applicable in a small subset of highly selected subjects with advanced emphysema, and therefore a high volume of COPD patients is essential for a sustainable BLVR program.
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http://dx.doi.org/10.1159/000520885DOI Listing
December 2021

Dual-Energy Computed Tomography Compared to Lung Perfusion Scintigraphy to Assess Pulmonary Perfusion in Patients Screened for Endoscopic Lung Volume Reduction.

Respiration 2021 10;100(12):1186-1195. Epub 2021 Aug 10.

COPD Center, Sahlgrenska University Hospital and Institute of Medicine, University of Gothenburg, Göteborg, Sweden.

Background: Endoscopic lung volume reduction (ELVR) using one-way endobronchial valves is a technique to reduce hyperinflation in patients with severe emphysema by inducing collapse of a severely destroyed pulmonary lobe. Patient selection is mainly based on evaluation of emphysema severity on high-resolution computed tomography and evaluation of lung perfusion with perfusion scintigraphy. Dual-energy contrast-enhanced CT scans may be useful for perfusion assessment in emphysema but has not been compared against perfusion scintigraphy.

Aims: The aim of the study was to compare perfusion distribution assessed with dual-energy contrast-enhanced computed tomography and perfusion scintigraphy.

Material And Methods: Forty consecutive patients with severe emphysema, who were screened for ELVR, were included. Perfusion was assessed with 99mTc perfusion scintigraphy and using the iodine map calculated from the dual-energy contrast-enhanced CT scans. Perfusion distribution was calculated as usually for the upper, middle, and lower thirds of both lungs with the planar technique and the iodine overlay.

Results: Perfusion distribution between the right and left lung showed good correlation (r = 0.8). The limits of agreement of the mean absolute difference in percentage perfusion per region of interest were 0.75-5.6%. The upper lobes showed more severe perfusion reduction than the lower lobes. Mean difference in measured pulmonary perfusion ranged from -2.8% to 2.3%. Lower limit of agreement ranged from -8.9% to 4.6% and upper limit was 3.3-10.0%.

Conclusion: Quantification of perfusion distribution using planar 99mTc perfusion scintigraphy and iodine overlays calculated from dual-energy contrast-enhanced CTs correlates well with acceptable variability.
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http://dx.doi.org/10.1159/000517598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8743912PMC
August 2021

Symptomatic mediastinal mass in a 32-year-old male.

Breathe (Sheff) 2021 Jun;17(2):210029

Dept of Cardiothoracic surgery, Maastricht University Medical Center+, Maastricht, The Netherlands.

https://bit.ly/3uQrFXo.
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http://dx.doi.org/10.1183/20734735.0029-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291925PMC
June 2021

Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort.

Thromb J 2021 May 31;19(1):35. Epub 2021 May 31.

Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism.

Methods: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants.

Results: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 μg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 μg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer.

Conclusion: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.
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http://dx.doi.org/10.1186/s12959-021-00286-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165953PMC
May 2021

Impact of the COVID-19 pandemic on incidence and severity of acute appendicitis: a comparison between 2019 and 2020.

BMC Emerg Med 2021 05 12;21(1):61. Epub 2021 May 12.

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Background: During the COVID-19 pandemic, a decrease in the number of patients presenting with acute appendicitis was observed. It is unclear whether this caused a shift towards more complicated cases of acute appendicitis. We compared a cohort of patients diagnosed with acute appendicitis during the 2020 COVID-19 pandemic with a 2019 control cohort.

Methods: We retrospectively included consecutive adult patients in 21 hospitals presenting with acute appendicitis in a COVID-19 pandemic cohort (March 15 - April 30, 2020) and a control cohort (March 15 - April 30, 2019). Primary outcome was the proportion of complicated appendicitis. Secondary outcomes included prehospital delay, appendicitis severity, and postoperative complication rates.

Results: The COVID-19 pandemic cohort comprised 607 patients vs. 642 patients in the control cohort. During the COVID-19 pandemic, a higher proportion of complicated appendicitis was seen (46.9% vs. 38.5%; p = 0.003). More patients had symptoms exceeding 24 h (61.1% vs. 56.2%, respectively, p = 0.048). After correction for prehospital delay, presentation during the first wave of the COVID-19 pandemic was still associated with a higher rate of complicated appendicitis. Patients presenting > 24 h after onset of symptoms during the COVID-19 pandemic were older (median 45 vs. 37 years; p = 0.001) and had more postoperative complications (15.3% vs. 6.7%; p = 0.002).

Conclusions: Although the incidence of acute appendicitis was slightly lower during the first wave of the 2020 COVID-19 pandemic, more patients presented with a delay and with complicated appendicitis than in a corresponding period in 2019. Spontaneous resolution of mild appendicitis may have contributed to the increased proportion of patients with complicated appendicitis. Late presenting patients were older and experienced more postoperative complications compared to the control cohort.
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http://dx.doi.org/10.1186/s12873-021-00454-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114672PMC
May 2021

Functional Outcomes and Their Association With Physical Performance in Mechanically Ventilated Coronavirus Disease 2019 Survivors at 3 Months Following Hospital Discharge: A Cohort Study.

Crit Care Med 2021 10;49(10):1726-1738

Department of Intensive Care Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

Objectives: We performed a comprehensive health assessment in mechanically ventilated coronavirus disease 2019 survivors to assess the impact of respiratory and skeletal muscle injury sustained during ICU stay on physical performance at 3 months following hospital discharge.

Design: Preregistered prospective observational cohort study.

Setting: University hospital ICU.

Patients: All mechanically ventilated coronavirus disease 2019 patients admitted to our ICU during the first European pandemic wave.

Measurements And Main Results: At 3 months after hospital discharge, 46 survivors underwent a comprehensive physical assessment (6-min walking distance, Medical Research Council sum score and handgrip strength), a full pulmonary function test, and a chest CT scan which was used to analyze skeletal muscle architecture. In addition, patient-reported outcomes measures were collected. Physical performance assessed by 6-minute walking distance was below 80% of predicted in 48% of patients. Patients with impaired physical performance had more muscle weakness (Medical Research Council sum score 53 [51-56] vs 59 [56-60]; p < 0.001), lower lung diffusing capacity (54% [44-66%] vs 68% of predicted [61-72% of predicted]; p = 0.002), and higher intermuscular adipose tissue area (p = 0.037). Reduced lung diffusing capacity and increased intermuscular adipose tissue were independently associated with physical performance.

Conclusions: Physical disability is common at 3 months in severe coronavirus disease 2019 survivors. Lung diffusing capacity and intermuscular adipose tissue assessed on CT were independently associated with walking distance, suggesting a key role for pulmonary function and muscle quality in functional disability.
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http://dx.doi.org/10.1097/CCM.0000000000005089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439632PMC
October 2021

The prognostic value of weight and body composition changes in patients with non-small-cell lung cancer treated with nivolumab.

J Cachexia Sarcopenia Muscle 2021 06 5;12(3):657-664. Epub 2021 May 5.

Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center +, Maastricht, The Netherlands.

Background: It is not well known to what extent effectiveness of treatment with immune checkpoint inhibitors in stage IV non-small-cell lung cancer (NSCLC) is influenced by weight loss and changes in body composition. Therefore, the goal of this study was to evaluate body composition changes in relation to early weight change and overall survival (OS) in stage IV NSCLC patients treated with second-line nivolumab.

Methods: All patients with stage IV NSCLC, who were treated with second-line nivolumab between June 2015 and December 2018 at Maastricht University Medical Center, were evaluated. Skeletal muscle mass (SMM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were assessed at the first lumbar level on computed tomography images obtained before initiation of nivolumab and at week 6 of treatment. The contribution of changes in body weight (defined as >2% loss), SMM, VAT, and SAT to OS was analysed by Kaplan-Meier method and adjusted for clinical confounders in a Cox regression analysis. The results from the study cohort were validated in another Dutch cohort from Erasmus Medical Center, Rotterdam.

Results: One hundred and six patients were included in the study cohort. Loss of body weight of >2% at week 6 was an independent predictor for poor OS (hazard ratio 2.39, 95% confidence interval 1.51-3.79, P < 0.001) when adjusted for gender, >1 organ with metastasis, pretreatment hypoalbumenaemia, and pretreatment elevated C-reactive protein. The result was confirmed in the validation cohort (N = 62). Loss of SMM as a feature of cancer cachexia did not significantly predict OS in both cohorts. Significant (>2%) weight loss during treatment was reflected by a significant loss of VAT and SAT, while loss of SMM was comparable between weight-stable and weight-losing patients.

Conclusions: Weight loss, characterized by loss of subcutaneous and visceral adipose tissues, at week 6 of treatment with nivolumab, is a significant poor prognostic factor for survival in patients with Stage IV NSCLC.
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http://dx.doi.org/10.1002/jcsm.12698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200425PMC
June 2021

Reply to Vijayakumar and Shah.

Am J Respir Crit Care Med 2021 06;203(11):1442-1443

Maastricht University Medical Centre Maastricht, the Netherlands.

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http://dx.doi.org/10.1164/rccm.202102-0468LEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456532PMC
June 2021

Idiopathic pulmonary fibrosis: Current knowledge, future perspectives and its importance in radiation oncology.

Radiother Oncol 2021 02 24;155:269-277. Epub 2020 Nov 24.

Department of Radiation Oncology, MAASTRO Clinic, Maastricht University Medical Center+, Maastricht, The Netherlands; GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic lung disease with an unknown cause. Uncertainties still remain regarding the pathogenesis of IPF, and the prognosis of this disease is poor despite some recent improvements in treatment. Radiation induced lung injury (RILI) is a common complication and a dose-limiting toxicity of thoracic radiotherapy. Importantly, IPF is a crucial risk factor for pulmonary toxicity after thoracic radiotherapy. Although IPF is not universally accepted as a definite contraindication for thoracic radiotherapy at present, it has been shown that IPF can increase the risk of severe and fatal complications after thoracic radiotherapy. Proton beam therapy has shown promising results in reducing the incidence of thoracic radiotherapy related life-threatening complications in IPF patients, but the current evidence is not sufficient to recommend the standard use of it. Many similarities are noticeable between IPF and RILI in terms of pathogenesis and underlying mechanisms. Better understanding of the mechanisms of IPF and RILI may enable clinicians to provide safer and more effective thoracic radiotherapy treatments in cancer patients with IPF. In this review, we summarize the current knowledge of IPF, present the importance of IPF in radiation oncology practice, and highlight the similarities and relationship between IPF and RILI.
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http://dx.doi.org/10.1016/j.radonc.2020.11.020DOI Listing
February 2021

Chest CT in the Emergency Department for Diagnosis of COVID-19 Pneumonia: Dutch Experience.

Radiology 2021 02 17;298(2):E98-E106. Epub 2020 Nov 17.

From the Department of Radiology, Nuclear Medicine and Anatomy (S.S., M.P.), Department of Internal Medicine, Division of Infectious Diseases, and Radboud Center for Infectious Diseases (C.P.B.R.), Department of Pulmonology (M.H.E.R.), and Department of Medical Microbiology and Radboud Center for Infectious Diseases (J.R.L.), Radboud University Medical Center, Geert Grooteplein zuid 10, 6525GA Nijmegen, the Netherlands; Department of Radiology (L.F.M.B.), Department of Medicine, Division of Infectious Diseases, Department of Internal Medicine (V.H.), Department of Respiratory Medicine (D.A.K.), and Department of Internal Medicine (L.P.S.), Amsterdam UMC, Location AMC, Amsterdam, the Netherlands; Departments of Radiology and Nuclear Medicine (H.M.E.Q.v.U., T.v.R.V.) and Pulmonology (C.K.), Haaglanden Medical Center, The Hague, the Netherlands; Department of Radiology and Nuclear Medicine (H.A.G.) and Department of Internal Medicine (P.M.S.), Maastricht University Medical Center+, Maastricht, the Netherlands; Departments of Radiology (J.L.S.), Infectious Diseases (H.S., R.W.), and Pulmonology (F.J.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands (V.H.); Departments of Radiology (M.V.) and Internal Medicine (A.S.M.D.), Canisius-Wilhelmina Ziekenhuis, Nijmegen, the Netherlands; and GROW School for Oncology and Developmental Biology, Maastricht, the Netherlands (H.A.G.).

Background Clinicians need to rapidly and reliably diagnose coronavirus disease 2019 (COVID-19) for proper risk stratification, isolation strategies, and treatment decisions. Purpose To assess the real-life performance of radiologist emergency department chest CT interpretation for diagnosing COVID-19 during the acute phase of the pandemic, using the COVID-19 Reporting and Data System (CO-RADS). Materials and Methods This retrospective multicenter study included consecutive patients who presented to emergency departments in six medical centers between March and April 2020 with moderate to severe upper respiratory symptoms suspicious for COVID-19. As part of clinical practice, chest CT scans were obtained for primary work-up and scored using the five-point CO-RADS scheme for suspicion of COVID-19. CT was compared with severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (RT-PCR) assay and a clinical reference standard established by a multidisciplinary group of clinicians based on RT-PCR, COVID-19 contact history, oxygen therapy, timing of RT-PCR testing, and likely alternative diagnosis. Performance of CT was estimated using area under the receiver operating characteristic curve (AUC) analysis and diagnostic odds ratios against both reference standards. Subgroup analysis was performed on the basis of symptom duration grouped presentations of less than 48 hours, 48 hours through 7 days, and more than 7 days. Results A total of 1070 patients (median age, 66 years; interquartile range, 54-75 years; 626 men) were included, of whom 536 (50%) had a positive RT-PCR result and 137 (13%) of whom were considered to have a possible or probable COVID-19 diagnosis based on the clinical reference standard. Chest CT yielded an AUC of 0.87 (95% CI: 0.84, 0.89) compared with RT-PCR and 0.87 (95% CI: 0.85, 0.89) compared with the clinical reference standard. A CO-RADS score of 4 or greater yielded an odds ratio of 25.9 (95% CI: 18.7, 35.9) for a COVID-19 diagnosis with RT-PCR and an odds ratio of 30.6 (95% CI: 21.1, 44.4) with the clinical reference standard. For symptom duration of less than 48 hours, the AUC fell to 0.71 (95% CI: 0.62, 0.80; < .001). Conclusion Chest CT analysis using the coronavirus disease 2019 (COVID-19) Reporting and Data System enables rapid and reliable diagnosis of COVID-19, particularly when symptom duration is greater than 48 hours. © RSNA, 2020 See also the editorial by Elicker in this issue.
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http://dx.doi.org/10.1148/radiol.2020203465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676748PMC
February 2021

Differentiation of COVID-19 Pneumonitis and ICI Induced Pneumonitis.

Front Oncol 2020 29;10:577696. Epub 2020 Oct 29.

Department of Pulmonary Medicine, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.

Immune checkpoint inhibitors (ICI) have become the standard of care treatment for several tumor types. ICI-induced pneumonitis is a serious complication seen with treatment with these agents. Cancer has been reported to be one of the risk factors for severe coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that has engulfed the world in the last couple of months. In patients with cancer treated with ICI who present at the emergency department with respiratory symptoms during the COVID-19 pandemic, correct diagnosis can be challenging. Symptoms and radiological features of ICI pneumonitis can be overlapping with those of COVID-19 related pneumonia. For the latter, dexamethasone and remdesivir have shown encouraging results, while vaccines are currently being evaluated in phase III trials. The mainstay of treatment in ICI pneumonitis is immunosuppressive therapy, as this is a potentially fatal adverse event. It has been speculated that immunosuppression may be associated with increased risk of progression to severe COVID-19, especially during the early stage of infection with SARS-CoV-2. Therefore, distinction between these two entities is warranted. We summarize the clinical, radiological features as well as additional investigations of both entities, and suggest a diagnostic algorithm for distinction between the two. This algorithm may be a supportive tool for clinicians to diagnose the underlying cause of the pneumonitis in patients treated with ICI during this COVID-19 pandemic.
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http://dx.doi.org/10.3389/fonc.2020.577696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658907PMC
October 2020

Spectrum of Vascular Involvement in Coronavirus Disease 2019 Pneumonia-Findings on CT Perfusion.

Crit Care Explor 2020 Oct 21;2(10):e0266. Epub 2020 Oct 21.

Department of Radiology, Haaglanden Medisch Centrum, The Hague, The Netherlands.

Objectives: There is accumulating evidence of a distinct coagulopathy in severe acute respiratory syndrome coronavirus 2 infection which is associated with poor prognosis in coronavirus disease 2019. Coagulation abnormalities in blood samples resemble systemic coagulopathies in other severe infections but demonstrate specific features such as a very high d-dimer. These clinical observations are consistent with histopathologic findings of locally disturbed pulmonary microvascular thrombosis and angiopathy in end-stage coronavirus disease 2019. However, exact underlying processes and the sequence of events are not fully understood.

Data Sources: CT perfusion may provide insight in the dynamic aspect of the vascularity in pulmonary lesions in coronavirus disease 2019 infection as, in contrast to dual energy CT, a multiphase perfusion pattern is displayed.

Study Selection: In six patients with coronavirus disease 2019 pneumonia, findings on additional CT perfusion series were correlated with known histopathologic vascular patterns upon pulmonary autopsy of patients who had died of coronavirus disease 2019.

Data Extraction: In this case series, we were able to show perfusion changes on CT scans in typical pulmonary lesions illustrating diverse patterns.

Data Synthesis: We demonstrated hyperperfusion in areas with ground glass and a severely decreased perfusion pattern in more consolidated areas often seen later in the course of disease. A combination was also observed, illustrating temporal heterogeneity.

Conclusions: These findings provide new insights into the pathophysiology of coronavirus disease 2019 pneumonia and further understanding of the mechanisms that lead to respiratory failure in these patients.
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http://dx.doi.org/10.1097/CCE.0000000000000266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587417PMC
October 2020

The prevalence of pulmonary embolism in patients with COVID-19 and respiratory decline: A three-setting comparison.

Thromb Res 2020 12 15;196:486-490. Epub 2020 Oct 15.

Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre+, Maastricht, the Netherlands; Thrombosis Expert Centre Maastricht and Department of Internal Medicine, Section Vascular Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.

Background: The risk of pulmonary embolism (PE) in patients with Coronavirus Disease 2019 (COVID-19) is recognized. The prevalence of PE in patients with respiratory deterioration at the Emergency Department (ED), the regular ward, and the Intensive Care Unit (ICU) are not well-established.

Objectives: We aimed to investigate how often PE was present in individuals with COVID-19 and respiratory deterioration in different settings, and whether or not disease severity as measured by CT-severity score (CTSS) was related to the occurrence of PE.

Patients/methods: Between April 6th and May 3rd, we enrolled 60 consecutive adult patients with confirmed COVID-19 from the ED, regular ward and ICU who met the pre-specified criteria for respiratory deterioration.

Results: A total of 24 (24/60: 40% (95% CI: 28-54%)) patients were diagnosed with PE, of whom 6 were in the ED (6/23: 26% (95% CI: 10-46%)), 8 in the regular ward (8/24: 33% (95% CI: 16-55%)), and 10 in the ICU (10/13: 77% (95% CI: 46-95%)). CTSS (per unit) was not associated with the occurrence of PE (age and sex-adjusted OR 1.06 (95%CI 0.98-1.15)).

Conclusion: The number of PE diagnosis among patients with COVID-19 and respiratory deterioration was high; 26% in the ED, 33% in the regular ward and 77% in the ICU respectively. In our cohort CTSS was not associated with the occurrence of PE. Based on the high number of patients diagnosed with PE among those scanned we recommend a low threshold for performing computed tomography angiography in patients with COVID-19 and respiratory deterioration.
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http://dx.doi.org/10.1016/j.thromres.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557291PMC
December 2020

Yield of Screening for COVID-19 in Asymptomatic Patients Before Elective or Emergency Surgery Using Chest CT and RT-PCR (SCOUT): Multicenter Study.

Ann Surg 2020 12;272(6):919-924

Department of Surgery, Sint Antonius Hospital, Nieuwegein, the Netherlands.

Objective: To determine the yield of preoperative screening for COVID-19 with chest CT and RT-PCR in patients without COVID-19 symptoms.

Summary Of Background Data: Many centers are currently screening surgical patients for COVID-19 using either chest CT, RT-PCR or both, due to the risk for worsened surgical outcomes and nosocomial spread. The optimal design and yield of such a strategy are currently unknown.

Methods: This multicenter study included consecutive adult patients without COVID-19 symptoms who underwent preoperative screening using chest CT and RT-PCR before elective or emergency surgery under general anesthesia.

Results: A total of 2093 patients without COVID-19 symptoms were included in 14 participating centers; 1224 were screened by CT and RT-PCR and 869 by chest CT only. The positive yield of screening using a combination of chest CT and RT-PCR was 1.5% [95% confidence interval (CI): 0.8-2.1]. Individual yields were 0.7% (95% CI: 0.2-1.1) for chest CT and 1.1% (95% CI: 0.6-1.7) for RT-PCR; the incremental yield of chest CT was 0.4%. In relation to COVID-19 community prevalence, up to ∼6% positive RT-PCR was found for a daily hospital admission rate >1.5 per 100,000 inhabitants, and around 1.0% for lower prevalence.

Conclusions: One in every 100 patients without COVID-19 symptoms tested positive for SARS-CoV-2 with RT-PCR; this yield increased in conjunction with community prevalence. The added value of chest CT was limited. Preoperative screening allowed us to take adequate precautions for SARS-CoV-2 positive patients in a surgical population, whereas negative patients needed only routine procedures.
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http://dx.doi.org/10.1097/SLA.0000000000004218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668335PMC
December 2020

Automated Assessment of COVID-19 Reporting and Data System and Chest CT Severity Scores in Patients Suspected of Having COVID-19 Using Artificial Intelligence.

Radiology 2021 01 30;298(1):E18-E28. Epub 2020 Jul 30.

From the Department of Radiology, Nuclear Medicine and Anatomy, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands (N.L., C.I.S., L.H.B., M.B., E.C., W.M.v.E., P.K.G., B.G., M.G., N.H., W.H., H.J.H., C.J., R.K., M.K., K.v.L., J.M., M.O., R.S., C. Schaefer-Prokop, S.S., E.T.S., C. Sital, J.T., K.V.V., C.d.V., W.X., B.d.W., M.P., B.v.G.); Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands (L.B.); Thirona, Nijmegen, the Netherlands (J.P.C., E.M.v.R.); Departments of Internal Medicine (T.D.) and Radiology (M.V.), Canisius-Wilhelmina Ziekenhuis, Nijmegen, the Netherlands; Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, the Netherlands (H.A.G.); GROW School of Oncology and Developmental Biology, Maastricht, the Netherlands (H.A.G.); Departments of Biomedical Physics and Engineering and Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands (L.v.H., I.I.); Department of Radiology, Zuyderland Medical Center, Heerlen, the Netherlands (J.K.); Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany (B.L.); Department of Radiology and Nuclear Medicine, Haaglanden Medical Center, The Hague, the Netherlands (T.v.R.V.); Department of Radiology, Meander Medical Center, Amersfoort, the Netherlands (C. Schaefer-Prokop, S.S.); and Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands (J.L.S.).

Background The coronavirus disease 2019 (COVID-19) pandemic has spread across the globe with alarming speed, morbidity, and mortality. Immediate triage of patients with chest infections suspected to be caused by COVID-19 using chest CT may be of assistance when results from definitive viral testing are delayed. Purpose To develop and validate an artificial intelligence (AI) system to score the likelihood and extent of pulmonary COVID-19 on chest CT scans using the COVID-19 Reporting and Data System (CO-RADS) and CT severity scoring systems. Materials and Methods The CO-RADS AI system consists of three deep-learning algorithms that automatically segment the five pulmonary lobes, assign a CO-RADS score for the suspicion of COVID-19, and assign a CT severity score for the degree of parenchymal involvement per lobe. This study retrospectively included patients who underwent a nonenhanced chest CT examination because of clinical suspicion of COVID-19 at two medical centers. The system was trained, validated, and tested with data from one of the centers. Data from the second center served as an external test set. Diagnostic performance and agreement with scores assigned by eight independent observers were measured using receiver operating characteristic analysis, linearly weighted κ values, and classification accuracy. Results A total of 105 patients (mean age, 62 years ± 16 [standard deviation]; 61 men) and 262 patients (mean age, 64 years ± 16; 154 men) were evaluated in the internal and external test sets, respectively. The system discriminated between patients with COVID-19 and those without COVID-19, with areas under the receiver operating characteristic curve of 0.95 (95% CI: 0.91, 0.98) and 0.88 (95% CI: 0.84, 0.93), for the internal and external test sets, respectively. Agreement with the eight human observers was moderate to substantial, with mean linearly weighted κ values of 0.60 ± 0.01 for CO-RADS scores and 0.54 ± 0.01 for CT severity scores. Conclusion With high diagnostic performance, the CO-RADS AI system correctly identified patients with COVID-19 using chest CT scans and assigned standardized CO-RADS and CT severity scores that demonstrated good agreement with findings from eight independent observers and generalized well to external data. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020202439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393955PMC
January 2021

CT in relation to RT-PCR in diagnosing COVID-19 in The Netherlands: A prospective study.

PLoS One 2020 9;15(7):e0235844. Epub 2020 Jul 9.

Department of Internal Medicine, Division of General Internal Medicine, Section Acute Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

Introduction: Early differentiation between emergency department (ED) patients with and without corona virus disease (COVID-19) is very important. Chest CT scan may be helpful in early diagnosing of COVID-19. We investigated the diagnostic accuracy of CT using RT-PCR for SARS-CoV-2 as reference standard and investigated reasons for discordant results between the two tests.

Methods: In this prospective single centre study in the Netherlands, all adult symptomatic ED patients had both a CT scan and a RT-PCR upon arrival at the ED. CT results were compared with PCR test(s). Diagnostic accuracy was calculated. Discordant results were investigated using discharge diagnoses.

Results: Between March 13th and March 24th 2020, 193 symptomatic ED patients were included. In total, 43.0% of patients had a positive PCR and 56.5% a positive CT, resulting in a sensitivity of 89.2%, specificity 68.2%, likelihood ratio (LR)+ 2.81 and LR- 0.16. Sensitivity was higher in patients with high risk pneumonia (CURB-65 score ≥3; n = 17, 100%) and with sepsis (SOFA score ≥2; n = 137, 95.5%). Of the 35 patients (31.8%) with a suspicious CT and a negative RT-PCR, 9 had another respiratory viral pathogen, and in 7 patients, COVID-19 was considered likely. One of nine patients with a non-suspicious CT and a positive PCR had developed symptoms within 48 hours before scanning.

Discussion: The accuracy of chest CT in symptomatic ED patients is high, but used as a single diagnostic test, CT can not safely diagnose or exclude COVID-19. However, CT can be used as a quick tool to categorize patients into "probably positive" and "probably negative" cohorts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235844PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347219PMC
July 2020

The Emerging Role of Radiomics in COPD and Lung Cancer.

Respiration 2020;99(2):99-107. Epub 2020 Jan 28.

The D-Lab, Department of Precision Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.

Medical imaging plays a key role in evaluating and monitoring lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. The application of artificial intelligence in medical imaging has transformed medical images into mineable data, by extracting and correlating quantitative imaging features with patients' outcomes and tumor phenotype - a process termed radiomics. While this process has already been widely researched in lung oncology, the evaluation of COPD in this fashion remains in its infancy. Here we outline the main applications of radiomics in lung cancer and briefly review the workflow from image acquisition to the evaluation of model performance. Finally, we discuss the current assessments of COPD and the potential application of radiomics in COPD.
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http://dx.doi.org/10.1159/000505429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949220PMC
April 2021

What you see is (not) what you get: tools for a non-radiologist to evaluate image quality in lung cancer.

Lung Cancer 2018 09 18;123:112-115. Epub 2018 Jul 18.

Department of Pulmonary Diseases, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands. Electronic address:

Medical images are an integral part of oncological patient records and they are reviewed by many different specialists. Therefore, it is important that besides imaging experts, other clinicians are also aware that the diagnostic value of a scan is influenced by the applied imaging protocol. Based on two clinical lung cancer trials, we experienced that, even within a study protocol, there is a large variability in imaging parameters, which has direct impact on the interpretation of the image. These two trials were: 1) the NTR3628 in which the added value of gadolinium magnetic resonance imaging (Gd-MRI) to dedicated contrast enhanced computed tomography (CE-CT) for detecting asymptomatic brain metastases in stage III non-small cell lung cancer (NSCLC) was investigated and 2) a sub-study of the NVALT 12 trial (NCT01171170) in which repeated 18 F-fludeoxyglucose positron emission tomography (F-FDG-PET) imaging for early response assessment was investigated. Based on the problems encountered in the two trials, we provide recommendations for non-radiology clinicians, which can be used in daily interpretation of imaging. Variations in image parameters cannot only influence trial results, but sub-optimal imaging can also influence treatment decisions in daily lung cancer care, when a physician is not aware of the scanning details.
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http://dx.doi.org/10.1016/j.lungcan.2018.07.014DOI Listing
September 2018

Semi-automatic classification of textures in thoracic CT scans.

Phys Med Biol 2016 08 20;61(16):5906-24. Epub 2016 Jul 20.

Image Sciences Institute, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

The textural patterns in the lung parenchyma, as visible on computed tomography (CT) scans, are essential to make a correct diagnosis in interstitial lung disease. We developed one automatic and two interactive protocols for classification of normal and seven types of abnormal lung textures. Lungs were segmented and subdivided into volumes of interest (VOIs) with homogeneous texture using a clustering approach. In the automatic protocol, VOIs were classified automatically by an extra-trees classifier that was trained using annotations of VOIs from other CT scans. In the interactive protocols, an observer iteratively trained an extra-trees classifier to distinguish the different textures, by correcting mistakes the classifier makes in a slice-by-slice manner. The difference between the two interactive methods was whether or not training data from previously annotated scans was used in classification of the first slice. The protocols were compared in terms of the percentages of VOIs that observers needed to relabel. Validation experiments were carried out using software that simulated observer behavior. In the automatic classification protocol, observers needed to relabel on average 58% of the VOIs. During interactive annotation without the use of previous training data, the average percentage of relabeled VOIs decreased from 64% for the first slice to 13% for the second half of the scan. Overall, 21% of the VOIs were relabeled. When previous training data was available, the average overall percentage of VOIs requiring relabeling was 20%, decreasing from 56% in the first slice to 13% in the second half of the scan.
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http://dx.doi.org/10.1088/0031-9155/61/16/5906DOI Listing
August 2016

Towards a close computed tomography monitoring approach for screen detected subsolid pulmonary nodules?

Eur Respir J 2015 Mar 27;45(3):765-73. Epub 2014 Nov 27.

Dept of Radiology, University Medical Center, Utrecht, The Netherlands.

Pulmonary subsolid nodules (SSNs) have a high likelihood of malignancy, but are often indolent. A conservative treatment approach may therefore be suitable. The aim of the current study was to evaluate whether close follow-up of SSNs with computed tomography may be a safe approach. The study population consisted of participants of the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Longkanker Screenings Onderzoek; NELSON). All SSNs detected during the trial were included in this analysis. Retrospectively, all persistent SSNs and SSNs that were resected after first detection were segmented using dedicated software, and maximum diameter, volume and mass were measured. Mass doubling time (MDT) was calculated. In total 7135 volunteers were included in the current analysis. 264 (3.3%) SSNs in 234 participants were detected during the trial. 147 (63%) of these SSNs in 126 participants disappeared at follow-up, leaving 117 persistent or directly resected SSNs in 108 (1.5%) participants available for analysis. The median follow-up time was 95 months (range 20-110 months). 33 (28%) SSNs were resected and 28 of those were (pre-) invasive. None of the non-resected SSNs progressed into a clinically relevant malignancy. Persistent SSNs rarely developed into clinically manifest malignancies unexpectedly. Close follow-up with computed tomography may be a safe option to monitor changes.
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http://dx.doi.org/10.1183/09031936.00005914DOI Listing
March 2015

Interscan variation of semi-automated volumetry of subsolid pulmonary nodules.

Eur Radiol 2015 Apr 21;25(4):1040-7. Epub 2014 Nov 21.

Department of Radiology, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Rationale: We aimed to test the interscan variation of semi-automatic volumetry of subsolid nodules (SSNs), as growth evaluation is important for SSN management.

Methods: From a lung cancer screening trial all SSNs that were stable over at least 3 months were included (N = 44). SSNs were quantified on the baseline CT by two observers using semi-automatic volumetry software for effective diameter, volume, and mass. One observer also measured the SSNs on the second CT 3 months later. Interscan variation was evaluated using Bland-Altman plots. Observer agreement was calculated as intraclass correlation coefficient (ICC). Data are presented as mean (± standard deviation) or median and interquartile range (IQR). A Mann-Whitney U test was used for the analysis of the influence of adjustments on the measurements.

Results: Semi-automatic measurements were feasible in all 44 SSNs. The interscan limits of agreement ranged from -12.0 % to 9.7 % for diameter, -35.4 % to 28.6 % for volume and -27.6 % to 30.8 % for mass. Agreement between observers was good with intraclass correlation coefficients of 0.978, 0.957, and 0.968 for diameter, volume, and mass, respectively.

Conclusion: Our data suggest that when using our software an increase in mass of 30 % can be regarded as significant growth.

Key Points: • Recently, recommendations regarding subsolid nodules have stressed the importance of growth quantification. • Volumetric measurement of subsolid nodules is feasible with good interscan agreement. • Increase of mass of 30 % can be regarded as significant growth.
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http://dx.doi.org/10.1007/s00330-014-3478-1DOI Listing
April 2015

Detection and quantification of the solid component in pulmonary subsolid nodules by semiautomatic segmentation.

Eur Radiol 2015 Feb 7;25(2):488-96. Epub 2014 Oct 7.

Department of Radiology, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Objective: To determine whether semiautomatic volumetric software can differentiate part-solid from nonsolid pulmonary nodules and aid quantification of the solid component.

Methods: As per reference standard, 115 nodules were differentiated into nonsolid and part-solid by two radiologists; disagreements were adjudicated by a third radiologist. The diameters of solid components were measured manually. Semiautomatic volumetric measurements were used to identify and quantify a possible solid component, using different Hounsfield unit (HU) thresholds. The measurements were compared with the reference standard and manual measurements.

Results: The reference standard detected a solid component in 86 nodules. Diagnosis of a solid component by semiautomatic software depended on the threshold chosen. A threshold of -300 HU resulted in the detection of a solid component in 75 nodules with good sensitivity (90%) and specificity (88%). At a threshold of -130 HU, semiautomatic measurements of the diameter of the solid component (mean 2.4 mm, SD 2.7 mm) were comparable to manual measurements at the mediastinal window setting (mean 2.3 mm, SD 2.5 mm [p = 0.63]).

Conclusion: Semiautomatic segmentation of subsolid nodules could diagnose part-solid nodules and quantify the solid component similar to human observers. Performance depends on the attenuation segmentation thresholds. This method may prove useful in managing subsolid nodules.

Key Points: • Semiautomatic segmentation can accurately differentiate nonsolid from part-solid pulmonary nodules • Semiautomatic segmentation can quantify the solid component similar to manual measurements • Semiautomatic segmentation may aid management of subsolid nodules following Fleischner Society recommendations • Performance for the segmentation of subsolid nodules depends on the chosen attenuation thresholds.
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http://dx.doi.org/10.1007/s00330-014-3427-zDOI Listing
February 2015

Semi-automatic quantification of subsolid pulmonary nodules: comparison with manual measurements.

PLoS One 2013 21;8(11):e80249. Epub 2013 Nov 21.

Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands ; Department of Radiology, Kennemer Gasthuis, Haarlem, The Netherlands.

Rationale: Accurate measurement of subsolid pulmonary nodules (SSN) is becoming increasingly important in the management of these nodules. SSNs were previously quantified with time-consuming manual measurements. The aim of the present study is to test the feasibility of semi-automatic SSNs measurements and to compare the results to the manual measurements.

Methods: In 33 lung cancer screening participants with 33 SSNs, the nodules were previously quantified by two observers manually. In the present study two observers quantified these nodules by using semi-automated nodule volumetry software. Nodules were quantified for effective diameter, volume and mass. The manual and semi-automatic measurements were compared using Bland-Altman plots and paired T tests. Observer agreement was calculated as an intraclass correlation coefficient. Data are presented as mean (SD).

Results: Semi-automated measurements were feasible in all 33 nodules. Nodule diameter, volume and mass were 11.2 (3.3) mm, 935 (691) ml and 379 (311) milligrams for observer 1 and 11.1 (3.7) mm, 986 (797) ml and 399 (344) milligrams for observer 2, respectively. Agreement between observers and within observer 1 for the semi-automatic measurements was good with an intraclass correlation coefficient >0.89. For observer 1 and observer 2, measured diameter was 8.8% and 10.3% larger (p<0.001), measured volume was 24.3% and 26.5% larger (p<0.001) and measured mass was 10.6% and 12.0% larger (p<0.001) with the semi-automatic program compared to the manual measurements.

Conclusion: Semi-automated measurement of the diameter, volume and mass of SSNs is feasible with good observer agreement. Semi-automated measurement makes quantification of mass and volume feasible in daily practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080249PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837004PMC
September 2014

Discriminating dominant computed tomography phenotypes in smokers without or with mild COPD.

Respir Med 2014 Jan 30;108(1):136-43. Epub 2013 Aug 30.

Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Background: Finding phenotypes within COPD patients may prove imperative for optimizing treatment and prognosis. We hypothesized that it would be possible to discriminate emphysematous, large airway wall thickening and small airways disease dominant phenotypes.

Methods: Inspiratory and expiratory CTs were performed in 1140 male smokers without or with mild COPD to quantify emphysema, airway wall thickness and air trapping. Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were measured. Dominant phenotype (emphysema, airway wall thickening or air trapping dominant) was defined as one of the respective CT measure in the upper quartile, with the other measures not in the upper quartile.

Results: 573 subjects had any of the three CT measures in the upper quartile. Of these, 367 (64%) were in a single dominant group and 206 (36%) were in a mixed group. Airway wall thickening dominance was associated with younger age (p < 0.001), higher body mass index (p < 0.001), more wheezing (p < 0.05) and lower FEV1 %predicted (p < 0.001). Emphysema dominant subjects had lower FEV1/FVC (p < 0.05) and Kco %predicted (p < 0.05). There was no significant difference in respiratory related hospitalizations (p = 0.09).

Conclusion: CT measures can discriminate three different CT dominant groups of disease in male smokers without or with mild COPD.

Trial Registration Number: ISRCTN63545820, registered at www.trialregister.nl.
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http://dx.doi.org/10.1016/j.rmed.2013.08.014DOI Listing
January 2014

Impact of emphysema and airway wall thickness on quality of life in smoking-related COPD.

Respir Med 2013 Aug 25;107(8):1201-9. Epub 2013 May 25.

Department of Radiology, University of British Columbia, Vancouver General Hospital, 855 12th Ave W, Vancouver, BC V5Z 1M9 Vancouver, BC, Canada.

Background: Limited data are available as to the relationship between computed tomography (CT) derived data on emphysema and airway wall thickness, and quality of life in subjects with chronic obstructive pulmonary disease (COPD). Such data may work to clarify the clinical correlate of the CT findings.

Methods: We included 1778 COPD subjects aged 40-75 years with a smoking history of at least 10 pack-years. They were examined with St George's Respiratory Questionnaire (SGRQ-C) and high-resolution chest CT. Level of emphysema was assessed as percent low-attenuation areas less than -950 Hounsfield units (%LAA). Airway wall thickness was estimated by calculating the square root of wall area of an imaginary airway with an internal perimeter of 10 mm (Pi10).

Results: In both men and women, the mean total score and most of the subscores of SGRQ-C increased with increasing level of emphysema and increasing level of airway wall thickness, after adjusting for age, smoking status, pack years, body mass index and FEV1. The highest gradient was seen in the relationship between the activity score and the emphysema level. The activity score increased by 35% from the lowest to the highest emphysema tertile. The relationship between level of emphysema and the total SGRQ-C score became weaker with increasing GOLD (Global initiative for Chronic Obstructive Lung Disease) stages (p < 0.001), while the impact of gender was limited.

Conclusion: In subjects with COPD, increasing levels of emphysema and airway wall thickness are independently related to impaired quality of life.
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http://dx.doi.org/10.1016/j.rmed.2013.04.016DOI Listing
August 2013

Early identification of small airways disease on lung cancer screening CT: comparison of current air trapping measures.

Lung 2012 Dec 12;190(6):629-33. Epub 2012 Oct 12.

Department of Radiology, University Medical Centre Utrecht, Heidelberglaan 100, HP E01.132, Postbus 85500, 3508 GA, Utrecht, The Netherlands.

Background: Lung cancer screening CT scans might provide valuable information about air trapping as an early indicator of smoking-related lung disease. We studied which of the currently suggested measures is most suitable for detecting functionally relevant air trapping on low-dose computed tomography (CT) in a population of subjects with early-stage disease.

Methods: This study was ethically approved and informed consent was obtained. Three quantitative CT air trapping measures were compared against a functional reference standard in 427 male lung cancer screening participants. This reference standard for air trapping was derived from the residual volume over total lung capacity ratio (RV/TLC) beyond the 95th percentile of predicted. The following CT air trapping measures were compared: expiratory to inspiratory relative volume change of voxels with attenuation values between -860 and -950 Hounsfield Units (RVC(-860 to -950)), expiratory to inspiratory ratio of mean lung density (E/I-ratio(MLD)) and percentage of voxels below -856 HU in expiration (EXP(-856)). Receiver operating characteristic (ROC) analysis was performed and area under the ROC curve compared.

Results: Functionally relevant air trapping was present in 38 (8.9 %) participants. E/I-ratio(MLD) showed the largest area under the curve (0.85, 95 % CI 0.813-0.883), which was significantly larger than RVC(-860 to -950) (0.703, 0.657-0.746; p < 0.001) and EXP(-856) (0.798, 0.757-0.835; p = 0.002). At the optimum for sensitivity and specificity, E/I-ratio(MLD) yielded an accuracy of 81.5 %.

Conclusions: The expiratory to inspiratory ratio of mean lung density (E/I-ratio(MLD)) is most suitable for detecting air trapping on low-dose screening CT and performs significantly better than other suggested quantitative measures.
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http://dx.doi.org/10.1007/s00408-012-9422-8DOI Listing
December 2012

Can low-dose unenhanced chest CT be used for follow-up of lung nodules?

AJR Am J Roentgenol 2012 Oct;199(4):777-80

Department of Radiology, University Medical Centre Utrecht, HP E.01.132, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

Objective: The purpose of this study is to establish the difference in lung nodule volume between standard-dose contrast-enhanced and low-dose unenhanced CT.

Subjects And Methods: Twenty patients with known pulmonary metastases underwent three CT examinations on 1 day: two unenhanced low-dose (120 kVp and 30 mAs) and a standard-dose (120-140 kVp and 75-200 mAs) contrast-enhanced chest CT examinations. For nodules<1000 mm3, nodule volume was quantified using dedicated software from the CT manufacturer. Wilcoxon's signed rank tests were used for analysis of nodules≤200 mm3 and >200 mm3 (approximately diameter of 8 mm).

Results: One hundred one nodules (n=69≤200 mm3) were analyzed in 15 of these subjects. Measured volume of nodules≤200 mm3 was systematically lower on both low-dose unenhanced CT examinations when compared with standard-dose contrast-enhanced CT (differences, 13.7% and 15.5%, respectively; p<0.0001), but nodule volume was not different between low-dose CT (median difference, 1.0%; p=0.10). Nodule volume was not systematically different between the protocols for nodules>200 mm3 (p>0.30).

Conclusion: For lung nodules≤200 mm3 (approximately 8 mm) the measured volume on low-dose unenhanced CT is significantly lower when compared with standard-dose contrast-enhanced CT. This effect is likely due to contrast administration rather than other imaging parameters, which should be taken into account in the follow-up of lung nodules because growth can remain undetected or doubling time underestimated.
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http://dx.doi.org/10.2214/AJR.11.7577DOI Listing
October 2012

Visual versus automated evaluation of chest computed tomography for the presence of chronic obstructive pulmonary disease.

PLoS One 2012 27;7(7):e42227. Epub 2012 Jul 27.

Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Incidental CT findings may provide an opportunity for early detection of chronic obstructive pulmonary disease (COPD), which may prove important in CT-based lung cancer screening setting. We aimed to determine the diagnostic performance of human observers to visually evaluate COPD presence on CT images, in comparison to automated evaluation using quantitative CT measures.

Methods: This study was approved by the Dutch Ministry of Health and the institutional review board. All participants provided written informed consent. We studied 266 heavy smokers enrolled in a lung cancer screening trial. All subjects underwent volumetric inspiratory and expiratory chest computed tomography (CT). Pulmonary function testing was used as the reference standard for COPD. We evaluated the diagnostic performance of eight observers and one automated model based on quantitative CT measures.

Results: The prevalence of COPD in the study population was 44% (118/266), of whom 62% (73/118) had mild disease. The diagnostic accuracy was 74.1% in the automated evaluation, and ranged between 58.3% and 74.3% for the visual evaluation of CT images. The positive predictive value was 74.3% in the automated evaluation, and ranged between 52.9% and 74.7% for the visual evaluation. Interobserver variation was substantial, even within the subgroup of experienced observers. Agreement within observers yielded kappa values between 0.28 and 0.68, regardless of the level of expertise. The agreement between the observers and the automated CT model showed kappa values of 0.12-0.35.

Conclusions: Visual evaluation of COPD presence on chest CT images provides at best modest accuracy and is associated with substantial interobserver variation. Automated evaluation of COPD subjects using quantitative CT measures appears superior to visual evaluation by human observers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042227PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407100PMC
January 2013

Variation in quantitative CT air trapping in heavy smokers on repeat CT examinations.

Eur Radiol 2012 Dec 14;22(12):2710-7. Epub 2012 Jun 14.

Radiology, University Medical Center Utrecht, Heidelberglaan 100, Postbus 85500, 3508 GA, Utrecht, The Netherlands.

Objectives: To determine the variation in quantitative computed tomography (CT) measures of air trapping in low-dose chest CTs of heavy smokers.

Methods: We analysed 45 subjects from a lung cancer screening trial, examined by CT twice within 3 months. Inspiratory and expiratory low-dose CT was obtained using breath hold instructions. CT air trapping was defined as the percentage of voxels in expiratory CT with an attenuation below -856 HU (EXP(-856)) and the expiratory to inspiratory ratio of mean lung density (E/I-ratio(MLD)). Variation was determined using limits of agreement, defined as 1.96 times the standard deviation of the mean difference. The effect of both lung volume correction and breath hold reproducibility was determined.

Results: The limits of agreement for uncorrected CT air trapping measurements were -15.0 to 11.7 % (EXP(-856)) and -9.8 to 8.0 % (E/I-ratio(MLD)). Good breath hold reproducibility significantly narrowed the limits for EXP(-856) (-10.7 to 7.5 %, P = 0.002), but not for E/I-ratio(MLD) (-9.2 to 7.9 %, P = 0.75). Statistical lung volume correction did not improve the limits for EXP(-856) (-12.5 to 8.8 %, P = 0.12) and E/I-ratio(MLD) (-7.5 to 5.8 %, P = 0.17).

Conclusions: Quantitative air trapping measures on low-dose CT of heavy smokers show considerable variation on repeat CT examinations, regardless of lung volume correction or reproducible breath holds.

Key Points: Computed tomography quantitatively measures small airways disease in heavy smokers. Measurements of air trapping vary considerably on repeat CT examinations. Variation remains substantial even with reproducible breath holds and lung volume correction.
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http://dx.doi.org/10.1007/s00330-012-2526-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486998PMC
December 2012
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