This paper presents a fully automatic and end-to-end optimised airway segmentation method for thoracic computed tomography, based on the U-Net architecture. We use a simple and low-memory 3D U-Net as ...backbone, which allows the method to process large 3D image patches, often comprising full lungs, in a single pass through the network. This makes the method simple, robust and efficient. We validated the proposed method on three datasets with very different characteristics and various airway abnormalities: (1) a dataset of pediatric patients including subjects with cystic fibrosis, (2) a subset of the Danish Lung Cancer Screening Trial, including subjects with chronic obstructive pulmonary disease, and (3) the EXACT'09 public dataset. We compared our method with other state-of-the-art airway segmentation methods, including relevant learning-based methods in the literature evaluated on the EXACT'09 data. We show that our method can extract highly complete airway trees with few false positive errors, on scans from both healthy and diseased subjects, and also that the method generalizes well across different datasets. On the EXACT'09 test set, our method achieved the second highest sensitivity score among all methods that reported good specificity.
Objectives
Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective ...cohort study, used to assess the discriminative performances of the PanCan models.
Methods
From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination.
Results
AUCs of 0.826–0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (
p
= 0.001 and
p
= 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (
p
= 0.047 and
p
= 0.040) in the DLCST.
Conclusions
High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor.
Key points
• High accuracy in logistic modelling for lung cancer risk stratification of nodules.
• Lung cancer risk prediction is primarily based on size of pulmonary nodules.
• Nodule spiculation, age and family history of lung cancer are significant predictors.
• Sex does not appear to be a useful risk predictor.
Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has ...recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39-61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the "Initiative for European Lung Screening (IELS)"-a large international group of physicians and other experts concerned with lung cancer-agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached.
Interstitial lung abnormalities (ILA) are common in participants of lung cancer screening trials and broad population-based cohorts. They are associated with increased mortality, but less is known ...about disease specific morbidity and healthcare utilisation in individuals with ILA.
We included all participants from the screening arm of the Danish Lung Cancer Screening Trial with available baseline CT scan data (n = 1990) in this cohort study. The baseline scan was scored for the presence of ILA and patients were followed for up to 12 years. Data about all hospital admissions, primary healthcare visits and medicine prescriptions were collected from the Danish National Health Registries and used to determine the participants' disease specific morbidity and healthcare utilisation using Cox proportional hazards models.
The 332 (16.7%) participants with ILA were more likely to be diagnosed with one of several respiratory diseases, including interstitial lung disease (HR: 4.9, 95% CI: 1.8-13.3, p = 0.008), COPD (HR: 1.7, 95% CI: 1.2-2.3, p = 0.01), pneumonia (HR: 2.0, 95% CI: 1.4-2.7, p < 0.001), lung cancer (HR: 2.7, 95% CI: 1.8-4.0, p < 0.001) and respiratory failure (HR: 1.8, 95% CI: 1.1-3.0, p = 0.03) compared with participants without ILA. These findings were confirmed by increased hospital admission rates with these diagnoses and more frequent prescriptions for inhalation medicine and antibiotics in participants with ILA.
Individuals with ILA are more likely to receive a diagnosis and treatment for several respiratory diseases, including interstitial lung disease, COPD, pneumonia, lung cancer and respiratory failure during long-term follow-up.
Airways segmentation is important for research about pulmonary disease but require a large amount of time by trained specialists. We used an openly available software to improve airways segmentations ...obtained from an artificial intelligence (AI) tool and retrained the tool to get a better performance. Fifteen initial airway segmentations from low-dose chest computed tomography scans were obtained with a 3D-Unet AI tool previously trained on Danish Lung Cancer Screening Trial and Erasmus-MC Sophia datasets. Segmentations were manually corrected in 3D Slicer. The corrected airway segmentations were used to retrain the 3D-Unet. Airway measurements were automatically obtained and included count, airway length and luminal diameter per generation from the segmentations. Correcting segmentations required 2–4 h per scan. Manually corrected segmentations had more branches (
p
< 0.001), longer airways (
p
< 0.001) and smaller luminal diameters (
p
= 0.004) than initial segmentations. Segmentations from retrained 3D-Unets trended towards more branches and longer airways compared to the initial segmentations. The largest changes were seen in airways from 6th generation onwards. Manual correction results in significantly improved segmentations and is potentially a useful and time-efficient method to improve the AI tool performance on a specific hospital or research dataset.
IntroductionPleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. ...Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment.Methods and analysisA national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life.Ethics and disseminationAll patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www.clinicaltrials.gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences.Trial registration numberNCT04095676.
Chronic inflammation such as asthma may lead to higher risks of malignancy, which may be inhibited by anti-inflammatory medicine such as inhaled corticosteroids (ICS). The aim of this study was to ...evaluate if patients with asthma-Chronic Obstructive Pulmonary Disease (COPD) overlap have a higher risk of malignancy than patients with COPD without asthma, and, secondarily, if inhaled corticosteroids modify such a risk in a nationwide multi-center retrospective cohort study of Danish COPD-outpatients with or without asthma. Patients with asthma-COPD overlap were propensity score matched (PSM) 1:2 to patients with COPD without asthma. The endpoint was cancer diagnosis within 2 years. Patients were stratified depending on prior malignancy within 5 years. ICS was explored as a possible risk modifier. We included 50,897 outpatients with COPD; 88% without prior malignancy and 20% with asthma. In the PSM cohorts, 26,003 patients without prior malignancy and 3331 patients with prior malignancy were analyzed. There was no association between asthma-COPD overlap and cancer with hazard ratio (HR) = 0.92, CI = 0.78–1.08, p = 0.31 (no prior malignancy) and HR = 1.04, CI = 0.85–1.26, and p = 0.74 (prior malignancy) as compared to patients with COPD without asthma. ICS did not seem to modify the risk of cancer. In conclusion, in our study, asthma-COPD overlap was not associated with an increased risk of cancer events.
Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent acute exacerbations and require repeated courses of corticosteroid therapy, which may lead to adverse effects. ...Methotrexate (MTX) has anti-inflammatory properties. The objective of this study was to describe the risk of COPD exacerbation in patients exposed to MTX. In this nationwide cohort study of 58,580 COPD outpatients, we compared the risk of hospitalization-requiring COPD exacerbation or death within 180 days in MTX vs. non-MTX users in a propensity-score matched study population as well as an unmatched cohort, in which we adjusted for confounders. The use of MTX was associated with a reduction in risk of COPD exacerbation in the propensity-score matched population at 180 days follow-up (HR 0.66, CI 0.66–0.66, p < 0.001). Similar results were shown in our sensitivity analyses at 180-day follow-up on unmatched population and 365-day follow-up on matched and unmatched population (HR 0.76 CI 0.59–0.99, HR 0.81 CI 0.81–0.82 and HR 0.92 CI 0.76–1.11, respectively). MTX was associated with a lower risk of COPD exacerbation within the first six months after study entry. The finding seems biologically plausible and could potentially be a part of the management of COPD patients with many exacerbations.
Haemoptysis is a common symptom and can be an early sign of lung cancer. Careful investigation of patients with haemoptysis may lead to early diagnosis. The strategy for investigation of these ...patients, however, is still being debated.
We studied whether the combination of computed tomography (CT) and bronchoscopy had a higher sensitivity for malignant and non-malignant causes of haemoptysis than CT alone.
The study was a retrospective, non-randomised, two-centre study and included patients who were referred from primary care for the investigation of haemoptysis.
A total of 326 patients were included in the study (mean age 60.5 SD 15.3 years, 63.3% male). The most common aetiologies of haemoptysis were cryptogenic (52.5%), pneumonia (16.3%), emphysema (8.0%), bronchiectasis (5.8%) and lung cancer (4.0%). In patients diagnosed with lung cancer, bronchoscopy, CT and the combination of bronchoscopy and CT had a sensitivity of 0.61, 0.92 (p<0.05) and 0.97 (p=0.58), respectively. In patients with non-malignant causes of haemoptysis, most aetiologies were diagnosed by CT and comprised mainly pneumonia, emphysema and bronchiectasis. Bronchoscopy did not reveal these conditions and the sensitivity to these conditions was not increased by combining CT and bronchoscopy.
CT can stand alone as a diagnostic workup for patients with haemoptysis referred to an outpatient clinic. Bronchoscopy does not identify any malignant aetiologies not already diagnosed by CT. Combining the two test modalities does not result in a significant increase in sensitivity for malignant or non-malignant causes of haemoptysis.
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