Lung cancer: a nationwide analysis of sex and age incidence trends from 1980 to 2022.

BACKGROUND: Lung cancer, once rare, has evolved into the global leading cause of cancer-related mortality, primarily driven by widespread cigarette smoking in the 20th century. This study explores the historical trends of lung cancer incidence in Denmark over four decades, emphasizing the impact of smoking prevalence, age, and gender on the observed patterns. MATERIALS AND METHODS: Drawing upon data from the Danish National Patient Register and information on smoking habits provided by the Danish Health Authority, this study investigates lung cancer incidence rates, demographic shifts, and smoking prevalence from 1980 to 2022. RESULTS: Smoking prevalence exhibited a consistent decline in males from 1950 to 2022, whereas female smoking prevalence maintained a stable level from 1950 to 1987, followed by a subsequent decline from 1987 to 2022. A peak in lung cancer crude incidence rates was identified during 2014-2017, with no significant difference observed before and after this period. Over the period, the gender distribution transitioned from a male majority to an equal male-female ratio, and age-specific disparities indicated declines in patients aged 50-59 and increases in those above 80 years. INTERPRETATION: The certainty of a decline in lung cancer incidence in the coming years remains unclear. Based on smoking prevalence, it might still be a decade away. To ensure a sustained decline in lung cancer incidence, targeted interventions are imperative, including customized smoking cessation programs that could be designed favorably for females. Given the modest decline in smoking prevalence over the last decade, legislation aimed at discouraging young individuals from smoking is pivotal. As of now, these efforts have not been implemented in Denmark.

Whole-blood culture-derived cytokine combinations for the diagnosis of tuberculosis.

Introduction: The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC. Methods: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-É£, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC. Results: In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-É£, ZYM-IFN-É£, ZYM-TNF-α, ZYM-IL-1ß, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%-73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-É£, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity. Discussion: Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.

FDG-PET/CT-based respiration-gated lung segmentation and quantification of lung inflammation in COPD patients.

OBJECTIVE AND RESULTS DESCRIPTION: The study objective was to investigate the potential of quantitative measures of pulmonary inflammation by [18 F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a surrogate marker of inflammation in COPD. Patients treated with anti-inflammatory Liraglutide were compared to placebo and correlated with inflammatory markers. 27 COPD-patients (14 receiving Liraglutide treatment and 13 receiving placebo) underwent 4D-respiratory-gated FDG-PET/CT before and after treatment. Two raters independently segmented the lungs from CT images and measured activity in whole lung, mean standard uptake values (SUVmean) corrected for lean-body-mass in the phase-matched PET images of the whole segmented lung volume, and total lesion glycolysis (TLG; SUVmean multiplied by volume). Inter-rater reliability was analyzed with Bland-Altman analysis and correlation plots. We found no differences in metabolic activity in the lungs between the two groups as a surrogate of pulmonary inflammation, and no changes in inflammation markers. The purpose of the research and brief summary of main findings. The degree of and changes in pulmonary inflammation in chronic obstructive pulmonary disease (COPD) may be difficult to ascertain. Measuring metabolic activity as a surrogate marker of inflammation by FDG-PET/CT may be useful, but data on its use in COPD including reproducibility is still limited, especially with respiration-gated technique, which should improve quantification in the lungs. We assessed several quantitative measures of metabolic activity and correlated them with inflammation markers, and we assessed reproducibility of the methods. We found no differences in metabolic activity between the two groups (before and after 40 weeks treatment with Liraglutide vs. placebo). Bland-Altman analysis showed good agreement between the two raters. TRIAL REGISTRATION: The study was conducted between February 2018 and March 2020 at the Department of Pulmonary Diseases at Hospital South West Jutland and Lillebaelt Hospital, Denmark, and registered from March 2018 at clinicaltrials.gov with trial registration number NCT03466021.

OPTIMAL: Titration of anti-IL5 biologics in severe asthma - An open label randomised controlled trial.

BACKGROUND: Anti-interleukin 5 (anti-IL5) biologics effectively reduce exacerbations and the need for maintenance oral corticosteroids (mOCS) in severe eosinophilic asthma. However, it is unknown how long anti-IL5 treatment should be continued. Data from clinical trials indicate a gradual but variable loss of control after treatment cessation. In this pilot study of titration, we evaluated a dose-titration algorithm in patients who had achieved clinical control on an anti-IL5 biologic. METHODS: In this open-label randomised controlled trial conducted over 52 weeks, patients with clinical control (no exacerbations or mOCS) on anti-IL5 treatment were randomised to continue with unchanged intervals or have dosing intervals adjusted according to a titration algorithm that gradually extended dosing intervals and reduced them again at signs of loss of disease control. The OPTIMAL algorithm was designed to down-titrate dosing until signs of loss of control, to enable assessment of the longest dosing interval possible. RESULTS: Among 73 patients enrolled, 37 patients were randomised to the OPTIMAL titration arm; 78% of patients tolerated down-titration of treatment. Compared to the control arm, the OPTIMAL arm tended to have more exacerbations during the study (32% versus 17% (p=0.13)). There were no severe adverse events related to titration, and lung function and symptoms scores remained stable and comparable in both study arms throughout. CONCLUSIONS: This study serves as a proof-of-concept for titration of anti-IL5 biologics in patients with severe asthma with clinical control on treatment, and the OPTIMAL algorithm provides a potential framework for individualising dosing intervals in the future.

Telephone follow-up as a substitute for standard out-clinic follow-up in CPAP therapy for obstructive sleep apnea patients: a randomized controlled trial.

PURPOSE: This study assessed the feasibility of telephone follow-up consultations (TC) using an online data sharing and editing function (Airview™), as alternative to standard out-clinic follow-up consultations (SC) on adherence to continuous positive airway pressure (CPAP) in obstructive sleep apnea (OSA) patients. Furthermore, we investigated compliance to follow-up consultations and examined potential influencing factors, including baseline AHI (apnea-hypopnea-index), age, and distance from home to the hospital on consultation compliance. METHODS: Two hundred OSA patients, with AHI ≥ 5 were randomly assigned (1:1) to receive TC or SC with follow-up after one month and 12 month of CPAP initiation. Adherence goal was defined as achieving ≥ 4 h of CPAP use daily in 70% of the days in a 365-days period. RESULTS: The proportion of participants achieving CPAP adherence was non-significantly lower in the TC group compared to the SC group (TC: 30% versus SC: 36%, adjusted OR 0.84, p = 0.59). Of participants who completed the study, the TC group had a significant average of 107 min less use of CPAP compared to the SC group (p = 0.048). However, a higher proportion of participants was compliant to consultations in the TC group. The only influencing factor found was increasing baseline AHI, which might be a predictor for compliance to consultations and adherence to CPAP therapy. CONCLUSION: TC might serve as substitute for SC in some part of the OSA population. If TC becomes a part of CPAP therapy management, it is important to consider patient characteristics and treatment-related issues to prevent decline in adherence.

Identification of patients' smoking status using an explainable AI approach: a Danish electronic health records case study.

BACKGROUND: Smoking is a critical risk factor responsible for over eight million annual deaths worldwide. It is essential to obtain information on smoking habits to advance research and implement preventive measures such as screening of high-risk individuals. In most countries, including Denmark, smoking habits are not systematically recorded and at best documented within unstructured free-text segments of electronic health records (EHRs). This would require researchers and clinicians to manually navigate through extensive amounts of unstructured data, which is one of the main reasons that smoking habits are rarely integrated into larger studies. Our aim is to develop machine learning models to classify patients' smoking status from their EHRs. METHODS: This study proposes an efficient natural language processing (NLP) pipeline capable of classifying patients' smoking status and providing explanations for the decisions. The proposed NLP pipeline comprises four distinct components, which are; (1) considering preprocessing techniques to address abbreviations, punctuation, and other textual irregularities, (2) four cutting-edge feature extraction techniques, i.e. Embedding, BERT, Word2Vec, and Count Vectorizer, employed to extract the optimal features, (3) utilization of a Stacking-based Ensemble (SE) model and a Convolutional Long Short-Term Memory Neural Network (CNN-LSTM) for the identification of smoking status, and (4) application of a local interpretable model-agnostic explanation to explain the decisions rendered by the detection models. The EHRs of 23,132 patients with suspected lung cancer were collected from the Region of Southern Denmark during the period 1/1/2009-31/12/2018. A medical professional annotated the data into 'Smoker' and 'Non-Smoker' with further classifications as 'Active-Smoker', 'Former-Smoker', and 'Never-Smoker'. Subsequently, the annotated dataset was used for the development of binary and multiclass classification models. An extensive comparison was conducted of the detection performance across various model architectures. RESULTS: The results of experimental validation confirm the consistency among the models. However, for binary classification, BERT method with CNN-LSTM architecture outperformed other models by achieving precision, recall, and F1-scores between 97% and 99% for both Never-Smokers and Active-Smokers. In multiclass classification, the Embedding technique with CNN-LSTM architecture yielded the most favorable results in class-specific evaluations, with equal performance measures of 97% for Never-Smoker and measures in the range of 86 to 89% for Active-Smoker and 91-92% for Never-Smoker. CONCLUSION: Our proposed NLP pipeline achieved a high level of classification performance. In addition, we presented the explanation of the decision made by the best performing detection model. Future work will expand the model's capabilities to analyze longer notes and a broader range of categories to maximize its utility in further research and screening applications.

Inhaled corticosteroid treatment and pneumonia in patients with chronic obstructive pulmonary disease - nationwide development from 1998 to 2018.

Background: A decreasing use of inhaled corticosteroids (ICS) in patients with a hospital-registered diagnosis of chronic obstructive pulmonary disease (COPD) has recently been documented in Denmark. ICS treatment is not recommended in patients with high pneumonia risk, and we aimed to assess the development of ICS treatment in relation to pneumonia occurrence. Methods: Annual nationwide register-based cross-sectional studies from 1998 to 2018 including all patients ≥40 years of age with a hospital-registered ICD-10 diagnosis of COPD on the 31st of December each year. We calculated the annual proportion of patients with at least one outpatient pneumonia (redeemed prescription of relevant antibiotics) or pneumonia hospitalization (hospitalization or ER visit), and stratified by ICS dose (No ICS, low dose, medium dose, or high dose). Results: The study population increased from 35,656 patients in 1998 to 99,057 patients in 2018. The annual proportion of patients experiencing a pneumonia decreased from 69.4% to 55.2%. The proportion of patients with at least one outpatient pneumonia, but no hospitalization, decreased (59.2% to 46.2%). The overall proportion of patients with at least one pneumonia hospitalization remained unchanged (10.2% to 9.0%), but this proportion increased in patients in high dose ICS (9.9% to 14.6%). The overall proportion of patients in high dose treatment decreased (12.7% to 5.7%), but not in patients with pneumonia hospitalization (16.5% to 15.1). Conclusions: Our study demonstrates a nationwide decrease from 1998 to 2018 in the proportion of patients who redeemed a prescription for antibiotics used mainly for respiratory tract infections, which may reflect a decrease in the number of outpatient pneumonias. This decrease was largely caused by an increase in the number of patients without pneumonia. No differences over time were seen regarding hospitalization-requiring pneumonia. High dose ICS treatment was unchanged in patients with hospitalization-requiring pneumonia.

Urban-rural and socio-economic differences in inhaled corticosteroid treatment for chronic obstructive pulmonary disease: A nationwide register-based cross-sectional study.

BACKGROUND: Urban-rural disparities within chronic obstructive pulmonary disease (COPD) have been documented in USA, but not in Europe. Inhaled corticosteroids (ICS) are widely used in COPD despite strict recommendations. We aimed to investigate urban-rural and socioeconomic differences in ICS treatment for COPD. METHODS: A Danish nationwide register-based cross-sectional study. All patients alive on the December 31, 2018 with a J44 ICD-10 diagnosis code (COPD) were included (99,057 patients). Daily average ICS dose was calculated from the accumulated ICS use during 2018 based on redeemed prescriptions. Patients were divided into groups: No ICS, low dose ICS, medium dose ICS, high dose ICS. A multinomial logistic regression model including educational level, co-habitation status, age, and sex was performed with "No ICS" as reference group. RESULTS: Compared to capital municipalities, living in other municipality types was associated with an increased probability of receiving medium and high dose ICS treatment, and increasing odds ratios (ORs) were seen with increasing ICS dose (medium dose ICS: ORs between 1.31 (95 % confidence interval (CI) 1.24-1.38) and 1.35 (95%CI 1.28-1.41), high dose ICS: ORs between 1.73 (95%CI 1.59-1.88) and 1.80 (95%CI 1.68-1.92)). Patients had increased probability of receiving ICS treatment if they were female, were co-habiting, or had completed only primary education. CONCLUSION: Patients with a hospital-registered COPD diagnosis in non-capital municipalities receive more ICS, and in higher doses, compared to patients in capital municipalities. This is the first study to confirm that such urban-rural differences exist in Europe, and further research on this area is warranted.

Pulmonary infections with nontuberculous mycobacteria.

This review focuses on the treatment of nontuberculous pulmonary disease caused by Mycobacterium avium complex and M. abscessus. It covers treatment indications, antibiotic choice, resistance and side effects. Treatment of nontuberculous pulmonary disease is complex, lengthy, and fraught with side effects. Increased attention on this disease is needed in order to alleviate the severe consequences of this growing disease. Cooperation between pulmonologists and infectious disease specialists is needed to ensure uniform treatment, and to account for the heterogeneity seen in patients and mycobacteria alike.

Risk of depression and anxiety in 7.302 patients with sarcoidosis: a nationwide cohort study.

BACKGROUND AND AIM: The aim was to investigate the association between sarcoidosis and anxiety and/or depression (A/D) in patients with sarcoidosis and comparators matched on age, gender, residency, and cohabitation status. METHODS: Patients with newly diagnosed sarcoidosis between 2001 and 2015 were identified in the Danish National Patient Register. Cases were matched 1:4 with non-sarcoidosis comparators. We estimated the cumulative incidence of A/D using the Cumulative Incidence Function and the subdistribution hazard ratio (sHR) for A/D using the Fine-Gray subdistribution hazard model. Estimates were adjusted for socio-economic status and Deyo-Charlson Comorbidity Index. RESULTS: We identified 7.302 cases and 26.145 matched comparators. The cumulative incidence of A/D after five years was 6.0% (95%CI 5.5-6.4) for cases and 4.2% (95%CI 4.0-4.4) for matched comparators. The cumulative incidence was higher among cases for both males and females and in all age-groups compared with the matched comparators. The adjusted-sHR for A/D was 1.38 (95%CI 1.24-1.53). The adjusted-sHR for A/D was 1.51 (95%CI 1.30-1.75) for male cases and 1.25 (95%CI 1.08-1.45) for female cases compared with the matched comparators. The adjusted-sHR for A/D was higher for cases in all age-groups compared with the matched comparators, although not statistically significant among cases aged 30-39 years (a-sHR 1.15; 95%CI 0.92-1.44). CONCLUSIONS: Sarcoidosis cases had a higher risk of A/D compared with matched comparators during 18 years of follow-up. The risk of developing A/D was greater for male and female cases and within all age-groups compared with the matched comparators.

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up.

BACKGROUND: The epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we sought to determine the incidence and prevalence of NTM infections and focus on social risk factors. In addition, we describe people with pulmonary and extrapulmonary NTM. RESEARCH QUESTION: What are the incidence and prevalence of NTM in Denmark, and what are the characteristics of the affected patients? STUDY DESIGN AND METHODS: This is a nationwide retrospective register-based cohort study in Denmark. Adult patients in the Danish national registers who received a diagnosis of NTM disease from 2000 to 2017 were classified as having either pulmonary or extrapulmonary NTM disease. RESULTS: We identified 1,146 adults with an NTM diagnosis. Of these, 661 patients had pulmonary NTM, of whom 50.4% were male, whereas 485 had extrapulmonary NTM, of whom 59.6% were male. The median age (interquartile range) was 66 (18) years and 57 (32) years, respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary NTM (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 inhabitants increased from 0.4 to 3.5 for pulmonary NTM and from 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest among those who were aged 70 years or older (19.3 per 100,000 inhabitants). Compared with patients with pulmonary NTM, patients with extrapulmonary NTM were more likely to be employed and had a higher educational level. INTERPRETATION: This study indicates that the prevalence of NTM disease in Denmark increased between 2000 and 2017. We found that patients with pulmonary NTM and patients with extrapulmonary NTM represent two distinct groups that differ in age, sex, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in older adults after exclusion of more common lung infections.

Description of an activity-based enzyme biosensor for lung cancer detection.

BACKGROUND: Lung cancer is associated with the greatest cancer mortality as it typically presents with incurable distributed disease. Biomarkers relevant to risk assessment for the detection of lung cancer continue to be a challenge because they are often not detectable during the asymptomatic curable stage of the disease. A solution to population-scale testing for lung cancer will require a combination of performance, scalability, cost-effectiveness, and simplicity. METHODS: One solution is to measure the activity of serum available enzymes that contribute to the transformation process rather than counting biomarkers. Protease enzymes modify the environment during tumor growth and present an attractive target for detection. An activity based sensor platform sensitive to active protease enzymes is presented. A panel of 18 sensors was used to measure 750 sera samples from participants at increased risk for lung cancer with or without the disease. RESULTS: A machine learning approach is applied to generate algorithms that detect 90% of cancer patients overall with a specificity of 82% including 90% sensitivity in Stage I when disease intervention is most effective and detection more challenging. CONCLUSION: This approach is promising as a scalable, clinically useful platform to help detect patients who have lung cancer using a simple blood sample. The performance and cost profile is being pursued in studies as a platform for population wide screening.

Lung cancer is responsible for more deaths worldwide than all other cancers. It is often detected with the appearance of symptoms when treatment is limited and outcomes for the patient are much worse. While imaging chest scans can detect disease, they are poorly used even in the United States where it is an approved screening method. When cancer is present, protease enzymes are responsible for making space and modifying the lung tissue for the growing tumor. This report describes a panel of 18 sensors that release a fluorescent signal when these enzymes are present in a blood sample. The signal acts like a fingerprint of activity that can be used to identify people with lung cancer. This sensor platform can detect patients with curable lung cancer and could provide a platform for screening very large populations of at-risk individuals.

Prevalence estimates of tuberculosis infection in adults in Denmark: a retrospective nationwide register-based cross-sectional study, 2010 to 2018.

BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.

The Danish lung cancer registry: A nationwide validation study.

BACKGROUND: This study evaluates the validity of the information in the Danish Lung Cancer Registry (DLCR). Since 2000, the DLCR has been a tool for monitoring interventions and outcome of all Danish lung cancer patients with the intent to streamline and improve treatment and survival. The DLCR receives information from the Danish Patient Registries in addition to clinical information from the treating physicians. In the year 2022, more than 50 papers have been published using DLCR as a data source. However, the DLCR has not previously been validated. METHODS: A random sample of 1000 patients diagnosed with non-small cell lung cancer from 2014 to 2016 and recorded in the DLCR were included for validation. Medical records were reviewed and were considered as the "gold standard" to which data listed in the DLCR were compared. RESULTS: Information was retrieved from medical charts for all patients. Agreement on stage at diagnosis was 90.1 % (95 % CI 88.0-91.9) and on date of diagnoses was 93.8 (95 % CI 92.1-93.2). Agreement on smoking status in pack years (+/- 10 pack years) was 91.2 % (95 % CI 88.6-93.2). The positive predictive value of treatment intent was 87.4 (95 % CI 85.1-89.6). CONCLUSION: The data in the DLCR are complete, detailed and accurate. The comparison of data from the DLCR with the medical records revealed overall high validity of the data in the registry.

National Development in the Use of Inhaled Corticosteroid Treatment in Chronic Obstructive Pulmonary Disease: Repeated Cross-Sectional Studies from 1998 to 2018.

Recommendations for the treatment of chronic obstructive pulmonary disease (COPD) have shifted towards a more restrictive use of inhaled corticosteroids (ICS). We aimed to identify the nationwide development over time in the use of ICS treatment in COPD. We conducted a register-based repeated cross-sectional study using Danish nationwide registers. On a yearly basis from 1998 to 2018, we included all patients in Denmark ≥ 40 years of age with an ICD-10 diagnosis of COPD (J44). Accumulated ICS use was calculated for each year based on redeemed prescriptions. Patients were divided into the following groups: No ICS, low-dose ICS, medium-dose ICS, or high-dose ICS. From 1998 to 2018, the yearly proportion of patients without ICS treatment increased (from 50.6% to 57.6%), the proportion of patients on low-dose ICS treatment increased (from 11.3% to 14.9%), and the proportion of patients on high-dose ICS treatment decreased (from 17.0% to 9.4%). We demonstrated a national reduction in the use of ICS treatment in COPD from 1998 to 2018, with an increase in the proportion of patients without ICS and on low-dose ICS treatment and a decrease in the proportion of patients on high-dose ICS treatment.

Introduction of the Danish Lung Nodule Registry: A part of the Danish Lung Cancer Registry.

BACKGROUND: The majority of lung cancer cases are diagnosed late, resulting in poor prognosis and high mortality rates. Early detection and management of lung cancer can improve patient outcomes and reduce mortality rates. Pulmonary nodules are key factors in the early detection of lung cancer, they are common in high-risk populations and require correct classification to determine whether they are benign or malignant. Over the last decade a steep increase in the number of thoracic CT scans has been seen in Denmark, resulting in substantial resources allocated to CT follow-up of incidentally detected pulmonary nodules. The implementation of a nationwide Danish prospective pulmonary nodule registry is to methodically record pulmonary nodules and thereby evaluate the scope of pulmonary nodule follow-up, the nature of the nodules, and the clinical progression of patients with pulmonary nodules. METHODS: A prospective pulmonary nodule registry (Danish Lung Nodule Registry) will be a natural appendix to the Danish Lung Cancer Registry. Three new ICD-10 classification codes will be introduced, defining the type of nodule: /DR91.1/ Solid nodule /DR91.2/ Part-solid nodule; /DR91.3/ Non-solid nodule. Furthermore, an additional letter will describe whether the imaging exam is performed on suspicion of lung cancer (A), or the finding is incidental (B). Registration of the nodules will be performed by the departments of respiratory medicine who manage follow-up of pulmonary nodules. It is estimated that around 7000 nodules will be registered annually. DISCUSSION: The registration of patients in the lung nodule registry complies with current Danish legislation. The registry will be seamlessly integrated with other nationwide Danish registries, including the Danish Lung Cancer Registry, to collect additional patient data and improve the quality and scope of the data acquired. The results from these comprehensive epidemiological studies will be of significant interest and offer valuable research opportunities.

Methylated Cell-Free Tumor DNA in Sputum as a Tool for Diagnosing Lung Cancer-A Systematic Review and Meta-Analysis.

Lung cancer is the leading cause of cancer-related mortality worldwide. Early diagnosis is pivotal for the prognosis. There is a notable overlap between lung cancer and chronic bronchitis, and the potential use of methylated tumor DNA in sputum as a biomarker for lung cancer detection is appealing. This systematic review and meta-analysis followed the PRISMA 2020 statement. A comprehensive search was conducted in Embase, Medline, Web of Science, and the Cochrane Library, using these search strings: Lung cancer, sputum, and methylated tumor DNA. A total of 15 studies met the eligibility criteria. Studies predominantly utilized a case-control design, with sensitivity ranging from 10 to 93% and specificity from 8 to 100%. A meta-analysis of all genes across studies resulted in a summary sensitivity of 54.3% (95% CI 49.4-59.2%) and specificity of 79.7% (95% CI 75.0-83.7%). Notably, two less explored genes (TAC1, SOX17) demonstrated sensitivity levels surpassing 85%. The study's findings highlight substantial variations in the sensitivity and specificity of methylated tumor DNA in sputum for lung cancer detection. Challenges in reproducibility could stem from differences in tumor site, sample acquisition, extraction methods, and methylation measurement techniques. This meta-analysis provides a foundation for prioritizing high-performing genes, calling for a standardization and refinement of methodologies before potential application in clinical trials.

Consequences of Losing Incidental Pulmonary Nodules to Follow-Up: Unmonitored Nodules Progressing to Stage IV Lung Cancer.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death globally. Incidental pulmonary nodules represent a golden opportunity for early diagnosis, which is critical for improving survival rates. This study explores the impact of missed pulmonary nodules on the progression of lung cancer. METHODS: A total of 4,066 stage IV lung cancer cases from 2019 to 2021 in Danish hospitals were investigated to determine whether a chest computed tomography (CT) had been performed within 2 years before diagnosis. CT reports and images were reviewed to identify nodules that had been missed by radiologists or were not appropriately monitored, despite being mentioned by the radiologist, and to assess whether these nodules had progressed to stage IV lung cancer. RESULTS: Among stage IV lung cancer patients, 13.6% had undergone a chest CT scan before their diagnosis; of these, 44.4% had nodules mentioned. Radiologists missed a nodule in 7.6% of cases. In total, 45.3% of nodules were not appropriately monitored. An estimated 2.5% of stage IV cases could have been detected earlier with proper surveillance. CONCLUSION: This study underlines the significance of monitoring pulmonary nodules and proposes strategies for enhancing detection and surveillance. These strategies include centralized monitoring and the implementation of automated registries to prevent gaps in follow-up.