Increased use of computed tomography in Denmark: stage shift toward early stage lung cancer through incidental findings.

BACKGROUND: Computed tomography (CT) examinations are increasingly used worldwide and incidental findings are growing likewise. Lung cancer stage at diagnosis is pivotal to survival. The earliest stage of lung cancer, stage IA is in most cases asymptomatic. Potentially, increased use of clinical CTs could induce a stage shift toward earlier lung cancer diagnosis. MATERIALS AND METHODS: Data on the number of CT thorax in Denmark and the stage distribution of Danish lung cancer patients 2013-2020 were acquired from, respectively, the Danish Health Data Authority and the Danish Lung Cancer Registry. Clinical auditing of stage IA lung cancer patients was performed in the period 2019-2021 in a Danish region to assess the reasons for referral. Auditing of stage IV lung cancer patients was done to see whether a CT thorax was performed in a two-year period before diagnosis. RESULTS: All regions showed an increase in CTs per 1000 inhabitants. However, the number of CTs performed in 2013 differed by more than 50% among regions, and the increase per year also differed, from an increase of 1.9 to 3.4 more examinations per year. A significant correlation between CTs and fraction of stage IA lung cancers was seen in four out of the five regions. The audit of stage IA lung cancer cases revealed that 86.8% were incidental findings. Audit of stage IV lung cancer found that 4.3% had a nodule/infiltrate on a previous CT within a 2-year period prior to the diagnosis of lung cancer that was the probable origin of stage IV lung cancer. CONCLUSION: The study found that the vast majority of early-stage lung cancers were incidental findings. It highlights that follow-up algorithms of incidental findings should be used in accordance with guidelines and it should be unequivocally how the CT follow-up of pulmonary infiltrates is managed.

Voluntary early retirement and mortality in patients with and without chronic diseases: a nationwide Danish Registry study.

OBJECTIVE: This study explores how the choice of voluntary early retirement (VER) affects mortality in a population where VER is available 5 years before regular retirement age. STUDY DESIGN: This retrospective cohort study uses a registry-based follow-up design with access to Nationwide Danish Registry Data. METHODS: The study includes all Danish individuals who between 2000 and 2015 were part of an unemployment insurance fund and working at the time of their 60th (P60) or 62nd (P62) birthday. Those alive 1 year from their 60th or 62nd birthday were included in the mortality analysis. Individuals were registered as VER recipients if they chose the benefit within 1 year from P60 or P62. Three-year mortality likelihood following the first year from inclusion was explored for both cohorts separately. Multiple subgroups were explored in the mortality analysis, including individuals with chronic obstructive pulmonary disease (COPD), heart failure, and diabetes. RESULTS: P60 included 627,278 individuals, and VER was chosen by 22.5%. P62 included 379,196 individuals, and VER was chosen by 33.4%. The likelihood of VER in the P60 was lower in healthy individuals (odds ratio [OR] 0.87, confidence interval [CI] 0.85-0.88) and higher in COPD (OR 1.15, CI 1.07-1.22) and heart failure patients (OR 1.15, CI 1.05-1.25). Three-year mortality was significantly higher in those choosing VER in P60 (OR 1.28, CI 1.22-1.34), which was also found for all health subgroups (healthy, OR 1.18, CI 1.07-1.30; COPD, OR 1.55, CI 1.16-2.07; heart failure, OR 1.42, CI 1.02-1.98; diabetes, OR 1.36, CI 1.12-1.65). The increased mortality risk was not found in the P62 cohort. CONCLUSION: The choice of VER is more likely in patients with COPD and heart failure. VER in the P60 cohort is associated with an increased mortality likelihood, which was not found in the P62 cohort, which may be explained by health selection bias.

Return to work after COVID-19 infection - A Danish nationwide registry study.

OBJECTIVES: This study aimed to explore return to work after COVID-19 and how disease severity affects this. STUDY DESIGN: This is a Nationwide Danish registry-based cohort study using a retrospective follow-up design. METHODS: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18-64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non-intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. RESULTS: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94-0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35-0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. CONCLUSION: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.

Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients.

OBJECTIVES: The role of Pseudomonas aeruginosa in the long-term prognosis of chronic obstructive pulmonary disease (COPD) is unknown. The purpose of this study was to determine whether P. aeruginosa is associated with increased risk of exacerbations or death in patients with COPD. METHODS: This is a multiregional epidemiological study based on complete data on COPD outpatients between 1 January 2010 and 31 October 2017 and corresponding microbiology and national register data. Time-dependent Cox proportional hazards models and propensity matching was used to estimate hospitalization-demanding exacerbations and death after 2 years, separately and in combination. RESULTS: A total of 22 053 COPD outpatients were followed for a median of 1082 days (interquartile-range: 427-1862). P. aeruginosa was present in 905 (4.1%) patients. During 730 days of follow-up, P. aeruginosa strongly and independently predicted an increased risk of hospitalization for exacerbation or all-cause death (HR 2.8, 95%CI 2.2-3.6; p <0.0001) and all-cause death (HR 2.7, 95%CI 2.3-3.4; p <0.0001) in analyses adjusted for known and suspected confounders. The signal remained unchanged in unadjusted analyses as well as propensity-matched subgroup analyses. Among patients 'ever colonized' with P. aeruginosa, the incidence of hospital-demanding exacerbations doubled after the time of the first colonization. CONCLUSIONS: COPD patients in whom P. aeruginosa can be cultured from the airways had a markedly increased risk of exacerbations and death. It is still not clear whether this risk can be reduced by offering patients targeted antipseudomonal antibiotics. A randomized trial is currently recruiting patients to clarify this (ClinicalTrials.gov: NCT03262142).

Fractional exhaled nitric oxide as a potential biomarker for radiation pneumonitis in patients with non-small cell lung cancer: A pilot study.

INTRODUCTION: The aim of the study was to investigate repetitive fractional exhaled nitric oxide (FeNO) measurements during high-dose radiation therapy (HDRT) and to evaluate the use of FeNO to predict symptomatic radiation pneumonitis (RP) in patients being treated for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A total of 50 patients with NSCLC referred for HDRT were enrolled. FeNO was measured at baseline, weekly during HDRT, one month- and every third month after HDRT for a one-year follow-up period. The mean FeNO(visit 0-6) was calculated using the arithmetic mean of the baseline and weekly measurements during HDRT. Patients with grade ≥ 2 of RP according to the Common Terminology Criteria for Adverse Events (CTCAE) were considered symptomatic. RESULTS: A total of 42 patients completed HDRT and weekly FeNO measurements. Grade ≥ 2 of RP was diagnosed in 24 (57%) patients. The mean FeNO(visit 0-6) ±â€¯standard deviation in patients with and without RP was 15.0 ±â€¯7.1 ppb (95%CI: 12.0-18.0) and 10.3 ±â€¯3.4 ppb (95%CI: 8.6-11.9) respectively with significant differences between the groups (p = 0.0169, 95%CI: 2.3-2.6). The leave-one-out cross-validated cut-off value of the mean FeNO(visit 0-6) ≥ 14.8 ppb was predictive of grade ≥ 2 RP with a specificity of 71% and a positive predictive value of 78%. CONCLUSIONS: The mean FeNO(visit 0-6) in patients with symptomatic RP after HDRT for NSCLC was significantly higher than in patients without RP and may serve as a potential biomarker for RP.

The established and future biomarkers of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a result of historic asbestos exposure in industrialized countries and continued use of asbestos in developing countries. Lack of accurate biomarkers makes diagnosis, prognostication and treatment prediction of MPM challenging. The aim of this review is to identify the front line of MPM biomarkers with current or potential clinical impact. Literature search using the PubMed and PLoS One databases, the related-articles function of PubMed and the reference lists of associated publications until April 26th 2015 revealed a plethora of candidate biomarkers. The current gold standard of MPM diagnosis is a combination of two positive and two negative immunohistochemical markers in the epithelioid and biphasic type, but sarcomatous type do not have specific markers, making diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as adjuvant diagnostic with high specificity but low sensitivity. Circulating proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test, transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N-ERC mesothelin and deformability cytometry may be important future markers. Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1 gene are potential markers of MPM susceptibility. In conclusion, the current status of MPM biomarkers is not satisfactory but encouraging as more sensitive and specific non-invasive markers are emerging. However, prospective validation is needed before clinical application.

Bacterial colonisation of lower airways in health and chronic lung disease.

BACKGROUND: To evaluate the colonisation rate and type in different groups of patients with chronic lung diseases, bronchial lavage (BL) fluid was investigated for bacteria. METHODS: All patients underwent fibre-optic bronchoscopy as part of routine investigation for remote haemoptysis or nodule investigation. The standard procedure included BL and microbiological culture providing the total number of colony forming units (cfu)/mL and the number of potential pathogenic bacteria (ppb)/mL. Three groups of patients were included: 48 persons had a final diagnosis of no pathology, 53 patients with chronic obstructive pulmonary disease in a stable phase and 32 patients with a final diagnosis of bronchiectasis. RESULTS: The median number of cfu cultured from patients with bronchiectasis was 10(5) cfu/mL compared to 5 10(3) cfu/mL in patients with COPD and 10(4) cfu/mL in persons with no pathology. The ppb colonisation rate varied from 10% in persons with no pathology to 43% in patients diagnosed with chronic obstructive pulmonary disease (COPD) and 63% in patients with bronchiectasis. The most frequent bacteria isolated was Haemophilus influenzae. Colonisation rates were associated with frequencies of respiratory infections; patients with bronchiectasis reported a median of three infections per year, patients with COPD reported one infection per year, and persons without pathology reported 0 infections per year (P < 0.05). Within each group a large patient-to-patient variation was found. CONCLUSIONS: Different groups of patients with chronic pulmonary diseases have very different colonisation rates. Patients with bronchiectasis have the highest colonisation rate. This correlates to the reported frequency of lower respiratory tract infections.