Opportunistic screening for COPD among socially marginalized patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease associated with premature death. Tobacco exposure is the main risk factor, but lower socioeconomic status, early life insults, and occupational exposures are also important risk factors. Socially marginalized people, facing homelessness, substance use disorder, and mental illness, are likely to have a higher risk of developing COPD, and, furthermore, experience barriers to healthcare access and consequently poorer outcomes. OBJECTIVE: This study aims to assess COPD prevalence and the impact of opportunistic screening among hospitalized patients who are in contact with hospital social nurses. These patients constitute a group of patients with a high prevalence of psychiatric and somatic diseases, substance use, low life expectancy, and are socially marginalized. METHODS: The present prospective longitudinal study includes a clinical examination at baseline. Participants will have spirometry done and be interviewed regarding risk factors, socioeconomic conditions, and respiratory symptoms. The 5-year follow-up assessment incorporates data from baseline and register data over the 5 years, including information on morbidity, use of COPD medication, hospital contacts, mortality, and socioeconomic factors. ANTICIPATED RESULTS: Referral for further diagnostic work-up and management after the screening, including COPD treatment and smoking cessation support, is expected to improve survival rates. The study is still enrolling patients. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov , NCT04754308 with study status: "enrolling".

High-Intensity Training Represses FXYD5 and Glycosylates Na,K-ATPase in Type II Muscle Fibres, Which Are Linked with Improved Muscle K+ Handling and Performance.

Na+/K+ ATPase (NKA) comprises several subunits to provide isozyme heterogeneity in a tissue-specific manner. An abundance of NKA α, ß, and FXYD1 subunits is well-described in human skeletal muscle, but not much is known about FXYD5 (dysadherin), a regulator of NKA and ß1 subunit glycosylation, especially with regard to fibre-type specificity and influence of sex and exercise training. Here, we investigated muscle fibre-type specific adaptations in FXYD5 and glycosylated NKAß1 to high-intensity interval training (HIIT), as well as sex differences in FXYD5 abundance. In nine young males (23.8 ± 2.5 years of age) (mean ± SD), 3 weekly sessions of HIIT for 6 weeks enhanced muscle endurance (220 ± 102 vs. 119 ± 99 s, p < 0.01) and lowered leg K+ release during intense knee-extensor exercise (0.5 ± 0.8 vs. 1.0 ± 0.8 mmol·min-1, p < 0.01) while also increasing cumulated leg K+ reuptake 0-3 min into recovery (2.1 ± 1.5 vs. 0.3 ± 0.9 mmol, p < 0.01). In type IIa muscle fibres, HIIT lowered FXYD5 abundance (p < 0.01) and increased the relative distribution of glycosylated NKAß1 (p < 0.05). FXYD5 abundance in type IIa muscle fibres correlated inversely with the maximal oxygen consumption (r = -0.53, p < 0.05). NKAα2 and ß1 subunit abundances did not change with HIIT. In muscle fibres from 30 trained males and females, we observed no sex (p = 0.87) or fibre type differences (p = 0.44) in FXYD5 abundance. Thus, HIIT downregulates FXYD5 and increases the distribution of glycosylated NKAß1 in type IIa muscle fibres, which is likely independent of a change in the number of NKA complexes. These adaptations may contribute to counter exercise-related K+ shifts and enhance muscle performance during intense exercise.

Increased respiratory morbidity in individuals with interstitial lung abnormalities.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Risk of Depression in the Offspring of Parents with Depression: The Role of Emotion Regulation, Cognitive Style, Parenting and Life Events.

Children of depressed parents are at heightened risk for developing depression, yet relatively little is known about the specific mechanisms responsible. Since preventive interventions for this risk group show small effects which diminish overtime, it is crucial to uncover the key risk factors for depression. This study compared various potential mechanisms in children of depressed (high-risk; n = 74) versus non-depressed (low-risk; n = 37) parents and explored mediators of parental depression and risk in offspring. A German sample of N = 111 boys and girls aged 8 to 17 years were compared regarding children's (i) symptoms of depression and general psychopathology, (ii) emotion regulation strategies, (iii) attributional style, (iv) perceived parenting style and (v) life events. Children in the high-risk group showed significantly more symptoms of depression and general psychopathology, less adaptive emotion regulation strategies, fewer positive life events and fewer positive parenting strategies in comparison with the low-risk group. Group differences in positive and negative attributional style were small and not statistically significant in a MANOVA test. Maladaptive emotion regulation strategies and negative life events were identified as partial mediators of the association between parental depression and children's risk of depression. The study highlights the elevated risk of depression in children of depressed parents and provides empirical support for existing models of the mechanisms underlying transmission. Interestingly, the high-risk group was characterised by a lack of protective rather than increased vulnerability factors. These results are crucial for developing more effective preventive interventions for this high-risk population.

Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling.

RATIONALE: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS: A total of 4,104 participants aged 50-70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group). MEASUREMENTS AND MAIN RESULTS: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66-1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, respectively; P < 0.001), particularly adenocarcinomas (58 vs. 18, respectively; P < 0.001). More early-stage cancers (stages I and II, 54 vs. 10, respectively; P < 0.001) and stage IIIa cancers (15 vs. 3, respectively; P = 0.009) were found in the screening group than in the control group. Stage IV cancers were nonsignificantly more frequent in the control group than in the screening group (32 vs. 23, respectively; P = 0.278). For the highest-stage cancers (T4N3M1, 21 vs. 8, respectively; P = 0.025), this difference was statistically significant, indicating an absolute stage shift. Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group. CONCLUSIONS: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung Screening Trial. Clinical trial registered with www.clinicaltrials.gov (NCT00496977).

Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis.

OBJECTIVES: Screening for lung cancer should be limited to a high-risk-population, and abnormalities in low-dose computed tomography (CT) screening images may be relevant for predicting the risk of lung cancer. Our aims were to compare the occurrence of visually detected emphysema and interstitial abnormalities in subjects with and without lung cancer in a screening population of smokers. METHODS: Low-dose chest CT examinations (baseline and latest possible) of 1990 participants from The Danish Lung Cancer Screening Trial were independently evaluated by two observers who scored emphysema and interstitial abnormalities. Emphysema (lung density) was also measured quantitatively. RESULTS: Emphysema was seen more frequently and its extent was greater among participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p = 0.002) and late examinations (OR 2.6, p < 0.001 and p < 0.001). No significant difference was found using quantitative measurements. Interstitial abnormalities were more common findings among participants with lung cancer (OR 5.1, p < 0.001 and OR 4.5, p < 0.001).There was no association between presence of emphysema and presence of interstitial abnormalities (OR 0.75, p = 0.499). CONCLUSIONS: Even early signs of emphysema and interstitial abnormalities are associated with lung cancer. Quantitative measurements of emphysema-regardless of type-do not show the same association. KEY POINTS: • Visually detected emphysema on CT is more frequent in individuals who develop lung cancer. • Emphysema grading is higher in those who develop lung cancer. • Interstitial abnormalities, including discrete changes, are associated with lung cancer. • Quantitative lung density measurements are not useful in lung cancer risk prediction. • Early CT signs of emphysema and interstitial abnormalities can predict future risk.

Ground-Glass Opacity Lung Nodules in the Era of Lung Cancer CT Screening: Radiology, Pathology, and Clinical Management.

The advent of computed tomography screening for lung cancer will increase the incidence of ground-glass opacity (GGO) nodules detected and referred for diagnostic evaluation and management. GGO nodules remain a diagnostic challenge; therefore, a more systematic approach is necessary to ensure correct diagnosis and optimal management. Here we present the latest advances in the radiologic imaging and pathology of GGO nodules, demonstrating that radiologic features are increasingly predictive of the pathology of GGO nodules. We review the current guidelines from the Fleischner Society, the National Comprehensive Cancer Network, and the British Thoracic Society. In addition, we discuss the management and follow-up of GGO nodules in the light of experience from screening trials. Minimally invasive tissue biopsies and the marking of GGO nodules for surgery are new and rapidly developing fields that will yield improvements in both diagnosis and treatment. The standard-of-care surgical treatment of early lung cancer is still minimally invasive lobectomy with systematic lymph node dissection. However, recent research has shown that some GGO lesions may be treated with sublobar resections; these findings may expand the surgical treatment options available in the future.

Protective effects of surfactant protein D treatment in 1,3-ß-glucan-modulated allergic inflammation.

Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity. SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin (OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with exogenous SP-D has therapeutic effects in such disease models. ß-Glucans are a diverse group of polysaccharides previously suggested to serve as fungal ligands for SP-D. We set out to investigate if SP-D could interact with 1,3-ß-glucan and attenuate allergic pulmonary inflammation in the presence of 1,3-ß-glucan. Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice by OVA sensitization and subsequent challenge with OVA, 1,3-ß-glucan, or OVA/1,3-ß-glucan together. Mice in the combined treatment group were further treated with a high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct interaction between SP-D and 1,3-ß-glucan. OVA-induced mucous cell metaplasia was increased in Sftpd(-/-) mice, supporting previously reported protective effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-ß-glucan, but were reversed with rfhSP-D treatment. 1,3-ß-Glucan treatment did, however, induce pulmonary neutrophilic infiltration and increased TNF-α levels in bronchoalveolar lavage, independently of OVA-induced allergy. This infiltration was also reversed by treatment with rfhSP-D. 1,3-ß-Glucan reduced OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-γ production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2 cytokine secretion to background levels. In summary, rfhSP-D treatment resulted in attenuation of both allergic inflammation and 1,3-ß-glucan-mediated neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D protects from mold-induced exacerbations of allergic asthma.

Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial.

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.

Smoking habits in the randomised Danish Lung Cancer Screening Trial with low-dose CT: final results after a 5-year screening programme.

BACKGROUND: We present the final results of the effect of lung cancer screening with low-dose CT on the smoking habits of participants in a 5-year screening trial. METHODS: The Danish Lung Cancer Screening Trial (DLCST) was a 5-year screening trial that enrolled 4104 subjects; 2052 were randomised to annual low-dose CT (CT group) and 2052 received no intervention (control group). Participants were current and ex-smokers (≥4 weeks abstinence from smoking) with a tobacco consumption of ≥20 pack years. Smoking habits were determined annually. Missing values for smoking status at the final screening round were handled using two different models. RESULTS: There were no statistically significant differences in annual smoking status between the CT group and control group. Overall the ex-smoker rates (CT + control group) significantly increased from 24% (baseline) to 37% at year 5 of screening (p<0.001). The annual point prevalence quit rate increased from 11% to 24% during the five screening rounds; the ex-smokers' relapse rate remained stable, around 11%, across the same period. CONCLUSIONS: Screening with low-dose CT had no extra effect on smoking status compared with the control group, but overall the screening programme probably promoted smoking cessation. CLINICAL TRIAL REGISTRATION: The DLCST is registered in Clinical Trials.gov Protocol Registration System (identification no. NCT00496977).

Emphysema progression is visually detectable in low-dose CT in continuous but not in former smokers.

OBJECTIVES: To evaluate interobserver agreement and time-trend in chest CT assessment of emphysema, airways, and interstitial abnormalities in a lung cancer screening cohort. METHODS: Visual assessment of baseline and fifth-year examination of 1990 participants was performed independently by two observers. Results were standardised by means of an electronic score sheet; kappa and time-trend analyses were performed. RESULTS: Interobserver agreement was substantial in early emphysema diagnosis; highly significant (p < 0.001) time-trends in both emphysema presence and grading were found (higher prevalence and grade of emphysema in late CT examinations). Significant progression in emphysema was seen in continuous smokers, but not in former smokers. Agreement on centrilobular emphysema subtype was substantial; agreement on paraseptal subtype, moderate. Agreement on panlobular and mixed subtypes was only fair. Agreement was fair regarding airway analysis. Interstitial abnormalities were infrequent in the cohort, and agreement on these was fair to moderate. A highly significant time-trend was found regarding interstitial abnormalities, which were more frequent in late examinations. CONCLUSIONS: Visual scoring of chest CT is able to characterise the presence, pattern, and progression of early emphysema. Continuous smokers progress; former smokers do not. KEY POINTS: • Substantial interobserver consistency in determining early-stage emphysema in low-dose CT. • Longitudinal analyses show clear time-trends for emphysema presence and grading. • For continuous smokers, progression of emphysema was seen in all lung zones. • For former smokers, progression of emphysema was undetectable by visual assessment. • Onset and progression of interstitial abnormalities are visually detectable.

Analysis of FEV1 decline in relatively healthy heavy smokers: implications of expressing changes in FEV1 in relative terms.

Progressive decline in lung function has been widely accepted as the hallmark of chronic obstructive pulmonary disease (COPD); however, recent evidence indicates that the rate of decline measured as decline in forced expiratory volume in one second (FEV1) is higher in mild to moderate COPD than in severe COPD. Usually changes in FEV1 are measured in ml that is "absolute"; however, changes can also be measured "relative" as a percentage of the actual FEV1. We hypothesize that relative measurements could be more appropriate than absolute measurements for describing changes in lung function. We analyzed data from 3,218 relatively healthy heavy smokers who participated in the Danish Lung Cancer Screening Trial. The influences of age, sex, height, body mass index, smoking, and severity of airflow limitation on FEV1 were analyzed in mixed effects models. In absolute terms those with the best lung function consistently showed the steepest decline, whereas in relative terms most fast decliners are found among those with low lung function. Measuring changes in relative terms implied statistically significant acceleration of decline with advancing age, smoking (pack-years) and severity of airflow limitation. Relative measurements may lead to a better understanding of changes in lung function. Smoking and severity of airflow limitation speed up the loss of lung function, and this emphasizes the importance of abstaining from smoking the sooner the better. Measuring changes in relative terms could have important implications for the interpretation of results from clinical trials where FEV1 is the primary outcome. DLCST; www.ClinicalTrials.org , registration number: NCT00496977.

Harms of exercise training in patients with cancer undergoing systemic treatment: a systematic review and meta-analysis of published and unpublished controlled trials.

Background: Exercise is recommended for people with cancer. The aim of this study was to evaluate the harms of exercise in patients with cancer undergoing systemic treatment. Methods: This systematic review and meta-analysis included published and unpublished controlled trials comparing exercise interventions versus controls in adults with cancer scheduled to undergo systemic treatment. The primary outcomes were adverse events, health-care utilization, and treatment tolerability and response. Eleven electronic databases and trial registries were systematically searched with no date or language restrictions. The latest searches were performed on April 26, 2022. The risk of bias was judged using RoB2 and ROBINS-I, and the certainty of evidence for primary outcomes was assessed using GRADE. Data were statistically synthesised using pre-specified random-effect meta-analyses. The protocol for this study was registered in the PROESPERO database (ID: CRD42021266882). Findings: 129 controlled trials including 12,044 participants were eligible. Primary meta-analyses revealed evidence of a higher risk of some harms, including serious adverse events (risk ratio [95% CI]: 1.87 [1.47-2.39], I2 = 0%, n = 1722, k = 10), thromboses (risk ratio [95% CI]: 1.67 [1.11-2.51], I2 = 0%, n = 934, k = 6), and fractures (risk ratio [95% CI]: 3.07 [3.03-3.11], I2 = 0%, n = 203, k = 2) in intervention versus control. In contrast, we found evidence of a lower risk of fever (risk ratio [95% CI]: 0.69 [0.55-0.87], I2 = 0% n = 1109, k = 7) and a higher relative dose intensity of systemic treatment (difference in means [95% CI]: 1.50% [0.14-2.85], I2 = 0% n = 1110, k = 13) in intervention versus control. For all outcomes, we downgraded the certainty of evidence due to imprecision, risk of bias, and indirectness, resulting in very low certainty of evidence. Interpretation: The harms of exercise in patients with cancer undergoing systemic treatment are uncertain, and there is currently insufficient data on harms to make evidence-based risk-benefits assessments of the application of structured exercise in this population. Funding: There was no funding for this study.

"I Am a Total Loser" - The Role of Interpretation Biases in Youth Depression.

Negative interpretation biases have been found to characterize adults with depression and to be involved in the development and maintenance of the disorder. However, less is known about their role in youth depression. The present study investigated i) whether negative interpretation biases characterize children and adolescents with depression and ii) to what extent these biases are more pronounced in currently depressed youth compared to youth at risk for depression (as some negative interpretation biases have been found already in high-risk youth before disorder onset). After a negative mood induction interpretation biases were assessed with two experimental tasks: Ambiguous Scenarios Task (AST) and Scrambled Sentences Task (SST) in three groups of 9-14-year-olds: children and adolescents with a diagnosis of major depression (n = 32), children and adolescents with a high risk for depression (children of depressed parents; n = 48), as well as low-risk children and adolescents (n = 42). Depressed youth exhibited substantially more negative interpretation biases than both high-risk and low-risk groups (as assessed with both tasks), while the high-risk group showed more negative interpretation biases than the low-risk group only as assessed via the SST. The results indicate that the negative interpretation biases that are to some extent already present in high-risk populations before disorder onset are strongly amplified in currently depressed youth. The different findings for the two tasks suggest that more implicit interpretation biases (assessed with the SST) might represent cognitive vulnerabilities for depression whereas more explicit interpretation biases (assessed with the AST) may arise as a consequence of depressive symptomatology.

Learning to Quantify Emphysema Extent: What Labels Do We Need?

Accurate assessment of pulmonary emphysema is crucial to assess disease severity and subtype, to monitor disease progression, and to predict lung cancer risk. However, visual assessment is time-consuming and subject to substantial inter-rater variability while standard densitometry approaches to quantify emphysema remain inferior to visual scoring. We explore if machine learning methods that learn from a large dataset of visually assessed CT scans can provide accurate estimates of emphysema extent and if methods that learn from emphysema extent scoring can outperform algorithms that learn only from emphysema presence scoring. Four Multiple Instance Learning classifiers, trained on emphysema presence labels, and five Learning with Label Proportions classifiers, trained on emphysema extent labels, are compared. Performance is evaluated on 600 low-dose CT scans from the Danish Lung Cancer Screening Trial and we find that learning from emphysema presence labels, which are much easier to obtain, gives equally good performance to learning from emphysema extent labels. The best performing Multiple Instance Learning and Learning with Label Proportions classifiers, achieve intra-class correlation coefficients around 0.90 and average overall agreement with raters of 78% and 79% compared to an inter-rater agreement of 83%.

Passing on the half-empty glass: A transgenerational study of interpretation biases in children at risk for depression and their parents with depression.

Children of parents with a history of depression have an increased risk of developing depression themselves. The present study investigated the role of interpretation biases (that have been found in adults and adolescents with depression but have rarely been examined in at-risk youth) in the transgenerational transmission of depression risk. Interpretation biases were assessed with two experimental tasks: Ambiguous Scenarios Task (AST) and Scrambled Sentences Task (SST) in 9-14-year-old children of parents with a history of depression (high risk; n = 43) in comparison to children of parents with no history of mental disorders (low risk; n = 35). Interpretation biases were also compared between the two groups of parents and relationships between children's and parents' bias scores were examined. As expected, we found more negative interpretation biases in high-risk children compared to low-risk children as well as in parents with a history of depression compared to never-depressed parents (assessed via the SST but not the AST). However, transgenerational correlations were only found for the AST. Our results indicate that negative interpretation biases are present in youth at risk for depression, possibly representing a cognitive vulnerability for the development of depression. Moreover, different measures of interpretation bias seemed to capture different aspects of biased processing with the more implicit measure (SST) being a more valid indicator of depressive processing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

[Treatment limitations or discontinuation in patients with benign pulmonary diseases].

The decision to limit or discontinue treatment is a difficult issue, which all physicians will face. Timely communication with information on treatment possibilities and limitations, respectful listening to patients' and informal caregivers' wishes and early palliation is recommended in a stable phase. In some situations, it is better to stop life-prolonging treatment and optimise quality of life in patients with benign pulmonary diseases. Decision on treatment limitations or discontinuation is best taken at a conference and should be based on the patient's wishes, the disease stage and progression and potential reversible components.

Interstitial lung abnormalities are associated with increased mortality in smokers.

OBJECTIVE: The aim of this study was to investigate whether smokers with incidental findings of interstitial lung abnormalities have an increased mortality during long-term follow-up, and review the contributing causes of death. METHODS: Baseline CT scans of 1990 participants from the Danish Lung Cancer Screening Trial were qualitatively assessed for predefined interstitial lung abnormalities of any severity. Inclusion criteria for this lung cancer screening trial included current or former smoking, > 20 pack-years, and age 50-70 years. Patients were followed up for up to 12 years. RESULTS: We found interstitial lung abnormalities in 332 participants (16.7%). Interstitial lung abnormalities were associated with increased all-cause mortality in the full cohort (HR: 2.0, 95% CI: 1.4-2.7, P < 0.001) and in lung cancer-free participants (HR: 1.6, 95% CI: 1.1-2.4, P = 0.007). The findings were associated with death from lung cancer (HR: 3.2, 95% CI: 1.7-6.2, P < 0.001) and non-pulmonary malignancies (HR: 2.1, 95% CI: 1.1-4.0, P = 0.02). Participants with fibrotic and non-fibrotic interstitial lung abnormalities had similar survival. CONCLUSION: Interstitial lung abnormalities were common in this lung cancer screening population of relatively healthy smokers and were associated with mortality regardless of the interstitial morphological phenotype. The increased mortality was partly due to an association with lung cancer and non-pulmonary malignancies.

Danish respiratory society position paper: palliative care in patients with chronic progressive non-malignant lung diseases.

Background:  Chronic non-malignant lung diseases such as chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) result in reduced quality of life (QoL), a high symptom burden and reduced survival. Patients with chronic non-malignant lung disease often have limited access to palliative care. The symptom burden and the QoL of these patients resembles patients with cancer and the general palliative approach is similar. However, the disease trajectory is often slow and unpredictable, and the palliative effort must be built on accessibility, continuity and professional competences. The Danish Health Authority as well as the WHO recommends that there is access to palliative care for all patients with life-threatening diseases regardless of diagnosis. In 2011, the Danish Health Authority requested that the national medical societies would to formulate guidelines for palliation. Methods: In 2015, a group of members of the Danish Respiratory Society (DRS) was appointed for this purpose. It was composed of experienced ILD and COPD researchers as well as clinicians from different parts of Denmark. A literature review was made, a draft was prepared, and all recommendations were agreed upon unanimously. Results: The Danish version of the position paper was finally submitted for review and accepted by all members of DRS. Conclusion: In this position paper we provide recommendations on the terminology of chronic and terminal lung failure, rehabilitation and palliative care, advanced care planning, informal caregivers and bereavement, symptom management, the imminently dying patient, and organization of palliative care for patients with chronic non-malignant lung diseases.

Geodesic Atlas-Based Labeling of Anatomical Trees: Application and Evaluation on Airways Extracted From CT.

We present a fast and robust atlas-based algorithm for labeling airway trees, using geodesic distances in a geometric tree-space. Possible branch label configurations for an unlabeled airway tree are evaluated using distances to a training set of labeled airway trees. In tree-space, airway tree topology and geometry change continuously, giving a natural automatic handling of anatomical differences and noise. A hierarchical approach makes the algorithm efficient, assigning labels from the trachea and downwards. Only the airway centerline tree is used, which is relatively unaffected by pathology. The algorithm is evaluated on 80 segmented airway trees from 40 subjects at two time points, labeled by three medical experts each, testing accuracy, reproducibility and robustness in patients with chronic obstructive pulmonary disease (COPD). The accuracy of the algorithm is statistically similar to that of the experts and not significantly correlated with COPD severity. The reproducibility of the algorithm is significantly better than that of the experts, and negatively correlated with COPD severity. Evaluation of the algorithm on a longitudinal set of 8724 trees from a lung cancer screening trial shows that the algorithm can be used in large scale studies with high reproducibility, and that the negative correlation of reproducibility with COPD severity can be explained by missing branches, for instance due to segmentation problems in COPD patients. We conclude that the algorithm is robust to COPD severity given equally complete airway trees, and comparable in performance to that of experts in pulmonary medicine, emphasizing the suitability of the labeling algorithm for clinical use.