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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., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. A. P. participates in an advisory board for Nordicinfu Care Denmark, which distributes ARIKAYCE (amikacin liposome inhalation suspension) for Insmed. A. F. participates in an advisory board for Nordicinfu Care Denmark, which distributes ARIKAYCE (amikacin liposome inhalation suspension) for Insmed. None declared (A. L., R. I., I. S. J., O. H.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:This work was supported by an unrestricted grant from Boehringer Ingelheim, grant number AGR- 2018- 731–5845, who were given the opportunity to review the manuscript for medical and scientific accuracy. The funding sources had no role in the design, analysis, or interpretation of the results. The authors declare that they have no additional conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal., Research Question: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment?, Study Design and Methods: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV 1 > 80%) and a six-question Asthma Control Questionnaire score ≤ 1.5 following 12 months of treatment., Results: Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy., Interpretation: Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: S. H. reports speaker fees from AstraZeneca; M. B. S. reports speaker fees from GSK; A. v. B. reports consulting fees from Novartis, speaker fees from Novartis, GSK, and AstraZeneca, travel grants from AstraZeneca, and participation in advisory boards with AstraZeneca and Novartis; A.-S. B. reports lecture fees from AstraZeneca and GSK; L. M. R. has received lecture fees from AstraZeneca, GSK, and Teva, support for attending meetings and/or travel received from AstraZeneca and Chiesi, and participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, GSK, and Teva; K. E. J. H. reports grants from SanofiGenzyme and AstraZeneca, lecture fees from AstraZeneca, GSK, Chiesi, TEVA, and SanofiGenzyme; O. H. reports support attending meetings from Sanofi, and participation in advisory boards with GSK, MSD, Sanofi, AstraZeneca, TEVA, and ALK; C. U. reports grants from Sanofi, Boehringer Ingelheim, AstraZeneca, and Novartis, consulting fees from Chiesi, Orion Pharma, AstraZeneca, GSK, Teva, Menarini, and Takeda, lecture fees from Orion Pharma, AstraZeneca, and TEVA, and participation in advisory boards with Novartis, GSK, AstraZeneca, Pfizer, Sanofi, Chiesi, and Boehringer Ingelheim; C. P. reports grants from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi, and ALK, consulting fees from AstraZeneca, GSK, Novartis, TEVA, Sanofi, Chiesi, and ALK, lecture fees from AstraZeneca, GSK, Novartis, TEVA, Sanofi, Chiesi, and ALK, participation in advisory boards with AstraZeneca, Novartis, TEVA, Sanofi, and ALK. None declared (J. S., C. R. J., T. I., S. L. J., M. B., K. D. A.)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: We examined the number of lung cancers diagnosed, the quality of care and the socio-economic and clinical characteristics among patients with lung cancer during the COVID-19 pandemic compared to previous years., Methods: We included all patients ≥ 18 years old diagnosed with lung cancer from 01 January 2018 to 31 August 2021 as registered in the Danish Lung Cancer Registry. Using a generalised linear model, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) of the associations between the pandemic and socioeconomic and clinical factors, and indicators of quality., Results: We included 18,113 patients with lung cancer (82.0% non-small cell lung cancer (NSCLC)), which was similar to the preceding years, although a decline in NSCLC cases occurred during the first lockdown period in 2020. No difference in distribution of income or educational level was observed. No difference was observed in the quality of treatment - as measured by curative intent, proportion of patients resected or who died within 90 days of diagnosis., Conclusion: Using nationwide population-based data, our study reassuringly shows no adverse effects of the COVID-19 pandemic on the diagnosis, socio-economic characteristics nor quality of treatment of lung cancer, as compared to the preceding years., Competing Interests: Declaration of Competing Interest The authors report that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Tuberculosis (TB) prevalence is high among socially marginalized citizens in Denmark, and management of latent TB infection (LTBI) may be part of preventing new cases. Patients with LTBI are offered either preventive treatment (TPT) or follow-up chest x-rays, but knowledge about the long-term outcome in terms of active TB is sparse., Methods: We performed a retrospective cohort study investigating the long-term outcomes for socially marginalized citizens who were diagnosed with LTBI or who had a positive interferon-gamma release assay (IGRA) but were lost to follow-up. Information on TB examinations, diagnostics, and treatment along with data on death were gathered from medical records from the date of positive IGRA to February 1, 2021., Results: We identified 119 patients with LTBI, 18 of which (15.1%) were diagnosed with TB during the follow-up period (mean, 4.5 years). TPT was completed by 36.1% and the TB incidence rate ratio of those completing TPT to those who did not was 0.78 (confidence interval, 0.25-2.17; P =.6). Of the patients with TB, 16 of 18 achieved treatment success., Conclusion: High rates of TB development are found among socially marginalized citizens with LTBI. Overall incidence of TB was not significantly reduced by administration of TPT, although TB did not develop in the first 2 years following TPT., Competing Interests: Conflict of interest statement The authors have no conflict of interest with regard to this work., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD) has been debated for 20 years. In our systematic literature review and meta-analysis, we addressed the following: Should patients with COPD and a blood eosinophil count (EOS) of, respectively, a) < 150 cells/μl, b) 150-300 cells/μl, and c) > 300 cells/μl continue treatment with ICS? Protocol registered in PROSPERO (CRD42020178110) and funded by the Danish Health Authority. We searched Medline, Embase, CINAHL and Cochrane Central on 22 nd July 2020 for randomized controlled trials (RCT) of ICS treatment in patients with COPD (≥40 years, no current asthma), which analyzed outcomes by EOS count and where >50% of patients used ICS prior. We used the GRADE method. Meta-analyzes for the outcomes were divided into EOS subgroups and analyzed for differences. We identified 11 RCTs with a total of 29,654 patients. A significant difference (p < 0.00001) between the three subgroups' reduction of risk of moderate to severe exacerbation was found. Rate ratios for EOS counts: <150 cells/μL was 0.88 (95%CI: 0.83, 0.94); 150-300 cells/μL was 0.80 (95%CI: 0.69, 0.94); >300 cells/μL was 0.57 (95%CI: 0.49, 0.66). Overall, the certainty of the effect estimates was low to very low due to risk of bias, unexplained heterogeneity, few RCTs, and wide confidence intervals. A clear correlation was demonstrated between effect of continued ICS treatment (number of exacerbations, lung function, and quality of life) and increasing EOS count. Our meta-analyses suggested that treatment with ICS seemed beneficial for everyone except patients with EOS count below 150 cells/μl., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The primary objective was to evaluate the prevalence and incidence of sarcoidosis, and secondly, to evaluate differences in incidence by age at diagnosis, gender, region, calendar year and treatment and to evaluate sarcoidosis-related diagnostic work-up., Methods: Patients diagnosed with sarcoidosis from 2001 to 2015 and information on diagnostic procedures three months before and after initial diagnosis were identified in the Danish National Patient Register. Incidence proportion and prevalence proportion were calculated using the total population count of Danish citizens., Results: We identified 8545 sarcoidosis cases. Mean age was 46.0 ± 15.0 years, male gender was overrepresented (56.2%) and systemic corticosteroid was initiated in 46% of cases. The prevalence was 77 per 100,000 citizens in 2015. From 2001 to 2015, the incidence varied from 11.3 to 14.8 per 100,000 per year. The age-associated incidence peaked at 30-39 years in both men (23.6 per 100,000 per year) and women (15.0 per 100,000 per year). Incidence varied from 10.4 to 15.7 per 100,000 per year among regions. In particular, the share of bronchoscopies and chest-computed tomography were high in the region with the highest incidence and low in the region with the lowest incidence. Invasive procedures were more frequently performed in patients treated with systemic corticosteroid., Conclusion: We find an increasing incidence and prevalence of sarcoidosis, with a peak incidence for both men and women between 30 and 39 years of age. The share of procedures performed seems to correlate well with incidence and disease severity., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Comorbidities are common in patients with idiopathic pulmonary fibrosis (IPF) and negatively impact health-related quality of life, health-care costs and mortality. Retrospective studies have focused on individual comorbidities, but clusters of multiple comorbidities have rarely been analysed. This study aimed to comprehensively and prospectively assess comorbidities in a multicentre, real-world cohort of patients with IPF, including prespecified conditions of special interest and to analyse clusters of comorbidities and examine characteristics, disease course and mortality of the clusters., Methods: Several measurements, questionnaires, medications and medical history were combined to assess comorbidities. Using self-organizing maps, clusters of comorbidities were identified and phenotypes characterized. Disease course was assessed using mixed effects models and mortality using Cox regression., Results: One-hundred and fifty IPF patients were included prospectively. All except one patient suffered from at least one comorbidity and multimorbidity was common. Arterial hypertension, gastro-oesophageal reflux disease, hypercholesterolemia, emphysema and obstructive sleep apnea were most prevalent. Four comorbidity clusters were identified. Each cluster had distinct comorbidity profiles, patient characteristics, symptom burden and disease severity. Patients with fewer comorbidities had better exercise capacity and less dyspnea at baseline, but a trend towards faster deterioration was observed. Mortality analyses showed no significant differences between clusters., Conclusions: Multimorbidity is prevalent in patients with IPF. Four specific clusters of comorbidities may represent phenotypes in IPF. A trend towards faster decline in exercise capacity and dyspnea was observed in patients with fewer comorbidities. Increased knowledge of comorbidities facilitates prevention and treatment of comorbidities in patients with IPF., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Concerns of increased time consumption and of the impact on clinical decisions may restrain doctors from shared decision making (SDM). This paper evaluates consultation length and decisions made when using an in-consult patient decision aid (PtDA)., Methods: This prospective cohort study compared an unexposed cohort with a cohort exposed to SDM and a PtDA in two preference-sensitive decision situations: invasive lung cancer diagnostics and adjuvant treatment for early breast cancer. Outcome measures were consultation length and decisions made., Results: The study included 261 consultations, 115 were in the SDM-exposed cohort. Consultations were inconsiderably longer in the SDM cohort; 2 min, 11 s (p = 0.2217) for lung cancer diagnostics and 3 min, 57 s (p = 0.1128) for adjuvant breast cancer treatment. In lung cancer diagnostics, consultation length became more uniform and decisions tended to become conservative after introduction of SDM. For adjuvant breast cancer, slightly more patients in the SDM cohort chose to decline treatment., Conclusion: Shared decision making did not take significantly longer time and led to slightly more conservative decisions., Practice Implications: SDM may be implemented without considerable impact on consultation length. The impact on clinical decisions depends mainly on the clinical situation., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Allergen immunotherapy (AIT) is a cost-effective treatment option in moderate-severe allergic rhino-conjunctivitis. Inequality in access to AIT and variation in compliance related to socioeconomic status or geographical location have not been described previously., Objective: The aim of the study was to evaluate access to grass pollen AIT at various educational attainment levels in the five regions of Denmark. Furthermore, grass pollen AIT treatment compliance was evaluated with respect to age, educational attainment and geographical area., Methods: The unique civil registration number of every citizen in Denmark was combined with the nationwide Danish National Health Service Prescription Database and Statistics Denmark Database to extract age, gender, residence and educational attainment of every citizen who collected prescribed AIT medication from 1998 to 2016. Then, compliance and use of AIT were calculated with respect to age, geographical location and educational attainment., Results: The use of subcutaneous AIT (SCIT) was significantly higher in the Capital Region; this difference was less predominant for sublingual AIT (SLIT). People who were educated only to primary school or vocational training levels were less frequent users of AIT. Compliance was especially low in the Capital Region and among people educated only to primary school level. In the age groups, compliance was similar, apart from SLIT users aged 0-9, for whom compliance was higher., Conclusion: This nationwide study finds that SLIT has the potential to reduce inequality in access to AIT. A focus intervention is needed to facilitate access to and compliance with AIT in groups with lower socioeconomic status., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Screening for TB (tuberculosis) among socially marginalized citizens has been implemented in many urban areas in countries with a low incidence of TB, including Denmark. This study aims to describe the findings of the screening programs for TB and latent tuberculosis (LTBI) used in the western part of Denmark in the period 2014-2019., Methods: Data was collected retrospectively on test results from interferon-gamma release assays (IGRA), spot sputum tests and chest X-rays performed as part of TB and LTBI screening among 1024 socially marginalized citizens in urban areas of western Denmark in 2014-2019., Results: The overall TB incidence was 2148/100.000 and number needed to screen to find one TB case was 39. The incidence of LTBI in the group screened using IGRA was 17.500/100.000. TB incidence when using spot sputum test was 2.5, while TB incidence when using IGRA as the primary screening test was 2.7. In total, 38.9% of TB diagnoses were obtained after the second or third round of screening., Conclusion: We demonstrated a high incidence of TB and LTBI among socially marginalized citizens in Denmark. Screening with spot sputum testing and IGRA generated comparable results in diagnosing TB in this setting., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Allergic rhino-conjunctivitis is a highly prevalent condition. In moderate to severe cases, allergen immunotherapy (AIT) is a cost-effective therapeutic option. Previous data have reported a large difference in treatment compliance of subcutaneously (SCIT) and sublingually (SLIT) administered AIT., Methods: By use of the unique civil registration number assigned to all Danish citizens and the Danish National Health Service Prescription Database, compliance rates of all patients prescribed with grass pollen AIT from January 1998 until December 2016 were analysed annually during the three-year treatment period., Results: The male/female ratio was close to 1:1 in SCIT, while SLIT was more frequently used by men. A large proportion of users was children or adolescents (32% and 45%, SCIT and SLIT, respectively). Compliance of both subcutaneous and sublingual treatment gradually fell each year; compliance in year 3 was 57% and 53% for subcutaneous and sublingual treatment, respectively. Compliance of grass pollen sublingual treatment was also analysed each year after registration on the Danish market. Compliance significantly increased following the introduction and stabilised on a relatively high level., Conclusion: Based on previous studies, we hypothesised that AIT compliance would be low, especially in SLIT. However, in Denmark, compliance in SCIT and SLIT was almost similar, and the majority of patients completed the three-year treatment period with a compliance in the last quintile., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to describe the impact on patient-reported outcomes of introducing Shared Decision Making (SDM) and a Patient Decision Aid (PtDA) in the initial process of lung cancer diagnostics., Methods: We conducted a prospective cohort study, where a control cohort was consulted according to usual clinical practice. After introducing SDM through a PtDA and training of the staff, the SDM cohort was enrolled in the study. All patients completed four questionnaires: the Decisional Conflict Scale (DCS) before and after the consultation, the CollaboRATE scale after the consultation, and the Decision Regret Scale (DRS)., Results: Patients exposed to SDM and a PtDA had significantly improved DCS scores after the consultation compared to the control group (a difference of 10.26, p = 0.0128) and significantly lower DRS scores (a difference of 8.98, p = 0.0197). Of the 82 control patients and 52 SDM patients 29% and 54%, respectively, gave the maximum score on the CollaboRATE scale (Pearson's chi 2 8.0946, p = 0.004)., Conclusion: The use of SDM and a PtDA had significant positive impact on patient-reported outcomes., Practice Implications: Our results may encourage the increased uptake of SDM in the initial process of lung cancer diagnostics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Sarcoidosis is a systemic disease that primarily affects the younger population. Longitudinal studies of the economic burden of sarcoidosis are scarce. This study evaluates overall the economic burden of sarcoidosis in Denmark before and after initial diagnosis., Methods: We identified patients with sarcoidosis in the Danish National Patient Registry (1998-2010). All controls were randomly selected and matched concerning age, gender and residence. Data on direct and indirect costs, including frequency of primary and secondary sector contacts and procedures, medication, unemployment benefits and social transfer payments were extracted from national databases for patients and controls., Results: We identified 9119 patients with sarcoidosis and 36,432 matching controls. Patients with sarcoidosis had significantly higher rates of health-related contacts, higher usage of medication and more received unemployment and social payments compared with controls. The total health expenses were significantly higher in the sarcoidosis group 11 years before and 11 years after diagnosis than among controls. Income from public transfer payments was significantly higher in the sarcoidosis group five years prior of diagnosis until nine years post diagnosis. Especially women between 40 and 59 years have a lower income than their controls., Conclusion: Sarcoidosis has a socioeconomic impact on adults especially during their prime working and providing years and this is evident several years prior to and post diagnosis. The authors advocate that further research should focus on identifying the proportion of patients with sarcoidosis that imposes the largest economic burden. Increased focus on early diagnosis and disease management may reduce the socioeconomic burden of sarcoidosis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Tracheal collapse is a weakness of the tracheal wall leading to expiratory central airway collapse of more than 50% compared to inspiration. It has previously been discussed whether the collapsibility of the greater airways is a stable or a dynamic condition. Indeed, other well-known lung diseases such as asthma are characterized by dynamic changes with respect to pulmonary function indices. There are several different morphologies of the trachea related to collapsibility such as the crescent type and the saber-sheath type both involving the tracheal cartilage and excess dynamic airway collapse only involving the posterior membranous part of the trachea. Is the morphology of the trachea important for the course of the disease? The effect or adverse effects of inhaled corticosteroids are thought to play a role in the increasing incidence of the excess tracheal collapse. In this pilot study, we hypothesized that the excess collapsibility of the tracheal wall is dynamic., Methods: We prospectively examined 20 patients with excessive tracheal collapse on previous CT scans performed primarily due to bronchiectasis. A repeat CT scan was performed in order to evaluate the collapsibility. Before the repeat scan, patients were trained in maximal inspiration, expiration and breathholding. CT was performed in full inspiration and at end-expiration. Image assessment was performed on a dedicated CT workstation using standard lung window display settings. The percentage expiratory collapse based on cross sectional areas from carina to the thoracic inlet was calculated. Pulmonary function tests were performed and analysed in accordance with the American Thoracic Society and the European Respiratory Society guidelines., Results: Repeat CT scan were performed after 24 month +/- 7.2. Six of the 20 participants (30%) were males. Mean age was 67 +/- 11.3 years. Mean FEV1 was 83% of predicted, FVC 96.6 % of predicted and FEV1/FVC-ratio 71%. In 45% of the patients tracheal expiratory collapse improved (by more than 10%) based on percentage change in cross sectional areas in expiration compared to inspiration. 35% of patients showed disease progression with increased collapse and in 20% the collapsibility remained unchanged., Conclusion: We demonstrate that the collapsibility in a large fraction of the patients had actually improved at the follow up examination. We do not find any dependency of the change in collapsibility on the morphology of the trachea after end expiration, use of corticosteroid, or recurrent infections. In addition, no correlation between the changes in collapse and changes in the pulmonary function tests and the symptoms is observed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Only few studies have addressed the prognostic impact of chronic obstructive pulmonary disease (COPD) among patients with rheumatoid arthritis (RA), although both diseases are frequent and smoking is a shared risk factor. The objectives of the present study were to investigate the burden of COPD among RA patients and the subsequent mortality., Methods: We included patients who had a first-time diagnosis of RA in the Danish National Patient Registry between 2004 and 2016. RA patients with COPD were identified and matched with RA patients without COPD for year of birth, gender, and age at RA diagnosis. Mortality risks were assessed using Kaplan-Meier mortality curves. Adjusted hazard rate ratios (aHRRs) for death were estimated using Cox regression models., Results: The study population included 31,333 individuals with RA. 3254 of those (10.4%) had a diagnosis of COPD and were matched to 9706 RA patients without COPD. The mortality risks in RA patients with COPD and RA patients without COPD were 4.5% and 1.5% within 2-6 months (aHRR = 3.0, CI 2.3-3.9), and 59.3% and 39.8% within 0.5-10 years (aHRR = 2.1, CI 1.9-2.1)., Conclusion: Mortality was significantly increased among RA patients with COPD. The relative mortality risk remained significantly increased throughout the course of follow up., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: This Danish study evaluated the association between psychiatric comorbidity and the course of chronic obstructive pulmonary disease (COPD), lung cancer and tuberculosis (TB) of an entire nation., Methods: Data from the Danish National Patient Registry (1998-2009), material status, gender, educational level, comorbidities, age at diagnosis and death, medication, and causes of death were extracted from national databases. We identified 71,874 patients with COPD and found 32,282 with a pre-index psychiatric comorbidity, 20,787 patients with lung cancer and found 8406 with a pre-index psychiatric comorbidity, and 3495 patients with TB and found 797 with a pre-index psychiatric morbidity. Within the three groups we compared the patients with/without a pre-index psychiatric comorbidity., Results: We found a reduced survival in patients with COPD or TB and a pre-existing psychiatric comorbidity. For all three pulmonary diseases, we found significantly higher age (p < .001) at time of diagnosis, higher Deyo-Charlson Comorbidity Index (p < .001), and an overrepresentation of singles (p < .001) in patients with a psychiatric comorbidity. COPD and lung cancer patients with a psychiatric comorbidity were significantly overrepresented by women (p < .001). Patients with COPD and a psychiatric comorbidity died most frequently of lung cancer (24%). Advancing age and Deyo-Charlson index were associated with a higher mortality rate whereas being a woman and married/co-habiting yielded a lower mortality rate for patients with a psychiatric comorbidity., Conclusion: To our knowledge, this is the first epidemiological study investigating the influence of a psychiatric comorbidity on the course of COPD, lung cancer and TB at a national level. Our results emphasize the importance of detecting these major respiratory diseases in patients with psychiatric comorbidities and intensifying the treatment and follow up of these patients., (Copyright © 2017. Published by Elsevier Ltd.)

Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatologic disease that occasionally is accompanied by extracutaneous manifestations, amongst these is pulmonary involvement. The etiology is unknown. More than 50% of PG cases are associated with an underlying systemic disease such as inflammatory bowel disease, rheumatoid arthritis, hematological disorder or malignancy. Extracutaneous manifestations are rare and only 29 cases of pulmonary involvement have been reported previously in the literature. Pyoderma gangrenosum is usually diagnosed in the third to sixth decade, but early debut in childhood is also described. Skin manifestations are usually evident before pulmonary involvement, although primary lung affection is seen. Pulmonary involvement is diagnosed simultaneously or from a few weeks up to several years after the diagnosis of cutaneous PG. The most important differential diagnoses are lung cancer, lung abscess and Wegener's granulomatosis. Histological specimens will exclude these diagnoses. The treatment of PG is immune modulation, but due to the rarity of the disease, only one randomized treatment trials exists [1] and the long term course of PG with pulmonary involvement is unknown. We present two cases of pulmonary manifestations of pyoderma gangrenosum and a review of the literature., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the economic burden of tuberculosis (TB) in Denmark,, Methods: 8,433 Danish TB-patients (1998-2010) were matched with 33,707 controls by age, gender, civil status and geography. Health-related costs (health system contacts and -procedures, medications) and socio-economic parameters (foregone earnings and social transfer expenses) were calculated on data from national databases. The same information was obtained for 3,485 spouses of TB-patients, and 17,403 controls., Results: Health-related costs were higher for cases throughout the period. Before diagnosis, cases posed € 1,180 more health costs per year than controls. Excess health costs in the 2 years around diagnosing and treating TB were € 10,509. Cases received an average excess public transfer income of € 3,345 before vs. € 3,121 after diagnosis. Average employment income deficiency was € 11,635 before vs. € 13,885 after diagnosis, but the increasing difference showed a linear shape throughout the period. Spouses also had lower income, more social transfer, and posed higher health-related costs than matched controls., Conclusion: We estimate the direct costs per TB patient to be €10,509. TB patients and their households are characterized by increasingly lower employment income, lower employment rate, and higher dependency on public transfer, but the socio/economic deterioration is rather a risk factor for TB than a direct consequence of the disease., (Copyright © 2015. Published by Elsevier Ltd.)

Introduction: Interstitial lung diseases (ILDs) form a heterogeneous group of diseases with varying degrees of inflammation and fibrosis. Epidemiological data based on the current diagnostic criteria are sparse., Objectives: To characterize the incidence rate of ILDs and idiopathic pulmonary fibrosis (IPF) in Danish patients diagnosed at a referral hospital, to evaluate disease severity and survival in these ILD patients and to compare the use of the 2001 and 2011 guidelines to diagnosis of IPF., Methods: Single-centre, retrospective, observational cohort study including incident patients diagnosed with ILD at Aarhus University Hospital between 2003 and 2009. All diagnoses were re-evaluated according to current diagnostic criteria. Disease severity in IPF was assessed using the GAP index., Results: The ILD incidence was 4.1 per 100,000 inhabitants/year. IPF was the most common diagnosis (28%) followed by connective tissue disease-related ILD (14%), hypersensitivity pneumonitis (7%) and non-specific interstitial pneumonia (NSIP) (7%). The GAP index was a strong predictor of survival in IPF. Twenty-three patients who had IPF based on the 2001 criteria had a "possible UIP" HRCT pattern but no lung biopsy, and IPF could therefore not be diagnosed based on the 2011 criteria., Conclusion: ILD and IPF incidence was 4.1 and 1.3 per 100,000 inhabitants/year. The diagnostic re-evaluation raised the number of IPF diagnoses, but a diagnostic "grey zone" was still evident in patients with UIP features not qualifying the patients to be diagnosed with IPF. The GAP index was valuable as a measure of IPF severity in this cohort., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. It is a serious and progressive lung disease with a median survival of three years. The role of comorbidities in the prognosis of IPF is not clear., Objectives: To describe comorbidity and co-medication in a Danish IPF cohort and the association between clinically important comorbidities and survival., Methods: The study cohort included all patients diagnosed with IPF at Aarhus University Hospital, Denmark between April 2003 and April 2009. Details on diagnostic examinations, pulmonary function, medication and comorbidities were registered based on medical records., Results: A total of 121 patients were included. The most frequently observed comorbidities were cardiovascular disease (20%), arterial hypertension (15%) and diabetes mellitus (11%). Cardiovascular disease diagnosed during follow-up significantly increased mortality (HR 4.7, 95% CI 2.0-11.1). No difference was found based on cardiovascular disease already present at the time of IPF diagnosis. Diabetes (HR 2.5, 95% CI 1.04-5.9) and anticoagulant treatment (HR 3.3, 95% CI 1.5-7.2) were also factors associated with a significantly higher mortality in this population-based cohort., Conclusion: These findings emphasize the need of careful diagnosis and treatment of comorbidities and their risk factors in patients with IPF. In the absence of efficient treatment options for the majority of patients diagnosed with IPF, this may play a role in the effort to optimize the survival of IPF patients. Further studies are needed to fully clarify the impact of comorbidities on prognosis in patients diagnosed with IPF., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The purpose of the present review is to summarize the current knowledge on PH in relation to COPD and ILD from a clinical perspective with emphasis on diagnosis, biomarkers, prevalence, impact, treatment, and practical implications. PH in COPD and ILD is associated with a poor prognosis, and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lung disease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which is not systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However, treatment with systemically administered pulmonary vasodilators implies the risk of worsening the ventilation-perfusion mismatch in patients with lung disease. Inhaled vasodilators may be better suited for PH in lung disease, but new treatment modalities are also required., (© 2013.)

Background: Pulmonary hypertension (PH) is an important complication to interstitial lung disease (ILD). The aim of the present study was to investigate the relation of NT-proBNP, fibrin D-dimer, troponin-T, uric acid and exhaled nitric oxide (NO) to the presence of PH and mortality in ILD., Methods: In a previously described cohort of 212 ILD patients of whom 29 had PH, levels of the above mentioned biomarkers were analyzed as routine tests., Results: A value of NT-proBNP below 95 ng/l had a negative predictive value for PH of 99% (95% CI: 94-100). Values of troponin-T were higher in patients with PH (median (inter quartile range) = 9 (9-20) vs. 9(9-10) ng/l), and the odds ratio (OR) for PH was increased in patients with abnormal levels of uric acid (OR (95% CI) = 3.1(1.1-8.8)). NT-proBNP and troponin-T values above the 50(th) percentile, and uric acid and fibrin D-dimer values above the 90th percentile were each associated with increased mortality., Conclusions: A value of NT-proBNP below 95 ng/l may be used as a rule-out test for PH in ILD, while an abnormal value of uric acid is a risk factor for PH. NT-proBNP, troponin-T, uric acid and fibrin D-dimer have prognostic value in ILD patients, while exhaled levels of NO do not seem to predict PH or mortality., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Pulmonary hypertension (PH) is an important complication to interstitial lung disease (ILD). The aim of the present study was to investigate the prevalence and impact of PH on prognosis and exercise capacity in ILD patients., Methods: 212 ILD patients were screened for PH by echocardiography. Criteria for PH were either a tricuspid pressure regurgitation gradient >40 mmHg, a tricuspid annular plane systolic excursion <1.8 cm or right ventricular dilatation. If possible, PH was confirmed by right heart catheterisation. Pulmonary function tests and 6 min walk tests (6MWT) were performed., Results: 29 patients (14%) had PH, 16 (8%) had mild and 13 (6%) had severe PH (mean pulmonary artery pressure ≥ 35 mmHg). Compared to patients without PH, lung function parameters were lower in PH patients, a larger proportion had idiopathic pulmonary fibrosis (IPF) (41 vs 21%, p = 0.006), and the hazard ratio for death was 8.5 (95% CI: 4-17). After correction for lung function parameters and the presence of IPF, 6MWT was significantly lower in patients with PH compared to non-PH patients (difference ± SEM: 58 ± 22 m, p = 0.01)., Conclusions: PH occurred in 14% of a cohort of patients with ILD and was associated to IPF and lower lung function parameters. Mortality was markedly higher in PH patients, and the presence of PH reduced 6MWT independently of lung function and the presence of IPF. The present results emphasize the need for intensified treatment of patients with ILD and PH., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The peptide apelin is localised in the vascular endothelium and highly expressed in pulmonary tissue. The aim of this study was to investigate whether apelin could be a potential lung-derived plasma marker for pulmonary hypertension, and study the effect of apelin in pulmonary arteries., Methods: Apelin protein levels were measured in the lung, right ventricle, and plasma from normoxic and chronic hypoxic rats with pulmonary hypertension. Isolated intrapulmonary arteries were mounted in microvascular myographs and the effect of apelin investigated. Finally, the distribution of apelin receptors in pulmonary tissue was visualised by immunohistochemistry., Results: Total pulmonary apelin content was not changed by hypoxia. Right ventricular apelin concentrations and content were lower than in the lung, but increased substantially in hypoxia in correlation with right ventricular pressure. Plasma apelin did not reflect pulmonary or right ventricular apelin levels. In pulmonary arteries from normoxic rats, apelin inhibited vasoconstriction to endothelin-1 and angiotensin-II. However, in arteries from hypoxic rats, apelin failed to inhibit contraction to angiotensin-II and endothelin-1. No difference in immunoreaction for apelin receptors was found in lung sections and arteries from normoxic versus chronic hypoxic rats., Conclusions: Apelin changes in the right ventricle seem more specific for pulmonary hypertension than do changes in pulmonary tissue, which does not speak in favour of apelin as a lung-derived marker for this disease. During normoxic conditions, apelin has a modulating effect on vasoconstriction which is lost in chronic hypoxia. This may reflect alterations in the signal transduction downstream of the apelin receptor.

The aim of this study was to examine a new technique based on sound reflections in a flexible tube for identifying obstructive sites of the upper airway during sleep. There was no significant difference between two nights in seven obstructive sleep apnoea (OSA) patients regarding the level distribution of pharyngeal narrowings, when the pharynx was divided into two segments (retropalatal and retrolingual). We also compared the level distribution determined by magnetic resonance imaging (MRI) with the level distribution found by flextube reflectometry in seven OSA patients. There was no significant difference between flextube and MRI level distributions during obstructive events, but due to few subjects the power of the test was limited. We found a statistically significant correlation between the number of flextube narrowings per hour of sleep and the number of obstructive apnoeas and hypopnoeas per hour of sleep determined by polysomnography (PSG) in 21 subjects (Spearman's correlation coefficient r = 0.79, P < 0.001). In conclusion, the flextube reflectometry system seems to be useful for level diagnosis in OSA before and after treatment.

The aim of this study was to examine an acoustic reflection method using a flexible tube for identifying the obstructive site of the upper airway in snorers and patients with obstructive sleep apnoea (OSA). As a preliminary study it was performed n models and subjects in the awake state. Flextube narrowing was produced in a model of the nose and pharynx and three blinded observers assessed the obstructive level. The correlation between pharyngeal narrowing assessed by endoscopy and by acoustic measurement during Müller manoeuvres was also examined in 10 OSA patients and 11 healthy non-snoring, adults. Three blinded observers dentified the level of 176 of 180 random cases of flextube narrowing in a polycarbonate model correctly The level of narrowing was always correctly evaluated within 1.9 mm. Pharyngeal area decrease was measured by the flextube method during the Müller manoeuvre but it was not closely related to the findings by endoscopy. In conclusion the flextube reflectometry method was able to demonstrate narrowng in a model of the nose and pharynx in a precise way. Narrowing was also observed during Müller manoeuvres. Flextube reflectometry may be a promising method to detect upper airway narrowing but further evaluation during sleep is required.