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Britt Overgaard Hedegaard,1 Kjell Erik Julius Håkansson,2 Frodi Fridason Jensen,2,3 Charlotte Suppli Ulrik,2,4 Ulla Møller Weinreich1,5 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Department of Respiratory Medicine, Copenhagen University Hospital - Hvidovre, Hvidovre, Denmark; 3Medical Department, National Hospital of the Faroe Islands, Tórshavn, Faroe Islands; 4Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 5The Clinical Institute, Aalborg University, Aalborg, DenmarkCorrespondence: Ulla Møller WeinreichDepartment of Respiratory Diseases, Aalborg University Hospital, Mølleparkvej 4, Aalborg, DK-9000, DenmarkEmail ulw@rn.dkIntroduction: Adherence with controller medication is a major challenge in asthma management. Thus, a reliable method of measurement is mandatory to assess adherence.Aim: To examine the test-retest reliability on adherence with inhaled corticosteroids in adults with asthma using, a self-reported adherence score (Foster score).Methods: Patients with asthma and > 1 routine follow-up appointment at a university hospital outpatient clinic reported Foster scores. The objective Medication Possession Ratio (MPR) was calculated based on pharmacy redemption data and physician-prescribed doses of inhaled corticosteroids. The difference between Foster score and MPR at the first and second visit was assessed using a Bland–Altman plot, outcomes reported as limits of agreements and bias. Foster scores from both visits were used to calculate an intraclass correlation coefficient (ICC).Results: Self-reported adherence with asthma controller medication measured by Foster score was significantly higher than the objective MPR (p < 0.0001). The Bland–Altman plot for MPR and Foster score at the first and second visit showed upper and lower limits of agreement of 83.5 – (− 1.6) and 80.9 – (− 6.9) and bias was 41.0 and 37.0, respectively. Of the included patients, 93.1% reported identical Foster scores between visits, resulting in an excellent ICC of 0.92. Absolute median difference between Foster scores and MPR at first and second visit was 8.7 percentage points (p = 0.049).Conclusion: Foster score shows an excellent ICC; however, its poor agreement with objective measures of adherence suggests that clinicians should not rely on Foster scores alone to assess adherence with inhaled corticosteroids in patients with asthma.Keywords: Foster score, medication possession ratio, controller medication, asthma, self-assessed adherence, self-reported outcome, adherence, persistence

Peter Ascanius Jacobsen,1,2 Kristian Hay Kragholm,2,3 Christian Torp-Pedersen,4 Daisy JA Janssen,5,6 Martijn A Spruit,5,7,8 Ulla Møller Weinreich1,2 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2The Clinical Institute, Aalborg University, Aalborg, Denmark; 3Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; 4Department of Clinical Research, Hillerød Hospital, Hillerød, Denmark; 5Department of Research and Development, Ciro, Horn, the Netherland; 6Department of Health Services Research, Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; 7Nutrim School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; 8Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, the NetherlandsCorrespondence: Peter Ascanius JacobsenDepartment of Respiratory Diseases, Aalborg University Hospital, Aalborg, DenmarkTel +45 97 66 48 00Email peter.jacobsen@rn.dkIntroduction: The understanding of whether and to what extent employment status affects readmission and mortality is limited in patients with COPD.Aim: To explore how employment status affects readmission and mortality after first admission to the hospital with acute exacerbation of COPD (AECOPD).Methods: This study used Danish national registry-based data. All patients admitted for the first time to the hospital between 1999 and 2014 with a diagnosis of AECOPD, age 35– 59, without a previous asthma diagnosis were included in the study. Employment status effect on 30-, 90-, and 365-day readmission and mortality was examined using logistic regression, adjusting for relevant confounders.Results: A total of 11,850 COPD patients were included in the study of which 3563 (30%) were working, 1368 (12%) unemployed, 840 (7%) on sick leave, and 6079 (51%) receiving early retirement. Patients receiving early retirement had, compared to patients working, an adjusted increased likelihood of readmission at 30, 90, and 365 days (odds ratio (OR) 1.26 (CI95% (1.06– 1.49)), 1.33 (CI95% (1.16– 1.53)), and 1.48 (CI95% (1.33– 1.66)), respectively). An increased likelihood was also seen in unemployed at 365 days follow-up (OR 1.44 (CI95% (1.22– 1.68))). Early retirement was associated with an increased mortality at 30, 90, and 365 days (OR 1.39 (CI95% (1.07– 1.80)) 1.37 (CI95% (1.09– 1.79)) and 1.48 (CI95% (1.25– 1.75)), respectively). An increased likelihood was also seen in patients receiving sick leave (OR 1.57 (CI95% (1.21– 2.04))).Conclusion: Patients with COPD who are not working at the time of first admission have a higher likelihood of readmission and mortality.Keywords: chronic obstructive pulmonary disease, employment, mortality, readmission

Rina Juel Kaptain,1,2 Tina Helle,1,2 Ann-Helen Patomella,2 Ulla Møller Weinreich,3,4 Anders Kottorp2,5 1Department of Occupational Therapy, University College of Northern Denmark, Aalborg, Denmark; 2Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden; 3Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 4The Clinical Institute, Aalborg University, Aalborg, Denmark; 5Faculty of Health and Society, Malmö University, Malmö, SwedenCorrespondence: Rina Juel Kaptain Selma Lagerloefs Vej 2, Aalborg 9220, DenmarkTel +4572690928Email rio@ucn.dkPurpose: There have been calls for more knowledge of activities of daily living (ADL) performance in order to address interventions in pulmonary rehabilitation effectively. Everyday technology (ET) has become an integrated dimension of ADL, impacting the ways in which ADL is performed. To improve everyday functioning and quality of life, the use of ADL and ET use needs to be evaluated and addressed effectively in interventions. Therefore, the aim of this study was twofold: 1) to explore the quality of ADL performance, and 2) to investigate the relationship between observation and self-reported ADL performance and ability to use everyday technologies in people living with COPD.Methods: This cross-sectional study involved 84 participants aged 46– 87 years. Participants were recruited through healthcare centres in the Northern Region of Denmark using a convenience sampling procedure. Data were collected using standardized assessments that investigated different ADL perspectives: self-reported ADL tasks and ET use, observed motor and process ability, and need for assistance. Data were analysed and presented using descriptive statistics and Pearson’s correlation coefficient.Results: The most affected ADL tasks were mobility within or outside the home, lower dressing, bathing, pedicuring, cooking, shopping, cleaning and washing clothes. New insights into the quality of ADL performance in people living with COPD were presented in terms of detailed ADL motor skills and ADL process skills, as well as the predicted need for support to function in the community. Moreover, new insights into the relationship between observation and self-reported ADL performance (r=0.546, p< 0.01; r=0.297, p< 0.01) and between ADL performance and self-perceived ability to use ET (r=0.524, p< 0.01; r=0.273, p< 0.05; r=0.044, p=0.692) were presented.Conclusion: Overall, the knowledge from the present study is valuable for focusing interventions that address challenging ADL performance and ET use through relevant and realistic activities. The ability to use ET is important to evaluate and target pulmonary rehabilitation.Keywords: ADL skills, AMPS, everyday technology, occupational therapy, pulmonary rehabilitation

Rina Juel Kaptain,1,2 Tina Helle,1,2 Ann-Helen Patomella,2 Ulla Møller Weinreich,3,4 Anders Kottorp2,5 1Department of Occupational Therapy, University College of Northern Denmark, Aalborg, Denmark; 2Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden; 3Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 4The Clinical Institute, Aalborg University, Aalborg, Denmark; 5Faculty of Health and Society, Malmö University, Malmö, SwedenCorrespondence: Rina Juel Kaptain Selma Lagerloefs Vej 2, Aalborg 9220, DenmarkTel +4572690928Email rio@ucn.dkPurpose: A decline in the ability to perform activities of daily living (ADL) and ability to use everyday technology can pose threats to independent living, healthcare management and quality of life (QOL) of patients suffering from chronic obstructive pulmonary disease (COPD). Evidence of the relationship between these variables remains limited. The dual aim of this study was, first, to investigate if health-related QOL (HRQOL) was associated with quality in ADL performance and everyday technology use; second, to examine whether lung function, years with COPD diagnosis, living status or educational level affected physical and mental domains of HRQOL.Methods: This cross-sectional study included (N=80) participants aged 46–87 years recruited at healthcare centres in the Northern Region of Denmark using a convenience sampling procedure. Data were gathered through standardized assessments and analysed using multiple regression analysis.Results: The regression model explained 50.6% (R2=0.506) of the variation in HRQOL–physical. The following four variables were statistically significantly associated with HRQOL – physical: years since COPD diagnosis (p=0.023), ability to use everyday technology (p=0.006), amount of relevant everyday technologies (p=0.015) and ADL motor ability (p

Line Hust Storgaard,1 Hans-Ulrich Hockey,2 Birgitte Schantz Laursen,3,4 Ulla Møller Weinreich1,3 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Biometrics Matters Limited, Hamilton, New Zealand; 3Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 4Clinical Nursing Research Unit, Aalborg University Hospital, Aalborg, Denmark Background: This study investigated the long-term effects of humidified high-flow nasal cannula (HFNC) in COPD patients with chronic hypoxemic respiratory failure treated with long-term oxygen therapy (LTOT).Patients and methods: A total of 200 patients were randomized into usual care ± HFNC. At inclusion, acute exacerbation of COPD (AECOPD) and hospital admissions 1 year before inclusion, modified Medical Research Council (mMRC) score, St George’s Respiratory Questionnaire (SGRQ), forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT) and arterial carbon dioxide (PaCO2) were recorded. Patients completed phone interviews at 1, 3 and 9 months assessing mMRC score and AECOPD since the last contact. At on-site visits (6 and 12 months), mMRC, number of AECOPD since last contact and SGRQ were registered and FEV1, FEV1%, PaCO2 and, at 12 months, 6MWT were reassessed. Hospital admissions during the study period were obtained from hospital records. Hours of the use of HFNC were retrieved from the high-flow device.Results: The average daily use of HFNC was 6 hours/day. The HFNC group had a lower AECOPD rate (3.12 versus 4.95/patient/year, p

Anne Pernille Toft-Petersen,1,2 Christian Torp-Pedersen,1,3 Ulla Møller Weinreich,1,4 Bodil Steen Rasmussen1,2 1Department of Clinical Medicine, Aalborg University, 2Department of Anaesthesia and Intensive Care, 3Department of Clinical Epidemiology, 4Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark Abstract: Low concentrations of hemoglobin have previously been demonstrated in many patients with COPD. There is evidence of anemia as a prognostic factor in acute exacerbations, but the detailed relationship between concentrations of hemoglobin and mortality is not known. A register-based cohort of patients admitted for the first time to Danish hospitals for acute exacerbations of COPD from 2007 through 2012 was established. Age, sex, comorbidities, medication, renal function, and concentrations of hemoglobin were retrieved. Sex-specific survival analyses were fitted for different rounded concentrations of hemoglobin. The cohort encompassed 6,969 patients. Hemoglobin below 130 g/L was present in 39% of males and below 120 g/L in 24% of females. The in-hospital mortality rates for patients with hemoglobin below or above these limits were 11.6% and 5.4%, respectively. After discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22–1.73), adjusted HR 1.37 (95% CI 1.15–1.64). Compared to hemoglobin 120 g/L, the HR for females with hemoglobin 110 g/L was 1.4 (95% CI 1.17–1.68), adjusted HR 1.28 (95% CI 1.06–1.53). In conclusion, low concentrations of hemoglobin are frequent in COPD patients with acute exacerbations, and predict long-term mortality. Keywords: pulmonary disease, chronic obstructive, anemia, mortality, polycythemia, epidemiology

Anne Pernille Toft-Petersen,1,2 Christian Torp-Pedersen,1,3 Ulla Møller Weinreich,1,4 Bodil Steen Rasmussen1,2 1Department of Clinical Medicine, Aalborg University, 2Department of Anaesthesia and Intensive Care, Aalborg University Hospital, 3Department of Health, Science and Technology, Aalborg University, Aalborg, 4Department of Respiratory Medicine, Aalborg University Hospital, Denmark Background: In general, previous studies have shown an association between prior exacerbations and mortality in COPD, but this association has not been demonstrated in the subpopulation of patients in need of assisted ventilation. We examined whether previous hospitalizations were independently associated with mortality among patients with COPD ventilated for the first time. Patients and methods: In the Danish National Patient Registry, we established a cohort of patients with COPD ventilated for the first time from 2003 to 2011 and previously medicated for obstructive airway diseases. We assessed the number of hospitalizations for COPD in the preceding year, age, sex, comorbidity, mode of ventilation, survival to discharge, and days to death beyond discharge. Results: The cohort consisted of 6,656 patients of whom 66% had not been hospitalized for COPD in the previous year, 18% once, 8% twice, and 9% thrice or more. In-hospital mortality was 45%, and of the patients alive at discharge, 11% died within a month and 39% within a year. In multivariate models, adjusted for age, sex, mode of ventilation, and comorbidity, odds ratios for in-hospital death were 1.26 (95% confidence interval [CI]: 1.11–1.44), 1.43 (95% CI: 1.19–1.72), and 1.56 (95% CI: 1.30–1.87) with one, two, and three or more hospitalizations, respectively. Hazard ratios for death after discharge from hospital were 1.32 (95% CI: 1.19–1.46), 1.76 (95% CI: 1.52–2.02), and 2.07 (95% CI: 1.80–2.38) with one, two, and three or more hospitalizations, respectively. Conclusion: Preceding hospitalizations for COPD are associated with in-hospital mortality and after discharge in the subpopulation of patients with COPD with acute exacerbation treated with assisted ventilation for the first time. Keywords: pulmonary disease, chronic obstructive, respiration, artificial, patient readmission, hospital mortality, critical care

Sabrina Storgaard Sørensen,1 Kjeld Møller Pedersen,1 Ulla Møller Weinreich,2,3 Lars Holger Ehlers,1 1Danish Center for Healthcare Improvements, Faculty of Social Sciences and Faculty of Health Sciences, Aalborg University, Aalborg East, Denmark; 2Department of Respiratory Medicine, Aalborg University Hospital, Aalborg, Denmark; 3The Clinical Institute, Aalborg University Hospital, Aalborg, Denmark Background: Case management interventions are recommended to improve quality of care and reduce costs in chronic care, but further evidence on effectiveness and cost-effectiveness is needed. The objective of this study is the reporting of the design and participant enrollment of a randomized controlled trial, conducted to evaluate the effectiveness and cost-effectiveness of a community-based case management model for patients suffering from chronic obstructive pulmonary disease (COPD). With a focus on support for self-care and care coordination, the intervention was hypothesized to result in a reduced number of COPD-related hospital admissions. Patients and methods: The design was a randomized controlled trial conducted from 2012 to 2014 with randomization and intervention at patient level. The study took place in Aalborg Municipality, a larger municipality in Denmark. A total of 150 COPD patients were randomized into two groups: the case-managed group and the usual-care group. Participant characteristics were obtained at baseline, and measures on effectiveness and costs were obtained through questionnaires and registries within a 12-month follow-up period. In the forthcoming analysis, effectiveness will be evaluated on COPD-related hospital admissions, mortality, health- related quality of life, and self-care. An economic evaluation will examine the cost-effectiveness of case management against current usual care from the perspective of the health care sector. Results: Baseline characteristics were comparable between the two groups except for the prevalence of cancer, which were borderline significantly higher in the case-managed group. This baseline difference will be adjusted for in the final analysis. A very low dropout rate for the intervention was observed, indicating that the intervention was well accepted. Conclusion: Presented in a forthcoming paper, the results of the study will provide new evidence to the future organization of case management. Keywords: personalized care, disease management, health-related quality of life, cost-effectiveness analysis

Ulla Møller Weinreich,1–3 Lars Pilegaard Thomsen,2 Barbara Bielaska,4 Vania Helbo Jensen,5,6 Morten Vuust,4 Stephen Edward Rees2 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2Respiratory and Critical Care Group (RCARE), Centre for Model-Based Medical Decision Support Systems, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark; 3The Clinical Institute, Aalborg University Hospital, Aalborg, Denmark; 4Department of Radiology, Vendsyssel Hospital, Hjørring, Denmark; 5Department of Radiology, Horsens Regional Hospital, Horsens, Denmark; 6Department of Radiology, Aalborg University Hospital, Aalborg, Denmark Introduction: Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from comorbidities. COPD severity may be evaluated by the Global initiative for chronic ­Obstructive Lung Disease (GOLD) combined risk assessment score (GOLD score). Spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HR-CT) measure lung function and elucidate pulmonary pathology. This study assesses associations between GOLD score and measurements of lung function in COPD patients with and without (≤1) comorbidities. It evaluates whether the presence of comorbidities influences evaluation by GOLD score of COPD severity, and questions whether GOLD score describes morbidity rather than COPD severity.Methods: In this prospective study, 106 patients with stable COPD were included. Patients treated for lung cancer were excluded. Demographics, oxygen saturation (SpO2), modified Medical Research Council Dyspnea Scale, COPD exacerbations, and comorbidities were recorded. Body plethysmography and DLCO were measured, and HR-CT performed and evaluated for emphysema and airways disease. COPD severity was stratified by the GOLD score. Correlation analyses: 1) GOLD score, 2) emphysema grade, and 3) airways disease and lung function parameters, described by: forced expiratory volume in the first second in percent of expected value (FEV1%), inspiratory capacity (IC%), total lung volume (TLC%), IC/TLC, and SpO2. Correlation analyses between subgroups and hierarchical cluster analysis were performed.Results: Significant associations were found between GOLD score and both emphysema grade (correlation coefficients [cc]: -0.2, P=0.03) and lung function parameters (cc: -0.5 to -0.7, P-values all 1 comorbidity (cc: -0.4 to -0.5, P-values all 0.001). Significant differences between subgroups were found in GOLD score and both FEV1% (cc: -0.2, P=0.02) and IC/TLC (cc: -0.2, P=0.02). Comorbidities were associated with GOLD score and composite measures in hierarchical cluster analysis. Conclusion: The presence of comorbidities influences the relationship between GOLD score and lung function measurements. GOLD score may be more representative of morbidity than of COPD severity. Keywords: GOLD, diffusing capacity of the lung for carbon monoxide, high resolution computerized tomography, mMRC, total lung capacity, inspiratory capacity

Understanding ethnic variations in body composition is crucial for assessing health risks. Universal models may not suit all ethnicities, and there is limited data on the Inuit population. This study aimed to compare body composition between Inuit and European adults using computed tomography (CT) scans and to investigate the influence of demographics on these measurements. A retrospective analysis was conducted on 50 adults (29 Inuit and 21 European) who underwent standard trauma CT scans. Measurements focused on skeletal muscle index (SMI), various fat indices, and densities at the third lumbar vertebra level, analyzed using the Wilcoxon-Mann-Whitney test and multiple linear regression. Inuit women showed larger fat tissue indices and lower muscle and fat densities than European women. Differences in men were less pronouncehd, with only Intramuscular fat density being lower among Inuit men. Regression indicated that SMI was higher among men, and skeletal muscle density decreased with Inuit ethnicity and age, while visceral fat index was positively associated with age. This study suggests ethnic differences in body composition measures particularly among women, and indicates the need for Inuit-specific body composition models. It higlights the importance of further research into Inuit-specific body composition measurements for better health risk assessment.

Background: Little is known about lung function in Inuit. The aim of this study was to describe lung function and the prevalence of obstructive and restrictive lung disease among Inuit in Greenland., Methods: During the 2017-2019 Health Survey, spirometry, with forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC ratio in liters (L), and percent of predicted value (pred%) were recorded according to Global Lung function Initiative standard reference values (GLI). Smoking history was obtained. Obstructive spirometry was defined as FEV 1 /FVC <70%. Restrictive spirometry was proposed by FVC < 80% and FEV1/FVC >90%., Results: Based on validated spirometries, 795/2084 persons were included in this cross-sectional, descriptive study. Of those, 54.6% were current- and 27.7% former smokers. In Inuit, normal lung function was higher than predicted GLI (FEV 1 107.2 pred%/FVC 113.5 pred%). In total, 106 (13.3%) were found to have an obstructive lung function measurement and 11 (1.4%) had a restrictive pattern. Among current smokers, the prevalence of obstructive lung function was 16.4%. An accelerated decline in lung function was observed > 50 years old (y.o), compared to <50 y.o., Conclusion: This study indicates that Inuit has higher absolute lung function values than standard GLI, despite the large proportion of smokers, which indicate a need for Inuit reference values in the daily clinical praxis. The high prevalence of obstructive lung function and rapid decline in lung function indicates the need for fucus on health issues that may affect lung health in Greenland., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes., Methods: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365., Results: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037., Conclusions: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial., Trial Registration: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25., (© 2024. The Author(s).)

Introduction: The health effects of alcohol are well established but the influence on pulmonary function remains debated. Studies indicate that small amounts of alcohol are beneficial and heavy consumption is harmful, suggesting a U-shaped association. Our objective is to determine whether there is an association between alcohol intake and changes in pulmonary function parameters, exploring the potential protective effect of moderate alcohol consumption and the harm caused by heavy drinking., Methods: A comprehensive search from PubMed, Embase, Cochrane and CINAHL was carried out, and studies were evaluated using the JBI methodological framework for scoping reviews. Two independent reviewers conducted parallel screening and data extraction. A data extraction form was utilised to organise key themes, with qualitative analysis and visual representation of the results., Results: Among 4427 screened abstracts, 179 underwent full-text review, resulting in 30 eligible studies. Of these, 10 showed a negative effect, nine reported no impact, nine exhibited a positive effect and two indicated a nonlinear U-shaped association between alcohol consumption and pulmonary function parameters., Conclusion: While the U-shaped curve hypothesis remains unconfirmed by the current literature, there are notable associations. Heavy alcohol consumption appears to negatively affect pulmonary function, while low to moderate intake shows a positive influence in included studies. However, the diversity in study quality, the nonstandardised alcohol intake quantification and the confounding role of smoking challenge definitive conclusions. The need for consistent, long-term international studies is evident to further explore this relationship while addressing the complex interplay between alcohol and smoking., Competing Interests: Conflict of interest: S.J. Riddersholm reports grants for post-doctoral employment from GE. U.M. Weinreich reports grants from Fisher & Paykel; lecture honoraria from AstraZeneca, GSK, ResMed, Fisher & Paykel, Orion Pharma, Boehringer Ingelheim and Pfizer; payment for expert testimony from GSK; travel support from Chiesi; advisory board participation for AstraZeneca, GSK, Novartis, TEVA and Boehringer Ingelheim; and leadership roles as Chairman of the Danish Respiratory Society, Chairman of the Lungeforeningens Research Grant, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Background and Aims: Inflammatory bowel disease (IBD) is associated with disease manifestations in organs other than the gastrointestinal tract. In this study, we aimed to estimate the odds of obstructive lung disease (OLD) before IBD onset and the risk of OLD after IBD onset., Methods: In a nationwide population-based Danish cohort study from 1999 to 2018, individuals with IBD and OLD were identified using the Danish registries. Between 2003 and 2013, 24,238 individuals with IBD were identified and matched 1:10 with non-IBD individuals. Logistic regression was used to estimate the prevalence odds ratio for OLD before IBD onset. Time-to-event analysis was performed to explore the risk of OLD after IBD onset. In a sensitivity analysis, the time-to-event analysis was repeated using the composite outcome OLD and the separate outcomes, chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis., Results: Individuals with IBD were 60% more likely to have OLD before onset (adjusted odds ratio: 1.60, 95% confidence interval [CI]: 1.53-1.67). Furthermore, their risk of OLD was more than 40% higher after IBD diagnosis (adjusted hazard ratio [aHR]: 1.43, 95% CI: 1.37-1.49). The sensitivity analysis increased the risk to 60% (aHR: 1.63, 95% CI: 1.53-1.73). Similar results were found for COPD and asthma separately, whereas the risk of bronchiectasis increased more than 2-fold (aHR: 2.44, 95% CI: 1.91-3.11)., Conclusion: The odds of OLD before- and the risk following an IBD diagnosis were increased. We encourage physicians to be vigilant of pulmonary symptoms in persons with IBD and gastrointestinal symptoms in individuals with OLD., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Oxygen supplementation is ubiquitous in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD) and acute hypoxaemia, but the optimal oxygenation target has not been established., Methods: This was a pre-planned subgroup analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial, which allocated patients with acute hypoxaemia to a lower oxygenation target (partial pressure of arterial oxygen [ P ao 2 ] of 8 kPa) vs a higher target ( P ao 2 of 12 kPa) during ICU admission, for up to 90 days; the allocation was stratified for presence or absence of COPD. Here, we report key outcomes for patients with COPD., Results: The HOT-ICU trial enrolled 2928 patients of whom 563 had COPD; 277 were allocated to the lower and 286 to the higher oxygenation group. After allocation, the median P ao 2 was 9.1 kPa (inter-quartile range 8.7-9.9) in the lower group vs 12.1 kPa (11.2-12.9) in the higher group. Data for arterial carbon dioxide ( P aco 2 ) were available for 497 patients (88%) with no between-group difference in time-weighted average; median P aco 2 6.0 kPa (5.2-7.2) in the lower group vs 6.2 kPa (5.4-7.3) in the higher group. At 90 days, 122/277 patients (44%) in the lower oxygenation group had died vs 132/285 patients (46%) in the higher (relative risk 0.98; 95% confidence interval 0.82-1.17; P =0.67). No statistically significant differences were found in any secondary outcome., Conclusions: In ICU patients with COPD and acute hypoxaemia, a lower vs a higher oxygenation target did not reduce mortality. There were no between-group differences in P aco 2 or in secondary outcomes., Clinical Trial Registration: NCT03174002, EudraCT number 2017-000632-34., (© 2024 The Authors.)

Background: Patients with chronic obstructive pulmonary disease (COPD) with low skeletal muscle mass and severe airway obstruction have higher mortality risks. However, the relationship between dynamic/static lung function (LF) and thoracic skeletal muscle measurements (SMM) remains unclear. This study explored patient characteristics (weight, BMI, exacerbations, dynamic/static LF, sex differences in LF and SMM, and the link between LF and SMM changes., Methods: A retrospective analysis of a 12-month prospective follow-up study patients with stable COPD undergoing standardized treatment, covering mild to severe stages, was conducted. The baseline and follow-up assessments included computed tomography and body plethysmography., Results: This study included 35 patients (17 females and 18 males). This study revealed that females had more stable LF but tended to have greater declines in SMM areas and indices than males (-5.4% vs. -1.9%, respectively), despite the fact that females were younger and had higher LF and less exacerbation than males. A multivariate linear regression showed a negative association between the inspiratory capacity/total lung capacity ratio (IC/TLC) and muscle fat area., Conclusions: The findings suggest distinct LF and BC progression patterns between male and female patients with COPD. A low IC/TLC ratio may predict increased muscle fat. Further studies are necessary to understand these relationships better.

Patients with end-stage chronic obstructive pulmonary disease (COPD) often develop persistent hypoxic or hypercapnic respiratory failure, or a combination of both. Ventilatory support, in terms of a long-term high-flow nasal cannula (LT-HFNC) and long-term non-invasive ventilation (LT-NIV), may be indicated. Often, clinicians choose either one or the other. This paper explores combined treatment with LT-HFNC and LT-NIV in a real-life setting. In total, 33 patients with COPD and persistent respiratory failure were included in this study. Of those, 17 were initiated on LT-HFNC and used it for 595 (374) days and 16 were initiated on LT-NIV and used it for 558 (479) days. On average, patients used respiratory support continuously for 908 (586) days. Baseline characteristics were comparable, apart from PaCO 2 at first ventilatory support initiation (LT-HFNC/LT-NIV 7.1 (1.1) kPa/8.8 (0.9) kPa respectively ( p = 0.002)). Both groups experienced a reduction in hospitalizations in the first twelve months after treatment initiation, compared to the twelve months before (LT-HFNC p = 0.022 and LT-NIV p = 0.014). In total, 25% of LT-NIV patients stopped treatment after HFNC initiation due to intolerance and 59% stopped LT-HFNC treatment 126 (36) days after LT-NIV initiation as monotherapy was sufficient. In 44% of these patients, LT-HFNC was re-initiated at the end of life. At the time of analysis, 70% of patients had died. In the last three months of life, patients stopped using LT-NIV, whereas 91% used LT-HFNC. In conclusion, the combined use of LT-NIV and LT-HFNC reduced hospitalizations in patients with COPD and persistent respiratory failure. The study indicates that LT-HFNC is well tolerated, and better tolerated than LT-NIV at the very end stages of COPD.

Background: Computed tomography (CT) is increasingly used in the clinical workup, and existing scan contains unused body composition data, potentially useful in a clinical setting. However, there is no healthy reference for contrast-enhanced thoracic CT-derived muscle measures. Therefore, we aimed at investigating whether there is a correlation between each of the thoracic and third lumbar vertebra level (L3) skeletal muscle area (SMA), skeletal muscle index (SMI), and skeletal muscle density (SMD) at contrast-enhanced CT in patients without chronic disease., Methods: A proof-of-concept retrospective observational study was based on Caucasian patients without chronic disease, who received CT for trauma between 2012 and 2014. Muscle measures were assessed using a semiautomated threshold-based software by two raters independently. Pearson's correlation between each thoracic level and third lumbar and intraclass correlation between two raters and test-retest with SMA as proxy parameters were used., Results: Twenty-one patients (11 males, 10 females; median age 29 years) were included. The second thoracic vertebra (T2) had the highest median of cumulated SMA (males 314.7 cm 2 , females 118.5 cm 2 ) and SMI (97.8 cm 2 /m 2 and 70.4 cm 2 /m 2 , respectively). The strongest SMA correlation was observed between T5 and L3 (r = 0.970), the SMI between T11 and L3 (r = 0.938), and the SMD between the T10 and L3 (r = 0.890)., Conclusions: This study suggests that any of the thoracic levels can be valid to assess skeletal muscle mass. However, the T5 may be most favourable for measuring SMA, the T11 for SMI, and T10 for SMD when using contrast-enhanced thoracic CT., Relevance Statement: In COPD patients, a CT-derived thoracic muscle mass assessment may help identify who would benefit from focused pulmonary rehabilitation: thoracic contrast-enhanced CT conducted as part of the standard clinical workup can be used for this evaluation., Key Points: • Any thoracic level can be used to assess thoracic muscle mass. • Thoracic level 5 is strongly associated with the 3rd lumbar muscle area. • A strong correlation between the thoracic level 11 and the 3rd lumbar muscle index. • Thoracic level 10 is strongly associated with the 3rd lumbar muscle density., (© 2023. The Author(s).)

Background: During the first weeks of the outbreak of the coronavirus disease 2019 (COVID-19), the North Denmark emergency medical services authorised paramedics to assess patients suspected of COVID-19 at home, and then decide if conveyance to a hospital was required. The aim of this study was to describe the cohort of patients who were assessed at home and their outcomes in terms of subsequent hospital visits and short-term mortality., Methods: This was a historical cohort study in the North Denmark Region with consecutive inclusion of patients suspected of COVID-19 who were referred to a paramedic's assessment visit by their general practitioner or an out-of-hours general practitioner. The study was conducted from 16 March to 20 May 2020. The outcomes were the proportion of non-conveyed patients who subsequently visited a hospital within 72 hours of the paramedic's assessment visit and mortality at 3, 7 and 30 days. Mortality was estimated using a Poisson regression model with robust variance estimation., Results: During the study period, 587 patients with a median age of 75 (IQR 59-84) years were referred to a paramedic's assessment visit. Three of four patients (76.5%, 95% CI 72.8;79.9) were non-conveyed, and 13.1% (95% CI 10.2;16.6) of the non-conveyed patients were subsequently referred to a hospital within 72 hours of the paramedic's assessment visit. Within 30 days from the paramedic's assessment visit, mortality was 11.1% [95% CI 6.9;17.9] among patients directly conveyed to a hospital and 5.8% [95% CI 4.0;8.5] among non-conveyed patients. Medical record review revealed that deaths in the non-conveyed group had happened among patients with 'do-not-resuscitate' orders, palliative care plans, severe comorbidities, age ≥ 90 years or nursing home residents., Conclusions: The majority (87%) of the non-conveyed patients did not visit a hospital for the following three days after a paramedic's assessment visit. The study implies that this newly established prehospital arrangement served as a kind of gatekeeper for the region's hospitals in regard to patients suspected of COVID-19. The study also demonstrates that implementation of non-conveyance protocols should be accompanied by careful and regular evaluation to ensure patient safety., (© 2023. The Author(s).)

Introduction: Long-term High Flow Nasal Cannula (LT-HFNC), defined as High Flow Nasal Cannula treatment provided to patients with chronic pulmonary conditions during stable phases, has emerged as a home treatment in different categories of patients with chronic lung diseases in recent years., Methods: This paper summarizes the physiological effects of LT-HFNC and evaluates the clinical knowledge to date about treatment in patients with chronic obstructive lung disease, interstitial lung disease and bronchiectasis. The guideline is translated and summarized in this paper and presented unabridged as an appendix to the paper., Results: The paper describes the working process behind the Danish Respiratory Society's National guideline for treatment of stable disease, which has been written to support clinicians in both evidence-based decision making and practical issues concerning the treatment., Competing Interests: Line Hust Storgaard has received funding for research and speaker’s fees from Fisher&Paykel Healthcare, and speaker’s fees from ResMed.Ulla Møller Weinreich has received funding for research and speaker’s fees from Fisher&Paykel Healthcare, and speaker’s fees and fees for advisory board participation from ResMed., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Hospital admissions are important contributors to the overall burden of chronic obstructive pulmonary disease (COPD). Understanding the patterns and causes of hospital admissions will help to identify targets for preventive interventions. This study aimed to determine the 5-year all-cause hospital admission trajectories of patients with COPD following their first ever exacerbation-related hospitalisation., Methods: Patients with COPD were identified from the Danish national registries. Patients experiencing their first ever exacerbation-related hospitalisation, defined as the index event, between 2000 and 2014 were included. All-cause hospital admissions were examined during a subsequent 5-year follow-up period, and categorised using the International Classification of Diseases, 10th revision., Results: In total, 82 964 patients with COPD were included. The mean±sd age was 72±10 years and 48% were male. Comorbidities were present in 58%, and 65% of the patients collected inhalation medication ≤6 months prior to the index event. In total, 337 066 all-cause hospital admissions were identified, resulting in a 5-year admission rate of 82%. Most admissions were due to nonrespiratory causes (59%), amongst which cardiac events were most common (19%)., Conclusion: Hospital admissions following a first exacerbation-related hospitalisation are common; nonrespiratory events constitute the majority of admissions. Besides the respiratory causes, treatment targeting the nonrespiratory causes of hospital admission should be considered to effectively decrease the burden of hospitalisation in COPD., Competing Interests: Conflict of interest: S.O. Simons has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Chiesi outside the submitted work. F.M.E. Franssen has received grants and personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, Glaxosmithkline, Novartis and MSD outside the submitted work. M.A. Spruit has received grants and personal fees from the Netherlands Lung Foundation, Stichting Asthma Bestrijding, AstraZeneca, Boehringer Ingeheim, TEVA and CHIESI outside the submitted work. C.T. Pedersen has received grants from Bayer and Novo Nordisk outside the submitted work. All authors declare no conflicts of interest in relation to the present study., (Copyright ©The authors 2023.)

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.)

Background: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma., Methods: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation., Discussion: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients., Trial Registration: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017., (© 2022. The Author(s).)

Approximately 7% of all dispatched ambulances in Denmark are for patients for whom breathing difficulties are the main cause for using ambulance services. Objective measurements are routinely carried out in the ambulances, but little is known of the patients' subjective experience of dyspnea. The purpose of this study was to investigate how patients with acute dyspnea, transported to hospital by ambulance, experience their situation, along with their experience of the use of a dyspnea scale. The study was carried out in the North Denmark Region. Transcribed patient interviews and field notes were analyzed and interpreted with inspiration from Paul Ricoeur. For interviews, we included 12 patients with dyspnea who were transported to the hospital by ambulance: six women and six men all aged 60 years or above. Observations were made over six ambulance transports related to dyspnea. Three themes emerged: "anxiety", "reassurance in the ambulance" and "acceptance of the dyspnea measurements in the ambulance". Several patients expressed anxiety due to their dyspnea, which was substantiated by observations in the ambulance. The patients expressed different perspectives on what improved the situation (treatment, reassurance by ambulance professionals). The patients and the ambulance personnel were, in general, in favor of the dyspnea scale.

Objective: Natural killer (NK) cells play an essential role in the immune response against cancer. However, immune escape mechanisms may cause inferior NK cell activity (NKA) in patients with cancer. This prospective study examined the relationship between NKA and lung cancer in a high-risk cohort., Methods: In a cohort study, 250 participants referred by their general practitioner for suspicion of lung cancer were included. Before clinical investigation, blood was collected into NK Vue tubes, and the level of interferon gamma after 24 hours served as a surrogate marker for NKA., Results: Among 250 patients, 79 were diagnosed with lung cancer. No difference in NKA was found between patients with lung cancer and control participants in which lung cancer was ruled out (median 226 pg/mL vs. 450 pg/mL). However, there was a significant difference in NKA between patients with late-stage lung cancer and controls (median 161 pg/mL vs. 450 pg/mL). A linear regression model showed that NKA was not influenced by age, sex or smoking status., Conclusions: The significantly lower NKA in patients with late-stage lung cancer warrants further investigation combining NKA with other biomarkers and examining the potential role of NKA as a marker of disseminated disease.

Background: Denmark is a low-incidence country for tuberculosis (TB) and multidrug-resistant (MDR) TB at 5 and 0.05 cases per 100,000 population, respectively. Until 2018, the transmission of MDR-TB was nonexistent except for a few pairwise related family cases. In this study, we describe the first MDR-TB outbreak in Denmark., Methods: On the basis of genotyping of all Mycobacterium tuberculosis (Mtb) culture-positive cases in Denmark spanning 3 decades, 6 molecular- and epidemiologically linked Danish-born cases were identified as the first cluster of an MDR-TB in Denmark. The primary case was diagnosed posthumously in 2010 followed by 5 epidemiologically linked cases from 2018 to 2019., Results and Conclusion: Through a combination of routine Mtb genotyping and clinical epidemiological surveillance data, we identified the first Danish MDR-TB outbreak spanning 10 years and were able to disclose the specific transmission pathways in detail, which helped guide the outbreak investigations. The occurrence of an MDR-TB outbreak in a resource-rich low TB incidence setting such as Denmark highlights the importance of a collaborative control system combining classic contact tracing; timely identification of drug-resistant TB through rapid diagnostics; and a close collaboration between clinicians and classical- and molecular epidemiologists for the benefit of TB control., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare pertaining to this work., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Social distancing measures introduced on March 12, 2020, in Denmark during the COVID-19 pandemic may affect non-COVID-19 admissions for severe acute exacerbation of chronic obstructive pulmonary disease (s-AECOPD). We compared rates of s-AECOPD in a nationwide, observational, semi-experimental cohort study using data from all Danish inhabitants between calendar week 1 through 25 in 2019 and 2020. In a sub-cohort of patients with chronic obstructive pulmonary disease, we examined incidence of s-AECOPD, admissions to an intensive care unit, and all-cause mortality. A total of 3.0 million inhabitants aged ≥40 years, corresponding to 3.0 million person-years, were followed for s-AECOPD. In the social distancing period in 2020, there were 6,212 incidents of s-AECOPD, compared with 11,260 incidents in 2019, resulting in a 45% relative risk reduction. In the cohort with chronic obstructive pulmonary disease (n = 16,675), we observed a lower risk of s-AECOPD in the social distancing period (subdistribution hazard ratio (HR) = 0.34, 95% confidence interval (CI): 0.33, 0.36; absolute risk: 25.4% in 2020 and 42.8% in 2019). The risk of admissions to an intensive care unit was reduced (subdistribution HR = 0.64, 95% CI: 0.47, 0.87), as was all-cause mortality (HR = 0.83, 95% CI: 0.76, 0.90). Overall, the social distancing period was associated with a significant risk reduction for hospital admittance with s-AECOPD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Interstitial Lung Diseases (ILD) affect the lung parenchyma and are often complicated by respiratory failure (RF) and impaired physical activity. High Flow Nasal Cannula (HFNC) has proved effective in other disease entities with RF. The aim of this study is to investigate the effect of domiciliary HFNC in ILD on dyspnea and walking distance., Methods: A 6 weeks cross-over study with domiciliary HFNC-treatment/6 weeks' observation in ILD-patients requiring ambulatory oxygen therapy or with newly prescribed (within 12 months) long term oxygen therapy. Patients were advised to use HFNC 8 h/day, recommended night-time use. Body phletysmography; 6-min walk test (6MWT) including BORG-score, oxygen saturation (SO 2 ) at start, minimum SO 2 and time to recovery after 6MWT; arterial blood gasses; modified Medical Research Council (mMRC)-score; quality of life, by the St George Respiratory Questionnaire (SGRQ) and QoS, by the Richards-Campbell Sleep Questionnaire (RCSQ) were investigated at baseline; six weeks and 12 weeks., Results: 10 patients were included; one later withdrew consent. Patients used HFNC between 8-<1 h/day. There were no differences in lung function; blood gasses; SGRQ or RCSQ over the observational period). Walking distance improved significantly (393-441 m p = 0.049) as did time to recovery (3.4-2-2 min, p = 0.001). When correcting for HFNC use (hours/day) significant improvement was also seen in mMRC-score ( p = 0.035) and minimum saturation during 6MWT ( p = 0.01)., Conclusion: Despite a very heterogenous group and no effect on quality of life and -sleep, the study indicates an improvement in dyspnea and physical ability of HFNC in ILD patients.

A gap exists between guidelines and real-world clinical practice for the management and treatment of chronic obstructive pulmonary disease (COPD). Although this has narrowed in the last decade, there is room for improvement in detection rates, treatment choices and disease monitoring. In practical terms, primary care practitioners need to become aware of the huge impact of COPD on patients, have non-judgemental views of smoking and of COPD as a chronic disease, use a holistic consultation approach and actively motivate patients to adhere to treatment.This article is based on discussions at a virtual meeting of leading Nordic experts in COPD (the authors) who were developing an educational programme for COPD primary care in the Nordic region. The article aims to describe the diagnosis and lifelong management cycle of COPD, with a strong focus on providing a hands-on, practical approach for medical professionals to optimise patient outcomes in COPD primary care., (© 2021. The Author(s).)

Patients admitted to hospital with coronavirus disease 2019 (COVID-19) may develop acute respiratory failure (ARF) with compromised gas exchange. These patients require oxygen and possibly ventilatory support, which can be delivered via different devices. Initially, oxygen therapy will often be administered through a conventional binasal oxygen catheter or air-entrainment mask. However, when higher rates of oxygen flow are needed, patients are often stepped up to high-flow nasal cannula oxygen therapy (HFNC), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or invasive mechanical ventilation (IMV). BiPAP, CPAP, and HFNC may be beneficial alternatives to IMV for COVID-19-associated ARF. Current evidence suggests that when nasal catheter oxygen therapy is insufficient for adequate oxygenation of patients with COVID-19-associated ARF, CPAP should be provided for prolonged periods. Subsequent escalation to IMV may be implemented if necessary.

Purpose: To evaluate the cost-effectiveness of long-term domiciliary high flow nasal cannula (HFNC) treatment in COPD patients with chronic respiratory failure., Patients and Methods: A cohort of 200 COPD patients were equally randomized into usual care ± HFNC and followed for 12 months. The outcome of the analysis was the incremental cost per quality-adjusted life-year (QALY) gained, and the analysis was conducted from a healthcare sector perspective. Data on the patients' health-related quality of life (HRQoL), gathered throughout the trial using the St. George's Respiratory Questionnaire (SGRQ), was converted into EQ-5D-3L health state utility values. Costs were estimated using Danish registers and valued in British pounds (£) at price level 2019. Scenario analyses and probabilistic sensitivity analyses were conducted to assess the uncertainty of the results., Results: The adjusted mean difference in QALYs between the HFNC group and the control group was 0.059 (95% CI: 0.017; 0.101), and the adjusted mean difference in total costs was £212 (95% CI: -1572; 1995). The analysis resulted in an incremental cost-effectiveness ratio (ICER) of £3605 per QALY gained. At threshold values of £20.000-30.000 per QALY gained, the intervention had an 83-92% probability of being cost-effective. The scenario analyses all revealed ICERs below the set threshold value and demonstrated the robustness of the main result., Conclusion: This is the first cost-effectiveness study on domiciliary HFNC in Europe. The findings demonstrate that long-term domiciliary HFNC treatment is very likely to be a cost-effective addition to usual care for COPD patients with chronic respiratory failure. The results must be interpreted in light of the uncertainty associated with the indirect estimation of health state utilities., Competing Interests: The study received funding from the company Fisher & Paykel Healthcare Ltd and the North Jutland Region, Denmark. Fisher & Paykel Healthcare Ltd provided the HFNC devices (myAIRVO™ 2) and consumables used in the study and some administration costs. None of the funders had any role in data analysis, data interpretation, or writing of the manuscript. The authors report no other conflicts of interest in this work., (© 2021 Sørensen et al.)

Background: Adherence to inhaled corticosteroids (ICS) in asthma is vital for disease control. However, obtaining reliable and clinically useful measures of adherence remains a major challenge. We investigated the association between patient-reported adherence and objectively measured adherence based on filled prescriptions with inhaled corticosteroids in adults with asthma., Methods: In total, 178 patients with asthma were asked to self-assess adherence during routine visits at a respiratory outpatient clinic. Self-assessment was performed using Foster score ("How many days in a 7-day week do you take your medication as prescribed?", with the answer divided by 7). Objective adherence was calculated as medication possession ratio (MPR). Bivariate and multivariable linear regression, adjusted for age, sex, FEV 1 , GINA treatment step, excessive use of SABA, and history of exacerbations were used for analyses., Results: Of the included patients, 87.6% reported a Foster score of 100%, while the mean ICS MPR was 54.0% (SD 25%). Complex regimens such as twice-daily dosing or dual inhaler-use were associated with lower adherence (p = 0.015 and p < 0.001, respectively). Foster score was predictive of ICS MPR, with an absolute 32% increase in MPR between patients reporting Foster scores of 0 and 100% (95% CI 13-50%, p < 0.001). Female sex predicted higher ICS MPR (p = 0.019). Previous asthma-related hospitalization(s) predicted lower ICS MPR (p = 0.039)., Conclusion: Although a weak association was found between Foster score and ICS MPR, findings do not support the use of Foster score, and by that self-reported adherence, as a reliable marker of controller adherence in asthma due to significant mismatch between patient-reported adherence and MPR. Future studies should address the complex interplay between patient-reported and objectively assessed adherence to controller medication in asthma.

Introduction: Patients with COPD are vulnerable to workforce detachment. Better knowledge of features associated with paid work loss might be of help to design and select appropriate interventions., Method: This cross-sectional study aimed to explore the presence of treatable traits in COPD patients without paid work. Patients with COPD below 65 years at first referral to a hospital-based patient clinic were included. Using binary logistic regression analysis, the relationship between paid work and the following characteristics was explored: low daily physical activity, exercise, active smoking, Medical Research Council dyspnea scale (MRC), poor nutritional status, exacerbations, and fatigue (checklist individual strength (CIS)). Variables were adjusted for age, sex, forced expiratory volume in 1 s (FEV 1), and education level., Results: In total, 191 patients (47.3%) were without paid work. The following treatable traits were related to not being in paid work: < 5000 steps/day (OR 2.36, 95% CI (1.52-3.68)), MRC ≥ 3 (OR 1.78, 95%CI (1.14-2.77)), CIS ≥ 36 points (OR 1.78, 95% CI (1.10-2.87)), six-minute walk distance (6MWD) < 70% of predicted (OR 2.62, 95% CI (1.69-4.06)), and ≥ 2 exacerbations per year (OR 1.80, 95% CI (1.12-2.92)). Significant differences were also seen in age (OR 1.06, 95% CI (1.02-1.10) per year), FEV 1% predicted (OR 0.98, 95% CI (0.97-1.00) per % predicted increase), and medium/high education level (OR 0.62, 95% CI (0.41-0.93)). When adjusting for all variables the only treatable trait that remained significant was 6MWD., Conclusion: Patients without paid work are more likely to have treatable traits with 6MWD revealing the most significant association.

Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2-10 mg/L, but was adjusted to 2-5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5-15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2-21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug-drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ.

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: Persistent hypercapnic failure in chronic obstructive pulmonary disease (COPD) is associated with poor prognosis. Long-term home non-invasive ventilation is recommended for patients with PaCO 2 >7.0 kPa. Domiciliary high-flow nasal cannula (HFNC) reduces PaCO 2 in short-term studies. This post-hoc analysis examines the effect of HFNC on PaCO 2 levels, exacerbations and admissions in patients with COPD with persistent hypercapnic and hypoxic failures., Methods: The original trial included 74 long-term oxygen-treated patients (31 HFNC treated/43 controls) with persistent hypercapnic failure (PaCO 2 >6 kPa) who completed the 12-month study period. Baseline data included age, sex, blood gases, exacerbations and hospital admissions in the previous year. Data on blood gases were also recorded at 6 and 12 months for all patients. In addition, acute changes in blood gases after 30 min of HFNC use at site visits were examined, as were exacerbations and hospital admissions during study., Results: Patients were comparable at baseline. After 12 months there was a 1.3% decrease in PaCO 2 in patients using HFNC and a 7% increase in controls before HFNC use on site (p=0.003). After 30 min of HFNC at visits PaCO 2 changed significantly, with comparable reductions, at 0, 6 and 12 months, including for controls who tried HFNC at study end (p<0.001). The exacerbation rate increased, compared with 12 months prestudy, by 2.2/year for controls (p<0.001) and 0.15/year for HFNC-treated patients (p=0.661). Hospital admission rates increased in the control group,+0.3/year from prestudy (p=0.180), And decreased by 0.67/year (p=0.013)for HFNC-treated patients., Conclusion: This post-hoc analysis indicates that HFNC stabilises patients with COPD with persistent hypoxic and hypercapnic failures, in terms of PaCO 2 , exacerbations and number of hospitalisations, whereas those not receiving HFNC worsened. This suggests that HFNC is a possible treatment for patients with persistent hypercapnic COPD., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease., Methods: The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis., Discussion: This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency., Trial Registration: ClinicalTrials.gov NCT04322396 . Registered on 26 March 2020.

Background: Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy., Methods: The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits., Results: CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group., Conclusion: Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02857842 . Submitted August 2nd, 2016.

Introduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has presented health-care systems worldwide with novel challenges and experiences and evidence is emerging during the pandemic. Patients requiring hospitalization frequently suffer from respiratory failure of different severities., Aim: The aim of this guideline is the treatment of patients with SARS CoV-2 (COVID-19) in hospital; in particular, it addresses the treatment of respiratory failure treated in general Internal Medical- and Pulmonary Medical wards., Results: Elderly patients and patients with chronic disease are particularly vulnerable to COVID-19. Target oxygen saturation should be between 92% and 96% in patients without chronic lung diseases. Treatment with >5 L oxygen/min should be in close collaboration with intensive care colleagues and >15 l/min preferably in intensive care units. High-flow nasal canula (HFNC) and long-term Continuous Positive Airway Pressure (CPAP) are recommended for patients not responding to conventional oxygen therapy. Non-invasive ventilation (NIV) is only recommended for selected patients, such as those with a ceiling of treatment or patients presenting with hypercapnic failure. With the use of humidification protective equipment as FFP2-3 masks should be used. Nebulized medication should be avoided, and spacers should be used instead., Conclusion: Respiratory failure is frequently the cause of hospitalization in patients with COVID-19 and should be monitored closely., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Acute dyspnoea is common among ambulance patients, but little is known of the patients' experience of symptom. We aimed to investigate ambulance patients initial perceived intensity of acute dyspnoea, and whether they experienced relief during prehospital treatment. Furthermore, to investigate the validity and feasibility of using a subjective dyspnoea score in the ambulance, and its association with objectively measured vital signs., Methods: We performed a prospective observational study in the North Denmark Region from 1. July 2017 to 30. March 2019. We studied patients over the age of 18 to whom an ambulance was dispatched. Patients with acute dyspnoea assessed either at the emergency call or by ambulance professionals on scene were included. Patients were asked to assess dyspnoea on a 0 to 10 verbal numeric rating scale at the primary contact with the ambulance personnel and immediately before release at the scene or arrival at the hospital. Patients received usual prehospital medical treatment. We used visual inspection and Wilcoxon matched-pairs signed-ranks test, to assess dyspnoea scores and change hereof. Scatterplots and linear regression analyses were used to assess associations between the dyspnoea score and vital signs., Results: We included 3199 patients with at least one dyspnoea score. Of these, 2219 (69%) had two registered dyspnoea scores. The initial median dyspnoea score for all patients was median 8 (interquartile range 6-10). In 1676 (76%) of patients with two scores, the first score decreased from 8 (6-9) to 4 (2-5) during prehospital treatment. The score was unchanged for 370 (17%) and increased for 51 (2%) patients. Higher respiratory rate, blood pressure, and heart rate was seen with higher dyspnoea scores whereas blood oxygen saturation lowered., Conclusions: We found that acute dyspnoea scored by ambulance patients, was high on a verbal numerical rating scale but decreased before arrival at hospital, suggesting relief of symptoms. The acute dyspnoea score was statistically associated with vital signs, but of limited clinical relevance; this stresses the importance of patients' experience of symptoms. To this end, the dyspnoea scale appears feasible in the prehospital setting.

Objective: To validate the discrimination and classification accuracy of a novel acute dyspnea scale for identifying outcomes of out-of-hospital patients with acute dyspnea., Methods: Prospective observational population-based study in the North Denmark Region. We included patients from July 1, 2017 to September 24, 2019 assessed as having acute dyspnea by the emergency dispatcher or by emergency medical services (EMS) personnel. Patients rated dyspnea using the 11-point acute dyspnea scale. The primary outcomes were hospitalization >2 days, ICU admission within 48 hours of ambulance run, and 30-day mortality. We used 5-fold cross-validation and area under receiver operating curves (AUC) to assess predictive properties of the acute dyspnea scale score alone and combined with vital data, age, and sex., Results: We included 3144 EMS patients with reported dyspnea. Median acute dyspnea scale score was 7 (interquartile range 5 to 8). The outcomes were: 1966 (63%) hospitalized, 164 (5%) ICU stay, and 224 (9%) died within 30 days of calling the ambulance. The acute dyspnea scale score alone showed poor discrimination for hospitalization (AUC 0.56, 95% confidence intervals: 0.54-0.58), intensive care unit admission (0.58, 0.53-0.62), and mortality (0.46, 0.41-0.50). Vital signs (respiratory rate, blood oxygen saturation, blood pressure, and heart rate) showed similarly poor discrimination for all outcomes. The combination of [vital signs + acute dyspnea scale score] showed better discrimination for hospitalization, ICU admission, and mortality (AUC 0.71-0.72). Patients not able to report an acute dyspnea scale score worse outcomes on all parameters., Conclusion: The dyspnea scale showed poor accuracy and discrimination when predicting hospitalization, stay at intensive care unit, and mortality on its own. However, the dyspnea scale may be beneficial as performance measure and indicator of out-of-hospital care., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. JACEP Open published by Wiley Periodicals, Inc. on behalf of the American College of Emergency Physicians.)

Introduction: Patients with bronchiectasis suffer from breathlessness, cough and sputum production, which impairs quality of life. The Bronchiectasis Health Questionnaire (BHQ), a short and disease-specific questionnaire, has previously been developed and validated in English. The aim of this study was to translate and validate the BHQ in Danish, using established cross-cultural validation methods., Methods: To create a Danish version of the questionnaire, this study used linguistic validation, a pilot study in 17 patients and forward-backward translation. Thereafter, 111 patients with bronchiectasis were asked to complete the BHQ (BHQ1) as well as the St George Respiratory Questionnaire (SGRQ), and one in three patients were asked to repeat the BHQ after two weeks had passed (BHQ2)., Results: There was a significant convergent validity between the BHQ1 and the SGRQ (ρ = -0,826, p = 0.0001), a satisfactory correlation coefficient between the BHQ1 and the BHQ2 (0.739) and a lower limit of agreement of -15.96 and 20.56 in the Bland Altmann plot., Conclusions: The BHQ is translated and validated in Danish and retains good validity properties. This questionnaire is ready for use in daily clinical practice among Danish-speaking patients., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Hemoptysis is an alarming and common symptom leading to thorough diagnostic evaluation with computed tomography and fiberoptic bronchoscopy. Increasing evidence suggests that bronchoscopy is not necessary in diagnosing lung cancer in hemoptysis patients because of high sensitivity of computed tomography. However, less attention has been paid to non-malignant etiologies of hemoptysis. Objective: We aimed to identify the etiologies established in hemoptysis patients with no malignancy suspected on computed tomography in order to assess the necessity of bronchoscopy in these patients. Design: We retrospectively reviewed clinical records of consecutive patients referred to evaluation for hemoptysis with no malignancy suspected on computed tomography at Aalborg University Hospital, Denmark, in an eleven-year period from 2006 to 2016. Results: One thousand one hundred and eighty-five patients (mean age 57.5 ± 15.44 years, 61.3% male) were included in the study. Bronchoscopy was performed in 91.9% of cases. Most patients (83.5%) had cryptogenic hemoptysis, while the most frequently identified etiologies were respiratory tract infection (12.6%) and bronchiectasis (2.2%). No patients had malignant disease as their etiology. Conclusions: The vast majority of hemoptysis cases with no malignancy suspected on computed tomography were cryptogenic and all were benign. Bronchoscopy may be reserved for patients with specific conditions suspected and those with persistent symptomatology., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

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)., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Domiciliary High-flow, humidified, nasal cannula (HFNC) is a possible add-on in patients with chronic respiratory diseases. This post-hoc study investigates benefit of HFNC in subgroups of advanced COPD patients with chronic hypoxic failure on reduction of exacerbations and hospitalizations., Methods: One hundred patients were randomized to HFNC in a previous trial. Subgroups with 0-1 (N = 32) respectively two or more (2+) (N = 68) exacerbations 12 months pre-study were investigated. Changes in number of exacerbations and hospitalizations pre- and in study were analyzed, corrected for HFNC days with HFNC., Results: Patients were comparable at baseline. Exacerbations increased in subgroup 0-1 (p = 0.01) and decreased in subgroup 2+ (p = 0.03). Correcting for HFNC days no correlation was seen in subgroup 0-1 (p = 0.08), but in subgroup 2+ (p<0.001). Number of hospitalizations increased in subgroup 0-1 (p = 0.01) with no change in days of hospitalization (p = 0.08). Number and days of hospitalization decreased in subgroup 2+ (p = 0.002 resp. 0.025). Correcting for HFNC days no correlation was found in number or days of hospitalization in subgroup 0-1 (p = 0.48 and p = 0.65). Positive correlation was found in subgroup 2+ (both p<0.001)., Conclusion: In patients with advanced COPD, chronic hypoxic failure and two or more exacerbations per year, HFNC significantly reduced exacerbations and hospitalizations., Competing Interests: The author has received travel funding from Fisher&Paykel. This does not alter my adherence to PLOS ONE policies on sharing data and materials.

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)  ± standard deviation in patients with and without RP was 15.0 ± 7.1 ppb (95%CI: 12.0-18.0) and 10.3 ± 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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ebba og Aksel Schølins Fond., (© 2019 The Author(s).)