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Background In early stage chronic obstructive pulmonary disease (COPD), dyspnea has been reported as the main symptom; but at the end of life, patients dying from COPD have a heavy symptom burden. Still, specialist palliative care is seldom offered to patients with COPD; they more often receive end of life care in hospitals. Furthermore, symptoms, symptom relief and care activities in the last week of life for COPD patients are rarely studied. The aim of this study was to compare patient and care characteristics in late stage COPD patients treated in specialized palliative care (SPC) versus hospital. Methods Two nationwide registers were merged, the Swedish National Airway Register (SNAR) and the Swedish Register of Palliative Care (SRPC). Patients with COPD and 1), who had died in inpatient or outpatient SPC (n = 159) or in hospital (n = 439), were identified. Clinical COPD characteristics were extracted from the SNAR, and end of life (EOL) care characteristics from the SRPC. Descriptive statistics were used to describe the sample and the registered care and treatments. Independent samples t-test, Mantel–Haenszel chi-square test and Fisher’s exact test was used to compare variables. To examine predictors of place of death, bivariate and multivariate logistic regression analyses were performed with a dependent variable with demographic and clinical variables used as independent variables. Results The patients in hospitals were older and more likely to have heart failure or hypertension. Pain was more frequently reported and relieved in SPC than in hospitals (p = 0.001). Rattle, anxiety, delirium and nausea were reported at similar frequencies between the settings; but rattle, anxiety, delirium, and dyspnea were more frequently relieved in SPC (all p p p Conclusion This study provides evidence for referring more COPD patients to SPC, which is more focused on symptom management and psychosocial and existential support.

Kjell Larsson,1 Ann Ekberg-Jansson,2 Caroline Stridsman,3 Malin Hanno,4 Lowie EGW Vanfleteren5,6 1Integrative Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden; 4Boehringer Ingelheim AB, Stockholm, Sweden; 5COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden; 6Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 413 45, SwedenCorrespondence: Kjell LarssonIntegrative Toxicology, National Institute of Environmental Medicine, IMM, Karolinska Institutet, Stockholm, SE-171 77 Tel +46 70 582 07 63Email kjell.larsson@ki.seIntroduction: Swedish guidelines adhere to the international GOLD document regarding management of chronic obstructive pulmonary disease (COPD). Based on data from the Swedish National Airway Register (SNAR) the aim was to evaluate adherence to guidelines of pharmacological treatment of COPD in Swedish primary and secondary care.Methods: During a period of 18 months, data on symptoms (CAT, mMRC), lung function, exacerbation history and pharmacological treatment from 15,595 COPD patients from 853 primary care and 125 secondary care clinics were collected from SNAR. Patients with a co-diagnosis of asthma were excluded. Patients were divided into four treatment groups: no pharmacological treatment, short-acting bronchodilators alone, long-acting bronchodilators alone and ICS alone or in combination with bronchodilators.Results: Of the patients, 29% were in GOLD group A, 58% in group B, 2% in group C and 11% in group D. CAT score was ≥ 10 and mMRC score was below 2 in 30.9% of the patients and mMRC score was ≥ 2 and CAT score < 10 in 4.2% of the patients. In 61.4% of the patients, no exacerbation was registered during the last year. Long-acting bronchodilators were prescribed for 78% and ICS for 46% of all patients. In groups A, B, C and D, respectively, 21%, 11%, 11% and 5% did not receive any inhaler therapy; 67%, 81%, 81% and 90% received long-acting bronchodilators; 33%, 46%, 55% and 71% received any ICS containing therapy and 19%, 34%, 39% and 61% received triple therapy.Discussion: Data from the SNAR indicate that only a minority of COPD patients were untreated. There was a liberal use of ICS containing drug combinations in subjects who do not have an indication for ICS. A considerable proportion of subjects at high risk of exacerbations did not receive ICS treatment.Keywords: chronic obstructive pulmonary disease, COPD, glucocorticoids, registry

Martina Sundqvist,1,* Kristina Andelid,2,* Ann Ekberg-Jansson,3 Johan Bylund,4 Anna Karlsson-Bengtsson,1,5 Anders Lindén6,7 1Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2COPD Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 5Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; 6Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 7Karolinska Severe COPD Center, Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden*These authors contributed equally to this workCorrespondence: Martina SundqvistDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, Gothenburg, S-413 46, SwedenEmail martina.sundqvist@rheuma.gu.sePurpose: The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations.Patients and Methods: The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth.Results: When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with HNS or LTS. Nor did this level of Galectin-3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations.Conclusion: Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting.Keywords: COPD, CRP, airflow limitation, exacerbation

Martina Sundqvist,1,* Kristina Andelid,2,* Ann Ekberg-Jansson,3 Johan Bylund,4 Anna Karlsson-Bengtsson,1,5 Anders Lindén6,7 1Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2COPD Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 5Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; 6Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 7Karolinska Severe COPD Center, Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden*These authors contributed equally to this workCorrespondence: Martina SundqvistDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, Gothenburg, S-413 46, SwedenEmail martina.sundqvist@rheuma.gu.sePurpose: The carbohydrate-binding protein Galectin-3 is increased in several inflammatory diseases and has recently been forwarded as a systemic biomarker in chronic obstructive pulmonary disease (COPD). In this longitudinal study, we characterized the level of systemic Galectin-3 using blood from smokers with a history of COPD and chronic bronchitis (COPD-CB), during stable clinical conditions and exacerbations.Patients and Methods: The study population comprised 56 long-term smokers with COPD-CB, 10 long-term smokers without lung disease (LTS) and 10 clinically healthy never-smokers (HNS). Blood samples were analyzed for levels of Galectin-3, leukocyte populations and C-reactive protein (CRP). In addition, sputum samples from the COPD-CB group were analyzed for bacterial growth.Results: When comparing stable clinical conditions and exacerbations in the COPD-CB group, we found that the level of Galectin-3, just like that of CRP, leukocytes and neutrophils, respectively, was increased during exacerbations. However, this exacerbation-associated increase of Galectin-3 was modest. During stable clinical conditions of COPD-CB, the level of Galectin-3 was not elevated in comparison with HNS or LTS. Nor did this level of Galectin-3 distinguish patients that remained in a clinically stable condition throughout the study to those that developed an exacerbation. In addition, neither during stable clinical conditions nor during exacerbations, did the presence of bacterial growth in sputum alter Galectin-3 levels. In contrast to Galectin-3, the level of CRP, leukocytes and neutrophils, respectively, were increased during clinical stable conditions in the COPD-CB group compared with the other groups and were further enhanced during exacerbations.Conclusion: Systemic Galectin-3 is increased in a reproducible but modest manner during exacerbations in smokers with COPD-CB. During stable clinical conditions, the level of systemic Galectin-3 does not distinguish patients that remain clinically stable from those that develop exacerbations. This makes it less likely that systemic Galectin-3 may become a clinically useful biomarker in the current setting.Keywords: COPD, CRP, airflow limitation, exacerbation

Kani Khalaf,1,* Sten Axelsson Fisk,1,* Ann Ekberg-Jansson,2,3 George Leckie,1,4 Raquel Perez-Vicente,1 Juan Merlo1,5 1Unit for Social Epidemiology, Faculty of Medicine, Lund University, Malmö, Sweden; 2Department of Research and Development, Region Halland, Halmstad, Sweden; 3Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Centre for Multilevel Modelling, University of Bristol, Bristol, UK; 5Center for Primary Health Care Research, Region Skåne, Malmö, Sweden*These authors contributed equally to this workCorrespondence: Kani Khalaf Email kani.khalaf@med.lu.seBackground: While discontinuation of COPD maintenance medication is a known problem, the proportion of patients with discontinuation and its geographical and sociodemographic distribution are so far unknown in Sweden. Therefore, we analyse this question by applying an innovative approach called multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA).Patients and Methods: We analysed 49,019 patients categorized into 18 sociodemographic contexts and 21 counties of residence. All patients had a hospital COPD diagnosis and had been on inhaled maintenance medication during the 5 years before the study baseline in 2010. We defined “discontinuation” as the absolute lack of retrieval from a pharmacy of any inhaled maintenance medication during 2011. We performed a cross-classified MAIHDA and obtained the average proportion of discontinuation, as well as county and sociodemographic absolute risks, and compared them with a proposed benchmark value of 10%. We calculated the variance partition coefficient (VPC) and the area under the receiver operating characteristics curve (AUC) to quantify county and sociodemographic differences. To summarize the results, we used a framework with 15 scenarios defined by the size of the differences and the level of achievement in relation to the benchmark value.Results: Around 18% of COPD patients in Sweden discontinued maintenance medication, so the benchmark value was not achieved. There were very small county differences (VPC=0.35%, AUC=0.54). The sociodemographic differences were small (VPC=4.98%, AUC=0.57).Conclusion: Continuity of maintenance medication among COPD patients in Sweden could be improved by reducing the unjustifiably high prevalence of discontinuation. The very small county and small sociodemographic differences should motivate universal interventions across all counties and sociodemographic groups. Geographical analyses should be combined with sociodemographic analyses, and the cross-classified MAIHDA is an appropriate tool to assess health-care quality.Keywords: COPD, socioeconomic inequity, multilevel analysis, equity in health care, health care quality, compliance, discriminatory accuracy

Background Both single factors and composite measures have been suggested to predict mortality in patients with chronic obstructive pulmonary disease (COPD) and there is a need to analyze the relative importance of each variable. Objective To explore the predictors of mortality for patients with COPD in relation to respiratory, cardiac, and malignant causes, as well as all causes of death. Methods After merging the Swedish Respiratory Tract Register (SRTR) and the Swedish Cause of Death Register, patients with respiratory, cardiac, and other causes of death were identified. Demographic and clinical variables from the deceased patients’ first registration with the SRTR were compared. Three univariable and multivariable Cox proportional hazards regression analyses were conducted for different causes of death, with time from first registration to either death or a fixed end date as dependent variable, and variables regarding demographics, respiration, and comorbidities as independent variables. Results In the multivariable Cox models, mortality for patients with all causes of death was predicted by older age 1.79 (CI 1.41, 2.27), lower percentage of predicted forced expiratory volume in 1 second (FEV1 %) 0.99 (CI 0.98, 0.99), lower saturation 0.92 (CI 0.86, 0.97), worse dyspnea 1.48 (CI 1.26, 1.74) (p

Ingela Henoch,1,2 Ann Ekberg-Jansson,3,4 Claes-Göran Löfdahl,5,6 Peter Strang7,8 1Department of Research and Development, Angered Local Hospital, Gothenburg, Sweden; 2Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Research and Development, Region Halland, Halmstad, Sweden; 4Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 5University of Lund, Lund, Sweden; 6COPD Center, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden; 7Karolinska Institute, Department of Oncology–Pathology, Stockholm, Sweden; 8Research and Development Unit, Stockholms Sjukhem Foundation, Stockholm, SwedenCorrespondence: Ingela HenochSahlgrenska Academy at the University of Gothenburg, Institute of Health and Care Sciences, Box 457, Gothenburg SE-405 30, SwedenTel +46317866092Email ingela.henoch@gu.seBackground: Both single factors and composite measures have been suggested to predict mortality in patients with chronic obstructive pulmonary disease (COPD) and there is a need to analyze the relative importance of each variable.Objective: To explore the predictors of mortality for patients with COPD in relation to respiratory, cardiac, and malignant causes, as well as all causes of death.Methods: After merging the Swedish Respiratory Tract Register (SRTR) and the Swedish Cause of Death Register, patients with respiratory, cardiac, and other causes of death were identified. Demographic and clinical variables from the deceased patients’ first registration with the SRTR were compared. Three univariable and multivariable Cox proportional hazards regression analyses were conducted for different causes of death, with time from first registration to either death or a fixed end date as dependent variable, and variables regarding demographics, respiration, and comorbidities as independent variables.Results: In the multivariable Cox models, mortality for patients with all causes of death was predicted by older age 1.79 (CI 1.41, 2.27), lower percentage of predicted forced expiratory volume in 1 second (FEV1 %) 0.99 (CI 0.98, 0.99), lower saturation 0.92 (CI 0.86, 0.97), worse dyspnea 1.48 (CI 1.26, 1.74) (p< 0.002 to p< 0.001), less exercise 0.91 (CI 0.85, 0.98), and heart disease 1.53 (CI 1.06, 2.19) (both p< 0.05). Mortality for patients with respiratory causes was predicted by higher age 1.67 (CI 1.05, 2.65) (p< 0.05), lower FEV1% 0.98 (CI 0.97, 0.99), worse dyspnea 2.05 (CI 1.45, 2.90), and a higher number of exacerbations 1.27 (CI 1.11, 1.45) (p< 0.001 in all comparisons). For patients with cardiac causes of death, mortality was predicted by lower FEV1% 0.99 (CI 0.98, 0.99) (p=0.001) and lower saturation 0.82 (CI 0.76, 0.89) (p< 0.001), older age 1.46 (CI 1.02, 2.09) (p< 0.05), and presence of heart disease at first registration 2.06 (CI 1.13, 3.73) (p< 0.05).Conclusion: Obstruction predicted mortality in all models and dyspnea in two models and needs to be addressed. Comorbidity with heart disease could further worsen the COPD patient’s prognosis and should be treated by a multidisciplinary team of professional specialists.Keywords: chronic obstructive pulmonary disease, COPD, mortality, quality register research

Background: Both single factors and composite measures have been suggested to predict mortality in patients with chronic obstructive pulmonary disease (COPD) and there is a need to analyze the relative importance of each variable. Objective: To explore the predictors of mortality for patients with COPD in relation to respiratory, cardiac, and malignant causes, as well as all causes of death. Methods: After merging the Swedish Respiratory Tract Register (SRTR) and the Swedish Cause of Death Register, patients with respiratory, cardiac, and other causes of death were identified. Demographic and clinical variables from the deceased patients' first registration with the SRTR were compared. Three univariable and multivariable Cox proportional hazards regression analyses were conducted for different causes of death, with time from first registration to either death or a fixed end date as dependent variable, and variables regarding demographics, respiration, and comorbidities as independent variables. Results: In the multivariable Cox models, mortality for patients with all causes of death was predicted by older age 1.79 (CI 1.41, 2.27), lower percentage of predicted forced expiratory volume in 1 second (FEV1 %) 0.99 (CI 0.98, 0.99), lower saturation 0.92 (CI 0.86, 0.97), worse dyspnea 1.48 (CI 1.26, 1.74) (p

Background: Severe asthma increases the risk of severe COVID-19 outcomes such as hospitalization and death. However, more studies are needed to understand the association between asthma and severe COVID-19. Methods: A cohort of 150,430 adult asthma patients were identified in the Swedish National Airway Register (SNAR) from 2013 to December 2020. Data on body mass index, smoking habits, lung function, and asthma control test (ACT) were obtained from SNAR, and uncontrolled asthma was defined as ACT ⩽19. Patients with severe COVID-19 were identified following hospitalization or in death certificates based on ICD-10 codes U07.1 and U07.2. The Swedish Prescribed Drug register was used to identify comorbidities and data from Statistics Sweden for educational level. Multivariate logistic regression analyses were used to estimate associations with severe COVID-19. Results: Severe COVID-19 was identified in 1067 patients (0.7%). Older age (OR = 1.04, 95% CI = 1.03–1.04), male sex (1.42, 1.25–1.61), overweight (1.56, 1.27–1.91), obesity (2.12, 1.73–2.60), high-dose inhaled corticosteroids in combination with long-acting β-agonists (1.40, 1.22–1.60), dispensed oral corticosteroids ⩾2 (1.48, 1.25–1.75), uncontrolled asthma (1.64, 1.35–2.00), cardiovascular disease (1.20, 1.03–1.40), depression (1.47, 1.28–1.68), and diabetes (1.52, 1.29–1.78) were associated with severe COVID-19, while current smoking was inversely associated (0.63, 0.47–0.85). When comparing patients who died from COVID-19 with those discharged alive from hospital until 31 December 2020, older age, male sex, and current smoking were associated with COVID-19 death. Conclusion: Patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, should be identified as risk patients for severe COVID-19. Furthermore, current smoking is strongly associated with COVID-19 death in asthma.

Background: Although chronic obstructive pulmonary disease (COPD) is a life-limiting disease with a significant symptom burden, the patients are more often referred to nursing homes (NH), than to specialist palliative care (SPC) at the end of life (EOL). This study aimed to compare patients with COPD in SPC with those in NH and to compare the care provided. Methods: A national register study was carried out where the Swedish National Airway Register and the Swedish Register of Palliative Care were merged. COPD patients who died in NHs or short-term facilities were included in the NH group (n = 415) and those who died in SPC were included in the SPC group (n = 355). Demographic and clinical variables were included from the Swedish National Airway Register and variables concerning EOL care from the Swedish Register of Palliative Care. Results: Symptom prevalence was similar in NHs and SPC, but symptom assessment (32% vs 20%), symptom relief medication (93-98% in SPC vs 74-90% in NH), EOL discussions (88% vs 66%), and bereavement support (94% vs 67%) were more likely in SPC (in all comparisons p

Kjell Larsson,1 Ann Ekberg-Jansson,2 Caroline Stridsman,3 Malin Hanno,4 Lowie EGW Vanfleteren5,6 1Integrative Toxicology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden; 4Boehringer Ingelheim AB, Stockholm, Sweden; 5COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, 413 45, Sweden; 6Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 413 45, SwedenCorrespondence: Kjell LarssonIntegrative Toxicology, National Institute of Environmental Medicine, IMM, Karolinska Institutet, Stockholm, SE-171 77 Tel +46 70 582 07 63Email kjell.larsson@ki.seIntroduction: Swedish guidelines adhere to the international GOLD document regarding management of chronic obstructive pulmonary disease (COPD). Based on data from the Swedish National Airway Register (SNAR) the aim was to evaluate adherence to guidelines of pharmacological treatment of COPD in Swedish primary and secondary care.Methods: During a period of 18 months, data on symptoms (CAT, mMRC), lung function, exacerbation history and pharmacological treatment from 15,595 COPD patients from 853 primary care and 125 secondary care clinics were collected from SNAR. Patients with a co-diagnosis of asthma were excluded. Patients were divided into four treatment groups: no pharmacological treatment, short-acting bronchodilators alone, long-acting bronchodilators alone and ICS alone or in combination with bronchodilators.Results: Of the patients, 29% were in GOLD group A, 58% in group B, 2% in group C and 11% in group D. CAT score was ≥ 10 and mMRC score was below 2 in 30.9% of the patients and mMRC score was ≥ 2 and CAT score < 10 in 4.2% of the patients. In 61.4% of the patients, no exacerbation was registered during the last year. Long-acting bronchodilators were prescribed for 78% and ICS for 46% of all patients. In groups A, B, C and D, respectively, 21%, 11%, 11% and 5% did not receive any inhaler therapy; 67%, 81%, 81% and 90% received long-acting bronchodilators; 33%, 46%, 55% and 71% received any ICS containing therapy and 19%, 34%, 39% and 61% received triple therapy.Discussion: Data from the SNAR indicate that only a minority of COPD patients were untreated. There was a liberal use of ICS containing drug combinations in subjects who do not have an indication for ICS. A considerable proportion of subjects at high risk of exacerbations did not receive ICS treatment.Keywords: chronic obstructive pulmonary disease, COPD, glucocorticoids, registry

It is unclear if patients with COPD are at increased risk of becoming infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1, 2]. However, after contracting SARS-CoV-2, patients with COPD are at high risk of severe coronavirus disease 2019 (COVID-19), a condition associated with morbidity and mortality [3, 4]. Although studies have described COVID-19 cohorts and investigated COPD as a risk factor, studies investigating patients with COPD in relation to risks of COVID-19 remain rare. Approved by the Swedish Ethical Review Authority (2020-02777), the current study was based on the Swedish National Airway Register (SNAR), which includes a large, well-characterised cohort of patients with COPD [5]. In the cohort, patients who have been hospitalised or died from COVID-19 were identified, which afforded a unique opportunity to study predictors of severe COVID-19 in COPD., Older age, male sex, low educational level, symptom burden, degree of obstruction, underweight, obesity, comorbidity and prior COPD inpatient or secondary care predict severe COVID-19 in patients with COPD https://bit.ly/2VHZIEm

Background While discontinuation of COPD maintenance medication is a known problem, the proportion of patients with discontinuation and its geographical and sociodemographic distribution are so far unknown in Sweden. Therefore, we analyse this question by applying an innovative approach called multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA). Patients and Methods We analysed 49,019 patients categorized into 18 sociodemographic contexts and 21 counties of residence. All patients had a hospital COPD diagnosis and had been on inhaled maintenance medication during the 5 years before the study baseline in 2010. We defined “discontinuation” as the absolute lack of retrieval from a pharmacy of any inhaled maintenance medication during 2011. We performed a cross-classified MAIHDA and obtained the average proportion of discontinuation, as well as county and sociodemographic absolute risks, and compared them with a proposed benchmark value of 10%. We calculated the variance partition coefficient (VPC) and the area under the receiver operating characteristics curve (AUC) to quantify county and sociodemographic differences. To summarize the results, we used a framework with 15 scenarios defined by the size of the differences and the level of achievement in relation to the benchmark value. Results Around 18% of COPD patients in Sweden discontinued maintenance medication, so the benchmark value was not achieved. There were very small county differences (VPC=0.35%, AUC=0.54). The sociodemographic differences were small (VPC=4.98%, AUC=0.57). Conclusion Continuity of maintenance medication among COPD patients in Sweden could be improved by reducing the unjustifiably high prevalence of discontinuation. The very small county and small sociodemographic differences should motivate universal interventions across all counties and sociodemographic groups. Geographical analyses should be combined with sociodemographic analyses, and the cross-classified MAIHDA is an appropriate tool to assess health-care quality.

Background: The Swedish National Airway Register (SNAR) was initiated in 2013 to ensure and improve the quality of care for patients with asthma and COPD. Aim: To describe the development and design of SNAR, and to study the 2019 data to evaluate its potential utility related to improvement of quality of care. Methods: SNAR includes data from patients with asthma (both children and adults) and COPD from primary, secondary and tertiary care, and also, for COPD inpatient care. Data on diagnostic investigations (e.g. spirometry, blood sample, skin prick test), symptom-scores, comorbidities and prescribed treatments are registered. The registrations are entered manually by healthcare professionals, or directly transferred from electronic medical records to a web-based platform. Results: In 2019, 1000 clinics participated and data were directly transferred by about 88% of them. The register included data on 205,833 patients with asthma and 80,372 with COPD (of these, 5% had both diagnoses). Registrations of new patients and follow-up visits from primary and secondary/tertiary care in 2019 were completed for 75,707 patients with asthma (11,818 children 17 yr) and 38,117 with COPD. Depending on age and disease group, 43–77% had performed spirometry, 36–65% Asthma Control Test, and 60% COPD Assessment Test. The prevalence of current smoking was about 2% in adolescents, 10% in adults with asthma, and 34% in COPD. For these, smoking cessation support was offered to 27%, 38% and 51%, respectively. Overall, limited data were available on investigation of allergy, 6-min walk test, patient education and written treatment plans. Regarding asthma, sex-differences in disease management were evident. Conclusion: SNAR has cumulatively registered data from over 270,000 individuals, and the register is important for patients, caregivers, authorities, politicians and researchers to evaluate the effect of treatment and to ensure high and equal quality of care nationwide.

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.

To study health inequalities between native and immigrant Swedes, we investigated differences in self-rated health (SRH), mental wellbeing (MW), common symptoms (CS), and persistent illness (PI), and if socioeconomic status (SES), negative status inconsistency, or social support could account for such differences. A secondary analysis was conducted on questionnaire data from a random adult population sample of 4,023 individuals and register data from Statistics Sweden. χ2 tests and binary logistic regressions were used to identify health differences and study these after accounting for explanatory variables. Compared with natives, immigrants more commonly reported negative status inconsistency, poorer SES, and poorer social support as well as poor SRH, very poor MW, and high level of CS but not PI. Significant differences were accounted for by work-related factors and social support. We encourage future research to address how pre- and peri-migration factors relate to immigrants’ post-migration SES, social support, and health status. Policy Implications Given the relationship between work-related factors (employment status, hours worked per week, and income) and all health outcomes in this study, labour market interventions that facilitate the integration of immigrants into the labour market, and into occupations that better correspond with their capacity, will arguably have public health benefits. Feelings of loneliness was, in our study, important in accounting for immigrants’ poorer self-rated health compared with natives’. Therefore, we endorse interventions that facilitate immigrants’ social networking and integration and thereby reduce feelings of loneliness. Common physical and mental symptoms may be important indicators of health and we, thus, suggest these to be taken into account when developing ill-health prevention programmes.

Background: Patients with obstructive lung diseases may be at risk of hospitalization and/or death due to COVID-19. Aim: To estimate the frequency of severe COVID-19, and COVID-19-related mortality in a well-defined large population of patients with asthma and chronic inflammatory lung disease (COPD). Further to assess the frequency of asthma and COPD as registered comorbidities at discharge from hospital, and in death certificates. Methods: At the start of the pandemic, the Swedish National Airway Register (SNAR) included 271,404 patients with a physician diagnosis of asthma and/or COPD. In September 2020, after the first COVID-19 wave in Sweden, the database was linked with the National Patient Register (NPR), the Swedish Intensive Care Register and the Swedish Cause of Death Register, which all provide data about COVID-19 based on International Classification of Diseases (ICD-10) codes. Severe COVID-19 was defined as hospitalization and/or intensive care or death due to COVID-19. Results: Among patients in SNAR, 0.5% with asthma, and 1.2% with COPD were identified with severe COVID-19. Among patients Conclusion: The frequency of severe COVID-19 in asthma and COPD was relative low. Mortality for those hospitalized was double as high in COPD compared to asthma. Comorbid asthma and COPD were not always identified among patients with severe COVID-19.

Ingela Henoch,1,2 Susann Strang,1,2 Claes-Göran Löfdahl,1,3 Ann Ekberg-Jansson1,4 1Angered Hospital, Research and Development Department, 2The Sahlgrenska Academy, Institute of Health and Care Sciences, University of Gothenburg, Gothenburg, 3University of Lund, Lund, 4Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden Abstract: Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease where treatment decisions should be based on disease severity and also should be equally distributed across age, gender, and social situation. The aim of this study was to determine to what extent patients with COPD are offered evidence-based interventions and how the interventions are distributed across demographic and clinical factors in the sample. Baseline registrations of demographic, disease-related, and management-related variables of 7,810patients in the Swedish National Airway Register are presented. One-third of the patients were current smokers. Patient-reported dyspnea and health-related quality of life were more deteriorated in elderly patients and patients living alone. Only 34% of currently smoking patients participated in the smoking cessation programs, and 22% of all patients were enrolled in any patient education program, with women taking part in them more than men. Less than 20% of the patients had any contact with physiotherapists or dieticians, with women having more contact than men. Men had more comorbidities than women, except for depression and osteoporosis. Women were more often given pharmacological treatments. With increasing severity of dyspnea, participation in patient education programs was more common. Dietician contact was more common in those with lower body mass index and more severe COPD stage. Both dietician contact and physiotherapist contact increased with deteriorated health-related quality of life, dyspnea, and increased exacerbation frequency. The present study showed that COPD management is mostly equally distributed across demographic characteristics. Only a minority of the patients in the present study had interdisciplinary team contacts. Thus, this data shows that the practical implementation of structured guidelines for treatment of COPD varies, to some extent, with regard to age and gender. Also, disease characteristics influence guideline implementation for each individual patient. Quality registers have the strength to follow-up on compliance with guidelines and show whether an intervention needs to be adapted prior to implementation in health care practice. Keywords: COPD, quality register, treatments, socioeconomic status, lung

Introduction: Chronic obstructive pulmonary disease (COPD) contributes to impaired health-related quality of life (HRQoL). Patient education and smoking cessation programs are recommended to reduce the number of exacerbations and hospitalizations, but the effects of such programs have yet to be explored in larger samples. Objective: The aim was to explore the longitudinal effects of patient education and smoking cessation programs on exacerbations and hospital admissions in patients with COPD. Design: This is a register study where data from the Swedish National Airway Register, including 20,666 patients with COPD, were used. Baseline measures of demographic, disease-related, and patient-reported variables were compared with a follow-up, 10–30 months after baseline. Descriptive statistics and changes between baseline and follow-up were calculated. Results: Comparing those not participating in education programs to those who did, HRQoL deteriorated significantly between baseline and follow-up in non-participants; there was no change in either exacerbations or hospitalizations in either group; there was a significant difference in baseline HRQoL between the two, and, when controlling for this, there was no significant change (p = 0.73). Patients who participated in smoking cessation programs were younger than the non-participants; mean 66.0 (standard deviations (SD) 7.8) vs. mean 68.1 (SD 8.8), p = 0.006. Among participants in smoking cessation programs, the proportion with continued smoking decreased significantly, from 76% to 66%, p

PURPOSE:To evaluate the effects of person-centred support via telephone in two chronically ill patient groups, chronic obstructive pulmonary disease (COPD) and/or chronic heart failure (CHF). METHOD:221 patients ≥ 50 years with COPD and/or CHF were randomized to usual care vs. usual care plus a person-centred telephone-support intervention and followed for six months. Patients in the intervention group were telephoned by a registered nurse initially to co-create a person-centred health plan with the patient and subsequently to discuss and evaluate the plan. The primary outcome measure was a composite score comprising General Self-Efficacy (GSE), re-hospitalization and death. Patients were classified as deteriorated if GSE had decreased by ≥ 5 points, or if they had been re-admitted to hospital for unscheduled reasons related to COPD and/or CHF or if they had died. RESULTS:At six-month follow-up no difference in the composite score was found between the two study groups (57.6%, n = 68 vs. 46.6%, n = 48; OR = 1.6, 95% CI: 0.9-2.7; P = 0.102) in the intention-to-treat analysis (n = 221); however, significantly more patients in the control group showed a clinically important decrease in GSE (≥ 5 units) (22.9%, n = 27 vs. 9.7%, n = 10; OR = 2.8, 95% CI: 1.3-6.0; P = 0.011). There were 49 clinical events (14 deaths, 35 re-admissions) in the control group and 41 in the intervention group (9 deaths, 32 re-admissions). Per-protocol analysis (n = 202) of the composite score showed that more patients deteriorated in the control group than in the intervention group (57.6%, n = 68 vs. 42.9%, n = 36; OR = 1.8, 95% CI 1.0-3.2; P = 0.039). CONCLUSION:Person-centred support via telephone mitigates worsening self-efficacy without increasing the risk of clinical events in chronically ill patients with CHF and/or COPD. This indicates that a patient-healthcare professional partnership may be established without the need for face-to-face consultations, even in vulnerable patient groups. TRIAL REGISTRATION:ISRCTN.com ISRCTN55562827.

To reduce healthcare costs associated with chronic obstructive pulmonary disease (COPD) and vacate hospital beds without compromising patient satisfaction with healthcare, alternatives for hospital treatment have been developed; however, few studies have qualitatively investigated patients’ experiences of these alternatives. This study aimed, first, to explore patients’ experiences of Sweden’s first COPD mobile care programme through semi-structured interviews with twelve patients, and, second, to evaluate if a human rights-based analysis could provide additional information. Data were, first, analysed using latent content analysis, resulting in three themes: security (effective follow-up, positive encounters), availability (convenience), and suggestions for improvement (increased amount of personnel, longer enrolment period, continued follow-up upon discharge from the programme). Security and availability contributed to high acceptability of and satisfaction with the programme; COPD mobile care can, thus, constitute an acceptable alternative to inpatient care for COPD patients. Findings were then further analysed using the AAAQ framework (availability, accessibility, acceptability, and quality) to determine how the COPD mobile care programme corresponds to the Right to health. This human rights-based analysis enabled the uncovering of certain groups being excluded from the programme, thereby generating valuable information for improving the programme by ensuring equal access and care for all COPD patients.

Kristina Andelid,1 Anders Andersson,1 Shigemi Yoshihara,2 Christina Åhrén,4 Pernilla Jirholt,3 Ann Ekberg-Jansson,1 Anders Lindén1,51Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; 2Department of Pediatrics, Dokkyo Medical University, Japan; 3Department of Rheumatology and Inflammation Research, Institute of Medicine, 4Department of Bacteriology, Institute of Laboratory Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg; 5Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenBackground: It is still unclear whether signs of neutrophil mobilization in the blood of patients with chronic obstructive pulmonary disease represent true systemic events and how these relate to bacterial colonization in the airways. In this study, we evaluated these issues during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease and chronic bronchitis (OPD-CB).Methods: Over a period of 60 weeks for each subject, blood samples were repeatedly collected from 60 smokers with OPD-CB during clinically stable periods, as well as during and after exacerbations. Myeloperoxidase (MPO) and neutrophil elastase (NE) protein and mRNA, growth of bacteria in sputum, and clinical parameters were analyzed. Ten asymptomatic smokers and ten never-smokers were included as controls.Results: We found that, during clinically stable periods, neutrophil and NE protein concentrations were increased in smokers with OPD-CB and in the asymptomatic smokers when compared with never-smokers. During exacerbations, neutrophil and MPO protein concentrations were further increased in smokers with OPD-CB, without a detectable increase in the corresponding mRNA during exacerbations. However, MPO and NE protein and mRNA displayed positive correlations. During exacerbations, only increased neutrophil concentrations were associated with growth of bacteria in sputum. Among patients with low transcutaneous oxygen saturation during exacerbations, PaO2 (partial oxygen pressure) correlated with concentrations of MPO and NE protein and neutrophils in a negative manner.Conclusion: There are signs of systemic neutrophil mobilization during clinically stable periods and even more so during exacerbations in chronic obstructive pulmonary disease. In this condition, MPO and NE may share a cellular origin, but its location remains uncertain. Factors other than local bacteria, including hypoxemia, may be important for driving systemic signs of neutrophil mobilization.Keywords: C-reactive protein, COPD, elastase, infection, myeloperoxidase, oxygen

Kristina Andelid,1 Sara Tengvall,1 Anders Andersson,1 Bettina Levänen,2 Karin Christenson,3 Pernilla Jirholt,3 Christina Åhrén,4 Ingemar Qvarfordt,1 Ann Ekberg-Jansson,1 Anders Lindén2 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; 2Unit of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 3Department of Rheumatology and Inflammation Research, Institute of Medicine, 4Department of Infectious Diseases, Infection ControlUnit, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Abstract: We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I–IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts. Keywords: COPD, exacerbation, infection, neutrophil, lung, opportunist&nbsp

Guilt is associated with an increased level of mood disturbance and a poorer quality of life. The aim of this study was to explore how patients with severe COPD view and experience guilt and the ways in which they cope with this guilt. A total of 31 COPD patients were interviewed about their perceptions and experiences of guilt. Qualitative content analysis was used to examine the interviews. In the descriptive (manifest) analysis, the categories “not feeling personal guilt” and “experiencing guilt” emerged; in the interpretative (latent) analysis, various strategies for dealing with guilt were identified — for example, acceptance or blaming others. Relatively few patients reported that they felt guilt on a conscious level, but those who did expressed anguish, and remorse before God; some felt blamed by others. It is important that healthcare providers acknowledge the guilt that their patients express, since guilt may have adverse effects on the patients’ overall health.

Objectives:Anxiety often arises in conjunction with dyspnoea in patients with severe COPD. Considering the provoking symptomatology and the high mortality rate for COPD, it is reasonable to believe that these conditions trigger death-related and existential anxiety. Although anxiety causes considerable distress and reduces quality of life, people's experience of anxiety has been studied relatively little. The aim of this study was to explore severely ill COPD patients’ experience of anxiety and their strategies to alleviate anxiety.Methods:This qualitative, in-depth interview study explored perceptions of anxiety and the alleviation strategies that are adopted. Interviews were analyzed using a thematic content analysis approach, involving interpretive coding and identification of themes. People suffering from COPD (stage III or IV) were recruited from a pulmonary outpatient clinic in the west of Sweden. Purposive sampling was used, and thirty-one (31) patients were included.Results:Most of the patients had experienced anxiety associated with COPD. Analyses revealed three major themes, death anxiety, life anxiety, and counterweights to anxiety. Death anxiety included fear of suffocation, awareness of death, fear of dying and separation anxiety. Life anxiety included fear of living and fear of the future. Counterweights to anxiety concerned coping with suffocation, avoiding strategy, and a sense of joy that defied their vulnerable situation.Significance of results:The majority of patients experienced anxiety, which limited their lives. Although the patients experienced both life anxiety and death anxiety, they were able to cope with the situation and find a defiant joy to some extent.

Background Chronic obstructive pulmonary disease (COPD) is a common cause of death. Despite the heavy symptom burden in late stages, these patients are relatively seldom referred to specialist palliative care. Methods A web-based survey concerning medical and organizational aspects of palliative care in COPD was distributed to respiratory physicians in Sweden. There were 93 respondents included in the study. Results Palliative care issues were regularly discussed with the patients according to a third of the respondents. About half of the respondents worked in settings where established routines for co-operation with palliative units were available at least to some extent. Less than half of the respondents (39%) were aware of current plans to develop palliative care, either as a co-operative effort or within the facility. Palliative care is focused on physical, psychological, social, and existential dimensions, and the proportions of respondents providing support within these dimensions, ‘always' or ‘often', were 83%, 36%, 32%, and 11%, respectively. Thus, to treat the physical dimensions was perceived as much more obvious than to address the other dimensions. Conclusions The survey indicates that the priorities and resources for palliative care in COPD are insufficient in Sweden. The data, despite limitations, reveal a lack of established team-work with specialized palliative care units and actual plans for such co-operation.

Background : In chronic obstructive pulmonary disease (COPD), various factors, such as dyspnoea, obstruction, exacerbations, smoking, exercise capacity, and body mass index, have been found to influence mortality and health-related quality of life (HRQOL). In order to identify subgroups of patients needing special attention, the aim of the present study was to explore the relationships between disease progression factors and HRQOL across COPD stages. Methods : Baseline registrations from the Swedish COPD register of demographic, clinical, and patient-reported variables of 7,810 patients are presented. Dyspnoea was measured by the modified Medical Research Council (mMRC) dyspnoea scale and HRQOL by the Clinical COPD Questionnaire (CCQ). Results : This study shows as expected that patients with spirometrically more severe COPD had a significantly higher number of exacerbations and hospitalisations, significantly increasing dyspnoea, significantly decreasing body mass index and exercise capacity, and significantly worsening HRQOL. When adjusting for spirometric stage of COPD, deteriorated HRQOL was predicted by increasing dyspnoea, depression/anxiety, increasing number of exacerbations, and decreased exercise capacity. Further, these data show that an mMRC value of 2 corresponds to a CCQ value of 1.9. Conclusion : The COPD patients suffered from a significant symptom burden, influencing HRQOL. A surprisingly great proportion of patients in spirometric stages II–IV showed marked changes of CCQ, indicating a need for an improved collaboration between clinical pulmonary medicine and palliative care. Keywords: COPD; quality register; health-related quality of life (Published: 27 May 2016) Citation: European Clinical Respiratory Journal 2016, 3: 31459 - http://dx.doi.org/10.3402/ecrj.v3.31459

Summary Background There is increasing evidence of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD), but there is very little information on the development of systemic inflammation in smokers without severe airway symptoms. In this longitudinal study, we examined whether smokers with mild or no airway symptoms develop signs of systemic inflammation by assessing inflammatory markers in blood over a 6-year period. Methods Forty smokers and 28 male never-smokers were investigated in 1995 (year 0) and 6 years later (year 6). At year 6, 11 smokers had stopped smoking (quitters); these subjects were analysed as a separate group. At year 0 and 6, we measured serum levels of myeloperoxidase (MPO), lysozyme and human neutrophil lipocalin (HNL), regarded as markers of activity in neutrophils plus monocyte-lineage cells, monocyte-lineage cells only and neutrophils only. Results All systemic markers of inflammation (MPO, HNL and lysozyme) were significantly higher in smokers than in never smokers at year 6. For MPO alone, smokers only displayed a unique pattern compared with the other groups; the concentration of MPO in blood increased among smokers during the 6-year period, and this increase was statistically significant compared with that observed in never-smokers. Even though quitters did not display any clear change in MPO, we observed a statistically significant negative correlation between the change in blood MPO and the duration of smoking cessation in this group. For HNL and lysozyme, the changes over time were similar in smokers and never-smokers, with no statistically significant difference compared with quitters. Conclusion This study provides evidence that male smokers without severe airway symptoms develop an increasing systemic inflammation during a 6-year period. The study forwards both direct and indirect evidence that MPO may be an early marker of this systemic inflammation. However, our study also forwards indirect evidence that ongoing tobacco smoking may “drive” the level of systemic HNL and lysozyme. The origin of the increased MPO and its value as an easily measured predictor for future COPD deserves to be further evaluated.

Background:Chronic obstructive pulmonary disease (COPD) comprises local and systemic neutrophilic inflammation. Neutrophils contain the intracellular enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) and these enzymes contribute to anti-bacterial activity in host defense. However, it is not known if hypoxia during COPD exacerbations is associated with systemic neutrophil activity resulting in MPO and NE release. Aims:To determine if hypoxia during COPD exacerbations is associated with systemic neutrophil activity resulting in MPO and NE release. Methods:Blood samples were harvested and hypoxia (ie. blood gas partial oxygen pressure)was analyzed from 18 smokers with COPD during exacerbations.In blood, neutrophil concentrations (blood differential count) as well as MPO (ELISA) and NE (latex bead concentration method) were analyzed. Results:Neutrophil concentrations were increased from [4.3(2.3-9.6)](baseline)to[6.0 (3.7-13)](exacerbation) during COPD exacerbations (n=18).There were statistically significant (p Conclusion:Hypoxia during COPD exacerbations is associated with systemic neutrophil activity resulting in MPO and NE release. Given that experimental hypoxia is known to cause neutrophil activity in vitro, it seems plausible that this phenomenon is relevant to COPD exacerbations as well. It can therefore be speculated that oxygen therapy may counteract this neutrophil activity during exacerbations of COPD.

Summary Background Dry powder inhaler (DPI) device switch in asthma treatment could potentially increase with the entrance of new devices. We examined the switch patterns of budesonide (BUD) DPI analogues available in Sweden. Methods This observational real-life study linked primary healthcare medical records data from the Vastra Gotaland region to national Swedish registries, and included asthma patients (ICD-10-CM J45) prescribed BUD in a multidose DPI. Index date: first dispense of BUD DPI. Switch date: prescription of another BUD DPI device. Study outcomes (switch vs. non-switch) were exacerbations and prescription of short-acting β2-agonists. Study period was 1 July 2005 to 31 October 2013. Results Overall, 15,169 asthma patients were on treatment with BUD DPI; 1178 (7.35%) switched to another BUD DPI during the study. Pair-wise 1:1 matching of switchers vs. non-switchers resulted in two groups of 463 patients each (mean age 36 years, 55% female patients). A 25% higher exacerbation rate was seen postswitch (0.40 vs. 0.32; p = 0.047). Switchers were 4.5 year younger and had lower medication possession rate than non-switchers. Switch without primary healthcare visit did not differ between groups regarding consultations and exacerbations (no visit 4.96 and 0.90; visit 4.29 and 0.77, respectively). However, patients without primary healthcare visit at switch had significantly more outpatient hospital visits (2.01 vs. 0.81; p

Kristina Andelid,1 Anders Andersson,1 Shigemi Yoshihara,2 Christina Åhrén,4 Pernilla Jirholt,3 Ann Ekberg-Jansson,1 Anders Lindén1,51Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; 2Department of Pediatrics, Dokkyo Medical University, Japan; 3Department of Rheumatology and Inflammation Research, Institute of Medicine, 4Department of Bacteriology, Institute of Laboratory Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg; 5Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SwedenBackground: It is still unclear whether signs of neutrophil mobilization in the blood of patients with chronic obstructive pulmonary disease represent true systemic events and how these relate to bacterial colonization in the airways. In this study, we evaluated these issues during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease and chronic bronchitis (OPD-CB).Methods: Over a period of 60 weeks for each subject, blood samples were repeatedly collected from 60 smokers with OPD-CB during clinically stable periods, as well as during and after exacerbations. Myeloperoxidase (MPO) and neutrophil elastase (NE) protein and mRNA, growth of bacteria in sputum, and clinical parameters were analyzed. Ten asymptomatic smokers and ten never-smokers were included as controls.Results: We found that, during clinically stable periods, neutrophil and NE protein concentrations were increased in smokers with OPD-CB and in the asymptomatic smokers when compared with never-smokers. During exacerbations, neutrophil and MPO protein concentrations were further increased in smokers with OPD-CB, without a detectable increase in the corresponding mRNA during exacerbations. However, MPO and NE protein and mRNA displayed positive correlations. During exacerbations, only increased neutrophil concentrations were associated with growth of bacteria in sputum. Among patients with low transcutaneous oxygen saturation during exacerbations, PaO2 (partial oxygen pressure) correlated with concentrations of MPO and NE protein and neutrophils in a negative manner.Conclusion: There are signs of systemic neutrophil mobilization during clinically stable periods and even more so during exacerbations in chronic obstructive pulmonary disease. In this condition, MPO and NE may share a cellular origin, but its location remains uncertain. Factors other than local bacteria, including hypoxemia, may be important for driving systemic signs of neutrophil mobilization.Keywords: C-reactive protein, COPD, elastase, infection, myeloperoxidase, oxygen

The N(2) slope is an index of inhomogeneous distribution of ventilation and has been suggested to be suited for early testing of chronic obstructive pulmonary disease (COPD) in smokers. The aim of the present study was to examine the association between the fraction of exhaled nitric oxide (FENO) and the N(2) slope in a random population of smoking and non-smoking men. Altogether 57 subjects were included in the study, 24 never-smokers, seven ex-smokers and 26 current smokers. Subjects were examined twice, in 1995 when they regarded themselves as healthy, and in a follow-up in 2001. Spirometry, N(2) slope and high-resolution computed tomography (HRCT) were performed in 1995 while the follow-up examination included also measurement of FENO. The FENO value was significantly lower and the N(2) slope higher in current smokers. In smokers but not in never- or ex-smokers FENO was correlated to the difference in N(2) slope between 1995 and 2001 (r(s)=0.49, P=0.01). We analysed the data by multiple linear regression adjusted for smoking, mild respiratory symptoms and inhaled steroids. There were significant associations between FENO and the N(2) slope both in 1995 and in 2001. The strongest association was found to exist with the change in N(2) slope during these years. Sixteen of the subjects could be classified as having COPD, six with mild and ten with moderate COPD. There was a trend for an increase in N(2) slope with increased severity of COPD; among subjects with no COPD the N(2) slope in 2001 was 2.3% N(2)/L, and those with mild and moderate COPD had 2.5% N(2)/L and 3.9% N(2)/L, respectively (P=0.0004). No such trend was seen for FENO (17.8, 15.5 and 20.3 parts per billion (ppb), respectively, P=0.8). The results show that FENO is associated with the N(2) slope, indicating that FENO reflects inflammatory changes in the peripheral airways of both non-smoking and smoking subjects.

Purpose: To elucidate whether emphysematous lesions and other high‐resolution computed tomography (HRCT) findings considered associated with smoking are part of a progressive process, and to measure the extent to which similar changes are found in never‐smokers. Material and Methods: Healthy smokers and never‐smokers were recruited from a randomized epidemiological study and investigated with a 6‐year interval. Emphysema, parenchymal and subpleural nodules, ground‐glass opacities, bronchial alterations, and septal lines were evaluated in 66 subjects (40 smokers, 11 of whom had stopped smoking in the interval, and 26 never‐smokers). Lung function was tested. Results: All except emphysematous lesions were present to some extent in never‐smokers. Emphysema, parenchymal nodules, and septal lines occurred significantly more in current smokers, and a progression in extent of emphysema, ground‐glass opacities, bronchial alterations and septal lines was seen. There was no significant change among those who stopped and never‐smokers except for bronchial alterations, which progressed in never‐smokers. Conclusion: In healthy, elderly never‐smokers a low extent of various HRCT findings has to be considered normal. Emphysema, parenchymal nodules, and ground‐glass opacities are indicative of smoking‐induced disease. Further progress may cease if smoking is stopped.

Respiratory diseases are an important health problem throughout the world. Whether caused by industrial pollutants, infections, smoking, cancer or metabolic diseases, damage to the lungs and airways often lead to morbidity or death. Bronchoalveolar lavage (BAL) obtained by fiber-optic bronchoscopy is a biofluid mirroring the expression of normally secreted pulmonary proteins and the products of activated cells and destructive processes. The characterization of the proteome within this compartment provides an opportunity to establish temporal and prognostic indicators of airway disease. The objective of this study was to develop methods of analysis of BAL samples, which achieved the highest level of annotation of the expression map of this proteome. We have optimized the process of sample preparation after investigating a variety of techniques including dialysis, ultramembrane filtration, precipitation and gel filtration. We have further studied methods to remove albumin from BAL in order to unmask proteins hidden on two-dimensional gels. In a pilot application of the method, BAL protein profiles obtained from healthy nonsmokers and smokers at risk for developing chronic obstructive pulmonary disease showed distinct differences.

The aim of this study was to evaluate the relationship between respiratory symptoms, lung function and inflammatory markers in ‘healthy’ smokers.The study population was recruited from an epidemiological study with subjects of the same age, 60 years. Only smokers who considered themselves healthy (n=58) and a random sample of never-smokers (n=34) were investigated. All subjects underwent lung function tests—spirometry, carbon monoxide transfer (DL co) and the single-breath N2method (N2test)—together with high-resolution computed tomography (HRCT). A flexible bronchoscopy with a bronchoalveolar lavage (BAL) was performed in 30 smokers and 18 never-smokers. Bronchial biopsies were also taken.Smokers who reported non-specific respiratory problems, chronic bronchitis and wheezing in a symptom questionnaire had a lower forced expiratory volume in 1 sec (FEV1), FEV% and specific airway conductance (sGaw), lung function tests supposed to reflect the more central airways, than smokers without respiratory symptoms. A limited number of smokers with occasional non-specific respiratory problems also had more cytotoxic T cells (CD8) in bronchial biopsies. No differences were found in DL co and the N2test, lung function tests supposed to reflect the more peripheral airways including the alveoli, HRCT-diagnosed emphysema or inflammatory markers in blood and BAL between smokers with and without respiratory symptoms.It is concluded that even when smokers consider themselves ‘healthy’ they have mild symptoms that are related more to physiological changes and inflammatory markers that may reflect events in the central airways than to changes that may reflect events in the peripheral airways.

In this study healthy never-smoking subjects (n = 18) were recruited from a population study. Bronchoalveolar lavage (BAL), blood lymphocytes and bronchial biopsies, analysed both in the epithelium and lamina propria, were stained for T and B lymphocytes, natural killer (NK) cells and different subpopulations of T lymphocytes. In BAL, significantly higher proportions of T lymphocytes (CD3), T lymphocyte activation markers; HLA-DR, CD26+, CD49a+, CD54+ and CD69+ helper T (CD3+4+) and memory helper T lymphocytes (CD4+45RO+29+) and memory T lymphocytes (CD3+45RO+) were found, compared to blood. However, the proportion of IL-2 receptor-positive T lymphocytes (CD25+) was lower in BAL than in blood. A previously described higher ratio of CD3+4+CD3+8+ in BAL than in blood (3·4 vs 1·7; P = 0·001) was confirmed. In bronchial biopsies, we found significantly higher numbers of CD8+ cell profiles per mm2 in the epithelial compared to the lamina propria compartment.We conclude that healthy never-smoking men have higher levels of activated memory T lymphocytes in BAL than in blood, and that the T-cell subpopulations differ in the epithelial compared to the lamina propria compartment in the bronchial mucosa and these compartments should be analysed separately. It is reasonable to think that there is a gradient from blood to the airway lumen where T cells are recruited from blood to take part in the defense towards damaging agents.

Papers p 1271 Exacerbations of chronic obstructive pulmonary disease affect quality of life and the cost of managing the disease. Though the long term effects of hypersecretion on the deterioration of ventilatory function in patients with chronic obstructive pulmonary disease have been debated for many years,1 recent data show a good correlation between hypersecretion and long term deterioration of ventilatory function in these patients.2 This is why mucolytics, which seem to have an effect on hypersecretory exacerbations,3 might also influence disease progression in chronic obstructive pulmonary disease. Exacerbations are important events for patients with chronic bronchitis in that they negatively affect quality of life.1 Exacerbations also have socio-economic consequences.2 Therapies aiming at reducing the occurrence and severity of exacerbations are therefore of interest. The Cochrane review in this week's issue of the BMJ reports a meta-analysis of drugs considered to have mucolytic effects (p 1271).3 Twenty two studies of 10 drugs were included. Treated patients showed a significant reduction over controls in the number of exacerbations …

Kristina Andelid,1 Sara Tengvall,1 Anders Andersson,1 Bettina Levänen,2 Karin Christenson,3 Pernilla Jirholt,3 Christina Åhrén,4 Ingemar Qvarfordt,1 Ann Ekberg-Jansson,1 Anders Lindén2 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; 2Unit of Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 3Department of Rheumatology and Inflammation Research, Institute of Medicine, 4Department of Infectious Diseases, Infection ControlUnit, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden Abstract: We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB). We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB. Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I–IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations. We characterized cytokine protein concentrations in blood and bacterial growth in sputum. Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups. During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations. Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora. During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner. In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways. Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts. Keywords: COPD, exacerbation, infection, neutrophil, lung, opportunist&nbsp

Background: The aim of this study was to determine whether relative qualitative and quantitative differences in protein expression could be related to smoke exposure or smoke-induced airway inflammation. We therefore explored and characterized the protein components found in bronchoalveolar lavage (BAL) fluid sampled from either lifelong smokers or never-smokers. Methods: BAL fluid samples obtained by bronchoscopy from 60-year-old healthy never-smokers (n = 18) and asymptomatic smokers (n = 30) were analyzed in either pooled or individual form. Initial global proteomic analysis used shotgun digestion approaches on unfractionated BAL fluid samples (after minimal sample preparation) and separation of peptides by gradient (90-min) liquid chromatography (LC) coupled with on-line linear ion trap quadropole mass spectrometry (LTQ MS) for identification and analysis. Results: LTQ MS identified 481 high- to low-abundance proteins. Relative differences in patterns of BAL fluid proteins in smokers compared with never-smokers were observed in pooled and individual samples as well as by 2-dimensional gel analysis. Gene ontology categorization of all annotated proteins showed a wide spectrum of molecular functions and biological processes. Conclusions: The described method provides comprehensive qualitative proteomic analysis of BAL fluid protein expression from never-smokers and from smokers at risk of developing chronic obstructive pulmonary disease. Many of the proteins identified had not been detected in previous studies of BAL fluid; thus, the use of LC-tandem MS with LTQ may provide new information regarding potentially important patterns of protein expression associated with lifelong smoking.

Purpose: To assess the ability of a conventional density mask method to detect mild emphysema by high‐resolution computed tomography (HRCT); to analyze factors influencing quantification of mild emphysema; and to validate a new algorithm for detection of mild emphysema. Material and Methods: Fifty‐five healthy male smokers and 34 never‐smokers, 61–62 years of age, were examined. Emphysema was evaluated visually, by the conventional density mask method, and by a new algorithm compensating for the effects of gravity and artifacts due to motion and the reconstruction algorithm. Effects of the reconstruction algorithm, slice thickness, and various threshold levels on the outcome of the density mask area were evaluated. Results: Forty‐nine percent of the smokers had mild emphysema. The density mask area was higher the thinner the slice irrespective of the reconstruction algorithm and threshold level. The sharp algorithm resulted in increased density mask area. The new reconstruction algorithm could discriminate between smokers with and those without mild emphysema, whereas the density mask method could not. The diagnostic ability of the new algorithm was dependent on lung level. At about 90% specificity, sensitivity was 65–100% in the apical levels, but low in the rest of the lung. Conclusion: The conventional density mask method is inadequate for detecting mild emphysema, while the new algorithm improves the diagnostic ability but is nevertheless still imperfect.

Purpose: To test the hypothesis that diffuse and/or focal air trapping are sensitive indicators of airflow obstruction in smoker's small airways disease, when age, gender and presence of emphysematous lesions were allowed for. Material and Methods: Fifty-eight smokers and 34 never smokers, recruited from a randomized population study of men born in 1933, were investigated by HRCT and by extended pulmonary function tests, including a sensitive test for small airways disease (N2 slope). Diffuse air trapping was evaluated by calculating a quotient of mean lung density at expiration and inspiration. Focal air trapping was scored visually by consensus. Results: Diffuse air trapping did not differ between non-emphysematous smokers and never smokers. Furthermore, diffuse air trapping correlated well to the quotient between the residual volume and total lung capacity (RV/TLC, p = 0.01) and was consequently higher in emphysematous smokers than in never smokers. Focal air trapping was found as frequently in smokers without emphysema as in never smokers. Smokers with emphysema showed significantly less focal air trapping. Neither the N2 slope nor any of the other lung function variables differed between those with and without focal air trapping among non-emphysematous smokers. Conclusion: Neither diffuse nor focal air trapping are sensitive indicators of smoker's small airways disease.

A study was undertaken to investigate the relationship between inflammatory cells and structural changes in the mucosa of the airways in an epidemiological sample of a group of asymptomatic smokers (smokers who had never sought medical attention for respiratory problems) and in non-smoking subjects.Bronchial biopsy specimens were taken from 29 smokers and 16 never smokers and stained with monoclonal antibodies HNL, EPO, AA1, CD68 in order to identify neutrophils, eosinophils, mast cells, and macrophages, respectively. The biopsy specimens were also stained with monoclonal antibodies to the cytokines interleukin (IL)-1beta and IL-8. Structural changes were identified by staining the biopsy specimens with antibodies to tenascin and laminin and by evaluating the condition of the epithelial layer.The numbers of all inflammatory cells and of cytokine staining cells were significantly increased in smokers. The thickness of the tenascin and laminin layers was increased in the smoking group and the integrity of the epithelial layer was significantly reduced. In smokers the epithelial integrity was negatively correlated with the number of eosinophils and macrophages. The thickness of the tenascin and laminin layers was positively correlated with AA1 and EPO positive cells only.High numbers of inflammatory cells are present in the bronchial mucosa of asymptomatic smokers which have a clear relationship with the impaired epithelial integrity. The increased thickness of the laminin and tenascin layers in these subjects was strongly related to the presence of eosinophils and mast cells, suggesting a role for these cells in tissue remodelling of the airways of smokers.

In this study we investigated if smoking subjects with a normal or slightly decreased lung function differ in the lymphocyte pattern compared to never-smokers. In a group of 'healthy' smokers (n = 58) and never-smokers (n = 34) 60 years old, we investigated the lymphocyte pattern in both BAL (n = 30 and n = 18 respectively), bronchial epithelium and lamina propria (n = 14 and n = 10 respectively) and blood. We found that all subjects, despite smoking history, had a higher number of CD8+ cells per mm2 in the epithelium compared to the lamina propria in the bronchial biopsies. In smokers, these CD8+ cells were significantly negatively correlated to FEV1 (r = -0.56, P = 0.04). In smokers, the number of CD8+ lymphocytes was higher and the T cell activation markers (CD57+ and CD28+) were lower in BAL, than in never-smokers. This last finding was also seen in blood for CD3+ 57+. We conclude, that in 'healthy' smokers the lymphocyte patterns are different compared to never-smokers, to some extent in BAL. There is also a relation between lymphocytes in the bronchial mucosa and lung function. This has previously been shown in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis but not in asymptomatic smokers.

The aim of the present study was to characterize the inflammatory pattern in "healthy"smokers and relate it to lung function, high resolution computed tomography (HRCT) findings and respiratory symptoms in order to identify smokers at risk to develop COPD. Subjects were recruited from a population study "Men born 1933 in Göteborg". Only smokers who considered themselves as healthy (n=58) were investigated. From the same population a random sample of healthy never-smokers (n=34) were recruited. All subjects underwent lung function tests, HRCT, and answered a questionnaire. Thirty smokers (30/58) and 18 never-smokers (18/34) accepted to undergo a bronchoscopy with bronchial lavage, bronchoalveolar lavage (BAL) and bronchial biopsies. The levels of neutrophil-associated soluble inflammatory markers e.g. human neutrophil lipocalin (HNL), were higher in smokers in both blood, bronchial lavage and BAL, as compared with never-smokers. Inflammatory markers in bronchial lavage and BAL were related to carbon monoxide transfer (DLCO) but not to forced expiratory volume in one second (FEV1). HRCT showed emphysematous changes in 25/57 smokers while only 1/32 never-smokers showed this. Such emphysematous changes in smokers were related to a decrease in transfer factor (DLCO/ VA) as well as to an increase in HNL in BAL. Smokers with emphysematous changes also had more alveolar macrophages in BAL as compared with smokers without changes. Bronchial biopsies were analysed according to some T cell subpopulations, in different compartments in never-smokers. In healthy never-smokers, an increased number of cytotoxic T cells (CD 8+) were found in the bronchial epithelium as compared with lamina propria. Also in smokers, the same gradient in bronchial biopsies was seen. Even if the number of CD8+ cells in lamina propria were not increased in smokers as compared with never-smokers, a relation between CD8+ cells and an impairment in FEV1 was demonstrated in smokers. In BAL in never-smokers, the proportion of different T cell activation markers were higher in BAL than in blood (e.g. HLA-DR, CD54+, CD69+). In BAL in smokers as compared with never-smokers, an increased proportion of CD8+ and decreased proportion of CD4+ T cells was seen. The CD4+/CD8+ ratio was also low. The occurrence of different respiratory symptoms in smokers who considered themselves as "healthy" were high. Smokers with symptoms had lower FEV1, FEV% and specific airway conductance (sGaw) as well as increased number of CD8+ cells in the bronchial biopsies as compared with smokers without symptoms. However, no relation between reported symptoms and soluble inflammatory markers in blood/BAL, emphysematous changes or lung function tests mainly reflecting the small airways, could be seen. In summary, smokers without any diagnosed pulmonary or bronchial disease, frequently report respiratory symptoms, have decreased lung function, emphysematous changes on HRCT and these findings are related to inflammatory markers in bronchial tissue and bronchial lavage, BAL and blood. Thus, "healthy" smokers have an inflammation in the bronchial mucosa suggesting early chronic obstructive pulmonary disease (COPD) or preclinical COPD.

N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis.Ekberg-Jansson A, Larson M, MacNee W, Tunek A, Wahlgren L, Wouters EF, Larsson S.Lung Division, Sahlgrenska University Hospital, Goteborg, Sweden.N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (pPublication Types: Clinical Trial Multicenter Study Randomized Controlled Trial

We aimed to study the occurrence of emphysematous lesions in symptom free smoking men of about 60 years of age and in a matching group of never-smoking men and the relationship between pulmonary changes at high resolution computed tomography (HRCT) and lung function tests.Our investigation included 57 smoking and 32 never-smoking healthy men from a randomized epidemiological study. HRCT was performed at full inspiration with a 1·5 mm slice thickness and a 3 cm inter-slice distance. Evaluation was made by two radiologists unaware of smoking history. Emphysematous lesions were scored visually. Pulmonary function tests were performed including spirometry and diffusion capacity test (DLCO).Emphysematous changes were demonstrated in 25 of 57 smokers but in only one never-smoker.DL CO/V A was the most sensitive test for early emphysematous lesions. It also correlated with radiographical scoring.Emphysematous lesions were evident in 44% of the healthy symptom free smokers. HRCT may reveal early emphysematous lesions in smokers before clinical symptoms have developed.

The pathologic mechanisms of chronic obstructive pulmonary disease (COPD) most certainly involves neutrophil granulocytes, cytotoxic T-cells, macophages and mast cells. The aim of this study was to investigate the relation between the number of mast cells in different compartments in bronchial biopsies of central proximal airways to structural changes, lung function tests and emphysema detected by high resolution computed tomography (HRCT). Twenty nine asymptomatic smoking and 16 never-smoking men from a population study were recruited. Central bronchial biopsies were stained to identify mast cells by immunohistochemistry. The number of mast cells in the epithelium, lamina propria and smooth muscle as well as epithelial integrity and thickness of the tenascin and laminin layer were determined. Smokers had increased numbers of mast cells in all compartments (P