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Dennis Bouhuis,1 Maaike Giezeman,1,2 Mikael Hasselgren,1,2 Christer Janson,3 Marta A Kisiel,4 Karin Lisspers,5 Scott Montgomery,6– 8 Anna Nager,9 Hanna Sandelowsky,7,9,10 Björn Ställberg,5 Josefin Sundh11 1School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 2Centre for Clinical Research and Education, Karlstad, Sweden; 3Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 4Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden; 5Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 6Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro, Sweden; 7Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; 8Department of Epidemiology and Public Health, University College, London, UK; 9Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 10Academic Primary Health Care Centre, Stockholm, Sweden; 11Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, SwedenCorrespondence: Josefin Sundh, Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden, Tel +46702349517, Email josefin.sundh@regionorebrolan.seBackground: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype.Methods: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor’s diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex.Results: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30– 9.92]), stage 2 (3.42 [2.13– 5.51]) and stage 3 (2.38 [1.46– 3.88]) compared with stage 4, and with CAT score < 10 (3.35 [2.34– 4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28– 0.79]) and (0.68 [0.48– 0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030).Conclusion: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.Keywords: COPD, exacerbations, lung function, CAT, body mass index, chronic bronchitis, sex, heart failure

Objective: To investigate whether one additional educational session about inhaler use, delivered to patients with COPD in primary healthcare, could affect the patients' skills in inhaler use. Specifically, to study the effects on errors related to handling the device, to inhalation technique, and to both. Methods: This nonrandomized controlled clinical trial included 64 patients who used devices and made errors. COPD nurses assessed inhaler use using a checklist and educated patients. Intervention group received one additional educational session after two weeks. Results: At baseline, patients in the IG had more devices (n = 2,1) compared to patients in the CG (n = 1,6) (p = 0.003). No other statistically significant differences were seen at baseline. At follow-up, intervention group showed a lower proportion of patients who made errors related to handling the device (p = 0.006). No differences were seen in the other categories. Conclusion: One additional educational session in inhaler use for patients with COPD was effective in reducing the proportion of patients making errors related to handling of their devices. Practice implications: Categorization of errors might help healthcare professionals to assess the suitability of patients' devices, tailor patient education, and thus improve patient health.

OBJECTIVES: The aim was to investigate if menstruation and use of exogenous sex hormones influence self-reported asthma related quality of life (QoL) and asthma control. METHODS: The study is based on two asthma cohorts randomly selected in primary and secondary care. A total of 622 female patients 18-65 years were included and classified as premenopausal ≤ 46 years (n = 338) and peri/postmenopausal 47-65 years (n = 284). Questionnaire data from 2012 and 2014 with demographics, asthma related issues and sex hormone status. Outcome measures were Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) and asthma control including Asthma Control Test (ACT) and exacerbations last six months. RESULTS: Premenopausal women with menstruation related asthma worsening, perimenstrual asthma (PMA) (9%), had a clinically relevant lower Mini-AQLQ mean score 4.9 vs. 5.8 (p

Background: Critical inhaler technique errors have been associated with lower treatment efficacy in chronic obstructive pulmonary disease (COPD). We aimed to assess and follow-up critical inhaler technique errors, and to investigate their association with COPD symptoms and exacerbations. Methods: COPD-diagnosed primary and secondary care outpatients (n = 310) demonstrated inhaler technique with inhaler devices they were currently using. Critical errors in opening, positioning and loading the inhaler device, and exhalation through dry-powder inhalers were assessed and corrected, and the assessment was repeated one year later. COPD Assessment Test, the modified Medical Research Council dyspnoea scale and history of exacerbations were collected at both visits. Results: The proportion of patients making >1 critical inhaler technique error was lower at follow-up in the total population (46% vs 37%, p = 0.01) and among patients with unchanged device models (46% vs 35%, p = 0.02), but not among patients with a new inhaler device model (46% vs 41%, p = 0.56). Not positioning the device correctly was the most common critical error at both visits (30% and 22%). Seventy-four percent of the patients had unchanged COPD treatment from baseline to follow-up. Treatment escalation, de-escalation, and switch was observed in 14%, 11%, and 1% of the patients, respectively. No association was found between critical errors and COPD symptoms or exacerbations. Conclusions: Assessment and correction of inhaler technique was associated with a decrease in critical inhaler technique errors. This effect was most pronounced in patients using the same device models throughout the follow-up period.

Kjell Larsson,1 Karin Lisspers,2 Björn Ställberg,2 Gunnar Johansson,2 Florian S Gutzwiller,3 Karen Mezzi,3 Bine Kjoeller Bjerregaard,4 Leif Jorgensen,4 Hyewon Koo,5 Christer Janson6 1Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 3Novartis Pharma AG, Basel, Switzerland; 4IQVIA Solutions, Copenhagen, Denmark; 5IQVIA Solutions, Solna, Sweden; 6Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, SwedenCorrespondence: Kjell Larsson, Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SE-171 77, Sweden, Tel +467 0582 0763, Email kjell.larsson@ki.seBackground: Patients with mild chronic obstructive pulmonary disease (COPD) account for more than half of the total COPD population but are often undiagnosed and sparsely studied. This real-world, longitudinal study compared the socioeconomic burden, clinical characteristics and treatment patterns in patients with mild COPD and age- and gender-matched controls.Patients and methods: Our population included mild COPD patients (forced expiratory volume in one second ≥ 80% of predicted value) and reference controls from 52 Swedish primary care centres over 15 years (2000– 2014). We linked electronic medical record (EMR) data to Sweden’s National Health Registries. The outcomes analyzed were socioeconomic status including annual income from work, presence of comorbidities and the use of medications.Results: 844 patients with mild COPD were included in this study and matched with 844 reference controls. Compared with the reference controls, mild COPD patients had a significantly lower annual income from work (mean difference, men: 12,559€ and women: 7143€) and were significantly less likely to be married or employed. The presence of comorbidities, including cardiovascular disease, anxiety and depression (only women) was significantly higher in mild COPD patients. The use of medications, such as proton pump inhibitors, antidepressants, central painkillers and sleep medications, was significantly higher in the mild COPD group.Conclusion: Mild COPD presents a considerable socioeconomic and clinical burden compared with reference controls The findings suggest that COPD constitutes a condition that influences health status even in mild disease clearly demanding an increased need for early detection and treatment.Keywords: chronic obstructive pulmonary disease, socioeconomic status, comorbidities, co-medications, annual income, exacerbation, Sweden

Acknowledgments: The iHARP database was funded by unrestricted grants from Mundipharma International Limited and Optimum Patient Care Global Ltd, which is a social enterprise that focuses on quality improvement in clinical practice. The sponsor was not involved in data analysis or the interpretation of the results.

Objective: Self-management is important for asthma control. We examined associations of patient- and healthcare-related factors with self-reported knowledge of self-management of worsening asthma.Methods: Two asthma patient cohorts from 2012 (n = 527) and 2015 (n = 915) were randomly selected from 54 primary health care centers (PHCC) in central Sweden. Data were collected using patient questionnaires and questionnaires to the PHCCs. Logistic regression analyzed associations of relevant variables with knowledge of self-management of worsening asthma.Results: In total, 63% of patients reported moderate to complete knowledge of self-management procedures. The adjusted OR for moderate to complete knowledge relative to high education level was 1.38 [95% CI 1.03-1.85)]; for physician continuity 2.19 (95% CI 1.62-2.96); for a written action plan 11.9 (95% CI 6.16-22.9); for Step 2 maintenance treatment 1.53 (95% CI 0.04-2.24); and 2.07 (95% CI 1.44-2.99) for Step 3. An asthma/COPD nurse visit within the previous 12 months was associated with greater knowledge in women but not in men (p for interaction = 0.042). Smoking [OR 0.56 (95% CI 0.34-0.95)], co-morbidities ≥1 [OR 0.68 (95% CI 0.49-0.93)], and self-rated moderate/severe disease [OR 0.68 (95% CI 0.51-0.90)] were associated with low self-management knowledge.Conclusion: Self-reported knowledge of self-management procedures was associated with a higher educational level, physician continuity, a written action plan, advanced treatment and, in women, visiting an asthma/COPD nurse. The results reinforce the importance of implementing guidelines of patient access to a specific physician, a written action plan, and structured education by an asthma/COPD nurse.

Aims and objective To investigate the effects on the quality of care of the Patient Report Informing Self-Management Support (PRISMS) form compared with usual care among patients with chronic obstructive pulmonary disease (COPD) consulting a COPD nurse in primary health care. Background Patients with COPD experience symptoms affecting their everyday lives, and there is a need for interventions in self-management support. The delivery of chronic care in an organised, structured and planned manner can lead to more productive relationships between professionals and patients. Design A multicentre randomised controlled trial with a post-test design, according to the CONSORT checklist, in one intervention group (n = 94) and one control group (n = 108). Methods In addition to usual care, the intervention group (n = 94) completed the PRISMS form to indicate areas where they wanted self-management support before the consultation with the COPD nurse. This form comprises 17 items that patients with COPD commonly experience as problems. The control group received usual care (n = 108). The primary outcome was patients' satisfaction with quality of care, assessed using the Quality from the Patient's Perspective (QPP) questionnaire. Means and (SD) are presented where applicable. Differences between the intervention and control group were analysed with Student's t test for independent groups for interval data, and the Mann-Whitney U test for ordinal data. Results Participants in the intervention group were more satisfied with the QPP domains "personal attention," regarding both "perceived reality" (p = .021) and "subjective importance" (p = .012). The PRISMS form revealed "shortness of breath" as the most commonly experienced problem and the issue most desired to discuss. Conclusion The PRISMS form improved patient satisfaction with quality of care regarding personal attention, which is an important factor in patient participation and improving relationships and communication. Relevance to clinical practice The PRISMS form can be a useful tool in improving person-centred care when delivering self-management support. Register id 192691 at http://www.researchweb.org/is/en/sverige/project/192691.

Background: This Swedish observational cohort study aimed to assess changes in patients’ perceived needs for information about COPD over 18 months and how these changes related to changes in patient characteristics. Methods: Data were obtained from 293 randomly selected primary care patients with COPD in GOLD stages 2-3. The Lung Information Needs Questionnaire (LINQ) was used to assess patients’ information needs at baseline and 18 months. Self-reported, descriptive patient data and spirometry results were collected. Results: Although the mean total LINQ score did not change between baseline and follow-up, 43.3% of the patients reported reduced and 56.7% increased or unchanged information needs. Reduced information needs were mainly associated with onset of pulmonary rehabilitation (OR=2.26 [95% CI 1.05-4.86]). Patients in a stable phase of COPD with no recent exacerbations tended to report greater needs than those with an unstable, deteriorated COPD. Conclusion: Patients’ information needs covary with current clinical status, so care providers should continuously be vigilant about offering patients support and education. Trial registration: Clinicaltrials.gov, 10 August 2014, Identifier NCT02213809.

Approximately 500 000 individuals in Sweden have chronic obstructive pulmonary disease (COPD). Co-morbid, especially cardiovascular, conditions are common in COPD and globally COPD is the third most common cause of mortality. Mortality in COPD is driven by dyspnea, exacerbations and comorbidities and is reduced by smoking cessation and lung rehabilitation. Also, pharmacological treatment, in particular inhaled corticosteroids, reduces mortality in COPD. The reduction in mortality that can be achieved by treatment with inhaled corticosteroids in combinations with long-acting bronchodilators is of the same order of magnitude as the effect on mortality by treatment of hyperlipidemia and hypertension.

Hanna Sandelowsky,1– 3 Björn Ställberg,4 Fredrik Wiklund,5 Gunilla Telg,6 Sofie de Fine Licht,6 Christer Janson7 1Karolinska Institutet, Department of Medicine, Division of Clinical Epidemiology, Solna, Sweden; 2Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Solna, Sweden; 3Academic Primary Health Care Centre, Region Stockholm, Sweden; 4Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 5Statisticon AB, Uppsala, Sweden; 6AstraZeneca Nordic, Södertälje, Sweden; 7Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, SwedenCorrespondence: Hanna Sandelowsky, Karolinska Institutet, Department of Medicine, Division of Clinical Epidemiology, Solna, Sweden, Tel +46738902565, Email hanna.sandelowsky@ki.seBackground: Symptom control has not improved in Swedish asthma patients during the last two decades. Guidelines recommend annual reviews for asthma patients treated with maintenance inhaled corticosteroids (ICS). We aimed to describe how visit patterns in an ICS-treated asthma population in Sweden were related to applicable asthma guidelines.Methods: Swedish electronic health data for incident asthma patients, ≥ 18 years, with at least one ICS collection (index date) between 2006 and 2017 were included. Exacerbations were defined as hospitalizations, emergency visits, or collection of oral corticosteroids (OCS). Probability of an asthma-related regular follow-up visit and probability of a follow-up visit after an exacerbation, both within 15 months, were estimated using the cumulative incidence function, time-to-event analysis, and incident rate ratios.Results: In 51,349 asthma patients (mean age 47.6 years, 63% females), 17,573 had a regular asthma visit in primary or secondary care within 15 months after the index, yielding an overall probability of a visit of 37.4%. Patients with a follow-up visit had higher ICS collection and lower OCS collection than patients without regular visits. Among 22,097 patients with acute exacerbations, the probability of a visit within 15 months after an exacerbation was 31.0%. The probability of having a visit increased during the study period.Conclusion: Only one-third of ICS-treated asthma patients, regardless of asthma severity, had a regular or post-exacerbation follow-up visit within a 15-month period. The consequences of this lack of adherence to guidelines need further evaluation to secure optimal asthma management.Keywords: asthma, disease management, follow-up visit, exacerbation

Hanna Sandelowsky,1– 3 Christer Janson,4 Fredrik Wiklund,5 Gunilla Telg,6 Sofie de Fine Licht,6 Björn Ställberg7 1Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden; 2Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Solna, Sweden; 3Academic Primary Health Care Centre, Region Stockholm, Stockholm, Sweden; 4Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 5Statisticon AB, Uppsala, Sweden; 6AstraZeneca Nordic, Stockholm, Sweden; 7Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, SwedenCorrespondence: Hanna Sandelowsky, Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, Tel +46738902565, Email hannasandelowsky@gmail.comObjective: The Swedish guidelines recommend that patients with chronic obstructive pulmonary disease (COPD) on maintenance treatment are monitored annually, and within six weeks after an exacerbation. We describe the patterns of COPD-related visits in Sweden, both regular follow-up and post-exacerbation visits.Methods: Patients (> 40 years) with a first-time COPD diagnosis between 2006 and 2017 were identified in primary care medical records and linked to hospital contacts and administered drug data. The index date was defined as the first collection of inhaled COPD maintenance treatment after the diagnosis. Regular COPD visits within 15-months after the index, and post-exacerbation visits for COPD within six weeks and 15-months after an exacerbation were estimated using the cumulative incidence function adjusted for competing risk. Visits without a ICD code for COPD were not included in the analyses.Results: A total of 19,857 patients (mean age 69 years, 57% females) were included. The overall probability of having a regular follow-up visit for COPD within 15 months post-index was 39.1%. In total, 15,095 (76%) patients experienced at least one COPD exacerbation during the observation period. Among them, the probability of having a post-exacerbation visit was 7.0% within six weeks and 29.7% within 15-months. Patients without a regular COPD follow-up visit claimed significantly more oral corticosteroids (25.6% vs 15.6%), more respiratory antibiotics (39.1% vs 23.1%), and less maintenance treatment (10.9% vs 16.5%).Conclusion: Only 39% of COPD patients attended a regular follow-up visit within 15-months from the COPD diagnosis and one-third had a post-exacerbation visit. The adherence to guideline recommendations need to be improved.Keywords: COPD, follow-up visit, exacerbation, guidelines

Objective: In Sweden, patients with chronic conditions, such as chronic obstructive pulmonary disease (COPD), often receive education at specialized nurse-led clinics at primary health care centers (PHCCs). Identifying patients’ needs for information about COPD is the key to individualized care. This study aimed to assess self-reported needs for information about COPD in primary care patients with either moderate (GOLD 2) or severe (GOLD 3) COPD and identify patient characteristics and exacerbation patterns associated with the findings. Design: A cross-sectional study. Setting: Twenty-four PHCCs in Stockholm, Sweden. Subjects: Randomly selected primary care patients with COPD in GOLD stages 2 and 3 (n = 542). Main outcome measures: The Lung Information Needs Questionnaire (LINQ) was used to assess perceived information needs. Spirometry results and descriptive, self-reported data on patient factors such as exacerbation history, treatment, smoking, weight/height, comorbidities, health care contacts, education and symptoms were collected. Results: Overall, the greatest reported needs were for information about self-management and diet. GOLD 2 patients (68%) expressed greater needs for information than GOLD 3 patients (32%). We found significant associations between high information needs and patient-related factors such as ‘No assigned GP’ (OR = 4.32 [95% CI 2.65–7.05]) and ‘No contact with COPD nurse in the past 12 months’ (OR = 1.83 [95% CI 1.19–2.81]). Conclusion: COPD patients felt they knew too little about self-management of their disease. Low information needs were strongly associated with continuity in patient-GP consultations and moderately associated with contact with a COPD nurse. These associations were strongest in patients with moderate COPD. Key points: As patients with COPD often have multimorbidity, identifying patients’ needs for information about COPD is essential to providing individualized patient education and care. In this study of 542 patients from 24 Swedish primary care centers, we found that:Patients with COPD, particularly those with moderate airflow limitation (i.e. GOLD 2) felt they needed more information about COPD than currently provided by health care professionals in primary care.Low information needs were strongly associated with continuity in patient-GP consultations and moderately associated with contact with a COPD nurse. GPs’ part in COPD patient education should not be overlooked, as individualized COPD care relies on GPs’ expertise in managing patients with multimorbidity. Patients with COPD, particularly those with moderate airflow limitation (i.e. GOLD 2) felt they needed more information about COPD than currently provided by health care professionals in primary care. Low information needs were strongly associated with continuity in patient-GP consultations and moderately associated with contact with a COPD nurse. GPs’ part in COPD patient education should not be overlooked, as individualized COPD care relies on GPs’ expertise in managing patients with multimorbidity.

Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD. Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization. Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P

Purpose: Women with chronic obstructive pulmonary disease (COPD) have more symptoms, more exacerbations, lower health status scores, and more comorbidity. However, it is unclear whether management of COPD differs by sex. The aim of the study was to investigate differences by sex in the care of patients with COPD. Patients and methods: The population included 1329 primary and secondary care patients with a doctor´s diagnosis of COPD in central Sweden. Data were obtained from patient questionnaires and included patient characteristics and data on achieved COPD care. Analyses included cross-tabulations, chi-squared test and multiple logistic regression using several measures in COPD management as dependent variables, female sex as independent variable, and with adjustment for age groups, previous exacerbations, COPD Assessment Test, level of dyspnea assessed by the modified Medical Research Council scale, comorbid conditions, self-rated moderate/severe disease, level of education and body mass index. Results: Women were more likely to receive triple therapy (OR 1.86 (95% CI 1.38-2.51)), to have any maintenance treatment (OR 1.82 (95% CI 1.31-2.55)), to be on sick leave (OR 2.16 (95% CI 1.19-3.93)), to have received smoking cessation support (OR 1.80 (95% CI 1.18-2.75)) and to have had pneumococcal vaccination (OR 1.82 (95% CI 1.37-2.43)), all independently of age, severity of disease or other potential confounders. Conclusion: Management of COPD differs by sex, with women being more actively managed than men. It is unclear whether this is due to patient- or care-related factors.

Ioanna Tsiligianni,1 Kristian Jong Hoeines,2 Christian Jensen,3 Janwillem WH Kocks,4– 6 Björn Ställberg,7 Claudia Vicente,8 Rudi Peché9 1Department of Social Medicine, University of Crete, Heraklion, Greece; 2Tananger Legesenter DA, Sola, Norway; 3Lægehuset Remisen, Præstø, Denmark; 4General Practitioners Research Institute, Groningen, the Netherlands; 5University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands; 6Observational and Pragmatic Research Institute, Singapore; 7Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 8Unidade Saúde Familiar Araceti, Arazede, Portugal; 9Department of Pneumology, ISPPC, CHU Charleroi, Charleroi, BelgiumCorrespondence: Ioanna TsiligianniDepartment of Social Medicine, University of Crete, Voutes Campus, Heraklion, Crete, 71003, GreeceTel +30 2810394607Email i.tsiligianni@uoc.grAbstract: COPD is a chronic disease, typically accompanied by multiple comorbid conditions. The need to apply several, and sometimes conflicting, disease-specific treatment guidelines, complicates the management of individual patients. Moreover, national and international recommendations evolve rapidly but provide limited guidance on the integrated approach in the multimorbid patient. Particularly bothersome is the fact that the presence of comorbidities may deteriorate the course of COPD, and inversely COPD may affect the outcome of the comorbid diseases. In addition, some effects of commonly prescribed COPD inhaler medications, including beta2-agonists, long-acting antimuscarinics and especially inhaled corticosteroids, mimic or worsen COPD-related comorbidities. Therefore, the authors combined their perspectives to formulate advice that may help physicians to improve COPD patient care in daily practice when comorbidities are present. Diabetes, atrial fibrillation, osteoporosis/fractures, infections (pneumonia and tuberculosis) and asthma were identified as areas where practicing clinicians should give special attention to the risk-benefit ratio of the inhaled medication. Overall, the presence of multimorbidity in a COPD patient should act as a signal to carefully reconsider the treatment choices.Keywords: comorbidity, multimorbidity, polypharmacy, inhaler medication

Kjell Larsson,1 Christer Janson,2 Karin Lisspers,3 Björn Ställberg,3 Gunnar Johansson,3 Florian S Gutzwiller,4 Karen Mezzi,4 Bine Kjoeller Bjerregaard,5 Leif Jorgensen5 1Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; 2Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 3Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 4Novartis Pharma AG, Global Patient Access, Basel, Switzerland; 5IQVIA Solutions, Real World Evidence Solutions, Copenhagen, DenmarkCorrespondence: Kjell LarssonIntegrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institute, Stockholm, SE-171 77, SwedenTel +467 0582 0763Email kjell.larsson@ki.sePurpose: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD.Patients and Methods: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000– 2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥ 2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis.Results: In total 18,586 COPD patients were analyzed. A majority of the patients (60– 70%) who either have had no exacerbation or frequent exacerbations (≥ 2/year) during the pre-index period remained in their group (ie, with 0 or ≥ 2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93– 2.20]) and ≥ 2 (4.58 [4.33– 4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥ 2/year) than in patients with no or one exacerbation annually (p< 0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis.Conclusion: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.Keywords: chronic obstructive pulmonary disease, exacerbations, mortality, lung function, healthcare cost, Sweden

BACKGROUND: Asthma severity can be estimated as the level of medication needed to achieve asthma control or by the patient's subjective assessment. Factors associated with self-assessed asthma severity are still incompletely explored. AIM: The aim was to study factors associated with self-assessed moderate or severe asthma. METHOD: In total, 1828 randomly selected asthma patients from primary (69%) and secondary (31%) care, completed a questionnaire including items about patient characteristics, comorbidity, the Asthma Control Test (ACT), emergency care visits and a scale for self-assessed asthma severity. Logistic regression was used to analyze associations with the dependent variable, self-assessed moderate or severe asthma in the entire study population and stratified by sex. RESULTS: Of the patients, 883 (45%) reported having moderate or severe asthma. Factors independently associated with self-assessed moderate or severe asthma were age >60 years (OR [95% CI] 1.98 [1.37-2.85]), allergic rhino-conjunctivitis (1.43 [1.05-1.95]), sinusitis (1.45 [1.09-1.93]), poor asthma control as measured by ACT

Objective The ability to predict impending asthma exacerbations may allow better utilization of healthcare resources, prevention of hospitalization and improve patient outcomes. We aimed to develop models using machine learning to predict risk of exacerbations. Methods Data from 29,396 asthma patients was collected from electronic medical records and national registers covering clinical and epidemiological factors (e.g. comorbidities, health care contacts), between 2000 and 2013. Machine-learning classifiers were used to create models to predict exacerbations within the next 15 days. Model selection was done using the mean cross validation score of area under precision-recall curve (AUPRC). Results The most important predictors of exacerbation were comorbidity burden and previous exacerbations. Model validation on test data yielded an AUPRC = 0.007 (95% CI: ± 0.0002), indicating that historic clinical information alone may not be sufficient to predict a near future risk of asthma exacerbation. Conclusions Supplementation with additional data on environmental triggers, (e.g. weather, pollen count, air quality) and from wearables, might be necessary to improve performance of the short-term predictive model to develop a more clinically useful tool.

Björn Ställberg,1 Karin Lisspers,1 Kjell Larsson,2 Christer Janson,3 Mario Müller,4 Mateusz Łuczko,5 Bine Kjøller Bjerregaard,6 Gerald Bacher,7 Björn Holzhauer,7 Pankaj Goyal,7 Gunnar Johansson1 1Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 2Integrative Toxicology, Karolinska Institutet, Stockholm, Sweden; 3Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 4Department of Data Science and Advanced Analytics, IQVIA, Frankfurt Am Main, Germany; 5Department of Data Science and Advanced Analytics, IQVIA, Warsaw, Poland; 6Department of Real World Evidence Solutions, IQVIA, Copenhagen, Denmark; 7Department of Clinical Development and Analytics, Novartis Pharma AG, Basel, SwitzerlandCorrespondence: Björn StällbergDepartment of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Box 564, Uppsala, SE-75122, SwedenTel +46-070-3149944Email b.stallberg@telia.comPurpose: Chronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations. We aimed to develop a model that predicts a patient’s risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data.Patients and Methods: Patient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013. Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days. Exacerbations occurring within this period were considered as one event. Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC). To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported. The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset.Results: The most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden. Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation.Conclusion: Our work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations.Keywords: COPD, machine learning, exacerbation, hospitalization

BACKGROUND: Underlying mechanism leading to impaired lung function are incompletely understood. OBJECTIVES: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function. METHODS: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV1%) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality. MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis, 22 proteins were associated with lower FEV1% in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV1%. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV1% per standard deviation of protein level -1.4, (95% CI, -2.5 to -0.3) for GDF-15, and -0.8, (95% CI, -1.5 to -0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV1%. CONCLUSIONS: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.