Publications by authors named "Gunnar Johansson"

127 Publications

Treatment Patterns, Socioeconomic Status and Clinical Burden in Mild COPD: A Swedish Real-World, Retrospective Cohort Study, the ARCTIC Study.

Int J Chron Obstruct Pulmon Dis 2022 21;17:1409-1421. Epub 2022 Jun 21.

Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Background: 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.
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http://dx.doi.org/10.2147/COPD.S364932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233559PMC
June 2022

Developing a short-term prediction model for asthma exacerbations from Swedish primary care patients' data using machine learning - Based on the ARCTIC study.

Respir Med 2021 Aug-Sep;185:106483. Epub 2021 May 26.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.1016/j.rmed.2021.106483DOI Listing
January 2022

The Impact of Exacerbation Frequency on Clinical and Economic Outcomes in Swedish COPD Patients: The ARCTIC Study.

Int J Chron Obstruct Pulmon Dis 2021;16:701-713. Epub 2021 Mar 18.

IQVIA Solutions, Real World Evidence Solutions, Copenhagen, Denmark.

Purpose: 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.
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http://dx.doi.org/10.2147/COPD.S297943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987259PMC
June 2021

Predicting Hospitalization Due to COPD Exacerbations in Swedish Primary Care Patients Using Machine Learning - Based on the ARCTIC Study.

Int J Chron Obstruct Pulmon Dis 2021;16:677-688. Epub 2021 Mar 16.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

Purpose: 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.
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http://dx.doi.org/10.2147/COPD.S293099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981164PMC
June 2021

Inhaled corticosteroids and the risk of type 2 diabetes among Swedish COPD patients.

NPJ Prim Care Respir Med 2020 10 20;30(1):47. Epub 2020 Oct 20.

Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.
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http://dx.doi.org/10.1038/s41533-020-00207-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576803PMC
October 2020

Inhibition properties of free and conjugated leupeptin analogues.

FEBS Open Bio 2020 12 2;10(12):2605-2615. Epub 2020 Nov 2.

Department of Chemistry-BMC, Biochemistry, Uppsala University, Uppsala, Sweden.

Leupeptin is a naturally occurring inhibitor of various proteases, in particular serine proteases. Following its discovery, the inhibitory properties of several other peptidyl argininals have been studied. The specificity of leupeptin is most likely due to the Leu-Leu-Argininal sequence, and its C-terminal aldehyde group has been suggested to enhance the binding efficiency and to be essential for function. The terminal aldehyde group makes the structure less vulnerable to carboxypeptidases. Here, we investigated whether the inhibitory function of leupeptin toward serine proteases is retained after oxidation or reduction of the aldehyde group. The oxidized form, which corresponds to the natural precursor, was shown to be superior to the reduced form in terms of inhibitory properties. However, the original leupeptin possessed enhanced inhibitory properties as compared with the oxidized form. Based on these results, new synthetic leupeptin analogues, 6-aminohexanoic acid (Ahx)-Phe-Leu-Arg-COOH and Ahx-Leu-Leu-Arg-COOH, were prepared by solid-phase peptide synthesis using the Fmoc strategy. In these analogues, the N-terminal capping acetyl group was replaced with a 6-aminohexanoyl group to allow conjugation. The structures of the modified leupeptin and the synthetic peptides were confirmed by mass spectrometry. Determination of the inhibitory properties against trypsin (IEC 3.4.21.4, Chymotrypsin IEC 3.4.21.1) revealed that these further modified tripeptides were tight binding inhibitors to their target enzyme, similar to the naturally occurring leupeptin, with K values generally in the micromolar range. The Ahx-Phe-Leu-Arg-COOH analogue was selected for conjugation to inorganic oxide nanoparticles and agarose gel beads. All conjugates exhibited inhibitory activity in the same range as for the free peptides.
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http://dx.doi.org/10.1002/2211-5463.12994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714073PMC
December 2020

Osteoporosis and fracture risk associated with inhaled corticosteroid use among Swedish COPD patients: the ARCTIC study.

Eur Respir J 2021 02 17;57(2). Epub 2021 Feb 17.

Intergrative Toxicology, National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.
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http://dx.doi.org/10.1183/13993003.00515-2020DOI Listing
February 2021

Impact of Comorbidities and Commonly Used Drugs on Mortality in COPD - Real-World Data from a Primary Care Setting.

Int J Chron Obstruct Pulmon Dis 2020 3;15:235-245. Epub 2020 Feb 3.

Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Background: Life expectancy is significantly shorter for patients with chronic obstructive pulmonary disease (COPD) than the general population. Concurrent diseases are known to infer an increased mortality risk in those with COPD, but the effects of pharmacological treatments on survival are less established. This study aimed to examine any associations between commonly used drugs, comorbidities and mortality in Swedish real-world primary care COPD patients.

Methods: Patients with physician-diagnosed COPD from a large primary care population were observed retrospectively, utilizing primary care records and mandatory Swedish national registers. The time to all-cause death was assessed in a stepwise multiple Cox proportional hazards regression model including demography, socioeconomic factors, exacerbations, comorbidities and medication.

Results: During the observation period (1999-2009) 5776 (32.5%) of 17,745 included COPD patients died. Heart failure (hazard ratio [HR]: 1.88, 95% confidence interval [CI]: 1.74-2.04), stroke (HR: 1.52, 95% CI: 1.40-1.64) and myocardial infarction (HR: 1.40, 95% CI: 1.24-1.58) were associated with an increased risk of death. Use of inhaled corticosteroids (ICS; HR: 0.79, 95% CI: 0.66-0.94), beta-blockers (HR: 0.86, 95% CI: 0.76-0.97) and acetylsalicylic acid (ASA; HR: 0.87, 95% CI: 0.77-0.98) was dose-dependently associated with a decreased risk of death, whereas use of long-acting muscarinic antagonists (LAMA; HR: 1.33, 95% CI: 1.14-1.55) and N-acetylcysteine (NAC; HR: 1.26, 95% CI: 1.08-1.48) were dose-dependently associated with an increased risk of death in COPD patients.

Conclusion: This large, retrospective, observational study of Swedish real-world primary care COPD patients indicates that coexisting heart failure, stroke and myocardial infarction were the strongest predictors of death, underscoring the importance of timely recognition and treatment of comorbidities. A decreased risk of death associated with the use of ICS, beta-blockers and ASA, and an increased risk associated with the use of LAMA and NAC, was also found.
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http://dx.doi.org/10.2147/COPD.S231296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006848PMC
February 2021

The Genetic Architecture of Gliomagenesis-Genetic Risk Variants Linked to Specific Molecular Subtypes.

Cancers (Basel) 2019 Dec 12;11(12). Epub 2019 Dec 12.

Department of Radiation Sciences, Oncology, Umeå University, 901 87 Umeå, Sweden.

Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including -mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in and were associated with increased risk of all glioma subtypes. Second, variants in , , and were associated with -wildtype glioma. Third, variants in (the 8q24 locus), (close to ), , , , and were associated with -mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.
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http://dx.doi.org/10.3390/cancers11122001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966482PMC
December 2019

Gender differences among Swedish COPD patients: results from the ARCTIC, a real-world retrospective cohort study.

NPJ Prim Care Respir Med 2019 12 10;29(1):45. Epub 2019 Dec 10.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000-2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.
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http://dx.doi.org/10.1038/s41533-019-0157-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904454PMC
December 2019

Characterization of Serine Protease Inhibitor from Conjugated to Soluble Dextran and Particle Carriers.

ACS Omega 2019 Nov 25;4(19):18456-18464. Epub 2019 Oct 25.

Department of Chemistry-BMC, Uppsala University, P.O. Box 576, SE-751 23 Uppsala, Sweden.

A serine protease inhibitor was extracted from potato tubers. The inhibitor was conjugated to soluble, prefractionated dextran and titanium dioxide and zinc oxide nanoparticles. Conjugation to dextran was achieved by periodate oxidation of the dextran, followed by Schiff base coupling to inhibitor amino groups, and finally reduction, whereas the conjugation to the oxide particles was carried out by aminosilanization and carbonyldiimidazole activation. The inhibitory effect of the conjugated inhibitor was compared to that of free inhibitor in solution and with gelatin gel as a direct substrate. A certain degree of inhibitory activity was retained for both the dextran-conjugated and particle-conjugated inhibitors. In particular, the apparent value of the dextran-conjugated inhibitor was found to be in the same range as that for free inhibitor. The dextran conjugate retained a higher activity than the free inhibitor after 1 month of storage at room temperature.
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http://dx.doi.org/10.1021/acsomega.9b02815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844106PMC
November 2019

Real-world evidence effect of budesonide+formoterol Spiromax on patients with asthma and chronic obstructive pulmonary disease in Sweden.

Eur Clin Respir J 2019 13;6(1):1660565. Epub 2019 Sep 13.

Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

 Despite improved asthma and chronic obstructive pulmonary disease (COPD) management, treatment remains inadequate in many patients. Understanding the impact of current treatment in settings outside of controlled trials would add important clinical decision-making information. This study evaluated costs and outcomes associated with budesonide+formoterol (BF) Spiromax® initiation among real-world Swedish patients with asthma and/or COPD. In this retrospective observational analysis of Swedish patients with asthma and/or COPD, data were collected from the National Patient Register, National Dispensed Drug Register, and Cause of Death Register 1 year before and after initiating BF Spiromax (index date). Outcomes included exacerbation occurrence, treatment patterns, inpatient care, and healthcare costs. The study included 576 patients (asthma: 51.6%; COPD: 32.8%; and asthma and COPD: 15.6%). Following BF Spiromax initiation in asthma patients, there were significant decreases in exacerbations (41.1% to 30.0%; < 0.001), mean comorbidity-related inpatient visits (0.5 to 0.2; < 0.001), and inpatient days (1.9 to 0.6; = 0.006), and a trend toward fewer asthma-related inpatient visits (mean, 0.2 to 0.1; = 0.056) and asthma-related inpatient days (mean, 0.7 to 0.3; = 0.060). Increased inpatient utilization was observed in patients with COPD or both diagnoses. All-cause and asthma-/COPD-related medication costs decreased in all groups. After switching to BF Spiromax, asthma patients had fewer exacerbations and hospital visits versus the prior year and COPD patients showed an increase in all-cause and COPD-related healthcare resource utilization. All-cause and asthma-/COPD-related medication costs decreased in all groups after switching to BF Spiromax.
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http://dx.doi.org/10.1080/20018525.2019.1660565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6758718PMC
September 2019

Light scattering determination of the stoichiometry for protease-potato serine protease inhibitor complexes.

Anal Biochem 2019 10 2;582:113357. Epub 2019 Jul 2.

Department of Chemistry - BMC Uppsala University, Box 576, SE-751 23, Uppsala, Sweden. Electronic address:

The interaction between pancreatic proteases and a serine protease inhibitor purified from potato tubers was investigated by chromatography-coupled light scattering measurements. The molar mass distribution in the chromatogram was compared to theoretical values calculated for the different possible combinations of complexes and free components by three different approaches, namely section analyses of the chromatograms, full mass average determination and mass distribution analysis. This revealed that the inhibitor was able to bind trypsin in a 2:1 complex, whereas the data for chymotrypsin clearly showed a limitation to 1:1 complex regardless of the molar ratio in the injected samples. The same experiment carried out with elastase and the potato inhibitor gave only weak indications of complex formation under the conditions used.
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http://dx.doi.org/10.1016/j.ab.2019.113357DOI Listing
October 2019

Impact of COPD diagnosis timing on clinical and economic outcomes: the ARCTIC observational cohort study.

Int J Chron Obstruct Pulmon Dis 2019 13;14:995-1008. Epub 2019 May 13.

Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD. 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. 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%; <0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; <0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; <0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; =0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis. Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.
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http://dx.doi.org/10.2147/COPD.S195382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526023PMC
January 2020

Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden).

PLoS One 2018 21;13(12):e0209268. Epub 2018 Dec 21.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Objective: Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD).

Methods: Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69-81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years.

Results: There was a significant genetic association with circulating levels of 25(OH)D (4.6-18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p < 0.005).

Conclusions: Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209268PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303094PMC
May 2019

The association between longer relative leukocyte telomere length and risk of glioma is independent of the potentially confounding factors allergy, BMI, and smoking.

Cancer Causes Control 2019 Feb 17;30(2):177-185. Epub 2018 Dec 17.

Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden.

Purpose: Previous studies have suggested an association between relative leukocyte telomere length (rLTL) and glioma risk. This association may be influenced by several factors, including allergies, BMI, and smoking. Previous studies have shown that individuals with asthma and allergy have shortened relative telomere length, and decreased risk of glioma. Though, the details and the interplay between rLTL, asthma and allergies, and glioma molecular phenotype is largely unknown.

Methods: rLTL was measured by qPCR in a Swedish population-based glioma case-control cohort (421 cases and 671 controls). rLTL was related to glioma risk and health parameters associated with asthma and allergy, as well as molecular events in glioma including IDH1 mutation, 1p/19q co-deletion, and EGFR amplification.

Results: Longer rLTL was associated with increased risk of glioma (OR = 1.16; 95% CI 1.02-1.31). Similar to previous reports, there was an inverse association between allergy and glioma risk. Specific, allergy symptoms including watery eyes was most strongly associated with glioma risk. High body mass index (BMI) a year prior diagnosis was significantly protective against glioma in our population. Adjusting for allergy, asthma, BMI, and smoking did not markedly change the association between longer rLTL and glioma risk. rLTL among cases was not associated with IDH1 mutation, 1p/19q co-deletion, or EGFR amplification, after adjusting for age at diagnosis and sex.

Conclusions: In this Swedish glioma case-control cohort, we identified that long rLTL increases the risk of glioma, an association not confounded by allergy, BMI, or smoking. This highlights the complex interplay of the immune system, rLTL and cancer risk.
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http://dx.doi.org/10.1007/s10552-018-1120-2DOI Listing
February 2019

Incidence of cardiovascular diseases and type-2-diabetes mellitus in patients with psychiatric disorders.

Nord J Psychiatry 2018 Oct 4;72(7):455-461. Epub 2018 Dec 4.

b Paris Cardiovascular Research Centre , University Paris Descartes, Sorbonne Paris Cité , Paris , France.

Objective: To assess the incidence of cardiovascular diseases (CVD) and type-2-diabetes in patients with psychiatric disorders.

Methods: A population-based study was conducted using the Swedish national health registries. Patients were identified from the Electronic Medical Records (EMR) in 20 primary care centers and were categorized in four diagnosis cohorts according to their first psychiatric diagnosis: bipolar disorder, schizophrenia, major depressive disorder, or other mood disorder. A control cohort of patients with no psychiatric disorders followed in the same primary care centers was also identified. Incident CVD and type-2-diabetes were defined as the presence of a diagnosis of CVD or diabetes during the follow-up period in patients without prior event.

Results: The age and sex standardized incidence rate of CVD was 13.5 per 1000 patient-year in the patients with any psychiatric disorder versus 6.3 per 1000 patient-year in the controls. A similar trend was observed for incident diabetes (5.7 versus 3.4 per 1000 patient-year, respectively). The bipolar disorder and the schizophrenia cohorts showed the highest standardized incidence rates.

Conclusion: Incidence of CVD and to a lesser extent type-2-diabetes was particularly high in patients with psychiatric disorders. This carries strong clinical implications for the prevention of CVD and type-2-diabetes in these patients.
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http://dx.doi.org/10.1080/08039488.2018.1463392DOI Listing
October 2018

Real-world retrospective cohort study ARCTIC shows burden of comorbidities in Swedish COPD versus non-COPD patients.

NPJ Prim Care Respir Med 2018 09 10;28(1):33. Epub 2018 Sep 10.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014. These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population. A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population. A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs. 30.7%). Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients. Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001). The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.
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http://dx.doi.org/10.1038/s41533-018-0101-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131165PMC
September 2018

 Identifying the associated risks of pneumonia in COPD patients: ARCTIC an observational study.

Respir Res 2018 Sep 10;19(1):172. Epub 2018 Sep 10.

Karolinska Institutet, Solna, Sweden.

Background: Inhaled corticosteroids (ICS) are associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD). Other factors such as severity of airflow limitation and concurrent asthma may further raise the possibility of developing pneumonia. This study assessed the risk of pneumonia associated with ICS in patients with COPD.

Methods: Electronic Medical Record data linked to National Health Registries were collected from COPD patients and matched reference controls in 52 Swedish primary care centers (2000-2014). Levels of ICS treatment (high, low, no ICS) and associated comorbidities were assessed. Patients were categorized by airflow limitation severity.

Results: A total of 6623 patients with COPD and 48,566 controls were analyzed. Patients with COPD had a more than 4-fold increase in pneumonia versus reference controls (hazard ratio [HR] 4.76, 95% confidence interval [CI]: 4.48-5.06). ICS use increased the risk of pneumonia by 20-30% in patients with COPD with forced expiratory volume in 1 s ≥ 50% versus patients not using ICS. Asthma was an independent risk factor for pneumonia in the COPD population. Multivariate analysis identified independent predictors of pneumonia in the overall population. The highest risk of pneumonia was associated with high dose ICS (HR 1.41, 95% CI: 1.23-1.62).

Conclusions: Patients with COPD have a greater risk of pneumonia versus reference controls; ICS use and concurrent asthma increased the risk of pneumonia further.
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http://dx.doi.org/10.1186/s12931-018-0868-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131919PMC
September 2018

Health care resource utilization and cost for asthma patients regularly treated with oral corticosteroids - a Swedish observational cohort study (PACEHR).

Respir Res 2018 Sep 3;19(1):168. Epub 2018 Sep 3.

The National Institute of Environmental Medicine, Karolinska Institute, Solna, Sweden.

Background: Patients with severe uncontrolled asthma may receive oral corticosteroid (OCS) treatment regularly. The present study investigated the health care resource utilization and cost in regularly OCS treated Swedish asthma patients.

Methods: Primary care medical records data were linked to data from Swedish national health registries. Patients ≥18 years with a drug claim for obstructive pulmonary diseases during 2007-2009 (index date) and a prior asthma diagnosis, were classified by their OCS claims during the 12-months' post index period: regular OCS equals ≥5 mg per day; periodic OCS less than 5 mg per day; or non-OCS users. Cost of asthma- and OCS-morbidity-related health care resource utilization were calculated.

Results: A total of 15,437 asthma patients (mean age 47.8, female 62.6%), whereof 223 (1.44%) were regular OCS users, 3054 (19.7%) were periodic, and 12,160 (78.7%) were non-OCS users. Regular OCS users were older and more often females, had lower lung function, greater eosinophil count and more co-morbidities at baseline compared with the other groups. Age-adjusted annual total health care cost was three-times greater in the regular OCS group (€5615) compared with the non-OCS users (€1980) and twice as high as in the periodic OCS group (€2948). The major cost driver in the non-OCS and periodic OCS groups were primary care consultations, whereas inpatient costs were the major cost driver in the regular OCS group. The asthma related costs represented 10-12% of the total cost in all three groups.

Conclusion: In this real-life asthma study in Sweden, the total yearly cost of health care resource utilization for a regular OCS user was three times greater than for a patient with no OCS use, indicating substantial economic and health care burden for asthma patients on regular oral steroid treatment.
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http://dx.doi.org/10.1186/s12931-018-0855-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122138PMC
September 2018

Prevalence, characteristics and management of frequently exacerbating asthma patients: an observational study in Sweden (PACEHR).

Eur Respir J 2018 08 2;52(2). Epub 2018 Aug 2.

The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

The aim of the study was to investigate the prevalence, management and characteristics of asthma patients with frequent exacerbations.Data from asthma patients (aged ≥18 years) identified in primary care medical records were linked to Swedish national health registries. Exacerbations were defined as hospitalisations, emergency visits and/or collection of oral steroids. Frequent exacerbations were defined as two or more exacerbations per year during the 3-year observation period.Of 18 724 asthma patients, 81.49% had no exacerbations and 6.3% had frequent exacerbations in the year prior to the index date. Frequent exacerbations were observed yearly for 1.8% of the patients. Frequent exacerbators were older, more often females, and had increased eosinophil and neutrophil counts, lower lung function, and more comorbidities than patients without exacerbations. There was a slight increase in asthma medication claims and a slight decrease in physician visits compared with baseline, both in the group with and the group without frequent exacerbations.Patients with frequent exacerbations were characterised by greater age, female predominance, high eosinophil and neutrophil counts, and high prevalence of comorbidities. This study indicates that the Swedish healthcare system lacks efficiency to adjust treatment and management for this patient group. With new treatment options targeting severe asthma available, identification of these patients should be in focus to ensure reduction of exacerbations.
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http://dx.doi.org/10.1183/13993003.01927-2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092688PMC
August 2018

Factors associated with lung cancer in COPD patients.

Int J Chron Obstruct Pulmon Dis 2018 6;13:1833-1839. Epub 2018 Jun 6.

Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Background: The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls. The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers.

Methods: To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients. Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392).

Results: Of the total cohort, 19,894 patients were included in the study. Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population. In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41-0.71), while the risk of lung cancer increased with increasing age. A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37-0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15-2.16).

Conclusion: In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk. The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies.
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http://dx.doi.org/10.2147/COPD.S162484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995277PMC
January 2019

[Protein deficiency - a rare nutrient deficiency].

Authors:
Gunnar Johansson

Lakartidningen 2018 05 21;115. Epub 2018 May 21.

Saknas - Saknas Halmstad, Sweden Saknas - Saknas Halmstad, Sweden.

There is a widespread myth that we have to be careful about what we eat so that we do not cause protein deficiency. We know today that it is virtually impossible to design a calorie-sufficient diet, whether it is based on meat, fish, eggs, various vegetarian diets or even unprocessed whole natural plant foods, which is lacking in protein and any of the amino acids. The body is capable of taking incomplete proteins and making them complete by utilizing the amino acid recycling mechanism. The majority of amino acids absorbed from the intestinal tract are derived from recycled body protein. Research shows that high levels of animal protein intake may significantly increase the risk of premature mortality from all causes, among them cardiovascular diseases, cancer and type 2 diabetes.
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May 2018

A clinical follow-up of omalizumab in routine treatment of allergic asthma monitored by CD-sens.

Immun Inflamm Dis 2018 09 7;6(3):382-391. Epub 2018 May 7.

Department of Clinical Science and Education, Södersjukhuset and Karolinska Institutet, Stockholm, Sweden.

Introduction: Omalizumab has been available for treatment of allergic asthma for more than a decade and thus, its efficacy in routine treatment was of interest to evaluate. Basophil allergen threshold sensitivity (CD-sens) has been shown to correlate with the bronchial allergen threshold sensitivity and can be used to objectively measure omalizumab treatment efficacy. We aimed to evaluate the effect of omalizumab treatment of allergic asthma by CD-sens, as an objective marker of the IgE-mediated inflammation, and related to SPT, spirometry, FeNO, Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE).

Methods: Thirty-two patients were treated with omalizumab for 16 weeks. CD-sens was used to define the response and related to clinical parameters. If CD-sens was negative (<0.1) (CD-sens low Group) the patient continued with the standard dose. If CD-sens was ≥0.1 (CD-sens high Group) a second 16 weeks period with 25-50% dosage increase was started and evaluated after a total of 32 weeks.

Results: Nine of 32 patients became CD-sens negative after treatment (CD-sens start: 8.0; 16 weeks: <0.01) and regarded as successful. 15/23 were unsuccessful (CD-sens start: 13; 16 weeks: 1.65) and the omalizumab dose was increased. CD-sens decreased significantly (p < 0.05) and further 3/15 patients became CD-sens negative (CD-sens at 32 weeks: 0.5). There was a significantly smaller IgE-ab fraction (IgE-ab/IgE) in the CD-sens low versus the CD-sens high Group (p < 0.0001). A significant decrease in ACQ was seen in both groups after 16 weeks treatment (p = 0.05 and 0.01, respectively). No significant changes could be detected for the other clinical parameters.

Conclusion: By the use of the objective laboratory method CD-sens, which effectively measure the direct effect of omalizumab, that is, the IgE-mediated part of the allergic asthma, in combination with clinical parameters it might be possible to more effectively monitor and treat IgE-mediated allergic asthma.
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http://dx.doi.org/10.1002/iid3.225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113766PMC
September 2018

Comorbidity, disease burden and mortality across age groups in a Swedish primary care asthma population: An epidemiological register study (PACEHR).

Respir Med 2018 03 31;136:15-20. Epub 2018 Jan 31.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.

Background: Asthma is often associated with other diseases. To identify and manage comorbidities is important, as these conditions may increase the disease burden.

Objective: To describe the prevalence of comorbidities, disease burden and mortality across age groups in a large Swedish primary care real-life asthma population.

Methods: Observational cohort study of asthma patients, all ages, identified from electronic medical records by ICD-10-CM code, data from 36 primary care centers. Data were linked to national mandatory Swedish health registers. Comorbidities were identified by ICD-10-CM codes and collected from electronic medical records and the National Patient Registers, mortality data from the Cause of Death Register. Exacerbations were defined as hospitalizations due to asthma, and/or emergency visits at hospital and/or prescription claims of oral steroids.

Results: In total 33,468 patients (58% women) were included. The most prevalent comorbidities were acute upper respiratory tract infection (53%), rhinitis (25%), acute lower respiratory tract infection (25%), hypertension (21%), anxiety and depression (20%). The comorbidities associated with highest risk for an exacerbation were COPD OR 1.98 (95%CI: 1.80-2.19), nasal polyps OR 1.75 (95%CI: 1.49-2.05) and rhinitis OR 1.52 (95%CI: 1.41-1.63). All-cause mortality was similar to the Swedish population, 1011 deaths per 100,000 person/year compared with 1058 deaths (standardized risk = 0.99 [95%CI:0.95-1.04]). The pulmonary related death rate was greater in the study population versus the Swedish population (122 versus 72 per 100,000person/year).

Conclusion: Comorbid disease was frequent in this large real-life asthma population with an impact on exacerbations. To identify and treat comorbidities with impact on asthma outcomes are essential to improve asthma care.
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http://dx.doi.org/10.1016/j.rmed.2018.01.020DOI Listing
March 2018

Kinetic studies of serine protease inhibitors in simple and rapid 'active barrier' model systems - Diffusion through an inhibitor barrier.

Anal Biochem 2018 04 31;546:43-49. Epub 2018 Jan 31.

Department of Chemistry - BMC Uppsala University, Box 576, SE-751 23 Uppsala, Sweden. Electronic address:

A model based on gelatin for protease activity studies was designed. The model is also extended to study the efficiency of inhibitors in a separate protective layer covering the layer containing the target substrate. A good correlation between protease concentration and the size of erosion wells formed in a plain gelatin layer was observed. Similarly, increased concentration of inhibitors gave a systematic decrease in well area. Kinetic analyses of the two-layer model in a spectrophotometric plate reader with a fixed concentration of substrate in the bottom layer displayed a strict dependence of both inhibitor concentration and thickness of the top "protective" layer. An apparent, but weaker inhibition effect was also observed without inhibitors due to diffusional and erosion delay of enzyme transport to the substrate-containing layer.
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http://dx.doi.org/10.1016/j.ab.2018.01.022DOI Listing
April 2018

Economic burden of COPD in a Swedish cohort: the ARCTIC study.

Int J Chron Obstruct Pulmon Dis 2018 11;13:275-285. Epub 2018 Jan 11.

Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala.

Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting.

Patients And Methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed.

Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population (€13,179) versus the reference population (€2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (~€28,000 per patient) were the largest economic burden in COPD patients of working age during 2013.

Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.
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http://dx.doi.org/10.2147/COPD.S149633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769573PMC
September 2018

Exacerbations and healthcare resource utilization among COPD patients in a Swedish registry-based nation-wide study.

BMC Pulm Med 2018 Jan 25;18(1):17. Epub 2018 Jan 25.

EPID Research, Metsänneidonkuja 12, FI-02130, Espoo, Finland.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality. We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.

Methods: Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death. Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits. Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.

Results: In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.

Conclusions: COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.
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http://dx.doi.org/10.1186/s12890-018-0573-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784707PMC
January 2018

Prevalence and management of severe asthma in primary care: an observational cohort study in Sweden (PACEHR).

Respir Res 2018 01 18;19(1):12. Epub 2018 Jan 18.

Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

Background: Severe and uncontrolled asthma is associated with increased risk of exacerbations and death. A substantial proportion of asthma patients have poor asthma control, and a concurrent COPD diagnosis often increases disease burden. The objective of the study was to describe the prevalence and managemant of severe asthma in a Swedish asthma popuöation.

Methods: In this observational cohort study, primary care medical records data (2006-2013) from 36 primary health care centers were linked to data from national mandatory Swedish health registries. The studied population (>18 years) had a record of drug collection for obstructive pulmonary disease (ATC code R03) during 2011-2012, and a physician diagnosed asthma (ICD-10 code J45-J46) prior to drug collection. Severe asthma was classified as collection of high dose inhaled steroid (> 800 budesonide or equivalent per day) and leukotriene receptor antagonist and/or long-acting beta-agonist. Poor asthma control was defined as either collection of ≥600 doses of short-acting beta-agonists, and/or ≥1 exacerbation(s) during the year post index date.

Results: A total of 18,724 asthma patients (mean 49 years, 62.8% women) were included, of whom 17,934 (95.8%) had mild to moderate and 790 (4.2%) had severe asthma. Exacerbations were more prevalent in severe asthma (2.59 [2.41-2.79], Relative Risk [95% confidence interval]; p < 0.001). Poor asthma control was observed for 28.2% of the patients with mild to moderate asthma and for more than half (53.6%) of the patients with severe asthma (<0.001). Prior to index, one in five severe asthma patients had had a contact with secondary care and one third with primary care. A concurrent COPD diagnosis increased disease burden.

Conclusion: Severe asthma was found in 4.2% of asthma patients in Sweden, more than half of them had poor asthma control, and most patients had no regular health care contacts.
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http://dx.doi.org/10.1186/s12931-018-0719-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774144PMC
January 2018
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