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1.
  • Koopman, M., et al. (författare)
  • Differential Outcomes Following 4 Weeks of Aclidinium/Formoterol in Patients with COPD: A Reanalysis of the ACTIVATE Study
  • 2022
  • Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - 1178-2005. ; 17, s. 517-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: It is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD. Methods: In the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate ( AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups. Results: A total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients. Conclusion: Individual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy.
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2.
  • Kulbacka-Ortiz, Katarzyna, et al. (författare)
  • Restricted spirometry and cardiometabolic comorbidities: results from the international population based BOLD study
  • 2022
  • Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities. Methods A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 +/- 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires. Results Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37-1.86) for CVD, 1.53 (95% CI 1.40-1.66) for hypertension, and 1.98 (95% CI 1.71-2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33-1.79) for CVD, 1.50 (95% CI 1.39-1.63) for hypertension, and 1.86 (95% CI 1.59-2.17) for diabetes. Conclusion In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account.
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3.
  • Triest, F. J. J., et al. (författare)
  • Airflow Obstruction and Cardio-metabolic Comorbidities
  • 2019
  • Ingår i: Copd-Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1541-2555 .- 1541-2563. ; 16:2, s. 109-117
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and often co-exists with cardiovascular disease (CVD), hypertension and diabetes. This international study assessed the association between airflow obstruction and these comorbidities. 23,623 participants (47.5% males, 19.0% current smokers, age: 55.1 +/- 10.8 years) in 33 centers in the Burden of Obstructive Lung Disease (BOLD) initiative were included. 10.4% of subjects had airflow obstruction. Self-reports of physician-diagnosed CVD (heart disease or stroke), hypertension and diabetes were regressed against airflow obstruction (post-bronchodilator FEV1/FVC < 5th percentile of reference values), adjusting for age, sex, smoking (including pack-years), body mass index and education. Analyses were undertaken within center and meta-analyzed across centers checking heterogeneity using the I-2-statistic. Crude odds ratios for the association with airflow obstruction were 1.42 (95% CI: 1.20-1.69) for CVD, 1.24 (1.02-1.51) for hypertension, and 0.93 (0.76-1.15) for diabetes. After adjustment these were 1.00 (0.86-1.16) (I-2:6%) for CVD, 1.14 (0.99-1.31) (I-2:53%) for hypertension, and 0.76 (0.64-0.89) (I-2:1%) for diabetes with similar results for men and women, smokers and nonsmokers, in richer and poorer centers. Alternatively defining airflow obstruction by FEV1/FVC < 2.5th percentile or 0.70, did not yield significant other results. In conclusion, the associations of CVD and hypertension with airflow obstruction in the general population are largely explained by age and smoking habits. The adjusted risk for diabetes is lower in subjects with airflow obstruction. These findings emphasize the role of common risk factors in explaining the coexistence of cardio-metabolic comorbidities and COPD.
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4.
  • Verberkt, C. A., et al. (författare)
  • Healthcare and Societal Costs in Patients with COPD and Breathlessness after Completion of a Comprehensive Rehabilitation Program
  • 2021
  • Ingår i: COPD: Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1541-2555 .- 1541-2563. ; 18:2, s. 170-180
  • Tidskriftsartikel (refereegranskat)abstract
    • Breathlessness is one of the most frequent symptoms in chronic obstructive pulmonary disease (COPD). COPD may result in disability, decreased productivity and increased healthcare costs. The presence of comorbidities increases healthcare utilization. However, the impact of breathlessness burden on healthcare utilization and daily activities is unclear. This study’s goal was to analyze the impact of breathlessness burden on healthcare and societal costs. In this observational single-center study, patients with COPD were followed-up for 24 months after completion of a comprehensive pulmonary rehabilitation program. Every three months participants completed a cost questionnaire, covering healthcare utilization and impact on daily activities. The results were compared between participants with low (modified Medical Research Council (mMRC) grade <2; LBB) and high baseline breathlessness burden (mMRC grade ≥2; HBB). Healthcare costs in year 1 were €7302 (95% confidence interval €6476–€8258) for participants with LBB and €10,738 (€9141–€12,708) for participants with HBB. In year 2, costs were €8830 (€7372-€10,562) and €14,933 (€12,041–€18,520), respectively. Main cost drivers were hospitalizations, contact with other healthcare professionals and rehabilitation. Costs outside the healthcare sector in year 1 were €682 (€520–€900) for participants with LBB and €1520 (€1210–€1947) for participants with HBB. In year 2, costs were €829 (€662–€1046) and €1457 (€1126–€1821) respectively. HBB in patients with COPD is associated with higher healthcare and societal costs, which increases over time. This study highlights the relevance of reducing costs with adequate breathlessness relief. When conventional approaches fail to improve breathlessness, a personalized holistic approach is warranted. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
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5.
  • Koopman, M., et al. (författare)
  • Effects of Non-Invasive Ventilation Combined with Oxygen Supplementation on Exercise Performance in COPD Patients with Static Lung Hyperinflation and Exercise-Induced Oxygen Desaturation: A Single Blind, Randomized Cross-Over Trial
  • 2019
  • Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of non-invasive ventilation (NIV) in addition to supplemental oxygen on exercise performance in patients with chronic obstructive pulmonary disease (COPD) with hyperinflation and exercise-induced desaturation (EID) remain unclear. We hypothesized that these patients would benefit from NIV and that this effect would be an add-on to oxygen therapy. Thirteen COPD patients with a residual volume >150% of predicted, normal resting arterial oxygen pressure (PaO2) and carbon-dioxide pressure (PaCO2) and EID during a six-minute walk test were included. Patients performed four constant work-rate treadmill tests, each consisting of two exercise bouts with a recovery period in between, wearing an oronasal mask connected to a ventilator and oxygen supply. The ventilator was set to the following settings in fixed order with clockwise rotation: Sham (continuous positive airway pressure (CPAP) 2 cm H2O, FiO(2) 21%), oxygen (CPAP 2 cm H2O, FiO(2) 35%), NIV and oxygen (inspiratory positive airway pressure (IPAP) 14 cm H2O/expiratory positive airway pressure (EPAP) 6 cm H2O, inspired oxygen fraction (FiO(2)) 35%), intermittent (walking: Sham setting, recovery: NIV and oxygen setting). During the first exercise, bout patients walked further with the oxygen setting compared to the sham setting (225 +/- 107 vs 120 +/- 50 meters, p < 0.05), but even further with the oxygen/NIV setting (283 +/- 128 meters; p < 0.05). Recovery time between two exercise bouts was shortest with NIV and oxygen. COPD patients with severe static hyperinflation and EID benefit significantly from NIV in addition to oxygen during exercise and recovery.
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6.
  • Uszko-Lencer, Nhmk, et al. (författare)
  • Clustering based on comorbidities in patients with chronic heart failure: an illustration of clinical diversity
  • 2022
  • Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 9:1, s. 614-626
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims It is increasingly recognized that the presence of comorbidities substantially contributes to the disease burden in patients with heart failure (HF). Several reports have suggested that clustering of comorbidities can lead to improved characterization of the disease phenotypes, which may influence management of the individual patient. Therefore, we aimed to cluster patients with HF based on medical comorbidities and their treatment and, subsequently, compare the clinical characteristics between these clusters. Methods and results A total of 603 patients with HF entering an outpatient HF rehabilitation programme were included [median age 65 years (interquartile range 56-71), 57% ischaemic origin of cardiomyopathy, and left ventricular ejection fraction 35% (26-45)]. Exercise performance, daily life activities, disease-specific health status, coping styles, and personality traits were assessed. In addition, the presence of 12 clinically relevant comorbidities was recorded, based on targeted diagnostics combined with applicable pharmacotherapies. Self-organizing maps (SOMs; ) were used to visualize clusters, generated by using a hybrid algorithm that applies the classical hierarchical cluster method of Ward on top of the SOM topology. Five clusters were identified: (1) a least comorbidities cluster; (2) a cachectic/implosive cluster; (3) a metabolic diabetes cluster; (4) a metabolic renal cluster; and (5) a psychologic cluster. Exercise performance, daily life activities, disease-specific health status, coping styles, personality traits, and number of comorbidities were significantly different between these clusters. Conclusions Distinct combinations of comorbidities could be identified in patients with HF. Therapy may be tailored based on these clusters as next step towards precision medicine. The effect of such an approach needs to be prospectively tested.
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7.
  • Brat, K., et al. (författare)
  • Introducing a new prognostic instrument for long-term mortality prediction in COPD patients: the CADOT index
  • 2021
  • Ingår i: Biomedical Papers-Olomouc. - : Palacky University Olomouc. - 1213-8118 .- 1804-7521. ; 165:2, s. 139-145
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. The BODE (BMI, Obstruction - FEV1, Dyspnoea - mMRC, Exercise - 6-MWT) and the ADO (Age, Dyspnoea - mMRC, Obstruction - FEV1) indices are widely used prognosis assessment tools for long-term mortality prediction in COPD patients but subject to limitations for use in daily clinical practice. The aim of this research was to construct a prognostic instrument that prevents these limitations and which would serve as a complementary prognostic tool for clinical use in these patients. Methods and Participants. The data of 699 COPD subjects were extracted from the Czech Multicentre Research Database (CMRD) of COPD patients (the derivation cohort) and analysed to identify factors associated with the long-term risk of mortality. These were entered into the ROC analysis and reclassification analysis. Those with the strongest discriminative power were used to construct the new index (CADOT). The new index was validated on 187 patients of the CIROCO+ cohort (Netherlands; the validation cohort). Results. The CADOT was constructed by adding two newly identified prognosis-determining factors, chronic heart failure (CHF) and TLCO, to the ADO index. In a head-to-head comparison, the CADOT index showed highest c-statistic values compared to the BODE and ADO indices (0.701 vs 0.677 vs 0.644, respectively). The prognostic power was more definitive when applied to the Dutch validation (CIROCO+) cohort (0.842 vs 0.799 vs 0.825, respectively). Conclusions. The CADOT index has comparable prognostic power to the BODE and ADO indices.The CADOT is complementary/an alternative to the BODE (if 6-MWT is not feasible) and ADO (with less dependence on the age factor) indices.
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8.
  • Franssen, F. M. E., et al. (författare)
  • Effects of a comprehensive, inpatient pulmonary rehabilitation programme in a cachectic patient with very severe COPD and chronic respiratory failure
  • 2019
  • Ingår i: Breathe. - : European Respiratory Society (ERS). - 1810-6838 .- 2073-4735. ; 15:3, s. 227-233
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary rehabilitation (PR) is a comprehensive intervention based on a thorough patient assessment followed by personalised interventions designed to improve the physical and psychological condition of patients with chronic respiratory diseases and to promote the long-term adherence to health-enhancing behaviours [1]. While the clinical importance of physical activity is recognised across all stages of disease, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 strategy for chronic obstructive pulmonary disease (COPD) states that patients that remain highly symptomatic and/or those with a history of moderate or severe exacerbations despite optimal pharmacotherapy are indicated for PR [2]. Improvements in symptoms, increases in quality of life and gains in functional capacity after PR are independent of age, sex or the baseline degree of airflow limitation [3, 4]. However, it is known that patients with higher symptoms of dyspnoea, worse functional capacity and poor health status at baseline are more likely to be good responders to PR [5]. While PR is traditionally applied in clinically stable patients, there is increasing evidence for its beneficial effects following hospitalisations [6] and in those with frequent exacerbations [5]. In patients with very severe disease awaiting lung transplantation significant improvements in exercise capacity and health status were reported after short-term comprehensive PR [7]. Moreover, an increasing number of specific (non-)pharmacological interventions are available and can be combined with PR in the subgroup of patients with very advanced disease, including neuromuscular electrical stimulation (NMES), noninvasive ventilatory support and anabolic agents. Finally, PR may be an appropriate setting to introduce advance care planning (ACP) [8]. The role of these personalised and targeted interventions will be highlighted in this case report.
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9.
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10.
  • Vanfleteren, Lowie E G W, et al. (författare)
  • Biomarker-based clustering of patients with chronic obstructive pulmonary disease
  • 2023
  • Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale COPD has been associated repeatedly with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways. This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterisation and examine how these differences may relate to altered biological pathways. Methods 213 patients with moderate-to-severe COPD in a clinically stable state were recruited and clinically characterised, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster. Results Four clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV), with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that three of the four clusters were enriched in Rage (receptor for advanced glycation end-products) and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterisation of clusters ranged from 1) better functional capacity and health status and fewer comorbidities; 2) more underweight, osteoporosis and static hyperinflation; 3) more metabolically deranged; and 4) older subjects with worse functional capacity and higher comorbidity load. Conclusions These new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.
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11.
  • Franssen, F. M. E., et al. (författare)
  • Lung Function Abnormalities in Smokers with Ischemic Heart Disease
  • 2016
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 194:5, s. 568-576
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: The aim of the ALICE (Airflow Limitation in Cardiac Diseases in Europe) study was to investigate the prevalence of airflow limitation in patients with ischemic heart disease and the effects on quality of life, healthcare use, and future health risk. Objectives: To examine prebronchodilator and post-bronchodilator spirometry in outpatients aged greater than or equal to 40 years with clinically documented ischemic heart disease who were current or former smokers. Methods: This multicenter, cross-sectional study was conducted in 15 cardiovascular outpatient clinics in nine European countries. Airflow limitation was defined as post-bronchodilator FEV1/FVC less than 0.70. Measurements and Main Results: Among the 3,103 patients with ischemic heart disease who were recruited, lung function was defined for 2,730 patients. Airflow limitation was observed in 30.5% of patients with ischemic heart disease: 11.3% had mild airflow limitation, 15.8% moderate airflow limitation, 3.3% severe airflow limitation, and 0.1% very severe airflow limitation. Most patients with airflow limitation (70.6%) had no previous spirometry testing or diagnosed pulmonary disease. Airflow limitation was associated with greater respiratory symptomatology, impaired health status, and more frequent emergency room visits (P < 0.05). Conclusions: Airflow limitation compatible with chronic obstructive pulmonary disease affects almost one-third of patients with ischemic heart disease. Although airflow limitation is associated with additional morbidity and societal burden, it is largely undiagnosed and untreated.
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12.
  • Knox-Brown, Ben, et al. (författare)
  • Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study : a multinational cross-sectional study
  • 2023
  • Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:1, s. E69-E82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters.Methods: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 mu g salbutamol) and post-bronchodilator (ie, after administration of 200 mu g salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis.Findings: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV3/FVC ratio and 25 961 participants for FEF25-75. Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF25-75, and for FEV 3/FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV 3/FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF25-75, except for increasing age, which was associated with reduced odds of small airways obstruction.Interpretation: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline.
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13.
  • Knox-Brown, Ben, et al. (författare)
  • The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life : results from the Burden of Obstructive Lung Disease (BOLD) study
  • 2023
  • Ingår i: Respiratory Research. - : BioMed Central (BMC). - 1465-9921 .- 1465-993X. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundSpirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown.MethodsUsing data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN).ResultsAlmost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease.ConclusionSpirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.
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14.
  • Skorodko, T., et al. (författare)
  • Excitation of the Roper resonance in single- and double-pion production in nucleon-nucleon collisions
  • 2008
  • Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 35:3, s. 317-319
  • Tidskriftsartikel (refereegranskat)abstract
    • In most investigations the Roper resonance is sensed only very indirectly via complex partial-wave analyses. We find indications for its excitation in the invariant n pi(+) mass spectrum of the pp -> np pi(+) reaction at M approximate to 1360 MeV with a width of approximate to 150 MeV . The values fit very favorably to the most recent phase shift results as well as to the observations at BES. In the near-threshold two-pion production pp -> pp pi(0)pi(0) , where the Roper excitation and its subsequent decays via the routes N* -> Delta pi -> N pi pi and N* -> N sigma are the only dominant processes, we find its direct decay into the N sigma channel to be the by far dominating decay process -in favor of a monopole excitation of the Roper resonance.
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15.
  • Abozid, Hazim, et al. (författare)
  • Prevalence of chronic cough, its risk factors and population attributable risk in the Burden of Obstructive Lung Disease (BOLD) study : a multinational cross-sectional study
  • 2024
  • Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 68
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition. Methods We analysed cross-sectional data from 33,983 adults (>= 40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random -effects metaanalysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors. Findings The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job. Interpretation Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors.
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16.
  • Austevoll, I. M., et al. (författare)
  • Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis
  • 2021
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 385:6, s. 526-538
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In patients with lumbar spinal stenosis and degenerative spondylolisthesis, it is uncertain whether decompression surgery alone is noninferior to decompression with instrumented fusion. Methods We conducted an open-label, multicenter, noninferiority trial involving patients with symptomatic lumbar stenosis that had not responded to conservative management and who had single-level spondylolisthesis of 3 mm or more. Patients were randomly assigned in a 1:1 ratio to undergo decompression surgery (decompression-alone group) or decompression surgery with instrumented fusion (fusion group). The primary outcome was a reduction of at least 30% in the score on the Oswestry Disability Index (ODI; range, 0 to 100, with higher scores indicating more impairment) during the 2 years after surgery, with a noninferiority margin of -15 percentage points. Secondary outcomes included the mean change in the ODI score as well as scores on the Zurich Claudication Questionnaire, leg and back pain, the duration of surgery and length of hospital stay, and reoperation within 2 years. Results The mean age of patients was approximately 66 years. Approximately 75% of the patients had leg pain for more than a year, and more than 80% had back pain for more than a year. The mean change from baseline to 2 years in the ODI score was -20.6 in the decompression-alone group and -21.3 in the fusion group (mean difference, 0.7; 95% confidence interval [CI], -2.8 to 4.3). In the modified intention-to-treat analysis, 95 of 133 patients (71.4%) in the decompression-alone group and 94 of 129 patients (72.9%) in the fusion group had a reduction of at least 30% in the ODI score (difference, -1.4 percentage points; 95% CI, -12.2 to 9.4), showing the noninferiority of decompression alone. In the per-protocol analysis, 80 of 106 patients (75.5%) and 83 of 110 patients (75.5%), respectively, had a reduction of at least 30% in the ODI score (difference, 0.0 percentage points; 95% CI, -11.4 to 11.4), showing noninferiority. The results for the secondary outcomes were generally in the same direction as those for the primary outcome. Successful fusion was achieved with certainty in 86 of 100 patients (86.0%) who had imaging available at 2 years. Reoperation was performed in 15 of 120 patients (12.5%) in the decompression-alone group and in 11 of 121 patients (9.1%) in the fusion group. Conclusions In this trial involving patients who underwent surgery for degenerative lumbar spondylolisthesis, most of whom had symptoms for more than a year, decompression alone was noninferior to decompression with instrumented fusion over a period of 2 years. Reoperation occurred somewhat more often in the decompression-alone group than in the fusion group. (NORDSTEN-DS ClinicalTrials.gov number, .) Decompression versus Fusion for Lumbar Spondylolisthesis In a randomized trial conducted in Norway, decompression surgery alone was noninferior to decompression with instrumented fusion with respect to the percentage of patients who had a 30% reduction on a scale of pain and disability over a period of 2 years, with a noninferiority margin of -15 percentage points.
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17.
  • Gille, T., et al. (författare)
  • ERS International Congress 2021: highlights from the Respiratory Clinical Care and Physiology Assembly
  • 2022
  • Ingår i: European Respiratory Journal Open Research (ERJ Open Research). - : European Respiratory Society (ERS). - 2312-0541. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, randomised controlled trials and qualitative research that were presented during the 2021 European Respiratory Society International Congress within the sessions from the five groups of the Assembly 1 - Respiratory clinical care and physiology. Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.
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18.
  • Hellum, C., et al. (författare)
  • Surgery in degenerative spondylolisthesis: does fusion improve outcome in subgroups? A secondary analysis from a randomized trial (NORDSTEN trial)
  • 2023
  • Ingår i: Spine Journal. - 1529-9430. ; 23:11, s. 1613-1622
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND CONTEXT: Patients with spinal stenosis and degenerative spondylolisthesis are treated surgically with decompression alone or decompression with fusion. However, there is debate regarding which subgroups of patients may benefit from additional fusion. PURPOSE: To investigate possible treatment effect modifiers and prognostic variables among patients operated for spinal stenosis and degenerative spondylolisthesis. DESIGN: A secondary exploratory study using data from the Norwegian Degenerative Spondylo-listhesis and Spinal Stenosis (NORDSTEN-DS) trial. Patients were randomized to decompression alone or decompression with instrumented fusion. PATIENT SAMPLE: The sample in this study consists of 267 patients from a randomized multi-center trial involving 16 hospitals in Norway. Patients were enrolled from February 12, 2014, to December 18, 2017. The study did not include patients with degenerative scoliosis, severe forami-nal stenosis, multilevel spondylolisthesis, or previous surgery. OUTCOME MEASURES: The primary outcome was an improvement of >= 30% on the Oswestry Disability Index score (ODI) from baseline to 2-year follow-up. METHODS: When investigating possible variables that could modify the treatment effect, we ana-lyzed the treatment arms separately. When testing for prognostic factors we analyzed the whole cohort (both treatment groups). We used univariate and multiple regression analyses. The selection of variables was done a priori, according to the published trial protocol. RESULTS: Of the 267 patients included in the trial (183 female [67%]; mean [SD] age, 66 [7.6] years), complete baseline data for the variables required for the present analysis were available for 205 of the 267 individuals. We did not find any clinical or radiological variables at baseline that modified the treatment effect. Thus, none of the commonly used criteria for selecting patients for fusion surgery influenced the chosen primary outcome in the two treatment arms. For the whole cohort, less comorbidity (American Society of Anesthesiologists Classification [ASA], OR = 4.35; 95% confidence interval (CI [1.16-16.67]) and more preoperative leg pain (OR = 1.23; CI [1.02 -1.50]) were significantly associated with an improved primary outcome. CONCLUSIONS: In this study on patients with degenerative spondylolisthesis, neither previously defined instability criteria nor other pre-specified baseline variables were associated with better clinical outcome if fusion surgery was performed. None of the analyzed variables can be applied to guide the decision for fusion surgery in patients with degenerative spondylolisthesis. For both treat-ment groups, less comorbidity and more leg pain were associated with improved outcome 2 years after surgery. TRIAL REGISTRATION: NORDSTEN-DS ClinicalTrials.gov, NCT02051374. (c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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19.
  • Hermansen, E., et al. (författare)
  • Comparable increases in dural sac area after three different posterior decompression techniques for lumbar spinal stenosis: radiological results from a randomized controlled trial in the NORDSTEN study
  • 2020
  • Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 29, s. 2254-2261
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose To investigate changes in dural sac area after three different posterior decompression techniques in patients undergoing surgery for lumbar spinal stenosis. Summary of background data Decompression of the nerve roots is the main surgical treatment for lumbar spinal stenosis. The aim of this study was to radiologically investigate three commonly used posterior decompression techniques. Methods The present study reports data from one of two multicenter randomized trials included in the NORDSTEN study. In the present trial, involving 437 patients undergoing surgery, we report radiological results after three different midline retaining posterior decompression techniques: unilateral laminotomy with crossover (UL) (n = 146), bilateral laminotomy (BL) (n = 142) and spinous process osteotomy (SPO) (n = 149). MRI was performed before and three months after surgery. The increase in dural sac area and Schizas grade at the most stenotic level was evaluated. Three different predefined surgical indicators of substantial decompression were used: (1) postoperative dural sac area of > 100 mm(2), (2) increase in the dural sac area of at least 50% and (3) postoperative Schizas grade A or B. Results No differences between the three surgical groups were found in the mean increase in dural sac area. Mean values were 66.0 (SD 41.5) mm(2)in the UL-group, 71.9 (SD 37.1) mm(2)in the BL-group and 68.1 (SD 41.0) mm(2)in the SPO-group (p = 0.49). No differences in the three predefined surgical outcomes between the three groups were found. Conclusion For patients with lumbar spinal stenosis, the three different surgical techniques provided the same increase in dural sac area.
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20.
  • Hermansen, E., et al. (författare)
  • Comparison of 3 Different Minimally Invasive Surgical Techniques for Lumbar Spinal Stenosis A Randomized Clinical Trial
  • 2022
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:3
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Operations for lumbar spinal stenosis is the most often performed surgical procedure in the adult lumbar spine. This study reports the clinical outcome of the 3 most commonly used minimally invasive posterior decompression techniques. OBJECTIVE To compare the effectiveness of 3 minimally invasive posterior decompression techniques for lumbar spinal stenosis. DESIGN, SETTING. AND PARTICIPANTS This randomized clinical trial used a parallel group design and included patients with symptomatic and radiologically verified lumbar spinal stenosis without degenerative spondylolisthesis. Patients were enrolled between February 2014 and October 2018 at the orthopedic and neurosurgical departments of 16 Norwegian public hospitals. Statistical analysis was performed in the period from May to June 2021. INTERVENTIONS Patients were randomized to undergo 1 of the 3 minimally invasive posterior decompression techniques: unilateral laminotomy with crossover, bilateral laminotomy, and spinous process osteotomy. MAIN OUTCOMES AND MEASURES Primary outcome was change in disability measured with Oswestry Disability Index (ODI; range 0-100), presented as mean change from baseline to 2-year follow-up and proportions of patients classified as success (>30% reduction in ODI). Secondary outcomes were mean change in quality of life, disease-specific symptom severity measured with Zurich Claudication Questionnaire (ZCQ), back pain and leg pain on a 10-point numeric rating score (NRS), patient perceived benefit of the surgical procedure, duration of the surgical procedure, blood loss, perioperative complications, number of reoperations, and length of hospital stay. RESULTS In total, 437 patients were included with a median (IQR) age of 68 (62-73) years and 230 men (53%). Of the included patients, 146 were randomized to unilateral laminotomy with crossover, 142 to bilateral laminotomy, and 149 to spinous process osteotomy. The unilateral laminotomy with crossover group had a mean change of -17.9 ODI points (95% CI, -20.8 to -14.9), the bilateral laminotomy group had a mean change of -19.7 ODI points (95% CI, -22.7 to -16.8), and the spinous process osteotomy group had a mean change of -19.9 ODI points (95% CI, -22.8 to-17.0). There were no significant differences in primary or secondary outcomes amongthe 3 surgical procedures, except a longer duration of the surgical procedure in the bilateral laminotomy group. CONCLUSIONS AND RELEVANCE No differences in clinical outcomes or complication rates were found among the 3 minimally invasive posterior decompression techniques used to treat patients with lumbar spinal stenosis.
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21.
  • Houben-Wilke, Sarah, et al. (författare)
  • Revealing Methodological Challenges in Chronic Obstructive Pulmonary Disease Studies Assessing Comorbidities: A Narrative Review.
  • 2019
  • Ingår i: Chronic obstructive pulmonary diseases (Miami, Fla.). - : COPD Foundation. - 2372-952X. ; 6:2, s. 166-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Beyond respiratory impairment, patients with chronic obstructive pulmonary disease (COPD) often suffer from comorbidities which are associated with worse health status, higher health care costs and worse prognosis. Reported prevalences of comorbidities largely differ between studies which might be explained by different assessment methods (objective assessment, self-reported assessment, or assessment by medical records), heterogeneous study populations, inappropriate control groups, incomparable methodologies, etc. This narrative review demonstrates and further evaluates the variability in prevalence of several comorbidities in patients with COPD and control individuals and discusses several shortcomings and pitfalls which need to be considered when interpreting comorbidity data. Like in other chronic organ diseases, the accurate diagnosis and integrated management of comorbidities is a key for outcome in COPD. This review highlights that there is a need to move from the starting point of an established index disease towards the concept of the development of multimorbidity in the elderly including COPD as an important and highly prevalent pulmonary component.
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22.
  • Posthuma, R., et al. (författare)
  • Differential Response to 12 Weeks of Once-Daily Tiotropium/Olodaterol Fixed Dose Combination in Patients with COPD: A Multidimensional Response Profiling in the TORRACTO Study
  • 2023
  • Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - 1178-2005. ; 18, s. 1091-1102
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM).Materials and Methods: This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 mu g) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O.Results: Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline.Conclusion: Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD.
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23.
  • Vaes, A. W., et al. (författare)
  • Endothelial function in patients with COPD: an updated systematic review of studies using flow-mediated dilatation
  • 2023
  • Ingår i: Expert Review of Respiratory Medicine. - : Informa UK Limited. - 1747-6348 .- 1747-6356. ; 17:1, s. 53-69
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionCardiovascular disease is a significant cause of morbidity and mortality in COPD. Endothelial dysfunction is suggested to be involved in cardiovascular disease pathogenesis, and multiple studies report endothelial dysfunction in COPD. This article summarized the current knowledge on endothelial function in COPD patients.Areas coveredDatabases were screened until November 2022 for studies using ultrasound-based flow-mediated dilation in patients with stable COPD. Pooled effect sizes were calculated using random effects model. Meta-regression analyses assessed the effects of demographic and clinical variables.Expert opinion34 studies were identified (1365 COPD patients; 617 controls). Pooled analysis demonstrated an impaired endothelial-dependent (-2.33%; 95%CI -3.30/-1.35; p < 0.001) and endothelial-independent dilation (-3.11%; 95%CI -5.14/-1.08; p = 0.003) in COPD patients when compared to non-COPD controls. Meta-regression identified that higher age, worse severity of airflow obstruction, and current smoking were significantly associated with impaired endothelial function. Studies evaluating the effects of pharmacological and non-pharmacological interventions on endothelial function in COPD patients demonstrated conflicting results.
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24.
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25.
  • Hermansen, E., et al. (författare)
  • Postoperative Dural Sac Cross-Sectional Area as an Association for Outcome After Surgery for Lumbar Spinal Stenosis Clinical and Radiological Results From the NORDSTEN-Spinal Stenosis Trial
  • 2023
  • Ingår i: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436. ; 48:10, s. 688-694
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Design.Prospective cohort study. Objective.The aim was to investigate the association between postoperative dural sac cross-sectional area (DSCA) after decompressive surgery for lumbar spinal stenosis and clinical outcome. Furthermore, to investigate if there is a minimum threshold for how extensive a posterior decompression needs to be to achieve a satisfactory clinical result. Summary of Background Data.There is limited scientific evidence for how extensive lumbar decompression needs to be to obtain a good clinical outcome in patients with symptomatic lumbar spinal stenosis. Materials and Methods.All patients were included in the Spinal Stenosis Trial of the NORwegian Degenerative spondylolisthesis and spinal STENosis (NORDSTEN)-study. The patients underwent decompression according to three different methods. DSCA measured on lumbar magnetic resonance imaging at baseline and at three months follow-up, and patient-reported outcome at baseline and at two-year follow-up were registered in a total of 393 patients. Mean age was 68 (SD: 8.3), proportion of males were 204/393 (52%), proportion of smokers were 80/393 (20%), and mean body mass index was 27.8 (SD: 4.2).The cohort was divided into quintiles based on the achieved DSCA postoperatively, the numeric, and relative increase of DSCA, and the association between the increase in DSCA and clinical outcome were evaluated. Results.At baseline, the mean DSCA in the whole cohort was 51.1 mm(2) (SD: 21.1). Postoperatively the area increased to a mean area of 120.6 mm(2) (SD: 46.9). The change in Oswestry disability index in the quintile with the largest DSCA was -22.0 (95% CI: -25.6 to -18), and in the quintile with the lowest DSCA the Oswestry disability index change was -18.9 (95% CI: -22.4 to -15.3). There were only minor differences in clinical improvement for patients in the different DSCA quintiles. Conclusion.Less aggressive decompression performed similarly to wider decompression across multiple different patient-reported outcome measures at two years following surgery.
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26.
  • Vanfleteren, Lowie E G W, et al. (författare)
  • ERS International Congress, Madrid, 2019: highlights from the General Pneumology Assembly
  • 2020
  • Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:1
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • This article contains highlights and a selection of the scientific advances from the European Respiratory Society's General Pneumology Assembly that were presented at the 2019 European Respiratory Society International Congress in Madrid, Spain. The most relevant topics from the different groups will be discussed, covering a wide range of areas including rehabilitation and chronic care, general practice and primary care and M-health and E-health. In this review, the newest research and actual data as well as award-winning abstracts and highlight sessions will be discussed.
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