Jørgen Vestbo

University of Southern Denmark, Odense, South Denmark, Denmark

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Publications (427)2218.37 Total impact

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    ABSTRACT: Real-world data on the benefit/risk profile of medicines is needed, particularly in patients who are ineligible for randomised controlled trials conducted for registration purposes. This paper describes the methodology and source data verification which enables the conduct of pre-licensing clinical trials of COPD and asthma in the community using the electronic medical record (EMR), NorthWest EHealth linked database (NWEH-LDB) and alert systems. Dual verification of extracts into NWEH-LDB was performed using two independent data sources (Salford Integrated Record [SIR] and Apollo database) from one primary care practice in Salford (N = 3504). A feasibility study was conducted to test the reliability of the NWEH-LDB to support longitudinal data analysis and pragmatic clinical trials in asthma and COPD. This involved a retrospective extraction of data from all registered practices in Salford to identify a cohort of patients with a diagnosis of asthma (aged ≥18) and/or COPD (aged ≥40) and ≥2 prescriptions for inhaled bronchodilators during 2008. Health care resource utilisation (HRU) outcomes during 2009 were assessed. Exacerbations were defined as: prescription for oral corticosteroids (OCS) in asthma and prescription of OCS or antibiotics in COPD; and/or hospitalisation for a respiratory cause. Dual verification demonstrated consistency between SIR and Apollo data sources: 3453 (98.6%) patients were common to both systems; 99.9% of prescription records were matched and of 29,830 diagnosis records, one record was missing from Apollo and 272 (0.9%) from SIR. Identified COPD patients were also highly concordant (Kappa coefficient = 0.98). A total of 7981 asthma patients and 4478 COPD patients were identified within the NWEH-LDB. Cohort analyses enumerated the most commonly prescribed respiratory medication classes to be: inhaled corticosteroids (ICS) (42%) and ICS plus long-acting β2-agonist (LABA) (40%) in asthma; ICS plus LABA (55%) and long-acting muscarinic antagonists (36%) in COPD. During 2009 HRU was greater in the COPD versus asthma cohorts, and exacerbation rates in 2009 were higher in patients who had ≥2 exacerbations versus ≤1 exacerbation in 2008 for both asthma (137.5 vs. 20.3 per 100 person-years, respectively) and COPD (144.6 vs. 41.0, respectively). Apollo and SIR data extracts into NWEH-LDB showed a high level of concordance for asthma and COPD patients. Longitudinal data analysis characterized the COPD and asthma populations in Salford including medications prescribed and health care utilisation outcomes suitable for clinical trial planning.
    BMC Medical Informatics and Decision Making 12/2015; 15(1). DOI:10.1186/s12911-015-0132-z · 1.50 Impact Factor
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    ABSTRACT: Poor health status has been associated with morbidity and mortality in patients with COPD. To date, the impact of changes in health status on these outcomes remains unknown. To explore the relationship of clinically relevant changes in health status with exacerbation, hospitalisation or death in patients with COPD. Characteristics and health status (St George's Respiratory Questionnaire, SGRQ) were assessed over a period of 3 years in 2138 patients with COPD enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study: a longitudinal, prospective, observational study. Associations between change in health status (=4 units in SGRQ score) during year 1 and time to first exacerbation, hospitalisation and death during 2-year follow-up were assessed using Kaplan-Meier plots and log-rank test. 1832 (85.7%) patients (age 63.4±7.0 years, 65.4% male, FEV1 48.7±15.6% predicted) underwent assessment at baseline and 1 year. Compared with those who deteriorated, patients with improved or stable health status in year 1 have a lower likelihood of exacerbation (HR 0.78 (95% CI 0.67 to 0.89), p<0.001 and 0.84 (0.73 to 0.97), p=0.016, respectively), hospitalisation (0.72 (0.58 to 0.90), p=0.004 and 0.77 (0.62 to 0.96), p=0.023, respectively) or dying (0.61 (0.39 to 0.95), p=0.027 and 0.58 (0.37 to 0.92), p=0.019, respectively) during 2-year follow-up. This effect persisted after stratification for age and the number of exacerbations and hospitalisations during the first year of the study. Patients with stable or improved health status during year 1 of ECLIPSE had a lower likelihood of exacerbation, hospitalisation or dying during 2-year follow-up. Interventions that stabilise and improve health status may also improve outcomes in patients with COPD. NCT00292552, registered at ClinicalTrials.gov. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Thorax 03/2015; DOI:10.1136/thoraxjnl-2014-205697 · 8.56 Impact Factor
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    ABSTRACT: Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that likely includes clinically relevant subgroups. Objectives: To identify subgroups of COPD in ECLIPSE subjects using unsupervised cluster analysis and to assess clinically meaningful outcomes of the clusters during 3 years of longitudinal follow-up. Methods: Factor analysis was used to reduce 41 variables determined at recruitment in 2,164 COPD patients to 13 main factors, and the variables with the highest loading were used for unsupervised cluster analysis. Clusters were then evaluated for their relationship with clinically meaningful outcomes during 3 years of follow-up. The relationships among clinical parameters were evaluated within clusters. Measurements and Main Results: Five subgroups were distinguished using cross-sectional clinical features. Importantly, these groups differed with regard to outcomes. Cluster A included milder patients and had fewer deaths and hospitalizations. Cluster B had less systemic inflammation at baseline but had notable changes in health status and emphysema extent. Cluster C had many comorbidities, evidence of systemic inflammation and the highest mortality. Cluster D had low FEV1, severe emphysema and the highest exacerbation and COPD hospitalization rate. Cluster E was intermediate for most variables and may represent a mixed group that includes further clusters. The relationships among clinical variables within clusters differed from that in the entire COPD population. Conclusions: Unsupervised cluster analysis using baseline data in ECLIPSE identified five COPD subgroups that differ in outcomes and inflammatory biomarkers and show different relationships between clinical parameters, suggesting the clusters represent clinically and biologically different subtypes of COPD.
    02/2015; DOI:10.1513/AnnalsATS.201403-125OC
  • Respiratory Medicine 02/2015; DOI:10.1016/j.rmed.2015.01.016 · 2.92 Impact Factor
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    ABSTRACT: Rationale: Radiographically-confirmed pneumonia risk has not been assessed with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD). Objectives: To determine the incidence of pneumonia, risk factors and clinical attributes with inhaled fluticasone furoate in COPD patients with an exacerbation history. Methods: Two replicate, 1-year, double-blind clinical trials enrolled COPD subjects with moderate to very severe airflow limitation and at least one exacerbation in the prior year. Subjects were randomized 1:1:1:1 to receive inhaled once-daily vilanterol 25 µg or vilanterol 25 µg combined with 50 µg, 100 µg, or 200 µg fluticasone furoate. Subjects were required to have a chest radiograph at screening and within 48 hours of any suspected pneumonia or exacerbation. Measurements and Main Results: Of 3255 randomized subjects, 205 pneumonia events occurred in 181 subjects. Chest imaging was available for 195 (95%) of these events. Chest radiographs were also obtained for 1793 (70%) of the 2545 moderate and severe exacerbations. For vilanterol alone and the combination with 50 µg, 100 µg, or 200 µg fluticasone furoate, reported pneumonia incidence was 3%, 6%, 6% and 7%, respectively. However, for events with compatible parenchymal infiltrates, respective incidences were 2%, 4%, 4% and 5%. Factors associated with at least a two-fold increase in the risk of pneumonia with FF/VI were being a current smoker, having prior pneumonia, BMI < 25kg/m2, and severe airflow limitation. Conclusions: Although the incidence of pneumonia is low, radiographically-confirmed pneumonia risk is increased with inhaled FF/VI, although lower than investigator-defined rates. Clinical trial registered with clinicaltrials.gov NCT01009463 (HZC102871); NCT01017952 (HZC102970).
    12/2014; DOI:10.1513/AnnalsATS.201409-413OC
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a multifaceted condition that cannot be fully described by the severity of airway obstruction. The limitations of spirometry and clinical history have prompted researchers to investigate a multitude of surrogate biomarkers of disease for the assessment of patients, prediction of risk, and guidance of treatment. The aim of this review is to provide a comprehensive summary of observations for a selection of recently investigated pulmonary inflammatory biomarkers (Surfactant protein D (SP-D), Club cell protein 16 (CC-16), and Pulmonary and activation-regulated chemokine (PARC/CCL-18)) and systemic inflammatory biomarkers (C-reactive protein (CRP) and fibrinogen) with COPD. The relevance of these biomarkers for COPD is discussed in terms of their biological plausibility, their independent association to disease, their hard clinical outcomes, their modification by interventions, and whether changes in clinical outcomes are reflected by changes in the biomarker.
    Respiratory Research 11/2014; 15(1):147. DOI:10.1186/s12931-014-0147-5 · 3.13 Impact Factor
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    ABSTRACT: Introduction: Non-invasive ventilation (NIV) as an add-on modality to medical treatment has been recom-mended in national guidelines for patients acutely admitted with chronic obstructive pulmonary disorder (COPD) exacerbation and hypercapnic respiratory failure. To address concerns regarding whether NIV is used appropriately, we conducted an audit of COPD patients admitted to a university hospital in Denmark. Material and methods: Data from medical records were retrieved for two cohorts in 2010: 1) all patients admitted to the Medical Emergency Ward with the diagnosis of COPD, and 2) all patients receiving NIV regardless of their diagnosis at the Respiratory Ward. Demographic data and outcome of treatment were registered. Results: Cohort 1 comprised 804 admissions fulfilling criteria for COPD at evaluation, and of the 804 admissions, NIV was initiated in 151 (18.7%) admissions. In 42 additional cases (5.2%), initial mild respiratory acidosis was registered at admission, fulfilling criteria for NIV treatment; and, in 36 cases, the clinical status was reported as improved or not reported at all; no deaths were observed. In cohort 2, 124 admissions were registered that comprised 110 admissions with COPD and 14 without a diagnosis of COPD (of which half had a 'not-to-intubate' order). The indication for NIV treatment was met in 92.7% of the COPD admissions. Conclusion: NIV was initiated in 18.8% of the COPD admissions, and in an additional 5.2%, NIV criteria were met without initiation. In 82.3% of the admissions receiving NIV, a COPD diagnosis and correct criteria for NIV treatment were met. C hronic obstructive pulmonary disease (COPD) is considered a global health issue (1). In Denmark, an estimated 400,000 subjects have COPD (2), and COPD is annually responsible for more than 20,000 acute hospital admissions (3). Non-invasive ventilation (NIV) as an add-on moda-lity to medical treatment is recommended in national guidelines for patients acutely admitted with COPD ex-acerbation and hypercapnic respiratory failure (4). This recommendation is based on randomized controlled trials showing lowered mortality rates in highly selected patients (5) and subsequent expert interpretation (6). A nation-wide COPD quality improvement program Á DrKOL, formerly NIP-KOL Á was launched in Denmark in 2008, where data on the use of NIV and mortality have been monitored in patients acutely admitted with a COPD exacerbation. In this program, recently published data show regional variations in practice (7). In the region of Southern Denmark, the ratio of acutely admitted COPD patients with exacerbation receiving NIV has been consistently higher than in other regions in Denmark throughout the years of registration (8). This practice has been partly explained by early implementa-tion of NIV in the Respiratory and Medical Emergency
    The Clinical Respiratory Journal 11/2014; http://dx.doi.org/10.3402/ecrj.v1.24506. DOI:10.3402/ecrj.v1.24506 · 1.66 Impact Factor
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    ABSTRACT: We performed an audit on all admissions with chronic obstructive pulmonary disease (COPD) in ex-acerbation to the Department of Emergency Medicine, Odense University Hospital (DEM) in the second half of 2012 to evaluate if an organisational change had altered visitation, treatment, initiation of non-invasive ventilation (NIV) and monitoring. We chose not to include the entire year to avoid data influenced by organisational start-up difficulties. The hypothesis was that NIV was initiated according to guidelines to the same extent as prior to the implementation of DEM.
    Danish Medical Journal 11/2014; 61(11):A4958. · 0.61 Impact Factor
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    ABSTRACT: Background and objectiveWe tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD).Methods Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms.ResultsIndividuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P < 0.001), and more of them had a history of respiratory infections (6.8 vs 1.4%, P < 0.001) than individuals with COPD but without gastro-esophageal reflux disease. Among individuals with COPD and gastro-esophageal reflux disease, those who did not use acid inhibitory treatment regularly had an increased risk of COPD exacerbations during follow-up, hazards ratio (HR): HR = 2.7 (1.3–5.4, P = 0.006). Individuals with gastro-esophageal reflux disease, using acid inhibitory treatment regularly did not have an increased risk of exacerbations, HR = 1.2 (0.6–2.7, P = 0.63).Conclusions Gastro-esophageal reflux disease was associated with an increased risk of medically treated exacerbations of COPD, but only in those individuals who did not use acid inhibitory treatment regularly.
    Respirology 11/2014; 20(1). DOI:10.1111/resp.12420 · 3.50 Impact Factor
  • Jørgen Vestbo, Bartolome Celli
    American Journal of Respiratory and Critical Care Medicine 11/2014; 190(9):968-70. DOI:10.1164/rccm.201409-1705ED · 11.04 Impact Factor
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    ABSTRACT: Objectives Oxygen-enhanced MRI (OE-MRI) biomarkers have potential value in assessment of COPD, but need further evaluation before treatment-induced changes can be interpreted. The objective was to evaluate how OE-MRI parameters of regional ventilation and oxygen uptake respond to standard pharmacological interventions in COPD, and how the response compares to that of gold standard pulmonary function tests. Materials and Methods COPD patients (n = 40), mean FEV1 58% predicted normal, received single-dose inhaled formoterol 9 μg, or placebo, followed by 8 weeks treatment bid with a combination of budesonide and formoterol Turbuhaler® 320/9 μg or formoterol Turbuhaler®. OE-MRI biomarkers were obtained, as well as X-ray computed tomography (CT) biomarkers and pulmonary function tests, in a two-center study. An ANCOVA statistical model was used to assess effect size of intervention measurable in OE-MRI parameters of lung function. Results OE-MRI data were successfully acquired at both study sites. 8-week treatment with budesonide/formoterol significantly decreased lung wash-out time by 31% (p < 0.01), decreased the change in lung oxygen level upon breathing pure oxygen by 13% (p < 0.05) and increased oxygen extraction from the lung by 58% (p < 0.01). Single-dose formoterol increased both lung wash-out time (+47%, p < 0.05) and lung oxygenation time (+47%, p < 0.05). FEV1 was improved by single-dose formoterol (+12%, p < 0.001) and 8 weeks of budesonide/formoterol (+ 18%, p < 0.001), consistent with published studies. Conclusions In COPD, OE-MRI parameters showed response to both single-dose bronchodilatory effects of a β2-agonist, formoterol, and 8-week treatment with an inhaled corticosteroid, budesonide, and the measurements are feasible in a small-scale multi-center trial setting.
    European Journal of Radiology 11/2014; 83(11). DOI:10.1016/j.ejrad.2014.08.004 · 2.16 Impact Factor
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    ABSTRACT: Background:Exacerbations of chronic obstructive pulmonary disease (COPD) requiring hospital admission have important clinical and societal implications. Objective:We sought to investigate the incidence, recurrence, risk factors, and mortality of COPD patients with exacerbations requiring hospital admission compared to those without hospital admission during 3-year follow-up in 2138 COPD patients from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) observational cohort. Methods:Time to first event of hospital admission analysis using Kaplan-Meier curves and Cox proportional hazard regression adjusting for possible confounders. Results:670 (31%) patients reported a total of 1452 COPD exacerbations requiring hospital admission during the study period; 313 patients (15%) reported multiple (>1) events. A prior history of exacerbation of COPD requiring hospital admission was the factor associated with the highest risk of a new hospitalization for exacerbation (hazard ratio 2.71, 95% confidence interval: 2.24-3.29, P <.001). Other risk factors included more severe airflow limitation, poorer health status, older age, radiological evidence of emphysema, and higher white blood cell count. Having been hospitalized for exacerbation significantly increased the risk of mortality (P <.001). Conclusions:Exacerbations of COPD requiring hospital admission occur across all stages of airflow limitation and are a significant prognostic factor of reduced survival across all COPD stages. COPD patients at a high risk of hospitalization can be identified by their past history for similar events, and other factors, including the severity of airflow limitation, poor health status, age, presence of emphysema, and leukocytosis. Trial registration:clinicaltrials.gov/show/NCT00292552.
    Chest 10/2014; DOI:10.1378/chest.14-0655 · 7.13 Impact Factor
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    ABSTRACT: BACKGROUND: We tested the hypothesis that statin use in individuals with COPD is associated with a reduced risk of exacerbations. METHODS: We identified 5794 individuals with COPD and a measurement of C reactive protein (CRP) in the Copenhagen General Population Study (2003-2008). During 3 years of follow-up we recorded exacerbations with hospital admissions or oral corticosteroid treatment. In a nested case-control design, matching on age, gender, smoking, COPD severity and comorbidity, we estimated the association between statin use and exacerbations. In addition, we examined the association between statin use and high CRP (>3 mg/L), and the association between high CRP and exacerbations during follow-up. RESULTS: Statin use was associated with reduced odds of exacerbations in crude analysis, OR=0.68 (95% CI 0.51 to 0.91, p=0.01), as well as in multivariable conditional logistic regression analysis, OR=0.67 (0.48 to 0.92, p=0.01). However, in the subgroup with the most severe COPD and without cardiovascular comorbidity, we observed a null association between statin use and exacerbations, OR=1.1 (0.5 to 2.1, p=0.83). Furthermore, statin use was associated with reduced odds of a high CRP, OR=0.69 (0.56 to 0.85, p<0.001), and a high CRP was associated with an increased risk of exacerbations, HR=1.62 (1.35 to 1.94, p<0.001). We estimated the percentage of excess risk of the association of statin use with exacerbations possibly mediated through a reduction of CRP to be 14% (4-51%). CONCLUSIONS: Statin use was associated with reduced odds of exacerbations in individuals with COPD from the general population, although this was not apparent in those with the most severe COPD without cardiovascular comorbidity. Statins may thus only associate with reduced risk of exacerbations in patients with COPD with coexisting cardiovascular disease.
    Thorax 10/2014; DOI:10.1136/thoraxjnl-2014-205795 · 8.56 Impact Factor
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    ABSTRACT: Background COPD patients with chronic bronchitis include a subgroup with persistent sputum production on most or every day. We hypothesized that COPD patients with persistent sputum production have a different profile of airway inflammation, and more severe clinical characteristics. Objective To compare the airway inflammation profile and clinical characteristics of COPD persistent and non-persistent sputum producers. Methods COPD persistent sputum producers (n = 26) and non-persistent sputum producers (n = 26) underwent sputum induction and pulmonary function tests. Exacerbation history was recorded; the St. George’s Respiratory Questionnaire, Modified Medical Research Council Dyspnoea scale and COPD Assessment Tool were completed. 33 COPD patients provided sputum for bacteriology. Results Persistent sputum producers had lower post-bronchodilator FEV1% predicted (p = 0.01), diffusion capacity (p = 0.04), 6 minute walk test distance (p = 0.05), and higher closing volume (p = 0.01), BODE index (p = 0.01), rate of bacterial colonization (p = 0.004) and exacerbations (p = 0.03) compared to non-persistent sputum producers. The mean SGRQ and CAT scores were higher in persistent sputum producers (p = 0.01 and 0.03 respectively). Sputum neutrophil and eosinophil total cell counts were higher in persistent sputum producers (p = 0.02 and 0.05 respectively). Sputum levels of eotaxin (p = 0.02), MCP-1 (p = 0.02), TNF-α (p = 0.03) and IL-6 (p = 0.05) were higher in persistent sputum producers. Conclusion COPD persistent sputum producers have more severe clinical characteristics and increased concentrations of some inflammatory mediators in the airways.
    Respiratory Medicine 10/2014; 108(12). DOI:10.1016/j.rmed.2014.09.020 · 2.92 Impact Factor
  • European Respiratory Society Annual Congress 2014; 10/2014
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    ABSTRACT: Background: The prevalence of obesity has increased during the last decades and varies from 10-20% in most European countries to approximately 32% in the United States. However, data on how obesity affects the presence of airflow limitation (AFL) defined as a reduced ratio between forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) are scarce. Methods: Data was derived from the third examination of the Copenhagen City Heart Study from 1991 until 1994 (n = 10,135). We examine the impact of different adiposity markers (weight, body mass index (BMI), waist circumference, waist-hip ratio, and abdominal height) on AFL. AFL was defined in four ways: FEV1/FVC ratio < 0.70, FEV1/FVC ratio < lower limit of normal (LLN), FEV1/FVC ratio <0.70 including at least one respiratory symptom, and FEV1/FVC ratio < LLN and FEV1% of predicted < LLN. Results: All adiposity markers were positively and significantly associated with FEV1/FVC independent of age, sex, height, smoking status, and cumulative tobacco consumption. Among all adiposity markers, BMI was the strongest predictor of FEV1/FVC. FEV1/FVC increased with 0.04 in men and 0.03 in women, as BMI increased with 10 units (kg · m-2). Consequently, diagnosis of AFL was significantly less likely in subjects with BMI ≥ 25 kg · m-2 with odds ratios 0.63 or less compared to subjects with BMI between 18.5–24.9 kg · m-2 when AFL was defined as FEV1/FVC < 0.70. Conclusion: High BMI reduces the probability of AFL. Ultimately, this may result in under-diagnosis and under-treatment of COPD among individuals with overweight and obesity.
    COPD Journal of Chronic Obstructive Pulmonary Disease 10/2014; 12(1). DOI:10.3109/15412555.2014.933955 · 2.73 Impact Factor
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    ABSTRACT: We tested the hypothesis that use of and adherence to maintenance medication is low among in-dividuals in the general population who have chronic obstructive pulmonary disease (COPD) , even in cases of severe and very severe COPD.
    Journal of General Internal Medicine 09/2014; DOI:10.1007/s11606-014-3029-0 · 3.42 Impact Factor
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    ABSTRACT: BackgroundCOPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.Methods59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis. Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n¿=¿3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.ResultsCOPD patients expressed higher levels (p¿<¿0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7). COPD sIL-6R levels were significantly correlated with sputum neutrophil (r¿=¿0.5, p¿<¿0.0001) and macrophage (r¿=¿0.3, p¿=¿0.01) counts. Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.Conclusion Enhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD. Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.
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    ABSTRACT: Background Microfibrillar-associated protein 4 (MFAP4) is a matricellular glycoprotein that co-localises with elastic fibres and is highly expressed in the lungs. The aim of this study was to test the hypothesis that plasma MFAP4 (pMFAP4) reflects clinical outcomes in chronic obstructive pulmonary disease (COPD). Methods pMFAP4 was measured by an AlphaLISA immunoassay in stable COPD (n=69) at baseline and at follow-up until 24 months after inclusion and in acute exacerbations of COPD (AECOPD) (n=14) at baseline and until 6 months after inclusion. Results The majority of patients (89%) were in GOLD II and III. Multiple linear regressions showed positive associations between pMFAP4 and the Global initiative for Obstructive Lung Disease (GOLD) grade (p=0.01), modified Medical Research Council score (p<0.0001) and BODE index (p=0.04). Negative associations were found with 6-minute walking distance (p=0.04) and bronchodilator-induced reversibility (p=0.02). The pMFAP4 levels varied less than 25% between the baseline and a 3-month follow-up in 83% of the patients. The pMFAP4 levels appeared unaffected in the acute phase of severe AECOPD but rose to an increased stable level within one month after hospitalization. Conclusion Increased pMFAP4 was associated to the severity in COPD and has the potential to serve as a stable disease biomarker. This observation warrants confirmation in a larger longitudinal COPD population.
    Respiratory Medicine 09/2014; 108(9). DOI:10.1016/j.rmed.2014.06.003 · 2.92 Impact Factor
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    ABSTRACT: COPD is today the third leading cause of death worldwide and its prevalence has steadily increased. Prevalence in Europe seems to be levelling, and in western and northern Europe, recent data even indicate a decrease. Beyond tobacco, other major risk factors have been identified, while objective possibilities for prevention exist. New medicines and treatment strategies can slow down disease progression. COPD heterogeneity is huge and restricts treatment options, and epidemiology can contribute to identifying clinically relevant phenotypes of COPD.
    Respiratory Epidemiology, Updated edition. edited by Isabella Annesi-Maesano, Bo Lundbäck, Giovanni Viegi, 09/2014: chapter 1: pages 1-17; European Respiratory Society Publications.., ISBN: 978-1-84984-052-1

Publication Stats

16k Citations
2,218.37 Total Impact Points


  • 2012–2014
    • University of Southern Denmark
      • Institute of Clinical Research
      Odense, South Denmark, Denmark
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2006–2014
    • The University of Manchester
      • • Respiratory Medicine Research Group
      • • Manchester Academic Health Science Centre
      • • School of Translational Medicine
      Manchester, England, United Kingdom
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada
    • University of Kentucky
      Lexington, Kentucky, United States
  • 2004–2014
    • Odense University Hospital
      • Department of Respiratory Medicine - J
      Odense, South Denmark, Denmark
    • University Hospital Of South Manchester NHS Foundation Trust
      Manchester, England, United Kingdom
  • 2013
    • University of Nebraska at Omaha
      • Division of Pulmonary, Critical Care, Sleep and Allergy
      Omaha, NE, United States
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 1991–2013
    • Copenhagen University Hospital Hvidovre
      • • Department of Pulmonary Medicine
      • • Department of Cardiology
      • • Department of Infectious Diseases
      Hvidovre, Capital Region, Denmark
    • Hillerød Hospital
      Hillerød, Capital Region, Denmark
  • 1998–2012
    • IT University of Copenhagen
      København, Capital Region, Denmark
    • Glostrup Hospital
      København, Capital Region, Denmark
  • 2010
    • Haukeland University Hospital
      • Department of Thoracic Medicine
      Bergen, Hordaland Fylke, Norway
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2007–2010
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom
    • University of Groningen
      Groningen, Groningen, Netherlands
  • 1999–2008
    • Institut for Sygdomsforebyggelse
      København, Capital Region, Denmark
  • 2002–2007
    • University of Copenhagen Herlev Hospital
      Herlev, Capital Region, Denmark
    • University of Antwerp
      Antwerpen, Flemish, Belgium
  • 2005
    • GlaxoSmithKline plc.
      • Worldwide Epidemiology
      London, ENG, United Kingdom
    • St George's, University of London
      Londinium, England, United Kingdom
    • Steno Diabetes Center
      Gjentofte, Capital Region, Denmark
  • 1997–2003
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Danish Cancer Society
      København, Capital Region, Denmark
  • 1988–2002
    • Bispebjerg Hospital, Copenhagen University
      • • Department of Cardiology
      • • Department of Pulmonary Medicine
      København, Capital Region, Denmark
  • 1996
    • Rigshospitalet
      København, Capital Region, Denmark
    • København Zoo
      København, Capital Region, Denmark
  • 1992
    • Sundhedsstyrelsen
      København, Capital Region, Denmark