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      Development and validation of a model to predict the risk of exacerbations in chronic obstructive pulmonary disease

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          Prediction models for exacerbations in patients with chronic obstructive pulmonary disease (COPD) are scarce. Our aim was to develop and validate a new model to predict exacerbations in patients with COPD.

          Patients and methods

          The derivation cohort consisted of patients aged 65 years or over, with a COPD diagnosis, who were followed up over 24 months. The external validation cohort consisted of another cohort of COPD patients, aged 50 years or over. Exacerbations of COPD were defined as symptomatic deterioration requiring pulsed oral steroid use or hospitalization. Logistic regression analysis including backward selection and shrinkage were used to develop the final model and to adjust for overfitting. The adjusted regression coefficients were applied in the validation cohort to assess calibration of the predictions and calculate changes in discrimination applying C-statistics.


          The derivation and validation cohort consisted of 240 and 793 patients with COPD, of whom 29% and 28%, respectively, experienced an exacerbation during follow-up. The final model included four easily assessable variables: exacerbations in the previous year, pack years of smoking, level of obstruction, and history of vascular disease, with a C-statistic of 0.75 (95% confidence interval [CI]: 0.69–0.82). Predictions were well calibrated in the validation cohort, with a small loss in discrimination potential ( C-statistic 0.66 [95% CI 0.61–0.71]).


          Our newly developed prediction model can help clinicians to predict the risk of future exacerbations in individual patients with COPD, including those with mild disease.

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          Most cited references 7

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          Should pulmonary embolism be suspected in exacerbation of chronic obstructive pulmonary disease?

          The cause of acute exacerbation of chronic obstructive pulmonary disease (COPD) is often difficult to determine. Pulmonary embolism may be a trigger of acute dyspnoea in patients with COPD.
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            Prevalence of deep-vein thrombosis of the leg in patients with acute exacerbation of chronic obstructive pulmonary disease.

            Acute exacerbation of chronic obstructive pulmonary disease (COPD) is associated with dyspnea and, consequently, reduced mobility. Immobility is a recognized risk factor of deep-vein thrombosis (DVT), but few data exist regarding the prevalence of DVT in patients with acute exacerbation of COPD. Real-time B-mode ultrasonography (US) is a noninvasive screening method for the diagnosis of DVT. We therefore used US to investigate the prevalence of DVT in patients with an acute exacerbation of COPD. In a prospective cohort study, 196 patients with COPD were studied [110 males, 86 females, age: 66.9 +/- 9.1 years, weight: 63.5 +/- 12.7 kg, forced expiratory volume in 1 s (FEV1): 0.7 +/- 0.2 liters, and a ratio of FEV1 to vital capacity (VC): 37 +/- 6%] in a respiratory intensive care unit on the day of admission. Patients with reduced mobility due to other disease were excluded. All US were performed by one experienced person with a 5-MHz linear scanner. The views of the lower extremity were subdivided into three segments: (1) the common femoral, (2) superficial femoral veins including the long saphenous vein and (3) the popliteal vein. In 21 of 196 COPD patients (10.7%), DVT were demonstrated; 18 of these were asymptomatic. Bilateral DVT were not found. In 6 patients, additional diagnoses were: Baker's cyst (n = 3), inguinal lymph node (n = 1) and knee joint effusion (n = 2). There were no differences between patients with and with DVT with respect to age, hemoglobin, PO2, PCO2, pH, FEV1, VC or dyspnea scale. DVT in the lower extremity, which was not detectable on clinical examination, was relatively common in patients with an acute exacerbation of COPD. All clinical variables measured (age, weight, dyspnea scale, lung function, hemoglobin, hematocrit and blood gases) failed to predict patients more likely to have DVT.
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              The importance of cardiovascular disease for mortality in patients with COPD: a prognostic cohort study.

              Cardiovascular diseases are the major cause of mortality in patients with chronic obstructive pulmonary disease (COPD), however, are rarely considered in prediction models in patients with COPD. To quantify the effect of cardiovascular determinants on mortality in patients with a GP's diagnosis of COPD. Four hundred and five patients aged ≥65 years with a diagnosis of COPD (244 with COPD by spirometry) were followed up for an average period of 4.2 (SD 1.4) years. Cox proportional hazard regression analyses with bootstrapping techniques were performed to identify independent predictors of all-cause mortality. In multivariable analysis, all-cause mortality was best predicted by age [hazard ratio (HR) 1.05 [95% confidence interval (CI): 1.01-1.10] per year of age], angina pectoris on history taking [HR 2.32 (95% CI: 1.50-3.58)], airflow obstruction [HR 1.02 (95% CI: 1.01-1.03) per percentage decrease in level of forced expiratory volume in one second (FEV(1)) as % predicted] and C-reactive protein [HR 1.04 (95% CI: 1.02-1.05] per milligram per millilitre increase), respectively. The final model had a C statistic of 0.78 (95% CI: 0.72-0.83) after bootstrapping, and the calibration of the model was very good. The model performed similarly in the subgroup of 244 patients with COPD according to the GOLD criteria (post-dilatory FEV(1)/forced vital capacity < 0.70). Physicians should consider ischaemic heart disease in the clinical evaluation of any patient with a GP's diagnosis of COPD. Angina pectoris on history taking is a strong predictor of all-cause mortality in these patients and should be treated adequately to improve prognosis.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                10 October 2013
                : 8
                : 493-499
                [1 ]Julius Center for Health Sciences and Primary Care, Utrecht, the Netherlands
                [2 ]Department of Pulmonology, Heart-Lung Center, University Medical Center Utrecht, Utrecht, the Netherlands
                Author notes
                Correspondence: Loes CM Bertens, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85060, Stratenum 6.131, 3508 AB Utrecht, the Netherlands, Tel +31 88 756 8375, Fax +31 88 756 9028, Email l.c.m.bertens-2@
                © 2013 Bertens et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Respiratory medicine

                exacerbation of copd, risk prediction, external validation, vascular disease


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