Acute exacerbation of COPD with pulmonary embolism: a new d dimer cut off value

Acute exacerbation of COPD with pulmonary embolism A new D dimer cut off value Egyptian Journal of Chest Diseases and Tuberculosis xxx (2017) xxx–xxx Contents lists available at ScienceDirect Egyptian[.]

Egyptian Journal of Chest Diseases and Tuberculosis xxx (2017) xxx–xxx Contents lists available at ScienceDirect Egyptian Journal of Chest Diseases and Tuberculosis journal homepage: www.sciencedirect.com Acute exacerbation of COPD with pulmonary embolism: A new D-dimer cut-off value Hesham A AbdelHalim a,⇑, Heba H AboElNaga b a b Respiratory Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt Respiratory Medicine Department, Faculty of Medicine, October University, Giza, Egypt a r t i c l e i n f o Article history: Received 17 December 2016 Accepted 29 January 2017 Available online xxxx Keywords: COPD D-dimer Pulmonary embolism a b s t r a c t Background: The clinical symptoms and signs of chronic obstructive pulmonary disease (COPD) exacerbation and pulmonary embolism (PE) may overlap; D-dimer is proven to be higher in patients suffering from COPD exacerbation Objective: To obtain a new cut-off value of D-dimer in subjects with exacerbation of COPD for prospecting those with PE and to avoid unnecessary imaging or contrast-enhanced investigations Methods: The study included 83 male subjects with acute exacerbation of COPD and 30 healthy control subjects Data on serum D-dimer levels, calculated age-adjusted D-dimer levels, and revised Geneva score were obtained for all participants COPD subjects were divided into three subgroups according to the revised Geneva score values; those with high D-dimer levels underwent chest computed tomography with pulmonary angiography (CTPA) Results: Comparisons among the three subgroups revealed significant differences regarding exacerbations, hospitalisations per year, revised Geneva score results, D-dimer values, and positive CTPA results While there were no significant differences between the three subgroups and the control group with respect to age, smoking, and BMI, the D-dimer values showed significant differences Receiver operating characteristic (ROC) curve was analysed to calculate the cut-off value of the serum D-dimer level Conclusion: Given that D-dimer levels are high in subjects having COPD exacerbation, determining a new cut-off value is mandatory to rule out PE and avoid unnecessary further investigations Ó 2017 The Egyptian Society of Chest Diseases and Tuberculosis Production and hosting by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/) Introduction The clinical symptoms and signs of chronic obstructive pulmonary disease (COPD) exacerbation and pulmonary embolism (PE) can be identical Thus, diagnosis of PE in patients having COPD exacerbation is a clinical challenge [1,2] Moreover, many studies have shown that COPD is an independent hazard for PE owing to several causes such as systemic inflammation, polycythaemia, and immobility [3] Patients with COPD have almost double the risk of PE and other venous thromboembolic incidents than those with no COPD [4] Besides, micro-thromboembolism may also Peer review under responsibility of The Egyptian Society of Chest Diseases and Tuberculosis ⇑ Corresponding author at: Respiratory Medicine Department, Ain Shams University, Cairo, 28C, Opera City Compound, Sheikh Zayed, P.O.: 12563 Giza, Egypt E-mail address: heshamatef@med.asu.edu.eg (H.A AbdelHalim) influence the clinical symptoms of an acute exacerbation of COPD; clinical manifestations of PE-like dyspnoea and chest pain are nonspecific, and it could be underestimated in subjects with COPD throughout episodes of exacerbation, which results in worsening of the disease and delay in anticoagulant therapy, thereby leading to poor outcomes [1] As COPD diagnosis depends mainly on the clinical characteristics, PE requires objective verification The real incidence of PE in COPD subjects who are suspected to have PE varies from 19% to 29% [1,5] In those patients with COPD who have diminished gas exchange and pulmonary vascular reserve, PE leads to an increased one-year mortality rate [6,7] It was proved that D-dimer is still the most useful test to exclude venous thromboembolism (VTE) with a negative predictive value of 98% An elevated D-dimer level gives a more precise risk assessment for VTE when combined with a clinical scoring system like the revised Geneva score [8] Moderate- and high-risk revised Geneva scores should identify almost all cases of PE [6,9] D-dimer measurement is a simple and rather noninvasive test that http://dx.doi.org/10.1016/j.ejcdt.2017.01.008 0422-7638/Ó 2017 The Egyptian Society of Chest Diseases and Tuberculosis Production and hosting by Elsevier B.V This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: H.A AbdelHalim, H.H AboElNaga, Acute exacerbation of COPD with pulmonary embolism: A new D-dimer cut-off value, Egypt J Chest Dis Tuberc (2017), http://dx.doi.org/10.1016/j.ejcdt.2017.01.008 H.A AbdelHalim, H.H AboElNaga / Egyptian Journal of Chest Diseases and Tuberculosis xxx (2017) xxx–xxx rules out PE without the need for additional imaging procedures; unfortunately, there is still a debate about the efficacy of D-dimer tests in diagnosing PE in patients suffering from acute exacerbation of COPD [10,11] Irrespective of the presence of venous thromboembolism, D-dimer levels are increased in patients with COPD exacerbation With the advent of chest computed tomography with pulmonary angiography (CTPA), it is now possible to visualise the clot by an imaging technique and reliably confirm the diagnosis of PE in COPD subjects This technique carries high risk in some patients who are allergic to the contrast agent or who have renal impairment and considerable risk of contrast nephropathy Additionally, radiation exposure and the high cost of CTPA manoeuvre necessitates the search for a tool to reduce the need for unnecessary radiological investigation [11–13] The aim of the current study was to define a cut-off value of D-dimer for PE in COPD patients with acute exacerbation D-dimer assessment D-dimer level was measured using the Tina-quantÒ D-dimer Test system (Boehringer, Mannheim, Sandhofer Strasse 116, Mannheim, Germany), which is a particle-enhanced immuneturbidimetric assay CTPA CTPA was performed on a 64-channel multi-detector row CT scanner (Aquillion; Toshiba medical systems, Milwaukee, Wis., USA); it was conducted within 48 h of admission Pulmonary embolism was diagnosed by direct visualisation of embolic material in the case of total occlusion of the pulmonary arterial lumen, by an intraluminal filling defect encircled by intravascular contrast at any level of the pulmonary arteries, or when vessel truncation implied the presence of occlusion Methods Data analysis The study included 83 male subjects who were recruited from the inpatient departments of respiratory medicine of Ain Shams University and October University Hospitals The subjects were diagnosed with acute exacerbation of COPD based on clinical manifestations according to the Anthonisen criteria [14] COPD was confirmed based on clinical manifestations and spirometry according to the criteria of the 2015 Global Initiative for Obstructive Lung Disease [15] Thirty healthy subjects were recruited from the health checkup programme department of the October University Hospital as a control group The exclusion criteria for the COPD group were as follows: any coagulation disorders, haematological diseases, hepatic or renal diseases, recent myocardial infarction, receiving oral anticoagulant or anti-platelet remedy, proven malignancies, any collagen vascular diseases, and surgery or transfusion of blood or blood component in the previous months The following data were collected from all participating subjects: full medical histories; anthropometric data, including body weight, height, and calculated body mass index (BMI); smoking history; and other clinical examinations such as chest radiography, electrocardiogram, arterial blood gas analysis, pre- and post-bronchodilator spirometry, kidney function tests, serum D-dimer, calculated age-adjusted D-dimer, revised Geneva scores, and CTPA Probability for pulmonary embolism was obtained from the revised Geneva score for each subject, following which the participants were classified into three groups: Group 1, low probability (31 subjects); group 2, intermediate probability (42 subjects); and group 3, high probability (10 subjects) The study was approved by the review board of the respiratory medicine department of Ain Shams University, and written informed consent was obtained from all subjects The data were compared using one-way ANOVA tests with post hoc Bonferroni corrections or Kruskal–Wallis H tests for multiple groups Simple correlations between variables were examined using the Pearson’s product correlation coefficient Receiver operating characteristic (ROC) curve was used to calculate cut-off points, area under the curve (AUC), sensitivity, and specificity The Statistical Package for the Social Sciences (SPSS version 17; SPSS, Inc., Chicago, IL, USA) statistical software was used for all statistical analyses All tests were considered significant at P < 0.05 Spirometry The spirometry tests were performed at Ain Shams University using a Spirometrics ENC Flowmate machine (Spring Valley, NY, USA) and at October University using a Spirobank G-USB, class II machine (MIR SRL, S/N 806734; Rome, Italy) The tests were performed before and 20 after b2-agonist inhalation (9% solution of mg/mL salbutamol), administered through a nebulizer The pre- and post-bronchodilator spirometry parameters were measured according to the American Thoracic Society/ European Respiratory Society standards in all subjects [16] Results Initially, 90 patients were enrolled, but chose to discontinue the study Finally, we included 83 male subjects (mean age, 56.18 ± 11.15) with COPD and 30 healthy male control subjects (mean age, 54.90 ± 7.88 years) who completed the study Table shows the patients’ demographic data COPD subjects were divided into three subgroups according to the revised Geneva score values Comparisons among the three subgroups revealed significant differences regarding exacerbations, hospitalisations per year, revised Geneva score results, D-dimer values, and positive CTPA results While there were no significant differences between the three subgroups and the control group regarding age, smoking, and BMI, the D-dimer values differed significantly (Table 2) The ROC curve was plotted to calculate the cut-off value of the serum D-dimer level along with calculation of the area under the curve (AUC), sensitivity, and specificity (Fig 1) Table Data description and comparison between the total COPD subjects and control subjects Age (years) Smoking (Pack Years) BMI (kg/m2) CAT mmRC Exacerbations (/year) Hospitalizations (/year) r-Geneva score D-Dimer (lg/ml) Mean ± SD Control p 56.18 ± 11.15 31.10 ± 17.29 19.93 ± 1.999 22.55 ± 8.05 3.45 ± 1.33 3.24 ± 2.099 2.23 ± 1.92 4.98 ± 4.01 3123.39 ± 920.43 54.90 ± 7.88 31.10 ± 4.75 19.35 ± 2.18 – – – – – 361.29 ± 77.88 0.56 0.999 0.19 – – – – –