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The prevalence and risk factors of pulmonary embolism in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Thrombosis Journal volume 23, Article number: 42 (2025) Cite this article

Abstract

Background

An increased prevalence of PE has been found in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Early identification of risk factors for the development of PE in patients with AECOPD and intervention is important. Therefore, we comprehensively pool and analyze the prevalence and risk factors of PE among patients experiencing AECOPD, aiming to provide valuable insights for clinical-based diagnostic determination and prevention of PE in the AECOPD patient population.

Methods

A systematic literature search was conducted for studies reporting the incidence and risk factors for PE in patients with AECOPD. Study quality was assessed using the modified Newcastle-Ottawa Quality Assessment Scale. The degree of heterogeneity was assessed by the I2 statistic. The publication bias (studies ≥ 10) was evaluated using Egger’s test.

Results

Among the 1421 studies initially retrieved, 22 articles were ultimately selected and incorporated into the analysis. Based on the meta-analysis and the review’s updated findings, the prevalence of PE in AECOPD is 17.82% (95% CI 12.72%-23.57%, P<0.001). The following factors were identified as risk factors for PE among patients with AECOPD: age(weighted mean difference [WMD] 2.0119, 95% CI 0.7126–3.3133, I2 = 51.8%, P = 0.02), males(odds ratio [OR] 0.9528, 95% CI 0.6869–1.3216, I2 = 65.0%, P<0.001), obesity(OR 1.3086, 95% CI 0.1895–9.0385, I2 = 74.5%, P = 0.02), malignant disease(OR 1.5902, 95%CI 0.9689–2.6097, I2 = 54.7%, P = 0.03), hypertension(OR 1.0663, 95%CI 0.7920–1.4355, I2 = 57.7%, P = 0.009), immobilization ≥ 3d(OR 3.9158, 95% CI 1.0925–14.0354, I2 = 91.6%, P<0.001), edema of lower limb(OR 2.1558, 95% CI 1.3365–3.4773, I2 = 75.4%, P<0.001), pulmonary hypertension(OR 1.3146, 95%CI 0.7481-2.3100, I2 = 70.1%, P = 0.04), cough(OR 0.7084, 95%CI 0.1304–3.8497, I2 = 88.8%, P<0.001), purulent sputum(OR 0.7570, 95%CI 0.4005–1.4309, I2 = 61.9%, P = 0.049), and D-dimer(WMD 0.8619, 95%CI 0.0449–1.6789, I2 = 91.4%, P<0.001), C-reactive protein(CRP)(WMD 0.8852, 95%CI -4.0639-5.8344, I2 = 76.4%, P = 0.005) or fibrinogen(WMD 0.8663, 95%CI -0.2572-1.9898, I2 = 92.2%, P<0.001) levels. Clinical risk factors(including S1Q3 pattern on electrocardiograph(ECG), hospital stay and home oxygen therapy) showed no significant association with the occurrence of PE (P>0.05).

Conclusions

This updated meta-analysis and systematic review revealed that the prevalence of pulmonary embolism in the AECOPD was 17.82%. This figure may vary depending on how the diagnostic procedure is carried out. Age, males, obesity, malignant disease, hypertension, immobilization ≥ 3d, edema of lower limb, pulmonary hypertension, cough, purulent sputum, and D-dimer, CRP or fibrinogen level may serve as potential risk factors for PE among patients with AECOPD.

Background

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition distinguished by chronic respiratory manifestations [1]. Findings from large-scale epidemiological investigations, including the Burden of Obstructive Lung Diseases (BOLD) program, suggest that the global prevalence of COPD is estimated to be 10.3% [2]. At present, COPD is counted among the three leading causes of mortality globally. Notably, 90% of the deaths attributed to COPD transpire in low- and middle- income countries [3, 4].

Acute exacerbation of COPD (AECOPD) represents a state where patients with COPD experience a deterioration that exceeds the normal daily variability. This condition elevates the risk of death and necessitates targeted prevention and treatment [1]. Multiple studies [5,6,7] have shown that individuals diagnosed with COPD exhibit an elevated susceptibility to various acute events. Among these, pulmonary embolism (PE) represents a particularly significant concern. Systemic inflammation and other comorbidities, which may also contribute to the development of AECOPD, play a role in this elevated risk. In addition, the signs and symptoms of PE closely resemble many of the clinical manifestations of AECOPD, such as dyspnea, increased sputum purulence and volume, along with augmented coughing and wheezing [8]. This similarity frequently poses challenges in differentiating between the two conditions [9, 10].

PE is typically characterized by a thrombus, specifically pulmonary thromboembolism. This thrombus travels through the bloodstream to the pulmonary arteries, causing embolism. Subsequently, this process gives rise to a progressive elevation in pulmonary artery pressure, right-heart failure, and ultimately, death [11]. Reportedly, the prevalence of PE among patients with COPD is roughly four-fold greater than that among patients without COPD [12]. Furthermore, the prevalence of PE has been found to be elevated in patients experiencing AECOPD [13]. However, the reported prevalence of PE among patients with AECOPD varies considerably from studies. Ali et al. [11] found that PE occurs in about 3.3-29.1% of AECOPD patients. In contrast, Yang et al. [14] found that the prevalence of comorbid PE among 636 patients with AECOPD was 29.6%.

Numerous meta-analyses and assessments of the prevalence of PE have been carried out in AECOPD recipients, however, these studies are not able to provide comprehensive information on the various risk factors that can affect the development of this condition. The objective of this review was therefore to update and analyse studies related to the prevalence of PE in patients with AECOPD and the various risk and morbidity factors associated with its development. Unlike previous meta-analyses, this systematic review placed greater emphasis on the analysis of risk factors. This, in turn, will provide valuable insights and serve as a reference for the prevention and management strategies of patients with AECOPD complicated by PE.

Methods

This review was conducted in accordance with the guidelines of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-analyses) [15]. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO, http://www.crd.york.ac.uk/PROSPERO): CRD42024519813.

Search strategy

Three reviewers (L.M.Z., J.Y.Q. and X.Y.) independently searched PubMed, Web of Science, Embase, and The Cochrane Library databases to identify relevant studies. The database searches were electronically performed on the respective database websites, starting from their inception dates. The most recent search was carried out on March 27, 2024. A combination of keywords was utilized, including “pulmonary embolism”, “thromboembolism”, “chronic obstructive pulmonary disease”, “acute exacerbation COPD”, “risk factors”, and “influencing factors”. The specific search strategy and the keyword combinations employed were presented in Supplementary Material 1.

The initial screening of the search results was carried out by evaluating the titles and abstracts of the retrieved studies. Subsequently, the full-text versions of the shortlisted studies underwent a meticulous and in-depth assessment according to the pre-established inclusion and exclusion criteria. Only those articles that met all the criteria were ultimately chosen for inclusion in this review. To ensure comprehensiveness, a manual examination of the references within the retrieved articles, as well as those of prior relevant reviews, was conducted. In cases of any discrepancies among the reviewers, they were systematically resolved through in-depth discussion.

Study selection

Three authors (L.M.Z., J.Y.Q., and X.Y.) independently carried out the screening of full-text articles and the inclusion of studies based on the following criteria. The authors were able to reach a consensus regarding the criteria for the inclusion of studies in the review:

Inclusion criteria: (1) Studies that looked into the prevalence of PE in AECOPD were included in the review including prospective, cross-sectional, and retrospective studies; (2) Studies that utilized CT data for diagnosis of PE.

Exclusion criteria: (1) Although studies reported the presence of PE in COPD patients, they did not examine the prevalence of this condition in AECOPD; (2) Studies identified instances of PE in COPD patients through other diagnostic methods; (3) Other references included case reports, editorials, and review articles. A study that had a larger sample size was selected for inclusion if it had two or more reports with duplicated data. No limitations were imposed with respect to the language in which the studies were published or the magnitude of their sample sizes.

Data extraction and quality assessment

The three reviewers(L.M.Z., J.Y.Q. and X.Y.) were independently responsible for extracting data from the articles. In case of any discrepancies, they reached a consensus through discussion. At the commencement of the review, a data extraction form was designed to systematically extract relevant details from the studies. The collected data included the study’s first author, the type of study, the target population, the diagnosis protocol, and the prevalence of PE. The demographic, clinical, and laboratory features were also extracted from the relevant studies. The principal outcome under investigation was to explore the risk factors for the development of PE in patients with AECOPD.

Three independent reviewers (L.M.Z., J.Y.Q. and X.Y.) assessed the risk of bias at the study level by the Newcastle-Ottawa Scale (NOS) criteria [16]. The maximum total score of the NOS is 9. Studies with a total score of ≥ 7 were classified as high-quality, those with scores ranging from 4 to 6 were considered fair-quality, and those with scores < 4 were regarded as low-quality.

Statistical analysis

Regarding the analysis of the prevalence of PE in AECOPD patients, the prevalence data of PE in AECOPD from the included studies were extracted. After collecting the data, the prevalence estimates were calculated using the R software(version 4.4.0). To pool the proportions, the data were transformed using an inverse sine transformation. The heterogeneity of the PE prevalence in AECOPD was explored based on different PE screening criteria, and subgroup analyses were performed to clarify the existing evidence.

For the risk factors of PE in AECOPD patients, the baseline information and clinical characteristics of the included literature were extracted to count the involved risk factors. These risk factors included demographic risk factors, clinical symptoms, complications, clinical risk factors, and laboratory risk factors. Only those risk factors commonly mentioned in ≥ 3 studies were included in the analysis.

For continuous variables, the weighted mean difference(WMD) with 95% confidence intervals (CI) was selected as the effect size, while for dichotomous variables, the odds ratio (OR) with 95% CI was used. All statistical analyses were conducted using the meta-packages and metaprop functions in R software version 4.4.0(The R Foundation for Statistical Computing, Vienna, Austria). The degree of heterogeneity was assessed by the I2 statistic. The publication bias (studies ≥ 10) was evaluated using Egger’s test [17]. P < 0.05 was considered as statistical significance.

Results

Literature retrieval results

The search process initially led to the identification of 1421 articles. Subsequently, 78 full-text studies were retrieved for more detailed evaluation. After a careful review process, 22 studies [5, 6, 14, 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36] were ultimately selected for both qualitative and quantitative analysis (Fig. 1). A rigorous evaluation of these included studies was carried out, and all were determined to have a low risk of bias (Table 1).

Fig. 1
figure 1

Flow chart of article selection

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Table 1 Basic features of included studies
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Basic features of included studies

Table 1 summarizes the studies that were included in the analysis. They involved the data of over 1131 individuals with PE and almost 5211 non-PE patients from various countries. Many of the studies were conducted in prospective cohorts, while others were retrospective case-control studies. The diagnostic workup protocol for PE exhibited significant variability among the studies. Among 13 studies, all subjects for the purpose of diagnosis underwent computed tomography (CT) scans. In some studies, CT was selectively carried out on patients based on the physician’s discretion [27, 32, 33], Geneva score [6], Wells score [5], echocardiography criteria [29], lower limb ultrasonography (USG) [5] or D-dimer levels [19, 24].

Prevalence of PE

A meta-analysis was performed to examine the data collected from 6342 individuals. It revealed that the prevalence of PE in the AECOPD was 17.82% (95% CI 12.72%-23.57%, P<0.0001) (Fig. 2). Different studies used different diagnostic methods for assessing PE in AECOPD patients (Table 1). Due to the varying nature of the diagnostic methods used for assessing PE, an estimate of its prevalence was carried out by subgroup analysis. This was done in studies that utilized similar protocols (Fig. 2). In studies where all patients underwent computed tomography angiogram (CTA) without any other diagnostic procedure or physician judgment, the prevalence was 23.81%(95% CI 16.69%-31.75%). In contrast, in studies that only utilized CTA after screening the subjects, the prevalence of PE was only 8.58% (95% CI 3.71%-15.22%). In studies that only utilized CTA according to clinician’s assessment, the prevalence of this condition was 14.32% (95% CI 8.63%-21.16%).

Fig. 2
figure 2

Sub-group analysis of prevalence of PE among AECOPD patients according to PE diagnostic method

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Risk factors for PE

Demographic risk factors

13 articles provided information regarding age. The pooled estimates revealed that the age of patients with PE were notably greater than that of non-PE patients (WMD 2.0119, 95%CI 0.7126–3.3133, I2 = 51.8%, P = 0.02) (Table 2; Fig. 3A). 16 studies provided information regarding sex. The result indicated that males had a higher likelihood of developing PE compared to females (OR 0.9528, 95%CI 0.6869–1.3216, I2 = 65.0%, P<0.001) (Table 2; Fig. 3B). 3 studies reported information about obesity (BMI > 30), showing an association with the development of PE (OR 1.3086, 95%CI 0.1895–9.0385, I2 = 74.5%, P = 0.02) (Table 2; Fig. 3C). Estimates for eight comorbidities were also pooled. Malignant disease(OR 1.5902, 95%CI 0.9689–2.6097, I2 = 54.7%, P = 0.03) (Table 2; Fig. 4A), hypertension(OR 1.0663, 95%CI 0.7920–1.4355, I2 = 57.7%, P = 0.009) (Table 2; Fig. 4B), immobilization ≥ 3 d(OR 3.9158, 95%CI 1.0925–14.0354, I2 = 91.6%, P<0.001) (Table 2; Fig. 4C), edema of lower limb(OR 2.1558, 95%CI 1.3365–3.4773, I2 = 75.4%, P<0.001) (Table 2; Fig. 4D) and pulmonary hypertension(OR 1.3146, 95%CI 0.7481-2.3100, I2 = 70.1%, P = 0.04) (Table 2; Fig. 4E) were found to be related to the occurrence of PE. No publication bias was detected in the studies that were included in the analysis.

Fig. 3
figure 3

Meta-analysis of demographical factors that could contribute to the development of PE among AECOPD. A, Age; B, Male; C, Obesity

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Fig. 4
figure 4

Meta-analysis of comorbidities that could contribute to the development of PE among AECOPD. A, Malignant disease; B, Hypertension; C, Immobilization ≥ 3 d; D, Edema of lower limb; E, Pulmonary hypertension

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Table 2 Meta-analysis results of the whole studies on PE risk factors in AECOPD
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Clinical symptom and risk factors

3 studies investigated the connection between cough and PE. The result demonstrated that patients experiencing cough had more likelihood for developing PE (OR 0.7084, 95%CI 0.1304–3.8497, I2 = 88.8%, P<0.001) (Table 2; Fig. 5A). Similarly, patients with purulent sputum also had a remarkably elevated rate of PE (OR 0.7570, 95%CI 0.4005–1.4309, I2 = 61.9%, P = 0.049) (Table 2; Fig. 5B). All clinical risk factors that were analyzed did not increase the likelihood of developing PE (I2 = 0-32.3%, P > 0.05).

Fig. 5
figure 5

Meta-analysis of clinlcal symptoms that could contribute to the development of PE among AECOPD. A, Cough; B, Purulent sputum

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Laboratory risk factors

Laboratory parameters were acquired at the time of hospital admission. In patients with PE, the values of D-dimer (WMD 0.8619, 95%CI 0.0449–1.6789, I2 = 91.4%, P<0.001), C-reactive protein(CRP) (WMD 0.8852, 95%CI -4.0639−5.8344, I2 = 76.4%, P = 0.005) and fibrinogen(WMD 0.8663, 95%CI -0.2572−1.9898, I2 = 92.2%, P<0.001) were significantly different from those of non-PE patients(Table 2; Fig. 6A, B, C). NT-proBNP (I2 = 49.3%, P = 0.12) did not affect the development of PE (Table 2).

Fig. 6
figure 6

Meta-analysis of laboratory factors that could contribute to the development of PE among AECOPD. A, D-dimer; B, CRP; C, Fibrinogen

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Discussion

This review revealed that the overall prevalence of pulmonary embolism (PE) among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was 17.82% (95%CI 12.72-23.57%). The prevalence of PE in the study was similar to the findings of prior meta-analyses [(16.1%, 95%CI 8.3-25.3%) [37] and (17.2%, 95%CI 13.4-21.3%) [38]]. The data included in our review were gathered from 22 studies, that is more than the number included in recent papers. Our results could be more reliable due to the large sample size. The stability of the results was maintained by the sensitivity analysis.

Prevalence of PE

In this review, we sought to explore the heterogeneity of PE prevalence in included studies based on PE diagnostic protocols. In studies where all patients underwent CT angiogram (CTA), a higher prevalence of PE was detected, amounting to 23.81% (95%CI 16.69-31.75%). Conversely, studies [5, 6, 19, 24, 26, 29] that utilized the predefined recommended CTA regimen reported a lower prevalence of PE, which was 8.58% (95%CI 3.71-15.22%). In three retrospective studies [27, 32, 33], all patients were evaluated by a physician and underwent CTA, and the prevalence in these cases was 14.32% (95%CI 8.63-21.16%).

The use of the CTA remains the preferred choice for diagnosis of PE due to its relatively high sensitivity (96 ~ 100%) and specificity (89 ~ 98%) [39]. When combined with a clinical scoring scheme, it has proven to be a cost-effective approach for diagnosing acute PE [40]. For example, the Wells Score and the revised Geneva Score are widely applied in clinical practice for predicting the risk stratification of PE [41, 42]. However, the diagnostic accuracy of these scores for the presence or absence of PE in AECOPD has had unsatisfactory results in relevant studies. In an included study, Furcada et al. [32] reported the sensitivity and specificity of the Wells score (cut-off > 4) for diagnosing PE occurring in AECOPD to be 24% and 90%, respectively, and that of the Geneva score (cut-off ≥ 3) to be 59% and 43%, respectively. Similar low diagnostic accuracy of these rules was also reported by other included studies [20, 23]. These scores are not universally used in COPD patients, and further studies are needed to analyze the diagnostic accuracy of the various methods for detecting PE among AECOPD, as well as the factors that can contribute to its development [43].

In another included study, Couturaud et al. [6] used a very high Geneva score (≥ 11) for the initial screening of patients with AECOPD, and the remaining patients were further screened by levels of D-dimer, a fibrin degradation product, whose levels are elevated during remodelling of an active blood clot such as in acute PE. However, the high false-positive rate of D-dimer testing, especially in patients with AECOPD, is a concern. Akpinar et al. [25] have also shown that due to the hypercoagulable state of COPD, D-dimer levels may be elevated even in patients with stable COPD compared to controls. To overcome this, several studies [25, 44] have shown the use of higher D-dimer thresholds and even age-adjusted D-dimer levels to reduce the use of validated CTAs in such patients. This may account for the finding in our review that the incidence of PE derived from the use of a predetermined recommended CT regimen was lower than that in studies where all patients underwent CTA. Although routine CTA can be used in most patients due to the risk associated with patients receiving intravenous contrast prior to CTA scanning, it is not always feasible to use it in every person [45]. Therefore, clinicians should use multiple screening tools and be highly sceptical based on risk factors for PE in AECOPD to recommend further confirmatory tests.

Risk factors for PE

Demographic risk factors

Previous studies [46] have shown that COPD is a risk factor that could contribute to the development of PE among AECOPD. In this study, we found that age(WMD 2.0119, P = 0.02) was associated with the risk of developing PE in patients with AECOPD. This finding is consistent with previous studies [47]. Besides, obesity(OR 1.3086, P = 0.02) and male gender(OR 0.9528, P<0.001) might also be the potential risk factors. Previous literature [48] confirmed this using multiple regression analysis.

According to Laurent B [49]. et al., in a study, individuals who had previously suffered from PE, especially those who had a history of VTE, were more prone to experiencing a fatal or recurrent PE compared to those with DVT-only. This is contrary to the results of our review(OR 2.5921, P = 0.06). The results of the study might have been explained by the small number of studies involved. It has been known that cancer patients are more prone to experiencing poor prognosis when they have a history of venous thrombosis [50]. The findings of this review suggest that malignant disease might be a risk factor for developing PE. In practice, in patients with COPD who develop pulmonary embolism, it is important that the clinicians consider the presence of an underlying cancer. The results of this review indicated that hypertension(OR 1.0663, P = 0.009) may be associated with the development of PE, whereas diabetes mellitus(P = 0.45) may not be. Prior to this review, no other review had comprehensively analyzed the relationship between these two comorbidities and PE, and the results of related studies were inconsistent. Therefore, more studies and systematic reviews are required to further explore their association with the occurrence of PE.

Patients with AECOPD were more prone to experiencing pulmonary embolism if they were immobile(OR 3.9158, P < 0.001). In patients with AECOPD, airway secretions are usually increased [51]. Immobilization leads to a reduction in physical activity, which in turn impairs normal mucociliary clearance mechanisms, leading to mucus stasis, increased airway obstruction, and an increased risk of infection. Patients with AECOPD are inherently in a state of systemic inflammation and have some degree of endothelial dysfunction, which increases their risk of developing blood clots. Immobilization can further exacerbate this risk by promoting blood stasis in the lower extremities [52].

Edema of the lower limb(OR 2.1558, P<0.001) were also found to increase the likelihood of developing PE, which is similar to previous findings [48]. COPD can also increase the risk of developing pulmonary hypertension. This condition can cause blood flow to stagnate and increase vascular resistance [53]. When pulmonary thromboembolism (PTE) occurs, the pulmonary artery and its branches are blocked by thrombus, which can lead to a rapid elevation in pulmonary artery pressure.

Clinical symptom and risk factors

The typical symptoms of PE include chest pain, sudden-onset dyspnea, and tachypnea. However, there have been limited studies on the differences between patients with and without PE [54]. The results of these studies revealed that the presence of dyspnea [55] and chest pain [37] was associated with the development of PE. However, this is contrary to the results of our review(P>0.05). The small sample size of the analysis might also explain the findings.

In this review, we identified two risk factors that were associated with the presence of PE in patients with a common condition known as AECOPD. These are cough(OR 0.7084, P<0.001) and purulent sputum(OR 0.7570, P = 0.049). This implied that when patients present with cough or purulent sputum, it is crucial to be vigilant about the potential risk of developing PE. However, Symptoms such as cough and purulent sputum, unlike factors such as age and obesity which may have clear measures, may be defined and assessed differently for different studies. For example, there may be differences in the frequency and severity of cough, the criteria for determining severity, and the description of purulent sputum such as colour and texture, which can lead to inconsistent results.

Furthermore, our analysis did not find a link between clinical risk factors (including S1Q3 pattern on ECG, hospital stay and home oxygen therapy) and the development of PE(P>0.05). However, given the insufficient sample size of the relevant indicators in this review, further studies are warranted to confirm their potential correlations with the incidence of PE.

Laboratory risk factors

D-dimer is derived from cross-linked fibrin clots dissolved by fibrinolytic enzymes and is a degradation product of fibrinolysis, mainly reflecting the function of fibrinolysis, and is an important marker for ruling out PE [56, 57]. Currently, 500ug/L is mostly used as the threshold, while some Japanese scholars have suggested 1100ug/L as the new threshold for D-dimer to exclude PE [58]. D-dimer is highly sensitive but not very specific, and in addition to being increased in acute venous thromboembolism, it is also elevated in the setting of nonthrombotic events such as cancer, systemic infections, pregnancy, etc. D-dimer has a good negative predictive value, and a normal level is the most valuable laboratory marker for ruling out DVT [59]. D-dimer levels have been also reported to be useful in the early diagnosis and assessment of pulmonary embolism in COPD patients [60]. Likewise in our review, D-dimer was associated with an increased likelihood of developing PE among patients experiencing AECOPD(WMD 0.8619, P<0.001). This suggests that the level of D-dimer could be an important factor that contributes to the development of PE in patients with AECOPD.

In addition, other risk factors such as fibrinogen(WMD 0.8663, P<0.001) and CRP(WMD 0.8852, P = 0.005) were also identified. It could be that they increases systemic inflammation and thrombosis during exacerbations [61, 62]. CRP is an acute time-phase reactive protein. AECOPD patients have airway inflammation themselves, and the sustained inflammatory response may lead to vascular endothelial cell damage, which puts the blood in a hypercoagulable state and increases the risk of PE [63, 64]. FIB is a protein with coagulant properties that increases the viscosity of the blood. In patients with AECOPD, the liver’s ability to synthesise FIB may be enhanced due to factors such as hypoxia and inflammation, leading to increased levels of FIB in the blood [65]. Increased blood viscosity slows down blood flow and makes it easier for blood clots to form, which can lead to pulmonary embolism when they are dislodged and travel with the blood circulation to the blood vessels in the lungs [66].

Several studies have shown that B-type natriuretic peptide (BNP) levels are associated with disease risk and prognosis in patients with COPD combined with PE, with higher BNP levels indicating higher risk stratification and poorer prognosis [67]. Our review yielded contrary results(P = 0.12), which may be due to the small number of studies that were included in the analysis did not provide enough evidence to support the findings.

In conclusion, in our review, to identify the potential risk factors for developing PE in AECOPD, we analyzed the various demographic and clinical indicators of the patients. The results of the analysis revealed that age, males, obesity, malignant disease, hypertension, immobilization ≥ 3d, edema of lower limb, pulmonary hypertension, cough, purulent sputum, and elevated D-dimer, CRP or fibrinogen level were risk factors for this condition. These results may suggest that when an elderly obese male patient with AECOPD has a combination of malignant disease, hypertension, braking for ≥ 3 days, lower limb oedema, or pulmonary hypertension, or develops cough, purulent sputum, or D-dimer, CRP, and fibrinogen elevation, the development of PE should be noted. Further CTA should be performed to clarify the diagnosis, and anticoagulation should be performed or not based on the results.

The strength of the review was reinforced by the inclusion of numerous studies. Our comprehensive approach allowed us to collect and analyze the largest amount of data on the prevalence of PE among patients with this condition. In addition, to the best of our knowledge, the findings of this review provide the first comprehensive analysis of the various risk factors that can increase the likelihood of developing PE in patients with AECOPD.

Limitations

Firstly, the review did not identify a link between the presence of various risk factors and the overall condition or the clinical prognosis of patients with this condition, but it did provide some preliminary evidence. Due to the limited sample size of some original studies, it is important that future studies are conducted in multicenter settings. We look forward to more future research, such as: prospective cohort studies to establish causal links between identified risk factors and PE, or randomized controlled trials assessing the utility of targeted CTA based on risk stratification models. Future studies will help us to gain a deeper understanding of the link between AECOPD and PE, and improve our current assessment.

Secondly, the studies included in this review were mainly from Asia and Europe, which limits the external validity of the findings in other regions (e.g., North America, Africa). There is a need for multicentre studies in more diverse populations in subsequent studies.

Thirdly, although Egger’s test did not show significant publication bias, potential language bias may have arisen due to the inclusion of only English and Chinese-language studies, where relevant studies published in other languages may have been excluded. The amount of literature on inclusion studies should be further expanded in subsequent studies. To enrich the inclusion studies in other languages, so as to reduce language bias and make the findings more credible.

Moreover, among patients who underwent CTA based on physician assessment, we did not assess the risk of bias due to the insufficient number of original studies mentioning smoking history, anticoagulant use, and activity status. Therefore, there may be confounding of indications in observational studies in which CTA was selectively performed.

Lastly, evaluated risk factors and data were mainly referred to in-patients and acute phase, a context where VTE prohylaxisis recommended. However, there were not enough data on the implementation of preventive measures (either mechanical or pharmacological) and their outcomes in the analyses included in this review. Only one or two papers were described and did not meet the criteria for inclusion in the analyses of this review. We look forward to more relevant studies in the future, more enough to further enrich the data about preventive measures and to provide more valuable support for the risk factors for the occurrence of PE in AECOPD patients.

Conclusion

Based on the meta-analysis and the review’s updated findings, the prevalence of PE in AECOPD is 17.82%, which may vary depending on the PE diagnostic workup protocol. The prevalence of PE was higher when all the patients had underwent CTA(23.81%), as opposed to when a study was carried out with a specific diagnostic protocol(8.58%). Additionally, age, male gender, obesity, malignant disease, hypertension, immobilization for ≥ 3 days, lower limb edema, pulmonary hypertension, cough, purulent sputum, and elevated D-dimer, CRP, or fibrinogen levels may be potential risk factors for PE among patients experiencing AECOPD.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

AECOPD:

Acute Exacerbation of Chronic Obstructive Pulmonary Disease

CI:

Confidence Intervals

COPD:

Chronic Obstructive Pulmonary Disease

CRP:

C-reactive Protein

CT:

Computed Tomography

ECG:

Electrocardiograph

NOS:

the Newcastle-Ottawa Scale

NT-proBNP:

N-terminal Pro-B-type Natriuretic Peptide

OR:

Odds Ratio

PE:

Pulmonary Embolism

WMD:

Weighted Mean Difference

References

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Funding

This work was supported by Research Fund of Anqing Health Science and Technology program (2022Z3017).

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Author notes

  1. Mingzhu Li, Yeqian Jiang and Ying Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Anqing First People’s Hospital of Anhui Medical University, 42 Xiaosu Road, Yingjiang District, Anqing, 246003, China

    Mingzhu Li, Yeqian Jiang, Ying Xu & Qianbing Li

  2. The Fifth Clinical College of Anhui Medical University, Hefei, China

    Mingzhu Li & Yeqian Jiang

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Contributions

ML: Writing– original draft, Study design, Screening, Data extraction, Data analysis. YJ: Writing– review & editing, Visualization, Screening, Data extraction. YX: Writing– review & editing, Visualization, Screening, Data extraction. QL: Writing– review & editing, Conceptualization.

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Li, M., Jiang, Y., Xu, Y. et al. The prevalence and risk factors of pulmonary embolism in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Thrombosis J 23, 42 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12959-025-00728-6

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Thrombosis Journal

ISSN: 1477-9560

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