This is a population-based study, which provides new data supporting the association of chronic lung diseases such as ILD and COPD with PE. The PE prevalence rates per 100,000 individuals from the study population with COPD, ILD, CTD without ILD, and the general population were 1185, 1746, 412, and 113, respectively, while the DVT prevalence rates were 637, 582, 563, and 138, respectively. The prevalence rates of VTE in patients with COPD, ILD, CTD without ILD, and the general population were 2339, 2793, 1346, and 482 per 100,000 individuals.
CTDs have been associated with an increased risk of PE and DVT development (Choi et al. 2013; Zoller et al. 2012; Ramagopalan et al. 2011; Matta et al. 2009). The risk of DVT in CTD patients was approximately 2–3 times higher than within the non-connective tissue disorder population (Choi et al. 2013; Zoller et al. 2012; Ramagopalan et al. 2011; Matta et al. 2009). In the present study, we evaluated all of the CTDs in the sample population and discovered that the odds ratio for developing DVT in CTD patients is approximately 3.6–4.0 compared to the general population. The risk of developing DVT in CTD patients found in our study is slightly higher than that found by previous studies, which is partly influenced by selection bias from the sample population. However, the results of present study are comparable to a previous study (Ramagopalan et al. 2011).
ILDs have been associated with an increased risk of VTE development (Sprunger et al. 2012; Hubbard et al. 2008; Sode et al. 2010). The risk of DVT in ILD was approximately 2–3 times higher than that found within the control population (Hubbard et al. 2008). The PE prevalence was higher in COPD patients (Tillie-Leblond et al. 2006; Rizkallah et al. 2009). In the present study, the risk of developing DVT or VTE in ILD and COPD patients was 4–6 times higher than that found within the control population.
The incidence of PE and DVT was similar in rheumatoid arthritis patients (Choi et al. 2013). However, the prevalence of PE was approximately 2 times higher than that of DVT in the COPD population (Tillie-Leblond et al. 2006; Rutschmann et al. 2007). In the present study, the prevalence of DVT was higher than PE in the general population and in CTD patients. In contrast to the general population and CTD patients, PE prevalence was 2–3 times higher than DVT in COPD and ILD patients. There are two possibilities as to why there was a higher prevalence of PE than DVT in ILD and COPD patients. First, COPD and ILD patients have thrombogenic potential within the pulmonary circulation (Magee et al. 1988; Wright et al. 1992; Keane et al. 1997; Cosgrove et al. 2004; Renzoni et al. 2003; Sakao et al. 2006). Therefore, COPD and ILD patients have a chance to develop in situ thrombosis. Another possibility is that vascular bed changes may cause delayed resolution of or no resolution of PE from DVT. The pulmonary artery pressure is 2–3 times higher than the central venous pressure, which means that blood flow is faster in the pulmonary artery than in the peripheral vein. The pulmonary artery, from the pulmonary circulation, accounted for 46 % of the total pulmonary resistance (Brody et al. 1968). From this point of view, stagnation of blood in a lower extremity is different from that experienced by the pulmonary artery. The arterial blood coagulation factor has a shorter length of stay in comparison to the venous coagulation factor, resulting in a relatively lower level of coagulation factors found in the artery. The exposure intensity of blood coagulation factors in the pulmonary vein is assumed to be low in comparison to that found in the lower extremity vein. However, this physiologic phenomenon may be reversed by lung local factors (Keane et al. 1997; Cosgrove et al. 2004; Renzoni et al. 2003; Sakao et al. 2006; Chaouat et al. 2008; Behr and Ryu 2008). This may explain the discrepancy of venous thrombosis prevalence between the lower extremity and pulmonary artery with or without the presence of chronic lung diseases.
The association between PE and infection is supported by several studies (Levi et al. 2010; Levi 2004; D’Angelo et al. 1988). Inflammatory condition may contribute the development of venous thrombosis. PE and DVT was significantly associated with COPD exacerbation as well as mortality (Gunen et al. 2010). The odds ratio of PE ranged from 1.7 to 5.0 in inflammatory conditions (D’Angelo et al. 1988; Bucciarelli et al. 1999; Wells et al. 2005). An inflammatory condition in conjunction with structural abnormalities may explain the high prevalence of pulmonary embolism in COPD and ILD.
In 2008, population-based statistics demonstrated that the PE and DVT incidence in the whole population was 5.3 and 7.0 per 100,000 individuals, respectively (Jang et al. 2011). When we confine this to those older than 40 years of age, DVT and PE reaches 13 and 24 per 100,000 individuals, respectively. The incidence of PE based on the number of hospitalized adults was 100–200 fold higher than that found in a population-based study in Korea, which is similar to the present study’s findings of PE prevalence (Choi et al. 2012). This population-based study used the whole population as the denominator. However, this HIRA data was based on individuals who visited a clinic at least once in the 2011 calendar year. This may lead to an overestimation of lung cancer prevalence in the HIRA data or an underestimation of venous thrombosis in the national statistics. Although there would be a discrepancy between this sample population data and the national data, a comparison of the PE prevalence among the groups in the sample data would be possible.
The man-to-woman VTE cancer ratio was 1.0 in those within the background population. The ratios of COPD, ILD, and CTD were 1.1, 1.2, and 1.0, respectively. There was no significant difference between the groups. We suspect that the prevalence of VTE is less influenced by sex even in patients with CTDs.
The HIRA database provided limited available patient data regarding age, sex, year, diagnostic code, and medication code. Therefore, we could not accurately validate patients by identification or exclusion of definition through review of the source medical records. The severity of patients with venous thromboembolism was not evaluated due to the limitation of access to the individual medical records. However, this large-scale data may provide new insights of PE prevalence in patients with COPD and ILD.
In conclusion, our study suggests that the PE prevalence in relation to DVT was significantly higher in patients with COPD or ILD than in patients with CTD without ILD or within the general population. Furthermore, our findings suggest that local inflammatory and physiologic factors may contribute to the development of PE.