Pharmacotherapy for pulmonary embolism: new anticoagulants

Pulmonary embolism is associated with reduced survival and considerable economic burden worldwide. In Korea, the incidence of pulmonary embolism has been gradually increasing. Older individuals are at an increased risk for pulmonary embolism and anticoagulation-related bleeding events. Typically, heparin and vitamin K antagonists are employed to treat pulmonary embolism; however, these agents present numerous limitations. Hence, novel anticoagulants with improved safety and efficacy profiles are urgently needed.Current Concepts: Direct oral anticoagulants (DOACs), including direct thrombin (coagulation factor II) inhibitors and selective inhibitors of coagulation factor Xa, have emerged as alternative agents. Phase III, large-scale clinical trials have revealed that DOACs are non-inferior to standard therapy during initial and long-term treatment of pulmonary embolism, considering the safety profile. Evidence-based clinical guidelines recommend that primary care clinicians employ DOACs over warfarin to achieve anticoagulation.Discussion and Conclusion: For over 70 years, the standard therapy for most patients with pulmonary embolism has involved heparin administration, overlapped and followed by a vitamin K antagonist. Recently developed DOACs against coagulation factor Xa or thrombin might overcome limitations of standard therapy, including the need for injection and regular dose adjustment with laboratory monitoring. These limitations hinder the management of patients with pulmonary embolism and negatively impact the patient’s quality of life. Four DOACs, including apixaban, dabigatran, edoxaban, and rivaroxaban, are currently available for treating pulmonary embolism in Korea, which could simplify the therapeutic strategy.

Incidence of Venous Thromboembolism: The 3 rd Korean Nationwide Study

Background@#The incidence of venous thromboembolism (VTE) has gradually increased in the Korean population. This study aimed to evaluate the annual age- and sex-adjusted incidence rates (ASR) of VTE and anticoagulation trends between 2014 and 2018. @*Methods@#Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified VTE patients between 2014 and 2018 using both diagnostic and medication anticoagulant codes assigned within 6 months of the initial index event. Anticoagulant patterns were classified as follows: direct oral anticoagulants (DOAC), panticoagulants, warfarin, and mixed anticoagulation regimens. @*Results@#We identified 95,205 patients with VTE (female, 56.8%). The ASR for VTE per 100,000 person-years increased from 32.8 in 2014 to 53.7 cases in 2018 (relative risk of 1.63; 95% confidence interval, 1.6–1.67). The VTE incidence rates were 25 times higher in the ≥ 80 group than in the 30s group. VTE occurred 1.29 times more often in women than in men. The proportion of DOAC prescriptions increased from 40.5% to 72.8%, whereas warfarin prescriptions decreased from 27% to 5.6% in 2014 and 2018. @*Conclusion@#In Korea, the ASRs of VTE continued to increase since 2014, but the rate of increase slowed in 2018. The VTE occurred more often in the elderly and in women. Five years after the introduction of DOACs in 2013, they accounted for 73% of all anticoagulants used to treat VTE.

Impact of gender on chronic obstructive pulmonary disease outcomes: a propensity scorematchedanalysis of a prospective cohort study

Background/Aims@#Despite increasing awareness of the burden of chronic obstructive pulmonary disease (COPD) in women, knowledge regarding gender differences in COPD outcomes is limited. Therefore, we aimed to evaluate whether COPD outcomes, including exacerbations, lung , and symptoms differ by gender. @*Methods@#We recruited patients with COPD from two Korean multicenter prospective cohorts. After propensity score matching, the main outcome, the incidence of moderate or severe exacerbations was analyzed using a negative binomial regression model. We also assessed changes in lung function and symptom scores including the St. George’s respiratory questionnaire for COPD (SGRQ-C), COPD assessment test (CAT), and the modified Medical Research Council (mMRC) dyspnea score. @*Results@#After propensity score matching, 74 women and 74 men with COPD were included. The incidence rates of exacerbations in women and men were not significantly different (incidence rate ratio, 1.49; 95% confidence interval [CI], 0.88 to 2.54). There was no significant difference in the incidence rates adjusted for medication possession ratios of long-acting muscarinic antagonists, long-acting β-agonists, and inhaled corticosteroids during the follow-up period (incidence rate ratio, 1.47; 95% CI, 0.86 to 2.52). Rates of decline in post-bronchodilator forced expiratory volume in 1 second and forced vital capacity did not differ between women and men during 48 months of follow-up. The changes in scores on the SGRQ-C, CAT, and mMRC Questionnaire in women were also similar to those in men. @*Conclusions@#We observed no gender differences in the rate of exacerbations of COPD in a prospective longitudinal study. Further studies are needed to confirm these findings in the general COPD population.

Incidence and Risk Factors of Recurrent Venous Thromboembolism after Pulmonary Embolism / 결핵

BACKGROUND: Information about the epidemiology of venous thromboembolism (VTE) recurrence in Korea is lacking. The purpose of this study was to investigate VTE cumulative recurrence rates and identify risk factors for VTE recurrence among Korean adults. METHODS: A retrospective cohort study was conducted on adult patients (≥18 years) admitted to a university teaching hospital for pulmonary embolism (PE) from 2005 to 2013. The main outcome of interest was a recurrence of VTE. We used Cox proportional hazard regression analyses to calculate the relative risk of VTE recurrence. RESULTS: Five-year cumulative incidence of recurrent VTE events was 21.5% (95% confidence interval [CI], 17.7–25.4) in all cases of PE; 17% after provoked and 27% after unprovoked PE. Multivariate analysis showed that body mass index (BMI) of ≥25 (hazard ratio [HR], 2.02; 95% CI, 1.17–3.46; p=0.01) and longer anticoagulation therapy duration (HR, 0.90; 95% CI, 0.84–0.96; p<0.01) were independently associated with risk of VTE recurrence. Risk factors not found to be statistically significant at the <0.05 level included history of VTE (HR, 1.81; 95% CI, 0.84–3.88; p=0.12), unprovoked PE (HR, 1.70; 95% CI, 0.89–3.25; p=0.10), symptomatic deep vein thrombosis (HR, 1.62; 95% CI, 0.89–2.94; p=0.10), and female sex (HR, 1.42; 95% CI, 0.78–2.55; p=0.24). We found that age, history of cancer, and other co-morbidities did not significantly affect the risk of VTE recurrence. CONCLUSION: Recurrence of VTE after PE is high. Patients with BMI ≥25 or reduced anticoagulation therapy duration have a higher risk of recurrent VTE.

Incidence and Risk Factors of Recurrent Venous Thromboembolism after Pulmonary Embolism / 결핵및호흡기질환

BACKGROUND@#Information about the epidemiology of venous thromboembolism (VTE) recurrence in Korea is lacking. The purpose of this study was to investigate VTE cumulative recurrence rates and identify risk factors for VTE recurrence among Korean adults.@*METHODS@#A retrospective cohort study was conducted on adult patients (≥18 years) admitted to a university teaching hospital for pulmonary embolism (PE) from 2005 to 2013. The main outcome of interest was a recurrence of VTE. We used Cox proportional hazard regression analyses to calculate the relative risk of VTE recurrence.@*RESULTS@#Five-year cumulative incidence of recurrent VTE events was 21.5% (95% confidence interval [CI], 17.7–25.4) in all cases of PE; 17% after provoked and 27% after unprovoked PE. Multivariate analysis showed that body mass index (BMI) of ≥25 (hazard ratio [HR], 2.02; 95% CI, 1.17–3.46; p=0.01) and longer anticoagulation therapy duration (HR, 0.90; 95% CI, 0.84–0.96; p<0.01) were independently associated with risk of VTE recurrence. Risk factors not found to be statistically significant at the <0.05 level included history of VTE (HR, 1.81; 95% CI, 0.84–3.88; p=0.12), unprovoked PE (HR, 1.70; 95% CI, 0.89–3.25; p=0.10), symptomatic deep vein thrombosis (HR, 1.62; 95% CI, 0.89–2.94; p=0.10), and female sex (HR, 1.42; 95% CI, 0.78–2.55; p=0.24). We found that age, history of cancer, and other co-morbidities did not significantly affect the risk of VTE recurrence.@*CONCLUSION@#Recurrence of VTE after PE is high. Patients with BMI ≥25 or reduced anticoagulation therapy duration have a higher risk of recurrent VTE.

Long-term rivaroxaban for the treatment of acute venous thromboembolism in patients with active cancer in a prospective multicenter trial

BACKGROUND/AIMS@#Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients.@*METHODS@#In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication.@*RESULTS@#Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died.@*CONCLUSIONS@#Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.

Does the GOLD 2017 Classification Improve the Ability to Predict Exacerbation and Mortality? / 결핵및호흡기질환

No abstract available.

Determinants of Nicotine Dependence in Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

BACKGROUND: Smoking cessation is the most powerful intervention to modify progress of chronic obstructive pulmonary disease (COPD), and nicotine dependence is one of the most important determinants of success or failure in smoking cessation. We evaluated nicotine dependence status and investigated factors associated with moderate to high nicotine dependence in patients with COPD. METHODS: We included 53 current smokers with COPD in the Korean Obstructive Lung Disease II cohort enrolled between January 2014 and March 2016. Nicotine dependence was measured by using Fagerstrom test for nicotine dependence (FTND). Cognitive function was assessed by Korean version of Montreal Cognitive Assessment. RESULTS: The median FTND score was 3, and 32 patients (60%) had moderate to high nicotine dependence. The median smoking amount was 44 pack-years, which was not related to nicotine dependence. Multiple logistic regression analysis revealed that high education status (odds ratio, 1.286; 95% confidence interval, 1.036–1.596; p=0.023), age <70 (odds ratio, 6.407; 95% confidence interval, 1.376–29.830; p=0.018), and mild to moderate airflow obstruction (odds ratio, 6.969; 95% confidence interval, 1.388–34.998; p=0.018) were related to moderate to high nicotine dependence. CONCLUSION: Nicotine dependence does not correlate with smoking amount, but with education level, age, and severity of airflow obstruction. Physicians should provide different strategies of smoking cessation intervention for current smokers with COPD according to their education levels, age, and severity of airflow obstruction.

The Perioperative Management of Antithrombotic Therapies Using Enoxaparin

Oral anticoagulant therapy is frequently and increasingly prescribed for patients at risk of arterial or venous thromboembolism (VTE). Although elective surgical or invasive procedures have necessitated temporary interruption of anticoagulants, managing these patients has been performed empirically and been poorly investigated. This study was designed to evaluate the adequacy of perioperative anticoagulation using enoxaparin. This was a retrospective, single-center study that evaluated the efficacy and safety of therapeutic-dose enoxaparin for bridging therapy in patients on long-term warfarin at Soonchunhyang University Hospital in Korea between August 2009 and July 2011. Warfarin was discontinued 5 days before surgery, and enoxaparin was administered twice daily by subcutaneous injection at a dose of 1 mg per kg from 3 days before the procedure to the last dose 24 hours before the procedure. Anticoagulation was restarted if proper hemostasis had been confirmed. There were 49 patients, of whom 25 (51%) were men, and the mean age was 63 years. Thirty-four (69%) received warfarin therapy for VTE, and 9 (18%) for atrial fibrillation. Twenty-nine patients (59%) underwent major surgery and 20 (41%) minor surgery. The mean postoperative duration of enoxaparin was 4 days. No patients had thromboembolic complications through 30 days after the procedure. The overall 30-day mortality rate was 0%. In conclusion, our findings demonstrate that bridging therapy with therapeutic-dose enoxaparin is feasible and associated with a low incidence of major bleeding and no thromboembolic complications. However, the optimal approach to managing patients perioperatively is uncertain and requires further evaluation.

Prevention of Venous Thromboembolism, 2nd Edition: Korean Society of Thrombosis and Hemostasis Evidence-Based Clinical Practice Guidelines

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.

Respiratory Review of 2013: Pulmonary Thromboembolism / 결핵및호흡기질환

Pulmonary embolism (PE), which can originate as a consequence of deep vein thrombosis (DVT), is the most frequent and potentially fatal venous thromboembolic event. Despite the fact that the incidence of venous thromboembolism (VTE) in Asians is lower than that in the Western populations, a recent epidemiologic study demonstrates an increasing incidence of VTE in the Korean population. Anticoagulants, including low molecular weight heparin (LMWH) and vitamin K antagonist (VKAs), have been the main treatments for PE, however, recently new oral anticoagulants (NOACs) were introduced. We will review how well patients with PE can be managed with the existing anticoagulants and NOACs along with the time span of treatment, which still pose some challenges for clinicians.

A Patient with Achalasia Misdiagnosed as Asthma Until Age 17 / 대한내과학회지

Achalasia is a primary esophageal motility disorder characterized by functional obstruction of the distal esophagus and subsequent dilation of the proximal esophagus. The most common symptoms in children and adolescents are vomiting, progressive dysphagia, weight loss, recurrent pneumonia, nocturnal cough, and chest pain. A girl who had been diagnosed with asthma poorly responsive to inhaled steroids until age 17, presented at the hospital with cough, sputum, and fever. Finally, she was diagnosed with achalasia and underwent esophageal balloon dilatation, which relieved her GI and pulmonary symptoms. We report this case with a literature review.

Risk Factors Influencing Rebleeding after Bronchial Artery Embolization on the Management of Hemoptysis Associated with Pulmonary Tuberculosis / 결핵및호흡기질환

BACKGROUND: Hemoptysis due to pulmonary tuberculosis (TB) frequently develops in Korea where the prevalence of TB is intermediate. The effect of bronchial artery embolization (BAE) on the control of massive hemoptysis has been well known. This study is designed to identify the risk factors contributing to rebleeding after BAE in patients with TB. METHODS: We retrospectively evaluated risk factors and the time for rebleeding after BAE in 72 patients presenting with hemoptysis. RESULTS: The overall immediate success rate of BAE was 93.1% (67 of 72 patients). Of the 29 patients (40.3%) who showed rebleeding after BAE, 13 patients experienced rebleeding within 1 month, and 14 patients between 1 month to 1 year. The existence of a shunt in angiographic finding, aspergilloma, and diabetes mellitus were risk factors of rebleeding after BAE in multivariate analysis. CONCLUSION: BAE was very effective for obtaining immediate bleeding control in hemoptysis associated with active TB or post-TB sequelae. It is important to observe whether or not rebleeding occurs up to 1 year of BAE especially in TB patients with aspergilloma, DM, or a shunt. Even rebleeding can be managed well by second BAE.

A Case of Chemical Pneumonitis Induced by Teflon Inhalation / 대한내과학회지

Chemical pneumonitis is defined as lung irritation caused by inhalation of substances toxic to the lungs. Acute chemical pneumonitis causes swelling of the lung tissue, movement of fluid into the air spaces in the lung, and a decreased ability to absorb oxygen and eliminate carbon dioxide. Teflon (polytetrafluoroethylene) is a commonly used synthetic fiber or insulator. To our knowledge, chemical pneumonitis and acute respiratory failure induced by Teflon inhalation has not been previously reported in Korea. We experienced a 44-year-old patient who had a cough and dyspnea that were aggravated 10 h after smoking tobacco wet by Teflon for 5 min at his workplace. Upon arrival at the emergency room, his blood pressure was low and his arterial blood gas analysis revealed hypoxemia. A chest radiograph showed diffuse haziness on both mid- to-lower lung fields. Following treatment by conservative therapy, including oxygen supply and steroid use, his condition was relatively good and his chest radiograph normalized.

A case of lung metastasis of papillary thyroid carcinoma presenting with tuberculous pleurisy / 대한내과학회지

Papillary thyroid carcinoma is the most prevalent type of thyroid cancer. Metastasis of this carcinoma commonly occurs in the lung and has been reported to present 5 to 30 years after the initial diagnosis of thyroid cancer. Pleural effusion can mask this metastatic spread. In patients with pleural effusion, laboratory measurement of the adenosine deaminase (ADA) level in the pleural fluid can be effective in identifying and ranking pulmonary metastasis in the differential diagnosis. A 70-year-old female patient visited our hospital with dyspnea. She presented with a considerable amount of pleural effusion. A pleural biopsy was performed and the Ziehl-Neelsen stains revealed a few acid-fast bacilli, but the ADA level in the pleural fluid was 2.4 IU/L. After drainage of the pleural effusions, we discovered pulmonary nodules by computed tomography (CT), which were later diagnosed through histologic examination as pulmonary metastasis from papillary thyroid carcinoma. We report this case.

A Case of Atypical Distribution of Pulmonary Tuberculosis in Bedridden Patient with Quadriplegia / 결핵및호흡기질환

Pulmonary tuberculosis has intermediate prevalence in Korea. It is known that tuberculosis infection predominantly involves the upper lobes, based on the fact that multiplication of Mycobacterium tuberculosis is favored in areas with decreased pulmonary blood flow, impaired lymphatic drainage, and high oxygen tension. We report this case of a 40-year-old man who was brought to our hospital with hemoptysis and dyspnea. Prior to admission, the patient had been in a bedridden state for 15 years due to an injury of the cervical spine 4~5. A 3-Dimensional computed tomography showed predominantly longitudinal distribution of centrilobular nodules along the anterior chest wall, in the left lung. MTB-PCR and AFB culture of bronchial washing fluid revealed pulmonary tuberculosis. This case shows that long-standing supine posture and decreased motion of the anterior chest wall may change the distribution of preferential infection site of Mycobacterium tuberculosis in the lung, resulting in a ventral predominance of tuberculosis infection in the quadriplegic patient.

A Case of Atypical Distribution of Pulmonary Tuberculosis in Bedridden Patient with Quadriplegia / 결핵및호흡기질환

Pulmonary tuberculosis has intermediate prevalence in Korea. It is known that tuberculosis infection predominantly involves the upper lobes, based on the fact that multiplication of Mycobacterium tuberculosis is favored in areas with decreased pulmonary blood flow, impaired lymphatic drainage, and high oxygen tension. We report this case of a 40-year-old man who was brought to our hospital with hemoptysis and dyspnea. Prior to admission, the patient had been in a bedridden state for 15 years due to an injury of the cervical spine 4~5. A 3-Dimensional computed tomography showed predominantly longitudinal distribution of centrilobular nodules along the anterior chest wall, in the left lung. MTB-PCR and AFB culture of bronchial washing fluid revealed pulmonary tuberculosis. This case shows that long-standing supine posture and decreased motion of the anterior chest wall may change the distribution of preferential infection site of Mycobacterium tuberculosis in the lung, resulting in a ventral predominance of tuberculosis infection in the quadriplegic patient.

Two Cases of Endobronchial Actinomycosis that were Cured by Operation and Short Term Antibiotics Therapy / 결핵및호흡기질환

Endobronchial actinomycosis is a rare chronic suppurative granulomatous infection of the bronchus, and this is sometimes related with a foreign body or a broncholith. The traditional treatment of endobroncial actinomycosis is intravenous antibiotics for 2 to 6 weeks and then oral antibiotics therapy for 6 to 12 months. We report here on 2 cases of endobronchial actinomycosis that were associated with a broncholith and a foreign body, respectively. Surgery followed by short term antibiotics therapy for only 20 days and 34 days, respectively, was effective as treatment for the endobronchial actinomycosis in our cases. After treatment, there were no complications or recurrence during the following period. We suggest that short term antibiotics therapy combined with a surgical operation might be effective as treatment for primary endobronchial actinomycosis, and especially when this illness is combined with a foreign body or a broncholith, as compared with traditional long term antibiotic therapy.