Association Between Air Pollution and Viral Infection in Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Background@#Respiratory pathogen infections and air pollution are main causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Air pollution has a direct effect on the airway epithelial barrier and the immune system, which can have an influence on infection. However, studies on the relationship between respiratory infections and air pollutants in severe AECOPD are limited. Thus, the objective of this study was to investigate the correlation between air pollution and respiratory pathogen in severe AECOPD. @*Methods@#This multicenter observational study was conducted by reviewing electronic medical records of patients with AECOPD at 28 hospitals in South Korea. Patients were divided into four groups according to the comprehensive air-quality index (CAI) used in Korea. Identification rates of bacteria and viruses of each group were analyzed. @*Results@#Viral pathogens were identified in 270 (36.7%) of 735 patients. Viral identification rate was different (P = 0.012) according to air pollution. Specifically, the virus detection rate was 55.9% in the group of CAI ‘D’ with the highest air pollution. It was 24.4% in the group of CAI ‘A’ with the lowest air pollution. This pattern was clearly seen for influenza virus A (P = 0.042). When further analysis was performed with particulate matter (PM), the higher/lower the PM level, the higher/lower the virus detection rate. However, no significant difference was found in the analysis related to bacteria. @*Conclusion@#Air pollution may make COPD patients more susceptible to respiratory viral infections, especially influenza virus A. Thus, on days with poor air quality, COPD patients need to be more careful about respiratory infections.

Chronic obstructive lung disease after ammonia inhalation burns: a report of two cases / 고신대학교의과대학학술지

Anhydrous ammonia is a commonly used chemical in industry. Ammonia gas inhalation causes thermal injuries and alkali burns in the airway and lung parenchyma. Previous case reports have stated that respiratory sequelae after acute ammonia inhalation burns were associated with structural lung disease, such as bronchiectasis or interstitial lung disease. We herein report two cases of long-term sequelae with persistent airflow limitation after ammonia inhalation burns.

A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea / 결핵및호흡기질환

Background@#Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. @*Methods@#A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. @*Results@#We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). @*Conclusion@#Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

Fibrinolysis with Lower Dose Urokinase in Patients with Complicated Parapneumonic Effusion / 결핵및호흡기질환

Background@#Intrapleural urokinase is one of the most widely used fibrinolytic agents in the treatment of complicated parapneumonic effusion (CPPE). However, little research has been performed on the optimal urokinase dosage. The aim of this study was to evaluate the treatment efficacy of half dose urokinase compared with conventional dose urokinase. @*Methods@#We retrospectively enrolled 92 patients with CPPE or empyema who underwent intrapleural urokinase treatment at two tertiary hospitals. Patients received antibiotics, chest tube drainage, and other treatments as part of routine care. The primary outcome was the treatment success rate in the half dose urokinase group (50,000 IU daily for maximal 6 days) and the conventional dose urokinase group (100,000 IU daily). Treatment success was defined as clinical and radiological improvements without surgical treatment or re-admission within one month. @*Results@#Forty-four patients received half dose urokinase, whereas 48 patients were treated with conventional dose urokinase. Both groups were relatively well matched at baseline, excluding higher serum white blood cell count and higher empyema prevalence in the half dose urokinase group. The treatment success rate was not different between the two groups (p=0.048). There were no differences in the rate of in-hospital death and surgical treatment, hospitalization duration, and indwelling catheter duration. In the multivariate analysis, urokinase dose was not a predictor of treatment success. @*Conclusion@#Half dose intrapleural urokinase is equally effective conventional dose urokinase in treating patients with CPPE or empyema.

A case of diacerein-induced DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome with thromboembolic complications

Diacerein is a safe drug for osteoarthritis due to its inhibitory effect on proinflammatory cytokines. Its common side effects, such as diarrhea, abdominal pain and skin rash, are relatively mild. There have been a few cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome accompanied by thromboembolic complications. We report the first case of diacerein-induced DRESS syndrome with thromboembolic complications. A 64-year-old man developed fever, skin rash, increase in liver enzymes, eosinophilia, deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) after taking diacerein. DVT and PTE were improved after anticoagulation therapy; however, fever, skin rash, eosinophilia and increase in liver enzymes were aggravated. A high-dose systemic corticosteroid (methylprednisolone 1 mg/kg/day) was administered, after which his clinical conditions improved.

The Need for a Well-Organized, Video-Assisted Asthma Education Program at Korean Primary Care Clinics / 결핵및호흡기질환

BACKGROUND: The purpose of this study was to assess the effect of our new video-assisted asthma education program on patients' knowledge regarding asthma and asthma control. METHODS: Adult asthmatics who were diagnosed by primary care physicians and followed for at least 1 year were educated via smart devices and pamphlets. The education sessions were carried out three times at 2-week intervals. Each education period lasted at most 5 minutes. The effectiveness was then evaluated using questionnaires and an asthma control test (ACT). RESULTS: The study enrolled 144 patients (mean age, 56.7±16.7 years). Half of the patients had not been taught how to use their inhalers. After participating in the education program, the participants' understanding of asthma improved significantly across all six items of a questionnaire assessing their general knowledge of asthma. The proportion of patients who made errors while manipulating their inhalers was reduced to less than 10%. The ACT score increased from 16.6±4.6 to 20.0±3.9 (p<0.001). The number of asthmatics whose ACT score was at least 20 increased from 45 (33.3%) to 93 (65.3%) (p<0.001). The magnitude of improvement in the ACT score did not differ between patients who received an education session at least three times within 1 year and those who had not. The majority of patients agreed to the need for an education program (95.8%) and showed a willingness to pay an additional cost for the education (81.9%). CONCLUSION: This study indicated that our newly developed education program would become an effective component of asthma management in primary care clinics.

Weekly irinotecan and carboplatin for patients with small cell lung cancer / 영남의대학술지

BACKGROUND: Lung cancer is the most common cause of cancer-related death worldwide and in Korea, and small cell lung cancer (SCLC) is the most deadly tumor type in the different lung cancer histology. Chemotherapy is the main strategy of the treatment for SCLC, and etoposide and platinum regimen has been the only standard chemotherapy for about 30 years. To test feasibility of weekly divided dose irinotecan and carboplatin for Korean patients is the aim of this study. METHODS: Patients with histologically or cytologically confirmed extensive stage SCLC were included. Patients with limited stage (LD), who could not tolerate concurrent chemoradiotherapy were also included. All the patients received irinotecan 60 mg/m2, carboplatin 2 area under the curve at day 1, 8, and 15 every 4 weeks. Study regimen was discontinued when the disease progressed or intolerable side effects occurred. No more than 6 cycles of chemotherapy were given. RESULTS: Total 47 patients were enrolled, among them 9 patients were LD. Overall response rate was 74.5% (complete response, 14.9%; partial response, 59.6%). Side effects greater than grade 3 were neutropenia (25.5%), fatigue (12.8%), thrombocytopenia (8.5%), sepsis (4.3%), and pancytopenia (2.1%). There was no treatment related death. CONCLUSION: Weekly divided irinotecan and carboplatin regimen is effective, and safe as a first line therapy for both stage of SCLC. Large scaled, controlled study is feasible.

Relationships between serum vitamin D levels and clinical characteristics of drug reaction with eosinophilia and systemic symptoms syndrome

PURPOSE: Vitamin D deficiency (VDD) is widely spread and on the increase throughout the world. Although vitamin D is essential for skeletal mineralization, VDD or vitamin D insufficiency (VDI) has been associated with nonskeletal disorders including cardiovascular disease, cancer, allergic disease and skin disease. However, a few reports showed the association of vitamin D and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Thereafter, we evaluated the association between vitamin D and DRESS syndrome. METHODS: We conducted a retrospective study on 45 patients with DRESS syndrome. Four hundred and ninty-eight healthy people who visited the health screening center were enrolled in the study as a control group. We investigated the clinical characteristics, the causative drugs and treatments in the patients with DRESS syndrome, and also analyzed the associations with serum 25-hydroxyvitamin D (25(OH)D3). RESULTS: Forty-four patients (97.8%) had low serum vitamin D levels; 21 patients were VDD (serum 25(OH)D3 <10 ng/mL), and 23 patients were VDI (serum 25(OH)D3 10 to 30 ng/mL). There were no significant differences in clinical parameters between two groups. Serum 25(OH)D3 level of the study patients was significantly lower that of the controls (12.3+/-9.6 ng/mL vs. 17.3+/-5.5 ng/mL, P<0.001). Serum 25(OH)D3 level showed a significant negative correlation with admission days (r=-0.377, P=0.011). CONCLUSION: The majority of the patients with DRESS syndrome showed low vitamin D levels. Serum 25(OH)D3 was inversely correlated with admission days.

Role of the Neutrophil-Lymphocyte Count Ratio in the Differential Diagnosis between Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia

BACKGROUND: Differential diagnosis between pulmonary tuberculosis (TB) and bacterial community-acquired pneumonia (CAP) is often challenging. The neutrophil-lymphocyte count ratio (NLR), a convenient marker of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. We investigated the usefulness of the NLR for discriminating pulmonary TB from bacterial CAP in an intermediate TB-burden country. METHODS: We retrospectively analyzed the clinical and laboratory characteristics of 206 patients suspected of having pulmonary TB or bacterial CAP from January 2009 to February 2011. The diagnostic ability of the NLR for differential diagnosis was evaluated and compared with that of C-reactive protein. RESULTS: Serum NLR levels were significantly lower in patients with pulmonary TB than in patients with bacterial CAP (3.67+/-2.12 vs. 14.64+/-9.72, P<0.001). A NLR <7 was an optimal cut-off value to discriminate patients with pulmonary TB from patients with bacterial CAP (sensitivity 91.1%, specificity 81.9%, positive predictive value 85.7%, negative predictive value 88.5%). The area under the curve for the NLR (0.95, 95% confidence interval [CI], 0.91-0.98) was significantly greater than that of C-reactive protein (0.83, 95% CI, 0.76-0.88; P=0.0015). CONCLUSIONS: The NLR obtained at the initial diagnostic stage is a useful laboratory marker to discriminate patients with pulmonary TB from patients with bacterial CAP in an intermediate TB-burden country.

Clinical Manifestations of 6 Cases of Septic Pulmonary Embolism at Increased Risk Recently / 고신대학교의과대학학술지

OBJECTIVES: The aim of this study was to investigate the clinico-radiologic features and microbiologic data of patients with SPE in a tertiary care hospital in Busan. METHODS: We retrospectively analyzed clinical and radiologic features of 6 cases with septic pulmonary embolism that occurred from March 2009 to March 2011 in Dong-A university medical center. RESULTS: The mean age of the study population was 58 years, and two men and four women were included. Clinical symptoms included general weakness (5 patients), febrile sensation (4 patients) and pleuritic chest pain (2 patients). Underlying conditions were chemoport infection (4 patients), dental abscess (1 patients), and cellulitis of hip (1 patient). Chest computed tomography revealed bilateral multiple nodular opacities in most patients, and cavitation, central necrosis, feeding vessels were identified. All patients received parenteral antimicrobial therapy with or without central catheter removal, drainage of the extrapulmonary infection. Causative organisms were Pseudomonas aeruginosa (2 patients), Candida albicans (1 patient), Bacillus species (1 patient), and Klebsiella pneumonia (1 patient). CONCLUSIONS: Clinical and radiologic features of septic pulmonary embolism were various and nonspecific. The diagnosis was usually suggested by the presence of a predisposing factor of septic pulmonary embolism and CT findings of bilateral multiple nodular opacities in patients with infectious signs and symptoms. Most important underlying condition was intravascular device infection.

The Current Status of Multidrug-Resistant Tuberculosis in One Tertiary Hospital in Busan, 2005~2009 / 결핵및호흡기질환

BACKGROUND: Although the prevalence of pulmonary tuberculosis has progressively decreased all over the world, drug-resistant tuberculosis is major obstacle in treating tuberculosis. This study was performed to examine the current prevalence and risk factors of drug resistant tuberculosis in a single tertiary hospital in Busan, Korea. METHODS: We enrolled 367 patients with active pulmonary tuberculosis on a retrospective basis who had undergone mycobacterium culture and drug sensitivity tests between January 2005 and December 2009. We analyzed all clinical and radiographic parameters to find predictors related to drug resistant tuberculosis. RESULTS: At least one incident of drug resistance was found in 75 (20.4%) patients. Isoniazid (18.8%) was the most frequent resistant drug, followed by rifampin (10.9%), ethambutol (7.1%), streptomycin (4.9%), and fluoroquinolone (2.7%). Resistance to second-line drugs was found in 37 (10.1%) patients. Multidrug resistance and extensively drug resistance was evident in 39 (10.6%) and 4 (1.1%) patients, respectively. Using multiple logistic regression analysis, history of previous treatment including relapse (odd ratio [OR], 11.3; 95% confidence interval [CI], 4.92~26.08; p<0.01), treatment failure (OR, 24.1; 95% CI, 5.65~102.79; p<0.01) and an age of below 46 years-old (OR, 3.8; 95% CI, 1.62~8.65; p<0.01) were found to be independent predictors of multidrug resistant tuberculosis. CONCLUSION: We found that the prevalence of drug resistant tuberculosis was considerably high. A careful consideration for possible drug resistant tuberculosis is warranted in patients with a history of previous treatment or for younger patients.

Absence of Hyper-Responsiveness to Methacholine after Specific Bronchial Provocation Tests in a Worker With Hydroxyapatite-Induced Occupational Asthma

Hydroxyapatite is commonly used as a filler to replace amputated bone or as a coating to promote bone ingrowth into prosthetic implants. Many modern implants, such as hip replacements and dental implants, are coated with hydroxyapatite. We report a patient with occupational asthma due to hydroxyapatite, proven by a specific inhalation challenge, who experienced an early asthmatic reaction after exposure to hydroxyapatite, without increased airway responsiveness to methacholine despite an increased eosinophil count in the peripheral blood. A 38-year-old male dental implant worker visited our allergy department for the evaluation of occupational asthma. He had treated dental implant titanium surfaces with hydroxyapatite for 1.5 years. One year after starting his employment, he noticed symptoms of rhinorrhea, paroxysmal cough, and chest tightness. His symptoms were aggravated during and shortly after work and subsided several hours after work. When he stopped working for 2 months because of his chest symptoms, he became asymptomatic. After restarting his work, his symptoms reappeared and were aggravated. A methacholine bronchial challenge test had a negative response. The following day, a specific bronchial provocation test with wheat powder was negative. On the third day, a specific bronchial provocation test with hydroxyapatite powder produced an early asthmatic response. On the fourth day, a methacholine bronchial challenge test was negative. Further studies are needed to evaluate the exact pathogenetic mechanism of hydroxyapatite-induced occupational asthma.

Quantification of Serum Free RNA as a Predictive Biomarker for the Response to Chemotherapy in Patients with Lung Cancer: A Pilot Study / 결핵및호흡기질환

BACKGROUND: It is well-known that cell-free nucleic acids rise in patients with many types of malignancies. Several recent experimental studies using cancer cell lines have shown that changes in cell-free RNA are predictive of the response to chemotherapy. The objective of this study was to determine whether quantification of free RNA can be used as a biomarker for clinical responses to chemotherapy in patients with lung cancer. METHODS: Thirty-two patients with lung cancer (non-small cell lung cancer, n=24; small cell lung cancer, n=8) were divided into 2 groups according to their responses to chemotherapy (response group, n=19; non-response group, n=13). Blood samples were collected before and after two cycles of chemotherapy. Real-time quantitative RT-PCR was used for transcript quantification of the glyceraldehyde-3-phosphate dehydrogenase gene. RESULTS: The pre chemotherapy values (Response group 41.36+/-1.72 vs. Non-response group 41.33+/-1.54, p=0.78) and post chemotherapy values (Response group 39.92+/-1.81 vs. Non-response group 40.41+/-1.47, p=0.40) for cell free RNA concentrations, expressed as Ct GAPDH (threshold cycle glyceraldehyde-3-phosphate dehydrogenase gene) levels, was not different between the two groups. There was no significant relationship between changes in the cell free RNA level clinical responses after chemotherapy (p=0.43). CONCLUSION: We did not find a correlation between quantification of serum cell free RNA levels and clinical responses to chemotherapy in patients with lung cancer. Further investigations are needed to determine whether the cell free RNA level is a useful predictor of responses to chemotherapy in patients with lung cancer.

Four Cases of a Cerebral Air Embolism Complicating a Percutaneous Transthoracic Needle Biopsy

A percutaneous transthoracic needle biopsy is a common procedure in the practice of pulmonology. An air embolism is a rare but potentially fatal complication of a percutaneous transthoracic needle biopsy. We report four cases of a cerebral air embolism that developed after a percutaneous transthoracic needle biopsy. Early diagnosis and the rapid application of hyperbaric oxygen therapy is the mainstay of therapy for an embolism. Prevention is the best course and it is essential that possible risk factors be avoided.

A Case of Mediastinal Teratoma Associated with Elevated Tumor Marker in Chronic Empyema / 결핵및호흡기질환

Most mediastinal teratomas are histologically well-differentiated tumors and benign. The majority of patients with a mediastinal teratoma are asymptomatic and their tumors are usually discovered incidentally on chest radiography. On rare occasions this tumor will rupture spontaneously into the adjacent organs. A 72-year-old female patient was admitted for dyspnea and she had a multiloculated pleural effusion in the left lung field. Although repeated pleural biopsy and pleural fluid cytology did not prove the presence of malignancy, we assumed that this was a malignant effusion because it revealed consistently high levels of carcinoembryonic antigen and carbohydrate antigen 19-9, and the chest CT scan did not show typical fat or bone density in the mass. Secondary infection and an uncontrolled septic condition due to pleural empyema finally compelled the patient to undergo a surgical operation. Mature teratoma was the final diagnosis and she has done well without recurrence for 2 months.

A Case of Bronchiectasis with Elevated Serum CA 125 Level / 결핵및호흡기질환

Serum CA 125 is the most useful marker for monitoring patients with epithelial ovarian cancer. However, it can be elevated above normal level in a variety of conditions other than ovarian cancer such as endometriosis, pelvic inflammation disease, and other malignant or nonmalignant disorders, including pulmonary diseases. Recently, we experienced a case of bronchiectasis in which the serum CA 125 level was elevated, changing with the patient's condition. There was no evidence of underlying malignant disease on positron emission tomography or on gynecologic examination, including transvaginal ultrasonography. During follow-up for 14 months, we could not find any clue of malignant disease that could have been the cause of the elevated levels of serum CA 125. Elevated serum CA 125 level should be interpreted carefully according to the patient's clinical condition. In addition, our case suggests that CA 125 may be used as a surrogate marker for acute inflammatory status for chronic pulmonary diseases.

A Case of Bronchiectasis with High Serum CA19-9 / 결핵및호흡기질환

An elevated serum CA19-9 level is an indication of pancreatic and biliary tract cancer. However, it has recently become known that nonmalignant gastrointestinal diseases and a variety of nonmalignant respiratory diseases, such as idiopathic interstial pneumonia, collagen vascular disease associated lung diseases, diffuse panbronchiolitis and bronchiectasis, can also show an elevated serum CA19-9 level. We recently encountered a case of bronchiectasis with persistently elevated serum CA19-9, but without any evidence of malignant disease in endoscopic retrograde pancreatocholangiography, abdominal computed tomography, and positron emission tomography. After serial follow-up of 3 years and 10 months, there was still no evidence of cancer. It is believed that the elevated serum CA19-9 level was due to bronchiectasis. An elevated serum CA19-9 level should be interpreted carefully with the patients' clinical condition.

Huge Aneurysm of the Sinus of Valsalva Compressing the Left Atrium

Sinus of Valsalva aneurysms are rare cardiac anomalies. They can be congenital or acquired, and mainly involve the right or non-coronary sinuses. Unruptured aneurysms are usually asymptomatic unless they compress other structures or produce thrombi. A sinus of Valsalva aneurysm can also produce myocardial infarction through thrombus formation secondary to the turbulent flow in the Valsalva aneurysm. We report a case of a huge sinus of Valsalva aneurysm involving the noncoronary sinus, which was diagnosed as the presumed source of acute myocardial infarction.

A Case with Patent Ductus Arteriosus Complicated by Pulmonary Artery Endarteritis

Infective endarteritis in the pulmonary artery is unusual. However, congenital heart disease such as patent ductus arteriosus (PDA) could be a predisposing factor of infective endarteritis. We report a patient with PDA complicated by infective endarteritis and large pulmonary artery vegetation. After three weeks of antibiotic treatment, the patient underwent surgical closure of the PDA and removal of the vegetation.

Diagnosis of Malignant Pleural Effusion by using Aberrant Methylation of p16 and RARB2 / 결핵및호흡기질환

BACKGROUND: A diagnosis of malignant pleural effusion is clinically important, as the prognosis of lung cancer patients with malignant pleural effusion is poor. The diagnosis will be difficult if a cytological test is negative. This study was performed to investigate whether the detection of hypermethylation of the p16 (CDKN2A) and retinoic acid receptor b2 (RARB2) genes in pleural fluid is useful for a diagnosis of malignant pleural effusion. METHODS: Pleural effusion was collected from 43 patients and was investigated for the aberrant promoter methylation of the RARB2 and CDKN2A genes by use of methylation-specific PCR. Results were compared with findings from a pleural biopsy and from pleural fluid cytology. RESULTS: Of 43 cases, 17 cases of pleural effusion were due to benign diseases, and 26 cases were from lung cancer patients with malignant pleural effusion. Hypermethylation of the RARB2 and CDKN2A genes was not detected in the case of benign diseases, independent of whether or not the patients had ever smoked. In 26 cases of malignant pleural effusion, hypermethylation of RARB2, CDKN2A or either of these genes was detected in 14, 5 and 15 cases, respectively. The sensitivities of a pleural biopsy, pleural fluid cytology, hypermethylation of RARB2, hypermethylation of CDKN2A, or hypermethylation of either of the genes were 73.1%, 53.8%, 53.8%, 19.2%, and 57.7%, respectively; negative predictive values were 70.8%, 58.6%, 58.6%, 44.7%, and 60.7%, respectively. If both genes are considered together, the sensitivity and negative predictive value was lower than that for a pleural biopsy, but higher than that for pleural fluid cytology. The sensitivity of hypermethylation of the RARB2 gene for malignant pleural effusion was lower in small cell lung cancers than in non-small cell lung cancers. CONCLUSION: These results demonstrate that detection of hypermethylation of the RARB2 and CDKN2A genes showed a high specificity, and sensitivity was higher than for pleural fluid cytology. With a better understanding of the pathogenesis of lung cancer according to histological types at the molecular level, and if appropriate genes are selected for hypermethylation testing, more precise results may be obtained.