Acute exacerbation of COPD increases the risk of hip fractures: a nested case-control study from the Korea National Health Insurance Service

Background/Aims@#Hip fracture and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) could increase mortality in patients with COPD. There are no data on the relationship between AE-COPD and hip fracture, which may significantly affect the prognosis of patients with COPD. Therefore, we conducted this study to determine the effects of AE-COPD on hip fractures in patients with COPD. @*Methods@#This retrospective, nested, case-control study included 253,471 patients with COPD (≥ 40 years of age) identified from the Korea National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) from 2002 to 2015. Among 176,598 patients with COPD, 1,415 patients with hip fractures were identified. Each case was matched to one control for age (within 10 years), sex, and year of COPD diagnosis. We estimated the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for hip fractures associated with AE-COPD using conditional logistic regression analysis, adjusting for underlying diseases and smoking history. @*Results@#In patients with AE-COPD, the risk of hip fracture was 2.50 times higher, regardless of systemic corticosteroid use and underlying disease (aOR, 2.50; 95% CI, 1.67 to 3.75). The risk of hip fracture increased if there was one episode of AE in the year before hip fractures (aOR, 2.25; 95% CI, 1.66 to 3.05). Moreover, the risk of hip fracture also increased in patients with more than two episodes of AE the year before hip fractures (aOR, 2.57; 95% CI, 1.61 to 4.10). @*Conclusions@#AE-COPD increases the risk of hip fracture regardless of underlying diseases, including osteoporosis, and treatment with systemic corticosteroids.

Treatment of pulmonary tuberculosis

Tuberculosis (TB) remains the world's leading cause of death from a single infectious disease. In addition, the incidence of TB is high in South Korea. Effective TB control requires early diagnosis and initiation of appropriate treatment. Therefore, it is very important for clinicians to understand evidence-based practical recommendations and to be familiar with up-to-date treatment regimens. In this review, we first describe anti-TB drugs, including new drugs. Secondly, we discuss the treatment of drug-susceptible TB. Finally, we present treatment strategies for drug-resistant TB, which is divided into isoniazid-resistant TB, rifampin-resistant TB, and multi-drug resistant TB. For the treatment of drug-susceptible TB, we recommend 2 months of 4 drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) followed by 4 months of 2 drugs (isoniazid and rifampin). For the treatment of isoniazid-resistant TB, we recommend 6 to 9 months of 4 drugs (rifampin, ethambutol, pyrazinamide, and levofloxacin or moxifloxacin). For the treatment of multi-drug resistant TB (MDR-TB), we recommend a minimum of 5 secondary drugs, including an injectable agent and quinolone. Although the World Health Organization recommended a shorter MDR-TB regimen in 2016, the Korean guidelines for tuberculosis have not yet accepted the shorter regimen. The treatment regimen of TB differs depending on the drug resistance pattern. Therefore, it is important to treat TB properly after confirming the drug resistance pattern. In addition, as new drugs are developed, new treatment guidelines for MDR-TB should be developed that are appropriate for circumstances in Korea.

Treatment of pulmonary tuberculosis

Tuberculosis (TB) remains the world's leading cause of death from a single infectious disease. In addition, the incidence of TB is high in South Korea. Effective TB control requires early diagnosis and initiation of appropriate treatment. Therefore, it is very important for clinicians to understand evidence-based practical recommendations and to be familiar with up-to-date treatment regimens. In this review, we first describe anti-TB drugs, including new drugs. Secondly, we discuss the treatment of drug-susceptible TB. Finally, we present treatment strategies for drug-resistant TB, which is divided into isoniazid-resistant TB, rifampin-resistant TB, and multi-drug resistant TB. For the treatment of drug-susceptible TB, we recommend 2 months of 4 drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) followed by 4 months of 2 drugs (isoniazid and rifampin). For the treatment of isoniazid-resistant TB, we recommend 6 to 9 months of 4 drugs (rifampin, ethambutol, pyrazinamide, and levofloxacin or moxifloxacin). For the treatment of multi-drug resistant TB (MDR-TB), we recommend a minimum of 5 secondary drugs, including an injectable agent and quinolone. Although the World Health Organization recommended a shorter MDR-TB regimen in 2016, the Korean guidelines for tuberculosis have not yet accepted the shorter regimen. The treatment regimen of TB differs depending on the drug resistance pattern. Therefore, it is important to treat TB properly after confirming the drug resistance pattern. In addition, as new drugs are developed, new treatment guidelines for MDR-TB should be developed that are appropriate for circumstances in Korea.

Peripheral Eosinophilia and Clinico-radiological Characteristics among Health Screening Program Recipients / 결핵및호흡기질환

BACKGROUND: Eosinophilia is well recognized in specific conditions. The objective of the present study was to determine clinico-radiologic characteristics of eosinophilia and changes in prevalence over 10 years in recipients of private health screening program at a tertiary hospital in Korea. METHODS: Data of private health screening program recipients at the health promotion center of Chung-Ang University Hospital from 2004 to 2013 were collected. Health-related questionnaires and laboratory findings of private health screening program with possible relation with eosinophilia were reviewed. Results of enzyme-linked immunosorbent assay (ELISA) for parasite, chest computed tomography, and pulmonary function test were also reviewed. RESULTS: The cumulative prevalence of eosinophilia was 4.0% (1,963 of 48,928). Prevalence of eosinophilia showed a decreased trend from 2004 to 2013. Most cases (96.6%) had mild degree of eosinophilia. Eosinophilic subjects were older and male-predominant. They showed lower levels of forced expiratory volume in 1 second (FEV₁%), forced vital capacity (FVC%), and FEV₁/FVC than those without eosinophilia. Eosinophilic subjects showed higher positive rate for common parasite in ELISA than those without eosinophilia. On radiologic findings, consolidation and ground glass opacities were positively associated with the degree of eosinophilia. When eosinophil was classified based on severity, statistically significant correlation between the severity of eosinophil and radiologic abnormalities was found. CONCLUSION: Eosinophilia is uncommon in healthy population. It usually occurs at a mild degree. Eosinophilic patients have more radiologic abnormalities compared to those without eosinophilia. Such radiologic abnormalities are associated with the severity of eosinophilia.

Epidemiological trend of pulmonary thromboembolism at a tertiary hospital in Korea

BACKGROUND/AIMS: Despite increasing interest in pulmonary thromboembolism (PTE), data on recent trends in PTE incidence are limited. This study evaluated the recent incidence rate of PTE. METHODS: We performed a retrospective chart review of patients with PTE admitted to Chung-Ang University Hospital during the 10-year period from 2006 to 2015. Age-standardized incidence and mortality rates were calculated by the direct method per 100,000 populations. To analyze the trend of risk factor, we also calculated the proportions of cancer, major operation, and recent major fracture over that time. RESULTS: Total crude incidence rate of PTE per 100,000 was 229.36 and the age-sex adjusted standardized incidence rate was 151.28 (95% confidence interval [CI], 127.88 to 177.10). The incidence rate have been significantly increased 1.083 times annually from 2006 (105.96 per 100,000) to 2015 (320.02 per 100,000) (95% CI, 1.049 to 1.118; p < 0.001). These incidences also increased annually in age group of 35 to 54, 55 to 74, and ≥ 75 years, and in both males (odds ratio [OR], 1.071; 95% CI, 1.019 to 1.127; p = 0.007) and females (OR, 1.091; 95% CI, 1.047 to 1.136; p < 0.001). Cancer accounted for most of the increase from 20.0% at 2006 to 2007 to 42.8% at 2014 to 2015 (OR, 1.154; 95% CI, 1.074 to 1.240; p < 0.001), while the proportions of recent fracture and major operation remained constant. CONCLUSIONS: The incidence of pulmonary embolism has gradually increased over the 10 years. The increase of PTE incidence was mainly due to increased proportion of cancer patients.

Bronchial Artery Aneurysm Presenting Hemoptysis, Initially Mis-diagnosed as Bronchial Arterio-venous Malformation: A Case Report

Normal bronchial arteries are small vessels that arise mostly from the descending thoracic aorta. Bronchial artery aneurysm is defined as a dilatation of the bronchial arteries with a diameter over 2 mm, and is reported in less than 1% of bronchial arterial angiography. A 70-year-old male patient was presented with hemoptysis. He had been treated for pulmonary tuberculosis 50 years ago. He also had a history of admission with hemoptysis 10 years ago, for which he was diagnosed as bronchiectasis on computed tomography imaging. Upon arrival to our hospital, abnormal vascular structure was detected on the mediastinum, arising from the descending thoracic aorta. It was dilated to 14 mm with a saccular form. Initially, we evaluated the structure as a bronchial arteriovenous malformation because it seemed to be drained into the pulmonary vein directly. For further evaluation, he had received a trans-catheter bronchial artery angiography. Both bronchial arteries were hypertrophied, but direct arteriovenous shunt was not detected; as such, we concluded this structure to be bronchial artery aneurysm. We performed embolization for both bronchial arteries and filled the aneurysm with coiling. He had no recurrence of hemoptysis and was discharged on 4 days post embolization. Our case reports an incidental bronchial artery aneurysm, which was initially misdiagnosed as bronchial arteriovenous anomaly, and finally treated with embolization and coiling.

Delayed diagnosis of allergic bronchopulmonary aspergillosis due to absence of asthmatic symptoms

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease with small prevalence. Exposure to aspergillus mold causes immunologic hypersensitivity and may cause ranges of symptoms from minimal to detrimental outcomes. Diagnosing and treating the disease before the development of bronchiectasis may save the patient from poor outcomes. This report presents a case of recurrent ABPA without any symptom of asthma, which impeded the correct diagnosis even after numerous hospitalizations.

Intravenous immunoglobulin therapy in a selective IgG3 deficient patient with recurrent respiratory infections and asthma attacks

The IgG subclass deficiency is defined as a significant decrease in the serum concentrations of one or more subclasses of IgG in a patient whose total IgG concentration is normal. IgG subclass deficiency can predispose to recurrent sinopulmonary infections. A 29-year-old female patient with a 4-year history of bronchial asthma presented with cough, sputum, dyspnea, and recurrent respiratory infections. She had frequently been treated with antibiotics and systemic steroids for recurrent respiratory infections and acute asthma exacerbations. Chest X-ray and computed tomography showed pectus excavatum and bronchial wall thickening without lung parenchymal abnormalities. On immunological evaluation, she was found to have a low serum IgG3, with normal total IgG concentration. Under diagnosis of selective IgG3 deficiency, she was started on monthly infusions of intravenous immunoglobulin (IVIG) therapy. The frequency and severity of respiratory infections and acute asthma exacerbations were markedly decreased during 3 years of IVIG therapy. Our case report suggests that a patient who has underlying selective IgG3 deficiency and asthma may benefit from IVIG therapy as this can significantly reduce the incidence and severity of recurrent respiratory infections and acute asthma exacerbations.

Lung Microbiome Analysis in Steroid-Naїve Asthma Patients by Using Whole Sputum / 결핵및호흡기질환

BACKGROUND: Although recent metagenomic approaches have characterized the distinguished microbial compositions in airways of asthmatics, these results did not reach a consensus due to the small sample size, non-standardization of specimens and medication status. We conducted a metagenomics approach by using terminal restriction fragment length polymorphism (T-RFLP) analysis of the induced whole sputum representing both the cellular and fluid phases in a relative large number of steroid naïve asthmatics. METHODS: Induced whole sputum samples obtained from 36 healthy subjects and 89 steroid-naїve asthma patients were analyzed through T-RFLP analysis. RESULTS: In contrast to previous reports about microbiota in the asthmatic airways, the diversity of microbial composition was not significantly different between the controls and asthma patients (p=0.937). In an analysis of similarities, the global R-value showed a statistically significant difference but a very low separation (0.148, p=0.002). The dissimilarity in the bacterial communities between groups was 28.74%, and operational taxonomic units (OTUs) contributing to this difference were as follows: OTU 789 (Lachnospiraceae), 517 (Comamonadaceae, Acetobacteraceae , and Chloroplast), 633 (Prevotella), 645 (Actinobacteria and Propionibacterium acnes), 607 (Lactobacillus buchneri, Lactobacillus otakiensis, Lactobacillus sunkii, and Rhodobacteraceae), and 661 (Acinetobacter, Pseudomonas, and Leptotrichiaceae), and they were significantly more prevalent in the sputum of asthma patients than in the sputum of the controls. CONCLUSION: Before starting anti-asthmatic treatment, the microbiota in the whole sputum of patients with asthma showed a marginal difference from the microbiota in the whole sputum of the controls.

Two Cases of Newly Diagnosed Asthma with Spontaneous Pneumomediastinum During Asthma Exacerbation

Pneumomediastinum, a condition in which air is present in the mediastinum, is generally regarded as a benign, self-limited process. Rare life-threatening causes such as esophageal rupture must be excluded. A 26-year-old woman with allergic rhinitis presented with a 3-day history of increasing dyspnea, wheezing, and chest pain. Her high resolution CT (HRCT) showed extensive pneumomediastinum and subcutaneous emphysema without visible airway injury on the CT scan. With application of oxygen through a nasal cannula, bronchodilator inhalation, and systemic steroids, her pneumomediastinum and asthma symptoms were improved. A 30-year-old man with acute exacerbation of newly diagnosed asthma and spontaneous pneumomediastinum was treated with application of oxygen and asthma medication. Here, we reported two cases of newly diagnosed asthma with spontaneous pneumomediastinum during asthma exacerbation.

Seven-Day Continuous Abstinence Rate from Smoking at 1, 2, or 3 Years after the Use of Varenicline / 결핵및호흡기질환

BACKGROUND: Varenicline, a selective partial agonist/antagonist of the alpha4beta2 nicotinic receptor, has proven effectiveness for smoking cessation by several randomized, controlled trials. Because few studies have evaluated the long-term efficacy of varenicline, we tried to evaluate the smoking status of varenicline users up to 3 years after the initial prescription of the drug. METHODS: We interviewed varenicline users who were prescribed the drug from June 2007 to May 2010 by telephone, from June 2010 to May 2011. RESULTS: One-hundred and thirty-three of 250 varenicline users (53.2%) were available for the survey. Seven-day continuous abstinence from smoking was adhered to by 17 of 39 respondents (43.6%) at 1 year, and 11 of 36 (30.6%) and 19 of 58 (32.8%) at 2 and 3 years since the first use of varenicline, respectively. Compared to current smokers, successful quitters were older (55.0 years vs. 49.9 years, p=0.01), had better compliance to the 12-week course (27.7 vs. 9.3%, p=0.01), and had taken varenicline longer (10.1 vs. 5.9 weeks, p=0.01). Fifty-four of 71 current smokers (76.1%) were willing to stop smoking in the near future. The preferred ways to cease smoking were will-power (48.1%), varenicline (25.9%), nicotine replacement therapy (11.1%), and others (14.9%). CONCLUSION: Smokers should be encouraged to stick to the proven way for recommended period of time for successful cessation of smoking.

Risk Factors for Death during Pulmonary Tuberculosis Treatment in Korea: A Multicenter Retrospective Cohort Study

The data regarding risk factors for death during tuberculosis (TB) treatment are inconsistent, and few studies examined this issue in Korea. The purpose of this study was to evaluate baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. A multicenter retrospective cohort study of 2,481 patients who received TB treatment at eight hospitals from January 2009 to December 2010 was performed. Successful treatment included cure (1,129, 45.5%) and treatment completion (1,204, 48.5%) in 2,333 patients (94.0%). Unsuccessful treatment included death (85, 3.4%) and treatment failure (63, 2.5%) occurred in 148 patients (6.0%). In multivariate analysis, male sex, anemia, dyspnea, chronic heart disease, malignancy, and intensive care unit (ICU) admission were significant risk factors for death during TB treatment. Therefore, male sex, anemia, dyspnea, chronic heart disease, malignancy, and ICU admission could be baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea.

Diagnosis and treatment of latent tuberculosis infection

Tuberculosis (TB) is still an important cause of morbidity and mortality worldwide. Nearly one-third of the world's population is latently infected with Mycobacterium tuberculosis, and 10% of them will develop active TB during their lifetime. The tuberculin skin test or interferon-gamma release assay (IGRA) is the method for diagnosis of latent TB infection. Although commercially available IGRAs have limitations in serial testing, and testing children and immunosuppressive patients, IGRAs have superior sensitivity and specificity compared with conventional tuberculin skin testing, especially in Bacillus Calmette-Guerin vaccinated populations. For the treatment of latent TB infection, 9 months isoniazid is the standard treatment in Republic of Korea. However, shorter treatment regimens, including 4 months of rifampin, 3 months of isoniazid/rifampin, and once weekly isoniazid/rifapentine are currently alternatives. Identification and treatment of latent TB infection has lowered the TB incidence in developed countries. Therefore, for TB control, diagnosis and treatment of latent TB infection is important. However, there is lack of research on latent TB infection in South Korea. To revise the guideline, a large prospective trial on the treatment of latent TB infection is needed.

Familial Occurrence of Pulmonary Embolism after Intravenous, Adipose Tissue-Derived Stem Cell Therapy

The therapeutic potential of human multipotent mesenchymal stromal cells, especially human adipose tissue-derived stem cells (hASC), is promising. However, there are concerns about the safety of infusion of hASC in human. Recently, we have experienced pulmonary embolism and infarct among family members who have taken multiple infusions of intravenous autologous hASC therapy. A 41-year-old man presented with chest pain for one month. Chest CT showed multiple pulmonary artery embolism and infarct at right lung. Serum D-dimer was 0.8 microg/mL (normal; 0-0.5 microg/mL). He had received intravenous autologous adipose tissue-derived stem cell therapy for cervical herniated intervertebral disc three times (one, two, and three months prior to the visit). His parents also received the same therapy five times and their chest CT also showed multiple pulmonary embolism. These cases represent artificial pulmonary embolisms and infarct after IV injection of hASC. Follow-up chest CT showed spontaneous resolution of lesions in all three patients.

A Case of Giant, Benign Schwannoma Associated with Total Lung Collapse by Bloody Effusion / 결핵및호흡기질환

Benign schwannoma is the most common neurogenic tumor in the mediastinum. Mediastinal benign schwannomas are most often asymptomatic and rarely accompanied by bloody pleural effusion. In the clinical analysis of 7 cases of pulmonary schwannomas, pleural effusion, and blood invasion were evident in 3 patients with malignant schwannoma. Herein, we report a rare case of giant, benign schwannoma presented with total collapse of right lung by massive, bloody pleural effusion.

Acute Eosinophilic Pneumonia Leading to Acute Respiratory Failure in a Current Systemic Corticosteroid User

A 69-year-old female patient visited the emergency room with fever (38.3degrees C) and dyspnea. She had been taking prednisolone (5 mg once per day) and methotrexate (2.5 mg once per week) for rheumatoid arthritis for 2 years. Chest computed tomography (CT) showed bilateral, multifocal ground glass opacity with interlobular septal thickening. Peripheral blood leukocyte count was 6,520/mm3 (neutrophils, 77.4%; eosinophils, 12.1%). During the night, mechanical ventilation was initiated due to the development of severe hypoxemia. Bronchoalveolar lavage fluid showed a high proportion of eosinophils (49%). Her symptoms improved dramatically after commencement of intravenous methylprednisolone therapy. This is the first report of idiopathic acute eosinophilic pneumonia developing in a current user of systemic corticosteroids.

Silicosis Caused by Chronic Inhalation of Snail Shell Powder

A 70-yr-old woman visited our hospital for shortness of breath. Chest CT showed ground glass opacity and traction bronchiectasis at right middle, lower lobe and left lingular division. Video-assisted thoracic surgical biopsy at right lower lobe and pathologic examination revealed mixed dust pneumoconiosis. Polarized optical microscopy showed lung lesions were consisted of silica and carbon materials. She was a housewife and never been exposed to silica dusts occupationally. She has taken freshwater snails as a health-promoting food for 40 yr and ground shell powder was piled up on her backyard where she spent day-time. Energy dispersive X-ray spectroscopy of snail shell and scanning electron microscopy with energy dispersive x-ray spectroscopy of lung lesion revealed that silica occupies important portion. Herein, we report the first known case of silicosis due to chronic inhalation of shell powder of freshwater snail.

A Fatal Case of Intravascular Coagulation After Bee Sting Acupuncture

Bee stings can cause severe adverse reactions, leading to anaphylaxis, cardiovascular collapse, and death. In some cases, bee venom also induces disseminated intravascular coagulation (DIC). However, to our knowledge, there has been no fatal case of intravascular coagulation accompanied by anaphylaxis caused by bee sting acupuncture. Here, we report a fatal case of a 65-year-old woman with DIC, following anaphylactic shock after bee sting acupuncture. This case emphasizes that practitioners should consider anaphylaxis followed by coagulation abnormalities when a patient's vital signs are unstable after bee sting acupuncture.

Four Year Trend of Carbapenem-Resistance in Newly Opened ICUs of a University-Affiliated Hospital of South Korea / 결핵및호흡기질환

BACKGROUND: Carbapenem-resistance is rapidly evolving among the pathogenic microbes in intensive care units (ICUs). This study aimed to determine annual trend of carbapenem-resistance in the ICU for 4 years, since the opening of a university-affiliated hospital in South Korea. METHODS: From 2005 to 2008, microbial samples from consecutive 6,772 patients were screened in the ICU. Three hundred and ninety-seven patients (5.9%) and their first isolates of carbapenem-resistant pathogens were analyzed. RESULTS: The percentage of patients infected with carbapenem-resistant organisms increased constantly during the initial three years (2.3% in 2005, 6.2% in 2006, 7.8% in 2007), then it declined to 6.5% in 2008. Acute Physiology and Chronic Health Evaluation (APACHE) III score at admission was 58.0+/-23.5, the median length of the ICU stay was 37 days, and the mortality rate was 37.5%. The sampling sites were endotracheal suction (67%), catheterized urine (17%), wound (6%) and others (10%). Bacteria with carbapenem-resistance were Pseudomonas aeruginosa (247 isolates, 62%), Acinetobacter baumannii (117 isolates, 30%), Enterobacteriaceae (12 isolates, 3%), and others (21, 5%). Of note, peak isolation of carbapenem-resistant microorganisms in medical ICU was followed by the same epidemic at surgical ICU. CONCLUSION: Taken together, carbapenem-resistant pathogens are of growing concern in the ICU.

Allergic Bronchopulmonary Aspergillosis Coupled with Sinusitis in a Nonasthmatic Patient / 결핵및호흡기질환

Allergic bronchopulmonary aspergillosis (ABPA) is a complex clinical entity resulting from an allergic immune response to Aspergillus species, and most often occurs in patients with asthma. ABPA is rarely observed in the absence of asthma, which is, in fact, the principal criterion for its diagnosis. Our patient was a 53-year-old woman with no history of bronchial asthma. She presented with a 1-month history of cough, mucopurulent nasal discharge, and localized pulmonary consolidation. Peripheral blood eosinophilia and elevated serum IgE were observed. Sinus radiography showed right maxillary sinusitis. Pathologic examination of bronchoscopic biopsy specimens revealed conglomerates of fungal hyphae. Pulmonary function and bronchial provocation tests were within normal ranges. The patient was successfully treated for 3 months with itraconazole and oral prednisolone. There has been no evidence of recurrence over a 7-month follow-up. ABPA coupled with sinusitis in a nonasthmatic patient is a very rare occurrence and warrants reporting.