Use of serology and polymerase chain reaction to detect atypical respiratory pathogens during acute exacerbation of chronic obstructive pulmonary disease

BACKGROUND/AIMS: To use serological and multiplex polymerase chain reaction (PCR) assays to examine sputum samples from patients experiencing acute exacerbation of chronic obstructive pulmonary disease (AECOPD) for the presence of atypical pathogens, including Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. METHODS: From September 2012 to February 2014, 341 patients with AECOPD attending outpatient clinics were enrolled as part of a randomized, double-blind, multicenter study. A commercial enzyme-linked immunosorbent assay was used to measure serum immunoglobulin M (IgM) and IgG antibody titers on the first day of the study and at 36 days post-enrollment. Multiplex PCR was used to test sputum samples for the presence of atypical pathogens. A urinary antigen test for L. pneumophila was performed on the first day. RESULTS: Nineteen patients (5.6%) showed serological evidence of acute infection with M. pneumoniae. Also, one and seven patients (2%) showed serological evidence of acute infection with C. pneumoniae and L. pneumophila, respectively. All DNA samples were negative for M. pneumoniae, C. pneumoniae, and L. pneumophila according to PCR. Only one urine sample was positive for L. pneumophila antigen, but serologic evidence was lacking. CONCLUSIONS: Serological testing suggested that infection by atypical pathogens during AECOPD was relatively uncommon. In addition, PCR provided no direct evidence of infection by atypical pathogens. Thus, atypical pathogens may not be a major cause of AECOPD in South Korea.

Quantitative PCR for Etiologic Diagnosis of Methicillin-Resistant Staphylococcus aureus Pneumonia in Intensive Care Unit / 결핵및호흡기질환

BACKGROUND: Ventilator-associated pneumonia (VAP) requires prompt and appropriate treatment. Since methicillin-resistant Staphylococcus aureus (MRSA) is a frequent pathogen in VAP, rapid identification of it, is pivotal. Our aim was to evaluate the utility of quantitative polymerase chain reaction (qPCR) as a useful method for etiologic diagnoses of MRSA pneumonia. METHODS: We performed qPCR for mecA, S. aureus-specific femA-SA, and S. epidermidis-specific femA-SE genes from bronchoalveolar lavage or bronchial washing samples obtained from clinically-suspected VAP. Molecular identification of MRSA was based on the presence of the mecA and femA-SA gene, with the absence of the femA-SE gene. To compensate for the experimental and clinical conditions, we spiked an internal control in the course of DNA extraction. We estimated number of colony-forming units per mL (CFU/mL) of MRSA samples through a standard curve of a serially-diluted reference MRSA strain. We compared the threshold cycle (Ct) value with the microbiologic results of MRSA. RESULTS: We obtained the mecA gene standard curve, which showed the detection limit of the mecA gene to be 100 fg, which corresponds to a copy number of 30. We chose cut-off Ct values of 27.94 (equivalent to 1x10(4) CFU/mL) and 21.78 (equivalent to 1x10(5) CFU/mL). The sensitivity and specificity of our assay were 88.9% and 88.9% respectively, when compared with quantitative cultures. CONCLUSION: Our results were valuable for diagnosing and identifying pathogens involved in VAP. We believe our modified qPCR is an appropriate tool for the rapid diagnosis of clinical pathogens regarding patients in the intensive care unit.

Role of Microbiologic Culture Results of Specimens Prior to Onset of Ventilator-Associated Pneumonia in the Patients Admitted to Intensive Care Unit / 결핵및호흡기질환

BACKGROUND: Patients with ventilator-associated pneumonia (VAP) in intensive care unit (ICU) have a high mortality rate. The routine surveillance cultures obtained previously or an ATS guideline for hospital-acquired pneumonia was used in selecting initial antimicrobials. The object of this study was to compare the respiratory samples before VAP and bronchoalveolar lavage (BAL) culture. METHODS: 54 patients underwent fiberoptic bronchoscopy to obtain BAL samples. We reviewed microbiologic specimen results of prior respiratory specimens (pre-VAP) and BAL. RESULTS: Among 51 patients with 54 VAP episodes, 52 microorganisms of pre-VAP and 56 BAL samples were isolated. Pre-VAP included 21.2% of MRSA, and 32.6% of multidrug resistant-Acinetobacter baumannii (MDR-AB). BAL samples comprised 25.0% of MRSA, 26.7% of MDR-AB, 14.3% of Stenotrophomonas maltophilia and 3.6% of Klebsiella pneumonia in order. In pre-VAP samples compared to BAL samples, only 35.2% were identical. In BAL samples compared to pre-VAP samples obtained in 5 days before the onset of VAP, only 43.6% were identical. However, among BAL samples compared to pre-VAP samples obtained after more than 5 days, 13.3% were identical (p=0.037). CONCLUSION: Based on these data, pre-VAP samples obtained prior to 5 day onset of VAP may help to predict the causative microorganisms and to select appropriate initial antimicrobials.

A Case of Miliary Tuberculosis Misdiagnosed as Pneumonia and ARDS Due to the Transient Improvement after Intravenous Injection of Levofloxacin / 결핵및호흡기질환

Miliary tuberculosis is quite a rare but serious cause of acute respiratory distress syndrome (ARDS). Therefore, the early detection of military tuberculosis as the underlying cause of ARDS is very important for the prognosis and survival of the patient. We report a case of military tuberculosis mimicking ARDS. A female patient was admitted due to repeated fever and dyspnea. The initial chest CT scan showed diffuse ground glass opacity, without a miliary pattern. The case was considered to be ARDS caused by pneumonia. She showed improvement after being treated with levofloxacin. However, she was re-admitted with fever seven days after discharge. The follow up chest CT scan showed micronodules in both lungs. An open lung biopsy confirmed the diagnosis of military tuberculosis.

Successful Embolization in the Patient with Hemoptysis Due to Right Inferior Phrenic Artery-pulmonary Artery Anastomosis and Pseudoaneurysm / 결핵및호흡기질환

The primary cause of hemoptysis is the bronchial artery. However, it should be noted that pulmonary artery and other vessels can cause hemoptysis. If the source of the bleeding is not determined after embolization, other evaluations are needed. Systemic-pulmonary anastomosis and pulmonary artery pseudo-aneurysm are rare vascular abnormalities with varying etiologies. An accurate and rapid diagnosis is needed in hemoptysis, since the cause may be life-threatening. We report a case of a 77-years-old man with persistent hemoptysis due to the right inferior phrenic artery - pulmonary artery anastomosis and pseudoaneurysm. After the embolization of the inferior phrenic artery, the hemoptysis was successfully treated.

Comparison of spirometry with cardiopulmonary exercise test of chronic obstructive pulmonary disease / 대한내과학회지

BACKGROUND/AIMS: Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible airflow limitation. Pulmonary function test (PFT) has been considered the gold standard test for diagnosis and severity evaluation in COPD. However, PFT by spirometry does not provide information about exercise performance in COPD patients. Therefore, the present study was performed to compare pulmonary function determined by spirometry with exercise function determined by cardiopulmonary exercise test (CPET) for grading of COPD. METHODS: A total of 105 patients with airway obstruction were examined. The patients' mean age was 65 years, and the mean smoking history was 27 pack-years. The patients underwent spirometry and CPET. The results were analyzed by categorical statistical comparison, based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and American Thoracic Society guidelines. RESULTS: The two methods agreed on the classification of only 44 patients (42%). Of the remaining patients, 21 (20%) were found to be less severe according to CPET than according to PFT, whereas 40 (38%) were more severe. Those who were more severe according to CPET had significantly low maximal minute ventilation, low anaerobic threshold, low oxygen pulse, and high breathing reserve. CONCLUSIONS: The present study revealed the large disagreement between the results of resting and exercise pulmonary function tests, and therefore suggests the need for a novel approach or guideline. Additional cardiological evaluation may be needed in patients classified as more severe according to CPET, who are assumed to have a greater degree of impairment of cardiovascular function.

Molecular Epidemiology and Antimicrobial Resistance of Methicillin-resistant Staphylococcus aureus Isolated from Nasal Swab at Intensive Care Unit / 결핵및호흡기질환

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the most common organism associated with nosocomial infections. MRSA infections are becoming increasing important because they have emerged no only as healthcare-associated (HA) infections but also as community-associated (CA) ones. This study examined the moleculo-epidemiology of MRSA, which was isolated from nasal swabs in the intensive care unit (ICU) at Konyang University Hospital. MRSA are classified into HA-MRSA and CA-MRSA. METHODS: From June to September 2006, 353 patients who were admitted to the ICU in Konyang University Hospital were enrolled in this study. Single nasal swabs were obtained for culture in the ICU on the 1st day. Pulsed-field gel electrophoresis and the antimicrobial resistant patterns were analyzed between HA- and CA-MRSA. An antimicrobial sensitivity test was also performed. RESULTS: Forty two strains of MRSA were isolated from 353 patients (11.9%). Among the 42 isolates, HA-MRSA and CA-MRSA were found in 33 (78.6%), and 9 (21.4%), respectively. Eleven different PFGE types (type A to K) were identified. Types A (n=9) and B (n=7) were the most common for HA-MRSA, and types A (n=2) and B (n=2) were identified in CA-MRSA. The proportion of types A and B in CA-MRSA (44.4%) was similar to that in HA-MRSA (48.5%). The rates of resistance rates to erythromycin and ciprofloxacin were higher in HA-MRSA than in CA-MRSA. CONCLUSION: The rate of isolation of MRSA in an ICU setting was 11.9%. HA-MRSA was isolated more frequently than CA-MRSA. The rate of resistance of HA-MRSA to erythromycin and ciprofloxacin was higher than that of CA-MRSA. Despite the small number of subjects, the main isolates (type A and B) of CA-MRSA were similar to those of HA-MRSA.

Efficacy and Safety of Weekly Low Dose Paclitaxel and Cisplatin as First Line Therapy in Advanced NSCLC of Elderly Patients

PURPOSE : Anti-cancer chemotherapeutic agents act by inhibiting tumor cell proliferation through cytotoxic action, therefore the generally tolerated maximum dose is administered to patients. However, this often results in the production of undesirable toxicities, such as bone marrow suppression, and a long interruption of treatment is necessary for recovery to occur before additional cycles of treatment are administered. Paclitaxel and cisplatin are well known effective chemotherapeutic agents used for the treatment of Non-Small Cell Lung Cancer (NCSLC), however, they have substantial toxicities. To evaluate efficacy and safety of a therapy consisting of a weekly low dose of paclitaxel and therapy in elderly patients with advanced NSCLC. MATERIALS AND METHODS : Thirteen treatment-naive, elderly patients over 65 years old who were diagnosed with stage IV NSCLC at Konyang University from April 2005 to October 2006 were enrolled in the present study. Paclitaxel at a dose of 55 mg/m2 in combination with cisplatin at a dose of 20 mg/m2 was administered intravenously on day 1, 8, and 15 with 1 week of interruption for a total of six cycles of chemotherapy. RESULTS : The mean age of the ten patients included in this study was 69.5 years. Following treatment, 50 % of the patients exhibited a partial response to treatment, whereas the disease remained stable in 40% of the patients, and progressed in 10% of the patients. The median survival time (Kaplan-Meier method) was 15 months (4~24 months), and the 6-month, 1-year, and 2-year survival rates were 80%, 50%, and 10%, respectively. The median progression survival time was 8 months (2~14 months) and the 6- and 12-month progression free survival rates were 60% and 10%, respectively. Grade 3 neutropenia occurred in only 1 case (10%). CONCLUSION : The results of this study indicated that chemotherapy consisting of a weekly low dose of paclitaxel and cisplatin could be more effective and have lesser toxicity when administered to elderly patients with advanced NSCLC. In addition, this treatment regimen showed a promising response rate

Diagnostic Accuracy and Safety of Medical Thoracoscopy / 결핵및호흡기질환

BACKGROUND: The causes of the pleural effusion are remained unclear in a the substantial number of patients with exudative effusions determined by an examination of the fluid obtained via thoracentesis. Among the various tools for diagnosing exudative pleural effusions, thoracoscopy has a high diagnostic yield for cancer and tuberculosis. Medical thoracoscopy can also be carried out under local anesthesia with mild sedation. The aim of this study was to determine diagnostic accuracy and safety of medical thoracoscopy. METHODS: Twenty-five patients with exudative pleural effusions of an unknown cause underwent medical thoracoscopy between October 2005 and September 2006 in Konyang University Hospital. The clinical data such as age, gender, preoperative pulmonary function, amounts of pleural effusion on lateral decubitus radiography were collected. The vital signs were recorded, and arterial blood gas analyses were performed five times during medical thoracoscopy in order to evaluate the cardiopulmonary status and acid-base changes. RESULTS: The mean age of the patients was 56.8 years (range 22-79). The mean depth of the effusion on lateral decubitus radiography (LDR) was 27.49 mm. The medical thoracoscopic pleural biopsy was diagnostic in 24 patients (96.0%), with a diagnosis of tuberculosis pleurisy in 9 patients (36%), malignant effusions in 8 patients (32%), and parapneumonic effusions in 7 patients (28%). Medical thoracoscopy failed to confirm the cause of the pleural effusion in one patient, who was diagnosed with tuberculosis by a pericardial biopsy. There were no significant changes in blood pressure, heart rate, acid-base and no major complications in all cases during medical thoracoscopy (p>0.05). CONCLUSIONS: Medical thoracoscopy is a safe method for patients with unknown pleural effusions with a relatively high diagnostic accuracy.

A Case of Behcet's Disease with Multiple Cavitary Lung Lesion / 결핵및호흡기질환

Behcet's disease is a systemic vasculitis of an unknown etiology involving the arteries and veins of all sizes. There are reports showing that a pulmonary artery aneurysm or thromboembolism and superior vena cava thrombosis are present in 5-10% of patients with Behcet's disease and that lung parenchymal lesions are mainly airway consolidations resulting from hemorrhage or infarction. We encountered a patient with increasing pulmonary cavitary changes and localized aspergilloma. The patient was a 43-year-old man diagnosed with Behcet's disease with a history of recurrent oro-genital ulceration and uveitis, and who was administered methotrexate, colchicines, prednisolone. During the follow up he developed progressive dyspnea upon exertion and finger clubbing. Therefore further evaluations were performed. Chest computed tomography showed more advanced consolidations and cavitations than the previous film with the previously known aspergilloma still observable. An open lung biopsy was carried out to determine the presence of malignant changes, which revealed nonspecific vasculitis. Azathioprine was added resultion in an improvement of symptoms.

Polymorphisms of Angiotensin-converting Enzyme Gene Associated in Patients with COPD with or without Bronchial Hyperresponsiveness / 결핵및호흡기질환

BACKGROUND: An insertion-deletion polymorphism of angiotensin converting enzyme (ACE) gene has been shown to be associated with enzyme activity levels of ACE. Reported results that have been mutually contradictory about asthmatic hypersensitiveness and occurrence according to ACE gene insertion (I)/deletion (D) polymorphism. Also, the involvement of the ACE genes as the genetic basis of bronchial asthma is currently controversy. We investigated whether there was any association between polymorphisms of the ACE genes and airway hyper-responsiveness in chronic obstructive pulmonary disease (COPD). METHODS: A total of 100 patients with COPD were enrolled in this study. The ACE genotypes were determined in all subjects by polymerase chain reaction. Pulmonary function test including bronchodilator response (BDR), methacholine bronchial provocation test (MBPT) were done in those patients. Airway hyper-responsiveness include any findings of positive BDR or MBPT. RESULTS: In COPD patients, the ACE genotype distribution did not differ significantly among groups of patients with severities of COPD, and with or without airway hyper-responsiveness. CONCLUSIONS: These results suggest that polymorphisms of the ACE gene may not be associated with airway hyper-responsiveness, development and severity of COPD.

A Clinical Analysis of Pneumonia in Acute Drug Intoxication / 결핵및호흡기질환

BACKGROUND: Acute drug intoxication has recently become an important issue in the social and clinical areas. There are various complications associated with acute drug intoxication such as pneumonia, but the process is was not fully understood. The aim of this study was to analyze our cases of pneumonia associated with acute drug intoxication and to determine the associated risk factors. METHOD: Forty four cases out of 237 patients, who were acute drug intoxicated from May 2000 to Feb. 2005, were diagnosed with pneumonia at the Konyang University hospital. These cases were analyzed by a retrospective review of their medical records. RESULTS: The incidence of pneumonia in acute drug intoxication was 18.6%. There was no gender difference in terms of the incidence, but the age group with the highest incidence was in the 5th decade (22.5%) followed by the 7th decade (17.9%). Most common drug of associated with pneumonia was organophosphate insecticides, and the others were herbicides. Suicidal attempts were the most common motive of intoxication. The incidence of pneumonia was increased in old age (beta=0.128, p<0.05). A drowsy or comatous mental status was an independent risk factors of pneumonia (beta=-0.209, p=0.006). A longer hospital duration was also a risk factor for pneumonia (beta=0.361, p<0.001). The intubated state, intensive care unit care and longer duration of admission correlated with the course of pneumonia in acute drug intoxicated patients (p<0.05). The culture study revealed MRSA to be most common pathogen. CONCLUSION: The incidence of pneumonia associated with acute drug intoxication was higher in the older aged patients, those with a decreased initial mental status and a longer hospital duration. The number of days in the intensive care unit and intubation were associated prognostic factors for pneumonia in acute drug intoxication patients.

A Case of Adrenocortical Carcinoma with Concurrent Cushing's Syndrome and Primary Aldosteronism / 대한내분비학회지

An adrenocortical carcinoma is a rare malignancy, which is associated with a poor prognosis. Eighty percent of adrenal tumors are functional, and commonly secrete glucocorticoids alone (45%), glucocorticoids and androgens (45%) or androgen alone (10%). Less than 1% of all cases secrete aldosterone. A case of a 75 year old female patient was experienced, presenting with anadrenocortical carcinoma and associated concurrent Cushing's syndrome and primary aldosteronism. She had complained of left flank pain for 5 months, and also showed clinical features of Cushing's syndrome, hypertension, hypokalemia and a left abdominal mass. An abdominal CT* demonstrated a large left adrenal mass, with necrosis, and a hemorrhage in the left upper abdomen. The plasma renin activity was 0.51 ng/ml/hr, and the serum aldosterone level was increased by 46.4 ng/dL. A low and high dose dexamethasone suppression test revealed no suppression. Histologically, the tumor was diagnosed as a adrenocortical carcinoma. After complete removal of the mass, she received mitotan and prednisolone as adjuvant therapies. Liver and bone metastasis occurred after 6 months of treatment, so was treated with palliative radiotherapy for the bone metastasis

A Case of Adrenocortical Carcinoma with Concurrent Cushing's Syndrome and Primary Aldosteronism / 대한내분비학회지

An adrenocortical carcinoma is a rare malignancy, which is associated with a poor prognosis. Eighty percent of adrenal tumors are functional, and commonly secrete glucocorticoids alone (45%), glucocorticoids and androgens (45%) or androgen alone (10%). Less than 1% of all cases secrete aldosterone. A case of a 75 year old female patient was experienced, presenting with anadrenocortical carcinoma and associated concurrent Cushing's syndrome and primary aldosteronism. She had complained of left flank pain for 5 months, and also showed clinical features of Cushing's syndrome, hypertension, hypokalemia and a left abdominal mass. An abdominal CT* demonstrated a large left adrenal mass, with necrosis, and a hemorrhage in the left upper abdomen. The plasma renin activity was 0.51 ng/ml/hr, and the serum aldosterone level was increased by 46.4 ng/dL. A low and high dose dexamethasone suppression test revealed no suppression. Histologically, the tumor was diagnosed as a adrenocortical carcinoma. After complete removal of the mass, she received mitotan and prednisolone as adjuvant therapies. Liver and bone metastasis occurred after 6 months of treatment, so was treated with palliative radiotherapy for the bone metastasis

Primary Primitive Neuroectodermal Tumor of the Kidney: Report of Two Cases

Primitive neuroectodermal tumor (PNET) is a small round cell neoplasm that mainly develops in the central nervous system and soft tissue of children. Primary occurrence in the kidney is rare and the identification of immunopositivity for CD99 and t(11;22)(q24;q12) is essential in differential diagnoses. We report two cases of PNET developed in a 21-year-old woman and a 44-year-old man. Resected tumors were composed of sheets of round or ovoid cells with hyperchromatic nuclei and minimal eosinophilic cytoplasm. Rosette formations, more prominent in the first case, were observed. The tumor cells of both cases were diffusely positive for CD99, vimentin, and neuron specific enolase, while they were negative for cytokeratin, desmin, and chromogranin. Synaptophysin was focally expressed only in the first case. The EWS-FLI1 chimeric gene was identified by a reverse transcriptase-polymerase chain reaction in the first case. The first patient is alive with a recurrent tumor two years after the diagnosis, and has received combination chemotherapy. The second patient is alive with no evidence of recurrence or metastasis nineteen months after the diagnosis.

A Case of Internal Myiasis of the Repiratory System Associated with Pneumonia / 결핵

Internal myiasis is a rare disease, which has not been reported in Korea, yet. This case report describes a patient with pneumonia associated with internal myiasis. She was 84-year old female who was admitted to the emergency department, Konyang University Hospital as a result of dyspnea and fever and a drowsy mental state. Approximately twenty fly maggots continuously crawled out from the nose at the third hospital day in the intensive care unit. These maggots were almost 7.2mm long and were identified as the genus lucilia belonging to the family Calliphoridae. In addition, a bronchial washing study showed eggs of the dipterous larvae. A lesion of this myiasis case might have been located in the respiratory system of patient. This case is the first internal myiasis of the respiratory system reported in Korea. This cases is discussed with a review of the relevant literature.

Antibacterial Effect of Polyphosphates on Porphyromonas gingivalis

Porphyromonas gingivalis is strongly implicated in the pathogenesis of adult periodontitis, the major cause of tooth loss in adults. Use of an antibacterial agent controlling P. gingivalis as a periodontal therapeutic agent has been rationalized. The present study was performed to observe the antibacterial effect of inorganic polyphosphates (polyP) on P. gingivalis. P. gingivalis 2561 was grown in half-strength brain-heart infusion broth containing hemin and vitamin K with or without polyP. Minimal inhibitory concentration (MIC) of polyP with various chain lengths was determined by measuring the absorbance of the grown cells at 540 nm. MIC of polyP for the bacterium was determined to be 0.05%. The effect of polyP with a chain length of 75 (polyP 75) was further examined. PolyP 75 added to the growing culture of P. gingivalis at its exponential phase was as effective in inhibiting the growth of P. gingivalis as polyP 75 added at the very beginning of the culture. More than 99% of the cells lost their viability determined by viable cell count when polyP 75 was added to the culture of growing P. gingivalis at the concentration of 0.06%, suggesting that polyP 75 has a bactericidal effect on the bacterium. Intracellular nucleotide release from the cells was increased by approx. 20% in the presence of polyP 75 but was not reversed by the addition of divalent cations like Ca++ and Mg++. Under the transmission electron microscope, only a small number of the growing P. gingivalis cells were actually lysed. However, the majority of the cells appeared to be atypical in their shape, demonstrating accumulation of highly electron-dense granules and bodies of condensed nucleic acid-like material in the cytoplasm. In the presence of polyP 75, the protein profile of P. gingivalis was changed as determined by SDS-polyacrylamide gel electrophoresis and immunoblot, and the proteolytic activity of the bacterium demostrated on the zymograms was decreased. The overall results suggest that polyP have a strong bactericidal activity against P. gingivalis in which lysis in relation to chelation may not play the major role but unknown mechanism that possibly affects the viability of the bacterium may be involved. PolyP may be used as an agent for prevention and treatment of periodontitis.