Effect of Depression on Pulmonary Symptoms and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease / 신경정신의학

OBJECTIVES@#Depression is a common comorbid condition in patients with chronic obstructive pulmonary disease (COPD) and has a higher prevalence than the general population. On the other hand, studies on the incidence of depression and quality of life in COPD patients often depend on a simple self-report questionnaire rather than a psychiatrist's clinical assessment. Starting with accurately diagnosing depression, the purpose of this study was to evaluate the factors related to depression as well as how depression influences the quality of life.@*METHODS@#The study included 30 patients diagnosed with COPD. All the patients were interviewed for a diagnosis of depression by a psychiatrist. They were divided into two groups: with and without depression. For dyspnea, the modified Medical Research Council (mMRC) scale was used to evaluate how it affected daily life. Short-Form Health Survey 36 and COPD assessment test (CAT) were used to assess the quality of life.@*RESULTS@#The degree of COPD and respiratory symptoms were related, but the severity of COPD did not influence the quality of life. In the presence of depression, mMRC and CAT were higher, whereas PCS and MCS were lower than in those without depression. Patients with depression suffered more from dyspnea and had a lower quality of life.@*CONCLUSION@#This study suggests that the degree of COPD was not related to depression. With depression, however, it led to the aggravation of dyspnea and a deteriorated quality of life. Combined treatment is essential to improving the patients' general well-being.

CT-Guided Percutaneous Transthoracic Needle Biopsy Using the Additional Laser Guidance System by a Pulmonologist with 2 Years of Experience in CT-Guided Percutaneous Transthoracic Needle Biopsy / 결핵및호흡기질환

BACKGROUND: We developed an additional laser guidance system to improve the efficacy and safety of conventional computed tomography (CT)–guided percutaneous transthoracic needle biopsy (PTNB), and we conducted this study to evaluate the efficacy and safety of our system. METHODS: We retrospectively analyzed the medical records of 244 patients who underwent CT-guided PTNB using our additional laser guidance system from July 1, 2015, to January 20, 2016. RESULTS: There were nine false-negative results among the 238 total cases. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of our system for diagnosing malignancy were 94.4% (152/161), 100% (77/77), 100% (152/152), 89.5% (77/86), and 96.2% (229/238), respectively. The results of univariate analysis showed that the risk factors for a false-negative result were male sex (p=0.029), a final diagnosis of malignancy (p=0.033), a lesion in the lower lobe (p=0.035), shorter distance from the skin to the target lesion (p=0.003), and shorter distance from the pleura to the target lesion (p=0.006). The overall complication rate was 30.5% (74/243). Pneumothorax, hemoptysis, and hemothorax occurred in 21.8% (53/243), 9.1% (22/243), and 1.6% (4/243) of cases, respectively. CONCLUSION: The additional laser guidance system might be a highly economical and efficient method to improve the diagnostic efficacy and safety of conventional CT-guided PTNB even if performed by inexperienced pulmonologists.

The Prognostic Value of the Tumor Shrinkage Rate for Progression-Free Survival in Patients with Non-Small Cell Lung Cancer Receiving Gefitinib / 결핵및호흡기질환

BACKGROUND: The efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy can be measured based on the rate of treatment response, based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria or progression-free survival (PFS). However, there are some patients harboring sensitive EGFR mutations who responded poorly to EGFR-TKI therapy. In addition, there is variability in the PFS after EGFR-TKI treatment. METHODS: We performed a retrospective analysis of the medical records of 85 patients with non-small cell lung cancer, who had achieved a stable disease or better response at the first evaluation of treatment response, after receiving a 2-month course of gefitinib. We calculated the tumor shrinkage rate (TSR) by measuring the longest and perpendicular diameter of the main mass on computed tomography before, and 2 months after, gefitinib therapy. RESULTS: There was a significant positive correlation between the TSR and PFS (R=0.373, p=0.010). In addition, a simple linear regression analysis showed that the TSR might be an indicator for the PFS (B+/-standard error, 244.54+/-66.79; p=0.001). On univariate analysis, the sex, histologic type, smoking history and the number of prior chemotherapy regimens, were significant prognostic factors. On multivariate regression analysis, both the TSR (beta=0.257, p=0.029) and adenocarcinoma (beta=0.323, p=0.005) were independent prognostic factors for PFS. CONCLUSION: Our results showed that the TSR might be an early prognostic indicator for PFS in patients receiving EGFR-TKI therapy.

Ethics in the Intensive Care Unit / 결핵및호흡기질환

The intensive care unit (ICU) is the most common place to die. Also, ethical conflicts among stakeholders occur frequently in the ICU. Thus, ICU clinicians should be competent in all aspects for ethical decision-making. Major sources of conflicts are behavioral issues, such as verbal abuse or poor communication between physicians and nurses, and end-of-life care issues including a lack of respect for the patient's autonomy. The ethical conflicts are significantly associated with the job strain and burn-out syndrome of healthcare workers, and consequently, may threaten the quality of care. To improve the quality of care, handling ethical conflicts properly is emerging as a vital and more comprehensive area. The ICU physicians themselves need to be more sensitive to behavioral conflicts and enable shared decision making in end-of-life care. At the same time, the institutions and administrators should develop their processes to find and resolve common ethical problems in their ICUs.

Malignant Mesothelioma Diagnosed by Bronchoscopic Biopsy / 결핵및호흡기질환

Malignant mesothelioma is a rare malignant neoplasm that arises from mesothelial surfaces of the pleural cavity, peritoneal cavity, tunica vaginalis, or pericardium. Typically, pleural fluid cytology or closed pleural biopsy, surgical intervention (video thoracoscopic biopsy or open thoracotomy) is conducted to obtain pleural tissue specimens. However, endobronchial lesions are rarely seen and cases diagnosed from bronchoscopic biopsy are also rarely reported. We reported the case of a 77-year-old male who was diagnosed as malignant mesothelioma on bronchoscopic biopsy from obstructing masses of the endobronchial lesion.

A Case of Eosinophilic Pleural Effusion Caused by Toxocariasis without Serum Eosinophilia

Human toxocariasis is a parasitic disease caused by Toxocara canis or Toxocara cati. We report a patient with toxocariasis who presented with dyspnea and left pleural effusion. All patients with toxocariasis in published case reports had serum eosinophilia. This is the first case report of eosinophilic pleural effusion without serum eosinophilia caused by toxocariasis infection, which was confirmed by using enzyme-linked immunosorbent assay (ELISA). Therefore, an antibody ELISA can be useful for diagnosing toxocariasis in patients with a pleural effusion of unknown cause, even in the absence of serum eosinophilia.

Pumpless extracorporeal interventional lung assist for bronchiolitis obliterans after allogenic peripheral blood stem cell transplantation for acute lymphocytic leukemia / 영남의대학술지

Bronchiolitis obliterans (BO), which is associated with graft-versus-host disease after allogenic hematopoietic stem cell transplantation, is a major obstacle to survival after bone marrow transplantation due to its gradual progress, eventually leading to respiratory failure. Pumpless extracorporeal interventional lung assist (iLA) is effective in treatment of reversible hypercapnic respiratory failure. In this paper, we present a 23-year-old female patient who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) for acute lymphocytic leukemia. After 6 months, she complained of shortness of breath and was diagnosed with BO. Five months later, she developed an upper respiratory tract infection that worsened her BO and caused life-threatening hypercapnia. Since mechanical ventilation failed to eliminate CO2 effectively, iLA was applied as rescue therapy. Her hypercapnia and respiratory acidosis showed significant improvement within a few hours, and she was successfully weaned off iLA after 12 days. This is the first case report of iLA application for temporarily aggravated hypercapnia of PBSCT-associated BO followed by successful weaning. This rescue therapy should be considered in ventilator-refractory reversible hypercapnia in BO patients.

Apigenin and Wogonin Regulate Epidermal Growth Factor Receptor Signaling Pathway Involved in MUC5AC Mucin Gene Expression and Production from Cultured Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: We investigated whether wogonin and apigenin significantly affect the epidermal growth factor receptor (EGFR) signaling pathway involved in MUC5AC mucin gene expression, and production from cultured airway epithelial cells; this was based on our previous report that apigenin and wogonin suppressed MUC5AC mucin gene expression and production from human airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with wogonin or apigenin for 15 minutes or 24 hours and then stimulated with epidermal growth factor (EGF) for 24 hours or the indicated periods. RESULTS: We found that incubation of NCI-H292 cells with wogonin or apigenin inhibited the phosphorylation of EGFR. The downstream signals of EGFR such as phosphorylation of MEK1/2 and ERK1/2 were also inhibited by wogonin or apigenin. CONCLUSION: The results suggest that wogonin and apigenin inhibits EGFR signaling pathway, which may explain how they inhibit MUC5AC mucin gene expression and production induced by EGF.

Progression-Free Survival: An Important Prognostic Marker for Long-Term Survival of Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals. METHODS: A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors. RESULTS: The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent prognostic markers for poor survival rates. CONCLUSION: In addition to other well-known prognostic factors, this study discovered relationships between the long-term survival rates and serum CRP levels, TNM staging, and PFS. In situations with unfavorable conditions, the PFS would be particularly helpful for managing SCLC patients.

Effects of Morus alba L. and Natural Products Including Morusin on In Vivo Secretion and In Vitro Production of Airway MUC5AC Mucin / 결핵및호흡기질환

BACKGROUND: It is valuable to find the potential activity of regulating the excessive mucin secretion by the compounds derived from various medicinal plants. We investigated whether aqueous extract of the root bark of Morus alba L. (AMA), kuwanon E, kuwanon G, mulberrofuran G, and morusin significantly affect the secretion and production of airway mucin using in vivo and in vitro experimental models. METHODS: Effect of AMA was examined on hypersecretion of airway mucin in sulfur dioxide-induced acute bronchitis in rats. Confluent NCI-H292 cells were pretreated with ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G, or morusin for 30 minutes and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 hours. The MUC5AC mucin secretion and production were measured by enzyme-linked immunosorbent assay. RESULTS: AMA stimulated the secretion of airway mucin in sulfur dioxide-induced bronchitis rat model; aqueous extract, ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G and morusin inhibited the production of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively. CONCLUSION: These results suggest that extract of the root bark and the natural products derived from Morus alba L. can regulate the secretion and production of airway mucin and, at least in part, explains the folk use of extract of Morus alba L. as mucoregulators in diverse inflammatory pulmonary diseases.

Effects of Lobetyolin, Lobetyol and Methyl linoleate on Secretion, Production and Gene Expression of MUC5AC Mucin from Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: In this study, we investigated whether lobetyolin, lobetyol, and methyl linoleate derived from Codonopsis pilosula affect MUC5AC mucin secretion, production, and gene expression from airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with lobetyolin, lobetyol, or methyl linoleate for 30 minutes and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 hours. The MUC5AC mucin gene expression, and mucin protein production and secretion were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Lobetyolin, lobetyol, and methyl linoleate inhibited the gene expression of MUC5AC mucin induced by PMA; lobetyolin did not affect PMA-induced MUC5AC mucin production. However, lobetyol and methyl linoleate inhibited the production of MUC5AC mucin; lobetyolin and lobetyol did not significantly affect PMA-induced MUC5AC mucin secretion from NCI-H292 cells. However, methyl linoleate decreased the MUC5AC mucin secretion. CONCLUSION: These results suggest that among the three compounds, methyl linoleate can regulate gene expression, production, and secretion of MUC5AC mucin by directly acting on the airway epithelial cells.

Extremely Increased Serum Carbohydrate Antigen 19-9 Levels Caused by New or Resistant Infections to Previous Antibiotics in Chronic Lung Diseases / 결핵및호흡기질환

In this paper, we describe 72-year-old female patient without evidence of malignant disease presented with significantly elevated serum carbohydrate antigen (CA) 19-9 levels by respiratory infections. She was diagnosed with respiratory infections due to Mycobacterium avium complex and Pseudomonas aeruginosa. The serum CA 19-9 levels remarkably increased (1,453-5,300 U/mL; reference range, <37 U/mL) by respiratory infection and abruptly decreased (357-534 U/mL) whenever infection was controlled by specific treatments. This case suggests that serum CA 19-9 levels may be used as a diagnostic marker to indicate new or resistant infections to previous antibiotics in chronic lung diseases without significant changes in chest X-ray findings.

A Case of Atypical Adenomatous Hyperplasia of Larger Than 2 cm / 결핵및호흡기질환

Atypical adenomatous hyperplasia (AAH) has been considered to be a precursor lesion of bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma. It usually coexists with BAC and/or an adenocarcinoma. Chest computed tomography reveals multiple well-defined nodules with ground-glass opacity. Usually, AAH does not exceed 10 mm in size. AAH with extensive involvement on one side of the lung field or one that is larger than 2 cm has not been previously reported. We herein report a case of a 71-year-old nonsmoking female with lung AAH of larger than 2 cm.

Effect of Prunetin on TNF-alpha-Induced MUC5AC Mucin Gene Expression, Production, Degradation of IkappaB and Translocation of NF-kappaB p65 in Human Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: We investigated whether prunetin significantly affects tumor necrosis factor-alpha (TNF-alpha)-induced MUC5AC mucin gene expression, production, inhibitory kappa B (IkappaB) degradation and nuclear factor kappa B (NF-kappaB) p65 translocation in human airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with prunetin for 30 minutes and then stimulated with TNF-alpha for 24 hours or the indicated periods. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effect of prunetin on TNF-alpha-induced degradation of IkappaB and translocation of NF-kappaB p65 was investigated by western blot analysis. RESULTS: We found that incubation of NCI-H292 cells with prunetin significantly inhibited mucin production and down-regulated the MUC5AC gene expression induced by TNF-alpha. Prunetin inhibited TNF-alpha-induced degradation of IkappaB and translocation of NF-kappaB p65. CONCLUSION: This result suggests that prunetin inhibits the NF-kappaB signaling pathway, which may explain its role in the inhibition of MUC5AC mucin gene expression and production regulated by the NF-kappaB signaling pathway.

A Multicenter Study of Pertussis Infection in Adults with Coughing in Korea: PCR-Based Study / 결핵및호흡기질환

BACKGROUND: Limited data on the incidence and clinical characteristics of adult pertussis infections are available in Korea. METHODS: Thirty-one hospitals and the Korean Centers for Disease Control and Prevention collaborated to investigate the incidence and clinical characteristics of pertussis infections among adults with a bothersome cough in non-outbreak, ordinary outpatient settings. Nasopharyngeal aspirates or nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and culture tests. RESULTS: The study enrolled 934 patients between September 2009 and April 2011. Five patients were diagnosed as confirmed cases, satisfying both clinical and laboratory criteria (five positive PCR and one concurrent positive culture). Among 607 patients with cough duration of at least 2 weeks, 504 satisfied the clinical criteria of the US Centers for Disease Control and Prevention (i.e., probable case). The clinical pertussis cases (i.e., both probable and confirmed cases) had a wide age distribution (45.7+/-15.5 years) and cough duration (median, 30 days; interquartile range, 18.0~50.0 days). In addition, sputum, rhinorrhea, and myalgia were less common and dyspnea was more common in the clinical cases, compared to the others (p=0.037, p=0.006, p=0.005, and p=0.030, respectively). CONCLUSION: The positive rate of pertussis infection may be low in non-outbreak, ordinary clinical settings if a PCR-based method is used. However, further prospective, well-designed, multicenter studies are needed.

Effect of Chrysin on Gene Expression and Production of MUC5AC Mucin from Cultured Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: We investigated whether chrysin affected MUC5AC mucin production and gene expression induced by phorbol ester (phorbol 12-myristate 13-acetate, PMA) or epidermal growth factor (EGF) from human airway epithelial cells. METHODS: Confluent NCI-H292 cells were pretreated with varying concentrations of chrysin for 30 minutes, and were then stimulated with PMA and EGF for 24 hours, respectively. MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Concentrations of 10microM and 100microM chrysin were found to inhibit the production of MUC5AC mucin protein induced by PMA; A concentration of 100microM chrysin also inhibited the production of MUC5AC mucin protein induced by EGF; 100microM chrysin inhibited the expression of MUC5AC mucin gene induced by PMA or EGF. The cytotoxicity of chrysin was checked by lactate dehydrogenase assay, and there was no cytotoxic effect observed for chrysin. CONCLUSION: These results suggest that chrysin can inhibit mucin gene expression and the production of mucin protein by directly acting on airway epithelial cells.

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.

Second Complete Remission of Relapsed Stage IV Non-Small Cell Lung Cancer Following Retreatment / 결핵및호흡기질환

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths. Most patients were presented with advanced disease at the time of diagnosis. In advanced NSCLC, it is almost impossible to anticipate complete remission by using only cytotoxic chemotherapy or molecularly targeted agents. In our case, two patients were diagnosed as advanced NSCLC and received chemotherapy. They achieved complete response (CR). After finishing treatment, disease recurred. They were retreated with the same regimens and achieved second CR. Until now, they have received each regimen, continuously, and the CR state has been maintained.

Clinical Characteristics of Patients Older than 76 with Lung Cancer / 대한내과학회지

BACKGROUND/AIMS: A significant proportion of elderly patients who have lung cancer do not receive treatment even though they may benefit from it. The aims of this study were to analyze the clinical characteristics of elderly patients with lung cancer, especially those aged 76 years and older. METHODS: In this retrospective study, we analyzed clinical data from 341 patients with lung cancer who were diagnosed at Chungnam National University Hospital from January 2003 to September 2010. RESULTS: The median age of patients was 79 years (76-91), and 39.6% (n = 135) of the total sample were older than 80. Squamous cell carcinoma was the most common type of lung cancer, and the performance status (Eastern Cooperative Oncology Group [ECOG] 0-1) of 40.6% (n = 116) of the sample was good. Of the 293 non small cell lung cancer (NSCLC) patients, 53.6% were untreated. About 68% of all patients knew about their disease (n = 232). CONCLUSIONS: Our data indicated that many elderly patients with lung cancer were undertreated. Elderly patients with lung cancer should receive education to help them understand their disease and to encourage them to receive appropriate treatment.

Effects of Curcumin and Genistein on Phorbol Ester or Tumor Necrosis Factor-alpha-Induced Mucin Production from Human Airway Epithelial Cells / 결핵및호흡기질환

BACKGROUND: We investigated whether curcumin and genistein affect the MUC5AC mucin production from human airway epithelial cells that is induced by phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-alpha (TNF-alpha). METHODS: Confluent NCI-H292 cells were pretreated with each agent for 30 min and then stimulated with PMA or TNF-alpha for 24 hours. MUC5AC mucin production was measured by an ELISA. RESULTS: (1) Curcumin dose-dependently inhibited the production of MUC5AC mucin that was induced by PMA or TNF-alpha; (2) Genistein inhibited PMA-induced MUC5AC mucin production. However, it did not decrease TNF-alpha-induced MUC5AC mucin production. CONCLUSION: These results suggest that curcumin and genistein inhibit the production of airway mucin induced by PMA.