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1.  Patient's Perception of Symptoms Related to Morning Activity in Chronic Obstructive Pulmonary Disease: The SYMBOL Study 
Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning. The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation.
Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study. A clinical symptom questionnaire was completed by patients at baseline. In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment.
The most frequently reported COPD symptom was breathlessness (90.8%). Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms. The most frequently reported morning activity was getting out of bed (82.9%). The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms. There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment.
Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities. These patients also have more prevalent and severe COPD symptoms. The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD.
PMCID: PMC3529242  PMID: 23269884
Perception; Morning; Symptoms; Activities; Chronic obstructive pulmonary disease
2.  Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE) 
This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC).
In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population.
A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%).
Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.
PMCID: PMC3538183  PMID: 23319992
Gefitinib; Receptor, Epidermal Growth Factor; Mutation; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival
3.  Triple-Combination Antiviral Drug for Pandemic H1N1 Influenza Virus Infection in Critically Ill Patients on Mechanical Ventilation ▿ § 
Antimicrobial Agents and Chemotherapy  2011;55(12):5703-5709.
A recent in vitro study showed that the three compounds of antiviral drugs with different mechanisms of action (amantadine, ribavirin, and oseltamivir) could result in synergistic antiviral activity against influenza virus. However, no clinical studies have evaluated the efficacy and safety of combination antiviral therapy in patients with severe influenza illness. A total of 245 adult patients who were critically ill with confirmed pandemic influenza A/H1N1 2009 (pH1N1) virus infection and were admitted to one of the intensive care units of 28 hospitals in Korea were reviewed. Patients who required ventilator support and received either triple-combination antiviral drug (TCAD) therapy or oseltamivir monotherapy were analyzed. A total of 127 patients were included in our analysis. Among them, 24 patients received TCAD therapy, and 103 patients received oseltamivir monotherapy. The 14-day mortality was 17% in the TCAD group and 35% in the oseltamivir group (P = 0.08), and the 90-day mortality was 46% in the TCAD group and 59% in the oseltamivir group (P = 0.23). None of the toxicities attributable to antiviral drugs occurred in either group of our study, including hemolytic anemia and hepatic toxicities related to the use of ribavirin. Logistic regression analysis indicated that the odds ratio for the association of TCAD with 90-day mortality was 0.58 (95% confidence interval, 0.24 to 1.42; P = 0.24). Although this study was retrospective and did not provide virologic outcomes, our results suggest that the treatment outcome of the triple combination of amantadine, ribavirin, and oseltamivir was comparable to that of oseltamivir monotherapy.
PMCID: PMC3232815  PMID: 21968371
4.  Effects of TNF-α and Leptin on Weight Loss in Patients with Stable Chronic Obstructive Pulmonary Disease 
Weight loss is common in patients with chronic obstructive pulmonary disease (COPD). However, the mechanisms of this weight loss are still unclear.
Sixty male patients with stable COPD and 45 healthy male controls participated in this study. The COPD patients were divided into two groups, that is, the emphysema and chronic bronchitis groups, by the transfer coefficient of carbon monoxide. The body composition, resting energy expenditure (REE), plasma leptin levels and serum tumor necrosis factor-alpha (TNF-α) were measured in all the study participants. The difference and correlation of these parameters were investigated between the two groups.
Emphysematous patients were characterized by a lower body mass index (BMI) and fat-mass (FM) compared with the chronic bronchitis patients (p<0.001). The plasma leptin levels, as corrected for the FM, were not different between the COPD patients and healthy controls (78.3±30.9 pg/mL/kg vs. 70.9±17.3 pg/mL/kg, respectively), and the plasma leptin levels, as adjusted for the FM, were also not different between the two groups of COPD patients. In the chronic bronchitis patients, the plasma leptin concentration was correlated with the BMI (r=0.866, p<0.001) but it was not correlated with the BMI in the emphysema patients. The serum TNF-α levels were higher in the stable COPD patients than those in the controls, but there was no statistical difference (10.7±18.6 pg/mL vs. 7.2×3.5 pg/mL, respectively, p0.05). The leptin concentration was well correlated with the BMI and %FM in the patients with chronic bronchitis and the leptin concentration was only correlated with the %FM (r=0.450, p=0.027) in emphysema patients. There was no correlation between the plasma leptin concentration, as adjusted for the fat mass, and the activity of the TNF-α system.
The interaction of leptin and the activity of the TNF-α system in the pathogenesis of tissue depletion may not play an important role in chronic stable COPD patients.
PMCID: PMC2687660  PMID: 18309683
COPD; Weight loss; Leptin; Tumor necrosis factor-alpha
5.  Clinical and Bronchoscopic Findings in Ugandans with Pulmonary Kaposi's Sarcoma 
Pulmonary Kaposi's sarcoma (PKS) directly affects the life expectancy of those infected and yet the clinical and radiographic features of Kaposi's sarcoma (KS) with pulmonary involvement are nonspecific, which makes diagnosis difficult. In Uganda, pulmonary tuberculosis, which has clinical features that closely resemble those of PKS, also occurs commonly and thus confusion is bound to arise. Bronchoscopy is a recognized diagnostic investigatory modality for PKS. The aim of present study was to identify unique or useful points for the differential diagnosis of PKS and other opportunistic infections.
The clinical, radiologic, and bronchoscopic findings in thirty-five Ugandan patients (age 20-50, median 32) with PKS were analyzed.
Cough and weight loss were most common and occurred in 97.1%, whereas fever occurred in 62.9%, and breathlessness in 57.1%. Thirty-four patients (97.1%) showed mucocutaneous KS, and palatal KS was most frequent and was observed in 74.3%. In addition, 25 patients (71.4%) showed the characteristic endobronchial plaques of KS. The most frequently observed radiographic abnormality was bilateral reticulonodular density. Histological examinations of bronchoscopic biopsies revealed KS in 7 (36.6%) cases. Five PFS patients (25%) also had co-existent tuberculosis.
The majority of patients with PKS showed no specific findings on physical examination, apart from mucocutaneous KS. Our findings indicate that palatal KS may be a strong predictor of PKS. In Uganda, pulmonary tuberculosis may be the most common concomitant pulmonary infection in PKS patients.
PMCID: PMC3891074  PMID: 16491826
Pulmonary Kaposi's sarcoma; Bronchoscopy; Tuberculosis
6.  A Case of Solitary Fibrous Pleura Tumor Associated with Severe Hypoglycemia: Doege-Potter Syndrome 
Solitary fibrous tumor of the pleura (SFTP) is a rare primary intrathoracic tumor that arises from mesenchymal tissue underlying the mesothelial layer of the pleura. It usually has an indolent clinical course. The hypoglycemia that accompanies SFTP was first described by Doege and Potter independently in 1930, hence the eponym Doege-Potter syndrome (DPS). The incidence of DPS is reported to be ~4%. In this report, we present a typical case of DPS that was cured through complete surgical resection.
PMCID: PMC4388895  PMID: 25861346
Solitary Fibrous Tumors; Pleura; Hypoglycemia
7.  Chronic Obstructive Pulmonary Disease Assessment Test Can Predict Depression: A Prospective Multi-Center Study 
Journal of Korean Medical Science  2013;28(7):1048-1054.
This study was conducted to investigate the association between the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD patients. The Korean versions of the CAT and patient health questionnaire-9 (PHQ-9) were used to assess COPD symptoms and depressive disorder, respectively. In total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence of depression was 23.8%. The CAT score correlated well with the PHQ-9 score (r=0.631; P<0.001) and was significantly associated with the presence of depression (β±standard error, 0.452±0.020; P<0.001). There was a tendency toward increasing severity of depression in patients with higher CAT scores. By assessment groups based on the 2011 Global Initiative for Chronic Obstructive Lung Disease guidelines, the prevalence of depression was affected more by current symptoms than by airway limitation. The area under the receiver operating characteristic curve for the CAT was 0.849 for predicting depression, and CAT scores ≥21 had the highest accuracy rate (80.6%). Among the eight CAT items, energy score showed the best correlation and highest power of discrimination. CAT scores are significantly associated with the presence of depression and have good performance for predicting depression in COPD patients.
PMCID: PMC3708076  PMID: 23853488
Pulmonary Disease, Chronic Obstructive; COPD Assessment Test; Depression
8.  Interstitial Lung Disease in a Patient with Dyskeratosis Congenita 
Dyskeratosis congenita is a rare congenital disorder characterized by a triad of reticular pigmentation of the skin, dystrophic nails, and leukoplakia of the mucous membrane. Sometimes it is associated with bone marrow failure, secondary malignancy and interstitial lung disease. Though it is rare, Dyskeratosis congenita is diagnosed relatively easily when clinicians suspect it. It can be diagnosed just by gross inspection with care. Dyskeratosis congenita should be considered as one cause associated with interstitial lung disease. In Korea, interstitial lung disease with dyskeratosis congenita has not been reported. We report a case and review the literature.
PMCID: PMC3591541  PMID: 23483786
Lung Diseases, Interstitial; Dyskeratosis Congenita; Anemia, Aplastic
9.  A Multicenter Study of Pertussis Infection in Adults with Coughing in Korea: PCR-Based Study 
Limited data on the incidence and clinical characteristics of adult pertussis infections are available in Korea.
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.
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).
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.
PMCID: PMC3517945  PMID: 23236318
Adult; Cough; Incidence; Whooping Cough; Signs and Symptoms
10.  The Effect of Body Composition on Pulmonary Function 
The pulmonary function test is the most basic test method to diagnosis lung disease. The purpose of this study was to research the correlation of the body mass index (BMI), the fat percentage of the body mass (fat%), the muscle mass, the fat-free mass (FFM) and the fat-free mass index (FFMI), waist-hip ratio (WHR), on the forced expiratory volume curve.
Between March and April 2009, a total of 291 subjects were enrolled. There were 152 men and 139 female (mean age, 46.3±9.92 years), and they were measured for the following: forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and forced expiratory flow during the middle half of the FVC (FEF25-75) from the forced expiratory volume curve by the spirometry, and the body composition by the bioelectrical impedance method. Correlation and a multiple linear regression, between the body composition and pulmonary function, were used.
BMI and fat% had no correlation with FVC, FEV1 in male, but FFMI showed a positive correlation. In contrast, BMI and fat% had correlation with FVC, FEV1 in female, but FFMI showed no correlation. Both male and female, FVC and FEV1 had a negative correlation with WHR (male, FVC r=-0.327, FEV1 r=-0.36; p<0.05; female, FVC r=-0.175, FEV1 r=-0.213; p<0.05). In a multiple linear regression of considering the body composition of the total group, FVC explained FFM, BMI, and FFMI in order (r2=0.579, 0.657, 0.663). FEV1 was explained only fat% (r2=0.011), and FEF25-75 was explained muscle mass, FFMI, FFM (r2=0.126, 0.138, 0.148).
The BMI, fat%, muscle mass, FFM, FFMI, WHR have significant association with pulmonary function but r2 (adjusted coefficient of determination) were not high enough for explaining lung function.
PMCID: PMC3475466  PMID: 23101008
Pulmonary Function Tests; Body Compostion; Factor Analysis, Statistical
11.  MAGE A1-A6 RT-PCR and MAGE A3 and p16 methylation analysis in induced sputum from patients with lung cancer and non-malignant lung diseases 
Oncology Reports  2011;27(4):911-916.
The melanoma antigen gene (MAGE) A1-A6 RT-PCR system was developed for the detection of lung cancer cells in the sputum. However, we identified MAGE expression in some patients with non-malignant lung diseases. To understand these patterns of MAGE expression, we performed MAGE A3 methylation-specific PCR (MSP) and p16 MSP. We collected 24 biopsy specimens of lung cancer tissue and performed MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16 MSP. RNA and DNA were simultaneously extracted from induced sputum specimens of 133 patients with lung diseases and 30 random sputum specimens of healthy individuals and the 3 molecular analyses were performed. The patients were diagnosed as 65 cases of lung cancer and 68 of benign lung diseases. Positive rates of MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16 MSP were as follows: in lung cancer tissue, 87.5, 58.3 and 70.8%; in the sputum of lung cancer patients, 50.8, 46.2 and 63.1%; benign lung diseases, 10.3, 30.9 and 39.7%; and healthy individuals, 3.3, 6.7 and 3.3%. Of the 40 MAGE-positive cases, 33 were diagnosed with lung cancer and 7 as having benign lung diseases. From the 7 cases of MAGE-positive benign lung diseases, 6 cases showed methylation abnormalities. The MAGE-positive group revealed significantly higher rates of methylation abnormalities. Of the 40 MAGE-positive cases, 39 cases were found to be lung cancer or benign lung diseases with abnormal methylation. Thus, MAGE expression in the sputum suggests the presence of lung cancer cells or pre-cancerous cells.
PMCID: PMC3583547  PMID: 22134685
lung cancer; sputum; melanoma antigen gene RT-PCR; melanoma antigen gene A3; p16; methylation
12.  Detection of Lung Cancer using MAGE A1-6 and SSX4 RT-PCR Expression Profiles in the Bronchial Wash Fluid 
Bronchial wash fluid may be a useful for detecting lung cancer. To increase the detection rates, we performed molecular analysis with using MAGE A1-6 and SSX4 RT-PCR on bronchial wash fluid specimens.
Materials and Methods
We obtained 57 lung cancer tissue specimens by bronchoscopic biopsy and 131 bronchial washes from 96 patients with lung cancer and 35 patients with benign lung diseases. The MAGE A1-6 and SSX4 gene expressions were investigated in the cancer tissue specimens and bronchial wash fluids. We evaluated the positive detection rates of these methods according to the cytology results and the clinical findings.
For the cancer tissue specimens and the bronchial wash fluid, the positive detection rate of MAGE or SSX4 was 91.2% and 75.0%, respectively. Combined MAGE and SSX4 PCR and cytology tests showed an 83.3% detection rate for the bronchial wash fluid. From bronchial washes of patients with benign lung diseases, the positive rates of using MAGE or SSX4 was 11.4%. In the bronchial wash fluid of lung cancer patients, 66.7% of the peripheral cancers were detected by MAGE or SSX4, while examination with cytology did not detect any peripheral lung cancer.
The application of both MAGE and SSX4 showed high sensitivity and specificity for the detection of lung cancer. Thus, MAGE and SSX4 RT-PCR may be effectively utilized as additional methods to improve detection of lung cancer with using bronchial wash fluids.
PMCID: PMC2739316  PMID: 19746211
MAGE; SSX; Cytology; Bronchial wash

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