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1.
J Enzyme Inhib Med Chem ; 35(1): 227-234, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31752563

RESUMO

A novel series of thieno[3,2-d]pyrimidine derivatives were synthesised and their inhibitory effects against diacylglycerol acyltransferase 1 (DGAT-1) were assessed. cis-Isomer 17a showed potent and selective inhibitory activity against DGAT-1 in SF9 cells. In addition, 17a had an acceptable pharmacokinetic profile and accumulated mainly in the small intestine and liver. Oral administration of 17a led to a significant reduction in plasma triacylglycerol level during an oral lipid tolerance test (OLTT) in murine and canine models. Taken together, 17a is a high-quality candidate that deserves further investigation.


Assuntos
Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Pirimidinas/farmacologia , Animais , Diacilglicerol O-Aciltransferase/metabolismo , Cães , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
2.
Artigo em Inglês | MEDLINE | ID: mdl-31190782

RESUMO

Introduction: The use of antibiotics is based on the clinician's experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events. Methods: We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission. Results: A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (P=0.010 and P=0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107-2.749; P=0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081-3.984; P=0.028] were higher in the group with eosinophil count less than 2%. Conclusion: In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.


Assuntos
Infecções Bacterianas/sangue , Infecções Bacterianas/microbiologia , Eosinófilos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/microbiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Tomada de Decisão Clínica , Progressão da Doença , Registros Eletrônicos de Saúde , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
4.
PLoS One ; 14(5): e0216397, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31059556

RESUMO

BACKGROUND: In patients with sepsis, an inflammatory response can lead to destruction of the glycocalyx. These alterations cause the progression of organ dysfunction. Destruction of the glycocalyx can also occur in chronic hyperglycemia. Glycated hemoglobin (HbA1c) is a reliable marker of premorbid hyperglycemia. We investigated the association between HbA1c level at admission and the degree of organ dysfunction progression 72 hours after admission and ICU mortality. METHODS AND FINDINGS: This study was a retrospective observational study. Logistic regression and correlation analyses were performed to evaluate the association between the HbA1c level and the degree of organ dysfunction progression 72 hours after ICU admission. We applied survival analysis to examine the association between HbA1c level and ICU mortality. A total of 90 patients were included in this study. The association between HbA1c level and degree of organ dysfunction progression was significant (r = 0.320; P = 0.002). Multivariable logistic regression analysis showed that high HbA1c level (≥6.5%) (OR, 2.98; 95% CI, 1.033-8.567; P = 0.043) were significant, independent predictors of severe organ dysfunction progression. Patients with an HbA1c level ≥6.5% exhibited significantly greater liver and kidney dysfunction progression 72 hours after ICU admission compared with those with an HbA1c level <6.5%. Kaplan-Meier analysis showed that the survival period was significantly shorter in patients with an HbA1c level ≥6.5% than in those with an HbA1c level <6.5% (P < 0.001). Multivariable Cox proportional hazard analysis showed that HbA1c level ≥6.5% (HR, 3.49; 95% CI, 1.802-6.760; P <0.001) were significant, independent predictors of ICU mortality. CONCLUSIONS: In patients with sepsis, the HbA1c level at ICU admission is associated with progression of organ dysfunction 72 hours later and with ICU mortality. It may be important to assess HbA1c level at ICU admission because it may be a predictor of ICU outcome. For patients with a high HbA1c level (≥6.5%), greater attention should be paid to the possibility of organ dysfunction progression.


Assuntos
Hemoglobina A Glicada/metabolismo , Mortalidade Hospitalar , Insuficiência de Múltiplos Órgãos , Sepse , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/mortalidade , Estudos Retrospectivos , Sepse/sangue , Sepse/mortalidade , Taxa de Sobrevida
5.
J Thorac Dis ; 11(2): 427-437, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30962986

RESUMO

Background: Because poverty is a multifaceted concept with a complex definition, this concept may not be useful when formulating economic policy. Thus, most governments use the relative poverty line to identify poor participants who may receive economic support. The aim of this study was to investigate the association between living below the relative poverty line and the prevalence of chronic obstructive pulmonary disease (COPD). Methods: We retrospectively analyzed data from 3,223 individuals included in South Korea. Living below the poverty line was defined as receiving a monthly income less than the minimum cost of living. Results: Of the 3,223 participants included in this analysis, 832 (25.8%) met the definition of living below the relative poverty line and 384 (11.9%) had COPD. Of the 3,223 participants, 161 of the 832 (19.4%) living below the poverty line and 223 of the 2,391 (9.3%) living above the poverty line had COPD. In our study, participants living below the poverty line had a 1.4-time higher risk of COPD development compared with those living above the poverty line (OR =1.4; P=0.012). Elderly people living below the poverty line were 1.5-time more likely to be at risk of COPD development than those living above the poverty line (OR =1.5; P=0.021). Conclusions: People living below the relative poverty line have an increased prevalence of COPD, especially older people with COPD. From the perspective of COPD disease control, policy makers should consider providing national economic support for the early detection and management of COPD in people living below the relative poverty line.

6.
BMC Pulm Med ; 19(1): 68, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30902075

RESUMO

BACKGROUND: Risk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke. METHODS: To investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts. In a multiple linear regression model, the standardized regression coefficient (ß) of biomass smoke exposure ≥25 years was most similar to that (ß') of tobacco smoke exposure ≥10 pack-years (ß = - 0.13 and ß' = - 0.14). We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass. The main outcome was the incidence of moderate or severe exacerbations. RESULTS: Among 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%). The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56-1.89; P = 0.921). No interaction between sex and tobacco and biomass smoke was observed. When propensity score matching with available covariates including age and sex was applied, a similar result was observed. CONCLUSIONS: Patients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations. This suggests that patients with COPD associated with biomass smoke should be treated actively.


Assuntos
Biomassa , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Fumar/efeitos adversos , Tabaco/efeitos adversos , Idoso , Progressão da Doença , Exposição Ambiental , Feminino , Volume Expiratório Forçado , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , República da Coreia/epidemiologia , Fumar/epidemiologia
7.
Tuberc Respir Dis (Seoul) ; 82(3): 211-216, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30841020

RESUMO

BACKGROUND: Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. METHODS: Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel 25 mg/m² on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. RESULTS: A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. CONCLUSION: Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.

8.
Lung ; 197(3): 303-313, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30859313

RESUMO

PURPOSE: The economic effect of regular follow-up and early management in patients with early chronic obstructive pulmonary disease (COPD) has not yet been clarified. Therefore, this study aimed to estimate the economic effect of regular follow-up and early management in these patients. METHODS: Patients with early COPD were identified from the Korea National Health and Nutrition Examination Survey. We analyzed medical utilization and cost for 2 years without any missing data by using the Korean National Health Insurance data. Patients with routine healthcare maintenance were defined as, after diagnosis, those with regular visits to the hospital and receiving early management of COPD. RESULTS: Among 1204 patients with early COPD, the patients who were classified as the group with routine healthcare maintenance (69/146; 47.3%) and the group with intermittent healthcare user (79/1058; 7.5%) visited to hospital for the next 2 years. The patients with routine healthcare maintenance had lower cost of inpatient service and frequencies of emergency room (ER) visit and intensive care unit (ICU) admission than intermittent healthcare users (cost of inpatient service, $4595 vs. $4953 per person; ER visit, 7.2 vs. 11.5; ICU admission, 4.3 vs. 7.7). Even in patients with COPD and FEV1 ≥ 80, early intervention through follow-up reduced the cost of inpatient service because these patients could have had less severe acute exacerbations than intermittent healthcare users. CONCLUSION: Patients with early COPD, even those with FEV1 ≥ 80, need regular follow-up for early management and disease control as well as for reducing the socioeconomic burden of the disease.

9.
ChemistryOpen ; 8(2): 188-191, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30788208

RESUMO

X-Linked adrenoleukodystrophy (X-ALD) is a severe metabolic disorder characterized by the accumulation of very long-chain fatty acids (VLCFAs). Recently, we demonstrated that levels of 25-hydroxycholesterol (25-HC) and cholesterol 25-hydroxylase (CH25H) were found to be elevated in X-ALD. Herein, we report that the exogenous addition of 25-HC significantly reduces C26:0 levels in X-ALD patient-derived fibroblasts and oligodendrocytes differentiated from induced pluripotent stem cells (iPSCs) derived from X-ALD patients. Moreover, 25-HC treatment was found to down-regulate the expression of ELOVL1, a key enzyme for the synthesis of C26. In addition, activation of liver X receptor (LXR), a molecular target of endogenous 25-HC, also reduced C26:0 level. The reduction of C26:0 levels by 25-HC treatment might result, at least partially, from the decrease of ELOVL1 expression as well as the activation of LXR. Our findings could provide a better understanding of the role of 25-HC in X-ALD and useful information to find therapeutic agents to treat X-ALD.

10.
Respirology ; 24(6): 551-557, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30681246

RESUMO

BACKGROUND AND OBJECTIVE: A cough-specific quality-of-life questionnaire is recommended to assess the impact of cough; however, a simple instrument to quantify cough is required for everyday clinical practice. This study was aimed to develop a short patient-completed questionnaire (COugh Assessment Test, COAT). METHODS: The COAT was developed and validated by comparison with the Korean version of Leicester Cough Questionnaire (K-LCQ) and cough numeric rating scale (NRS, 0-10, 11-point scale) for chronic cough patients. RESULTS: Item selection identified five items regarding cough frequency, daily activity, sleep disturbance, fatigue and cough hypersensitivity (0-4 scaling of items, 0-20 score range) through reliability test cohort (n = 78). Test-retest reliability was strong (intra-class correlation coefficient = 0.88). The final COAT was compared with K-LCQ and cough NRS in a validation cohort (n = 323). In Rasch analysis, COAT fitted well to a unidimensional model. Pearson correlations of COAT versus K-LCQ (i) before treatment, (ii) after treatment; COAT versus cough NRS (iii) before treatment, (iv) after treatment; (v) delta-COAT versus delta-cough NRS, (vi) delta-COAT versus delta-K-LCQ were (i) -0.71, (ii) -0.81, (iii) 0.69, (iv) 0.82, (v) -0.66 and (vi) 0.72, respectively. CONCLUSION: The COAT is a useful, simple questionnaire for assessing and monitoring cough.

11.
Yonsei Med J ; 60(2): 216-222, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30666844

RESUMO

PURPOSE: The most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is respiratory infection. Most studies of bacterial or viral cause in AECOPD have been conducted in Western countries. We investigated bacterial and viral identification rates in AECOPD in Korea. MATERIALS AND METHODS: We reviewed and analyzed medical records of 736 cases of AECOPD at the Korea University Guro Hospital. We analyzed bacterial and viral identification rates and classified infections according to epidemiological factors, such as Global Initiative for Chronic Obstructive Lung Disease stage, mortality, and seasonal variation. RESULTS: The numbers of AECOPD events involving only bacterial identification, only viral identification, bacterial-viral co-identification, and no identification were 200 (27.2%), 159 (21.6%), 107 (14.5%), and 270 (36.7%), respectively. The most common infectious bacteria identified were Pseudomonas aeruginosa (13.0%), Streptococcus pneumoniae (11.4%), and Haemophilus influenzae (5.3%); the most common viruses identified were influenza virus (12.4%), rhinovirus (9.4%), parainfluenza virus (5.2%), and metapneumovirus (4.9%). The bacterial identification rate tended to be higher at more advanced stages of chronic obstructive pulmonary disease (p=0.020 overall, p=0.011 for P. aeruginosa, p=0.048 for S. pneumoniae). Staphylococcus aureus and Klebsiella pneumoniae were identified more in mortality group (p=0.003 for S. aureus, p=0.009 for K. pneumoniae). All viruses were seasonal (i.e., greater prevalence in a particular season; p<0.050). Influenza virus and rhinovirus were mainly identified in the winter, parainfluenza virus in the summer, and metapneumovirus in the spring. CONCLUSION: This information on the epidemiology of respiratory infections in AECOPD will improve the management of AECOPD using antibiotics and other treatments in Korea.


Assuntos
Progressão da Doença , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/virologia , Doença Aguda , Idoso , Bactérias/isolamento & purificação , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , República da Coreia/epidemiologia , Estações do Ano , Vírus/isolamento & purificação
12.
Bioorg Chem ; 84: 51-62, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30481646

RESUMO

Two series of erlotinib-alkylphospholipid hybrids were prepared and evaluated for their antiproliferative activities against a panel of four cell lines representing lung, breast, liver and skin cancers using erlotinib and miltefosine as reference standards. Amide analogs elicited more enhanced cytotoxic activity than analogous esters. Amide derivatives 8d and 8e exhibited promising broad-spectrum antiproliferative activity and higher efficacy than reference erlotinib and miltefosine. Their cellular GI50 values was in the ranges of 24.7-46.9 µM and 26.8-43.1 µM for 8e and 8d respectively. Assay results of the inhibitory activity of the prepared compounds on EGFR kinase reaction and Akt phosphorylation in conjugation with statistical correlation analysis indicated that other mechanisms might contribute to their elicited cytotoxicities. In addition, statistical correlation analysis revealed that mechanisms of elicited cytotoxicities for amide series might be different from ester series. In addition, correlation analysis indicated variations in the mechanisms according to the types of cell line.


Assuntos
Antineoplásicos/farmacologia , Cloridrato de Erlotinib/farmacologia , Fosfolipídeos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/química , Humanos , Estrutura Molecular , Fosfolipídeos/química , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade
13.
Eur J Med Chem ; 163: 660-670, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576901

RESUMO

Transforming growth factor-ß activated kinase-1 (TAK1) is a potential therapeutic target for cancers and inflammatory diseases. We synthesized a series of novel imidazopyrazine derivatives, which were found to exhibit potent inhibitory effect against TAK1. Compound 22a, which possesses a good pharmacokinetic profile, showed excellent in vitro kinase activity and significant in vivo efficacy in mice xenografted with SW620, a KRAS-dependent colon cancer cell line.


Assuntos
MAP Quinase Quinase Quinases/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Pirazinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Xenoenxertos , Humanos , Inflamação/tratamento farmacológico , Camundongos , Neoplasias/tratamento farmacológico , Pirazinas/síntese química , Pirazinas/farmacocinética , Pirazinas/farmacologia
14.
Bioorg Med Chem Lett ; 29(3): 477-480, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30554954

RESUMO

Discovery of mutant-selective kinase inhibitors is one of the challenges in medicinal chemistry and is a main issue for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. We tried to improve the selectivity of pan-HER inhibitors for mutant EGFRs. Utilizing click chemistry, triazole-tethered quinazoline derivatives were synthesized, based on a quinazoline scaffold showing pan-HER inhibition. The representative compound 5j exhibited 17- and 52-fold improved selectivity for EGFR L858R/T790M over wild-type EGFR and HER2, respectively, and demonstrated 6.7-fold more potent antiproliferative activity against PC9 cells harboring EGFR-activating mutation than gefitinib. Although the described quinazolines did not surpass pyrimidines as 3rd generation EGFR inhibitors in terms of selectivity for mutant EGFRs, our approach might provide information that would help in the identification of mutant-selective compounds among pan-HER inhibitors using the quinazoline scaffold.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Click , Relação Dose-Resposta a Droga , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Humanos , Estrutura Molecular , Mutação , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade
15.
Tuberc Respir Dis (Seoul) ; 82(1): 81-85, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29926544

RESUMO

BACKGROUND: Bronchoscopy is a useful diagnostic and therapeutic tool. However, the clinical use of high-flow nasal cannula (HFNC) in adults with acute respiratory failure for diagnostic and invasive procedures has not been well evaluated. We present our experiences of well-tolerated diagnostic bronchoscopy as well as cases of improved saturation in hypoxaemic patients after a therapeutic bronchoscopic procedure. METHODS: We retrospectively reviewed data of hypoxaemic patients who had undergone bronchoscopy for diagnostic or therapeutic purposes from October 2015 to February 2017. RESULTS: Ten patients (44-75 years of age) were enrolled. The clinical purposes of bronchoscopy were for diagnosis in seven patients and for intervention in three patients. For the diagnoses, we performed bronchoalveolar lavage in six patients. One patient underwent endobronchial ultrasonography with transbronchial needle aspiration of a lymph node to investigate tumour involvement. Patients who underwent bronchoscopy for therapeutic interventions had endobronchial mass or blood clot removal with cryotherapy for bleeding control. The mean saturation (SpO2) of pre-bronchoscopy in room air was 84.1%. The lowest and highest mean saturation with HFNC during the procedure was 95% and 99.4, respectively. The mean saturation in room air post-bronchoscopy was 87.4%, which was 3.3% higher than the mean room air SpO2 pre-bronchoscopy. Seven patients with diagnostic bronchoscopy had no hypoxic event. Three patients with interventional bronchoscopy showed improvement in saturation after the procedure. Bronchoscopy was well tolerated in all 10 cases. CONCLUSION: This study suggests that the use of HFNC in hypoxaemic patients during diagnostic and therapeutic bronchoscopy procedures has clinical effectiveness.

16.
Int J Chron Obstruct Pulmon Dis ; 13: 3381-3387, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425468

RESUMO

Purpose: Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE). However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology. The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD. Patients and methods: We performed a multicenter cross-sectional cohort study. We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD. Results: Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD. Although the FEV1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD. CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD. According to a multivariate logistic regression analysis, FEV1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD. IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P<0.001). Conclusion: Patients with T-COPD have higher levels of inflammatory markers, and IL-6 has a predictive value for AE in T-COPD.


Assuntos
Proteína C-Reativa/imunologia , Interleucina-6/sangue , Doença Pulmonar Obstrutiva Crônica , Fumar/efeitos adversos , Exacerbação dos Sintomas , Tuberculose Pulmonar/complicações , Idoso , Biomarcadores/sangue , Sedimentação Sanguínea , Correlação de Dados , Estudos Transversais , Dispneia/diagnóstico , Dispneia/etiologia , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/imunologia , República da Coreia , Testes de Função Respiratória/métodos , Escarro , Avaliação de Sintomas/métodos
17.
Int J Chron Obstruct Pulmon Dis ; 13: 3411-3417, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425470

RESUMO

Purpose: Improvement in the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), and identification of biomarkers for phenotype recognition will encourage good patient care by providing optimal therapy. We investigated club cell secretory protein (CC-16), a protective and anti-inflammatory mediator, as a new candidate biomarker for diagnosing ACO. Patients and methods: We performed a multicenter cohort study. A total of 107 patients were divided into three groups - asthma, COPD, and ACO - according to the Spanish guidelines algorithm, and enrolled into the study. Serum CC-16 levels were measured using commercial ELISA kits. Results: Serum CC-16 levels were the lowest in patients with ACO. Low serum CC-16 levels were a significant marker for the ACO even after adjustment for age, sex, and smoking intensity. Serum CC-16 levels were positively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%-75% of FVC, FEV1/FVC, vital capacity, and diffusing capacity of the lung for carbon monoxide, and were negatively correlated with smoking amount (pack-years), bronchodilator response, fractional residual capacity, residual volume, and number of exacerbations per year. FEV1 and serum CC-16 levels were significantly lower in patients with frequent exacerbations. Conclusion: Serum CC-16 has the potential to be a biomarker for ACO diagnosis and also treat frequent exacerbations in patients with chronic inflammatory airway diseases.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Fumar/sangue , Uteroglobina/sangue , Idoso , Asma/sangue , Asma/complicações , Asma/diagnóstico , Biomarcadores/sangue , Estudos de Coortes , Correlação de Dados , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Proteção , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Testes de Função Respiratória/métodos , Capacidade Vital
18.
J Thorac Dis ; 10(9): 5246-5253, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30416771

RESUMO

Background: Patients with tuberculosis-destroyed lungs (TDLs), with airflow limitation, have clinical characteristics similar to those of patients with chronic obstructive pulmonary disease (COPD). Acute exacerbation is an important factor in the management of TDL. Therefore, the aim of this study was to investigate the factors associated with acute exacerbations in patients with stable TDL with airflow limitation. Methods: We evaluated the clinical characteristics, such as lung function, image findings, and serum laboratory findings, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and interleukin (IL)-6, in patients with TDL with chronic airflow limitation (n=94). We evaluated the correlation of these parameters with acute exacerbation. Results: We found that patients with exacerbation were more likely to have bronchiectasis than those without exacerbation (patients with exacerbation, 66.7%; patients without exacerbation, 30.5%; P=0.001). CRP and IL-6 levels were significantly higher in patients with exacerbation than in those without exacerbation (P=0.001 and P<0.001, respectively). Bronchiectasis [OR, 3.248; 95% confidence interval (CI), 1.063-9.928; P=0.039] and elevated IL-6 levels (OR, 1.128; 95% CI, 1.013-1.257; P=0.028) were the most important parameters associated with acute exacerbation in patients with TDL with airflow limitation. Conclusions: Patients with bronchiectasis and high IL-6 levels may require more intensive treatment to prevent acute exacerbation.

19.
Int J Chron Obstruct Pulmon Dis ; 13: 3077-3083, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323578

RESUMO

Introduction: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified. Methods: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission. Results: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296-17.041; P=0.019). Conclusion: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients.


Assuntos
Progressão da Doença , Readmissão do Paciente/estatística & dados numéricos , Infecções por Pseudomonas/diagnóstico , Doença Pulmonar Obstrutiva Crônica/microbiologia , Idoso , Distribuição de Qui-Quadrado , Estudos de Coortes , Bases de Dados Factuais , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Universitários , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , República da Coreia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas
20.
Medicine (Baltimore) ; 97(31): e11683, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075563

RESUMO

Combined pulmonary fibrosis and emphysema (CPFE) patients visit hospitals frequently due to acute exacerbations (AEs); however, the predictors of CPFE AE have not been comprehensively described in literature. Thus, we investigated the predicting factors of AE in CPFE patients.We retrospectively reviewed medical records from the past 12 years at Korea University Guro Hospital. We selected CPFE patients by computed tomography findings. Rapid deterioration (RD) was defined as acute worsening of dyspnea requiring hospitalization and the presence of newly developed radiologic abnormalities. AE was defined as RD with newly acquired bilateral pulmonary infiltrates without evidence of pulmonary infection or other known causes. We evaluated the following variables in CPFE patients: age, sex, smoking history and amount, body mass index, past medical history, pulmonary function test, gender, age, and physiology (GAP) score, and the presence of lung cancer.Among 227 CPFE patients, 108 had RD and 31 developed AE. The most common cause of RD was infection (n = 60, 55.6%) and 28.7% (n = 31) developed AE. Lung cancer [hazard ratio (HR), 3.274; 95% confidence interval (95% CI) 1.444-7.425; P < .01] and GAP score (HR, 1.434; 95% CI 1.072-1.918; P = .02) were significant predictors of AE. The presence of lung cancer and AE were significant predictors of mortality.In conclusion, CPFE patients with lung cancer and high GAP scores should be carefully observed for AE.


Assuntos
Progressão da Doença , Enfisema Pulmonar/fisiopatologia , Fibrose Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Fatores Etários , Idoso , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Enfisema Pulmonar/complicações , Enfisema Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/complicações , Fibrose Pulmonar/diagnóstico por imagem , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Tomografia Computadorizada por Raios X
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