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RATIONALE: Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. OBJECTIVES: We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. METHODS: Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. MEASUREMENTS AND MAIN RESULTS: Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. CONCLUSIONS: These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.
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Autofagia/imunologia , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Pneumonia/imunologia , Sepse/imunologia , Sepse/fisiopatologia , Idoso , Animais , Autofagia/fisiologia , Infecções Comunitárias Adquiridas/imunologia , Infecções Comunitárias Adquiridas/fisiopatologia , Modelos Animais de Doenças , Feminino , Imunofluorescência , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/fisiologia , Pneumonia/fisiopatologia , Estudos ProspectivosRESUMO
BACKGROUND AND OBJECTIVE: Aclidinium bromide ('aclidinium') is a novel, inhaled long-acting muscarinic antagonist. Therapeutic effects of aclidinium on chronic obstructive pulmonary disease (COPD) have been demonstrated in Caucasian populations in several clinical trials. This was a randomized, double-blind, multi-centre phase-3 clinical trial to evaluate the efficacy and safety of aclidinium in a Korean population. METHODS: A total of 263 Korean patients with moderate-to-severe COPD were randomized to receive aclidinium (400 µg, bd) (Genuai) or placebo via a dry-powder inhaler. The primary end point was change in trough forced expiratory volume in one second (FEV1 ) at 12 weeks. Other lung function measurements, COPD exacerbation, health status (St George's Respiratory Questionnaire (SGRQ), dyspnoea (Transition Dyspnea Index (TDI) and safety were assessed throughout the study period. RESULTS: A significant improvement in trough FEV1 from baseline was shown with aclidinium compared with the placebo (0.126 L, P < 0.0001). Significant improvements were also demonstrated in peak FEV1 (0.190 L, P < 0.0001), SGRQ and TDI. Furthermore, aclidinium significantly reduced the prevalence of exacerbations (aclidinium, 5.4%; placebo, 15.6%, P < 0.05), and the duration of exacerbations was shorter compared with placebo (rate ratio: 0.27; P < 0.05). Aclidinium (400 µg) was well tolerated and the prevalence of adverse events was comparable with the placebo. CONCLUSIONS: Inhaled aclidinium (400 µg) was shown to be safe and efficacious in Korean patients with moderate-to-severe COPD. CLINICAL TRIAL REGISTRATION: NCT01636401 at Clinicaltrials.gov.
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Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tropanos/uso terapêutico , Idoso , Broncodilatadores/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Progressão da Doença , Método Duplo-Cego , Inaladores de Pó Seco , Dispneia/etiologia , Feminino , Volume Expiratório Forçado , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , República da Coreia , Índice de Gravidade de Doença , Tropanos/efeitos adversosRESUMO
BACKGROUND: Spirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. METHODS: The current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. RESULTS: PID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung. CONCLUSIONS: We have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.
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Pulmão/fisiopatologia , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Fatores Etários , Idoso , Proteínas de Transporte/genética , Estudos de Casos e Controles , Feminino , Proteínas Ativadoras de GTPase/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Fenótipo , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , República da Coreia , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , EspirometriaRESUMO
OBJECTIVE: Current dry powder inhalers (DPIs), introduced to overcome problems associated with pressurized metered dose inhalers (pMDIs), possess not only difficulties originating from their designs but also other barriers that prevent their correct usage. The authors of this study investigated the ease and correctness of use of Swinghaler, a new device in the form of multidose DPI, as well as the preference of the study participants for either a Swinghaler or a Turbuhaler. METHODS: A total of 260 patients from Korea, China, Indonesia, the Philippines, Taiwan, and Thailand were prospectively recruited. Patients who had stable asthma, were more than 12 years old, had no experience with DPIs, and provided informed consents were included, whereas those with limited physical or intellectual ability and prior experience with any DPIs were excluded. RESULTS: There were no group or time effects between the patients who were assigned to use a Swinghaler or a Turbuhaler first. Forty-one (16.1%) participants correctly performed the inhalation maneuver with a Swinghaler, whereas 28 (10.9%) did so with a Turbuhaler; the difference was not statistically significant. The overall assessment on the precise use of the devices indicated that there were no differences between Swinghaler and Turbuhaler usage. Comparing the preference scales between the two devices, the participants gave higher scores to the Swinghaler for all assessment items and were more satisfied with the Swinghaler compared with the Turbuhaler (78.5% vs. 55.0%, p < .001). CONCLUSIONS: The participants showed no difference in their ability to correctly use a Swinghaler when compared with a Turbuhaler and preferred the Swinghaler. These results suggest that the Swinghaler may be an effective and valuable tool for the management of airway diseases.
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Asma/tratamento farmacológico , Inaladores de Pó Seco , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Estudos ProspectivosRESUMO
BACKGROUND/AIMS: There is insufficient quality data to recommend the use of herbs for the treatment of acute bronchitis. Small number of randomized trials of plant extracts for this purpose were determined to be low quality and there are concerns for the safety. HL301 is a combined product of seven medicinal plants. In the present study, we tried to evaluate the efficacy and safety of HL301 for the treatment of acute bronchitis with a randomized, double-blind, placebo-controlled, multicenter trial design. METHODS: A total of 166 patients with acute bronchitis were randomized to receive placebo or HL301 (600 mg/day) for 7 days. The primary endpoint was change in bronchitis severity score (BSS) from baseline visit (visit 2) to the end of treatment (visit 3). Other efficacy variables were the change of each component of the BSS (cough, sputum, dyspnea, chest pain, and crackle) with treatment, response rate, improvement rate, satisfaction rate and number of rescue medications taken. RESULTS: Changes in the BSS from visit 2 to visit 3 were higher in the HL301 group than in the placebo group both in the full analysis set (4.57 ± 1.82 vs. 3.15 ± 3.08, p < 0.01) and in the per protocol set (4.62 ± 1.81 vs. 3.30 ± 3.03, p < 0.01). Four BSS components (cough, sputum, dyspnea, and chest pain) improved more with HL301 treatment than with placebo treatment. Participants treated with HL301 showed higher response, improvement, and satisfaction rates and less use of rescue medication than the placebo group. CONCLUSION: HL301 (600 mg/day) was effective and safe for symptomatic treatment of acute bronchitis.
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Bronquite , Fitoterapia , Doença Aguda , Bronquite/diagnóstico , Bronquite/tratamento farmacológico , Método Duplo-Cego , Humanos , Extratos Vegetais/efeitos adversos , Resultado do TratamentoRESUMO
Objective: HL301 is a combination product of seven medicinal plants that has been proven effective in acute bronchitis by two phase II studies. In the present study, its efficacy and safety compared with those of Umckamin in the treatment of acute bronchitis were evaluated in phase III, randomized, controlled, double-blind, multicenter trial design.Methods: A total of 246 acute bronchitis patients were randomized to receive either HL301 (600 mg/day) or Umckamin (333 mg/day) for seven days. The primary outcome was the difference in their baseline (visit 2) and end of treatment (visit 3) bronchitis severity score (BSS). Other efficacy variables included the change in each BSS component (cough, sputum, dyspnea, chest pain, and crackle), response rate, improvement rate, and satisfaction rate with treatment.Results: A full analysis set and per protocol set analysis of both groups revealed that the difference of BSS between visit 2 and visit 3 in the HL301 and Umckamin group was not significantly different (4.58 ± 1.79 versus 4.29 ± 1.88, p = .37 and 4.60 ± 1.81 versus 4.33 ± 1.88, p = .42, respectively). The change in five BSS components (cough, sputum, dyspnea, chest pain, and crackle) of the HL301 and Umckamin groups did not differ after treatment. HL301 or Umckamin treated participants showed an equal level of response, improvement, and satisfaction rates with treatment. Both the HL301 group and Umckamin group showed the same safety profile.Conclusions: HL301 (600 mg/day) was as effective and safe as Umckamin (333 mg/day) in treating acute bronchitis.
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Bronquite/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Doença Aguda , Adulto , Tosse/tratamento farmacológico , Método Duplo-Cego , Dispneia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Hyaluronic acid (HA) is widely used in medicine, especially for contouring or volumizing soft tissue and intra-articular injection. However, it is not well known that HA injection can cause life-threatening pulmonary complications. We recently experienced a case of a woman who was diagnosed with diffuse alveolar hemorrhage (DAH) after receiving an illegal vaginal HA filler injection. A 54-year-old female visited our clinic complaining of hemoptysis and dyspnea. Chest computed tomographic (CT) scan showed diffuse ground glass opacities and consolidation in both lower lobes. Bronchoalveolar lavage (BAL) disclosed hemorrhagic feature in sequential samples compatible with DAH. There were no relevant drugs or past medical histories, and no positive result in autoantibodies tests. During detailed history taking, she recalled that she got an illegal HA filler injection in her vaginal wall performed by nonmedical personnel the very day before the onset of symptoms. Although the procedure itself or an additive of HA preparation could be a cause, HA that might have been introduced into circulation was thought to be the most possible cause for the development of DAH. The clinical symptoms and lung lesions were dramatically improved after the treatment with systemic steroid. Pulmonary complications after HA injections were scarcely reported. Only one case of HA-related DAH has been previously described so far. Our present case emphasizes that physician and other health care providers must be aware of possible pulmonary complications of this most widely-using injectable agent.
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Background and objective: Although depression is considered one of the comorbidities of COPD, the clinical characteristics of depression in patients with early COPD remain unknown. We aimed to use national-level data to identify the clinical features and risk factors of depression in patients with early COPD. Methods: We examined 7,550 subjects who were registered in the Korean National Health and Nutrition Examination Survey database of 2014 because that was the only year in which the Patient Health Questionnaire-9 for depression status was administered. Spirometry was used to identify patients with COPD whose forced expiratory volume in 1 second was 50% or more, and these patients were included in the analysis. Results: Of the 211 subjects with early COPD, 14.2% also had depression, whereas 85.8% did not. The patients with depression were predominantly living alone and had a greater prevalence of diabetes compared with the patients without depression. The overall quality of life of the subjects with depression was lower than that of those without depression, and only the quality of life index correlated significantly with depression severity. In the multivariate regression analysis, female sex (adjusted OR, 1.79; 95% CI, 1.38-2.31; p<0.01), living alone (adjusted OR, 1.86; 95% CI, 1.37-2.51; p<0.01), and low income (adjusted OR, 2.17; 95% CI, 1.55-3.04; p<0.01) were identified as significant risk factors for depression. Conclusion: In patients with early COPD, depression was associated with a low quality of life, and female sex, living alone and low income were significant risk factors for depression.
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Depressão/psicologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Idoso , Distribuição de Qui-Quadrado , Comorbidade , Bases de Dados Factuais , Depressão/diagnóstico , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/psicologia , Diagnóstico Precoce , Feminino , Volume Expiratório Forçado , Humanos , Renda , Modelos Logísticos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos Nutricionais , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , Pessoa Solteira , Espirometria , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor (EGFR)-negative lung adenocarcinoma. METHODS: A total of 114 patients with EGFR-negative lung adenocarcinoma who were treated with platinum doublet were retrospectively enrolled. We compared the survival rates between patients received pemetrexed maintenance after four-cycled pemetrexed/cisplatin and those received at least four-cycled platinum doublet without maintenance chemotherapy as a first-line treatment. RESULTS: Forty-one patients received pemetrexed maintenance and 73 received conventional platinum doublet. Median progression-free survival (PFS), which was defined as the time from the day of response evaluation after four cycles of chemotherapy to disease progression or death, was significantly higher in the pemetrexed maintenance group compared to conventional group (5.8 months vs. 2.2 months, p<0.001). Median overall survival showed an increasing trend in the pemetrexed maintenance group (22.3 months vs. 16.1 months, p=0.098). Multivariate analyses showed that pemetrexed maintenance chemotherapy was associated with better PFS (hazard ratio, 0.73; 95% confidence interval, 0.15-0.87). CONCLUSION: Compared to conventional platinum-based chemotherapy, premetrexed continuation maintenance treatment is associated with better clinical outcome for the patients with EGFR wild-type lung adenocarcinoma.
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Hypothyroidism is relatively rare etiology of serositis with effusion, but massive pleural effusion is very unusual. This is a report of massive pleural effusion in patient taking methimazole after surgical resection of thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma). The patient was clinically and biochemically hypothyroid and responded well to discontinuation of methimazole and thyroid hormone replacement therapy. When assessing patients with pleural effusion, we should not rely on laboratory test results alone, as a detailed medical history and thorough physical examination could be more useful.
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Hipotireoidismo , Derrame Pericárdico , Neoplasias Hipofisárias , Derrame Pleural , Antitireóideos/efeitos adversos , Antitireóideos/uso terapêutico , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/complicações , Masculino , Metimazol/efeitos adversos , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiologia , Derrame Pericárdico/terapia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Derrame Pleural/terapia , Tireotropina/metabolismoRESUMO
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. CONCLUSION: 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.
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Chlamydophila pneumoniae , Legionella pneumophila , Mycoplasma pneumoniae , Reação em Cadeia da Polimerase , Doença Pulmonar Obstrutiva Crônica , Idoso , Chlamydophila pneumoniae/isolamento & purificação , Método Duplo-Cego , Feminino , Humanos , Legionella pneumophila/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/isolamento & purificação , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/microbiologia , República da Coreia , Testes SorológicosRESUMO
Bronchoscopic electrocautery is an easy, safe and rapid local method for the removal of a tracheal metastasis. Recently, we experienced a case of papillary serous carcinoma of the ovary with tracheal metastasis in a 45-year-old woman. Twelve years after the initial diagnosis of ovarian cancer, the patient presented with dyspnea. A chest CT scan showed that the trachea was nearly obstructed with a polypoid mass. The mass, later shown to be a metastatic papillary serous carcinoma, was removed by flexible bronchoscopic electrocautery with a snare. To our knowledge, this report is the first to describe the successful removal of an endotracheal metastasis of ovarian cancer using bronchoscopic electrocautery.
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Broncoscopia/métodos , Eletrocoagulação/métodos , Neoplasias da Traqueia/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/diagnóstico por imagemRESUMO
Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (nâ=â53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (nâ=â91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3âng/mL, which was significantly higher than that in benign pleural effusions (Pâ<â0.001). The optimal cutoff value of Romo1 to discriminate lung cancer-associated malignant effusion from benign effusions was 67.0âng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750-0.886), which was significantly better than that of cytokeratin 19 fragments (Pâ<â0.001). Pleural fluid Romo1 could discriminate lung cancer from benign diseases with considerable sensitivity and specificity. Our findings suggest a diagnostic potential of Romo1 for lung cancer-associated malignant effusion.
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Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteínas de Membrana/análise , Proteínas Mitocondriais/análise , Derrame Pleural Maligno/química , Adulto , Idoso , Antígenos de Neoplasias/análise , Biomarcadores/análise , Antígeno Carcinoembrionário/análise , Feminino , Humanos , Queratina-19/análise , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROCRESUMO
RATIONALE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft tissue manifestations including hyperextensibility of skin and joint hypermobility but also by early mortality due to rupture of arteries or vital organs. Although pulmonary complications are not common, vEDS cases complicated by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When a patient initially presents only with pulmonary complications, it is not easy for clinicians to suspect vEDS. PATIENT CONCERNS: We report a case of an 18-year-old high school student, with a past history of cryptorchidism, presenting with recurrent pneumothorax. DIAGNOSES: Routine laboratory findings were unremarkable. Chest high resolution computed tomographic scan showed age-unmatched hyperinflation of both lungs, atypical cystic changes and multifocal ground glass opacities scattered in both lower lobes. His slender body shape, hyperflexible joints, and hyperextensible skin provided clue to suspicion of a possible connective tissue disorder. INTERVENTIONS: The histological examination of the lung lesions showed excessive capillary proliferation in the pulmonary interstitium and pleura allowing the diagnosis of pulmonary capillary hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site mutation confirming his diagnosis as vEDS. OUTCOMES: Although his diagnosis vEDS is notorious for fatal vascular complication, there was no evidence of such complication at presentation. Fortunately, he has been followed up for 10 months without pulmonary or vascular complications. LESSONS: To the best of our knowledge, both cryptorchidism and PCH-like foci have never been reported yet as complications of vEDS, suggesting our case might be a new variant of this condition. This case emphasizes the importance of comprehensive physical examination and history-taking, and the clinical suspicion of a possible connective tissue disorder when we encounter cases with atypical presentation and/or unique chest radiologic findings especially in young patients.
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Criptorquidismo/etiologia , Síndrome de Ehlers-Danlos/complicações , Hemangioma Capilar/etiologia , Hipertensão Pulmonar/etiologia , Neoplasias Pulmonares/etiologia , Pneumotórax/etiologia , Adolescente , Colágeno Tipo III/análise , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Humanos , Masculino , RecidivaRESUMO
PURPOSE: NANOG is a master transcription factor that regulates stem cell pluripotency and cellular reprograming. Increased NANOG expression has been associated with poor survival in several human malignancies. However, the clinical significance of NANOG overexpression in lung cancer has been scarcely evaluated. The aim of this study was to investigate whether NANOG levels are associated with clinical outcomes of patients with non-small cell lung cancer (NSCLC) who were treated with platinum-based chemotherapy. METHODS: NANOG levels were evaluated immunohistochemically using the histologic score (H-score) in tumor tissues from patients with advanced NSCLC who received platinum-based doublet treatment. We performed survival analyses according to the NANOG levels and evaluated the association between clinicopathological parameters and levels of NANOG. RESULTS: Multivariate analyses using 112 tumor specimens showed that high NANOG levels were independently associated with short progression-free survival (hazard ratio [HR] =3.09, 95% confidence interval [CI]: 2.01-4.76) and with short overall survival (HR =3.00, 95% CI: 1.98-4.54). Similar results were shown in the subgroup analyses for patients with adenocarcinoma and squamous cell carcinoma. NANOG expression was not associated with any clinicopathological parameter such as age, gender, smoking status, stage, differentiation, or histological subtypes. CONCLUSION: NANOG overexpression was associated with poor response and short overall survival in patients with advanced NSCLC who were treated with platinum-based chemotherapy, suggesting that NANOG could be a potential adverse predictive marker in this setting.
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PURPOSE: The efficacy and safety of Chinese herbs for symptomatic treatment of bronchitis is not well established. We evaluated the efficacy and safety of a combination product of seven herbs (HL301) for the treatment of acute bronchitis (AB) and acute exacerbation of chronic bronchitis (AECB) using a randomized, double-blind, placebo-controlled, multicenter trial design. METHODS: A total of 160 patients with AB or with AECB were randomized to receive placebo or one of three doses of HL301 (0.6 g/day, 1.2 g/day, or 1.8 g/day) for a total of 7 days. The primary study endpoint was the change in bronchitis severity score (BSS) from the baseline visit (visit 2) to the end of treatment visit (visit 3). Other efficacy variables were percentage BSS systemic sign efficacy after treatment and change in individual BSS parameters after treatment. FINDINGS: Changes in BSS from visit 2 to visit 3 in the three treatment groups (4.63 ± 2.24, 4.08 ± 1.63, and 4.15 ± 1.74 in the HL301 0.6 g/day, 1.2 g/day, and 1.8 g/day groups, respectively) were higher than that of the placebo group (2.88 ± 2.57) in the per protocol set (PPS) (P < .05), and it was also valid in the full analysis set (FAS). The number of participants whose symptoms (measured by BSS) improved at least 30% after treatment was higher in all three treatment groups compared to the placebo group in both the FAS and the PPS (P < .05, for all). IMPLICATIONS: Three different doses of HL301 (0.6 g/day, 1.2 g/day, and 1.8 g/day) were effective in decreasing the BSS index compared to placebo. HL301 may be effective for symptomatic treatment of both AB and AECB. LIMITATIONS: Essential components of HL301 have not been delineated in the study and patients with AB and AECB were indiscriminately enrolled in the present study. Respective evaluation of the efficacy of HL301 for AB and AECB will be necessary in the future.
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Bronquite Crônica/tratamento farmacológico , Bronquite/tratamento farmacológico , Fitoterapia/métodos , Doença Aguda , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Pulmonary tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD); however, few clinical studies have investigated treatment effectiveness in COPD patients with destroyed lung by TB. The Indacaterol effectiveness in COPD patients with Tuberculosis history (INFINITY) study assessed the efficacy and safety of once-daily inhaled indacaterol 150 µg for the treatment of Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation. METHODS: This was a multicenter, double-blind, parallel-group study, in which eligible patients were randomized (1:1) to receive either once-daily indacaterol 150 µg or placebo for 8 weeks. The primary efficacy endpoint was change from baseline in trough forced expiratory volume in 1 s at Week 8; the secondary endpoints included changes in transition dyspnea index score and St George's Respiratory Questionnaire for COPD score at Week 8. Safety was evaluated over 8 weeks. RESULTS: Of the 136 patients randomized, 119 (87.5%) completed the study treatment. At Week 8, indacaterol significantly improved trough forced expiratory volume in 1 s versus placebo (treatment difference [TD] 140 mL, P<0.001). Statistically significant improvement in transition dyspnea index score (TD =0.78, P<0.05) and numerical improvement in St George's Respiratory Questionnaire for COPD score (TD =-2.36, P=0.3563) were observed with indacaterol versus placebo at Week 8. Incidence of adverse events was comparable between the treatment groups. CONCLUSION: Indacaterol provided significantly superior bronchodilation, significant improvement in breathlessness and improved health status with comparable safety versus placebo in Korean COPD patients with destroyed lung by TB and moderate-to-severe airflow limitation.
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Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Indanos/administração & dosagem , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/administração & dosagem , Tuberculose Pulmonar/complicações , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Idoso , Broncodilatadores/efeitos adversos , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Nível de Saúde , Humanos , Indanos/efeitos adversos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolonas/efeitos adversos , Recuperação de Função Fisiológica , República da Coreia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/fisiopatologiaRESUMO
PURPOSE: The Xpert MTB/RIF assay is a novel real-time polymerase chain reaction technique for the detection of the Mycobacterium tuberculosis (MTB) complex and rifampin (RIF) resistance. We evaluated the performance of this assay in identifying MTB and resistance to RIF in clinical specimens. MATERIALS AND METHODS: We analyzed clinical specimens from 383 patients with suspected TB who were hospitalized at a secondary hospital in Korea. Specimens were processed using the Xpert MTB/RIF assay, acid-fast bacilli smear and culture, and drug susceptibility test (DST). RESULTS: Among the 444 clinical samples analyzed, the Xpert MTB/RIF assay identified MTB in 56 (13.8%) of 405 respiratory specimens, but did not detect MTB in the remaining 39 non-respiratory specimens. Of the 65 pulmonary TB patients, 52 (80.0%) were confirmed by using mycobacterial culture as a reference standard. The sensitivity, specificity, PPV, and NPV of the Xpert MTB/RIF assay were 73.85%, 99.03%, 94.12%, and 94.72%, respectively. Among five patients with RIF resistance determined by the Xpert MTB/RIF assay, four (80%) were confirmed as suffering from multidrug-resistant (MDR) TB by DST. CONCLUSIONS: The Xpert MTB/RIF assay appears to be an accurate, simple, and useful technique for detecting MTB, especially in respiratory specimens. However, RIF resistance, if detected, should be verified with DST.
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Farmacorresistência Bacteriana/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Kit de Reagentes para Diagnóstico , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Rifampina , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologiaRESUMO
A new quinolone, zabofloxacin, has now been developed; hence, a non-inferiority trial is needed to compare this new compound with another widely used quinolone to examine its efficacy and safety for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. This was a prospective, multicenter, double-blind, double-dummy, randomized, controlled, parallel-group, Phase III, non-inferiority clinical trial designed to compare oral zabofloxacin (367 mg once daily for 5 days) with moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. In all, 345 COPD patients with a moderate COPD exacerbation were enrolled in the study via the outpatient clinics at 31 university hospitals. Clinical per protocol analysis revealed that the clinical cure rate for zabofloxacin was 86.7% and that for moxifloxacin was 86.3% (the rate difference, 0.4%; 95% confidence interval, -7.7%-8.6%). Intention-to-treat analysis revealed clinical cure rates of 77.1% and 77.3% (difference, -0.2%; 95% confidence interval, -9.0%-8.8%), respectively. These results confirm that zabofloxacin is not inferior to moxifloxacin. The favorable microbiological response rate for zabofloxacin was 67.4% and that for moxifloxacin was 79.5% (P=0.22). Patients in the zabofloxacin group showed better patient-oriented outcomes, as measured by EXAcerbations of Chronic Pulmonary Disease Tool-Patient-Reported Outcome and the COPD assessment test scores, than patients in the moxifloxacin group. Adverse drug reactions related to zabofloxacin occurred in 9.7% of cases and those related to moxifloxacin occurred in 9.6% of cases (P=0.97). The dropout rate due to adverse events was 0% (0/175) in the zabofloxacin group and 1.8% (3/167) in the moxifloxacin group (P=0.12). Oral zabofloxacin (367 mg once daily for 5 days) was not inferior to oral moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation.
Assuntos
Fluoroquinolonas , Doença Pulmonar Obstrutiva Crônica , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Testes de Função Respiratória/métodos , Resultado do TratamentoRESUMO
BACKGROUND: In South Korea, chronic obstructive pulmonary disease (COPD) is one of the ten leading causes of death. COPD exacerbations are significantly associated with mortality in COPD patients. This study was conducted to investigate the epidemiology of COPD in South Korea, specifically the clinical characteristics of South Korean COPD patients, the COPD exacerbation rate and the risk factors associated with COPD exacerbations. METHODS: This study covers a 2-year interval. One year was data collected retrospectively and the second year was prospectively obtained data. RESULTS: A total of 1,114 subjects were enrolled in the study. These subjects were observed for a period of 1 year from the enrollment, and a total of 920 subjects completed the study. A total of 1,357 COPD exacerbations occurred in 711 subjects (63.8%) out of the total of 1,114 subjects during the study period of 2 years. Multivariate logistic regression results showed that if patients had had a pneumonia before the retrospective year of analysis, they had a 18 times greater chance of having an exacerbation during the prospective year when other variables were controlled. Also, the subjects who had a history of two or more exacerbations during the retrospective year were approximately 6 times more likely to experience the COPD exacerbation compared to those who did not. CONCLUSIONS: This study examined the demographic and clinical characteristics of South Korean COPD patients and found that a history of pneumonia and two or more occurrences of exacerbation within 1 year was significantly associated with a higher rate of COPD exacerbation.