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1.
PLoS One ; 19(3): e0299484, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478558

RESUMO

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Fibrose Pulmonar Idiopática , Neoplasias Pulmonares , Humanos , Feminino , Masculino , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/diagnóstico , Programas Nacionais de Saúde , República da Coreia/epidemiologia , Estudos Retrospectivos
2.
Cancer Imaging ; 22(1): 6, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022068

RESUMO

BACKGROUND: To demonstrate and analyze the relatively common imaging findings in this rare primary pleural angiosarcoma (PPA). CASE PRESENTATION: Three cases of PPA, proven by video-assisted thoracic surgery biopsies are retrospectively reviewed. Patients were all male. Age ranges from 65 to 75 years old age (mean; 69). Major chief complaints were dyspnea and chest pain. One has a history of colon cancer, the other has a tuberculosis history and the other has no known history. Multidetector chest CT and PET CT were all done. Immunohistochemical studies were performed including CD31, CD34, or factor VIII-related antigen, vimentin, and cytokeratin. We also review the literatures on recently published PPA. All masses were from 1 to 10 cm. All three patients had multiple pleural based masses, which were ovoid in shape with relatively sharp margin in unilateral hemithorax. Multiple small circumscribed pleural masses are limited in the pleural space in two patients, whereas two, huge lobulated masses about up to 10 cm were present with pleural and extrapleural involvement in one patient. In two patients with pleural mass only, multiple pleural masses were only seen in parietal pleura in one patient and were in both visceral and parietal pleura in one patient. Pleural effusion were found in one side in one patient and in both sides in one patient. One angiosarcoma was arised from chronic tuberculotic pleurisy sequelae. All pleural masses are heterogenous with irregular internal low densities in all patients. Hematogenous metastases were found in liver, vertebra, rib in one patient, and were in lungs with mediastinal lymph node metastases in the other patient. Three patients survived for longer than 3months after diagnosis, but continued to deteriorate rapidly. Two patients underwent chemotherapy after surgical excision, and the other one with multiple metastases treated chemotherapy after CT-guided biopsy, but eventually all died. As a result of comparative analysis of a total of 13 patients' images including 10 cases previously published, there was pleural effusion in all except 2 cases. CONCLUSIONS: PPA were all necrotic without any vascularized enhancing nature, and manifested as unilateral circumscribed or localized pleural-based masses.


Assuntos
Hemangiossarcoma , Derrame Pleural , Idoso , Hemangiossarcoma/diagnóstico por imagem , Humanos , Masculino , Pleura/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
3.
PLoS One ; 16(12): e0261684, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34941933

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. METHODS: This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. RESULTS: Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48-0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37-0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. CONCLUSIONS: Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.


Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Piridonas/administração & dosagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
5.
J Thorac Dis ; 13(7): 4195-4206, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34422348

RESUMO

BACKGROUND: Asthma and lipid metabolism are associated with systemic inflammation. However, the studies about the relationship between lipid profile, fractional exhaled nitric acid (FeNO) and pulmonary function test (PFT) results are currently lacking. METHODS: We enrolled asthma patients who had serum lipid profiles including apolipoprotein levels from March 1, 2019 to December 31, 2019. We classified the asthma patients into two groups according to the diagnosis method: (I) patients who were diagnosed based on clinical symptoms/signs and PFT results and (II) patients diagnosed with clinical symptoms/signs. Clinical characteristics including age, underlying diseases, smoking status, allergy test results and treatment agents were compared between the two groups. The associations between blood cholesterol levels including apolipoprotein and pulmonary functions were analyzed. Moreover, patients were divided into two groups according to the median value of apolipoprotein B (Apo B), and lung function test results were compared between the patients who had high and low Apo B levels. RESULTS: Among the 167 patients, 93 (55.7%) were PFT-proven asthma patients. In PFT-proven asthma patients, the levels of total cholesterol (TC) (r =0.37, P=0.03), low-density lipoprotein (LDL) (r =0.46, P=0.01) and Apo B (r =0.38, P=0.02) showed a significant correlation with FeNO, which had no statistical significance in physician-diagnosed asthma group. In multivariate regression analysis, log (FeNO) showed a significant correlation with Apo B (P<0.01) after adjustment for presence of PFT-proven asthma (P=0.01) and current smoking (P=0.01). Patients with high Apo B levels had a lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (69.8 vs. 74.9, P=0.02) and lower post-BD FEV1 (%) (77.5 vs. 85.0, P=0.04) compared with those showing low Apo B levels. CONCLUSIONS: The levels of Apo B and FeNO had positive correlations and high Apo B levels were associated with severe airflow obstruction and low FEV1 (%). Apo B could reflect the uncontrolled status of bronchial asthma and poor lung function.

6.
Korean J Intern Med ; 36(4): 1001-1013, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34237826

RESUMO

BACKGROUND/AIMS: Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. METHODS: This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. RESULTS: Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). CONCLUSION: Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.


Assuntos
Antiasmáticos , Asma , Adulto , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Omalizumab/efeitos adversos , Qualidade de Vida , República da Coreia , Inquéritos e Questionários , Resultado do Tratamento
7.
J Thorac Dis ; 13(3): 1306-1314, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33841924

RESUMO

BACKGROUND: There are limited data on the association between bronchial colonization and respiratory infections in people with lung cancer requiring cytotoxic chemotherapy. We investigated whether bronchial colonization in initial bronchoscopy specimens can predict the development of pneumonia after chemotherapy in patients with lung cancer. METHODS: Four hundred thirteen patients with lung cancer included in the Catholic Medical Center lung cancer registry were enrolled from March 2015 to August 2018. Demographic data, microbiology results, development of pneumonia after chemotherapy, and clinical information about lung cancer were analyzed retrospectively. RESULTS: A total of 206 lung cancer patients treated with chemotherapy were included in the analysis. Forty patients (19.4%) had positive results for the bronchial washing culture during the initial evaluation of lung cancer. The most common organisms were Klebsiella pneumoniae (n=14) and Streptococcus pneumoniae (n=6) in the surveillance culture, and Pneumocystis jirovecii (n=12) and Staphylococcus aureus (n=8) at the time of pneumonia development. Eighty-nine patients (43.2%) had pneumonia after chemotherapy, but the occurrence of pneumonia did not differ according to the colonization. There were no patients for whom the initial isolated organism was a causative microbe for the development of pneumonia after or during chemotherapy. The pneumonia group had poorer prognosis than the non-pneumonia group (378 vs. 705 days, P=0.0004). CONCLUSIONS: Microbial colonization in bronchoscopy specimens was not associated with pneumonia development or mortality after chemotherapy for lung cancer. This finding suggests that testing surveillance culture may not be helpful for predicting pneumonia or improving survival in lung cancer patients with chemotherapy.

8.
J Thorac Dis ; 11(6): 2392-2401, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31372276

RESUMO

BACKGROUND: The purpose of this study was to determine whether semi-automated region of interest (ROI) measurement of CT attenuations of solitary pulmonary nodule (SPN) is an accurate approach in differentiating malignant from benign SPN. METHODS: Ninety cases of pathologically proven SPN were retrospectively reviewed. CT attenuations of SPN before and after contrast injection were measured using semi-automated ROI selection method. Attenuations within a range of -100 to 200 Hounsfield units (HU) as soft tissue density range were set. The ROI included the entire SPN regardless of its internal soft tissue contents after automatic elimination of airs, calcific, or bony densities. RESULTS: There were 42 (46.7%) malignant SPN and 48 (53.3%) benign SPN, which were grouped into A (18 tuberculoma, 13 fungus), B (5 focal organizing pneumonia, 5 abscess), and C (7 other benign tumors). The malignant SPN showed significantly higher mean attenuations of enhancement and net-enhancement than all benign SPN (P<0.001). Using the area under the receiver operating characteristic curve (AUC), the cut-off net-enhancement of 15 HU gave 83% sensitivity, 65% specificity and 73% accuracy for predicting malignancy. Malignant SPN (mean 67.9 HU) had significantly higher enhancement than group A (mean 52.6 HU, P<0.001, 95% CI: 8.73, 21.81) and group B (mean 57.0 HU, P=0.025, 95% CI: -1.43, 20.34) while group C showed no significant difference (mean 68.1 HU, P=0.97). Net enhancements were higher in group B (mean 18.8 HU) than in group A (mean 8.8 HU) (P<0.001, 95% CI: 11.8, 23.18). CONCLUSIONS: The semi-automated ROI measurement of SPN's attenuations on CT is an accurate approach in distinguishing indeterminate SPN.

9.
BMC Pulm Med ; 19(1): 120, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272428

RESUMO

BACKGROUND: Patients with interstitial lung disease (ILD) who show features related to autoimmunity without meeting criteria for a defined connective tissue disease are categorized as interstitial pneumonia with autoimmune features (IPAF). The present study compared clinical characteristics and clinical outcomes of patients with IPAF to patients with connective tissue disease related-interstitial lung disease (CTD-ILD) and patients with idiopathic pulmonary fibrosis (IPF). METHODS: ILD patients who were consecutively enrolled in a single institution ILD cohort between 2008 and 2015 were evaluated for the study. Clinical data had been prospectively collected, while radiologic imaging and pathologic findings were re-reviewed for the present study. RESULTS: Out of 305 patients with ILD, 54 (17.7%) patients met the classification of IPAF, 175 (57.4%) patients had IPF, and 76 (24.9%) patients were diagnosed with CTD-ILD. Compared to IPF, incidences of acute exacerbations in 1,3 and 5 years were significantly less in the IPAF group (p = 0.022, p = 0.026 and p = 0.007, respectively). From multivariate analysis for mortality, age (p = 0.034, HR 1.022, 95% CI: 1.002-1.044), FVC (p < 0.001, HR 0.970, 95% CI: 0.955-0.984), ILD exacerbation (p = 0.001, HR 2.074, 95% CI: 1.366-3.148), and ILD type (p = 0.047, HR 0.436, 95% CI: 0.192-0.984 (IPAF vs IPF), respectively) showed significant association. CONCLUSIONS: Compared to the other ILD groups, IPAF showed distinct clinical characteristics. The IPAF group showed better survival and less episodes of exacerbation when compared to the IPF group.


Assuntos
Autoimunidade , Doenças do Tecido Conjuntivo/complicações , Fibrose Pulmonar Idiopática/mortalidade , Doenças Pulmonares Intersticiais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doenças do Tecido Conjuntivo/imunologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , República da Coreia/epidemiologia , Análise de Sobrevida , Tomografia Computadorizada por Raios X
10.
Tuberc Respir Dis (Seoul) ; 82(1): 71-80, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30574690

RESUMO

BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

11.
Eur J Radiol ; 100: 147-153, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29496074

RESUMO

OBJECTIVES: To determine what computed tomographic (CT) dimensions can predict obstructive lung disease on routine chest CT scans by comparing morphological and densitometric CT findings with pulmonary function test (PFT) in normal subjects and patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Consecutive patients (n = 646; 260 females and 386 males; mean age 54.9 years, ranged 20-90 years) who received chest CT scans with densitometry during a 3-month period were retrospectively analyzed in single center. PFT was undertaken in 235 patients (152 males, 83 females) at same times of CT scanning. The patients were grouped by age (<30 years, 31-45 years, 46-60 years, and >61 years). CT parameters including tracheal, azygoesophageal, thoracic vertical, anterior-posterior (AP), transverse diameters, transverse cardiac diameter, diameters of main, right, and left pulmonary arteries, and CT densitometric values including lung volume and density (-900 to -1000 Hounsfield Units, HU), low attenuation value cluster (default threshold: -950 HU) were compared with PFT values. Spearman correlation coefficients was used to evaluate the relationship between the CT indices and PFT. RESULTS: Ninety of 235 patients with PFT were smokers (76 males, 14 females). Obstructive PFT was detected in 65 patients (27.7%: 46 males, 19 females). Male smokers with obstructive PFT displayed significantly larger thoracic anterior-posterior (mean: normal, 172.3 cm versus COPD, 185.9 cm, p = 0.0001) and smaller transverse diameters (mean: normal, 247.0 cm vs. COPD, 235.8 cm, p = 0.01), and increased right pulmonary artery diameter (mean: normal, 20.3 cm v s. COPD, 22.1 cm, p < 0.001), and increased left pulmonary artery diameter (mean: normal, 19.7 cm vs. COPD, 20.6 cm, p < 0.025). The lung parenchyma density (-1000 to -900 HU) and greater concentration of largest cluster on densitometry were significantly different between normal and obstructive PFT pattern in male smoker. Residual volume and total lung capacity are positively correlated with lung volume and lung density (-1000 to -800) of densitometry. CONCLUSIONS: CT findings of the overexpansion of the lungs, such as increases in the vertical diameter of the lung and decreases in the transverse diameter of the heart, can be significant as indirect findings of early chronic obstructive diseases. However, despite the significant CT findings in male smokers, particularly those in their 40s, most lung function parameters were not decidedly abnormal.


Assuntos
Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Volume de Ventilação Pulmonar , Tomografia Computadorizada Espiral/métodos , Capacidade Pulmonar Total , Adulto Jovem
12.
J Thorac Dis ; 10(11): 6077-6087, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30622779

RESUMO

BACKGROUND: The Glasgow Prognostic Score (GPS) reflects the host systemic inflammatory response and is a validated, independent prognostic factor for various malignancies. We investigated the clinical significance of the GPS in patients with tuberculosis (TB) pleurisy, focusing on treatment outcomes including paradoxical response (PR). METHODS: This was a retrospective study performed between January 2010 and December 2015 in two referral and university hospitals in South Korea, with intermediate incidences of TB. In all, 462 patients with TB pleurisy were registered in the study. The patients were classified into three groups based on GPS score, as follows: (I) GPS of 2, elevated CRP level (>1.0 mg/dL) and hypoalbuminemia (<3.5 g/dL); (II) GPS of 1, elevated CRP level or hypoalbuminemia; and (III) GPS of 0, neither elevated CRP level nor hypoalbuminemia. RESULTS: A total of 367 patients with TB pleurisy were finally included. PR occurred in 102 (27.8%) patients after a mean of 75 days following initiation of anti-TB treatment. The proportion of PR occurrence was significantly lower in the GPS 2 group (P=0.007). Successful treatment outcomes including cure and completion were also significantly lower in the GPS 2 group (P=0.001), while all-cause mortality and TB-specific mortality were higher in the GPS 2 group (P=0.001 and <0.001, respectively). Old age over than 65 years old was an independent predicting factor for high mortality and lower PR occurrence. However, the TB relapse rate was not different among the three GPS groups. CONCLUSIONS: Higher GPS value and elderly age were identified as prognostic factors for poor outcomes in TB pleurisy and as predicting factors for lower PR occurrence. More prospective studies are needed to clarify the utility of GPS in patients with TB pleurisy.

13.
Exp Lung Res ; 43(1): 29-37, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28394654

RESUMO

PURPOSE: The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells. MATERIALS AND METHODS: Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot. The concentrations of vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Cell growth in PC9 and HCC827 cells was synergistically suppressed by co-treatment with gefitinib and linsitinib. Gefitinib did not affect H1975 cell growth; however, linsitinib suppressed cell proliferation. Co-treatment with gefitinib and linsitinib inhibited pAKT and pERK, and linsitinib treatment profoundly reduced IGF-1-induced pIGF-1R expression in PC9 and HCC827 cells. Dual treatment increased the number of Annexin-V-positive HCC827 and H1975 cells, and expression of cleaved caspase 3 and cleaved PARP increased in H1975 cells following linsitinib treatment. Gefitinib inhibited HIF-1α and VEGF expression in HCC827 cells, and linsitinib inhibited VEGF production in H1975 cells. CONCLUSION: IGF-1R TKIs had modest anti-tumor efficacy and their effects were explained by blocking the EGFR and IGF-1R pathway in IGF-1R expressing EGFR-sensitive cells. IGF-1R TKI had pro-apoptotic activity and inhibited cellular growth in EGFR-resistant cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Inibidores de Proteínas Quinases/farmacologia , Receptor IGF Tipo 1/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
14.
Pulm Pharmacol Ther ; 36: 37-45, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26778828

RESUMO

OBJECTIVES: We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. METHODS: Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. RESULTS: Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. CONCLUSIONS: This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.


Assuntos
Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Asma/patologia , Azitromicina/uso terapêutico , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Animais , Asma/induzido quimicamente , Hiper-Reatividade Brônquica/tratamento farmacológico , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Interleucinas/metabolismo , Elastase de Leucócito/metabolismo , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ovalbumina , Pneumonia/induzido quimicamente , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos
15.
Korean J Intern Med ; 30(4): 478-88, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26161014

RESUMO

BACKGROUND/AIMS: The clinical outcomes of patients with hematologic malignancies who were treated with extracorporeal membrane oxygenation (ECMO) after the failu re of optimal conventional therapy were determined. METHODS: The medical records of all patients administered ECMO during their stay in a medical intensive care unit of Seoul St. Mary's Hospital between February 2010 and July 2013 were reviewed retrospectively. RESULTS: In total, 15 patients with hematologic malignancies were compared to 33 immunocompetent patients with documented cardiorespiratory failure. Underlying hematologic malignancies were significantly associated with lower overall survival (0.0% vs. 24.2%, p = 0.044). Mortality was significantly associated with a higher 24 hours ECMO inspired fraction of oxygen (0.71 ± 0.24 vs. 0.47 ± 0.13, p = 0.015), the development of infection after ECMO (87.5% vs. 25.0%, p = 0.001), and the presence of hyperbilirubinemia (70.0% vs. 0.0%, p < 0.001). Matching of the patients based on their Acute Physiology and Chronic Health Evaluation II scores confirmed the greater risk of mortality in patients with hematologic malignancies (survival: 0.0% vs. 40.0%, p = 0.017). The mean difference in inotropic-equivalent scores after ECMO was significantly lower in the immunocompetent patients than in those with hematologic malignancies (-59.22 ± 97.83 vs. 53.87 ± 164.46, p = 0.026). CONCLUSIONS: Patients with hematologic malignancies who require ECMO for respiratory support have poor outcomes. The incidence of complications in these patients did not significantly differ from that in immunocompetent patients.


Assuntos
Oxigenação por Membrana Extracorpórea , Neoplasias Hematológicas/terapia , APACHE , Adulto , Idoso , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Registros Médicos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
16.
J Cardiothorac Surg ; 9: 113, 2014 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-24952611

RESUMO

Although a solitary fibrous tumor of the pleura (SFTP) is a rare disease, and usually has a benign course, it has a malignant potential. We report a case of malignant SFTP treated surgically. A 75-year-old female was admitted with a chief complaint of hemoptysis of two weeks duration. Computed tomography of the chest imaged a large mass in the right hemithorax, which compressed adjacent organs; however, there was no evidence of invasion. We reviewed the patient's medical records and found that the mass had been presented for 17 years. Complete resection was achieved through a right thoracotomy and histopathologic examination confirmed a malignant SFTP.


Assuntos
Diagnóstico Tardio , Neoplasias Pleurais/diagnóstico , Tumor Fibroso Solitário Pleural/diagnóstico , Toracotomia/métodos , Idoso , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Biópsia Guiada por Imagem , Neoplasias Pleurais/cirurgia , Doenças Raras , Tumor Fibroso Solitário Pleural/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X
17.
Clin Interv Aging ; 8: 1393-403, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24204129

RESUMO

BACKGROUND AND OBJECTIVES: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. METHODS: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA) for 1 month (n = 8-12 per group). We analyzed inflammatory cells and T-helper (Th)2 cytokines in bronchoalveolar lavage (BAL) fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. RESULTS: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old) mice than in the young (6-week-old) mice. Interleukin (IL) 4 (IL-4) concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. Periodic acid-Schiff (PAS) staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. CONCLUSION: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.


Assuntos
Envelhecimento/fisiologia , Remodelação das Vias Aéreas/fisiologia , Asma/etiologia , Receptores Muscarínicos/metabolismo , Animais , Western Blotting , Líquido da Lavagem Broncoalveolar/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoquímica , Interleucinas/análise , Pulmão/imunologia , Pulmão/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Receptor Muscarínico M2/análise , Receptor Muscarínico M3/análise
18.
Tuberc Respir Dis (Seoul) ; 75(2): 47-51, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24023556

RESUMO

Interstitial lung diseases are heterogeneous entities with diverse clinical presentations. Among them, idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease are specific categories that pulmonologists are most likely to encounter in the clinical field. Despite the accumulated data from extensive clinical trial and observations, we continue to have many issues which need to be resolved in this field. In this update, we present the review of several articles regarding the clinical presentation, prognosis and treatment of patients with idiopathic pulmonary fibrosis or connective tissue disease-associated interstitial lung disease.

19.
J Asthma ; 50(7): 712-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23713676

RESUMO

OBJECTIVE: The aim of this study was to measure the level of nerve growth factor (NGF) in bronchial specimens from humans and to determine whether it correlated with not only clinical characteristics of asthma such as percent eosinophils, Th2 cytokine levels, and pulmonary function, but also metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1). METHODS: Fifty-three people participated; 42 had asthma. The participants underwent bronchoscopy and the specimens were analyzed. The participants' clinical data including pulmonary function tests were reviewed. RESULTS: Bronchoalveolar lavage fluid (BALF) from patients with asthma had a significantly higher level of NGF compared with that from participants without asthma. NGF level showed a positive correlation with the percentage of eosinophils in both BALF and serum. The concentration of NGF did not correlate with that of Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 in BALF or parameters of pulmonary function including degree of airway hyperresponsiveness (ARH). The levels of MMP-9 and TIMP-1 in BALF were higher in asthma patients than in participants without asthma. The levels of NGF correlated with TIMP-1 levels but not with MMP-9 in the whole participants. CONCLUSIONS: This study shows that NGF correlates with levels of eosinophils, a major effector cell in asthma. The high expression of NGF and TIMP-1 in asthma patients and the moderate correlation between NGF and TIMP-1 in the entire group of asthma subjects suggest a possible association between NGF and TIMP-1, which may influence asthma pathogenesis.


Assuntos
Asma/metabolismo , Metaloproteinase 9 da Matriz/biossíntese , Fator de Crescimento Neural/biossíntese , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Adolescente , Adulto , Idoso , Asma/sangue , Asma/enzimologia , Asma/imunologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Eosinofilia/imunologia , Eosinofilia/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Interleucinas/imunologia , Masculino , Metaloproteinase 9 da Matriz/imunologia , Pessoa de Meia-Idade , Fator de Crescimento Neural/imunologia , Estudos Prospectivos , Testes de Função Respiratória , Estatísticas não Paramétricas , Inibidor Tecidual de Metaloproteinase-1/imunologia , Adulto Jovem
20.
Tuberc Respir Dis (Seoul) ; 73(2): 115-21, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23166544

RESUMO

Pulmonary mucosa-associated lymphoid tissue-derived (MALT) lymphoma is a rare disease. This disorder is considered to be a model of antigen-driven lymphoma, which is driven either by autoantigens or by chronic inflammatory conditions. Low-grade B-cell MALT lymphoma may develop from a nonneoplastic pulmonary lymphoproliferative disorder, such as lymphocytic interstitial pneumonitis (LIP). A recent estimate predicts that less than 5% of LIP patients acquire malignant, low-grade, B-cell lymphoma. In Korea, there has been no previous report of malignant low-grade, B-cell lymphoma, acquired from LIP. Here, we present the case of a patient with LIP that developed into pulmonary MALT lymphoma, six years after diagnosis.

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