RESUMEN
Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells from mouse naïve CD8+T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+T and IL-17-producing CD8+T cell-mediated immune responses.
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Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfisema Pulmonar/inmunología , Anciano , Animales , Circulación Sanguínea , Diferenciación Celular , Células Cultivadas , Fumar Cigarrillos/efectos adversos , Modelos Animales de Enfermedad , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Enfisema Pulmonar/inducido químicamenteRESUMEN
OBJECTIVE: To compare the safety and efficacy between using a small-diameter tube-assisted bronchoscopic balloon dilatation (BBD) and the traditional BBD in the treatment of benign tracheal stenosis. METHODS: A retrospective study included 58 patients with benign tracheal stenosis from August 2009 to December 2014 was made. The patients who underwent traditional BBD were divided into group A, and who underwent a small-diameter tube-assisted BBD were divided into group B. The tracheal diameter, dyspnea index and blood gas analysis results were detected before and after BBD. Efficacy and complications were evaluated after BBD. RESULTS: There were significant differences in oxygen saturation (PaO2 ) during the operations comparing with before and after operations in group A (P = .005), while there was no significant difference in group B (P = .079). The tracheal diameter obviously increased (in group A, from 4.16 ± 1.43 mm to 12.47 ± 1.41 mm, P = .000; in group B: from 4.94 ± 1.59 mm to 12.61 ± 1.41 mm, P = .000). Dyspnea index obviously decreased (group A: from 3.21 ± 0.93 to 0.50 ± 0.59, P = .000; group B: from 3.24 ± 0.89 to 0.65 ± 0.69, P = .000). The immediately cure rate in both groups was 100%. Long-term effect was significantly better in group B than that in group A (85.3% vs 59.1%, P = .021), at the end of the follow-up period. CONCLUSIONS: Small-diameter tube-assisted BBD obtains better safety and long-term efficacy than the traditional BBD in the treatment of benign tracheal stenosis. However, close attention should be given to the risk of the adverse effects caused by carbon dioxide retention.
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Broncoscopios , Broncoscopía/instrumentación , Dilatación/instrumentación , Estenosis Traqueal/terapia , Adolescente , Adulto , Anciano , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estenosis Traqueal/diagnóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Neutrophil extracellular traps (NETs) represent a distinct strategy by which neutrophils trap, confine and eliminate invading microorganisms. Emerging evidence suggests that NETs exert a deleterious effect to the host in the absence of microbial stimuli. However, the role of NETs in smoking-related lung diseases remains to be elucidated. OBJECTIVES: To evaluate the formation of NETs in the context of chronic inflammation induced by cigarette smoking and explore its potential role in an experimental mouse model of emphysema. METHODS: The formation and degradation of NETs in cigarette smoke exposed mice was assessed with a fluorescence microscope. The potential influences of NETs on plasmacytoiddendritic cells were also investigated. RESULTS: NETs were more prone to formation by polymorphonuclearneutrophils but defective in degradation in cigarette smoke exposed mice. Cigarette smoke extract (CSE) served as an important facilitator that triggered neutrophils to undergo NETosis in vitro. Furthermore, CSE-induced NETs were capable of driving plasmacytoiddendritic cell maturation and activation, thereby initiating a T-cell-mediated immune response. CONCLUSIONS: NETs may represent a critical connection between innate and adaptive immune responses under conditions of chronic inflammation induced by cigarette smoke exposure.
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Células Dendríticas/inmunología , Trampas Extracelulares/inmunología , Neutrófilos/inmunología , Enfisema Pulmonar/inmunología , Contaminación por Humo de Tabaco/efectos adversos , Inmunidad Adaptativa , Animales , Linfocitos T CD4-Positivos/inmunología , Comunicación Celular/inmunología , Diferenciación Celular/inmunología , Técnicas de Cocultivo , Inmunidad Innata , Inflamación/inmunología , Masculino , Ratones Endogámicos BALB C , Enfisema Pulmonar/etiología , Células TH1/inmunología , Células Th17/inmunologíaRESUMEN
IFN-γ-producing CD4+ T (Th1) cells and IL-17-producing CD4+ T (Th17) cells play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immune regulation between Th1 and Th17 cells remains unclear. Previous studies have demonstrated that interleukin-27 (IL-27)/WSX-1 exerted pro- or anti-inflammatory effects in many acute inflammatory diseases by modulating T cell-mediated immune response, but little was known about its role in chronic inflammatory disease, especially in smoking-related lung diseases. Considering IL-27 is an important regulator in T lymphocytes immune responses and was found markedly increased in patients with COPD, we hypothesized that IL-27/WSX-1 may exert immuno-regulatory effects on the differentiation of Th1 and Th17 cells in smoking-related COPD. In this study, we aimed to evaluate the expression of IL-27 in patients with COPD and explore the role of IL-27/WSX-1 on Th1 and Th17 cells differentiation in a smoking mouse model of emphysema. We found that elevated expression of IL-27 was associated with increased proportion of Th1 cells and Th17 cells in patients with COPD and demonstrated parallel findings in cigarette smoke-exposed mice. In addition, cigarette smoke exposure upregulated the expression of IL-27R (WSX-1) by naive CD4+ T cells in mice. In vitro, IL-27 significantly augmented the secretion of IFN-γ by naive CD4+ T cells via a T-bet, p-STAT1, and p-STAT3-dependent manner, but inhibited the production of IL-17 by a ROR-γt and p-STAT1-dependent way. Furthermore, anti-IL27 treatment dramatically decreased the expression of IFN-γ-producing CD4+ T cells in cigarette smoke-exposed mice. These findings proposed that IL-27 has functions for promoting the expression of Th1 cells but inhibiting the expression of Th17 cells in vitro and IL-27 neutralization-attenuated Th1-mediated inflammation in vivo, suggesting targeting IL-27/WSX-1 may provide a new therapeutic approach for smoking-related COPD.
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Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.
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Antígenos CD40/fisiología , Ligando de CD40/fisiología , Células Dendríticas/fisiología , Enfisema Pulmonar/inmunología , Humo/efectos adversos , Animales , Linfocitos T CD8-positivos , Diferenciación Celular , Células Cultivadas , Citocinas/biosíntesis , Citocinas/genética , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Recuento de Linfocitos , Ratones Endogámicos C57BL , Ratones Noqueados , Enfisema Pulmonar/etiología , Enfisema Pulmonar/metabolismo , Transducción de Señal , Fumar/efectos adversos , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Nicotiana/efectos adversosRESUMEN
Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease associated with the accumulation of activated T cells. To date, there is little information concerning the intrinsic association among Th17, Tc17, and regulatory T (Treg) cells in COPD. The objective of this study was to investigate the variation of lungs CD4(+)Foxp3(+) Treg cells and IL-17-producing CD4 and CD8 (Th17 and Tc17) lymphocytes in mice with cigarette-induced emphysema. Groups of mice were exposed to cigarette smoke or room air. At weeks 12 and 24, mice were sacrificed to observe histological changes by HE stain. The frequencies of Th17 (CD4(+)IL-17(+)T), Tc17 (CD8(+)IL-17(+)T), and Treg (CD4(+)Foxp3(+)T) cells in lungs from these mice were analyzed by flow cytometry. The mRNA levels of orphan nuclear receptor ROR γt and Foxp3 were performed by real-time quantitative polymerase chain reaction. The protein levels of interleukin-17 (IL-17), IL-6, IL-10, and transforming growth factor-beta (TGF-ß1) were measured by enzyme-linked immunosorbent assay. Cigarette smoke caused substantial enlargement of the air spaces accompanied by the destruction of the normal alveolar architecture and led to emphysema. The frequencies of Th17 and Tc17 cells, as well as the expressions of IL-6, IL-17, TGF-ß1, and ROR γt were greater in the lungs of cigarette smoke (CS)-exposed mice, particularly in the 24-week CS-exposed mice. The frequencies of Treg cells and the expressions of IL-10 and Foxp3 were lower in CS-exposed mice compared to control group. More important, the frequencies of Tregs were negatively correlated with Th17 cells and with Tc17 cells. Interestingly, a significant portion of the cells that infiltrate the lungs was skewed towards a Tc17 phenotype. Our findings suggest the contribution of Th17, Tc17, and Treg cells in the pathogenesis of COPD. Rebalance of these cells will be helpful for developing and refining the new immunological therapies for COPD.
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Enfisema/patología , Linfocitos T Reguladores/citología , Células Th17/citología , Animales , Movimiento Celular , Modelos Animales de Enfermedad , Enfisema/etiología , Inmunohistoquímica , Pulmón/patología , Ratones , Enfermedad Pulmonar Obstructiva Crónica/patología , Humo/efectos adversosRESUMEN
Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 µg/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)α expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-δ/Akt pathway and enhancing GRα expression.
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Corticoesteroides/farmacología , Dexametasona/farmacología , Eritromicina/farmacología , Leucocitos Mononucleares/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Glucocorticoides/metabolismo , Fumar/efectos adversos , Antiinflamatorios/farmacología , Western Blotting , Estudios de Casos y Controles , Quimioterapia Combinada , Fármacos Gastrointestinales/farmacología , Histona Desacetilasa 2/metabolismo , Humanos , Interleucina-8/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Células U937RESUMEN
BACKGROUND: A limitation of bronchoscopic balloon dilatation (BBD) is that airflow must be completely blocked for as long as possible during the operation. However, the patient often cannot hold his or her breath for a long period affecting the efficacy of the procedure. In this study, we used an extra-small-diameter tube to provide assisted ventilation to patients undergoing BBD and assessed the efficacy and safety of this technique. METHODS: Bronchoscopic balloon dilatation was performed in 26 patients with benign tracheal stenosis using an extra-small-diameter tube. The tracheal diameter, dyspnea index, blood gas analysis results, and complications were evaluated before and after BBD. Statistical analyses were performed by SPSS version 16.0 for Windows (SPSS, Inc., Chicago, IL, USA). RESULTS: Sixty-three BBD procedures were performed in 26 patients. Dyspnea immediately improved in all patients after BBD. The tracheal diameter significantly increased from 5.5 ± 1.5 mm to 13.0 ± 1.3 mm (P < 0.001), and the dyspnea index significantly decreased from 3.4 ± 0.8 to 0.5 ± 0.6 (P < 0.001). There was no significant change in the partial pressure of oxygen during the operation (before, 102.5 ± 27.5 mmHg; during, 96.9 ± 30.4 mmHg; and after, 97.2 ± 21.5 mmHg; P = 0.364), but there was slight temporary retention of carbon dioxide during the operation (before, 43.5 ± 4.2 mmHg; during, 49.4 ± 6.8 mmHg; and after, 40.1 ± 3.9 mmHg; P < 0.001). CONCLUSION: Small-diameter tube-assisted BBD is an effective and safe method for the management of benign tracheal stenosis.
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Broncoscopía/métodos , Dilatación/métodos , Estenosis Traqueal/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Pathogenic mechanisms underlying the development of lung cancer are very complex and not yet entirely clarified. T lymphocytes and their immune-regulatory cytokines play a pivotal role in controlling tumor growth and metastasis. Following activation by unique cytokines, CD4+ T helper cells differentiate into Th1, Th2, Th17, and regulatory T cells (Tregs). Traditionally, research in lung cancer immunity has focused almost exclusively on Th1/Th2 cell balance. Recently, Th17 cells and Tregs represent an intriguing issue to be addressed in lung cancer pathogenesis. Tregs play an important role in the preservation of self-tolerance and modulation of overall immune responses against tumor cells. Th17 cells directly or via other proinflammatory cytokines modulate antitumor immune responses. Notably, there is a close relation between Tregs and Th17 cells. However, the possible interaction between these subsets in lung cancer remains to be elucidated. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent a useful tool for lung cancer treatment in the future. The purpose of this review is to discuss recent findings of the role of these novel populations in lung cancer immunity and to highlight the pleiotropic effects of these subsets on the development and regulation of lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas/inmunología , Neoplasias Hepáticas/inmunología , Pulmón/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Citocinas/biosíntesis , Citocinas/inmunología , Humanos , Tolerancia Inmunológica , Neoplasias Hepáticas/patología , Pulmón/patología , Linfocitos T Reguladores/patología , Células TH1/inmunología , Células TH1/patología , Balance Th1 - Th2 , Células Th17/patología , Células Th2/inmunología , Células Th2/patologíaRESUMEN
Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People's Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD.
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Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Neumología/normas , China/epidemiología , Consenso , Progresión de la Enfermedad , Humanos , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria/normas , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Penicillium marneffei is a thermally dimorphic pathogenic fungus that causes systemic infection similar to disseminated cryptococcosis. P. marneffei is endemic in Southeast Asia, usually infecting HIV-infected individuals; infection of HIV-negative individuals is extremely rare. Here, we describe a disseminated P. marneffei infection within an osteolytic lesion in an HIV-negative patient. A 40-year-old Chinese woman presented with intermittent fever, generalized lymphadenopathy, and a skin rash. Following a sternum biopsy, the patient was diagnosed with P. marneffei infection. An emission computed tomography bone scan revealed the presence of increased radioactivity in the left clavicle and sternum, indicative of an osteolytic lesion. In addition to reporting this very rare case, we also present a brief review of the literature, highlighting the differences in clinical manifestations between HIV-positive and HIV-negative patients infected with P. marneffei as it applies to our case.
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Micosis/diagnóstico , Osteólisis/microbiología , Penicillium/aislamiento & purificación , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Asia Sudoriental , Pueblo Asiatico , Femenino , Infecciones por VIH , Humanos , Micosis/tratamiento farmacológico , Osteólisis/diagnóstico , Osteólisis/tratamiento farmacológico , Tomografía Computarizada de EmisiónRESUMEN
Pulmonary sparganosis mansoni is rare in humans and bronchial sparganosis mansoni has not been reported. We reported a patient with a soft-tissue mass in the right hilum area on a chest computed tomography (CT) scan that was suspected of being lung cancer. Bronchoscopy identified sparganum larvae. Bronchial sparganosis mansoni accompanied by abnormal hyperplasia was diagnosed by histopathology. We introduced our experience and reviewed the clinical characteristics of three pulmonary sparganosis mansoni cases and three pleural cavity sparganosis mansoni cases that have been reported.
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Bronquios/patología , Enfermedades Bronquiales/patología , Broncoscopía , Esquistosomiasis mansoni/patología , Esparganosis/patología , Anciano , Humanos , Hiperplasia , MasculinoRESUMEN
Heavy smoking can induce airway inflammation and emphysema. Macrolides can modulate inflammation and effector T-cell response in the lungs. However, there is no information on whether erythromycin can modulate regulatory T-cell (Treg) response. This study is aimed at examining the impact of erythromycin on Treg response in the lungs in a rat model of smoking-induced emphysema. Male Wistar rats were exposed to normal air or cigarette smoking daily for 12 weeks and treated by gavage with 100 mg/kg of erythromycin or saline daily beginning at the forth week for nine weeks. The lung inflammation and the numbers of inflammatory infiltrates in bronchoalveolar lavage fluid (BALF) were characterized. The frequency, the number of Tregs, and the levels of Foxp3 expression in the lungs and IL-8, IL-35, and TNF-α in BALF were determined by flow cytometry, RT-PCR and ELISA, respectively. Treatment with erythromycin reduced smoking-induced inflammatory infiltrates, the levels of IL-8 and TNF-α in the BALF and lung damages but increased the numbers of CD4+Foxp3+ Tregs and the levels of Foxp3 transcription in the lungs, accompanied by increased levels of IL-35 in the BALF of rats. Our novel data indicated that erythromycin enhanced Treg responses, associated with the inhibition of smoking-induced inflammation in the lungs of rats.
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Linfocitos T CD4-Positivos/metabolismo , Eritromicina/uso terapéutico , Factores de Transcripción Forkhead/metabolismo , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Fumar/efectos adversos , Animales , Ensayo de Inmunoadsorción Enzimática , Interleucina-8/metabolismo , Neumonía/inmunología , Neumonía/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: To detect the protein markers in serum and bronchoalveolar lavage fluid (BALF) of the patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technology, and to explore if they can be used as markers for the diagnosis of lung cancer. METHODS: SELDI-TOF-MS technology and protein chips weak cation exchange (WCX-2 chip) were used to detect the protein mass spectrum in serum and BALF of 35 patients with lung cancer and 18 cases of benign pulmonary diseases. The different protein markers were analyzed by Biomarker Pattern Software and the initial diagnosis models were set up. The diagnosis models were verified further by blind screen to confirm the efficacy of diagnosis. RESULTS: Five protein peaks in the sera of the patients with lung cancer were significantly higher (P < 0.05). The protein peak with a mass/charge ratio (M/Z) of 5639 was selected to establish the classification tree model. The sensitivity of diagnosis was 80% (28/35) and the specificity was 78% (14/18). The results verified by blind screen showed a sensitivity of 85% (17/20), a specificity of 90% (9/10), a crude accuracy (CA) of 87% (26/30) and Youden's index (γ) of 0.7. Eight protein peaks in the BALF of the patients with lung cancer were significantly higher (P < 0.05). The different protein peaks with M/Z of 7976 and 11 809 respectively were selected to establish the classification tree model. The sensitivity of diagnosis was 86% (30/35) and the specificity was 72% (13/18). The results verified by blind screen showed a sensitivity of 90% (18/20), a specificity of 90% (9/10), a CA of 90% (27/30) and γ of 0.8. There was a complementary role in combination of differential proteins in serum and BALF and the sensitivity, specificity and accuracy of diagnosis for lung cancer were 100% by parallel test. CONCLUSIONS: The SELDI-TOF-MS technology can screen out the differential protein markers in serum and BALF of the patients with lung cancer, which show high sensitivity and specificity as tumor markers. The differential proteins in the BALF may be more promising for clinical application.
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Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/análisis , Neoplasias Pulmonares/diagnóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Adenocarcinoma/sangre , Adenocarcinoma del Pulmón , Adulto , Anciano , Biomarcadores de Tumor/sangre , Líquido del Lavado Bronquioalveolar/química , Femenino , Humanos , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Análisis por Matrices de Proteínas , Suero/químicaRESUMEN
OBJECTIVE: To scan the protein mass spectra in the sera and bronchoalveolar lavage fluid (BALF) from patients with peripheral lung cancer, screen out the differential proteins, and explore the clinical significance of the differential proteins. METHODS: SELDI-TOF-MS was used to detect the protein mass spectra and to screen out the differential proteins in the sera and BALF collected before and after lung biopsy in 20 patients with peripheral lung cancer and 20 patients with benign pulmonary diseases. The differential proteins were analyzed and the initial diagnostic models were set up. RESULTS: (1) There were 6 differential protein peaks in the sera of the 2 groups (P < 0.05). The protein with a mass/charge ratio (M/Z) of 6637 was selected to establish the diagnostic model. The sensitivity of diagnosing peripheral lung cancer was 70% (14/20), the specificity 90% (18/20), the accuracy 80% (32/40), the positive predictive value (PV+) 88% (14/16), the negative predictive value (PV-) 75% (18/24), and the area under the ROC curve (AUC) was 0.73. (2) There were 11 differential protein peaks in the BALF collected before lung cancer biopsy of the 2 groups (P < 0.05). The protein with a M/Z of 7982 was selected to establish the diagnostic model. The sensitivity of diagnosing peripheral lung cancer was 85% (17/20), the specificity 90% (18/20), the accuracy 88% (35/40), the PV+ 89% (17/19), the PV- 86% (18/21), and the AUC was 0.94. (3) There were 14 differential protein peaks in the BALF collected after lung cancer biopsy of the 2 groups (P < 0.05). The protein with a M/Z of 7671 was selected to establish the diagnostic model. The sensitivity of diagnosing peripheral lung cancer was 85% (17/20), the specificity 100% (20/20), the accuracy 93% (37/40), the PV+ 100% (17/17), the PV- 87% (20/23), and the AUC was 0.93. CONCLUSIONS: There were more differential proteins in BALF as compared with sera. There were more differential proteins in the BALF collected after lung biopsy as compared to that before lung biopsy. The AUC of the diagnostic models set up by proteins in BALF collected before and after lung biopsy were all above 0.9 and showed higher efficiency for the diagnosis of peripheral lung cancer as compared to proteins in sera. These differential proteins may be better tumor markers for the diagnosis of peripheral lung cancer at the early stage.
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Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/análisis , Proteoma/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Adenocarcinoma del Pulmón , Anciano , Líquido del Lavado Bronquioalveolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/sangreRESUMEN
OBJECTIVE: To study the pathological characteristics of intra-acinar pulmonary artery inflammation and its correlation with smoking index and disease progression in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). METHODS: Patients requiring lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function, n = 10), group B (smokers with normal lung function, n = 13), and group C (smokers with stable COPD, n = 10). The lung tissue far away from tumor were resected to compare the pathological changes of intra-acinar pulmonary arteries and infiltration level of inflammatory cell in pulmonary non-muscularized arteries (NMA), pulmonary partially muscularized arteries (PMA) and muscularized arteries (MA) among the three groups. The correlation analysis was made among infiltration level, smoking index, percentage of predicted value of forced expiratory volume in one second (FEV(1)%Pred), six-minute-walk distance (6MWD) and BODE index. RESULTS: (1) Both group B and group C showed the intima and media thickness of MA was significantly higher, the lumen area of MA was narrower and the proportion of MA was higher, and collagenous fiber of MA adventitial proliferated and area increased in group C (P < 0.05 or P < 0.01). (2) In group B and group C, the percentage of the intra-acinar pulmonary arteries that contained leukocytes, T lymphocytes, CD(8)(+)T lymphocytes and the number of these positive cells infiltrating the intra-acinar pulmonary arteries were increased, especially an increased number of CD(8)(+)T lymphocytes infiltrating in the arterial adventitia as compared with group A, moreover there were significant difference between group C and group B (P < 0.05 or P < 0.01). In group B and group C, the degree of these positive cells infiltrating NMA, PMA and MA presented a decreasing sequence (P < 0.05 or P < 0.01). Among the intima, media and adventitia of MA, the infiltration of these positive cells was the highest in the adventitia. Among group A, group B and group C, infiltration degree of CD(4)(+)T lymphocyte, B lymphocyte, macrophage and neutrophil demonstrated no significant difference, also among NMA, PMA and MA (P > 0.05). (3) The number of leukocytes, T lymphocytes, CD(8)(+)T lymphocytes infiltrating MA showed a positive correlation with the thickness of MA (r = 0.563, 0.627, 0.589, P < 0.01, respectively) and smoking index (r = 0.551, 0.665, 0.600, P < 0.01, respectively), moreover the degree of these cells infiltrating MA demonstrated negative correlation with FEV(1)%Pred (r = -0.763, -0.703, -0.767, P < 0.01, respectively). Also infiltrating degree of T lymphocytes and CD(8)(+)T lymphocytes was positively correlated with BODE (r = 0.390, 0.476, P < 0.05, respectively). Furthermore the infiltrating degree of CD(8)(+)T lymphocytes had negative correlation with 6MWD (r = -0.356, P < 0.05). CONCLUSIONS: (1) Pulmonary arterial inflammation appears in smokers with normal lung function and smokers with COPD patients. It involves in all types of intra-acinar pulmonary arteries especially NMA and infiltrates whole layer of MA with a characteristic of CD(8)(+)T lymphocytes infiltrating in the adventitia of intra-acinar pulmonary arteries. (2) Pulmonary inflammation is closely correlated to cigarette smoking and clinical parameters such as BODE index, FEV(1)% pred and 6MWD. It is one of the key factors affecting the progression of COPD.
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Inflamación/patología , Arteria Pulmonar/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Fumar/efectos adversos , Anciano , Linfocitos T CD8-positivos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función RespiratoriaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of intubation dilatation under flexible bronchoscopic guidance in the management of benign tracheal stenosis. METHODS: A retrospective analysis of the clinical data was performed for 12 patients with benign tracheal stenosis from March 2010 to August 2011. There were 5 males and 7 females with a mean age of 37 ± 11 years old (range: 27 - 65). They were treated by intubation dilatation with different sizes under bronchoscopic guidance. And balloon dilatation was also performed for left or right main stem bronchial stenosis. And metal stents were implanted if necessary. Airway diameter, dyspnea index, complications and blood gas analysis were evaluated in all patients. And the forced expiratory volume in one second (FEV(1)) was tested in 9 cases before and after the treatments of intubation dilation, balloon dilation and other interventions. RESULTS: One to five attempts of intubation dilation were required to achieve satisfactory dilatation. There was immediate postoperative relief of dyspnea for all 12 cases. And PaO2 and SaO2 rose markedly, but PaCO2 declined after intervention. The effective rate of intubation dilation was 100%. The average airway diameter increased from (5.7 ± 1.2) to (12.2 ± 2.1) mm and FEV(1) improved from (0.67 ± 0.13) to (1.73 ± 0.37) L (P < 0.01). CONCLUSION: The minimally invasive management of benign tracheal stenosis with intubation dilatation is both safe and efficacious.
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Broncoscopía , Intubación/métodos , Estenosis Traqueal/cirugía , Adulto , Anciano , Dilatación/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the expression of Treg in a cigarette smoke-induced rat model of emphysema and after smoking cessation in the rats. METHODS: Fifty male Wistar rats were randomly divided into control group 1 (12 weeks), control group 2 (24 weeks), smoke-exposure group 1 (12 weeks), smoke-exposure group 2 (24 weeks) and smoking cessation group, with 10 rats in each group. Alveolar airspace enlargement was observed by hematoxylin-eosin (HE) staining. IL-8 and TNF-α levels in bronchoalveolar lavage fluid (BALF) were tested by ELISA. The proportion of CD4(+)Foxp3(+) Treg in peripheral blood and lungs of rats was determined by flow cytometry. The mRNA expression of Foxp3 was measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test was used for comparison between 2 groups. RESULTS: The mean linear intercept (MLI) in smoke-exposure group 1 and group 2 [(64.9 ± 5.3) µm, (77.9 ± 11.5) µm] was higher than those in the control group 1 and group 2 [(39.0 ± 3.8) µm, (40.3 ± 2.7) µm], all P < 0.01. Compared with smoke-exposure group 2, the MLI in smoking cessation group (71.5 ± 5.8) µm showed a lower value (P < 0.01), but still higher than that in smoke-exposure group 1 (P < 0.01). The IL-8 and TNF-α levels in BALF of smoke-exposure group 1 and group 2 [(68 ± 17) ng/L, (85 ± 16) ng/L], [(14.1 ± 1.8) ng/L, (20.1 ± 8.7) ng/L] were higher than those in control group 1 and group 2 [(44 ± 8) ng/L, (43 ± 9) ng/L], [(6.3 ± 2.3) ng/L, (5.8 ± 1.6) ng/L], all P < 0.05. The IL-8 and TNF-α levels were not statistically different between in smoking cessation group (56 ± 6) ng/L, (14.7 ± 4.7) ng/L and smoke-exposure group 1. The percentage of Treg in the lungs of smoke-exposure group 1 and group 2 [(6.6 ± 0.8)%, (5.3 ± 0.9)%] was significantly decreased as compared to control group 1 and group 2 [(9.0 ± 1.0)%, (9.6 ± 0.9)%], all P < 0.01. The percentage of Treg in lungs was not statistically different between smoke-exposure group 1 and smoking cessation group (7.2 ± 0.6)%. In peripheral blood, there was no significant difference between groups in the percentage of Treg. In the lung, Foxp3 mRNA expression in smoke-exposure group 1 and group 2 [(17 ± 7), (9 ± 7)] was less than that in control group 1 and group 2 [(39 ± 6), (42 ± 7)], all P < 0.01. The Foxp3 mRNA expression was not statistically different between smoke-exposure group 1 and smoking cessation group (21 ± 9). No significant differences in peripheral blood Foxp3 mRNA expression was found between groups. CONCLUSIONS: Decreased Treg was present in lungs of cigarette smoke-induced model of emphysema despite 12 weeks' smoking cessation, suggesting that down-regulation of Treg may be involved in the amplified and persistent inflammation after smoking cessation.
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Factores de Transcripción Forkhead/metabolismo , Inflamación/inmunología , Enfisema Pulmonar/inmunología , Cese del Hábito de Fumar , Linfocitos T Reguladores/inmunología , Animales , Inflamación/patología , Masculino , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/patología , Ratas , Ratas Wistar , Fumar/efectos adversos , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation and is associated with acute exacerbations. Macrolide antibiotics have been shown to exhibit anti-inflammatory effects in some chronic airway inflammatory diseases. OBJECTIVE: The aim of this study was to assess the effect of treatment with erythromycin on airway inflammation and health outcome in COPD patients. METHODS: We conducted a randomized, placebo-controlled, double-blind trial of erythromycin for a period of 6 months. Thirty-six COPD patients were randomized to treatment with oral erythromycin (125 mg, three times/day) or placebo. The primary outcomes were neutrophil number in sputum and exacerbations. RESULTS: Thirty-one patients completed the study. At the end of treatment, neutrophil counts in the sputum were significantly decreased in the group treated with erythromycin compared with placebo-treated patients (p = 0.005). Total cells in the sputum and neutrophil elastase in sputum supernatant were also significantly decreased in those treated with erythromycin compared with the placebo group (p = 0.021 and p = 0.024, respectively). The mean exacerbation rate was lower in the erythromycin group than in the placebo group (relative risk = 0.554, p = 0.042). Kaplan-Meier survival analysis showed that erythromycin significantly delayed the time to the first COPD exacerbation compared with placebo (p = 0.032). CONCLUSIONS: Erythromycin treatment in COPD patients can reduce airway inflammation and decrease exacerbations and may therefore be useful in the management of COPD.
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Antibacterianos/administración & dosificación , Eritromicina/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Esputo/efectos de los fármacos , Anciano , Antibacterianos/efectos adversos , Método Doble Ciego , Eritromicina/efectos adversos , Femenino , Humanos , Recuento de Leucocitos , Elastasa de Leucocito/análisis , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Calidad de Vida , Esputo/citología , Esputo/inmunología , Esputo/microbiología , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the clinical features of 3 cases of Burkholderia pseudomallei septicemia in Guangxi Province, and therefore to improve its diagnosis and treatment. METHOD: The clinical features, treatment and prognosis of 3 cases of acute septicemic melioidosis admitted to this hospital from October 2006 to December 2008 were retrospectively analyzed. RESULTS: The 3 male patients were local farmers, with an average age of (42 ± 2) years. Two of them had a history of frequent trauma and contact with polluted water, and another had a history of exposure to the dust and soil. All patients had an acute onset, manifested as septicemia with chills, high-grade fever, anemia and weight loss. At the same time, the disease was often complicated with multiple organ abscesses. The pus was characterized by smelling like mud. One case was manifestated with lung abscess, with right calf skin pyogenic infection, and the another case was with liver, spleen, pancreas and mediastinal abscess, and the third presented with right facial and ankle soft tissue abscess. The leukocyte counts [(11.6 ± 0.5) × 10(9)/L] and neutrophils [(8.3 ± 0.4) × 10(9)/L] in 2 patients were slightly increased, but decreased in the other patient. There were significant increase of erythrocyte sedimentation rate (63.5 ± 2.7) mm/1 h and c-reactive protein (155 ± 4) mg/L, and liver dysfunction and elevated blood glucose occurred in 3 patients. Chest radiology and CT showed a number of patchy infiltrates, consolidation, and nodules with varying sizes in the upper lung lobes. Abscess in other organs mainly occurred in liver, spleen, and skin. The final diagnosis was confirmed as infection with Burkholderia pseudomallei by repeated blood or pus culture. The isolated Burkholderia pseudomallei was sensitive to carbapenem, and ß-lactam + ß-lactamase inhibitors. One patient was treated effectively with Imipenem, and other 2 patients with ß-lactam + ß-lactamase inhibitors. After 3 - 4 days of treatment with antibiotics, the body temperature of these patients gradually decreased, and the intravenous drug was used as long as 4 to 8 weeks, and a total course of antibiotic therapy would continue for 4 to 6 months. CONCLUSIONS: Human melioidosis exists in the south and southwest of Guangxi. Repeated blood or pus culture can confirm the diagnosis. A relatively long course of antibiotic treatment with ß-lactam/ß-lactamase inhibitors or carbapenem is recommended.