RESUMO
OBJECTIVE: The diagnostic value of emphysema extent in consistent air flow limitation remains controversial. Therefore, we aimed to assess the value of emphysema extent on computed tomography (CT) on the diagnosis of persistent airflow limitation. Furthermore, we developed a diagnostic criterion for further verification. MATERIALS AND METHODS: We retrospectively enrolled patients who underwent chest CT and lung function test. To be specific, 671 patients were enrolled in the derivation group (Group 1.1), while 479 patients were in the internal validation group (Group 1.2). The percentage of lung volume occupied by low attenuation areas (LAA%) and the percentile of the histogram of attenuation values were calculated. RESULTS: In patients with persistent airflow limitation, the LAA% was higher and the percentile of the histogram of attenuation values was lower, compared with patients without persistent airflow limitation. Using LAA% with a threshold of -950 HU >1.4% as the criterion, the sensitivity was 44.3% and 47.2%, and the specificity was 95.2% and 95.7%, in Group 1.1 and Group 1.2, respectively. The specificity was influenced by the coexistence of interstitial lung disease, pneumothorax, and post-surgery, rather than the coexistence of pneumonia, nodule, or mass. Multivariable models were also developed. CONCLUSION: The emphysema extent on CT is a highly specific marker in the diagnosis of persistent airflow limitation.
Assuntos
Pulmão/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , China , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/fisiopatologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Capacidade VitalRESUMO
OBJECTIVE: To evaluate the long-term efficacy and safety of bronchial thermoplasty (BT) in the treatment of patients with moderate-to-severe persistent asthma. METHODS: We therefore performed a systematic literature review of peer-reviewed studies focusing on BT intervention in asthma control published between January 2000 and June 2014. Three randomized controlled studies and extension studies met the inclusion criteria (n = 6). Outcomes assessed after BT included spirometric data, adverse respiratory events, emergency room (ER) visits and hospitalization for respiratory illness. One-year and 5-year follow-up data were defined as V1 and V5, respectively. RESULTS: There were 249 BT-treated subjects in total who had a 1-year follow-up (V1), whereas 216 of them finished a 5-year follow-up (V5). No evidence of significant decline was found in pre-bronchodilator FEV1 (% predicted) (WMD = 0.75; 95% CI: 3.36 to 1.85; p = 0.57), or in post-bronchodilator FEV1 (% predicted) (WMD = 0.62; 95% CI: 3.32 to 2.08; p = 0.65) between V1 and V5. In addition, the frequency of respiratory adverse events was reduced significantly during the follow-up (RR = 3.41, 95% CI: 2.96-3.93, p < 0.00001). The number of ER visits for adverse respiratory events remained unchanged (RR = 1.06, 95% CI: 0.77-1.46, p = 0.71) after BT treatment. There was no statistically significant increase in the incidence of hospitalization for respiratory adverse events (V5 vs. V1, RR = 1.47, 95% CI: 0.69-3.12, p = 0.32). CONCLUSIONS: These data demonstrate long-term benefits of BT with regard to both asthma control and safety for moderate-to-severe asthmatic patients.
Assuntos
Asma/terapia , Broncoscopia , Tratamento por Radiofrequência Pulsada , Asma/fisiopatologia , Broncoscopia/efeitos adversos , Humanos , Tratamento por Radiofrequência Pulsada/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with antioxidant and anti-inflammatory properties, such as N-acetylcysteine, might provide a useful therapeutic approach for COPD. We aimed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD. METHODS: In our prospective, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 40-80 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <0·7 and FEV1 of 30-70% of predicted) at 34 hospitals in China. We stratified patients according to use of inhaled corticosteroids (regular use or not) at baseline and randomly allocated them to receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for 1 year. The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after randomisation. This study is registered with the Chinese Clinical Trials Registry, ChiCTR-TRC-09000460. FINDINGS: Between June 25, 2009, and Dec 29, 2010, we screened 1297 patients, of whom 1006 were eligible for randomisation (504 to N-acetylcysteine and 502 to placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit (1·16 exacerbations per patient-year) and 641 acute exacerbations in 482 patients in the placebo group (1·49 exacerbations per patient-year; risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011). N-acetylcysteine was well tolerated: 146 (29%) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495 patients who received at least one dose of placebo (46 serious). The most common serious adverse event was acute exacerbation of COPD, occurring in 32 (6%) of 495 patients in the N-acetylcysteine group and 36 (7%) of 495 patients in the placebo group. INTERPRETATION: Our findings show that in Chinese patients with moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations, especially in disease of moderate severity. Future studies are needed to explore efficacy in patients with mild COPD (GOLD I). FUNDING: Hainan Zambon Pharmaceutical.
Assuntos
Acetilcisteína/administração & dosagem , Sequestradores de Radicais Livres/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento , Capacidade VitalRESUMO
In the immune system, CD4+CD25+Foxp3+ regulatory T cells (Tregs) maintain selftolerance and Th17 cells mediate inflammatory responses. CD39 is expressed on the surface of a subset of naturally occurring human Tregs that are important in constraining pathogenic Th17 cells. Additional studies have shown that Tregs differentiate into interleukin17 (IL17)+Foxp3+ T cells. Our previous study indicated an imbalance of Th17 and Tregs in allergic asthma; however, the underlying mechanisms remain poorly understood. Using quantitative PCR (qPCR), CD39 and CD73 mRNA levels in CD4+ T cells were investigated. Flow cytometry was used to analyze the proportion of IL17+Foxp3+ T cells, and CD39 and CD73 expressed by CD4+ T cells and Tregs in the peripheral blood of the subjects. The results of the present study demonstrated an increased frequency of CD4+Foxp3+IL17+ T cells in moderate to severe asthma. A deficiency in CD39 expressed on the surface of CD4+ T cells and Tregs was observed in asthma patients. The expression of CD39 and CD73 on the surface of CD4+ T cells and Tregs was negatively correlated with the number of Th17 cells. These results indicated that the plasticity of Tregs transforming to IL17+Foxp3+CD4+ T cells, the reduced frequency of CD39+ Tregs and less effective suppression of IL17 production by residual CD39+ Tregs leads to an imbalance of Th17 and Tregs in asthma. Therefore, enhanced CD39 activity is hypothesized to prevent the progression of asthma.
Assuntos
5'-Nucleotidase/imunologia , Antígenos CD/imunologia , Apirase/imunologia , Asma/imunologia , Linfócitos T CD4-Positivos/imunologia , Interleucina-17/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , 5'-Nucleotidase/metabolismo , Adulto , Antígenos CD/metabolismo , Apirase/metabolismo , Asma/metabolismo , Asma/patologia , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Interleucina-17/metabolismo , Masculino , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismoRESUMO
Squamous cell lung cancer is a major histotype of non-small cell lung cancer (NSCLC) that is distinct from lung adenocarcinoma. We used whole-exome sequencing to identify novel non-synonymous somatic mutations in squamous cell lung cancer. We identified 101 single-nucleotide variants (SNVs) including 77 non-synonymous SNVs (67 missense and 10 nonsense mutations) and 11 INDELs causing frameshifts. We also found four SNVs located within splicing sites. We verified 62 of the SNVs (51 missense, 10 nonsense and 1 splicing-site mutation) and 10 of the INDELs as somatic mutations in lung cancer tissue. Sixteen of the mutated genes were also mutated in at least one patient with a different type of lung cancer in the Catalogue of Somatic Mutation in Cancer (COSMIC) database. Four genes (LPHN2, TP53, MYH2 and TGM2) were mutated in approximately 10% of the samples in the COSMIC database. We identified two missense mutations in C10orf137 and MS4A3 that also occurred in other solid-tumor tissues in the COSMIC database. We found another somatic mutation in EP300 that was mutated in 4.2% of the 2,020 solid-tumor samples in the COSMIC database. Taken together, our results implicate TP53, EP300, LPHN2, C10orf137, MYH2, TGM2 and MS4A3 as potential driver genes of squamous cell lung cancer.
Assuntos
Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Exoma , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Sítios de Splice de RNA/genética , Análise de Sequência de DNA/métodosRESUMO
Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS). ACE2 plays a critical counterbalancing role by degrading angiotensin II (Ang II) to Ang 1-7. Recent studies suggest that RAS influences tumor growth and development by its paracrine effects on the tumor microenvironment. Epithelialmesenchymal transition (EMT) is now thought to be a process that plays a fundamental role in tumor progression and metastasis. In the present study, we investigated the role of ACE2 in lung cancer metastasis and the mechanism of EMT. This is the first study to elucidate the mechanism through which the overexpression of ACE2 in the A549 lung cancer cell line decreases metastasis formation in vivo and upregulates the expression of E-cadherin both in vitro and in vivo. We also observed the downregulation of vimentin, which supports a role of ACE2 in influencing EMT in lung cancer. Further analysis indicated that ACE2 abrogated the upregulation of TGF-ß1-induced EMT markers, such as vimentin and α-smooth muscle actin (αSMA) in vitro in A549 cells. Finally, exposing A549 cells stably expressing ACE2 to DX600, an inhibitor of ACE2, recovered the sensitivity of lung cancer cells to TGF-ß1-mediated induction of EMT. Our study demonstrated that ACE2 attenuated the metastasis of lung cancer and may serve as a target for new strategies to inhibit EMT in cancer cells.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/enzimologia , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/enzimologia , Peptidil Dipeptidase A/fisiologia , Enzima de Conversão de Angiotensina 2 , Animais , Antígenos CD , Biomarcadores Tumorais/metabolismo , Caderinas/genética , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Proteínas Nucleares/metabolismo , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta1/fisiologia , Proteína 1 Relacionada a Twist/metabolismo , Regulação para Cima , Homeobox 1 de Ligação a E-box em Dedo de ZincoRESUMO
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.
Assuntos
Acetilcisteína/administração & dosagem , Progressão da Doença , Expectorantes/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Acetilcisteína/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Expectorantes/efeitos adversos , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Projetos de Pesquisa , Fatores de Tempo , Capacidade VitalRESUMO
To determine the susceptibility genes of lung cancer, we investigated the frequency distributions of the xeroderma pigmentosum complementary group D (XPD) and cytidine deaminase (CDA) genes in patients. A case-control study was conducted involving lung cancer patients and healthy controls. The genotypic distributions of XPD exon 10 GâA (Asp312Asn) and 23 TâG (Lys751Gln), and CDA 79 AâC (Lys27Gln) and 208 GâA (Ala70Thr), were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results demonstrated that the XPD Asp312Asn genotype distribution was G/G (82.52%) and A/G (17.48%) in the lung cancer patients, and G/G (82.52%), A/G (16.50%) and A/A (10.98%) in the controls. The genotypes of Lys751Gln were T/T (83.49%) and T/G (16.50%) in the lung cancer patients, and T/T (84.47%) and T/G (15.53%) in the controls. Mutations in the XPD single nucleotide polymorphism loci did not demonstrate a significant difference between the two groups (P>0.05). The risk of lung cancer in individuals with mutations at positions 312 and 751 increased 6.13-fold (P=0.047). The CDA Lys27Gln genotype distribution was A/A (78.65%), A/C (20.39%) and C/C (0.98%) in the lung cancer patients, and A/A (79.61%), A/C (19.42%) and C/C (0.98%) in the controls (P=0.985). The CDA Ala70Thr genotype distribution was G/G (98.06%) and A/G (1.94%) in the controls, while all the genotypes were wild-type in the lung cancer patients. The difference between the lung cancer patients and the controls was not statistically significant (P=0.155). There was also no significant difference in the frequency distribution of XPD or CDA between the different pathological types (P>0.05). Our findings demonstrate that the mutation of XPD codons 312 and 751 increases the risk of lung cancer. By contrast, polymorphisms of CDA appear to have little association with lung cancer.
RESUMO
Suppressor of cytokine signaling-1 (SOCS1) is a protein that negatively regulates cytokine and growth factor signaling. However, little is known regarding the precise role it plays in idiopathic pulmonary fibrosis. The aim of the present study was to construct a recombinant lentiviral vector for RNA interference targeting the SOCS1 gene and to detect the expression in human alveolar epithelial cells. A lentiviral vector-mediated RNA interference method was used to establish a SOCS1-negative cell line of alveolar origin (A549). Three pairs of complementary small hairpin RNA (shRNA) oligonucleotides targeting the SOCS1 gene were designed, synthesized and inserted into the pPll3.7 vector. Packaged lentivirus particles were obtained after 48 h, and the supernatant was used to transfect the human alveolar epithelial cell line A549. The expression of the SOCS1 protein was detected by Western blotting. MTT assay was used to detect the cell proliferation of alveolar epithelial cells with SOCS1 knockdown. The recombinant plasmids were confirmed by sequencing. The lentivirus-containing supernatant effectively infected the A549 cell line, and the expression of SOCS1 protein was inhibited, which was confirmed by Western blotting in the target cells. MTT assay indicated the inhibition effect for cell proliferation of A549 cells in the SOCS1-RNA interference group, compared to the control group with no interference-mediated silencing of the SOCS1 gene. A lentiviral vector for RNA interference targeting the SOCS1 gene was successfully constructed, and cell survival tests showed that knockdown of the SOCS1 gene promotes the apoptosis of alveolar cells.
Assuntos
Apoptose , Células Epiteliais/citologia , Lentivirus/genética , Interferência de RNA , Proteínas Supressoras da Sinalização de Citocina/antagonistas & inibidores , Proteínas Supressoras da Sinalização de Citocina/genética , Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patologia , Sequência de Bases , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Inativação Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Dados de Sequência Molecular , RNA Interferente Pequeno/metabolismo , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
Mutations of the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC) were identified by re-sequencing all exons of this gene to evaluate the frequencies of EGFR gene mutation and identify rare or novel EGFR mutations. A total of 55 NSCLC samples from 55 patients were included in the study. Genomic DNA was extracted and exons 1-28 of the EGFR gene were sequenced to identify mutations. The cDNA of the EGFR gene with P848L and T790M double mutants was constructed by introducing point mutations into the wild-type EGFR vector using a site-directed mutagenesis kit. Among the 55 patients with NSCLC, 8 patients carried mutations of the EGFR gene. Notably, of the mutation-harboring patients with a pathological type of adenocarcinoma, 6 were non-smokers. The in vitro study demonstrated that the P848L mutant had a similar response to that of the wild-type EGFR after gefitinib treatment, and the P848L and T790M double mutant exhibited high resistance to gefitinib. These EGFR mutations preferentially occurred in lung adenocarcinoma patients, most of whom were non-smokers. In the in vitro study, P848L mutant EGFR had a similar response as the wild-type EGFR to gefitinib treatment, suggesting that lung cancer patients with a rare mutation of EGFR, such as the P848L mutation, do not respond to gefitinib treatment.
RESUMO
OBJECTIVE: To classify the high-resolution CT (HRCT) phenotypes of COPD, and to investigate the clinical characteristics of various phenotypes and the relationship with airway inflammation. METHODS: Chest HRCT and pulmonary function tests were performed in 84 COPD patients. The patients were classified into 3 phenotypes according to the visual HRCT findings. Exhaled breath condensate was gathered from 30 patients and the interleukin (IL)-6 level was measured by ELISA. RESULTS: The COPD patients were classified into 3 phenotypes: Phenotype A, absence of emphysema, with or without bronchial wall thickening (n = 34); Phenotype E, emphysema without bronchial wall thickening (n = 23); and Phenotype M, emphysema with bronchial wall thickening (n = 27). The 3 phenotypes of COPD showed different characteristics in several aspects. Patients with phenotype A showed a higher body mass index [(25.1 +/- 4.4) kg/m(2) vs phenotype E (22.5 +/- 4.1) kg/m(2) and phenotype M (21.3 +/- 3.4) kg/m(2), F = 6.732, P < 0.01]. The prevalence of patients with milder dyspnea was lower in phenotype A compared with others (15/34) vs phenotype E (2/23) and phenotype M (6/27), chi(2) = 9.097, P < 0.05. The patients who complained of severe expectoration in phenotype E were fewer than those in other groups (0/23) vs phenotype A (2/34) and phenotype M (4/27), chi(2) = 8.702, P < 0.05. The FEV(1)/FVC and FEV(1)% in phenotype M [(53 +/- 14)% and (51 +/- 25)%] were significantly lower as compared with those in other phenotypes [(67 +/- 11)% and (72 +/- 24)% in phenotype A, and (53 +/- 14)% and (52 +/- 26)% in phenotype E], F = 10.252, F = 6.508, P < 0.01. The ratio of inspiratory capacity to total lung capacity (IC/TLC) in phenotype A was higher [phenotype A (41 +/- 17)%, phenotype E (33 +/- 13)%, phenotype M (28 +/- 13)%, F = 5.964, P < 0.01], while the ratio of residual volume to total lung capacity (RV/TLC) was lower [phenotype A (37 +/- 9)%, phenotype E (44 +/- 10)%, phenotype M (45 +/- 8)%, F = 6.954, P < 0.01]. Patients with different phenotypes showed various levels of IL-6 in exhaled breath condensate [phenotype A (19.9 +/- 6.3) ng/L, phenotype E (16.7 +/- 2.1) ng/L, phenotype M (25.6 +/- 4.4) ng/L, F = 7.749, P < 0.01]. CONCLUSION: Various morphological phenotypes of COPD based on HRCT showed different clinical characteristics and airway inflammation.
Assuntos
Interleucina-6/análise , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/patologia , Testes de Função Respiratória , Tomografia Computadorizada por Raios XRESUMO
Serum cell-free DNA concentrations have been reported to increase in many acute diseases as well as in some chronic conditions such as cancer and autoimmune diseases. The aim of this study was to examine whether serum DNA concentrations were elevated in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). The effects of nasal continuous positive airway pressure (nCPAP) on serum DNA were also investigated. One hundred twenty-seven people diagnosed with OSAHS by polysomnography (PSG) were admitted into the OSAHS group, and 52 subjects without OSAHS were recruited for the control group. The OSAHS group was further divided into mild, moderate, and severe OSAHS subgroups based on their apnea-hypopnea index (AHI) during sleep. Ten patients with moderate and severe OSAHS were treated with nCPAP. Serum DNA, interleukin-6 (IL-6), and malonaldehyde (MDA) concentrations were measured and were found to be significantly higher in patients with moderate and severe OSAHS groups than those in the mild OSAHS and control groups (p < 0.05). Univariate analysis showed that serum DNA correlated positively with AHI, oxygen desaturation index (ODI), IL-6, and MDA, and negatively correlated with minimal oxygen saturation (miniSaO(2)) (all p < 0.05). In stepwise multiple regression analysis, only MDA and miniSaO(2) were suggested as significant independent predictors for the serum DNA concentrations. After 6 months of nCPAP therapy, serum concentrations of DNA, IL-6, and MDA were significantly decreased (p < 0.05). The increasing concentration of serum DNA in patients with OSAHS was positively correlated with disease severity. Serum DNA may become an important parameter for monitoring the severity of OSAHS and effectiveness of therapy.
Assuntos
DNA/sangue , Apneia Obstrutiva do Sono/genética , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , China , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Interleucina-6/sangue , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Análise de Regressão , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/terapia , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: It has been shown that neurohumoral factors other than mechanical obstruction are involved in the pathophysiology of acute pulmonary thromboembolism (APTE). The aim of this study was to investigate the effects of thrombolytic drugs, a selective endothelin-1 receptor (ET-1R) antagonist alone or their combination on APTE in a canine model. METHODS: Twenty dogs were randomly assigned to five groups: sham, model, urokinase (UK), BQ123, and combination (UK plus BQ123). The dogs in the sham group underwent sham surgery. APTE was induced in the other four groups by intravenous injection of autologous blood clots. Dogs in the UK, BQ123 and combination groups received UK, BQ123 (a selective ET-1R antagonist), or UK plus BQ123, respectively. The dogs in the model group were given saline. Mean pulmonary artery pressure (mPAP), serum concentrations of ET-1, thromboxane (TXB2), and tumor necrosis factor (TNF)-alpha were determined at different time points following the induction of APTE. RESULTS: UK and BQ123 alone markedly decreased mPAP in APTE. By comparison, the reduction was more significant in the combination group. Compared with the sham group ((-0.90 +/- 0.61) mmHg), mPAP increased by (7.44 +/- 1.04), (3.42 +/- 1.12) and (1.14 +/- 0.55) mmHg in the model group, UK alone and BQ123 alone groups, respectively, and decreased by (2.24 +/- 0.67) mmHg in the combination group (P < 0.01). Serum ET-1 concentrations in the BQ123 and combination groups were (52.95 +/- 8.53) and (74.42 +/- 10.27) pg/ml, respectively, and were significantly lower than those in the model and UK groups ((84.56 +/- 7.44) and (97.66 +/- 8.31) pg/ml respectively; P < 0.01). Serum TNF-alpha concentrations were significantly lower in the BQ123 group than in the model, UK and combination groups (P < 0.05). CONCLUSIONS: Our results indicate that the selective ET-1R antagonist BQ123 not only reduces the increase of mPAP and serum ET-1 level, but also inhibits the production of TNF-alpha, and attenuates the local inflammatory response induced by APTE. Selective ET-1R antagonists may be beneficial to the treatment of APTE, particularly when used in combination with a thrombolytic agent.
Assuntos
Antagonistas do Receptor de Endotelina A , Fibrinolíticos/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Animais , Cães , Endotelina-1/sangue , Embolia Pulmonar/sangue , Embolia Pulmonar/patologia , Distribuição Aleatória , Tromboxanos/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Mimecan mRNA was present in a limited number of mouse and human tissues, however, abundant mimecan mRNA was observed in the lung tissue. Therefore, we hypothesize that mimecan could serve as a biomarker for differentiating various histological types of lung cancers. In humans, the mimecan mRNA was found most abundant in ovary and less abundant in lung by using Northern blot analysis. Moreover, the mimecan was expressed strongly in the epithelial cells of the bronchial wall and weaker in the epithelial cells of the alveolar sacs by in situ hybridization and immunohistochemical analysis. Furthermore, the mimecan immunoreactivity was found in 103 (97.2%) of 106 non-small cell lung cancers (NSCLCs). Nevertheless, a large majority of small cell lung cancers (SCLCs) (50/56, 89.3%) showed negative immunoreactivity to mimecan polyclonal antibody. A significant difference of mimecan immunoreactivity was found between NSCLC and SCLC (P<0.00001). This is the first study showing that mimecan could serve as an excellent pathological biomarker to distinguish NSCLCs from SCLCs.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Biomarcadores Tumorais/genética , Northern Blotting , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Casos e Controles , Diagnóstico Diferencial , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Prognóstico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismoRESUMO
OBJECTIVE: To investigate if type II alveolar epithelial cells express Toll-like receptor 4 (TLR4) and to investigate the role of TLR4 in airway inflammation of chronic obstructive pulmonary diseases (COPD). METHODS: A549, the line of human type II alveolar epithelial cells were cultured and divided into 3 groups: normal control group, E1A(+) group transfected with adenovirus E1A plasmid, E1A(-) group transferred with blank plasmid without adenovirus E1A. Lipopolysaccharide (LPS) of the concentrations of 0, 0.1, 1, and 10 microg/ml, IL-1 beta of the concentrations of 0, and 0.1 ng/ml, and cigarette smoking extract (CSE) of the concentrations of 0, 10%, 20%, and 40% were used to stimulated the A549 cells for 12 and 24 h. Reverse transcription polymerase chain reaction was used to detect the mRNA expression of IL-8 and TLR4. Western blotting was used to detect the protein expression of nuclear factor kappaB (NF-kappaB) subunit P65. RESULTS: Twenty-four hours after the stimulation of 10 microg/ml LPS, 0.1 ng/ml IL-1beta, and 20% CSE, the IL-8 mRNA expression of the E1A(+) group was 2.82, 1.87, and 4.70 respectively, all significantly higher than those of the normal control group (0.95, 0.78, and 1.02 respectively, all P < 0.05) and those of the E1A(-) group (0.97, 0.81, and 1.12 respectively, all P < 0.05). Twelve and twenty-four hours after the stimulation of 10 microg/ml of LPS, the TLR4 mRNA expression of the E1A+ group were 4.52 and 7.99, both significantly higher than those of the normal control group (1.91 and 3.81 respectively, both P < 0.05) and those of the E1A(-) group (2.00 and 3.88 respectively, both P < 0.05). IL-1beta increased the expression of TLR4 mRNA too, but CSE did not change the expression of TLR4 mRNA in all these groups. LPS, IL-1beta, and CSE all increased the expression levels of NF-kappaB subunit P65 protein. CONCLUSIONS: Pulmonary type II epithelial cells express TLR4. LPS and IL-1beta up-regulate the release of IL-8 which may be mediated via the activation of NF-kappaB induced by TLR4.
Assuntos
Células Epiteliais/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Receptor 4 Toll-Like/biossíntese , Proteínas E1A de Adenovirus/genética , Proteínas E1A de Adenovirus/metabolismo , Proteínas E1A de Adenovirus/fisiologia , Western Blotting , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/fisiopatologia , Interleucina-1beta/farmacologia , Interleucina-8/biossíntese , Interleucina-8/genética , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Nicotiana/química , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/fisiologia , TransfecçãoRESUMO
BACKGROUND: Gemcitabine plus cisplatin is a standard treatment for stages IIIB and IV nonsmall cell lung cancer (NSCLC). This randomized phase II study evaluated a 3-week versus a 4-week schedule of gemcitabine-cisplatin as first line treatment for Chinese patients with advanced NSCLC. METHODS: Patients were randomized to receive cisplatin 75 mg/m(2) on day 1 plus either gemcitabine 1250 mg/m(2) on days 1 and 8 of a 21-day cycle (3-week group) or gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle (4-week group). RESULTS: One hundred patients were enrolled in this study. The response rate was 24% (12/51 patients) in the 3-week group and 27% (13/49 patients) in the 4-week group. There were no statistically significant differences between the two treatment groups in survival (hazard ratio: 1.19; 95% CI: 0.68 - 2.09) with a median survival of 12.1 months and 13.8 months in the 3-week group and the 4-week group respectively. The rate of grade 3/4 toxicity in the 3-week group was 55% compared with 86% in the 4-week group (P = 0.001). The difference in the incidence of grade 3/4 haematological toxicities did not reach statistical significance (3-week: 37%, 4-week: 57%), however grade 3/4 drug related neutropenia (3-week: 27%, 4-week: 51%) and thrombocytopenia (3-week: 8%, 4-week: 31%) were significantly lower in the 3-week group. Grade 3/4 nonhaematological toxicities were less in the 3-week group (33% cf 63%; P = 0.005). CONCLUSIONS: The differences in the efficacy endpoints were all in favour of the 4-week schedule of gemcitabine plus cisplatin, however these differences did not reach statistical significance. Fewer grade 3/4 toxicities were observed in the 3-week group compared with the 4-week group.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Povo Asiático/estatística & dados numéricos , Carcinoma Pulmonar de Células não Pequenas/etnologia , China , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Smoking is the major cause of airway inflammation in chronic obstructive pulmonary disease (COPD), and smoking cessation is regarded as one of the important strategies for prevention and treatment of the inflammation. The inflammation of the chronic airway may be present and deteriorated even if the COPD patients stop smoking. Whether and how early smoking cessation affects the progress of inflammation is still obscure. This study was conducted to find the appropriate time for smoking cessation to terminate the airway inflammation in rats with smoke-induced chronic bronchitis. METHODS: A rat model of COPD was established by passively inhaling smoke mixture. Fifty-four young male Sprague-Dawley rats were randomly divided into 9 groups with different periods of smoke exposure and different time points of cessation. The inflammation markers to be detected included inflammatory cells in the bronchoalveolar lavage fluid (BALF), the myeloperoxidose (MPO) activity, the morphologic changes and the expression of ICAM-1 on the airway epithelium. RESULTS: When smoking was terminated at early stage, the inflammatory markers and related indexes were different from those of the typical chronic bronchitis group (group M7) (P < 0.01). The pathologic score of group SC7 (2 weeks of smoking cessation after occurrence of typical chronic bronchitis) was not different from that of group M7, and the level of ICAM-1 was still up-regulated (compared to group M7, P > 0.05). Meanwhile, most of inflammatory cells in BALF were neutrophils compared to other groups (P < 0.01). When smoking was terminated, the MPO activity was significantly lower than that of group M7 (P < 0.01). CONCLUSIONS: Smoking cessation at early stage can effectively inhibit the inflammatory reaction of COPD. Once chronic bronchitis occurs, little could be improved by smoking cessation.
Assuntos
Bronquite/patologia , Inflamação/prevenção & controle , Pulmão/patologia , Abandono do Hábito de Fumar , Animais , Doença Crônica , Molécula 1 de Adesão Intercelular/análise , Masculino , Neutrófilos/fisiologia , Peroxidase/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To improve the understanding of pulmonary sclerosing hemangioma (PSH). METHODS: The clinical data of 15 cases of PSH were analyzed, and the literature was reviewed. The etiology, clinical manifestations, differential diagnosis, treatment and outcome of PSH were described. RESULTS: The etiology and histological origin of PSH were unclear. Most cases were asymptomatic or only with mild symptoms. The radiology of PSH often showed isolated nodule with distinct margin in the lung field. The characteristics of its pathological manifestation were as follows: (1) background of cell gathering or mucin matrix with scattered white blood cells; (2) proliferation of hemangioma with sclerosis of vessel wall; (3) papillary proliferation of small vessels intruding into the air space; (4) existence of hemorrhage or sclerosis zone. Immunohistological studies had not defined the correct histological origin of PSH. A pre-operation diagnosis of PSH was difficult. Thirteen cases had been misdiagnosed as malignancy. The outcome of the disease was good when early surgical resection was performed. CONCLUSIONS: PSH is an uncommon disease, and can be easily misdiagnosed. More attention should be paid to its clinical features and management.
Assuntos
Hemangioma Esclerosante Pulmonar/diagnóstico , Hemangioma Esclerosante Pulmonar/patologia , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine the number of goblet cells, the change of MUC5AC expression in chronic obstructive pulmonary disease (COPD) patients and the relationship of smoking with goblet cell, MUC5AC, and lung function. METHODS: Eighteen patients undergoing lung resections for a solitary peripheral carcinoma were classified by lung function as having COPD. Twenty patients with normal lung function served as the control group. Normal lobe bronchioles far away from the lesion site were taken for paraffin section. Goblet cells were identified by AB/PAS staining and the expression of MUC5AC in the paraffin's section was tested by immunohistochemistry. RESULTS: Goblet cell hyperplasia was observed in the COPD group. The positive rate of goblet cell in COPD group (0.20% +/- 0.10%) was significantly higher than that in the normal lung function group (0.13% +/- 0.06%, P < 0.05). The positive rate of MUC5AC expression in the COPD group (0.27% +/- 0.09%) was higher than that in the normal lung function group (0.20% +/- 0.10%, P < 0.05). The positive rate of goblet cell in smokers (27.93% +/- 9.00%) of the COPD group and normal lung function group was higher than that in non-smokers (17.70% +/- 9.37%, P < 0.05), while MUC5AC expression had no significant difference between smokers and non-smokers (17.88% +/- 6.44% and 10.88% +/- 7.10%, respectively). CONCLUSION: For COPD patients with declined lung function, there were goblet cell hyperplasia and increased expression of MUC5AC. MUC5AC expression up-regulation may due to goblet cell hyperplasia. Smoking may be an important factor for goblet cell hyperplasia.
Assuntos
Células Caliciformes/patologia , Mucinas/biossíntese , Doença Pulmonar Obstrutiva Crônica/metabolismo , Idoso , Brônquios/patologia , Proliferação de Células , Epitélio/patologia , Glândulas Exócrinas/metabolismo , Humanos , Hiperplasia , Pessoa de Meia-Idade , Mucina-5AC , Doença Pulmonar Obstrutiva Crônica/patologia , Fumar , Regulação para CimaRESUMO
BACKGROUND: Platinum-based chemotherapy has been proved effective in patients with advanced non-small cell lung cancer (NSCLC). This study evaluated the effectiveness and safety of first-line chemotherapy with gemcitabine plus cisplatin (GEM-Cis) 3-week regimen in routine care of Chinese patients with advanced NSCLC. METHODS: Two hundred and twenty-one patients with NSCLC stage IIIb or IV were enrolled and 209 were eligible for effectiveness and safety analysis. The median age was 58 (range 29 to 79) years. The percents of cases in stage IV and stage IIIb were 52.2% and 47.8%; of Karnofsky performance score (KPS) less than 80 and 80 - 100 were 37.3% and 62.7% and of adeno-cancer and non-adeno-cancer were 59.8% and 40.2%. The average number of completed chemotherapy cycles was three. Measures of effectiveness included clinical benefit, significant clinical response (SCR) and adverse effects of GEM-Cis in the treatment of NSCLC at stages IIIb/IV. RESULTS: KPS increased from 79 +/- 9 at baseline to 86 +/- 10 after chemotherapy (P < 0.01). Lung cancer symptom scale (LCSS) score of pain, dyspnea and cough increased from 77 +/- 24, 74 +/- 22 and 63 +/- 19 to 92 +/- 15, 90 +/- 14 and 86 +/- 15, respectively (P < 0.01). The clinical benefit rate was 85.2% [95% confidence interval (CI) 80.3% - 90.0%]. The SCR was 89.5% (95% CI 85.3% - 93.7%). Median survival time was 7.8 months (95% CI 7.1 months-9.1 months). Sixty-four patients (30.6%) experienced an adverse effect that was deemed clinically significant. Only one patient (0.5%) was hospitalized due to chemotherapy related adverse effects. Life-threatening toxicity was observed in two patients (1.0%). CONCLUSION: First-line chemotherapy with GEM-Cis in the routine care of Chinese patients with advanced NSCLC is effective and safe.