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1.
Artigo em Inglês | MEDLINE | ID: mdl-31881512

RESUMO

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are prevalent ailments with a great challenge to distinguish them based on symptoms only. Since they require different treatments, it is important to find non-invasive methods capable to readily diagnose them. Moreover, COPD increases the risk of lung cancer development, leading to their comorbidity. In this pilot study the N-glycosylation profile of pooled human serum samples (90 patients each) from lung cancer, COPD and comorbidity (LC with COPD) patients were investigated in comparison to healthy individuals (control) by capillary gel electrophoresis with high sensitivity laser-induced fluorescence detection. Sample preparation was optimized for human serum samples introducing a new temperature adjusted denaturation protocol to prevent precipitation and increased endoglycosidase digestion time to assure complete removal of the N-linked carbohydrates. The reproducibility of the optimized method was <3.5%. Sixty-one N-glycan structures were identified in the pooled control human serum sample and the profile was compared to pooled lung cancer, COPD and comorbidity of COPD with lung cancer patient samples. One important finding was that no other sugar structures were detected in any of the patient groups, only quantitative differences were observed. Based on this comparative exercise, a panel of 13 N-glycan structures were identified as potential glycobiomarkers to reveal significant changes (>33% in relative peak areas) between the pathological and control samples. In addition to N-glycan profile changes, alterations in the individual N-glycan subclasses, such as total fucosylation, degree of sialylation and branching may also hold important glycobiomarker values.


Assuntos
Eletroforese Capilar/métodos , Neoplasias Pulmonares , Polissacarídeos , Doença Pulmonar Obstrutiva Crônica , Comorbidade , Glicômica , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/metabolismo , Projetos Piloto , Polissacarídeos/sangue , Polissacarídeos/química , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Reprodutibilidade dos Testes
2.
Zhonghua Nei Ke Za Zhi ; 58(10): 770-776, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31594176

RESUMO

Objective: To observe the levels of serum reactive oxygen species (ROS) and hydrogen sulfide(H(2)S) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and nicotinamide adenine dinucleotide phosphate-reduced (NADPH) oxidase 4 (NOX4) and cystathionine-γ-lyase (CSE) in lung tissue of patients with stable chronic obstructive pulmonary disease (COPD). Methods: (1) A total of 60 patients with AECOPD admitted to the Department of Respiratory Medicine at Ningxia Hui People's Hospital from November 2015 to December 2016 were recruited. According to the results of pulmonary function and echocardiography, the participants were divided into AECOPD-related pulmonary hypertension (PH) group(A) and AECOPD non-PH group (B).Other 30 healthy subjects were selected as the control group (C).Serum ROS and H(2)S of group A, B and C were detected by enzyme-linked immunosorbent assay (ELISA).(2)The lung tissues of patients undergoing lobectomy for lung cancer from November 2012 to April 2017 were collected, who were divided into COPD-related PH group (D), COPD non-PH group (E) and negative control (F). The expression of NOX4 and CSE protein in lung tissue was detected by immunohistochemistry and the thickness of pulmonary arteriole wall was measured. Results: (1)The serum ROS level in group A was higher than group B and C which were (613.52±69.66)IU/ml,(565.76±71.33)IU/ml, (294.63±60.39)IU/ml, respectively with that in group B higher than that in group C (P<0.05). Serum H(2)S level in group A was lower than group B and C, with that in group B lower than group C [(18.59±5.50) nmol/ml, (20.49±4.97) nmol/ml, (38.03±4.43) nmol/ml, respectively P<0.05]. ROS level was positively correlated with pulmonary systolic pressure (PASP) (r=0.59, P<0.05), H(2)S level was negatively correlated with PASP(r=-0.62, P<0.05).(2)The lung tissue expression of NOX4 in group D was higher than group E and F (P<0.05), which were 0.08±0.01,0.06±0.01,0.03±0.01, respectively,while the level of NOX4 in group E was higher than group F (P<0.05). The expression of CSE between group D, E and F were all significantly different (P<0.05),which were 0.03±0.01, 0.07±0.02,0.12±0.02, respectively.(3)Smooth muscle thickness of pulmonary arterioles as a percentage of vascular diameter (WT%) between group D, E and F was all different(P<0.05), which were (40.58±6.63)%,(36.87±5.60)%,(31.27±6.24)%, respectively; so was smooth muscle area of pulmonary arterioles as a percentage of total vascular area(WA%) with (32.33±6.27)%, (30.20±5.28)%, (25.20±4.31)%, respectively (P<0.05). (4)The expression of NOX4 was positively correlated with WT% and WA%, r was 0.81 and 0.66, respectively (P<0.05). The expression of CSE was negatively correlated with WT% and WA%, r was -0.55 and -0.39 respectively (P<0.05). Conclusions: NOX4/ROS and CSE/H(2)S signaling pathways may play an important role in the pathogenesis of COPD related PH.


Assuntos
Cistationina gama-Liase/metabolismo , Cistationina/metabolismo , Sulfeto de Hidrogênio/sangue , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , NADPH Oxidase 4/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Espécies Reativas de Oxigênio/sangue , Estudos de Casos e Controles , Humanos , Hipertensão Pulmonar/sangue , Oxirredutases , Doença Pulmonar Obstrutiva Crônica/sangue
3.
Pak J Pharm Sci ; 32(4): 1697-1701, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31608892

RESUMO

Chronic Obstructive Pulmonary Disease (COPD), which is caused by various proinflammatory cytokines, will present some kinds of complication with progression such as Pulmonary Artery Hypertension (PAH). CRP (C-Reactive Protein) and ET-1(Endotheline-1) play pivotal function in inflammatory responses. The aim of this study is to investigate the prognosis value of CRP and ET-1 in COPD patients with pulmonary artery hypertension. CRP and ET-1 were measured in the plasma, sputum and exhaled breath condensate (EBC) of 55 COPD patients, 75 COPD patients with PAH and 57 healthy controls. Then, we analyzed the influence of these two proteins on the lung function, pulmonary artery pressure, exercise capacity and other clinical indices. The amount of CRP and ET-1 were the highest in COPD patients with PAH, followed by the COPD patients and the healthy controls. And there were statistically significant differences (p<0.05). The amount of CRP and ET-1 were negatively correlated with the lung function and exercise capacity, positively correlated with the pulmonary artery pressure. CRP and ET-1 are two valuable indicators in the diagnosis of COPD patients with PAH in clinic.


Assuntos
Proteína C-Reativa/análise , Endotelina-1/sangue , Hipertensão Pulmonar/etiologia , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Testes Respiratórios , Estudos de Casos e Controles , Endotelina-1/metabolismo , Exercício , Feminino , Humanos , Hipertensão Pulmonar/sangue , Masculino , Prognóstico , Artéria Pulmonar/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Fumar , Escarro
4.
Monaldi Arch Chest Dis ; 89(3)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31505917

RESUMO

Chewing ability is essential to maintain nutrition status and can be associated with oral conditions, sarcopenia, and lung function in patients with chronic obstructive pulmonary disease (COPD). Herein, our pilot study investigated the chewing ability and degree of desaturation during chewing in patients with COPD (n = 41) and control subjects (n = 22). Subjects chewed a color-changing chewing gum for 1 minute and chewing ability was assessed by the color of the chewed gum, which was scored from 1 (very poor) to 5 (very good). Arterial oxygen saturation (SpO2) was monitored using a pulse oximeter and the difference in SpO2 was determined by comparison between before and during chewing. The mean color score of the chewed gum was lower in the COPD group than in the control group (3.1±0.7 vs 4.2±0.9, p<0.0001). Muscle mass loss (p<0.05), <20 remaining teeth (p<0.005), and COPD (p<0.001) were risk factors for poor chewing ability. The mean SpO2 decreased by 0.78±1.46% during gum chewing for 1 min. The mean SpO2 during gum chewing (95.1±2.4%) was lower than before gum chewing (95.9±1.7%) (p<0.05). The reduction of SpO2 was greater in COPD patients who had fewer remaining teeth (p<0.05). COPD patients with SpO2 reduction >4% during the 6-minute walk test showed greater reduction during gum chewing (p<0.05). Our results suggest that COPD patients with fewer remaining teeth exhibit poor chewing ability and greater desaturation during chewing.


Assuntos
Mastigação/fisiologia , Oxigênio/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Perda de Dente/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Goma de Mascar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Oximetria , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de Risco , Perda de Dente/complicações , Teste de Caminhada
5.
Respir Res ; 20(1): 178, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391053

RESUMO

BACKGROUND: Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting ß2-agonist and long-acting muscarinic antagonist). METHODS: In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution. RESULTS: Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included. Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/µL. Patients with ≥2 exacerbations or eosinophil count ≥400 cells/µL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/µL (76.8% vs 76.5%), respectively in the follow-up year. In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/µL; patients with eosinophil count < 150 cells/µL had the lowest variability. Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/µL across the databases. CONCLUSION: A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions. A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/µL.


Assuntos
Eosinófilos/metabolismo , Vigilância da População , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Exacerbação dos Sintomas , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos Retrospectivos , Reino Unido/epidemiologia , Estados Unidos/epidemiologia
6.
Int J Chron Obstruct Pulmon Dis ; 14: 1527-1537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371938

RESUMO

Purpose: Cigarette smoke produces a high level of acrolein, which is thought to be pathogenically involved in the development of chronic obstructive pulmonary disease (COPD). The present study investigated the pathological role of acrolein in the development of COPD. Patients and methods: Acrolein concentration was measured in plasmas obtained from 47 patients with COPD and 18 current smokers without COPD, and in supernatants of homogenized lung tissues obtained from 10 never-smokers, 8 current smokers, and 8 patients with COPD by high-performance liquid chromatography. Oxidant status and antioxidant activity were measured using derivatives of reactive oxygen metabolite (d-ROM) and bio-antioxidant power (BAP), respectively, in the Free Radical Elective Evaluation FRAS4 system. In addition, immunohistochemistry was used to evaluate the over-presentation of acrolein in lung tissues of patients with COPD. Results: Plasma concentrations of acrolein were significantly higher in the patients with COPD than the non-COPD smokers (P<0.001), which significantly correlated with the oxidant status in patients with COPD (R=0.69, P<0.05). Similar pathological alterations in acrolein concentrations were found in the lung tissue supernatants of patients with COPD, which significantly correlated with the oxidant status in patients with COPD. Furthermore, acrolein was strongly expressed in the lung tissues of patients with COPD. Conclusion: The increased acrolein concentrations were highly involved in the pathogenesis of COPD through interference in the balance of oxidative stress versus antioxidant potentiality.


Assuntos
Acroleína/sangue , Pulmão/metabolismo , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/sangue , Fumar/efeitos adversos , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , não Fumantes , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumantes , Fumar/sangue
7.
Respir Res ; 20(1): 180, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399091

RESUMO

BACKGROUND: CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor. This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD). METHODS: This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study. Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months. Patients received CHF6001 800 or 1600 µg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler). Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32. Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32. RESULTS: Of 61 randomised patients, 54 (88.5%) completed the study. There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes. CHF6001 800 µg significantly decreased the absolute number and percentage of macrophages vs placebo. In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1ß, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα). In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo. CHF6001 1600 µg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide). CONCLUSION: The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov ( NCT03004417 ).


Assuntos
Mediadores da Inflamação/sangue , Inibidores da Fosfodiesterase 4/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Sulfonamidas/administração & dosagem , para-Aminobenzoatos/administração & dosagem , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Broncodilatadores/administração & dosagem , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Escarro/metabolismo , Resultado do Tratamento
8.
Transplant Proc ; 51(6): 2009-2013, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399181

RESUMO

BACKGROUND: The aim of the study was to investigate the serum concentration of cytokines and biochemical markers of malnutrition in correlation with frailty syndrome in patients qualified for lung transplantation (LTx). METHODS: The study population comprised 31 potential lung recipients, including 18 patients with idiopathic lung disease, 12 patients with chronic obstructive pulmonary disease, and 1 patient with bronchiectasis who qualified for a LTx. Cytokine serum levels were assessed using commercially available enzyme-linked immunosorbent assay kits and the Luminex 200 platform (ProcartaPlex Hu Cytokine/Chemokine Panel 1A 34plex, Invitrogen, Carlsbad, Calif., United States). The patients were also asked to complete a questionnaire, the Clinical Frailty Scale. RESULTS: All patients were found to have higher cytokine concentrations (IL6, IL 2,IL18, IL23, IL 12p70, IL 10, IL 7). No statistically significant differences in the analyzed cytokines were noted when the men's results were compared to those of the women. There were no significant differences between patients who scored 6 vs 7 points on the Canadian Study of Health and Aging Function Scale. In comparing chronic obstructive pulmonary disease to idiopathic lung disease patients, no significant differences were observed in the analyzed cytokine values. Significant correlations were observed between the analyzed cytokines and age of the patients, C-reactive protein, triglycerides, transferrin, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. CONCLUSIONS: Our findings indicate that cytokines may not have a statistically significant effect on the parameters of the frailty syndrome. The results require further investigations on larger study groups. The findings suggest that the analyzed cytokines may play a proinflammatory role in the end stages of lung diseases, but further studies are needed to evaluate whether these cytokines could be used as biomarkers in this group of patients.


Assuntos
Citocinas/sangue , Fragilidade/sangue , Pneumopatias/sangue , Transplante de Pulmão/efeitos adversos , Desnutrição/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Canadá , HDL-Colesterol , Contraindicações de Procedimentos , Ensaio de Imunoadsorção Enzimática , Feminino , Fragilidade/complicações , Fragilidade/cirurgia , Humanos , Interleucina-10/sangue , Pulmão/fisiopatologia , Pneumopatias/complicações , Pneumopatias/cirurgia , Masculino , Desnutrição/complicações , Desnutrição/cirurgia , Pessoa de Meia-Idade , Seleção de Pacientes , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/cirurgia , Triglicerídeos/sangue , Adulto Jovem
9.
Respir Res ; 20(1): 176, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382977

RESUMO

BACKGROUND: Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality following an acute exacerbation of COPD (AECOPD). METHODS: Gene expression in whole blood was profiled using the Affymetrix Human Gene 1.1 ST microarray chips from two cohorts: 1) a prednisone cohort with 37 stable COPD patients randomly assigned to prednisone 30 mg/d + standard therapy for 4 days or standard therapy alone and 2) the Rapid Transition Program (RTP) cohort with 218 COPD patients who experienced AECOPD and were treated with systemic corticosteroids. All gene expression data were adjusted for the total number of white blood cells and their differential cell counts. RESULTS: In the prednisone cohort, 51 genes were differentially expressed between prednisone and standard therapy group at a false discovery rate of < 0.05. The top 3 genes with the largest fold-changes were KLRF1, GZMH and ADGRG1; and 21 genes were significantly enriched in immune system pathways including the natural killer cell mediated cytotoxicity. In the RTP cohort, 27 patients (12.4%) died within 1 year after hospitalisation of AECOPD; 32 of 51 genes differentially expressed in the prednisone cohort significantly changed from AECOPD to the convalescent state and were enriched in similar cellular immune pathways to that in the prednisone cohort. Of these, 10 genes including CX3CR1, KLRD1, S1PR5 and PRF1 were significantly associated with 1-year mortality. CONCLUSIONS: Short-term daily prednisone therapy produces a distinct blood gene signature that may be used to determine and monitor treatment responses to prednisone in COPD patients during AECOPD. TRIAL REGISTRATION: The prednisone cohort was registered at clinicalTrials.gov ( NCT02534402 ) and the RTP cohort was registered at ClinicalTrials.gov ( NCT02050022 ).


Assuntos
Glucocorticoides/administração & dosagem , Prednisona/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/genética , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
10.
Int J Chron Obstruct Pulmon Dis ; 14: 1323-1332, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417249

RESUMO

Background: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments. Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry. Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P<0.001, respectively; 8-fold higher for SAA2, P<0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; P<0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed. Conclusions: The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.


Assuntos
Reação de Fase Aguda , Pulmão , Linfócitos/imunologia , Artéria Pulmonar , Doença Pulmonar Obstrutiva Crônica , Proteína Amiloide A Sérica/análise , Proteínas da Fase Aguda/análise , Proteínas da Fase Aguda/imunologia , Reação de Fase Aguda/sangue , Reação de Fase Aguda/imunologia , Correlação de Dados , Feminino , Humanos , Pulmão/imunologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/imunologia , Artéria Pulmonar/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/patologia , Espirometria/métodos
11.
Int J Chron Obstruct Pulmon Dis ; 14: 1559-1566, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409982

RESUMO

Objective: The purpose of this study was to explore the insulin level in the serum of chronic obstructive pulmonary disease (COPD) patients during acute exacerbation (AE). Methods: The study population consisted of 22 acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients, 20 COPD patients and 20 healthy controls. Fasting blood glucose, insulin and serum lipid levels were measured. After the patients recovered from AE, the insulin and glucose levels were also analyzed. Results: Insulin level, glucose level and homeostasis model assessment of insulin resistance (HOMA-IR) of AECOPD patients were higher than healthy controls (7.19±6.02 vs 3.28±1.09 µIU/mL, P<0.05, 126.61±50.92 vs 96.21±12.66 mg/dL, P<0.05, 2.66±2.72 vs 0.78±0.26, P<0.05). For stable COPD patients, the insulin level, glucose level and HOMA-IR were 6.52±2.56 µIU/mL, 95.58±11.44 mg/dL, and 1.52±0.53, respectively. The triglyceride (TG) level, total cholesterol (CHOL) level and low-density lipoprotein cholesterol (LDL-CHOL) level were decreased in AECOPD patients (0.78±0.33 vs 1.05±0.35 mmol/L, P<0.05, 3.88±0.72 vs 4.49±0.7 mmol/L, P<0.05, 2.01±0.59 vs 2.59±0.58 mmol/L, P<0.05). When the patients had recovered from AE, the insulin levels increased (10.67±6.22 vs 7.12±6.19 µIU/mL, P<0.05) and the glucose levels decreased (122.69±41.41 vs 134.08±53.19 mg/dL, P>0.05). Conclusion: A high insulin level and a high HOMA-IR status in COPD patients were demonstrated. Downregulated levels of insulin during AE compared with the convalescent state were detected, while the variation in the glucose level was not as great as expected, indicating a potentially important role for insulin in AECOPD.


Assuntos
Resistência à Insulina , Insulina , Doença Pulmonar Obstrutiva Crônica , Colesterol/sangue , Convalescença , Correlação de Dados , Regulação para Baixo , Retroalimentação Fisiológica , Feminino , Humanos , Insulina/sangue , Insulina/genética , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Exacerbação dos Sintomas , Triglicerídeos/sangue
12.
Int J Chron Obstruct Pulmon Dis ; 14: 1611-1631, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413557

RESUMO

Background: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown. Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD. Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated. Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P<0.05 and P<0.01, respectively). A similar pattern was observed for PBMC chitotriosidase mRNA expression (P<0.001). YKL-40 serum concentrations were elevated in healthy smokers and COPD subjects compared to healthy never-smokers (P<0.001 and P<0.01, respectively). In sputum, YKL-40 levels were increased in COPD compared to healthy never-smokers (P<0.01). PBMC YKL-40 mRNA expression was increased in COPD and healthy smokers compared to healthy never-smokers (P<0.0001). No associations were found between chitotriosidase or YKL-40 peripheral blood levels and sputum levels. Conclusions: Our results demonstrate that chitotriosidase and YKL-40 are overexpressed in peripheral blood and airways in both healthy smokers and COPD subjects which may indicate smoking-related activation of macrophages, neutrophils, and epithelial cells.


Assuntos
Proteína 1 Semelhante à Quitinase-3 , Hexosaminidases , Doença Pulmonar Obstrutiva Crônica , Fumar , Escarro/metabolismo , Proteína 1 Semelhante à Quitinase-3/sangue , Proteína 1 Semelhante à Quitinase-3/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Hexosaminidases/sangue , Hexosaminidases/metabolismo , Humanos , Leucócitos Mononucleares/imunologia , Ativação de Macrófagos , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Fumar/sangue , Fumar/metabolismo , Fumar/patologia
13.
Int J Chron Obstruct Pulmon Dis ; 14: 1669-1680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440043

RESUMO

Background: The temporally dynamic changes of CD25 and Foxp3 expression in CD4+ T cells are initiated by T cell receptor (TCR) signals strength or frequency. There is a deficiency of peripheral markers for assessing COPD activity, and the current study was conducted to explore whether peripheral CD4+ T cell populations based on CD25 and Foxp3 expression could serve as an indicator for COPD inflammatory activity. Methods: The distribution and phenotypic characteristics of CD4+CD25±Foxp3± T cells from peripheral blood in different populations were determined by flow cytometry. The model for the differentiation of CD4+ T cells populations by CD25 and Foxp3 expression was explored in vitro. Results: The frequencies of peripheral CD4+CD25+Foxp3- T cells and CD4+CD25+Foxp3+ T cells were increased in AECOPD patients, whereas the frequency of CD4+CD25-Foxp3+ T cells was increased in SCOPD patients without receiving systemic treatment. Phenotypic analysis revealed that CD4+CD25+Foxp3- T cells, CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells had received antigenic stimulation and resembled central memory or effector memory T cells. The differentiation of CD4+ T cells populations by CD25 and Foxp3 expression was dictated by TCR signals. The paired study indicated that the frequencies of CD4+CD25+Foxp3- T cells, CD4+CD25+Foxp3+ T cells and CD4+CD25- Foxp3+ T cells were decreased while the frequency of CD4+CD25-Foxp3- T cells were increased in the same patients from AECOPD to convalescence. Conclusions: Collectively, we propose that the dynamic changes of CD4+ T cell populations by CD25 and Foxp3 expression could function as potential biomarkers for reflecting inflammatory activity in COPD.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Fatores de Transcrição Forkhead/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Doença Pulmonar Obstrutiva Crônica , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/imunologia , Subpopulações de Linfócitos T/imunologia
14.
Trials ; 20(1): 465, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362776

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common cause of chronic respiratory failure and its course is punctuated by a series of acute exacerbations which commonly lead to hospital admission. Exacerbations are managed through the application of non-invasive ventilation and, when this fails, tracheal intubation and mechanical ventilation. The need for mechanical ventilation significantly increases the risk of death. An alternative therapy, extracorporeal carbon dioxide removal (ECCO2R), has been shown to be efficacious in removing carbon dioxide from the blood; however, its impact on respiratory physiology and patient outcomes has not been explored. METHODS/DESIGN: A randomised controlled open label trial of patients (12 in each arm) with acute exacerbations of COPD at risk of failing conventional therapy (NIV) randomised to either remaining on NIV or having ECCO2R added to NIV with a primary endpoint of time to cessation of NIV. The change in respiratory physiology following the application of ECCO2R and/or NIV will be measured using electrical impedance tomography, oesophageal pressure and parasternal electromyography. Additional outcomes, including patient tolerance, outcomes, need for readmission, changes in blood gases and biochemistry and procedural complications, will be measured. Physiological changes will be compared within one patient over time and between the two groups. Healthcare costs in the UK system will also be compared between the two groups. DISCUSSION: COPD is a common disease and exacerbations are a leading cause of hospital admission in the UK and worldwide, with a sizeable mortality. The management of patients with COPD consumes significant hospital and financial resources. This study seeks to understand the feasibility of a novel approach to the management of patients with acute exacerbations of COPD as well as to understand the underlying physiological changes to explain why the approach does or does not assist this patient cohort. Detailed respiratory physiology has not been previously undertaken using this technique and there are no other randomised controlled trials currently in the literature. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02086084.


Assuntos
Dióxido de Carbono/sangue , Circulação Extracorpórea , Hipercapnia/terapia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração , Biomarcadores/sangue , Terapia Combinada , Progressão da Doença , Circulação Extracorpórea/efeitos adversos , Humanos , Hipercapnia/sangue , Hipercapnia/diagnóstico , Hipercapnia/fisiopatologia , Londres , Ventilação não Invasiva , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
15.
Ned Tijdschr Geneeskd ; 1632019 08 22.
Artigo em Holandês | MEDLINE | ID: mdl-31449361

RESUMO

Most patients with asthma do not receive antibiotics when they experience an exacerbation. In contrast, most patients with COPD exacerbations do indeed receive antibiotics. However, studies have shown that while some subgroups of patients with asthma or COPD may benefit from antibiotics, others do not. In this era of antibiotic stewardship, it is of crucial importance to use objective criteria when deciding whether or not to give antibiotics. Biomarkers, such as procalcitonin, could be helpful when making this decision. There is a clear need for well-designed and high-quality studies with enough power to evaluate the usage of these kinds of biomarkers.


Assuntos
Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Asma/sangue , Biomarcadores/sangue , Tomada de Decisão Clínica , Progressão da Doença , Humanos , Pró-Calcitonina/sangue , Doença Pulmonar Obstrutiva Crônica/sangue
16.
Respir Res ; 20(1): 152, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299954

RESUMO

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking. Yet, how do immune cells relate within and between these two biological compartments, how the pulmonary infiltrate influences the lung transcriptome, and what is the role of active smoking vs. presence of disease is unclear. METHODS: To investigate these questions, we simultaneously collected lung tissue and blood from 65 individuals stratified by smoking habit and presence of the disease. The immune cell composition of both tissues was assessed by flow cytometry, whole lung transcriptome was determined with Affymetrix arrays, and we used Weighted Gene Co-expression Network Analysis (WGCNA) to integrate results. RESULTS: Main results showed that: (1) current smoking and the presence of COPD were both independently associated with a reduction in the proportion of lung T cells and an increase of macrophages, specifically those expressing CD80 + CD163+; (2) changes in the proportion of infiltrating macrophages, smoking status or the level of airflow limitation were associated to different WGCNA modules, which were enriched in iron ion transport, extracellular matrix and cilium organization gene ontologies; and, (3) circulating white blood cells counts were correlated with lung macrophages and T cells. CONCLUSIONS: Mild-moderated COPD lung immune infiltrate is associated with the active smoking status and presence of disease; is associated with changes in whole lung tissue transcriptome and marginally reflected in blood.


Assuntos
Imunidade Celular/fisiologia , Pulmão/imunologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Transcriptoma/fisiologia , Idoso , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Linfócitos T/imunologia , Linfócitos T/metabolismo
17.
Biosens Bioelectron ; 142: 111453, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295711

RESUMO

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death nowadays, and its underdiagnosis is still a great challenge. More effective diagnosis method is in urgent need since the traditional spirometry has many limitations in the practical application. The electrochemical (EC) detection methods have their unique advantages of high accuracy, short response time and easy integration of the system. In this review, recent works on the EC methods for COPD biomarkers including interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) are summarized. Five types of EC methods are highlighted in this study, as enzyme-labelled immunosensors, nanoparticle-labelled immunosensors, capacitive or impedimetric immunosensors, magnetoimmunosensors, and field effect transistor (FET) immunosensors. To date, EC immunosensors have been exhibiting high analytical performance with a detection limit that can achieve several pg/mL or even lower. The simplicity of EC immunosensors makes them a perfect solution for a future point-of-care device to use in settings for COPD diagnosis and follow-up. Nevertheless, more efforts need to be paid on the simultaneous detection of multiple biomarkers, a demand for the clinical diagnosis, and processes of assay simplification towards achieving one-step detection.


Assuntos
Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Animais , Biomarcadores/análise , Biomarcadores/sangue , Técnicas Biossensoriais/instrumentação , Proteína C-Reativa/análise , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Interleucina-6/análise , Interleucina-6/sangue , Interleucina-8/análise , Interleucina-8/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Doença Pulmonar Obstrutiva Crônica/sangue , Saliva/química
18.
PLoS One ; 14(7): e0218932, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291271

RESUMO

BACKGROUND: Factors associated with hospital mortality are unclear in patients with acute exacerbation of COPD (AECOPD) requiring intensive care unit (ICU) admission. We aimed to characterize these patients and identify factors associated with hospital mortality. PATIENTS AND METHODS: We used a retrospective observational case-control design and recruited patients between January 2015 and March 2017. Of 146 patients enrolled, 24 (16.4%) died during their hospital stay, while 122 survived. RESULTS: Multivariate logistic regression analyses revealed factors associated with hospital mortality: age (adjusted odds ratio [AOR] 1.12, 95% CI: 1.03-1.23), C-reactive protein (CRP) level >7.5 mg/dL at the emergency room (AOR 4.52, 95% CI: 1.27-16.04), peak eosinophil-to-neutrophil ratio (ENR)×102 on days 8-14 of treatment (AOR 0.22, 95% CI: 0.08-0.63), and in-hospital complications (AOR 4.23, 95% CI: 1.12-15.98) (all P<0.05). After receiver operating characteristic curve analyses, cutoff level for peak ENR×102 was 0.224. To examine the synergistic effects of CRP level and peak ENR, we divided patients into four groups: (G0, reference group) Peak ENR×102 >0.224 on days 8-14 and initial CRP <7.5 mg/dL; (G1) Peak ENR×102 >0.224 on days 8-14 and initial CRP >7.5 mg/dL; (G2) Peak ENR×102 <0.224 on days 8-14 and initial CRP <7.5 mg/dL; and (G3) Peak ENR×102 <0.224 on days 8-14 and initial CRP >7.5 mg/dL. For G2 and G3 patients, the AOR of mortality was significantly different from that of the reference group (G2: AOR 10.00, P = 0.020; G3: AOR 61.79, P<0.001). The relationship between 28-day mortality and the four groups was statistically significant (log-rank test, P<0.001). CONCLUSION: Older age, initial CRP >7.5 mg/dL, peak ENR on days 8-14, and in-hospital complications were associated with hospital mortality in patients with AECOPD requiring ICU admission. Patients with both biomarkers, initial CRP >7.5 mg/dL, and peak ENR×102 <0.224 on days 8-14 of treatment, had an increased risk of hospital mortality.


Assuntos
Eosinófilos/patologia , Mortalidade Hospitalar/tendências , Hospitalização , Neutrófilos/patologia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Aguda , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Unidades de Terapia Intensiva , Modelos Logísticos , Masculino , Razão de Chances , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Curva ROC , Estudos Retrospectivos
19.
N Engl J Med ; 381(2): 111-120, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31291514

RESUMO

BACKGROUND: Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority). RESULTS: A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was -0.19 points (two-sided 90% CI, -0.33 to -0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation. CONCLUSIONS: CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.).


Assuntos
Antibacterianos/uso terapêutico , Proteína C-Reativa/análise , Prescrição Inadequada/prevenção & controle , Testes Imediatos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Biomarcadores/sangue , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/sangue
20.
Respir Res ; 20(1): 145, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291952

RESUMO

INTRODUCTION: Airway eosinophilic inflammation is a characteristic of asthmatic patients and of a sub group of COPD subjects. Blood eosinophils are deemed as a good surrogate marker of sputum eosinophilic inflammation; however, controversial data have been published particularly in COPD. The aim of our study was to compare blood and sputum eosinophils in COPD and asthmatic patients in "real life". METHODS: Sputum was induced in stable patients with COPD or asthma with hypertonic saline solution and blood eosinophils were evaluated. Frequency of comorbidities was recorded. Correlations were performed stratifying patients by disease and comorbidities. RESULTS: 146 patients, 57 with COPD and 89 with asthma were evaluated. Blood and sputum eosinophils expressed as percentages were correlated in COPD (rho = 0.40; p = 0.004), but the entity of correlation was lower compared with asthmatic subjects (rho = 0.71; p < 0.0001). When blood eosinophils were expressed as counts the correlation was slightly lower than when expressed as percentages in COPD (rho = 0.35; p = 0.01) and in asthmatic patients (rho = 0.68; p < 0.0001). In COPD patients older than 73 years or with blood eosinophils higher than the median value (210.6 eos/µl), or co-diagnosed with hypertension, ischemic heart disease or atrial fibrillation no correlation between blood and sputum eosinophils was found. However, the effect of ischemic heart disease and atrial fibrillation could be driven by hypertension since most of these patients have this comorbidity. CONCLUSION: Blood eosinophils correlated with sputum eosinophils to a lesser degree in COPD than in asthmatic patients. Older age, high blood eosinophils and hypertension affected the correlation between blood and sputum eosinophils, more studies are needed to evaluate the role of other cardiac comobidities.


Assuntos
Asma/sangue , Asma/diagnóstico , Eosinófilos/metabolismo , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Escarro/metabolismo , Idoso , Asma/imunologia , Eosinófilos/imunologia , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/imunologia , Escarro/imunologia
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