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1.
J Korean Med Sci ; 39(6): e51, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374625

RESUMO

BACKGROUND: Lung dysfunction and high apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio are both recognized risk factors for cardiovascular disease. However, few studies have examined the association between the apoB/ApoA-I ratio and lung function. Therefore, we investigated whether this ratio is associated with decreased lung function in a large healthy cohort. METHODS: We performed a cohort study on 68,418 healthy Koreans (34,797 males, mean age: 38.1 years) who underwent a health examination in 2019. ApoB/apoA-I ratio was categorized into quartiles. Spirometric values at the fifth percentile in our population were considered the lower limit of normal (LLN), which was used to define lung function impairment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs), using the lowest quartile as the reference, were estimated to determine lung function impairment. RESULTS: Mean apoB/apoA-I ratio was 0.67 ± 0.21. Subjects with the highest quartile of this ratio had the lowest predicted forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) after controlling for covariates (P < 0.001). However, FEV1/FVC ratio was not significantly different among the four quartiles (P = 0.059). Compared with the lowest quartile (Q1, reference), the aORs (95% CI) for FEV1% < LLN across increasing quartiles (from Q2 to Q4) were 1.216 (1.094-1.351), 1.293 (1.156-1.448), and 1.481 (1.311-1.672) (P for trend < 0.001), respectively. Similarly, the aORs for FVC% < LLN compared with the reference were 1.212 (1.090-1.348), 1.283 (1.147-1.436), and 1.502 (1.331-1.695) with increasing quartiles (P for trend < 0.001). However, the aORs for FEV1/FVC < LLN were not significantly different among groups (P for trend = 0.273). CONCLUSION: High apoB/apoA-I ratio was associated with decreased lung function. However, longitudinal follow-up studies are required to validate our findings.


Assuntos
Apolipoproteína A-I , Pneumopatias , Adulto , Humanos , Masculino , Apolipoproteínas B , Estudos de Coortes , Volume Expiratório Forçado , Pulmão/patologia , Espirometria , Capacidade Vital , Pneumopatias/sangue , Pneumopatias/diagnóstico
2.
J Heart Lung Transplant ; 41(1): 24-33, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34602310

RESUMO

BACKGROUND: Chronic lung allograft dysfunction in lung transplant recipients (LTxRs) has 2 phenotypes: obstructive bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Our goal was to define distinct immunologic markers of exosomes from LTxRs with BOS or RAS. METHODS: Plasma was collected from LTxRs with BOS (n = 18), RAS (n = 13), and from stable LTxRs (n = 5). Antibodies to lung self-antigens (SAgs) were determined by ELISA. Exosomes were isolated by ultracentrifugation. Donor specific antibodies to HLA were quantified using Luminex. Exosomes were characterized for lung SAgs, transcription factors, 20S proteasome, HLA class I and II, and polymeric immunoglobulin receptor protein using western blot. Exosome miRNA was analyzed using NanoString. The exosome-induced immune response was determined in mice. RESULTS: LTxRs with RAS, but not BOS, had donor specific antibodies at diagnosis. CIITA, NFkB, polymeric immunoglobulin receptor protein, 20S proteasome, HLA-DQ, and HLA-DR were significantly higher in RAS exosomes than in BOS exosomes. RAS plasma had high levels of proinflammatory cytokines and distinct exosomal miRNA. Immunization of C57BL/6 mice with RAS exosomes showed severe inflammation and peribronchial fibrosis, whereas BOS exosomes induced patchy inflammation and fibrosis. CONCLUSION: LTxRs with BOS or RAS had exosomes with distinct molecular and immunologic profiles. RAS samples had a higher concentration of proinflammatory factors, HLA class II, lung SAgs, and antibodies to HLA class II molecules, indicating severe allograft injury. Mice immunized with RAS exosomes developed lesions in airways, pleura, interlobular septum, and alveoli, whereas BOS exosomes induced mild to patchy inflammation with lung fibrosis.


Assuntos
Bronquiolite Obliterante/diagnóstico , Exossomos , Pneumopatias/diagnóstico , Transplante de Pulmão , Complicações Pós-Operatórias/diagnóstico , Animais , Bronquiolite Obliterante/sangue , Bronquiolite Obliterante/imunologia , Humanos , Pneumopatias/sangue , Pneumopatias/imunologia , Camundongos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Síndrome
3.
PLoS One ; 16(11): e0259707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34788325

RESUMO

OBJECTIVE: To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. PATIENTS AND METHODS: A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. RESULTS: Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60-80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01-1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5-8.6), low Norton score (OR, 0.87; 95% CI 0.79-0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14-3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12-4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04-1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21-0.78). CONCLUSIONS: Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.


Assuntos
Bactérias Gram-Negativas/patogenicidade , Pneumopatias/sangue , Pneumopatias/microbiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Intervalos de Confiança , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Pneumopatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
4.
Respir Res ; 22(1): 244, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526035

RESUMO

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease. METHOD: This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected. RESULTS: A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004). CONCLUSIONS: Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease.


Assuntos
Hepatopatias/sangue , Pneumopatias/sangue , Polímeros/metabolismo , Deficiência de alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Pneumopatias/diagnóstico , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/epidemiologia
5.
Sci Rep ; 11(1): 19044, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561515

RESUMO

Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94-3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.


Assuntos
Antígeno Carcinoembrionário/sangue , Pneumopatias/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Criança , Comorbidade , Diabetes Mellitus/epidemiologia , Diagnóstico Diferencial , Doenças do Sistema Endócrino/epidemiologia , Feminino , Humanos , Pneumopatias/sangue , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
Nutrients ; 13(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34444684

RESUMO

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years; 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration <50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.


Assuntos
Biomarcadores/sangue , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/sangue , Estado Nutricional/fisiologia , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Disponibilidade Biológica , Estudos de Coortes , Feminino , Genótipo , Humanos , Pneumopatias/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética
7.
Clin Immunol ; 229: 108764, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34089860

RESUMO

C57BL/6 mice with pristane-induced lupus develop macrophage-dependent diffuse alveolar hemorrhage (DAH), which is blocked by treatment with liver X receptor (LXR) agonists and is exacerbated by low IL-10 levels. Serp-1, a myxomavirus-encoded serpin that impairs macrophage activation and plasminogen activation, blocks DAH caused by MHV68 infection. We investigated whether Serp-1 also could block DAH in pristane-induced lupus. Pristane-induced DAH was prevented by treatment with recombinant Serp-1 and macrophages from Serp1-treated mice exhibited an anti-inflammatory M2-like phenotype. Therapy activated LXR, promoting M2 polarization and expression of Kruppel-like factor-4 (KLH4), which upregulates IL-10. In contrast, deficiency of tissue plasminogen activator or plasminogen activator inhibitor had little effect on DAH. We conclude that Serp-1 blocks pristane-induced lung hemorrhage by enhancing LXR-regulated M2 macrophage polarization and KLH4-regulated IL-10 production. In view of the similarities between DAH in pristane-treated mice and SLE patients, Serp-1 may represent a potential new therapy for this severe complication of SLE.


Assuntos
Lúpus Eritematoso Sistêmico/terapia , Macrófagos/efeitos dos fármacos , Serpinas/farmacologia , Proteínas Virais/farmacologia , Animais , Coagulação Sanguínea , Feminino , Hemorragia/sangue , Hemorragia/patologia , Hemorragia/prevenção & controle , Interleucina-10/biossíntese , Fator 4 Semelhante a Kruppel , Receptores X do Fígado/metabolismo , Pneumopatias/sangue , Pneumopatias/patologia , Pneumopatias/prevenção & controle , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/imunologia , Macrófagos/classificação , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Myxoma virus/genética , Células RAW 264.7 , Serpinas/genética , Terpenos/toxicidade , Proteínas Virais/genética
8.
Saudi J Kidney Dis Transpl ; 32(1): 240-244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34145139

RESUMO

Double-positive disease, defined by double-seropositivity for serum anti-glomerular basement membrane (GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA) is a rare cause of pulmonary-renal syndrome. Here, we present an exceptional course of a 20-year-old male with seropositivity for anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies and anti-GBM antibody, who presented first with renal impairment due to focal necrotizing crescentic glomerulonephritis. After receiving treatment, he presented two years later with a relapse manifesting with diffuse alveolar hemorrhage and multiple splenic infarcts. We discuss the clinical presentation patterns and treatment strategies of this entity.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Autoanticorpos/sangue , Glomerulonefrite/sangue , Hemorragia/sangue , Pneumopatias/sangue , Infarto do Baço/sangue , Glomerulonefrite/complicações , Hemorragia/complicações , Humanos , Pneumopatias/complicações , Masculino , Infarto do Baço/complicações , Adulto Jovem
9.
Am J Trop Med Hyg ; 104(6): 1970-1972, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33872210

RESUMO

Based on a previous study and by incorporating new knowledge, the goal of our study was to understand more fully the pathogenesis of hemorrhagic pneumonia of severe human leptospirosis, highlighting the onset of capillary lesions by Leptospira itself and/or its antigenic/toxic products acting on the endothelium and binding to cadherins. Both events lead to loss of endothelial integrity, alter permeability, cause rupture, and open intercellular junctions, contributing to the hemorrhagic phenomena associated with severe leptospirosis.


Assuntos
Hemorragia/microbiologia , Leptospira/patogenicidade , Leptospirose/complicações , Pneumopatias/microbiologia , Animais , Zoonoses Bacterianas/complicações , Humanos , Pneumopatias/sangue , Roedores/microbiologia
10.
J Med Internet Res ; 23(4): e27503, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33857011

RESUMO

BACKGROUND: A decrease in the level of pulse oxygen saturation as measured by pulse oximetry (SpO2) is an indicator of hypoxemia that may occur in various respiratory diseases, such as chronic obstructive pulmonary disease (COPD), sleep apnea syndrome, and COVID-19. Currently, no mass-market wrist-worn SpO2 monitor meets the medical standards for pulse oximeters. OBJECTIVE: The main objective of this monocentric and prospective clinical study with single-blind analysis was to test and validate the accuracy of the reflective pulse oximeter function of the Withings ScanWatch to measure SpO2 levels at different stages of hypoxia. The secondary objective was to confirm the safety of this device when used as intended. METHODS: To achieve these objectives, we included 14 healthy participants aged 23-39 years in the study, and we induced several stable plateaus of arterial oxygen saturation (SaO2) ranging from 100%-70% to mimic nonhypoxic conditions and then mild, moderate, and severe hypoxic conditions. We measured the SpO2 level with a Withings ScanWatch on each participant's wrist and the SaO2 from blood samples with a co-oximeter, the ABL90 hemoximeter (Radiometer Medical ApS). RESULTS: After removal of the inconclusive measurements, we obtained 275 and 244 conclusive measurements with the two ScanWatches on the participants' right and left wrists, respectively, evenly distributed among the 3 predetermined SpO2 groups: SpO2≤80%, 80%

Assuntos
Hipóxia , Oximetria , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , COVID-19/sangue , COVID-19/complicações , Voluntários Saudáveis , Hipóxia/sangue , Hipóxia/complicações , Pneumopatias/sangue , Pneumopatias/complicações , Monitorização Fisiológica , Oximetria/efeitos adversos , Oximetria/normas , Oxigênio/sangue , Estudos Prospectivos , Método Simples-Cego , Punho
11.
Lab Med ; 52(5): 493-498, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33928380

RESUMO

OBJECTIVE: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. METHODS: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. RESULTS: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). CONCLUSION: We found that MR-proADM could represent a prognostic biomarker of COVID-19.


Assuntos
Adrenomedulina/sangue , COVID-19/diagnóstico , Hipertensão/diagnóstico , Pneumopatias/diagnóstico , Precursores de Proteínas/sangue , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Feminino , Humanos , Hipertensão/sangue , Hipertensão/mortalidade , Hipertensão/virologia , Interleucina-6/sangue , Pneumopatias/sangue , Pneumopatias/mortalidade , Pneumopatias/virologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Análise de Sobrevida , Triagem/métodos
13.
Syst Rev ; 10(1): 77, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726854

RESUMO

BACKGROUND: Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We summarise the literature on the performance of different rapid tests for exertional desaturation and draw on this evidence base to provide guidance in the context of acute Covid-19. MAIN RESEARCH QUESTIONS: 1. What exercise tests have been used to assess exertional hypoxia at home or in an ambulatory setting in the context of Covid-19 and to what extent have they been validated? 2. What exercise tests have been used to assess exertional hypoxia in other lung conditions, to what extent have they been validated and what is the applicability of these studies to acute Covid-19? METHOD: AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases were searched to September 2020. Studies where participants had Covid-19 or another lung disease and underwent any form of exercise test which was compared to a reference standard were eligible. Risk of bias was assessed using QUADAS 2. A protocol for the review was published on the Medrxiv database. RESULTS: Of 47 relevant papers, 15 were empirical studies, of which 11 described an attempt to validate one or more exercise desaturation tests in lung diseases other than Covid-19. In all but one of these, methodological quality was poor or impossible to fully assess. None had been designed as a formal validation study (most used simple tests of correlation). Only one validation study (comparing a 1-min sit-to-stand test [1MSTST] with reference to the 6-min walk test [6MWT] in 107 patients with interstitial lung disease) contained sufficient raw data for us to calculate the sensitivity (88%), specificity (81%) and positive and negative predictive value (79% and 89% respectively) of the 1MSTST. The other 4 empirical studies included two predictive studies on patients with Covid-19, and two on HIV-positive patients with suspected pneumocystis pneumonia. We found no studies on the 40-step walk test (a less demanding test that is widely used in clinical practice to assess Covid-19 patients). Heterogeneity of study design precluded meta-analysis. DISCUSSION: Exertional desaturation tests have not yet been validated in patients with (or suspected of having) Covid-19. A stronger evidence base exists for the diagnostic accuracy of the 1MSTST in chronic long-term pulmonary disease; the relative intensity of this test may raise safety concerns in remote consultations or unstable patients. The less strenuous 40-step walk test should be urgently evaluated.


Assuntos
COVID-19/sangue , Teste de Esforço , Exercício Físico , Pneumopatias/diagnóstico , Oxigênio/sangue , Esforço Físico , COVID-19/patologia , COVID-19/virologia , Dispneia , Teste de Esforço/efeitos adversos , Humanos , Hipóxia , Pneumopatias/sangue , Pneumopatias/patologia , Pneumopatias/virologia , Valor Preditivo dos Testes , SARS-CoV-2 , Sensibilidade e Especificidade
14.
Int J Mol Sci ; 22(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671651

RESUMO

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.


Assuntos
COVID-19/imunologia , Proteína Ligante Fas/imunologia , Pneumopatias/imunologia , Pulmão/imunologia , Fatores Etários , Idoso , COVID-19/sangue , Morte Celular/imunologia , Proteína Ligante Fas/sangue , Humanos , Imunidade , Pneumopatias/sangue , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Linfócitos T/imunologia
15.
Clin Epigenetics ; 13(1): 60, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752734

RESUMO

BACKGROUND: DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. RESULTS: We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. CONCLUSIONS: Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.


Assuntos
Células Sanguíneas , Fumar Cigarros/efeitos adversos , Fumar Cigarros/genética , Metilação de DNA , Expressão Gênica , Pneumopatias/induzido quimicamente , Pneumopatias/genética , Proteínas do Tecido Nervoso/genética , Receptores Nicotínicos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Epigenoma , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Pneumopatias/sangue , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Receptores Nicotínicos/metabolismo , Reprodutibilidade dos Testes
16.
Heart Surg Forum ; 24(1): E004-E008, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33635256

RESUMO

BACKGROUND: Cardiac surgery can cause similar inflammatory reactions with infection; antibacterial treatment may be inappropriately used. Early and accurate diagnosis of infection still is a difficult problem worldwide. Procalcitonin (PCT) helps to identify sepsis caused by bacterial infections. However, its application in the diagnosis of pulmonary infections after off-pump coronary artery bypass grafting (OPCABG) has not been well studied. We investigated the early predictive value of PCT for the diagnosis of pulmonary infections after OPCABG. METHODS: We retrospectively analyzed the clinical data, including conditions in the intensive care unit, postoperative complications, mortality rate, plasma PCT in the morning on the first postoperative day, routine white blood cell (WBC) count, and high-sensitivity C-reactive protein (hs-CRP) levels of patients who underwent elective OPCABG. Patients were divided into an infection group and a noninfection group, according to the occurrence of pulmonary infections. A receiver operating characteristic (ROC) curve was used to analyze the predictive value of PCT for the diagnosis of postsurgical infections. RESULTS: In total, 131 patients who underwent OPCABG were included, of whom 23 (17.6%) developed pulmonary infections. The plasma PCT level significantly was higher in the infection group than in the noninfection group (6.0 ± 6.3 ng/ml vs. 2.0 ± 2.2 ng/ml, P = 0.007). WBC and hs-CRP values were not significantly different between the infection group and the noninfection group (12.3 ± 3.9×109/L vs. 11.1 ± 2.8×109/L, P = 0.171 and 12.4 ± 0.7 mg/L vs. 12.4 ± 0.8 mg/L, P = 0.903, respectively). The area under the ROC for predicting pulmonary infections after OPCABG by plasma PCT was 0.783 (P < 0.001, with a 95% confidence interval of 0.674-0.893), with a cut-off value of 3.55 ng/ml, a sensitivity of 0.609, and a specificity of 0.861. CONCLUSION: From our study results, we postulate that PCT has a high early predictive value for the diagnosis of pulmonary infections after OPCABG.


Assuntos
Bactérias/isolamento & purificação , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Pneumopatias/sangue , Pró-Calcitonina/sangue , Infecção da Ferida Cirúrgica/diagnóstico , Biomarcadores/sangue , China/epidemiologia , Doença da Artéria Coronariana/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Pneumopatias/epidemiologia , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/sangue , Infecção da Ferida Cirúrgica/epidemiologia , Taxa de Sobrevida/tendências
17.
Int J Environ Health Res ; 31(7): 823-834, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31722538

RESUMO

Exposure to benzo[a]pyrene (B[a]P) may be a risk factor for pulmonary diseases. To investigate the correlations among B[a]P exposure level, DNA strand breaks and pulmonary inflammation, we recruited 83 children diagnosed with pulmonary diseases and 63 healthy children from Guangzhou, China. Results showed that the levels of Benzo[a]pyrene diol epoxide (BPDE) DNA adduct in blood and IL-8 in serum in case group were significantly higher than those in control group (p < 0.01). Moreover, levels of atmospheric B[a]P in case group was about twice of those in control group, which was consistent with the levels of BPDE-DNA adduct in blood. Significant positive correlations were observed among the levels of BPDE-DNA adduct, IL-8 and DNA strand breaks (p < 0.05). Our findings indicate that environmental air is an important exposure source of B[a]P and higher B[a]P exposure may contribute to the occurrence of pulmonary inflammation and lead to high health risks.


Assuntos
Adutos de DNA/sangue , Interleucina-8/sangue , Pneumopatias/sangue , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Adolescente , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/urina , Monitoramento Biológico , Criança , Pré-Escolar , China , Ensaio Cometa , Quebras de DNA , Feminino , Humanos , Pneumopatias/genética , Linfócitos , Masculino , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/urina , Medição de Risco
18.
Sci Rep ; 10(1): 22042, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33328527

RESUMO

The objective of this study was to evaluate a novel microstream method by comparison with PaCO2 and the more standard mainstream capnometer in intubated pediatric patients. We hypothesized that the novel microstream method would superior compared to the traditional mainstream method in predicting PaCO2. This was a prospective single-center comparative study. The study was carried out on 174 subjects with a total of 1338 values for each method. Data were collected prospectively from mainstream and microstream capnometer simultaneously and compared with PaCO2 results. Although both mainstream PetCO2 (mainPetCO2) and microstream PetCO2 (microPetCO2) were moderately correlated (r = 0.63 and r = 0.68, respectively) with PaCO2 values, mainPetCO2 was in better agreement with PaCO2 in all subjects (bias ± precision values of 3.8 ± 8.9 and 7.3 ± 8.2 mmHg, respectively). In those with severe pulmonary disease, the mainPetCO2 and microPetCO2 methods were highly correlated with PaCO2 (r = 0.80 and r = 0.81, respectively); however, the biases of both methods increased (14.8 ± 9.1 mmHg and 16.2 ± 9.0 mmHg, respectively). In cases with increased physiologic dead space ventilation, the agreement levels of mainPetCO2 and microPetCO2 methods became distorted (bias ± precision values of 20.9 ± 11.2 and 25.0 ± 11.8 mm Hg, respectively) even though mainPetCO2 and microPetCO2 were highly correlated (r = 0.78 and r = 0.78, respectively). It was found that the novel microstream capnometer method for PetCO2 measurements provided no superiority to the traditional mainstream method. Both capnometer methods may be useful in predicting the trend of PaCO2 due to significant correlations with the gold standard measurement in cases with severe pulmonary disease or increased physiological dead space -despite reduced accuracy.


Assuntos
Capnografia , Dióxido de Carbono/sangue , Pneumopatias/sangue , Pneumopatias/terapia , Respiração Artificial , Monitorização Transcutânea dos Gases Sanguíneos , Criança , Pré-Escolar , Estado Terminal , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
19.
Comput Math Methods Med ; 2020: 7984565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133226

RESUMO

OBJECTIVE: This paper was aimed at investigating the effects of bronchoalveolar lavage (BAL) with ambroxol hydrochloride (AH) on treating pulmonary infection and on serum proinflammatory cytokines and oxidative stress responses in patients with cerebral infarction (CI). METHODS: One hundred and two patients with cerebral infarction complicated with pulmonary infection (CIPI) who were treated in our hospital were enrolled as research objects, divided into an observation group (52 cases; AH combined with BAL) and a control group (50 cases; single AH) based on therapeutic schemes. They were compared in terms of the therapeutic effect and pre- and posttreatment serum inflammatory cytokines, pulmonary function, and serum indices of oxidative stress. Their adverse reactions during treatment were also recorded and compared. RESULTS: The therapeutic effect in the observation group was remarkably better than that in the control group (P < 0.05). After treatment, the serum inflammatory cytokines, pulmonary function, and serum indices of oxidative stress were remarkably improved in the two groups (P < 0.05), but the improvement was remarkably better in the observation group (P < 0.05). The differences were not significant in intratreatment adverse reactions between the two groups (P > 0.05). CONCLUSION: For CIPI patients, BAL with AH has a better therapeutic effect and higher safety and can control the patients' systemic inflammatory responses and oxidative stress responses, so it is worthy of further promotion in clinical practice.


Assuntos
Ambroxol/administração & dosagem , Infarto Cerebral/complicações , Pneumopatias/complicações , Pneumopatias/tratamento farmacológico , Infecções Respiratórias/complicações , Infecções Respiratórias/tratamento farmacológico , Lavagem Broncoalveolar , Estudos de Casos e Controles , Infarto Cerebral/sangue , Biologia Computacional , Citocinas/sangue , Expectorantes/administração & dosagem , Feminino , Humanos , Mediadores da Inflamação/sangue , Pneumopatias/sangue , Masculino , Malondialdeído/sangue , Conceitos Matemáticos , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Infecções Respiratórias/sangue , Superóxido Dismutase/sangue
20.
Respir Res ; 21(1): 273, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076916

RESUMO

BACKGROUND: Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification. METHODS: Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes. RESULTS: The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial. CONCLUSIONS: Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.


Assuntos
Imunoglobulina G/sangue , Pneumopatias/sangue , Pneumopatias/diagnóstico por imagem , Testes de Função Respiratória/tendências , Adulto , Idoso , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Plasmócitos/metabolismo , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
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