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1.
Int J Mol Sci ; 22(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34281240

RESUMO

In smoking-induced chronic obstructive pulmonary disease (COPD), various comorbidities are linked to systemic inflammation and infection-induced exacerbations. The underlying mechanisms are unclear but might provide therapeutic targets. T-cell activity is central in systemic inflammation and for infection-defense mechanisms and might be influenced by comorbidities. Hypothesis: Circulating biomarkers of comorbidities modulate the activity of T-cells of the T-helper type 1 (Th1) and/or T-cytotoxic type 1 (Tc1). T-cells in peripheral blood mononuclear cells (PBMCs) from non-smokers (NS), current smokers without COPD (S), and COPD subjects (total n = 34) were ex vivo activated towards Th1/Tc1 and were then stimulated with biomarkers for metabolic and/or cardiovascular comorbidities (Brain Natriuretic Peptide, BNP; chemokine (C-C motif) ligand 18, CCL18; C-X3-C motif chemokine ligand 1, CX3CL1; interleukin-18, IL-18) or for asthma- and/or cancer-related comorbidities (CCL22; epidermal growth factor, EGF; IL-17; periostin) each at 10 or 50 ng/mL. The Th1/Tc1 activation markers interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in culture supernatants by Enzyme-Linked Immunosorbent Assay (ELISA). Ex-vivo activation induced IFNγ and TNFα without differences between the groups but GM-CSF more in S vs. NS. At 10 ng/mL, the different biomarkers increased or reduced the T-cell activation markers without a clear trend for one direction in the different categories of comorbidities or for the different T-cell activation markers. At 50 ng/mL, there was a clear shift towards suppressive effects, particularly for the asthma- and cancer-related biomarkers and in cells of S and COPD. Comorbidities might suppress T-cell immunity in COPD. This could explain the association of comorbidities with frequent exacerbations.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumar/efeitos adversos , Linfócitos T/fisiologia , Estudos de Casos e Controles , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumantes , Fumar/sangue
2.
Vasc Health Risk Manag ; 17: 103-109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790567

RESUMO

Introduction: Smoking can cause vascular damage in the form of an inflammatory reaction characterized by endothelial activation. Endothelial activation forms a pathological adaptation pattern so that it can induce the atherogenesis process. Several markers, such as E-selectin, platelet-derived micro particles (PMPs) and hematopoietic stem cell (HSC) can identify the activation of endothelial in circulating blood. Therefore, the deviation of vascular adaptation due to smoking can be detected early through the feedback mechanism between E-selectin, PMPs, and HSC. Purpose: This study aims to analyze the initial picture of the negative impact of smoking on vascular adaptation by measuring E-selectin, PMPs, and HSC in the peripheral blood circulation. Participant criteria and methods: Peripheral blood samples (5 mL) were taken from each participant, both the smoking group (n = 30) and the non-smoker group (n = 31) to obtain peripheral blood mononuclear cells (PBMNC). PBMNC was isolated using ficoll-based gradient centrifugation. The flow cytometry assay method used to measure the E-selectin, PMPs and hematopoietic stem cells. Results: The mean of circulating E-selectin in smokers was higher than that of non-smokers. On the other hand, the average number of PMPs and HSCs in smokers was lower than non-smokers. Conclusion: Smoking increases the risk of accelerated vascular block formation, as indicated by an increase in the amount of circulating E-selectin. The increase in E-selectin in the blood vessels mediates the increased adhesion of PMPs in the vascular area so that the number of circulating PMPs in smokers decreases. The decrease in circulating PMPs decreases the signal of vascular repair, which is characterized by a decline in the number of HSCs.


Assuntos
Plaquetas/metabolismo , Doenças Cardiovasculares/diagnóstico , Micropartículas Derivadas de Células/metabolismo , Selectina E/sangue , Células Endoteliais/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Fumantes , Fumar/efeitos adversos , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Precoce , Células Endoteliais/patologia , Humanos , não Fumantes , Valor Preditivo dos Testes , Fumar/sangue , Fatores de Tempo
3.
BMC Cancer ; 21(1): 130, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549031

RESUMO

BACKGROUND: The RAS family protooncogenes, including KRAS, NRAS and HRAS, encode proteins responsible for the regulation of growth, differentiation and survival of many cell types. The HRAS and KRAS oncogene mutations are well defined, however, the clinical significance of RAS expressions in non-small-cell lung cancer (NSCLC) is still uncertain. METHODS: A total of 39 whole blood samples of NSCLC (the investigated group), collected at three points of time: at the time of diagnosis, 100 days and 1 year after the surgery as well as 35 tissue samples obtained during the surgery were included in this study. HRAS and KRAS genes mRNA expression were assessed using quantitative real-time polymerase chain reaction techniques. RESULTS: Increased relative HRAS mRNA level in blood was found significantly more frequently in the group of smokers (p = 0.008). Patients with squamous cell carcinoma subtypes of NSCLC were more likely to show an overexpression of HRAS gene in blood, but not statistically significant (p = 0.065). In tumor tissue overexpression of HRAS gene was associated with adenocarcinoma subtype (p = 0.049). No statistically significant associations were found for the expression of KRAS with any clinicopathological parameters, except the age of patients, within the study. There were no differences between the relative HRAS and KRAS genes expression levels in blood samples taken from the same patients during the 3 observation points, as well as between blood collected from patients before surgery and tissue samples obtained during operation. CONCLUSION: The potential associations between high HRAS expression levels, age, smoking status and histological type of cancer were observed, which emphasizes the need for further study of the RAS family. Therefore, subsequent research involving larger numbers of patients and a longer follow-up, as well as multicenter study are necessary to confirm our findings.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Expressão Gênica , Genes ras , Neoplasias Pulmonares/genética , RNA Mensageiro/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras)/sangue , Estudos Retrospectivos , Fumar/sangue , Fatores de Tempo
4.
Acta Neurol Scand ; 143(4): 367-374, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33528038

RESUMO

OBJECTIVE: We aimed to estimate the status of risk factor control after ischemic stroke or transient ischemic attack (IS/TIA), and the influence on recurrent stroke in rural communities of northeastern China. METHODS: This population-based, prospective cohort study enrolled adults aged ≥35 years residing in rural northeastern China. We conducted cardiovascular health examinations in 2012-2015 and followed up in 2018 to record any cardiovascular event. Control of risk factors after IS/TIA was determined through a baseline survey. The Cox proportional hazard model was used to evaluate the relationship between uncontrolled risk factors and stroke recurrence. RESULTS: Of the 10,700 participants, 575 were diagnosed with IS/TIA and were included in the analysis. At baseline, the rates of control of risk factors were as follows: fasting plasma glucose (FPG), 81.6%; not currently smoking, 65.7%; and achieving physical activity targets, 61%. Blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and body mass index (BMI) were poorly controlled (28.3%, 26.3%, and 37.4%, respectively). The rate of stroke recurrence was 12% during a median follow-up of 4.43 years. After adjusting for age, sex, ethnicity, family history of stroke, and current drinking, uncontrolled BP and not achieving physical exercise targets were associated with an increased risk of recurrence (hazard ratios: 2.081, 1.685, respectively; p < .05). Uncontrolled FPG, BMI, or LDL-C and current smoking did not significantly influence recurrent risk (p > .05). CONCLUSIONS: Control of risk factors after IS/TIA needs to be improved in rural communities of northeastern China to prevent recurrence and thus alleviate the public health and economic burden of stroke.


Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/epidemiologia , AVC Isquêmico/sangue , AVC Isquêmico/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Isquemia Encefálica/diagnóstico , China/epidemiologia , LDL-Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Humanos , Ataque Isquêmico Transitório/diagnóstico , AVC Isquêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , População Rural/tendências , Fumar/efeitos adversos , Fumar/sangue , Fumar/epidemiologia
5.
Sci Rep ; 11(1): 680, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436844

RESUMO

Active smoking has been linked to modulated gene expression in blood. However, there is a need for a more thorough understanding of how quantitative measures of smoking exposure relate to differentially expressed genes (DEGs) in whole-blood among ever smokers. This study analysed microarray-based gene expression profiles from whole-blood samples according to smoking status and quantitative measures of smoking exposure among cancer-free women (n = 1708) in the Norwegian Women and Cancer postgenome cohort. When compared with never smokers and former smokers, current smokers had 911 and 1082 DEGs, respectively and their biological functions could indicate systemic impacts of smoking. LRRN3 was associated with smoking status with the lowest FDR-adjusted p-value. When never smokers and all former smokers were compared, no DEGs were observed, but LRRN3 was differentially expressed when never smokers were compared with former smokers who quit smoking ≤ 10 years ago. Further, LRRN3 was positively associated with smoking intensity, pack-years, and comprehensive smoking index score among current smokers; and negatively associated with time since cessation among former smokers. Consequently, LRRN3 expression in whole-blood is a molecular signal of smoking exposure that could supplant self-reported smoking data in further research targeting blood-based markers related to the health effects of smoking.


Assuntos
Biomarcadores/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Fumar/efeitos adversos , Fumar/genética , Transcriptoma/efeitos dos fármacos , Adulto , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Noruega/epidemiologia , Estudos Prospectivos , Fumar/sangue , Fumar/epidemiologia , Abandono do Hábito de Fumar/estatística & dados numéricos
6.
PLoS One ; 16(1): e0241623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33434198

RESUMO

Smoking, metabolic syndrome (MetS), and major adverse cardiovascular events (MACEs) are important global health problems. We aimed to investigate the association between smoking, alteration in MetS status, and the consequent risk of MACE. We performed a nationwide observational cohort study based on the claims database of Korea. We included people with ≥ 3 national health screenings from 2009 to 2013. Total 6,099,717 people, including 3,576,236 nonsmokers, 862,210 ex-smokers, 949,586 light-to-moderate smokers, and 711,685 heavy smokers, at the first health screening, were investigated. First, we performed a logistic regression analysis using smoking status at the first screening as the exposure variable and MetS development or recovery as the outcome variable. Second, we performed a Poisson regression using smoking status at the third screening as the exposure variable and the outcome was risk of incident MACEs. Among those previously free from MetS (N = 4,889,493), 347,678 people developed MetS, and among those who had previous MetS (N = 1,210,224), 347,627 people recovered from MetS. Smoking was related to a higher risk of MetS development [for heavy smokers: adjusted OR 1.71 (1.69 to 1.73)] and a lower probability of MetS recovery [for heavy smokers: adjusted OR 0.68 (0.67 to 0.69)]. Elevated triglycerides was the MetS component with the most prominent association with smoking. The risk for incident MACEs (78,640 events during a median follow-up of 4.28 years) was the highest for heavy smokers, followed in order by light-to-moderate, ex-smokers and nonsmokers, for every MetS status. Therefore, smoking may promote MetS or even hinder recovery from MetS. Smoking cessation should be emphasized to reduce MACE risk even for those without MetS.


Assuntos
Doenças Cardiovasculares , Síndrome Metabólica , Fumar , Triglicerídeos/sangue , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar/sangue , Fumar/epidemiologia
7.
Clin Hemorheol Microcirc ; 77(1): 27-36, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32651309

RESUMO

INTRODUCTION: Adipose derived Stem Cells (ASCs) have been proven to play a key role in tissue regeneration. However, exposure to large amounts of cigarette smoke can drastically diminish their function. Erythropoetin (EPO), can modulate cellular response to injury. Therefore, we investigated the ability of EPO to restore the regenerative function and differentiation capacity of ASCs. MATERIAL AND METHODS: Human ASCs were isolated from abdominoplasty samples using standard isolation procedures. Cell identity was established by means of Fluorescence Activated Cell Scanning. Subsequently, isolated ASCs were cultivated with cigarette smoke extract both with and without EPO. Parameters investigated included cellular metabolic activity, adipogenic and osteogenic differentiation capacity, and in vitro wound closure capacity. For further enhancing wound closure, EPO was combined with Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) or Stromal Derived Factor-1 alpha (SDF-1 a). RESULTS: Cigarette smoke reduces adipogenic differentiation, the osteogenic differentiation capacity as well as the in vitro wound healing ability of human derived ASCs. EPO did not change metabolic activity of ASCs significantly. The addition of EPO could partially restore their function. The combination of EPO with GM-CSF or SDF-1 did not result in a synergistic effect regarding wound healing ability. CONCLUSION: Exposure to cigarette smoke significantly reduced the regenerative potential of ASCs. Treatment of ASCs exposed to cigarette smoke with EPO has the potential to partially restore their function.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Eritropoetina/uso terapêutico , Fumar/efeitos adversos , Células-Tronco/metabolismo , Adipócitos/citologia , Tecido Adiposo/citologia , Diferenciação Celular , Eritropoetina/farmacologia , Humanos , Fumar/sangue , Células-Tronco/citologia
8.
Nutr Metab Cardiovasc Dis ; 31(1): 153-161, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32981798

RESUMO

BACKGROUND AND AIMS: Limited number of studies investigated lipid profile in chronic obstructive pulmonary disease (COPD) with inconsistent results. This study aimed to investigate lipid parameters in sera of patients with stable COPD and their associations with disease severity, smoking, comorbidities and therapy. METHODS AND RESULTS: The study included 137 COPD patients and 95 controls. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were assessed. Non-HDL-C (NHC), atherogenic coefficient (AC), TG/HDL-C, atherogenic index of plasma (AIP), Castelli's risk index I and II (CRI-I, CRI-II), and monocyte to HDL ratio (MHR) were calculated. HDL-C and MHR were increased, while other lipid parameters and indices were decreased in COPD patients compared to healthy individuals. Smoking did not influence lipid parameters. However, lipid profile was altered only in more severe disease stages. AC, CRI-I and CRI-II showed positive association with lung function parameters in COPD patients, and negative with COPD multicomponent indices (ADO, BODCAT, BODEx, CODEx and DOSE). Combined model that included CRI-II, C-reactive protein, fibrinogen and white blood cells showed great diagnostic performances, and correctly classified 72% of study participants with an AUC of 0.800 (0.742-0.849), P < 0.001. Bronchodilator monotherapy and statins have opposite impact on TC, LDL-C and NHC, while TG, TG/HDL-C and AIP were increased in COPD patients with cardiovascular diseases. CONCLUSION: Lipid disbalance is present in COPD, and it seems to occur later as the disease progresses. Further studies are needed to illuminate the underlying mechanism of dyslipidaemia.


Assuntos
Aterosclerose/sangue , Dislipidemias/sangue , Lipídeos/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Broncodilatadores/uso terapêutico , Comorbidade , Dislipidemias/diagnóstico , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fumar/efeitos adversos , Fumar/sangue
9.
Clin Neurol Neurosurg ; 200: 106368, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33260085

RESUMO

AIM: To reveal the correlation between total cerebrovascular disease load and primary lacunar infarction. BACKGROUND: Cerebral small vessel disease (CSVD) is the lack of specific clinical manifestations, whose clinical diagnoses are highly dependent on neuroimaging results. Total CSVD load scores may be more suitable for the assessment of overall brain function damage caused by CSVD. Little is known about whether the association between imaging markers of CSVD and CSVD total load scores at the time of first-ever lacunar infarction (LI). METHODS: clinical data of 396 patients hospitalised from September 2016 to May 2018 due to a first-ever LI (case group), along with patients diagnosed with CSVD based on imaging alone and those with no abnormalities (control group) based on magnetic resonance imaging (MRI). Binary logistic regression and multiple ordered logistic regression were used to analyse the characteristics of imaging markers of CSVD in patients with first-ever LI, including different total score burden and distribution, and the relationship between different markers. RESULTS: In 396 patients, smoking, cholesterol level and total small vessel disease (SVD) score were all significantly associated with the first-ever LI. There were more LI, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and moderate to severe enlarged perivascular spaces (EPVS) in the first-ever LI group, relative to controls (p < 0.01). The Fazekas scores for periventricular WMH, deep WMH, and total Fazekas score were all significantly higher in patients with first-ever LI relative to those with no cerebral abnormalities (p < 0.01). An analysis of various imaging markers of CSVD revealed a significant correlation between the presence and degree of any marker and the severity of other markers, even after adjusting for the presence of other markers (p < 0.05). CONCLUSIONS: The first-ever LI group exhibited higher total CSVD score loads, a greater number of lacunae, CMB, severe WMH and moderate to severe EPVS. Smoking is an independent risk factor in patients with first-ever LI.


Assuntos
Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças de Pequenos Vasos Cerebrais/sangue , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/tendências , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fumar/sangue , Fumar/epidemiologia , Fumar/tendências , Acidente Vascular Cerebral Lacunar/sangue
10.
Am J Addict ; 30(1): 88-91, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32488890

RESUMO

BACKGROUND AND OBJECTIVES: In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, ß-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking. METHODS: Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests. RESULTS: We found significant positive correlations for cotinine and oxytocin (P = .002), ß-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These preliminary results suggest a relationship between cotinine and oxytocin, ß-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).


Assuntos
Alcoolismo/sangue , Cotinina/metabolismo , Orexinas/sangue , Ocitocina/sangue , Tabagismo/sangue , beta-Endorfina/sangue , Adulto , Consumo de Bebidas Alcoólicas/sangue , Feminino , Humanos , Masculino , Melatonina/sangue , Pessoa de Meia-Idade , Saliva/química , Fumar/sangue , Substância P/sangue , alfa-MSH/sangue , gama-Glutamiltransferase/sangue
11.
Psychopharmacology (Berl) ; 238(3): 825-831, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33270145

RESUMO

RATIONALE: The degree to which the EU version of Juul with 20 mg/ml nicotine (Juul EU) delivers nicotine to users is likely to determine its treatment potential. OBJECTIVES: To compare the pharmacokinetic profile and user ratings of Juul EU, Juul US (59 mg/ml nicotine), cigarettes and other e-cigarette (EC) products. METHODS: In a within-subjects crossover design, 18 vapers used, at separate sessions, their own brand cigarette (OBC), Juul US and Juul EU for 5 min ad libitum, after overnight abstinence. Seven of the participants also tested eight other EC previously. Blood samples were taken at baseline and 2, 4, 6, 8, 10 and 30 min after initiating product use. Products were rated on a range of characteristics. RESULTS: Juul EU delivered less nicotine than OBC (t(13) = -4.64 p < .001) and than Juul US (t(13) = -6.40, p < .001): AUC0 ≥ 30 77.3, 324.8 and 355.9, respectively. Maximum nicotine concentration (Cmax) was also much lower for Juul EU than Juul US (z = -3.59, p < .001): Cmax 3.8 ng/ml vs 21.1 ng/ml, respectively. Juul EU was perceived to relieve urges to smoke less than Juul US (z = -2.29, p = .022) and to provide less nicotine (z = -2.57. p = 0.010). Juul EU delivered less nicotine than refillable EC (Cmax: t(6) = 3.02, p = 0.023; AUC0 ≥ 30: z = -2.20, p = 0.028) and also less than cig-a-like EC, though the difference did not reach significance (Cmax: t(6) = 2.49, p = 0.047; AUC0 ≥ 30: z = -1.99, p = 0.046). Subjective ratings of Juul EU and other EC products were similar. CONCLUSIONS: Juul EU delivers much less nicotine to users than Juul US, and also less than refillable EC products. It may thus have more limited potential to help smokers quit.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina/administração & dosagem , Nicotina/sangue , Fumantes/psicologia , Fumar , Estudos Cross-Over , Feminino , Humanos , Masculino , Fumar/sangue , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Redução do Consumo de Tabaco/psicologia , Produtos do Tabaco
12.
Eur J Pharmacol ; 891: 173762, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33253680

RESUMO

Little information is available on the influence of sex in combination with smoking habits and combined oral contraceptives (COC) use on cellular inflammatory indexes such as neutrophil/lymphocyte ratio (NLR), derived NRL (dNLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), mean platelet volume/platelet count (MPV/PLT), aggregate inflammation systemic index (AISI), and systemic inflammation response index (SIRI), which are cost-effective biomarkers to assessing inflammation. Therefore, the effect of COC was studied alone or in association with smoking and compared with results from healthy COC-free women and men. Furthermore, the association of cellular inflammatory indexes with endothelial function (arginine (Arg), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and lipid peroxidation (malondialdehyde MDA) biomarkers was evaluated. Blood was collected for hematological and biochemical analysis, which were used to calculate PLR, NLR, dNLR, MLR, MPV/PLT, AISI, and SIRI. Serum samples were assayed for Arg, ADMA, SDMA, and MDA. Monocytes, MLR, SIRI, and MPV/PLT were higher in men, while PLT count was higher in women. COC use increased lymphocytes and lowered PLR and MLR. Smoking reduced sexually divergent parameters, especially in COC users: smoking and non-smoking COC-free women displayed six divergent parameters, while COC users displayed only two (monocytes and MPV). In addition, COC affected endothelial function, reducing ADMA and Arg. Moreover, COC-free women had lower Arg levels than men. In conclusion, COC use strongly influence the effects of tobacco smoking, which are sex and parameter specific. Further, these data stress that COC use and smoking attitude select different cohorts indicating that sex and gender studies need intersectionality.


Assuntos
Plaquetas/efeitos dos fármacos , Anticoncepcionais Orais Combinados/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Inflamação/etiologia , Leucócitos/efeitos dos fármacos , Fumar/efeitos adversos , Adulto , Biomarcadores/sangue , Plaquetas/imunologia , Plaquetas/metabolismo , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Inflamação/sangue , Inflamação/imunologia , Leucócitos/imunologia , Leucócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fumar/sangue , Fumar/imunologia
13.
Psychopharmacology (Berl) ; 238(3): 665-676, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33230696

RESUMO

INTRODUCTION: The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment. METHODS: Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. RESULTS: The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01). DISCUSSION: In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine.


Assuntos
Antipsicóticos/sangue , Monitoramento de Medicamentos/métodos , Olanzapina/sangue , Transtornos Psicóticos/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/uso terapêutico , Transtornos Psicóticos/sangue , Transtornos Psicóticos/psicologia , Fumar/sangue , Resultado do Tratamento , Ganho de Peso/efeitos dos fármacos
14.
J Urol ; 205(5): 1321-1325, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33356484

RESUMO

PURPOSE: Cigarette smoking is a risk factor for developing nonmuscle invasive bladder cancer, and continued smoking exposure after diagnosis may increase the likelihood of adverse clinical outcomes. We compare self-reported vs biochemically verified nicotine exposure to determine the accuracy of self-report among recently diagnosed nonmuscle invasive bladder cancer patients. MATERIALS AND METHODS: This cross-sectional analysis consisted of 517 nonmuscle invasive bladder cancer patients who contributed a urine or saliva specimen the same day as self-reporting their smoking, use of e-cigarettes, nicotine replacement therapy and whether they lived with a smoker. Cotinine, the primary metabolite of nicotine, was used as an objective biomarker of recent nicotine exposure. RESULTS: The prevalence of high, low and no cotinine exposure was 13%, 54% and 33%, respectively. Overall, 7.3% of patients (38/517) reported being a current cigarette smoker, while 13% (65/517) had cotinine levels consistent with active smoking exposure. Of these 65 patients 27 denied current smoking, resulting in a sensitivity of self-reported current smoking of 58%. After considering other sources of nicotine exposure such as e-cigarettes, cigars, nicotine replacement therapy and living with a smoker, the sensitivity was higher, at 82%. Nearly all patients with low cotinine denied any smoking-related exposure. CONCLUSIONS: Our findings suggest either biochemical verification with cotinine or additional questions about other sources of nicotine are needed to accurately identify nonmuscle invasive bladder cancer patients who have smoking-related exposures. Accurate classification of active and passive smoking exposure is essential to allow clinicians to advise cessation and help researchers estimate the association between post-diagnosis smoking-related exposure and nonmuscle invasive bladder cancer recurrence risk.


Assuntos
Cotinina/sangue , Cotinina/urina , Autorrelato , Fumar/sangue , Fumar/urina , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Reprodutibilidade dos Testes , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Adulto Jovem
15.
Cochrane Database Syst Rev ; 12: CD013413, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33284989

RESUMO

BACKGROUND: Populations experiencing homelessness have high rates of tobacco use and experience substantial barriers to cessation. Tobacco-caused conditions are among the leading causes of morbidity and mortality among people experiencing homelessness, highlighting an urgent need for interventions to reduce the burden of tobacco use in this population. OBJECTIVES: To assess whether interventions designed to improve access to tobacco cessation interventions for adults experiencing homelessness lead to increased numbers engaging in or receiving treatment, and whether interventions designed to help adults experiencing homelessness to quit tobacco lead to increased tobacco abstinence. To also assess whether tobacco cessation interventions for adults experiencing homelessness affect substance use and mental health. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register, MEDLINE, Embase and PsycINFO for studies using the terms: un-housed*, homeless*, housing instability, smoking cessation, tobacco use disorder, smokeless tobacco. We also searched trial registries to identify unpublished studies. Date of the most recent search: 06 January 2020. SELECTION CRITERIA: We included randomized controlled trials that recruited people experiencing homelessness who used tobacco, and investigated interventions focused on the following: 1) improving access to relevant support services; 2) increasing motivation to quit tobacco use; 3) helping people to achieve abstinence, including but not limited to behavioral support, tobacco cessation pharmacotherapies, contingency management, and text- or app-based interventions; or 4) encouraging transitions to long-term nicotine use that did not involve tobacco. Eligible comparators included no intervention, usual care (as defined by the studies), or another form of active intervention. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. Tobacco cessation was measured at the longest time point for each study, on an intention-to-treat basis, using the most rigorous definition available. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study where possible. We grouped eligible studies according to the type of comparison (contingent reinforcement in addition to usual smoking cessation care; more versus less intensive smoking cessation interventions; and multi-issue support versus smoking cessation support only), and carried out meta-analyses where appropriate, using a Mantel-Haenszel random-effects model. We also extracted data on quit attempts, effects on mental and substance-use severity, and meta-analyzed these outcomes where sufficient data were available. MAIN RESULTS: We identified 10 studies involving 1634 participants who smoked combustible tobacco at enrolment. One of the studies was ongoing. Most of the trials included participants who were recruited from community-based sites such as shelters, and three included participants who were recruited from clinics. We judged three studies to be at high risk of bias in one or more domains. We identified low-certainty evidence, limited by imprecision, that contingent reinforcement (rewards for successful smoking cessation) plus usual smoking cessation care was not more effective than usual care alone in promoting abstinence (RR 0.67, 95% CI 0.16 to 2.77; 1 trial, 70 participants). We identified very low-certainty evidence, limited by risk of bias and imprecision, that more intensive behavioral smoking cessation support was more effective than brief intervention in promoting abstinence at six-month follow-up (RR 1.64, 95% CI 1.01 to 2.69; 3 trials, 657 participants; I2 = 0%). There was low-certainty evidence, limited by bias and imprecision, that multi-issue support (cessation support that also encompassed help to deal with other challenges or addictions) was not superior to targeted smoking cessation support in promoting abstinence (RR 0.95, 95% CI 0.35 to 2.61; 2 trials, 146 participants; I2 = 25%). More data on these types of interventions are likely to change our interpretation of these data. Single studies that examined the effects of text-messaging support, e-cigarettes, or cognitive behavioral therapy for smoking cessation provided inconclusive results. Data on secondary outcomes, including mental health and substance use severity, were too sparse to draw any meaningful conclusions on whether there were clinically-relevant differences. We did not identify any studies that explicitly assessed interventions to increase access to tobacco cessation care; we were therefore unable to assess our secondary outcome 'number of participants receiving treatment'. AUTHORS' CONCLUSIONS: There is insufficient evidence to assess the effects of any tobacco cessation interventions specifically in people experiencing homelessness. Although there was some evidence to suggest a modest benefit of more intensive behavioral smoking cessation interventions when compared to less intensive interventions, our certainty in this evidence was very low, meaning that further research could either strengthen or weaken this effect. There is insufficient evidence to assess whether the provision of tobacco cessation support and its effects on quit attempts has any effect on the mental health or other substance-use outcomes of people experiencing homelessness. Although there is no reason to believe that standard tobacco cessation treatments work any differently in people experiencing homelessness than in the general population, these findings highlight a need for high-quality studies that address additional ways to engage and support people experiencing homelessness, in the context of the daily challenges they face. These studies should have adequate power and put effort into retaining participants for long-term follow-up of at least six months. Studies should also explore interventions that increase access to cessation services, and address the social and environmental influences of tobacco use among people experiencing homelessness. Finally, studies should explore the impact of tobacco cessation on mental health and substance-use outcomes.


Assuntos
Pessoas em Situação de Rua , Abandono do Hábito de Fumar/métodos , Fumar/terapia , Adulto , Viés , Monóxido de Carbono/análise , Terapia Cognitivo-Comportamental , Cotinina/análise , Aconselhamento/métodos , Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Estilo de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fumar/sangue , Envio de Mensagens de Texto , Dispositivos para o Abandono do Uso de Tabaco
16.
Sci Rep ; 10(1): 21258, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277550

RESUMO

We characterised changes in reproductive hormones-LH, FSH, SHBG and AMH-by chronological age and time around the menopause (reproductive age) in mid-life women and explored their associations with lifestyle and reproductive factors. We used data from 1608 women from a UK cohort who had repeat hormone measures and experienced a natural menopause. Multilevel models were used to assess: (i) changes in hormones (outcomes) by reproductive age and chronological age (these age variables being the key exposures) and (ii) associations of body mass index (BMI), smoking, alcohol intake, parity and age at menarche with changes in hormones by reproductive age. Both LH and FSH increased until ~ 5 and 7 years postmenopause, respectively, after which they declined, but not to premenopausal levels. SHBG decreased slightly until ~ 4 years postmenopause and increased thereafter. AMH decreased markedly before menopause and remained low subsequently. For all hormones, the best fitting models included both reproductive and chronological age. BMI, smoking and parity were associated with hormone changes; e.g., higher BMI was associated with slower increase in LH and FSH and decrease in AMH. Reproductive and chronological age contribute to changes in LH, FSH, SHBG and AMH across mid-life in women, and BMI, smoking and parity are associated with these hormone changes.


Assuntos
Menopausa/sangue , Índice de Massa Corporal , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Estudos Longitudinais , Hormônio Luteinizante/sangue , Pais , Pós-Menopausa/fisiologia , Reprodução/fisiologia , Fatores de Risco , Fumar/sangue , Fumar/fisiopatologia
17.
Sci Rep ; 10(1): 19980, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33235307

RESUMO

Smokers who switch completely to e-cigarettes may reduce their relative risk of tobacco-related disease. Effective nicotine delivery from e-cigarettes is important in consumer acceptance. We assessed whether protonated nicotine and e-cigarette devices delivering greater aerosol mass increase nicotine delivery and product liking. A randomised controlled non-blinded eight-arm crossover study was used to assess plasma nicotine pharmacokinetics and product liking for two e-cigarettes (Vype ePen3 and Vype ePen) with various nicotine e-liquid formulations and a conventional cigarette among 24 healthy dual-users of cigarettes and e-cigarettes. Product use and puff count were also assessed. Results show that nicotine bioavailability was greater for Vype ePen3 with greater aerosol mass delivery than for Vype ePen (Cmax, p = 0.0073; AUC0-120 min, p = 0.0102). Protonated nicotine (18 mg/mL, medium protonation) e-liquid yielded higher nicotine bioavailability than unprotonated nicotine (18 mg/mL) e-liquid (Cmax, p = 0.0001; AUC0-120 min, p = 0.0026). There was no significant difference in Tmax between e-liquids. Nicotine bioavailability did not differ between nicotine benzoate formulation (30 mg/mL nicotine, high protonation) and combustible cigarettes (Cmax, p = 0.79; AUC0-120 min, p = 0.13). Vype ePen3 with protonated nicotine delivers nicotine more efficiently with the potential to increase product liking relative to earlier devices using unprotonated e-liquid.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Nicotina/farmacocinética , Adulto , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/sangue , Fumantes , Fumar/sangue , Tabaco , Produtos do Tabaco
18.
PLoS One ; 15(11): e0241580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33137158

RESUMO

Inflammatory biomarkers have been associated with clinical outcomes in non-small cell lung cancer (NSCLC). However, the best prognostic marker(s) has not been identified, and the association between inflammatory markers and clinical characteristics is poorly understood. We selected 1,237 patients with resected NSCLC from Kyushu University (2003-2015) and Kyushu Cancer Center (2009-2015) in Japan. Pearson product-moment correlation coefficient among inflammatory markers and area under curve (AUC) of receiver operating characteristic (ROC) curve analyses for overall survival (OS) were calculated. We analyzed the associations between inflammatory markers and clinical factors using Student's t-test. Univariate and multivariate analyses with Cox proportional hazards regression analyses were performed to evaluate the relationship between survival and clinical factors. The cut-off values for neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio, and derived NLR (dNLR) were determined by ROC curve analyses for OS. We found a strong positive correlation between NLR and dNLR (r = 0.9629). The AUC of LMR was the highest amongst the measured metrics, and the AUC of NLR was higher than dNLR. Levels of some inflammatory markers were associated with sex, smoking, squamous cell carcinoma, and pathological stage. LMR ≥ 5.11 and lactate dehydrogenase (LDH) concentration ≥ 222 (U/L) were independent predictors of both disease-free survival (DFS) and OS (LMR; P = 0.0009 and 0.0008, LDH; P = 0.0195 and 0.0187, respectively). Certain inflammatory markers, potentially linked to smoking, were associated with an advanced pathological stage in NSCLC. LMR and LDH were independent predictors of both DFS and OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Inflamação/diagnóstico , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Fumar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Contagem de Células Sanguíneas , Plaquetas/imunologia , Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Japão/epidemiologia , L-Lactato Desidrogenase/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica Humana/análise , Fumar/sangue , Fumar/imunologia
19.
J Am Heart Assoc ; 9(22): e018217, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33170061

RESUMO

Background Whether circulating growth differentiation factor 15 (GDF-15) levels differ according to smoking status and whether smoking modifies the relationship between GDF-15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF-15 and the impact of smoking status on the association between GDF-15 and all-cause death. GDF-15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF-15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log-transformed GDF-15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF-15. The prognostic value of GDF-15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Fator 15 de Diferenciação de Crescimento/sangue , Fumar/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
20.
Sci Rep ; 10(1): 19507, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177548

RESUMO

Exhaled carbon monoxide (COex) level has been proposed as a noninvasive and easily-obtainable cardiovascular risk marker, however, with limited prospective evidence, and its association with stroke risk has been rarely explored. Measurements of COex were performed during 2004-2008 baseline examinations in the China Kadoorie Biobank study among 512,891 adults aged 30-79 years from 10 diverse study areas. After excluding participants with baseline cardiopulmonary diseases, stroke and cancer, 178,485 men and 267,202 women remained. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of cardio-cerebral-vascular disease (CCVD) associated with COex levels, with sequential addition of adjustment for proxy variables for CO exposure, including study area indexing ambient CO variations at large, and smoking and solid fuel use, apart from adjusting for traditional cardiovascular risk factors. During 7-year follow-up, we documented 1744 and 1430 major coronary events (myocardial infarction plus fatal ischemic heart disease), 8849 and 10,922 ischemic strokes, and 2492 and 2363 hemorrhagic strokes among men and women, respectively. The HRs with 95% CIs comparing the highest with lowest COex quintile were 2.15 [1.72, 2.69] for major coronary events, 1.65 [1.50, 1.80] for ischemic stroke, and 1.35 [1.13, 1.61] for hemorrhagic stroke among men, while among women higher associated risk was only observed for major coronary events (1.64 [1.35, 2.00]) and ischemic stroke (1.87 [1.73, 2.01]). The elevated risks were consistent when COex level was over 3 ppm. However, these associations were all attenuated until null by sequential addition of stratification by study areas, and adjustments of smoking and solid fuel use. Nevertheless, the association with ischemic stroke was maintained among the subgroup of male smokers even with adjustment for the depth and amount of cigarette smoking (HR [95% CI]: 1.37 [1.06, 1.77]), while a negative association with hemorrhagic stroke also appeared within this subgroup. Higher COex level (over 3 ppm) was associated with elevated risk of ischemic CCVD, but not independently of CO exposure. Our finding suggests that, though not an independent risk factor, COex could potentially provide a cost-effective biomarker for ischemic cardio-cerebral-vascular risk, given that CO exposure is ubiquitous.


Assuntos
Monóxido de Carbono/análise , Doenças Cardiovasculares/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Fumar/sangue , Adulto , Idoso , Bancos de Espécimes Biológicos , Monóxido de Carbono/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/metabolismo , China , Exposição Ambiental , Expiração , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fumantes , Fumar/efeitos adversos
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