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1.
BMC Cardiovasc Disord ; 24(1): 292, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840064

ABSTRACT

BACKGROUND: Tobacco use is recognized as a major cause of cardiovascular disease, which is associated with endothelial dysfunction. Endothelial function is evaluated using flow-mediated dilation (FMD), which is a noninvasive method. This meta-analysis aimed to investigate the association between smoking exposure and endothelial function evaluated using FMD values. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for cohort studies of smokers or passive smokers that used FMD to assess endothelial function. The primary outcome of the study was the change in the rate of FMD. The risk of bias was evaluated using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. Further, the weighted mean difference was used to analyze the continuous data. RESULTS: Overall, 14 of 1426 articles were included in this study. The results of these articles indicated that smoking is a major cause of endothelial dysfunction and altered FMD; a pooled effect size of - 3.15 was obtained with a 95% confidence interval of (- 3.84, - 2.46). Notably, pregnancy status, Asian ethnicity, or health status did not affect heterogeneity. CONCLUSIONS: We found that smoking has a significant negative impact on FMD, and measures such as medication or education for smoking cessation may improve endothelial function and reduce the risk of cardiovascular disease. TRIAL REGISTRATION: The meta-analysis was registered with PROSPERO on April 5th, 2023 (CRD42023414654).


Subject(s)
Cardiovascular Diseases , Endothelium, Vascular , Vasodilation , Humans , Endothelium, Vascular/physiopathology , Female , Male , Middle Aged , Adult , Risk Assessment , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/etiology , Cardiovascular Diseases/epidemiology , Aged , Risk Factors , Tobacco Smoke Pollution/adverse effects , Predictive Value of Tests , Smoking/adverse effects , Smoking/physiopathology , Young Adult , Smokers , Brachial Artery/physiopathology , Brachial Artery/diagnostic imaging , Heart Disease Risk Factors
2.
Am J Respir Crit Care Med ; 209(10): 1208-1218, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38175920

ABSTRACT

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).


Subject(s)
Lung , Pulmonary Disease, Chronic Obstructive , Spirometry , Tomography, X-Ray Computed , Adult , Female , Humans , Male , Middle Aged , Young Adult , Disease Progression , Forced Expiratory Volume/physiology , Lung/physiopathology , Lung/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Smokers/statistics & numerical data , Smoking/adverse effects , Smoking/physiopathology , Case-Control Studies
4.
Nature ; 616(7957): 525-533, 2023 04.
Article in English | MEDLINE | ID: mdl-37046096

ABSTRACT

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Adenocarcinoma of Lung/etiology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/etiology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mutation , Neoplasm Recurrence, Local/genetics , Phylogeny , Treatment Outcome , Smoking/genetics , Smoking/physiopathology , Mutagenesis , DNA Copy Number Variations
6.
Circ Res ; 130(4): 496-511, 2022 02 18.
Article in English | MEDLINE | ID: mdl-35175843

ABSTRACT

Peripheral artery disease (PAD) is a prevalent condition that confers substantial morbidity and mortality and remains underdiagnosed as well as undertreated in the overall population. Although PAD prevalence is similar or higher in women compared with men, associations of traditional and nontraditional risk factors with PAD and clinical manifestations of PAD differ by sex and may contribute to delayed or lack of diagnosis in women. Such sex-based differences in the manifestation of PAD may arise from sexual dimorphism in the vascular substrate in health as well as sex variation in the responses to vascular stressors. Despite the availability of proven therapies for improving symptoms and reducing risk of ischemic cardiovascular and limb events among patients with diagnosed PAD, important sex differences in treatment and outcomes have been observed. We provide an overview of current knowledge regarding sex differences in the epidemiology, pathophysiology, clinical presentation, and management of PAD.


Subject(s)
Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/epidemiology , Sex Characteristics , Ankle Brachial Index/methods , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Diabetes Mellitus/physiopathology , Diabetes Mellitus/therapy , Exercise Therapy/methods , Female , Fibrinolytic Agents/therapeutic use , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Hypertension/therapy , Male , Peripheral Arterial Disease/physiopathology , Peripheral Arterial Disease/therapy , Sex Factors , Smoking/adverse effects , Smoking/epidemiology , Smoking/physiopathology
7.
Sci Rep ; 12(1): 1832, 2022 02 03.
Article in English | MEDLINE | ID: mdl-35115625

ABSTRACT

The objective of this study was to evaluate the relationship between random capillary glucose levels in healthy pregnant women and infant size at birth and childhood growth to the age of five years. This population-based cohort study comprised 10,937 healthy mother-child dyads. Data on highest maternal random capillary glucose level during pregnancy and sequential anthropometric data on their children during the first five years of life were gathered from the Uppsala County Mother and Child Cohort. Statistical analyses were performed with linear regression and linear mixed effect regression models. We found that higher glucose level during pregnancy was associated with higher weight z-score (ß 0.10, 95% confidence interval (CI) 0.08-0.11), length z-score (ß 0.05, 95% CI 0.03-0.07) and BMI z-score (ß 0.09, 95% CI 0.07-0.12) at birth, adjusted for maternal BMI and country of birth, smoking during pregnancy and parity. The association did not remain at 1½, 3, 4 and 5 years of age. There was a positive relationship between higher glucose level during pregnancy and a decrease in weight z-score, height z-score and BMI z-score from birth to 5 years of age. In conclusion, higher random capillary glucose levels in pregnant healthy women were associated with greater infant size at birth, as well as decreased growth velocity in early childhood.


Subject(s)
Birth Weight/physiology , Blood Glucose/metabolism , Child Development/physiology , Anthropometry , Body Height , Body Mass Index , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Parity/physiology , Pregnancy , Regression Analysis , Risk Factors , Smoking/physiopathology
8.
Sci Rep ; 12(1): 1139, 2022 01 21.
Article in English | MEDLINE | ID: mdl-35064168

ABSTRACT

Previously, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we showed that sons of fathers who had started smoking regularly before puberty (< 13 years) had increased fat mass during childhood, adolescence, and early adulthood. We now show that if the paternal grandfather had started smoking pre-puberty, compared with later in childhood (13-16 years), his granddaughters, but not grandsons, had evidence of excess fat mass at two ages: mean difference + 3.54 kg; (P with 1-tailed test) = 0.043 at 17 years, and + 5.49 kg; (P1 = 0.016) at age 24. When fathers of maternal grandfathers had started smoking pre-puberty, their great-granddaughters, but not great-grandsons, had excess body fat: + 5.35 kg (P1 = 0.050) at 17, and + 6.10 kg (P1 = 0.053) at 24 years. Similar associations were not found with lean mass, in a sensitivity analysis. To determine whether these results were due to the later generations starting to smoke pre-puberty, further analyses omitted those in subsequent generations who had smoked regularly from < 13 years. The results were similar. If these associations are confirmed in another dataset or using biomarkers, this will be one of the first human demonstrations of transgenerational effects of an environmental exposure across four generations.


Subject(s)
Adiposity/physiology , Grandparents , Parents , Smoking/epidemiology , Adolescent , Child , Humans , Longitudinal Studies , Risk Factors , Sex Factors , Smoking/adverse effects , Smoking/physiopathology , Time Factors , Young Adult
9.
Biomed Res Int ; 2022: 4286621, 2022.
Article in English | MEDLINE | ID: mdl-35028314

ABSTRACT

Around the whole world, smoking is considered harmful to human health, such as increasing the risk of cardiovascular disease (CVD, such as coronary heart disease and stroke) and lung cancer. The purpose of this study was to explore whether nicotine, the main component of tobacco, has adverse effects on heart rate variability (HRV) in adolescents, so as to remind adolescents not to smoke and not to take pleasure in abusing nicotine. In this study, 40 male and 40 female young healthy nonsmoking subjects were selected to analyze the changes of HRV after taking 4 mg nicotine orally. We found that nicotine reduced HRV in young healthy male and female subjects, and there was no gender difference in this effect (P > 0.05). In conclusion, smoking is harmful to the cardiac system of young people, especially when nicotine content ≥4 mg dosage.


Subject(s)
Heart Rate/drug effects , Nicotine/pharmacology , Adolescent , Adult , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/physiopathology , Female , Humans , Male , Smoking/adverse effects , Smoking/physiopathology , Young Adult
10.
Respir Res ; 23(1): 19, 2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35093071

ABSTRACT

BACKGROUND: Optimism is the general belief that good things will occur in the future; optimism is modifiable by cognitive behavioral therapy (CBT). Previous studies have associated higher optimism with improved health outcomes and lower all-cause mortality. RESEARCH QUESTION: Investigate association between optimism and disease-related characteristics in chronic obstructive pulmonary disease (COPD). STUDY DESIGN AND METHODS: Current and former smokers with/without COPD and Preserved Ratio Impaired Spirometry (PRISm) from the 10-year follow-up visit for the Genetic Epidemiology of COPD (COPDGene) study were included. Optimism was assessed at the 10-year visit using the Life Orientation Test-Revised. Models of optimism as a predictor of lung function, COPD-associated phenotypes including exacerbations, and functional assessments, were adjusted for demographic confounders, smoking status, and comorbidities. RESULTS: Among 1967 subjects, higher optimism was significantly associated with older age, non-Hispanic white race, marital status, quitting smoking status, absence of COPD, and absence of depression. In multivariable analysis, higher optimism was independently associated with fewer prior exacerbations of COPD (coef = - 0.037, P < 0.001). Higher optimism was also related to better MMRC scores (coef = - 0.041, P < 0.001), CAT scores (coef = - 0.391, P < 0.001), SGRQ scores (coef = - 0.958, P < 0.001), BODE index (coef = - 0.059, P < 0.001), and longer 6-min walk distance (coef = 10.227, P < 0.001). After stratification by severity of COPD, these associations with optimism were still significant in all groups. No significant association was observed for cross-sectional FEV1 (%) or FVC (%) with optimism score. INTERPRETATION: Fewer exacerbations and less severe respiratory symptoms and higher functional capacity were associated with higher optimism, which may impact health outcomes in current and former smokers with and without COPD. Optimism is a modifiable trait and these results may further support a role for CBT to improve outcomes in COPD.


Subject(s)
Forced Expiratory Volume/physiology , Forecasting , Functional Status , Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Quality of Life , Smoking/adverse effects , Aged , Aged, 80 and over , Comorbidity , Cross-Sectional Studies , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Retrospective Studies , Severity of Illness Index , Smoking/physiopathology , Spirometry , Surveys and Questionnaires
11.
Sci Rep ; 12(1): 1435, 2022 01 26.
Article in English | MEDLINE | ID: mdl-35082306

ABSTRACT

We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1-4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p < 0.05 each), but not the decline of FEV1 and FVC. These results were confirmed using multiple regression and propensity score analyses. Our findings demonstrate an association between the annual decline of lung diffusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging effects of metformin as reflected in a surrogate marker of emphysema.


Subject(s)
Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Pulmonary Diffusing Capacity/drug effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Emphysema/drug therapy , Age Factors , Aged , Body Mass Index , Cohort Studies , Diabetes Mellitus/physiopathology , Female , Forced Expiratory Volume/drug effects , Humans , Lung/drug effects , Lung/physiopathology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Emphysema/physiopathology , Sex Factors , Smoking/physiopathology , Vital Capacity/drug effects
12.
Addict Biol ; 27(1): e13083, 2022 01.
Article in English | MEDLINE | ID: mdl-34363643

ABSTRACT

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments.


Subject(s)
Brain/physiopathology , Craving/physiology , Cues , Smoking Cessation , Smoking/physiopathology , Tobacco Use Disorder/physiopathology , Adult , Behavior, Addictive/physiopathology , Brain Mapping , Female , Functional Neuroimaging , Gyrus Cinguli/physiopathology , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged , Smokers/psychology , Substance Withdrawal Syndrome/physiopathology , Young Adult
13.
Anesthesiology ; 136(1): 206-236, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34710217

ABSTRACT

The development of pulmonary atelectasis is common in the surgical patient. Pulmonary atelectasis can cause various degrees of gas exchange and respiratory mechanics impairment during and after surgery. In its most serious presentations, lung collapse could contribute to postoperative respiratory insufficiency, pneumonia, and worse overall clinical outcomes. A specific risk assessment is critical to allow clinicians to optimally choose the anesthetic technique, prepare appropriate monitoring, adapt the perioperative plan, and ensure the patient's safety. Bedside diagnosis and management have benefited from recent imaging advancements such as lung ultrasound and electrical impedance tomography, and monitoring such as esophageal manometry. Therapeutic management includes a broad range of interventions aimed at promoting lung recruitment. During general anesthesia, these strategies have consistently demonstrated their effectiveness in improving intraoperative oxygenation and respiratory compliance. Yet these same intraoperative strategies may fail to affect additional postoperative pulmonary outcomes. Specific attention to the postoperative period may be key for such outcome impact of lung expansion. Interventions such as noninvasive positive pressure ventilatory support may be beneficial in specific patients at high risk for pulmonary atelectasis (e.g., obese) or those with clinical presentations consistent with lung collapse (e.g., postoperative hypoxemia after abdominal and cardiothoracic surgeries). Preoperative interventions may open new opportunities to minimize perioperative lung collapse and prevent pulmonary complications. Knowledge of pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should provide the basis for current practice and help to stratify and match the intensity of selected interventions to clinical conditions.


Subject(s)
Intraoperative Complications/physiopathology , Intraoperative Complications/therapy , Perioperative Care/methods , Pulmonary Atelectasis/physiopathology , Pulmonary Atelectasis/therapy , Humans , Intraoperative Complications/diagnostic imaging , Intraoperative Complications/epidemiology , Lung/diagnostic imaging , Lung/physiopathology , Manometry/methods , Manometry/trends , Obesity/diagnostic imaging , Obesity/epidemiology , Obesity/physiopathology , Perioperative Care/trends , Positive-Pressure Respiration/adverse effects , Positive-Pressure Respiration/trends , Pulmonary Atelectasis/diagnostic imaging , Pulmonary Atelectasis/epidemiology , Respiration, Artificial/adverse effects , Respiration, Artificial/trends , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , Smoking/physiopathology
14.
Sci Rep ; 11(1): 21719, 2021 11 05.
Article in English | MEDLINE | ID: mdl-34741061

ABSTRACT

Vascular dysfunctions can progress and lead to stroke and cardiovascular disease, especially in smokers. The presence of particular vascular changes according to sex has been described and they can be identified by the Doppler method. This study evaluated Doppler velocimetry parameters of the Ophthalmic Artery (OA) and the Middle Cerebral Artery (MCA) according to sex in smokers regarding a non-smoker group. This cross-sectional observational study included 178 subjects: 93 women and 85 men. Doppler parameters were assessed in OA and MCA. Student's t-test was used, with p < 0.05. There were no significant differences in OA and MCA Doppler velocimetry data between male non-smokers and smokers. However, female smokers presented several differences compared with non-smokers: lower pulsatility index (PI) and higher peak ratio in OA, and higher PI and resistance index and lower end diastolic velocity in MCA. There were different brain vascular waveforms in the group of female smokers compared with non-smokers. Cigarette smoking also led to opposite arterial patterns in OA and MCA in the female group, with signs of falling impedance in OA and increased impedance in MCA. An individualized approach regarding arterial changes according to sex is desirable.


Subject(s)
Middle Cerebral Artery/physiopathology , Ophthalmic Artery/physiopathology , Smoking/physiopathology , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Middle Cerebral Artery/diagnostic imaging , Ophthalmic Artery/diagnostic imaging , Sex Characteristics , Smoking/adverse effects , Ultrasonography, Doppler , Young Adult
15.
PLoS One ; 16(11): e0259500, 2021.
Article in English | MEDLINE | ID: mdl-34793496

ABSTRACT

The objective was to investigate the persistence of sleep difficulties for over 16 years amongst a population of working age. In this prospective cohort study, a group-based trajectory analysis of repeated surveys amongst 66,948 employees in public sector (mean age 44.7 [SD 9.4] years, 80% women) was employed. The main outcome measure was sleep difficulties based on Jenkins Sleep Scale (JSS). Up to 70% of the respondents did not experience sleep difficulties whereas up to 4% reported high frequency of notable sleep difficulties through the entire 16-year follow-up. Heavy drinking predicted sleep difficulties (OR 2.3 95% CI 1.6 to 3.3) except for the respondents younger than 40 years. Smoking was associated with sleep difficulties amongst women younger than 40 years (OR 1.2, 95% CI 1.0 to 1.5). Obesity was associated with sleep difficulties amongst men (OR 1.9, 95% CI 1.4 to 2.7) and women (OR 1.2, 95% CI 1.1 to 1.3) of middle age and amongst women older than 50 (OR 1.5, 95% CI 1.2 to 1.8) years. Physical inactivity predicted sleep difficulties amongst older men (OR 1.3, 95% CI 1.1 to 1.6). In this working-age population, sleep difficulties showed a great persistence over time. In most of the groups, the level of sleep difficulties during the follow-up was almost solely dependent on the level of initial severity. Depending on sex and age, increasing sleep problems were sometimes associated with high alcohol consumption, smoking, obesity and physical inactivity, but the strength of these associations varied.


Subject(s)
Sleep Initiation and Maintenance Disorders/physiopathology , Adolescent , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , Sedentary Behavior , Smoking/physiopathology , Young Adult
16.
Acta Otolaryngol ; 141(11): 989-993, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34694199

ABSTRACT

BACKGROUND: The effect of Covid-19 infection on nasal mucociliary clearance (MCC) is unknown. AIMS/OBJECTIVES: The aim of this study is to investigate the relationship between Covid-19 and nasal MCC in terms of smoking, Covid-19 symptoms and treatment. METHODS: Thirty-six patients who were hospitalized in the pandemic ward due to Covid-19 and 36 volunteers (Covid-19 negative test result) who presented to the otolaryngology outpatient clinic with non-nasal symptoms were included in this study. The Saccharin test was performed in both groups to evaluate nasal MCC. RESULTS: The patients and control groups were not significantly different in terms of age and gender. The nasal MCC time was significantly higher in the patient group compared to the control group (19.18 ± 10.84 min and 13.78 ± 8.18 min, p = .003). CONCLUSIONS AND SIGNIFICANCE: In this study, we found that Covid-19 prolonged nasal MCC time regardless of age. We suggest that corticosteroids should be included in the treatment of Covid-19, both with its symptom reduction and its positive effect on MCC duration.


Subject(s)
COVID-19/physiopathology , Mucociliary Clearance/physiology , Nasal Mucosa/physiopathology , Smoking/physiopathology , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Adult , Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/complications , Case-Control Studies , Female , Humans , Hydroxychloroquine/adverse effects , Length of Stay , Male , Middle Aged , Mucociliary Clearance/drug effects , Pyrazines/therapeutic use , COVID-19 Drug Treatment
17.
Nat Commun ; 12(1): 5945, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642315

ABSTRACT

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.


Subject(s)
HLA Antigens/immunology , Human papillomavirus 16/immunology , Immunity, Humoral , Mouth Neoplasms/immunology , Oropharyngeal Neoplasms/immunology , Papillomavirus Infections/immunology , Aged , Antibodies, Viral/biosynthesis , Capsid Proteins/genetics , Capsid Proteins/immunology , Case-Control Studies , Female , Gene Expression , Genetic Predisposition to Disease , Genome-Wide Association Study , HLA Antigens/classification , HLA Antigens/genetics , Haplotypes , Human papillomavirus 16/pathogenicity , Humans , Male , Meta-Analysis as Topic , Middle Aged , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Mouth Neoplasms/virology , Oncogene Proteins, Viral/genetics , Oncogene Proteins, Viral/immunology , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/genetics , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Quantitative Trait Loci , Repressor Proteins/genetics , Repressor Proteins/immunology , Risk Factors , Smoking/physiopathology
18.
Lipids Health Dis ; 20(1): 105, 2021 Sep 12.
Article in English | MEDLINE | ID: mdl-34511127

ABSTRACT

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up. METHODS: Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD. RESULTS: Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m2, and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58-4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15-2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87-1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This association was particularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015). CONCLUSIONS: There is an inverse relationship between LDL-C levels and the risk of all-cause mortality, and this association is statistically significant.


Subject(s)
Alcohol Drinking/blood , Cardiovascular Diseases/blood , Cholesterol, LDL/blood , Diabetes Mellitus/blood , Independent Living , Longevity/physiology , Smoking/blood , Age Factors , Aged , Alcohol Drinking/mortality , Alcohol Drinking/physiopathology , Body Mass Index , Cardiovascular Diseases/mortality , Cardiovascular Diseases/physiopathology , Cholesterol, HDL/blood , Cohort Studies , Diabetes Mellitus/mortality , Diabetes Mellitus/physiopathology , Female , Humans , Japan , Kidney Function Tests , Male , Middle Aged , Prognosis , Proportional Hazards Models , Risk Factors , Sex Factors , Smoking/mortality , Smoking/physiopathology , Triglycerides/blood , Uric Acid/blood
19.
Clin Epigenetics ; 13(1): 177, 2021 09 19.
Article in English | MEDLINE | ID: mdl-34538263

ABSTRACT

BACKGROUND: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. RESULTS: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. CONCLUSIONS: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696 .


Subject(s)
Ascorbic Acid/pharmacology , DNA Methylation/drug effects , Placenta/physiopathology , Smoking/adverse effects , Adult , Ascorbic Acid/administration & dosage , Dietary Supplements/standards , Dietary Supplements/statistics & numerical data , Female , Humans , Placenta/pathology , Pregnancy , Prenatal Exposure Delayed Effects/genetics , Smoking/physiopathology
20.
Lipids Health Dis ; 20(1): 110, 2021 Sep 20.
Article in English | MEDLINE | ID: mdl-34544446

ABSTRACT

BACKGROUND: Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population. METHODS: This longitudinal cohort research examined 7,316 participants (age range: 22-93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m2 per year or > 30 % decrease in eGFR from baseline. RESULTS: The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03-1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21-3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12-3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05-6.38, P = 0.04). CONCLUSIONS: The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population.


Subject(s)
Cholesterol, HDL/blood , Kidney/physiopathology , Renal Insufficiency, Chronic/blood , Triglycerides/blood , Adult , Age Factors , Aged , Aged, 80 and over , Alcohol Drinking/blood , Alcohol Drinking/epidemiology , Alcohol Drinking/physiopathology , China/epidemiology , Cholesterol, LDL/blood , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Diabetes Mellitus/physiopathology , Female , Glomerular Filtration Rate , Heart Diseases/blood , Heart Diseases/epidemiology , Heart Diseases/physiopathology , Humans , Hypertension/blood , Hypertension/epidemiology , Hypertension/physiopathology , Kidney/metabolism , Lipid Metabolism/physiology , Longitudinal Studies , Male , Middle Aged , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/physiopathology , Sex Factors , Smoking/blood , Smoking/epidemiology , Smoking/physiopathology , Stroke/blood , Stroke/epidemiology , Stroke/physiopathology , Waist Circumference
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