scholarly journals No association between DNA methylation and COPD in never and current smokers

2018 ◽  
Vol 5 (1) ◽  
pp. e000282 ◽  
Author(s):  
Maaike de Vries ◽  
Diana A van der Plaat ◽  
Judith M Vonk ◽  
H Marike Boezen
Keyword(s):  
Dna Methylation ◽  
Robust Regression ◽  
Smoking Status ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Cpg Sites ◽  
Cpg Site ◽  
Genome Wide ◽  
Never Smokers

IntroductionChronic obstructive pulmonary disease (COPD) is a progressive inflammatory lung disease with cigarette smoke as the main risk factor for its development. Since not every smoker develops COPD, other factors likely underlie differences in susceptibility to develop COPD. Here, we tested if DNA methylation may be such a factor by assessing the association between DNA methylation levels and COPD in never and current smokers from the general population.MethodsFor the current study, 1561 subjects were non-randomly selected from the LifeLines cohort study. We included 903 never smokers and 658 current smokers with and without COPD, defined as pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <70%. Subsequently, we performed robust regression analysis on whole blood DNA methylation levels of 420 938 CpG sites with COPD as outcome.ResultsNone of the CpG sites in both the never and the current smokers were genome-wide significantly associated with COPD. CpG site cg14972228 annotated to SIPAL3 was most significant (p=5.66×10−6) in the never smokers, while CpG site cg08282037 annotated to EPS8L1 was most significant (p=1.45×10−5) in the current smokers.ConclusionIn contrast to a previous, smaller study, we did not observe any significant association between DNA methylation levels and the presence of COPD, independent of smoking status. Apparently, DNA methylation studies are highly variable.

Never-smokers with occupational COPD have better exercise capacities and ventilatory efficiency than matched smokers with COPD

2020 ◽  
Vol 129 (6) ◽  
pp. 1257-1266
Author(s):  
Thibaud Soumagne ◽  
Alicia Guillien ◽  
Nicolas Roche ◽  
Jean-Charles Dalphin ◽  
Bruno Degano
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Vital Capacity ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Exertional Dyspnea ◽  
Obstructive Pulmonary Disease ◽  
Ventilatory Efficiency ◽  
Never Smokers ◽  
Occupational Copd ◽  
Lower Limit Of Normal

It is unknown whether or not never-smokers with chronic obstructive pulmonary disease (COPD) behave like their smoking counterparts during exercise. This is the first study showing that never-smokers with mild to moderate COPD [defined by a postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < lower limit of normal] have preserved exercise capacities. They also have lower exertional dyspnea than patients with smoking-related COPD. This suggests that the two COPD groups should not be managed in the same way.

scholarly journals Differences in regional air trapping in current smokers with normal spirometry

2017 ◽  
Vol 49 (1) ◽  
pp. 1600345 ◽  
Author(s):  
Reza Karimi ◽  
Göran Tornling ◽  
Helena Forsslund ◽  
Mikael Mikko ◽  
Åsa M. Wheelock ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Structural Changes ◽  
Forced Expiratory Volume ◽  
Wall Thickening ◽  
Chronic Obstructive ◽  
Air Trapping ◽  
Obstructive Pulmonary Disease ◽  
Never Smokers ◽  
Detection Of Smoking ◽  
Specific Manifestation

We investigated regional air trapping on computed tomography in current smokers with normal spirometry. It was hypothesised that presence of regional air trapping may indicate a specific manifestation of smoking-related changes.40 current smokers, 40 patients with chronic obstructive pulmonary disease (COPD), and 40 healthy never- smokers underwent computed tomography scans. Regional air trapping was assessed on end-expiratory scans and emphysema, micronodules and bronchial wall thickening on inspiratory scans. The ratio of expiratory and inspiratory mean lung attenuation (E/I) was calculated as a measure of static (fixed) air trapping.Regional air trapping was present in 63% of current smokers, in 45% of never smokers and in 8% of COPD patients (p<0.001). Current smokers with and without regional air trapping had E/I ratio of 0.81 and 0.91, respectively (p<0.001). Forced expiratory volume in 1 s (FEV1) was significantly higher and emphysema less frequent in current smokers with regional air trapping.Current smokers with regional air trapping had higher FEV1 and less emphysema on computed tomography. In contrast, current smokers without regional air trapping resembled COPD. Our results highlight heterogeneity among smokers with normal spirometry and may contribute to early detection of smoking related structural changes in the lungs.

Abstract P215: Association Of Lung Function In Mid-life With Central Artery Stiffness Later In Life, The Atherosclerosis Risk In Communities Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Kennedy Peter ◽  
James R Pike ◽  
John Preisser ◽  
Anna Kucharska-newton ◽  
Michelle Meyer ◽  
...  
Keyword(s):  
Lung Function ◽  
Arterial Stiffness ◽  
Smoking Status ◽  
Later Life ◽  
Forced Expiratory Volume ◽  
Sensitivity Analyses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Central Artery ◽  
Artery Stiffness

Introduction: Poor lung function and aortic stiffness often co-occur, but causal and temporal relationships are equivocal. Investigating relationships between mid-life lung function and arterial stiffness later in life may highlight modifiable targets to slow arterial aging. Objective: Assess whether lung function in mid-life is associated with central artery stiffness later in life, and whether this relationship is modified by baseline smoking status, hypertension, or diabetes. Methods: We included 3,529 ARIC cohort participants (60% women; 22% Black; mean baseline age 51.4 (SD: 4.9)) who attended visits 1 (1987-1989) and 5 (2011-2013). Spirometry included forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) of high-quality grades. Central artery stiffness (carotid-femoral pulse wave velocity (cfPWV)) was measured at visit 5. Associations of mid-life lung function with later-life central artery stiffness (cfPWV>75 th percentile) were evaluated by multivariable Poisson and logistic regressions adjusted for covariates. Sensitivity analyses excluded participants with chronic obstructive pulmonary disease identified from surveillance of hospitalizations occurring in follow up (N=109). Results: Mean FEV1 at visit 1 was 3.04 L (SD: 0.73) and FVC was 3.99 L (SD: 0.96). Lung function varied by thoracic height. Visits 1 and 5 were a mean of 23.8 years apart, and mean cfPWV at visit 5 was 1167 cm/s (SD: 379). Lung function at visit 1 was inversely associated with adjusted prevalence and odds of later cfPWV>75 th percentile among those present at visit 5 (Table). Stratum-specific estimates suggested modification by baseline smoking status, hypertension, and diabetes, but were not nominally statistically different. Sensitivity analyses did not alter inferences. Conclusion: Lung function at mid-life is inversely associated with central artery stiffness in later life. Whether change in mid-life pulmonary function is associated with arterial stiffness later in life warrants further examination.

scholarly journals The effects of marijuana smoking on lung function in older people

2019 ◽  
Vol 54 (6) ◽  
pp. 1900826 ◽  
Author(s):  
Wan C. Tan ◽  
Jean Bourbeau ◽  
Shawn D. Aaron ◽  
James C. Hogg ◽  
François Maltais ◽  
...  
Keyword(s):  
Lung Function ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Long Term Effects ◽  
Obstructive Pulmonary Disease ◽  
Before And After ◽  
Rate Of Decline ◽  
Never Smokers

BackgroundPrevious studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear.MethodsWe determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively.Results∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55–3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1 by 29.5 mL·year−1 (p=0.0007) and 21.1 mL·year−1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year−1 (p<0.0001).InterpretationHeavy marijuana smoking increases the risk of COPD and accelerates FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.

scholarly journals Investigation of the Obesity Paradox in Chronic Obstructive Pulmonary Disease, According to Smoking Status, in the United States

2019 ◽  
Vol 188 (11) ◽  
pp. 1977-1983 ◽  
Author(s):  
Tianshi David Wu ◽  
Chinedu O Ejike ◽  
Robert A Wise ◽  
Meredith C McCormack ◽  
Emily P Brigham
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Proportional Hazards ◽  
Smoking Status ◽  
Obesity Paradox ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Never Smokers

Abstract An obesity paradox in chronic obstructive pulmonary disease (COPD), whereby overweight/obese individuals have improved survival, has been well-described. These studies have generally included smokers. It is unknown whether the paradox exists in individuals with COPD arising from factors other than smoking. Nonsmoking COPD is understudied yet represents some 25%–45% of the disease worldwide. To determine whether the obesity paradox differs between ever- and never-smokers with COPD, 1,723 adult participants with this condition were examined from 2 iterations of the National Health and Nutrition Examination Survey (1988–1994, 2007–2010), with mortality outcomes followed through December 2011. Using Cox proportional hazards models, adjusted for sociodemographic factors, lung function, and survey cycle, ever/never-smoking was found to modify the association between body mass index and hazard of death. Compared with normal-weight participants, overweight/obese participants had lower hazard of death among ever-smokers (for overweight, adjusted hazard ratio (aHR) = 0.56, 95% confidence interval (CI): 0.43, 0.74; for obesity, aHR = 0.66, 95% CI: 0.48, 0.92), but never-smokers did not (overweight, aHR = 1.41, 95% CI: 0.66, 3.03; obesity, aHR = 1.29, 95% CI: 0.48, 3.48). An obesity paradox appeared to be absent among never-smokers with COPD. This, to our knowledge, novel finding might be explained by pathophysiological differences between smoking-related and nonsmoking COPD or by smoking-associated methodological biases.

scholarly journals SNPs associated withHHIPexpression have differential effects on lung function in males and females

2019 ◽  
Author(s):  
KA Fawcett ◽  
M Obeidat ◽  
CA Melbourne ◽  
N Shrine ◽  
AL Guyatt ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Tissue ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Interacting Protein ◽  
Obstructive Pulmonary Disease ◽  
Differential Effects ◽  
Genome Wide ◽  
Males And Females ◽  
The Uk

AbstractAdult lung function is highly heritable and 279 genetic loci were recently reported as associated with spirometry-based measures of lung function. Though lung development and function differ between males and females throughout life, there has been no genome-wide study to identify genetic variants with differential effects on lung function in males and females. Here, we present the first genome-wide genotype-by-sex interaction study on four lung function traits in 303,612 participants from the UK Biobank. We detected five SNPs showing genome-wide significant (P<5 × 10−8) interactions with sex on lung function, as well as 21 suggestively significant interactions (P<1 × 10−6). The strongest sex interaction signal came from rs7697189 at 4:145436894 on forced expiratory volume in 1 second (FEV1) (P = 3.15 × 10−15), and was replicated (P = 0.016) in 75,696 individuals in the SpiroMeta consortium. Sex-stratified analyses demonstrated that the minor (C) allele of rs7697189 increased lung function to a greater extent in males than females (untransformed FEV1β = 0.028 [SE 0.0022] litres in males vs β = 0.009 [SE 0.0014] litres in females), and this effect was not accounted for by differential effects on height, smoking or age at puberty. This SNP resides upstream of the gene encoding hedgehog-interacting protein (HHIP) and has previously been reported for association with lung function andHHIPexpression in lung tissue. In our analyses, whileHHIPexpression in lung tissue was significantly different between the sexes with females having higher expression (most significant probeset P=6.90 × 10−6) after adjusting for age and smoking, rs7697189 did not demonstrate sex differential effects on expression. Establishing the mechanism by whichHHIPSNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases, such as chronic obstructive pulmonary disease (COPD), in both sexes.

scholarly journals Dysregulation of the Tryptophan Pathway Evidences Gender Differences in COPD

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 212 ◽  
Author(s):  
Naz ◽  
Bhat ◽  
Ståhl ◽  
Forsslund ◽  
Sköld ◽  
...  
Keyword(s):  
T Cells ◽  
Kynurenic Acid ◽  
Tryptophan Hydroxylase ◽  
Immune Cell ◽  
Smoking Status ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tryptophan Metabolites ◽  
Never Smokers ◽  
The Individual

Increased activity of indoleamine 2,3-dioxygenase (IDO) and tryptophan hydroxylase (TPH) have been reported in individuals with chronic obstructive pulmonary disease (COPD). We therefore investigated the effect of gender stratification upon the observed levels of tryptophan metabolites in COPD. Tryptophan, serotonin, kynurenine, and kynurenic acid were quantified in serum of never-smokers (n = 39), smokers (n = 40), COPD smokers (n = 27), and COPD ex-smokers (n = 11) by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). The individual metabolite associations with lung function, blood, and bronchoalveolar lavage (BAL) immune-cell composition, as well as chemokine and cytokine levels, were investigated. Stratification by gender and smoking status revealed that the observed alterations in kynurenine and kynurenic acid, and to a lesser extent serotonin, were prominent in males, irrespective of COPD status (kynurenine p = 0.005, kynurenic acid p = 0.009, and serotonin p = 0.02). Inferred serum IDO activity and kynurenine levels decreased in smokers relative to never-smokers (p = 0.005 and p = 0.004, respectively). In contrast, inferred tryptophan hydroxylase (TPH) activity and serotonin levels showed an increase with smoking that reached significance with COPD (p = 0.01 and p = 0.01, respectively). Serum IDO activity correlated with blood CXC chemokine ligand 9 (CXCL9, p = 0.0009, r = 0.93) and chemokine (C-C motif) ligand 4 (CCL4.(p = 0.04, r = 0.73) in female COPD smokers. Conversely, serum serotonin levels correlated with BAL CD4+ T-cells (%) (p = 0.001, r = 0.92) and CD8+ T-cells (%) (p = 0.002, r = −0.90) in female COPD smokers, but not in male COPD smokers (p = 0.1, r = 0.46 and p = 0.1, r = −0.50, respectively). IDO- and TPH-mediated tryptophan metabolites showed gender-based associations in COPD, which were primarily driven by smoking status.

Abstract MP55: DNA Methylation Mediates The Effects Of Obesity On Insulin Resistance In African American Youth And Young Adults

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Xiaojing Xu ◽  
Shaoyong Su ◽  
Vernon Barnes ◽  
Harold Snieder ◽  
Xiaoling Wang
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Young Adults ◽  
African American ◽  
African American Youth ◽  
Fasting Insulin ◽  
Cpg Sites ◽  
Cpg Site ◽  
Genome Wide ◽  
Youth And Young Adults

Obesity and its related cardiovascular disease and type 2 diabetes have imposed huge burdens on public health worldwide. Insulin resistance is considered one of the key players in the development of obesity related comorbidities. However, the underlying mechanisms are still largely unknown. In this study, we aim to examine whether and to what extent peripheral blood DNA methylation can mediate obesity’s effect on insulin resistance using a genome-wide approach. Illumina 450k data were obtained for 456 black youth and young adults (226 obese cases vs. 230 lean controls) aged 14-34 years with fasting insulin levels available for 293 subjects and genome-wide gene expression data available for 92 subjects. As shown in figure 1, obesity and fasting insulin associated differentially methylated CpG sites were identified separately. Among the overlap of these 2 lists (n=69), 32 CpG sites mapping to 28 genes significantly mediated obesity’s effect on fasting insulin. Principal component analysis found that, in total, these 32 methylation sites explained up to 17.3% of the effect of obesity on insulin. Among these mediators, the top CpG site is located in the promoter region of the LIPA (lipase A) gene, and this single CpG site explained 8.4% of the effect of obesity on insulin. Consistent with the higher methylation levels observed in the obese group, LIPA expression was decreased in the obese group (p=0.038). A significant negative partial correlation was also found between LIPA methylation levels and its expression levels (p=0.01, r=-0.26). Genetic variants in LIPA have been suggested to contribute to the interindividual variability in metabolic traits observed among obese individuals. In summary, we observed that peripheral blood DNA methylation mediates obesity’s effect on insulin resistance in African American youth and young adults, explaining up to 17% of the effect.

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