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1.
Firdaus A. A. Mohamed Hoesein Els Wauters Wim Janssens Harry J. M. Groen Joanna Smolonska Cisca Wijmenga Dirkje S. Postma H. Marike Boezen Pim A. De Jong Marc Decramer Jan-Willem J. Lammers Diether Lambrechts Pieter Zanen 《PloS one》2013,8(1)
Genetic variation in nicotinic acetylcholine receptor subunit genes (nAChRs) is associated with lung function level and chronic obstructive pulmonary disease (COPD). It is unknown whether these variants also predispose to an accelerated lung function decline. We investigated the association of nAChR susceptibility variants with lung function decline and COPD severity. The rs1051730 and rs8034191 variants were genotyped in a population-based cohort of 1,226 heavy smokers (COPACETIC) and in an independent cohort of 883 heavy smokers, of which 653 with COPD of varying severity (LEUVEN). Participants underwent pulmonary function tests at baseline. Lung function decline was assessed over a median follow-up of 3 years in COPACETIC. Current smokers homozygous for the rs1051730 A-allele or rs8034191 G-allele had significantly greater FEV1/FVC decline than homozygous carriers of wild-type alleles (3.3% and 4.3%, p = 0.026 and p = 0.009, respectively). In the LEUVEN cohort, rs1051730 AA-carriers and rs8034191 GG-carriers had a two-fold increased risk to suffer from COPD GOLD IV (OR 2.29, 95% confidence interval [CI] = 1.11–4.75; p = 0.025 and OR = 2.42, 95% [CI] = 1.18–4.95; p = 0.016, respectively). The same risk alleles conferred, respectively, a five- and four-fold increased risk to be referred for lung transplantation because of end-stage COPD (OR = 5.0, 95% [CI] = 1.68–14.89; p = 0.004 and OR = 4.06, 95% [CI] = 1.39–11.88; p = 0.010). In Europeans, variants in nAChRs associate with an accelerated lung function decline in current smokers and with clinically relevant COPD. 相似文献
2.
Epidemiological studies show that approximately 20–30% of chronic smokers develop chronic obstructive pulmonary disease (COPD) while 10–15% develop lung cancer. COPD pre-exists lung cancer in 50–90% of cases and has a heritability of 40–77%, much greater than for lung cancer with heritability of 15–25%. These data suggest that smokers susceptible to COPD may also be susceptible to lung cancer. This study examines the association of several overlapping chromosomal loci, recently implicated by GWA studies in COPD, lung function and lung cancer, in (n = 1400) subjects sub-phenotyped for the presence of COPD and matched for smoking exposure. Using this approach we show; the 15q25 locus confers susceptibility to lung cancer and COPD, the 4q31 and 4q22 loci both confer a reduced risk to both COPD and lung cancer, the 6p21 locus confers susceptibility to lung cancer in smokers with pre-existing COPD, the 5p15 and 1q23 loci both confer susceptibility to lung cancer in those with no pre-existing COPD. We also show the 5q33 locus, previously associated with reduced FEV1, appears to confer susceptibility to both COPD and lung cancer. The 6p21 locus previously linked to reduced FEV1 is associated with COPD only. Larger studies will be needed to distinguish whether these COPD-related effects may reflect, in part, associations specific to different lung cancer histology. We demonstrate that when the “risk genotypes” derived from the univariate analysis are incorporated into an algorithm with clinical variables, independently associated with lung cancer in multivariate analysis, modest discrimination is possible on receiver operator curve analysis (AUC = 0.70). We suggest that genetic susceptibility to lung cancer includes genes conferring susceptibility to COPD and that sub-phenotyping with spirometry is critical to identifying genes underlying the development of lung cancer. 相似文献
3.
《PloS one》2014,9(7)
Background
Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.Methods
We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.Results
The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 × 10-7). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 × 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.Conclusions
In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function. 相似文献4.
Background
Research on the effects of dietary nutrients on respiratory health in human populations have not investigated curcumin, a potent anti-oxidant and anti-inflammatory compound present principally in turmeric used in large amounts in Asian curry meals.Objectives
To examine the association of curry intake with pulmonary function among smokers and non-smokers.Design
The frequency of curry intake, respiratory risk factors and spirometry were measured in a population-based study of 2,478 Chinese older adults aged 55 and above in the Singapore Longitudinal Ageing Studies.Results
Curry intake (at least once monthly) was significantly associated with better FEV1 (b = 0.045±0.018, p = 0.011) and FEV1/FVC (b = 1.14±0.52, p = 0.029) in multivariate analyses that controlled simultaneously for gender, age, height, height-squared, smoking, occupational exposure and asthma/COPD history and other dietary or supplementary intakes. Increasing levels of curry intake (‘never or rarely’, ‘occasional’, ‘often’, ‘very often’) were associated with higher mean adjusted FEV1 (p for linear trend = 0.001) and FEV1/FVC% (p for linear trend = 0.048). Significant effect modifications were observed for FEV1 (curry* smoking interaction, p = 0.028) and FEV1/FVC% (curry*smoking interaction, p = 0.05). There were significantly larger differences in FEV1 and FEV1/FVC% between curry intake and non-curry intake especially among current and past smokers. The mean adjusted FEV1 associated with curry intake was 9.2% higher among current smokers, 10.3% higher among past smokers, and 1.5% higher among non-smokers.Conclusion
The possible role of curcumins in protecting the pulmonary function of smokers should be investigated in further clinical studies. 相似文献5.
Masamichi Mineshita Hirotaka Kida Hiroshi Handa Hiroki Nishine Naoki Furuya Seiichi Nobuyama Takeo Inoue Shin Matsuoka Teruomi Miyazawa 《PloS one》2014,9(9)
Background
Regional lung sound intensity in chronic obstructive pulmonary disease (COPD) patients is influenced by the severity and distribution of emphysema, obstructed peripheral airways, and altered ribcage and diaphragm configurations and movements due to hyperinflation. Changes in the lung sound distribution accompanied by pulmonary function improvements in COPD patients were observed after bronchodilator inhalation. We investigated the association of lung sound distribution with pulmonary functions, and the effects of emphysematous lesions on this association. These studies were designed to acquire the basic knowledge necessary for the application of lung sound analysis in the physiological evaluation of COPD patients.Methods
Pulmonary function tests and the percentage of upper- and lower-lung sound intensity (quantitative lung data [QLD]) were evaluated in 47 stable male COPD patients (54 - 82 years of age). In 39 patients, computed tomography taken within 6 months of the study was available and analyzed.Results
The ratio of lower QLD to upper QLD showed significant positive correlations with FEV1 %predicted (%FEV1; ρ = 0.45, p<0.005) and MEF50 %predicted (%MEF50; ρ = 0.46, p<0.005). These correlations were not observed in COPD patients with dominant emphysema (% low attenuation area >40%, n = 20) and were stronger in less emphysematous patients (n = 19, %FEV1; ρ = 0.64, p<0.005, %MEF50; ρ = 0.71, p<0.001).Conclusions
In COPD patients, the ratio of lower- to upper-lung sound intensities decreased according to the severity of obstructive changes, although emphysematous lesions considerably affected lung sound distribution. 相似文献6.
Louise V. Wain Linda Odenthal-Hesse Razan Abujaber Ian Sayers Caroline Beardsmore Erol A. Gaillard Sally Chappell Cristian M. Dogaru Tricia McKeever Tamar Guetta-Baranes Noor Kalsheker Claudia E. Kuehni Ian P. Hall Martin D. Tobin Edward J. Hollox 《PloS one》2014,9(1)
Lung function measures are heritable, predict mortality and are relevant in diagnosis of chronic obstructive pulmonary disease (COPD). COPD and asthma are diseases of the airways with major public health impacts and each have a heritable component. Genome-wide association studies of SNPs have revealed novel genetic associations with both diseases but only account for a small proportion of the heritability. Complex copy number variation may account for some of the missing heritability. A well-characterised genomic region of complex copy number variation contains beta-defensin genes (DEFB103, DEFB104 and DEFB4), which have a role in the innate immune response. Previous studies have implicated these and related genes as being associated with asthma or COPD. We hypothesised that copy number variation of these genes may play a role in lung function in the general population and in COPD and asthma risk. We undertook copy number typing of this locus in 1149 adult and 689 children using a paralogue ratio test and investigated association with COPD, asthma and lung function. Replication of findings was assessed in a larger independent sample of COPD cases and smoking controls. We found evidence for an association of beta-defensin copy number with COPD in the adult cohort (OR = 1.4, 95%CI:1.02–1.92, P = 0.039) but this finding, and findings from a previous study, were not replicated in a larger follow-up sample(OR = 0.89, 95%CI:0.72–1.07, P = 0.217). No robust evidence of association with asthma in children was observed. We found no evidence for association between beta-defensin copy number and lung function in the general populations. Our findings suggest that previous reports of association of beta-defensin copy number with COPD should be viewed with caution. Suboptimal measurement of copy number can lead to spurious associations. Further beta-defensin copy number measurement in larger sample sizes of COPD cases and children with asthma are needed. 相似文献
7.
《PLoS genetics》2012,8(12)
Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P
JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P
JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P
JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects. 相似文献
8.
Ana Maria B. Menezes Rogelio Pérez-Padilla Fernando César Wehrmeister Maria Victorina Lopez-Varela Adriana Mui?o Gonzalo Valdivia Carmen Lisboa José Roberto B. Jardim Maria Montes de Oca Carlos Talamo Renata Bielemann Mariana Gazzotti Ruy Laurenti Bartolomé Celli Cesar G. Victora for the PLATINO team 《PloS one》2014,9(10)
Objective
To determine whether the presence of chronic obstructive lung disease (COPD) and reduction of lung function parameters were predictors of mortality in a cohort.Materials/Patients and Methods
Population based cohorts were followed in Montevideo, Santiago and Sao Paulo during 5, 6 and 9 years, respectively. Outcomes included all-cause, cardiovascular, respiratory and cancer mortality; exposures were COPD, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Cox regression was used for analyses. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics curves and Youden''s index were calculated.Results
Main causes of death were cardiovascular, respiratory and cancer. Baseline COPD was associated with overall mortality (HR = 1.43 for FEV1/FVC<LLN; 2.01 for GOLD 2-4; 1.46 for GOLD 1-4; 1.50 for FEV1/FEV6 <LLN). For cardiovascular mortality, significant associations were found with GOLD 2-4 (HR = 2.68) and with GOLD 1-4 (HR = 1.78) for both genders together (not among women). Low FEV1 was risk for overall and respiratory mortality (both genders combined). FVC was not associated with overall mortality. For most COPD criteria sensitivity was low and specificity high. The area under the curve for FEV1 was greater than for FVC for overall and cardiovascular mortality.Answer to the Question
COPD and low FEV1 are important predictors for overall and cardiovascular mortality in Latin America. 相似文献9.
Ravi Kalhan Betty T. Tran Laura A. Colangelo Sharon R. Rosenberg Kiang Liu Bharat Thyagarajan David R. Jacobs Jr. Lewis J. Smith 《PloS one》2010,5(7)
Background
Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain.Methodology/Principal Findings
We evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001) and forced expiratory volume in 1 second (FEV1) (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001) independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001) and FEV1 (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001). Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR) per standard deviation 1.51 (95% confidence interval (CI): 1.30–1.75) for fibrinogen and 1.35 (95% CI: 1.14–1.59) for CRP). Higher year 5 fibrinogen was additionally associated with abnormal FEV1. A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08–2.16).Conclusion/Significance
Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke.Trial Registration
ClinicalTrials.gov NCT00005130相似文献10.
Jorge Zagaceta Javier J. Zulueta Gorka Bastarrika Inmaculada Colina Ana B. Alcaide Arantza Campo Bartolome R. Celli Juan P. de Torres 《PloS one》2013,8(6)
Rationale
Epicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population. COPD patients have an increased risk of cardiovascular disease, however nothing is known about the EAT volume in this population.Objectives
To assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity.Methods
We measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI. We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC). EAT volume were compared between groups. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables.Results
COPD patients had a higher EAT volume [143.7 (P25–75, 108.3–196.6) vs 129.1 (P25–75, 91.3–170.8) cm3, p = 0.02)] and the EAT volume was significantly associated with CAC (r = 0.38, p<0.001) and CRP (r = 0.32, p<0.001) but not with microalbuminuria (r = 0.12, p = 0.13). In COPD patients, EAT volume was associated with: age, pack-years, BMI, gender, FEV1%, 6 MWD, MMRC and HTN. Multivariate analysis showed that only pack-years (B = 0.6, 95% CI: 0.5–1.3), BMI (B = 7.8, 95% CI: 5.7–9.9) and 6 MWD (B = −0.2, 95% CI: −0.3–−0.1), predicted EAT volume.Conclusions
EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events. 相似文献11.
Bianca Harris Ronald Klein Michael Jerosch-Herold Eric A. Hoffman Firas S. Ahmed David R. Jacobs Jr Barbara E. K. Klein Tien Y. Wong Joao A. C. Lima Mary Frances Cotch R. Graham Barr 《PloS one》2012,7(12)
Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45–84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV1) (P<0.001) and FEV1/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV1 (P = 0.002) but not FEV1/FVC. Myocardial blood flow (n = 126) was associated with lower FEV1 (P = 0.02), lower FEV1/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition. 相似文献
12.
M. Patricia George Mouhamed Kannass Laurence Huang Frank C. Sciurba Alison Morris 《PloS one》2009,4(7)
Background
Prevalence and risk factors for respiratory symptoms and airway obstruction in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART) are unknown. We evaluated respiratory symptoms and measured airway obstruction to identify the impact of HAART and other risk factors on respiratory symptoms and pulmonary function.Methodology/Principal Findings
Two hundred thirty-four HIV-infected adults without acute respiratory symptoms were recruited from an HIV clinic. All subjects were interviewed and performed spirometry. Multivariate linear and logistic regressions were performed to determine predictors of respiratory symptoms, forced expiratory volume in one second (FEV1) percent predicted, and FEV1/forced vital capacity (FEV1/FVC). Thirty-one percent of subjects reported at least one respiratory symptom. Smoking status (current or former versus never) (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.41–5.22, p = 0.003), higher log plasma HIV viral levels (OR = 1.12, 95%CI = 1.02–1.24, p = 0.02), and lower FEV1/FVC (OR = 1.06 for every 0.01 decrease in FEV1/FVC, 95%CI = 1.02–1.14, p = 0.001) were independent predictors of respiratory symptoms. Age (p = 0.04), pack-year smoking history (p<0.001), previous bacterial pneumonia (p = 0.007), and HAART use (p = 0.04) were independent predictors of decreased FEV1/FVC.Conclusions/Significance
Respiratory symptoms remain common in HIV-infected subjects, especially in those with a smoking history. Subjects who were older, had a greater pack-year history of smoking, or previous bacterial pneumonia had lower FEV1/FVC ratios. Interestingly, use of HAART was independently associated with a decreased FEV1/FVC, possibly secondary to an immune response to subclinical infections, increased autoimmunity, or other factors associated with HAART use. 相似文献13.
Jill Koshiol Melissa Rotunno Dario Consonni Angela Cecilia Pesatori Sara De Matteis Alisa M. Goldstein Anil K. Chaturvedi Sholom Wacholder Maria Teresa Landi Jay H. Lubin Neil E. Caporaso 《PloS one》2009,4(10)
Background
Chronic obstructive pulmonary disease (COPD) has been consistently associated with increased risk of lung cancer. However, previous studies have had limited ability to determine whether the association is due to smoking.Methodology/Principal Findings
The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based case-control study recruited 2100 cases and 2120 controls, of whom 1934 cases and 2108 controls reported about diagnosis of chronic bronchitis, emphysema, COPD (chronic bronchitis and/or emphysema), or asthma more than 1 year before enrollment. We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. After adjustment for smoking, other previous lung diseases, and study design variables, lung cancer risk was elevated among individuals with a history of chronic bronchitis (OR = 2.0, 95% CI = 1.5–2.5), emphysema (OR = 1.9, 95% CI = 1.4–2.8), or COPD (OR = 2.5, 95% CI = 2.0–3.1). Among current smokers, association between chronic bronchitis and lung cancer was strongest among lighter smokers. Asthma was associated with a decreased risk of lung cancer in males (OR = 0.48, 95% CI = 0.30–0.78).Conclusions/Significance
These results suggest that the associations of personal history of chronic bronchitis, emphysema, and COPD with increased risk of lung cancer are not entirely due to smoking. Inflammatory processes may both contribute to COPD and be important for lung carcinogenesis. 相似文献14.
Hui Wang Lei Yang Linnan Zou Dongsheng Huang Yuan Guo Mingan Pan Yigang Tan Haibo Zhong Weidong Ji Pixin Ran Nanshan Zhong Jiachun Lu 《PloS one》2012,7(9)
Background
Lung cancer and chronic obstructive pulmonary disease (COPD) share a common risk factor in cigarette smoking and a large portion of patients with lung cancer suffer from COPD synchronously. We therefore hypothesized that COPD is an independent risk factor for lung cancer. Our aim was to investigate the intrinsic linkage of COPD (or emphysema, chronic bronchitis and asthma) and lung cancer.Methods
The present hospital-based case-control study included 1,069 patients with newly diagnosed lung cancer and 1,132 age frequency matched cancer-free controls. The odds ratios (ORs) for the associations between each previous pulmonary disease and lung cancer were estimated with logistic regression models, adjusting for age, sex, family history of cancer, BMI and pack year smoking. In meta-analysis, the pooled effects of previous pulmonary diseases were analyzed with random effects models; and stratification analyses were conducted on smoking status and ethnicity.Results
In the case-control study, previous COPD was associated with the odds for increased risk of lung cancer (OR = 1.29, 95% confidence interval [CI] = 1.00∼1.68); so were emphysema (OR = 1.55, 95%CI = 1.03∼2.32) and chronic bronchitis (OR = 1.22, 95%CI = 0.99∼1.67); while asthma was associated with odds for decreased risk of lung cancer (OR = 0.29, 95%CI = 0.16∼0.53). These associations were more pronounced in smokers (P<.05 for all strata), but not in non-smokers. In meta-analysis, 35 studies (22,010 cases and 44,438 controls) were identified. COPD was significantly associated with the odds for increased risk of lung cancer (pooled OR = 2.76; 95% CI = 1.85–4.11), so were emphysema (OR = 3.02; 95% CI = 2.41–3.79) and chronic bronchitis (OR = 1.88; 95% CI = 1.49–2.36); and these associations were more pronounced in smokers than in non-smokers (P<.001 respectively). No significant association was observed for asthma.Conclusion
Previous COPD could increase the risk of lung cancer, especially in smokers. 相似文献15.
Obeidat M Wain LV Shrine N Kalsheker N Soler Artigas M Repapi E Burton PR Johnson T Ramasamy A Zhao JH Zhai G Huffman JE Vitart V Albrecht E Igl W Hartikainen AL Pouta A Cadby G Hui J Palmer LJ Hadley D McArdle WL Rudnicka AR Barroso I Loos RJ Wareham NJ Mangino M Soranzo N Spector TD Gläser S Homuth G Völzke H Deloukas P Granell R Henderson J Grkovic I Jankovic S Zgaga L Polašek O Rudan I Wright AF Campbell H Wild SH Wilson JF Heinrich J Imboden M Probst-Hensch NM Gyllensten U Johansson Å 《PloS one》2011,6(5):e19382
Rationale
Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium).Objectives
To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample.Methods
We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/−10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations.Results
The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV1 or FEV1/FVC traits using a carefully defined significance threshold of 1.3×10−5. The most significant loci associated with FEV1 include SNPs tagging MACROD2 (P = 6.81×10−5), CNTN5 (P = 4.37×10−4), and TRPV4 (P = 1.58×10−3). Among ever-smokers, SERPINA1 showed the most significant association with FEV1 (P = 8.41×10−5), followed by PDE4D (P = 1.22×10−4). The strongest association with FEV1/FVC ratio was observed with ABCC1 (P = 4.38×10−4), and ESR1 (P = 5.42×10−4) among ever-smokers.Conclusions
Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV1 among smokers in the general population. 相似文献16.
Jan Bergstr?m Kerstin Cederlund Barbro Dahlén Ann-Sofie Lantz Maria Skedinger Lena Palmberg Britt-Marie Sundblad Kjell Larsson 《PloS one》2013,8(3)
The association between chronic obstructive pulmonary disease (COPD) and periodontal disease is sparsely studied. The aim was to describe the co-variation of periodontitis and lung function impairment in smokers. The hypothesis was that the destructive processes in the mouth and the lungs are interdependent due to a general individual susceptibility to detrimental effects of tobacco smoke. Smokers with COPD (n = 28) stage II and III according to GOLD guidelines and smokers without COPD (n = 29) and healthy non-smokers (n = 23) participated in the study. The groups of smokers were matched for cumulative exposure to tobacco smoke. Radiographic, general and dental clinical examination, lung function measurements and quality of life (SF-36) assessment were conducted. The relationship between respiratory and dental outcomes was analyzed. Dental health, assessed by plaque, gingival bleeding, periodontal pocket depth and loss of teeth was impaired in the smokers compared with non-smokers with no major differences between smokers with and without COPD. There was, however, a weak correlation between periodontitis and emphysema/impaired diffusion capacity. Impaired quality of life was associated with smoking and impaired lung function but not influenced by dental status. In conclusion periodontitis was strongly associated with smoking, weakly associated with lung tissue destruction and very weakly or even not at all associated with chronic airflow limitation. The results indicate that, although there was a co-variation between periodontitis and pathologic lung processes in smokers, the risk of developing COPD, as defined by spirometric outcomes, is not associated with the risk of impaired dental health in smokers. 相似文献
17.
Onno M. Mets Pim A. de Jong Bram van Ginneken Cas L. J. J. Kruitwagen Mathias Prokop Matthijs Oudkerk Jan-Willem J. Lammers Pieter Zanen 《PloS one》2013,8(4)
Purpose
We aimed to study the association between lung function decline and quantitative computed tomography (CT) air trapping.Materials and Methods
Current and former heavy smokers in a lung cancer screening trial underwent volumetric low-dose CT in inspiration and expiration. Spirometry was obtained at baseline and after 3 years. The expiratory to inspiratory ratio of mean lung density (E/I-ratioMLD) was used to quantify air trapping. CT emphysema was defined as voxels in inspiratory CT below −950 Hounsfield Unit. Linear mixed modeling was used to determine the association between CT air trapping and lung function.Results
We included 985 subjects with a mean age of 61.3 years. Independent of CT emphysema, CT air trapping was significantly associated with a reduction in forced expiratory volume in one second (FEV1) and the ratio of FEV1 over the forced vital capacity (FEV1/FVC); FEV1 declines with 33 mL per percent increase in CT air trapping, while FEV1/FVC declines 0.58% per percent increase (both p<0.001). CT air trapping further elicits accelerated loss of FEV1/FVC (additional 0.24% reduction per percent increase; p = 0.014).Conclusion
In a lung cancer screening cohort, quantitatively assessed air trapping on low-dose CT is independently associated with reduced lung function and accelerated decline of FEV1/FVC. 相似文献18.
Background
Risk of substance dependence (SD) and obesity has been linked to the function of melanocortin peptides encoded by the proopiomelanocortin gene (POMC).Methods and Results
POMC exons were Sanger sequenced in 280 African Americans (AAs) and 308 European Americans (EAs). Among them, 311 (167 AAs and 114 EAs) were affected with substance (alcohol, cocaine, opioid and/or marijuana) dependence and 277 (113 AAs and164 EAs) were screened controls. We identified 23 variants, including two common polymorphisms (rs10654394 and rs1042571) and 21 rare variants; 12 of which were novel. We used logistic regression to analyze the association between the two common variants and SD or body mass index (BMI), with sex, age, and ancestry proportion as covariates. The common variant rs1042571 in the 3′UTR was significantly associated with BMI in EAs (Overweight: P adj = 0.005; Obese: P adj = 0.018; Overweight+Obese: P adj = 0.002) but not in AAs. The common variant, rs10654394, was not associated with BMI and neither common variant was associated with SD in either population. To evaluate the association between the rare variants and SD or BMI, we collapsed rare variants and tested their prevalence using Fisher’s exact test. In AAs, rare variants were nominally associated with SD overall and with specific SD traits (SD: P FET,1df = 0.026; alcohol dependence: P FET,1df = 0.027; cocaine dependence: P FET,1df = 0.007; marijuana dependence: P FET,1df = 0.050) (the P-value from cocaine dependence analysis survived Bonferroni correction). There was no such effect in EAs. Although the frequency of the rare variants did not differ significantly between the normal-weight group and the overweight or obese group in either population, certain rare exonic variants occurred only in overweight or obese subjects without SD.Conclusion
These findings suggest that POMC exonic variants may influence risk for both SD and elevated BMI, in a population-specific manner. However, common and rare variants in this gene may exert different effects on these two phenotypes. 相似文献19.
Jin Hwa Lee Merry-Lynn N McDonald Michael H Cho Emily S Wan Peter J Castaldi Gary M Hunninghake Nathaniel Marchetti David A Lynch James D Crapo David A Lomas Harvey O Coxson Per S Bakke Edwin K Silverman Craig P Hersh the COPDGene ECLIPSE Investigators 《Respiratory research》2014,15(1)
Background
Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.Methods
We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.Results
Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10−8).Conclusions
In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0097-y) contains supplementary material, which is available to authorized users. 相似文献20.
Ruyang Zhang Yang Zhao Minjie Chu Amar Mehta Yongyue Wei Yao Liu Pengcheng Xun Jianling Bai Hao Yu Li Su Hongxi Zhang Zhibin Hu Hongbing Shen Feng Chen David C. Christiani 《PloS one》2013,8(3)