scholarly journals Meta-analysis of exome array data identifies six novel genetic loci for lung function

2018 ◽  
Vol 3 ◽  
pp. 4 ◽  
Author(s):  
Victoria E. Jackson ◽  
Jeanne C. Latourelle ◽  
Louise V. Wain ◽  
Albert V. Smith ◽  
Megan L. Grove ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
African Ancestry ◽  
Regulation Of Gene Expression ◽  
Forced Expiratory Volume ◽  
European Ancestry ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Array Data

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

scholarly journals Meta-analysis of exome array data identifies six novel genetic loci for lung function

2017 ◽  
Author(s):  
Victoria E Jackson ◽  
Jeanne C Latourelle ◽  
Louise V Wain ◽  
Albert V. Smith ◽  
Megan L. Grove ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
African Ancestry ◽  
Regulation Of Gene Expression ◽  
Forced Expiratory Volume ◽  
European Ancestry ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Array Data

AbstractOver 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease (COPD). We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. eQTL analyses found evidence for regulation of gene expression at three signals and implicated several genes including TYRO3 and PLAU. Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

scholarly journals Meta-analysis of exome array data identifies six novel genetic loci for lung function

2018 ◽  
Vol 3 ◽  
pp. 4 ◽  
Author(s):  
Victoria E. Jackson ◽  
Jeanne C. Latourelle ◽  
Louise V. Wain ◽  
Albert V. Smith ◽  
Megan L. Grove ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
African Ancestry ◽  
Regulation Of Gene Expression ◽  
Forced Expiratory Volume ◽  
European Ancestry ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Array Data

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

scholarly journals Meta-analysis of exome array data identifies six novel genetic loci for lung function

2018 ◽  
Vol 3 ◽  
pp. 4
Author(s):  
Victoria E. Jackson ◽  
Jeanne C. Latourelle ◽  
Louise V. Wain ◽  
Albert V. Smith ◽  
Megan L. Grove ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
African Ancestry ◽  
Regulation Of Gene Expression ◽  
Forced Expiratory Volume ◽  
European Ancestry ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Array Data

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

scholarly journals Serum Albumin Concentrations in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (2) ◽  
pp. 269
Author(s):  
Elisabetta Zinellu ◽  
Alessandro G. Fois ◽  
Elisabetta Sotgiu ◽  
Sabrina Mellino ◽  
Arduino A. Mangoni ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Obstructive Pulmonary Disease ◽  
Serum Albumin ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Standard Mean Difference ◽  
Copd Patients

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.

scholarly journals Prognostic and Functional Impact of Perioperative LAＭA/LABA Inhaled Therapy In Patients With Lung Cancer and Chronic Obstructive Pulmonary Disease 

2021 ◽  
Author(s):  
Yoko Azuma ◽  
Atsushi Sano ◽  
Takashi Sakai ◽  
Satoshi Koezuka ◽  
Hajime Otsuka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Postoperative Complications ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Long Acting

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. The utility of several perioperative bronchodilators in patients with COPD requiring surgery for lung cancer has been reported, but the most suitable agent and its specific effect on postoperative long-term prognosis remain unclear. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients.Methods: Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical records. Patients were divided into 3 groups according to perioperative management: LAMA/LABA (n=64), LAMA (n=23) and rehabilitation only (no bronchodilator) (n=43). Results: Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p<0.001 for both forced expiratory volume in 1 second (FEV1) and percentage of predicted forced expiratory volume in 1 second (FEV1 %pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, 223.1 mL vs 130.0 mL, ΔFEV1 %pred, 10.8% vs 6.8%; both p<0.05). There was a trend toward a lower incidence of postoperative complications in the LAMA/LABA group compared with the LAMA and rehabilitation-only groups. In patients with moderate to severe air flow limitation (n=61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with patients in the other groups. Perioperative LAMA/LABA therapy was also associated with lower recurrence rates. Conclusions: Patients who receive perioperative LAMA/LABA for moderate to severe COPD have improved prognosis and better pulmonary function with surgery for lung cancer. We believe this treatment combination is optimal for patients with lung cancer and COPD.

scholarly journals Inspiratroy Capacity and Exercise Tolerance in Chronic Obstructive Pulmonary Disease

2000 ◽  
Vol 7 (3) ◽  
pp. 282-285 ◽  
Author(s):  
Joseph Milic-Emili
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Airway Obstruction ◽  
Pulmonary Disease ◽  
Exercise Tolerance ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Peripheral Muscle ◽  
Past Half Century

During the past half-century, many studies have investigated the correlation of exercise tolerance to routine lung function in patients with obstructive pulmonary disease. In virtually all of these studies, the degree of airway obstruction was assessed in terms of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Because in most studies only a weak correlation was found between exercise tolerance and degree of airway obstruction, it has been concluded that factors other than lung function impairment (eg, deconditioning and peripheral muscle dysfunction) play a predominant role in limiting exercise capacity in patients with chronic airway obstruction. Recent work, however, suggests that in patients with chronic obstructive pulmonary disease, the inspiratory capacity is a more powerful predictor of exercise tolerance than FEV1 and FVC.

scholarly journals Análise da Revisão Cochrane: Uso de Corticoterapia Sistémica nas Exacerbações Agudas da Doença Pulmonar Obstrutiva Crónica. Cochrane Database Syst Rev. 2014,9:CD001288

2014 ◽  
Vol 27 (5) ◽  
pp. 537
Author(s):  
Pedro Azevedo ◽  
João Costa ◽  
António Vaz-Carneiro
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Treatment Failure ◽  
Pulmonary Disease ◽  
Hospital Admissions ◽  
Cochrane Review ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Early Improvement

<p>Acute exacerbations of chronic obstructive pulmonary disease are a major cause of hospital admissions and mortality, contributing to the decline in lung function, exercise capacity and quality of life. Infections are the major cause of exacerbations and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti- inflammatory agents. This Cochrane review compared: 1. use of oral and parenteral corticosteroids with placebo use; 2. routes of administration among themselves. The results indicate that there is evidence for the use of corticosteroids in the treatment of chronic obstructive pulmonary disease exacerbations since early improvement in lung function [assessed by forced expiratory volume in one second (FEV1)] has been noted, the likelihood of treatment failure and relapse in the first month has been reduced and it shortens the hospital stay in patients who do not require intensive care regimen. However, corticosteroid therapy causes an increase in adverse effects associated with drug, namely hyperglycaemia, especially if the route of administration is parenteral. Parenteral route has not shown to be superior to oral route in treatment failure, relapse, or death. Mortality up to 30 days does not seem to be affected by the use of corticosteroids.</p><p><br /><strong>Keywords:</strong> Adrenal Cortex Hormones; Pulmonary Disease, Chronic Obstructive /drug therapy; Pulmonary Disease, Chronic Obstructive/ complications; Randomized Controlled Trials as Topic.</p>

scholarly journals Association of β-blocker use with survival and pulmonary function in patients with chronic obstructive pulmonary and cardiovascular disease: a systematic review and meta-analysis

2020 ◽  
Vol 41 (46) ◽  
pp. 4415-4422 ◽  
Author(s):  
Yan-Li Yang ◽  
Zi-Jian Xiang ◽  
Jing-Hua Yang ◽  
Wen-Jie Wang ◽  
Zhi-Chun Xu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Forced Expiratory Volume ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Difference

Abstract Aims The aim of this study was to clarify the effect of β-blockers (BBs) on respiratory function and survival in patients with chronic obstructive pulmonary disease with cardiovascular disease (CVD), as well as the difference between the effects of cardioselective and noncardioselective BBs. Methods and results We searched for relevant literature in four electronic databases, namely, PubMed, EMBASE, Cochrane Library, and Web of Science, and compared the differences in various survival indicators between patients with chronic obstructive pulmonary disease taking BBs and those not taking BBs. Forty-nine studies were included, with a total sample size of 670 594. Among these, 12 studies were randomized controlled trials (RCTs; seven crossover and five parallel RCTs) and 37 studies were observational (including four post hoc analyses of data from RCTs). The hazard ratios (HRs) of chronic obstructive pulmonary disease exacerbation between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.77 [95% confidence interval (CI) 0.67, 0.89], 0.72 [95% CI 0.56, 0.94], and 0.98 [95% CI 0.71, 1.34, respectively] (HRs &lt;1 indicate favouring BB therapy). The HRs of all-cause mortality between patients with chronic obstructive pulmonary disease who were not treated with BBs and those who were treated with BBs, cardioselective BBs, and noncardioselective BBs were 0.70 [95% CI 0.59, 0.83], 0.60 [95% CI 0.48, 0.76], and 0.74 [95% CI 0.60, 0.90], respectively (HRs &lt;1 indicate favouring BB therapy). Patients with Chronic obstructive pulmonary disease treated with cardioselective BBs showed no difference in ventilation effect after the use of an agonist, in comparison with placebo. The difference in mean change in forced expiratory volume in 1 s was 0.06 [95% CI −0.02, 0.14]. Conclusion The use of BBs in patients with chronic obstructive pulmonary disease is not only safe but also reduces their all-cause and in-hospital mortality. Cardioselective BBs may even reduce chronic obstructive pulmonary disease exacerbations. In addition, cardioselective BBs do not affect the action of bronchodilators. Importantly, BBs reduce the heart rate acceleration caused by bronchodilators. BBs should be prescribed freely when indicated in patients with chronic obstructive pulmonary disease and heart disease.

Objectively Measured Steps/Day in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 13 (11) ◽  
pp. 1275-1283 ◽  
Author(s):  
Travis Saunders ◽  
Nerissa Campbell ◽  
Timothy Jason ◽  
Gail Dechman ◽  
Paul Hernandez ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Pulmonary Rehabilitation ◽  
Meta Analysis ◽  
Airflow Obstruction ◽  
Forced Expiratory Volume ◽  
Activity Level ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Objectively Measured

Background:Although individual studies have reported on the number of steps/day taken by individuals with chronic obstructive pulmonary disease (COPD), this evidence has not been systematically reviewed or synthesized.Methods:MEDLINE and PsycINFO were searched for studies reporting objectively-measured steps/day and percent predicted forced expiratory volume in 1 second (FEV1%) in patients with COPD. Meta-analyses were used to estimate steps/day across studies, while metaregression was used to estimate between-study variance based on clinical and demographic factors (year and location of study, activity monitor brand, number of days wearing the monitor, whether participants were about to enter pulmonary rehabilitation, 6-minute walk distance (6MWD), FEV1%, age, and sex).Results:38 studies including 2621 participants met inclusion criteria. The pooled mean estimate was 4579 steps/day (95% CI:4310 to 5208) for individuals with COPD. Only 6MWD, FEV1% and whether patients were about to undergo pulmonary rehabilitation explained a significant portion of the variance (P < 0.1) in univariate meta-regression. In a multivariate model including the above risk factors, only FEV1% was associated with steps/day after adjustment for other covariates.Conclusions:These results indicate that patients with COPD achieve extremely low levels of physical activity as assessed by steps/day, and that severity of airflow obstruction is associated with activity level.

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