scholarly journals Surfactant protein D is a causal risk factor for COPD: results of Mendelian randomisation

2017 ◽  
Vol 50 (5) ◽  
pp. 1700657 ◽  
Author(s):  
Ma'en Obeidat ◽  
Xuan Li ◽  
Stephen Burgess ◽  
Guohai Zhou ◽  
Nick Fishbane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Function ◽  
Human Leukocyte ◽  
Surfactant Protein ◽  
Causal Link ◽  
Mendelian Randomisation ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease

Surfactant protein D (SP-D) is produced primarily in the lung and is involved in regulating pulmonary surfactants, lipid homeostasis and innate immunity. Circulating SP-D levels in blood are associated with chronic obstructive pulmonary disease (COPD), although causality remains elusive.In 4061 subjects with COPD, we identified genetic variants associated with serum SP-D levels. We then determined whether these variants affected lung tissue gene expression in 1037 individuals. A Mendelian randomisation framework was then applied, whereby serum SP-D-associated variants were tested for association with COPD risk in 11 157 cases and 36 699 controls and with 11 years decline of lung function in the 4061 individuals.Three regions on chromosomes 6 (human leukocyte antigen region), 10 (SFTPDgene) and 16 (ATP2C2gene) were associated with serum SP-D levels at genome-wide significance. In Mendelian randomisation analyses, variants associated with increased serum SP-D levels decreased the risk of COPD (estimate −0.19, p=6.46×10−03) and slowed the lung function decline (estimate=0.0038, p=7.68×10−3).Leveraging genetic variation effect on protein, lung gene expression and disease phenotypes provided novel insights into SP-D biology and established a causal link between increased SP-D levels and protection against COPD risk and progression. SP-D represents a very promising biomarker and therapeutic target for COPD.

scholarly journals Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

2019 ◽  
Vol 53 (4) ◽  
pp. 1801795 ◽  
Author(s):  
Herman T. den Dekker ◽  
Kimberley Burrows ◽  
Janine F. Felix ◽  
Lucas A. Salas ◽  
Ivana Nedeljkovic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Function ◽  
Life Course ◽  
Cord Blood ◽  
Childhood Asthma ◽  
Respiratory Health ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Life Course

RationaleWe aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.MethodsWe meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7–13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.ResultsWe identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.InterpretationOur findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.

scholarly journals Emphysema and extrapulmonary tissue loss in COPD: a multi-organ loss of tissue phenotype

2018 ◽  
Vol 51 (2) ◽  
pp. 1702146 ◽  
Author(s):  
Bartolome R. Celli ◽  
Nicholas Locantore ◽  
Ruth Tal-Singer ◽  
John Riley ◽  
Bruce Miller ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Forced Expiratory Volume ◽  
Fat Free Mass ◽  
Tissue Loss ◽  
Cell Protein ◽  
Surfactant Protein D ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Club Cell ◽  
Body Compartments

We tested whether emphysema progression accompanies enhanced tissue loss in other body compartments in 1817 patients from the ECLIPSE chronic obstructive pulmonary disease (COPD) cohort.Clinical and selected systemic biomarker measurements were compared in subjects grouped by quantitative tomography scan emphysema quartiles using the percentage of low attenuation area (LAA%). Lowest and highest quartile patients had amino-acid metabolomic profiles. We related LAA% to 3 years decline in lung function (forced expiratory volume in 1 s (FEV1)), body mass index (BMI), fat-free mass index (FFMI) and exacerbations, hospitalisations and mortality rates.Participants with more baseline emphysema had lower FEV1, BMI and FFMI, worse functional capacity, and less cardiovascular disease but more osteoporosis. Systemic C-reactive protein and interleukin-6 levels were similar among groups, but club cell protein 16 was higher and interleukin-8, surfactant protein D and soluble receptor for advanced glycation end product were lower with more emphysema. Metabolomics differed between extreme emphysema quartiles. Patients with more emphysema had accelerated FEV1, BMI and FFMI decline and more exacerbations, hospitalisations and mortality.COPD patients with more emphysema undergo excessive loss of pulmonary and extrapulmonary tissue, which is probably related to abnormal tissue maintenance. Because of worse clinical outcomes, we propose this subgroup be named the multi-organ loss of tissue (MOLT) COPD phenotype.

scholarly journals Lung function, forced expiratory volume in 1 s decline and COPD hospitalisations over 44 years of follow-up

2015 ◽  
Vol 47 (3) ◽  
pp. 742-750 ◽  
Author(s):  
Suneela Zaigham ◽  
Per Wollmer ◽  
Gunnar Engström
Keyword(s):  
Lung Function ◽  
Airflow Obstruction ◽  
Fixed Ratio ◽  
Population Based ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Hazard Ratios

The use of baseline lung function in the prediction of chronic obstructive pulmonary disease (COPD) hospitalisations, all-cause mortality and lung function decline was assessed in the population-based “Men Born in 1914” cohort.Spirometry was assessed at age 55 years in 689 subjects, of whom 392 had spirometry reassessed at age 68  years. The cohort was divided into three groups using fixed ratio (FR) and lower limit of normal (LLN) criterion: forced expiratory volume in 1 s (FEV1)/vital capacity (VC) ≥70%, FEV1/VC <70% but ≥LLN (FR+LLN−), and FEV1/VC <70% and <LLN (FR+LLN+).Over 44 years of follow-up, 88 men were hospitalised due to COPD and 686 died. Hazard ratios (95% CI) for incident COPD hospitalisation were 4.15 (2.24–7.69) for FR+LLN− and 7.88 (4.82–12.87) for FR+LLN+ (reference FEV1/VC ≥70%). Hazard ratios for death were 1.30 (0.98–1.72) for FR+LLN− and 1.58 (1.25–2.00) for FR+LLN+. The adjusted FEV1 decline between 55 and 68 years of age was higher for FR+LLN− and FR+LLN+ relative to the reference. Of those with FR+LLN− at 55 years, 53% had progressed to the FR+LLN+ group at 68 years.Airflow obstruction at age 55 years is a powerful risk factor for future COPD hospitalisations. The FR+LLN− group should be carefully evaluated in clinical practice in relation to future risks and potential benefit from early intervention. This is reinforced by the increased FEV1 decline in this group.

scholarly journals BMI is associated with FEV1 decline in chronic obstructive pulmonary disease: a meta-analysis of clinical trials

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yilan Sun ◽  
Stephen Milne ◽  
Jen Erh Jaw ◽  
Chen Xi Yang ◽  
Feng Xu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Clinical Trials ◽  
Lung Function ◽  
Protective Effect ◽  
Obesity Paradox ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Meta Regression ◽  
The Relationship

Abstract Background There is considerable heterogeneity in the rate of lung function decline in chronic obstructive pulmonary disease (COPD), the determinants of which are largely unknown. Observational studies in COPD indicate that low body mass index (BMI) is associated with worse outcomes, and overweight/obesity has a protective effect – the so-called “obesity paradox”. We aimed to determine the relationship between BMI and the rate of FEV1 decline in data from published clinical trials in COPD. Methods We performed a systematic review of the literature, and identified 5 randomized controlled trials reporting the association between BMI and FEV1 decline. Four of these were included in the meta-analyses. We analyzed BMI in 4 categories: BMI-I (< 18.5 or <  20 kg/m2), BMI-II (18.5 or 20 to < 25 kg/m2), BMI-III (25 to < 29 or < 30 kg/m2) and BMI-IV (≥29 or ≥ 30 kg/m2). We then performed a meta-regression of all the estimates against the BMI category. Results The estimated rate of FEV1 decline decreased with increasing BMI. Meta-regression of the estimates showed that BMI was significantly associated with the rate of FEV1 decline (linear trend p = 1.21 × 10− 5). Conclusions These novel findings support the obesity paradox in COPD: compared to normal BMI, low BMI is a risk factor for accelerated lung function decline, whilst high BMI has a protective effect. The relationship may be due to common but as-of-yet unknown causative factors; further investigation into which may reveal novel endotypes or targets for therapeutic intervention.

scholarly journals Role of Diet in Chronic Obstructive Pulmonary Disease Prevention and Treatment

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1357 ◽  
Author(s):  
Egeria Scoditti ◽  
Marika Massaro ◽  
Sergio Garbarino ◽  
Domenico Maurizio Toraldo
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Dietary Patterns ◽  
Scientific Evidence ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Prevention And Treatment ◽  
The Impact

Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem. Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment. This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action. Several dietary options can be considered in terms of COPD prevention and/or progression. Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD. Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health.

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