Effects of testosterone and sex hormone binding globulin on lung function in males and females: a multivariable Mendelian Randomisation study.

Background: Observational studies suggest that total testosterone (TT) and sex hormone-binding globulin (SHBG) may have beneficial effects on lung function, but these findings might be spurious due to confounding and reverse causation. We addressed these limitations by using multivariable Mendelian randomisation (MVMR) to investigate the independent causal effects of TT and SHBG on lung function.

Methods: We first identified genetic instruments by performing genome-wide association analyses of TT and SHBG in the large UK Biobank, separately in males and females.

SNPs inandgenes are associated with FeNO in adult subjects with asthma.

Nitric oxide has different roles in asthma as both an endogenous modulator of airway function and a pro-inflammatory mediator. Fractional exhaled nitric oxide (FeNO) is a reliable, quantitative, non-invasive, simple, and safe biomarker for assessing airways inflammation in asthma. Previous genome-wide and genetic association studies have shown that different genes and single nucleotide polymorphisms (SNPs) are linked to FeNO.

Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort.

Background: The prevalence of obstructive sleep apnea is higher in women after menopause. This is suggested to be a result of an altered sex hormone balance but has so far not been confirmed in a population-based study.

Objective: To investigate whether serum concentration of estrogens and progesterone are associated with the prevalence of sleep apnea symptoms in middle-aged women of the general population.

Pulmonary Function and Blood DNA Methylation: A Multiancestry Epigenome-Wide Association Meta-analysis.

Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

Impact of COVID-19 pandemic on sickness absence for mental ill health in National Health Service staff.

Objective: To explore the patterns of sickness absence in National Health Service (NHS) staff attributable to mental ill health during the first wave of the COVID-19 epidemic in March-July 2020.

Design: Case-referent analysis of a secondary dataset.

Setting: NHS Trusts in England.

Ethnic differences in risk of severe Covid-19: To what extent are they driven by exposure?

Background: This study quantifies the risk of Covid-19 among ethnic groups of healthcare staff during the first pandemic wave in England.

Methods: We analysed data on 959 356 employees employed by 191 National Health Service trusts during 1 January 2019 to 31 July 2020, comparing rates of Covid-19 sickness absence in different ethnic groups.

Results: In comparison with White ethnic groups, the risk of short-duration Covid-19 sickness absence was modestly elevated in South Asian but not Black groups.

Changing patterns of sickness absence among healthcare workers in England during the COVID-19 pandemic.

Background: Patterns of sickness absence shed useful light on disease occurrence and illness-related behaviours in working populations.

Methods: We analysed prospectively collected, pseudonymized data on 959 356 employees who were continuously employed by National Health Service trusts in England from 1 January 2019 to 31 July 2020, comparing the frequency of new sickness absence in 2020 with that at corresponding times in 2019.

Results: After exclusion of episodes directly related to COVID-19, the overall incidence of sickness absence during the initial 10 weeks of the pandemic (March-May 2020) was more than 20% lower than in corresponding weeks of 2019.

Risks of COVID-19 by occupation in NHS workers in England.

Objective: To quantify occupational risks of COVID-19 among healthcare staff during the first wave (9 March 2020-31 July 2020) of the pandemic in England.

Methods: We used pseudonymised data on 902 813 individuals employed by 191 National Health Service trusts to explore demographic and occupational risk factors for sickness absence ascribed to COVID-19 (n=92 880). We estimated ORs by multivariable logistic regression.

The use of two-sample methods for Mendelian randomization analyses on single large datasets.

Background: With genome-wide association data for many exposures and outcomes now available from large biobanks, one-sample Mendelian randomization (MR) is increasingly used to investigate causal relationships. Many robust MR methods are available to address pleiotropy, but these assume independence between the gene-exposure and gene-outcome association estimates. Unlike in two-sample MR, in one-sample MR the two estimates are obtained from the same individuals, and the assumption of independence does not hold in the presence of confounding.

ERS International Congress 2020: highlights from the Epidemiology and Environment Assembly.

In this article, early career members of the Epidemiology and Environment Assembly of the European Respiratory Society (ERS) summarise a selection of five sessions from the ERS 2020 Virtual International Congress. The topics covered include risk factors for chronic respiratory diseases over the life course, from early life origins to occupational exposures in adulthood, and the interplay between these risk factors, including gene-environment interactions. Novel results were also presented on smoking prevention and potential risks of vaping.

Epigenome-wide association study identifies DNA methylation markers for asthma remission in whole blood and nasal epithelium.

Background: Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission.

Methods: Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness.

Lung function changes over 8 years and testosterone markers in both sexes: UK Biobank.

Higher levels of testosterone have been associated with better lung function in cross-sectional population-based studies. The role of testosterone in lung function in women and in lung function decline in men or women is unclear. We studied 5114 men and 5467 women in the UK Biobank with high-quality spirometry at baseline (2006-2010) and 8.

A cross-omics integrative study of metabolic signatures of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis.

Methods: We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function.

Low serum DHEA-S is associated with impaired lung function in women.

Background: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS).

Methods: Lung function and serum DHEA-S concentrations were measured in  = 2,045 and  = 1,725 women in 1999-2002 and in 2010-2013, respectively.

Analyzing degraded DNA and challenging samples using the ForenSeq™ DNA Signature Prep kit.

Typing short tandem repeats (STRs) is the basis for human identification in current forensic testing. The standard method uses capillary electrophoresis (CE) to separate amplicons by length and fluorescent labeling. In recent years new methods, including massively parallel sequencing (MPS), have been developed which increased the discriminative power of STRs through sequencing.

Antioxidant genes and susceptibility to air pollution for respiratory and cardiovascular health.

Oxidative stress occurs when antioxidant defences, which are regulated by a complex network of genes, are insufficient to maintain the level of reactive oxygen species below a toxic threshold. Outdoor air pollution has long been known to adversely affect health and one prominent mechanism of action common to all pollutants is the induction of oxidative stress. An individual's susceptibility to the effects of air pollution partly depends on variation in their antioxidant genes.

DNA methylation is associated with lung function in never smokers.

Background: Active smoking is the main risk factor for COPD. Here, epigenetic mechanisms may play a role, since cigarette smoking is associated with differential DNA methylation in whole blood. So far, it is unclear whether epigenetics also play a role in subjects with COPD who never smoked.

Age at menopause and lung function: a Mendelian randomisation study.

In observational studies, early menopause is associated with lower forced vital capacity (FVC) and a higher risk of spirometric restriction, but not airflow obstruction. It is, however, unclear if this association is causal. We therefore used a Mendelian randomisation (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function.

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression.

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels.

Epigenome-wide association study of lung function level and its change.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.