Publications
180 results found
van der Plaat DA, Lenoir A, Dharmage S, et al., 2024, Effects of testosterone and sex hormone binding globulinon lung function in males and females: a multivariable Mendelian Randomisation study, Thorax, ISSN: 0040-6376
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. We then assessed the independent effects of TT and SHBG on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC using one-sample MVMR. We addressed pleiotropy, which could bias MVMR, using several methods that account for it. We performed subgroup MVMR analyses by obesity, physical activity and menopausal status, and assessed associations between TT and SHBG with lung function decline. Finally, we compared the MVMR results with those of observational analyses in the UK Biobank. FINDINGS: In the MVMR analyses, there was evidence of pleiotropy, but results were consistent when accounting for it. We found a strong beneficial effect of TT on FVC and FEV1 in both males and females, but a moderate detrimental effect of SHBG on FEV1 and FEV1/FVC in males only. Subgroup analyses suggested stronger effects of TT among obese and older males. The observational analyses, in line with previous studies, agreed with MRMV for TT, but not for SHBG. INTERPRETATION: These findings suggest that testosterone improves lung function in males and females, while SHBG has an opposite independent effect in males.
Accordini S, Lando V, Calciano L, et al., 2024, SNPs in FAM13A and IL2RB genes are associated with FeNO in adult subjects with asthma, Journal of Breath Research: volatiles for medical diagnosis, Vol: 18, ISSN: 1752-7155
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. We aimed at identifying SNPs in candidate genes or gene regions that are associated with FeNO in asthma. We evaluated 264 asthma cases (median age 42.8 years, female 47.7%) who had been identified in the general adult population within the Gene Environment Interactions in Respiratory Diseases survey in Verona (Italy; 2008–2010). Two hundred and twenty-one tag-SNPs, which are representative of 50 candidate genes, were genotyped by a custom GoldenGate Genotyping Assay. A two-step association analysis was performed without assuming an a priori genetic model: step (1) a machine learning technique [gradient boosting machine (GBM)] was used to select the 15 SNPs with the highest variable importance measure; step (2) the GBM-selected SNPs were jointly tested in a linear regression model with natural log-transformed FeNO as the normally distributed outcome and with age, sex, and the SNPs as covariates. We replicated our results within an independent sample of 296 patients from the European Community Respiratory Health Survey III. We found that SNP rs987314 in family with sequence similarity 13 member A (FAM13A) and SNP rs3218258 in interleukin 2 receptor subunit beta (IL2RB) gene regions are significantly associated with FeNO in adult subjects with asthma. These genes are involved in different mechanisms that affect smooth muscle constriction and endothelial barrier function responses (FAM13A), or in immune response processes (IL2RB). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with
Nafees AA, Allana A, Kadir MM, et al., 2024, A cluster randomised controlled trial to reduce respiratory effects of cotton dust exposure among textile workers: the MultiTex RCT study., Eur Respir J, Vol: 63
BACKGROUND: We determined the effectiveness of an intervention to reduce cotton dust-related respiratory symptoms and improve lung function of textile workers. METHODS: We undertook a cluster randomised controlled trial at 38 textile mills in Karachi, Pakistan. The intervention comprised: training in occupational health for workers and managers, formation of workplace committees to promote a health and safety plan that included wet mopping and safe disposal of cotton dust, provision of simple face masks, and further publicity about the risks from cotton dust. Participating mills were randomised following baseline data collection. The impact of the intervention was measured through surveys at 3, 12 and 18 months using questionnaires, spirometry and dust measurements. The primary outcomes were 1) changes in prevalence of a composite respiratory symptom variable, 2) changes in post-bronchodilator percentage predicted forced expiratory volume in 1 s (FEV1) and 3) changes in cotton dust levels. These were assessed using two-level mixed effects linear and logistic regression. RESULTS: Of 2031 participants recruited at baseline, 807 (40%) were available at the third follow-up. At that point, workers in the intervention arm were more likely to report an improvement in respiratory symptoms (OR 1.58, 95% CI 1.06-2.36) and lung function (FEV1 % pred: β 1.31%, 95% CI 0.04-2.57%). Personal dust levels decreased, more so in intervention mills, although we did not observe this in adjusted models due to the small number of samples. CONCLUSION: We found the intervention to be effective in improving the respiratory health of textile workers and recommend scaling-up of such simple and feasible interventions in low- and middle-income countries.
Amaral A, Potts J, Knox-Brown B, et al., 2023, Cohort profile: Burden of Obstructive Lung Disease (BOLD) study, International Journal of Epidemiology, Vol: 52, Pages: e364-e373, ISSN: 0300-5771
Valencia-Hernández CA, Del Greco M F, Sundaram V, et al., 2023, Asthma and incident coronary heart disease: an observational and Mendelian randomisation study, European Respiratory Journal, Vol: 62, ISSN: 0903-1936
Observational studies suggest asthma is a risk factor for coronary heart disease (CHD) and sex modifies the risk, but they may suffer from methodological limitations. To overcome these, we applied a "triangulation approach", where different methodologies, with different potential biases, were leveraged to enhance confidence in findings.First, we conducted an observational study using U.K. medical records to match asthma patients, by age, sex and GP practice, 1:1 to the general population. We measured the association between asthma and incident CHD (myocardial infarction: hospitalisation/death) by applying minimal sufficient adjustment: model 1, smoking, body mass index, oral corticosteroids, atopy and deprivation; model 2, additionally adjusting for healthcare behaviour (GP consultation frequency). Second, we conducted a Mendelian Randomisation (MR) study using data from the UK Biobank, Trans-National Asthma Genetic Consortium, and Coronary Artery Disease Genome-wide Replication and Meta-analysis consortium. Using 64 asthma SNPs, the effect of asthma on CHD was estimated with inverse variance-weighted meta-analysis and methods that adjust for pleiotropy.In our observational study (N=1 522 910), we found asthma was associated with 6% increased risk of CHD (model 1: HR=1.06, 95%CI=1.01-1.13), after accounting for healthcare behaviour, we found no association (model 2: HR=0.99, 95% CI=0.94-1.05). Asthma severity did not modify the association, but sex did (females: HR=1.11, 95%CI=1.01-1.21; males: HR=0.91, 95%CI=0.84-0.98). Our MR study (N=589 875) found no association between asthma and CHD (OR=1.01; 95%CI=0.98-1.04) and no modification by sex.Our findings suggest that asthma is not a risk factor for CHD. Previous studies may have suffered from detection bias or residual confounding.
Knox-Brown B, Potts J, Quintero Santofimio V, et al., 2023, Isolated small airways obstruction predicts future chronic airflow obstruction: A multinational longitudinal study, BMJ Open Respiratory Research, Vol: 10, ISSN: 2052-4439
Background Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life.Methods We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF25–75) if a result was less than the lower limit of normal (<LLN) in the presence of a normal forced expiratory volume in 1 s to FVC ratio (FEV1/FVC). We also used the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) to define small airways obstruction. We defined chronic airflow obstruction as post-bronchodilator FEV1/FVC<LLN. We performed mixed effects regression analyses to model the association between baseline isolated small airways obstruction and chronic airflow obstruction at follow-up. We assessed discriminative and predictive ability by calculating the area under the receiver operating curve (AUC) and Brier score. We replicated our analyses in 26 512 participants of the UK Biobank study.Results Median follow-up time was 8.3 years. Chronic airflow obstruction was more likely to develop in participants with isolated small airways obstruction at baseline (FEF25-75 less than the LLN, OR: 2.95, 95% CI 1.02 to 8.54; FEV3/FVC less than the LLN, OR: 1.94, 95% CI 1.05 to 3.62). FEF25-75 was better than the FEV3/FVC ratio to discriminate future chronic airflow obstruction (AUC: 0.764 vs 0.692). Results were similar among participants of the UK Biobank study.Conclusion Measurements of small airways obstruction can be used as early markers of future obstructive lung disease.
Konstantinoudis G, Minelli C, Lam HCY, et al., 2023, Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019, Thorax, Vol: 78, Pages: 875-881, ISSN: 0040-6376
BACKGROUND: Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space. METHODS: We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays). RESULTS: After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable. CONCLUSION: This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.
Patel J, Amaral A, Minelli C, et al., 2023, Chronic airflow obstruction attributable to poverty in the multinational Burden of Obstructive Lung Disease study, Thorax, Vol: 78, Pages: 942-945, ISSN: 0040-6376
Poverty is strongly associated with all-cause and chronic obstructive pulmonary disease (COPD) mortality. Less is known about the contribution of poverty to spirometrically defined chronic airflow obstruction (CAO) – a key characteristic of COPD. Using cross-sectional data from an asset-based questionnaire to define poverty in 21 sites of the Burden of Obstructive Lung Disease study, we estimated the risk of CAO attributable to poverty. Up to 6% of the population over 40 years had CAO attributable to poverty. Understanding the relationship between poverty and CAO might suggest ways to improve lung health, especially in low- and middle-income countries.
Burgess S, Davey Smith G, Davies NM, et al., 2023, Guidelines for performing Mendelian randomization investigations: update for summer 2023, Wellcome Open Research, Vol: 4, Pages: 186-186
<ns3:p>This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into ten sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust statistical methods and one on other approaches), extensions and additional analyses, data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 24 months.</ns3:p>
Reynolds CJ, Minelli C, 2023, Reply: Confounding in Mendelian randomisation studies, EUROPEAN RESPIRATORY JOURNAL, Vol: 62, ISSN: 0903-1936
Lando V, Calciano L, Minelli C, et al., 2023, <i>IL18</i> Gene Polymorphism Is Associated with Total IgE in Adult Subjects with Asthma, JOURNAL OF CLINICAL MEDICINE, Vol: 12
Reynolds CJ, Del Greco M F, Allen RJ, et al., 2023, The causal relationship between gastro-esophageal reflux disease and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study., Eur Respir J
BACKGROUND: Gastro-esophageal reflux disease (GERD) is associated with idiopathic pulmonary fibrosis (IPF) in observational studies. It is not known if this association arises because GERD causes IPF, or IPF causes GERD, or because of confounding by factors, such as smoking, associated with both GERD and IPF. We used bidirectional Mendelian randomisation (MR), where genetic variants are used as instrumental variables to address issues of confounding and reverse causation, to examine how, if at all, GERD and IPF are causally related. METHODS AND RESULTS: A bidirectional two-sample MR was performed to estimate the causal effect of GERD on IPF risk, and of IPF on GERD risk, using genetic data from the largest GERD (78 707 cases and 288 734 controls) and IPF (4125 cases and 20 464 controls) genome-wide association meta-analyses currently available. GERD increased the risk of IPF, with an odds ratio (OR) of 1.6 (95% Confidence Interval, CI: 1.04-2.49; p=0.032). There was no evidence of a causal effect of IPF on the risk of GERD, with an OR of 0.999 (95%CI: 0.997-1.000; p=0.245). CONCLUSION: We found that GERD increases the risk of IPF, but found no evidence that IPF increases the risk of GERD. GERD should be considered in future studies of IPF risk, and interest in it as a potential therapeutic target should be renewed. The mechanisms underlying the effect of GERD on IPF should also be investigated.
Sara DM, Minelli C, Broccia G, et al., 2023, COVID-19 and non-Hodgkin's lymphoma: A common susceptibility pattern?, PLOS ONE, Vol: 18, ISSN: 1932-6203
Reynolds CJ, Sisodia R, Barber C, et al., 2023, What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case-control study, OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, Vol: 80, Pages: 97-103, ISSN: 1351-0711
- Author Web Link
- Cite
- Citations: 2
Hoffmann J, Amici C, Minelli C, et al., 2023, Biomechanics of suplex in Greco-Roman wrestling: a qualitative and time-motion analysis of international competitions, INTERNATIONAL JOURNAL OF PERFORMANCE ANALYSIS IN SPORT, Vol: 23, Pages: 1-14, ISSN: 2474-8668
Lessof C, Cooper R, Wong A, et al., 2023, Comparison of devices used to measure blood pressure, grip strength and lung function: A randomised cross-over study., PLoS One, Vol: 18
BACKGROUND: Blood pressure, grip strength and lung function are frequently assessed in longitudinal population studies, but the measurement devices used differ between studies and within studies over time. We aimed to compare measurements ascertained from different commonly used devices. METHODS: We used a randomised cross-over study. Participants were 118 men and women aged 45-74 years whose blood pressure, grip strength and lung function were assessed using two sphygmomanometers (Omron 705-CP and Omron HEM-907), four handheld dynamometers (Jamar Hydraulic, Jamar Plus+ Digital, Nottingham Electronic and Smedley) and two spirometers (Micro Medical Plus turbine and ndd Easy on-PC ultrasonic flow-sensor) with multiple measurements taken on each device. Mean differences between pairs of devices were estimated along with limits of agreement from Bland-Altman plots. Sensitivity analyses were carried out using alternative exclusion criteria and summary measures, and using multilevel models to estimate mean differences. RESULTS: The mean difference between sphygmomanometers was 3.9mmHg for systolic blood pressure (95% Confidence Interval (CI):2.5,5.2) and 1.4mmHg for diastolic blood pressure (95% CI:0.3,2.4), with the Omron HEM-907 measuring higher. For maximum grip strength, the mean difference when either one of the electronic dynamometers was compared with either the hydraulic or spring-gauge device was 4-5kg, with the electronic devices measuring higher. The differences were small when comparing the two electronic devices (difference = 0.3kg, 95% CI:-0.9,1.4), and when comparing the hydraulic and spring-gauge devices (difference = 0.2kg, 95% CI:-0.8,1.3). In all cases limits of agreement were wide. The mean difference in FEV1 between spirometers was close to zero (95% CI:-0.03,0.03), limits of agreement were reasonably narrow, but a difference of 0.47l was observed for FVC (95% CI:0.53,0.42), with the ndd Easy on-PC measuring higher. CONCLUSION: Our study highlights po
Gayle A, Lenoir A, Minelli C, et al., 2022, Are we missing lifetime COPD diagnosis among people with COPD recorded death?, British Journal of General Practice Open, Vol: 6, ISSN: 2398-3795
Background: The British Lung Foundation previously estimated that 2.2 million symptomatic but undiagnosed people with COPD live in the UK. Aim: This study investigates the proportion of patients with a missed COPD diagnosis among those with COPD as the cause of death on their death certificate and how this has changed over the past 17 years. Design and Setting: We linked Clinical Practice Research Datalink Aurum and GOLD primary care data with Office for National Statistics mortality data and Hospital Episode Statistics data. We included adults who died between 2000 and 2017 with COPD as their main cause of death. Method: Using a range of diagnostic COPD criteria, we estimated the proportion of patients with a missed COPD diagnosis, and described the demographic and clinical characteristics of patients with and without prior COPD diagnosis using a mixed effect logistic regression model. Results: Depending on the COPD definition used, between 96% and 27% of the 78,621 patients included received a diagnosis of COPD prior to death. Using presence of a COPD Read or SNOMED CT code and performed spirometry as a main definition, just over half of the patients (52%) had received a COPD diagnosis overall, with a proportion of those who did not decreasing from 91% in 2000 to 31% in 2017 (p-trend <0.001). Conclusion: The proportion of people with COPD-recorded death who had received a diagnosis of COPD has improved over time and currently represents the majority of them, suggesting that few patients are being missed.
Konstantinoudis G, Cosetta M, Vicedo Cabrera AM, et al., 2022, Ambient heat exposure and COPD hospitalisations in England: a nationwide case-crossover study during 2007-2018, Thorax, Vol: 77, Pages: 1098-1104, ISSN: 0040-6376
Background: There is emerging evidence suggesting a link between ambient heat exposure and chronic obstructive pulmonary disease (COPD) hospitalisations. Individual and contextual characteristics can affect population vulnerabilities to COPD hospitalisation due to heat exposure. This study quantifies the effect of ambient heat on COPD hospitalisations and examines population vulnerabilities by age, sex and contextual characteristics.Methods: Individual data on COPD hospitalisation at high geographical resolution (postcodes) during 2007–2018 in England was retrieved from the small area health statistics unit. Maximum temperature at 1 km ×1 km resolution was available from the UK Met Office. We employed a case-crossover study design and fitted Bayesian conditional Poisson regression models. We adjusted for relative humidity and national holidays, and examined effect modification by age, sex, green space, average temperature, deprivation and urbanicity.Results: After accounting for confounding, we found 1.47% (95% Credible Interval (CrI) 1.19% to 1.73%) increase in the hospitalisation risk for every 1°C increase in temperatures above 23.2°C (lags 0–2 days). We reported weak evidence of an effect modification by sex and age. We found a strong spatial determinant of the COPD hospitalisation risk due to heat exposure, which was alleviated when we accounted for contextual characteristics. 1851 (95% CrI 1 576 to 2 079) COPD hospitalisations were associated with temperatures above 23.2°C annually.Conclusion: Our study suggests that resources should be allocated to support the public health systems, for instance, through developing or expanding heat-health alerts, to challenge the increasing future heat-related COPD hospitalisation burden.
Leavy OC, Kawano-Dourado L, Stewart ID, et al., 2022, Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>A usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid arthritis (RA) related Interstitial Lung Disease (RA-ILD). The RA-UIP phenotype could result from either a causal relationship of RA on UIP or vice versa, or from a simple co-occurrence of RA and IPF due to shared demographic, genetic or environmental risk factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used two-sample bidirectional Mendelian Randomisation (MR) to investigate the causal effects of RA on UIP and of UIP on RA, using variants from genome-wide association studies of RA (separately for seropositive and seronegative RA) and of IPF as genetic instruments. We conducted inverse-variance-weighted fixed-effect MR as a primary analysis and undertook sensitivity analyses to assess potential violations of the key MR assumption of no (horizontal) pleiotropy.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Seropositive RA showed a significant protective effect on IPF (Odds Ratio, OR = 0.93; 95% Confidence Interval, CI: 0.87-0.99; <jats:italic>P</jats:italic>=0.032), while the MR in the other direction showed a strongly significant causal effect of IPF on seropositive RA (OR = 1.06, 95% CI: 1.04-1.08, <jats:italic>P</jats:italic>=1.22×10<jats:sup>−11</jats:sup>).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our findings support the hypothesis that RA-UIP may be due to a cause-effect relationship between IPF and RA, rather than due to a coincidental occurrence of IPF in patients with RA. The causal effect of IPF on seropositive RA sugg
Adamson A, Portas L, Accordini S, et al., 2022, Communication of personalised disease risk by general practitioners to motivate smoking cessation in England: a cost-effectiveness and research prioritisation study, ADDICTION, Vol: 117, Pages: 1438-1449, ISSN: 0965-2140
- Author Web Link
- Cite
- Citations: 2
Stone P, Minelli C, Feary J, et al., 2022, NEWS2’ as an objective assessment of hospitalised COPD exacerbation severity, International Journal of COPD, Vol: 17, Pages: 763-772, ISSN: 1176-9106
Introduction: There is currently no accepted way to risk-stratify hospitalised exacerbations of chronic obstructive pulmonary disease (COPD). We hypothesised that the revised UK National Early Warning Score (NEWS2) calculated at admission would predict inpatient mortality, need for non-invasive ventilation (NIV) and length-of-stay.Methods: We included data from 52,284 admissions for exacerbation of COPD. Data were divided into development and validation cohorts. Logistic regression was used to examine relationships between admission NEWS2 and outcome measures. Predictive ability of NEWS2 was assessed using area under receiver operating characteristic curves (AUC). We assessed the benefit of including other baseline data in the prediction models and assessed whether these variables themselves predicted admission NEWS2.Results: 53% of admissions had low risk, 24% medium risk and 23% a high risk NEWS2 in the development cohort. The proportions dying as an inpatient were 2.2%, 3.6% and 6.5% by NEWS2 risk category, respectively. The proportions needing NIV were 4.4%, 9.2% and 18.0%, respectively. NEWS2 was poorly predictive of length-of-stay (AUC: 0.59[0.57– 0.61]). In the external validation cohort, the AUC (95% CI) for NEWS2 to predict inpatient death and need for NIV were 0.72 (0.68– 0.77) and 0.70 (0.67– 0.73). Inclusion of patient demographic factors, co-morbidity and COPD severity improved model performance. However, only 1.34% of the variation in admission NEWS2 was explained by these baseline variables.Conclusion: The generic NEWS2 risk assessment tool, readily calculated from simple physiological data, predicts inpatient mortality and need for NIV (but not length-of-stay) at exacerbations of COPD. NEWS2 therefore provides a classification of hospitalised COPD exacerbation severity.
Gayle A, Minelli C, Quint J, 2022, Respiratory-related death in individuals with incident asthma and COPD: a competing risk analysis, BMC Pulmonary Medicine, Vol: 22, ISSN: 1471-2466
Background Distinguishing between mortality attributed to respiratory causes and other causes among people with asthma, COPD, and asthma-COPD overlap (ACO) is important. This study used electronic health records in England to estimate excess risk of death from respiratory-related causes after accounting for other causes of death.Methods We used linked Clinical Practice Research Datalink (CPRD) primary care and Office for National Statistics mortality data to identify adults with asthma and COPD from 2005-2015. Causes of death were ascertained using death certificates. Hazard ratios (HR) and excess risk of death were estimated using Fine-Gray competing risk models and adjusting for age, sex, smoking status, body mass index and socio economic status.Results 65,021 people with asthma and 45,649 with COPD in the CPRD dataset were frequency matched 5:1 with people without the disease on age, sex and general practice. Only 14 in 100,000 people with asthma are predicted to experience a respiratory-related death up to 10 years post-diagnosis, whereas in COPD this is 98 in 100,000. Asthma is associated with an 0.01% excess incidence of respiratory related mortality whereas COPD is associated with an 0.07% excess. Among people with asthma-COPD overlap (N=22,145) we observed an increased risk of respiratory-related death compared to those with asthma alone (HR=1.30; 95%CI: 1.21 – 1.40) but not COPD alone (HR=0.89; 95%CI: 0.83 – 0.94).Conclusions Asthma and COPD are associated with an increased risk of respiratory-related death after accounting for other causes; however, diagnosis of COPD carries a much higher probability. ACO is associated with a lower risk compared to COPD alone but higher risk compared to asthma alone.
Perret JL, Vicendese D, Simons K, et al., 2021, Ten-year prediction model for post-bronchodilator airflow obstruction and early detection of COPD: development and validation in two middle-aged population-based cohorts, BMJ OPEN RESPIRATORY RESEARCH, Vol: 8
- Author Web Link
- Cite
- Citations: 4
Amaral A, Burney P, Patel J, et al., 2021, Chronic airflow obstruction and ambient particulate air pollution, Thorax, Vol: 76, Pages: 1236-1241, ISSN: 0040-6376
Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.
Minelli C, Del Greco FM, van der Plaat DA, et al., 2021, The use of two-sample methods for Mendelian randomization analyses on single large datasets, International Journal of Epidemiology, Vol: 50, Pages: 1651-1659, ISSN: 0300-5771
BackgroundWith 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.MethodsWith simulations mimicking a typical study in UK Biobank, we assessed the performance, in terms of bias and precision of the MR estimate, of the fixed-effect and (multiplicative) random-effects meta-analysis method, weighted median estimator, weighted mode estimator and MR-Egger regression, used in both one-sample and two-sample data. We considered scenarios differing by the: presence/absence of a true causal effect; amount of confounding; and presence and type of pleiotropy (none, balanced or directional).ResultsEven in the presence of substantial correlation due to confounding, all two-sample methods used in one-sample MR performed similarly to when used in two-sample MR, except for MR-Egger which resulted in bias reflecting direction and magnitude of the confounding. Such bias was much reduced in the presence of very high variability in instrument strength across variants ( of 97%).ConclusionsTwo-sample MR methods can be safely used for one-sample MR performed within large biobanks, expect for MR-Egger. MR-Egger is not recommended for one-sample MR unless the correlation between the gene-exposure and gene-outcome estimates due to confounding can be kept low, or the variability in instrument strength is very high.
Elfadaly FG, Adamson A, Patel J, et al., 2021, BIMAM-a tool for imputing variables missing across datasets using a Bayesian imputation and analysis model, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, Vol: 50, Pages: 1419-1425, ISSN: 0300-5771
Roisin M, Kim SY, Van der Plaat D, et al., 2021, LSC-2021-Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair-A multidisciplinary approach, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Perret J, Vicendese D, Simons K, et al., 2021, Predictions of post-bronchodilator airflow obstruction by longitudinal asthma and wheeze patterns in middle-age, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Patel J, Amaral AFS, Minelli C, et al., 2021, Poverty and chronic airflow obstruction in the multinational Burden of Obstructive Lung Disease (BOLD) study: An update, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Burney P, Patel J, Minelli C, et al., 2021, Prevalence and population attributable risk for chronic airflow obstruction in a large multinational study, American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 1353-1365, ISSN: 1073-449X
Rationale: The Global Burden of Disease programme identified smoking, and ambient and household air pollution as the main drivers of death and disability from Chronic Obstructive Pulmonary Disease (COPD). Objective: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a post-bronchodilator one-second forced expiratory volume to forced vital capacity ratio < lower limit of normal, and the relative risks associated with different risk factors. Local RR were estimated using a Bayesian hierarchical model borrowing information from across sites. From these RR and the prevalence of risk factors, we estimated local Population Attributable Risks (PAR). Measurements and Main Results: Mean prevalence of CAO was 11.2% in men and 8.6% in women. Mean PAR for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index (BMI), and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: While smoking remains the most important risk factor for CAO, in some areas poor education, low BMI and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.