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- Shrine, N, et al.
(author)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Journal article (peer-reviewed)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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- Lytras, T., et al.
(author)
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Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts
- 2021
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In: Annals of the American Thoracic Society. - New York : American Thorax Society. - 1546-3222 .- 2329-6933 .- 2325-6621 .- 1943-5665. ; 18:2, s. 238-246
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Journal article (peer-reviewed)abstract
- Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up. Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts. Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
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- Marcon, A., et al.
(author)
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The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories
- 2021
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:5
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Journal article (peer-reviewed)abstract
- Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden. Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477). Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated. Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life. The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.
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- Markevych, I., et al.
(author)
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Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study
- 2023
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
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Journal article (peer-reviewed)abstract
- Background: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected.Objective: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey.Methods: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures.Results: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval:-2.18 to-0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent asso-ciations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. Conclusions: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detri-mental association requires verification in future studies.
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