Imperial College London

DR ANDRE F S AMARAL

Faculty of MedicineNational Heart & Lung Institute

Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 7940a.amaral Website

 
 
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Location

 

G07Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

79 results found

Wielscher M, Amaral AFS, van der Plaat D, Wain LV, Sebert S, Mosen-Ansorena D, Auvinen J, Herzig K-H, Dehghan A, Jarvis DL, Jarvelin M-Ret al., 2021, Genetic correlation and causal relationships between cardio-metabolic traits and lung function impairment, Genome Medicine, Vol: 13

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Associations of low lung function with features of poor cardio-metabolic health have been reported. It is, however, unclear whether these co-morbidities reflect causal associations, shared genetic heritability or are confounded by environmental factors.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We performed three analyses: (1) cardio-metabolic health to lung function association tests in Northern Finland Birth cohort 1966, (2) cross-trait linkage disequilibrium score regression (LDSC) to compare genetic backgrounds and (3) Mendelian randomisation (MR) analysis to assess the causal effect of cardio-metabolic traits and disease on lung function, and vice versa (bidirectional MR). Genetic associations were obtained from the UK Biobank data or published large-scale genome-wide association studies (<jats:italic>N</jats:italic> &gt; 82,000).</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We observed a negative genetic correlation between lung function and cardio-metabolic traits and diseases. In Mendelian Randomisation analysis (MR), we found associations between type 2 diabetes (T2D) instruments and forced vital capacity (FVC) as well as FEV1/FVC. Body mass index (BMI) instruments were associated to all lung function traits and C-reactive protein (CRP) instruments to FVC. These genetic associations provide evidence for a causal effect of cardio-metabolic traits on lung function. Multivariable MR suggested independence of these causal effects from other tested cardio-metabolic traits and diseases. Analysis of lung function specific SNPs revealed a potential causal effect of FEV1/FVC on blood pres

Journal article

Migliori GB, Marx FM, Ambrosino N, Zampogna E, Schaaf HS, van der Zalm MM, Allwood B, Byrne AL, Mortimer K, Wallis RS, Fox GJ, Leung CC, Chakaya JM, Seaworth B, Rachow A, Marais BJ, Furin J, Akkerman OW, Yaquobi FA, Amaral A, Borisov S, Caminero JA, Carvalho ACC, Chesov D, Codecasa LR, Teixeira RC, Dalcolmo MP, Datta S, Dinh-Xuan A-T, Duarte R, Evans CA, García-García J-M, Günther G, Hoddinott G, Huddart S, Ivanova O, Laniado-Laborín R, Manga S, Manika K, Mariandyshev A, Mello FCQ, Mpagama SG, Muñoz-Torrico M, Nahid P, Ong CWM, Palmero DJ, Piubello A, Pontali E, Silva DR, Singla R, Spanevello A, Tiberi S, Udwadia ZF, Vitacca M, Centis R, DAmbrosio L, Sotgiu G, Lange C, Visca Det al., 2021, Clinical standards for the assessment, management, and rehabilitation of post-TB lung disease, International Journal of Tuberculosis and Lung Disease, ISSN: 1027-3719

Journal article

Ratanachina J, Amaral A, De Matteis S, Cullinan P, Burney Pet al., 2021, Farming, pesticide exposure and respiratory health: a cross-sectional study in Thailand, Occupational and Environmental Medicine, ISSN: 1351-0711

Objective: To assess the association of lung function and respiratory symptoms with farming, particularly pesticide use, in an agricultural province in Thailand.Methods: We undertook a cross-sectional survey of adults aged 40–65 in Nan province, Thailand, between May and August 2019. We randomly recruited 345 villagers and enriched the sample with 82 government employees. All participants performed post-bronchodilator spirometry and completed a questionnaire covering information on respiratory symptoms, farming activities, pesticide use and known risk factors for respiratory disease. Associations of respiratory outcomes with farming and pesticide exposures were examined by multivariable regression analysis.Results: The response rate was 94%. The prevalence of chronic airflow obstruction among villagers was 5.5%. Villagers had, on average, a lower percent predicted post-bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) than government employees (98.3% vs 100.3%; p=0.04). There was no evidence of association of lung function with farming activities, the use of specific herbicides (glyphosate and paraquat), insecticides (organophosphates and pyrethroids) or fungicides. The exceptions were poultry farming, associated with chronic cough and an increase of FEV1/FVC, and atrazine, for which duration (p-trend <0.01), intensity (p-trend <0.01) and cumulative hours (p-trend=0.01) of use were all associated with higher FEV1/FVC in an exposure–response manner. Cumulative hours (−280 mL/hour), low duration (−270 mL/year) and intensity (−270 mL/hour/year) of atrazine use were associated with lower FVC.Conclusions: Chronic airflow obstruction is uncommon among villagers of an agricultural province in Nan, Thailand. Farming and pesticide use are unlikely to be major causes of respiratory problems there.

Journal article

Burney P, Patel J, Minelli C, Gnatiuc L, Amaral A, Kocabas A, Cherkaski H, Gulsvik A, Nielsen R, Bateman E, Jithoo A, Mortimer K, Sooronbaev T, Lawin H, Nejjari C, Elbiaze M, El Rhazi K, Zheng J-P, Ran P, Welte T, Obaseki D, Erhabor G, Elsony A, Osman N, Ahmed R, Nizankowska -Mogilnicka E, Mejza F, Mannino D, Barbara C, Wouters E, Idolor L, Loh L-C, Rashid A, Juvekar S, Gislason T, Al Ghobain M, Studnicka M, Harrabi I, Denguezli M, Koul P, Jenkins C, Marks G, Jogi R, Hafizi H, Janson C, Tan W, Aquart-Stewart A, Mbatchou B, Nafees A, Gunasekera K, Seemungal T, Mahesh PA, Enright P, Vollmer W, Blangiardo M, Elfadaly F, Buist ASet 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.

Journal article

Amaral A, Burney P, Patel J, Minelli C, Mejza F, Mannino D, Seemungal T, Padukudru Anand M, Loh LC, Janson C, Juvekar S, Denguezli M, Harrabi I, Wouters E, Cherkaski H, Mortimer K, Jogi R, Bateman E, Fuertes E, Al Ghobain M, Tan W, Obaseki D, El Sony A, Studnicka M, Aquart-Stewart A, Koul P, Lawin H, Nafees A, Awopeju O, Erhabor G, Gislason T, Welte T, Gulsvik A, Nielsen R, Gnatiuc L, Kocabas A, Marks G, Sooronbaev T, Mbatchou Ngahane B, Barbara C, Buist ASet al., 2021, Chronic airflow obstruction and ambient particulate air pollution, Thorax, 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.

Journal article

van Nunen E, Hoek G, Tsai M-Y, Probst-Hensch N, Imboden M, Jeong A, Naccarati A, Tarallo S, Raffaele D, Nieuwenhuijsen M, Vlaanderen J, Gulliver J, Amaral A, Vineis P, Vermeulen Ret al., 2021, Short-term personal and outdoor exposure to ultrafine and fine particulate air pollution in association with blood pressure and lung function in healthy adults, Environmental Research, Vol: 194, ISSN: 0013-9351

Studies reporting on associations between short-term exposure to outdoor fine (PM2.5), and ultrafine particles (UFP) and blood pressure and lung function have been inconsistent. Few studies have characterized exposure by personal monitoring, which especially for UFP may have resulted in substantial exposure measurement error. We investigated the association between 24-h average personal UFP, PM2.5, and soot exposure and dose and the health parameters blood pressure and lung function. We further assessed the short-term associations between outdoor concentrations measured at a central monitoring site and near the residences and these health outcomes.We performed three 24-h personal exposure measurements for UFP, PM2.5, and soot in 132 healthy adults from Basel (Switzerland), Amsterdam and Utrecht (the Netherlands), and Turin (Italy). Monitoring of each subject was conducted in different seasons in a one-year study period. Subject's activity levels and associated ventilation rates were measured using actigraphy to calculate the inhaled dose. After each 24-h monitoring session, blood pressure and lung function were measured. Contemporaneously with personal measurements, UFP, PM2.5 and soot were measured outdoor at the subject's residential address and at a central site in the research area. Associations between short-term personal and outdoor exposure and dose to UFP, PM2.5, and soot and health outcomes were tested using linear mixed effect models.The 24-h mean personal, residential and central site outdoor UFP exposures were not associated with blood pressure or lung function. UFP mean exposures in the 2-h prior to the health test was also not associated with blood pressure and lung function. Personal, central site and residential PM2.5 exposure were positively associated with systolic blood pressure (about 1.4 mmHg increase per Interquartile range). Personal soot exposure and dose were positively associated with diastolic blood pressure (1.2 and 0.9 mmHg increase per

Journal article

Russell MA, Dharmage S, Fuertes E, Marcon A, Carsin A-E, Pascual Erquicia S, Heinrich J, Johannessen A, Abramson MJ, Amaral A, Cerveri I, Demoly P, Garcia-Larsen V, Jarvis D, Martinez-Moratalla J, Nowak D, Palacios-Gomez L, Squillacioti G, Raza W, Emtner M, Garcia-Aymerich Jet al., 2021, The effect of physical activity on asthma incidence over 10 years: population-based study, ERJ Open Research, Vol: 7, ISSN: 2312-0541

Journal article

Burney P, Amaral AFS, 2020, Asthma exacerbations, air pollution, and allergens - Authors' reply., Lancet, Vol: 396, Pages: 753-754

Journal article

Allwood B, van der Zalm M, Amaral A, Byrne A, Datta S, Egere U, Evans C, Evans D, Gray D, Hoddinott G, Ivanova O, Jones R, Makanda G, Marx F, Meghji J, Mpagama S, Pasipanodya J, Rachow A, Schoeman I, Shaw J, Stek C, van Kampen S, von Delft D, Walker N, Wallis R, Mortimer Ket al., 2020, Post-tuberculosis lung health: perspectives from the firstInternational symposium, International Journal of Tuberculosis and Lung Disease, Vol: 24, Pages: 820-828, ISSN: 1027-3719

Tuberculosis, although curable, frequently leaves the individual with chronic physical and psycho-social impairment, yet these consequences have to-date been largely neglected. The 1st International Post-Tuberculosis Symposium was devoted entirely to impairment after tuberculosis, and covered a number of multi-disciplinary topics. Using the Delphi process, consensus was achieved for the terms “post-tuberculosis”, “post-tuberculosis lung disease/s (PTLD)”, and “post-tuberculosis economic, social and psychological well-being” (Post-TB ESP)”, to overcome the historical challenge of varied terminology in the literature. A minimum case-definition was proposed by consensus for PTLD in adults and children. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of PTLD, but highlighted the dire need for research and priorities were identified. The heterogeneity of respiratory outcomes and previously employed research methodologies complicates the accurate estimation of disease burden. However, consensus was reached proposing a toolkit for future PTLD measurement, and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including tuberculosis recurrence and increased mortality. Patient advocates emphasised the need for addressing the psychological and social impacts post tuberculosis, and called for clinical guidance. Increased awareness and more research addressing post-tuberculosis complications is urgently needed.

Journal article

Amaral AFS, Imboden M, Wielscher M, Rezwan F, Minelli C, Garcia-Aymerich J, Peralta GP, Auvinen J, Jeong A, Schaffner E, Beckmeyer-Borowko A, Holloway JW, Jarvelin M-R, Probst-Hensch NM, Jarvis DLet al., 2020, Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study, BMC PULMONARY MEDICINE, Vol: 20, ISSN: 1471-2466

Journal article

van Nunen E, Vermeulen R, Tsai M-Y, Probst-Hensch N, Ineichen A, Imboden M, Naccarati A, Tarallo S, Raffaele D, Ranzi A, Nieuwenhuijsen M, Jarvis D, Amaral AFS, Vlaanderen J, Meliefste K, Brunekreef B, Vineis P, Gulliver J, Hoek Get al., 2020, Associations between modeled residential outdoor and measured personal exposure to ultrafine particles in four European study areas, ATMOSPHERIC ENVIRONMENT, Vol: 226, ISSN: 1352-2310

Journal article

Peralta GP, Marcon A, Carsin A-E, Abramson MJ, Accordini S, Amaral AF, Antó JM, Bowatte G, Burney P, Corsico A, Demoly P, Dharmage S, Forsberg B, Fuertes E, Garcia-Larsen V, Gíslason T, Gullón J-A, Heinrich J, Holm M, Jarvis DL, Janson C, Jogi R, Johannessen A, Leynaert B, Rovira JM-M, Nowak D, Probst-Hensch N, Raherison C, Sánchez-Ramos J-L, Sigsgaard T, Siroux V, Squillacioti G, Urrutia I, Weyler J, Zock J-P, Garcia-Aymerich Jet al., 2020, Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study., Thorax, Vol: 75, Pages: 313-320

BACKGROUND: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). METHODS: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. RESULTS: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV1 declines. We found no association between weight change profiles and FEV1/FVC decline. CONCLUSION: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life.

Journal article

Rezwan F, Imboden M, Amaral AFS, Wielscher M, Jeong A, Triebner K, Real FG, Jarvelin M-R, Jarvis D, Probst-Hensch NM, Holloway JWet al., 2020, Association of adult lung function with accelerated biological aging, AGING-US, Vol: 12, Pages: 518-542, ISSN: 1945-4589

Journal article

Jankowski M, Amaral A, 2020, ERS international congress, Madrid, 2019: Highlights from the Epidemiology and Environment Assembly, ERJ Open Research, Vol: 6, Pages: 1-4, ISSN: 2312-0541

At the European Respiratory Society's International Congress of 2019, which was held in Madrid, Spain, there were several sessions with exciting poster and oral presentations within the fields of epidemiology and tobacco control. This article is the summary of two of these sessions. One was on the use of Big Data in epidemiology and the other, on the global burden of respiratory disease and tobacco.

Journal article

Burney P, Amaral AFS, 2019, Air pollution and chronic airway disease: is the evidence always clear?, LANCET, Vol: 394, Pages: 2198-2200, ISSN: 0140-6736

Journal article

Janson C, Malinovschi A, Amaral A, Accordini S, Bousquet J, Buist AS, Garcia-Aymerich J, Gnatiuc L, Tan W, Toren K, Zuberbier T, Burney Pet al., 2019, Testing bronchodilator responsiveness, European Respiratory Journal, Vol: 54, ISSN: 0903-1936

Journal article

Allwood B, van der Zalm M, Makanda G, Mortimer K, Amaral AFS, Egere U, Evans D, Gray D, Hoddinott G, Ivanova O, Jones R, Marx FM, Meghji J, Mpagama S, van Kampen S, Rachow A, Schoeman I, Stek C, von Delft D, Walker N, Wallis Ret al., 2019, The long shadow post-tuberculosis, LANCET INFECTIOUS DISEASES, Vol: 19, Pages: 1170-1171, ISSN: 1473-3099

Journal article

van der Plaat D, Pereira M, Pesce G, Potts J, Amaral A, Dharmage S, Garcia-Aymerich J, Thompson J, Gomez-Real F, Jarvis D, Minelli C, Leynaert Bet al., 2019, Age at menopause and lung function: a mendelian randomization study, European Respiratory Journal, Vol: 54, Pages: 1-10, ISSN: 0903-1936

In observational studies, early menopause is associated with lower 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 randomization (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function. We included 94,742 naturally post-menopausal women from UK Biobank and performed MR analyses on the effect of age at menopause on FEV1, FVC, FEV1/FVC, spirometric restriction (FVC<LLN) and airflow obstruction (FEV1/FVC<LLN). We used the inverse variance-weighted (IVW) method, as well as methods that adjust for pleiotropy, and compared MR with observational analyses. The MR analyses showed higher FEV1/FVC and a 15% lower risk of airflow obstruction for women with early (<45 years) compared to normal (45-55) menopause. Despite some evidence of pleiotropy, the results were consistent when using MR methods robust to pleiotropy. Similar results were found among never- and ever-smokers, while the protective effect seemed less strong in women ever using menopause hormone treatment and in overweight women. There was no strong evidence of association with FVC or spirometric restriction. In observational analyses of the same dataset, early menopause was associated with a pronounced reduction in FVC and a 13% higher spirometric restriction risk.Our MR results suggest that early menopause has a protective effect on airflow obstruction. Further studies are warranted to better understand the inconsistency with observational findings, and to investigate the underlying mechanisms and role of female sex hormones.

Journal article

Janson C, Malinovschi A, Amaral A, Accordini S, Bousquet J, Buist S, Canonica G, Dahlen B, Garcia Aymerich J, Gnatiuc L, Kowalski M, Patel J, Tan W, Toren K, Zuberbier T, Burney P, Jarvis Det al., 2019, Bronchodilator reversibility in asthma and COPD: Findings from three large population studies, European Respiratory Journal, Vol: 54, ISSN: 0903-1936

Bronchodilator response (BDR) testing is used as a diagnostic method in obstructive airway diseases. The aim of this investigation was to compare different methods for measuring BDR in participants with asthma and COPD and to study to the extent to which BDR was related to symptom burden and phenotypic characteristics.Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) was measured before and 15 min after 200 μg of salbutamol in 35 628 subjects aged 16 years and older from three large international population studies. The subjects were categorised in three groups: current asthma (n=2833), COPD (n=1146), and no airway disease (n=31 649). Three definitions for flow related (increase in FEV1) and three for volume related (increase in FVC) were used.The prevalence of bronchodilator reversibility expressed as increase FEV1≥12% and 200 mL was 17.3% and 18.4% in participants with asthma and COPD, respectively, while the corresponding prevalence was 5.1% in those with no airway disease. In asthma, bronchodilator reversibility was associated with wheeze (OR (95% CI): 1.36 (1.04–1.79)), atopy (OR 1.36 (1.04–1.79)) and higher FeNO while in COPD neither flow nor volume related bronchodilator reversibility was associated with symptom burden, exacerbations or health status after adjusting for prebronchodilator FEV1.Bronchodilator reversibility was at least as common in participants with COPD as those with asthma. This indicates that measures of reversibility are of limited value for distinguishing asthma from COPD in population studies. In asthma, however, bronchodilator reversibility may be a phenotypic marker.

Journal article

Imboden M, Wielscher M, Rezwan FI, Amaral AFS, Schaffner E, Jeong A, Beckmeyer-Borowko A, Harris SE, Starr JM, Deary IJ, Flexeder C, Waldenberger M, Peters A, Schulz H, Chen S, Sunny SK, Karmaus WJJ, Jiang Y, Erhart G, Kronenberg F, Arathimos R, Sharp GC, Henderson AJ, Fu Y, Piirila P, Pietilainen KH, Ollikainen M, Johansson A, Gyllensten U, de Vries M, van der Plaat DA, de Jong K, Boezen HM, Hall IP, Tobin MD, Jarvelin M-R, Holloway JW, Jarvis D, Probst-Hensch NMet al., 2019, Epigenome-wide association study of lung function level and its change, EUROPEAN RESPIRATORY JOURNAL, Vol: 54, ISSN: 0903-1936

Journal article

Jeong A, Imboden M, Ghantous A, Novoloaca A, Carsin A-E, Kogevinas M, Schindler C, Lovison G, Herceg Z, Cuenin C, Vermeulen R, Jarvis D, Amaral A, Kronenberg F, Vineis P, Probst-Hensch Net al., 2019, DNA methylation in inflammatory pathways modifies the association between BMI and adult-onset non-atopic asthma, International Journal of Environmental Research and Public Health, Vol: 16, ISSN: 1660-4601

A high body mass (BMI) index has repeatedly been associated with non-atopic asthma, but the biological mechanism linking obesity to asthma is still poorly understood. We aimed to test the hypothesis that inflammation and/or innate immunity plays a role in the obesity-asthma link. DNA methylome was measured in blood samples of 61 non-atopic participants with asthma and 146 non-atopic participants without asthma (non-smokers for at least 10 years) taking part in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) study. Modification by DNA methylation of the association of BMI or BMI change over 10 years with adult-onset asthma was examined at each CpG site and differentially methylated region. Pathway enrichment tests were conducted for genes in a priori curated inflammatory pathways and the NLRP3-IL1B-IL17 axis. The latter was chosen on the basis of previous work in mice. Inflammatory pathways including glucocorticoid/PPAR signaling (p = 0.0023), MAPK signaling (p = 0.013), NF-κB signaling (p = 0.031), and PI3K/AKT signaling (p = 0.031) were enriched for the effect modification of BMI, while NLRP3-IL1B-IL17 axis was enriched for the effect modification of BMI change over 10 years (p = 0.046). DNA methylation measured in peripheral blood is consistent with inflammation as a link between BMI and adult-onset asthma and with the NLRP3-IL1B-IL17 axis as a link between BMI change over 10 years and adult-onset asthma in non-atopic participants.

Journal article

de Vries M, Axson E, Ratanachina J, Dumas O, De Matteis S, Bedard A, Roda C, Moitra S, Dagli E, Dimanti A, Dilektasli AG, Ravara S, Amaral Aet al., 2019, European Respiratory Society International Congress 2018: Four shades of epidemiology and tobacco control, ERJ Open Research, Vol: 5, ISSN: 2312-0541

In this article, early career members and experienced members of the Epidemiology and Environment Assembly of the European Respiratory Society (ERS) highlight and summarise a selection of six sessions from the society’s annual congress, which in 2018 was held in Paris. The topics covered in these sessions span from cutting-edge molecular epidemiology of lung function to environmental, occupational and clinical epidemiology of respiratory disease and from emergent tobacco products to tobacco control.

Journal article

Amaral AFS, Quint J, 2018, Cottage by the sea or house above the trees: Which is better for my lungs?, Thorax, Vol: 73, Pages: 1103-1104, ISSN: 1468-3296

Journal article

Mostafavi N, Vermeulen R, Ghantous A, Hoek G, Probst-Hensch N, Herceg Z, Tarallo S, Naccarati A, Kleinjans JCS, Imboden M, Jeong A, Morley D, Amaral AFS, van Nunen E, Gulliver J, Chadeau M, Vineis P, Vlaanderen Jet al., 2018, Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: a panel study in four European countries, Environment International, Vol: 120, Pages: 11-21, ISSN: 0160-4120

BackgroundOne of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites.ObjectiveWe investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes.MethodsWe collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM2.5), PM2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects.ResultsPersonal exposure to PM2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM2.5, 16 DMRs with ambient PM2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate.ConclusionThis study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation.

Journal article

Amaral AFS, 2018, Highlights from the European Respiratory Society 2018 Annual Congress: environment and epidemiology (assembly 6), Journal of thoracic disease, ISSN: 2077-6624

Journal article

Beckmeyer-Borowko A, Imboden M, Rezwan FI, Wielscher M, Amaral AFS, Jeong A, Schaffner E, Auvinen J, Sebert S, Karhunen V, Bettschart R, Turk A, Pons M, Stolz D, Kronenberg F, Arathimos R, Sharp GC, Relton C, Henderson AJ, Jarvelin M-R, Jarvis D, Holloway JW, Probst-Hensch NMet al., 2018, SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts., Respir Res, Vol: 19

BACKGROUND: The pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort. METHODS: DNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models. RESULTS: Methylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV1/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing. CONCLUSIONS: The results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed.

Journal article

Waage J, Standl M, Curtin JA, Jessen LE, Thorsen J, Tian C, Schoettler N, 23andMe Research Team, AAGC collaborators, Flores C, Abdellaoui A, Ahluwalia TS, Alves AC, Amaral AFS, Antó JM, Arnold A, Barreto-Luis A, Baurecht H, van Beijsterveldt CEM, Bleecker ER, Bonàs-Guarch S, Boomsma DI, Brix S, Bunyavanich S, Burchard EG, Chen Z, Curjuric I, Custovic A, den Dekker HT, Dharmage SC, Dmitrieva J, Duijts L, Ege MJ, Gauderman WJ, Georges M, Gieger C, Gilliland F, Granell R, Gui H, Hansen T, Heinrich J, Henderson J, Hernandez-Pacheco N, Holt P, Imboden M, Jaddoe VWV, Jarvelin M-R, Jarvis DL, Jensen KK, Jónsdóttir I, Kabesch M, Kaprio J, Kumar A, Lee Y-A, Levin AM, Li X, Lorenzo-Diaz F, Melén E, Mercader JM, Meyers DA, Myers R, Nicolae DL, Nohr EA, Palviainen T, Paternoster L, Pennell CE, Pershagen G, Pino-Yanes M, Probst-Hensch NM, Rüschendorf F, Simpson A, Stefansson K, Sunyer J, Sveinbjornsson G, Thiering E, Thompson PJ, Torrent M, Torrents D, Tung JY, Wang CA, Weidinger S, Weiss S, Willemsen G, Williams LK, Ober C, Hinds DA, Ferreira MA, Bisgaard H, Strachan DP, Bønnelykke Ket al., 2018, Author correction: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis, Nature Genetics, ISSN: 1061-4036

In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.

Journal article

Minelli C, van der Plaat DA, Leynaert B, Granell R, Amaral AFS, Pereira M, Mahmoud O, Potts J, Sheehan NA, Bowden J, Thompson J, Jarvis D, Smith GD, Henderson Jet al., 2018, Age at puberty and risk of asthma: A Mendelian randomisation study, PLoS Medicine, Vol: 15, ISSN: 1549-1277

BackgroundObservational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males.Methods and findingsMR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (<12), normal (12–14), or late (>14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10−5) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10−4), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking.ConclusionsThis large MR stud

Journal article

Waage J, Standl M, Curtin JA, Jessen L, Thorsen J, The 23andMe Research Team, AAGC Collaborators, Abdellaoui A, Ahluwalia TS, Alves A, Amaral AFS, Anto JM, Arnold A, Flores C, Baurecht H, Beijstervedldt TCEM, Bleecker ER, Bonas-Guarch S, Boomsma D, Brix S, Bunyavanich S, Burchard E, Chen Z, Curjuric I, Custovic A, den Dekker M, Dharmage SC, Dmitrieva J, Duijts L, Ege M, Barreto-Luis A, Gauderman WJ, Georges M, Gieger C, Gilliland F, Granell R, Gui H, Hansen T, Heinrich J, Henderson J, Hernandez-Pacheco N, Hinds DA, Holt P, Imboden M, Jaddoe V, Jarvelin M, Jarvis D, Jensen KK, Jonsdottir I, Kabesch M, Kaprio J, Kumar A, Lee Y, Levin AM, Li X, Lorenz-Diaz F, Melen E, Mercader JM, Meyers DA, Nicolae DL, Nohr E, Palvianinen T, Paternoster L, Pennell C, Pershagen G, Pino-Yanes M, Probst-Hensch NM, Ruschendorf F, Schoettler N, Simpson A, Stefansson K, Sunyer J, Sveinbjornsson G, Thiering E, Thompson PJ, Tian C, Torrent M, Torrents D, Tung JY, Wang C, Weidinger S, Weiss S, Willemsen G, Williams LK, Ober C, Ferreira MA, Bisgaard H, Strachan D, Bonnelykke Ket al., 2018, Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis, Nature Genetics, Vol: 50, Pages: 1072-1080, ISSN: 1061-4036

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, and with increasing incidence in westernized countries.1,2 To elucidate the genetic architecture and understand disease mechanisms of allergic rhinitis, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implied genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants of importance for antigen binding. We further performed GWASs of allergic sensitization against inhalant allergens and non-allergic rhinitis suggesting shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

Journal article

Amaral AFS, Patel J, Kato BS, Obaseki DO, Lawin H, Tan WC, Juvekar SK, Harrabi I, Studnicka M, Wouters EFM, Loh L-C, Bateman ED, Mortimer K, Buist AS, Burney PGJet al., 2018, Airflow Obstruction and Use of Solid Fuels for Cooking or Heating BOLD (Burden of Obstructive Lung Disease) Results, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 197, Pages: 595-610, ISSN: 1073-449X

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