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

 

G48Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

103 results found

Muller A, Mraz T, Wouters EFM, van Kuijk SMJ, Amaral A, Breyer-Kohansal R, Breyer M-K, Hartl S, Janssen Det al., 2023, Prevalence of dyspnea in general adult populations: a systematic review and meta-analysis, Respiratory Medicine, Vol: 218, ISSN: 0954-6111

IntroductionDyspnea is a commonly described symptom in various chronic and acute conditions. Despite its frequency, relatively little is known about the prevalence and assessment of dyspnea in general populations. The aims of this review were: 1) to estimate the prevalence of dyspnea in general adult populations; 2) to identify associated factors; and 3) to identify used methods for dyspnea assessment.MethodsA systematic literature search was conducted using MEDLINE/PubMed, Embase, CINAHL and JAMA network. Records were screened by two independent reviewers and quality was assessed by using the Joanna Briggs Institute checklist for risk of bias in prevalence studies. Multi-level meta-analysis was performed to estimate pooled prevalence. The protocol was registered on PROSPERO (CRD42021275499).ResultsTwenty original articles, all from studies in high-income countries, met the criteria for inclusion. Overall, their quality was good. Pooled prevalence of dyspnea in general adult populations based on 11 studies was 10% (95% CI 7, 15), but heterogeneity across studies was high. The most frequently reported risk factors were increasing age, female sex, higher BMI and respiratory or cardiac disease. The MRC or the modified MRC scale was the most used tool to assess dyspnea in general populations.ConclusionsDyspnea is a common symptom in adults in high-income countries. However, the high heterogeneity across studies and the lack of data from low- and middle-income countries limit the generalizability of our findings. Therefore, more research is needed to unveil the prevalence of dyspnea and its main risk factors in general populations around the world.

Journal article

Amaral A, Potts J, Knox-Brown B, Bagkeris E, Harrabi I, Cherkaski HH, Agarwal D, Juvekar S, Padukudru Anand M, Gislason T, Nafees AA, Mortimer K, Janson C, Loh LC, Paraguas SN, Denguezli M, Al Ghobain M, Mannino D, Njoroge M, Devereux G, Seemungal T, Barbara C, Kocabas A, Ahmed R, Aquart-Stewart A, Studnicka M, Welte T, Tan WT, van Zyl-Smit RN, Koul P, Garcia Larsen V, Minelli C, Buist AS, Burney Pet al., 2023, Cohort profile: Burden of Obstructive Lung Disease (BOLD) study, International Journal of Epidemiology, ISSN: 0300-5771

Journal article

Oosterwegel MJ, Ibi D, Portengen L, Probst-Hensch N, Tarallo S, Naccarati A, Imboden M, Jeong A, Robinot N, Scalbert A, Amaral AFS, van Nunen E, Gulliver J, Chadeau-Hyam M, Vineis P, Vermeulen R, Keski-Rahkonen P, Vlaanderen Jet al., 2023, Variability of the Human Serum Metabolome over 3 Months in the EXPOsOMICS Personal Exposure Monitoring Study., Environ Sci Technol, Vol: 57, Pages: 12752-12759

Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) and untargeted metabolomics are increasingly used in exposome studies to study the interactions between nongenetic factors and the blood metabolome. To reliably and efficiently link detected compounds to exposures and health phenotypes in such studies, it is important to understand the variability in metabolome measures. We assessed the within- and between-subject variability of untargeted LC-HRMS measurements in 298 nonfasting human serum samples collected on two occasions from 157 subjects. Samples were collected ca. 107 (IQR: 34) days apart as part of the multicenter EXPOsOMICS Personal Exposure Monitoring study. In total, 4294 metabolic features were detected, and 184 unique compounds could be identified with high confidence. The median intraclass correlation coefficient (ICC) across all metabolic features was 0.51 (IQR: 0.29) and 0.64 (IQR: 0.25) for the 184 uniquely identified compounds. For this group, the median ICC marginally changed (0.63) when we included common confounders (age, sex, and body mass index) in the regression model. When grouping compounds by compound class, the ICC was largest among glycerophospholipids (median ICC 0.70) and steroids (0.67), and lowest for amino acids (0.61) and the O-acylcarnitine class (0.44). ICCs varied substantially within chemical classes. Our results suggest that the metabolome as measured with untargeted LC-HRMS is fairly stable (ICC > 0.5) over 100 days for more than half of the features monitored in our study, to reflect average levels across this time period. Variance across the metabolome will result in differential measurement error across the metabolome, which needs to be considered in the interpretation of metabolome results.

Journal article

Lakoh S, Vamboi P, Ouedrago A, Adekanmbi O, Deen G, Russell J, Sankoh-Hughes A, Kamara J, Kanu J, Yendewa G, Firima E, Amaral Aet al., 2023, High prevalence of TB multimorbidity among adults of a tertiary hospital in Sierra Leone: a cross-sectional study, BMC Research Notes, ISSN: 1756-0500

Journal article

Patel J, Amaral A, Minelli C, lfadaly FGE, Mortimer K, Elsony A, El Rhazi K, Seemungal T, PA M, Obaseki D, Denguezli M, Ahmed R, Cherkaski HH, Koul P, Rashid A, Loh LC, Lawin H, Al Ghobain M, Nafees A, Aquart-Stewart A, Harrabi I, Buist AS, Burney Pet 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.

Journal article

Hannemann J, Thorarinnsdottir EH, Amaral A, Schwedhelm E, Schmidt-Hutten L, Stang H, Benediktsdottir B, Gunnarsdóttir I, Gíslason T, Böger Ret al., 2023, Biomarkers of the L-arginine / dimethylarginine / nitric oxide pathway in people with chronic airflow obstruction and obstructive sleep apnoea, Journal of Clinical Medicine, ISSN: 2077-0383

Journal article

Markevych I, Zhao T, Fuertes E, Marcon A, Dadvand P, Vienneau D, Aymerich JG, Nowak D, de Hoogh K, Jarvis D, Abramson M, Accordini S, Amaral A, Bentouhami H, Bertelsen RJ, Boudier A, Bono R, Bowatte G, Casas L, Dharmage S, Forsberg B, Gislason T, Gnesi M, Holm M, Jacquemin B, Janson C, Jogi R, Johannessen A, Keidel D, Leynaert B, Maldonado Perez JA, Marchetti P, Migliore E, Martínez-Moratalla J, Orru H, Pin I, Potts J, Probst-Hensch N, Ranzi A, Sánchez-Ramos JL, Siroux V, Soussan D, Sunyer J, Urrutia Landa I, Villani S, Heinrich Jet al., 2023, Residential greenspace and lung function decline over 20 years in a prospective cohort: the ECRHS study, Environment International, Vol: 178, Pages: 1-10, ISSN: 0160-4120

BackgroundThe 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.ObjectiveWe 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.MethodsForced 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.ResultsA 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 associations 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.ConclusionsMore residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declin

Journal article

Burney P, Knox-Brown B, Amaral A, 2023, Addressing the origins and health effects of small lungs – Authors' reply, The Lancet Respiratory Medicine, Vol: 11, Pages: e74-e74, ISSN: 2213-2600

Journal article

Knox-Brown B, Sylvester K, Amaral A, 2023, The association of cardiorespiratory fitness with spirometric small airways obstruction, ERJ Open Research, Vol: 9, Pages: 1-4, ISSN: 2312-0541

Journal article

Knox-Brown B, Patel J, Potts J, Ahmed R, Aquart-Stewart A, Barbara C, Buist AS, Cherkaski HH, Denguezli M, Elbiaze M, Erhabor G, Franssen F, Al Ghobain M, Gislasson T, Janson C, Kocabas A, Mannino D, Marks G, Mortimer K, Nafees AA, Obaseki D, Paraguas S, Loh LC, Rashid A, Salvi S, Seemungal T, Studnicka M, Tan W, Wouters E, Abozid H, Mueller A, Burney P, Amaral Aet al., 2023, The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: Results from the Burden of Obstructive Lung Disease (BOLD) study, Respiratory Research, Vol: 24, ISSN: 1465-9921

Background:Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown.Methods:Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN).Results:Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease.Conclusion:Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.

Journal article

Feary J, Quintero Santofimio V, Potts J, Vermeulen R, Kromhout H, Knox-Brown B, Amaral Aet al., 2023, Occupational exposures and small airways obstruction in the UK Biobank Cohort, ERJ Open Research, Vol: 9, Pages: 1-9, ISSN: 2312-0541

Background Small airways obstruction (SAO) is a key feature of both Chronic Obstructive Pulmonary Disease and asthma, which have been associated with workplace exposures. Whether SAO, which may occur early in the development of obstructive lung disease and without symptoms, also associates with occupational exposures is unknown.Methods Using UK Biobank data, we derived measurements of SAO from the 65,145 participants with high quality spirometry and lifetime occupational histories. The ALOHA+ Job Exposure Matrix was used to assign lifetime occupational exposures to each participant. The association between SAO and lifetime occupational exposures was evaluated using a logistic regression model adjusted for potential confounders. A second logistic regression model was run to also account for potential co-exposures.Results SAO was present in varying proportions of the population depending on definition used: 5.6% (FEF25–75<LLN)and 21.4% (FEV3/FEV6<LLN). After adjustment for confounders and co-exposures, people in the highest category of exposure to pesticides were significantly more likely to have SAO (FEV3/FEV6<LLN: OR 1.24, 95%CI 1.06–1.44). The association between pesticides and SAO showed an exposure-response pattern. SAO was also less likely among people in the highest exposure categories of aromatic solvents (FEV3/FEV6<LLN: OR 0.85, 95%CI 0.73–0.99) and metals (FEV3/FEV6<LLN: OR 0.77, 95%CI 0.62–0.94).Conclusion Our findings suggest that occupational exposure to pesticides play a role in the SAO. However, further work is needed to determine causality, and identify the specific component(s) responsible and the underlying mechanisms involved.

Journal article

Burney P, Knox-Brown B, Amaral A, 2023, Small lung syndrome: the need to re-classify chronic lung disease, The Lancet Respiratory Medicine, Vol: 11, Pages: 405-406, ISSN: 2213-2600

Journal article

Ahmed R, Osman R, Nightingale R, Nagem D, Thomson R, Malmborg R, Elmustafa M, Amaral A, Patel J, Burney P, Elsony A, Mortimer Ket al., 2023, Prevalence and determinants of chronic respiratory diseases in adults in rural Sudan, International Journal of Tuberculosis and Lung Disease, ISSN: 1027-3719

Journal article

Ratanachina J, Amaral A, De Matteis S, Lawin H, Mortimer K, Obaseki D, Harrabi I, Denguezli M, Wouters E, Janson C, Nielsen R, Gulsvik A, Cherkaski H, Mejza F, Anand M, Elsony A, Ahmed R, Tan W, Loh LC, Rashid A, Studnicka M, Nafees A, Seemungal T, Aquart-Stewart A, Al Ghobain M, Zheng J, Juvekar S, Salvi S, Jogi R, Mannino D, Gislason T, Buist AS, Cullinan P, Burney Pet al., 2023, Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study, European Respiratory Journal, Vol: 60, Pages: 1-16, ISSN: 0903-1936

Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study.We analysed cross-sectional data from 28,823 adults (≥40years) in 34 countries. Eleven occupations were considered and grouped by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, FEV1/FVC and FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income (GNI).Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20years were more likely to have chronic cough (OR=1.52, 95%CI 1.19-1.94), wheeze (OR=1.37, 95%CI 1.16-1.63), and dyspnoea (OR=1.83, 95%CI 1.53-2.20), but not lower FVC (β=0.02L, 95%CI -0.02L to 0.06L) or lower FEV1/FVC (β=0.04%, 95%CI -0.49% to 0.58%). Some findings differed by sex and GNI. In summary, at a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they associate with more respiratory symptoms. As not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.

Journal article

Knox-Brown B, Patel J, Potts J, Ahmed R, Aquart-Stewart A, Cherkaski HH, Denguezli M, Elbiaze M, Elsony A, Franssen FME, Ghobain MA, Harrabi I, Janson C, Jõgi R, Juvekar S, Lawin H, Mannino D, Mortimer K, Nafees AA, Nielsen R, Obaseki D, Paraguas SNM, Rashid A, Loh L-C, Salvi S, Seemungal T, Studnicka M, Tan WC, Wouters EEFM, Barbara C, Gislason T, Gunasekera K, Burney P, Amaral AFSet al., 2023, Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study, The Lancet Global Health, Vol: 11, Pages: e69-e82, ISSN: 2214-109X

Journal article

Ahmed R, Osman N, Noory B, Osman R, ElHassan H, Eltigani H, Nigththingale R, Amaral A, Patel J, Burney P, Mortimer K, Elsony Aet al., 2022, Prevalence and determinants of chronic respiratory diseases in adults in Khartoum State, Sudan, International Journal of Tuberculosis and Lung Disease, ISSN: 1027-3719

Background:Chronic respiratory diseases are considered a significant cause of morbidity and mortality worldwide, although data from Africa are limited. This study aimed to determine the prevalence and determinants of chronic respiratory diseases in Khartoum, Sudan.Methods:Data was collected from 516 participants, aged ≥ 40, who had completed a questionnaire and undertook pre- and post-bronchodilator spirometry testing. Trained field workers conducted questionnaires and spirometry. Survey-weighted prevalence of respiratory symptoms and spirometric abnormalities were estimated. Regression analysis models were used to identify risk factors for chronic lung diseases.Results:Using the NHANESIII reference equations, the prevalence of Chronic Airflow Obstruction (CAO) was 10%. The main risk factor was older age 60-69 years (Odds ratio 3.16, 95% Confidence Interval 1.20 – 8.31). Lower education, high body mass index and a history of tuberculosis were also identified as significant risk factors. The prevalence of a low forced vital capacity (FVC) using NHANES III was 62.7% [SE 2.2] and 11.3% [SE 1.4] using locally derived values.Conclusion:The prevalence of spirometric abnormality mainly (low FVC); was high suggesting that chronic respiratory disease is of substantial public health importance in urban Sudan. Strategies for the prevention and control of these problems are needed.

Journal article

Knox-Brown B, Amaral AF, Burney P, 2022, Concerns about PRISm., Lancet Respir Med, Vol: 10, Pages: e51-e52

Journal article

Moitra S, Carsin A-E, Abramson M, Accordini S, Amaral A, Anto J, Bono R, Casas Ruiz L, Cerveri I, Chatzi L, Demoly P, Dorado-Arenas S, Forsberg B, Gilliland F, Gislason T, Gullon J, Heinrich J, Holm M, Janson C, Jogi R, Gomez Real F, Jarvis D, Leynaert B, Nowak D, Probst-Hensch N, Sanchez-Ramos J, Semjen C, Siroux V, Guerra S, Kogevinas M, Garcia-Aymerich Jet al., 2022, Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS, Thorax, ISSN: 0040-6376

Journal article

Nafees AA, Muneer MZ, De Matteis S, Amaral A, Burney P, Cullinan Pet al., 2022, Impact of using different predictive equations on the prevalence of chronic byssinosis in textile workers in Pakistan, Occupational and Environmental Medicine, Vol: 79, Pages: 242-244, ISSN: 1351-0711

<jats:sec><jats:title>Objective</jats:title><jats:p>Byssinosis remains a significant problem among textile workers in low/middle-income countries. Here we share our experience of using different prediction equations for assessing ‘chronic’ byssinosis according to the standard WHO classification using measurements of forced expiratory volume in 1 s (FEV<jats:sub>1</jats:sub>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We enrolled 1910 workers in a randomised controlled trial of an intervention to improve the health of textile workers in Pakistan. We included in analyses the 1724 (90%) men who performed pre-bronchodilator spirometry tests of acceptable quality. We compared four different equations for deriving lung function percentage predicted values among those with symptoms-based byssinosis: the third US National Health and Nutrition Examination Survey (NHANES-III, with ‘North Indian and Pakistani’ conversion factor); the Global Lung Function Initiative (GLI, ‘other or mixed ethnicities’); a recent equation derived from survey of a western Indian population; and one based on an older and smaller survey of Karachi residents.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>58 men (3.4%) had symptoms-based byssinosis according to WHO criteria. Of these, the proportions with a reduced FEV<jats:sub>1</jats:sub> (&lt;80% predicted) identified using NHANES and GLI; Indian and Pakistani reference equations were 40%, 41%, 14% and 12%, respectively. Much of this variation was eliminated when we substituted FEV<jats:sub>1</jats:sub>/forced vital capacity (FVC) ratio (&lt;lower limit of normality) as a measure of airway obstruction.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Accurate measures

Journal article

Knox-Brown B, Mulhern O, Feary J, Amaral AFSet al., 2022, Spirometry parameters used to define small airways obstruction in population-based studies: systematic review., Respir Res, Vol: 23

BACKGROUND: The assessment of small airways obstruction (SAO) using spirometry is practiced in population-based studies. However, it is not clear what are the most used parameters and cut-offs to define abnormal results. METHODS: We searched three databases (Medline, Web of Science, Google Scholar) for population-based studies, published by 1 May 2021, that used spirometry parameters to identify SAO and/or provided criteria for defining SAO. We systematically reviewed these studies and summarised evidence to determine the most widely used spirometry parameter and criteria for defining SAO. In addition, we extracted prevalence estimates and identified associated risk factors. To estimate a pooled prevalence of SAO, we conducted a meta-analysis and explored heterogeneity across studies using meta regression. RESULTS: Twenty-five studies used spirometry to identify SAO. The most widely utilised parameter (15 studies) was FEF25-75, either alone or in combination with other measurements. Ten studies provided criteria for the definition of SAO, of which percent predicted cut-offs were the most common (5 studies). However, there was no agreement on which cut-off value to use. Prevalence of SAO ranged from 7.5% to 45.9%. As a result of high heterogeneity across studies (I2 = 99.3%), explained by choice of spirometry parameter and WHO region, we do not present a pooled prevalence estimate. CONCLUSION: There is a lack of consensus regarding the best spirometry parameter or defining criteria for identification of SAO. The value of continuing to measure SAO using spirometry is unclear without further research using large longitudinal data. PROSPERO registration number CRD42021250206.

Journal article

Amaral A, 2022, Prevalence of chronic airflow obstruction in sub-Saharan Africa, International Journal of Tuberculosis and Lung Disease, Vol: 26, Pages: 181-182, ISSN: 1027-3719

Journal article

Kulbacka-Ortiz K, Triest FJJ, Franssen FME, Wouters EFM, Studnicka M, Vollmer WM, Lamprecht B, Burney PGJ, Amaral AFS, Vanfleteren LEGWet al., 2022, Restricted spirometry and cardiometabolic comorbidities: results from the international population based BOLD study., Respir Res, Vol: 23

BACKGROUND: Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities. METHODS: A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires. RESULTS: Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37-1.86) for CVD, 1.53 (95% CI 1.40-1.66) for hypertension, and 1.98 (95% CI 1.71-2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33-1.79) for CVD, 1.50 (95% CI 1.39-1.63) for hypertension, and 1.86 (95% CI 1.59-2.17) for diabetes. CONCLUSION: In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account.

Journal article

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

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, 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.

Journal article

Knox-Brown B, Mulhern O, Amaral A, 2021, Spirometry parameters used to define small airways obstruction in population-based studies: Systematic review protocol, BMJ Open, Vol: 11, ISSN: 2044-6055

Introduction: In recent years, there has been increasing interest in the use of spirometry for the assessment of small airways obstruction (SAO) driven by the idea that these changes occur prior to development of established obstructive lung disease. Maximal mid-expiratory and distal flow rates have been widely used despite a lack of agreement regarding parameter selection or definition of an abnormal result. We aim to provide evidence from population-based studies, describing the different parameters, definitions of normal range and the resulting impact on prevalence estimates for SAO. Summarising this evidence is important to inform development of future studies in this area.Methods and analysis: A systematic review of population-based studies will be conducted. MEDLINE, Web of Science and Google Scholar will be searched from database inception to May 2021. Primary outcomes will include the spirometry parameter used to define SAO, and the definition of an abnormal result. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed for study selection. Study methods will be assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation working group methodology. Narrative synthesis will be conducted for all included studies. Meta-analysis will also be conducted for prevalence estimates and associated risk factors where data quality and availability allow. Random effects models will be used to conduct the meta-analysis and I2 statistics will be used to assess heterogeneity across studies. Where appropriate subgroup analysis will be conducted to explore heterogeneity.Ethics and dissemination: There is no requirement for ethical approval for this project. Findings will be disseminated via peer-reviewed publications and other formats, for example, conferences, congresses or symposia.

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, Vol: 25, Pages: 797-813, ISSN: 1027-3719

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

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, Vol: 79, 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

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

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

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