Publications
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Feary J, Quintero Santofimio V, Potts J, et al., 2023, Occupational exposures and small airways obstruction in the UK Biobank Cohort, ERJ Open Research, ISSN: 2312-0541
Burney P, Knox-Brown B, Amaral A, 2023, "Small lung syndrome": the need to re-classify chronic lung disease, The Lancet Respiratory Medicine, ISSN: 2213-2600
Ratanachina J, Amaral A, De Matteis S, et 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.
Knox-Brown B, Patel J, Potts J, et 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
Ahmed R, Osman N, Noory B, et 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.
Knox-Brown B, Amaral AF, Burney P, 2022, Concerns about PRISm., Lancet Respir Med, Vol: 10, Pages: e51-e52
Moitra S, Carsin A-E, Abramson M, et al., 2022, Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS, Thorax, ISSN: 0040-6376
Nafees AA, Muneer MZ, De Matteis S, et 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> (<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 (<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
Knox-Brown B, Mulhern O, Feary J, et 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.
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
Kulbacka-Ortiz K, Triest FJJ, Franssen FME, et 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.
Wielscher M, Amaral AFS, van der Plaat D, et 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> > 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
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.
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.
Migliori GB, Marx FM, Ambrosino N, et 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
Ratanachina J, Amaral A, De Matteis S, et 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.
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.
van Nunen E, Hoek G, Tsai M-Y, et 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
Russell MA, Dharmage S, Fuertes E, et al., 2021, The effect of physical activity on asthma incidence over 10 years: population-based study, ERJ Open Research, Vol: 7, ISSN: 2312-0541
Burney P, Amaral AFS, 2020, Asthma exacerbations, air pollution, and allergens - Authors' reply., Lancet, Vol: 396, Pages: 753-754
Allwood B, van der Zalm M, Amaral A, et 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.
Amaral AFS, Imboden M, Wielscher M, et 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
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van Nunen E, Vermeulen R, Tsai M-Y, et 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
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Peralta GP, Marcon A, Carsin A-E, et 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.
Rezwan F, Imboden M, Amaral AFS, et al., 2020, Association of adult lung function with accelerated biological aging, AGING-US, Vol: 12, Pages: 518-542, ISSN: 1945-4589
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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.
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
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Janson C, Malinovschi A, Amaral A, et al., 2019, Testing bronchodilator responsiveness, European Respiratory Journal, Vol: 54, ISSN: 0903-1936
Allwood B, van der Zalm M, Makanda G, et al., 2019, The long shadow post-tuberculosis, LANCET INFECTIOUS DISEASES, Vol: 19, Pages: 1170-1171, ISSN: 1473-3099
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van der Plaat DA, Pereira M, Pesce G, et al., 2019, Age at menopause and lung function: a Mendelian randomisation study., Eur Respir J, Vol: 54
In observational studies, early menopause is associated with lower forced vital capacity (FVC) and a higher risk of spirometric restriction, but not airflow obstruction. It is, however, unclear if this association is causal. We therefore used a Mendelian randomisation (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function.We included 94 742 naturally post-menopausal women from the UK Biobank and performed MR analyses on the effect of age at menopause on forced expiratory volume in 1 s (FEV1), FVC, FEV1/FVC, spirometric restriction (FVC<lower limit of normal (LLN)) and airflow obstruction (FEV1/FVC<LLN). We used the inverse variance-weighted 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 years) 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 who had ever used menopause hormone treatment and in overweight women. There was no strong evidence of an 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 risk of spirometric restriction.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.
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