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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.

Introduction: Previous population-based studies, mainly from high-income countries, have shown that a higher forced vital capacity (FVC) is associated with a lower risk of developing cardiometabolic diseases. The aim of this study was to assess the longitudinal association between spirometry measures and the onset of cardiometabolic diseases across sites in low-income, middle-income and high-income countries., Methods: The study population comprised 5916 individuals from 15 countries participating in the Burden of Obstructive Lung Disease baseline and follow-up assessments. Postbronchodilator forced expiratory volume in 1 s (FEV1), FVC and FEV1/FVC were measured at baseline. Participants who reported having doctor-diagnosed hypertension, diabetes, heart disease and stroke at follow-up but not at baseline were considered new cases of these diseases. The association between lung function and the onset of participant-reported cardiometabolic diseases was assessed in each site using regression models, and estimates were combined using random effects meta-analysis. Models were adjusted for sex, age, smoking, body mass index and educational level., Results: Participants with greater per cent predicted FVC were less likely to have new-onset diabetes (OR per 10%=0.91, 95% CI 0.84 to 0.99), heart disease (OR per 10%=0.86, 95% CI 0.80 to 0.92) and stroke (OR per 10%=0.81, 95% CI 0.73 to 0.89) during the follow-up period (mean±SD 9.5±3.6 years). A greater percentage of FEV 1 was associated with a lower risk of onset of heart disease and stroke. No significant association was found between FEV 1 /FVC and onset of reported cardiometabolic diseases, except for a higher risk of diabetes (OR per 10%=1.21, 95% CI 1.08 to 1.35) in participants with higher FEV 1 /FVC., Conclusions: The findings of this study suggest that a low FVC is more important than a low FEV 1 /FVC as a risk factor for developing cardiometabolic diseases. The value of including FVC in risk score models to improve their precision in predicting the onset of cardiometabolic diseases should be explored., Competing Interests: Competing interests: RN declares support from Astra Zenenca related to and the Norwegian Respiratory Society not related to the manuscript. AØR declares support from Boehringer Ingelheim and the Endowment of Timber Merchant A. Delphin and Wife unrelated to the manuscript. PGJB declares support from the Wellcome Trust related to the manuscript. AFSA declares support from the Colt Foundation not related to the manuscript. None of the other authors declare any conflicts of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Objectives: To estimate the prevalence of allergic rhinitis (AR), atopic dermatitis (AD), and wheezing, and to describe their patterns of co-occurrence according to different characteristics in adolescence and early adulthood., Methods: Cross-sectional analyses from the 15-year and 22-year follow-ups of the 1993 Pelotas (Brazil) Birth Cohort. The outcomes were assessed based on self-reported data, and the patterns of co-occurrence were determined using cluster analysis. The sample was described using absolute and relative frequencies according to the independent variables. Venn diagrams were generated to visualize the co-occurrence of AR, AD, and wheezing., Results: Data on AR, AD, and wheezing were available for 4,286 participants at 15 years and 3,789 at 22 years. At 15 years, AR was reported by 20.9% of participants, AD by 25.2%, and wheezing by 33.4%. Meanwhile, at 22 years, AR was reported by 24.6%, AD by 14.2%, and wheezing by 30.7%. Notably, the overlap between AR and wheezing was greater than that of the other conditions (6.9% at 15 years and 8.3% at 22 years). Participants with lower maternal education and lower income were more likely to report having "no health condition". At 15 years, White individuals most frequently reported "three conditions" (4.1%; p<0.001), whereas at 22 years, they primarily reported "two conditions" (15.6%; p<0.001). The co-occurrence of all three health conditions was found to be greater than expected, with an observed rate 2.1 times higher (95% CI 1.4 - 3.0) at 22 years., Conclusions: This study highlights the social gradient in the diagnosis and reporting of co-occurrence of AR, AD, and wheezing.

Exposure to high levels of harmful agents in the workplace can significantly impact workers' health, contributing to morbidity and mortality. Levels of these exposures are often measured in high-income countries in research studies and, in some places, to monitor levels in line with health and safety regulations. However, less is known about workplace exposure levels in low- and middle-income countries (LMICs). Our aim was to describe the quantitative exposure measurements of different occupational agents across industries within LMICs. We conducted a scoping review of peer-reviewed publications available on Web of Science and PubMed from inception to 1 September 2023. Our search focused on quantitative occupational exposure measurements across industries in LMICs. We identified a total of 8,676 publications. After screening, 58 studies from 25 countries were retained for final review. China, Iran, and Tanzania contributed the greatest number of studies. Manufacturing, mining, and agriculture were the most studied sectors, with factory workers and miners being the most common job titles. Exposure measurements included vapour, gases, dust, and fumes (VGDF), solvents, metals, pesticides and particulate matter. Occupational exposure levels for the same industry varied widely across geographical regions. This review provides a comprehensive overview of occupational exposures in LMICs and highlights the absence of data in certain geographical areas and industries. The study contributes valuable insights for directing future research, and the need to optimise the assessment of occupational exposures in LMICs with the aim ultimately of reducing disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Quintero Santofimio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases, and progression to COPD over time. Whether SAO predicts mortality is largely unknown., Research Question: Is spirometry-defined SAO associated with increased mortality?, Methods: Data were analyzed from 252,877 adult participants, aged 40 to 69 years at baseline, in the UK Biobank who had provided good-quality spirometry measurements. SAO was defined as the ratio of the forced expiratory volume in 3 s to the forced expiratory volume in 6 s less than the lower limit of normal. SAO was considered to be isolated if present when the FEV 1 /forced expiratory volume in 6 s ratio was normal (ie, greater than the lower limit of normal). A multivariable Cox regression model was used to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. Sex differences were investigated in these associations, and the primary analysis was repeated, excluding those who ever smoked. All models were adjusted for potential confounders such as sex, BMI, smoking status, smoking pack-years, assessment center, Townsend deprivation index, and ethnicity., Results: A total of 59,744 participants with SAO were identified, of whom 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (hazard ratio [HR], 1.31; 95% CI, 1.26-1.36), cardiovascular (HR, 1.39; 95% CI, 1.29-1.51), respiratory (HR, 2.20; 95% CI, 1.92-2.51), and neoplasm (HR, 1.23; 95% CI, 1.17-1.29) mortality risk. These associations were not modified by sex. However, in those who never smoked, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR, 1.14; 95% CI, 1.07-1.20)., Interpretation: Individuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Contemporary data on the burden of chronic respiratory diseases in sub-Saharan Africa is limited. More so, their economic burden is not well described. This study aims to establish a chronic respiratory disease observatory for Africa. Specific study aims are (1) to describe the prevalence and determinants of asthma with a target to screen up to 4000 children and adolescents across four African cities; (2) to determine the prevalence and determinants of chronic obstructive pulmonary disease (COPD) with a target to screen up to 3000 adults (≥18 years) across five African cities; (3) to describe the disease burden by assessing the frequency and severity of symptoms and exacerbations, medication use, emergency healthcare utilisation and hospitalisation; and (4) to assess the economic burden and affordability of the medicines for these diseases., Methods and Analysis: Surveys will be conducted in schools to identify children and adolescents with asthma using the Global Asthma Network screening questionnaire in Ghana, Nigeria, the Democratic Republic of Congo, and Uganda. Community surveys will be conducted among adults using an adapted version of the Burden of Obstructive Lung Disease Questionnaire to identify persons with COPD symptoms in Nigeria, Burkina Faso, Mozambique, Rwanda, and Sierra Leone. Fractional exhaled nitric oxide and pre-bronchodilator and post-bronchodilator spirometry will be done for children with asthma or asthma symptoms and for all adult participants. Children and adults with respiratory symptoms or diagnoses will complete the health economic questionnaires. Statistical analysis will involve descriptive and analytical statistics to determine outcomes., Ethics and Dissemination: Ethical approval has been obtained from participating institutions. This study's results will inform deliberations at the United Nations General Assembly high-level meeting on non-communicable diseases in 2025. The results will be shared through academic conferences and journals and communicated to the schools and the communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Small airways obstruction (SAO) has been associated with occupational exposures. Whether exposure to harmful occupational agents impacts the survival of people with SAO is unknown. Our aim was to estimate the mortality risk associated with occupational exposures among people with SAO., Methods: We used data from UK Biobank participants with SAO, defined as a ratio of forced expiratory volume in three seconds to forced expiratory volume in six seconds (FEV3/FEV6) below the lower limit of normal. We assigned lifetime occupational exposures to participants with available occupational histories using the ALOHA+ Job Exposure Matrix. Mortality data were provided by the National Death Registries. We used Cox regression to assess the association of all-cause mortality with lifetime occupational exposures (vapours, gases, dusts, fumes-VGDF; solvents; pesticides; metals), adjusting for potential confounders., Results: The 13,942 participants with SAO had a mean age of 56±7 years, 59% were females and 94.2% were of White ancestry. Overall, there were 457 deaths over a median follow-up of 12.8 years. A greater mortality risk was associated with exposure to VGDF, with hazard ratios of 1.32 (95%CI: 1.04-1.78) for low levels and 1.41 (95%CI: 1.11-1.78) for moderate levels of cumulative exposure. There was no evidence of association for the other occupational exposures., Conclusion: Lifetime occupational exposure to VGDF in people with SAO may have a detrimental effect on their survival. Future respiratory health surveillance programmes of people exposed to VGDF should consider assessment for SAO and focus on primary prevention through adequate exposure control., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Quintero-Santofimio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function., Methods: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis., Results: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC1 /FVC

The London Underground (LU) employs over 19,000 staff, some of whom are exposed to elevated concentrations of particulate matter (PM) within the network. This study quantified the occupational exposure of LU staff to subway PM and investigated the possible association with sickness absence (SA). A job exposure matrix to quantify subway PM 2.5 staff exposure was developed by undertaking measurement campaigns across the LU network. The association between exposure and SA was evaluated using zero-inflated mixed-effects negative binomial models. Staff PM 2.5 exposure varied by job grade and tasks undertaken. Drivers had the highest exposure over a work shift (mean: 261 µg/m 3 ), but concentrations varied significantly by LU line and time the train spent subway. Office staff work in office buildings separate to the LU network and are unexposed to occupational subway PM 2.5 . They were found to have lower rates of all-cause and respiratory infection SA compared to non-office staff, those who work across the LU network and are occupational exposed to subway PM 2.5 . Train drivers on five out of eight lines showed higher rates of all-cause SA, but no dose-response relationship was seen. Only drivers from one line showed higher rates of SAs from respiratory infections (incidence rate ratio: 1.24, 95% confidence interval 1.10-1.39). Lower-grade customer service (CS) staff showed higher rates of all-cause and respiratory infection SA compared to higher grade CS staff. Doctor-certified chronic respiratory and cardiovascular SAs were associated with occupational PM 2.5 exposure in CS staff and drivers. While some groups with higher occupational exposure to subway PM reported higher rates of SA, no evidence suggests that subway PM is the main contributing factor to SA. This is the largest subway study on health effects of occupational PM 2.5 exposure and may have wider implications for subway workers, contributing to safer working environments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no competing financial interests that could have influenced the work reported in this paper. The funder had no role in the design of the study, the analysis and interpretation of data, and the decision to publish the results., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition., Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors., Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job., Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors., Funding: Wellcome Trust., Competing Interests: Fatima Rodrigues declares grants and personal fees from A. Menarini, Boehringer Ingelheim, Teva Pharma, Novartis, GlaxoSmithKline, AstraZeneca, VitalAire and Nippon Gases outside the submitted work. Wan C. Tan received grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93,326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd. for conducting the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study on COPD. David Mannino is a consultant to GSK, AstraZeneca, Regeneron, Genentech, COPD Foundation, and expert witness on behalf of people suing Tobacco Industry (Schlesinger Law Firm). Sonia Buist is Chair of the Data Safety & Monitoring Board for the RELIANCE Clinical Trial. Frits Franssen declares personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, MSD, Pieris, and Verona Pharma. Robab Breyer-Kohansal declares consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Novartis Pharma, and Sanofi, and participation on advisory boards for AstraZeneca, Menarini, and Sanofi. Thorarinn Gislason received a grant from the Icelandic Research Fund. Kevin Mortimer declares participation on advisory boards for AstraZeneca and GlaxoSmithKline. Sylvia Hartl declares grants from GSK, Chiesi Farma, Menarini Pharma, and AstraZeneca, and participation on advisory boards for Menarini Pharma and GSK. AFSA declares a grant from the COLT Foundation (CF/01/21)., (© 2024 The Author(s).)

Objective: Tuberculosis (TB) is a leading cause of death globally, with approximately 1.5 million deaths in 2020. TB often coexists with chronic communicable and non-communicable diseases, but data to determine the extent of comorbid diseases are limited. In this study, we aimed to assess the prevalence of TB multimorbidity and its risk factors in a tertiary hospital in Sierra Leone. This is a cross-sectional study of 240 adults with microbiologically-confirmed TB at Connaught Hospital in Freetown, between March and May 2022. Logistic regression analysis was used to identify factors associated with TB multimorbidity., Results: The mean age of the patients was 37 years. More than two-thirds were males and about the same number had two or more chronic diseases. The most common were hypertension (47.9%) and diabetes (24.2%). Patients under 35 years of age were less likely to have TB multimorbidity (< 25 years: adjusted OR 0.07, 95%CI 0.01-0.6; 25-34 years: adjusted OR 0.2, 95%CI 0.01-0.9). We report a high prevalence of comorbid diseases among TB patients in the largest treatment center in Sierra Leone, with hypertension and diabetes being the most common. These findings support the current call for addressing comorbid non-communicable diseases in TB patients through integrated care., (© 2023. The Author(s).)

Background: Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life., Methods: We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF 25-75 ) if a result was less than the lower limit of normal (1 /FVC). We also used the forced expiratory volume in 3 s to FVC ratio (FEV 3 /FVC) to define small airways obstruction. We defined chronic airflow obstruction as post-bronchodilator FEV 1 /FVC25-75 less than the LLN, OR: 2.95, 95% CI 1.02 to 8.54; FEV 3 /FVC less than the LLN, OR: 1.94, 95% CI 1.05 to 3.62). FEF 25-75 was better than the FEV 3 /FVC ratio to discriminate future chronic airflow obstruction (AUC: 0.764 vs 0.692). Results were similar among participants of the UK Biobank study., Conclusion: Measurements of small airways obstruction can be used as early markers of future obstructive lung disease., Competing Interests: Competing interests: RN reports grants and personal fees from AstraZeneca and GlaxoSmithKline and grants from Boehringer Ingelheim and Novartis, outside of the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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-income and middle-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Spirometric small airway obstruction is associated with impaired ventilatory response to exercise independently of FEV 1 /FVC ratio https://bit.ly/3pre4sk., Competing Interests: Conflict of interest: B. Knox-Brown has nothing to disclose. Conflict of interest: K. Sylvester has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose., (Copyright ©The authors 2023.)

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.

Background: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are common chronic diseases that are associated with chronic and intermittent hypoxemia, respectively. Patients affected by the overlap of COPD and OSA have a particularly unfavourable prognosis. The L-arginine/nitric oxide (NO) pathway plays an important role in regulating pulmonary vascular function. Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) interfere with NO production., Methods: We analysed the serum concentrations of ADMA, SDMA, L-arginine, L-citrulline, and L-ornithine in a large sample of the Icelandic general population together with chronic airflow obstruction (CAO), a key physiological marker of COPD that was assessed by post-bronchodilator spirometry (FEV1/FVC < LLN). OSA risk was determined by the multivariable apnoea prediction (MAP) index., Results: 713 individuals were analysed, of whom 78 (10.9%) showed CAO and 215 (30%) had MAP > 0.5. SDMA was significantly higher in individuals with CAO (0.518 [0.461-0.616] vs. 0.494 [0.441-0.565] µmol/L; p = 0.005), but ADMA was not. However, ADMA was significantly associated with decreasing FEV1 percent predicted among those with CAO ( p = 0.002). ADMA was 0.50 (0.44-0.56) µmol/L in MAP ≤ 0.5 versus 0.52 (0.46-0.58) µmol/L in MAP > 0.5 ( p = 0.008). SDMA was 0.49 (0.44-0.56) µmol/L versus 0.51 (0.46-0.60) µmol/L, respectively ( p = 0.004). The highest values for ADMA and SDMA were observed in individuals with overlap of CAO and MAP > 0.5, which was accompanied by lower L-citrulline levels., Conclusions: The plasma concentrations of ADMA and SDMA are elevated in COPD patients with concomitant intermittent hypoxaemia. This may account for impaired pulmonary NO production, enhanced pulmonary vasoconstriction, and disease progression.

BACKGROUND: Chronic respiratory diseases (CRDs) greatly contribute to worldwide mortality. Despite new data emerging from Africa, prevalence estimates and determinants of CRDs in rural settings are limited. This study sought to extend the existing research conducted in urban Sudan by conducting a rural comparison. METHODS: Participants aged ≥18 years ( n = 1,850), living in rural Gezira State completed pre-and post-bronchodilator spirometry and a questionnaire. Prevalence of respiratory symptoms and spirometric abnormalities were reported. Regression analyses were used to identify risk factors for CRDs. RESULTS: Prevalence of chronic airflow obstruction (CAO) was 4.1% overall and 5.5% in those aged ≥40 years. Reversibility was seen in 6.4%. Low forced vital capacity (FVC) was seen in 58.5%, and at least one respiratory symptom was present in 40.7% of the participants. CAO was more common among people aged 60-69 years (OR 2.07, 95% CI 1.13-3.82) and less common among highly educated participants (OR 0.50, 95% CI 0.27-0.93). Being underweight was associated with lower FVC (OR 3.07, 95% CI 2.24-4.20). CONCLUSIONS: A substantial burden of CRD exists among adults in rural Sudan. Investment in CRD prevention and management strategies is needed.

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 (FEF 25-75 ) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV 3 /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 FEV 1 /FVC ≥ LLN)., Results: Almost a fifth of the participants had spirometric SAO (19% for FEF 25-75 ; 17% for FEV 3 /FVC). Using FEF 25-75, 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 FEV 3 /FVC. Isolated spirometric SAO (10% for FEF 25-75 ; 6% for FEV 3 /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 FEF 25-75 and FEV 3 /FVC, in addition to traditional spirometry parameters., (© 2023. The Author(s).)

Background: Small airways obstruction (SAO) is a key feature of both COPD 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 also run to account for potential co-exposures., Results: SAO was present in varying proportions of the population depending on definition used: 5.6% (forced expiratory flow between 25 and 75% of the forced vital capacity (FEF 25-75 ) < lower limit of normal (LLN)) and 21.4% (forced expiratory volume in 3 s (FEV 3 )/forced expiratory volume in 6 s (FEV 6 ) 3 /FEV 6 3 /FEV 6 3 /FEV 6

BACKGROUND: Chronic respiratory diseases (CRDs) 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 CRDs in Khartoum, Sudan. METHODS: Data were collected from 516 participants aged ≥40 years, who had completed a questionnaire and undertook pre- and post-bronchodilator spirometry testing. Trained field workers administered the questionnaires and conducted 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 Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) reference equations, the prevalence of chronic airflow obstruction (CAO) was 10%. The main risk factor was older age, 60-69 years (OR 3.16, 95% CI 1.20-8.31). Lower education, high body mass index and a history of TB 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 CRD is of substantial public health importance in urban Sudan. Strategies for the prevention and control of these problems are needed.

Competing Interests: PB receives research funding from the Wellcome Trust (085790/Z/08/Z) and the Medical Research Council (MR/R011192/1). AFSA receives research funding from The Colt Foundation. We declare no competing interests.

Introduction: Obesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults., Methods: We used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I ( t ) to ECRHS II ( t+1 ), and from ECRHS II ( t ) to ECRHS III ( t+1 ). We excluded obese (body mass index≥30 kg/m 2 ) individuals at visit t . The relative risk (RR) of obesity at t+1 associated with asthma at t was estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity., Results: We included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II-III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association., Conclusion: This is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids., Competing Interests: Competing interests: SM reports Long-Term Research fellowship and Young Scientist Sponsorship from the European Respiratory Society, outside the submitted work. MJA holds investigator-initiated grants for unrelated research from Pfizer and Boehringer-Ingelheim. He has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi and has also received a speaker’s fee from GSK, outside the submitted work. PD reports personal fees from ALK, Stallergenes Greer, IQVIA, Chiesi, AstraZeneca, Thermo Fisher Scientific, Ménarini, Bausch & Lomb, Mylan, ASIT Biotech, Novartis, Sanofi, Regeneron, outside the submitted work. RJ reports grants from Estonian Research Council Personal Research Grant no 562, during the conduct of the study; personal fees from Consultancy, grants from Grants/grants pending, personal fees from Payment for lectures, personal fees from Travel/accommodations/meeting expenses, outside the submitted work. CR-S reports personal fees from ALK, Astra Zeneca, GSK, Novartis, outside the submitted work., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Methods: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 )/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., Results: 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 ≥20 years 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=0.02 L, 95% CI -0.02-0.06 L) or lower FEV 1 /FVC (β=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income., Conclusion: 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 are associated with more respiratory symptoms. Because 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., Competing Interests: Conflict of interest: J. Ratanachina, A.F.S. Amaral, S. De Matteis, H. Lawin, K. Mortimer, D.O. Obaseki, I. Harrabi, M. Denguezli, E.F.M. Wouters, C. Janson, A. Gulsvik, H.H. Cherkaski, F. Mejza, P.A. Mahesh, A. Elsony, R. Ahmed, W. Tan, L.C. Loh, A. Rashid, M. Studnicka, A.A. Nafees, T. Seemungal, A. Aquart-Stewart, M. Al Ghobain, J. Zheng, S. Juvekar, S. Salvi, R. Jogi, T. Gislason, A.S. Buist, P. Cullinan and P. Burney have no conflict of interest to disclose. R. Nielsen reports grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis, and receipt of equipment/material/services from ResMed Norway; and is President of the Norwegian Respiratory Society. D. Mannino reports royalties from Up to Date; personal fees from GlaxoSmithKline, AstraZeneca and Schlesinger Law Firm; honoraria from American Association of Respiratory Care; and stock in GlaxoSmithKline; and is the Medical Director of the COPD Foundation., (Copyright ©The authors 2023.)

Background: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters., Methods: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF 25-75 ) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV 3 /FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 μg salbutamol) and post-bronchodilator (ie, after administration of 200 μg salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis., Findings: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV 3 /FVC ratio and 25 961 participants for FEF 25-75 . Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF 25-75 , and for FEV 3 /FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV 3 /FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF 25-75 , except for increasing age, which was associated with reduced odds of small airways obstruction., Interpretation: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline., Funding: National Heart and Lung Institute and Wellcome Trust., Translations: For the Dutch, Estonian, French, Icelandic, Malay, Marathi, Norwegian, Portuguese, Swedish and Urdu translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests DM declares being a consultant to and receiving royalties from GlaxoSmithKline, AstraZeneca, and the COPD Foundation (royalty payments are up to date) and acting as an expert witness for Schlesinger Law Firm, outside of the submitted work. RN reports grants and personal fees from AstraZeneca and GlaxoSmithKline and grants from Boehringer Ingelheim and Novartis, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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 FEF 25-75 , 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 (I 2  = 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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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 (PM 2.5 ) using negative binomial regression. The prevalence of CAO was not independently associated with PM 2.5 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., Competing Interests: Competing interests: RN reports grants and personal fees from Boehringer Ingelheim, AstraZeneca and Novartis outside the submitted work. EDB reports personal fees from Novartis, AstraZeneca, Orion, Menarirni, Boehringer Ingelheim and ALK outside the submitted work. KM reports grants from GlaxoSmithKline during the conduct of the study. TW reports grants from Boehringer Ingelheim and Pfizer during the conduct of the study. FM reports fees from Medycyba Praktyczna, Sandoz and Chiesi outside the submitted work. DM reports salary and shares from GlaxoSmithKline outside the submitted work. IH reports grants from Boehringer Ingelheim during the conduct of the study., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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 I 2 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., Prospero Registration Number: CRD42021250206., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Methods: 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 (N > 82,000)., Results: 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 pressure., Conclusions: The present study overcomes many limitations of observational studies by using Mendelian Randomisation. We provide evidence for an independent causal effect of T2D, CRP and BMI on lung function with some of the T2D effect on lung function being attributed to inflammatory mechanisms. Furthermore, this analysis suggests a potential causal effect of FEV1/FVC on blood pressure. Our detailed analysis of the interplay between cardio-metabolic traits and impaired lung function provides the opportunity to improve the quality of existing intervention strategies.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: 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 postbronchodilator FEV 1 -to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk 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, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Although there are many health benefits from being active, there was no benefit observed in this study from vigorous physical activity in reducing the risk of asthma onset in middle-aged adults https://bit.ly/3bEtHDn., Competing Interests: Conflict of interest: M.A. Russell has nothing to disclose. Conflict of interest: S. Dharmage has nothing to disclose. Conflict of interest: E. Fuertes has nothing to disclose. Conflict of interest: A. Marcon has nothing to disclose. Conflict of interest: A-E. Carsin has nothing to disclose. Conflict of interest: S. Pascual Erquicia has nothing to disclose. Conflict of interest: J. Heinrich has nothing to disclose. Conflict of interest: A. Johannessen has nothing to disclose. Conflict of interest: M.J. Abramson has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose. Conflict of interest: I. Cerveri has nothing to disclose. Conflict of interest: P. Demoly reports board fees from Chiesi, IQVIA, Ménarini and Sanofi; board and speaker bureau fees from AstraZeneca, Bausch & Lomb and ThermoFisher Scientific; and speaker fees from Mylan and Novartis, all outside the submitted work. Conflict of interest: V. Garcia-Larsen has nothing to disclose. Conflict of interest: D. Jarvis has nothing to disclose. Conflict of interest: J. Martinez-Moratalla has nothing to disclose. Conflict of interest: D. Nowak has nothing to disclose. Conflict of interest: L. Palacios-Gómez has nothing to disclose. Conflict of interest: G. Squillacioti has nothing to disclose. Conflict of interest: W. Raza has nothing to disclose. Conflict of interest: M. Emtner has nothing to disclose. Conflict of interest: J. Garcia-Aymerich has nothing to disclose., (Copyright ©The authors 2021.)

Studies reporting on associations between short-term exposure to outdoor fine (PM 2.5 ), 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, PM 2.5 , 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, PM 2.5 , 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, PM 2.5 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, PM 2.5 , 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 PM 2.5 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 Interquartile range). No consistent associations between PM 2.5 or soot exposure and lung function were observed. Short-term personal, residential outdoor or central site exposure to UFP was not associated with blood pressure or lung function. Short-term personal PM 2.5 and soot exposures were associated with blood pressure, but not lung function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Reasons why pancreatic ductal adenocarcinoma (PDAC) continues to have poor survival are only partly known. No previous studies have analyzed the combined influence of KRAS mutations, persistent organic pollutants (POPs), and trace elements upon survival in PDAC or in any other human cancer., Objective: To analyze the individual and combined influence of KRAS mutations, POPs, and trace elements upon survival from PDAC., Methods: Incident cases of PDAC (n = 185) were prospectively identified in five hospitals in Eastern Spain in 1992-1995 and interviewed face-to-face during hospital admission. KRAS mutational status was determined from tumour tissue through polymerase chain reaction and artificial restriction fragment length polymorphism. Blood and toenail samples were obtained before treatment. Serum concentrations of POPs were analyzed by high-resolution gas chromatography with electron-capture detection. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Multivariable Cox proportional hazards regression was used to assess prognostic associations., Results: Patients with a KRAS mutated tumor had a 70% higher risk of early death than patients with a KRAS wild-type PDAC (hazard ratio [HR] = 1.7, p = 0.026), adjusting for age, sex, and tumor stage. KRAS mutational status was only modestly and not statistically significantly associated with survival when further adjusting by treatment or by treatment intention. The beneficial effects of treatment remained unaltered when KRAS mutational status was taken into account, and treatment did not appear to be less effective in the subgroup of patients with a KRAS mutated tumor. POPs did not materially influence survival: the adjusted HR of the highest POP tertiles was near unity for all POPs. When considering the joint effect on survival of POPs and KRAS, patients with KRAS mutated tumors had modest and nonsignificant HRs (most HRs around 1.3 to 1.4). Higher concentrations of lead, cadmium, arsenic, vanadium, and aluminium were associated with better survival. When KRAS status, POPs, and trace elements were simultaneously considered along with treatment, only the latter was statistically significantly related to survival., Conclusions: In this study based on molecular, clinical, and environmental epidemiology, KRAS mutational status, POPs, and trace elements were not adversely related to PDAC survival when treatment was simultaneously considered; only treatment was independently related to survival. The lack of adverse prognostic effects of POPs and metals measured at the time of diagnosis provide scientific and clinical reassurance on the effects of such exposures upon survival of patients with PDAC. The weak association with KRAS mutations contributes to the scant knowledge on the clinical implications of a genetic alteration highly frequent in PDAC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1 st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on 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 TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.