Burden of Obstructive Lung Disease Follow-up in low/middle income countries (BOLD II)

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute


Chronic lung disease is one of the most common causes of death in the world and is particularly high in low income countries. In spite of this there is very little research on the subject and almost none in low income countries that uses adequate quality assurance for the measurements of lung function. The baseline BOLD study measured lung function and collected information on the background, exposures, symptoms, quality of life and treatment of more than 31,000 people in 44 sites in 36 countries.
The results of the study so far have shown that many of the assumptions that have been made about chronic lung disease in these countries (and in high income countries also) may be wrong. The prevalence of narrowing of the airways (obstructive spirometry) alone does not explain the high mortality estimated for these diseases in low income settings. A more likely explanation for the high mortality ascribed to chronic lung disease is the smaller size of lungs (restrictive spirometry). This pattern of lung function has largely been ignored for the last half century but a high mortality in those with low lung volumes has been observed in the United States and can explain the higher mortality seen in African Americans who also have smaller lungs on average than white Americans. Although there is no direct evidence for this at the current time, this seems to be the most likely explanation for the high recorded mortality from COPD in South Asia, South-East Asia and Sub-Saharan Africa. Understanding whether this is the case or not is, however, critical for deciding the emphasis of future research and future health policy as obstructive and restrictive diseases have different risk factors and will require different preventive and treatment strategies.
This proposal, which will follow up 15,000 people in 20 sites in 15 low or middle income countries, will answer four important questions. First, how far the high mortality from Chronic Respiratory Disease is associated with narrow airways (obstructive disease) or small lungs (restrictive disease). Second how far the low level of lung function found in older people in poorer countries is due to changes in early life that they have never recovered from, or whether their lung function continues to decline more rapidly in later life. Third whether people with poor lung function in low income countries die from respiratory failure or whether the increased risk of death is also due to a higher mortality from heart disease and related problems, as seems to be the case in richer countries. Finally the study will investigate a number of possible risk factors that we believe are important for determining lung health in low income countries focussing particularly on diet and exposure to unregulated industries. Although smoking is by far the most important risk factor for chronic obstruction of the airways there are countries that have been exposed to very little tobacco and yet still have substantial problems with respiratory disease. Other risk factors that have been suggested such as smoke from cooking fires do not seem to explain this discrepancy. By collecting more detailed information in a highly standardised way and by investigating the effects of these and other risk factors on how they influence the rate of decline in lung function over time we will be able to improve considerably our ability to interpret the associations (and sometimes the lack of associations) that we have found in the earlier study.
The centres included in this study cover a wide variety of environments and populations in East Asia, South Asia, Central Asia, North Africa, Sub-Saharan Africa and the Caribbean. All of the centres have shown that they are able to collect high quality data, and the co-ordinating centre at the National Heart and Lung Institute in London has a long history of managing large international studies of lung disease. An international advisory board will help to optimise dissemination of results.

Technical Summary

A follow up survey of 15,000 participants from 20 sites in 15 low/middle income countries from the Burden of Obstructive Lung Disease (BOLD) study will establish, from death certificates where available and verbal autopsies everywhere, the date and cause of death of those who have died. FEV1/FVC and FVC will be measured after bronchodilation with 200 micrograms salbutamol administered through a spacer using the same equipment, same protocol and same centralised training and quality control as at the baseline survey.
The influence of FVC and FEV1 on mortality will be assessed mutually adjusting for each and also adjusting for other confounders such as tobacco consumption, age and sex. Sub-analyses will assess whether any excess mortality associated with poor lung function is associated with particular causes of death including chronic lung disease and cardiovascular disease.
Differences between the decline of lung function with age measured in cross-sectional and longitudinal analyses will be used to estimate the change in lung function with age that is due to differences between birth cohorts.
Rate of change in lung function in individuals will be assessed against risk factors including tobacco consumption, history of tuberculosis, exposure to household air pollution, occupational history, poverty, education and diet after adjusting for age and stratifying by sex. Methods for assessing these risks will mostly be the same as those used in the baseline survey. Occupational history will be assessed more fully using a modified OSCAR protocol and dietary habits will be described using GA2LEN food frequency questionnaires designed to collect standardised dietary information from diverse food cultures.
Results will be publicised locally and through national and international meetings. Information will be provided to government departments both directly by study members and through an advisory committee chaired by a senior member of WHO.

Planned Impact

The study's results relate to the xth most common cause of death and the yth most common cause of disability worldwide, problems that are particularly concentrated in low income countries and proportions that are likely to increase as the populations in these countries age. The results are therefore widely relevant to a wide range of end users.
Understanding the nature and causes of chronic respiratory disease in low income countries is an essential basis for formulating evidence-based policy. Chronic lung disease has been identified by the United Nations as one of the four priority non-communicable diseases that need to be addressed particularly in low income countries. There is very little information available on the subject currently and inadequate information on which to make reliable decisions. This includes decisions about setting priorities as well as concrete plans for service development. These include decisions about research needs, health protection, infrastructure planning and health care delivery.
Most policy decisions carry with them substantial costs, including costs to government but also and importantly costs to industry, to individuals and to public services. Having adequate information to ensure good decision making is cost saving. Introducing ineffective measures, supporting research that is unlikely to lead to better decision making, planning irrelevant infrastructure is all detrimental. On the other hand failing to act effectively in a condition that causes so much loss of capacity is also wasteful.
At a clinical level a better understanding of chronic lung disease is also essential to delivering good services. There is a strong feeling that chronic lung disease is a major clinical burden in low income countries, but so far we have failed to show that this is associated with a high burden of obstructive lung disease. Understanding this disparity may help to improve the effectiveness of the services being offered in these countries.
Though these results are not expected to be commercially exploitable in the usual sense, they will also be of value to commercial enterprises. For the sales companies they will clarify the target patient populations likely to benefit from known treatments. They will also identify the size of other problems and help to prioritise the search for new solutions.
The sites involved in this project themselves represent key departments interested in chronic respiratory disease which have for the most part strong local support. They will have the opportunity to extend their skills adding additional techniques, but also have the opportunity to discuss the prioritisation of research questions with colleagues in different regions but tacking similar problems.
Many of the benefits from this programme will be felt more or less immediately in that the results will be fed directly in to the local and international policy makers. More general effects will be dependent on the speed of development of the policy response. Other fairly immediate effects will be seen in the development of local research agendas and research capacity.


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Conyette L (2020) Prevalence and risk factors of airflow obstruction in a Caribbean population. in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

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Nafees AA (2021) Indoor air quality and its relationship with cluster type in urban Pakistani households. in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

Description NIHR Global Health Research Unit on Lung Health and Tuberculosis in Africa at LSTM 
Organisation Liverpool School of Tropical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We have supported fieldwork including the Chikwawa lung health cohort and provided technical support for a PhD student.
Collaborator Contribution This collaboration has strengthened the BOLD II programme in Sub-Saharan Africa and supported some related work including the Chikwawa lung health cohort and other related work in centres that are associated with both the BOLD II and IMPALA programmes.
Impact The collaboration is broader, but this collaboration involves epidemiology, statistics and economics.
Start Year 2017
Description Scandanavian BOLD 
Organisation Uppsala University
Country Sweden 
Sector Academic/University 
PI Contribution We will co-ordinate four centres in Scandanavia to complete the BOLD II study.
Collaborator Contribution The partners will provide information according to the BOLD II protocol from four sites in Northern Europe. There will be a financial contribution from Uppsala University for this but this is not yet received.
Impact None yet.
Start Year 2018