Lung health after pulmonary TB: designing strategies to improve long-term patient outcomes
Lead Research Organisation:
Liverpool School of Tropical Medicine
Department Name: Clinical Sciences
Abstract
Medical treatment of adults with lung tuberculosis typically lasts for 6-months: patients take daily medication during this period, but once they have completed the tablets they are largely discharged from health services as 'cured' with no ongoing follow up available.
However, data from resource poor settings suggests that a high proportion of adult patients - both those with and without HIV infection - sustain a significant amount of lung scarring from TB disease such that even when treatment is completed, and the TB bacteria infection is gone, much damage is left behind. Almost 10% of adults are left with complete destruction of one lobe or area of the lung, 44% have damaged airways, and over one third have abnormal breathing tests. These patients are likely at risk of long term lung complications, including ongoing symptoms such as cough or breathlessness, and frequent chest
infections.
The aim of this project is to understand how the subgroup of patients with severe lung scarring after TB treatment can be identified, and what the health systems in these settings should be doing to support them over time, so that they stay well and these complications are limited. This is particularly important because TB is often a disease of young, economically active adults living in relative poverty - the consequences of long-term respiratory disability for individuals and their households can be severe.
In this study we will:
1. Use existing data from a follow-up study of adults who have had lung TB in Malawi to design a screening tool, which could be used locally to identify the patients with the worst damage at the point of TB treatment completion.
2. Collect sputum and airway samples from patients with/without lung damage from TB in settings such as Malawi and Uganda, to better understand the bacteria that live in the lungs and cause chest infections in those with bad lung damage. This will guide appropriate antibiotic treatment, so that ongoing chest infections are managed quickly and correctly, and the damage they cause is limited.
3. Complete an analysis of the challenges we might face in trying to introduce a pathway for follow up of patients with severe post-TB lung damage: TB treatment services and chronic lung services are usually kept very separate in resource poor settings, and linking them may be challenging for both providers and health systems.
4. Develop an international network of researchers working on post-TB lung damage, in order to share research findings, agree on how to measure and describe post-TB lung damage, determine priorities for research & clinical care, and generate opportunities for collaboration.
However, data from resource poor settings suggests that a high proportion of adult patients - both those with and without HIV infection - sustain a significant amount of lung scarring from TB disease such that even when treatment is completed, and the TB bacteria infection is gone, much damage is left behind. Almost 10% of adults are left with complete destruction of one lobe or area of the lung, 44% have damaged airways, and over one third have abnormal breathing tests. These patients are likely at risk of long term lung complications, including ongoing symptoms such as cough or breathlessness, and frequent chest
infections.
The aim of this project is to understand how the subgroup of patients with severe lung scarring after TB treatment can be identified, and what the health systems in these settings should be doing to support them over time, so that they stay well and these complications are limited. This is particularly important because TB is often a disease of young, economically active adults living in relative poverty - the consequences of long-term respiratory disability for individuals and their households can be severe.
In this study we will:
1. Use existing data from a follow-up study of adults who have had lung TB in Malawi to design a screening tool, which could be used locally to identify the patients with the worst damage at the point of TB treatment completion.
2. Collect sputum and airway samples from patients with/without lung damage from TB in settings such as Malawi and Uganda, to better understand the bacteria that live in the lungs and cause chest infections in those with bad lung damage. This will guide appropriate antibiotic treatment, so that ongoing chest infections are managed quickly and correctly, and the damage they cause is limited.
3. Complete an analysis of the challenges we might face in trying to introduce a pathway for follow up of patients with severe post-TB lung damage: TB treatment services and chronic lung services are usually kept very separate in resource poor settings, and linking them may be challenging for both providers and health systems.
4. Develop an international network of researchers working on post-TB lung damage, in order to share research findings, agree on how to measure and describe post-TB lung damage, determine priorities for research & clinical care, and generate opportunities for collaboration.
Technical Summary
The Fellowship will build on the networks, cohort, and data generated during during the ongoing follow up of a cohort of post-TB patients in Blantyre, Malawi. Specific tasks to be completed include:
1. Data generated from the existing cohort follow up will be used to (a) Design a screening tool to identify patients with extensive post-TB lung damage at TB treatment completion in resource poor settings, and (b) Construct a multilevel longitudinal model to identify factors predicting adverse patient outcomes in the 2-4 years following treatment completion.
2. A case control study will be nested within the ongoing cohort follow up in Malawi, to determine the microbiology of colonising/infecting organisms amongst adults with PTLD.
Molecular tools will be used to identity differences in microbiology between adults completing PTB treatment with/without evidence of PTLD, and well, community based controls with no history of PTB, with a focus on organisms commonly seen in those with structural lung damage that may require targeted management (Eg. P.aeruginosa, S.aureus, non-tuberculous mycobacteria).
3. Formal training in Health Systems, and a consolidative placement in a Health Policy institution will be used to produce a health systems analysis describing the challenges facing integration of acute TB services and chronic respiratory services in resource poor settings. Strategies to facilitate change in health service delivery models will be outlined.
This document will be focused on care delivery in Blantyre, Malawi & Kampala, Uganda, with a view to further research / interventions in these areas as part of an Intermediate Fellowship.
4. An international collaborative network for PTLD research and clinical service delivery will be established, in order to share data and information on ongoing PTLD studies, agree on terminology to be used when describing PTLD, determine priorities for research & clinical care, and generate opportunities for collaboration.
1. Data generated from the existing cohort follow up will be used to (a) Design a screening tool to identify patients with extensive post-TB lung damage at TB treatment completion in resource poor settings, and (b) Construct a multilevel longitudinal model to identify factors predicting adverse patient outcomes in the 2-4 years following treatment completion.
2. A case control study will be nested within the ongoing cohort follow up in Malawi, to determine the microbiology of colonising/infecting organisms amongst adults with PTLD.
Molecular tools will be used to identity differences in microbiology between adults completing PTB treatment with/without evidence of PTLD, and well, community based controls with no history of PTB, with a focus on organisms commonly seen in those with structural lung damage that may require targeted management (Eg. P.aeruginosa, S.aureus, non-tuberculous mycobacteria).
3. Formal training in Health Systems, and a consolidative placement in a Health Policy institution will be used to produce a health systems analysis describing the challenges facing integration of acute TB services and chronic respiratory services in resource poor settings. Strategies to facilitate change in health service delivery models will be outlined.
This document will be focused on care delivery in Blantyre, Malawi & Kampala, Uganda, with a view to further research / interventions in these areas as part of an Intermediate Fellowship.
4. An international collaborative network for PTLD research and clinical service delivery will be established, in order to share data and information on ongoing PTLD studies, agree on terminology to be used when describing PTLD, determine priorities for research & clinical care, and generate opportunities for collaboration.
Planned Impact
1. Post-TB lung disease network:
At present there are several academic respiratory groups working on post-TB lung internationally, but with little collaboration between them. As a result, a wide range of disease and outcome definitions are being used when describing this condition and research efforts risk being replicative rather than complimentary.
One of the key impacts of this Fellowship would be a closer network of these research groups, with a meeting organised in early 2019 in order to reach consensus around disease definitions, and to discuss research priorities in the coming years.
2. Advocacy for chronic respiratory infection work in resource poor settings:
Recent years have seen an increase in interest in bronchiectasis and chronic respiratory infection from respiratory academics in the UK / North America. To date the focus of this work has largely been at home, with little attention paid to the likely very high burden of disease in resource poor settings.
I hope that the work completed in this fellowship will involve several key UK based respiratory collaborators who are actively involved in advocating for chronic respiratory infection research, in order to increase their interest in disease in resource poor settings.
3. Provision of a model for integration of 'acute' and chronic respiratory services:
Health services in resource poor settings are struggling with an increasing burden of NCDs - these include respiratory disease, but also diabetes and cardio/cerebrovascular disease. One of the key challenges facing service provision for patients with these problems is the integration of acute and chronic care, using models that are feasible and acceptable.
If designed carefully, health systems that integrate tuberculosis treatment programmes with ongoing care provision for those with respiratory sequelae may provide a model for integration of this type, which could be more widely applied.
4. Direct impact on patients completing TB treatment:
Our data from Malawi suggest that almost one third of patients completing treatment for a first episode of pulmonary TB are left with either spirometric deficit or chronic respiratory symptoms, 1 year after treatment, with a high proportion having bronchiectasis on imaging. Our data suggest that ever-smoking - another key respiratory insult - is extremely common in this patient population.
This group is young, and economically active. The combination of these respiratory insults in this cohort has the potential to significantly impact their lives and livelihoods in the years following treatment completion. Interventions to mitigate these impacts are likely to benefit large numbers of individuals, and will hasten progress towards the WHO End TB aim of mitigating the financial impact of TB disease on patients and their families.
5. Training opportunities:
Where possible, training opportunities for Masters and PhD students will be built into the primary data collection projects proposed in this Fellowship application - one focused on microbiology and the other on qualitative research. I anticipate that this will make a positive and genuine contribution to local capacity building.
At present there are several academic respiratory groups working on post-TB lung internationally, but with little collaboration between them. As a result, a wide range of disease and outcome definitions are being used when describing this condition and research efforts risk being replicative rather than complimentary.
One of the key impacts of this Fellowship would be a closer network of these research groups, with a meeting organised in early 2019 in order to reach consensus around disease definitions, and to discuss research priorities in the coming years.
2. Advocacy for chronic respiratory infection work in resource poor settings:
Recent years have seen an increase in interest in bronchiectasis and chronic respiratory infection from respiratory academics in the UK / North America. To date the focus of this work has largely been at home, with little attention paid to the likely very high burden of disease in resource poor settings.
I hope that the work completed in this fellowship will involve several key UK based respiratory collaborators who are actively involved in advocating for chronic respiratory infection research, in order to increase their interest in disease in resource poor settings.
3. Provision of a model for integration of 'acute' and chronic respiratory services:
Health services in resource poor settings are struggling with an increasing burden of NCDs - these include respiratory disease, but also diabetes and cardio/cerebrovascular disease. One of the key challenges facing service provision for patients with these problems is the integration of acute and chronic care, using models that are feasible and acceptable.
If designed carefully, health systems that integrate tuberculosis treatment programmes with ongoing care provision for those with respiratory sequelae may provide a model for integration of this type, which could be more widely applied.
4. Direct impact on patients completing TB treatment:
Our data from Malawi suggest that almost one third of patients completing treatment for a first episode of pulmonary TB are left with either spirometric deficit or chronic respiratory symptoms, 1 year after treatment, with a high proportion having bronchiectasis on imaging. Our data suggest that ever-smoking - another key respiratory insult - is extremely common in this patient population.
This group is young, and economically active. The combination of these respiratory insults in this cohort has the potential to significantly impact their lives and livelihoods in the years following treatment completion. Interventions to mitigate these impacts are likely to benefit large numbers of individuals, and will hasten progress towards the WHO End TB aim of mitigating the financial impact of TB disease on patients and their families.
5. Training opportunities:
Where possible, training opportunities for Masters and PhD students will be built into the primary data collection projects proposed in this Fellowship application - one focused on microbiology and the other on qualitative research. I anticipate that this will make a positive and genuine contribution to local capacity building.
Organisations
- Liverpool School of Tropical Medicine (Lead Research Organisation)
- World Health Organization (WHO) (Collaboration)
- UNIVERSITY OF LEICESTER (Collaboration)
- Stellenbosch University (Collaboration)
- International Union Against Tuberculosis and Lung Disease (The Union) (Collaboration)
- Imperial College London (Fellow)
Publications
Allwood B
(2019)
The long shadow post-tuberculosis.
in The Lancet. Infectious diseases
Allwood BW
(2021)
Post-Tuberculosis Lung Disease: Clinical Review of an Under-Recognised Global Challenge.
in Respiration; international review of thoracic diseases
Allwood BW
(2020)
Post-tuberculosis lung health: perspectives from the First International Symposium.
in The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
Harlow C
(2020)
Republished: Rifampicin induced shock during re-exposure for treatment of latent tuberculosis
in Drug and Therapeutics Bulletin
Karanja S
(2022)
Stakeholder perspectives around post-TB wellbeing and care in Kenya and Malawi
in PLOS Global Public Health
Kumar K
(2022)
Recovering from COVID-19: lessons learnt from an intensive secondary care follow-up service.
in Future healthcare journal
Mallia P
(2021)
Symptomatic, biochemical and radiographic recovery in patients with COVID-19.
in BMJ open respiratory research
Meghji J
(2021)
Lung health in LMICs: tackling challenges ahead - Authors' reply
in The Lancet
Meghji J
(2021)
The long term effect of pulmonary tuberculosis on income and employment in a low income, urban setting.
in Thorax
Meghji J
(2021)
Improving lung health in low-income and middle-income countries: from challenges to solutions.
in Lancet (London, England)
Description | Co-supervisor of MSc, LSHTM |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Will inform guidelines for post-TB care and use of diagnostics amongst symptomatic post-TB survivors |
Description | Contribution to the 'Orange book' for TB practitioners, published by The Union |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Together with collaborators from the UK and SA, I contributed to the post-TB management section in the guide to practice released by The Union, for TB health care workers globally (Allwood B, Meghji J (2019) 'Management of post-TB lung damage', in Dlodlo R, Brigden G, Heldal E (eds.) Management of Tuberculosis: A guide to essential practice. 7th Edition. The International Union against Tuberculosis and Lung Disease. Paris, France). These expert guidelines are used to inform patient care, in multiple countries globally. |
Description | MSc supervision for systematic review |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | I am supervising a Malawian physician who is an MSc student in International Health at the Liverpool School of Tropical Medicine, as he conducts a systematic review of interventions to improve the clinical outcomes of adults with post-TB Lung damage. This is a key review, which will inform the development of future post-TB care strategies. |
Description | UK All Parliamentary Group for TB |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Developing models of care for symptomatic former TB patients in urban Malawi, Directors Catalyst Fund |
Amount | £50,000 (GBP) |
Organisation | Liverpool School of Tropical Medicine |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2021 |
End | 11/2022 |
Description | MRC Confidence in Concept: Pulmonary arterial hypertension agents as adjunctive host-directed therapy for tuberculosis - a dual benefit of enhanced mycobacterial control and prevention of post-TB lung disease? |
Amount | £46,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2020 |
End | 04/2021 |
Description | NIHR130307: GHPSR Project: POst tuberculosis lung damage amongst pulmonary tuberculiss survivors in East Africa: health system challenges and research priorities |
Amount | £99,926 (GBP) |
Funding ID | NIHR130307 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 03/2020 |
End | 12/2020 |
Description | 1st International Post-TB symposium, Stellenbosch |
Organisation | University of Stellenbosch |
Country | South Africa |
Sector | Academic/University |
PI Contribution | I was a member of the steering committee for the 1st International post-TB symposium, held in Stellenbosch SA in July 2019 (https://www.post-tuberculosis.com). As part of this symposium, I was co-chair of the clinical workshop entitled 'Lung complications after Pulmonary Tuberculosis'. |
Collaborator Contribution | There were 11 other members of the Steering committee, with whom I worked closely as part of the symposium team. We are still in close contact, with a view to organising a follow-up meeting in 2-years. This group includes members of TB-affected communities, with whom I continue to work closely in grant applications and publications. |
Impact | I have been co-author on a letter published in the Lancet ID after this workshop, workshop proceedings which have been published on the symposium website, and a summary article submitted to the IJTLD journal detailing the outcomes of this Symposium. |
Start Year | 2019 |
Description | Lung health and wellbeing after Tuberculosis symposium, The Union World Conference on Lung Health |
Organisation | International Union Against Tuberculosis and Lung Disease (The Union) |
Country | Global |
Sector | Academic/University |
PI Contribution | Following the international symposium on post-TB wellbeing in Stellenbosch in July 2019, I organised and chaired a symposium focused on 'Lung Health and well being after Tuberculosis' at The Union World COnference in Lung Health in Hyderabad, India in October 2019. This brought together many of the partners from the initial symposium to present our findings to a broader respiratory and TB policy and advocacy audience. |
Collaborator Contribution | This seminar included presentations from several collaborators, from across the world, speaking on post-TB wellbeing. |
Impact | No specific publications, but ongoing discussions re. future grant submissions were engendered by this seminar. This was a multidisciplinary team including: TB affected community representatives, medical specialists (paediatrics and adult medicine), health economists / those with a focus on socioeconomic outcomes of disease. |
Start Year | 2019 |
Description | NIHR Programme Grant application, UK |
Organisation | University of Leicester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Co-investigator and PPIE lead on this NIHR Programme Grant application, for a UK-based programme of research around post-TB wellbeing in the UK. Grant being led by senior UK academics in the University of Leicester and Queen Mary's University London. |
Collaborator Contribution | Has required liason with the TB-ALERT team and TB patient advisory group in the UK, in order to develop the PPI component of the grant applciation. Also input in to the content and aims and objectives of the grant programme. Stage I to be re-submitted in April 2023. |
Impact | NIHR grant application to be re-submitted to Stage I in April 2023 |
Start Year | 2022 |
Description | Post-TB symposium, 2023 |
Organisation | University of Stellenbosch |
Country | South Africa |
Sector | Academic/University |
PI Contribution | Co-lead for Academic Working Group on post-TB lung diseases, for the 2nd international post-TB symposium to be held in SA in April 2023 |
Collaborator Contribution | Co-lead of the working group, steering a small team to complete reviews and data summaries of key new data, identify critical research gaps, and develop a theory of change for improving post-TB care. Has involved working with a global group of collaborators from Europe, North America, Africa and Asia Will run plenary session and workshop at the symposium |
Impact | Expected to lead to a policy statement, and pubmications, following the symposium |
Start Year | 2022 |
Description | The Union guidelines for post-TB care |
Organisation | International Union Against Tuberculosis and Lung Disease (The Union) |
Country | Global |
Sector | Academic/University |
PI Contribution | I am an invited co-author in these guidelines for post-TB care, which have been funded and commissioned by The Union, and aim to establish standards of care for multiple sequelae of TB disease. |
Collaborator Contribution | The Union advocated for, funded and commissioned the development of these guielines, which is being delivered through the Liverpool School of Tropical Medicine |
Impact | Guidelines have been submitted with proofs under review |
Start Year | 2021 |
Description | WHO Scoping review of Interventions for TB-associated respiratory disability |
Organisation | World Health Organization (WHO) |
Department | Global TB Program |
Country | Switzerland |
Sector | Public |
PI Contribution | Co-lead of a scoping review focused on inerventions for the prevention and management of TB associated respiratory disability, in order to inform policy and guideline development at WHO |
Collaborator Contribution | Co-lead of review, together with a partner at University of Witzwatersrand in Jo'berg, South Africa, and in collaboration with the WHO Global TB Pgoramme |
Impact | Scoping review report submitted to WHO Report presented at 2023 WHO TB Program meeting on translation of research in to policy |
Start Year | 2022 |
Description | WHO TB multimorbidity review |
Organisation | World Health Organization (WHO) |
Country | Global |
Sector | Public |
PI Contribution | I was an invited collaborator and co-author of a commissioned WHO scoping review to address tuberculosis and selected comorbidities, to inform the update of recommendations and identification of research gaps around integrated TB care. |
Collaborator Contribution | The WHO commissioned and funded this report after a competitive application process, which was won by our team at LSTM. |
Impact | Scoping review report submitted to WHO, not for publication |
Start Year | 2021 |
Description | Invited speaker - London Advanced TB course |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited to present / teach on post-TB care within the London Advanced TB Course - a national course attended by UK TB clinicians (nurses and Drs) |
Year(s) Of Engagement Activity | 2022 |
Description | Invited speaker, British Thoracic Society |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited speaker at the BRitish Thoracic Society Winter meeting session on 'Africa's Big Five' , and presented on post-TB lung disease. Attendance was from both British and AFrican attendees to the meeting, and numbered ~260 people. |
Year(s) Of Engagement Activity | 2020 |
Description | Invited speaker, ESCMID mycobacterial disease course |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker on post-TB lung diseases at the international ESCMID post-graduate course on mycobacterial diseases |
Year(s) Of Engagement Activity | 2022 |
Description | Invited speaker, The Union world conference on lung health |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Invited speaker at plenery session of the The Union 52nd World Conference on Lung Health Speaking on 'From burden of disease to solutions: A spotlight on post-TB and post COVID-19 guidelines and research' |
Year(s) Of Engagement Activity | 2021 |
Description | Membershop of BTS Respiratory Infection Specialist Advisory Group |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Elected member of the British Thoracic Society Specialist Advisory Group, working together with a small team to advise and consult on national infection guidelines, develop workshops for the bi-annual national BTS meetings, and support ongoing BTS guidelinde development |
Year(s) Of Engagement Activity | 2022 |
Description | Panel on post-TB wellbeing, at The Union meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Participation in a post-TB wellbeing expert panel, which was broadcast and live-tweeted, from The Union World Conference on TB and Lung Health in Hyderabad, India in October 2019. |
Year(s) Of Engagement Activity | 2019 |
Description | Stakeholder engagement workshops around post-TB care in Eastern Africa |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Organised and facilitated two online workshops with clinicians, policy makers, parliamentarians, patient advocates, and researchers around post-TB care in Eastern Africa. |
Year(s) Of Engagement Activity | 2021 |