Lung health after pulmonary TB: designing strategies to improve long-term patient outcomes

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.

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. 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.