Introduction to PTLD

Post-TB lung disease refers to a chronic respiratory condition that occurs as a result of previous tuberculosis (TB) infection. The disease results in damage to the lungs, which can lead to symptoms such as shortness of breath, chest pain, and coughing. The First International Post-TB Lung Symposium met in 2019 and agreed on the following definition of PTLD:

‘Survivors with evidence of chronic respiratory abnormality, with or without symptoms, attributable at least in part to previous pulmonary TB.’

It has replaced the old names such as ‘post-pulmonary TB structural lung disease’

PTLD encompasses a heterogenous group of clinical patterns that are associated with varied clinical, physiological and radiological abnormalities.

The 2019 Post-TB Symposium proposed eight clinical patterns of PTLD:

1. TB-associated obstructive lung disease (FEV1/FVC <0.7 OR <LLN, thought primarily related to small airway disease)
2. Bronchiectasis (CT definition – evidence of airway dilatation > diameter of adjacent vessel, or non-tapering, or CXR definition – evidence of ring shadows and tramlines)
3. Parenchymal Cavitation (a gas-filled space either within an area of pulmonary consolidation or surrounded by a thin wall)
4. Parenchymal Destruction (extensive destruction of lung tissue, with a gas-filled space/collapsed parenchyma occupying the volume of >=1 lobe)
5. Parenchymal Fibrosis (area of parenchymal scarring with associated volume loss)
6. Chronic pleural disease (evidence if pleural thickening on CXR or CT imaging)
7. Pulmonary Hypertension (elevated pulmonary artery pressures, as estimated using Doppler echocardiography or measured right heart catheterisation)
8. Aspergillus-related lung disease (evidence of aspergilloma on imaging or chronic pulmonary aspergillosis on imaging and blood testing).

There is not yet evidence available on the physiology, prognosis or management for each specific clinical pattern of PTLD.

PTLD is the result of a complex interplay between host, organism and environmental factors and pathology and sequelae remain poorly understood.

Some survivors of pTB have no residual disease whilst others have severe cavitation, destruction, bronchiectasis etc. We are not sure why, but it likely involves genetic factors regulating the immune response in the pathogenesis of TB infection, key components being:

• Granuloma formation and resolution
• Cytokine production (TNFa and Interleukins)
• Transcription factors (e.g. Hypoxia-inducible factor)
• Enzymes (e.g. matrix metalloproteinases) – these are implicated in lung injury and remodelling

Perhaps when we can understand the immunopathogenesis further this may open the door to immune-modulating host-directed pTB and PTLD therapies.

The prognosis for people with post-TB lung disease can vary depending on the extent of lung damage and the presence of other medical conditions. In general, the earlier the disease is diagnosed and treated, the better the outcome is likely to be. However, even with treatment, some people may experience long-term breathing problems and a decreased ability to exercise. In cases where the lung damage is severe, the prognosis may be more guarded. Thus far it has been shown that people with PTLD have:

• Higher mortality (3-to-6 fold compared to the general population)
• Persistent chronic airflow obstruction (2-to-4-fold higher odds compared to those without previous TB)
• Persistent disabling chest symptoms that interfere with the ability to work (in fact it’s estimated nearly 50% of DALY’s due to TB are attributed to post-tuberculosis sequalae!)

Don’t worry your detective skills have not failed you…

Unfortunately PTLD does not yet find it’s way into global targets or political declarations. There has definitely been an expansion of interest in PTLD in recent years however it remains under-recognised and under-researched global health concern. The targets set by WHO are aimed at reducing the number of new TB cases and deaths, and by achieving these targets, the number of people who develop post-TB lung disease would also be expected to decrease.

End TB targets refer to the targets set by the World Health Organization (WHO) to end the tuberculosis (TB) epidemic by 2035. These targets include reducing TB deaths by 95% and cutting new TB cases by 90% compared to 2015 levels.

The targets for TB control are:

• To diagnose at least 70% of the estimated number of new TB cases
• To treat at least 85% of the diagnosed cases
• To achieve a TB death rate of less than 10% of the number of diagnosed cases
• To treat at least 30% of the estimated number of cases of drug-resistant TB

By achieving these targets, the number of people affected by TB and its sequelae, such as post-TB lung disease, would be expected to decrease, thus improving the overall health of the population.