Mechanisms, Biomarkers and Pulmonary Rehabilitation in Post-TB Lung Disease

Tuberculosis (TB) affects millions of people worldwide, and many individuals continue to experience long-term health problems even after completing TB treatment. One of the most important of these complications is post-tuberculosis lung disease (PTLD), which can cause persistent breathing problems, reduced physical capacity, and poor quality of life. Despite its high burden, PTLD is still poorly understood, and effective strategies for prevention, early detection, and long-term management are limited. The AFTER-TB study aims to address these gaps by combining long-term follow-up of people with TB with the evaluation of pulmonary rehabilitation (PR) strategies for those who develop PTLD. The study includes three groups: people with active TB who are followed over time, people with established PTLD, and healthy individuals without TB to provide basal values. By following people from the start of TB treatment, the study will identify who develops PTLD and which clinical, biological, and imaging factors contribute to lung damage or recovery. In addition, the study will collect detailed information on symptoms, lung function, imaging, and biological samples over time. Advanced laboratory techniques will be used to identify biomarkers linked to disease progression or protection, as well as bacterial genetic factors that may influence long-term lung outcomes. This information will help improve early diagnosis and risk stratification. AFTER-TB study will also implement a comprehensive pulmonary rehabilitation programme that includes exercise training, respiratory physiotherapy, education for healthy habits, and psychosocial support. The impact of rehabilitation on physical capacity, lung function, and quality of life will be assessed over time. Overall, the AFTER-TB study combines clinical follow-up, biological research, and pulmonary rehabilitation to generate new knowledge that can improve the prevention and management of PTLD, ultimately supporting better long-term health and quality of life for TB survivors.

Inclusion Criteria: \*Criteria aplicable to all participants:\* * Ability and willingness to provide written informed consent (or assent with parental/legal guardian consent for minors). * Willingness and ability to comply with study procedures and scheduled visits. * Willingness and ability to participate in a pulmonary rehabilitation programme, including: supervised exercise, respiratory physiotherapy, health education and psychosocial support. * Enrolment at one of the participating study sites. \*COHORT 1: People with pulmonary tuberculosis\* * Diagnosis of pulmonary TB confirmed by bacteriological methods (genotypic or phenotypic assays). * Drug-susceptible or drug-resistant TB are both eligible. * Initiation of anti-TB treatment within ≤14 days prior to enrolment. * Identified through passive, active or intensified case finding strategies, including healthcare facilities, contact tracing, or community screening. \*COHORT 2: People with PTLD\* * History of bacteriologically confirmed pulmonary TB and completion of anti-TB treatment. * No evidence of active TB disease at the time of enrolment. * Enrolment must occur within 6 months after completion of TB treatment, or at study entry if the participant already has a previously established diagnosis of PTLD. * Presence of post-tuberculosis lung disease (PTLD), defined as abnormalities in at least two of the following domains: * \_Impaired lung function\_ * \_Persistent respiratory symptoms (e.g., cough, dyspnoea)\_ * \_Structural abnormalities on chest imaging\_ Exclusion Criteria: * Diagnosis with extrapulmonary TB without pulmonary TB. * Anti-TB treatment initiated more than 14 days before study enrolment. * Pregnant women or those with suspected pregnancy will be excluded from the study, since chest X-rays are contraindicated to avoid any potential adverse effect on foetal development. * Participants who are unable or unwilling to give their written informed consent to participate in the study or whose parents/legal guardians are unable or unwilling to provide consent for paediatric participants. * Participants aged \65 years old due to age-related biological response impairments that can bias the analyses.