Post-Tuberculosis Lung Disease (PTLD) is defined by the 2019 consensus from First International Symposium on Post-TB Lung Health, as “evidence of chronic respiratory abnormality, with or without symptoms attributable at least in part to previous pulmonary TB” [5]. While this consensus definition has since been widely adopted, it remains general in scope and insufficiently specific, underscoring the necessity for refinement and a framework to classify severity. Epidemiological evidence indicates that PTLD affects nearly half of TB survivors, though prevalence varies significantly by geography, TB treatment adequacy, and population characteristics [6–8]. For instance, a 2025 Australian cohort, reported a 68% prevalence, primarily manifesting as obstructive or restrictive deficits accompanied by fibrosis or bronchiectasis on imaging [9]. By contrast, a South African retrospective cohort reported only 18% lung impairment at an average 4.6 years post-TB diagnosis, while a Tanzanian study found 74% impairment, albeit assessed at just 20 weeks of treatment [10,11]. These persistent impairments significantly diminish quality of life and drive excess mortality among TB survivors [12–14].

PTLD remains a significant clinical and public health challenge, particularly in high TB-burden countries [15,16]. Emerging data indicate that up to 87% of survivors experience persistent sequelae, primarily due to irreversible pulmonary damage sustained during TB disease [17]. Modelling studies suggest that globally, post-TB sequelae accounts for up to half of the total TB-related disability-adjusted life years (DALYs) [18]. Economically, PTLD imposes significant burdens through increased healthcare utilization, frequent hospitalizations, and decreased productivity [14]. Such financial strain is evident in a study across five Brazilian cities, where average monthly post-diagnosis costs reached R$4161.86 (∼USD $800), consuming up to 40% of annual income among the extremely poor [19]. A 2024 systematic review echoed this, reporting a weighted mean post-diagnostic cost of USD $680 across studies [20]. These data call for broader global post-TB care investment, even in low-incidence countries facing rising TB rates among migrants and growing survivors needs.

Increasing awareness of chronic sequelae following TB treatment has accelerated PTLD research [14]. Yet, translating findings into clinical and TB programmatic practice remains challenging due to the high degree of variability and inconsistency in existing data. This review summarizes emerging data on PTLD risk factors, disease mechanisms, clinical manifestations, diagnostic approaches and treatment options while highlighting key barriers and future research priorities. Beyond microbiological cure, a shift towards the long-term recovery is needed to foster a more holistic, patient-centred TB management.

Host inflammation is triggered by the invading microbe and in a healthy immune response, a balancing act between pro- and anti-inflammatory cytokines ensures clearance of the microbe with resolution of inflammation returning the immune system back to homeostasis [25,26]. In TB disease, chronic inflammation occurs with dysregulated pro-inflammatory response involving cytokines such as tumour necrosis factor-α (TNF-α), interleukin 1 β (IL1β), interleukin 12 (IL-12) & interleukin 6 (IL-6) leading to cell necrosis, granuloma formation and lung remodelling [17,23,27]. Mtb itself may skew host inflammation towards pro-inflammation that favours cavity formation and onwards transmission of Mtb for its survival benefit [28].

PTLD likely involves persistent inflammation and inability to restore homeostasis even after Mtb clearance[29]. However, residual Mtb antigens may sustain chronic inflammation. A PET-CT (Positron Emission Tomography-Computed Tomography) study reported the formation of new lesions and ongoing inflammation in lung lesions of patients 6 months post- treatment, with detection of Mtb mRNA suggesting viable but non-culturable bacilli that can elicit a chronic immune response [30]. A clinical case study also reported inflammatory post-TB lesion but with no viable Mtb[31]. Together, these findings suggest ongoing inflammation contribute to persisting lung damage in PTLD, though a role for Mtb or its antigen cannot be excluded.

In pulmonary TB (PTB), lung remodelling involves tissue destruction, caused by proteases such as host's matrix metalloproteinases (MMPs) leading to cavitation, and aberrant wound healing, with fibrosis driven by profibrotic cytokines such as transforming growth factor-β (TGF-β) and IL-6 through excessive extracellular matrix deposition [24,32–34]. The three most common residual lung damage namely fibrosis, cavities and bronchiectasis are believed to occur during PTB but remain unresolved after TB treatment [6,35]. Between 20 and 50% of TB cavities persisted after TB treatment completion with healing taking place post-TB treatment. Cavity resolution can either be complete i.e. closed with scar or calcified foci or incomplete with the cavity airspace remaining. Incomplete resolution with fibrotic scarring increases the risk of respiratory infection such as fungal infection but the mechanism of cavity closure remains unknown [17,28]. Residual cavity resolution in post-TB treatment may contribute to formation of fibrosis and abnormal dilation of airways leading to bronchiectasis. Clinical evidence of development of bronchiectasis after post-TB supports this postulation [36].

A small study of 30 PTB patients showed a lesser magnitude of decline in concentrations of profibrotic cytokine, TGF-β and IL-6 associated with greater lung impairment in PTB after TB treatment completion [37]. This potentially supports ongoing fibrosis with new fibrotic lesions post-TB which may also result from cavity resolution [17,28].

A study reported elevated plasma S100A8, MMP-1, MMP-9 and IL-8 in patients with poor lung recovery post-TB suggesting neutrophil activity and persistent leucocytes infiltration contributed to unresolved lung damage [38]. MMPs are capable of degrading extracellular matrix which makes up the structural lung tissues and this potentially drives the persistent residual damage in PTLD [33]. The immunopathology underlying the unresolved lung damage is unclear, but potentially ongoing lung remodelling involves leucocytes, lung tissue destruction and fibrosis. Further investigation is warranted to address these gaps.

A key approach is the prevention of TB disease at the outset. Prevention would reduce the risk of PTLD and mitigate PTLD signs and symptoms and progression [35,40,46]. Furthermore, other respiratory co-morbidities such as infections in residual cavities including Aspergillus and non-tuberculosis mycobacteria, bronchiectasis and lung cancer and non-respiratory co-morbidities would be prevented [52–55]. Key in preventing TB disease is preventing individuals from being infected by M. tuberculosis and subsequent TB disease, utilizing all existing preventive measures (infection control, vaccination-ideally with new vaccines, treatment of TB infection) [40]. Rapid diagnosis and effective treatment after TB disease diagnosis are key pillars for breaking the chain of transmission, a core aim of all global TB programmes [40]. Reducing environmental risks factors, such as air pollution and tobacco exposure, also plays an important role [40].

Recent evidence suggests the important preventive role of vaccinations in adults and children [5,46,56–59]. On completion of anti-TB treatment, children should be ensured to be updated in vaccinations as per national immunization schedule specifically tetanus, diphtheria, pertussis and measles [58]. In adults, vaccination against influenza, pneumococcal disease, and COVID-19 can be of help to avoid exacerbations as PTLD is a chronic respiratory disease [58]. Host-directed therapies targeting pathology or bacillary clearance are described elsewhere in this review [35,60]. For PTLD, managing of co-existing conditions – asthma and COPD – is essential, often requiring inhaled steroids and bronchodilators [40,46,59].

Diagnosing and treating recurrent TB (e.g. relapses if diagnosed after established treatment success) is of obvious importance. Whenever superimposed infections occur, tailored antibiotic treatment is indicated. In selected patients, surgical interventions such as lobectomy or pleurectomy may be indicated, while bronchiectasis may benefit from anti-inflammatory treatment. Finally, availability of palliative care and end-of-life support is mandatory for patients with unfavourable prognosis. The Union's Clinical Standards highlights the importance to undergo quality health education and counselling for PTLD patients [40].

The Clinical Standards and other documents emphasized the importance of pulmonary rehabilitation as one of the pillars of PTLD management [15,35,40,46,59,61–65]. This panel of global expert highlighted that most of the evidence available on pulmonary rehabilitation was based on a few retrospective and uncontrolled studies with a limited sample size of 30–40 patients [40,64]. Therefore, evidence was extrapolated from COPD. A recent multicenter study in Brazil enrolled 85 PTLD patients undergoing rehabilitation and 96 controls, with one year follow-up [15,62,64]. Rehabilitated patients achieved significant improvements in spirometry (FEV1, FVC), DLCO, the distance walked at 6MWT and oxygen saturation. Although benefit was most pronounced in those with COPD, all rehabilitated PTLD had a significant improvement, while non-rehabilitated patients deteriorated. This pivotal study unfortunately did not evaluate the Quality of Life (QoL) [64].

Beyond the Union's Clinical Standards on PTLD, ad-hoc algorithms are needed at the national level to screen patients completing anti-TB regimens for PTLD. Suspected cases should be evaluated and referred for pulmonary rehabilitation when indicated. Through pre- versus post- analysis of the core variables, the effectiveness of rehabilitation will be established. Patients should receive training on maintaining improvements through home-care interventions and tailored follow-up.

Raising awareness of PTLD as a global health priority is essential, as it accounts for nearly half of TB-related DALYs [40]. Unfortunately, most National TB programmes (NTP) focus solely on reducing incidence and mortality, considering their work done at TB cure [1]. Limited resources and lack of understanding that PTLD is both preventable and treatable – especially in high-burden countries – hinders implementation of pulmonary rehabilitation [62,64]. The lack of evidence from priority countries further impedes progress. While rehabilitation has been shown to benefit PTLD patients, in settings with high incidence but scarce resources it may not be feasible to provide it universally. Prioritization of those most likely to benefit within locally adapted rehabilitation schemes is therefore critical. After Brazil published the first-ever national guidelines on PTLD management [46], and the Latin American Society of Pulmonology (ALAT) published its regional guidance [59], failure to offer rehabilitation when feasible has to be considered unethical. WHO has begun addressing this gap with a policy brief (Integrated approach to tuberculosis and lung health) [78], and upcoming PTLD management guidance. A coordinated global effort is needed to identify suitable, country- and setting-specific models allowing programmatic implementation.

WHO revised treatment outcome definitions include ‘sustained treatment success’ to capture relapses after initial cure, recommending re-evaluation 6–12 months post-treatment [79]. However, most NTPs from high-TB burden countries lack the resources for routine follow-up. It is more feasible under special conditions, such as clinical trials, observational studies, or ongoing rehabilitation. Currently, no TB registry worldwide records rehabilitation outcomes to generate meaningful indicators. This gap could be addressed through pilot programmes in settings where PTLD rehabilitation has been implemented.

Earlier publications outlining future research priorities for PTLD, proposed approaches for screening, diagnosis, treatment and rehabilitation [5,40,56,61]. However, not all evidence was available and there was a lack of validation of a suitable approach, often extrapolated from COPD [40]. A recent meta-analysis further emphasized significant data heterogeneity, limiting evidence synthesis [6]. At the time of the Union's Clinical Standards and the proceedings of the Stellenbosch Symposia, most studies were small, retrospective, and lacked controls or follow-up [5,40,56]. Key research questions requiring urgent attention are summarized in Fig. 5.

• a)

  Screening and diagnosis. How should assessments for PTLD be conducted in patients who complete TB treatment? Can assessment be done during TB treatment? Which investigations can be done across different resource settings? Are some more important than others? Should all patients be screened or only those with signs and symptoms? Can a symptom-based questionnaire reduce the number of patients to be screened for PTLD?

• b)

  Prevention and treatment. Beyond early diagnosis and effective treatment of TB disease, which other prevention and treatment approaches to PTLD are effective? What is the real role of vaccination? How do we differentiate PTLD with or without COPD to better tailor the respective treatment? What is the role of host-directed therapies?

• c)

  Rehabilitation. What models for rehabilitation can be used in resource-limited settings? What is the minimum number of variables to use to evaluate its effectiveness? How do we ensure follow-up to maintain the clinical outcomes achieved?

Fig. 5.

Future research priorities for post-tuberculosis lung disease (PTLD). COPD=chronic obstructive pulmonary disease; QoL=quality of life.

A recent Brazilian trial, which included a control group of non-rehabilitated PTLD patients, demonstrated the feasibility of prospective controlled studies to evaluate the efficacy of interventions including rehabilitation and the importance to stratify PTLD based on COPD status and severity [62,64]. The role of co-morbidities needs to be investigated, including the triangulation existing between PTLD, COPD, aspergillosis and bronchiectasis, as well as the systemic involvement (cardiovascular, renal, neurological). Beyond feasibility and efficacy, future studies should investigate effectiveness through economic analysis and unravel the relationships between clinical patterns, lung damage, disability and QoL.

Evidence gaps need to be tackled through existing clinical experiences across different continents before there is capacity to manage PTLD on a TB programmatic basis. In Latin America Brazil was pivotal in issuing its national programmatic guidelines [46]; which enabled the first national controlled study on the effectiveness of rehabilitation [62,64]. In parallel, ALAT has created a framework guidance allowing all NTPs to develop own national guidelines [59]. Furthermore, ALAT is presently developing the region's first ever PTLD registry to document prevalence, gauge disease severity, and test the feasibility and efficacy of its rehabilitation.

In Mexico outreach activities to diagnose and manage PTLD started in spring 2025 building on an existing pilot COPD project. In Bangladesh, Damien Foundation's TB REACH project, is implementing PTLD management in four rural districts: several hundred patients have already been screened, and dozens are undergoing pulmonary rehabilitation [15]. The comprehensive project – covering prevention, screening, treatment support, and referral rehabilitation – integrates seamlessly with active case-finding, TB infection management, and smoking-cessation services. This game-changing model demonstrates how single studies or pilot experiences can be scaled into programmatic public health interventions, taking into account the present funding difficulties in the USA [80].

The difficulties to implement complex interventions like those necessary to manage PTLD, which include screening, diagnosis, prevention, treatment and rehabilitation, are well known. A rational approach to PTLD is particularly urgent in resource-limited settings, where TB and PTLD are more prevalent [52,53]. Ongoing trials of host-directed therapies like doxycycline and NAC may expand treatment options. Clinicians, researchers and patients are called to collaborate with scientific societies and journals in order to share best practices and advocate for funding, more research and quality clinical services to alleviate the significant burden PTLD patients face.