Clinical standards for the assessment, management and rehabilitation of post-TB lung disease

B A C K G R O U N D : Increasing evidence suggests that postTB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR). M E T H O D S : A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement). R E S U LT S : Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR. C O N C L U S I O N : This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD. K E Y W O R D S : tuberculosis; post-TB lung disease; sequelae; pulmonary rehabilitation; clinical standards

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease S U M M A R Y B A C K G R O U N D : Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR). M E T H O D S : A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement). R E S U LT S : Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situa-tions); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR. C O N C L U S I O N : This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD. K E Y W O R D S : tuberculosis; post-TB lung disease; sequelae; pulmonary rehabilitation; clinical standards Historically, national TB programmes (NTPs) have emphasised the need to ensure rapid diagnosis and effective treatment of individuals with infectious TB to reduce transmission and the epidemiological trend of the disease. 1,2 Over the past 20 years, the number of individuals successfully treated for TB has increased substantially, with an estimated 155 million TB survivors alive in 2020. 3,4 However, a substantial proportion of people considered cured (or with TB treatment completed) report residual cough, weakness, dyspnoea, difficulties in climbing stairs or managing every-day or work activities, which affect their quality of life (QoL) and increase the risk of death. [5][6][7][8][9][10] These long-term sequelae from TB treatment are identified using a series of tests, including chest imaging (e.g., fibrosis, cavities, pleural thickening, bronchiectasis, pulmonary hypertension, secondary bacterial and fungal infections); pulmonary function testing (PFT), including spirometry, plethysmography and diffusing capacity of the lungs for carbon monoxide (DLCO) to detect obstructive, restrictive and mixed patterns; and cardiopulmonary exercise testing (CPET) to assess the integrative responses of the cardiovascular, respiratory and musculoskeletal systems to incremental exercise in patients with PTLD. [11][12][13][14][15][16][17][18][19][20] Delayed diagnosis and inappropriate regimens used during treatment may play a role in the development of PTLD. 21,22 Also, former TB patients experience increased non-pulmonary morbidity and mortality, particularly cardiovascular diseases, despite successful completion of treatment. 23,24 The aetiology of these illnesses is uncertain, but they may in part reflect the systemic effects of sustained lung inflammation and enzymatic degradation, which persist after TB cure. 25,26 Moreover, individuals who previously completed TB treatment continue to be at high risk of developing TB again due to either endogenous reactivation or exogenous reinfection. 27,28 Distinguishing between recurrent TB vs. post-TB sequelae can be particularly challenging. [29][30][31] For this document, we adopted the definition of PTLD developed at the First International Symposium on Post-TB disease: ''Evidence of chronic respiratory abnormality, with or without symptoms attributable at least in part to previous (pulmonary) tuberculosis''. 32 In recent years, PTLD has attracted increasing interest from the research and medical community. Several studies indicate that up to 50% of TB patients report health problems consistent with PTLD after completion of treatment. [11][12][13][33][34][35][36][37][38] PTLD is likely to cause a considerable burden of disease globally, suggesting opportunities for prevention and management. Recent modelling indicates that 138-171 million TB survivors were alive in 2020, of whom nearly one fifth were treated in the past 5 years. 4 PTLD was estimated to account for approximately half of lifetime disability-adjusted life-years (DALYs) caused by incident TB. [38][39][40] In preparing this document, our aim was to define clinical standards for PTLD, focusing primarily on pulmonary disease. Standards are different from guidelines, which are based on 'Grading of Recommendations, Assessment, Development, and Evalua-tion' (GRADE) and 'Patient, Intervention, Comparison, Outcome (PICO) questions. Standards prescribe a widely accepted level of diagnosis and care, for all healthcare providers and clinicians, both public and private, to achieve optimal standards in managing patients who have, or who are presumed to suffer from, a given disease. 41,42 The IJTLD Clinical Standards do not compete with existing WHO or other guidelines, but rather complement and integrate their recommendations to provide a specific clinical focus. The standards are universal principles and might need to be adapted for specific settings and situations for future programmatic implementation due to legal, organisational or economic reasons.
Because specific evidence on PTLD is limited in some technical areas, the available evidence on other lung diseases was used (e.g., for chronic obstructive pulmonary disease [COPD]), although such studies exclude patients with TB. Also, research into paediatric care is currently limited, but recommendations were added where appropriate. The clinical standards will be updated to capture new evidence as it accumulates over time. Finally, although these standards pertain to evaluations and interventions after a patient has completed TB treatment, a small but growing body of research indicates that patients at risk for PTLD can be identified using chest radiography (CXR) at the time of TB diagnosis. 43 The use of adjunctive therapies during TB treatment may therefore help to avert PTLD or reduce its impact. 44,45 Physicians are urged to consider such atrisk patients for enrolment in clinical trials to expand our understanding of this area.

AIM OF THE CLINICAL STANDARDS
This consensus-based document aims to describe the following activities: 1) Assessing patients at the end of TB treatment for sequelae and PTLD (Standard 1). A universal standard was defined, with special considerations for children and possible adaptation in different settings and situations (for organisational, legal or economic reasons). 2) Identifying patients with PTLD for pulmonary rehabilitation (PR) (Standard 2). 3) Adapting the PR programme for specific patient needs and different settings (Standard 3). 4) Evaluating the effectiveness of PR and follow-up (Standard 4). 5) Education and counselling for a patient (Standard 5) to help manage their condition. 6) A public health standard highlighting the need to record changes in patient outcome resulting from PR (Standard 6). 7) Priorities for future research into PTLD.

METHODS
A panel of 67 global experts was identified to represent the main scientific societies, associations and groups active in the field of TB and PR, including TB clinicians (n ¼ 34), TB public health (n ¼ 18), TB paediatricians (n ¼ 3), PR experts (n ¼ 6), PFT/lung diseases experts (n ¼ 3), methodologists (n ¼ 2) and psychologist (n ¼ 1). Out of the 67 experts invited, 3 declined and 2 did not respond. The 62 respondents were asked to comment via a Delphi process on an initial draft including seven standards (Standards 1-6 being clinical and Standard 7 on public health) developed by a core coordination team (with 17 members). A 5-point Likert scale was used (5: high agreement; 1: low agreement). Sixty experts submitted a valid Delphi questionnaire (two did not answer). At the first Delphi round, agreement was high, with a median value of 5 for Standards 1-6, and 4 for Standard 7. Based on substantial agreement on the seven Standards and the document outline, a draft document was jointly developed by the expert panel. This underwent seven rounds of revision and the final form was approved by consensus (100% agreement), with a reduction in the number of standards to 6 in total (5 clinical and 1 on public health).

STANDARD 1
Every patient completing TB treatment should be clinically evaluated for PTLD. The assessment should be conducted as soon as possible at the end of treatment and organised by the TB programme. In special settings and situations, post-TB treatment evaluation can be simplified and/or modified to include a set of basic examinations with the aim to identify patients with sequelae at risk of deterioration (or even death) and those likely to benefit from PR. The following set of basic examinations is considered essential upon clinical suspicion of either the presence of, or risk factors for, PTLD: clinical examination/ history, CXR, PFT, six-minute walking test (6MWT), complemented by symptom score and QoL questionnaire evaluation. Other examinations are considered conditional.
The complete list of examinations to assess the presence of post-TB treatment sequelae and the indications for PR (see Standards 2-3 for details) are summarised in Table 1. Completion of treatment affords the opportunity to (safely) evaluate the patient's microbiological and radiological status, and the relationship with baseline assessments. Although the focus of this document is on PTLD, it is important to note that bacteriological results (sputum smear microscopy and culture) are important at diagnosis, during follow-up and at the end of treatment to determine the TB treatment outcome (cured or treatment completed, see also Standard 6). 46 CXR is also important. Computed tomography (CT) scan, which is not always available, allows a more thorough evaluation of the lung parenchyma that is often not visible (or fully appreciated) on CXR. For example, it may offer higher sensitivity to detect bronchiectasis, cavities or pulmonary nodules as a basis to improve current and future clinical management (sputum expectoration, risk of recurrent infection, risk of chronic fungal infection and risk of TB relapse). Pulmonary nodules may be a consequence of TB but can also represent other infections or cancer. 47 The advantages of a CT scan must be weighed against the harms of radiation exposure. Use of CT scans should therefore be reserved for instances when differential diagnostic imaging beyond CXR is highly desirable to inform clinical decision making. In patients with cavitary TB, who develop progressive respiratory symptoms after treatment completion, additional testing may be warranted to evaluate for TB relapse, chronic infections (aspergilloma, nontuberculous mycobacteria [NTM] infections, bronchiectasis) and other lung disease (e.g., cancer). Further investigations may include chest CT, culture of sputum or fluid collected by bronchoalveolar lavage (e.g., for M. tuberculosis, Aspergillus and other respiratory pathogens) and Aspergillus serology. 48 In settings with sufficient resources, additional assessments would add important clinical and functional information to PTLD management, particularly as it relates to lung health (for details on rehabilitation, see Standards 3-4) and mortality risk.
A focused respiratory history needs to be recorded including vaccination history (e.g., COVID-19, influenza, pneumococcal vaccines), risk factors (e.g., previous incarceration) and co-morbidities (e.g., HIV co-infection and diabetes, among others) as well as exposure to health hazards (such as cigarette smoking, silica and biomass fuel). Known respiratory co-morbidities and related previous treatments for any lung condition also need to be recorded, as these are likely to be relevant for the management of PTLD. Examples include asthma, bronchiectasis, pulmonary fibrosis and COPD as well as a history of pulmonary TB (PTB) and/or frequent lower respiratory tract infections in childhood.
A clinical examination at the end of TB treatment, when performed thoroughly, helps guide appropriate further investigations. Recordings for weight, height and vital signs (temperature, respiratory and heart rates, blood pressure and oxygen saturations) is considered essential. The presence of low arterial oxygen saturations (,94%, ideally complemented by arterial blood gases analysis, if feasible), changes in body mass index (BMI) and its trend over time, digital clubbing, coarse crackles, raised jugular-venous pressure or peripheral oedema may suggest pathology other than TB or concurrent pathologies. A subsequent nutritional assessment includes, among others, 49 simple investigations (e.g., urine analysis and blood tests) to identify treatable conditions that commonly cause morbidity. 50 For example, anaemia caused by iron deficiency can be diagnosed by blood tests and is amenable to oral supplementation, and unexpected glycosuria could lead to a diagnosis of diabetes. Desirable blood tests include complete blood count with white cell differential, fasting blood glucose, electrolytes, urea, creatinine and liver function tests, including serum albumin. Unexplained or persistent biochemical abnormalities should be complemented by the appropriate investigation (or referral) to diagnose and treat the underlying condition. Comorbid medical conditions associated with TB that are known to increase mortality, particularly if untreated, should be noted. These include but are not limited to HIV, diabetes mellitus, chronic kidney diseases, chronic liver diseases (including chronic hepatitis B and C), anaemia and iron deficiency. 11,32,50 Recently, the importance of COV-ID-19 has also been highlighted, and opportunities exist to combine efforts supporting rehabilitation approaches for patients with both TB and COVID-19 related sequelae. [51][52][53][54] Given the high rates of PTB and the body of evidence linking TB with chronic respiratory diseases (CRDs), PFT should be routinely performed on completion of TB treatment in all settings where it is available and compared with previous PFT results. For example, preand post-bronchodilator spirometry performed according to the European Respiratory Society (ERS)/ American Thoracic Society (ATS) standards, 55 with appropriate equipment provides essential information on lung function and is the diagnostic test of choice for CRDs. When feasible and available, spirometry can be complemented by plethysmography (to assess total lung capacity and resistance), DLCO or carbon monoxide transfer coefficient (KCO) to assess ventilatory inhomogeneity for comprehensive assessment of lung function. 11,32 The six-minute walking test (6MWT), performed according to international guidelines, is a simple tool largely used to evaluate functional exercise capacity, assess prognosis and evaluate treatment response in CRDs. 56 The 6MWT is generally considered reliable for chronic respiratory diseases and requires limited resources. 11,32 Furthermore, the 6MWT is useful for the evaluation of exercise-induced desaturation as assessed using pulse oximetry (SpO2), although the reference values to be used may be an issue. Clinical examination might justify the need for additional investigations in specific patients, for example, echocardiography to evaluate pulmonary hypertension and secondary right heart failure, or evidence of lesions that put patients at risk of spontaneous pneumothorax (or history of previous pneumothorax) or of possible broncho-pleural fistula. Similarly, some patients may benefit from assessment of cardiovascular risks, including determination of blood lipids, C-reactive protein and N terminal pro brain natriuretic peptide (Nt-proBNP).
The persistence of symptoms such as breathlessness or cough are associated with disease progression, contributing to a decline in physical function and health-related QoL. Therefore, the evaluation should include the subjective perception of symptoms and the corresponding impact on daily life. There are numerous questionnaires validated for use in subjects with CRDs, although not PTLD specifically. It is recommended that questionnaires are administered by trained personnel, when needed, respecting their specific indications. The choice of the questionnaire or scales also depends on the time available and the education level of the patient.

Specific considerations for paediatric care
Despite increasing global awareness of PTLD, there is a lack of data for children. Numerous cohort studies have shown that there is an association between lung function in childhood and adulthood. PTB in childhood could therefore have long-lasting consequences on lung health later in life. 57,58 A better understanding of the impact of PTB on long-term respiratory morbidity in children is therefore urgently needed.
End of TB treatment assessment should follow standards as proposed in adults, with some considerations specific to children. Just over half of children diagnosed with TB will have a clinical diagnosis (''unconfirmed TB cases'') and no microbiological confirmation due to the often paucibacillary nature of paediatric TB. 59 This results in the majority of children having an outcome of ''treatment completed'' instead of ''cured''. Radiological imaging can be considered at the end of treatment for use as a comparative tool in case TB recurs. CT scans of the chest are usually not indicated due to challenges of investigation in children and radiation exposure, but can be considered in specific cases (substantial chronic symptoms and radiological abnormalities) to evaluate the extent of PTLD or exclude a different diagnosis.
Lung function should be considered in all children with severe TB lung involvement 60 over the age of 4-6 years, and include pre-and post-bronchodilation flow/ volume curves. Tidal breathing techniques, including forced oscillometry and multiple breath washouts, can be considered in children younger than 4 years of age. Data on lung function impairment in children is currently lacking and is a priority for research.
Quality of life questionnaires such as EQ-5D-Y and Toddler and Infant (TANDI) can be used to assess health-related QoL in children -although these need local adaptation for the youngest children. Functional exercise capacity can be measured using the 6MWT in children from the age of 4 years. Reference ranges were established in a Caucasian population and might require adaptation in different settings. 61

STANDARD 2
Evaluation for PR. Former TB patients with clinical and radiological signs and symptoms consistent with post-TB treatment sequelae, evidence of obstruction and/or restriction, desaturations and/or low oxygen levels, reduced exercise tolerance and related impairment in quality of life should be evaluated for PR.
PR is a core component in the management of CRDs and is described as an 'individually tailored and designed, multidisciplinary programme of care' for patients with chronic respiratory impairment. 62 There is strong evidence that PR improves health status, exercise capacity, fatigue, and social functioning, and is recommended in international guidelines. 63,64 There is currently a lack of data in children, but tools used in children with other chronic respiratory illnesses can also be used in paediatric PTLD. Growing evidence indicates that PTB causes CRD in a proportion of patients with lung damage at different levels: in the bronchial airways (e.g., nonreversible airflow obstruction, bronchiectasis, trachea-bronchial stenosis) and in the lung parenchyma (cavities, fibrosis, restrictive lung disease); it can also cause mixed patterns. 11,[65][66][67] The severity of pulmonary sequelae is usually related to a delay in diagnosis or treatment and/or inadequate/inappropriate treatment, leading to extensive lung damage and longer treatment duration, likely to be more evident in patients with multidrugresistant or extensively drug-resistant TB or TB relapse/recurrence. 11,12 Although adequate clinical and radiological evaluation of patients at the beginning of anti-TB treatment and during treatment monitoring can identify initial sequelae, the end of treatment provides an opportunity to adequately study the patient without risk of infection for family members, health staff or other contacts. 7,63,68 A careful patient assessment at the end of TB treatment (patient cured or with treatment completed) is needed to evaluate if there are indications for PTLD and therefore if such patients would potentially benefit from PR. After excluding cardiovascular risks, PR is an appropriate measure for patients with persistent symptoms (dyspnoea, chest pain, cough, muscular fatigue), or reduced exercise tolerance, a restriction in activities because of their disease, exercise-induced oxygen desaturation, or impaired health status.

STANDARD 3
The PR programme should be organised according to feasibility, effectiveness and cost-effectiveness criteria, based on the local organisation of health services and tailored to the individual patient's needs.
Most of what is known about PR is derived from CRDs, where it has been shown to be relatively more cost-effective than pharmacotherapy. 86 Obviously, there are differences between these conditions and PTLD, and important evidence gaps are highlighted in this document. To qualify as PR, programmes must include, at the very least, comprehensive baseline and post-PR outcome measurements, a structured and supervised exercise training programme, an education/behavioural programme intended to foster longterm health-enhancing behaviour, and provision of recommendations for home-based exercise and self or supervised physical activity programmes. 87 Evidence on specific PR programmes tailored to PTLD patients exists in settings with adequate resources, logistics, and expert healthcare providersand these were generally effective. [88][89][90][91] At the same time, simplified programmes with no need for major capital outlay and equipment were successfully adapted and applied to specific circumstances without hampering the activities of the NTP. 92,93 The possibility of modulating PR programmes by adapting them to the context and resources available (to prevent unmanageable workload), makes PR potentially accessible to individuals (including children and adolescents) in different settings. 12,92,[94][95][96][97][98][99] The core components of a PR programme are summarised in Table 3. 100-109

STANDARD 4
Evaluating the effectiveness of PR for former TB patients. The standard includes a short description on how to evaluate the effectiveness of PR by comparing the core variables before and after rehabilitation. The standard also suggests how to organise follow-up for the patient.
As discussed in Standard 1 and 2, on completion of TB treatment and before starting a PR programme tailored to a patient's needs, a comprehensive assessment is necessary. The easiest way to evaluate the effectiveness of PR is to assess the core variables 'at the end' vs. 'at the beginning' of the programme, [88][89][90]92 as summarised in Table 4. As a minimum, the patient's functional exercise capacity, dyspnoea and health status should be assessed. 11,12,32 Recently, a list of health outcomes including social, economic and psychological impact has been recommended as a core component of the evaluation. 11,32 The measure of exercise capacity most frequently used is the 6MWT. [88][89][90]95 However, the cardiopulmonary exercise test or the incremental shuttle walk test and the 5 repetition sit to stand test are also applied. 70,92 PR in PTLD patients has been shown to significantly improve the distance covered during the 6MWT (by approximately 35-45 m), an improvement similar to that recorded in subjects with COPD. 110 QoL was evaluated by questionnaires, all different from each other, and no study used diseasespecific questionnaires. However, the results seem to confirm significant improvement when QoL was evaluated using the St George's Respiratory Questionnaire, Short Form Health Survey 36 and Clinical Chronic Obstructive Pulmonary Disease questionnaire. 111,112 Similarly, the symptom evaluation was conducted for dyspnoea, chest pain, haemoptysis and cough by using different scales.
No data are available on other strong outcomes such as mortality and morbidity. It is desirable to use validated and shared tools to consolidate knowledge on PR for PTLD.

Follow-up
Follow-up is desirable for patients undergoing PR to assess if any clinical problem has arisen, and to ensure that the benefits achieved after PR are maintained. The follow-up needs to be organised based on local feasibility and organisation of health services. Individuals who complete an episode of TB treatment, especially those with residual pulmonary sequelae (e.g., residual cavitation) and with other infections (e.g., aspergilloma and NTM) remain at elevated risk of TB. 29,30 Recurrent TB may be due to endogenous reactivation or exogenous reinfection 27,28 and is frequently observed, particularly in settings with a high incidence of TB. 113,114 Follow-up should therefore include appropriate measures to detect recurrent TB at an early stage and refer individuals with disease recurrence for prompt treatment. Recurrent TB can be identified based on clinical or radiographic findings, in addition to microbiological evidence, after excluding other causes (NTM, fungal or other chronic bacterial infections).
If feasible, follow-up of patients with sequelae not requiring (or with contra-indications for) PR can also be considered. Table 5 includes a generic scheme for follow-up visits. Considering the risk of recurrence, infection control and prevention measures and reassessment of the patient's potential contagiousness are recommended during all steps of the process.

STANDARD 5
Each patient completing PR should undergo counselling/health education, including a follow-up plan to maintain/improve the results achieved, organised according to feasibility and cost-effectiveness criteria, based on the local organisation of health services and tailored to the individual patient's needs.     Health education is an essential part of PR. 87 The multidisciplinary education component includes information on PTB and most frequent respiratory comorbidities. This generally covers lung anatomy, physiology of various lung impairments, exercise physiology, benefits and methods of daily training, nutrition, drug therapy, oxygen therapy, how to cope with exacerbations and how to manage daily life. 88 Health education should also involve patients and their families. This is especially important for children, where education about TB prevention, smoking, cough etiquette and other topics (see Table 6) is recommended for the whole household.
Educating patients to self-manage sputum clearance contributes to reducing the frequency of exacerbations and the unnecessary use of antibiotics (thus preventing antibiotic resistance development and spread). In addition, WHO recommends integrating early and effective smoking cessation measures and risks posed by alcohol abuse, starting at the primary health care level, into TB control plans. 115,116 Health education or counselling should be organised according to international guidelines. 117 Importantly, health education sessions should be age-specific, gender-sensitive and delivered in the patient's own language. 41,42 Recommendations to deliver an effective educational session are summarised in Table 6.

STANDARD 6 (PUBLIC HEALTH)
Each change in outcome for a patient (cured or treatment completed as per WHO guidelines) occurring during or after PR should be promptly notified to public health services and be included in the TB register. If the TB register/surveillance database allows, for research purposes the results of the PR programme should be recorded and updated over time. Patients with permanent sequelae and disability need to be supported by social protection schemes whenever possible, according to the legal framework in place.
Standard 6 is the only public health standard included in this clinically oriented document. The WHO has introduced outcomes definitions, which have recently been revised. 46 These definitions are used by TB programmes for monitoring and evaluation purposes, e.g., to allow them to measure rapidly the proportion of patients achieving treatment success (cure, if evidence of bacteriological negativity in a previously positive patient exists, otherwise treatment completion) against those with negative outcomes (e.g., treatment failure, lost to follow-up, or died). [118][119][120][121] When revising the definition of cure, the WHO recommended, when possible, to continue the followup of patients for a period of 6 months or 1 year. 46 This was based on evidence that relapses or reinfections can occur, and introduced the concept of 'sustained cure'. Patients undergoing PR allows for follow-up to occur, as they remain in care after completing their TB treatment.
Standard 6 calls for the need to update the TB register if any change occurs in the final outcome (cure or treatment completion), e.g., if the patient develops relapse (or recurrence with evidence of reinfection), or if death occurs. If the TB programme's surveillance system/TB register allows, information that the patient has been evaluated for PTLD should also be recorded. Together with this, if there was an indication for PR implementation and evaluation, the outcome could be recorded. These inclusions will improve the information globally available on PTLD and contribute to its better management. If the surveillance system/TB register does not allow for this, the information could be collected at the clinical centre level and periodically collected/evaluated for research purposes. Communication between the TB register and the clinical staff is encouraged.
An additional important element of Standard 6 is the importance of prioritising patients with severe PTLD to ensure access to social protection schemes, based on existing legislation (but which we recommend should be revised to capture this concept). This element is fully in line with Pillar 2 of the WHO End TB Strategy. 122,123  Clinical standards for post-TB lung disease

PRIORITIES FOR FUTURE RESEARCH
There is a need for additional research on the epidemiology, assessment and management of PTLD in adults and children to guide the development of future standards and guidelines. To enable research in the forthcoming years, political commitment and appropriate funding mechanisms will be essential. Key research priorities are highlighted in Table 7.

CONCLUSION
There is a need for continued care for TB patients who successfully complete TB treatment but continue to suffer from PTLD. 124 This document represents the views of a large body of experts who have reached consensus on clinical standards for the assessment and management of PTLD and, as necessary, the implementation of PR. The document also presents a set of research priorities to improve our understanding of the measures that will prove to be most effective (and cost-effective) to prevent, detect and treat PTLD. Because the evidence currently available is modest, this document will be revised periodically to guide clinicians, TB programme managers and public health officers towards evidence-based planning and implementation of adequate measures to assess and manage PTLD. 3) To quantify the health and economic impact of PTLD at the individual and population level, including the impact of managing PTLD on health systems Health economic/mathematical modelling studies 4) To identify feasible, accurate and cost-effective tools to evaluate patients at the end of TB treatment for their risk of PTLD and subsequent poor health outcomes (Standard 1) Diagnostic accuracy studies, diagnostic randomised-controlled trials 5) To develop optimal approaches and algorithms to diagnose and manage PTLD, and to discriminate between PTLD and recurrent TB (Standards 1, 2) Diagnostic accuracy studies, diagnostic randomised-controlled trials 6) To identify effective and cost-effective strategies to prevent PTLD during anti-TB treatment, including, for example, adjuvant therapies and interventions to reduce concomitant risk factors for poor lung health outcomes (e.g., smoking cessation programmes) Randomised-controlled trials

7)
To identify effective and cost-effective strategies to deliver pulmonary rehabilitation in specific sub-groups (using standard measures of minimum clinically important difference), including individual patient follow-up in different settings and populations (Standards 2-5) Randomised-controlled trials