Clinical standards for the assessment, management and rehabilitation of post-TB lung disease
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
INT J TUBERC LUNG DIS 25(10):797–813 CLINICAL STANDARDS FOR LUNG HEALTH
Q 2021 The Union
http://dx.doi.org/10.5588/ijtld.21.0425
Clinical standards for the assessment, management and
rehabilitation of post-TB lung disease
SUMMARY
B A C K G R O U N D : Increasing evidence suggests that post- tions); Standard 2, to identify patients with PTLD for PR;
TB lung disease (PTLD) causes significant morbidity and Standard 3, tailoring the PR programme to patient needs
mortality. The aim of these clinical standards is to provide and the local setting; Standard 4, to evaluate the
guidance on the assessment and management of PTLD and effectiveness of PR; and Standard 5, to conduct education
the implementation of pulmonary rehabilitation (PR). and counselling. Standard 6 addresses public health aspects
M E T H O D S : A panel of global experts in the field of TB of PTLD and outcomes due to PR.
care and PR was identified; 62 participated in a Delphi C O N C L U S I O N : This is the first consensus-based set of
process. A 5-point Likert scale was used to score the Clinical Standards for PTLD. Our aim is to improve
initial ideas for standards and after several rounds of patient care and quality of life by guiding clinicians,
revision the document was approved (with 100% programme managers and public health officers in
agreement). planning and implementing adequate measures to assess
R E S U LT S : Five clinical standards were defined: Standard and manage PTLD.
1, to assess patients at the end of TB treatment for PTLD K E Y W O R D S : tuberculosis; post-TB lung disease; se-
(with adaptation for children and specific settings/situa- quelae; pulmonary rehabilitation; clinical standards
Historically, national TB programmes (NTPs) have these illnesses is uncertain, but they may in part
emphasised the need to ensure rapid diagnosis and reflect the systemic effects of sustained lung inflam-
effective treatment of individuals with infectious TB mation and enzymatic degradation, which persist
to reduce transmission and the epidemiological trend after TB cure.25,26 Moreover, individuals who previ-
of the disease.1,2 Over the past 20 years, the number ously completed TB treatment continue to be at high
of individuals successfully treated for TB has risk of developing TB again due to either endogenous
increased substantially, with an estimated 155 million reactivation or exogenous reinfection.27,28 Distin-
TB survivors alive in 2020.3,4 However, a substantial guishing between recurrent TB vs. post-TB sequelae
proportion of people considered cured (or with TB can be particularly challenging.29–31
treatment completed) report residual cough, weak- For this document, we adopted the definition of
ness, dyspnoea, difficulties in climbing stairs or PTLD developed at the First International Sympo-
managing every-day or work activities, which affect sium on Post-TB disease: ‘‘Evidence of chronic
their quality of life (QoL) and increase the risk of respiratory abnormality, with or without symptoms
death.5–10 These long-term sequelae from TB treat- attributable at least in part to previous (pulmonary)
ment are identified using a series of tests, including tuberculosis’’.32 In recent years, PTLD has attracted
chest imaging (e.g., fibrosis, cavities, pleural thicken- increasing interest from the research and medical
ing, bronchiectasis, pulmonary hypertension, second- community. Several studies indicate that up to 50%
ary bacterial and fungal infections); pulmonary of TB patients report health problems consistent with
function testing (PFT), including spirometry, plethys- PTLD after completion of treatment.11–13,33–38 PTLD
mography and diffusing capacity of the lungs for is likely to cause a considerable burden of disease
carbon monoxide (DLCO) to detect obstructive, globally, suggesting opportunities for prevention and
restrictive and mixed patterns; and cardiopulmonary management. Recent modelling indicates that 138–
exercise testing (CPET) to assess the integrative 171 million TB survivors were alive in 2020, of whom
responses of the cardiovascular, respiratory and nearly one fifth were treated in the past 5 years.4
musculoskeletal systems to incremental exercise in PTLD was estimated to account for approximately
patients with PTLD.11–20 half of lifetime disability-adjusted life-years (DALYs)
Delayed diagnosis and inappropriate regimens used caused by incident TB.38–40
during treatment may play a role in the development In preparing this document, our aim was to define
of PTLD.21,22 Also, former TB patients experience clinical standards for PTLD, focusing primarily on
increased non-pulmonary morbidity and mortality, pulmonary disease. Standards are different from
particularly cardiovascular diseases, despite success- guidelines, which are based on ‘Grading of Recom-
ful completion of treatment.23,24 The aetiology of mendations, Assessment, Development, and Evalua-
Article submitted 12 July 2021. Final version accepted 12 July 2021.798 The International Journal of Tuberculosis and Lung Disease
tion’ (GRADE) and ‘Patient, Intervention, Comparison, METHODS
Outcome (PICO) questions. Standards prescribe a
A panel of 67 global experts was identified to
widely accepted level of diagnosis and care, for all
represent the main scientific societies, associations
healthcare providers and clinicians, both public and
and groups active in the field of TB and PR, including
private, to achieve optimal standards in managing
TB clinicians (n ¼ 34), TB public health (n ¼ 18), TB
patients who have, or who are presumed to suffer from,
paediatricians (n ¼ 3), PR experts (n ¼ 6), PFT/lung
a given disease.41,42 The IJTLD Clinical Standards do
diseases experts (n ¼ 3), methodologists (n ¼ 2) and
not compete with existing WHO or other guidelines,
psychologist (n ¼ 1). Out of the 67 experts invited, 3
but rather complement and integrate their recommen-
declined and 2 did not respond. The 62 respondents
dations to provide a specific clinical focus. The
were asked to comment via a Delphi process on an
standards are universal principles and might need to
initial draft including seven standards (Standards 1–6
be adapted for specific settings and situations for future
being clinical and Standard 7 on public health)
programmatic implementation due to legal, organisa-
developed by a core coordination team (with 17
tional or economic reasons.
members). A 5-point Likert scale was used (5: high
Because specific evidence on PTLD is limited in
agreement; 1: low agreement). Sixty experts submit-
some technical areas, the available evidence on other ted a valid Delphi questionnaire (two did not answer).
lung diseases was used (e.g., for chronic obstructive At the first Delphi round, agreement was high, with a
pulmonary disease [COPD]), although such studies median value of 5 for Standards 1–6, and 4 for
exclude patients with TB. Also, research into paedi- Standard 7. Based on substantial agreement on the
atric care is currently limited, but recommendations seven Standards and the document outline, a draft
were added where appropriate. The clinical standards document was jointly developed by the expert panel.
will be updated to capture new evidence as it This underwent seven rounds of revision and the final
accumulates over time. Finally, although these form was approved by consensus (100% agreement),
standards pertain to evaluations and interventions with a reduction in the number of standards to 6 in
after a patient has completed TB treatment, a small total (5 clinical and 1 on public health).
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 STANDARD 1
The use of adjunctive therapies during TB treatment Every patient completing TB treatment should be
may therefore help to avert PTLD or reduce its clinically evaluated for PTLD. The assessment should
impact.44,45 Physicians are urged to consider such at- be conducted as soon as possible at the end of
risk patients for enrolment in clinical trials to expand treatment and organised by the TB programme. In
our understanding of this area. special settings and situations, post-TB treatment
evaluation can be simplified and/or modified to
AIM OF THE CLINICAL STANDARDS include a set of basic examinations with the aim to
identify patients with sequelae at risk of deterioration
This consensus-based document aims to describe the (or even death) and those likely to benefit from PR.
following activities: The following set of basic examinations is considered
1) Assessing patients at the end of TB treatment for essential upon clinical suspicion of either the presence
sequelae and PTLD (Standard 1). A universal of, or risk factors for, PTLD: clinical examination/
standard was defined, with special considerations history, CXR, PFT, six-minute walking test (6MWT),
for children and possible adaptation in different complemented by symptom score and QoL question-
settings and situations (for organisational, legal or naire evaluation. Other examinations are considered
economic reasons). conditional.
2) Identifying patients with PTLD for pulmonary The complete list of examinations to assess the
rehabilitation (PR) (Standard 2). presence of post-TB treatment sequelae and the
3) Adapting the PR programme for specific patient indications for PR (see Standards 2–3 for details)
needs and different settings (Standard 3). are summarised in Table 1. Completion of treatment
4) Evaluating the effectiveness of PR and follow-up affords the opportunity to (safely) evaluate the
(Standard 4). patient’s microbiological and radiological status,
5) Education and counselling for a patient (Standard and the relationship with baseline assessments.
5) to help manage their condition. Although the focus of this document is on PTLD, it
6) A public health standard highlighting the need to is important to note that bacteriological results
record changes in patient outcome resulting from (sputum smear microscopy and culture) are impor-
PR (Standard 6). tant at diagnosis, during follow-up and at the end of
7) Priorities for future research into PTLD. treatment to determine the TB treatment outcomeClinical standards for post-TB lung disease 799
Table 1 Standard 1: Recommended examinations to be conducted at the end of treatment and in special settings and situations
because of legal, organisational or economic reasons
Adaption for special settings
Essential and conditional examinations/investigations and situations
Clinical assessment Clinical history, symptom assessment and clinical Clinical history, symptom assessment
examination and clinical examination
Imaging Chest radiography (digital) Chest radiography
Computed tomography
Functional evaluation Spirometry, including pre- and post-bronchodilator test Spirometry
Plethysmography SpO2
Diffusion capacity assessment (DLCO, KCO) 6MWT
Tidal breathing techniques (oscillometry/MBW)
Arterial blood gas analysis, and pulse oximetry (SpO2)
6MWT
CPET
Subjective evaluation QoL questionnaire QoL questionnaire
Frequent symptoms score Frequent symptoms score
DLCO ¼ diffusing capacity of the lungs for carbon monoxide; KCO ¼ carbon monoxide transfer coefficient; MBW ¼ multiple breath washout; SpO2 ¼ peripheral
capillary oxygen saturation; 6MWT ¼six-minute walking test; CPET ¼cardiopulmonary exercise testing; QoL ¼ quality of life.
(cured or treatment completed, see also Standard any lung condition also need to be recorded, as these
6).46 CXR is also important. Computed tomography are likely to be relevant for the management of PTLD.
(CT) scan, which is not always available, allows a Examples include asthma, bronchiectasis, pulmonary
more thorough evaluation of the lung parenchyma fibrosis and COPD as well as a history of pulmonary
that is often not visible (or fully appreciated) on CXR. TB (PTB) and/or frequent lower respiratory tract
For example, it may offer higher sensitivity to detect infections in childhood.
bronchiectasis, cavities or pulmonary nodules as a A clinical examination at the end of TB treatment,
basis to improve current and future clinical manage- when performed thoroughly, helps guide appropriate
ment (sputum expectoration, risk of recurrent infec- further investigations. Recordings for weight, height
tion, risk of chronic fungal infection and risk of TB and vital signs (temperature, respiratory and heart
relapse). Pulmonary nodules may be a consequence of rates, blood pressure and oxygen saturations) is
TB but can also represent other infections or cancer.47 considered essential. The presence of low arterial
The advantages of a CT scan must be weighed against oxygen saturations (,94%, ideally complemented by
the harms of radiation exposure. Use of CT scans arterial blood gases analysis, if feasible), changes in
should therefore be reserved for instances when body mass index (BMI) and its trend over time, digital
differential diagnostic imaging beyond CXR is highly clubbing, coarse crackles, raised jugular-venous
desirable to inform clinical decision making. In pressure or peripheral oedema may suggest pathology
patients with cavitary TB, who develop progressive other than TB or concurrent pathologies. A subse-
respiratory symptoms after treatment completion, quent nutritional assessment includes, among oth-
additional testing may be warranted to evaluate for ers,49 simple investigations (e.g., urine analysis and
TB relapse, chronic infections (aspergilloma, non- blood tests) to identify treatable conditions that
tuberculous mycobacteria [NTM] infections, bron- commonly cause morbidity.50 For example, anaemia
chiectasis) and other lung disease (e.g., cancer). caused by iron deficiency can be diagnosed by blood
Further investigations may include chest CT, culture tests and is amenable to oral supplementation, and
of sputum or fluid collected by bronchoalveolar unexpected glycosuria could lead to a diagnosis of
lavage (e.g., for M. tuberculosis, Aspergillus and diabetes. Desirable blood tests include complete
other respiratory pathogens) and Aspergillus serolo- blood count with white cell differential, fasting blood
gy.48 In settings with sufficient resources, additional glucose, electrolytes, urea, creatinine and liver
assessments would add important clinical and func- function tests, including serum albumin. Unexplained
tional information to PTLD management, particular- or persistent biochemical abnormalities should be
ly as it relates to lung health (for details on complemented by the appropriate investigation (or
rehabilitation, see Standards 3–4) and mortality risk. referral) to diagnose and treat the underlying
A focused respiratory history needs to be recorded condition. Comorbid medical conditions associated
including vaccination history (e.g., COVID-19, influ- with TB that are known to increase mortality,
enza, pneumococcal vaccines), risk factors (e.g., particularly if untreated, should be noted. These
previous incarceration) and co-morbidities (e.g., include but are not limited to HIV, diabetes mellitus,
HIV co-infection and diabetes, among others) as well chronic kidney diseases, chronic liver diseases (in-
as exposure to health hazards (such as cigarette cluding chronic hepatitis B and C), anaemia and iron
smoking, silica and biomass fuel). Known respiratory deficiency.11,32,50 Recently, the importance of COV-
co-morbidities and related previous treatments for ID-19 has also been highlighted, and opportunities800 The International Journal of Tuberculosis and Lung Disease
exist to combine efforts supporting rehabilitation function in childhood and adulthood. PTB in child-
approaches for patients with both TB and COVID-19 hood could therefore have long-lasting consequences
related sequelae.51–54 on lung health later in life.57,58 A better understanding
Given the high rates of PTB and the body of evidence of the impact of PTB on long-term respiratory
linking TB with chronic respiratory diseases (CRDs), morbidity in children is therefore urgently needed.
PFT should be routinely performed on completion of End of TB treatment assessment should follow
TB treatment in all settings where it is available and standards as proposed in adults, with some consider-
compared with previous PFT results. For example, pre- ations specific to children. Just over half of children
and post-bronchodilator spirometry performed accord- diagnosed with TB will have a clinical diagnosis
ing to the European Respiratory Society (ERS)/ (‘‘unconfirmed TB cases’’) and no microbiological
American Thoracic Society (ATS) standards,55 with confirmation due to the often paucibacillary nature of
appropriate equipment provides essential information paediatric TB.59 This results in the majority of children
on lung function and is the diagnostic test of choice for having an outcome of ‘‘treatment completed’’ instead of
CRDs. When feasible and available, spirometry can be ‘‘cured’’. Radiological imaging can be considered at the
complemented by plethysmography (to assess total end of treatment for use as a comparative tool in case
lung capacity and resistance), DLCO or carbon TB recurs. CT scans of the chest are usually not
monoxide transfer coefficient (KCO) to assess ventila- indicated due to challenges of investigation in children
tory inhomogeneity for comprehensive assessment of and radiation exposure, but can be considered in
lung function.11,32 specific cases (substantial chronic symptoms and
The six-minute walking test (6MWT), performed radiological abnormalities) to evaluate the extent of
according to international guidelines, is a simple tool PTLD or exclude a different diagnosis.
largely used to evaluate functional exercise capacity, Lung function should be considered in all children
assess prognosis and evaluate treatment response in with severe TB lung involvement60 over the age of 4–6
CRDs.56 The 6MWT is generally considered reliable years, and include pre- and post-bronchodilation flow/
for chronic respiratory diseases and requires limited volume curves. Tidal breathing techniques, including
resources.11,32 Furthermore, the 6MWT is useful for forced oscillometry and multiple breath washouts, can
the evaluation of exercise-induced desaturation as be considered in children younger than 4 years of age.
assessed using pulse oximetry (SpO2), although the Data on lung function impairment in children is
reference values to be used may be an issue. Clinical currently lacking and is a priority for research.
examination might justify the need for additional Quality of life questionnaires such as EQ-5D-Y and
investigations in specific patients, for example, Toddler and Infant (TANDI) can be used to assess
echocardiography to evaluate pulmonary hyperten- health-related QoL in children – although these need
sion and secondary right heart failure, or evidence of local adaptation for the youngest children. Functional
lesions that put patients at risk of spontaneous exercise capacity can be measured using the 6MWT
pneumothorax (or history of previous pneumotho- in children from the age of 4 years. Reference ranges
rax) or of possible broncho-pleural fistula. Similarly, were established in a Caucasian population and
some patients may benefit from assessment of might require adaptation in different settings.61
cardiovascular risks, including determination of
blood lipids, C-reactive protein and N terminal pro
brain natriuretic peptide (Nt-proBNP). STANDARD 2
The persistence of symptoms such as breathlessness Evaluation for PR. Former TB patients with clinical
or cough are associated with disease progression, and radiological signs and symptoms consistent with
contributing to a decline in physical function and post-TB treatment sequelae, evidence of obstruction
health-related QoL. Therefore, the evaluation should and/or restriction, desaturations and/or low oxygen
include the subjective perception of symptoms and levels, reduced exercise tolerance and related impair-
the corresponding impact on daily life. There are ment in quality of life should be evaluated for PR.
numerous questionnaires validated for use in subjects
with CRDs, although not PTLD specifically. It is PR is a core component in the management of CRDs
recommended that questionnaires are administered and is described as an ‘individually tailored and
by trained personnel, when needed, respecting their designed, multidisciplinary programme of care’ for
specific indications. The choice of the questionnaire patients with chronic respiratory impairment.62
or scales also depends on the time available and the There is strong evidence that PR improves health
education level of the patient. status, exercise capacity, fatigue, and social function-
ing, and is recommended in international guide-
Specific considerations for paediatric care lines.63,64 There is currently a lack of data in children,
Despite increasing global awareness of PTLD, there is a but tools used in children with other chronic
lack of data for children. Numerous cohort studies respiratory illnesses can also be used in paediatric
have shown that there is an association between lung PTLD. Growing evidence indicates that PTB causesClinical standards for post-TB lung disease 801
Table 2 Standard 2: Indications for pulmonary rehabilitation69–84
Essential and conditional Adaption to special settings
Indications examinations/investigations and situations
Pulmonary rehabilitation should be evaluated in all cases of TB cured (smear- or culture-negative in the last month) and TB treatment
completed with:
Impaired exercise capacity32,56,69,70 Cardiopulmonary exercise test and/or Six-minute walking test and/or
Six-minute walking test and/or Five repetition sit to stand test
Five repetition sit to stand test and/or
Maximal voluntary contraction
Reported respiratory symptoms (dyspnoea, Modified Medical Research Council Modified Medical Research Council
cough, sputum, wheeze, chest pain, Modified Borg Scale Modified Borg Scale
fatigue)71–74 Visual Analogue Scale Visual Analogue Scale
Presence of comorbid conditions, including Clinical history Clinical history
chronic obstructive pulmonary disease, Diagnostic test or examinations Diagnostic test or examinations
asthma, bronchiectasis, pulmonary fibrosis,
pulmonary hypertension, and/or need for
surgery12,13,75
At least 1 hospitalisation or 2 exacerbations in Clinical history Clinical history
the last 12 months11,32,76,77
Impaired pulmonary function showing airflow Spirometry with plethysmography, if Spirometry
obstruction or restriction or mixed available
abnormalities and bronchodilator response Diffusing capacity for carbon monoxide
and/or impaired diffusing capacity for
carbon monoxide78
Abnormal blood gas PaO2 ,80 mmHg/10.6 Blood gas analysis and/or Pulse oximetry
kPa and/or PaCO2 .45 mmHg/6.0 kPa and/ Pulse oximetry
or nocturnal and exercise-induced
desaturation79
Ineffective cough and/or difficult to clear Clinical examination and/or Clinical examination
bronchial secretions80,81 Lung function tests (reduction of vital
capacity ,1.5 L and/or reduction of
peak cough flow ,160–200 L/min and/
or reduction of maximal inspiratory
pressure and/or reduction of maximal
expiratory pressure)
Impaired quality of life82–84 TB-specific questionnaire: EUROHIS- TB-specific questionnaire: EUROHIS-
QOL 8 16 QOL 8 16
Disease specific questionnaire: SGRQ Disease-specific questionnaire: SGRQ
.25 .25
Generic questionnaire WHOQOL-BREF Generic questionnaire WHOQOL-BREF
,60 (subjects aged 60) ,60 (subjects aged 60 years)
EUROHIS-QOL ¼ European Health Interview Survey-Quality of Life; SGRQ ¼ St George’s Respiratory Questionnaire; WHOQOL-BREF ¼ abbreviated World Health
Organization Quality of Life.
CRD in a proportion of patients with lung damage at therefore if such patients would potentially benefit
different levels: in the bronchial airways (e.g., non- from PR. After excluding cardiovascular risks, PR is
reversible airflow obstruction, bronchiectasis, tra- an appropriate measure for patients with persistent
chea-bronchial stenosis) and in the lung parenchyma symptoms (dyspnoea, chest pain, cough, muscular
(cavities, fibrosis, restrictive lung disease); it can also fatigue), or reduced exercise tolerance, a restriction in
cause mixed patterns.11,65–67 activities because of their disease, exercise-induced
The severity of pulmonary sequelae is usually oxygen desaturation, or impaired health status.
related to a delay in diagnosis or treatment and/or A comprehensive assessment should be performed
inadequate/inappropriate treatment, leading to ex- in order to detect and quantify the possible impair-
tensive lung damage and longer treatment duration, ment due to PTLD (see Standard 1).11,12,32 The
likely to be more evident in patients with multidrug- assessment (see Table 269–84) should focus on TB
resistant or extensively drug-resistant TB or TB sequelae and their functional impact, as well as on
relapse/recurrence.11,12 Although adequate clinical pulmonary interventions needed (e.g., long-term
and radiological evaluation of patients at the begin- oxygen therapy, ventilation) and include radiological
ning of anti-TB treatment and during treatment aspects, spirometry findings and bronchodilator
monitoring can identify initial sequelae, the end of response, assessment of lung volumes, DLCO,
treatment provides an opportunity to adequately arterial blood gases, nocturnal and exercise-induced
study the patient without risk of infection for family desaturations, 6MWT and QoL. PR (specifically
members, health staff or other contacts.7,63,68 A covered in Standards 3–4) is a comprehensive
careful patient assessment at the end of TB treatment package of interventions, which can include exercise,
(patient cured or with treatment completed) is needed education, nutrition, self-management activities and
to evaluate if there are indications for PTLD and psychosocial support.85802 The International Journal of Tuberculosis and Lung Disease
STANDARD 3 test and the 5 repetition sit to stand test are also
applied.70,92 PR in PTLD patients has been shown to
The PR programme should be organised according to
significantly improve the distance covered during the
feasibility, effectiveness and cost-effectiveness crite-
6MWT (by approximately 35–45 m), an improve-
ria, based on the local organisation of health services
ment similar to that recorded in subjects with
and tailored to the individual patient’s needs.
COPD.110 QoL was evaluated by questionnaires, all
Most of what is known about PR is derived from different from each other, and no study used disease-
CRDs, where it has been shown to be relatively more specific questionnaires. However, the results seem to
cost-effective than pharmacotherapy.86 Obviously, confirm significant improvement when QoL was
there are differences between these conditions and evaluated using the St George’s Respiratory Ques-
PTLD, and important evidence gaps are highlighted tionnaire, Short Form Health Survey 36 and Clinical
in this document. To qualify as PR, programmes must Chronic Obstructive Pulmonary Disease question-
include, at the very least, comprehensive baseline and naire.111,112 Similarly, the symptom evaluation was
post-PR outcome measurements, a structured and conducted for dyspnoea, chest pain, haemoptysis and
supervised exercise training programme, an educa- cough by using different scales.
tion/behavioural programme intended to foster long- No data are available on other strong outcomes
term health-enhancing behaviour, and provision of such as mortality and morbidity. It is desirable to use
recommendations for home-based exercise and self or validated and shared tools to consolidate knowledge
supervised physical activity programmes.87 on PR for PTLD.
Evidence on specific PR programmes tailored to
PTLD patients exists in settings with adequate Follow-up
resources, logistics, and expert healthcare providers – Follow-up is desirable for patients undergoing PR to
and these were generally effective.88–91 At the same assess if any clinical problem has arisen, and to ensure
time, simplified programmes with no need for major that the benefits achieved after PR are maintained. The
capital outlay and equipment were successfully adapted follow-up needs to be organised based on local
and applied to specific circumstances without hamper- feasibility and organisation of health services. Individ-
ing the activities of the NTP.92,93 The possibility of uals who complete an episode of TB treatment,
modulating PR programmes by adapting them to the especially those with residual pulmonary sequelae
context and resources available (to prevent unmanage- (e.g., residual cavitation) and with other infections
able workload), makes PR potentially accessible to (e.g., aspergilloma and NTM) remain at elevated risk
individuals (including children and adolescents) in of TB.29,30 Recurrent TB may be due to endogenous
different settings.12,92,94–99 The core components of a reactivation or exogenous reinfection27,28 and is
PR programme are summarised in Table 3.100–109 frequently observed, particularly in settings with a
high incidence of TB.113,114 Follow-up should there-
STANDARD 4 fore include appropriate measures to detect recurrent
TB at an early stage and refer individuals with disease
Evaluating the effectiveness of PR for former TB recurrence for prompt treatment. Recurrent TB can be
patients. The standard includes a short description on identified based on clinical or radiographic findings, in
how to evaluate the effectiveness of PR by comparing addition to microbiological evidence, after excluding
the core variables before and after rehabilitation. The other causes (NTM, fungal or other chronic bacterial
standard also suggests how to organise follow-up for infections).
the patient. If feasible, follow-up of patients with sequelae not
As discussed in Standard 1 and 2, on completion of TB requiring (or with contra-indications for) PR can also
treatment and before starting a PR programme be considered. Table 5 includes a generic scheme for
tailored to a patient’s needs, a comprehensive assess- follow-up visits. Considering the risk of recurrence,
ment is necessary. The easiest way to evaluate the infection control and prevention measures and re-
effectiveness of PR is to assess the core variables ‘at the assessment of the patient’s potential contagiousness
end’ vs. ‘at the beginning’ of the programme,88–90,92 as are recommended during all steps of the process.
summarised in Table 4. As a minimum, the patient’s
functional exercise capacity, dyspnoea and health
STANDARD 5
status should be assessed.11,12,32
Recently, a list of health outcomes including social, Each patient completing PR should undergo counsel-
economic and psychological impact has been recom- ling/health education, including a follow-up plan to
mended as a core component of the evaluation.11,32 maintain/improve the results achieved, organised
The measure of exercise capacity most frequently according to feasibility and cost-effectiveness criteria,
used is the 6MWT.88–90,95 However, the cardiopul- based on the local organisation of health services and
monary exercise test or the incremental shuttle walk tailored to the individual patient’s needs.Clinical standards for post-TB lung disease 803
Table 3 Standard 3: Summary of the core components of a rehabilitation programme100–109
Methods
Adaption to special setting
Components Indication Interventions and situations
Aerobic exercise: Impaired exercise capacity, Treadmill and/or cycle-ergometer Free walking
endurance training limited by dyspnoea and or 30 min 2–5 times/week for 4–8 30 min 2–5 times/week for 4–8
other respiratory symptoms weeks weeks
Restriction in daily life Intensity set according to maximal Intensity set according to
activities.11,32 oxygen consumption or the perceived dyspnoea
equation of Luxton or 80% of Outpatients or home setting
heart rate max adjusted on Suggest maintenance
dyspnoea programme
In or out-patients or tele-
monitoring
Suggest maintenance programme
Strength training: Reduced muscle mass and Free weights (dumbbells and Free weights (dumbbells and
upper and lower strength of peripheral ankle-brace) ankle-brace)
extremities (limited muscles. Lower muscle 20–30 min 2–5 times/week for 4– 20–30 min 2–5 times/week for
evidence on TB) weakness with risk for falls. 8 weeks 4–8 weeks
Impaired activities of daily 2–3 set of 6–12 repetitions 2–3 set of 6–12 repetitions
living involving the upper Intensity set to 80% of maximal Intensity set according to
extremities (including voluntary contraction and/or perceived muscles fatigue
dressing, bathing, and adjusted on muscles fatigue Out-patients or home setting
household tasks)11 In or out-patients or tele- Suggest maintenance
monitoring programme
Suggest maintenance programme
Inspiratory muscle Impaired respiratory muscle Load threshold devices, seated Not applicable
training (limited function, altered respiratory and using a nose clip
evidence on TB) mechanics, decreased chest Interval training: 10 exercises
wall compliance or followed by 10 seconds break
pulmonary hyperinflation100 between each.
15–20 min 2–5 times/week for 4–
8 weeks
Loads from 30% to 80% of
maximal inspiratory pressure
Airway clearance Difficult to remove secretions or Choose the technique suitable for Choose the technique suitable
techniques mucous plugs the subject among those for the subject among those
Frequent bronchial available, based on respiratory available, based on respiratory
exacerbations (2/year) capacity, mucus rheology, capacity, mucus rheology,
Concomitant diagnosis of collaboration and patient collaboration and patient
bronchiectasis101 preferences preferences
15–30 min one or more times/day 15–30 min one or more times/
Choose the duration of treatment day choose the duration of
based on chronic (long term) or treatment based on chronic
acute problem (short term) (long term) or acute problem
Suggest maintenance programme (short term)
when needed Suggest maintenance
programme when needed
Long-term oxygen Resting hypoxaemia despite Titrate oxygen flow that maintain Titrate oxygen flow that
therapy (limited stable condition and optimal oxygen saturation .92–93% maintain oxygen saturation
evidence on TB) medical therapy (partial Long-term oxygen therapy should .92–93%
pressure of oxygen ,7.3 kPa be initiated on a flow rate of 1 L/ Long term oxygen therapy
(,55 mmHg) or 8 kPa (60 min and titrated up in 1 L/min should be initiated on a flow
mmHg) with evidence of increments until oxygen rate of 1 L/min and titrated up
peripheral oedema, saturation .90%. An arterial in 1 L/min increments until
polycythaemia (haematocrit blood gas analysis should then be oxygen saturation .90% at rest
55%) or pulmonary performed to confirm that a has been achieved
hypertension)102,103 target partial pressure of oxygen Non-hypercapnic patients
8 kPa (60 mm Hg) at rest has initiated on long term oxygen
been achieved therapy should increase their
Ambulatory and nocturnal flow rate by 1 L/min during
oximetry may be performed to sleep in the absence of any
allow more accurate flow rates to contraindications
be ordered for exercise and sleep, Ambulatory oximetry may be
respectively during rest, sleep and performed to allow more
exertion accurate flow rates to be
Provide formal education to ordered for exercise
patients referred to home Provide formal education to
Schedule periodic re-assessment patients referred to home
at 3 months Schedule periodic re-assessment
at 3 months804 The International Journal of Tuberculosis and Lung Disease
Table 3 (continued)
Methods
Adaption to special setting
Components Indication Interventions and situations
Long-term nocturnal Chronic stable hypercapnia Not initiating long-term non- Probably not applicable
non-invasive (partial pressure of carbon invasive ventilation during
mechanical dioxide .6–8 kPa (45–60 admission for acute on-chronic
ventilation (limited mmHg)), despite optimal hypercapnic respiratory failure,
evidence on TB) medical therapy favouring reassessment at 2–4
Non-invasive ventilation could weeks after resolution
be applied during aerobic Titrate non-invasive ventilation
training in case of severe setting
breathlessness or reduced Titrate mask
exercise resistance91,104 Plan education
Consider non-invasive ventilation
during exercise
Schedule an educational meeting
and verifies the ability of the
subject and/or a caregiver to
manage the non-invasive
ventilation at home
Nutritional support Malnutrition (body mass index Nutritional assessment Nutritional assessment
,16 kg/m2 or body mass Tailored treatment from foods Tailored treatment from foods
index ,17 kg/m2 in patients and medical supplements and medical supplements
with TB-HIV, MDR-TB, or Need for financial incentives, and Need for financial incentives,
pregnant and lactating transportation access should be and transportation access
mothers)105–107 evaluated should be evaluated
Psychological Social isolation, depression and Psychological assessment Psychological assessment
support anxiety. Impaired health Psychological support Psychological support
status and/or quality of life Consider self-help group Consider self-help group
despite optimal
pharmacological treatment.
Low adherence to medical
treatment108,109
MDR-TB ¼ multidrug-resistant TB.
Table 4 Standard 4: Evaluation of pulmonary rehabilitation effectiveness
Type of measure
Essential and conditional Adaption to special setting
Outcomes examinations/investigations and situations
Functional Lung function Spirometry (FEV1, FVC, FEV1/FVC) Spirometry (FEV1, FVC, FEV1/FVC)
Plethysmography
Gas transfer PaO2, Pulse oximetry (SpO2, % desaturation)
PaCO2
Pulse oximetry (SpO2, % desaturation)
DLCO, KCO
Exercise capacity 6MWT 6MWT
VO2max 5STS
ISWT
5STS
TB-specific Health-related quality of life EUROHIS-QOL 8 EUROHIS-QOL 8
SGRQ SGRQ
WHOQOL-BREF WHOQOL-BREF
Paediatric: EQ-5D-Y and TANDI paediatric: EQ-5D-Y and TANDI
Self-reported symptoms mMRC mMRC
VAS VAS
Modified Borg Modified Borg
Generic Acute infectious exacerbations Number of episodes Number of episodes
(e.g., in bronchiectasis)
requiring antibiotic and/or
steroid treatment
Hospitalisation Number of episodes/hospital days Number of episodes/hospital days
Mortality (see Standard 6) Number of deaths Number of deaths
FEV1 ¼ forced expiratory volume in the first second; FVC ¼ forced vital capacity; PaO2 ¼ partial pressure of arterial oxygen; PaCO2 ¼ partial pressure of arterial
carbon dioxide; SpO2 ¼ peripheral capillary oxygen saturation; DLCO ¼ diffusing capacity of the lungs for carbon monoxide; KCO ¼ carbon monoxide transfer
coefficient; 6MWT ¼six-minute walking test; ISWT ¼ incremental shuttle walk test; 5STS ¼ 5 repetitions of sit to stand test; VO2max ¼maximal oxygen consumption;
EUROHIS-QOL ¼ EUROHIS-QOL ¼ European Health Interview Survey-Quality of Life; SGRQ ¼ St George’s Respiratory Questionnaire; WHOQOL-BREF ¼ abbreviated
World Health Organization Quality of Life; TANDI ¼ Toddler and Infant; mMRC ¼ modified Medical Research Council; VAS ¼ Visual Analogue Scale.Clinical standards for post-TB lung disease 805
Table 5 Recommended examinations during anti-TB treatment and post-treatment follow-up
M3† M6‡ M12¶
Time point/ after after after
assessment M0* M2/3*† EOT* EOT EOT EOT Rationale Comments
Microbiological x x x (x) (x) (x) Microbiological status before Integrated in WHO or NTP
examination of treatment initiation guidelines
sputum (culture, Monitoring treatment response
microscopy or and recurrent TB
Xpert/NAAT) Determination of
(microbiological) TB
treatment outcome
Clinical examination, x (x) x x x x Identification of (potential) Suggested use of a checklist to
including BMI permanent TB sequelae and monitor for adverse drug
adverse effects of TB events
treatment
Establish status quo at EOT to
observe trend over time
Respiratory history x x (x) x x Identification and evaluation of Depending on the setting this
and status of potential risk factors that may should also include history
comorbidities (HIV have an influence on the such as vaccination status,
infection, diabetes prognosis and the exposure to silica and
mellitus, COPD, management of PTLD biomass fuel, investigations
CVD, nutrition Planning for interventions and such as serology for hepatitis
status, cigarette education program B/C, Sars-CoV-2,
smoking) Observing trend over time aspergillosis, nutritional
status associated conditions
such as anaemia
Chest radiography x x (x) Establish dimension of If available, digital radiography
(permanent) pulmonary should be performed due to
destruction before and after advantages regarding expert
TB treatment analysis, remote reading,
Status quo at EOT to compare automated analysis and data
with future chest X-rays, e.g., storage
assessment of respiratory
exacerbations or recurrent TB
Presence of cavities may
increase risk of TB relapse
and more severe PTLD
sequelae
Spirometry/ pre-TB (x) x x x x Capture lung function results ERS/ATS guidelines should be
(plethysmography) before TB treatment, where followed
available Adequate reference standards
Establish status quo at EOT to should be used for result
compare with future interpretation
spirometry testing Appropriate equipment,
Identification of subjects for including maintenance of
rehabilitation equipment needed
Body-plethysmography, only for
research purpose or in
specific patients and settings
Computed (x) (x) Allows a more refined Recommended in symptomatic
tomography investigation of pulmonary patients or in patients with
structures and pathologies, TB-related abnormalities,
e.g., bronchiectasis, fibrosis, which cannot be well
aspergillosis of the lung investigated on chest
Presence of cavities may radiography
increase risk of TB relapse
and more severe PTLD
sequelae
6MWT pre-TB x x x x Establish physical exercise Very useful to observe trend
capacity (before –if available- over time
and) after TB treatment May be additionally indicated
Status quo at EOT to compare after recovery of exacerbated
with future 6MWTs patients
Identification of subjects, who Validated for other respiratory
may potentially benefit from conditions including
rehabilitation prognosis evaluation806 The International Journal of Tuberculosis and Lung Disease
Table 5 (continued)
M3† M6‡ M12¶
Time point/ after after after
assessment M0* M2/3*† EOT* EOT EOT EOT Rationale Comments
SpO2 (x) x x x x Severity staging of respiratory Integrated part of 6MWT
failure Less accurate than BGA
Evaluation of nocturnal and/or
exercise-associated oxygen
desaturation
Information for the indication
of LTOT
May be helpful for evaluation of
patients with acute
exacerbations
BGA (x) (x) (x) Diagnosis and severity staging Only for research purpose or in
of respiratory failure specific patients and settings
Information for the indication More accurate and provides
of LTOT more information compared
to SpO2
Metabolic disturbance diagnosis
Appropriate equipment,
including maintenance of
equipment needed
DLCO, KCO (x) (x) (x) To assess CO-diffusion capacity Only for research purpose or in
and identify the underlying specific patients and settings
cause of impaired lung gas- Useful for consideration of
exchange pulmonary hypertension and
other causes of dyspnoea
Appropriate equipment,
including maintenance of
equipment needed
Tidal breathing (x) (x) (x) (x) (x) (x) Assessment of small airways and Only for research purpose or in
techniques of ventilation heterogeneity specific patients and settings
(oscillometry/ seen in complex structural Oscillometry easy to perform in
MBW) lung disease children and other patients,
who cannot perform
spirometry
QoL questionnaire (x) (x) x x x x Establish the severity of Depending on the context and
(including respiratory symptoms and educational level, validated
dyspnoea score) quality of life impairment scales and questionnaires
after TB treatment suitable for the patient
Status quo to compare with should be chosen
future evaluations
Identification of subjects with
potential benefit from
rehabilitation
ECG (x) (x) (x) Supports diagnosis of secondary Only for research purpose or in
cardiac damage due to specific patients and settings
chronic lung diseases,
including PTLD
Differential diagnosis between
primary and secondary
cardiac diseases
Cardiac-ultrasound (x) (x) (x) Allows diagnosis of secondary Only for research purpose or in
(echo) conditions due to TB or PTLD specific patients and settings
such as constrictive pericarditis, Could be complemented by
pulmonary hypertension, right measurement of NT-pro-BNP
heart failure to rule out heart failure
Differential diagnosis between
primary and secondary cardiac
disease
* x ¼ all centres; (x) ¼ research-oriented centres, specific settings or patients (depending on comorbidities, symptoms, exacerbations or abnormal findings in other tests).
†
Optional evaluation during TB treatment/at the end of the intensive treatment phase; depending on patients’ symptoms (e.g., re-evaluation of TB- or PTLD-
diagnosis, diagnosing special conditions such as IRIS or co-infections such as Sars-CoV-2) or specific situations and settings.
‡
Follow-up visits at M3 and M6 after EOT may overlap with pulmonary rehabilitation activities and assessments.
¶
Further follow-up of patients with (high risk for) PTLD; 6–12 monthly follow-up visits, depending on clinical patterns, diseases severity, disease dynamics and
comorbidities.
NAAT ¼ nucleic acids amplification test; M ¼ month; EOT ¼end of treatment for TB; NTP ¼ National Tuberculosis Programme; BMI ¼ body mass index; COPD ¼
chronic obstructive pulmonary disease; CVD ¼ cardiovascular disease; QoL ¼ quality of life; PTLD ¼ post-TB lung disease; ERS ¼ European Respiratory Society; ATS ¼
American Thoracic Society; 6MWT ¼ 6 minutes walking test; SpO2 ¼ oxygen saturation using pulse oximetry; LTOT ¼ long-term oxygen therapy; BGA ¼ blood gases
analysis; DLCO ¼ diffusing capacity of the lung for carbon monoxide; KCO ¼ carbon monoxide transfer coefficient; MBW ¼ multiple breath washout; ECG ¼
electrocardiogram; NT-pro-BNP-N ¼ terminal pro brain natriuretic peptide.Clinical standards for post-TB lung disease 807
Health education is an essential part of PR.87 The STANDARD 6 (PUBLIC HEALTH)
multidisciplinary education component includes
Each change in outcome for a patient (cured or
information on PTB and most frequent respiratory
treatment completed as per WHO guidelines) occur-
comorbidities. This generally covers lung anatomy,
ring during or after PR should be promptly notified to
physiology of various lung impairments, exercise
public health services and be included in the TB
physiology, benefits and methods of daily training,
register. If the TB register/surveillance database
nutrition, drug therapy, oxygen therapy, how to
allows, for research purposes the results of the PR
cope with exacerbations and how to manage daily
programme should be recorded and updated over
life.88 Health education should also involve pa- time. Patients with permanent sequelae and disability
tients and their families. This is especially impor- need to be supported by social protection schemes
tant for children, where education about TB whenever possible, according to the legal framework
prevention, smoking, cough etiquette and other in place.
topics (see Table 6) is recommended for the whole
household. Standard 6 is the only public health standard included
Educating patients to self-manage sputum clearance in this clinically oriented document. The WHO has
contributes to reducing the frequency of exacerbations introduced outcomes definitions, which have recently
and the unnecessary use of antibiotics (thus preventing been revised.46 These definitions are used by TB
antibiotic resistance development and spread). In programmes for monitoring and evaluation purposes,
addition, WHO recommends integrating early and e.g., to allow them to measure rapidly the proportion
effective smoking cessation measures and risks posed of patients achieving treatment success (cure, if
by alcohol abuse, starting at the primary health care evidence of bacteriological negativity in a previously
level, into TB control plans.115,116 Health education or positive patient exists, otherwise treatment comple-
counselling should be organised according to interna- tion) against those with negative outcomes (e.g.,
tional guidelines.117 Importantly, health education treatment failure, lost to follow-up, or died).118–121
When revising the definition of cure, the WHO
sessions should be age-specific, gender-sensitive and
recommended, when possible, to continue the follow-
delivered in the patient’s own language.41,42 Recom-
up of patients for a period of 6 months or 1 year.46
mendations to deliver an effective educational session
This was based on evidence that relapses or re-
are summarised in Table 6.
infections can occur, and introduced the concept of
‘sustained cure’. Patients undergoing PR allows for
Table 6 Standard 5: Summary of the components of the
counselling/health education session follow-up to occur, as they remain in care after
completing their TB treatment.
Components:
Structured and comprehensive educational programmes are an
Standard 6 calls for the need to update the TB
integral and essential component of the management of PTLD register if any change occurs in the final outcome
and pulmonary rehabilitation (cure or treatment completion), e.g., if the patient
Educational programmes should be age-specific, gender-
sensitive, delivered in the local language and extended to
develops relapse (or recurrence with evidence of re-
families/households infection), or if death occurs. If the TB programme’s
Education should be delivered by professionals who are
surveillance system/TB register allows, information
competent in the relevant subject areas and trained to deliver
educational sessions that the patient has been evaluated for PTLD should
Educational materials and technological support used to deliver also be recorded. Together with this, if there was an
them needs to be evaluated in the setting-specific context indication for PR implementation and evaluation, the
Recommended topics: outcome could be recorded. These inclusions will
Basic principles of TB: epidemiology, clinical aspects and
transmission (reinforcing what is ideally provided at diagnosis) improve the information globally available on PTLD
Importance of treatment (and treatment adherence/retention in
and contribute to its better management. If the
care) to stop transmission, protect contacts and prevent relapses
Simple concepts of infection control and safety procedures surveillance system/TB register does not allow for
Advantages/importance of smoking cessation and risk of this, the information could be collected at the clinical
comorbidities (e.g., HIV co-infection, diabetes, etc.) in centre level and periodically collected/evaluated for
household/families
Importance of physical activity and exercise to improve quality of research purposes. Communication between the TB
life register and the clinical staff is encouraged.
Maintaining results achieved with pulmonary rehabilitation
(follow-up plan)
An additional important element of Standard 6 is
Ensuring adequate nutrition the importance of prioritising patients with severe
Importance of adhering to medical prescriptions in terms of
PTLD to ensure access to social protection schemes,
management of comorbidities and vaccinations
Recognising deterioration of clinical conditions and what actions based on existing legislation (but which we recom-
to undertake to prevent relapse mend should be revised to capture this concept). This
Achieving an optimal healthy life style
element is fully in line with Pillar 2 of the WHO End
PTLD ¼ post-TB lung disease. TB Strategy.122,123808 The International Journal of Tuberculosis and Lung Disease
Table 7 Research priorities
Research priority Type of studies
1) To describe the frequency and severity of PTLD in different populations and subgroups of Cross-sectional studies, cohort studies
TB patients over time since the completion of TB treatment, including in children and
adolescents
2) To establish risk factors for severe PTLD and associated poor health outcomes, including Cohort studies (case-control studies)
elevated mortality
3) To quantify the health and economic impact of PTLD at the individual and population Health economic/mathematical
level, including the impact of managing PTLD on health systems modelling studies
4) To identify feasible, accurate and cost-effective tools to evaluate patients at the end of TB Diagnostic accuracy studies, diagnostic
treatment for their risk of PTLD and subsequent poor health outcomes (Standard 1) randomised-controlled trials
5) To develop optimal approaches and algorithms to diagnose and manage PTLD, and to Diagnostic accuracy studies, diagnostic
discriminate between PTLD and recurrent TB (Standards 1, 2) randomised-controlled trials
6) To identify effective and cost-effective strategies to prevent PTLD during anti-TB Randomised-controlled trials
treatment, including, for example, adjuvant therapies and interventions to reduce
concomitant risk factors for poor lung health outcomes (e.g., smoking cessation
programmes)
7) To identify effective and cost-effective strategies to deliver pulmonary rehabilitation in Randomised-controlled trials
specific sub-groups (using standard measures of minimum clinically important
difference), including individual patient follow-up in different settings and populations
(Standards 2–5)
8) To investigate the role of patient education programmes in improving long-term health Randomised-controlled trials
outcomes post-TB (Standard 5)
9) To investigate the role of social protection and support programmes in improving health Randomised-controlled trials
outcomes and quality of life among former TB patients (Standard 6)
10) To identify a set of standard indicators for the surveillance of PTLD that are feasible to Operational research studies
implement within national TB programmes (Standard 6)
PTLD ¼ post-TB lung disease.
PRIORITIES FOR FUTURE RESEARCH J. M. Chakaya,13,14 B. Seaworth,15,16 A. Rachow,17,18
B. J. Marais,19 J. Furin,20 O. W. Akkerman,21,22
There is a need for additional research on the
F. Al Yaquobi,23 A. F. S. Amaral,24 S. Borisov,25
epidemiology, assessment and management of PTLD
J. A. Caminero,26,27 A. C. C. Carvalho,28
in adults and children to guide the development of
D. Chesov,29,30 L. R. Codecasa,31 R. C. Teixeira,32,33
future standards and guidelines. To enable research in
M. P. Dalcolmo,34 S. Datta,35,36,37 A-T. Dinh-Xuan,38
the forthcoming years, political commitment and
R. Duarte,39 C. A. Evans,36,37,40 J-M. Garcı́a-Garcı́a,41
appropriate funding mechanisms will be essential.
G. Günther,42 G. Hoddinott,2 S. Huddart,43,44
Key research priorities are highlighted in Table 7.
O. Ivanova,17,18 R. Laniado-Laborı́n,45 S. Manga,46
K. Manika,47 A. Mariandyshev,48 F. C. Q. Mello,49
CONCLUSION S. G. Mpagama,50 M. Muñoz-Torrico,51 P. Nahid,43,44
There is a need for continued care for TB patients C. W. M. Ong,52,53 D. J. Palmero,54 A. Piubello,55
who successfully complete TB treatment but continue E. Pontali,56 D. R. Silva,57 R. Singla,58
to suffer from PTLD.124 This document represents A. Spanevello,5,59 S. Tiberi,60,61 Z. F. Udwadia,62
the views of a large body of experts who have reached M. Vitacca,63 R. Centis,1 L. D’Ambrosio,64
consensus on clinical standards for the assessment G. Sotgiu,65 C. Lange,66,67,68 D. Visca5,59
and management of PTLD and, as necessary, the * GBM, FMM, NA, EZ and HSS contributed equally to
implementation of PR. this Clinical Standard.
1Respiratory Diseases Clinical Epidemiology Unit,
The document also presents a set of research
priorities to improve our understanding of the Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy;
2Desmond Tutu TB Centre, Department of Paediatrics
measures that will prove to be most effective (and
cost-effective) to prevent, detect and treat PTLD. and Child Health, Faculty of Medicine and Health
Because the evidence currently available is modest, Sciences, Stellenbosch University, Cape Town, 3DSI-
this document will be revised periodically to guide NRF South African Centre of Excellence in
clinicians, TB programme managers and public Epidemiological Modelling and Analysis (SACEMA),
health officers towards evidence-based planning and Stellenbosch University, Stellenbosch, South Africa;
4Division of Pulmonary Rehabilitation, Istituti Clinici
implementation of adequate measures to assess and
manage PTLD. Scientifici Maugeri IRCCS, Montescano (PV), 5Division
of Pulmonary Rehabilitation, Istituti Clinici Scientifici
G. B. Migliori,1 F. M. Marx,2,3 N. Ambrosino,4 Maugeri, IRCCS, Tradate, Italy; 6Division of
E. Zampogna,5 H. S. Schaaf,2 M. M. van der Zalm,2 Pulmonology, Department of Medicine, Stellenbosch
B. Allwood,6 A. L. Byrne,7,8 K. Mortimer,9 University & Tygerberg Hospital, South Africa; 7Heart
R. S. Wallis,10 G. J. Fox,11 C. C. Leung,12 Lung Clinic St Vincent’s Hospital and Clinical School,You can also read
