TABLE 2.

Summary of epidemiological studies investigating pulmonary impairment after tuberculosis (TB)

First author [ref.]	Type of study	Setting	Sample size n	Exposure	Outcome	Association/finding	Major limitation
Akkara [ 18 ]	Cross-sectional	India	257	Treated TB (2 weeks post-treatment completion)	Airflow obstruction measured by FEV1 and FVC	Airflow obstruction in 86.8% of patients	Lung impairment before TB treatment initiation was not measured to relate to lung impairment after treatment completion and determine causality. Long-term lung disability was not assessed.#
Willcox [ 13 ]	Cross-sectional	South Africa	71	History of TB (up to age 16 years)	Airflow obstruction defined as RV >120% pred and/or FEV1/FVC ratio <70% pred with TLC >80% of pred	Obstruction in 68% of patients Obstruction with some restriction in 20% Non-obstructive decrease in lung volume in 17%	Lung impairment before TB treatment initiation was not measured to relate to lung impairment after treatment completion and determine causality. Lung function was evaluated only in patients who could be traced after several years of attending a TB clinic. Selection of patients in this way may have contributed to survivor bias and underestimated lung dysfunction.
Manji [ 19 ]	Cross-sectional	Tanzania	501	Treated TB (20 weeks of anti-TB therapy)	Airflow defects measured by FEV1 and FVC	Lung impairment in 74% of patients Obstruction in 42% Restriction in 13% Mixed pattern in 19%	Lung impairment before TB treatment initiation was not measured to relate to lung impairment after treatment completion and determine causality. Long-term lung disability was not assessed.#
Hnizdo [ 2 ]	Retrospective	South Africa	27 660	History of 1, 2 or ≥3 episodes of TB	Airflow obstruction defined as FEV1 <80%	Prevalence of airflow obstruction after 1 episode of TB (18.4%), 2 episodes of TB (27.1%) and ≥3 episodes of TB (35.2%) Lung impairment is greatest in the first 6 months following TB diagnosis and stabilises 6 months post-TB treatment completion	Only male mine workers were assessed.
Ross [ 4 ]	Matched retrospective	South Africa	185 TB cases versus 185 age-matched controls without history of TB	History of TB	Lung function loss over time measured by FEV1 and FVC	History of TB was associated with an adjusted mean loss of 40.3 mL·year−1 in FEV1 (95% CI 25.4–55.1) and 42.7 mL·year−1 in FVC (95% CI 27–58.5) compared to controls	Only male mine workers were assessed. Patients were included in the study only if they were still working in the mines at follow-up, nearly 4.5 years after baseline measures. Several subjects had left the mines by follow-up. Selecting only those still working at the mines may have contributed to survivor bias and underestimated lung function.
Rhee [ 20 ]	Retrospective	Republic of Korea	595	Destroyed lung resulting from a past history of TB	Lung function loss measured by FEV1 and FVC	Lung impairment after TB in 76.8% of patients	Cohort consisted of hospitalised TB patients with destroyed lungs, thereby limiting the generalisability of findings to less advanced patients. PFTs were not standardised.
Plit [ 3 ]	Prospective cohort	South Africa	74	TB treatment	Lung function at the end of TB treatment	54% of patients had an improvement in lung function 28% of patients had obstructed airflow 24% of patients had restricted airflow Only study to date that has investigated an association between inflammation and lung function: elevated C-reactive protein correlated with decreased FEV1 % after TB treatment completion, independent of smoking	Cohort consisted of hospitalised patients with severe TB, thereby limiting the generalisability of findings to less advanced patients. Long-term lung disability was not assessed.#
Maguire [ 7 ]	Prospective cohort	Indonesia	69	TB treatment	Lung function over the course of TB treatment	Lung function improved over the course of TB treatment; however, 25% of the patients had residual moderate-to-severe TB (FEV1 <60%) at treatment completion	Study was restricted to 69 of 115 patients who attended all follow-up visits. Those included were more likely to have been cured and had better lung function at diagnosis compared to those not included. This may have underestimated the extent of lung dysfunction among patients with a history of TB. Long-term lung disability was not assessed.#
Ralph [ 8 ]	Prospective cohort	Indonesia	200	TB treatment	Lung function over the course of treatment and at treatment completion	47% of TB patients had moderate-to-severe pulmonary impairment at baseline 27% of TB patients had residual moderate-to-severe pulmonary impairment at the end of treatment	Long-term lung disability was not assessed.#
Pasipanodya [ 5 ]	Case–control	USA	107 active TB cases versus 210 latent TB controls	Treated TB (20 weeks of anti-TB therapy)	Airway obstruction defined as FEV1/FVC <70% pred and FVC >80% pred	TB patients on anti-TB therapy have significantly higher odds of pulmonary impairment versus controls with latent TB, OR 5.4 (95% CI 2.98–9.68)	Lung impairment before TB treatment initiation was not measured to relate to lung impairment at treatment completion and determine causality. Long-term lung disability was not assessed.#
Amaral [ 10 ]	Cross-sectional, population-based study of adults	18 high and low-/middle-income countries	14 050	History of TB	Airflow defects: obstruction defined as post-bronchodilator FEV1/FVC less than LLN; restriction defined as post-bronchodilator FVC less than LLN	Obstruction: adjusted OR 2.51 (95% CI 1.8–3.42) Restriction: adjusted OR 2.31 (95% CI 1.42–3.19)	Self-report of TB was used to determine association with airflow obstruction. This approach may have resulted in recall bias.
Menezes [ 12 ]	Cross-sectional, population-based	5 Latin American cities	5571 patients; 132 with a diagnosis of TB	History of TB	COPD	Prevalence of COPD in 30.7% versus 13.9% comparing those with and without history of TB, respectively Smoking adjusted OR 2.33 (95% CI 1.5–3.62)	History of TB was not confirmed by medical records. Lung function was not measured
Lee [ 21 ]	Retrospective	Taiwan	3176 pulmonary TB cases versus 15 880 matched controls	History of TB	COPD	History of TB is an independent risk factor of COPD (HR 2.05, 95% CI 1.77–2.39)	Patients were considered to have a history of TB and COPD based on medical treatment records. Lung function was not measured.
Byrne [ 11 ]	Systematic review and meta-analysis	Multiples countries		History of TB	COPD	History of TB was significantly associated with COPD in adults over 40 years (pooled OR 3.05, 95% CI 2.42–3.85)	All studies included in the meta-analysis were cross-sectional. Thus, precluding determination of a temporal and causal effect of TB on COPD.

FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; RV: residual volume; TLC: total lung capacity; PFT: pulmonary function test; LLN: lower limit of normal; COPD: chronic obstructive pulmonary disease. ^#: the study by Hnizdo et al. [2] demonstrated that lung impairment peaks 6 months after diagnosis, but improves 6 months post-treatment completion before stabilising to become chronic. These studies determined lung function at treatment completion, thus their findings may not represent residual lung impairment.