ABSTRACT

Objective: To compare patients with and without previous lung disease, in terms of the spirometry results after they had been treated for pulmonary tuberculosis (PTB) and cured, as well as to analyze risk factors related to functional severity. Methods: This was a cross-sectional, multicenter study conducted at four referral centers in Brazil. Patients were divided into two groups: those with a history of lung disease or smoking (LDS+ group); and those with no such history (LDS− group). Patients underwent spirometry (at least six months after being cured). Sociodemographic and clinical data were collected. Results: A total of 378 patients were included: 174 (46.1%) in the LDS+ group and 204 (53.9%) in the LDS− group. In the sample as a whole, 238 patients (62.7%) had spirometric changes. In the LDS+ group, there was a predominance of obstructive lung disease (in 33.3%), whereas restrictive lung disease predominated in the LDS− group (in 24.7%). Radiological changes were less common in the LDS− group than in the LDS+ group (p < 0.01), as were functional changes (p < 0.05). However, of the 140 (79.1%) LDS− group patients with a normal or minimally altered chest X-ray, 76 (54%) had functional changes (p < 0.01). The risk factors associated with functional severity in the LDS− group were degree of dyspnea (p = 0.03) and moderate or severe radiological changes (p = 0.01). Conclusions: Impaired pulmonary function is common after treatment for PTB, regardless of the history of lung disease or smoking. Spirometry should be suggested for patients who develop moderate/severe dyspnea or relevant radiological changes after treatment for PTB.

Keywords: Tuberculosis, pulmonary; Respiratory function tests; Airway obstruction/complications.

RESUMO

Objetivo: Comparar os resultados da espirometria de pacientes tratados e curados para tuberculose pulmonar (TBP) com e sem doença pulmonar prévia e analisar os fatores de risco relacionados à gravidade funcional. Métodos: Estudo transversal, multicêntrico, em quatro centros de referência no Brasil. Os pacientes foram classificados em dois grupos: grupo com doença pulmonar prévia ou história de tabagismo (grupo DPT+) e grupo sem doença pulmonar prévia e sem tabagismo (grupo DPT−). Os pacientes realizaram espirometria (pelo menos seis meses após a cura), e foram coletados dados sociodemográficos e clínicos. Resultados: Foram incluídos 378 pacientes: 174 (46,1%) no grupo DPT+ e 204 (53,9%) no grupo DPT−. Na amostra total, 238 pacientes (62,7%) apresentaram alguma alteração espirométrica. No grupo DPT+ houve predominância de distúrbio ventilatório obstrutivo (em 33,3%), e distúrbio ventilatório restritivo predominou no grupo DPT− (em 24,7%). Quando comparados com o grupo DPT+, os pacientes do grupo DPT− apresentaram menos frequentemente alteração radiológica (p < 0,01) e funcional (p < 0,05). Porém, dos 140 (79,1%) do grupo DPT− com radiografia de tórax normal ou minimamente alterada, 76 (54%) apresentaram alguma alteração funcional (p < 0,01). Os fatores de risco relacionados com a gravidade funcional no grupo DPT− foram grau de dispneia (p = 0,03) e alterações radiológicas moderadas ou acentuadas. Conclusões: O comprometimento da função pulmonar é frequente após o tratamento da TBP independentemente do histórico de tabagismo ou doença pulmonar prévia. A espirometria deve ser sugerida para esses pacientes que evoluem com grau moderado/grave de dispneia e/ou alteração radiológica relevante após o tratamento da TBP.

Palavras-chave: Tuberculose pulmonar; Testes de função respiratória; Obstrução das vias respiratórias/complicações.

INTRODUCTION

Tuberculosis is recognized as a global public health problem, and its control has been a challenge in recent decades.(1) In 2015, Brazil met the millennium goals by decreasing the incidence of and mortality from tuberculosis. Among the so-called BRICS countries (Brazil, Russia, India, China, and South Africa), Brazil has the lowest tuberculosis incidence rate, although the prevalence of the disease remains steady.(2) However, there are still major obstacles to controlling tuberculosis in Brazil, such as impediments to investigating contacts, to making an early diagnosis, and to initiating antituberculosis therapy in primary care.(2)

Delayed diagnosis and the low effectiveness of antituberculosis therapy, which may be due to sociocultural factors associated with patients, physicians, and the organization of the health care system, promote the spread of the disease and increase the risk of progression of lung lesions.(3-5)

One of the aspects rarely addressed in the literature is the clinical and social impact of pulmonary sequelae among patients who have completed the treatment regimen. Pulmonary tuberculosis (PTB) can lead to chronic airflow obstruction, depending on the degree of anatomical distortion present, and to restricted ventilation caused by fibrotic scarring associated with reduced TLC. Greater lung injury, related to disability and impaired quality of life, has been associated with delayed diagnosis of tuberculosis, quantity of previous treatments, smoking, malnutrition, and a high bacillary load at the initiation of antituberculosis therapy.(6-10)

The functional changes resulting from PTB that are observed after treatment manifest as restrictive lung disease (RLD), obstructive lung disease (OLD), or mixed obstructive-restrictive lung disease (MORLD), regardless of the history of exposure to smoking.(11) The most commonly described functional change is OLD.(6,7,12) The prevalence of OLD after treatment for PTB is estimated to range from 15% to 77%,(10,12) whereas that of MORLD, the second most prevalent, is estimated to range from 9% to 34%.(9,12) At one center in Brazil, MORLD was reported to be the most common functional change, with a prevalence of 34%. (11) However, OLD was observed in 33% of the patients evaluated by Di Naso et al.(13) and in 49% of those evaluated by Nihues et al.(14) At another center, RLD was the most prevalent (in 41%).(15)

In Brazil, there have been few studies reporting the proportion of patients with radiological and functional changes after treatment for PTB, and in those few studies(9-15) there was no exclusion of patients with a history of lung disease or smoking prior to treatment for PTB. Therefore, given the prevalence of PTB in Brazil, it is relevant to have knowledge of the magnitude of spirometric changes in this population.

The objective of the present study was to compare patients with a history of lung disease or smoking and those with no such history, on the basis of the spirometry results after treatment for PTB, at one of four referral centers in Brazil, as well as to analyze risk factors related to functional severity in the patients with no history of lung disease or smoking.

METHODS

Study design

This was a cross-sectional, multicenter study involving non-probability purposive sampling. The study population consisted of 418 patients recruited between 2014 and 2015 from one of the following referral centers in Brazil: the Federal University of Minas Gerais Hospital das Clínicas (a tertiary referral center), in the city of Belo Horizonte; the Brazilian Institute for Tuberculosis Research (a secondary referral center), in the city of Salvador; the Dourados Municipal Program for Tuberculosis Control (a secondary referral center), in the city of Dourados; and the Thoracic Diseases Institute of the Federal University of Rio de Janeiro School of Medicine Clementino Fraga Filho University Hospital, (a tertiary referral center), in the city of Rio de Janeiro.

We included patients who were ≥ 18 years of age; had been diagnosed with PTB, confirmed by sputum smear microscopy or mycobacterial culture; had received a single treatment for PTB at one of the four referral centers; had been cured; and had undergone spirometry. We excluded patients whose spirometry results did not meet the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association) acceptability and reproducibility criteria(16) or who had a condition that made it impossible to perform the test or was a contraindication to it, such as hemoptysis, an altered level of consciousness, acute myocardial infarction or ischemic stroke in the last 3 months, uncontrolled systemic arterial hypertension, and aortic aneurysm.

All patients who had been cured of PTB were invited to participate in the study. Participants completed a standardized questionnaire that collected information on sociodemographic and clinical characteristics, such as gender, age, smoking, alcoholism, and comorbidities. In addition, the time from symptom onset to diagnosis of PTB was determined. Smokers were defined as individuals who had smoked at least 100 cigarettes (or equivalent) in their lifetime, and former smokers were defined as those who had quit smoking more than 12 months prior.(17) Alcoholism was assessed with the Cut down, Annoyed, Guilty, and Eye-opener questionnaire.(18)

Sociodemographic and clinical characteristics were categorized as follows: skin color, defined as White or Non-White; marital status, defined as married/living as married or other (widowed, separated/divorced, or single); level of education, defined as ≤ 9 or > 9 years of schooling; and self-reported comorbidities. Diagnoses of lung disease (asthma, COPD, bronchiectasis, interstitial lung disease, and silicosis) prior to treatment for PTB were reviewed by the pulmonologists involved in the present study, who followed the definitions proposed in the Global Initiative for Asthma guidelines and the Global Initiative for Chronic Obstructive Lung Disease guidelines, as well as in a national practice guideline.(19-21)

With regard to signs and symptoms, participants were evaluated for the presence of dyspnea, as classified by the modified Medical Research Council (mMRC) scale,(22) cough, expectoration, and wheezing. These data were obtained on the day of the spirometry.

Patients were divided into two groups: those with a history of lung disease or smoking prior to treatment for PTB (LDS+ group); and those with no such history (LDS− group). Spirometry was performed at least 6 months after the PTB had been cured.

Functional assessment

Spirometry was performed with a Koko spirometer (Pulmonary Data Service Inc., Louisville, CO, USA). All tests were performed and interpreted following the recommendations of the SBPT guidelines.(16) Post-bronchodilator values were compared with pre-bronchodilator values and were expressed as absolute values and as a percentage of predicted values, according to Knudson et al.(23) for female and male patients under 20 and 25 years of age, respectively, and according to Pereira et al.(24) for patients older than that. The technicians who performed the tests were certified by the SBPT. Spirometry results were classified as follows: normal spirometry; OLD; OLD with reduced (F)VC; and RLD. The severity of obstruction was graded on the basis of FEV1 and FEV1/FVC, in % of predicted, as follows(16): mild, ≥ 60%; moderate, 41-59%; and severe, ≤ 40%. The severity of restriction was graded on the basis of (F)VC, in percentage of predicted, as follows(16): mild, ≥ 60%; moderate, 51-59%; and severe, ≤ 50%.

Radiological assessment

Chest X-rays were performed on dates close to those on which spirometry was performed, were evaluated by radiologists, and were classified by pulmonologists. Chest X-rays showing no changes were classified as normal. The remaining chest X-rays were classified as defined in the National Tuberculosis Association (NTA) classification(25): NTA-I, or minimal; NTA-II, or moderately advanced (in one or both lungs, there may be lesions, the total extent of which should not exceed the total volume of one lung if the lesions are not confluent and should not exceed one third of the volume of one lung if they are confluent); and NTA-III, or far advanced (if the lesions are even more extensive).

Statistical analysis

The study variables were entered into an Excel database and were analyzed using the IBM SPSS Statistics software package, version 22.0 (IBM Corporation, Armonk, NY, USA). The distribution of the variables was assessed by the Kolmogorov-Smirnov test. Continuous variables are expressed as means and standard deviations or as medians and interquartile ranges, whereas categorical variables are expressed as absolute and relative frequencies. Clinical, demographic, radiological, and functional characteristics were compared between the two groups by using the chi-square test or the Student's t-test, as appropriate. The spirometric classifications of the LDS− group patients were analyzed, in terms of clinical, demographic, and radiological characteristics, with Pearson's chi-square test and were divided into two groups: no disease (normal spirometry results) or mild disease; and moderate or severe disease. Values of p < 0.05 were considered significant.

Ethical considerations

The study was approved by the Research Ethics Committee of the Federal University of Minas Gerais (Reference no. 14606113.7.0000.5149). All participating patients gave written informed consent.

RESULTS

Of the 418 patients initially recruited, 40 (10.5%) were excluded because the spirometry tests did not meet acceptability and reproducibility criteria. There were no significant clinical, demographic, or radiological differences between the patients who were included in the study and those who were excluded.

Therefore, the final sample comprised 378 patients, of whom 174 (46%) were in the LDS+ group and 204 (54%) were in the LDS− group. The characteristics of the patients are described in Table 1. The proportions of patients who were male, were > 49 years of age, had completed ≤ 9 years of schooling, had at least one comorbidity (systemic arterial hypertension, heart disease, or diabetes mellitus), were alcoholics, and had respiratory symptoms were significantly higher in the LDS+ group than in the LDS− group (Table 1).




Chest X-rays classified as normal or NTA-I were more common in the LDS− group than in the LDS+ group (p < 0.01; Table 1). Pre- and post-bronchodilator absolute and percentage of predicted FEV1, FEF25-75%, FEV1/FVC, and FEF25-75%/FVC were significantly higher in the LDS− group than in the LDS+ group (Table 2).



Of the 378 patients evaluated, 238 (62.7%) had spirometric changes. Normal spirometry was more common in the LDS− group (p < 0.01). As can be seen in Table 3, the most common spirometric changes in the LDS+ group were OLD, in 58 patients (33.3%) and OLD with reduced FVC, in 49 (28.2%), whereas the most common spirometric changes in the LDS− group were RLD, in 50 (24.7%) and OLD, in 42 (20.6%).



With regard to the severity of OLD and RLD, there was a predominance of mild disease in both groups. Among the patients who had OLD with reduced FVC, severe disease was more common in those in the LDS+ group, whereas moderate disease was more common in those in the LDS− group (Table 3).

Table 4 shows the radiological grading and spirometric classification of the LDS− group patients (n = 177). Of the 140 (79.1%) LDS− group patients whose chest X-ray was classified as normal or NTA-I, 76 (54.0%) had functional changes (p < 0.01).



Analysis of the classification of the LDS− group patients, based on spirometry results and clinical, demographic, and radiological characteristics, revealed that age > 49 years, mMRC grade 2-4 dyspnea, and radiological changes classified as NTA-II/III were associated with moderate and severe functional changes. There was no significant association between the time from symptom onset to diagnosis of tuberculosis and the severity of spirometric changes (Table 5).



DISCUSSION

The main finding of the present study is that, after having been treated for PTB and cured, 238 (62.7%) of the patients had spirometric changes. Comparison of the two groups revealed that functional and radiological changes were less common in the LDS− group. However, of the 140 (79.1%) LDS− group patients whose chest X-ray was classified as normal or NTA-I, 76 (54.0%) had functional changes. These data suggest that impaired pulmonary function after PTB is a major cause of chronic lung disease. The risk factors related to functional severity in this group were age > 49 years, mMRC grade 2-4 dyspnea, and radiological changes classified as NTA-II/III.

Investigation of changes in pulmonary function after completion of treatment for PTB has been gaining prominence in the literature.(6,7,9,11-15,26,27) In our study, the most common functional change in the LDS− group was RLD (24.7%). Cruz et al.(15) also described RLD as the main functional change after treatment for PTB; however, that study included patients who underwent more than one treatment for PTB.

In the literature, the reported frequency of OLD ranges from 15% to 77%.(6,7,9,12,28,29) The combination of PTB and airflow obstruction can occur regardless of the presence of smoking,(30) suggesting that the obstruction found in the LDS− group patients may be due to their PTB lesions. Some population-based studies have also described OLD as the most common functional change; however, those studies included smokers, former smokers, and patients with a history of lung disease,(28,29) similar to what was observed in the LDS+ group in the present study.

PTB can affect the airways and lung parenchyma, leading to mucosal edema, hypertrophy/hyperplasia of the mucous glands, increased mucus secretion, smooth muscle layer hypertrophy, and increased activity of metalloproteinases. Consequently, there can be changes in airway caliber (caused by stenosis, distortion, bronchiectasis, and emphysema), increased airway resistance, and reduced airflow.(31) In addition, fibrotic scarring can reduce lung compliance, leading to restriction.(27) This heterogeneity of lung lesions should be more extensively studied, especially with regard to pathophysiology and inflammatory phenomena.

Functional changes, which may persist after PTB has been cured, are associated with disability and reduced quality of life.(32,33) Lee et al.(4) stated that early diagnosis and prompt initiation of therapy translate to a lower likelihood of significant functional changes. In our study, there was no association between the time from symptom onset to diagnosis of PTB and the severity of spirometric changes, suggesting that PTB may lead to functional changes, regardless of the timing of the initiation of therapy, as also reported by Manji et al.(34)

Specifically in the LDS− group patients, dyspnea can be explained by structural (NTA-II and NTA-III) lesions leading to airway obstruction, with small airways involvement and bronchiectasis,(10) as well as destruction of the lung parenchyma. Other studies have identified an association between the extent of radiographic changes and changes in pulmonary function.(13,15,32,34-36) Those studies suggest that greater lesion extent translates to greater tissue damage, these sequelae being reflected in changes in pulmonary function. However, those studies did not assess the severity of spirometric changes.(13,15,32,34-36) Disease overlap could explain the higher frequency of symptoms (dyspnea, cough, expectoration, and wheezing) in the LDS+ group. Some limitations of the present study should be noted. The first limitation is that functional changes were not assessed longitudinally, rather being assessed 24 months after completion of the antituberculosis therapy. That could provide different results if the lesions have yet to stabilize.(37) The second limitation is the use of chest X-ray, a method that may underestimate the extent of sequelae. Chest CT can more accurately characterize the changes caused by PTB sequelae. However, in a recent study, chest CT and chest X-ray were in disagreement in only 7% of the examinations in patients with PTB sequelae.(26) In addition, chest X-ray is inexpensive and is available at tuberculosis treatment centers in Brazil, in contrast to chest CT, to which access is limited. Another limitation is that pulmonary function was assessed by spirometry only, without plethysmography or DLCO measurement. However, the equipment needed for those tests is unavailable at most centers in Brazil. Finally, the relationship between greater functional severity and being > 49 years of age was not investigated.

Functional changes constitute knowledge gaps that warrant further studies, especially studies aimed at determining whether airway obstruction due to PTB is a different entity from COPD due to exposure to cigarette smoke or smoke from wood-burning stoves, silicosis, etc.(38) In addition, further studies could assess responses to treatments such as the use of specific inhaled medication and pulmonary rehabilitation to improve patient quality of life.

In conclusion, impaired pulmonary function is common after treatment for PTB, regardless of the history of smoking or lung disease. Spirometry should be suggested for patients who develop mMRC grade 2-4 dyspnea or relevant radiological changes after treatment for PTB.

ACKNOWLEDGMENTS

The authors would like to thank the following institutions for their collaboration: the Federal University of Minas Gerais; the Brazilian Institute for Tuberculosis Research; the Thoracic Diseases Institute; and the Dourados Municipal Program for Tuberculosis Control.

AUTHOR CONTRIBUTIONS

All authors contributed to all stages of this study, including study conception and design, data acquisition and analysis, data interpretation, preparation and revision of the manuscript, and approval of the final manuscript.

REFERENCES

1. World Health Organization [homepage on the Internet]. Geneva: World Health Organization [cited 2018 May 10]. Global tuberculosis report 2017. Available from: http://www.who.int/tb/publications/global_report/en/
2. Brasil. Ministério da Saúde. Programa Nacional de Controle da Tuberculose. Incidência de Tuberculose no Brasil. Brasília: Ministério da Saúde; 2009.
3. Altet Gómez MN, Alcaide Megías J, Canela Soler J, Milá Augé C, Jiménez Fuentes MA, de Souza Galvão ML, et al. Pulmonary symptomatic tuberculosis' diagnostic delay study [Article in Spanish]. Arch Bronconeumol. 2003;39(4):146-52. https://doi.org/10.1157/13045947
4. Lee CH, Lee MC, Lin HH, Shu CC, Wang JY, Lee LN, et al. Pulmonary tuberculosis and delay in anti-tuberculous treatment are important risk factors for chronic obstructive pulmonary disease. PLoS One. 2012;7(5):e37978. https://doi.org/10.1371/journal.pone.0037978
5. Job JR, Gozzano JO, Bernardes Júnior OR, Garcia RH, Miralhes OJ, de Miranda MA. Data preceding the diagnosis of pulmonary tuberculosis and time elapsed till the beginning of treatment in patients enrolled at a health center, São Paulo (Brazil) [Article in Portuguese]. Rev Saude Publica. 1986;20(1):21-5. https://doi.org/10.1590/S0034-89101986000100002
6. Chushkin MI, Ots ON. Impaired pulmonary function after treatment for tuberculosis: the end of the disease? J Bras Pneumol. 2017;43(1):38-43. https://doi.org/10.1590/s1806-37562016000000053
7. de la Mora I, Martínez-Oceguera D, Laniado-Laborín R. Chronic airway obstruction after successful treatment of tuberculosis and its impact on quality of life. Int J Tuberc Lung Dis. 2015;19(7):808-10. https://doi.org/10.5588/ijtld.14.0983
8. Muñoz-Torrico M, Rendon A, Centis R, Ambrosio L, Fuentes Z, Torres-Duque C, et al. Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis? J Bras Pneumol. 2016;42(5):374-385. https://doi.org/10.1590/S1806-37562016000000226
9. Byrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: a systematic review. Int J Infect Dis. 2015;32:138-46. https://doi.org/10.1016/j.ijid.2014.12.016
10. Sarkar M, Srinivasa, Madabhavi I, Kumar K. Tuberculosis associated chronic obstructive pulmonary disease. Clin Respir J. 2017;11(3):285-295. https://doi.org/10.1111/crj.12621
11. Ramos LM, Sulmonett N, Ferreira CS, Henriques JF, de Miranda SS. Functional profile of patients with tuberculosis sequelae in a university hospital. J Bras Pneumol. 2006;32(1):43-7. https://doi.org/10.1590/S1806-37132006000100010
12. Allwood BW, Myer L, Bateman ED. A systematic review of the association between pulmonary tuberculosis and the development of chronic airflow obstruction in adults. Respiration. 2013;86(1):76-85. https://doi.org/10.1159/000350917
13. Di Naso FC, Pereira JS, Schuh SJ, Unis G. Functional evaluation in patients with pulmonary tuberculosis sequelae [Article in Portuguese]. Rev Port Pneumol. 2011;17(5):216-21. https://doi.org/10.1016/j.rppneu.2011.06.010
14. Nihues Sde S, Mancuzo EV, Sulmonetti N, Sacchi FP, Viana Vde S, Netto EM, et al. Chronic symptoms and pulmonary dysfunction in post-tuberculosis Brazilian patients. Brazilian J Infect Dis. 2015;19(5):492-7. https://doi.org/10.1016/j.bjid.2015.06.005
15. Cruz Rde C, De Albuquerque Mde F, Campelo AR, Costa e Silva EJ, Mazza E, Menezes RC, et al. Pulmonary tuberculosis: association between extent of the residual pulmonary lesion and alteration in the lung function [Article in Portuguese]. Rev Assoc Med Bras. 2008;54(5):406-10. https://doi.org/10.1590/S0104-42302008000500012
16. Pereira CA. Espirometria. J Bras Pneumol. 2002;28(Suppl 3):S1-82.
17. Centers for Disease Control and Prevention (CDC). Cigarette smoking among adults and trends in smoking cessation - United States, 2008. MMWR Morb Mortal Wkly Rep. 2009;58(44):1227-32.
18. Mayfield D, McLeod G, Hall P. The CAGE questionnaire: validation of new alcoholism screening instrument. Am J Psychiatry. 1974;131(10):1121-3.
19. Global Initiative for Chronic Obstructive Lung Disease (GOLD) [homepage on the Internet]. Bethesda: GOLD [cited 2018 May 10]. GOLD 2017 Global Strategy for the Diagnosis, Management and Prevention of COPD. Available from http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/
20. Global Initiative for Asthma (GINA) homepage on the Internet]. Bethesda: GINA [cited 2018 May 10]. Global Strategy for Asthma Management and Prevention, 2017. Available from: https://ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/
21. Maciel R, Aidé MM, editors. Prática Pneumológica. 2nd ed. Rio de Janeiro: Guanabara Koogan; 2017.
22. Ferrer M, Alonso J, Morera J, Marrades RM, Khalaf A, Aguar MC, et al. Chronic obstructive pulmonary disease stage and health-related quality of life. The Quality of Life of Chronic Obstructive Pulmonary Disease Study Group. Ann Inter Med. 1997;127(12):1072-9. https://doi.org/10.7326/0003-4819-127-12-199712150-00003
23. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127(6):725-34.
24. Pereira CA, Sato T, Rodrigues SC. New reference values for forced spirometry in white adults in Brazil. J Bras Pneumol. 2007;33(44):397-406. https://doi.org/10.1590/S1806-37132007000400008
25. Ribeiro SN, Gehardt FG, Silva JRL, Fonseca L, Gontijo P, Sant'Anna CC. Tuberculose. In: Bethlem N, editor. Pneumologia. 4th ed. São Paulo: Atheneu; 1995. p. 379-448.
26. Ko Y, Lee YM, Lee HY, Lee YS, Song JW, Hong GY, et al. Changes in lung function according to disease extent before and after pulmonary tuberculosis. Int J Tuberc Lung Dis. 2015;19(5):589-95. https://doi.org/10.5588/ijtld.14.0454
27. Pasipanodya JG, McNabb SJ, Hilsenrath P, Bae S, Lykens K, Vecino E, et al. Pulmonary impairment after tuberculosis and its contribution to TB burden. BMC Public Health. 2010;10:259. https://doi.org/10.1186/1471-2458-10-259
28. Caballero A, Torres-Duque CA, Jaramillo C, Bolívar F, Sanabria F, Osorio P, et al. Prevalence of COPD in five Colombian cities situated at low, medium, and high altitude (PREPOCOL study). Chest. 2008;133(2):343-9. https://doi.org/10.1378/chest.07-1361
29. Amaral AF, Coton S, Kato B, Tan WC, Studnicka M, Janson C, et al. Tuberculosis associates with both airflow obstruction and low lung function: BOLD results. Eur Respir J. 2015;46(4):1104-12. https://doi.org/10.1183/13993003.02325-2014
30. Kim HJ, Baek S, Kim HJ, Lee JS, Oh YM, Lee SD, et al. The impact of smoking on airflow limitation in subjects with history of asthma and inactive tuberculosis. PLoS One. 2015;10(4):e0125020. https://doi.org/10.1371/journal.pone.0125020
31. Elkington PT, Friedland JS. Matrix metalloproteinases in destructive pulmonary pathology. Thorax. 2006;61(3):259-66. https://doi.org/10.1136/thx.2005.051979
32. Radovic M, Ristic L, Ciric Z, Dinic-Radovic V, Stankovic I, Pejcic T, et al. Changes in respiratory function impairment following the treatment of severe pulmonary tuberculosis - limitations for the underlying COPD detection. Int J Chron Obstruct Pulmon Dis. 2016;11:1307-16. https://doi.org/10.2147/COPD.S106875
33. Maguire GP, Anstey NM, Ardian M, Waramori G, Tjitra E, Kenangalem E, et al. Pulmonary tuberculosis, impaired lung function, disability and quality of life in a high-burden setting. Int J Tuberc Lung Dis. 2009;13(12):1500-6.
34. Manji M, Shayo G, Mamuya S, Mpembeni R, Jusabani A, Mugusi F. Lung functions among patients with pulmonary tuberculosis in Dar es Salaam - a cross-sectional study. BMC Pulm Med. 2016;16(1):58. https://doi.org/10.1186/s12890-016-0213-5
35. Menezes AM, Hallal PC, Perez-Padilla R, Jardim JR, Muiño A, Lopez MV, et al. Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America. Eur Respir J. 2007;30(6):1180-5. https://doi.org/10.1183/09031936.00083507
36. Akkara AS, Shah AD, Adalja M, Akkara AG, Rathi A, Shah DN. Pulmonary tuberculosis: the day after. Int J Tuberc Lung Dis. 2013;17(6):810-3. https://doi.org/10.5588/ijtld.12.0317
37. Chung KP, Chen JY, Lee CH, Wu HD, Wang JY, Lee LN, et al. Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis. Clinics (Sao Paulo). 2011;66(4):549-56. https://doi.org/10.1590/S1807-59322011000400005
38. Allwood BW, Gillespie R, Galperin-Aizenberg M, Bateman M, Olckers H, Taborda-Barata L, et al. Obstructive pulmonary disease in patients with previous tuberculosis: Pathophysiology of a community-based cohort. S Afr Med J. 2017;107(5):440-445. https://doi.org/10.7196/SAMJ.2017.v107i5.12118