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Published in: BMC Pulmonary Medicine 1/2020

01-12-2020 | Tuberculosis | Research article

Development of chronic lung impairment in Mozambican TB patients and associated risks

Authors: Celso Khosa, Nilesh Bhatt, Isabel Massango, Khalide Azam, Elmar Saathoff, Abhishek Bakuli, Friedrich Riess, Olena Ivanova, Michael Hoelscher, Andrea Rachow

Published in: BMC Pulmonary Medicine | Issue 1/2020

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Abstract

Background

Pulmonary tuberculosis (PTB) is frequently associated with chronic respiratory impairment despite microbiological cure. There are only a few clinical research studies that describe the course, type and severity as well as associated risk factors for lung impairment (LI) in TB patients.

Methods

A prospective cohort study was conducted at TB Research Clinic of Instituto Nacional de Saúde in Mavalane, Maputo, from June 2014 to June 2016. PTB patients were prospectively enrolled and followed for 52 weeks after TB diagnosis. Lung function was evaluated by spirometry at 8, 26 and 52 weeks after TB treatment initiation, and spirometric values of below the lower limit of normality were considered as LI. Descriptive statistical analysis was performed to summarize the proportion of patients with different lung outcomes at week 52, including type and severity of LI. Risk factors were analysed using multinomial regression analysis.

Results

A total of 69 PTB patients were enrolled, of which 62 had a valid spirometry result at week 52 after TB treatment start. At week 8, 26 and 52, the proportion of patients with LI was 78, 68.9 and 64.5%, respectively, and 35.5% had moderate or severe LI at week 52. The majority of patients with LI suffered from pulmonary restriction. Female sex, low haemoglobin and heavy smoking were significantly associated with LI.

Conclusion

Moderate or severe LI can be observed in a third of cured TB patients. Further research is urgently needed to gain deeper insight into the characteristics of post TB LI, the causal pathways and potential treatment strategies.
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Literature
1.
go back to reference World Health Organization. Global Tuberculosis Report 2019. Geneva: World Health Organization; 2019. World Health Organization. Global Tuberculosis Report 2019. Geneva: World Health Organization; 2019.
2.
go back to reference Ravimohan S, Kornfeld H, Weissman D, Bisson GP. Tuberculosis and lung damage: from epidemiology to pathophysiology. Eur Respir Rev. 2018;27(147):170077. Ravimohan S, Kornfeld H, Weissman D, Bisson GP. Tuberculosis and lung damage: from epidemiology to pathophysiology. Eur Respir Rev. 2018;27(147):170077.
3.
go back to reference Pasipanodya JG, Miller TL, Vecino M, Munguia G, Garmon R, Bae S, Drewyer G, Weis SE. Pulmonary impairment after tuberculosis. Chest. 2007;131(6):1817–24.CrossRef Pasipanodya JG, Miller TL, Vecino M, Munguia G, Garmon R, Bae S, Drewyer G, Weis SE. Pulmonary impairment after tuberculosis. Chest. 2007;131(6):1817–24.CrossRef
4.
go back to reference Plit M, Anderson R, Van Rensburg C, Page-Shipp L, Blott J, Fresen J, Feldman C. Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis. Eur Respir J. 1998;12(2):351–6.CrossRef Plit M, Anderson R, Van Rensburg C, Page-Shipp L, Blott J, Fresen J, Feldman C. Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis. Eur Respir J. 1998;12(2):351–6.CrossRef
5.
go back to reference 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 Pulmonary Medicine. 2016;16:58.CrossRef 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 Pulmonary Medicine. 2016;16:58.CrossRef
6.
go back to reference Akkara SA, 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.CrossRef Akkara SA, 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.CrossRef
7.
go back to reference Harries AD, Ade S, Burney P, Hoa NB, Schluger NW, Castro JL. Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment. Int J Tuberc Lung Dis. 2016;20(8):1010–4.CrossRef Harries AD, Ade S, Burney P, Hoa NB, Schluger NW, Castro JL. Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment. Int J Tuberc Lung Dis. 2016;20(8):1010–4.CrossRef
8.
go back to reference van Kampen SC, Wanner A, Edwards M, Harries AD, Kirenga BJ, Chakaya J, Jones R. International research and guidelines on post-tuberculosis chronic lung disorders: a systematic scoping review. BMJ Glob Health. 2018;3(4):e000745. van Kampen SC, Wanner A, Edwards M, Harries AD, Kirenga BJ, Chakaya J, Jones R. International research and guidelines on post-tuberculosis chronic lung disorders: a systematic scoping review. BMJ Glob Health. 2018;3(4):e000745.
9.
go back to reference Duong M, Islam S, Rangarajan S, Leong D, Kurmi O, Teo K, Killian K, Dagenais G, Lear S, Wielgosz A, et al. Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV<sub>1</sub> (PURE): an international, community-based cohort study. Lancet Glob Health. 2019;7(5):e613–23.CrossRef Duong M, Islam S, Rangarajan S, Leong D, Kurmi O, Teo K, Killian K, Dagenais G, Lear S, Wielgosz A, et al. Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV<sub>1</sub> (PURE): an international, community-based cohort study. Lancet Glob Health. 2019;7(5):e613–23.CrossRef
10.
go back to reference Maguire GP, Anstey NM, Ardian M, Waramori G, Tjitra E, Kenangalem E, Handojo T, Kelly PM. 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.PubMed Maguire GP, Anstey NM, Ardian M, Waramori G, Tjitra E, Kenangalem E, Handojo T, Kelly PM. 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.PubMed
11.
go back to reference Fiogbe AA, Agodokpessi G, Tessier JF, Affolabi D, Zannou DM, Ade G, Anagonou S, Raherison-Semjen C, Marcy O. Prevalence of lung function impairment in cured pulmonary tuberculosis patients in Cotonou, Benin. Int J Tuberc Lung Dis. 2019;23(2):195–202.CrossRef Fiogbe AA, Agodokpessi G, Tessier JF, Affolabi D, Zannou DM, Ade G, Anagonou S, Raherison-Semjen C, Marcy O. Prevalence of lung function impairment in cured pulmonary tuberculosis patients in Cotonou, Benin. Int J Tuberc Lung Dis. 2019;23(2):195–202.CrossRef
12.
go back to reference Ralph AP, Kenangalem E, Waramori G, Pontororing GJ, Sandjaja TE, Maguire GP, Kelly PM, Anstey NM. High morbidity during treatment and residual pulmonary disability in pulmonary tuberculosis: under-recognised phenomena. PLoS One. 2013;8(11):e80302.CrossRef Ralph AP, Kenangalem E, Waramori G, Pontororing GJ, Sandjaja TE, Maguire GP, Kelly PM, Anstey NM. High morbidity during treatment and residual pulmonary disability in pulmonary tuberculosis: under-recognised phenomena. PLoS One. 2013;8(11):e80302.CrossRef
13.
go back to reference Hnizdo E, Singh T, Churchyard G. Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment. Thorax. 2000;55(1):32–8.CrossRef Hnizdo E, Singh T, Churchyard G. Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment. Thorax. 2000;55(1):32–8.CrossRef
14.
go back to reference Gingo MR, George MP, Kessinger CJ, Lucht L, Rissler B, Weinman R, Slivka WA, McMahon DK, Wenzel SE, Sciurba FC, et al. Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era. Am J Respir Crit Care Med. 2010;182(6):790–6.CrossRef Gingo MR, George MP, Kessinger CJ, Lucht L, Rissler B, Weinman R, Slivka WA, McMahon DK, Wenzel SE, Sciurba FC, et al. Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era. Am J Respir Crit Care Med. 2010;182(6):790–6.CrossRef
15.
go back to reference Gingo MR, He J, Wittman C, Fuhrman C, Leader JK, Kessinger C, Lucht L, Slivka WA, Zhang Y, McMahon DK, et al. Contributors to diffusion impairment in HIV-infected persons. Eur Respir J. 2014;43(1):195–203.CrossRef Gingo MR, He J, Wittman C, Fuhrman C, Leader JK, Kessinger C, Lucht L, Slivka WA, Zhang Y, McMahon DK, et al. Contributors to diffusion impairment in HIV-infected persons. Eur Respir J. 2014;43(1):195–203.CrossRef
16.
go back to reference Patil S, Patil R, Jadhav A. Pulmonary functions' assessment in post-tuberculosis cases by spirometry: obstructive pattern is predominant and needs cautious evaluation in all treated cases irrespective of symptoms. Int J Mycobacteriol. 2018;7(2):128–33.CrossRef Patil S, Patil R, Jadhav A. Pulmonary functions' assessment in post-tuberculosis cases by spirometry: obstructive pattern is predominant and needs cautious evaluation in all treated cases irrespective of symptoms. Int J Mycobacteriol. 2018;7(2):128–33.CrossRef
17.
go back to reference Ross J, Ehrlich RI, Hnizdo E, White N, Churchyard GJ. Excess lung function decline in gold miners following pulmonary tuberculosis. Thorax. 2010;65(11):1010–5.CrossRef Ross J, Ehrlich RI, Hnizdo E, White N, Churchyard GJ. Excess lung function decline in gold miners following pulmonary tuberculosis. Thorax. 2010;65(11):1010–5.CrossRef
18.
go back to reference Plit ML, Anderson R, Van Rensburg CE, Page-Shipp L, Blott JA, Fresen JL, Feldman C. Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis. Eur Respir J. 1998;12(2):351–6. Plit ML, Anderson R, Van Rensburg CE, Page-Shipp L, Blott JA, Fresen JL, Feldman C. Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis. Eur Respir J. 1998;12(2):351–6.
19.
go back to reference Allwood B, van der Zalm M, Makanda G, Mortimer K, Andre F. S a, Uzochukwu E, Denise E, Diane G, Graeme H, Olena I et al: the long shadow post-tuberculosis. Lancet Infect Dis. 2019;19(11):1170–1.CrossRef Allwood B, van der Zalm M, Makanda G, Mortimer K, Andre F. S a, Uzochukwu E, Denise E, Diane G, Graeme H, Olena I et al: the long shadow post-tuberculosis. Lancet Infect Dis. 2019;19(11):1170–1.CrossRef
20.
go back to reference O'Dell MW, Lubeck DP, O'Driscoll P, Matsuno S. Validity of the Karnofsky performance status in an HIV-infected sample. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10(3):350–7.PubMed O'Dell MW, Lubeck DP, O'Driscoll P, Matsuno S. Validity of the Karnofsky performance status in an HIV-infected sample. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10(3):350–7.PubMed
21.
go back to reference Ralph AP, Ardian M, Wiguna A, Maguire GP, Becker NG, Drogumuller G, Wilks MJ, Waramori G, Tjitra E, Sandjaja, et al. A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax. 2010;65(10):863–9.CrossRef Ralph AP, Ardian M, Wiguna A, Maguire GP, Becker NG, Drogumuller G, Wilks MJ, Waramori G, Tjitra E, Sandjaja, et al. A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax. 2010;65(10):863–9.CrossRef
22.
go back to reference Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38.CrossRef Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38.CrossRef
23.
go back to reference Koegelenberg CFN, Swart F, Irusen EM. Guideline for office spirometry in adults, 2012. S Afr Med J. 2012;103(1):52–62.CrossRef Koegelenberg CFN, Swart F, Irusen EM. Guideline for office spirometry in adults, 2012. S Afr Med J. 2012;103(1):52–62.CrossRef
24.
go back to reference Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MSM, Zheng J, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;40(6):1324–43.CrossRef Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MSM, Zheng J, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;40(6):1324–43.CrossRef
25.
go back to reference van Zyl Smit RN, Pai M, Yew WW, Leung CC, Zumla A, Bateman ED, Dheda K. Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD. Eur Respir J. 2010;35(1):27–33.CrossRef van Zyl Smit RN, Pai M, Yew WW, Leung CC, Zumla A, Bateman ED, Dheda K. Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD. Eur Respir J. 2010;35(1):27–33.CrossRef
26.
go back to reference Culver BH, Graham BL, Coates AL, Wanger J, Berry CE, Clarke PK, Hallstrand TS, Hankinson JL, Kaminsky DA, MacIntyre NR, et al. Recommendations for a standardized pulmonary function report. An official American Thoracic Society technical statement. Am J Respir Crit Care Med. 2017;196(11):1463–72.CrossRef Culver BH, Graham BL, Coates AL, Wanger J, Berry CE, Clarke PK, Hallstrand TS, Hankinson JL, Kaminsky DA, MacIntyre NR, et al. Recommendations for a standardized pulmonary function report. An official American Thoracic Society technical statement. Am J Respir Crit Care Med. 2017;196(11):1463–72.CrossRef
27.
go back to reference Criée CP, Baur X, Berdel D, Bösch D, Gappa M, Haidl P, Husemann K, Jörres RA, Kabitz HJ, Kardos P, et al. Standardization of Spirometry: 2015 Update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine. Pneumologie. 2015;69(3):147–64.CrossRef Criée CP, Baur X, Berdel D, Bösch D, Gappa M, Haidl P, Husemann K, Jörres RA, Kabitz HJ, Kardos P, et al. Standardization of Spirometry: 2015 Update. Published by German Atemwegsliga, German Respiratory Society and German Society of Occupational and Environmental Medicine. Pneumologie. 2015;69(3):147–64.CrossRef
28.
go back to reference Pohlert T: The Pairwise Multiple Comparison of Mean Ranks Package (PMCMR) 2014. http://CRANR-projectorg/package=PMCMR. Pohlert T: The Pairwise Multiple Comparison of Mean Ranks Package (PMCMR) 2014. http://CRANR-projectorg/package=PMCMR.
30.
go back to reference Organization WH: Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity: World Health Organization; 2011. Organization WH: Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity: World Health Organization; 2011.
32.
go back to reference Willcox PA, Ferguson AD. Chronic obstructive airways disease following treated pulmonary tuberculosis. Respir Med. 1989;83(3):195–98. Willcox PA, Ferguson AD. Chronic obstructive airways disease following treated pulmonary tuberculosis. Respir Med. 1989;83(3):195–98.
33.
go back to reference Romanowski K, Balshaw RF, Benedetti A, Campbell JR, Menzies D, Ahmad Khan F, Johnston JC. Predicting tuberculosis relapse in patients treated with the standard 6-month regimen: an individual patient data meta-analysis. Thorax. 2019;74(3):291.CrossRef Romanowski K, Balshaw RF, Benedetti A, Campbell JR, Menzies D, Ahmad Khan F, Johnston JC. Predicting tuberculosis relapse in patients treated with the standard 6-month regimen: an individual patient data meta-analysis. Thorax. 2019;74(3):291.CrossRef
34.
go back to reference Ranzani OT, Rodrigues LC, Bombarda S, Minto CM, Waldman EA, Carvalho CRR. Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010–15: a population-based, longitudinal study. Lancet Infect Dis. 2020;20(1):123–32.CrossRef Ranzani OT, Rodrigues LC, Bombarda S, Minto CM, Waldman EA, Carvalho CRR. Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010–15: a population-based, longitudinal study. Lancet Infect Dis. 2020;20(1):123–32.CrossRef
35.
go back to reference Vecino M, Pasipanodya JG, Slocum P, Bae S, Munguia G, Miller T, Fernandez M, Drewyer G, Weis SE. Evidence for chronic lung impairment in patients treated for pulmonary tuberculosis. J Infect Public Health. 2011;4(5–6):244–52.CrossRef Vecino M, Pasipanodya JG, Slocum P, Bae S, Munguia G, Miller T, Fernandez M, Drewyer G, Weis SE. Evidence for chronic lung impairment in patients treated for pulmonary tuberculosis. J Infect Public Health. 2011;4(5–6):244–52.CrossRef
36.
go back to reference Stek C, Allwood B, Walker NF, Wilkinson RJ, Lynen L, Meintjes G. The immune mechanisms of lung parenchymal damage in tuberculosis and the role of host-directed therapy. Front Microbiol. 2018;9:2603.CrossRef Stek C, Allwood B, Walker NF, Wilkinson RJ, Lynen L, Meintjes G. The immune mechanisms of lung parenchymal damage in tuberculosis and the role of host-directed therapy. Front Microbiol. 2018;9:2603.CrossRef
37.
go back to reference Ravimohan S, Tamuhla N, Kung S-J, Nfanyana K, Steenhoff AP, Gross R, Weissman D, Bisson GP. Matrix Metalloproteinases in tuberculosis-immune reconstitution inflammatory syndrome and impaired lung function among advanced HIV/TB co-infected patients initiating antiretroviral therapy. EBioMedicine. 2015;3:100–7.CrossRef Ravimohan S, Tamuhla N, Kung S-J, Nfanyana K, Steenhoff AP, Gross R, Weissman D, Bisson GP. Matrix Metalloproteinases in tuberculosis-immune reconstitution inflammatory syndrome and impaired lung function among advanced HIV/TB co-infected patients initiating antiretroviral therapy. EBioMedicine. 2015;3:100–7.CrossRef
38.
go back to reference George MP, Kannass M, Huang L, Sciurba FC, Morris A. Respiratory symptoms and airway obstruction in HIV-infected subjects in the HAART era. PLoS One. 2009;4(7):–e6328. George MP, Kannass M, Huang L, Sciurba FC, Morris A. Respiratory symptoms and airway obstruction in HIV-infected subjects in the HAART era. PLoS One. 2009;4(7):–e6328.
39.
go back to reference Pefura-Yone EW, Kengne AP, Balkissou AD, Magne-Fotso CG, Ngo-Yonga M, Boulleys-Nana JR, Efe-de-Melingui NR, Ndjeutcheu-Moualeu PI, Mbele-Onana CL, Kenmegne-Noumsi EC, et al. Prevalence of obstructive lung disease in an African country using definitions from different international guidelines: a community based cross-sectional survey. BMC Res Notes. 2016;9(1):124.CrossRef Pefura-Yone EW, Kengne AP, Balkissou AD, Magne-Fotso CG, Ngo-Yonga M, Boulleys-Nana JR, Efe-de-Melingui NR, Ndjeutcheu-Moualeu PI, Mbele-Onana CL, Kenmegne-Noumsi EC, et al. Prevalence of obstructive lung disease in an African country using definitions from different international guidelines: a community based cross-sectional survey. BMC Res Notes. 2016;9(1):124.CrossRef
Metadata
Title
Development of chronic lung impairment in Mozambican TB patients and associated risks
Authors
Celso Khosa
Nilesh Bhatt
Isabel Massango
Khalide Azam
Elmar Saathoff
Abhishek Bakuli
Friedrich Riess
Olena Ivanova
Michael Hoelscher
Andrea Rachow
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-1167-1

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