Get Permission Shettar, Sandhya, Sreelatha J, LakshmiDevi B P, Cleetus, Nandish Kumar K, and Srinivasan S: A study on association of obstructive airway disease in previously treated pulmonary tuberculosis patients


Introduction

Pulmonary tuberculosis (TB) and obstructive airway diseases are of growing concern in a developing country like India as we enter modernization. It has emerged as a global health challenge affecting all age groups, and the inflow of such sufferers has multiplied in the recent past, rendering it a burden on the healthcare system. An extensive number of TB patients develop post-tubercular respiratory disease. This COPD phenotype has been variably termed as post-tubercular obstructive respiratory disease.1

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, and pulmonary tuberculosis is the most common form.2 It is associated with frequent pulmonary damage despite microbiological cure, which causes progressive destruction of lung tissue, and this damage might not absolutely resolve after treatment.3, 4, 5 Patients with treated TB may remain lifelong sufferers of disabling structural and functional sequelae of the disease, which eventually impair quality of life.6, 7

Chronic Obstructive Pulmonary Disease (COPD), a common, preventable, and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with increased chronic inflammatory response in the airways and the lung to noxious particles or gases.8 Patients with treated pulmonary TB present signs of permanent impairment of their lung function. Impairment is variable in pattern and severity, ranging from none to severe, and indicates restrictive, obstructive or mixed patterns.9, 10, 11 Patients are segregated based on the clinical and radiological criteria and the GOLD classification as referred to in the study. Thus, establishing the pattern of obstructive airway involvement in post-PTB and determining the most effective relief regimen is crucial in the management of the same.

COPD and TB constitute significant public health challenges, especially in low and middle-income countries. Individuals with chronic respiratory disease additionally face higher all-cause mortality, even with only mild lung impairment.12, 13 In addition to pulmonary damage, extrapulmonary tuberculosis disease and drug toxicity can cause permanent impairment to other organ systems, as well as social and psychological sequelae.5

The World Health Organisation has envisioned that the prevalence will increase in the next 30 years, with a total of annual death higher than 4.5 million (TOPD).14 According to World Health Organization (WHO) reports that 9.6 million people developed active tuberculosis and 1.5 million died due to tuberculosis each year, making it the leading infectious cause of death globally.15, 16 In a nationwide survey of 13, 86 adults in South Africa results suggested that the strongest predictor of COPD was a history of PTB. Furthermore, the risk of COPD was more strongly associated with PTB than the tobacco smoking or exposure to smoke from biomass fuel.17 The history PTB increased the risk of COPD by 4.1 times for men and 1.7 times for women. The burden of Obstructive Lung Disease (BOLD) study had also proved the history of tuberculosis as a risk factor for developing airflow obstruction in later life. 4

There are few Indian studies evaluating the relationship between the history of pulmonary tuberculosis and COPD that reported a 13-46% of prevalence of airflow obstruction, and the prevalence increased with duration after treatment completion.18, 19, 20 It was also reported that the association of COPD with PTB constitutes a significant proportion of COPD patients in India, it affects younger people than the patient with conventional COPD, and they have more hospitalizations, reaffirming the idea that TOPD is a distinct clinical entity. 1 Very recently it has been that young patients, previously healthy and non-smokers, can develop residual chronic changes post-PTB, one year after completing the treatment. 21

Pulmonary tuberculosis has a substantial adverse impact on a patient’s quality of life. Patients perceived Health-Related Quality of Life (HRQoL) is decreased in all patients diagnosed with PTB.22 Perceptions of both mental and physical quality of life remain below the normal population.23 However, in a population of multi-drug resistant (MDR) tuberculosis (TB) patients, the decreased perception of HRQoL was still prevalent 18 months after the patients were deemed cured of TB.24 Adult PTB survivors have two-to-four fold higher odds of persistently abnormal spirometry compared with those without previous TB, which is associated with respiratory symptoms and reduced quality of life.25

India stands as the highest affected rate of TB burden and hence, there are more chances of getting a significant burden in TB-associated COPD. India is found to be placed in the second position after China in the mortality and morbidity cases due to obstructive airway diseases. There are very few studies done on TB-associated COPD in the present geographical location.1

It is still not known whether there is any difference in clinical presentation between smoking-related COPD and TB-associated chronic pulmonary disease.26 The majority of published studies available in the literature have been centered on investigating the effects of TB history on COPD prevalence though there are very limited data available regarding the effects of TB-associated COPD on Health-Related Quality of Life (HRQoL).27 Hence the objective of the present study was to evaluate the prevalence of obstructive airway disease in previously treated tuberculosis patients and evaluate the impact of post-TB obstructive airway disease on Quality of Life using St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C).

Materials and Methods

Prospective, Observational cross-sectional study was carried out over a period of 6 months in the Government Wellesley TB and Chest disease hospital attached to Vijayanagara Institute of Medical Sciences, Ballari District, Karnataka. The study was approved by the Institutional Ethics Committee and provided IEC number as TVMCP/IEC/V PD/2021-22/02. A total of 116 patients were involved in the study. Out of them 84 patients were diagnosed as PTB associated COPD and 32 patients were diagnosed as COPD. An informed consent was obtained from the study subjects after explaining about the methodology.

Patients with relapsed PTB or active PTB, with history of other pulmonary disorders such as interstitial lung cancer, unstable angina, congestive heart failure, Obstructive sleep apnea and pregnant women were excluded from the study.

The demographic questionnaire was constructed to obtain data on key variables like age, sex and weight. The medical data includes the duration of the disease, pharmacological treatment of the disease, duration of the therapy, smoking history and previous history of PTB. We performed the spirometry using MIR Spirobank Smart App-Based Spirometer (Ispirometer App) and the test was performed on Sputum smear negative patients. And then the patients were classified into four stages of airflow limitation (FEV1) as per the COPD GOLD Guidelines 2022. The Quality of Life of both groups of patients was assessed and compared by using a standard questionnaire St. George’s Respiratory Questionnaire (SGRQ-C) and the airflow limitation (FEV1) obtained by performing spirometry. We evaluated the prevalence of PTB associated COPD and compared the impact of TB associated COPD and COPD on the quality of life of the patients.

Statistical analysis

Data were compared as mean±SD. A probability value <0.05 was considered for statistical significance. Data from and survey-derived information was entered into an electronic spreadsheet (MS Excel). Results were summarized using MS Excel. Demographic characteristics, previous history, pulmonary function tests, and SGRQ-C data were used to assess response rates by comparing PTB associated COPD and COPD. All the tests were performed using IBM SPSS Statistics for Windows, version 23.0. (Armonk, NY: IBM Corp).

Results

Baseline characteristics of study subjects

In our study males were predominant compared to females and most of the patients fall under the age group of 51-70 yrs. Major population of the study subjects comprised of smokers than non- smokers shown in Figure 1. Prevalence of TB associated COPD among the COPD population was 72% shown in Figure 2. Symptoms of dyspnea and cough with sputum were significantly seen in both the study groups and the symptom of Hemoptysis was only seen in PTB associated COPD patients. Using the COPD GOLD guidelines 2022 study subjects based on airflow limitation (FEV1) were classified as mild, moderate, severe and very severe as detailed in Table 1. Clinically significant pulmonary impairment defined as an FEV1 <80% of the predicted value, was identified in all the study subjects being attributed to obstructive pattern and the obstruction was slightly more in TB associated COPD patients compared to COPD patients explaining more obstruction as shown in Figure 3.

Table 1

Characteristics of the patients in the study sample (n=116)

Characteristic

TB associated COPD

COPD

Gender

Male

65(77.4%)

27(84.4%)

Female

19(22.6%)

05(15.6%)

Age

18-30yrs

06(7.1%)

00(0.00%)

31-40yrs

07(8.3%)

00(0.00%)

41-50yrs

14(16.7%)

04(12.5%)

51-60yrs

25(29.8%)

10(31.3%)

61-70yrs

24(28.6%)

10(31.3%)

71-80yrs

07(8.3%)

07(21.8%)

Above 80yrs

01(1.2%)

01(3.1%)

Smoking

Smoker

52(61.9%)

24(75%)

Non-smoker

32(38.1%)

08(25%)

Previous history

With PTB

84(100%)

00(0.00%)

Without PTB

00(0.00%)

32(100%)

Symptoms

Dyspnea

77(94.04%)

31(93.75%)

Cough with sputum

60(71.42%)

19(50%)

Fever

26(33.33%)

08(29.42%)

Edema

08(8.3%)

06(17.64%)

Hemoptysis

04(5.9%)

00(0.00%)

Chest pain

02(1.1%)

01(5.8%)

COPD Stage

Mild

00(0.00%)

00(0.00%)

Moderate

04(4.8%)

02(6.3%)

Severe

21(25%)

08(25%)

Very severe

59(70.2%)

22(68.7%)

FEV1(mean±SD)

25.65±10.22

26.4±14.97

P-value

0.863

0.063

P-value (b/w groups)

0.039

Impact of demographic and clinical features on SGRQ-C components in terms of quality of life

Mean SGRQ scale scores in the study subjects were weighed according to demographic and clinical features. Symptoms scale score was greater among men and activity scale was significantly higher in women. SGRQ scores were significantly greater in older groups for all scales. Smokers presented significantly higher scores for only activity scales. SGRQ scores also worsened in a statistically significant manner as FEV1% over decreased. The impact of SGRQ components on the quality of life between two groups assessed, which presented that patients with TB associated COPD showed poor quality of life compared to patients with COPD shown in Figure 4.

Figure 1

a: Distribution of patients according to smoking status in two different groups; b: Distribution of the total study subjects according to smoking status

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/2406d9d6-492d-44f3-80bc-a1fa89a94858image1.png
Figure 2

Distribution of the total study subjects according to previoushistory of PTB

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/2406d9d6-492d-44f3-80bc-a1fa89a94858image2.png
Figure 3

Impact of lung function with TB associated COPD and COPD

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/2406d9d6-492d-44f3-80bc-a1fa89a94858image3.png
Figure 4

Impact of SGRQ-C components with TB associated COPD and COPD

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/2406d9d6-492d-44f3-80bc-a1fa89a94858image4.png
Table 2

St. George’s Respiratory Questionnaire scale scores by demographical and clinical characteristics

Symptoms

Activity

Impacts

Overall

Gender

Male

68.74

83.78

62.15

69.95

Female

68.51

91.86

66.65

74.72

Age

18-30yrs

73.5±19.5

89.2±18.7

65.6±28.9

74.3±23.4

31-40yrs

60.8±11.4

86.2±19.4

65.5±19.6

71±13.6

41-50yrs

69.5±12.5

85.6±16.7

61.3±23.2

70.2±15.8

51-60yrs

69.5±16.9

83.5±15.5

60.6±21.8

69.2±14.8

61-70yrs

69.8±14.2

86±8.5

64.8±23.8

71.7±18.2

71-80yrs

67±15.8

83.3±17.3

57.3±22.7

67±17.4

>80yrs

60.6±7.66

100±0

83.5±7.0

84.5±5.0

Symptoms(PTB associated COPD)

Dyspnea

69.4±15.2

86±17

66±20.2

72.5±15

Cough with sputum

72±15.1

85.2±17.2

66.6±20.9

73±15.5

Fever

72.9±14.5

84.1±15.8

67.7±19.8

73.7±14

Edema

60.2±9

94.2±12.2

66.3±18.3

73.7±8.6

Hemoptysis

69.8±9.2

77.2±17.5

47.6±27.8

60.6±20

Chest pain

82.9

59.34

59.34

63.51

(COPD)

Dyspnea

66.8±15

83.5±17.4

55.9±25.4

66.3±19.1

Cough with sputum

69.9±11

87.1±16.6

63±18.1

71.6±13.7

Fever

70.5±13

79.2±18.3

59.4±20.9

67.5±16.1

Edema

75.5±8.3

94.6±9.78

68±19

77.5±12.4

Hemoptysis

00

00

00

00

Chest pain

70.1±5.8

95.8±5.95

89.2±1.07

87.6±0.6

Smoking(PTB associated COPD)

Smoker

69.6±15.2

83.8±16.6

65.5±21.9

71.6±15.4

Non smoker

69.1±15.1

89.4±16.6

63.07±20

72.2±15.5

(COPD)

Smoker

66.7±16.8

81.3±18.4

53±26.2

64.1±20.4

Non smoker

68.9±5.5

90.7±11.9

68.3±17.2

75.3±10.2

P value

PTB associated COPD

69.57

85.83

65.02

72.04

COPD

66.92

83.96

55.78

66.38

P-value

0.198

0.298

0.023

0.049

Discussion

The present study was conducted to find the hospital-based prevalence of TB associated COPD and to evaluate its characteristic features. The result showed that almost two third of COPD (72%) patients had associated TB in the past. It was seen that patients with TB associated COPD had almost similar grades of airway obstruction as compared to smoking related COPD. This gives strong evidence in favor of the casual association between TB and the development of COPD.

In the present study, out of 116 patients male 92 (79.3%) predominates over female 24 (20.7%) which is similar to the study conducted by Aggarwal et al.,1 Upadhyay et al.,26 of FEV1 in patients.27

In the present study, the predicted value of FEV1 in patients with airflow limitation was 25.65±10.22 in TB associated COPD patients and 26.40±14.97 in COPD patients which is comparable to COPD of GOLD stage IV which is in contrast to the study that had airflow limitation comparable to COPD of GOLD stage III conducted by Kim et al.28 This different rate of FEV1 decline may reflect differences like airflow limitation between destroyed lung by TB and COPD.

In the present study, we found a high symptom burden and poor HRQoL across all components of the SGRQ, particularly in activity and impact components. Increasing dyspnea showed a significant association with poor HRQoL across all component scores and fev1 was also strongly associated with poor HRQoL which is in comparable to the study conducted by Ozoh et al.29

In our study among 84 TB associated COPD patients, 52(61.9%) were smokers and 32(38.1%) were nonsmokers. This result indicates that there is a significant contribution of smoking to parenchymal destruction as well as decreased FEV1 values. Hence, smoking is one of the confounding factors in our study compared to the study conducted by Kim et al.28

In the current study, the prevalence of TB associated COPD among the sample population was 72%. A similar study showed a prevalence of 16% among 500 patients conducted by Mohamed A et al and another similar study showed a prevalence of 32.4% conducted by Upadhyay et al.26

Various mechanisms have been proposed for the development of COPD in TB patients. It includes endobronchial involvement leading to airway obstruction, bronchiolar narrowing, and bronchiolitis obliterans caused from peribronchial fibrosis and extensive emphysematous changes caused by residual chronic or recurrent inflammation affecting lung compliance. A common link to the pathogenesis of both conditions may lie in the destruction of the pulmonary extracellular matrix due to the increased activity of matrix metalloproteinase enzymes precipitated by TB.

The risk of COPD has been found to increase with the increase in the radiological extent of TB, an increase in the number of previous TB episodes as well as with delay in initiating anti-TB therapy. In our study, we found that there is extensive parenchymal damage on Chest X-rays in TB associated COPD patients. Radiological findings are correlating with FEV1 values.

Conclusion

TB associated COPD constitutes a significant proportion of COPD in a hospital setting. It is an independent risk factor for obstructive airway disease in high TB burden countries. Post tubercular COPD as a cause of COPD in non-smokers should now be more recognized in countries where TB burden is high. The results of our study indicated that early diagnosis of TB and appropriate management and control of TB is as important as smoking cessation for reducing obstructive airway disease. Early identification of Post tubercular COPD and early initiation of treatment in these patients improves quality of life and reduces morbidity as well as mortality.

Conflicts of Interests

None declared.

Source of Funding

None.

Acknowledgements

None.

References

1 

D Aggarwal A Gupta A K Janmeja M Bhardwaj Evaluation of tuberculosis-associated chronic obstructive pulmonary disease at a tertiary care hospital: A case-control studyLung India20173454159

2 

S Patil R Patil A Jadhav Pulmonary functions' assessment in post-tuberculosis cases by spirometry: Obstructive pattern is predominant and needs cautious evaluation in all treated cases irrespective of symptomsIntl J Mycobacteriology20187212833

3 

S Ravimohan H Kornfeld D Weissman GP Bisson Tuberculosis and lung damage: from epidemiology to pathophysiologyEuro Respir Rev2018312714717007710.1183/16000617.0077-2017

4 

AF Amaral S Coton B Kato WC Tan M Studnicka C Janson 4.Amaral AF, Coton S, Kato B, Tan WC, Studnicka M, Janson C, Gislason T, Mannino D, Bateman ED, Buist S, Burney PG. Tuberculosis associates with both airflow obstruction and low lung function: BOLD results. European Respiratory Journal. 2015 Oct 1;46(4):1104-12.Eur Respir J2015464110412

5 

BW Allwood MM Van Der Zalm AF Amaral A Byrne S Datta U Egere Post-tuberculosis lung health: perspectives from the First International SymposiumInt J Tuberculosis Lung Dis20202488208

6 

G Birath J Caro R Malmberg BG Simonsson Airways obstruction in pulmonary tuberculosisScand J Respir Dis19664712736

7 

JH Lee JH Chang Lung function in patients with chronic airflow obstruction due to tuberculous destroyed lungRespir Med20039711123742

8 

JY Oh YS Lee KH Min GY Hur SY Lee KH Kang Difference in systemic inflammation and predictors of acute exacerbation between smoking-associated COPD and tuberculosis-associated COPDInt J Chronic Obstr Pulm Dis2018133381710.2147/COPD.S177371

9 

ML Plit R Anderson CE Van Rensburg L Page-Shipp JA Blott JL Fresen Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosisEur Respir J1998122351610.1183/09031936.98.12020351

10 

JG Pasipanodya TL Miller M Vecino G Munguia R Garmon S Bae Pulmonary impairment after tuberculosisChest20071316181724

11 

LM Ramos N Sulmonett C S Ferreira JF Henriques SS Miranda Functional profile of patients with tuberculosis sequelae in a university hospitalJ Bras Pneumol2006321437

12 

K Romanowski B Baumann CA Basham FA Khan GJ Fox JC Johnston Long-term all-cause mortality in people treated for tuberculosis: a systematic review and meta-analysisLancet Infect Dis20191910112937

13 

M Duong S Islam S Rangarajan D Leong O Kurmi K Teo Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort studyLancet Glob Health20197561323

14 

WHO. Projection of mortality and causes of death, 2015 and 2030World Health Organisation2015https://globaltrends.thedialogue.org/publication/projections-of-mortality-and-causes-of-death-2015-and-2030/

15 

CR Horsburgh CE Barry C Lange Treatment of TuberculosisN Engl J Med201537322214960

16 

WHO. Global tuberculosis report Geneva: World Health Organisation2015https://iris.who.int/bitstream/handle/10665/191102/9789241565059_eng.pdf?sequence=1

17 

RI Ehrlich N White R Norman R Laubscher K Steyn C Lombard Predictors of chronic bronchitis in South African adultsInt J Tuberc Lung Dis20048336976

18 

B Brashier S Gangavane S Valsa S N Gaikwad S V Ghorpade S Mandrekar Almost half the patients treated for pulmonary tuberculosis (TB) show evidence of obstructive airways disease (OAD)Eur Respir J200730159

19 

D Gothi DV Shah JM Joshi 19.Gothi D, Shah DV, Joshi JM. Clinical profile of diseases causing chronic airflow limitation in a tertiary care centre in India. JAPI. 2007 Aug;55:551-5.JAPI2007555515

20 

SK Verma KV Narayan S Kumar A study on prevalence of obstructive airway disease among post pulmonary tuberculosis patientsPulmon200911147

21 

BW Allwood E Maasdorp GJ Kim CB Cooper J Goldin RN Van Zyl-Smit Transition from Restrictive to Obstructive Lung Function Impairment During Treatment and Follow-Up of Active TuberculosisInt J Chron Obstruct Pulmon Dis20201510394710.2147/COPD.S219731

22 

CA Marra F Marra L Colley S Moadebi RK Elwood JM Fitzgerald Health-related quality of life trajectories among adults with tuberculosis: differences between latent and active infectionChest20081332396403

23 

AN Aggarwal D Gupta AK Janmeja SK Jindal Assessment of health-related quality of life in patients with pulmonary tuberculosis under programme conditionsInt J Tuberc Lung Dis201317794753

24 

E Hnizdo T Singh G Churchyard Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatmentThorax2000551328

25 

O Nkereuwem E Nkereuwem O Owolabi P Johm U Egere K Mortimer Perspectives of TB survivors and policymakers on post-TB disabilityPublic Health Action20231311722

26 

G Upadhyay P Damor Prevalence of TB associated chronic obstructive pulmonary disease in patients with COPD attending at tertiary care hospital in Ahmedabad: A case control studyIp J Immunol Respir Med2018326871

27 

HI Yakar H Gunen E Pehlivan S Aydogan The role of tuberculosis in COPDInt J Chron Obstruct Pulmon Dis201717323910.2147/COPD.S116086

28 

SJ Kim J Lee YS Park CH Lee SM Lee JJ Yim Effect of airflow limitation on acute exacerbations in patients with destroyed lungs by tuberculosisJ Korean Med Sci201530673742

29 

OB Ozoh OO Ojo MG Dania SK Dede OA Adegboyega NK Irurhe Impact of post-tuberculosis lung disease on health-related quality of life in patients from two tertiary hospitals inAfr J Thorac Crit Care Med20212724652



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Received : 28-07-2023

Accepted : 10-10-2023


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https://doi.org/10.18231/j.ijirm.2023.020


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