Indian J Allergy Asthma Immunol 2009; 23(2) : 95-99

95
Address for correspondence: Dr. S.K. Verma, Professor, Department
of Pulmonary Medicine, Chhatrapati Sahuji Maharaj Medical
University, UP, Lucknow, India-226003, Phone No: 0522-2254346,
e-mail:drskverma@rediffmail.com
IJAAI, 2009, XXIII (2) p 95-99.
Post Tubercular Obstructive Airway Impairment
S.K. Verma, S. Kumar, Kiran Vishnu Narayan, R. Sodhi
Department of Pulmonary Medicine, Chhatrapati Sahuji Maharaj Medical University,
Lucknow, Uttar Pradesh, India
Abstract
Obstructive airway disease has many causes. Tuberculosis, which can be a cause of this has not been
studied in detail. Even the organisations, like GOLD and GINA, authority figures in chronic
obstructive pulmonary disease (COPD) and ASTHMA, respectively have not recognized, treated
pulmonary TB as an etiological factor, which again shows that post pulmonary tuberculosis obstructive
airway disease is a clinical entity in its infancy. Post tubercular impairment can manifest as reversible
or irreversible obstructive airway disease, mixed defect or as pure restrictive defects. Immunological
mechanisms have been postulated as a cause of Post tubercular asthma. Cavitation, extensive fibrosis,
bulla formation and bronchiectasis implicated in the genesis of COPD caused by the destroyed lung
due to pulmonary tuberculosis. Only a few studies have been done to identify this entity, but all the
studies have definitely concluded that such an entity exists. However, the exact abnormality that results
from tuberculosis infection has to be considered in detail with future studies and a better understanding
of the pathophysiology of airflow limitation may point the way to therapeutic strategies for control
of symptoms in these patients.
Key Words: Pulmonary Tuberculosis, Post tubercular airway impairment, Obstructive airway disease
Tuberculosis, which can be a cause of this, has not
been studied in detail. For many persons with
tuberculosis, microbiological cure is just the
beginning, not the end of their illness. Post tuberculosis
pulmonary impairment has emerged as a distinct
clinical entity, which is almost indistinguishable
from other forms
2,3
and hence we review this topic
further.
PREVIOUS STUDIES
Studies show that in patients with obstructive
airway impairement, post pulmonary tuberculosis can
be an important cause. It was observed to be an
etiologic factor of both COPD
4-7
and asthma.
8,9
Cavitation, extensive fibrosis, bulla formation and
REVIEW ARTICLE
INTRODUCTION
Tuberculosis, a disease of great antiquity has
become the most important communicable disease in
the world. With over 8.8 million new cases occurring
every year, 1.9 million belong to India (21%). It is
estimated that 2 out of every 5 Indians are infected
with TB and three lakh twenty two thousand Indians
die of TB every year.
1
In other words, it is estimated
that two persons die of tuberculosis every minute
1
.
Obstructive airway disease has many causes.
96 INDIAN J ALLERGY ASTHMA IMMUNOL 2009; 23(2)
bronchiectasis have been implicated in the genesis of
COPD caused by the destroyed lung due to pulmonary
Tuberculosis
5,6,10
. Nefedov and Popova attributed
that the main cause of better lung function was the
resolution of fresh inflammatory changes and that of
worse lung function was cicatricial transformation of
lung tissue.
11
Some workers have found association of history of
smoking in post tubercular patients who have
developed obstructive airway disease
4
. Pasipanodya
et al concluded that pulmonary impairment was more
common in cigarette smokers, but after adjusting for
demographic and other risk factors the difference did
not reach statistical significance(p=0.074)
12
. However,
the PLATINO study
13
found that airflow obstruction
remained unchanged even after adjustment for
confounding by age, sex, schooling, ethnicity, smoking,
exposure to dust and smoke, respiratory morbidity in
childhood and current morbidity.
The average duration of onset of obstructive airway
disease has been found variable. Study undertaken by
Hnizdo et al found that the average time between the
diagnosis of the last episode of tuberculosis and the
lung function test was 4.6 years (range one month to
31 years)
14
. The loss of lung function was highest
within six months of the diagnosis of tuberculosis and
stabilised after 12 months when the loss was
considered to be chronic.
The most common complex clinico-physiological
manifestations of pulmonary dysfunctions was found
by Nefedov and Smirnova as functional changes in
lung tissue characterised by hyperinflation and
restriction of the lungs and rise or decline of their
elasticity. Disorders of bronchial patency and
pulmonary gas exchange were second in their detection
rate, most commonly manifested by impaired minor
bronchi flow rate and decline in lung capacity
15
.
An association between type of healed lesions
present and degree of impairment present was also
sought. A study of Rajasekharan et al.
8
concluded
that patients with moderate and far advanced healed
lesions on chest skiagram had more persistent
symptoms and low PEFR requiring prolonged
corticosteroid administration and there was no relapse
of pulmonary tuberculosis even after prolonged
steroid administration. Pathological changes such as
emphysematous change on the radiograph could be
considered as an important cause of obstructive
ventilatory impairment
16
. Plit et al found that the
extent of lung infiltration (radiographic score) both at
the outset and after chemotherapy was significantly
and negatively related to forced expiratory volume in
one second (FEV1).
17
Patients of post pulmonary tuberculosis had
variable presentation in lung function testing. Lee and
Chang, 2003
18
compared lung function in patients
with chronic airflow limitation due to tuberculous
destroyed lung and COPD patients and concluded that
forced vital capacity (FVC) and post bronchodilator
forced expiratory volume in 1st second (FEV1) of
post tuberculous patients were lower compared to
those of COPD. Here bronchodilator therapy could be
useful for treating chronic airflow limitation in post
tubercular cases especially those presenting with
wheezing. Similarly case control study by
Pasipanodya et al comparing pulmonary function in
107 prospectively identified pulmonary tuberculosis
patients and 210 latent tuberculosis infection (LTBI)
patients who had completed at least 20 weeks of
therapy showed that impairment was present in 59%
of tuberculosis subjects and 20% of latent tuberculosis
infection controls. Forced vital capacity (FVC),
Forced expiratory volume in 1 second (FEV1), and
FEV1: FVC ratio and Mid Forced Expiratory Flow
(FEF25-75) were significantly lower in treated
pulmonary tuberculosis patients than the comparison
group. After adjusting for risk, it was found that
survivors of tuberculosis were 5.4 times more likely
to have abnormal PFTs than LTBI patients.
12
De
Valliere and Barker in a study to find out the residual
lung damage after completion of treatment for
multidrug resistant tuberculosis showed that, 31 out
of the 33 patients had abnormal lung function tests.
The median FEV1 was 63% and FVC was 57% of the
predicted value. Restrictive and combined obstructive
and restrictive lung function patterns were the
predominant abnormalities
10
. A Japanese study
investigated 102 patients for blood gases, spirometry,
and right cardiac catheterization and divided patents
into Group A (n = 38) had FEV1% of 55% or lower
and Group B (n = 64), FEV1% above 55%. Results
published by them showed that the patients of Group
A tended to show more severe hypoxemia and tissue
hypoxia than the patients of Group B and the patients
of Group A tended to show worse values of pulmonary
hemodynamics than the patients of Group B.
12
Plit et
al investigated 74 patients who completed the
treatment programme. Improvement in lung function
occurred in 54% of patients, but residual airflow
limitation or a restrictive pattern was evident in 28%
and 24% of patients, respectively.
17
A study
undertaken by Hnizdo et al found that the estimated
average chronic deficit in forced expiratory volume in
one second (FEV (1)) after one, two, and three or more
episodes of tuberculosis was 153 ml, 326 ml, and 410
ml, respectively. The corresponding deficits for forced
vital capacity (FVC) were 96 ml, 286 ml, and 345 ml.
The percentage of subjects with chronic airflow
impairment (FEV1<80% predicted) was 18.4% in
those with one episode, 27.1% in those with two, and
35.2% in those with three or more episodes of
tuberculosis.
14
. In the PLATINO study,
13
the overall
prevalence of airflow obstruction (forced expiratory
volume in one second/forced vital capacity post-
bronchodilator <0.7) was 30.7% among those with a
history of tuberculosis, compared with 13.9% among
those without a history. The association of TB with
FEV1 values (mean difference 0.35 mL) was stronger
than for FVC (0.25 mL) and, as a result, the FEV1/
FVC ratio showed a marked reduction, characterised
by an obstructive pattern.
Even lung diffusion capacity of pulmonary
tuberculosis patients was changed in post pulmonary
tuberculosis. Study by Nefedov et al in 159 patients
with focal, infiltrative, disseminated and fibro
cavernous tuberculosis showed a decrease in DLCO
in half of the patients with disseminated and fibro
cavernous tuberculosis and in less than one/fifth of
the patients with focal and infiltrative tuberculosis.
19
It has been also observed that effective
chemotherapy decreases the likelihood of development
of obstructive lung disease. Deterioration of lung
function was seen mainly during ineffective
chemotherapy, while rarely during successful
chemotherapy
16
Hence the results underline the importance of
controlling tuberculosis and occupational exposures
as well as smoking in reducing chronic respiratory
morbidity
19
.
PERSONAL EXPERIENCE
A prospective study was conducted on 92 patients
in the Department of Pulmonary medicine, Chhatrapati
Shahuji Maharaj Medical University, Uttar Pradesh,
Lucknow from September 2007 to August 2008
20
.
Patients diagnosed as a case of pulmonary
tuberculosis, taken a full course of anti tubercular
chemotherapy, with more than 12 years of age, sputum
smear for AFB negative, had healed radiological
lesions at time of presentation and had negative history
of obstructive airway disease before occurrence of
pulmonary tuberculosis were included. Pregnant and
moribund patients were excluded from the study.
The authors found that only 15(16.3%) patients had
obstructive airway disease by spirometry criteria.
Out of the 15 patients, only 3 (20%) were having
reversible phenomenon; 12(80%) having irreversible
phenomenon.21 patients had mixed obstructive with
restrictive disorder (22.80%). Restrictive pathology
was seen in 37 patients (40.21%). Among the 21
patients with mixed defect, 4 patients (19.04%) had
reversible type of obstruction and 17 patients
(80.95%) had irreversible obstruction along with
restrictive defect. After 6 weeks of therapy with
medications, 11 patients showed improvement of post
bronchodilator FEV1<10% and 5 patients had
improvement in post bronchodilator FEV1of >10%.
After 12 weeks of therapy, 14 patients had improved
by <10% and 5 patients sustained their improvement
in post bronchodilator FEV1% of 10%. Patients with
minimal healed lesion had a post bronchodilator
FEV1% of 50-80% in majority (8 patients or 53.6%).
Six patients with minimal healed lesions (40%) had a
post bronchodilator (BD) FEV1% of 31 50% and 1
patient had post bronchodilator FEV1% <30%.
DISCUSSION
Pulmonary impairment associated with obstructive
airways disease is recognised as a common
complication of advanced tuberculosis. Post-
tuberculosis airway obstruction is a separate clinical
entity. It requires insight, understanding and evaluation
of its evolution, clinical course and management. The
exact pathogenesis of the development of this disorder
is unclear. A hypothesis has been created based on
immunological mechanisms. Both Pulmonary
tuberculosis and obstructive airway disease especially
POST TUBERCULAR OBSTRUCTIVE AIRWAY IMPAIRMENT 97
98 INDIAN J ALLERGY ASTHMA IMMUNOL 2009; 23(2)
bronchial asthma do not reach peak of activity at the
same time due to different immunological mechanisms.
The Th1 and Th2 subgroups of lymphocytes regulate
development of tuberculosis and bronchial asthma,
respectively and their levels are not enhanced
simultaneously. Studies support this hypothesis by
demonstrating an increased proportion of Th-2
lymphocytes in the peripheral blood and airway of
patients with asthmatic disorders
20,21
. After
antitubercular treatment, the enhanced levels of Th-
1 come down and a proportion of patients develop Th-
2 mediated airway obstruction which on aggravation
emerges as bronchial asthma
22,23
.
Studies on genetics, immuno-pathogenesis and
molecular biology are, in fact, required to better
understand this clinical condition. Majority of the
patients affected are more than 40 years of age as
observed in many studies. The time of occurrence of
post-tuberculosis airway disease was variable, nearly
50% of the study group in various studies developed
it within one year of stopping chemotherapy
8
, while
the rest developed later
14
.
Tuberculosis can cause chronic impairment of lung
function which increases incrementally with the
number of episodes of tuberculosis
14
. However, some
studies say that tobacco smoking and biomass smoke
inhalation, in addition to the risk of TB, may compound
the airflow obstruction caused by TB
24-27
. A review
suggest that subjects smoking 20 cigarettes/ day are
two to four times more likely to present with TB than
in nonsmokers
27.
In the Platino study
13
, prevalence of
smoking was found to be 29.2%. The study conducted
by Rajasekharan et al.
8
, showed that 20 patients out
of 55 were smokers (36%). The study conducted by
Mohan et al.,
7
showed that all males were smokers
with 22.311.2 pack and all women were exposed to
domestic biomass.
Majority of the studies, including that of ours,
observed that, most common abnormality on
spirometry was restrictive lung disease, followed by
irreversible obstructive airway disease. Nefedov and
Smirnova
15
showed that among 100 patients with
destructive pulmonary TB, majority had a restrictive
lung pathology. Yasuda et al.,
16
found that out of 102
patients selected, 38 patients had FEV1% of 55%
or lower and 64 patients had FEV1% of above 55%.
Most tuberculsis patients with moderate to far
advanced post-treatment residual lung lesions exhibit
symptoms of impaired pulmonary functions due to
persistent airways obstruction. The study carried out
by Rajasekharan et al.,
8
showed that there were 14
patients out of 55 patients with minimal healed lesions;
33 had moderate healed lesion and 3 had far advanced
lesions. Possible mechanisms postulated by him
include bronchial stenosis and lung scarring, and, in
addition, similarly to exposure to smoke. TB increases
the activity of the matrix metalloproteinase enzymes,
contributing to pulmonary damage
28
. It is postulated
that the leading factor of a decrease in DLCO in the
patients with disseminated and fibro cavernous
tuberculosis was the reduction of the lung respiratory
surface resulting from a decrease in the effective
alveolar volume, the leading factor in infiltrative
tuberculosis was a decrease in alveolo-capillary
membrane permeability
29
.
CONCLUSION
Concluding all the studies up to date there is
indeed an important contribution of tuberculosis

to
airflow obstruction, linking two of the most common
ailments

in the world. For many persons with
tuberculosis, microbiological cure is just the
beginning, not the end of their illness. The prevention
and adequate treatment of tuberculosis would reduce
the burden

of airflow obstruction in all countries
especially the developing countries.

However, the
exact abnormality that results from tuberculosis
infection has to be considered in detail with future
studies and a better understanding of the patho-
physiology of airflow limitation may point the way to
therapeutic strategies for control of symptoms in these
patients.
REFERENCES
1. Global tuberculosis control: surveillance, planning, financing.
WHO report 2007. Geneva, World Health Organization (WHO/
HTM/TB/2007.376).
2. Macnee W. Chronic Bronchitis and Emphysema: Seaton A,
Seaton D, Leitch AG. Crofton and Douglass Respiratory
Disease, United Kingdom: Blackwell Science 2002; pp 616-
617.
3. Leitch AG. Pulmonary tuberculosis: Clinical features in: Seaton
A, Seaton D, Leitch AG, editors. Crofton and Douglasss
Respiratory Disease, United Kingdom: Blackwell Science 2002;
523.
4. Snider GL, Doctor L, Demas TA, Shaw AR: Obstructive
airway disease in patients with treated pulmonary tuberculosis.
Am Rev Respir Dis 1971; 103: 625-640.
5. Hassan IS, Al-Jahdali HH: Obstructive airways disease in
patients with significant post tuberculous lung scarring. Saudi
Med J 2005; 26: 1155-7.
6. Willcox PA, Ferguson AD. Chronic obstructive airways disease
following treated pulmonary tuberculosis. Respir Med 1989;
83: 195-198.
7. Mohan A, Premanand R, Reddy LN, Rao MH, Sharma SK.
Epidemiology and outcome of acute exacerbation of chronic
obstructive pulmonary disease; experience at a tertiary care
centre. Am J Respir Crit Care Med 2002; 165: A590.
8. Rajasekharan S, Savitri S, Jeyaganesh D. Post tuberculosis
bronchial Asthma. Ind J Tub 2001; 48: 139.
9. Ehrlich RI, White N, Norman R, Laubscher R, Steyn K,
Lombard C, Bradshaw D. Wheeze, asthma diagnosis and
medication use: a national adult survey in a developing country:
Thorax 2005; 60: 895-901.
10. De valliere S, Barker RD. Residual Lung damage after
completion of treatment for multi drug- resistant tuberculosis.
Int J Tuberc Lung Dis 2004 Jun; 8: 767-71
11. Nefedov VB, Popova LA. Study on patients with recurrent
tuberculosis and ineffective primary treatment in the intensive
phase of controlled chemotherapy: Probl Tuberk 2002; 12:
29-32.
12. Pasipanodya JG, Miller TL, Vecino M, Munguia G, Garmon
R, Bae S, Drewyer G, Weis SE. Post Tuberculosis pulmonary
impairment. Chest 2007 Jun; 131: 1817-24.
13. Menezes AMB, Hallal PC, Perez-Padilla R, Jardim JRB,
Muio A, Lopez MV, et al., Latin American Project for the
Investigation of Obstructive Lung Disease (PLATING) Team
Tuberculosis and airflow obstruction: evidence from the
PLATINO study in Latin America: Eur Respir J 2007; 30:
1180-1185.
14. Hnizdo E, Singh T, Churchyard GJ. Chronic pulmonary
function impairment caused by initial and recurrent pulmonary
tuberculosis following treatment. Thorax 2000; 55: 32-38.
15. Nefedov VB, Smirnova DG. Disorders of the pulmonary
function in patients with destructive tuberculosis. Probl Tuberk
1991; 11: 51-4
16. Yasuda J, Okada O, Kuriyama T, Nagao K, Yamagishi F,
Hashizume I, Suzuki A. Investigation of pulmonary
hemodynamics and chest X-ray findings in patients with
pulmonary tuberculosis sequelae and obstructive ventilatory
impairment. Kekkaku 1999 Jan; 74: 5-18.
17. Plit ML, Anderson R, Van Rensburg CEJ, 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: 351-356.
18. Lee JH, Chang JH. Lung function in patients with chronic
airflow limitations due to tuberculous destroyed lung. Respir
Med 2003; 97: 1237-1242.
19. Nefedov VB, Shergina EA, Popova LA. Pulmonary function
in patients with disseminated pulmonary tuberculosis: Probl
Tuberk Bolezn Legk 2007; 9: 27-30.
20. Verma SK, Narayan KV, Kumar S. A study on prevalence of
obstructive airway disease among post pulmonary tuberculosis
patients. Pulmon 2009; 11(1): 4-7
21. Romagnani S. Lymphocyte production by Human T-cells in
disease states. Ann Rev Immunol 1994; 12: 227.
22. Romagnani S. Role of the Th2 lymphocytes in the genesis of
allergic disorders and mechanics involved in their development
in Holgate S.T et al. (eds). Asthma: Physiology
Immunopathology and treatment Academic Press, London,
1993; Ch-13.
23. Holgate S. Mediator and cytokine mechanisms in asthma.
Thorax 1993; 48: 103.
24. Lowe CR. An association between smoking and respiratory
tuberculosis. BMJ 1956; 2: 1081-1086.
25. McKenna MT, Hutton M, Cauthen G, Onorato .IM. The
association between occupation and tuberculosis. A population-
based survey. Am J Respir Crit Care Med 1996; 154: 587-
593.
26. Mishra VK, Retherford RD, Smith KR. Biomass cooking
fuels and prevalence of tuberculosis in India. Int J Infect Dis
1999; 3: 119-129.
27. Perez-Padilla R, Perez-Guzman C, Baez-Saldana R, Torres-
Cruz A. Cooking with biomass stoves and tuberculosis: a
case control study. Int J Tuberc Lung Dis 2001; 5: 441-447.
28. Elkington PT, Friedland JS. Matrix metalloproteinases in
destructive pulmonary pathology. Thorax 2006; 61: 259-266.
29. Nefedov VB, Izmailova ZF, Dzhenzhera En. Lung diffusion
capacity of pulmonary tuberculosis patients: Ter Arkh 1987;
59: 65-9.
POST TUBERCULAR OBSTRUCTIVE AIRWAY IMPAIRMENT 99