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TUBERCULOSIS
&
ASTHMA:
ANY LINK?
Professor of Clinical Medicine, Saint George Hospital UMC
Joudy BAHOUS, MD. Associate Dean for Clinical Affairs, University of Balamand
Definition of Tuberculosis
Tuberculosis (TB) is a potentially serious infectious disease
that affects mainly the lung.
Mycobacterium Tuberculosis, is the bacteria that causes
tuberculosis, and is spread from one person to another through
tiny droplets released into the air via coughs and sneezes.
Pathophysiology of Tuberculosis
Successful containment of Tuberculosis is dependent on the
cellular immune system, mediated primarily through T-helper
cells (Th1 response). T cells and macrophages form a
granuloma with a center that contains necrotic material
(caseous center)
Definition of Asthma
Asthma is an heterogeneous disease, usually characterized
by chronic airway inflammation. It is defined by the history of
respiratory symptoms such as wheeze, shortness of breath,
chest tightness and cough that vary over time and in intensity,
together with variable expiratory airflow limitation
Pathophysiology of Asthma
Inhaled antigen activates mast cells and Th2 cells in the
airway. They in turn induce the production of mediators of
inflammation (such as histamine and leukotrienes) and
cytokines including interleukin-4 and interleukin-5
Tuberculosis and Asthma : Any link?
Pulmonary Tuberculosis In Asthma Cases
The most important aspect of these observations is the fact
that an active and open tuberculosis can be concealed for a
lengthy period under the guise of a bronchial asthma with
both eosinophilia and skin reactions against specific proteins.
Fraenkel, E. M. (1934). British Medical Journal, 2 (3845), 513–514.
The relationship of bronchial asthma
(and hay fever) to pulmonary tuberculosis
Opinions most frequently expressed by previous writers may be
grouped as follows:
1. Asthma and pulmonary tuberculosis are antagonistic and
therefore are rarely, if ever, found together.
2. Asthma and tuberculosis may occur together, but their
coexistence is purely coincidental and no causal relationship
exists between the two.
Tocker, A. M. (1944). Journal of Allergy, 15(2), 108-119.
3. In all or in the vast majority of instances, asthma is of
tuberculous origin.
4. Views less frequently expressed include the following:

Asthma, at the outset, frequently starts as a result of an allergy to the
tubercle bacillus (tuberculo-allergic asthma), but hypersensitiveness to
other allergens may develop later.

Asthma predisposes to pulmonary tuberculosis.

Asthma is favorably influenced by pulmonary tuberculosis.
Tocker, A. M., (1944). Journal of Allergy, 15(2), 108-119.
Tuberculosis and Asthma Prevalence: Any link?
Mycobacterium tuberculosis infection and the subsequent
development of asthma and allergic conditions
Study design

Subjects (n=1162) were individuals identified with active
tuberculosis from 1 January, 1966 and December 31, 1969,
who were 20 years of age or younger.

Subjects were followed for 28 to 32 years
Von Hertzen, L. (1999). Journal of allergy and clinical immunology,104(6), 1211-1214.
Mycobacterium tuberculosis infection and the subsequent
development of asthma and allergic conditions
Results

In women a significantly lower prevalence of persistent asthma
was found among those aged 16 years or younger at the time
of M tuberculosis infection than among the control subjects
(3.7% vs 8.3%, respectively; P = .035).

Women with a history of tuberculosis also showed a
significantly lower prevalence of allergic conditions than the
control subjects (8.3% vs 14.0%, respectively; P = .003) when
the whole study population of women was considered
Von Hertzen, L. (1999). Journal of allergy and clinical immunology,104(6), 1211-1214.

By contrast, no suppressive effect of M tuberculosis infection in
childhood or adolescence on the later development of asthma or
allergic conditions could be observed in men.

The differences in the natural history of atopic disease between the
sexes and the occurrence of tuberculosis mostly in later childhood
and adolescence may largely explain our findings.
Von Hertzen, L. (1999). Journal of allergy and clinical immunology,104(6), 1211-1214.
International patterns of tuberculosis and the prevalence
of symptoms of asthma, rhinitis, and eczema
Methods

Tuberculosis notification rates were obtained from the
World Health Organization. (WHO)

Data on the prevalence of symptoms of Asthma, rhinitis
and eczema in 235 477 children aged 13-14 years were
based on the responses to the written and video
questionnaires from the International Study of Asthma and
Allergies on Childhood. (ISAAC)
Von Mutius, E. (2000). Thorax, 55(6), 449-453.
International patterns of tuberculosis and the prevalence
of symptoms of asthma, rhinitis, and eczema
Results

Tuberculosis notification rates were significantly inversely
associated with the lifetime prevalence of wheeze and
asthma and the 12 month period prevalence of wheeze at rest
as assessed by the video questionnaire.

An increase in the tuberculosis notification rates of 25 per
100 000 was associated with an absolute decrease in the
prevalence of wheeze ever of 4.7%
Von Mutius, E. (2000). Thorax, 55(6), 449-453.
An inverse correlation between estimated tuberculosis
notification rates and asthma symptoms
Methods

Estimated tuberculosis incidence rates obtained from the
World Health Organization. (WHO)

Asthma symptoms data obtained from the International
Study of Asthma and Allergies on Childhood (ISAAC) for
both the 6-7 and 13-14 years age groups.
Shirtcliffe, P. (2002). Respirology, 7(2), 153-155.
An inverse correlation between estimated tuberculosis
notification rates and asthma symptoms
Results

For the 6-7 year-old children, there was a significant inverse
relationship between estimated tuberculosis incidence and the
prevalence of key asthma symptoms.

However, in the 13–14 year age group, a significant inverse
relationship was only demonstrated for ‘asthma ever’.
Shirtcliffe, P. (2002). Respirology, 7(2), 153-155.
The prevalence of asthma appears to be inversely related to the
incidence of typhoid and tuberculosis

Data from the World Health Organization confirms that these
two infectious diseases occur very rarely in those communities
where the asthma is high.

It may be that the clean and infection-free environment of
Australia and New Zealand is responsible for the region of
Oceania having the dubious honor of having the highest
prevalence of asthma in the world.
Jones, P. D. (2000). Medical hypotheses, 55(1), 40-42.
How can we explain the effect of Tuberculosis
on the prevalence of Asthma and Atopy
Schematic representation of the roles played by Th land Th 2 lymphocytes in tuberculosis and bronchial asthma
Rajasekaran, S. (2001). Indian J Tub, 48, 139-42.
Hygiene Hypothesis
The hygiene hypothesis is a hypothesis that states that
a lack of early childhood exposure to infectious
agents, symbiotic microorganisms (such as the gut
flora or probiotics), and parasites increases
susceptibility to allergic diseases by suppressing the
natural development of the immune system.
The effect of neonatal BCG vaccination on atopy and
asthma at age 7 to 14 years
Methods

An historical cohort study was conducted among 7to14-year
old children who were born in two districts in Sydney
Australia and whose mothers were born in South East Asia.
One district had routinely administered BCG vaccination to
infant born to overseas-born mothers and the other had not.

Consenting subjects completed questionnaires, performed
spirometry and airway hyperresponsiveness testing, and had
had allergen skin prick testing and tuberculin skin testing
Marks, G. B. (2003). Journal of allergy and clinical immunology, 111(3), 541-549.
The effect of neonatal BCG vaccination on atopy and
asthma at age 7 to 14 years
Results

Neonatal BCG vaccination has an effect on T-cell allergen responsiveness 7
to 14 years after vaccination and that among a subgroup of subjects with an
inherited predisposition to allergic disease, this is associated with clinically
relevant beneficial effects.

The findings of this study encourage the view that external influences on
the immune system in the neonatal period have consequences that extend
into later childhood and influence the expression of asthma.

Genetic factors are likely to modify the effect of those external factors
Marks, G. B. (2003). Journal of allergy and clinical immunology, 111(3), 541-549.
Does the effect of neonatal BCG vaccination on atopy and asthma
mean that effort to try to reduce the disease burden will be most
effective if one is able to help guide the immune system to
respond in a th1 manner?
Tuberculosis and Airway: Any link?
Endobronchial Tuberculosis Simulating Bronchial Asthma

It has been said that a normal chest X-ray almost always
exclude pulmonary tuberculosis with the exception of
endobronchial tuberculosis

Endobronchial tuberculosis can present in variety of ways.
It can be mistaken as a case of lung cancer , foreign body
aspiration and case of bronchial asthma
Post-tuberculosis Bronchial Asthma
Methods
Fifty-five adult wheezers, as confirmed pulmonary
Tuberculosis patients for which they had complete courses of
anti-tuberculosis treatment and proven post-tuberculosis
bronchial asthma were assessed for pulmonary functions
before and after bronchodilator therapy.
Rajasekaran, S. (2001). Indian J Tub, 48, 139-42.
Post-tuberculosis Bronchial Asthma
Results

Bronchial asthma had emerged within 3 years of stopping antituberculosis treatment in 42(76.3%) patients.

Two-thirds had no familial history of asthma. Patients with
moderate and far-advanced residual lung lesions had more
persistent symptoms and low PEFR levels requiring prolonged
corticosteroid administration.

None of the 55 patients studied had relapsed in the 2 year followup despite most of them being on prolonged corticosteroid
therapy.
Rajasekaran, S. (2001). Indian J Tub, 48, 139-42.
Post-tuberculosis Bronchial Asthma
Conclusion
Post-tuberculosis bronchial asthma patients, with
moderate or far advanced residual lesion, had persistent
symptoms needing continued corticosteroids therapy
Rajasekaran, S. (2001). Indian J Tub, 48, 139-42.
Tuberculosis and Asthma Treatment:
Any link?
Corticosteroids and Tuberculosis

Corticosteroids is the main treatment of severe uncontrolled
asthma.

Corticosteroids decrease T-cell immunity

Could we use Corticosteroids in asthmatic patients with
active or latent Tuberculosis?
Corticosteroids and Tuberculosis
Prospective controlled trials have shown a benefit:

In tuberculous meningitis, pericardial and pleural disease.

In fever, be a drug-related or from systemic disease.

When adrenal suppression is a concern, supplemental
Corticosteroids are indicated
Corticosteroids for prevention of mortality
in people with tuberculosis
According to a systemic review and meta-analysis of corticosteroids use in
Tuberculosis:

Steroids could be effective in reducing mortality for all
forms of tuberculosis, including pulmonary tuberculosis.

However, further evidence is needed since few recent trials
have assessed the effectiveness of corticosteroids in
patients with pulmonary tuberculosis.
Critchley, J. A. (2013). The Lancet infectious diseases, 13(3), 223-237.
Conclusion

Inverse correlation between estimated Tuberculosis rates
and asthma symptoms

Decrease of Asthma prevalence in Tuberculosis patients is
linked to the switch Th1 lymphocyte response over Th2
response (hygiene hypothesis)

Endoluminal Tuberculosis could mimic Asthma.

Corticosteroids in Tuberculosis patients can be used
whenever indicated
Thank you