220 Tuberculosis

Pulmonary Tuberculosis
14
VK Vijayan, Sajal De

INTRODUCTION coughed out by ‘open’ [sputum-positive] pulmonary TB

patients who have received no treatment, or have not
Pulmonary tuberculosis [TB] is a chronic infectious
been treated fully. The initial contact with the organism
disease caused by Mycobacterium tuberculosis (1). Other
results in few or no clinical symptoms or signs. The
mycobacteria can also produce pulmonary TB and these
tubercle bacillus sets up a localised infection in the
include Mycobacterium africanum and Mycobacterium bovis.
periphery of the lung. Four to six weeks later, tuberculin
Usually, patients with pulmonary TB who have cavitary
hypersensitivity along with mild fever and malaise
lesions are an important source of infection. These
develops. In the majority of patients, the process is
patients are usually sputum smear-positive. Coughing
contained by local and systemic defenses. Rupture of the
produces tiny infectious droplets. Usually, one bout of
sub-pleural primary pulmonary focus into the pleural
cough produces 3000 droplet nuclei and these can stay
cavity may result in the development of TB pleurisy with
in the air for a long period of time. Ventilation removes
effusion.
these infectious nuclei. Mycobacterium tuberculosis can
Less commonly, tubercle bacilli may be ingested and
survive in the dark for several hours. Direct exposure to
lodge in the tonsil or in the wall of the intestine. This
sunlight quickly kills these bacilli. Of the several factors,
form of TB occurs following the ingestion of contami-
determining an individual’s risk of exposure, two factors
nated milk or milk products. Rarely, TB can occur as a
are important. These include the concentration of droplet
result of direct implantation of the organisms into the
nuclei in contaminated air and the length of time that air
skin through cuts and abrasions. This form of TB is a
is breathed. The risk of transmission of infection from a
health hazard faced by health care workers and labora-
person with sputum smear-negative pulmonary TB and
tory staff who handle materials infected with
miliary TB is low and with extrapulmonary TB is even
Mycobacterium tuberculosis. These lesions were termed
lower. However, infection with Mycobacterium bovis is
“prosector’s warts” (2). Interestingly, Laennec, the
rare in India because milk is often boiled before use. Even
inventor of the stethoscope, acquired TB in this fashion
though nontuberculous mycobacteria [NTM] are
which eventually led to his death (2).
harmless, some can cause human disease especially in
immunocompromised individuals (2). Primary Tuberculosis
From the implantation site, the organisms disseminate
NATURAL HISTORY OF TUBERCULOSIS
via the lymphatics to the regional lymph nodes. The
The cardinal event in the pathogenesis of TB, whether lesion at the primary site of involvement, draining
inapparent or overt is the implantation of Mycobacterium lymphatics and the inflamed regional lymph node
tuberculosis in the tissues. Lung is the most frequent portal constitute the primary complex. When the primary site of
of entry [Figure 14.1]. The organism enters the lung from implantation is in the lung, it is called Ghon’s focus. The
the inhalation of air borne droplets which have been draining lymphatics and the involved lymph nodes

Figure 14.1A: Chest radiograph [postero-anterior view] showing a
cavity in left upper zone. Sputum culture was positive for Mycobac-
terium tuberculosis
together with Ghon’s focus constitute the primary complex
[Ghon complex]. In children, the lymph node component
may be much larger than the Ghon’s focus.
Having secured entry the tubercle bacilli then,
disseminate via the haematogenous route to other parts
of the lung and many organs of the body. Thus, primary
TB is a widely disseminated infection. This fact is often
not realised by clinicians. Most of these metastatic foci
heal. However, some of these metastatic foci may remain
dormant and may reactivate at a later date when the host
resistance decreases. The subsequent course of the events
varies considerably. In most of the patients, the primary
complex resolves without becoming clinically apparent.
This occurs when the immune status of the host is good,
and healing occurs by fibrosis and calcification. In a
minority of patients, progressive primary TB due to the
extension of the inflammatory process at the site of the
primary focus can occur. In the lung, this can present as
an area of consolidation [TB pneumonia]. This form of
the disease was often encountered in the prechemothera-
peutic era and was termed “galloping consumption” or
“pneumonia alba” [white pneumonia]. This form is
encountered in the present era in patients with human
Pulmonary Tuberculosis 221
Figure 14.1B: Chest radiograph [postero-anterior view] of the same
patient at 24 months of follow-up. The patient had received six
months short-course chemotherapy. The left upper zone cavity has
disappeared
immunodeficiency virus [HIV] infection. Caseation
necrosis at the Ghon’s focus may lead to liquefaction.
Expectoration of the liquefied material can leave a cavity
with shaggy margins in the pulmonary parenchyma
which may be apparent on the chest radiograph.
Mediastinal and tracheobronchial lymph nodes may
produce compression of the adjacent bronchus. If this
obstruction is complete, the lung distal to the site of
bronchial obstruction becomes atelectatic [epitubercu-
losis] (3). If the obstruction is incomplete, it may act as a
“ball-valve” and results in obstructive emphysema. The
inflammed caseous lymph nodes may erode through the
walls of the bronchus and result in bronchogenic dissemi-
nation. Bronchial mucosal involvement may result in TB
bronchitis. In a patient with overwhelming infection, large
number of Mycobacterium tuberculosis may gain access to
the circulation and result in miliary and meningeal TB.
In majority of the patients, the initial focus of infection
subsides. Cicatrisation, scar formation and often
calcification develop. Repeated episodes of extension of
infection followed by healing and fibrosis may result in
the formation of “onion skin” or “coin lesion” (2).
222 Tuberculosis
Post-primary Tuberculosis
Rarely, the primary lesion may progress directly to the
post-primary form characterised by extensive caseation
necrosis and cavitation. More commonly, the primary
lesion remains quiescent, and may remain so for decades
or for the remainder of the individual’s life time. The
precise mechanism[s] underlying this phenomenon have
not yet been clarified as yet. However, reactivation or
reinfection TB may occur due to old age, malnutrition,
malignant disease, HIV infection and acquired immuno-
deficiency syndrome [AIDS], use of immunosuppressive
drugs and intercurrent infections.
While reactivation can occur at any site, post-
primary TB classically involves the apical posterior
segments of the upper lobes, or, the superior segment of
the lower lobes in more than 95 per cent of the cases.
Balasubramanian V and co-workers (4) have critically
reviewed the pathway to the apical localisation in TB
and proposed the integrated model for the pathogenesis
of TB.
Post-primary lesions are different from primary
lesions in that, local progression and central caseation
necrosis are much more marked in post-primary TB as
compared to primary TB. Tuberculosis cavities are
abundant sites for the growth of Mycobacterium tuber-
culosis as the temperature in them is optimal, there is
abundance of oxygen and various nutrients derived form
the cell wall are readily available. The bacilli in the wall
of the cavity gain free access into the sputum and are
expectorated. Such patients are said to have “open
tuberculosis” and are infectious to the community. If
these bacilli are aspirated from the cavity to other parts
of the lung via the bronchi, many secondary pulmonary
lesions develop. Early in the illness, TB cavities are
moderately thick walled, usually have a smooth inner
surface, lack an air-fluid level and are surrounded by an
area of consolidation. Later, in the chronic phase of the
disease, the wall may become thin, and the cavities may
appear spherical.
SYMPTOMS
Pulmonary TB is a disease of protean manifestations and
can mimic many diseases. Previous accounts referred to
the development of erythema nodosum, phlyctenular
conjunctivitis and fever at the time of tuberculin conver-
sion (2). However, this presentation is uncommonly seen
today.
The patient may develop symptoms insidiously and
some may remain asymptomatic. Usually patients with
pulmonary TB present with constitutional and respi-
ratory symptoms (3). Constitutional symptoms include
tiredness, headache, weight loss, fever, night sweats and
loss of appetite. The classic symptoms and signs of TB
were noted in a significantly higher proportion of the
younger group than elderly: fever [62% versus 31%],
weight loss [76% versus 34%], night sweats [48% versus
6%], sputum production [76% versus 48%], and haemop-
tysis [40% versus 17%] (5). Clinical manifestation of TB
in HIV infected patients vary and generally depends
upon the severity of immuno-suppression. In early stages
of HIV disease, clinical presentation of TB tends to simu-
late that observed in persons without immunodeficiency.
Fever is often present in the late afternoon or evening,
and is low-grade at the onset and becomes high-grade
with the progression of disease. Weight loss may precede
the symptoms. Some patients may remain a febrile.
Associated laryngeal TB can result in hoarseness of the
voice. Amenorrhoea can occur in severe diseases. The
most common respiratory symptom of pulmonary TB is
cough which lasts for three or more weeks. Cough may
be dry or productive. It is nearly impossible to differen-
tiate cough due to pulmonary TB from cough due to other
respiratory diseases including smoking and it is often
passed off as a smoker’s cough. Sputum may be mucoid,
muco-purulent, purulent or blood-tinged and is usually
scanty. Haemoptysis, although observed in many
diseases, is an important and often the presenting
symptom of pulmonary TB. Furthermore, TB is the most
common cause of haemoptysis in India. Severity of
haemoptysis in pulmonary TB varies from blood-stained
sputum to massive haemoptysis. Massive haemoptysis
usually results from rupture of a bronchial artery (1).
Chest pain may be dull aching in character. Acute chest
pain can occur in TB pleurisy or in pneumothorax; with
severe pain occurring at the height of inspiration. In
diaphragmatic pleurisy, pain is referred to the ipsilateral
shoulder when central part of the diaphragm is involved.
Occasionally chest pain can occur from fracture of ribs
due to violent coughing. Breathlessness results from
extensive disease or if complications such as bronchial
obstruction, pneumothorax or pleural effusion occur.
Localised wheeze can occur due to endobronchial TB or

because of the pressure of enlarged lymph nodes on the
bronchus.
PHYSICAL SIGNS
A thorough general physical examination should be done
in all patients with pulmonary TB. Anaemia and cachexia
may be observed in severe cases. Tachycardia can occur
and is usually proportional to the fever. Digital clubbing
occurs rarely in advanced cases and with superadded
suppuration. There can be an increase in the respiratory
rate. Extrapulmonary TB foci such as cold abscess,
enlarged cervical and mesenteric lymph nodes, defor-
mity or localised immobility of the spine, epididymitis,
etc., can be discovered on general physical examination.
In addition, general physical examination may also reveal
phlyctenular conjunctivitis or keratitis. Further, signs of
meningeal irritation and focal neurological signs may be
apparent in patients with extrapulmonary focus in the
nervous system. Associated signs of protein energy
malnutrition such as anasarca, change in hair colour and
leuconychia may occur. Adult patients with chronic
disease can present with lower body mass index [BMI].
Respiratory system examination may reveal displace-
ment of the trachea and the heart depending on the
underlying pathology. Asymmetrical abnormalities of
the chest wall such as retraction, fibrosis or collapse and
prominence in pleural effusion, emphysema or pneumo-
thorax may be observed. Undue prominence of the
clavicular head of the sternocleidomastoid muscle [Trail’s
sign] on one side may be indicative of apical fibrosis due
to TB. Mobility of any part of the chest wall may be
restricted on the affected side. A dull percussion note
can occur as a result of consolidation, collapse of the lung,
or thickened pleura or extensive infiltration of the lung
due to TB. A stony dull note can be elicited over a pleural
effusion or empyema. Hyperresonance on percussion is
encountered in pneumothorax. Cracked-pot sound may
be elicited in cases where percussion is practiced over a
cavity which communicates with bronchus of moderate
size and is most distinct when the mouth is open. It
results due to a sudden expulsion of air through a
constricted orifice. It has a hissing character, combined
with a clinking sound like that produced by shaking coins
together. It is a rare finding. Cracked-pot sound is often
produced in healthy children when percussion is
performed during crying. Myotactic irritability/myoi-
dema can occur due to hyperirritability of malnourished
Pulmonary Tuberculosis 223
muscles in front of the thorax. A light tap over the
sternum produces fibrillary contractions, at some
distance off, in the pectoral muscles.
High-pitched [tubular] bronchial breathing can be
heard in patients with TB pneumonia. Bronchial
breathing can be low-pitched [cavernous] if there is an
underlying cavity in the lung or an open pneumothorax.
A special type of high-pitched bronchial breathing with
an “echo-like” quality [amphoric breathing] is indicative
of a large cavity with smooth walls or of a pneumothorax
communicating with a bronchus. It resembles the sound
produced by blowing across the mouth of a bottle and
consists of one or more low-pitched fundamental tones
and a number of high-pitched overtones. Vocal fremitus
is increased when lung is consolidated or contains a large
cavity near the surface. Vocal fremitus is diminished
when the corresponding bronchus is obstructed and is
absent when there is pleural effusion or thickening. The
presence of fine crepitations, especially post-tussive
crepitations, is an important sign of TB infiltration. A
pleural rub is characteristic of pleurisy.
Hippocratic succussion is the splashing sound which
can be heard when a patient who has both air and fluid
in the pleural cavity is shaken or moved suddenly. Post-
tussive suction, a sucking noise resembling that produced
by an India-rubber ball that is springing open again, can
be heard after a coughing, over a cavity in the lung when
its walls are not too rigid. It occurs due to re-entry of air.
DIAGNOSIS
The diagnosis of pulmonary TB [primary and post-
primary forms of the disease] involves detection and
isolation of Mycobacterium tuberculosis (6-12). In addition,
identification of the mycobacterial species and determi-
nation of susceptibility of mycobacteria to antimycobac-
terial drugs are required for management.
Tuberculin Skin Test
Tuberculin skin test is useful for the detection of infection
with Mycobacterium tuberculosis which leads to the
development of sensitivity to certain antigenic compo-
nents of the organisms called “tuberculins”. Intracuta-
neous injection of tuberculin results in classic delayed
[cellular] hypersensitivity reaction. A delayed hypersensi-
tivity reaction to tuberculin may indicate previous natural
infection with non-tuberculous mycobacteria or vaccination
with bacille Calmette–Guérin.
224 Tuberculosis

Figure 14.2: Chest radiograph [postero-anterior view] showing

extensive parenchymal lesions in the left lung. Few scattered lesions Figure 14.3A: Chest radiograph [postero-anterior view] showing
are also seen in the right lung. The sputum smear and culture extensive parenchymal infiltrates in the right lung. Few scattered
were positive for Mycobacterium tuberculosis infiltrates are also seen in the left lung. The patient had multidrug-
resistant pulmonary tuberculosis

Haematology
Haematological abnormalities in pulmonary TB include
anaemia, leucocytosis, leucopenia, purpura, leukaemoid
reaction and polycythaemia vera.

Radiology
Standard posterior-anterior and lateral radiographs of
the chest should be obtained in patients who have signs
and symptoms suggestive of pulmonary TB. Initial radio-
logical manifestations include parenchymal infiltration
with ipsilateral lymph node enlargement. Hilar or
mediastinal lymph node enlargement in TB is usually
unilateral and this lymph nodal enlargement persists
longer than the parenchymal lesions. Calcification of the
lymph nodes and the lung lesions could occur several
years after infection. In adults, the lesions may be patchy
or nodular infiltrates and may occur in any segment.
Dense and homogeneous lesions with lobar, segmental Figure 14.3B: Chest radiograph [postero-anterior view] of the same
or subsegmental distributions are also encountered patient taken a year later showing pneumothorax on the right side
and a large cavity in the left lung. The patient did not respond to
frequently [Figures 14.1A, 14.1B, 14.2, 14.3A, 14.3B and
treatment and died
14.4]. Cavitation, often multiple, occurs in immuno-
competent individuals, but is rare in immunocompro- particularly in the late stage of HIV infection, with non-
mised individuals. The X-ray features of pulmonary TB cavitary disease, lower lobe infiltrates, hilar lymph-
in HIV positive patients are frequently atypical, adenopathy and pleural effusion. More typical post-

Figure 14.4: Chest radiograph [postero-anterior view] of a patient
with sputum smear negative and culture positive pulmonary
tuberculosis
primary TB with upper lobe infiltrates and cavitations is
seen in the earlier stages of HIV infection.
Computerised tomographic [CT] scan is more
sensitive than chest radiograph in detecting subtle
parenchymal changes and mediastinal involvement.
Primary TB typically appears as air-space consolidation
with hilar or mediastinal lymphadenitis. Post-primary
TB most commonly appears as nodular and linear
opacities at the lung apex. CT findings of early broncho-
genic spread of post-primary TB are centrilobular 2 to 4
mm nodules or branching linear structures and poorly
defined nodules on CT scan correspond to caseous
materials filling the bronchioles (13) and this is referred
as “tree-in-bud” appearance. Cavitations usually occur
at the centrilobular area and may progress to a larger
coalescent cavity. The CT scan can document miliary
disease even when chest radiograph is normal. CT
findings of early miliary dissemination commonly
include ground-glass opacification with barely discerni-
ble nodules. On high-resolution computed tomography
[HRCT], miliary TB typically shows fine, nodular or
reticulonodualr pattern with nodules involving both
intralobular interstitium, interlobular septa and
subpleural, and perivascular regions. Nodules are evenly
Pulmonary Tuberculosis 225
distributed throughout the lung. CT more accurately
defines the group of lymph nodes involved, their extent
and size. The lymph nodes with central low attenuation
and peripheral rim enhancement especially with contrast
strongly suggest a diagnosis of mycobacterial infection.
Complications of TB like post-TB bronchiectasis,
aspergilloma etc. are better diagnosed with the help of a
CT scan.
Other radiographic findings in pulmonary TB include
atelectasis and fibrotic scarring with retraction of the hila
and deviation of the trachea. Unilateral pleural effusion
may be the only radiographic abnormality in pleural TB.
Rarely, chest radiographs may be normal especially in
patients with endobronchial TB and HIV infection. It is
important to compare the current chest radiographs with
the previous radiographs done months or years earlier
so that subtle changes can be detected. Progression of
lesions on serial chest radiographs indicates active
disease.
Apical-lordotic or oblique view of chest may aid in
visualisation of lesions obscured by bony structures or
the heart. Contrast-enhanced computed tomographic
scan [CECT scan] and magnetic resonance imaging [MRI]
of the chest may be useful in defining intrathoracic lymph
nodes, nodules, cavities, cysts, calcification and vascular
details in the lung parenchyma. Bronchial stenosis or
bronchiectasis can be defined by bronchography and CT
scan of the chest. Fluoroscopy may be useful in the
detection of the mobility of thoracic structures.
Fibreoptic Bronchoscopy
Patients with positive skin tests and abnormal chest
radiographs compatible with TB pose diagnostic
problems and therapeutic dilemma [to treat or not to treat
for TB] to chest physicians. Microbiologic confirmation
of TB among sputum smear negative is increasingly
important because of an increasing incidence of smear
negativity especially among immunocompromised hosts.
Fibreoptic bronchoscopic studies provide various types
of specimens [aspirate, brush, lavage fluid and biopsy]
for early diagnosis of sputum smear-negative pulmonary
TB. An early diagnosis of TB is possible in nearly one-
third of sputum smear-negative pulmonary TB if
different bronchoscopic procedures are employed
instead of a single procedure alone during bronchoscopy
(14-17). The overall yield of bronchoscopy is greater than
90 per cent especially when culture were included in
226 Tuberculosis
analysis (18). Examination and culture of post-broncho-
scopy sputum had also high diagnostic yield [93 per cent]
(19). The topical anaesthetic agents that are used during
bronchoscopic procedure had inhibitory effect on
Mycobacteria. Therefore, these agents should be carefully
used. Bronchoscopic examination may show normal
bronchial mucosa to ulcerative lesions, granulomatous
lesions, and ulcerative-granulomatous tumour-like
lesions and residual fibrotic stenosis. Because of high
mortality in miliary TB, it is imperative that the diagnosis
is confirmed as quickly as possible. In miliary TB, bron-
choscopy is diagnostic in 73-83 per cent of cases (20). The
yield of bronchoscopy for diagnosis of pulmonary TB in
HIV infected patients is similar to that in patients without
HIV infection and transbronchial biopsy provides
incremental diagnostic information (14). In pediatric
patients the gastric lavage is superior to bronchoalveolar
lavage [BAL] for bacteriologic confirmation of pulmo-
nary TB. The overall bacteriologic yield was 34 per cent
while gastric lavage alone was positive in 32 per cent of
the cases (21).
Indications for bronchoscopy as a diagnostic tool for
pulmonary TB may include: [a] patients suspected of
having pulmonary TB with negative smears and in
whom treatment must be started due to clinical status;
[b] suspicion of associated neoplasia; [c] selected patients
with negative cultures; [d] lack of material being obtained
by simpler methods. However, it has been demonstrated
that sputum induction is a safe procedure with a high
diagnostic yield and high agreement with the results of
fiberoptic bronchoscopy for the diagnosis of pulmonary
TB in both HIV-seronegative and HIV-seropositive
patients. Sputum induction was well tolerated, involved
low-cost, and provided the same, if not better, diagnostic
yield compared with bronchoscopy in the diagnosis of
smear-negative pulmonary TB (22,23). In a decision
analysis model to assess the overall utility of BAL in
clinically suspected sputum smear negative pulmonary
TB, it has been suggested that, in a region of high TB
prevalence, empirical treatment is the best course of
action (17).
Diagnostic Mycobacteriology
The definitive diagnosis of pulmonary TB is made by
the isolation and identification of the infecting organism.
All patients presenting with cough and sputum for more
than three weeks must have their sputum examined for
Mycobacterium tuberculosis. In addition, Mycobacterium
tuberculosis can be isolated from blood, gastric aspirate,
bronchial washings, BAL fluid, pleural fluid, pus,
cerebrospinal fluid, urine, bone marrow biopsy and other
tissue biopsy specimens. All diagnostic specimens should
be collected before the patient is given antituberculosis
treatment.
Sputum microscopy is the earliest and quickest
procedure for the preliminary diagnosis of pulmonary
TB. Patients should be instructed that the material
brought out from the lungs after a productive cough, not
the nasopharyngeal discharge and saliva, should be
submitted. The patient should rinse his/her mouth with
water before specimen collection to remove materials that
interfere with the culture. Sputum collection should be
done in an isolated, well-ventilated area. Sputum speci-
men should be collected in a wide-mouth, rigid container
with tight-fitting screw tops. If the patient cannot
produce sputum, deep coughing may be induced by
inhalation of an aerosol of warm hypertonic [3% to 15%]
saline. Sputum containers should be examined in each
patient. The bacilli can be stained with basic fuchsin dyes
[Ziehl-Neelsen or Kinyoun method] or with a fluoro-
chrome [auramine-rhodamine] staining. The positive
predictive value of a properly performed smear is more
than 90 per cent for pulmonary TB.
DIFFERENTIAL DIAGNOSIS
Tuberculosis can practically involve all organs of the
body and can simulate most of the diseases. Diseases
which are to be differentiated from pulmonary TB are
listed in Table 14.1. However, by no means this list is
exhaustive.
Bacterial Pneumonia
Bacterial pneumonia, especially occurring in the upper
part of the lung, may mimic TB. In acute pneumonia,
symptoms occur suddenly and a raised white blood cell
count may point to the diagnosis. If sputum is negative
for Mycobacterium tuberculosis, antibiotics which have no
effect on Mycobacterium tuberculosis can be given for seven
to ten days. A rapid fall in temperature may occur follow-
ing treatment with antibiotics if the lesion is due to acute
pneumonia. The patient may be re-evaluated after a
course of antibiotics with a chest radiograph which may
show clearance of the lesions in acute pneumonia.
However, it should be noted that shadows may look

Table 14.1: Differential diagnosis of pulmonary
tuberculosis
Infections
Bacterial pneumonia
Lung abscess
Fungal and miscellaneous bacterial infections
Bronchogenic carcinoma
Bronchiectasis
Bronchial asthma
Sarcoidosis
Pneumoconiosis
Congenital diseases
Other causes
Hyperthyroidism
Diabetes mellitus
smaller after the antibiotic course if there is collapse of
the part of the lung or pneumonia due to obstruction of
a bronchus. Pneumonia due to Pneumocystis jiroveci is
common in patients with AIDS. If the sputum exami-
nation is non-contributory, BAL fluid examination for
Mycobacterium tuberculosis and Pneumocystis jiroveci cysts
is indicated (17,24).
Lung Abscess
Patients with lung abscess often produce foul-smelling
purulent sputum. Clubbing of fingers is a prominent
feature in these patients. Peripheral blood examination
reveals neutrophilic leucocytosis. Ziehl-Neelsen staining
is negative for Mycobacterium tuberculosis.
Fungal and Miscellaneous Bacterial Infections
The important fungal diseases of the lung that may mimic
pulmonary TB include aspergillosis, blastomycosis,
coccidioidomycosis, cryptococcosis, and histoplasmosis.
Other miscellaneous bacterial infections can also simulate
pulmonary TB and these include nocardiosis and
actinomycosis. Nocardia microorganisms are common
bacterial inhabitants of soil. Examination of sputum or
pus reveals crooked, branching, beaded, Gram-positive
filaments. Most nocardia microorganisms are acid-fast
in direct smears if a weak acid is used for decolourisation.
The organisms often take up silver stains. Actinomycosis
is an indolent, slowly progressive bacterial infection
caused by a variety of Gram-positive, non-spore forming
anaerobic or microaerophilic rods. The most characteri-
stic feature of actinomycosis is the demonstration of
Pulmonary Tuberculosis 227
“sulphur granules” in sputum, pus or tissue specimens.
These are usually yellow and consist of aggregated
microorganisms. Aspergillus is responsible for four types
of pulmonary manifestations, viz: allergic broncho-
pulmonary aspergillosis [ABPA], aspergilloma, chronic
necrotising pulmonary aspergillosis and invasive
aspergillosis. ABPA is characterised by asthma-like
symptoms, eosinophilia, fleeting pulmonary infiltrates,
a positive immediate skin test response to aspergillin,
elevated serum IgE and anti-aspergillus IgG antibodies.
Aspergilloma occurs in patients with pre-existing TB or
other cavities and these patients can have high serum
IgG antibody titres of aspergillus. Invasive aspergillosis
usually occurs in immunocompromised patients.
Blastomycosis can be diagnosed by demonstration of
yeast-like organisms with a highly refractile cell wall and
multiple nuclei in sputum samples. Patients with cocci-
dioidomycosis can be diagnosed by showing spherules
in the sputum stained with Gomori’s or Papanicolaou’s
stains. Cryptococcosis can be identified by staining the
biological specimens with India ink and demonstration
of doubly refractile cell wall, the presence of budding
and the clean capsule. Viable organisms in macrophages
can be seen in histoplasmosis. Candidiasis can occur in
the pulmonary TB patients with immunodeficiency.
Bronchogenic Carcinoma
A solid round tumour in the chest radiography may be
difficult to distinguish from a well-circumscribed TB
lesion. Both bronchogenic carcinoma and pulmonary TB
cause loss of weight, cough, blood-streaked sputum and
fever. Bronchogenic carcinoma may also cavitate.
Bronchogenic carcinoma can produce post-obstructive
pneumonitis and lung abscess. The patient with broncho-
genic carcinoma is usually a chronic smoker and sputum
will be negative for Mycobacterium tuberculosis. Confir-
mation of diagnosis requires bronchoscopic biopsy in
these patients.
Bronchiectasis
Patients with bronchiectasis have a long history of
respiratory symptoms especially since childhood. They
produce purulent sputum. Clubbing of fingers is a
prominent sign and coarse bubbling crepitations can be
heard on auscultation. Sputum examination is negative
228 Tuberculosis
for Mycobacterium tuberculosis. The middle and lower
lobes [or lingula on the left side] are commonly involved
in bronchiectasis. The CT scan of the chest and broncho-
graphy will aid in the diagnosis.
Bronchial Asthma
Patients with bronchial asthma often manifest wheezing.
They often give history of allergy to inhalants or
ingestants. However, localised wheeze can occur in TB
if a bronchus is obstructed by an enlarged lymph node
or if there is TB bronchitis. Bronchial asthma can be
diagnosed by demonstrating reversibility in pulmonary
function after inhalation of bronchodilator aerosols.
Sarcoidosis
Sarcoidosis usually presents with bilateral hilar
lymphadenopathy and pulmonary infiltration. It can also
present with pulmonary infiltrates or nodular lesions
without mediastinal lymphadenopathy. In these
situations it is difficult to differentiate these lesions from
pulmonary TB especially miliary TB. These patients have
negative tuberculin test and the sputum is negative for
Mycobacterium tuberculosis (25). Almost every organ of
the body can be involved in sarcoidosis and the tissue
biopsy reveals non-caseating epitheleoid cell granulo-
mas.
Pneumoconiosis
Occupational exposure to silicon dioxide, asbestos, coal
dust, beryllium, ferrous oxide etc., and hypersensitivity
reactions to organic inhalants can cause pulmonary
infiltration that may mimic pulmonary TB. Conglomerate
masses and even cavitation can occur in silicosis.
Sometimes TB develops in a patient with silicosis [silico-
tuberculosis]. Coal miners suffering from rheumatoid
arthritis can develop round shadows in the lung
resembling TB. Some patients with pneumoconiosis
develop progressive massive fibrosis. A carefully elicited
occupational history and absence of Mycobacterium
tuberculosis in the sputum help in the diagnosis.
Cardiovascular Diseases
Haemoptysis can occur in patients with mitral stenosis.
In addition, hoarseness of voice occurs in mitral stenosis
when enlarged left atrium compresses the left recurrent
laryngeal nerve [Ortner’s syndrome] and this may be
mistaken for hoarseness due to TB. Radiographic abnor-
malities seen in haemosiderosis due to long-standing
mitral stenosis can be confused with miliary TB.
Haemoptysis can also occur in patients with primary or
secondary pulmonary arterial hypertension and in severe
pulmonic stenosis. Careful examination of the heart and
appropriate investigations [electrocardiogram and
echocardiogram] will help in the differential diagnosis.
Congential Abnormalities
Dermoid cysts, arteriovenous fistulae and hamartomas
may require differentiation from pulmonary TB.
Sequestration of the lung may produce difficulty in
diagnosis, if associated with bronchiectasis or purulent
sputum and fever. Bronchoscopy, aortography, CT scan
and sputum examination can facilitate the diagnosis.
Other Diseases
Hyperthyroidism and diabetes mellitus can have
symptoms such as loss of weight, easy fatigability and
malaise which can be mistaken for the constitutional
symptoms associated with TB. Appropriate investiga-
tions will facilitate the diagnosis.
PRACTICAL APPROACH TO THE DIAGNOSIS OF
ACTIVE PULMONARY TUBERCULOSIS
Even in a country like India where TB is highly endemic,
diagnosis of active pulmonary TB can be diagnostic
dilemma. The following criteria would indicate active
pulmonary TB. These include: [i] clinical signs of infection
and features of TB toxemia [fever with evening rise, night
sweats, malaise, weight loss etc.]; [ii] progressive radio-
graphic changes; [iii] microbiological/histopathological
evidence of TB infection; and [iv] response to therapeutic
trial with antituberculosis treatment. Of these, micro-
biological/histopathological evidence [Figure 14.5] is
conclusive and the remaining are suggestive.
TREATMENT
The reader is referred to the chapter “Treatment of
tuberculosis” [Chapter 48B], for details on this topic.

Figure 14.5: Pulmonary tuberculosis. Photomicrograph showing
bronchial cartilage with ossification, marrow development and
bronchial mucosal glands [upper panel, left; Haematoxylin and eosin
x 60], bronchial tissue exhibiting epithelioid granulomas,
lymphocytic infiltration, bronchial mucosal acini [upper panel right;
Haematoxylin and eosin x 60; lower panel right; Haematoxylin and
eosin x 200] and alveoli with anthracotic pigment [lower panel, left;
Haematoxylin and eosin x 60]
Kind courtesy: Dr M Kumaraswamy Reddy, Department of
Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati,
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