550
U N I T 6
Respiratory Function
clinical disease. This commonly occurs at the site of the
primary lesion or at a distant site as a result of hematog-
enous spread. Clinical symptoms, such as pleuritic pain
due to extension of the infection to the pleural surfaces
between the lung and chest wall are common as the dis-
ease progresses.
Persons with secondary tuberculosis commonly pres-
ent with low-grade fevers, night sweats, easy fatigability,
anorexia, and weight loss.
2
A cough initially is dry but
later becomes productive with purulent and sometimes
blood-tinged sputum. Dyspnea and orthopnea develop
as the disease advances.
Diagnosis
A definitive diagnosis of active pulmonary tuberculosis
requires identification of the organism from cultures
or DNA amplification techniques.
33,35
Culture remains
the gold standard for laboratory confirmation of infec-
tion and is required for drug sensitivity testing. Culture
specimens may be obtained from early morning spu-
tum specimens, gastric aspirations, or bronchial wash-
ings obtained during fiber-optic bronchoscopy. Because
M. tuberculosis
grows slowly, cultures in liquid media
require several days, and cultures on solid media require
up to 12 weeks. Several nucleic acid amplification
[NAA] tests are available. These permit the diagnosis of
tuberculosis in as quickly as several hours.
35
However,
their applicability is limited by variable sensitivity and
high cost. Chest radiographs are used to determine the
extent of lung involvement. In patients with secondary
tuberculosis, CT scanning may also be performed.
The tuberculin skin test, which measures the delayed
hypersensitivity response to an intradermal injection of
tuberculin, a sterile liquid containing proteins derived
from the tubercle bacillus, is used for tuberculosis screen-
ing. The test is recommended for high-risk populations,
including persons who are in close contact with some-
one who has confirmed active tuberculosis, residents
and employees in congregate settings (e.g., corrections
facilities, homeless shelters, long-term care facilities),
and health care workers with high-risk patients.
32,35
The tuberculin test cannot distinguish between active
and latent infection, and has several other limitations.
Because the hypersensitivity response to the test depends
on cell-mediated immunity, false-negative test results can
occur in immunocompromised persons; that is, a nega-
tive tuberculin test result can mean that the person has a
true lack of exposure to tuberculosis or is anergic (unable
to mount a normal immune response to the test). False-
positive results can also occur; for example, in persons
who have nontuberculosis mycobacteria infection or
who have received the Bacillus Calmette-Guérin (BCG)
vaccine for tuberculosis prevention. Although the BCG
vaccine is not used in the United States for tuberculosis
prevention, many immigrants will have received it.
Recently, two interferon gamma release assays have
come on the market. These tests are in vitro assays of
CD4
+
T-cell-interferon gamma release in response to
stimulation by specific
M. tuberculosis
antigens. Since
the antigens are absent from all BCG strains and most
nontuberculous mycobacteria, the test is superior to the
tuberculin skin test.
16,34
Genotyping can be done to identify different strains
of
M. tuberculosis
in persons who have been diagnosed
with active tuberculosis. It can be used to evaluate
second episodes of tuberculosis to determine whether
the second episode was due to relapse or reinfection.
Genotyping also permits the evaluation of isolates with
different patterns of drug susceptibility.
35
In addition,
it is useful in investigating outbreaks of infection and
determining sites and patterns of
M. tuberculosis
trans-
mission in communities.
Treatment
The goals of therapy are to treat infected individuals
by eliminating the tubercle bacilli while preventing the
spread of infection and development of drug-resistant
forms of the disease. The tubercle bacillus is an aerobic
organism that multiplies slowly and remains relatively
dormant in oxygen-poor caseous material. However, it
undergoes a high rate of mutation and tends to acquire
resistance to any one drug. For this reason, multidrug
regimens are used for treating persons with active tuber-
culosis, and treatment typically continues for 6 months or
longer. Treatment duration is prolonged due to the slow-
growing nature of the tuberculosis bacteria that impairs
the effectiveness of antibiotics that target actively repli-
cating organisms.
The basic principles of tuberculosis treatment are:
(1) to administer multiple drugs to which the organisms
are susceptible, (2) to add at least two new drugs when
treatment failure is suspected, (3) to provide the safest
and most effective therapy in the shortest period of time,
and (4) to ensure adherence to therapy.
16
Adherence to
treatment can be improved by providing detailed educa-
tion about the disease and its treatment in addition to
a case manager who supervises all aspects of an indi-
vidual’s care. Direct observed therapy (DOT), which
FIGURE 22-8.
Cavitary tuberculosis in the apex of the left
upper lobe of the lung. (From Beasley MB,TravisWD, Rubin E.
The respiratory system. In: Rubin R, Strayer DS, eds. Rubin’s
Pathology: Clinicopathologic Foundations of Medicine. 6th ed.
Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &
Wilkins; 2012:550.)
