YOURE THE FLIGHT SURGEON

This article was prepared by Col. Mary T. Brueggemeyer, denies any history of tuberculosis exposure, BCG vaccination, or fam-
ily history of tuberculosis. Your examination is essentially normal.
USAF, MC, FS. 3. What are the next steps in the work-up of this patient?
A. Computed tomography (CT) scan of the chest.
B. Complete blood count with differential, liver and renal function
You have had an exhausting morning in the flight medicine clinic at
tests, human immunodeficiency virus (HIV), and urinalysis.
a busy U.S. Air Force (USAF) Air Education and Training Command
C. Three consecutive sputum specimens over 8-24 h, including one
base, having seen at least 20 cases of influenza-like illness. You are just
early morning specimen sent for acid fast stain, nucleic acid
about to go to lunch when you receive a call from the radiologist about
amplification, and culture.
a chest x-ray on a foreign exchange student pilot. The x-ray was done
D. Tuberculin skin test.
as a routine part of the medical screening prior to the start of pilot
E. Admission to the hospital for respiratory isolation until active
training. The chest x-ray shows a patchy, nodular airspace opacity in
pulmonary TB is ruled out or adequate initial treatment and
the right upper lobe. The student pilot, who is from Afghanistan, is
three negative sputum smears are achieved.
reportedly asymptomatic.
F. All of the above.
1. What are some possible causes for the finding on the chest x-ray?
A. Community-acquired pneumonia.
B. Malignancy. ANSWER/DISCUSSION
C. Active pulmonary tuberculosis. 3. F. Chest radiography is the most appropriate first step to diagnose
D. Influenza pneumonia. active pulmonary TB. The most common finding (7087%) in reactiva-
E. Aspiration. tion pulmonary TB is an infiltrate in the apical-posterior segments of
the upper lobes with or without air/fluid levels and cavitation (5). The
remainder (1330%) will have atypical findings such as hilar lymph-
ANSWER/DISCUSSION
adenopathy, pleural effusion, lower lobe infiltrates, and solitary nod-
1. A, B, C, and D. The nonspecific findings on the chest x-ray could
ules (5). Up to 510% of patients may have a negative chest film (5). In
be caused by many different inflammatory processes, but your suspi-
uncertain cases, such as this, CT of the chest is more sensitive and usu-
cion for active tuberculosis (TB) should be raised by the history of for-
ally shows pulmonary nodules with linear opacities known as a tree
eign birth in a TB endemic area and the x-ray changes in the right
in bud pattern (6). This pattern is characteristic of endobronchial
upper lobe. The top risk factors for active pulmonary TB in the United
spread of TB. Sputum samples should be obtained from all patients
States are foreign-born status or travel to an endemic region. In 2008,
suspected of having active TB and nucleic acid amplification testing
59% of active TB cases in the U.S. were in foreign-born persons (3). The
should be done on the first specimen. Nucleic acid amplification is
rate of active TB was 10 times higher in foreign-born than in U.S.-born
a rapid diagnostic test for TB with results within 24-48 h. It is useful
persons (3). In addition, the World Health Organization has identified
to distinguish infection due to tuberculous versus non-tuberculous
Afghanistan as a high burden country for TB, with a rate of 168 cases
Mycobacterium with a sensitivity of > 95% in the presence of smear
per 100,000 population (9). Early recognition and prompt diagnosis of
positive sputum (4). It is also valuable for determining infection when
active TB are important for initiation of proper treatment and mini-
the sputum smear is negative (sensitivity of 5080%) (4). When nucleic
mizing risk of community transmission.
acid amplification is negative, it is not specific enough to rule out TB (4).
Tuberculin skin testing is not a first line diagnostic tool for active TB,
Although you are concerned about the possibility of tuberculosis,
but can be used as additional evidence when other diagnostic studies
you are perplexed by the reported lack of symptoms. You make ar-
are not definitive. Other laboratory evaluation should include HIV,
rangements to evaluate the patient today.
complete blood count, liver and renal function tests, uric acid, and uri-
2. What are the next most important steps in the care of this patient?
nalysis. Admission to the hospital with respiratory isolation is appro-
A. Obtain a complete history of the present illness including the
priate when social or clinical circumstances preclude outpatient
presence of cough, hemoptysis, chest pain, fever, chills, night
treatment. In this case, the patient lived in a communal setting that
sweats, weight loss, and a complete review of systems.
presented a risk of spread to the community.
B. Inquire about any past medical history of tuberculosis, bacille
Calmette-Guerin (BCG) vaccination, and exposure to ill family
The CT of the chest showed multiple, scattered pulmonary nodules,
members or close contacts.
both calcified and non-calcified, patchy tree in bud opacities in the
C. Make arrangements to meet the patient outside of the clinic to
right upper lobe, and bronchiectasis. Multiple sputum specimens were
have him put on a mask.
obtained; all had negative acid fast smears and a negative nucleic acid
D. Begin a contact investigation for active pulmonary tuberculosis.
amplification test. One culture eventually grew Mycobacterium tuberculosis
E. Report a possible case of tuberculosis to the local public health
resistant to streptomycin. A tuberculin skin test measured 23 mm.
department.
4. What is the most appropriate initial treatment for this patient?
A. Isoniazid 300 mg z d21 for 9 mo.
ANSWER/DISCUSSION B. Empiric treatment with rifampin, isoniazid, pyrazinamide, and
2. A, B, C, and E. A thorough history and examination will be help- ethambutol daily for 8 wk on DOT.
ful in further defining the risk for active pulmonary tuberculosis. Any C. Rifamycin, isoniazid, pyrazinamide, and ciprofloxacin for 8 wk.
person with a potentially infectious respiratory infection should be D. Rifampin, isoniazid, pyrazinamide, and streptomycin for 8 wk.
asked to wear a mask prior to entry into a healthcare facility. Active E. Levaquin for suspected community-acquired pneumonia.
pulmonary TB is a reportable disease in the United States. In some
states, contact with the public health department must be made within ANSWER/DISCUSSION
24 h of identification of a suspect case (2). The public health team will 4. B. Based on the radiographic evidence of TB, positive tuberculin
be important partners in the care of the patient, especially with di- skin test, and high risk for TB based on birth in an endemic region,
rectly observed therapy (DOT). The public health team will conduct empiric initial treatment is appropriate despite the initially negative
the contact investigation to identify new cases of tuberculosis and pre- sputum smears. The treatment for active pulmonary TB is divided into
vent spread of the disease in the community. initial treatment and continuation of treatment. The goal of initial
treatment is to rapidly kill bacilli to reduce infectiousness and prevent
You interview and examine the patient. He does not appear ill and emergence of drug resistance. The first line drugs for initial treatment
denies coughing, night sweats, and fever. After some prodding, he
does report a 10-kg weight loss in the past month, which he attributed
to American food aversion and stress. He also reports a negative
screening chest x-ray done at the time of entry into the country. He DOI: 10.3357/ASEM.3042.2011

Aviation, Space, and Environmental Medicine x Vol. 82, No. 7 x July 2011 743
YOURE THE FLIGHT SURGEONBRUEGGEMEYER
are rifampin, isoniazid, pyrazinamide, and ethambutol, which can be
given in various dosages and frequencies over an 8-wk period (1). The
goal of continuation therapy is to eliminate persistent bacilli from host
tissue to prevent relapse and it must be of sufficient length to achieve
this goal. The first line drugs for continuation treatment are isoniazid
and rifampin for 4 mo. Patients with cavitary disease and positive cul-
tures at 2 mo require extension of the continuation treatment to 7 mo
for a total of 9 mo of treatment (1). All treatment regimens are preferably
administered under direct observation (DOT) (1). Fluoroquinolones
can play a role in treatment of definitively diagnosed TB as a second
line drug. The use of fluoroquinolones for the empiric treatment of
community-acquired pneumonia in a patient at high risk for active
pulmonary TB can contribute to a delay in adequate treatment, contin-
ued risk to the community, and can promote drug resistance (1).
The patient responds well to therapy, with a progressive weight
gain and improved overall feeling of well-being. He is discharged
home to the dormitories after 10 d.
5. Additional steps that should be taken in the care of this patient
include:
A. Visual acuity and red-green color testing prior to the start of
ethambutol.
B. Hepatitis B and C testing due to the higher risk of hepatotoxicity
in infected patients.
C. Repeat sputum smear and culture at the completion of 2 mo of
initial therapy.
D. Continued respiratory isolation until initial treatment with clin-
ical response and three subsequent negative sputum smears.
ANSWER/DISCUSSION
5. A, B, C, and D. Ethambutol is known to cause dose-related (> 15
mg z kg21 z d21) retrobulbar neuritis manifested with decreased visual
acuity and red-green color deficiency. Baseline and monthly testing
are required prior to and during treatment (1). Isoniazid, rifampin,
and pyrazinamide are all associated with hepatotoxicity that is in-
creased with combination therapy, underlying liver disease (hepatitis
B and C), heavy alcohol consumption, pregnancy, and early postpar-
tum period (1). Monthly monitoring of liver function is required under
these higher risk circumstances. Respiratory isolation, whether inpa-
tient or outpatient, should continue until initial treatment with clinical
response and three consecutive sputum smears are negative. Repeat
sputum smear and culture is recommended at the completion of 2 mo
of initial therapy to determine the risk of relapse and the duration of
continuation therapy (1).
The flying training squadron commander calls you and wants to
know how long the student pilot will be down, what the risk of infec-
tion is to his instructor pilots, and what will happen if any of his in-
structor pilots (IP) also have TB. He reminds you of the high-visibility,
fast-paced nature of this program and the need to prevent an interna-
tional incident. You politely tell him that active pulmonary TB is not
very common in the United States or in the USAF population, and you
will get back with him as soon as possible with an answer.
6. Possible answers to the commander might include:
A. The student pilot was infectious for the period of time before
treatment started, and subsequent testing has shown that he is
no longer infectious. Initial treatment will involve multiple anti-
biotics, some with side effects dangerous to flying, and he will
have to be down at least for the 8 wk of this treatment. Return to
flying can be considered during continuation treatment depend-
ing on the toleration of medications and clinical recovery.
B. The contact investigation is underway to determine how many
of the IPs were infected with TB. You explain the difference be-
tween active and latent TB, that IPs with positive skin tests will
require treatment with isoniazid for 9 mo, and that isoniazid is
waiverable after a minimum 72-h ground trial.
C. The student pilot is infectious for an extended period and will
require long and complicated treatment, therefore, you recom-
mend the students removal from the program and return to
Afghanistan. You ask for a long period of leave until all this
blows over.
ANSWER/DISCUSSION
6. A and B. The aeromedical considerations of active pulmonary TB
can be divided into the effects of the disease itself and the adverse effects
of treatment. First, the aviator must not be infectious, which will be
744
indicated by three consecutive negative sputum smears and at least
2 wk of treatment. The aviator must be clinically recovered from infec-
tion, including resolution of fatigue, weight loss, cough, and any pulmo-
nary symptoms. Complications of pulmonary TB are hemoptysis,
pneumothorax, bronchiectasis, extensive pulmonary destruction, and
treatment failure. The advent of effective chemotherapy has made these
more serious complications rare. Treatment failure or relapse is most
likely to occur in the first 6 to 12 mo (1). Prior to consideration for waiver,
the aviator should have his pulmonary status fully evaluated, which
may include chest radiography, chest CT (if indicated), pulmonary func-
tion tests, oxygen saturation levels, and sputum smear and cultures.
The antibiotics for initial therapy are pyrazinamide, ethambutol, ri-
fampin, and isoniazid. The adverse effects of pyrazinamide are hepa-
totoxicity (1%), nongouty polyarthralgia (40%), hyperuricemia, rash,
and photosensitive dermatitis. The adverse effects of ethambutol are
retrobulbar neuritis with decreased visual acuity and red-green color
discrimination, which is a serious consideration for the aviator. This
adverse effect appears to be dose-related with little effect at the usual
dosage of 15 mg z kg21 z d21, but a rate as high as 18% at doses 30 mg
z kg21 z d21 (1). Ethambutol may be discontinued earlier than 8 wk if
the Mycobacterium is shown to be sensitive to isoniazid (1). The ad-
verse effects of rifampin include pruritis (6%), flu-like syndrome
(0.40.7%) that is more common with intermittent dosing, hepatotox-
icity, orange discoloration of body fluids, and severe autoimmune re-
actions such as thrombocytopenia and hemolytice anemia (< 0.1%) (1).
The adverse effects of isoniazid include hepatotoxicity, peripheral
neuropathy (< 0.2%), lupus-like syndrome (< 1%), and optic neuritis
(rare). Central nervous system effects such as dysarthria, irritability,
seizures, dysphoria, and inability to concentrate have been reported,
but have not been quantified (1). Peripheral neuropathy is dose-related
and more common in patients with nutritional deficiency, alcoholism,
pregnancy, diabetes, HIV, and renal failure. This side effect is easily
prevented with pyridoxine supplementation. The safety of isoniazid
in aviators was shown in a study of 58 aviators taking chemoprophy-
laxis for 1 yr. Of the 58, 2 discontinued the therapy due to arthralgias
and hepatotoxicity, but most tolerated the medication without safety
of flight issues (8). Hepatotoxicity and chemical hepatitis are a concern
with isoniazid, rifampin, and pyrazinamide. The incidence increases
from 1 to 2.7% when isoniazid and rifampin are combined (1). Careful
monitoring of liver enzymes and symptoms will allow for early recog-
nition and prevention of adverse outcomes in the aviator.
In summary, the combined side effects of multi-drug therapy and
the effects of Mycobacterium tuberculosis infection warrant restriction
from flying duty during the first 2 mo of therapy. When the aviator is
put on continuation therapy of isoniazid and rifampin, the aviator can
be assessed for return to flying based on clinical recovery and toler-
ance of medication (7). The aviator should be followed closely for the
duration of therapy and for 12 mo after. In the case of this aviator, he
experienced dysequilibrium on the days he took the medication. An
adjustment of dosage and schedule resolved the symptoms.
The diagnosis of active pulmonary TB is disqualifying for flying du-
ties according to the physical standards of the USAF, U.S. Army (USA),
and U.S. Navy (USN). For the Federal Aviation Administration (FAA),
it would fall under the category of any condition that adversely affects
the ability of the aviator to perform his duties. Return to flying status
will require submission for a waiver or special issuance. At this time,
there is not specific guidance in the USAF or USN aeromedical waiver
guides or the FAA Aerospace Medicine Examiner guide on the time
frame or requirements for waiver consideration. Waiver can be consid-
ered at the completion of initial therapy based on clinical status and
tolerance of medication (7). A review of the USAF waiver database
reveals that only one case of active pulmonary TB has been reviewed
with a waiver granted for a Flying Class III Load Master. With the in-
crease in foreign pilot training programs and joint operations in TB
endemic areas, the possibility of active pulmonary TB should be con-
sidered in aviators with cough greater than 2-3 wk duration, foreign
birth, or travel to endemic regions.
BRUEGGEMEYER MT. Youre the ight surgeon: active pulmonary
tuberculosis. Aviat Space Environ Med 2011; 82:7435.
AKNOWLEDGMENTS
The author wishes to thank Kevin West, M.D., M.P.H., FAAFP, Col.
(ret.), USAF, MC, SFS, for the valuable use of his time and expert assis-
tance in the preparation of this article. Dr. West is the tuberculosis, pre-
ventive, and occupational medicine program manager at Lackland Air
Force Base. The opinions expressed in this paper are those of the author
Aviation, Space, and Environmental Medicine x Vol. 82, No. 7 x July 2011
YOURE THE FLIGHT SURGEONBRUEGGEMEYER
and do not necessarily reflect the opinions or official policy of the U.S.
Air Force, U.S. Air Force School of Aerospace Medicine, Federal Aviation
Administration, or any other agency of the United States of America.
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