During March-August 2003, a total of 19 U.S. military personnel deployed
in the Central Command (CENTCOM) area of responsibility had bilateral pneumonitis
requiring intubation and mechanical ventilation; two patients died. This report
summarizes the results of the U.S. Army's investigation of these cases and
describes the ongoing investigation to determine the cause(s). Cases of rapidly
progressive respiratory failure among former or current CENTCOM personnel
should be reported to state health departments and to the Department of Defense
Of the 19 patients (median age: 25 years; range: 19-47 years), 18 were
men; 12 were full-time active duty personnel, and seven were in the Reserve
Component or National Guard (based in Arkansas, Illinois, Indiana, Kansas,
Missouri, New Mexico, and North Dakota). Seventeen were in the Army, one was
in the Navy, and one was in the Marine Corps; 11 were junior enlisted personnel,
seven were noncommissioned officers, and one was an officer. Military specialties
included combat arms (eight), engineering (three), transportation (two), signal
corps (two), medical services (two), supply (one), and military police (one).
Illness onset occurred a median of 81 days (range: 1-189 days) after arrival
in the area of responsibility. Ten patients had evidence of elevated eosinophils
in at least one of the following: peripheral blood (eight), bronchoalveolar
lavage fluid (three), pulmonary tissue (one), or pleural fluid (one). Among
the eight patients with peripheral eosinophilia, the maximum absolute number
of eosinophils was 2,000-6,600 µ/L of blood (normal: <600 µ/L).
The peripheral eosinophilia was detected a median of 6 days (range: 4-11 days)
after illness onset.
An interim case definition has been established. A confirmed case of
severe acute pneumonitis with elevated eosinophils is defined as an illness
occurring in a current or former member of the U.S. armed forces or a U.S.
government employee deployed to the CENTCOM area of responsibility who had
(1) bilateral pneumonitis (i.e., radiographically confirmed pulmonary infiltrates)
that required mechanical ventilation and that did not result from a complication
of another medical condition and (2) elevated pulmonary eosinophils (identified
histologically, in bronchoalveolar lavage fluid [>5%] or in pleural fluid
[>5%]). A probable case is defined as an illness in a person deployed to the
CENTCOM area of responsibility who had bilateral pneumonitis requiring mechanical
ventilation and the presence of peripheral eosinophilia (≥600 µ/L
blood absolute count). A suspect case is defined as an illness in a person
deployed to the CENTCOM area of responsibility who had bilateral pneumonitis
requiring mechanical ventilation only.
As of September 8, four cases were confirmed, six were probable, and
nine were suspect. Four patients had laboratory evidence of infection with
a microbial agent. Streptococcus pneumoniae was isolated
from sputum culture in one probable case. Three patients with suspect cases
showed evidence of infection (S. pneumoniae based
on urine antigen, Coxiella burnettii based on serology,
and Acinetobacter baumannii from bronchoscopic culture).
All patients were treated with broad-spectrum antibiotics, and six received
corticosteroids, including two patients whose cases were confirmed and three
whose cases were probable. The course of illness varied (median duration of
intubation: 6 days; range: 2-35 days). For some patients, infiltrates and
respiratory failure resolved rapidly (i.e., 2-3 days) with or without steroids,
and other patients required longer periods of mechanical ventilation. All
17 surviving patients either have been placed on convalescent leave or have
returned to duty.
When they became ill, 13 patients were in Iraq, and six were in other
countries (Kuwait [three], Djibouti [one], Qatar [one], and Uzbekistan [one]).
Other than two patients from the same unit with suspect cases and with onset
of illness 4 months apart, no apparent geographic or unit-level clustering
has been identified. Of the 19 patients, 15 (79%) smoked cigarettes or cigars,
including the 10 patients whose cases were either confirmed or probable. Nine
of these 10 patients had begun smoking tobacco after deployment, compared
with none of the nine patients whose cases were suspect. Two recent-onset
smokers reported smoking non-U.S.-brand cigarettes. All troops in the CENTCOM
area of responsibility have been exposed to heat, dust, and various amounts
of environmental pollution (e.g., smoke).
The U.S. Army is conducting a clinical and epidemiologic investigation
to identify the cause(s) of this disease, including intensive testing of clinical
material (i.e., blood, urine, bronchoalveolar lavage fluid, and acute and
convalescent sera) to identify potential microbial pathogens and toxins. In
addition, military personnel are interviewing patients systematically to identify
any common exposures or practices. Environmental testing to identify potential
toxins will be guided by clinical diagnostic and patient surveys. Initial
data analysis suggests that medications, vaccines, and biologic weapons are
not associated with the disease.
Operation Iraqi Freedom Severe Acute Pneumonitis Epidemiology Group,
U.S. Army Medical Command. National Center for Infectious Diseases; National
Center for Environmental Health, CDC.
The majority of cases of acute lower respiratory illness (LRI) among
U.S. military personnel in Southwest Asia have been comparable clinically
and have occurred at a rate similar to those in other military populations
and settings.1 In contrast, the rapidly progressive LRI cases described
in this report were life-threatening and required intensive medical care,
including mechanical ventilation with high-end expiratory pressures.
Although investigations are ongoing, preliminary findings suggest a
subset of these cases are compatible with the diagnosis of acute eosinophilic
pneumonia (AEP). AEP is an acute febrile illness without an identifiable infectious
cause that is characterized by the rapid onset and progression of respiratory
failure, diffuse bilateral infiltrates on chest radiographs, and elevated
eosinophils in lung biopsy specimens or bronchoalveolar lavage fluid.2 Cigarette smoking (particularly of recent onset) is a risk factor
for AEP,3-7 and some affected persons have experienced acute respiratory
distress when exposed to cigarette smoke in a laboratory setting.5,6 The finding that nine of the 10 persons whose cases were severe and
who had documented elevated eosinophils started smoking cigarettes after their
deployment suggests the possibility of a toxin or allergen exposure; however,
no single brand of cigarette or location of production has been implicated
in this association. DoD has advised CENTCOM personnel that cigarette smoking,
particularly the initiation of smoking, might be associated with the development
of severe acute pneumonitis with elevated eosinophils.
In 1997, two U.S. soldiers had rapidly progressive acute respiratory
distress syndrome and elevated eosinophils shortly after returning from field
training in the Mojave Desert in California.8 The occurrence of
these cases in troops who were not deployed overseas suggests that exposures
unique to Iraq (e.g., abandoned buildings, unexploded ordnance, and war-damaged
vehicles or equipment) or to any of the countries in which the cases occurred
(e.g., indigenous food, water, and materials) might not be necessary or sufficient
for the development of this disease.
No U.S.-based military personnel are known to have had severe acute
pneumonitis with increased eosinophils during this period. However, the return
of troops from Southwest Asia raises the possibility that U.S. health-care
providers might be the first to observe members of this population who experience
otherwise unexplained, acute respiratory failure. Clinicians should elicit
the travel histories of patients with rapidly progressive respiratory failure
of unknown etiology and report cases occurring among persons, particularly
military personnel, who have returned recently from the CENTCOM area of responsibility
to their state health department and to the U.S. Army Center for Health Promotion
and Preventive Medicine, telephone 410-436-4655.
References: 8 available
Severe Acute Pneumonitis Among Deployed U.S. Military Personnel—Southwest Asia, March-August 2003. JAMA. 2003;290(14):1845–1846. doi:10.1001/jama.290.14.1845