key: cord-0006851-r5hkv4me authors: Huprikar, Nikhil A.; Deas, Steven D.; Skabelund, Andrew J. title: Non-traumatic Pulmonary Emergencies in the Deployed Setting date: 2017-05-27 journal: Curr Pulmonol Rep DOI: 10.1007/s13665-017-0180-1 sha: 111b2c45e45849325feb7176183f88672d549e85 doc_id: 6851 cord_uid: r5hkv4me PURPOSE OF REVIEW: Pulmonary disorders accounted for up to 8% of the over 70,000 medical evacuations conducted from Iraq and Afghanistan in the past 15 years. This review of non-traumatic pulmonary emergencies provides an overview of deployed military medical treatment capabilities and highlights pulmonary emergencies requiring aeromedical evacuation from theater. RECENT FINDINGS: Recent studies have improved the epidemiologic evaluation of non-traumatic pulmonary disease, highlighted specific parenchymal diseases, and revealed infection pathologies unique to the deployed setting. Literature regarding possible chemical exposures in the current deployed environment remains limited. SUMMARY: Respiratory disorders requiring medical evacuation represent a wide variety of diseases. Complications such as pulmonary emboli, infectious pathogens, and hazardous chemical exposures threaten the deployed warfighter. Adequate medical care requires an understanding of these potential environmental exposures. This review serves as a general overview of this topic; however, more research regarding epidemiologic and environmental exposures is required. Since the initiation of combat operations in 2001, more than two million military personnel have been deployed to Southwest Asia. From 2003 to 2011, over 70,000 service members were evacuated from combat zones in Southwest Asia for non-combat-related illnesses and injuries. Pulmonary conditions were responsible for 3-8% of these evacuations. The management of pulmonary diseases in the deployed setting is complicated due to numerous environmental hazards, toxic exposures, and limited resources. This review will summarize the respiratory conditions that require aeromedical evacuation (AE). First, in-theater medical capabilities and then the treatment and diagnosis of pulmonary diseases in the deployed setting will be reviewed. Finally, unique infections and inhalational threats to service members in Southwest Asia will be discussed. An appreciation of combat medical care is necessary to understand the diagnosis, treatment, and disposition of deployment-related respiratory emergencies. Deployed medical resources are asymmetrically distributed, as the goal of combat medicine is to perform immediate lifesaving interventions and stabilize casualties for transport to higher levels of care. Military doctrine describes a five-tiered disbursement of medical resources through increasing echelons of care [1•] . Echelon I facilities are forward aid medical stations without This article is part of the Topical Collection on Pulmonology in Combat Medicine surgical capabilities. Echelon II comprises medical facilities that perform lifesaving "damage control" surgery. These facilities have basic laboratory and radiologic capabilities but have minimal holding capacity and lack the ability to perform bronchoscopies or other advanced medical interventions [2] . Echelon III provides surgical subspecialties, robust intensive care capabilities, and more extensive holding capacity. These facilities provide the highest level of in-theater medical care but are often limited by manpower and bed availability. Echelon IV facilities are military hospitals located outside of combat zones, but not within the U.S.A. Echelon V facilities are military hospitals located within the U.S.A. More exhaustive descriptions of AE and military medical doctrine are described elsewhere [1•, 2, 3] . Specialized teams exist to transport patients between higher echelons of care. These include critical care air transport teams (CCATT), a burn flight team, and an acute lung rescue team (ALRT) [1•, 4, 5•] . Over the past 15 years, more than two million service members have been deployed to Southwest Asia [6] . During a 12-month combat deployment, approximately 4% of army personnel, 2% of marine corps, and 1% of navy and air force members are medically evacuated [7] . From 2003 to 2011, 50,634 service members were evacuated from Iraq. Of those evacuations, 41,690 (82.3%) were for disease and non-battle injuries (DNBI). Pulmonary symptoms and diagnoses accounted for 1167 (2.6%) of evacuations [6] . An echelon II facility in Iraq reported that of 4831 encounters, 4663 (93%) were for DNBI. Of those outpatient encounters, 191 (4%) were for upper respiratory complaints and 56 (1.2%) for asthma or other respiratory issues. During the survey, one soldier was evacuated for asthma [8] . Another analysis of 343 patients evacuated for DNBI showed 3% had underlying pulmonary conditions [9] . Of 875 intensive care unit admissions to a combat support hospital, 125 were admitted for DNBI and 8% were admitted for pulmonary etiologies [10] . Over 11 years, 23,719 personnel were evacuated from Afghanistan. DNBI accounted for 18,144 (76.2%) of these evacuations and 442 (1.9%) were for pulmonary complications [11] . A review of 10 years of CCATT data reveals that of 673 DNBI CCATT missions, 107 (15.9%) were related to pulmonary conditions [12] . Due to the large spectrum of diseases, diverse exposures, variable environments, and sporadic reporting, the precise characterization of non-traumatic pulmonary emergencies in deployed personnel is difficult. However, with nearly 80000 soldier days lost to DNBI over a 2 year period [13] and with pulmonary disease representing 3-8% of DNBI evacuations [6, 7, 11] , the impact of non-traumatic downrange pulmonary emergencies is a relevant topic for bother service members and medical providers. For the purposes of this article, pulmonary emergencies will be defined as any pulmonary condition associated with respiratory failure, death or requiring medical evacuation from the theater of operations. Other pulmonary conditions such as altitude illness and thromboembolic disease are addressed elsewhere. Acute eosinophilic pneumonia (AEP) is an acute, hypersensitivity-like reaction resulting in eosinophilic infiltration of the lung parenchyma. Common inciting factors include parasitic infection, drug hypersensitivity, tobacco use, and systemic eosinophilic disorders [14] . AEP presents with fever, hypoxia, diffuse pulmonary infiltrates, and eosinophilia. Symptoms develop over the course of hours, days, or weeks [15] . Diagnostic criteria include an acute respiratory illness, bilateral pulmonary infiltrates, hypoxemia, and greater than 25% eosinophils on bronchoalveolar lavage [16, 17] . AEP is treated with corticosteroids and supportive care and frequently requires mechanical ventilation [18] [19] [20] . In 2004, 18 cases of AEP were described among personnel evacuated from Iraq. Most of the patients were men and reported dust exposure. All used tobacco [19] . A follow-up study described 43 additional cases of AEP among military members from 2003 to 2014 [20] . Nearly 90% of the patients smoked, and more than 70% had recently started smoking or increased cigarette use. This is consistent with the known association of AEP and tobacco use [21] . All patients required oxygen supplementation or mechanical ventilation and were evacuated from theater. The diagnosis may be delayed in the deployed setting due to limited access to bronchoscopy and laboratory resources. In patients with a history suggestive of AEP, early empiric antibiotics and steroids should be considered. AE to higher levels of care is mandatory. Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse lung inflammation and hypoxic respiratory failure [21] . Trauma and trauma resuscitation are the most common etiologies for ARDS in the deployed setting. Other etiologies include inhalational injuries, infection, and pancreatitis [22] . Treatment of ARDS in the deployed setting is similar to that employed elsewhere [22] with an emphasis on treatment of the underlying etiology, lung protective ventilation, and conservative fluid management. In the downrange setting, ARDS is most commonly associated with combat trauma. A review of the U.S. DOD trauma registry revealed approximately 3% of trauma patients developed ARDS. Risk factors for developing ARDS included female sex, more severe injuries, hypotension, and tachycardia on presentation [23] . Patients with ARDS also had higher risk of death and used more resources. Prolonged respiratory support and rehabilitation preclude maintaining these patients in theater [3] . Severe ARDS is the most common reason for activation of the ALRT [4] . Chemical weapons have a storied history. They have been used in numerous conflicts throughout history and were used by Iraq in the Iraq-Iran war and against Kurdish Iraqi citizens [24••] . The threat of chemical weapon exposures played a prominent role in the planning and strategies of the first Gulf War and the most recent conflicts in Iraq and Afghanistan. In these conflicts, there have been multiple reports of individual exposures, but the medical literature regarding these exposures is limited [25] [26] [27] . Classically, chemical agents are classified into choking agents, blood agents, blister agents, and nerve agents. Choking agents are sub-categorized into centrally acting agents and peripherally acting agents. Centrally acting agents, such as chlorine, are highly water soluble and mainly affect the upper airway, larynx, trachea, and large airways; symptoms begin soon after exposure. Peripherally acting agents such as phosgene are less water soluble, affect the distal airways, and often have a delayed onset of symptoms [28] . Management of inhalation injuries requires early recognition, limiting additional exposure, and respiratory support. Definitive therapies are limited. Chlorine is a readily available chemical used for sanitation and for public works projects. When combined with explosives, chlorine can be vaporized and dispersed as a chemical weapon. Acute exposure causes bronchoconstriction resulting in wheezing, coughing, and chest tightness. Hypoxemia and infiltrates may also be present. Treatments include respiratory support, bronchodilators, and inhaled corticosteroids [28, 29] . Inhaled sodium bicarbonate may scavenge chlorine free radicals and minimize long-term effects [30] . Long-term sequelae from chlorine exposure include reactive airway dysfunction syndrome (RADS) and bronchiolitis obliterans syndrome [31] . The use of chlorine tankers in vehicle-based improvised explosive devices has occurred on multiple occasions during the recent conflicts [29, [32] [33] [34] . Additionally, attacks conducted with "chlorine-filled rockets" have been reported [35] . Although the clinical course of service members exposed to chlorine is unavailable, news reports cite substantial civilian and military casualties from chlorine exposure [29, 32, 35, 36] . Given the easy accessibility and facile disbursement, weaponized chlorine has and will continue to play an important role in military operations. Phosgene is the prototypical peripheral choking agent and has previously been used in numerous conflicts. Phosgene is a chemical solvent widely used by the pharmaceutical and chemical industries [24••, 37] . Nasopharyngeal pain and irritation are the initial complaints. Over several hours, progressive dyspnea, cough, and foamy sputum production will develop. Hypoxia on room air is predictive of lung injury and ARDS [24••] . No specific antidote exists for phosgene toxicity. Treatment is limited to supportive care and lung-protective ventilation [38] , though the administration of corticosteroids and nebulized N-acetylcysteine may be beneficial [39] . There are no recent reports of phosgene exposure in military members in Southwest Asia; however, due to its relatively common availability and potential for significant harm, phosgene remains an agent of clinical and tactical concern. Hydrofluoric Acid Heptafluoropropane is a hydrofluorocarbon used for fire suppression and was part of the automated fire suppression systems in military vehicles. At high temperatures, heptafluoropropane breaks down to hydrofluoric acid. Vaporized hydrofluoric acid from vehicle fires has been linked to two soldier deaths and two patients requiring ALRT evacuation [40] . The soldiers presented in respiratory distress and had diffuse peripheral lung infiltrates on radiograph. Treatments include decontamination and early respiratory support. Nebulized calcium and sodium bicarbonate may be beneficial [40] . A heptafluoropropane-based fire suppression system continues to be used in military vehicles, and therefore, there remains a potential inhalational hazard to military personnel. Sulfur dioxide (SO 2 ) and hydrogen sulfide (H 2 S) result from the combustion of elemental sulfur. SO 2 is water soluble and causes skin and airway irritation [41] . H 2 S is a toxic gas that is a major contaminant of natural gas reservoirs [42] . Intense exposure to SO 2 and H 2 S causes upper airway obstruction, laryngospasm, hypoxemia, and pulmonary edema [41, 43] . Therapy for acute exposure includes minimizing additional exposure, bronchodilators, and respiratory support [41] . In 2003, the Al-Mishraq sulfur mine fire potentially exposed thousands of U.S. troops to high levels of SO 2 and H 2 S [44] . Firefighters and support elements had the highest exposure; however, no serious health consequences were noted [45] . No long-term sequelae were clearly identified in these firefighters; however, there is a controversial association between exposure to this event and constrictive bronchiolitis and RADS [46] . The mine was reignited in October 2016 during the ongoing battle for Mosul [50] . Media reports associated with the 2016 fire indicate there have been 2 civilian deaths and more than 1000 respiratory complaints from the fires [47] . U.S. and coalition troops remain in the area and are at high risk for exposure to these agents. Mustard agents are strongly lipophilic liquids that can be dispersed by explosive blasts and contaminate numerous individuals. Brief high-intensity exposures cause skin and eye injury. Aerosolized exposure can provoke respiratory failure. Tachypnea, bronchospasm, increased secretions, and a productive cough are common respiratory complaints after intense exposures [48] . Treatment includes decontamination, use of sodium thiosulfate, vitamin E, and steroids soon after exposure. Mechanical ventilation is necessary for respiratory compromise [48] . The medical literature cites one case of a soldier being exposed to chemical agents in Iraq [48] ; however, there are numerous news reports of other exposures, and weaponized mustard agents have been uncovered throughout Iraq [25] [26] [27] . In addition, the Islamic State of Iraq and the Levant (ISIL) have recently used mustard agents against U.S. troops [49, 50] . The non-traditional tactics and adversaries faced in the current conflicts make exposure to banned chemical warfare agents more likely. Nerve agents inhibit synaptic cholinesterase activity and cause unopposed cholinergic activity [51] . Aerosolized agents can be absorbed through the skin or respiratory tract and then distributed throughout the body. Symptoms include meiosis, rhinorrhea, salivation, bronchostriction, and bronchorrhea. Cardiovascular autonomic lability, coma, seizures, and central apnea are also reported [24••, 52] . The diagnosis of nerve agent exposure is based on clinical presentation and history. Therapy involves decontamination, respiratory support, and pharmacologic therapy with atropine, pralidoxime chloride, and diazepam [24••] . During the First Gulf War, service members were exposed to sarin while destroying a munitions depot in Khamisiyah, Iraq, in 1991 [53] . In the current conflict, there are no reports in the medical literature of nerve agents causing military casualties. However, several soldiers attempting to disarm warheads had symptoms suggestive of nerve agent exposure [25, 26] . Sarin was recently used in the region, and there is concern ISIL may acquire old nerve agent munitions [54] . Burn injury often requires extensive resuscitation and hemodynamic monitoring. Although burn injuries often present in patients with traumatic injuries, inhalational burn injuries are not isolated to traumatic incidents. Reviews of military combat trauma and burn care can be found elsewhere [55, 56•] . Inhalational burns are categorized into flash burns or smoke inhalation injuries. Flash burns expose the upper airways to thermal injury. Smoke inhalation injury involves chemical burns of the lower airway. In both scenarios, the airway epithelium is denuded and reactive pulmonary changes occur. The subsequent edema and inflammation can cause an exudative cast formation of denuded epithelium [55] . Common inhalation burn manifestations include laryngeal edema and respiratory compromise. Smoke inhalation can result in bronchoconstriction and pulmonary edema [55] . Individuals with facial burns require airway visualization for assessment of inhalation injury [57] . Treatment options including endotracheal intubation for airway protection, routine use of inhaled heparin/N-acetylcysteine, chest physiotherapy, and bronchoscopies to improve airway hygiene have been suggested [58] [59] [60] . Between 2003 and 2005, burn injuries accounted for 5% of theater evacuations. Facial burns were seen in 77% of those patients and 26% had inhalation injuries [61] . Given the lack of necessary equipment to diagnose airway injuries at echelon I and II facilities, prophylactic intubation and subsequent AE is necessary in any patient with suspected inhalational injuries [55] . Reactive airway dysfunction syndrome (RADS) is an acute-onset respiratory syndrome occurring minutes to hours after a single high-intensity exposure to a respiratory irritant. Following the exposure, an asthma-like syndrome with airway hyperreactivity persists. Traditional RADS diagnostic criteria include symptoms within 24 h of exposure and a positive methacholine challenge test [62] . The current diagnostic criteria also require airway hyperreactivity for greater than 3 months [62] . Sulfuric acid, ammonia, chlorine, diesel, fire/smoke, mustard gas, and sulfur dioxide have all been associated with RADS [63, 64] . With an acute presentation, the differential may include pneumonia, asthma, non-cardiogenic pulmonary edema, and AEP. While the incidence of RADS is difficult to ascertain in deployed personnel, numerous service members have developed symptoms following an acute high-intensity exposure to inhalational irritants. Deployed individuals are frequently exposed to many of the irritants known to cause RADS. RADS should also be a consideration in any mass causality situation with fire, gas, or munition exposure. Treatment consists of corticosteroids and bronchodilators [65] . Prior to 2003, individuals with asthma were not eligible for military service. Currently, individuals with asthma are permitted to enter the military with a proper waiver and may be deployed if their symptoms are well controlled [66] . A post-deployment survey of 1200 soldiers returning from Southwest Asia showed that 61 (5%) reported being asthmatics [67] . Those with asthma experienced more respiratory complaints than non-asthmatics. Half of asthmatics sought treatment for respiratory complaints while deployed, and 10 (16%) reported missing duty days or being hospitalized for respiratory symptoms [67] . A review of ICD-9 codes in 6000 charts at a single VA center suggested there were higher rates of "new asthma" in soldiers who had been deployed between 2003 and 2007 than those who had not been (6.6 vs 4.3%) [68] . Deployed service members are exposed to airborne particulate matter (PM) from geological dusts, burn pit emissions, wasted munitions, and regional pollutants. Many service members complain of respiratory symptoms while deployed [69, 70] ; however, this is particularly true for asthmatics [67] . The perpetual exposure to environmental irritants increases the likelihood of asthma exacerbations. Most echelon I and II facilities have the required medications and equipment to treat mild exacerbations; however, these facilities lack the manpower and expertise to manage severe exacerbations. Symptoms will not improve if patients are not removed from the irritation. Given these factors, most moderate and severe asthma exacerbations are evacuated from theater. Community-acquired pneumonia, influenza, and theater-specific organisms affect numerous service members in the deployed setting. These infections can cause severe respiratory illnesses leading to septic shock and respiratory failure. At the height of the conflicts in Southwest Asia, there were multiple evacuations every month for severe respiratory infections [71] . The topics included here represent a small subset of potential infectious etiologies that have been linked to respiratory failure and required evacuation from theater. Common infectious agents are not included. Q-fever is a zoonotic infection caused by inhalation of Coxiella burnetti. It is highly infectious and is considered a category B biologic agent [72] . Q-fever often develops after individuals are in close proximity to cattle, goats, and sheep. Acute infections present with a flu-like illness that can progress to severe pneumonia and acute hepatitis. Other manifestations include meningoencephalitis, endocarditis, and osteomyelitis [73] . Serologic testing is required for a diagnosis; however, the testing is not available in theater [72] . Q-fever markedly impacted military operations in Iraq [74, 75] . Serologic evaluations of 909 service members with febrile illnesses showed 10% likely had Q-fever and 22 members required AE out of theater [76] . In 2005, a marine platoon suffered an outbreak of Q-fever. No marine required evacuation from theater, but 64 duty days were lost due to the illness [74] . Subsequent reports describe Q-fever-associated cholecystitis and ARDS in deployed service members [75] . The treatment of choice is doxycycline. Given the outbreak potential and the difficulty in diagnosing Q-fever, doxycycline is often added empirically to treat respiratory infections of soldiers in theater [66] . Numerous viral infections have been reported in the deployed environment. Surveillance conducted by the Medical Surveillance Monthly Report has attempted to quantify the prevalence of significant infections, but the data is from retrospective chart reviews without PCR testing. A serologic analysis of 1000 troops deployed to Southwest Asia revealed that while deployed over 30% seroconverted to at least one of the following infections: influenza, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, adenovirus, parainfluenza, or respiratory syncytial virus [77•] . During the H1N1 influenza pandemic, 6344 Afghan soldiers were seen for respiratory complaints and 319 were deemed to be infected with H1N1. Sixty-one of these soldiers were evacuated to higher levels of care, and 58 of those 61 required treatment for severe pneumonia [78] . Viral infections decrease individual and unit readiness and in the setting of limited resources often prompt AE to higher levels of care. Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening viral illness endemic to Africa and the Middle East. Caused by an infection from a tick or contact with blood/bodily fluids of infected animals, the disease presents with high fevers, followed by an altered mental status and hemorrhagic manifestations. There is estimated 30-50% mortality within 14 days of symptom onset. Ribavarin therapy and supportive care are the standard treatments. In addition to therapy for an infected individual, infection control measures must be undertaken to limit exposure. One case of CCHF has been reported in an American soldier. The soldier was serving in Afghanistan and had been exposed to tick bites and undercooked goat meat. He initially sought treatment for 4 days of diarrhea and hematemesis. He soon developed bloody diarrhea, gingival bleeding, hypoxia, and alveolar hemorrhage. He was transferred to an echelon IV facility where he received numerous units of blood and was started on Ribavarin therapy. The patient died from massive cerebral edema and herniation after 7 days in the ICU [79] . A high degree of suspicion is required to diagnose and expedite AE of patients with viral hemorrhagic fever. The multi-organ system failure, respiratory support, and intensive laboratory requirements preclude managing these patients in the deployed environment. Additionally, vigorous infection control and outbreak control measures must be managed throughout AE and at higher echelons of care. Acinetobacter is a gram-negative coccobacillus native to the soil of Southwest Asia. It readily colonizes the skin, wounds, and respiratory and gastrointestinal tracts [80] . It readily develops antimicrobial resistance making nosocomial strains particularly concerning. Acinetobacter has caused numerous ventilator-associated pneumonias and wound-site infections [80] . Rarely, primary pneumonias are caused by Acinetobacter, but it more commonly causes secondary infections in patients being mechanically ventilated or with open wounds [81, 82] . Treatment options are guided based on susceptibilities, most commonly with use of carbapenem and polymyxin therapy [81] [82] [83] . In the recent conflicts in Iraq and Afghanistan, nearly 2000 service members have been evacuated for pulmonary-related conditions. With an array of underlying etiologies, the diagnostic and treatment capabilities of these patients in the deployed environment are often limited. Awareness of the potential pulmonary diseases affecting soldiers downrange is crucial to optimizing health care in the deployed environment. 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