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Role of respiratory physicians in preparing for bioterrorist attacks
Bioterrorism is a “hot topic”; a search of the literature and the internet reveals an explosion of publications, government strategies, and guidelines, as well as advice for the general public. Bioterrorism differs from “biowarfare” in the sense that the threat emanates from terrorist groups rather than nation states. Unlike conventional warfare, where the enemy, underlying circumstances and likely mode of warfare are known and understood, terrorism is less easy to predict—being sometimes aimed against seemingly random targets with little regard for the lives of civilian victims or that of the perpetrator. Chemical and biological weapons are very effective agents for terrorists whose strategy is not only to injure but also to instil terror and disorder into daily life, which may have long lasting psychological, economic, and political consequences. The terrorist attacks on the World Trade Center on 11 September 2001 and subsequent deliberate release of anthrax into the community in the USA in October 2001 has focused our attention on the threat of terrorism. Thus, at the recent Winter Meeting of the British Thoracic Society, the British Association for Lung Research organised a symposium which they called “Bioterrorism: The Lung Under Attack”. In addition, in this issue of Thorax O’Riordan and Smaldone address the need for preparedness by the respiratory community—particularly clinical and supporting services—to combat acts of terrorism.1
Germ warfare is not new.2,3 The Greeks and Romans polluted their enemy’s drinking water with animal corpses; the dead bodies of plague victims were catapulted by the Tartars into Kaffa in the 14th century; the British distributed blankets from smallpox victims amongst local American Indian populations during the 18th century destroying a high proportion of the population; during the first World War Germany attempted to obstruct food supplies by infecting cattle with anthrax and glanders; during the second World War the British developed an anthrax bomb which was tested on the Island of Gruinard, as well as producing five million anthrax loaded pieces of cattle cake with the intention of dropping these over Germany to reduce meat supplies by 30%. Remarkably, no chemical or biological agents were used as weapons during World War II.
Bioterrorism is often taken to mean terrorist acts that involve the use of biological materials such as bacteria, bacterial spores, and viruses. This is a limited definition: terrorists could elect to use a range of agents that lie along a spectrum from classical chemical warfare agents at one extreme to biologically viable particles such as bacteria at the other. The lung is a target for all compounds that can be dispersed as gases or aerosols, and chest physicians may be among the first to recognise and deal with casualties exposed to such compounds. Understanding the effects of these substances on the lung is therefore important.
EFFECTS OF BIOTERRORIST AGENTS ON THE LUNG
The lung’s range of response to injury is limited—for example, bronchoconstriction and pulmonary oedema are the major effects of inhaled chemical compounds. This is well understood, but the absence of specific antidotes makes our therapeutic approach limited. Chlorine and phosgene are widely used industrial chemicals and, although they have been known to be very dangerous since before their large scale use in World War I, no specific antidotes to their effects have been found.3,4 It is a sad fact that our capacity to treat the effects of exposure to phosgene is little better today than it was in 1915. Why is this?
Chemical agents
One reason is that lung damaging compounds such as phosgene do not interact with a single pharmacologically defined receptor. On the contrary, they damage cell membranes and inhibit a range of vital enzyme systems.3,4 If we knew better the biochemical pathways involved, then developing specific antidotes might be possible. One line of attack is to oppose free radical generation by replacing depleted antioxidants such as glutathione. Some success has been achieved in animal models but little clinical benefit has been reported. Another approach is to treat the inflammation that may occur: the case of steroids has been strongly supported by some authorities but, again, hard evidence of efficacy in man is lacking. The increase in pulmonary capillary permeability produced by phosgene cannot be reversed by drug treatment. Support of adequate exchange of oxygen and carbon dioxide is vital and the use of positive end expiratory pressure ventilation has long been recommended. Recent animal studies have shown the value of limiting the tidal volume while maintaining an adequate minute volume in the management of respiratory failure caused by exposure to phosgene (personal communication, Dr Paul Rice, 2003).
Mustard gas (sulphur mustard) is an alkylating vesicant which may be dispersed by aerosolisation and slowly vaporises.3,4 It can be synthesised with limited equipment. Unlike chlorine and phosgene which reach the distal respiratory units, mustard gas deposits in and damages the conducting airways and adjacent alveoli. Stripping of epithelium occurs and infection may follow. Again, there is no antidote. However, although the effects may be severe, the lethality of exposure to mustard gas is likely to be low: during World War I only 1–2% of those exposed died later.
Nerve agents (nerve gases) which date from the 1930s occur as more or less volatile liquids and are the most toxic of the classical chemical warfare agents, causing death at very low doses. The case of the nerve agent sarin (GB, isopropyl methylphosphonofluoridate3,4) released by a religious terrorist group in Japan in the mid 1990s showed that well organised and well funded groups can produce deadly compounds in sufficient quantities to kill or injure large numbers of people. Because the mechanism of action of nerve agents is understood, there are a number of drugs available but treatment should be rapid. Prolonged ventilatory support may be needed for those who survive the initial exposure.
The use of chemical agents by terrorists should not be confused with the potential military use of such compounds—and even more so of biological agents—as weapons of mass destruction. It is more likely that the use of chemicals by terrorists would produce a limited number of casualties, the death rate depending on the compounds deployed and the extent of exposure both in terms of the concentration–time product and the number of people affected. Development in understanding the mechanisms of action of chemicals that might be used will aid in the development of rational treatment, although this will often be mainly supportive.
Biological agents
Biological materials that may be used by terrorists include bacteria such as Bacillus anthracis (anthrax),2–4 viruses such as Variola major (smallpox),2,4 and biological toxins such as ricin.3–5 Ricin is a less well known compound but was studied extensively as a potential warfare agent during World War II and was used in the assassination of the Bulgarian journalist Georgi Markov in London in 1978. It is derived in relatively large quantities during processing of castor oil from Ricinis communis seeds.5 Ricin is highly toxic: the lethal dose in man may be less than 1 mg (injected). Importantly, it is particularly toxic when inhaled, causing fever, chest tightness, dyspnoea, and cough within 4–8 hours. It is believed that death is due to multiple organ failure. Treatment is supportive.
Bacillus anthracis occurs commonly in the environment, but terrorists would need the technical expertise to obtain virulent strains, purify spores, and develop an effective dispersal system.2 However, the events of October 2001 show that this is possible. A problem with identification of an anthrax attack involving exposure by inhalation is that the early symptoms resemble “flu” and treatment has a poor prognosis if delayed. This is complicated by the lack of clinical trials and the possibility of resistance to antimicrobial agents. Despite access to antibiotics, five of 11 patients who contracted anthrax died in the October 2001 incident. Rapid identification of anthrax exposure and antimicrobial therapy within the first week considerably improves the prognosis.
The smallpox virus would be very much more difficult to obtain as it is known to be kept in only two places in the world; however, it may be that there are other stores.2 Current stores of vaccine were produced from animal lymph and have been in storage for over 20 years. Recent use of these vaccines (by Israel and the USA) has highlighted some previously expected side effects, most notably myopericarditis.6 Consequently, new safer vaccines and safer vaccination strategies need to be developed and stockpiled to ensure effective rapid vaccination following exposure.2,6 In addition, since its eradication, smallpox might not immediately be recognised by younger physicians.
The effects of inhaled particles on the lung following the terrorist attack on the World Trade Center in September 2001 were also addressed at the BTS/BALR symposium under the broad umbrella of bioterrorism. In addition to the thousands of people who were killed immediately, there were also exceptional environmental hazards for residents and workers in New York City. The collapse of the World Trade Center released huge quantities of material into the air and the plume of debris and smoke engulfed and contaminated a large area. Although the ambient concentration of fine particulate matter (which would affect peripheral lung regions) rarely exceeded government guidelines, the larger particles—which are not subject to regulation and which contained irritants such as fibre glass and were alkaline—caused respiratory irritation (for example, “World Trade Center cough”),7 probably due to effects on the large airways. In addition, new onset respiratory symptoms are significantly higher in those who live near the World Trade Center, while a small subset displays more bronchial hyperresponsiveness.
HOW SHOULD RESPIRATORY PHYSICIANS PREPARE FOR BIOTERRORIST ATTACKS?
An ongoing theme of the BTS/BALR meeting was the necessity for the emergency services, hospitals, and physicians to be prepared.4 It is important that decontamination is rapid and effective, and that none of those providing aid becomes contaminated in the process. Thus, staff must be protected and must be able to work in protective clothing. Furthermore, they must be able to use specialist equipment, which requires training and practice, and have access to appropriate therapeutic agents. O’Riordan and Smaldone1 stress the need for a cohesive strategy by respiratory societies such as the British Thoracic Society to ensure rapid identification of respiratory symptoms consistent with an act of bioterrorism, to summon a rapid and effective response, and to promote the need for respiratory research in the area. That chest physicians should be familiar with recent developments in this area is beyond doubt.
Role of respiratory physicians in preparing for bioterrorist attacks