Acute inhalation injury may result from frequent and widespread use of household cleaning agents and industrial gases (including chlorine and ammonia). The airways and lungs receive continuous first-pass exposure to non-toxic and irritant or toxic gases via inhalation. Irritant gases are those that, on inhalation, dissolve in the water of the respiratory tract mucosa and provoke an inflammatory response, usually from the release of acidic or alkaline radicals.Bessac BF, Jordt SE. (2010) Sensory detection and responses to toxic gases: mechanisms, health effects, and countermeasures. Proc Am Thorac Soc. 7: 269-77.do Pico GA. (1995) Toxic gas inhalation. Curr Opin Pulm Med. 1:102-8. Smoke, chlorine, phosgene, sulfur dioxide, hydrogen chloride, hydrogen sulfide, nitrogen dioxide, ozone, and ammonia are common irritants.
Depending on the type and amount of irritant gas inhaled, victims can experience symptoms ranging from minor respiratory discomfort to acute airway and lung injury and even death. A common response cascade to a variety of irritant gases includes inflammation, edema and epithelial sloughing, which if left untreated can result in scar formation and pulmonary and airway remodeling. Currently, mechanical ventilation remains the therapeutic mainstay for pulmonary dysfunction following acute inhalation injury.
Causes Smoke inhalation Smoke inhalation injury, either by itself but more so in the presence of body surface burn, can result in severe lung-induced morbidity and mortality.Clark WR Jr. (1992) Smoke inhalation: diagnosis and treatment. World J Surg. 16: 24-9. The most common cause of death in burn centers is now respiratory failure. The September 11 attacks in 2001 and forest fires in U.S. states such as California and Nevada are examples of incidents that have caused smoke inhalation injury.Mauer MP, Cummings KR. (2010) Impulse oscillometry and respiratory symptoms in World Trade Center responders, 6 years post-9/11. Lung 188:107-13.Buyantseva LV, Tulchinsky M, Kapalka GM, Chinchilli VM, Qian Z, Gillio R, Roberts A, Bascom. (2007) Evolution of lower respiratory symptoms in New York police officers after 9/11: a prospective longitudinal study. Occup Environ Med. 49:310-7. Injury to the lungs and airways is not only due to deposition of fine particulate soot but also due to the gaseous components of smoke, which include phosgene, carbon monoxide, and sulfur dioxide.
Chlorine Chlorine is a relatively common gas in industry with a variety of uses. It is used to disinfect water as well as being a part of the sanitation process for sewage and industrial waste. Chlorine is also used as a bleaching agent during the production of paper and cloth. Many household cleaning products, including bleach, contain chlorine. Given the volume and ease of chlorine for industrial and commercial use, exposure could occur from an accidental spill or a deliberate attack. The National Institute for Occupational Safety and Health recommends that a person wear splash proof goggles, a face shield and a respirator mask when working in the vicinity of chlorine gas. Because chlorine is a gas at room temperature, most exposure occurs via inhalation. Exposure may also occur through skin or eye contact or by ingesting chlorine-contaminated food or water. Chlorine is a strong oxidizing element causing the hydrogen to split from water in moist tissue, resulting in nascent oxygen and hydrogen chloride that cause corrosive tissue damage. Additionally oxidation of chlorine may form hypochlorous acid, which can penetrate cells and react with cytoplasmic proteins destroying cell structure.Martin JG, Campbell HR, Iijima H, Gautrin D, Malo JL, Eidelman DH, Hamid Q, Maghni K. (2003). Chlorine-induced injury to the airways in mice, Am J Respir Crit Care Med. 168:568-74.Matalon S, Maull EA. (2010) Understanding and treating chlorine-induced lung injury. Proc Am Thorac Soc. 7: 253 Chlorine's odor provides early warning signs of exposure but causes olfactory fatigue or adaptations, reducing awareness of exposure at low concentrations. With increased exposure, symptoms may progress to labored respirations, severe coughing, chest tightness, wheezing, dyspnea, and bronchospasm associated with a decrease in oxygen saturation level. .Kennedy SM, Enarson DA, Janssen RG, Chan-Yeung M. (1991) Lung health consequences of reported accidental chlorine gas exposures among pulpmill workers. Am Rev Respir Dis. 143:74-9. Severe exposure may result in changes in upper and lower airways resulting in an acute lung injury, which may not be present until several hours after exposure. Chlorine gas has been used as a weapon of warfare since World War I, most recently in 2007 in Iraq.
Phosgene Phosgene, notably used as a chemical weapon during World War I, is also used as an industrial reagent and building block in synthesis of pharmaceuticals and other organic compounds. Because of safety issues, phosgene is almost always produced and consumed within the same plant and extraordinary measures are made to contain this gas. In low concentrations, phosgene's odor resembles freshly cut hay or grass. Because of this, the gas may not be noticed and symptoms may appear slowly. Phosgene directly reacts with amine, sulfhydryl, and alcohol groups, adversely affecting cell macromolecules and metabolism. The direct toxicity to the cells leads to an increase in capillary permeability.Grainge C, Rice P. (2010) Management of phosgene-induced acute lung injury. Clin Toxicol. 48:497-508.Gift JS, McGaughy R, Singh DV, Sonawane B. (2008)Health assessment of phosgene: approaches for derivation of reference concentration. Regul Toxicol Pharmacol. 51:98-107 Furthermore, when phosgene hydrolyzes it forms hydrochloric acid, which can damage the cell surface and cause cell death in the alveoli and bronchioles. The hydrochloric acid triggers an inflammatory response that attracts neutrophils to the lungs, which causes pulmonary edema.Lazarus AA, Devereaux A. (2002) Potential agents of chemical warfare. Worst-case scenario protection and decontamination methods. Postgrad Med. 112:133-40.
Ammonia Ammonia is generally used in household cleaning products, as well as on farms and in some industrial and commercial locations, and this makes it easy for accidental or deliberate exposure to occur.Lalić H, Djindjić-Pavicić M, Kukuljan M. (2009) Ammonia intoxication on workplace--case report and a review of literature. Coll Antropol. 33:945-9.Weiss SM, Lakshminarayan S. (1994) Acute inhalation injury. Clin Chest Med. 15:103-16.Witschi H. (1977) Environmental agents altering lung biochemistry. Fed Proc. 36:1631-4. Ammonia interacts with moist surfaces to form ammonium hydroxide, which causes necrosis of tissues. Exposure to high concentrations can cause bronchiolar and alveolar edema and airway destruction resulting in respiratory distress or failure. Although ammonia has a pungent odor, it also causes olfactory fatigue or adaptation, reducing awareness of prolonged exposure.
Mustard gas Sulfur mustard, commonly known as mustard gas, was used as a chemical weapon in World War I and more recently in the Iran–Iraq War. Sulfur mustard is a vesicant alkylating agent with strong cytotoxic, mutagenic, and carcinogenic properties. After exposure, victims show skin irritations and blisters.Adelipour M, Imani Fooladi AA, Yazdani S, Vahedi E, Ghanei M, Nourani MR. (2011) Smad molecules expression pattern in human bronchial airway induced by sulfur mustard. Iran J Allergy Asthma Immunol. 10:147-54.Ghabili K, Agutter PS, Ghanei M, Ansarin K, Panahi Y, Shoja MM. (2011) Sulfur mustard toxicity: history, chemistry, pharmacokinetics, and pharmacodynamics. Crit Rev Toxicol. 41:384-403. This agent also causes respiratory tract lesions, bone marrow depression, and eye damage, the epithelial tissues of these organs being predominately affected. Inhalation of high doses of this gas causes lesions in the larynx, trachea, and large bronchi with inflammatory reactions and necrosis. The alkylating agent affects more the upper parts of the respiratory tract, and only intensely exposed victims showed signs like bronchiolitis obliterans in the distal part. Secondary effects of sulfur mustard exposure lead to chronic lung diseases such as chronic bronchitis.
Chloramine A common exposure involves accidental mixing of household ammonia with cleansers containing bleach, causing the irritant gas monochloramine to be released.
Methyl isocyanate Methyl isocyanate is an intermediate chemical in the production of carbamate pesticides (such as carbaryl, carbofuran, methomyl, and aldicarb).Mansour SA. (2004) Pesticide exposure--Egyptian scene. Toxicology 198: 91-115.Beckett WS. (1998) Persistent respiratory effects in survivors of the Bhopal disaster. Thorax 53:S43-6. It has also been used in the production of rubbers and adhesives. As a highly toxic and irritating material, it is hazardous to human health, and was involved in the Bhopal disaster—which killed nearly 8,000 people initially and approximately 17,000 people in total. When inhaled the vapor produces a direct inflammatory effect on the respiratory tract.
Pathophysiology Respiratory damage is related to the concentration of the gas and its solubility. Irritant gas exposures predominantly affect the airways, causing tracheitis, bronchitis, and bronchiolitis. Other inhaled agents may be directly toxic (e.g. cyanide, carbon monoxide), or cause harm simply by displacing oxygen and producing asphyxia (e.g. methane, carbon dioxide). The effect of inhaling irritant gases depends on the extent and duration of exposure and on the specific agentDemnati R, Fraser R, Ghezzo H, Martin JG, Plaa G, Malo JL. (1998) Time-course of functional and pathological changes after a single high acute inhalation of chlorine in rats, Eur Respir J. 11:922-8.Kirkhorn SR, Garry VF. (2008) Agricultural lung diseases. Environ Health Perspect 108:705-12.Hlastala MP, Ralph DD, Babb AL, Influence of gas physical properties on pulmonary gas exchange, Adv Exp Med Biol. 227 (1988) 33-8. Chlorine, phosgene, sulfur dioxide, hydrogen chloride, hydrogen sulfide, nitrogen dioxide, ozone, and ammonia are among the most important irritant gases. Hydrogen sulfide is also a potent cellular toxin, blocking the cytochrome system and inhibiting cellular respiration. More water-soluble gases (e.g. chlorine, ammonia, sulfur dioxide, hydrogen chloride) dissolve in the upper airway and immediately cause mucous membrane irritation, which may alert people to the need to escape the exposure. Permanent damage to the upper respiratory tract, distal airways, and lung parenchyma occurs only if escape from the gas source is impeded. Less soluble gases (e.g. nitrogen dioxide, phosgene, ozone) may not dissolve until they are well into the respiratory tract, often reaching the lower airways.Anderson JC, Hlastala MP. (2007) Breath tests and airway gas exchange. Pulm Pharmacol Ther. 20:112-7. These agents are less likely to produce early warning signs (phosgene in low concentrations has a pleasant odor), are more likely to cause severe bronchiolitis, and often have a lag of ≥ 12 h before symptoms of pulmonary edema develop.
Acute lung injury