Reactive airways dysfunction syndrome and irritant-induced asthma
- Catherine Lemière, MD
Catherine Lemière, MD
- Professor of Medicine
- University of Montreal Medical School
- Louis-Philippe Boulet, MD
Louis-Philippe Boulet, MD
- Professor of Medicine
- Laval University
- André Cartier, MD
André Cartier, MD
- Clinical Professor of Medicine
- University of Montreal Medical School, Canada
Reactive airways dysfunction syndrome (RADS) and irritant-induced asthma (IrIA) are closely related forms of asthma that result from the nonimmunologic provocation of prolonged bronchial hyperresponsiveness with or without reversible airflow obstruction by inhaled irritants [1-3]. Irritant-induced respiratory problems were initially described among industrial workers and World War I combatants in the early part of the 20th century [4,5]. These reports focused on acute effects such as pulmonary edema and death, but also described chronic respiratory sequelae of intense, brief exposure to inhaled irritants .
Subsequently, bronchitic symptoms, such as cough and wheezing, were described following a chlorine spill in 1969, although bronchial responsiveness was not assessed . Persistent airway hyperresponsiveness was noted in five of seven subjects four years after an acute exposure to sulfur dioxide . Further studies have led to a growing awareness and understanding of RADS and IrIA, especially in firefighters, rescue personnel, and people living in the vicinity of the World Trade Center site in September 2001 [1,8,9].
The diagnosis and management of RADS and IrIA will be reviewed here. The diagnosis of asthma and the causes, evaluation, and management of occupational asthma are discussed separately. (See "Diagnosis of asthma in adolescents and adults" and "Occupational asthma: Definitions, epidemiology, causes, and risk factors" and "Occupational asthma: Clinical features and diagnosis" and "Occupational asthma: Management, prognosis, and prevention".)
Reactive airways dysfunction syndrome (RADS) is described as the development of respiratory symptoms in the minutes or hours after a single accidental inhalation of a high concentration of irritant gas, aerosol, vapor, or smoke; these initial symptoms are followed by asthma-like symptoms and airway hyperresponsiveness that persist for a prolonged period (table 1) . RADS can occur after exposure to a variety of chemicals generated as gas or aerosol, or exposure to high levels of particulates (table 2). Clinical and functional criteria for the diagnosis of RADS are listed in the table (table 1) .
Irritant-induced asthma (IrIA) is a more general term to describe an asthmatic syndrome that results from a single or multiple high dose exposure to irritant products . When only a single, high-dose exposure has been responsible, the term RADS or "acute onset IrIA" is used . IrIA caused by multiple exposures to high doses of irritants which induce acute symptoms requiring acute medical care has also been reported . The term "sub-acute IrIA" has been proposed to describe instances of multiple high exposures to irritants where the onset of symptoms may be more insidious, as seen following the World Trade Center catastrophe [8,9], or less well-documented exposures in which the affected individuals are able to identify the timing, nature, and frequency of events [10,12]. When IrIA is caused by workplace exposures, it is considered a type of occupational asthma, the non-immunologic type.
- Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. Chest 1985; 88:376.
- Tarlo SM, Balmes J, Balkissoon R, et al. Diagnosis and management of work-related asthma: American College Of Chest Physicians Consensus Statement. Chest 2008; 134:1S.
- Vandenplas O, Wiszniewska M, Raulf M, et al. EAACI position paper: irritant-induced asthma. Allergy 2014; 69:1141.
- Das R, Blanc PD. Chlorine gas exposure and the lung: a review. Toxicol Ind Health 1993; 9:439.
- Winternitz, MC. Collected studies on the pathology of war gas poisoning, Yale University Press, New Haven 1920. p.1.
- Weill H, George R, Schwarz M, Ziskind M. Late evaluation of pulmonary function after acute exposure to chlorine gas. Am Rev Respir Dis 1969; 99:374.
- Härkönen H, Nordman H, Korhonen O, Winblad I. Long-term effects of exposure to sulfur dioxide. Lung function four years after a pyrite dust explosion. Am Rev Respir Dis 1983; 128:890.
- Prezant DJ, Weiden M, Banauch GI, et al. Cough and bronchial responsiveness in firefighters at the World Trade Center site. N Engl J Med 2002; 347:806.
- Banauch GI, Alleyne D, Sanchez R, et al. Persistent hyperreactivity and reactive airway dysfunction in firefighters at the World Trade Center. Am J Respir Crit Care Med 2003; 168:54.
- Lemière C, Malo JL, Gautrin D. Nonsensitizing causes of occupational asthma. Med Clin North Am 1996; 80:749.
- Chang-Yeung M, Lam S, Kennedy SM, Frew AJ. Persistent asthma after repeated exposure to high concentrations of gases in pulpmills. Am J Respir Crit Care Med 1994; 149:1676.
- Gautrin, D, Bernstein, et al. Reactive airways dysfunction syndrome or irritant-induced asthma. In: Asthma in the workplace, Bernstein, IL, Chan-Yeung, M, Malo, JL, Bernstein, DI (Eds), Marcel Dekker Inc, New York 1999. p.565.
- Kipen HM, Blume R, Hutt D. Asthma experience in an occupational and environmental medicine clinic. Low-dose reactive airways dysfunction syndrome. J Occup Med 1994; 36:1133.
- Brooks SM, Hammad Y, Richards I, et al. The spectrum of irritant-induced asthma: sudden and not-so-sudden onset and the role of allergy. Chest 1998; 113:42.
- Gautrin D, et al.. Reactive airways dysfunction syndrome and irritant-induced asthma. In: Asthma in the workplace, 3rd ed, Bernstein IL, Chan-Yeung M, Malo JL, Bernstein DI (Eds), Taylor & Francis, New York 2006. p.581.
- Blanc PD, Galbo M, Hiatt P, et al. Symptoms, lung function, and airway responsiveness following irritant inhalation. Chest 1993; 103:1699.
- Cullinan P, Acquilla S, Dhara VR. Respiratory morbidity 10 years after the Union Carbide gas leak at Bhopal: a cross sectional survey. The International Medical Commission on Bhopal. BMJ 1997; 314:338.
- Dhara VR, Cullinan P. Bhopal priorities. Int J Occup Environ Health 2004; 10:107.
- Tarlo SM. Workplace irritant exposures: do they produce true occupational asthma? Ann Allergy Asthma Immunol 2003; 90:19.
- Gautrin D, Leroyer C, L'Archevêque J, et al. Cross-sectional assessment of workers with repeated exposure to chlorine over a three year period. Eur Respir J 1995; 8:2046.
- Kern DG. Outbreak of the reactive airways dysfunction syndrome after a spill of glacial acetic acid. Am Rev Respir Dis 1991; 144:1058.
- Bhérer L, Cushman R, Courteau JP, et al. Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: II. Follow up of affected workers by questionnaire, spirometry, and assessment of bronchial responsiveness 18 to 24 months after exposure ended. Occup Environ Med 1994; 51:225.
- Gautrin D, Leroyer C, Infante-Rivard C, et al. Longitudinal assessment of airway caliber and responsiveness in workers exposed to chlorine. Am J Respir Crit Care Med 1999; 160:1232.
- Kogevinas M, Antó JM, Sunyer J, et al. Occupational asthma in Europe and other industrialised areas: a population-based study. European Community Respiratory Health Survey Study Group. Lancet 1999; 353:1750.
- Rosenman KD, Reilly MJ, Schill DP, et al. Cleaning products and work-related asthma. J Occup Environ Med 2003; 45:556.
- Henneberger PK, Derk SJ, Davis L, et al. Work-related reactive airways dysfunction syndrome cases from surveillance in selected US states. J Occup Environ Med 2003; 45:360.
- Vizcaya D, Mirabelli MC, Orriols R, et al. Functional and biological characteristics of asthma in cleaning workers. Respir Med 2013; 107:673.
- Vandenplas O, D'Alpaos V, Evrard G, et al. Asthma related to cleaning agents: a clinical insight. BMJ Open 2013; 3:e003568.
- Le Moual N, Varraso R, Siroux V, et al. Domestic use of cleaning sprays and asthma activity in females. Eur Respir J 2012; 40:1381.
- Tarlo SM, Broder I. Irritant-induced occupational asthma. Chest 1989; 96:297.
- Wheeler K, McKelvey W, Thorpe L, et al. Asthma diagnosed after 11 September 2001 among rescue and recovery workers: findings from the World Trade Center Health Registry. Environ Health Perspect 2007; 115:1584.
- Banauch GI, Dhala A, Prezant DJ. Pulmonary disease in rescue workers at the World Trade Center site. Curr Opin Pulm Med 2005; 11:160.
- Feldman DM, Baron SL, Bernard BP, et al. Symptoms, respirator use, and pulmonary function changes among New York City firefighters responding to the World Trade Center disaster. Chest 2004; 125:1256.
- Andersson E, Olin AC, Hagberg S, et al. Adult-onset asthma and wheeze among irritant-exposed bleachery workers. Am J Ind Med 2003; 43:532.
- Karjalainen A, Martikainen R, Karjalainen J, et al. Excess incidence of asthma among Finnish cleaners employed in different industries. Eur Respir J 2002; 19:90.
- de la Hoz RE, Shohet MR, Wisnivesky JP, et al. Atopy and upper and lower airway disease among former World Trade Center workers and volunteers. J Occup Environ Med 2009; 51:992.
- Sherman CB, Barnhart S, Miller MF, et al. Firefighting acutely increases airway responsiveness. Am Rev Respir Dis 1989; 140:185.
- Kim H, Herbert R, Landrigan P, et al. Increased rates of asthma among World Trade Center disaster responders. Am J Ind Med 2012; 55:44.
- Lemière C, Malo JL, Boulet LP, Boutet M. Reactive airways dysfunction syndrome induced by exposure to a mixture containing isocyanate: functional and histopathologic behaviour. Allergy 1996; 51:262.
- Lemière C, Malo JL, Boutet M. Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment. Eur Respir J 1997; 10:241.
- Demnati R, Fraser R, Martin JG, et al. Effects of dexamethasone on functional and pathological changes in rat bronchi caused by high acute exposure to chlorine. Toxicol Sci 1998; 45:242.
- Martin JG, Campbell HR, Iijima H, et al. Chlorine-induced injury to the airways in mice. Am J Respir Crit Care Med 2003; 168:568.
- McGovern TK, Goldberger M, Allard B, et al. Neutrophils mediate airway hyperresponsiveness after chlorine-induced airway injury in the mouse. Am J Respir Cell Mol Biol 2015; 52:513.
- McGovern T, Day BJ, White CW, et al. AEOL10150: a novel therapeutic for rescue treatment after toxic gas lung injury. Free Radic Biol Med 2011; 50:602.
- Takeda N, Maghni K, Daigle S, et al. Long-term pathologic consequences of acute irritant-induced asthma. J Allergy Clin Immunol 2009; 124:975.
- Gautrin D, Boulet LP, Boutet M, et al. Is reactive airways dysfunction syndrome a variant of occupational asthma? J Allergy Clin Immunol 1994; 93:12.
- Cone JE, Wugofski L, Balmes JR, et al. Persistent respiratory health effects after a metam sodium pesticide spill. Chest 1994; 106:500.
- Meggs WJ. RADS and RUDS--the toxic induction of asthma and rhinitis. J Toxicol Clin Toxicol 1994; 32:487.
- White CW, Martin JG. Chlorine gas inhalation: human clinical evidence of toxicity and experience in animal models. Proc Am Thorac Soc 2010; 7:257.
- Malo JL, L'archevêque J, Castellanos L, et al. Long-term outcomes of acute irritant-induced asthma. Am J Respir Crit Care Med 2009; 179:923.
- Mauer MP, Cummings KR, Hoen R. Long-term respiratory symptoms in World Trade Center responders. Occup Med (Lond) 2010; 60:145.
- Shusterman, D. Upper and lower airway sequelae of irritant inhalations. Clin Pulm Med 1999; 6:18.
- Courteau JP, Cushman R, Bouchard F, et al. Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: I. Exposure and symptomatology. Occup Environ Med 1994; 51:219.
- Vandenplas O, Fievez P, Delwiche JP, et al. Persistent asthma following accidental exposure to formaldehyde. Allergy 2004; 59:115.
- Charan NB, Lakshminarayan S, Myers GC, Smith DD. Effects of accidental chlorine inhalation on pulmonary function. West J Med 1985; 143:333.
- Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2015. www.ginasthma.org (Accessed on January 26, 2016).
- de la Hoz RE. Occupational lower airway disease in relation to World Trade Center inhalation exposure. Curr Opin Allergy Clin Immunol 2011; 11:97.
- Leroyer C, Perfetti L, Cartier A, Malo JL. Can reactive airways dysfunction syndrome (RADS) transform into occupational asthma due to "sensitisation" to isocyanates? Thorax 1998; 53:152.
- Mendelson DS, Roggeveen M, Levin SM, et al. Air trapping detected on end-expiratory high-resolution computed tomography in symptomatic World Trade Center rescue and recovery workers. J Occup Environ Med 2007; 49:840.
- Zock JP, Kogevinas M, Sunyer J, et al. Asthma characteristics in cleaning workers, workers in other risk jobs and office workers. Eur Respir J 2002; 20:679.
- Perkner JJ, Fennelly KP, Balkissoon R, et al. Irritant-associated vocal cord dysfunction. J Occup Environ Med 1998; 40:136.
- Quirce S. Eosinophilic bronchitis in the workplace. Curr Opin Allergy Clin Immunol 2004; 4:87.
- Tanaka H, Saikai T, Sugawara H, et al. Workplace-related chronic cough on a mushroom farm. Chest 2002; 122:1080.
- National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051) www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (Accessed on January 26, 2016).
- Malo JL, Cartier A, Boulet LP, et al. Bronchial hyperresponsiveness can improve while spirometry plateaus two to three years after repeated exposure to chlorine causing respiratory symptoms. Am J Respir Crit Care Med 1994; 150:1142.
- Leroyer C, Malo JL, Girard D, et al. Chronic rhinitis in workers at risk of reactive airways dysfunction syndrome due to exposure to chlorine. Occup Environ Med 1999; 56:334.
- Jones RN, Hughes JM, Glindmeyer H, Weill H. Lung function after acute chlorine exposure. Am Rev Respir Dis 1986; 134:1190.
- Emad A, Rezaian GR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases. Chest 1997; 112:734.
- Aldrich TK, Gustave J, Hall CB, et al. Lung function in rescue workers at the World Trade Center after 7 years. N Engl J Med 2010; 362:1263.
- Skloot GS, Schechter CB, Herbert R, et al. Longitudinal assessment of spirometry in the World Trade Center medical monitoring program. Chest 2009; 135:492.
- CAUSES AND RISK FACTORS
- PATHOLOGY AND MECHANISMS
- CLINICAL MANIFESTATIONS
- Laboratory testing
- Skin and immunologic testing
- Pulmonary function testing
- - Spirometry
- - Nonspecific bronchoprovocation challenge
- - Specific bronchoprovocation challenge
- DIFFERENTIAL DIAGNOSIS
- Acute presentation
- Persistent symptoms
- Acute management of RADS
- Management of chronic RADS or IrIA
- EXPOSURE AVOIDANCE
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS