Chlorine gas exposure and evolutive patterns of reactive airways dysfunction syndrome: a systematic review

Vianna, Angelica dos Santos; Bhering, Ana Clara Poyares de Mello; Silva, Fernanda Antunes Cavalcante da; Vianna, Rosa Cristina dos Santos; Santos, Aline de Souza Espindola

doi:10.1590/2317-6369/30021en2023v48e12

Angelica dos Santos Vianna

conception and design of the study

contributed to the survey, analysis, interpretation of the data

elaboration and critical review of the manuscript

the approval of the final version

assume full responsibility for the study performed and published content

Universidade Federal do Rio de Janeiro, Instituto de Estudos em Saúde Coletiva. Rio de Janeiro, RJ, Brazil.

http://orcid.org/0000-0003-0657-2141

Ana Clara Poyares de Mello Bhering

conception and design of the study

contributed to the survey, analysis, interpretation of the data

elaboration and critical review of the manuscript

the approval of the final version

assume full responsibility for the study performed and published content

Universidade Federal do Rio de Janeiro, Faculdade de Medicina. Rio de Janeiro, RJ, Brazil.

http://orcid.org/0000-0002-4417-3638

Fernanda Antunes Cavalcante da Silva

conception and design of the study

contributed to the survey, analysis, interpretation of the data

elaboration and critical review of the manuscript

the approval of the final version

assume full responsibility for the study performed and published content

Universidade Federal do Rio de Janeiro, Faculdade de Medicina. Rio de Janeiro, RJ, Brazil.

http://orcid.org/0000-0003-3058-242X

Rosa Cristina dos Santos Vianna

contributed to the survey, analysis, interpretation of the data

elaboration and critical review of the manuscript

the approval of the final version

assume full responsibility for the study performed and published content

Instituto D’OR de Pesquisa e Ensino, Faculdade IDOR de Ciências Médicas. Rio de Janeiro, RJ, Brazil.

http://orcid.org/0000-0003-3214-8299

Aline de Souza Espindola Santos

contributed to the survey, analysis, interpretation of the data

elaboration and critical review of the manuscript

the approval of the final version

assume full responsibility for the study performed and published content

Universidade Federal do Rio de Janeiro, Instituto de Estudos em Saúde Coletiva. Rio de Janeiro, RJ, Brazil.

http://orcid.org/0000-0002-5498-3992

Contact: Angelica dos Santos Vianna E-mail: angelica@iesc.ufrj.br

The authors declare that the study was not subsidized, and there is no conflict of interest.

Editor-in-Chief: Eduardo Algranti

*Original criteria* ^(d)	*Modified criteria* ^(e)
- New-onset symptoms simulating asthma	- New-onset symptoms simulating asthma or recurrence of childhood asthma
- The onset of symptoms occurred after a single exposure incident or accident	- Symptom onset related to one or more high-level exposures
- Onset of symptoms ≤24 hours after exposure	- Symptoms can begin >24 hours after exposure
- Exposure to a gas, smoke, fume, or vapor in very high concentrations and with irritant qualities to its nature	- Any high-level exposure to gas, fume, vapor, sprays, or even dust
- Symptoms persistent for ≥3 months	- No mention
- Pulmonary function tests may show airflow obstruction	- No mention
- Methacholine challenge test was positive	- No mention
- Other types of pulmonary diseases were ruled out	- Difficulty in excluding previous airway disease associated with smoking or atopy may occur

*CASE REPORT*
Author (s)	Study patient description	Patient history description	Patient clinical condition description	Diagnostic test description	Patient treatment description	Post-treatment description	Adverse events identification	Summary of lessons learned		Overall classification (risk)
Donnelly and FitzGerald³⁷37. Donnelly SC, FitzGerald MX. Reactive airways dysfunction syndrome (RADS) due to chlorine gas exposure. I J Med Sci. 1990;159(9-12):275-7.	No	Yes	Yes	No	Yes	Yes	No	Yes		Low
Moore and Sherman²³23. Moore BB, Sherman M. Chronic reactive airway disease following acute chlorine gas exposure in an asymptomatic atopic patient. Chest. 1991;100(3):855-6.	No	No	No	No	Yes	Yes	No	Yes		High
Deschamps et al. ⁽²⁴24. Deschamps D, Soler P, Rosenberg N, Baud F, Gervais P. Persistent asthma after inhalation of a mixture of sodium hypochlorite and hydrochloric acid. Chest. 1994;105(6):1895-6.	No	Yes	No	Yes	Yes	No	No	Yes		Moderate
Schönhofer et al. ⁽²⁵25. Schönhofer B, Voshaar T, Köhler D. Long-term lung sequelae following accidental chlorine gas exposure. Respiration. 1996;63(3):155-9.	No	Yes	Yes	Yes	Yes	Yes	No	Yes		Low
Lemière et al. ⁽²⁶26. Lemière C, Malo J-L, Boutet M. Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment. Eur Respir J. 1997;10(1):241-4.	No	Yes	No	Yes	Yes	Yes	No	Yes		Low
Williams²⁷27. Williams JG. Inhalation of chlorine gas. Postgrad Med J. 1997;73(865):697-700.	No	No	No	No	No	No	No	Yes		High
Solà et al. ⁽³⁵35. Solà RC, Galla XM, Huertasa BA, Martíneza ME, Martíneza RO. Síndrome de disfunción reactiva de las vías respiratorias: estudio de 18 casos: Med Clin. 2005;124(11):419-22.	No	No	No	No	No	No	No	Yes		High
Hannu et al. ⁽³¹31. Hannu TJ, Riihimäki VE, Piirilä PL. Reactive airways dysfunction syndrome from acute inhalation of dishwasher detergent powder. Can Resp J. 2012;19(3):e25-7.	No	Yes	No	Yes	Yes	Yes	No	Yes		Low
*CROSS-SECTIONAL STUDY*
Author (s)	Clear inclusion criteria	Study subjects and environment description	Exposure measurement	Condition measurement criteria	Confounding factors identification	Confounding factors strategies	Outcome measurement	Appropriate statistical analysis		Overall classification (risk)
Salisbury et al. ⁽⁴²42. Salisbury DA, Enarson DA, Chan-Yeung M, Kennedy SM. First-aid reports of acute chlorine gassing among pulpmill workers as predictors of lung health consequences. Am J Ind Med. 1991;20(1):71-81.	Yes	No	No	Yes	No	No	Yes	Yes		Moderate
Gautrin et al. ³⁰30. Gautrin D, Boulet LP, Boutet M, Dugas M, Bhérer L, L'Archevêque J, et al. Is reactive airways dysfunction syndrome a variant of occupational asthma? J Allergy Clin Immunol. 1994;93(1 Pt1):12-22.	Yes	No	No	Yes	No	No	Yes	No		High
CDC⁴⁰40. Center for Disease Control and Prevention. Chlorine gas release associated with employee language barrier - Arkansas, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(48):981-5.	Yes	No	No	Yes	No	No	Yes	No		High
*CASE SERIES*
Author (s)	Clear inclusion criteria	Condition measurement	Methods for condition identification	Consecutive inclusion	Total inclusion of participants	Study patients description	Clinical information description	Reporting of follow-up results	Site information description	Appropriate statistical analysis	Overall classification (risk)
Brooks et al. ¹²12. Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high-level irritant exposures. Chest. 1985;88(3):376-84.	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	No	Low
Boulet³⁶36. Boulet LP. Increases in airway responsiveness following acute exposure to respiratory irritants. Chest. 1988;94(3):476-81.	Yes	Yes	Yes	No	No	No	Yes	Yes	No	No	Moderate
Meggs et al. ⁽³⁴34. Meggs WJ, Elsheik T, Metzger WJ, Albernaz M, Bloch RM. Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure. J Toxicol Clin Toxicol. 1996;34(4):383-96.	Yes	No	Yes	No	No	No	Yes	No	No	No	High
Chatkin et al. ⁽²⁸28. Chatkin JM, Tarlo SM, Liss G, Banks D, Broder I. The outcome of asthma related to workplace irritant exposures. Chest. 1999;116(6):1780-5.	No	No	No	Yes	Yes	No	Yes	Yes	No	No	High
Hickmann et al. ⁽⁸8. Hickmann MA, Nelson ED, Siegel EG, Bernstein JA. Are high-dose toxic exposures always associated with reactive airways dysfunction syndrome (RADS)? Arch Environ Health. 2001;56(5):439-42.	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	No	Low
Gorguner et al. ⁽³²32. Gorguner M, Aslan S, Inandi T, Cakir Z. Reactive airways dysfunction syndrome in housewives duo to a bleach-hydrochloric acid mixture. Inhal Toxicol. 2004;16(2):87-91.	No	Yes	No	Yes	Yes	No	No	No	No	Yes	High
Malo et al. ⁽³³	Yes	Yes	Yes	Yes	Yes	No	No	Yes	Yes	No	Low
Mohan et al. ⁽³⁹39. Mohan A, Kumar SN, Rao MH, Bollineni S, Manohar IC. Acute accidental exposure to chlorine gas: clinical presentation, pulmonary functions and outcomes. Indian J Chest Dis Allied Sci. 2010;52(3):149-52.	No	Yes	No	Yes	Yes	No	No	Yes	No	No	High
Patel et al. ²⁹29. Patel RK, Patel PD, Patel NJ. Reactive airways dysfunction syndrome (RADS) after high level irritant exposures. Int Res J Pharm. 2012;3(8):254-6.	No	Yes	No	Yes	Yes	No	No	Yes	No	No	High
Chierakul et al. ⁽³⁸38. Chierakul N, Rittayamai N, Passaranon P, Chamchod C, Suntiwuth B. Respiratory health effect of persons accidentally expose to high concentration of chlorine gas. J Med Assoc Thai. 2013;96(Suppl 2):S17-21.	Yes	Yes	Yes	No	No	No	No	No	No	No	High
Kim et al. ⁽⁴¹41. Kim JA, Yoon SY, Cho SY, Yu JH, Kim HS, Lim GI, Kim JS. Acute health effects of accidental chlorine gas exposure. Ann Occup Environ Med. 2014;26:29.	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	No	Low

*Author, year, country*	*Study characteristics (design; number; exposure site)*	*Cases of RADS due to chlorine gas*				*Complementary exams*		*Evolution pattern*
*Author, year, country*	*Study characteristics (design; number; exposure site)*	*Number with documented evolution*	*Age (years)*	*Sex*	*Ethnicity*	*Spirometry (result)*	*Methacholine bronchial challenge test (result)*	*Evolution pattern*
Brooks et al., 1985, United States¹²12. Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high-level irritant exposures. Chest. 1985;88(3):376-84.	CS; n=10; Environmental/Occupational	1 (Occup)	34	1 F	1 NI	1 (obstruction)	1 (positive)	1 Chronic
Boulet, 1988, Canada³⁶36. Boulet LP. Increases in airway responsiveness following acute exposure to respiratory irritants. Chest. 1988;94(3):476-81.	CS; n=5; Environmental/Occupational	1 (Occup)	69	1 M	1 NI	1 (obstruction)	1 (positive)	1 Chronic
Donnelly and FitzGerald, 1990, Ireland³⁷37. Donnelly SC, FitzGerald MX. Reactive airways dysfunction syndrome (RADS) due to chlorine gas exposure. I J Med Sci. 1990;159(9-12):275-7.	CR; n=1; Occupational	1	30	1 M	1 NI	1 (obstruction)	1 (not done)	1 Chronic
Moore and Sherman, 1991, United States²³23. Moore BB, Sherman M. Chronic reactive airway disease following acute chlorine gas exposure in an asymptomatic atopic patient. Chest. 1991;100(3):855-6.	CR; n=1; Occupational	1	25	1 M	1 NI	1 (obstruction)	1 (not done)	1 Chronic
Salisbury et al., 1991, Canada⁴²42. Salisbury DA, Enarson DA, Chan-Yeung M, Kennedy SM. First-aid reports of acute chlorine gassing among pulpmill workers as predictors of lung health consequences. Am J Ind Med. 1991;20(1):71-81.	Cross-sect; n=174; Occupational	37	37 NI	37 M	37 NI	37 (obstruction)	37 (NI)	37 Chronic
Deschamps et al., 1994, France²⁴24. Deschamps D, Soler P, Rosenberg N, Baud F, Gervais P. Persistent asthma after inhalation of a mixture of sodium hypochlorite and hydrochloric acid. Chest. 1994;105(6):1895-6.	CR; n=1; Environmental	1	39	1 F	1 NI	Obstruction	1 (positive)	1 Chronic
Gautrin et al., 1994, Canada³⁰30. Gautrin D, Boulet LP, Boutet M, Dugas M, Bhérer L, L'Archevêque J, et al. Is reactive airways dysfunction syndrome a variant of occupational asthma? J Allergy Clin Immunol. 1994;93(1 Pt1):12-22.	Cross-sect; n= 45; Occupational	5	35;36;52; 56;56	5 M	5 NI	5 (obstruction)	5 (positive)	5 Chronic
Meggs et al., 1996, United States³⁴34. Meggs WJ, Elsheik T, Metzger WJ, Albernaz M, Bloch RM. Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure. J Toxicol Clin Toxicol. 1996;34(4):383-96.	CS; n=13; Occupational	13	30-61 (mean 48)	1 M; 12 F	13 Cauc	7 (obstruction); 6 (NI)	7 (positive); 6 (NI)	13 Chronic
Schönhofer et al., 1996, Germany²⁵25. Schönhofer B, Voshaar T, Köhler D. Long-term lung sequelae following accidental chlorine gas exposure. Respiration. 1996;63(3):155-9.	CR; n=3; Occupational	3	31;42;54	3 M	3 NI	3 (obstruction [2]; normal [1])	3 (positive)	3 Chronic
Lemière et al., 1997, Canada²⁶26. Lemière C, Malo J-L, Boutet M. Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment. Eur Respir J. 1997;10(1):241-4.	CR; n=1; Occupational	1	36	1 M	1 NI	1 (obstruction)	1 (positive)	1 Late resolution
Williams, 1997, United States²⁷27. Williams JG. Inhalation of chlorine gas. Postgrad Med J. 1997;73(865):697-700.	CR; n=3; Occupational	2	41;53	2 M	2 NI	1 (normal); 1 (NI)	2 (NI)	2 Chronic
Chatkin et al., 1999, Canada²⁸28. Chatkin JM, Tarlo SM, Liss G, Banks D, Broder I. The outcome of asthma related to workplace irritant exposures. Chest. 1999;116(6):1780-5.	CS; n= 89; Occupational	1	40	1 M	1 NI	1 (not done)	1 (positive)	1 Chronic
Hickmann et al., 2001, United States⁸8. Hickmann MA, Nelson ED, Siegel EG, Bernstein JA. Are high-dose toxic exposures always associated with reactive airways dysfunction syndrome (RADS)? Arch Environ Health. 2001;56(5):439-42.	CS; n=20; Occupational	6	35;39;42; 47;52	5 M; 1 F	4 Cauc; 2 Afrodesc	6 (normal)	6 (negative)	6 Late resolution
Gorguner et al., 2004, Turkey³²32. Gorguner M, Aslan S, Inandi T, Cakir Z. Reactive airways dysfunction syndrome in housewives duo to a bleach-hydrochloric acid mixture. Inhal Toxicol. 2004;16(2):87-91.	CS; n=55; Environmental	55	33 ± 11.3	55 F	55 NI	55 (not done)	55 (not done)	48 Rapid resolution; 1 death; 6 ND
Solà et al., 2005, Spain³⁵35. Solà RC, Galla XM, Huertasa BA, Martíneza ME, Martíneza RO. Síndrome de disfunción reactiva de las vías respiratorias: estudio de 18 casos: Med Clin. 2005;124(11):419-22.	CR; n=18; Occupational	5	35;36;40; 42;56	3 M; 2 F	5 NI	5 (obstruction)	5 (not done)	5 Chronic
Malo et al., 2009, Canada³³33. Malo JL, L'Archevêque J, Castellanos L, Lavoie K, Ghezzo H, Maghni K. Long-term outcomes of acute irritant-induced asthma. Am J Respir Crit Care Med. 2009;179(10):923-8.	CS; n=35; Occupational	20	20 NI	20 M	20 NI	20 (obstruction)	20 (positive)	20 Chronic
Mohan et al., 2010, India³⁹39. Mohan A, Kumar SN, Rao MH, Bollineni S, Manohar IC. Acute accidental exposure to chlorine gas: clinical presentation, pulmonary functions and outcomes. Indian J Chest Dis Allied Sci. 2010;52(3):149-52.	CS; n=64; Environmental	3	3 NI	3 NI	3 NI	3 (altered)	3 (not done)	3 Late resolution
Hannu et al., 2012, Finland³¹31. Hannu TJ, Riihimäki VE, Piirilä PL. Reactive airways dysfunction syndrome from acute inhalation of dishwasher detergent powder. Can Resp J. 2012;19(3):e25-7.	CR; n=1; Occupational	1	43	1 M	1 NI	1 (obstruction)	1 (positive)	1 Chronic
Patel et al., 2012, India²⁹29. Patel RK, Patel PD, Patel NJ. Reactive airways dysfunction syndrome (RADS) after high level irritant exposures. Int Res J Pharm. 2012;3(8):254-6.	CS; n=19; Occupational	5	27;33;47; 50;52	5 M	5 NI	5 (obstruction)	5 (NI)	5 Chronic
CDC, 2012, United States⁴⁰40. Center for Disease Control and Prevention. Chlorine gas release associated with employee language barrier - Arkansas, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(48):981-5.	Cross-sect; n=545; Occupational	6	6 NI	6 NI	6 Latino	6 (NI)	6 (3 positive; 3 borderline)	3 Late resolution; 3 ND
Chierakul et al., 2013, Thailand³⁸38. Chierakul N, Rittayamai N, Passaranon P, Chamchod C, Suntiwuth B. Respiratory health effect of persons accidentally expose to high concentration of chlorine gas. J Med Assoc Thai. 2013;96(Suppl 2):S17-21.	CS; n=21; Environmental	1	1 NI	1 NI	1 NI	1 (obstruction)	1 (positive)	1 ND
Kim et al., 2014, South Korea⁴¹41. Kim JA, Yoon SY, Cho SY, Yu JH, Kim HS, Lim GI, Kim JS. Acute health effects of accidental chlorine gas exposure. Ann Occup Environ Med. 2014;26:29.	CS; n=211; Environmental/Occupational	1 (Envir)	38	1 M	1 Asian	1 (normal)	1 (negative)	1 Late resolution

[1] Contact: Angelica dos Santos Vianna E-mail: angelica@iesc.ufrj.br

Brasil

Brasil

Chlorine gas exposure and evolutive patterns of reactive airways dysfunction syndrome: a systematic review

Abstract

Introduction:

Objective:

Methods:

Results:

Conclusions: