RADS) in a Chemistry Teacher Induced by Fumes of Mixed Iodine Compounds

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Industrial Health 2009, 47, 681–684 Case Report Reactive Airway Dysfunction Syndrome (RADS) in a Chemistry Teacher Induced by Fumes of Mixed Iodine Compounds

Timo HANNU1*, Vesa RIIHIMÄKI2 and Päivi PIIRILÄ3

1Occupational Medicine, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FI-02500 Helsinki, Finland 2Kalenteritie 10 A, FI-02200 Espoo, Finland 3Laboratory of Clinical Physiology, Helsinki University Central Hospital, Helsinki, Finland

Received March 18, 2009 and accepted June 4, 2009

Abstract: The reactive airway dysfunction syndrome (RADS) is a type of occupational asthma without a latency period, and it is induced by irritating vapour, fume, or smoke. Although the onset of RADS has been related to over 30 different agents, it has not been previously associated with acute exposure to iodine, aluminium iodide, or hydrogen iodide. The diagnosis was based on exposure data, clinical symptoms and signs, as well as respiratory function tests and bronchoscopy. A 48-yr-old non-atopic, never-smoking female chemistry teacher developed respiratory symptoms immediately after a demonstration of oxidation-reduction reactions in a school classroom. Spirometry showed bronchial obstruction, and the histamine challenge test revealed bronchial hyperresponsiveness. These findings were still evident seven years after the incident. The prognosis of RADS was unfavourable: the patient had to quit her job as a teacher. A case of RADS following acute exposure to mixed iodine compounds is presented for the first time. Demonstrations of potentially dangerous chemical reactions should always be carried out in a fume cupboard, and appropriate personal protective equipment should be worn.

Key words: Aluminium iodide, Hydrogen iodide, Iodine, Occupational exposure, Occupational lung disease, RADS

Introduction avoid possible health-threatening effects. In spite of these, however, unexpected events can occur. Reactive airways dysfunction syndrome (RADS) is We present a case of RADS in a chemistry teacher after characterized by the immediate onset of asthma after a exposure to irritating fumes of iodine compounds released single exposure to irritating vapour, fume, or smoke1). from a standard experiment involving powdered alumini- According to a recent systematic review, the most com- um, powdered iodine and water. To our best knowledge, monly reported agents related to RADS are chlorine, this association has not been previously reported. toluene-di-isocyanate, and oxides of nitrogen2). Over 30 different substances have been associated with the onset Case Report of RADS2, 3). Chemical experiments are conducted in school chem- At the time of the incident, the patient was a 48-yr-old istry classes to demonstrate typical chemical reactions. woman who had taught mathematics, physics, and chem- Strict safety precautions, including appropriate personal istry for 16 yr. Her past medical history did neither protection and the use of a fume cupboard, are needed to include atopic dermatitis nor perennial rhinitis. She was a never-smoker, and there was no family history of asth- *To whom correspondence should be addressed. ma. She had not had any respiratory complaints prior to E-mail: [email protected] the incident. 682 T HANNU et al.

During a school chemistry class, our patient gave a In a histamine challenge test performed 15 months after demonstration of oxidation-reduction reactions with a the incident, slight bronchial hyperresponsiveness was mixture of powdered aluminium, powdered iodine and observed, and spirometry showed mild obstruction water, which generates a spectacular colourful plume of (Table 1). The pulmonary diffusing capacity was normal. reaction products. For an unknown reason, the intended Skin prick tests showed no indication of atopy. The con- chemical reaction did not start in the fume cupboard. The sulting phoniatrician found functional impairments in the teacher therefore removed the reagents from the cupboard, clinical examination and suspected that the patients’ voice wrapped them in a hand towel and placed them in a waste problems also were associated with the inhalation acci- basket. However, the chemical reaction started in the dent, which would imply that a toxic laryngitis had devel- waste basket. To protect the pupils from exposure, the oped acutely. Hoarseness of voice was aggravated espe- teacher immediately picked up the waste basket and cially by non-specific irritants, stress or coughing. After placed it into the fume cupboard, which took some time. these examinations, treatment with inhaled budesonide After the chemical reaction was over, the bottom of the 400 µg daily was started. waste basket had burnt away. Because the teacher had Despite her medication, the patient continued to suffer no respiratory protection, she inhaled some of the fumes from cough and dyspnoea. In addition, hoarseness of released from the high-temperature chemical reaction. voice and speech problems occurred, especially, on expo- The fumes consisted mostly of iodine and aluminium sure to non-specific irritants making her teaching work iodide, but ultimately also hydrogen iodide. impossible. The symptoms were so disabling that she had Immediately after the incident, the teacher felt a burn- to quit her job as a teacher, and she was granted ulti- ing sensation in her throat, followed by cough, dyspnoea, mately disability pension from her pension insurance and hoarseness of voice, but surprisingly, hardly any eye company. Seven years later, when examined at the symptoms. To treat her persisting cough, a physician pre- Finnish Institute of Occupational Health, spirometry still scribed several regimens of antibiotics, but these did not revealed mild obstruction with a significant bronchodi- relieve the cough. Two months after the incident, the latation effect, and in the histamine challenge test, slight patient was examined at the department of pulmonology bronchial hyperresponsiveness was still evident (Table 1). of a regional hospital. Spirometry showed slight obstruc- tion4) (Table 1). Bronchoscopy was suggested, but was Discussion postponed because of the patient’s hoarseness of voice. Bronchoscopy was performed nine months after the Our case met the diagnostic criteria for RADS, as sug- incident, as the cough still persisted. The patient’s gested by Brooks et al.1). These criteria include docu- bronchial mucous membranes showed a mild diffuse red- mented absence of previous respiratory complaints and ness, and the biopsy specimen indicated a slight chronic the onset of respiratory symptoms after a single specific inflammation with lymphocytic infiltration. In the hista- exposure to a gas, smoke, fume or vapour present at very mine challenge test5), performed also nine months after high concentrations and exhibiting irritant qualities. In the incident, slight bronchial hyperresponsiveness was addition, the onset of symptoms should occur within 24 noted, and spirometry showed mild restriction (Table 1). h after the exposure and persist for at least three months,

Table 1. Results of spirometric examinations and bronchial hyperresponsiveness in the follow-up

Time from the FEV1, liter Bronchodilatation FVC, liter FEV1/FVC, % MEF50, PD15, mg incident, months response1, ≥ 12% liter/second

2 2.60 (79) no 3.54 (87) 73.5 (81) 1.96 (43) NM 9 2.9 (90) NM 3.1 (78) 93.5 (115) NM 0.93 15 2.75 (85) no 3.87 (97) 71.0 (87) 1.99 (44) 0.67 79 2.39 (79) yes 3.36 (90) 71.1 (88) 1.49 (35) 0.85 Data presented as observed and as % of the predicted value (reference: Viljanen 1982). 1Assessed as shown in reference 15.

FEV1 = forced expiratory volume in 1 s. FVC = forced vital capacity.

MEF50 = maximal expiratory flow at the volume level of 50% of the FVC. NM = not measured.

PD15 = provocative dose of histamine disulphate causing a reduction of at least 15% in the FEV1 value (bronchial hyperresponsiveness graded as PD15 <0.1 mg strong, PD15 0.1–0.4 mg moderate, PD15 0.4–1.6 mg slight, and PD15>1.6 mg no hyperreactivity (reference: Sovijärvi et al. 1993).

Industrial Health 2009, 47, 681–684 RADS IN A CHEMISTRY TEACHER 683 and the symptoms should be consistent with asthma having been caused by exposure to hydrofluoric acid and (cough, wheezing, chest tightness, and dyspnoea). thermal degradation of fluorocarbons9–11), as well as Furthermore, although pulmonary function tests might hydrobromic acid12). In addition, several cases of RADS show airflow obstruction, methacholine challenge testing have been attributed to chlorine or chlorine-containing should be positive, and other pulmonary diseases should chemicals13, 14). However, there are no previous reports be ruled out. of RADS caused by reaction products of iodine. In the presently reported incident, two parallel exother- The prognosis of RADS in our patient was unfortu- mic chemical reactions were involved: nately unfavourable. Due to the prominent respiratory

(1) 2 Al + 6 H2O → 3 H2 + 2 Al(OH)3 symptoms and some physical disability, our patient had (2) 2 Al + 3 I2 → 2 AlI3 to give up her teaching career, which led to socio-eco- The reaction chain is initiated by oxidation of the fresh, nomic problems. Her lung disease was ultimately, eight finely ground aluminium by water; heat is generated, set- years after the incident, accepted as an occupational dis- ting off the second exothermic reaction between alumini- ease entitled to compensation by her insurance company. um and iodine, yielding aluminium iodide. As the reac- Today RADS, as a disease entity, is more familiar to both tion temperature rises above 1,000˚C, excess iodine pulmonologists and occupational health physicians than (b.p. 184˚C) and water, and a significant fraction of the previously. This makes it more likely that new cases of formed aluminium iodide (b.p. 360˚C) are vaporized. A RADS are diagnosed properly. copious violet cloud of iodine is seen, in addition to a In conclusion, a case of RADS induced by acute expo- bright flame and sparks from the burning aluminium. In sure to mixed iodine compounds is described here for the addition to the formed vapours, solid particles of alu- first time. Our case points out that the demonstration of minium iodide and aluminium oxide are envisaged. In chemical reactions in the classroom, although a tempting the presence of water in the fume, and in the humid envi- spectacular show in the chemistry class, is not risk-free. ronment of the airways and ultimately in the respiratory Such demonstrations should therefore be carried out with mucosa, the aluminium iodide is hydrolysed to hydrogen caution, always in the fume cupboard, and appropriate iodide. personal protection should be ensured. According to the documentation of the American Conference of Industrial Hygienists, irritation of the upper Acknowledgements respiratory tract and mucous membranes occurs following acute exposure to high concentrations of iodine We thank Dr. Seppo Lindroos from the Laboratory of vapour6). Aluminium iodide is extremely destructive to Inorganic Chemistry, University of Helsinki, for valuable the tissues of the respiratory tract and mucous membranes information concerning the described chemical reaction. due to its hydrolysis to hydrogen iodide (anhydrous hydri- odic acid) which is very corrosive7). Iodine is only slight- References ly soluble in water, whereas aluminium iodide reacts vio- lently with water, generating heat and producing hydro- 1) Brooks SM, Weiss MA, Bernstein IL (1985) Reactive gen iodide fumes. Inhalation exposure can therefore lead airways dysfunction syndrome (RADS). Persistent asth- to respiratory effects all the way from the pharynx/larynx ma syndrome after high level irritant exposures. Chest down to the lungs. If fine particles of aluminium iodide 88, 376–84. were also present in the fume, as anticipated, the toxic 2) Shakeri MS, Dick FD, Ayres JG (2008) Which agents cause reactive airways dysfunction syndrome (RADS)? substance was even more likely to enter deep into the res- A systematic review. Occup Med (Lond) 58, 205–11. piratory system and to cause mucosal damage in the ter- 3) Gautrin D, Bernstein IL, Brooks SM, Henneberger PK minal airways, typical of RADS. (2006) Reactive airways dysfunction syndrome and irri- As far as we know, RADS caused by mixed exposure tant-induced asthma. In: Asthma in the workplace, 3rd to iodine, aluminium iodide and hydrogen iodide has not Ed., Bernstein IL, Chan-Yeung M, Malo J-L, Bernstein been previously reported. Although Simonsson et al. DI (Eds.), 581–630, Taylor & Francis, New York. have described persistent bronchial hyperresponsiveness 4) Viljanen AA (1982) Reference values for spirometric, in workers exposed to aluminium fluoride or sulphate8), pulmonary diffusing capacity and body plethysmo- most aluminium compounds appear to be rather inert. The graphic studies. Scand J Clin Invest 42 (Suppl 159), I–1 anion imparts chemical reactivity to aluminium iodide. 1–50. Iodine belongs to the halogens; other important elements 5) Sovijärvi ARA, Malmberg LP, Reinikainen K, Rytilä P, Poppius H (1993) A rapid dosimetric method with con- of this group are fluorine, bromine, and chlorine. Halogen trolled tidal breathing for histamine challenge: repeata- compounds and their reaction products are harmful to the bility and distribution of bronchial reactivity in a clini- respiratory tract. There are earlier case reports of RADS 684 T HANNU et al.

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Industrial Health 2009, 47, 681–684