Another Hot Tub Hazard

and change the filters. This may be all that is necessary to prevent the buildup of M avium complex in hot tubs. M avium complex is resistant to chlorination and so it is found in domestic water. 32 The high chlorine concentrations needed for sterilization may be unpleasant for hot tub use. Superheating the water, if possible, to 70°C for up to an hour may help. 3 ·5 If our findings prove to occur more frequently in hot tubs, then a study of how to control the growth of M avium complex must be done. ACKNOWLEDGMENT: We acknowledge the consultation from Dr. A.Pan on the first case, the radiologic ass istance of Dr. B. Maycher for the CT scan, the work of Ms. J. Wolfe in the Mycobacterial Laboratory, Winnipeg, and the expertise of Charlotte Smith for serologic testing in the Centers for Disease Control and Prevention, Atlanta. REFERENCES 1 Scully RE, Mark EJ, McNeely WF, et al. Case 6-1996. Case records of the Massachusetts General Hospital. N Eng! JMed 1996; 334:521-26 2 Prince DS, Peterson DD, Steiner RM , e t al. Infection with Mycobacterium avium complex in patients without predisposing conditions. N Eng! J M ed 1989; 321:863-68 3 von Reyn CF, Maslow JN, Barber TW, e t a!. Persistent colonisation of potable water as a source of Mycobacterium avium infection in AIDS. Lancet 1994; 343:1137-41 4 Marinkovich VA, Novey HS . Humidifier lung. Clin Rev Allergy 1983; 1:533-36 5 du Moulin GC, Stottmeier KD , Pelletier PA, eta!. Concentration of Mycobacterium aviwn by hospital hot water systems. JAMA 1988; 260:1599-1601 6 Yakrus MA, Reeves MW, Hunter SB. Characterization of isolates of Mycobacterium avium serotypes 4 and 8 from patients with AIDS by multilocus enzyme e el ctrophoresis. J Clin Microbial 1992; 30:1474-78 7 Gruft H, Katz J, Blanchard DC. Postulated source of Mycobacterium intracellulare (Battey) infection. Am J Epidemiol 1975; 102:311-18 8 Wendt SL, George KL, Parker BC, et a!. Epidemiology of infection by nontuberculous Mycobacteria: III. Isolation of potentially pathogenic mycobacteria from aerosols. Am Rev Respir Dis 1980; 122:259-63 9 Parker BC, Ford MA, Gruft H, et a!. Epidemiology of infection by nontuberculous Mycobacteria: IV. Preferential aerosolization of Mycobacterium intracellulare from natural waters . Am Rev Respir Dis 1983; 128:652-56 10 Rosenzweig DY. Pulmonary mycobacterial disease due to Mycobacterium intracellulare-avium complex: clinical features and course in 100 consecutive cases. Chest 1979; 75:115-19 11 Engback HC, Vergmann B, Bentzon MW. Lung disease caused by Mycobacterium avium!Mycobacterium intracellulare. An analysis of Danish patients during the period 196276. Eur J Resp Dis 1981; 62:72-83 12 Hawkins CC, Gold JWM, Whimbey E, et a!. Mycobacterium aviurn complex infection in patients with the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105:184-88 13 Teirstein AS, Damsker B, Kirschner PA, et al. Pulmonary infection with Mycoba~terium avium-intracellulare: diagnosis, clinical patterns, treatment. Mt Sinai JMed 1990; 57:209-15 14 Banaszak EF, Thiede WH, Fink JN. Hypersensitivity pneumonitis due to contamination of an air conditioner. N Engl J Med 1970; 283:271-76 15 Hodges GR, Fink JN , Schlueter DP. Hypersensitivity pneumonitis caused by a contaminated cool mist vaporizer. Ann Intern Med 1974; 80:501-04 816

16 Miller MM , Patterson R, Fink JN, et al. Chronic hypersensitivity lung disease with recurrent episodes of hypersensitivity pneumonitis due to a contaminated central humidifier. Clin Allergy 1976; 6:451-62 17 Friend JAR, Pickering CAC, Palmer KNV, et a!. Extrinsic allergic alveolitis and contaminated cooling-water in a factory machine. Lancet 1977; 1:297-300 18 Muittari A, Kuusisto P, Virtanen P, et al. An epidemic of extrinsic allergic alveolitis caused by tap water. Clin Allergy 1980; 10:77-90 19 Lynch DA, Rose CS , Way D, et a!. Hypersensitivity pneumonitis: sensitivity of high-resolution CT in a population-based study. AJR 1992; 159:469-72 20 Metzger WJ, Patterson R, Fink J, eta!. Sauna-takers diseases: hypersensitivity pneumonitis due to contaminated water in a home sauna. JAMA 1976; 236:2209-11 21 Atterholm I, Hallberg T, Ganrot-Norlin K , eta!. Unexplained acute fever after a hot bath. Lancet 1977; 2:684-86 22 Coleman A, Colby TV. Histologic diagnosis of extrinsic allergic alveolitis. Am J Surg Pathol. 1988; 12:514-18 23 Baur X, Behr J, Dewair M, et al. Humidifier lung and humidifier fever. Lung 1988; 166:113-24 24 Solley GO, Hyatt RE. Hypersensitivity pneumonitis induced b y Penicillium species. J Allergy Clin Immunol 1980; 65:65-70 25 Edwards JH, Griffiths AJ, Mullins J. Protozoa as sources of antigen in "humidifier fever." Nature 1976; 264:438-39 26 Kane GC, Marx JJ, Prince DS. Hypersensitivity pneumonitis secondary to Klebsiella oxytoca: a new cause of humidifier lung. Chest 1993; 104:627-29 27 Muittari A, Rylander R, Salkinoja-Salonen M. Endotoxin and bath water [letter]. Lancet 1980; 2:89 28 Sauske r WF, Aeling JL, Fitzpatrick JE , et a!. Pseudomonas folliculitis acquired from a health spa whirlpool JAMA 1978; 239:2362-65 29 Rose HD, Franson TR, Sheth NK, et a!. Pseudomonas pneumonia associated with use of a home whirlpool spa. JAMA 1983; 250:2027-29 30 Aubuchon C, Hill JJ, Graham DR. Atypical mycobacterial infection of soft tissue associated with use o f ahot tub. J Bone Joint Surg 1986; 68A:766-68 31 Montecalvo MA, Forester G, Tsang AY, eta!. Colonisation of potable water with Mycobacterium avium complex in homes of HIV-infected patients [letter]. Lancet 1994; 343:1639 32 Pelletier PA, du Moulin GC, Stottmeier KD. Mycobacteria in public water supplies: comparative resistance to chlorine. Microbial Sci 1988; 5:147-48

Another Hot Tub Hazard* Toxicity Secondary to Bromine and Hydrobromic Acid Exposure Michael]. Burns, MD; and Christopher H. Linden, MD

We describe the clinical course of two patie nts w ho develope d acute pne umonitis followed b y er active *From the Section in Toxicology, Division of Emergency Medicine, Beth Israel Hospital, Boston (Dr. Burns); and the Department of Emergency Medicine, Division of Toxicology, University of Massachusetts Medical Center, Worcester (Dr. Linden). Manuscript received April 29, 1996; revision accepted September 19. Reprint requests: Dr. Michael Burns, 26 Edmunds Way , Northboro, MA 01532 Selected Reports

airways dysfunction syndrome after bathing in a hot tub. Additional findings were present and suggested that exposure to a corrosive agent was responsible. Bromine and hydrobromic acid generated from a widely used water disinfectant were implicated as the underlying cause. Physicians should be alert to the possibility that such exposures may initiate or exacerbate inflammatory pulmonary disease. (CHEST 1997; 111:816-19) Key words: bromine; hot tub; hydrobromic acid; RADS Abbreviations: Br2 =aqueous or gaseous bromine; HEr= hydrobromic acid; HOBr=hypobromous acid; HOCl=hypochlorous acid; RADS=reactive airways dysfunction syndrome

H ot tub bathing is a popular recreational activity.

Although generally considered safe, public facilities usually have signs warning against hot tub use by individuals who are pregnant, take certain medicines, or have diabetes or cardiovascular disease. A variety of medical problems have been linked to hot tub bathing. 1 · 3 Except for hypersensitivity pneumonitis due to the fungus, Cladosporium, however, pulmonary complications have not been described previously (to our knowledge). 4 We describe two patients who developed signs and symptoms of acute bromine toxicity followed by reactive airways dysfunction syndrome (RADS) after bathing in a hot tub and discuss the pathogenesis and pathophysiology of their disease. CASE REPORTS CASE

1

A 42-year-old woman presented with burning eyes, chest, and throat, shortness of breath, and wheezing that began during a 10-min bath in a hot tub 2 h earlier. She reported a strong odor of "bleach" in the hot tub area, a glass-enclosed room measuring 8Xll feet, located inside a local health club. Black discoloration of her gold jewelry and green bathing suit was also noted. She had been in good health previously and did not smoke. Mild inspiratory stridor, expiratory wheezing, and a bleach-like odor to the breath were noted on examination. Vital signs were normal and the eyes, nose, throat, and skin were unremarkable. Oxygen saturation was 98% on room air. Chest radiograph and results of routine laboratory analyses were unremarkable. She was treated with humidified oxygen and nebulized albuterol during a 24-h hospitalization. She reported intermittent rectal bleeding and generalized alopecia during the following week and month, respectively. Dyspnea and chest burning continue to occur on exertion and exposure to cold air and strong odors. Symptoms respond to inhaled albuterol. Pulmonary function tests performed 3 and 10 months after exposure revealed normal results of spirometry and lung volumes with a strongly positive methacholine challenge. The provocative doses required to produce a 20% fall in FEY 1 were 0.008 and 0.007 j..l.mol, respectively. An a 1 -antitrypsin level was normal. Flexible sigmoidoscopy performed 13 months after her exposure revealed nonspecific proctitis. CASE 2

A 32-year-old woman presented with burning eyes, throat, and chest; hoarseness; nonproductive cough; and mild dyspnea that

developed during a single 5-min bath in the same hot tub at the same time as patient l. She, too, reported a strong acrid odor while bathing in the hot tub. She was previously healthy and did not smoke. Results of physical examination were normal. Oxygen saturation was 99% on room air. Chest radiograph and results of arterial blood gas analysis were normal. No treatment was administered. Cough, sore throat, and hoarseness persisted for 7 months. She continues to have chest burning with exertion. Pulmonary function tests performed 10 months after exposure revealed normal lung volumes and normal results of spirometry but a strongly positive methacholine challenge (provocative dose required to produce a 20% fall in FEV1 , 0.447 j..l.mol). DISCUSSION

Clinical manifestations and the temporal course of events suggested exposure to an irritant chemical in the hot tub water and atmosphere as the etiology of our patients' signs and symptoms. Bleach (hypochlorous acid, HOC!) or a chlorine-based disinfectant was initially suspected. Investigation, however, revealed that a brominebased agent was used in the hot tub in question . Three brominating compounds are available for recreational hot tub, spa, and swimming pool sanitation: elemental bromine, sodium bromide/monopotassium persulfate, and bromochlorodimethylhydantoin. All three compounds generate aqueous hypobromous acid (HOBr), the primary bactericidal agent, when dissolved in water. In the present incident, 1-bromo-3-chloro-5,5-dimethylhydantoin ("Brom Tabs," "Brominating Tablets") was identified as the brominating agent. When added to pool water, this compound hydrolyzes to HOBr and HOC1. 5 Bromide ions are subsequently generated when HOBr reacts with microorganisms. In an acidic pH, as occurs at high concentrations, bromide also exists as hydrobromic acid (HBr). Unless the pH is kept relatively neutral (eg, by adding potassium carbonate), these two compounds readily react to form aqueous bromine (Br2 ). The subsequent liberation of Br2 (and possibly HBr) vapors increases as water temperatures increase. Chlorine gas is not generated because HOC! reacts with bromide ions resulting in the reformation of HOBr. 5 Pool water bromination is achieved similarly with the sodium bromide/monopotassium persulfate method. When these compounds are added to water, bromide ions are oxidized by monopotassium persulfate to HOBr. 5 Subsequent reactions are the same. Aqueous Br 2 concentrations between 2 and 4 ppm are recommended for residential spas and 4 to 6 ppm for commercial spas. 5 Water pH should be between 7.2 and 7.6 optimally. Br2 and HBr liquids and their vapors are skin and mucous membrane irritants. The extent of tissue injury is dependent on their concentration, duration of contact, and water content of exposed tissue. Pathologic effects include edema, inflammation, and necrosis. Exposure to atmospheric concentrations of 10 ppm of Br2 is considered immediately dangerous to life and 0.3 ppm is the current short-term (15-min) exposure limit. 6 Human volunteers could not tolerate a Br2 concentration of 0.9 ppm for greater than 5 min. 7 Br2 is two to three times more corrosive than HBr. Nasal irritation occurs at HBr vapor concentrations of 5 to 6 ppm. 8 CHEST I 111 I 3 I MARCH, 1997

817

Like chlmine, the major cytotoxic effects of Br2 are presumed to be secondary to the oxidizing effects of nascent oxygenY Br2 reacts rapidly with tissue water to form HBr and HOBr. HOBr may subsequently break down into HBr and oxygen free radicals. 10 The corrosive action of the acids generated and reaction of Br2 and these acids with cellular proteins to form bromamine and thiol radicals may contribute to toxicity. Greater water solubility, and, thus, tissue permeability may explain why bromine is more toxic than chlorine. Clinical manifestations usually begin immediately after vapor inhalation but may be delayed for up to 10 h.1 1 Generally, low-concentration exposures will result in eye, nose, and upper airway injury and higher concentrations will additionally result in lower airway damage. Sequelae are infrequent and usually consist of subjective complaints without objective findings to correlate with symptoms. 12 One patient developed chemical pneumonitis and a restrictive pattern of pulmonary dysfunction following short-term exposure to a mixture of HBr and phosphorus tribromide.13 Persistent bronchiolar spasm has been observed in animals exposed to Br2 vapors but not in humans. 14 Both patients described fulfill the criteria for RADS.l 5 The abrupt onset of irritant symptoms within minutes of a single bath suggest high-concentration irritant exposure. Circumstances strongly implicate exposure to bromine and HBr as the precipitating event. Allergic asthma (hypersensitivity pneumonitis) was not considered likely because it is typically insidious in onset, requiring repetitive exposures to elicit an inflammatory reaction. Even with acute hypersensitivity pneumonitis, symptoms do not develop until 4 to 6 h after exposure. In addition, patients with hypersensitivity pneumonitis typically have constitutional symptoms, abnormal chest radiographs, and restrictive pulmonary disease, findings that were not seen in our patients. The pathophysiologic state of RADS has not been fully elucidated. Nonspecific bronchial hyperresponsiveness is operative and may be mediated by structural airway abnormalities, immunogenic inflammation, and dysregulation of neurogenic inflammation.l6 Bronchial biopsy specimens from patients with RADS have revealed epithelial destruction, squamous cell hyperplasia, subepithelial basement membrane and connective tissue thickening, and variable nonspecific inflammatory cell response (lymphocytes and plasma cells). 15 ·17 ·18 Structural bronchial damage is closely linked to heightened airway responsiveness. RADS has been reported following inhalation of chlorine gas 19 and pulmonary toxic reactions have resulted from the inhalation of vapors generated by swimming pool chlorinating tablets.l 0 Given the widespread use of bromine compounds as bathing water disinfectants, the lack of previously reported cases of toxic reactions from brominating agents is surprising, particularly in the setting of hot tub use, where high water temperatures would be expected to promote the liberation of toxic vapors. This may reflect greater safety of bromine-containing disinfectants as compared with chlorinated ones. The greater water solubility of bromine allows for less vapor liberation 818

from aqueous solutions. Alternatively, similar cases may have occurred but gone unrecognized or unreported. We suspect that the bromine concentration and pH of the hot tub water in which our patients bathed were higher and lower, respectively, than recommended. The jewelry and bathing suit discoloration noted by patient 1 supports this contention. We were unable, however, to obtain any information from the health club management in regards to these parameters. Although not previously described, alopecia and proctitis are also consistent with the known toxicity (ie, corrosive effects) of bromine and its halogen acid and exposure by way of immersion. An abnormally high bromine concentration or abnormally low pH in the hot tub water would also have resulted in greater production and liberation of Br2 and HBr vapors, and, hence, respiratory tract exposure. The fact that the hot tub was located in a small room rather than outdoors or in a larger (eg, poolside) indoor area may have created a situation similar to that of smoke inhalation, where exposure in an enclosed space is well known to increase the risk of respiratory tract injury. Since both of our patients reported that no one else was present in the hot tub at the same time as they were, we were unable to determine whether other people used the hot tub in question and were similarly affected. We suspect that when our patients reported their symptoms to the health club management at the time of exposure, the hot tub area was closed to use until the situation could be investigated and corrected. The known chemistry of brominating compounds, their reported use in the hot tub in question, the temporal relationship between exposure and toxic effects, clinical signs and symptoms that were consistent with the known toxicity of halogen gases and their acids, and the absence of alternative explanations strongly implicate Br2 and HBr as the cause of our patients' illnesses. Bromine poisoning should be added to the list of potential hot tub hazards . As with chlorine gas exposure, inhalation of Br2 and HBr vapors may cause RADS. Patients with new-onset RADS or exacerbation of preexisting pulmonary disease should be questioned about hot tub use and exposure to halogen gases or vapors as a precipitating factor. Further study is necessary to determine the incidence of poisoning resulting from such exposures. REFERENCES 1 Press E. The health hazards of saunas and spas and how to minimize them. Am J Public Health 1991; 81:1034-37 2 Sausker WF, Aeling JL, Fitzpatrick JE, et a!. Pseudomonas folliculitis acquired from a health spa whirlpool. JAMA 1978; 239:2362-65 3 Spitalny KC, Vogt RL, Witherell LE. National survey on outbreaks associated with whirlpool spas. Am J Public Health 1984; 74:725-26 4 Jacobs RL, Thorner RE, Holcomb JR, et a!. Hypersensitivity pneumonitis caused by Cladosporium in an enclosed hot-tub area. Ann Intern Med 1986; 105:204-06 5 Mitchell PK. The proper man agement of pool and spa water: catalog 88-83735. Decatur, Ga: Hydrotech Chemical Corporation, 1988; 17-28 6 Stokinger HE. The halogens and the nometals boron and silicon. In: Clayton CD, Clayton FE, eds. Patty's industrial Selected Reports

7

8

9 10

ll

12

13 14 15 16 17

18 19

hygiene and toxicology. 3rd ed (vol liB). New York: John Wiley, 1981; 2965-72 Rupp H, Henschler D. Wirkungen g eringer chlor- und brom-konzentrationen auf den M enschen. Int Arch Gewerbepathologie Gewerbehygiene 1967; 23:79-90 Alexandrov DD. Bromine and compounds. In: Parmeggiani L, ed. Encyclopedia of occupational health and safety. 3rd ed (vol 1). G eneva, Switzerland: International Labour Organisation, 1983; 326-29 Decker WJ, Koch HF. Chlorine poisoning at the swimming pool: an overlooked hazard. Clin Toxicol 1978; 13:377-81 Wood BR, Colombo JL, Benson BE. Chlorine inhalation toxicity from vapors generated by swimming pool chlorinator tablets. Pediatrics 1987; 79:427-30 Champeix J, Catilina P, Andraud G, et la. Etude clinique e t ]' par vapeurs de brome. Pouexpe rimentale de intoxication mon Coeur 1970; 26:895-903 Carel RS , Belmaker I , Potashnik G, e t !a. Delayed h ealth sequelae of accidental exposure to bromine gas. J Toxicol Environ Health 1992; 36:273-77 Kraut A, Lilis R. Chemical pneumonitis due to exposure to bromine compounds. Chest 1988; 94:208-10 Schlagbauer M , Henschler D. Toxicitat von chlor und brom bei einmaliger und wiederholter Inhalation. Int Arch Gewerbepathologie Gewerbehygiene 1967; 23:91-8 Brooks SM , Weiss MA, Berstein IL. Reactive airways dysfunction syndrome (RADS ): persistent asthma syndrome after high level irritant exposures. Chest 1985; 88:376-84 Meggs WJ. RADS and RUDS-the toxic induction of asthma and rhinitis. Clin Toxicol 1994; 3 2:487-501 Deschamps D,Soler P, Rosenberg N, et al. Persistent asthma after inhalation of a mixture of sodium hypochlotite and hydrochloric acid. Chest 1994; 105:1895-96 Gautrin D, Boulet LP, Boutet M, e t l.a Is reactive air.vays dysfunction syndrome a variant of occupational asthma? J Allergy Clin Immunol 1994; 93:12-22 Decker WJ. Reactive airway dysfunction syndrome (RADS ) followin g single acute exposure to chlorine gas [abstract]. Vet Hum Toxicol1988; 30:344

Neurocardiogenic Syncope and Prinzmetal's Angina Associated With Bronchogenic Carcinoma* Paolo Angelini, MD; and Paul Y. Holoye, MD

A clinical case is presented illustrating a previously unreported association of (I) neurocardiogenic syncope of new onset in a 57-year-old man, (2) Prinzmetal's angina, and (3) bronchogenic carcinoma of the lung. Initiation of aggressive chemotherapy resulted in immediate suppression of both cardiac manifestations. This newly described paraneoplastic *From the Depa1tments of Adult Cardiology (Dr. Angelini ) and Medical Oncology (Dr. Holoye), St. Luke's Episcopal Hospital and the Texas Hea1t Institute, and the Department of Internal Medicine, Baylor College of Medicine, Houston. Manuscript received January 10, 1996; revision accepted April 24. Reprint requests: Dr. Angelini, Leachman Cardiology Associates, PO Box 20206, Houston, TX 7722.5-0206

syndrome is discussed.

(CHEST 1997; 111:819-22) Key words: bronchogenic carcinoma; neurocardiogenic syncope; Prinzmetal's angina

N eurocardiogenic syncope is a w ell-defined cardiovas-

cular condition; its cause, however, is still poorly understood. 1·2 Although several pathophysiologic interpretations regarding its cause have been proposed, various mechanisms may contribute to the cause in different patients or even simultaneously in one patient. 2 -4 We present an unusual case of neurocardiogenic syncope, which was associated with a malignant form of Prinzmetal's angina. In this patient, the causative factor, bronchogenic carcinoma, could be substantiated by empirical and clinical proof. Treatment of carcinoma by chemotherapy was indeed sufficient for prompt elimination of the cardiovascular symptoms. CASE REPORT A 67-year-old Hispanic man , who was a long-time cigarette smoker (2 packs per day), was well until February 1995 when h e began to experience episodes of syncope . Initially, he related the syncope to changing from the supine to the e rect position; eventually, he began to experience these episodes even during bed r est. On March 30, 1995, he was dmitted a to a hospital in Mexico City because of prolonged r esting pain, accompanied by near syncope. After the ECG showed anterior ST-T segment changes, he was immediately taken to the catheteri zation laboratory; a tentative diagnosis was made of acute anterior myocardial infarction. During the cathete1ization procedure, the patient was sedated and the pain disappeared. At that time, coronary angiography revealed a normal coronary flow pattern, with the appearance of a l eft anterior descending coronary arte1y lesion that show ed about 50% diameter narrowing. While the patient was being prepared for balloon angioplasty, he again complained of chest pain and developed s evere hypotension and bradycardia. New coronary angiograms clearly revealed an uneven flow pattern with slow flow limited to the left anterior descending coronary artery tenitory, without discrete narrowing. The ECG showed anterior T-wave changes and mild ST elevation, with advanced atrioventricular block. Intracoronary nitroglycerin and temporary ventricular pacing alleviated the bradycardia and ischemia. The new angiograms revealed no fixed stenosis and brisk flow in all the coronary branches . The procedure was thus aborted. Because of recurrent episodes of syncope and atrioventricular block with long periods of asystole, the patient eventually received a p ermanent atrioventricular sequential pacemaker. Medications were changed to disopyramide (100 mg, 3 times a day), fludrocortisone (0.1 mg daily), famotidine (40 mg daily), and sedatives. The patient continued to be bedridden b ecause of recurrent dizziness and chest pain until his admission to St. Luke's Episcopal Hospital on May 5, 1995. At that time, physical examination revealed an anxious, diaphoretic, acutely ill patient. No significant abnormalities w ere discovered at the time of physical examination, which included a d teailed neurologic examination. BP was 110/70 mm Hg. ECGs obtained over the next several days (F ig 1) showedsinus or electronic pacemaker atrial rhythm or intermittent atrial fibrillation, with normally conducted QRS complex and transient T-wave changes th at correlated \vith chest pain. A chest x-ray film was read as normal, with possible linear atelectasis in the left pe rihilar r egion. CHEST I 111 I 3 I MARCH, 1997

819