Chemical Pneumonitis and Acute Lung Injury Caused by Inhalation of Nickel Fumes

□ CASE REPORT □

Kei Kunimasa, Machiko Arita, Hiromasa Tachibana, Kazuya Tsubouchi, Satoshi Konishi, Yohei Korogi, Akihiro Nishiyama and Tadashi Ishida

Abstract

A 50-year-old man with a 30-year occupational history of welding presented with low-grade fever, fatigue and persistent dry cough. Computed tomography (CT) of the chest revealed interlobular septal thickening and bilateral non-segmental patchy ground-glass opacities except in the sub-pleural zone. He revealed that he had inhaled nickel fumes 3 days previously at work. These findings suggested a diagnosis of pneumonitis induced by inhalation of nickel fumes. Fewer reports describe pneumonitis associated with the inhalation of nickel compared with zinc fumes. Although nickel compounds are particularly pernicious among the transition metals and more toxic than zinc compounds, nickel fume inhalation rarely induces lethal acute respiratory distress syndrome. Our patient was successfully treated with corticosteroid.

Key words: nickel fumes, chemical pneumonitis, acute lung injury

(Intern Med 50: 2035-2038, 2011) (DOI: 10.2169/internalmedicine.50.5557)

lessness Fletcher-Hugh-Jones (FHJ) criteria that had per- Introduction sisted for 3 days. A combination cold remedy taken on the fourth day had no effect and his symptoms had worsened. The health effects of exposure to metal fumes have been As fatigue progressed, he had difficulty in standing up from extensively studied (1). Numerous studies have evaluated the a seated position and perfoming activities requiring even pulmonary effects of exposing workers to metal fumes (2). minimal effort. He had a history of ureteral lithiasis. He had Respiratory effects arising in full-time welders include bron- no known allergies to food or medications. He had a fifteen chitis, siderosis, asthma, and a possible increase in the inci- pack-year smoking history and did not consume alcohol nor dence of lung cancer (1-5). Although the most frequent use illicit drugs. acute respiratory complaint of welders is metal fume fever, On physical examination, his body temperature, 38.3°C; some reports have also described interstitial pneumonia and respiratory rate, 32 breaths per minute; blood pressure, 143/ acute lung injury induced by inhalation of metal 82 mmHg; pulse rate, 102 beats per minute and oxygen fumes (1, 6). Nickel fumes inhalation can cause bronchial saturation of 92% while breathing ambient air. No abnormal asthma and pulmonary infiltrates with eosinophilia syn- breath sounds were identified, but vesicular sounds were de- drome; however acute lung injury is very rare (7, 8). We creased. Skin lesions were absent. A chest X-ray upon ad- present a patient with chemical pneumonitis and acute lung mission revealed reticular opacities in both middle and injury caused by the inhalation of nickel fumes. lower lung fields (Fig. 1a). Axial chest CT showed bilateral non-segmental ground-glass opacities except in the sub- Case Report pleural zone (Fig. 1b). Based on these chest CT findings, we obtained more details of his history regarding antigen inha- A 50-year-old man with a 30-year history of occupational lation. welding was admitted to our hospital with low-grade fever, At that time he was a field superintendent and had walked fatigue, persistent dry cough and grade III exertional breath- into an area where nickel was being sprayed on metal sur-

Department of Respiratory Medicine, Kurashiki Central Hospital, Japan Received for publication March 25, 2011; Accepted for publication June 6, 2011 Correspondence to Dr. Kei Kunimasa, [email protected]

2035 Intern Med 50: 2035-2038, 2011 DOI: 10.2169/internalmedicine.50.5557

(A) (B)

Figure 1. (A) Chest X ray shows bilateral reticular opacities in middle and lower lung fields. Bilat- eral costophrenic angles are sharply pointed. (B) High-resolution chest CT (lung windowing) at first admission shows interlobular septal thickening (crazy paving) and bilateral non-segmental patchy ground-glass opacities, except in the sub-pleural zone.

faces via a metal-arc process, without wearing splash-proof dyspnea, we prescribed prednisolone (50 mg/day). Subjec- chemical safety goggles or a face protective mask. Although tive symptoms and chest imaging findings remarkably im- he usually paid special attention to the use of personal pro- proved as the levels of serum markers decreased. The pred- tective equipment as part of the responsibility of his posi- nisolone dose was tapered over a period of 1 month and dis- tion, he had accidentally neglected these precautions on this continuation did not result in relapse. The bilateral non- occasion. Unfortunately, he inhaled nickel fumes when the segmental ground-glass opacities on chest CT improved wind shifted as he was passing by the area. Soon after in- (Fig. 3). haling nickel fumes, he developed a strong cough, but as- sumed based on his experience that his cough would sponta- Discussion neously resolve. Two laborers working nearby had not expe- rienced any symptoms due to adequate protection. In his in- Fumes comprise airborne particles of vapor, gas or smoke dustry, most welding fumes are generated using mild steel formed, for example, when a metal vaporizes into the at- or carbon steel materials which usually contain iron and mosphere and then coalesces back into a solid. The inhala- manganese, but they happened to be using nickel fumes on tion of metal fumes can induce a wide range of lung patho- this occasion. He said that he had never been exposed to physiology, including airway disorders, cancer and diffuse nickel fumes before. parenchymal lung diseases (1-5). In Japan, the Ministry of Laboratory tests (Table 1) showed leukocytosis, increased Labor lists nickel carbonyl as a hazardous substance (9). serum C-reactive protein (CRP), lactic dehydrogenase The inhalation of metal fumes increases susceptibility to in- (LDH) and surfactant protein A (SP-A). Arterial blood gas fectious pneumonia and induces occupational asthma. Many analysis showed hypoxemia. Differential cell counts of bron- organizations have evaluated evidence regarding the carcino- choalveolar lavage fluid (BALF) revealed an increased ratio genic effects of nickel (5, 10). The most frequent acute res- of neutrophils (22.0%). BAL PCR assay of Pneumocystis ji- piratory complaint of welders is metal fume fever (1). The roveci was negative. Tissue samples from transbronchial condition is a self-limited, flu-like illness characterized by lung biopsy revealed infiltration of lymphocytes and mono- acute onset within 4 - 8 hr and symptoms may include cytes within the interstitium, intra-alveolar fibrin deposition thirst, dry cough, chills, fever, dyspnea, malaise, headache, and the development of interstitial fibrosis (Fig. 2). No and nausea. Although exposure to zinc oxide fumes is the poorly formed granulomas were observed. A skin patch test most frequent and best-characterized cause of metal fume of nickel sulfate was negative. Although unfortunately we fever, other metal oxides including arsenic, boron, cadmium, were unable to obtain samples of the gas and dust he in- chromium, copper, magnesium, manganese, nickel and tita- haled or demonstrate nickel particles in lung tissue, we diag- nium are also suggested causes (11). The toxicity of individ- nosed acute lung injury induced by inhalation of nickel ual metals might depend on their oxidation state. Nickel is fumes based on the obtained findings and his clinical one of a large group of transition metals found in ambient course. air, and hence it exhibits several common oxidative states His symptoms were relieved somewhat spontaneously af- that play an important roles in catalyzing biologic oxidative ter admission. For treating the prolonged severe cough and reactions (12). Inhalation is the primary route of occupa-

2036 Intern Med 50: 2035-2038, 2011 DOI: 10.2169/internalmedicine.50.5557

Table 1. Laboratory Findings

CBC Immunoserology BALF WBC 12000 /ȝL IgG 869 mg/dL Recovery rate 68 % Neu. 82.7 % IgA 83.0 mg/dL Total cell count 300 /ȝL Lym. 9.9 % IgM 77.0 mg/dL DCC Neu. 22.0 % Mon. 5.3 % IgE 44 mg/dL Lym. 7.0 % Eos. 1.9 % RF 0.0 IU/mL Eos. 3.0 % RBC 4.56×106 /ȝL KL-6 299 U/mL Mĳ . 68.0 % Hb 14.2 g/dL ANA 20 CD4/CD8 1.56 Plt. 22.3×104 /ȝL ANCA < 20 PCR for P.jiroveci negative SP-D 35.8 ng/mL PCR for CMV negative Biochemistry SP-A 89.9 ng/mL Pulmonary function tests TP 6.4 g/dL Arterial blood gas (ambient air) VC 3.67 L Alb 3.6 g/dL pH 7.420 %VC 97.6 %

AST 31 IU/L PaO2 50.6 Torr FEV1.0 2.75 L

ALT 20 IU/L PaCO2 41.9 Torr FEV1.0% 84.6 % - LDH 315 IU/L HCO3 25.9 mM %DLco 46.8 % ALP 152 IU/L Infection CK 339 IU/L ȕ-D glucan 7.3 pg/mL BUN 19 mg/dL Chlamydia pneumoniae Cr 0.86 mg/dL IgA index 0.04 Na 140 mEq/L IgG index 0.03 K 4.1 mEq/L IgM index 0.77 Cl 105 mEq/L Mycoplasma pneumoniaeAb.(PA) 40 CRP 16.47 mg/dL Urinary Legionella pneumophila Ag. negative

(A) (B)

Figure 2. Transbronchial lung biopsy specimens show (A) slight lymphocyte and monocyte infiltration into alveolar septa and (B) fibrinous exudates in the alveolar space adjacent to the bronchio- lo-vascular bundle. tional exposure to nickel compounds that preferentially ac- case of acute respiratory distress syndrome due to the inha- cumulate in the lungs and the kidneys (13). Although nickel lation of nickel fumes from a metal arcing process (14). fumes inhalation can cause bronchial asthma and pulmonary Pneumonitis induced by inhalation of metal fumes is infiltrates with eosinophilia syndrome, exposure to high roughly divided into chemical pneumonitis and hypersensi- doses of nickel fumes causes chemical pneumonitis and pul- tivity pneumonitis (9). The present case had no signs of al- monary edema (7, 8). Lethal events are unusual and recov- lergic reaction on physical examination and there was no ery is usually complete, but there was a report of a fatal elevation of lymphocyte or eosinophil count in BALF. We

2037 Intern Med 50: 2035-2038, 2011 DOI: 10.2169/internalmedicine.50.5557

are important to avoid potential lethality. Of course there is no question that the use of appropriate personal protective equipment in the work environment is a necessity.

The authors state that they havenoConflictofInterest(COI).

References

1. Kelleher P, Pacheco K, Newman LS. Inorganic dust pneumonias: the metal-related parenchymal disorders. Environ Health Perspect 108: 697-704, 2000. 2. Antonini JM. Health effects of welding. Crit Rev Toxicol 157: Figure 3. High-resolution chest CT (lung windowing) shows 227-233, 2003. improved shadow after steroid administration. 3. Fernandez-Nieto M, Quirce S, Sastre J. Occupational asthma in industry. Allergol Immunopathol 34: 212-223, 2006. 4. Lombardo LJ, Balmes JR. Occupational asthma: a review. Environ therefore diagnosed chemical pneumonitis and acute lung in- Health Perspect 108: 697-704, 2000. 5. Hansen KS, Lauritsen JM, Skytthe A. Cancer incidence among jury induced by inhalation of nickel fumes. mild steel and stainless steel welders and other metal workers. Am No guidelines are currently available regarding the treat- JIndMed30: 373-382, 1996. ment of pneumonitis induced by metal fume inhalation. Pul- 6. Fontenot AP, Amicosante M. Metal-induced diffuse lung disease. monary inflammation in acute hypersensitivity pneumonitis Semin Respir Crit Care Med 29: 662-669, 2008. is often reversible by removing the inhaled antigens (9). 7. Malo JL, Cartier A, Doepner M, Nieboer E, Evans S, Dolovich J. Occupational asthma caused by nickel sulfate. J Allergy Clin Im- When inflammation persists even after antigens are re- munol 69: 55-59, 1982. moved, steroids are the mainstay of medical therapy. Cytoki- 8. Hisatomi K, Ishii H, Hashiguchi K, et al. Interstitial pneumonia nes are considered to mediate the pathological respiratory caused by inhalation of fumes of nickel and chrome. Respirology conditions associated with inhalation of metal fumes (15). 11: 814-817, 2006. The characteristic symptoms are elicited by cytokines pro- 9. Kusaka Y, Sato K, Suganuma N, Hosoda Y. Metal-induced lung duced in the lung as a direct response to the inhaled metal disease: lessons from Japan’s experience. J Occup Health 43:1- 23, 2001. fumes. The persistent severe cough and dyspnea in the pre- 10. Goodman JE, Prueitt RL, Dodge DG, Thakali S. Carcinogenicity sent patient were thought to be the consequence of pro- assessment of water-soluble nickel compounds. Crit Rev Toxicol longed bronchial inflammation. Metal fumes differ in both 39: 365-417, 2009. metal content and solubility (16). Studies of animal models 11. Newman L. Metals. In: Occupational and Environmental Respira- have demonstrated that stainless steel welding fumes, which tory Disease. 1st ed. Harber P, Schenker MB, Balmes J, Eds. Mosby, St. Louis, MO, 1996: 469-513. contain significant levels of nickel and chromium, induce 12. Snow ET, Costa M. Nickel toxicity and carcinogenesis. In: Envi- more lung injury and inflammation, and are retained in the ronmental and Occupational Medicine. 3rd ed. Rom WN, Ed. lungs for longer periods than mild steel welding fumes, Lippincott-Raven, Philadelphia, 1998: 1057-1064. which contain mostly iron (17). Toxicity might be associated 13. Zhao J, Shi X, Castranova V, Ding M. Occupational toxicology of with the content of nickel and chromium in the stainless nickel and nickel compounds. J Eviron Pathol Toxicol Oncol 28: 177-208, 2009. steel welding fumes, which are absent in mild steel welding 14. Rendall RE, Phillips JI, Renton KA. Death following exposure to fumes. Short-term exposure of rats to stainless steel welding fine particulate nickel from a metal arc process. Ann Occup Hyg fumes causes significant acute lung damage and prolongs 38: 921-930, 1994. pulmonary inflammation (18). We suspect that because our 15. Blanc PD, Boushey HA, Wong H, Wintermeyer SF, Bernstein MS. patient inhaled nickel fumes, he might develop not merely Cytokines in metal fume fever. Am Rev Respir Dis 147: 134-138, 1993. fume fever, but also chemical pneumonitis and acute lung 16. Taylor MD, Roberts JR, Leonard SS, Shi X, Antonini JM. Effects injury. We would have preferred to understand the precise of welding fumes of differing composition and solubility on free chemical components of his inhaled fumes and the industrial radical production and acute lung injury and inflammation in rats. process that he encountered, but such information was un- Toxicol Sci 75: 181-191, 2003. available. 17. Antonini JM, Taylor MD, Zimmer AT, Roberts JR. Pulmonary responses to welding fumes: role of metal constituents. J Toxicol The characteristic chest CT findings at the first medical Environ Health A 67: 233-249, 2004. examination of our patient indicated a need to question him 18. Antonini JM, Stone S, Roberts JR, et al. Effect of short-term about inhaled antigens and his answers and the findings led stainless steel welding fume inhalation exposure on lung inflam- to an early diagnosis. Early identification and management mation, injury, and defense responses in rats. Toxicol Appl Phar- of chemical pneumonitis caused by metal fumes inhalation macol 223: 234-245, 2007.

2038