Metal Allergy pp 533-544 | Cite as

Metal Allergy and the Lungs

  • Cezary Pałczyński
  • Maciej Kupczyk


Metals may induce diseases of the upper and lower respiratory tract, with clinical presentations including asthma, rhinosinusitis, acute bronchitis, acute pneumonitis, carcinoma, and interstitial lung disease. Several metals have a wide range of industrial applications, thus leading to occupational exposure. The current knowledge of airway allergy to metals (impact of metals on the immune system, metals causing immunological asthma, diagnostic problems of metal-induced asthma) has been presented in the chapter. Only a few metals may cause immunological asthma, and all belong to transition metals of the fourth (chromium, cobalt, nickel, manganese, zinc), fifth (rhodium, palladium), and sixth (platinum, iridium) periods of the periodic table. The underlying immune and nonimmune mechanisms involved in asthma caused by metals or metal salts are various and have not yet been fully elucidated. Laboratory tests (skin and serological tests, lymphocyte proliferation test) have limited value in the diagnosis of metal-induced immunological asthma. Specific inhalation challenge tests play a key role in the diagnostics of metal-induced asthma. Exposure to beryllium may lead to sensitization and chronic granulomatous lung disease. Other metals such as indium, zirconium, titanium, cobalt, aluminum, and copper sulfate may also sporadically induce lung pathologies.


Metals Metal salts Metal-induced airway allergy Metal-induced asthma 


  1. 1.
    Merget R, Gautrin D. Metals. In: Malo JL, Chan-Yeung M, Bernstein DI, editors. Asthma in the workplace. 4th ed. London/New York: CRC Press/Taylor & Francis Group; 2013. p. 290–304.Google Scholar
  2. 2.
    Rice RH, Cohen DE. Toxic responses of the skin. In: Klassen CD, editor. Casarett and Doull’s toxicology, The basic science of poisons. New York, NY: McGraw-Hill; 1995. p. 529–46.Google Scholar
  3. 3.
    Zhang M, Jian L, Bin P, Xing M, Lou J, Cong L, Zou H. Workplace exposure to nanoparticles from gas metal arc welding process. J Nanopart Res. 2013;15:1–14.Google Scholar
  4. 4.
    Ding M, Kisin ER, Zhao J, Bowman L, Lu Y, Jiang B, Leonard S, Vallyathan V, Castranova V, Murray AR, Fadeel B, Shvediva AA. Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical production and activation of cell signaling pathways in murine epidermal cells. Tox Appl Prarmacol. 2009;241:260–8.CrossRefGoogle Scholar
  5. 5.
    Park JW, Lee IC, Shin NR, Jeon CM, Kwon OK, Ko JW, Kim JC, Oh SR, Shin J, Ahn KS. Copper oxide nanoparticles aggravate airway inflammation and mucus production in asthmatic mice via MAPK signaling. Nanotoxicology. 2016;10:445–52.CrossRefGoogle Scholar
  6. 6.
    Huang KL, Lee YH, Chen HI, Liao HS, Chang BL, Cheng TJ. Zinc oxide nanoparticles induce eosinophil inflammation in mice. J Hazard Mater. 2015;297:304–12.CrossRefGoogle Scholar
  7. 7.
    Park HS, Kim KH, Jang S, Park JW, Cha HR, Lee JE, Kim JO, Kim SY, Lee CS, Kim JP, Jung SS. Attenuation of allergic airway inflammation and hyperresponsiveness in a murine model of asthma by silver nanoparticles. Int J Nanomedicine. 2012;5:505–15.Google Scholar
  8. 8.
    Agricola G. De re metallica. In: Translated by Hoover HC, Hoover LH. The mining magazine. London: Mining Journal, Ltd.; 1912.Google Scholar
  9. 9.
    Brooks SM. Lung disorders resulting from the inhalation of metals. Clin Chest Med. 1981;2:235–54.PubMedGoogle Scholar
  10. 10.
    Malo JL. Occupational rhinitis and asthma due to metal salts. Allergy. 2005;60:138–9.CrossRefGoogle Scholar
  11. 11.
    Farkhondeh T, Sarkhandian S, Sadikhara P. Lead exposure and asthma: an overview of observational and experimental studies. Toxin Rev. 2016;34:6–10.CrossRefGoogle Scholar
  12. 12.
    Rosa MJ, Benedetti C, Pell IM, Filippo D, Nazarro M, Fedrighi C, Zoni S, Marcon A, Zimmermann N, Wright R, Lucchini R. Association between personal exposure to ambient metals and respiratory disease in Italian adolescents: a cross-sectional study. BMC Pulm Med. 2016;16:6.CrossRefGoogle Scholar
  13. 13.
    Esterhuizen TM, Hnido E, Ress D. Occurrence and causes of occupational asthma in South Africa – results from SORDSA’s occupational Astma registry, 1977–1999. S Afr Med J. 2001;91:509–13.PubMedGoogle Scholar
  14. 14.
    Wittczak T, Dudek W, Walusiak-Skorupa J, Swierczynska-Machura D, Cader W, Kowalczyk M, Pałczynski C. Metal-induced asthma and chest x-ray changes in welders. Int J Occup Environ Health. 2012;25:242–50.Google Scholar
  15. 15.
    Antonini JM, Taylor MD, Zimmer AT, Roberts JR. Pulmonary responses to welding fumes: role of metal constituents. J Toxicol Environ Health. 2004;67:233–49.CrossRefGoogle Scholar
  16. 16.
    Huvinen M, Uitti J, Oksa P, Palmroos P, Laippala P. Respiratory health effects of long-term exposure to different chromium species in stainless steel production. Occup Med. 2002;52:203–12.CrossRefGoogle Scholar
  17. 17.
    Rehfisch P, Anderson M, Berg P, Lampa E, Nordling Y, Swartengren M, Westberg H, Gunnarson LG. Lung function and respiratory symptoms in hard metal workers exposed to cobalt. J Occup Environ Med. 2012;54:409–13.CrossRefGoogle Scholar
  18. 18.
    Venables KM, Dally MB, Burge PS, Pickering CA, Newman-Taylor AJ. Occupational asthma in a steel coating plant. Br J Ind Med. 1985;42:517–24.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Malo JL, Cartier A, Gagnon G. Isolated late asthmatic reaction due to nickel sulphate without antibodies to nickel. Clin Allergy. 1985;15:95–9.CrossRefGoogle Scholar
  20. 20.
    Merget R, Schultze-Werninghaus G, Bode F. Quantitative skin prick and bronchial provocation tests with platinum salt. Br J Ind Med. 1991;48:830–7.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Merget R, Schultze-Werninghaus G, Muthorst T. Asthma due to complex salts of platinum – a cross sectional survey of workers in a platinum refinery. Clin Allergy. 1988;18:569–80.CrossRefGoogle Scholar
  22. 22.
    Murdoch RD, Pepys J, Hughes EG. IgE antibody responses to platinum group metals: a large scale refinery survey. Br J Ind Med. 1986;43:37–43.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Merget R, Reineke M, Ruckmann A. Nonspecific and specific bronchial responsiveness in occupational asthma due to platinum salts after allergen avoidance. Am J Respir Crit Care Med. 1994;150:1146–9.CrossRefGoogle Scholar
  24. 24.
    Biagini RE, Bernstein IL, Gallagher JS, Moorman WJ, Brecks S, Gann PH. The diversity of reaginic immune responses to platinum and palladium metallic salts. J Allergy Clin Immunol. 1985;76:794–802.CrossRefGoogle Scholar
  25. 25.
    Smith AR. Chrome poisoning with manifestation of sensitization: report of a case. JAMA. 1931;97:95–8.CrossRefGoogle Scholar
  26. 26.
    Joules H. Asthma from sensitization to chromium. Lancet. 1932;2:182–3.CrossRefGoogle Scholar
  27. 27.
    Card WI. A case of asthma sensitivity to chromates. Lancet. 1935;229:1348–9.CrossRefGoogle Scholar
  28. 28.
    Olaguibel JM, Basomba A. Occupational asthma induced by chromium salts. Allergol Immunopathol. 1989;17:133–6.Google Scholar
  29. 29.
    Park HS, Yu HJ, Jung KS. Occupational asthma caused by chromium. Clin Exp Allergy. 1994;24:676–81.CrossRefGoogle Scholar
  30. 30.
    De Raeve H, Vandecasteele C, Demedts M, Nemery B. Dermal and respiratory sensitization to chromate in a cement floorer. Am J Ind Med. 1998;34:169–76.CrossRefGoogle Scholar
  31. 31.
    Fernandez-Nieto M, Quirce S, Carnes J. Occupational asthma due to chromium and nickel salts. Int Arch Occup Environ Health. 2006;79:483–6.CrossRefGoogle Scholar
  32. 32.
    Sastre J, Fernandez-Nieto M, Maranon F, Fernandez-Caldas E, Pelta R, Quirce S. Allergenic cross-reactivity between nickel and chromium salts in electroplating-induced asthma. J Allergy Clin Immunol. 2001;108:650–1.CrossRefGoogle Scholar
  33. 33.
    Novey HS, Habib M, Wells ID. Asthma and IgE antibodies induced by chromium and nickel salts. J Allergy Clin Immunol. 1983;72:407–12.CrossRefGoogle Scholar
  34. 34.
    Walters GI, Moore VC, Robertson AS, Burge CBSG, Vellore AD, Burge PS. An outbreak of occupational asthma due to chromium and cobalt. Occup Med. 2012;62:533–9.CrossRefGoogle Scholar
  35. 35.
    Eastlander T, Kanerva L, Tupasela O, Keskinen H, Jolanki R. Immediate and delayed allergy to nickel with contact urticaria, rhinitis, asthma and contact dermatitis. Clin Exp Allergy. 1993;23:306–10.CrossRefGoogle Scholar
  36. 36.
    Dolovich J, Evans SL, Nieboer E. Occupational asthma from nickel sensitivity: human serum albumin in the antigenic determinant. Br J Ind Med. 1984;41:51–5.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Bright P, Burge PS, O’ Hickey SP. Occupational asthma due to chrome and nickel electroplating. Thorax. 1997;52:28–32.CrossRefGoogle Scholar
  38. 38.
    Cruz MJ, Costa R, Marquilles E. Occupational asthma caused by chromium and nickel. Arch Broncopneumol. 2006;42:302–6.Google Scholar
  39. 39.
    Leroyer C, Dewitte JD, Bassanets A. Occupational asthma due to chromium. Respiration. 1998;65:403–5.CrossRefGoogle Scholar
  40. 40.
    Kusaka Y, Yokoyama K, Sera Y. Respiratory diseases in hard metal workers: an occupational hygiene study in a factory. Br J Ind Med. 1986;43:474–45.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Sauni R, Linna A, Oksa P. Cobalt asthma – a case series from a cobalt plant. Occup Med. 2010;60:301–6.CrossRefGoogle Scholar
  42. 42.
    Shirakawa T, Kusaka Y, Fujimura N. Occupational asthma from cobalt sensitivity in workers exposed to hard metal dust. Chest. 1989;95:29–37.CrossRefGoogle Scholar
  43. 43.
    Shirakawa T, Kusaka Y, Fujimura N, Goto S, Morimoto K. The existence of specific antibodies to cobalt in hard metal asthma. Clin Allergy. 1988;18:451–60.CrossRefGoogle Scholar
  44. 44.
    Forni A. Bronchoalveolar lavage in the diagnosis of hard metal disease. Sci Tot Environ. 1994;150:69–76.CrossRefGoogle Scholar
  45. 45.
    Kusaka Y, Nakano Y, Shirakawa T, Morimoto K. Lymphocyte transformation with cobalt in hard metal asthma. Ind Health. 1989;27:155–63.CrossRefGoogle Scholar
  46. 46.
    Krecisz B, Kiec-Swierczynska M, Krawczyk P, Chomiczewska D, Pałczynski C. Cobalt-induced anaphylaxis, contact urticaria, and delayed allergy in a ceramics decorator. Contact Dermatitis. 2009;60:173–4.CrossRefGoogle Scholar
  47. 47.
    Wittczak T, Walusiak J, Krakowiak A, Pałczyński C. Occupational asthma and interstitial cobalt-induced changes in a dental technician: a case report. Med Pr. 2003;54:159–64. PolishPubMedGoogle Scholar
  48. 48.
    Saakadze VP, Vasilov BG. Occupational bronchial asthma from exposure to manganese. Gig Tr Prof Zabol. 1977;6:19–23. RussianGoogle Scholar
  49. 49.
    Wittczak T, Dudek W, Krakowiak A, Walusiak J, Pałczynski C. Occupational asthma due to manganese exposure: a case report. Int J Occup Med Environ Health. 2008;21:81–3.PubMedGoogle Scholar
  50. 50.
    Bergman A, Svedberg U, Nilsson E. Contact urticaria with anaphylactic reactions caused by occupational exposure to iridium salt. Contact Dermatitis. 1995;32:14–7.CrossRefGoogle Scholar
  51. 51.
    Daenen M, Rogiers P, Van der Walle C. Occupational asthma caused by palladium. Eur Respir J. 1999;13:213–6.CrossRefGoogle Scholar
  52. 52.
    Merget R, Sander I, Van Kampen V. Occupational immediate-type asthma due to rhodium salts. Am J Ind Med. 2010;53:42–6.PubMedGoogle Scholar
  53. 53.
    Malo JL, Cartier A, Dolovich J. Occupational asthma due to zinc. Eur Respir J. 1993;6:447–50.PubMedGoogle Scholar
  54. 54.
    Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. Chest. 1985;88:376–84.CrossRefGoogle Scholar
  55. 55.
    Sjaheim T, Halstensen TS, Lund MB. Airway inflammation in aluminium potroom asthma. Occup Environ Med. 2004;61:779–85.CrossRefGoogle Scholar
  56. 56.
    Sorgdrager B, de Loof A, de Monchy J, Pal T, Dijk F. Factors affecting FEV1 in workers with potroom asthma after their removal from exposure. Int Arch Occup Environ Health. 2001;74:55–8.CrossRefGoogle Scholar
  57. 57.
    Sorgdrager B, de Loof A, de Monchy J, Pal T, Dubois E, Rijcken B. Occurrence of occupational asthma in aluminium potroom workers in relation to preventive measures. Int Arch Occup Environ Health. 1998;71:53–9.CrossRefGoogle Scholar
  58. 58.
    Vandenplas O, Delwiche JP, Vanbilsen ML. Occupational asthma caused by aluminium welding. Eur Respir J. 1998;11:1182–4.CrossRefGoogle Scholar
  59. 59.
    Musk AW, Tees JG. Asthma caused by occupational exposure to vanadium compounds. Med J Aust. 1982;1:183–4.PubMedGoogle Scholar
  60. 60.
    Calverley AE, Rees D, Dowdeswell RJ. Platinum salt sensitivity in refinery workers: incidence and effects of smoking exposure. Occup Environ Med. 1995;52:661–6.CrossRefGoogle Scholar
  61. 61.
    Venables KM, Dally MB, Nunn AJ, Stevens JV, Stephens R, Farrer N. Smoking and occupational allergy in workers in a platinum refinery. Br Med J. 1989;299:939–42.CrossRefGoogle Scholar
  62. 62.
    Merget R, Caspari C, Dierkes-Globish A. Effectiveness of a medical surveiilance programme for the prevention of occupational asthma due to platinum salts. A nested case-control study. J Allergy Clin Immunol. 2001;107:707–12.CrossRefGoogle Scholar
  63. 63.
    Jakubowski M, Palczynski C. Beryllium. In: Nordberg GF, Fowler BA, Nordberg M, editors. Handbook on the toxicology of metals, vol. 2. 4th ed. Amsterdam: Academic Press, Elsevier B.V; 2015. p. 635–53.CrossRefGoogle Scholar
  64. 64.
    Balmes JR, Abraham JL, Dweik RA, Fireman E, Fontenot AP, Maier LA, Muller-Quernheim J, Ostiguy G, Pepper LD, Saltini C, Schuler CR, Takaro TK, Wambach PF, ATS Ad Hoc Committee on Beryllium Sensitivity and Chronic Beryllium Disease. An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit Care Med. 2014;190(10):e34–59.CrossRefGoogle Scholar
  65. 65.
    Mayer A, Hamzeh N. Beryllium and other metal-induced lung disease. Curr Opin Pulm Med. 2015;21:178–84.CrossRefGoogle Scholar
  66. 66.
    Cummings KJ, Nakano M, Omae K, et al. Indium lung disease. Chest. 2012;13:1512–21.CrossRefGoogle Scholar
  67. 67.
    Wilkinson KE, Palmberg L, Witasp E, Kupczyk M, Feliu N, Gerde P, Seisenbaeva GA, Fadeel B, Dahlen SE, Kessler VG. Solution-engineered palladium nanoparticles: model for health effect studies of automotive particulate pollution. ACS Nano. 2011;5(7):5312–24.CrossRefGoogle Scholar
  68. 68.
    Nemery B, Verbeken EK, Demedts M. Giant cell interstitial pneumonia (hard metal lung disease, cobalt lung). Semin Respir Crit CareMed. 2001;22:435–48.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Diseases, Asthma and AllergyMedical University of ŁódźŁódźPoland

Personalised recommendations