A clinical and immunological study on 92 workers occupationally exposed to anhydrides

  • Xaver Baur
  • Adam B. Czuppon
  • Iris Rauluk
  • Frank B. Zimmermann
  • Bernhard Schmitt
  • Monika Egen-Korthaus
  • Norbert Tenkhoff
  • Paul O. Degens
Original Article

Abstract

This study aimed at investigating sensitizing and hazardous effects of a new acid anhydride, pyromellitic dianhydride (PMDA), in addition to those of phthalic anhydride, maleic anhydride and trimellitic anhydride, in a group of 92 exposed workers in two German chemical plants. Of the 92 workers, 56 reported work-related complaints with a predominance of phlegm and dyspnoea in those exposed to anhydride dust for less than 1 year. Haemorrhagic rhinitis occurred only after a prolonged exposure of more than 15 years. Specific IgE antibodies to anhydride-HSA conjugates could be detected in 15 exposed subjects, 12 of whom had work-related symptoms. The IgE-positive group had significantly more impaired lung function parameters than the IgE-negative group. The proportion of IgE-positive subjects was highest in the groups with dyspnoea (5/18), cough (6/24) and rhinitis (11/44) whereas only 1 of 11 workers with haemorrhagic rhinitis had such antibodies. A follow-up study of 23 affected workers was performed after 10 months to assess clinical symptoms, lung function and IgE antibody levels. This follow-up study showed the absence of obstructive ventilation patterns in three out of six subjects in addition to cessation of symptoms in most initially affected workers who were no longer exposed. On the other hand, 14 workers under continuous exposure had comparable pathological findings on re-examination. Our results confirm that anhydrides including the lesser known PMDA, behave as respiratory irritants and as immediate-type sensitizers. They predominantly induced reversible symptoms in workers whose exposure stopped after a working period of about 0.7 years. Abnormal lung function parameters normalized in nearly 50% of these subjects.

Key words

Anhydrides Occupational asthma Specific IgE antibodies Skin tests Haemorrhagic rhinitis 

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References

  1. 1.
    Boxer MB, Grammer LC, Harris KE, Roach DE, Patterson R (1987) Six-year clinical and immunologic follow-up of workers exposed to trimellitic anhydride. J Allergy Clin Immunol 80:147–152Google Scholar
  2. 2.
    Grammer LC, Shaughnessy MA, Henderson J, Zeiss CR, Kavich DE, Collins MJ, Pecis KM, Kenamore BD (1993) A clinical and immunologic study of workers with trimelliticanhydride-induced immunologic lung disease after transfer to low exposure jobs. Am Rev Respir Dis 148:54–57Google Scholar
  3. 3.
    Liss GM, Bernstein D, Genesove L, Roos JO, Lim J (1993) Assessment of risk factors for IgE-mediated sensitization to tetrachlorophthalic anhydride. J Allergy Clin Immunol 92:237–247Google Scholar
  4. 4.
    McGrath KG, Roach D, Zeiss CR, Patterson R (1984) Four-year evaluation of workers exposed to trimellitic anhydride. J Occup Med 26:671–675Google Scholar
  5. 5.
    Meadway J (1981) Asthma and atopy in workers with an epoxy adhesive. J Allergy Clin Immunol 68:188–193Google Scholar
  6. 6.
    Moller DR, Gallagher JS, Bernstein DI, Wilcox TG, Burroughs HE, Bernstein IL (1985) Detection of IgE mediated respiratory sensitization in workers exposed to hexahydrophthalic anhydride. J Allergy Clin Immunol 75:663–672Google Scholar
  7. 7.
    Nielsen J, Bensryd I, Almquist H, Dahlqvist M, Welinder H, Alexandersson R, Skerfving S (1991) Serum IgE and lung function in workers exposed to phthalic anhydride. Int Arch Occup Environ Health 63:199–204Google Scholar
  8. 8.
    Nielsen J, Welinder H, Horstmann V, Skerfving S (1992) Allergy to methyltetrahydrophthalic anhydride in epoxy resin workers. Br J Ind Med 49:769–775Google Scholar
  9. 9.
    Pien LC, Zeiss CR, Leach CL, Hatoum NS, Levitz D, Garvin PJ, Patterson R (1988) Antibody response to trimellityl hemoglobin in trimellitic anhydride-induced lung injury. J Allergy Clin Immunol 82:1098–1103Google Scholar
  10. 10.
    Topping MD, Venables KM, Luczynska DM, Howe W, Taylor AIN (1986) Specificity of the human IgE response to inhaled anhydrides. J Allergy Clin Immunol 77:834–842Google Scholar
  11. 11.
    Venables KM, Topping MD, Howe W, Luczynska CM, Hawkins R, Newman Taylor AJ (1985) Interaction of smoking and atopy in producing specific IgE antibody against a hapten protein conjugate. BMJ 290:201–204Google Scholar
  12. 12.
    Venables KM, Topping MD, Nunn AJ, Howe W, Newman Taylor AJ (1987) Immunologic and functional consequences o1 chemical (tetrachlorophthalic anhydride)-induced asthma after four years of avoidance of exposure. J Allergy Clin Immunol 80:212–218Google Scholar
  13. 13.
    Venables KM, Newman Taylor AJ (1990) Exposure-response relationships in asthma caused by tetrachlorophthalic anhydride. J Allergy Clin Immunol 85:55–58Google Scholar
  14. 14.
    Ward MJ, Davies D (1983) Asthma due to grinding epoxy resin cured with phthalic anhydride. Clin Allergy 13:165–168Google Scholar
  15. 15.
    Welinder H, Nielsen I (1991) Immunologic tests of specific antibodies to organic anhydrides. Allergy 46:601–609Google Scholar
  16. 16.
    Wernfors M, Nielsen J, Schuetz A, Skerfving S (1986) Phthalic anhydride-induced occupational asthma. Int Arch Allergy Appl Immunol 79:77–82Google Scholar
  17. 17.
    Zeiss CR (1991) Reactive chemicals in industrial asthma. J Allergy Clin Immunol 87:755–761Google Scholar
  18. 18.
    Zeiss CR, Wolkonsky P, Chacon R, Tuntland PA, Levitz D, Pruzansky JJ, Patterson R (1983) Syndromes in workers exposed to trimellitic anhydride: a longitudinal clinical and immunologic study. Ann Intern Med 98:8–12Google Scholar
  19. 19.
    Gerhardsson L, Grammer LC, Shaughnessy MA, Patterson R (1992) IgG subclass antibody against trimellitic anhydride in workers with and without immunologic lung diseases. J Occup Med 34:989–992Google Scholar
  20. 20.
    Czuppon AB, Kaplan V, Speich R, Baur X (1994) Acute autoimmune response in a case of pyromellitic acid dianhydrideinduced haemorrhagic alveolitis. Allergy 49:337–341Google Scholar
  21. 21.
    Kaplan V, Baur X, Czuppon AB, Ruegger M, Russi E, Speich R (1993) Pulmonary hemorrhage due to inhalation of vapor containing pyromellitic dianhydride. Chest 104:644–645Google Scholar
  22. 22.
    Quanjer PhH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault J-C (1993) Lung volumes and forced ventilatory flows. In: Standardized lung function testing. Report Working Party “Standardization of lung function tests” — Official Statement of the European Respiratory Society. Eur Respir J 6 (Suppl 16):5–40Google Scholar
  23. 23.
    Ammon J, Marek W, Baur X (1993) Erstellung eines Normalkollektivs fuer den Metacholin-Provokationstest. Atemw Lungenkrkh 19:303–304Google Scholar
  24. 24.
    Cockcroft D, Killian D, Mellon J, Hargreave F (1977) Bronchial reactivity to histamine: a method and clinical survey. Clin Allergy 7:235–243Google Scholar
  25. 25.
    Aas K, Belin L (1973) Standardization of diagnostic work in allergy. Int Arch Allergy 45:57–60Google Scholar
  26. 26.
    Hollander M, Wolfe DA (1973) Nonparametric statistical methods. John Wiley & Sons. New YorkGoogle Scholar
  27. 27.
    Cytel Software Corporation (1992) StatXact — Statistical software for exact nonparametric inference. Cambridge, Mass.Google Scholar
  28. 28.
    Nielsen J, Welinder H, Bensryd I, Andersson P, Skerfving S (1994) Symptoms and immunologic markers induced by exposure to methyltetrahydrophthalic anhydride. Allergy 49:281–286Google Scholar
  29. 29.
    Grammer LC, Shaughnessy MA, Lowenthal M (1993) Hemorrhagic rhinitis. An immunologic disease due to hexahydrophthalic anhydride. Chest 104:1792–1794Google Scholar
  30. 30.
    Ahmad D, Morgan WKC, Patterson R, Williams T, Zeiss CR (1979) Pulmonary haemorrhage and haemolytic anaemia due to trimellitic anhydride. Lancet 1:326–328Google Scholar
  31. 31.
    Baur X (1983) Immunologic cross-reactivity between different albumin-bound isocyanates. J Allergy Clin Immunol 7:197–205Google Scholar
  32. 32.
    Chen Z, Baur X, Czuppon AB (1994) IgE induction and hypersensitization by pyromellitic acid dianhydride (PMDA) in chemical plant workers. J Allergy Clin Immunol 93:264Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Xaver Baur
    • 1
  • Adam B. Czuppon
    • 1
  • Iris Rauluk
    • 1
  • Frank B. Zimmermann
    • 1
  • Bernhard Schmitt
    • 1
  • Monika Egen-Korthaus
    • 1
  • Norbert Tenkhoff
    • 1
  • Paul O. Degens
    • 1
  1. 1.BGFABochumGermany

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