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278 A study of diphemylmethane diisocyanate (MDI)-induced asthma
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MEALWORM ASTHMA: A NEW OCCUPATIONAL DISEASE. D.I. Bernstein, M.D., J.S. Gallagher, Ph.D., and I.L. Bernstein, M.D., Cincinnati, OH. Mealworms are larvae of the beetle Tennebrio molitor (TM) which is used as fishing bait. Four of 5 exposed workers in a TM distributing company reported immediate onset rhinorrhea, asthma or contact urticaria while unwrapping Positive cutaneous and packaging mealworms. prick tests to a 1:lOO extract of TM exoskeletons and excrement were demonstrated in Two workers with all 4 symptomatic workers. rhinitis and asthma associated with handling TM exhibited positive PD2 responses following P :I000 and l:lOO,OOO bronchial challenge with dilutions of TM extract, respectively. No late The onset asthmatic responses were observed. same 2 asthmatic patients demonstrated PAST binding of 14.6 and 22.5%, respectively (negative control: 4% binding). The specificity of -__ in vivo and -__ in vitro methods was confirmed by the RAST inhibition technique. Varying dilutions of TM (l:lO, I:100 and 1: 1000) inhibited RAST by 73.4, 58.4 and 36.6%, Three asthmatic and 3 nonrespectively. asthmatic controls had negative prick tests and bronchial provocation tests to I:1000 dilutions of TM. This study demonstrates that inhaled particles of TM excreta and exoskeletons are potent sensitizers and can result in IgE mediated respiratory responses.
DY OF DIPHEN
279
NICKEL ANTIBODIES REACT WITH A Ni"'/HSA COE&gx. S. Evans, B.A., E. Nieboer, Ph.D. andL M.D., Hamilton, Ontario, Canada. -Dolovich, Serum of a patient with nickel sulfate occu-. pational asthma exhibited positive Ni2+/HSA IgE RAST and 63Ni2+ ammonium sulfate and antiIgG coprecipitation tests demonstrating serum antibody with Nizi-related specificity. Preincubation of 63Ni2+ with HSA improved the discrimination between the patient's serum and control sera. The pattern of inhibition of the test by cations (blocking with Ni*+, Cu2f, Co*+, and protons but not by Zn*+, Mn** and Crx+) indicated a necessity for binding oi the labelled Ni2+ at the primary copper transport site (PCTS) of HSA for interaction with antibody. Ni*+ binding ligands other than HSA (Lhistidine, copper-binding tripeptide and EDTA) all inhibited the test. Coprecipitation tests involving antigen-antibody reactions unrelated to nickel were unaffected by the various cations or the Ni*+-binding ligands. These data demonstrate that antibodies with Ni*+-related specificity react with a Ni*+/HSh complex with Ni*+ bound at the PCTS of HSA, which involves the three N- terminal amino acids. It is considered that the basis of the antigenic determinant probably is ii structural alteration of HSA inherent in the formation of a square planar complex with Ni*+ al. this binding site.
280
OCCUPATIONAL ASTHMA DUE TO PFPSIN. L$.ne Pineau, R.T., Andre Cartier, M.D., Jean-Lmc'Melo,'M,R~, Joseph Parisi and Jerry Dolovich, M.D., Montreal and Hamilton, Canada. A 30-year-old subject noticed an increase in his nasoconjunctival and asthma symptoms after starting to work for a pharmaceutical company which manufactured a variety of natural products. His asthma symptoms were increased at work and improved when he was away from work. Among the products which seemed to increase notably his symptomatology, he mentioned pepsin. Recardings of peak expiratory flow rates at work and off work revealed significant falls on work days, Prick skin tests done with a battery of common inhaled antigens showed several positive immediate reactions. In addition, a large immediate reaction was documented to pepsin. Skin tests with pepsin were negative in 4 control atopic individuals. Specific inhalation challenges with pepsir powder which the subject poured from one tray to another for only one minute induced rhinoconjunctivitis and dyspnea. A drop in FEVl from 3.2 1 to 1.05 1 was noticed 10 minutes after the end of exposure. The subject had to be treated with bronchodilators and hydrocortisone.'The FEVl returned to baseline values but again fell to 2.6 1 14 hours after the end of challenge. Specific IgE antibodies to pepsin assessed by RAST were significantly increased (345 cpm ws 117 and 112 cpm for control sera), Selective inhibition with pepsin 10 mM of the pepsin l&ST (61%) but not a control grass RAST (-14%), a test to which he was also positive, confirmed the specificity of the test. To our knowledge, this is the first report of pepsin-induced occupational asthma and pepsin-specific IgE antibodies.
@I.D.> Vancouver, Canada The effect of occupational exposure to MD1 is less well known than that from.exposure to toluene diisocyanate. A survey of 78 steel foundry workers with occupational exposure to MD1 used in the mold casting process identified 11 subjects with asthmatic symptoms (asthmatic group AG), 41 with other types of respiratory complaints (RG) and 26 asymptomatic workers. Bronchoprovocation with MD1 induced a combined immediate and late asthmatic response in 2 and a late reaction in another 4 subjects in the AG. After a single challenge, 4 of the 6 reactors developed recurrent nocturnal asthmatic reactions lasting for as long as a week. A greater degree of bronchial reactivity to nethacholine was shown in the reactors. Among the 78 workers, elevated IgE antibody level as measured by the RAST, using antigen discs containing MDI-HSA (human serum albumin) conjugates, was found in one subject in the AG and one in the RG. The specificity of the IgE antibody was confirmed by RAST inhibition with MDI-HSA and cross reactivity with p-tolyl-monoisocyanate was also demonstrated. Elevated IgG antibody level, as measured by a double antibody radioimmunoassay using I25I labelled MDI-HSA, was found in 3 subjects in the AG and 1 in the RG. Among the 26 asymptomatic workers, 1 also had elevated IgG antibody level. The results of bronchoprovocation confirmed that MD1 could induce occupational asthmabut the role of IgE and IgG antibodies in this condition requires further investigation.
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278
MEALWORM ASTHMA: A NEW OCCUPATIONAL DISEASE. D.I. Bernstein, M.D., J.S. Gallagher, Ph.D., and I.L. Bernstein, M.D., Cincinnati, OH. Mealworms are larvae of the beetle Tennebrio molitor (TM) which is used as fishing bait. Four of 5 exposed workers in a TM distributing company reported immediate onset rhinorrhea, asthma or contact urticaria while unwrapping Positive cutaneous and packaging mealworms. prick tests to a 1:lOO extract of TM exoskeletons and excrement were demonstrated in Two workers with all 4 symptomatic workers. rhinitis and asthma associated with handling TM exhibited positive PD2 responses following P :I000 and l:lOO,OOO bronchial challenge with dilutions of TM extract, respectively. No late The onset asthmatic responses were observed. same 2 asthmatic patients demonstrated PAST binding of 14.6 and 22.5%, respectively (negative control: 4% binding). The specificity of -__ in vivo and -__ in vitro methods was confirmed by the RAST inhibition technique. Varying dilutions of TM (l:lO, I:100 and 1: 1000) inhibited RAST by 73.4, 58.4 and 36.6%, Three asthmatic and 3 nonrespectively. asthmatic controls had negative prick tests and bronchial provocation tests to I:1000 dilutions of TM. This study demonstrates that inhaled particles of TM excreta and exoskeletons are potent sensitizers and can result in IgE mediated respiratory responses.
DY OF DIPHEN
279
NICKEL ANTIBODIES REACT WITH A Ni"'/HSA COE&gx. S. Evans, B.A., E. Nieboer, Ph.D. andL M.D., Hamilton, Ontario, Canada. -Dolovich, Serum of a patient with nickel sulfate occu-. pational asthma exhibited positive Ni2+/HSA IgE RAST and 63Ni2+ ammonium sulfate and antiIgG coprecipitation tests demonstrating serum antibody with Nizi-related specificity. Preincubation of 63Ni2+ with HSA improved the discrimination between the patient's serum and control sera. The pattern of inhibition of the test by cations (blocking with Ni*+, Cu2f, Co*+, and protons but not by Zn*+, Mn** and Crx+) indicated a necessity for binding oi the labelled Ni2+ at the primary copper transport site (PCTS) of HSA for interaction with antibody. Ni*+ binding ligands other than HSA (Lhistidine, copper-binding tripeptide and EDTA) all inhibited the test. Coprecipitation tests involving antigen-antibody reactions unrelated to nickel were unaffected by the various cations or the Ni*+-binding ligands. These data demonstrate that antibodies with Ni*+-related specificity react with a Ni*+/HSh complex with Ni*+ bound at the PCTS of HSA, which involves the three N- terminal amino acids. It is considered that the basis of the antigenic determinant probably is ii structural alteration of HSA inherent in the formation of a square planar complex with Ni*+ al. this binding site.
280
OCCUPATIONAL ASTHMA DUE TO PFPSIN. L$.ne Pineau, R.T., Andre Cartier, M.D., Jean-Lmc'Melo,'M,R~, Joseph Parisi and Jerry Dolovich, M.D., Montreal and Hamilton, Canada. A 30-year-old subject noticed an increase in his nasoconjunctival and asthma symptoms after starting to work for a pharmaceutical company which manufactured a variety of natural products. His asthma symptoms were increased at work and improved when he was away from work. Among the products which seemed to increase notably his symptomatology, he mentioned pepsin. Recardings of peak expiratory flow rates at work and off work revealed significant falls on work days, Prick skin tests done with a battery of common inhaled antigens showed several positive immediate reactions. In addition, a large immediate reaction was documented to pepsin. Skin tests with pepsin were negative in 4 control atopic individuals. Specific inhalation challenges with pepsir powder which the subject poured from one tray to another for only one minute induced rhinoconjunctivitis and dyspnea. A drop in FEVl from 3.2 1 to 1.05 1 was noticed 10 minutes after the end of exposure. The subject had to be treated with bronchodilators and hydrocortisone.'The FEVl returned to baseline values but again fell to 2.6 1 14 hours after the end of challenge. Specific IgE antibodies to pepsin assessed by RAST were significantly increased (345 cpm ws 117 and 112 cpm for control sera), Selective inhibition with pepsin 10 mM of the pepsin l&ST (61%) but not a control grass RAST (-14%), a test to which he was also positive, confirmed the specificity of the test. To our knowledge, this is the first report of pepsin-induced occupational asthma and pepsin-specific IgE antibodies.
@I.D.> Vancouver, Canada The effect of occupational exposure to MD1 is less well known than that from.exposure to toluene diisocyanate. A survey of 78 steel foundry workers with occupational exposure to MD1 used in the mold casting process identified 11 subjects with asthmatic symptoms (asthmatic group AG), 41 with other types of respiratory complaints (RG) and 26 asymptomatic workers. Bronchoprovocation with MD1 induced a combined immediate and late asthmatic response in 2 and a late reaction in another 4 subjects in the AG. After a single challenge, 4 of the 6 reactors developed recurrent nocturnal asthmatic reactions lasting for as long as a week. A greater degree of bronchial reactivity to nethacholine was shown in the reactors. Among the 78 workers, elevated IgE antibody level as measured by the RAST, using antigen discs containing MDI-HSA (human serum albumin) conjugates, was found in one subject in the AG and one in the RG. The specificity of the IgE antibody was confirmed by RAST inhibition with MDI-HSA and cross reactivity with p-tolyl-monoisocyanate was also demonstrated. Elevated IgG antibody level, as measured by a double antibody radioimmunoassay using I25I labelled MDI-HSA, was found in 3 subjects in the AG and 1 in the RG. Among the 26 asymptomatic workers, 1 also had elevated IgG antibody level. The results of bronchoprovocation confirmed that MD1 could induce occupational asthmabut the role of IgE and IgG antibodies in this condition requires further investigation.
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