Occupational Asthma Reference

Park H-S, Kim K-U, Lee Y-M, Choi J-H, Lee J-H, Park S-W, Jang A-S, Park C-S, Occupational asthma and IgE sensitization to 7-aminocephalosporanic acid, J Allergy Clin Immunol, 2004;113:785-787,

Keywords: 7-aminocephalosporanic acid, challenge, korea, pharmacutical manufacturer, skin prick test, NSBR, challenge,

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Hae-Sim Park, Korea Hae-Sim Park

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Abstract

Cephalosporins cause occupational asthma, and it has been suggested that the pathogenesis is mediated by IgE. 7-ACA (amimocephalosporanic acid) is a major intermediate metabolite in the synthesis of cephalosporin. There has been one published report of occupational asthma caused by 7-ACA, in which a nonimmunologic mechanism was suggested. Ours is the first investigation to detect serum IgE specific to 7-ACA–HSA (human serum albumin) conjugate in an exposed worker with occupational asthma.

This report describes the clinical findings in two asthmatic workers in a pharmaceutical plant who were exposed to 7-ACA powder used to synthesize ceftriaxone. To evaluate the IgE response, skin prick tests (SPTs) were performed in 5 exposed workers. To confirm bronchial sensitization in the two symptomatic workers, a methacholine bronchial challenge and specific bronchial provocation tests (BPTs) with 7-ACA and ceftriaxone were done. 7-ACA–HSA and ceftriaxone-HSA conjugates were prepared in our laboratory according to a method described previously. For IgE-ELISA, sera was incubated in 7-ACA–HSA conjugate or sham HSA coated well, and anti-human IgE and second antibody were added. Twenty nonatopic, healthy subjects with no history of exposure, who had negative SPTs to ACA and ceftriaxone, were enrolled as control subjects. Final absorbance value was determined by subtraction from that of sham HSA coated well. The positive cutoff value for specific IgE was determined by using the mean±3 SD of the absorbance values (patient LB). For the ELISA inhibition test, serum with high levels of specific IgE was preincubated with the free forms of 7-ACA and ceftriaxone, as well as with 7-ACA–HSA and ceftriaxone-HSA conjugates, and then subjected to IgE ELISA.

None of the asymptomatic workers had positive responses to 7-ACA or ceftriaxone on SPT. However, two asthmatic subjects with work-related respiratory symptoms with or without rhinitis were found. Both patients had airway hyperresponsiveness to methacholine. Patient LB had a strong positive response to 7-ACA on SPT and had immediate bronchoconstriction after inhaling 7-ACA–powder solution during the specific BPT. Furthermore, high serum-specific IgE binding to 7-ACA–HSA conjugate was noted on ELISA Patient NS had a negative response to 7-ACA on SPT but developed significant bronchoconstriction on 7-ACA BPT. Serum-specific IgE antibody was not detected. None of the workers had positive responses to ceftriaxone on specific BPT. When the IgE-ELISA inhibition test was performed by using the serum from patient LB, significant inhibition was noted in a dose-dependent manner with the serial addition of 7-ACA–HSA conjugate, whereas there was partial inhibition with free 7-ACA (Fig 1, B). Minimal inhibition was noted with free ceftriaxone, sham HSA, or ceftriaxone-HSA conjugate

Plain text: Cephalosporins cause occupational asthma, and it has been suggested that the pathogenesis is mediated by IgE. 7-ACA (amimocephalosporanic acid) is a major intermediate metabolite in the synthesis of cephalosporin. There has been one published report of occupational asthma caused by 7-ACA, in which a nonimmunologic mechanism was suggested. Ours is the first investigation to detect serum IgE specific to 7-ACA-HSA (human serum albumin) conjugate in an exposed worker with occupational asthma. This report describes the clinical findings in two asthmatic workers in a pharmaceutical plant who were exposed to 7-ACA powder used to synthesize ceftriaxone. To evaluate the IgE response, skin prick tests (SPTs) were performed in 5 exposed workers. To confirm bronchial sensitization in the two symptomatic workers, a methacholine bronchial challenge and specific bronchial provocation tests (BPTs) with 7-ACA and ceftriaxone were done. 7-ACA-HSA and ceftriaxone-HSA conjugates were prepared in our laboratory according to a method described previously. For IgE-ELISA, sera was incubated in 7-ACA-HSA conjugate or sham HSA coated well, and anti-human IgE and second antibody were added. Twenty nonatopic, healthy subjects with no history of exposure, who had negative SPTs to ACA and ceftriaxone, were enrolled as control subjects. Final absorbance value was determined by subtraction from that of sham HSA coated well. The positive cutoff value for specific IgE was determined by using the mean+-3 SD of the absorbance values (patient LB). For the ELISA inhibition test, serum with high levels of specific IgE was preincubated with the free forms of 7-ACA and ceftriaxone, as well as with 7-ACA-HSA and ceftriaxone-HSA conjugates, and then subjected to IgE ELISA. None of the asymptomatic workers had positive responses to 7-ACA or ceftriaxone on SPT. However, two asthmatic subjects with work-related respiratory symptoms with or without rhinitis were found. Both patients had airway hyperresponsiveness to methacholine. Patient LB had a strong positive response to 7-ACA on SPT and had immediate bronchoconstriction after inhaling 7-ACA-powder solution during the specific BPT. Furthermore, high serum-specific IgE binding to 7-ACA-HSA conjugate was noted on ELISA Patient NS had a negative response to 7-ACA on SPT but developed significant bronchoconstriction on 7-ACA BPT. Serum-specific IgE antibody was not detected. None of the workers had positive responses to ceftriaxone on specific BPT. When the IgE-ELISA inhibition test was performed by using the serum from patient LB, significant inhibition was noted in a dose-dependent manner with the serial addition of 7-ACA-HSA conjugate, whereas there was partial inhibition with free 7-ACA (Fig 1, B). Minimal inhibition was noted with free ceftriaxone, sham HSA, or ceftriaxone-HSA conjugate

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