title: Sensitization to Empynase(pronase B) in exposed hospital personnel and identification of the Empynase allergen.
abstract: BACKGROUND
  Empynase is a proteolytic enzyme that is widely used as an anti-inflammatory drug in Korea. We evaluated the prevalence of sensitization to Empynase in association with respiratory allergy symptoms in exposed hospital personnel, and identified the IgE-binding components in the Empynase extract, using sera with high levels of specific IgE antibodies.
  
  
  METHODS
  A total of 154 hospital personnel (135 nurses and 19 pharmacists) who worked in a university hospital and 123 unexposed healthy control subjects were enrolled. A questionnaire was administered that addressed demographics, job category, history of atopic diseases, diverse symptoms including nasal and lower respiratory symptoms, and the association of symptoms with work. Skin prick tests (SPTs) to common aeroallergens and Empynase extract were performed. Empynase-specific IgE antibody was detected by ELISA, and ELISA inhibition tests were conducted. IgE-binding components were identified by SDS-PAGE and IgE immunoblotting.
  
  
  RESULTS
  Forty-two subjects (27.3%) complained of work-related respiratory symptoms (WRRS). Five nurses (3.7%) and one pharmacist (5.3%) had work-related asthma symptoms, and 34 nurses (25.2%) and six pharmacists (31.6%) had work-related rhinitis symptoms. The prevalence of sensitization to Empynase on SPTs was 20.1%, and tended to be higher in pharmacists (31.6%) than in nurses (18.5%). It was estimated that 3.9-8.4% of hospital personnel had WRRS attributable to Empynase. The duration of exposure was longer in positive SPT responders than in negative responders (51.9+/-27.5 vs. 39.2+/-27.3 months, respectively; P<0.05), and the prevalence of Empynase-positive SPTs was significantly higher in subjects with asthma than in those without asthma (57.1% vs. 18.4%, respectively; P<0.05). The levels of Empynase-specific IgE antibodies were significantly higher in pharmacists (76.1+/-83.4 OD units) and nurses (56.3+/-103.0 OD units) than in normal controls (39.8+/-12.7 OD units; P<0.05). Seven subjects (two pharmacists and five nurses) had high serum levels of Empynase-specific IgE antibodies; six of these subjects had WRRS. ELISA inhibition tests were performed with the sera of these six subjects, revealing significant inhibition only with the addition of Empynase. Four strongly staining protein bands (sizes: 36, 33, 16, and 10 kDa) from Empynase extract were observed to bind to the IgE antibodies of sensitized subjects. Conclusion Exposure to Empynase powder may cause rhinitis and asthma in hospital personnel, and the pathogenic mechanism appears to be IgE mediated.
authors.affiliation: Department of Internal Medicine, College of Medicine, Hallym University, Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Bahn
authors.forename: J-Y
authors.initials: JY
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Jang
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: H-M
authors.initials: HM
authors.lastname: Kim
authors.forename: H-S
authors.initials: HS
authors.lastname: Park
mesh_terms: D000328:Adult; D000485:Allergens / Q000032:analysis*; D001249:Asthma / Q000139:chemically induced / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D009741:Nursing Staff, Hospital; D009784:Occupational Diseases / Q000139:chemically induced* / Q000276:immunology; D016273:Occupational Exposure / Q000009:adverse effects; D010564:Personnel, Hospital; D010595:Pharmacists; D011402:Pronase / Q000009:adverse effects* / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology; D012220:Rhinitis / Q000139:chemically induced / Q000276:immunology; D012882:Skin Tests / Q000379:methods
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D011402:Pronase