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Dander-Induced asthma associated with normal airway reactivity
261
HYPERSENSITIVITY ANGIITIS CAUSED BY OCCUPATIONAL EXPOSURE TO DRY SILVER (PHOTOCOPY) PAPER FUMES. John R. Tencati~ M.D. and Harold S. Noveyp M.D., Orange, California. A 53 yr. old woman whose recurrent bouts of palpable purpura were diagnosed histologically as a hypersensitivity angiitis had no evidence of systemic disease. Exacerbations and remissions related to her presence or absence from work prompted a study of the job site. There she was in contact with photocopying devices that used a dry silver paper designed to copy microfilm. Challenge studies were performed by exposing the patient to fumes generated by developing photocopy paper. Her eruption was reproduced within 4 hours. Control photocopy paper similarly treated produced no reaction. When the patient was challenged with 4 different components of the paper, only behenic acid fumes caused a positive response. Patch tests were negative to all ingredients. Immunofluorescence studies of specimens from new (<6 hr) lesions showed C3, but no IgG, M, or A deposits in dermal venules. Measurements of 17 individual complement components failed to confirm activation of either complement pathway (courtesy J.G. Curd, M.D., Scripps, La Jolla, California) and no circulating immune complexes were detected by the Raji cell method. There were no significant changes in the WBC, total eosinophil, platelet, or absolute neutrophil counts, ESR, or peak expiratory flow rates as result of the challenge~. This is the first reported case of a chemical fume causing palpable purpura, presumably by the inhalation route.
262 INTRACTABLE SNEEZING DUE TO IGE MEDIATED TRIETHANOLAMINE SENSITIVITY. James Jay Herman, M.D. Chicago, Illinois Sneezing has been commonly recognized as part of the nasal allergic reaction in response to pollen and inhalant allergens; isolated intractable sneezing is an unusual presentation in allergic patients. An 8 y/o white female developed intractable sneezing in the fall while walking past an area where fresh roofing tar was being prepared. Her past history and family history were negative for allergic disease or symptoms. Positive physical findings were boggy nasal mucosa; pollen and inhalant skin tests were negative. Response to topical cromolyn and beclomethasone intranasally was only partial; antihistamines were l i t t l e help. Upon careful review of history, exposure to clothes washed in Miracle White Laundry Soil and Stain Remover~corre lated to symptoms; removal from clothing by extensive washing relieved the sneezing which recurred upon exposure. Prick test was positive to Triethanolamine (TEA) at lO-~- lO-~ M and not the other ingredients of this product. Investigation demonstrated dose dependent leukocyte histamine release (25-27% specific release)to TEA (lO -~ - lO-~ M); this release (50% at lO"s M) was inhibited by preincubation with cromolyn sodium (5xlO-6M). Passive cutaneous anaphylaxis was demonstrated to TEA (lO-~-lO-~M); ' specific IgE to TEA was demonstrated by polystyrene tube radioimmunoassay. Controls had no histamine release or specific IgE. Thus, exposure to Triethanolamine caused IgE mediated intractable sneezing.
263 ASTHMA INDUCED BY EXPOSURE TO LIVING CATS. T Van Metre, MD, NF Adkinson, MD, J Fish, MD, A Ka@ey-Sobotka, PhD, D Lev~, MD, L Lichtenstein, MD, M Mardine~, MD, D Marsh, PhD, P Norman, MD, G Rosenberg, MD, Baltimore, Maryland 16 patients (pts) with cat-induced asthma were studied to develop quantitative methods of exposure to living cats and to analyze effects on airway function. Intradermal skin tests showed 2+ skin reactions to cat pelt in a range of -4 to -6 (log) dilution of extract containing 54 ~g/ml Cat Allergen i. Leukocytes from 14 pts released histamine in vitro to extract. Methacholine (Mch) reactivity determined by the (log) Mch dose causing > 20% fall in FEV 1 (10g PD20) was similar to othe~ asthmatics in t~is laboratory (x 0.62 ~ SE 0.12). Two cats were placed in a 3'x3'x5' plexiglass chamber. Air was drawn from the chamber at a f l o w o f 3 2 - 3 7 L/min through a tube connected to a Hepa filter. Pts inspired from the tube via a "T" piece for up to 2 hours or until FEV. fell > 15%. Nine pts had > 15% fall in FEV 1 (x ~7.7 ~ E 4.1) and were considered responders (R); 7 pts with <15% fall in FEV 1 (R 3.8 + SE 2.0) were considered poor respond~rs (PR).-- Compared to PR, R had greater Mch sensitivity (R 0.42 + SE 0.13 (R), vs. 0.91 + SE 0.20 (NR); p < 0.i~), and greater skin sens--itivity (x -5.22 + SE 0.22 (R), vs. -4.28 + SE 0.18 (PR); p <0.01~. Exposure times for R ranged from i0 to 31 min. All pts had < 10% fall in FEV 1 (x 4.56 + SE0.66) after sham e x ~ s u r e (tube disconnected fr--om chamber). The antigen content of inspired air will be measured in future studies. Thus, a quantitative, natural bronchial challenge technique suitable for studies of immunotherapy in naturally occurring allergic asthma will be developed.
264
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DANDER-INDUCED ASTHMA ASSOCIATED WITH NORMAL AIRWAY REACTIVITY. D A Levy~ MD~ H Mak~ MD~ and J Fish~ MD, Baltimore, Maryland Studies were carried out with research laboratory personnel to examine the significance of the role of non-speciflc airway reactivity in IgE-mediated asthma caused by exposure to laboratory animals, i0 subjects (ages 25-37 years; 4 males, 6 females) with skin and respiratory tract sensitivity to laboratory animal dander (LAD) were studied. Each gave a history of asthma occurring exclusively with exposure to laboratory animals but denied asthma precipitated by other factors, including exercise, infection or non-dander allergens. Airway reactivity was determined by the dose of methacholine (Mch) producing 20% fall in FEV I (log PD20). Mch reactivity in the LAD group was compared to reactivity determined in the following age and sex-matched groups: (i) 15 subjects with mixed asthma caused by exercise, infection and/or pollen exposure (MA); (2) 14 non-asthmatic subjects with allergic rhinitis (AR); (3) 12 nonallergic normal subjects (N). Log PD20 in LAD subjects (x) 2.03) was indistinguishable from N subjects (x 9 and AR subjects (x >2.12), and significantly less reactive than subjects with MA (x = 0.90; P ~ 0.00001). Differences in log PD20 could not be explained by differences in prechallenge pulmonary function. These findings indicate that non-speciflc airway hyperreactivity is not a prerequisite for dander-induced IgE-mediated asthma. Further, we conclude that methacholine challenge may not be a useful screening test for detecting occupational asthma caused by IgE-mediated mechanisms.
HYPERSENSITIVITY ANGIITIS CAUSED BY OCCUPATIONAL EXPOSURE TO DRY SILVER (PHOTOCOPY) PAPER FUMES. John R. Tencati~ M.D. and Harold S. Noveyp M.D., Orange, California. A 53 yr. old woman whose recurrent bouts of palpable purpura were diagnosed histologically as a hypersensitivity angiitis had no evidence of systemic disease. Exacerbations and remissions related to her presence or absence from work prompted a study of the job site. There she was in contact with photocopying devices that used a dry silver paper designed to copy microfilm. Challenge studies were performed by exposing the patient to fumes generated by developing photocopy paper. Her eruption was reproduced within 4 hours. Control photocopy paper similarly treated produced no reaction. When the patient was challenged with 4 different components of the paper, only behenic acid fumes caused a positive response. Patch tests were negative to all ingredients. Immunofluorescence studies of specimens from new (<6 hr) lesions showed C3, but no IgG, M, or A deposits in dermal venules. Measurements of 17 individual complement components failed to confirm activation of either complement pathway (courtesy J.G. Curd, M.D., Scripps, La Jolla, California) and no circulating immune complexes were detected by the Raji cell method. There were no significant changes in the WBC, total eosinophil, platelet, or absolute neutrophil counts, ESR, or peak expiratory flow rates as result of the challenge~. This is the first reported case of a chemical fume causing palpable purpura, presumably by the inhalation route.
262 INTRACTABLE SNEEZING DUE TO IGE MEDIATED TRIETHANOLAMINE SENSITIVITY. James Jay Herman, M.D. Chicago, Illinois Sneezing has been commonly recognized as part of the nasal allergic reaction in response to pollen and inhalant allergens; isolated intractable sneezing is an unusual presentation in allergic patients. An 8 y/o white female developed intractable sneezing in the fall while walking past an area where fresh roofing tar was being prepared. Her past history and family history were negative for allergic disease or symptoms. Positive physical findings were boggy nasal mucosa; pollen and inhalant skin tests were negative. Response to topical cromolyn and beclomethasone intranasally was only partial; antihistamines were l i t t l e help. Upon careful review of history, exposure to clothes washed in Miracle White Laundry Soil and Stain Remover~corre lated to symptoms; removal from clothing by extensive washing relieved the sneezing which recurred upon exposure. Prick test was positive to Triethanolamine (TEA) at lO-~- lO-~ M and not the other ingredients of this product. Investigation demonstrated dose dependent leukocyte histamine release (25-27% specific release)to TEA (lO -~ - lO-~ M); this release (50% at lO"s M) was inhibited by preincubation with cromolyn sodium (5xlO-6M). Passive cutaneous anaphylaxis was demonstrated to TEA (lO-~-lO-~M); ' specific IgE to TEA was demonstrated by polystyrene tube radioimmunoassay. Controls had no histamine release or specific IgE. Thus, exposure to Triethanolamine caused IgE mediated intractable sneezing.
263 ASTHMA INDUCED BY EXPOSURE TO LIVING CATS. T Van Metre, MD, NF Adkinson, MD, J Fish, MD, A Ka@ey-Sobotka, PhD, D Lev~, MD, L Lichtenstein, MD, M Mardine~, MD, D Marsh, PhD, P Norman, MD, G Rosenberg, MD, Baltimore, Maryland 16 patients (pts) with cat-induced asthma were studied to develop quantitative methods of exposure to living cats and to analyze effects on airway function. Intradermal skin tests showed 2+ skin reactions to cat pelt in a range of -4 to -6 (log) dilution of extract containing 54 ~g/ml Cat Allergen i. Leukocytes from 14 pts released histamine in vitro to extract. Methacholine (Mch) reactivity determined by the (log) Mch dose causing > 20% fall in FEV 1 (10g PD20) was similar to othe~ asthmatics in t~is laboratory (x 0.62 ~ SE 0.12). Two cats were placed in a 3'x3'x5' plexiglass chamber. Air was drawn from the chamber at a f l o w o f 3 2 - 3 7 L/min through a tube connected to a Hepa filter. Pts inspired from the tube via a "T" piece for up to 2 hours or until FEV. fell > 15%. Nine pts had > 15% fall in FEV 1 (x ~7.7 ~ E 4.1) and were considered responders (R); 7 pts with <15% fall in FEV 1 (R 3.8 + SE 2.0) were considered poor respond~rs (PR).-- Compared to PR, R had greater Mch sensitivity (R 0.42 + SE 0.13 (R), vs. 0.91 + SE 0.20 (NR); p < 0.i~), and greater skin sens--itivity (x -5.22 + SE 0.22 (R), vs. -4.28 + SE 0.18 (PR); p <0.01~. Exposure times for R ranged from i0 to 31 min. All pts had < 10% fall in FEV 1 (x 4.56 + SE0.66) after sham e x ~ s u r e (tube disconnected fr--om chamber). The antigen content of inspired air will be measured in future studies. Thus, a quantitative, natural bronchial challenge technique suitable for studies of immunotherapy in naturally occurring allergic asthma will be developed.
264
158
DANDER-INDUCED ASTHMA ASSOCIATED WITH NORMAL AIRWAY REACTIVITY. D A Levy~ MD~ H Mak~ MD~ and J Fish~ MD, Baltimore, Maryland Studies were carried out with research laboratory personnel to examine the significance of the role of non-speciflc airway reactivity in IgE-mediated asthma caused by exposure to laboratory animals, i0 subjects (ages 25-37 years; 4 males, 6 females) with skin and respiratory tract sensitivity to laboratory animal dander (LAD) were studied. Each gave a history of asthma occurring exclusively with exposure to laboratory animals but denied asthma precipitated by other factors, including exercise, infection or non-dander allergens. Airway reactivity was determined by the dose of methacholine (Mch) producing 20% fall in FEV I (log PD20). Mch reactivity in the LAD group was compared to reactivity determined in the following age and sex-matched groups: (i) 15 subjects with mixed asthma caused by exercise, infection and/or pollen exposure (MA); (2) 14 non-asthmatic subjects with allergic rhinitis (AR); (3) 12 nonallergic normal subjects (N). Log PD20 in LAD subjects (x) 2.03) was indistinguishable from N subjects (x 9 and AR subjects (x >2.12), and significantly less reactive than subjects with MA (x = 0.90; P ~ 0.00001). Differences in log PD20 could not be explained by differences in prechallenge pulmonary function. These findings indicate that non-speciflc airway hyperreactivity is not a prerequisite for dander-induced IgE-mediated asthma. Further, we conclude that methacholine challenge may not be a useful screening test for detecting occupational asthma caused by IgE-mediated mechanisms.