213 BETA-ADRENERGIC LIGAND BINDING ANTIBODIES (BLA) IN ADULT, STEROID DEPENDENT ASTHMATICS. J. R. Baker, Jr., M.D., R.J.M. Engler, M.D., K.D. Burman, M.D., and Y. Djuh M.S., Wash, DC

Recent studies demonstrating beta- adrenergic receptor antibodies (BRAyin asth- matics have used beta ligand displacement (from receptors) to identify BRA. However, this displacement could also be the result of antibodies against beta ligands, especially since most of these patients use beta ago- nists. We screened 24 asthmatics for binding to 112510do-Cyanopindolol (ICYP, a high af- finity beta ligand) and to lung beta recep- tors. ICYP was mixed with serum, then bound ICYP was separated by molecular weight column or protein A beads. Beta receptor binding was determined by displacement of ICYP from bovine lung membranes, or from direct anti- body binding by ELISA. BLA were found in 6 of 12 asthmatics on daily steroids, 2 of 6 asthmatics on less than 20 mg prednisone; 1 of 6 asthmatics not on steroids and 2 of 31 normals (p <.OOl by ANOVA). Eight of 9 patients with BLA and only 7/15 asthmatics without BLA were taking oral beta agonists (p <.Ol). BRA were found in 6/9 patients with BLA, but only l/15 patients without them (p <.Ol). Thus, BLA are present in asthmatics associated with corticosteroid and beta ago- nist use. The correlation between BRA and BLA suggests that care must be taken in analyzing results of ligand displacement assays and opens the possibility that an anti-idiotypic response to BLA is involved in the formation of beta receptor antibodies in asthmatics.

214 ANOMALOUS EFFECTS OF STEROID TREATMENT ON CIRCULATING LEUKOCYTES J.H. Toogood, M.D., J. Baskerville, Ph.D., S.-A. Johanseon, Ph.D., London, Canada, and Lund, Sweden.

In a 4 month double-blind. ulacebo- controlled comparison of graduated doses of oral prednisone (P) vs. inhaled budesonide (B) in 31 chronic asthmatics, differential WBC counts were performed every 14 days, 24 hours after the last P dose and 10 hours after the last B dose. A dose-dependent neutrophilia (p=.OOl), lymphocytosis (p=.Ol) and monocytosis (p=.O8) were observed with the P but not with B treatment. AM serum cortisol (SC) levels dropped with the highest dose of each drug (p=.O5) without significant accompanying eosinopenia (EOS) (p=.20). The same leukocyte changes were again observed in a different patient group treated in- dependently with the same drugs and doses.

This lymphocytosis and monocytosis is the opposite of the response expected with steroid treatment. Its dose dependency and reproducibility have not been reported previously. The changes presumably represent an influx or redistribution of cells previously depleted from the circulation by glucocorticoid action. As indicators of systemic glucocorticoid effect, these indices discriminated more efficiently between the two steroid drugs than EOS or SC did.'

The exact mechanism of these changes, their relationship to different gluco- corticoid drug regimens, and their prognostic implications merit further investigation.

215 ti~&ZOCD.?TiSiilE Al&l AI;<FLO’,f ii;iPAI;II”Xt~T IN ASFI,?Ii.I-INDUCED ASTIWA. 5. Niiankovr- ska, l'l.D., G. Czernirrnska-Mysil<, F4.3., J.Drewniak. ;i.N. and A. Szczeklik ,M.D., Cracow, Poland

.:ecently , sporadic cases of acute idiosyncratic reactions to hydrocort- isone were described in patients with asthma and aspirin hypersensitivity. This prompted us to study the effects of intravenous injection of 1.00 and 300 mg of hydrocortisone, and to compare it with those of solvent in 31 patients with aspirin-induced asthma. Mean FiVl fell significantly 5 minutes after 300 mg of hydrocortisone, but not after the solvent,and returned to the initial values one hour later. Three to 5 hours after the drug injection mean FEVi increased significantly. In 3 patients clinical symptoms of eorly broncho- constriction were observed. In these patients i.v. prednisolone,

injection og 20 mg methyl- 4 mg dexamethasone or 4

mg bctamethosone produced no changes in pulmonary function tests. Intra- venous storoids other than hydrocort- isone should be used irl aspirin-induced nsthma. It is hypothetizcd thot hydro- cortisone might induce early 3roncho- constriction through its inhibitory effect on prostnnoid biosynthesis.

216 TX EFFECT OF DIFLUNISAL ON PULMOWAY FUNCTIOid IfJ ASPII?IICSZNSITIV~ ASTIWIA

;.;: 2 Szczeklik, E,i.iJ. and S. tiitankowska, . , Cracow, Poland Diflunisal /%#,3#-uifluoro-4-hydroxy-

3 biphenyl-corboxylic acid/, a new syn- thetic nonsteroidal antiinflammatory analgesic, is ;i liloderately active, ro- versible inhibitor of cyclooxygcnase.

In 16 aspirin-sensitive asthmatics TIC studied the effects of increasing doses 0.15 Diflunisnl /SO, 100, 250, 500, and 1000 mg/ as compared to placebo, on FVC, FiV., and i,,EFs during 480 minutes observation. Zight patients tolerated all the doses very nell, while in 5 others mild, transient side effects: rhinorrhea, lacrimation, slight tight- ness in the chest and/or temporary dccreose in FCV+ occurred. In 5 remain- ing patients 31 lunlsal provoked late, but clear-cut symptoms of bronchocon- striction resembling very much those precipitated by aspirin. :Jhen patients I.J~O tolerated acute challenge very nell were given 1000 my of the drug for one week, no side effects occurred.

If potent analgesic ~~ith prolonged action is required by aspirin-intoler- ant patient with asthma, o trial of Diflunisal can be undertaken, preceded by oral challenge vJit1-i 50-150 mg of that drug.

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