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Inhibitory effect of inhaled berotec on exercise induced bronchospasm (EIB)
241 INHIBITORY EFFECT OF INHALED BEROTEC ON EXERCISE INDUCED BRONCHOSPASM (EIB). R.R. Rosenthal, M.D., K. Napier, B.S., C. Serby, M.D. and P.S. Norman, M.D.~ Baltimore, Maryland and Ridgefield, Connecticut The ability of Berotec, a new selective beta 2 agonist, to protect against exercise challenge was studied in 12 asthmatic patients. Patients were first exercised on two "standardization days" to confirm the presence of a reproducible response and then studied in a double blind manner after taking placebo or Berotec. There was no difference in the baseline FEV I on any of the four study days. The FEV 1 was recorded prior to the inhalation of 400 ~g of Berotec or placebo and at i0 minutes after. Following 6 minutes of exercise at 90% predicted maximum heart rate, the FEV 1 was monitored at 1,5,10,15 and 30 minutes. The average FEV. at i0 minutes after Berotec inhalation was 1188 of predrug baseline but was 98% of predrug baseline after placebo (p < 0.001~ After study drug treatment the average lowest FEV. after exercise was 111.5% of the predrug i ~ baseline and after placebo 63.6% (p < 0.001). When the lowest FEV. after exercise was expressi ed as a function of the post-medication baseline the average after Berotec treatment was 98% and after placebo treatment 66% (p < 0.O01). Moreover the average FEV. as a percent of the post' i drug baseline was significantly lower for at least 30 minutes post exercise on the placebo day but remained undiminished on the drug day. It is concluded that Berotec has direct bronchodilating activity similar to atropine but unlike our experience with atropine is independently preventative of EIB.
243 EFFECT OF DALLY AEROSOLIZED LODOXAMIDE TROMETHAMINE IN CHRONIC ASTHMATICS. James D. Wolfe~ M.D. r Theodore J. Chu~ M.D.~ Arthur A. Biedermann, M.D.~ Earle R. Sloan, M.D. and Minoru Yamate, M.D., San Jose, Calif. Lodoxamide tromethamine (LT) is a new drug which has pharmacologic properties similar to cromolyn sodium. LT has been shown to protect asthmatics from allergen and exercise-induced bronchoconstriction. We evaluated the efficacy and safety of a 4 week course of aerosolized LT. Using a double-blind placebo-controlled parallel design, 43 adults with chronic stable asthma (baseline FEV l 36-98% predicted, mean 69%) received either aerosolized LT 0.5 mg, LT O.l mg, or placebo (P) 4 times a day for 4 weeks. Twice daily symptom diaries and Wright Peak Flow (WPF) measurements, twice weekly spirometry and weekly hematologic, hepatic and renal studies were obtained. An attempt was made during the study to decrease baseline oral and aerosolized bronchodilator therapy. No significant difference in pulmonary symptoms, WPF, spirometric indices, or ability to reduce baseline bronchodilator medications was observed between LT and P groups (P>O.05). No laboratory abnormalities in hematologic, hepatic or renal indices were noted. A sense of increased body heat occured in 2L/28 subjects receiving LT; this side effect was mild in the LT O.l mg group, but moderate to severe in 6/13 subjects receiving LT 0.5 mg. In conclusion, regular use of LT over a 4 week period did not appear to be beneficial in the treatment of asthma. However, longer term administration of LT may be necessary to demonstrate efficacy.
242 COMPARISON OF LODOXAMIDE AND CROMOLYN PRETREAT-
244 EVALUATION OF THERAPY WITIt AEROSOLIZED BITOLTEROL MESYLATE (BMA) AND ORAL THEOPHYLLINE GIVEN ALONE AND CONCOMITANTLY TO PATIENTS WITH ASTHMA. P. Chervinsky, M . D . , J . H . Noyes~ M.D-~'~ and T . S . M i n g o , New B e d f o r d , MA Double-blind bronchodilator therapy was g i v e n d a i l y for 6 consecutive weeks t o 36 a s t h m a t i c p a t i e n t s divided into 3 g r o u p s o f ]2 p a t i e n t s each. Group l r e c e i v e d BMA, Group 2 t h e o p h y l l i n e , and Group 3 BMA and t h e o p h y ] l i n e .
MENT IN EXERCISE-CHALLENGED ASTHMATICS. A.q. Sheridan~ M.D.t J.A. Nelson~ B.S.N.~ M.H. Maile~ M.S.~ C,D. Brooksp M.D., Kalamazoo, MI Lodoxamide tromethamine like cromolyn sodium is thought to exert an anti-allergic influence by stabilizing mast cells. Comparisons with placebo have shown that the drug protects asthmatics challenged with exercise or inhaled allergen. In this study we compared single doses of cromolyn 20 mg., lodoxamide 0.i mg. and 0.5 mg., and placebo for their protective effect in exercise-challenged asthmatics. We enrolled 14 asthmatics whose exercise sensitivity had been documented by a fall of 40% in specific conductance (SGAw) during preliminary testing. The volunteers received the drugs by inhalation 15 minutes before exercise. Doses were blinded and given in random order. We assessed patient response by multiple measurements of pulmonary function over a 50 minute follow-up. Cromolyn and both lodoxamide doses protected against exercise-associated falls in SGAw better than placebo. Though there were no statistical differences among the active treatments~ SGAw measurements tended to be Nigher with high dose lodoxamide or cromolyn treatments than with low dose lodoxamide. Peak flow rates showed the same general pattern. Side effects with cromolyn were limited to dryness in the throat. After lodoxamide the majority of volunteers exhibited variable degrees of heat, headache, nausea, and in 2 cases, vomiting. Side effect severity was dose related.
Serial s p i r o m e t r i c determinations for up to 8 h o u r s post m e d i c a t i o n w e r e p e r f o r m e d prestudy and then o n c e e v e r y 2 weeks. Assessment of e f f e c t s on c a r d i a c r h y t h m w e r e m a d e by 2 4 - h o u r ECG m o n i t o r i n g using Halter recorders. Each p a t i e n t m a i n t a i n e d a d a i l y s y m p t o m d i a r y and r e c o r d e d P E F R t w i c e e a c h day. The m e a n d u r a t i o n of b r o n c h o d i l a t o r a c t i v i t y r a n g e d b e t w e e n 4-5 h o u r s w i t h BMA g i v e n a l o n e . The m e a n d u r a t i o n was 2-3 h o u r s w i t h t h e o p h y l l i n e given alone. In the g r o u p g i v e n b o t h BMA and t h e o p h y l l i n e the d u r a t i o n of a c t i v i t y was 4-5 h o u r s . T h e r e w e r e no d i f f e r e n c e s a m o n g the 3 treatments in t e r m s of a d v e r s e effects, cardiac rhythm, asthma symptoms or d a i l y PEFR. BMA a l o n e p r o v i d e d b e t t e r a n t i a s t h m a t h e r a p y than t h e o p h y l l i n e alone and was as e f f e c t i v e as the c o m b i n a t i o n of BMA and t h e o p h y l l l n e .
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243 EFFECT OF DALLY AEROSOLIZED LODOXAMIDE TROMETHAMINE IN CHRONIC ASTHMATICS. James D. Wolfe~ M.D. r Theodore J. Chu~ M.D.~ Arthur A. Biedermann, M.D.~ Earle R. Sloan, M.D. and Minoru Yamate, M.D., San Jose, Calif. Lodoxamide tromethamine (LT) is a new drug which has pharmacologic properties similar to cromolyn sodium. LT has been shown to protect asthmatics from allergen and exercise-induced bronchoconstriction. We evaluated the efficacy and safety of a 4 week course of aerosolized LT. Using a double-blind placebo-controlled parallel design, 43 adults with chronic stable asthma (baseline FEV l 36-98% predicted, mean 69%) received either aerosolized LT 0.5 mg, LT O.l mg, or placebo (P) 4 times a day for 4 weeks. Twice daily symptom diaries and Wright Peak Flow (WPF) measurements, twice weekly spirometry and weekly hematologic, hepatic and renal studies were obtained. An attempt was made during the study to decrease baseline oral and aerosolized bronchodilator therapy. No significant difference in pulmonary symptoms, WPF, spirometric indices, or ability to reduce baseline bronchodilator medications was observed between LT and P groups (P>O.05). No laboratory abnormalities in hematologic, hepatic or renal indices were noted. A sense of increased body heat occured in 2L/28 subjects receiving LT; this side effect was mild in the LT O.l mg group, but moderate to severe in 6/13 subjects receiving LT 0.5 mg. In conclusion, regular use of LT over a 4 week period did not appear to be beneficial in the treatment of asthma. However, longer term administration of LT may be necessary to demonstrate efficacy.
242 COMPARISON OF LODOXAMIDE AND CROMOLYN PRETREAT-
244 EVALUATION OF THERAPY WITIt AEROSOLIZED BITOLTEROL MESYLATE (BMA) AND ORAL THEOPHYLLINE GIVEN ALONE AND CONCOMITANTLY TO PATIENTS WITH ASTHMA. P. Chervinsky, M . D . , J . H . Noyes~ M.D-~'~ and T . S . M i n g o , New B e d f o r d , MA Double-blind bronchodilator therapy was g i v e n d a i l y for 6 consecutive weeks t o 36 a s t h m a t i c p a t i e n t s divided into 3 g r o u p s o f ]2 p a t i e n t s each. Group l r e c e i v e d BMA, Group 2 t h e o p h y l l i n e , and Group 3 BMA and t h e o p h y ] l i n e .
MENT IN EXERCISE-CHALLENGED ASTHMATICS. A.q. Sheridan~ M.D.t J.A. Nelson~ B.S.N.~ M.H. Maile~ M.S.~ C,D. Brooksp M.D., Kalamazoo, MI Lodoxamide tromethamine like cromolyn sodium is thought to exert an anti-allergic influence by stabilizing mast cells. Comparisons with placebo have shown that the drug protects asthmatics challenged with exercise or inhaled allergen. In this study we compared single doses of cromolyn 20 mg., lodoxamide 0.i mg. and 0.5 mg., and placebo for their protective effect in exercise-challenged asthmatics. We enrolled 14 asthmatics whose exercise sensitivity had been documented by a fall of 40% in specific conductance (SGAw) during preliminary testing. The volunteers received the drugs by inhalation 15 minutes before exercise. Doses were blinded and given in random order. We assessed patient response by multiple measurements of pulmonary function over a 50 minute follow-up. Cromolyn and both lodoxamide doses protected against exercise-associated falls in SGAw better than placebo. Though there were no statistical differences among the active treatments~ SGAw measurements tended to be Nigher with high dose lodoxamide or cromolyn treatments than with low dose lodoxamide. Peak flow rates showed the same general pattern. Side effects with cromolyn were limited to dryness in the throat. After lodoxamide the majority of volunteers exhibited variable degrees of heat, headache, nausea, and in 2 cases, vomiting. Side effect severity was dose related.
Serial s p i r o m e t r i c determinations for up to 8 h o u r s post m e d i c a t i o n w e r e p e r f o r m e d prestudy and then o n c e e v e r y 2 weeks. Assessment of e f f e c t s on c a r d i a c r h y t h m w e r e m a d e by 2 4 - h o u r ECG m o n i t o r i n g using Halter recorders. Each p a t i e n t m a i n t a i n e d a d a i l y s y m p t o m d i a r y and r e c o r d e d P E F R t w i c e e a c h day. The m e a n d u r a t i o n of b r o n c h o d i l a t o r a c t i v i t y r a n g e d b e t w e e n 4-5 h o u r s w i t h BMA g i v e n a l o n e . The m e a n d u r a t i o n was 2-3 h o u r s w i t h t h e o p h y l l i n e given alone. In the g r o u p g i v e n b o t h BMA and t h e o p h y l l i n e the d u r a t i o n of a c t i v i t y was 4-5 h o u r s . T h e r e w e r e no d i f f e r e n c e s a m o n g the 3 treatments in t e r m s of a d v e r s e effects, cardiac rhythm, asthma symptoms or d a i l y PEFR. BMA a l o n e p r o v i d e d b e t t e r a n t i a s t h m a t h e r a p y than t h e o p h y l l i n e alone and was as e f f e c t i v e as the c o m b i n a t i o n of BMA and t h e o p h y l l l n e .
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