- Email: [email protected]
HIGH-DOSE CORTICOSTEROID INHALERS FOR ASTHMA
576 albumin
or lactase will be IRT retested before sweat testing. The retesting cut-off should be 25 µg/1, because of the fast decreasing of IRT during the first weeks of life in some CF (upper normal limit of non CF infants at 2-4 weeks age=21 µg/1). By this strategy (see table) we have reduced the false positive rate (at the conclusive sweat test) from 0-96%, after the initial IRT test, to 0 - 19% after lactase evaluation and to 0 -06% after IRT retesting.
G. MASTELLA F. PEDERZINI E. GIRELLA G. RIGHETTI M. ZANCHETTA P. RIZZOTTI
Regional Cystic Fibrosis Centre and Clinical Enzymology Centre, Istituti Ospitalieri,
37126 Verona, Italy
NICOTINIC-ACID-RESPONSIVE PHOTOSENSITIVITY
SIR,-Monographs on sensitivity to sunlight 1,2 do not suggest the use
of nicotinic acid for
treatment
of
photosensitivity except
in
pellagra, where it becomes a "cure-all" for the symptoms of chronic photodermatitis, diarrhoea, and depression. A 59-year-old White man had become sensitive to summer sunlight 7 years earlier. The exposed areas of his ears, forehead, and forearms would become erythematous, pruritic, and sometimes vesicular after 5 min exposure to direct sunlight. The eruption was transitory but had kept him indoors during daylight hours. 13 years previously he had had a gastrectomy in which two-thirds of the stomach had been removed. He took no medication, used ’Ivory’ soap, and limited alcohol consumption to an occasional beer. He did not eat or sleep well and stated that he felt nervous. There was no history of diarrhoea or mental disturbance. His skin appeared normal. However, phototesting with direct sunlight in July showed minimum erythema dose of 5 min. 20 min exposure resulted in a papular erythematous rash which persisted for 3 days. A control area pretreated with sun screen (’Solbar Plus 15’) showed no reaction. Biopsy of the sunlight-induced reaction after 24 h showed a normal epidermic, mild oedema and telangiectasia, and a diffuse superficial inflammatory infiltrate of lymphocytes, histiocytes, and neutrophils. Laboratory results were normal, including complete blood count, chemistry profile (20 factor), serological test for syphilis, T4, LE cell test, and urine screen for a
porphobilinogen and coproporphyrins. Despite the absence of a persistent dermatitis or other signs of pellagra, nicotinic acid (100 mg twice daily) was prescribed. On the 10th day the patient had no reaction to a 2 h test of direct exposure to sunlight. Since then he has continued to take nicotinic acid daily for a year with no evidence of photosensitivity. The patient’s poor diet and history of gastrectomy suggested that his photosensitivity might be the solitary sign of nicotinic acid deficiency. The immediate complete success of nicotinic acid supplementation favours this hypothesis. It is unlikely that this drug had a primary photoprotective action since three control patients with photosensitivity (discoid lupus erythematosus, polymorphic light eruption, and photo-contact dermatitis) were given nicotinic acid without improvement. The many factors affecting the need for nicotinic acid include isoniazid therapy, alcoholism, thyrotoxicosis, porphyria, carcinoid syndrome, No deficiencies of riboflavin, pyridoxine, ascorbic acid, or copper.and such factor could be specifically discerned in -our patient. Inadequate dietary intake and malabsorption remain the most likely causes of his difficulty. We feel that nicotinic acid deserves consideration in the treatment of any photosensitivity state of obscure nature. Division of Dermatology,
Department of Medicine, Medical College of Ohio, Toledo, Ohio 43699, USA LC, Bickers DR.
WALTER B. SHELLEY E. DORINDA SHELLEY
Harper Photosensitivity diseases principles of diagnosis and treatment. Philadelphia: WB Saunders, 1981. 2 Magnur IA. Dermatological photobiology: clinical and experimental aspects. Oxford: Blackwell Scientific Publications, 1976. 3. Weiner M, Van Eys J. Nicotinic acid: nutrient-cofactor-drug. New York: Marcel Dekker, 1983. 1.
HIGH-DOSE CORTICOSTEROID INHALERS FOR ASTHMA
SIR,-In your editorial (July 7, p 23) you commented on the need a prospective trial of high-dose inhalers. We have conducted a comparative study of inhaled high-dose beclomethasone dipropionate (BDP) (750 µg bd) and budesonide (800 J.lg bd). We studied 28 chronic asthmatics (20 males) with a mean age of 54 years. They were normally treated with BDP (mean dose 887’55 µg daily) but judged to be poorly controlled. None was on oral steroids or had been given oral steroids in the month preceding the study. The two drugs were administered with a double-blind, doubledummy cross-over technique for two 6-week periods. 16 of the 28 patients also had a 2-week period on their existing therapy, and this period was compared with the last 21 days of each of the two highdose treatment periods for morning and evening peak expiratory flow rates and number of puffs of inhaled bronchodilator used (other bronchodilator treatment remaining constant). In 9 patients there was a statistically significant increase in peak expiratory flow rates
for
and/or a significant decrease in use of inhaled bronchodilator on the high-dose corticosteroids. The mean dosage of BDP during this 2-week period was 906 µg per day. Only 2 patients showed a significant deterioration in these measurements (mean dose 775 µg BDP daily), and in 2 patients there was no change (mean dose 600 µg daily). The 3 remaining patients showed falls in both peak expiratory flow rates and use of inhaled bronchodilator. On only 3 occasions during high-dose treatment was an oropharyngeal infection with Candida albicans proven. The majority of patients seem to have benefited from high-dose corticosteroid treatment, with little trouble from oropharyngeal candida infections. Mean cortisol levels in all 28 patients taken at 0900 h after 6 weeks’ treatment were lower than the starting levels with both budesonide (p<0.01) and BDP (p<0.05). Treatment had no effect on the rise in cortisol 30 min after 0 - 25 mg of tetracosactrin. Start
of study
Plasma cortisol 0900 h, mean:tSD (mmolll) Rise in plasma cortisol 30 min after tetracosactrin (mmol/l) Plasma cortisol 30 min
after tetracosactrin (mmolll)
Budesonide Beclomethasone
period
period
309±29
222±18
248±21
269±27
245±13
246±18
577±36
467±18
495±20
Our results support Gaddie’s finding of adrenal suppression after a dose of 1600 pig BDP daily. In their retrospective study Smith and Hodson2had only 4 patients on 1500 J.lg BDP per day, and it is difficult to draw general conclusions from the normal ’Synacthen’ tests that they found. We suggest that at doses of BDP 1500 µg daily and budesonide 1600 µg daily there is adrenal suppression. Asthma Research Unit,
P. EBDEN B. H. DAVIES
Sully Hospital, Sully, South Glamorgan
J, Petrie GR, Reid IW, Sinclair DJM, Skinner C, Palmer KNV. Aerosol beclomethasone dipropionate: a dose-response in chronic bronchial asthma. Lancet 1973; ii: 280-81. 2. Smith MJ, Hodson ME. Effects of long term inhaled high dose beclomethasone dipropionate on adrenal function. Thorax 1983; 38: 676-81. 1. Gaddie
ITCHING AND ASTHMA
SIR,-Occasionally adults, as well as children (July 21, p 154), experience itching of the chin, neck, or back as a warning of an impending asthma attack. These sensations can be associated with seasonal peaks of mould spore concentrations, as confirmed by the production of identical symptoms by nasal or bronchial provocation tests out of season. The itching usually occurs just before the onset of airway obstruction. Pain can also be a prodromal symptom. A woman had intermittent pain in the left upper jaw in August and September for which her dentist could find no cause. She was very senstitive to the seasonal mould Botrytis, which caused asthma and rhinitis, and this was confirmed by a positive nasal provocation test in the winter. The patient commented that besides the sneezing which resulted from the test, she also had pain in the jaw identical to that she had experienced every summer for several years. It was then found that
or lactase will be IRT retested before sweat testing. The retesting cut-off should be 25 µg/1, because of the fast decreasing of IRT during the first weeks of life in some CF (upper normal limit of non CF infants at 2-4 weeks age=21 µg/1). By this strategy (see table) we have reduced the false positive rate (at the conclusive sweat test) from 0-96%, after the initial IRT test, to 0 - 19% after lactase evaluation and to 0 -06% after IRT retesting.
G. MASTELLA F. PEDERZINI E. GIRELLA G. RIGHETTI M. ZANCHETTA P. RIZZOTTI
Regional Cystic Fibrosis Centre and Clinical Enzymology Centre, Istituti Ospitalieri,
37126 Verona, Italy
NICOTINIC-ACID-RESPONSIVE PHOTOSENSITIVITY
SIR,-Monographs on sensitivity to sunlight 1,2 do not suggest the use
of nicotinic acid for
treatment
of
photosensitivity except
in
pellagra, where it becomes a "cure-all" for the symptoms of chronic photodermatitis, diarrhoea, and depression. A 59-year-old White man had become sensitive to summer sunlight 7 years earlier. The exposed areas of his ears, forehead, and forearms would become erythematous, pruritic, and sometimes vesicular after 5 min exposure to direct sunlight. The eruption was transitory but had kept him indoors during daylight hours. 13 years previously he had had a gastrectomy in which two-thirds of the stomach had been removed. He took no medication, used ’Ivory’ soap, and limited alcohol consumption to an occasional beer. He did not eat or sleep well and stated that he felt nervous. There was no history of diarrhoea or mental disturbance. His skin appeared normal. However, phototesting with direct sunlight in July showed minimum erythema dose of 5 min. 20 min exposure resulted in a papular erythematous rash which persisted for 3 days. A control area pretreated with sun screen (’Solbar Plus 15’) showed no reaction. Biopsy of the sunlight-induced reaction after 24 h showed a normal epidermic, mild oedema and telangiectasia, and a diffuse superficial inflammatory infiltrate of lymphocytes, histiocytes, and neutrophils. Laboratory results were normal, including complete blood count, chemistry profile (20 factor), serological test for syphilis, T4, LE cell test, and urine screen for a
porphobilinogen and coproporphyrins. Despite the absence of a persistent dermatitis or other signs of pellagra, nicotinic acid (100 mg twice daily) was prescribed. On the 10th day the patient had no reaction to a 2 h test of direct exposure to sunlight. Since then he has continued to take nicotinic acid daily for a year with no evidence of photosensitivity. The patient’s poor diet and history of gastrectomy suggested that his photosensitivity might be the solitary sign of nicotinic acid deficiency. The immediate complete success of nicotinic acid supplementation favours this hypothesis. It is unlikely that this drug had a primary photoprotective action since three control patients with photosensitivity (discoid lupus erythematosus, polymorphic light eruption, and photo-contact dermatitis) were given nicotinic acid without improvement. The many factors affecting the need for nicotinic acid include isoniazid therapy, alcoholism, thyrotoxicosis, porphyria, carcinoid syndrome, No deficiencies of riboflavin, pyridoxine, ascorbic acid, or copper.and such factor could be specifically discerned in -our patient. Inadequate dietary intake and malabsorption remain the most likely causes of his difficulty. We feel that nicotinic acid deserves consideration in the treatment of any photosensitivity state of obscure nature. Division of Dermatology,
Department of Medicine, Medical College of Ohio, Toledo, Ohio 43699, USA LC, Bickers DR.
WALTER B. SHELLEY E. DORINDA SHELLEY
Harper Photosensitivity diseases principles of diagnosis and treatment. Philadelphia: WB Saunders, 1981. 2 Magnur IA. Dermatological photobiology: clinical and experimental aspects. Oxford: Blackwell Scientific Publications, 1976. 3. Weiner M, Van Eys J. Nicotinic acid: nutrient-cofactor-drug. New York: Marcel Dekker, 1983. 1.
HIGH-DOSE CORTICOSTEROID INHALERS FOR ASTHMA
SIR,-In your editorial (July 7, p 23) you commented on the need a prospective trial of high-dose inhalers. We have conducted a comparative study of inhaled high-dose beclomethasone dipropionate (BDP) (750 µg bd) and budesonide (800 J.lg bd). We studied 28 chronic asthmatics (20 males) with a mean age of 54 years. They were normally treated with BDP (mean dose 887’55 µg daily) but judged to be poorly controlled. None was on oral steroids or had been given oral steroids in the month preceding the study. The two drugs were administered with a double-blind, doubledummy cross-over technique for two 6-week periods. 16 of the 28 patients also had a 2-week period on their existing therapy, and this period was compared with the last 21 days of each of the two highdose treatment periods for morning and evening peak expiratory flow rates and number of puffs of inhaled bronchodilator used (other bronchodilator treatment remaining constant). In 9 patients there was a statistically significant increase in peak expiratory flow rates
for
and/or a significant decrease in use of inhaled bronchodilator on the high-dose corticosteroids. The mean dosage of BDP during this 2-week period was 906 µg per day. Only 2 patients showed a significant deterioration in these measurements (mean dose 775 µg BDP daily), and in 2 patients there was no change (mean dose 600 µg daily). The 3 remaining patients showed falls in both peak expiratory flow rates and use of inhaled bronchodilator. On only 3 occasions during high-dose treatment was an oropharyngeal infection with Candida albicans proven. The majority of patients seem to have benefited from high-dose corticosteroid treatment, with little trouble from oropharyngeal candida infections. Mean cortisol levels in all 28 patients taken at 0900 h after 6 weeks’ treatment were lower than the starting levels with both budesonide (p<0.01) and BDP (p<0.05). Treatment had no effect on the rise in cortisol 30 min after 0 - 25 mg of tetracosactrin. Start
of study
Plasma cortisol 0900 h, mean:tSD (mmolll) Rise in plasma cortisol 30 min after tetracosactrin (mmol/l) Plasma cortisol 30 min
after tetracosactrin (mmolll)
Budesonide Beclomethasone
period
period
309±29
222±18
248±21
269±27
245±13
246±18
577±36
467±18
495±20
Our results support Gaddie’s finding of adrenal suppression after a dose of 1600 pig BDP daily. In their retrospective study Smith and Hodson2had only 4 patients on 1500 J.lg BDP per day, and it is difficult to draw general conclusions from the normal ’Synacthen’ tests that they found. We suggest that at doses of BDP 1500 µg daily and budesonide 1600 µg daily there is adrenal suppression. Asthma Research Unit,
P. EBDEN B. H. DAVIES
Sully Hospital, Sully, South Glamorgan
J, Petrie GR, Reid IW, Sinclair DJM, Skinner C, Palmer KNV. Aerosol beclomethasone dipropionate: a dose-response in chronic bronchial asthma. Lancet 1973; ii: 280-81. 2. Smith MJ, Hodson ME. Effects of long term inhaled high dose beclomethasone dipropionate on adrenal function. Thorax 1983; 38: 676-81. 1. Gaddie
ITCHING AND ASTHMA
SIR,-Occasionally adults, as well as children (July 21, p 154), experience itching of the chin, neck, or back as a warning of an impending asthma attack. These sensations can be associated with seasonal peaks of mould spore concentrations, as confirmed by the production of identical symptoms by nasal or bronchial provocation tests out of season. The itching usually occurs just before the onset of airway obstruction. Pain can also be a prodromal symptom. A woman had intermittent pain in the left upper jaw in August and September for which her dentist could find no cause. She was very senstitive to the seasonal mould Botrytis, which caused asthma and rhinitis, and this was confirmed by a positive nasal provocation test in the winter. The patient commented that besides the sneezing which resulted from the test, she also had pain in the jaw identical to that she had experienced every summer for several years. It was then found that