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Steroid tapering in acute asthma
772
around the UK dedicated to continuous information exchange and to implementing clinical trials based on novel approaches coming out of the laboratory, and the cancer charities play a major part in this effort. Meetings, of course, are especially important in disseminating information and concepts and in bringing together people with a common purpose, in this case reducing the incidence and improving survival in breast cancer. I am sure that The Lancet meeting to be held in Brugge will take some steps along this road. This achievement will depend on having good presentations, vigorous discussion, and commitment to applying novel approaches in a structured manner. We would, however, not want the meeting to start off with the premise that we have "lost our way" at a time when quite a number of road signs seem to be emerging. These signs should, in fact, provided we read them correctly, help us in finding our way to the improvements in the clinical treatment of breast cancer that we seek and the patients so urgently need.
ICI Pharmaceuticals keep extensive records of adverse events associated with tamoxifen and have received a few reports of bronchoconstriction, although a causal relation was never established. In most Western countries, carcinoma of the breast is the most common cause of cancer in women. Because many of these patients will be taking tamoxifen, prescribers should be aware of this potentially serious adverse effect of the drug. Department of Respiratory Medicine, Kings Cross Hospital, Dundee, DD3 8EA, UK; and Department of Radiotherapy and Ninewells Hospital, Dundee
1. Gibson GJ. Adverse pulmonary effects of drugs and radiation. In: Brewis RAL, Gibson GJ, Geddes DM, eds. Respiratory medicine. London: Baillière and 2.
Tindall, 1990: 1151. Keaney NP. Respiratory disorders. In: Davies DM, ed. The textbook of adverse drug reactions. 4th ed. Oxford: Oxford University Press, 1991: 179-80.
Imperial Cancer Research Fund, Epithelial Cell Biology Laboratory, Lincoln’s Inn Fields, London WC2A 3PX, UK
R. P. SMITH J. A. DEWAR J. H. WINTER
Oncology,
Steroid
JOYCE TAYLOR-PAPADIMITRIOU
tapering
in acute asthma
SIR,-Dr O’Driscoll and colleagues (Feb 6, p 324) show that
Tamoxifen-induced asthma SIR,-Asthma induced by non-steroidal anti-inflammatory drugs is characterised by bronchospasm, rhinitis, and nasal polyps.l Other drugs can idiosyncratically precipitate asthma.2 We report a woman with analgesic-induced asthma in whom tamoxifen produced symptomatic and objective airways obstruction. A 53-year-old woman had asthma, rhinitis, and recurrent nasal polyposis for 20 years. There was no history of eczema or hayfever. Her symptoms were initially well controlled with inhaled salbutamol. In 1984 she developed seronegative arthritis and was prescribed naproxen, which resulted in a severe asthma attack requiring admission. Over the following years, her arthritic pain became
more
severe
and various other non-steroidal anti-
inflammatory drugs were tried. These agents provided symptomatic relief but also resulted in rhinitis and a deterioration in her asthma control. Desensitisation to diclofenac in 1989 was unsuccessful. In December, 1990, carcinoma of the breast was diagnosed and, after surgery, she was started on tamoxifen. This therapy was associated with deterioration in asthma control, especially for a few hours after ingesting tamoxifen. Therefore we arranged to study the effect of tamoxifen upon her pulmonary function tests. Three preparations were compared: her own tamoxifen preparations (CP Pharmaceuticals), Nolvadex (ICI Pharmaceuticals), and Nolvadex placebo. The constituents of each are available from R. P. S. In a random double-blind fashion, these preparations were compared on three consecutive days. The patient was asked to omit her tamoxifen and bronchodilator each morning before testing. With both preparations containing tamoxifen, forced expiratory volume in 1 s (FEV1) fell by nearly 70% over 45 min (figure). In both cases, salbutamol reversed this effect. With the placebo, there was also a drop in the FEV but by only 39%, which could be a placebo effect or hypersensitivity to one of the constituents of the placebo. We concluded that tamoxifen provoked bronchospasm in our
patient.
doses of steroids have no advantages over abrupt termination in patients recovering from acute severe asthma. In 1990/91, because of lack of information on this. aspect of asthma therapy, to which the British Thoracic Society guidelines drew attention,l,2 we did an open, randomised, prospective comparison of the two methods of discontinuing steroid treatment. Apart from the open design, which was regarded as satisfactory for a comparative study of two treatment regimens said to be in common use, the protocol was similar to that of O’Driscoll and colleagues with respect to patient’s age and sex, entry criteria, outcome measures, use of inhaled steroids after discharge, and provision of a self-management plan. Over twelve months, 33 patients (mean age 31, SD 13) were randomly allocated to abrupt termination (group A) or to a tapering dose regimen over 10 days (group B). All patients received prednisolone 40 mg daily and were discharged from hospital only in the morning. Peak expiratory flow (PEF) was greater than 70% of predicted and PEF diurnal variation was less than 20%. Prednisolone 40 mg/day was then continued for a further 3 days before randomisation, both groups receiving a minimum of 7 days at this dose. At the end of four weeks’ follow-up 14 patients from group A and 14 from group B could be evaluated. 5 patients failed to attend for follow-up or did not keep satisfactory records from group A, 3 from group B). Mean (SD) PEF values for the two groups were: At days:
tapering
(2
At admission
10
14
27
174 (103) 396 (135) 422 (127) 412 (114) 403 (132) 391 (53) 389 (66) 387 (75) 372 (92) 175 (66) PEF did not differ significantly between the two groups at any stage
during the 4-week follow-up. Mean total dose of prednisolone per patient was 346 mg for group A and 494 mg for group B. 2 patients from each group initiated their self-management plans because of worsening asthma in the 4 weeks after discharge. These findings lend support to the recommendation that tapering doses of steroids are unncessary after recovery from acute severe asthma in asthmatic patients who are young with good reversibility of airways obstruction. Abrupt termination may not be advisable when lung function is chronically impaired or in patients on long-term steroid therapy. Whatever regimen is adopted patients should be encouraged to monitor PEF and warned not to discontinue steroid therapy if their asthma deteriorates in the days after
discharge from hospital.
Newcastle General Hospital, Newcastle NE4 6BE, UK
Department of Respiratory Medicine, South Cleveland Hospital,
Middlesbrough 1. British Thoracic
Respiratory function after challenge.
1
Group A Group B
JANE SKINNER RASHID SIDDIQUI HARRY GRIBBIN DAVID SINCLAIR
Society. Guidelines for management of asthma in adults. I-chronic persistent asthma. BMJ 1990; 301: 651-53. 2. British Thoracic Society. Guidelines for management of asthma in adults II-acute severe asthma. BMJ 1990; 301: 797-800.
around the UK dedicated to continuous information exchange and to implementing clinical trials based on novel approaches coming out of the laboratory, and the cancer charities play a major part in this effort. Meetings, of course, are especially important in disseminating information and concepts and in bringing together people with a common purpose, in this case reducing the incidence and improving survival in breast cancer. I am sure that The Lancet meeting to be held in Brugge will take some steps along this road. This achievement will depend on having good presentations, vigorous discussion, and commitment to applying novel approaches in a structured manner. We would, however, not want the meeting to start off with the premise that we have "lost our way" at a time when quite a number of road signs seem to be emerging. These signs should, in fact, provided we read them correctly, help us in finding our way to the improvements in the clinical treatment of breast cancer that we seek and the patients so urgently need.
ICI Pharmaceuticals keep extensive records of adverse events associated with tamoxifen and have received a few reports of bronchoconstriction, although a causal relation was never established. In most Western countries, carcinoma of the breast is the most common cause of cancer in women. Because many of these patients will be taking tamoxifen, prescribers should be aware of this potentially serious adverse effect of the drug. Department of Respiratory Medicine, Kings Cross Hospital, Dundee, DD3 8EA, UK; and Department of Radiotherapy and Ninewells Hospital, Dundee
1. Gibson GJ. Adverse pulmonary effects of drugs and radiation. In: Brewis RAL, Gibson GJ, Geddes DM, eds. Respiratory medicine. London: Baillière and 2.
Tindall, 1990: 1151. Keaney NP. Respiratory disorders. In: Davies DM, ed. The textbook of adverse drug reactions. 4th ed. Oxford: Oxford University Press, 1991: 179-80.
Imperial Cancer Research Fund, Epithelial Cell Biology Laboratory, Lincoln’s Inn Fields, London WC2A 3PX, UK
R. P. SMITH J. A. DEWAR J. H. WINTER
Oncology,
Steroid
JOYCE TAYLOR-PAPADIMITRIOU
tapering
in acute asthma
SIR,-Dr O’Driscoll and colleagues (Feb 6, p 324) show that
Tamoxifen-induced asthma SIR,-Asthma induced by non-steroidal anti-inflammatory drugs is characterised by bronchospasm, rhinitis, and nasal polyps.l Other drugs can idiosyncratically precipitate asthma.2 We report a woman with analgesic-induced asthma in whom tamoxifen produced symptomatic and objective airways obstruction. A 53-year-old woman had asthma, rhinitis, and recurrent nasal polyposis for 20 years. There was no history of eczema or hayfever. Her symptoms were initially well controlled with inhaled salbutamol. In 1984 she developed seronegative arthritis and was prescribed naproxen, which resulted in a severe asthma attack requiring admission. Over the following years, her arthritic pain became
more
severe
and various other non-steroidal anti-
inflammatory drugs were tried. These agents provided symptomatic relief but also resulted in rhinitis and a deterioration in her asthma control. Desensitisation to diclofenac in 1989 was unsuccessful. In December, 1990, carcinoma of the breast was diagnosed and, after surgery, she was started on tamoxifen. This therapy was associated with deterioration in asthma control, especially for a few hours after ingesting tamoxifen. Therefore we arranged to study the effect of tamoxifen upon her pulmonary function tests. Three preparations were compared: her own tamoxifen preparations (CP Pharmaceuticals), Nolvadex (ICI Pharmaceuticals), and Nolvadex placebo. The constituents of each are available from R. P. S. In a random double-blind fashion, these preparations were compared on three consecutive days. The patient was asked to omit her tamoxifen and bronchodilator each morning before testing. With both preparations containing tamoxifen, forced expiratory volume in 1 s (FEV1) fell by nearly 70% over 45 min (figure). In both cases, salbutamol reversed this effect. With the placebo, there was also a drop in the FEV but by only 39%, which could be a placebo effect or hypersensitivity to one of the constituents of the placebo. We concluded that tamoxifen provoked bronchospasm in our
patient.
doses of steroids have no advantages over abrupt termination in patients recovering from acute severe asthma. In 1990/91, because of lack of information on this. aspect of asthma therapy, to which the British Thoracic Society guidelines drew attention,l,2 we did an open, randomised, prospective comparison of the two methods of discontinuing steroid treatment. Apart from the open design, which was regarded as satisfactory for a comparative study of two treatment regimens said to be in common use, the protocol was similar to that of O’Driscoll and colleagues with respect to patient’s age and sex, entry criteria, outcome measures, use of inhaled steroids after discharge, and provision of a self-management plan. Over twelve months, 33 patients (mean age 31, SD 13) were randomly allocated to abrupt termination (group A) or to a tapering dose regimen over 10 days (group B). All patients received prednisolone 40 mg daily and were discharged from hospital only in the morning. Peak expiratory flow (PEF) was greater than 70% of predicted and PEF diurnal variation was less than 20%. Prednisolone 40 mg/day was then continued for a further 3 days before randomisation, both groups receiving a minimum of 7 days at this dose. At the end of four weeks’ follow-up 14 patients from group A and 14 from group B could be evaluated. 5 patients failed to attend for follow-up or did not keep satisfactory records from group A, 3 from group B). Mean (SD) PEF values for the two groups were: At days:
tapering
(2
At admission
10
14
27
174 (103) 396 (135) 422 (127) 412 (114) 403 (132) 391 (53) 389 (66) 387 (75) 372 (92) 175 (66) PEF did not differ significantly between the two groups at any stage
during the 4-week follow-up. Mean total dose of prednisolone per patient was 346 mg for group A and 494 mg for group B. 2 patients from each group initiated their self-management plans because of worsening asthma in the 4 weeks after discharge. These findings lend support to the recommendation that tapering doses of steroids are unncessary after recovery from acute severe asthma in asthmatic patients who are young with good reversibility of airways obstruction. Abrupt termination may not be advisable when lung function is chronically impaired or in patients on long-term steroid therapy. Whatever regimen is adopted patients should be encouraged to monitor PEF and warned not to discontinue steroid therapy if their asthma deteriorates in the days after
discharge from hospital.
Newcastle General Hospital, Newcastle NE4 6BE, UK
Department of Respiratory Medicine, South Cleveland Hospital,
Middlesbrough 1. British Thoracic
Respiratory function after challenge.
1
Group A Group B
JANE SKINNER RASHID SIDDIQUI HARRY GRIBBIN DAVID SINCLAIR
Society. Guidelines for management of asthma in adults. I-chronic persistent asthma. BMJ 1990; 301: 651-53. 2. British Thoracic Society. Guidelines for management of asthma in adults II-acute severe asthma. BMJ 1990; 301: 797-800.