1099
Salmeterol SIR,-Dr Britton and colleagues (Feb 2, p 300) miss the point of study (Dec 1, p 1338), which was that salmeterol is able to abolish the sequelae of allergen challenge at 32 and 34 h after allergen exposure, a time when other known actions of salmeterol such as bronchodilatation and functional antagonism of bronchoconstriction could not be shown. We would not disagree that salmeterol may not have abolished completely the late-phase responses between 1-5 and 9-5 h after allergen exposure. However, this result is similar to that with corticosteroids where late-phase responses are only attenuated 7 h after allergen, but inhibited our
completely at 30 h.l The action of salmeterol on this model asthma is remarkably similar to the action of corticosteroids.
of
Whether the effects of salmeterol at 32 and 34 h should be called
anti-inflammatory is debatable, but they would seem to be important additional actions of salmeterol distinct from immediate bronchodilatation and antagonism of bronchoconstrictor stimuli. Such effects on late-phase responses are often interpreted as indicative of "anti-inflammatory" or "prophylactic anti-asthmatic" activity and correlate with a favourable clinical responsePerhaps the term "anti-asthmatic" would be preferable to "antiinflammatory" until the mechanism of this effect of salmeterol becomes clear. The published data are compatible with the hypothesis that such an anti-asthmatic action of salmeterol is clinically valuable.3 In a
double-blind, placebo-controlled,
crossover
study, significant
clinical and objective benefit from salmeterol was observed; these effects carried over into the washout period after the drug had been stopped.3 Such actions are similar to those of corticosteroids.4 There are at least three peer reviewed articles in reputable journals, other than ours, which present original data on different 6 aspects of the actions of salmeterol. 3,5,6 These provide good evidence of efficacy for bronchodilatation,5 relief of nocturnal asthma symptoms,6 and improvement in control of day-time
variations in the prevalence of reversible airways obstruction in genetically similar populations living in different environments. In an exercise-challenge study of 2055 Zimbabwean primary-school children living in three different areas,4 we found the prevalence of reversible airways obstruction to be 5-8% in richer urban children, 3-1% in poorer urban children, and 0-1% in rural children. Such differences can only be explained by environmental factors. While anti-asthma treatment is available in Zimbabwe and is more common in urban rather than rural populations, its use is less widespread than in industrialised countries. Few children would have received &bgr;2-agonists regularly; only 7 of the urban sample of 1368 children were known by their teachers to be asthmatic. The hypothesis that &bgr;2-agonists contribute to observed increases in asthma prevalence and severity deserves consideration, but should be assessed in the light of epidemiological evidence. We believe that &bgr;2-agonist use in Zimbabwean children is unlikely to have been sufficiently widespread to have contributed significantly to the prevalence of reversible airways obstruction found in our urban sample. 4 Witley Road, London N 19 5SQ, UK University of Zimbabwe,
PAUL NEILL
Harare, Zimbabwe
1. Burr M, Butland B, King S, Vaughan-Williams E. Changes in asthma prevalence: two surveys 15 years apart. Arch Dis Child 1989; 64: 1452-56. 2. Bumey PG, Chinn S, Rona RJ. Has the prevalence of asthma increased in children? Evidence from the national study of health and growth 1973-86. Br MedJ 1990; 300: 1306-10. 3. Van Niekerk CH, Weinberg EG, Shore MC, Heese H de V, Van Schalkwyk DJ. Prevalence of asthma: a comparative study of urban and rural Xhosa children. Clin Allergy 1979; 9: 319-24. 4. Keeley DJ, Neill P, Gallivan S. A comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children. Thorax (in press).
Acupuncture for asthma
symptoms.3
SiR,—The Californian acupuncturist you mention in your Feb 9
Chest Medical Unit,
needs to learn a few facts about the treatment of asthma. Pneumothorax is a fairly common complication when a long needle is used. Moxibustion or acupuncture with a short needle would have been a better choice.1,2 note
Papworth Hospital,
Cambridge CB3 8RE,
DUNCAN KEELEY
O. P. TWENTYMAN
UK
Southampton General Hospital, Southampton
J. P. FINNERTY
1. Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol 1987; 79: 734-40. 2. Durham SR. Late asthmatic responses. Respir Med 1990; 84: 263-68. 3. Ullman A, Hedner J, Svedmyr N. Inhaled salmeterol and salbutamol m asthmatic patients an evaluation of asthma symptoms and possible development of tachyphylaxis Am Rev Respir Dis 1990; 142: 571-75. 4. Kraan J, Koeter GH, van der Mark TW, Sluiter HJ, De Vries K. Changes in bronchial hyperreactivity induced by 4 weeks of treatment with anti-asthmatic drugs in patients with allergic asthma a comparison between budesonide and terbutaline. J Allergy Clin Immunol 1985; 76: 628-36. 5. Ullman A, Svedmyr N. Salmeterol, a new long acting inhaled beta-2-adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax 1988; 43: 674-78. 6 Fitzpatrick MF, Mackay T, Driver H, Douglas NJ. Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled &bgr;2 agonist. Br Med J 1990, 301: 1365-68.
Asthma paradox SIR,-Dr Page (March 23, p 717) seeks to explain the paradox of worldwide increases in morbidity and mortality from asthma despite advances in understanding of pathogenesis, improved clinical awareness of the disease, and more widespread application of apparently effective treatments. The same environmental factors that are responsible for increased asthma prevalence are also likely to be responsible for increased severity. It is impossible to make an entirely clear distinction between prevalence and severity; bronchial reactivity is a continuous variable and the definition of asthma, whether clinical or physiological, involves drawing an arbitrary line on a continuum between normal and pathological. There is good epidemiological evidence of increasing asthma prevalence in the industrialised world,l,2 while studies in developing countries3 including our own in Zimbabwe’ have shown large
6744 Clayton, St Louis, Missouri 63117, USA 1. Ishida Y.
YASUO ISHIDA
Acupuncture today. South Med J 1988; 81: 885-87. Med J 1989; 82: 499-505.
2. Ishida Y. Oriental medicine today. South
Terbutaline
powder in acute bronchial obstruction
SiR,—p-agonists presented as pressurised aerosols containing fluorocarbon propellants have long been first-choice treatment in obstructive lung diseases. Multidose powder inhalers containing pure drug (and thus "environmentally friendly") are now on the market, but their use in the treatment of patients with acute bronchial obstructive lung disease is controversial.1 The major concern is that patients might not be able to produce a sufficient inspiratory flow rate to benefit. 1,2 We have done an open, randomised study in patients attending the emergency room with acute bronchial obstruction. 68 patients were treated with terbutaline powder (’Bricanyl Turbuhaler’) 2-5 mg (five 0-5 mg doses) twice or with the conventional pressurised aerosol (’Bricanyl’) 2-5 mg (ten 0-25 doses) twice with the 750 ml ’Nebuhaler’ spacer device. 6 patients were excluded because they had irreversible bronchial obstruction and showed no more than a 10% increase in forced expiratory volume in 1 s (FEV1) on the day of admission and at follow-up within 2 months. Lung function was assessed on admission (baseline) and after inhalation of terbutaline sulphate powder or aerosol 25 min after admission. 33 patients (11I men, 22 women, mean age 50 years [range 19-88]) were treated with the powder and 29 (11 men, 18 women, mean age 51 years [range 18-85]) were treated with the conventional aerosol. The two groups of patients were comparable in respect of use of previous
Salmeterol SIR,-Dr Britton and colleagues (Feb 2, p 300) miss the point of study (Dec 1, p 1338), which was that salmeterol is able to abolish the sequelae of allergen challenge at 32 and 34 h after allergen exposure, a time when other known actions of salmeterol such as bronchodilatation and functional antagonism of bronchoconstriction could not be shown. We would not disagree that salmeterol may not have abolished completely the late-phase responses between 1-5 and 9-5 h after allergen exposure. However, this result is similar to that with corticosteroids where late-phase responses are only attenuated 7 h after allergen, but inhibited our
completely at 30 h.l The action of salmeterol on this model asthma is remarkably similar to the action of corticosteroids.
of
Whether the effects of salmeterol at 32 and 34 h should be called
anti-inflammatory is debatable, but they would seem to be important additional actions of salmeterol distinct from immediate bronchodilatation and antagonism of bronchoconstrictor stimuli. Such effects on late-phase responses are often interpreted as indicative of "anti-inflammatory" or "prophylactic anti-asthmatic" activity and correlate with a favourable clinical responsePerhaps the term "anti-asthmatic" would be preferable to "antiinflammatory" until the mechanism of this effect of salmeterol becomes clear. The published data are compatible with the hypothesis that such an anti-asthmatic action of salmeterol is clinically valuable.3 In a
double-blind, placebo-controlled,
crossover
study, significant
clinical and objective benefit from salmeterol was observed; these effects carried over into the washout period after the drug had been stopped.3 Such actions are similar to those of corticosteroids.4 There are at least three peer reviewed articles in reputable journals, other than ours, which present original data on different 6 aspects of the actions of salmeterol. 3,5,6 These provide good evidence of efficacy for bronchodilatation,5 relief of nocturnal asthma symptoms,6 and improvement in control of day-time
variations in the prevalence of reversible airways obstruction in genetically similar populations living in different environments. In an exercise-challenge study of 2055 Zimbabwean primary-school children living in three different areas,4 we found the prevalence of reversible airways obstruction to be 5-8% in richer urban children, 3-1% in poorer urban children, and 0-1% in rural children. Such differences can only be explained by environmental factors. While anti-asthma treatment is available in Zimbabwe and is more common in urban rather than rural populations, its use is less widespread than in industrialised countries. Few children would have received &bgr;2-agonists regularly; only 7 of the urban sample of 1368 children were known by their teachers to be asthmatic. The hypothesis that &bgr;2-agonists contribute to observed increases in asthma prevalence and severity deserves consideration, but should be assessed in the light of epidemiological evidence. We believe that &bgr;2-agonist use in Zimbabwean children is unlikely to have been sufficiently widespread to have contributed significantly to the prevalence of reversible airways obstruction found in our urban sample. 4 Witley Road, London N 19 5SQ, UK University of Zimbabwe,
PAUL NEILL
Harare, Zimbabwe
1. Burr M, Butland B, King S, Vaughan-Williams E. Changes in asthma prevalence: two surveys 15 years apart. Arch Dis Child 1989; 64: 1452-56. 2. Bumey PG, Chinn S, Rona RJ. Has the prevalence of asthma increased in children? Evidence from the national study of health and growth 1973-86. Br MedJ 1990; 300: 1306-10. 3. Van Niekerk CH, Weinberg EG, Shore MC, Heese H de V, Van Schalkwyk DJ. Prevalence of asthma: a comparative study of urban and rural Xhosa children. Clin Allergy 1979; 9: 319-24. 4. Keeley DJ, Neill P, Gallivan S. A comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children. Thorax (in press).
Acupuncture for asthma
symptoms.3
SiR,—The Californian acupuncturist you mention in your Feb 9
Chest Medical Unit,
needs to learn a few facts about the treatment of asthma. Pneumothorax is a fairly common complication when a long needle is used. Moxibustion or acupuncture with a short needle would have been a better choice.1,2 note
Papworth Hospital,
Cambridge CB3 8RE,
DUNCAN KEELEY
O. P. TWENTYMAN
UK
Southampton General Hospital, Southampton
J. P. FINNERTY
1. Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol 1987; 79: 734-40. 2. Durham SR. Late asthmatic responses. Respir Med 1990; 84: 263-68. 3. Ullman A, Hedner J, Svedmyr N. Inhaled salmeterol and salbutamol m asthmatic patients an evaluation of asthma symptoms and possible development of tachyphylaxis Am Rev Respir Dis 1990; 142: 571-75. 4. Kraan J, Koeter GH, van der Mark TW, Sluiter HJ, De Vries K. Changes in bronchial hyperreactivity induced by 4 weeks of treatment with anti-asthmatic drugs in patients with allergic asthma a comparison between budesonide and terbutaline. J Allergy Clin Immunol 1985; 76: 628-36. 5. Ullman A, Svedmyr N. Salmeterol, a new long acting inhaled beta-2-adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. Thorax 1988; 43: 674-78. 6 Fitzpatrick MF, Mackay T, Driver H, Douglas NJ. Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled &bgr;2 agonist. Br Med J 1990, 301: 1365-68.
Asthma paradox SIR,-Dr Page (March 23, p 717) seeks to explain the paradox of worldwide increases in morbidity and mortality from asthma despite advances in understanding of pathogenesis, improved clinical awareness of the disease, and more widespread application of apparently effective treatments. The same environmental factors that are responsible for increased asthma prevalence are also likely to be responsible for increased severity. It is impossible to make an entirely clear distinction between prevalence and severity; bronchial reactivity is a continuous variable and the definition of asthma, whether clinical or physiological, involves drawing an arbitrary line on a continuum between normal and pathological. There is good epidemiological evidence of increasing asthma prevalence in the industrialised world,l,2 while studies in developing countries3 including our own in Zimbabwe’ have shown large
6744 Clayton, St Louis, Missouri 63117, USA 1. Ishida Y.
YASUO ISHIDA
Acupuncture today. South Med J 1988; 81: 885-87. Med J 1989; 82: 499-505.
2. Ishida Y. Oriental medicine today. South
Terbutaline
powder in acute bronchial obstruction
SiR,—p-agonists presented as pressurised aerosols containing fluorocarbon propellants have long been first-choice treatment in obstructive lung diseases. Multidose powder inhalers containing pure drug (and thus "environmentally friendly") are now on the market, but their use in the treatment of patients with acute bronchial obstructive lung disease is controversial.1 The major concern is that patients might not be able to produce a sufficient inspiratory flow rate to benefit. 1,2 We have done an open, randomised study in patients attending the emergency room with acute bronchial obstruction. 68 patients were treated with terbutaline powder (’Bricanyl Turbuhaler’) 2-5 mg (five 0-5 mg doses) twice or with the conventional pressurised aerosol (’Bricanyl’) 2-5 mg (ten 0-25 doses) twice with the 750 ml ’Nebuhaler’ spacer device. 6 patients were excluded because they had irreversible bronchial obstruction and showed no more than a 10% increase in forced expiratory volume in 1 s (FEV1) on the day of admission and at follow-up within 2 months. Lung function was assessed on admission (baseline) and after inhalation of terbutaline sulphate powder or aerosol 25 min after admission. 33 patients (11I men, 22 women, mean age 50 years [range 19-88]) were treated with the powder and 29 (11 men, 18 women, mean age 51 years [range 18-85]) were treated with the conventional aerosol. The two groups of patients were comparable in respect of use of previous
