Regular inhaled beta-agonist treatment in bronchial asthma

89 subjects with stable asthma took part in a double-blind, placebo-controlled, randomized, crossover study of the effects of regular versus on-demand inhaled bronchodilator therapy. The subjects inhaled fenoterol or placebo by a dry powder delivery system for 24 weeks. Control of asthma was judged by daily morning and evening peak expiratory flow rates, symptom diaries, use of additional inhaled bronchodilator, and requirement for short courses of prednisone. Of 64 subjects who completed the trial, 57 showed a clear difference in degree of control of asthma between the fenoterol and placebo periods: in 17 (30% [95% confidence interval 18.4-43.4%]) asthma was better controlled during regular inhaled bronchodilator treatment, whereas in 40 (70% [56.6-81.6%]) control was better during placebo treatment with bronchodilator for symptom relief only. Mean airway responsiveness to methacholine increased slightly during the fenoterol period. The adverse effect of regular bronchodilator inhalation occurred not only among subjects who used a bronchodilator as sole treatment (2 were better and 10 were worse during regular bronchodilator treatment) but also among those who took inhaled corticosteroids (14 were better and 29 were worse). Thus, regular inhalation of a beta-sympathomimetic agent was associated with deterioration of asthma control in the majority of subjects. The trends to use of regular, higher doses or longer-acting inhaled beta-sympathomimetic treatment may be an important causal factor in the worldwide increase in morbidity from asthma.

[1]  D. Knapp,et al.  Asthma drug therapy trends in the United States, 1972 to 1985. , 1987, The Journal of allergy and clinical immunology.

[2]  S. Larsson,et al.  Formoterol, a new long-acting bronchodilator for inhalation. , 1989, The European respiratory journal.

[3]  H. Sluiter,et al.  Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline. , 1985, The Journal of allergy and clinical immunology.

[4]  H. Anderson.  Increase in hospital admissions for childhood asthma: trends in referral, severity, and readmissions from 1970 to 1985 in a health region of the United Kingdom. , 1989, Thorax.

[5]  T. E. V. Metre.  Adverse effects of inhalation of excessive amounts of nebulized isoproterenol in status asthmaticus. , 1969 .

[6]  A. Ullman,et al.  Salmeterol, a new long acting inhaled beta 2 adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients. , 1988, Thorax.

[7]  N. Pride,et al.  Use of exercise challenge to investigate possible tolerance to beta-adrenoceptor stimulation in asthma. , 1978, British journal of diseases of the chest.

[8]  S. Holgate,et al.  The effect of an increase in inhaled allergen dose after rimiterol hydrobromide on the occurrence and magnitude of the late asthmatic response and the associated change in nonspecific bronchial responsiveness. , 1989, The American review of respiratory disease.

[9]  R. Rothwell,et al.  A comparison between aerosol and inhaled powder administration of fenoterol in adult asthmatics. , 1981, The New Zealand medical journal.

[10]  J. Wilson,et al.  HAS THE CHANGE TO BETA-AGONISTS COMBINED WITH ORAL THEOPHYLLINE INCREASED CASES OF FATAL ASTHMA? , 1981, The Lancet.

[11]  A. Tattersfield,et al.  Airway response to salbutamol: effect of regular salbutamol inhalations in normal, atopic, and asthmatic subjects. , 1982, Thorax.

[12]  T. Higenbottam,et al.  HAS THE MANAGEMENT OF ASTHMA IMPROVED? , 1987, The Lancet.

[13]  J. Prior,et al.  High-dose inhaled terbutaline in the management of chronic severe asthma: comparison of wet nebulisation and tube-spacer delivery. , 1982, Thorax.

[14]  F. Hargreave,et al.  Bronchial reactivity to inhaled histamine: a method and clinical survey , 1977, Clinical allergy.

[15]  A. Rebuck,et al.  Asthma: 2. Trends in pharmacologic therapy. , 1987, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[16]  M. Sears,et al.  Use of anti-asthma drugs in New Zealand. , 1987, Thorax.

[17]  P. W. Kent,et al.  The composition of tracheal mucus and the nervous control of its secretion in the cat , 1975, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[18]  R. Schoeffel,et al.  Effect of aerosol fenoterol on the severity of bronchial hyperreactivity in patients with asthma. , 1983, Thorax.

[19]  J. Allegra,et al.  Paradoxic bronchospasm after inhalation of isoptroterenol. , 1976, Chest.

[20]  C. Newth,et al.  Viewpoint: untoward effects of beta-adrenoceptor agonists in asthma. , 1990, The European respiratory journal.

[21]  N. Pearce,et al.  PRESCRIBED FENOTEROL AND DEATH FROM ASTHMA IN NEW ZEALAND, 1981-83; CASE-CONTROL STUDY , 1989, The Lancet.

[22]  T. Clark,et al.  Can the morbidity of asthma be reduced by high dose inhaled therapy? A prospective study. , 1990, Respiratory medicine.

[23]  A. Woolcock.  Inhaled drugs in the prevention of asthma. , 1977, The American review of respiratory disease.

[24]  R. Reisman,et al.  Asthma induced by adrenergic aerosols. , 1970, Chest.

[25]  Eisenstadt Ws,et al.  The adverse effect of adrenergic aerosols in bronchial asthma. , 1969 .

[26]  D. Stǎnescu.  High doses of sympathomimetics in severe bronchial asthma. , 1989, The European respiratory journal.

[27]  C. van Weel,et al.  Increased bronchial hyperresponsiveness after inhaling salbutamol during 1 year is not caused by subsensitization to salbutamol. , 1990, The Journal of allergy and clinical immunology.

[28]  M. Sears,et al.  International trends in asthma mortality: 1970 to 1985. , 1988, Chest.

[29]  T J Clark,et al.  Regular versus symptomatic aerosol bronchodilator treatment of asthma. , 1981, British journal of diseases of the chest.

[30]  V. Tsara,et al.  Intermittent and continuous salbutamol rotacaps inhalation in asthmatic patients. , 1988, Respiration; international review of thoracic diseases.

[31]  S. Holgate,et al.  A self management plan in the treatment of adult asthma. , 1989, Thorax.