In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.
Salmeterol is a new inhaled 2 adrenoceptor agonist, which has been shown in animal experiments to produce a more prolonged bronchodilator effect than currently available f2 adrenoceptor agonists. It was studied in eight adult asthmatic patients. Each patient received on separate test days salbutamol 200 pg and salmeterol 50, 100, and 200 pg according to a randomised, double blind, crossover design. FEV1, peak expiratory flow (PEF), heart rate, blood pressure, and tremor were recorded in the clinic for six hours after drug inhalation; PEF was recorded for a further six hours at home. All three doses ofsalmeterol produced peak increases in FEV1 (mean 0*5-048 1) and PEF (71-100 I/min) similar to those produced by salbutamol 200 yg (051 and 74 1/min). After salbutamol FEVy and PEF had returned to baseline within six hours, but after all three doses of salmeterol more than half of the maximum bronchodilator effect remained after 12 hours. The effects ofsalbutamol and the two lower doses ofsalmeterol (50 and 100 ug) on cardiovascular measurements and on tremor were similar, whereas after salmeterol 200 pg there was a small decrease in diastolic blood pressure and an increase in heart rate and tremor. Thus inhaled salmeterol has a long acting bronchodilator action in asthmatic patients. This effect may be of value in the treatment of asthma, particularly in patients with nocturnal symptoms.
Background-Formoterol and salmeterol are new long acting P2 adrenoceptor agonists. The maximum relaxant effect, potency and functional antagonism against carbachol induced contraction for salmeterol, formoterol and salbutamol have been compared in the guinea pig isolated trachea. In addition, the possibility of inducing a non-fl adrenoceptor mediated relaxation by salmeterol was studied. Methods-Concentration response experiments were conducted with isolated tracheal preparations (n = 4-6 in all experiments), precontracted by carbachol to cause either 40% (60 nmol/l), 80% (0.3,umol/l) 75% (5%) v 71% (12%) of precontraction). In the non-cumulative experiments, formoterol displayed more relaxant effect than salmeterol (remaining active tension: 51% (6%) v 65% (6%) of precontraction). Finally, formoterol significandy relaxed salmeterol relaxed airways (relaxant effect: 22% (8%) of precontraction) whereas there was no significant response to salmeterol in formoterol relaxed airways (relaxant effect: 5% (12%) of precontraction). Conclusions-In the guinea pig isolated trachea, formoterol and salbutamol produce more relaxant effect than salineterol, suggesting that salmeterol is a partial #2 agonist. Very high concentrations of salmeterol may induce non-fl adrenoceptor mediated relaxation. Formoterol is more potent than both salbutamol and salmeterol. There is no pronounced difference in the magnitude of antagonism against carbachol induced contractions between salmeterol, formoterol, and salbutamol. (Thorax 1993;48:547-553) In acute severe asthma there is a high level of airway smooth muscle contraction.' 2 Clinical trials of fl2 adrenoceptor agonists are, however, often performed in subjects with mild to moderate asthma3-5 and in vitro studies often examine the relaxant effect of /32 agonists on airway smooth muscle at a single moderate level of precontraction.6-l0The /2 agonists salmeterol and formoterol produce bronchodilation of long duration in human subjects3-5 11-13 as well as in guinea pig isolated airways.67 1O1F17 It is not known whether the rank order of the maximum relaxant effect and potency of salmeterol and formoterol differ at various levels of airway smooth muscle contraction and are different from salbutamol.
The Formoterol and Corticosteroids Establishing Therapy (FACET) study has provided the first opportunity to examine the long-term effects of inhaled steroids and long-acting b 2 -agonists on asthma-specific quality of life. The objectives of the present study were to: evaluate the effects of long-term (1 yr) formoterol and increasing doses of budesonide on asthma quality of life; 2) to determine whether initial improvements in quality of life are sustained when improvements in clinical indices persist; and 3) to evaluate the long-term relationship between changes in clinical indices and changes in quality of life.Of the 852 asthmatic adults enrolled, 470 from five countries participated in this quality of life evaluation. After a 4-week run-in on 1,600 mg budesonide, patients were randomized to either 200 mg (Bud200) or 800 mg budesonide (Bud800) in combination with either 24 mg formoterol (F) or placebo daily for 1 yr. The Asthma Quality of Life Questionnaire (AQLQ) was completed and conventional clinical indices measured at enrolment and randomization and on seven occasions during the following 12 months.During the run-in, there was an improvement in AQLQ score (changes (D) in overall score<0.50; p<0.0001). After randomization, there was a further improvement in the Bud800+F group (D=0.21; p=0.028). One month post-randomization, improvements in all groups stabilized and were sustained throughout the 12 months in a pattern very similar to that observed for the conventional clinical indices. The correlation of individual patient changes in clinical indices and changes in AQLQ score during the 12-month randomized period were weak to moderate (maximum r=0.51).Improvements in quality of life, which were greatest in the 800 mg budesonide plus 24 mg formoterol group, were sustained throughout the 12 months in a similar manner to the clinical indices. Long-term changes in conventional clinical indices cannot be used to predict the effect of treatment on individual patient experience. Eur Respir J 1999; 14: 1038±1043. Supported by Astra Draco AB, Sweden.The primary hypothesis tested in the Formoterol and Corticosteroids Establishing Therapy (FACET) study was that the addition of regular treatment with the long-acting inhaled b 2 -agonist, formoterol, to a lower and higher dose of the inhaled glucocorticosteroid budesonide would result in improved control of symptoms and lung function, without any long-term deterioration in the control of asthma over a 12-month period [1]. The results showed that the addition of formoterol to both doses of inhaled steroid improved asthma symptoms and resulted in a decrease in the rate of severe and mild asthma exacerbations.A secondary objective of the FACET study was to determine the effect of these interventions on health-related quality of life (HRQL). Although short-term studies have shown that both inhaled steroids and long-acting b 2 -agonists are associated with an improvement in asthma-specific quality of life [2±8], there have been no longer-term studies ($1 yr) of th...
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