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ABSTRACT: The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept and to identify possible patient characteristics at baseline which would predict a better response to a higher than standard maintenance dose. A total of 8,424 patients with symptomatic asthma when using an inhaled corticosteroid (ICS) with or without a long-acting β(2)-agonist were randomised to budesonide/formoterol 160/4.5 μg, one (1 × 2) or two (2 × 2) inhalations b.i.d. Patients used the same inhaler as needed for symptom relief. The primary outcome variable was time to first severe asthma exacerbation. In the total study population, the time to first severe asthma exacerbation was prolonged by 18% with 2 × 2 versus 1 × 2 (hazard ratio 0.82; p = 0.03). Lung function (peak expiratory flow) was the only statistically significant predictor of a better response to 2 × 2. The mean daily ICS doses were 737 and 463 μg in the 2 × 2 and 1 × 2 groups, respectively. In a real-life setting, budesonide/formoterol maintenance and reliever therapy at the 2 × 2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load. Patients with low lung function benefited most from the higher maintenance dose.
European Respiratory Journal 09/2010; 36(3):524-30. · 5.89 Impact Factor
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ABSTRACT: The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure. In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 microg Turbuhaler, budesonide 160 microg/formoterol 4.5 microg Turbuhaler and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD(20)), exhaled nitric oxide fraction (F(eNO)), sputum eosinophils and prostaglandin D(2), and diary card recordings of symptoms (on a scale of 0-10), short-acting beta(2)-agonist use and evening forced expiratory volume in one second (FEV(1)). With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD(20): 397 (98) microg before versus 168 (82) microg after), F(eNO) (mean+/-sd 46+/-31 ppb before versus 73+/-46 ppb after) and asthma symptom score (mean+/-sd 0.39+/-0.55 before versus 0.68+/-0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV(1). Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation. Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.
European Respiratory Journal 02/2009; 33(4):747-53. · 5.89 Impact Factor
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ABSTRACT: To evaluate direct asthma-related costs in Swedish primary care in a real-life setting.
12-month open-label study.
Swedish primary care in a real-life setting.
1776 patients with persistent asthma.
Patients with persistent asthma were randomised to one of three treatments: a free adjustable combination of budesonide (100-400 microg/inhalation) and formoterol (4.5 or 9 microg/inhalation) via separate inhalers plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, two inhalations twice daily) plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, one inhalation twice daily or two inhalations once daily), for maintenance plus additional inhalations as needed. Doses depended on previous inhaled corticosteroid dose. Patients attended the clinic at 0, 1.5, and 12 months. Telephone interviews were conducted at 4, 6, 8, and 10 months.
The primary endpoint was direct asthma-related healthcare costs.
Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol (-13%, P<0.001) and fixed-dose budesonide/formoterol plus terbutaline (-20%, P<0.001). Time to first severe exacerbation did not differ significantly across treatment groups, with a mean reduction of 28% versus the free adjustable combination of budesonide and formoterol (P=0.076). Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide compared with the conventional (P<0.001).
This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy.
Respiratory medicine 11/2008; 102(10):1360-70. · 2.33 Impact Factor
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ABSTRACT: Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned. The current study compared as-needed use of a rapid-acting beta2-agonist with as-needed use of a beta2-agonist and corticosteroid combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled beta2-agonist as needed (28 males, 64 females; mean age 37 yrs; mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) > or =20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis Turbuhaler) 4.5 microg as needed (n = 47) or budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg as needed (n = 45) in a double-blind, parallel-group 24-week study. The primary variable of efficacy was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions in FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5-23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% CI -4.7- -0.7). In the budesonide/formoterol group, use of > or =4 inhalations x day(-1) of study medication was seen on 21 treatment days compared with 74 in the formoterol group. In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a beta2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown.
European Respiratory Journal 10/2006; 28(4):748-55. · 5.89 Impact Factor
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ABSTRACT: A guided, adjustable-dosing regimen with budesonide/formoterol was investigated in asthma patients. In a randomised, open, multicentre study, 1034 patients received budesonide/ formoterol (Symbicort, Turbuhaler,) 80/4.5 microg or 160/4.5 microg (depending on pre-study inhaled corticosteroid dose) two inhalations twice daily for four weeks, followed by adjustable or fixed maintenance dosing for six months. Patients receiving adjustable dosing stepped down to one inhalation twice daily if symptoms were controlled and could, if symptoms worsened, step up to four inhalations twice daily for one or two weeks according to a self-guided management plan. The primary efficacy variable was occurrence of exacerbations. Compared with fixed dosing, adjustable dosing was associated with fewer patients experiencing exacerbations (6.2% vs 9.5%, NNT 30, p<0.05), fewer daily inhalations of budesonide/formoterol (2.35 vs 3.95, p<0.001), lower costs (six-month saving Euros 98, p<0.001) and was similarly well tolerated. Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control than fixed dosing, and reduces costs.
International Journal of Clinical Practice 11/2003; 57(8):656-61. · 2.41 Impact Factor
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ABSTRACT: Patients with moderate persistent asthma (n = 523; mean FEV1 77.4%) not fully controlled with inhaled corticosteroids (ICS; 400-1000 microg/day) were randomized to receive either once-daily budesonide/formoterol (160/4.5 microg, two inhalations); or twice-daily budesonide/formoterol (160/4.5 microg, one inhalation); or budesonide (400 microg) once-daily for 12 weeks. Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening. All patients received twice-daily budesonide (200 microg) during a 2-week run-in. Compared with budesonide alone, change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group (27 and 171 min(-1), respectively; P < 0.001) and twice-daily budesonide/formoterol group (23 and 24 l min(-1), respectively; P < 0.001). Night awakenings, symptom-free days, reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide (P < or = 0.05). Similar improvements were also seen with twice-daily budesonide/formoterol (P < or = 0.05). The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide (38% and 35%, respectively; P < 0.002). All treatments were well tolerated. Budesonide/formoterol, once- or twice-daily, in a single inhaler improved asthma symptoms and exacerbations compared with budesonide. In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists, once-daily formoterol/budesonide provided sustained efficacy over 24 h, similar to twice-daily dosing.
Respiratory Medicine 04/2003; 97(4):323-30. · 2.47 Impact Factor
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ABSTRACT: To identify important factors that can influence patient compliance with prescribed medication and to elucidate aspects of asthma care from the patient's point of view.
Field investigation; the interviewer used a semi-structured questionnaire.
Patients with asthma in primary health care settings in Sweden.
A sample of 77 patients was randomly selected from 11 primary health care centres in southern Sweden; 63 of these patients participated in the study.
The factors of importance for self-reported compliance with prescribed medication were age, gender, duration of the disease, the attitude of the staff and information/education about asthma. The patients expressed important aspects of care, and these are in accordance with how an asthma nurse practice functions in Sweden.
International Journal for Quality in Health Care 11/2001; 13(5):375-83. · 1.96 Impact Factor
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ABSTRACT: Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.
European Respiratory Journal 08/2001; 18(2):262-8. · 5.89 Impact Factor
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ABSTRACT: Asthma guidelines recommend that long-acting inhaled beta-agonists should be used as maintenance therapy for patients with asthma inadequately controlled on an inhaled corticosteroid. We studied the safety and efficacy of the long-acting beta-agonist formoterol compared with terbutaline, each taken as needed, in patients with moderate to severe asthma.
Patients were taking an inhaled corticosteroid (mean dose 870 microg daily) and had a forced expiratory volume in 1 s (FEV1) of at least 50% predicted (mean 74%). Those requiring an inhaled beta-agonist three to eight times a day during the study run-in period (362 of 621 who started) were randomly assigned formoterol 4.5 microg or terbutaline 0.5 mg as needed by Turbuhaler in daily doses up to 54 microg and 6 mg, respectively, for 12 weeks in a double-blind, parallel-group study. Analyses were by intention to treat.
The 362 randomised patients (157 men, 205 women) had a mean age of 47 years. Patients taking formoterol had a longer time to their first severe asthma exacerbation (relative-risk ratio 0.55 [95% CI 0.34-0.89]), took fewer inhalations of study drug, and had larger increases in FEV1 (5%) and morning and evening peak expiratory flow (mean difference in increase 11 L/min and 8 L/min) than those taking terbutaline. No safety issues were identified.
When taken as needed, formoterol 4.5 microg provided better asthma control than terbutaline 0.5 mg in patients requiring moderate doses of relief medication despite inhaled corticosteroid treatment. Safety studies should be extended to a wider population of patients with asthma.
The Lancet 02/2001; 357(9252):257-61. · 38.28 Impact Factor
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ABSTRACT: This two-group prospective study evaluated the effect of anti-reflux surgery (fundoplication) on 24 patients with severe gastro-oesophageal reflux disease (GORD) and concomitant asthma (n=13) or chronic cough (n=11). Twenty-four hour oesophageal pH monitoring and lung function tests (FEV1, FVC) were done before and within 1 year after anti-reflux surgery. A diary was kept by the patient during the 4-week period prior to surgery and during 4-week periods 6 and 12 months postoperatively, with daily monitoring of peak expiratory flow rate, respiratory and reflux symptoms and medication. In non-asthmatic patients, coughing was reduced by 47% and 80% during the day and night, respectively, 12 months after surgery (P < 0.01). Concomitant hoarseness and expectoration were also significantly reduced (P<0.05). No effect on lung function was seen. In patients with asthma, small, non-significant reductions in asthma symptom scores and consumption of rescue medication were seen. Twenty-two patients were completely free from their GORD symptoms after surgery. In conclusion, anti-reflux surgery in patients with GORD had a more favourable effect on concomitant cough than concomitant asthma.
Respiratory Medicine 12/2000; 94(12):1166-70. · 2.47 Impact Factor
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ABSTRACT: To evaluate each item in a patient questionnaire for the purpose of investigating whether the validity of each item is acceptable.
The questionnaire was completed by the patients at an ordinary follow-up visit for their asthma, and within 1 week a nurse interviewed them by telephone with the aim of analysing the validity of each item through the use of predetermined criteria.
Patients with asthma in primary health care settings in Sweden.
Fifty-one patients were consecutively included from three different primary health care units.
Nine of 13 items had an acceptable validity. The four items that were not found to have acceptable validity were developed further.
Evaluating each item in a questionnaire by means of interviews with the specific patient population is a useful method of assuring that the intention of the patient questionnaire has been met.
International Journal for Quality in Health Care 03/2000; 12(1):19-24. · 1.96 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the efficacy of an Asthma Nurse Practice (ANP) in primary health care. A 12-month (September 1994-August 1995) open, prospective intervention study with pre- and post-test comparisons was performed on patients with asthma treated at a primary care centre in Sweden. Sixty-three patients with mild or moderate asthma participated and medication, structured follow-up and education in self-management at an ANP were assessed over a 12-month period. The main outcome measures assessed were pulmonary function, eosinophil cationic protein (ECP) in serum, respiratory symptoms, patient knowledge of asthma and emergency visits. ANP in primary health care increased patient knowledge of asthma and medication. The number of patients with nocturnal symptoms decreased significantly. Pulmonary function was improved: vital capacity (VC) 98-106, forced expiratory volume in 1 sec (FEV1) 93-100 and peak expiratory flow (PEF) 98-115% of predicted (P < 0.001). Variation in PEF fell from 21 to 12% (P < 0.001). ECP was significantly reduced. Visits to the emergency room were 60% fewer during the year of intervention (P < 0.01). In conclusion, patients attending an Asthma Nurse Practice, comprising a structured programme for asthma management, improve their knowledge and asthma control.
Respiratory Medicine 08/1999; 93(8):584-8. · 2.47 Impact Factor
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ABSTRACT: Oxis Turbuhaler is a new dry powder formulation of long-acting beta2-agonist formoterol. This study compared the efficacy and safety of regular use of the long-acting beta2-agonist formoterol and the short-acting terbutaline for 3 months in patients with asthma.
After 1-week run-in, 343 patients received either formoterol 12 microg bid (F) (delivered dose of 9 microg), terbutaline 500 microg qid (T) or placebo qid, in a parallel-group, double-blind, randomized manner. They had a mean of 61% of predicted forced expiratory volume in 1 second (FEV1) and a mean reversibility of 26%. Eighty-nine percent used inhaled corticosteroids.
During run-in mean morning peak expiratory flow (PEF L/min) for F was 366 and 348 for T, and 344 for placebo (P). The F group improved morning PEF significantly compared with P (P = .0022) and T (P = .0001). Changes from run-in were + 18, -1.5, and +5 L/min after F, T, and P, respectively. The F group was statistically significantly better than P and T in increasing evening PEF and in reducing night-time asthma. The F and T statistically significantly reduced the use of rescue medication compared with P. The bronchodilating response to the study drug and to an additional 1.25 mg terbutaline was of the same magnitude before and throughout the study. No statistically significant treatment-by-time interaction was observed (P > .20). There were no adverse effects of clinical relevance.
Formoterol Turbuhaler, 12 microg bid, was more effective than terbutaline Turbuhaler, 0.5 mg qid, and placebo. Regular use of formoterol or terbutaline did not significantly influence the response to additional inhalation of terbutaline.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 10/1998; 81(3):225-30. · 2.83 Impact Factor
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ABSTRACT: This study compared the efficacy of a low dose of formoterol Turbuhaler 6 micrograms b.i.d. (F) with that of terbutaline 0.5 mg q.i.d. (T), and placebo (P) from Turbuhaler. After a 2-week run-in, 397 adults with mild to moderate asthma were randomly allocated to one of the treatments for 12 weeks. During run-in, the mean morning peak expiratory flow (PEF) was 360 (F), 368 (T) and 367 1 min-1 (P). F was better than T (P = 0.014) and P (P = 0.0001) in improving morning PEF [mean changes from run-in: 20 (F), 9 (T), and 21 min-1 (P)]. F was statistically significantly more effective than either T or P in reducing asthma symptoms. F gave also statistically significantly higher evening PEF and less use of rescue medication than P. Bronchodilator response to study drugs and additional 1.25 mg terbutaline was similar before and after the 12-week treatment period. There were no adverse effects of clinical relevance. In conclusion, formoterol Turbuhaler, 6 micrograms b.i.d. was more effective in improving PEF and offered better asthma control than either terbutaline Turbuhaler, 0.5 mg q.i.d. or placebo. Regular use of formoterol did not reduce the bronchodilator response to additional terbutaline. There were no clinically relevant adverse effects.
Respiratory Medicine 09/1998; 92(8):1040-5. · 2.47 Impact Factor
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Lakartidningen 10/1997; 94(37):3135-9.
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Lakartidningen 06/1997; 94(19):1817-9.
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ABSTRACT: Antihistamines have been shown to be effective in patients with allergic asthma, but their role in chronic and more severe asthma is uncertain.
To evaluate whether loratadine, a selective H1 receptor antagonist, given as an adjunct to standard asthma medication would have any effect in patients with moderate-to-severe asthma.
Thirty-five patients with moderate-to-severe asthma, most receiving inhaled steroids, were enrolled in this double-blind, crossover study. In addition to their maintenance therapy patients received either loratadine, 20 mg once daily, or placebo for 4 weeks before crossing over to the other preparation for a further 4 weeks. Variables of efficacy were daily and nocturnal respiratory symptoms, lung function (PEF, FEV1, FVC), and bronchodilator use.
Three subjects were withdrawn from the study because of deteriorating asthma. There was a trend in favor of loratadine treatment with regard to global assessment of drug efficacy but the difference was not statistically significant. There was no objective improvement in asthma control comparing loratadine with placebo but if each treatment week were compared with the run-in period, PEF was significantly (P < .01) improved during the initial phase of loratadine treatment. This effect gradually decreased with time, suggesting tolerance to any bronchodilatory effect of the antihistamine.
Loratadine, given as an adjunct to standard asthma therapy, has little if any role to play in the treatment of moderate-to-severe asthma.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 09/1995; 75(3):287-9. · 2.83 Impact Factor
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ABSTRACT: The relative dose potency of cumulative doses of terbutaline sulfate inhaled via Turbuhaler and via a pressurized metered dose inhaler was estimated with respect to lung efficacy and systemic effect.
The study was an open, crossover, randomized, multicenter study including 31 adult patients with asthma [forced expiratory volume in one second (FEV1), 65% of predicted]. The patients inhaled terbutaline doses of 0.125, 0.125, 0.25, 0.5, 1.0, and 2.0 mg (a total of 4 mg) at 30-minute intervals. Lung function [FEV1, forced vital capacity (FVC), forced expiratory flow at 75% of FVC (FEF75%), and peak expiratory flow (PEF)], and systemic effect variables (serum potassium, tremor, pulse, blood pressure) were monitored prior to the first inhalation and 15 to 25 minutes after each inhaled dose.
The mean relative dose potency of terbutaline inhaled via Turbuhaler compared with pressurized metered dose inhaler was 1.5 (95% confidence interval: 1.2 to 1.8) with respect to FEV1 and serum potassium, respectively. The corresponding relative dose potencies for PEF, FVC, and FEF75% were 1.0, 1.2, and 1.6, respectively, with no statistically significant difference between the two devices. No differences between the devices were evident with regard to blood pressure and pulse.
The results suggest that Turbuhaler is more efficient in the delivery of inhaled terbutaline to the lungs compared with the conventional pressurized metered dose inhaler.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 05/1995; 74(4):328-32. · 2.83 Impact Factor
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Lakartidningen 09/1992; 89(32-33):2579-80.
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ABSTRACT: It is believed that GER can trigger asthma by the stimulation of acid-sensitive receptors in the esophagus. The aim of this study was to determine whether esophageal acid stimulation in asthmatic patients can provoke clinically detectable bronchospasm and if a possible response is correlated to bronchial reactivity. Eight patients with chronic asthma and GER disease were investigated on three occasions with a histamine challenge test followed by acid provocation of the esophagus. Assessment of bronchial function was made by FEV1, chest auscultation, and respiratory symptoms. While symptoms and signs of bronchoconstriction induced by esophageal acid stimulation were not detected clinically on any occasion, there was a significant correlation between histamine reactivity and the subclinical bronchospasm following acid provocation. It is concluded that esophageal acid stimulation during daytime in the majority of asthmatic patients is not a strong and immediate trigger of asthma.
Chest 12/1989; 96(5):995-8. · 5.25 Impact Factor
