Nitrate leaching, yields and carbon sequestration after noninversion tillage, catch crops, and straw retention.

Crop management factors, such as tillage, rotation, and straw retention, need to be long-term to allow conclusions on effects on crop yields, nitrate leaching, and carbon sequestration. In 2002, two field experiments, each including four cash crop rotations, were established on soils with 9 and 15% clay, under temperate, coastal climate conditions. Direct drilling and harrowing to two different depths were compared to plowing with respect to yield, nitrate N leaching, and carbon sequestration. For comparison of yields across rotations, grain and seed dry matter yields for each crop were converted to grain equivalents (GE). Leaching was compared to yields by calculating yield-scaled leaching (YSL, g N kg GE), and N balances were calculated as the N input in manure minus the N output in products removed from the fields. Direct drilling reduced yields, but no effect on leaching was found. Straw retention did not significantly increase yields, nor did it reduce leaching, while fodder radish ( L.) as a catch crop was capable of reducing nitrate leaching to a low level. Thus, YSL of winter wheat ( L.) was higher than for spring barley ( L.) grown after fodder radish due to the efficient catch crop. Soil organic carbon (SOC) did not increase significantly after 7 yr of straw incorporation or noninversion tillage. There was no correlation between N balances calculated for each growing season and N leaching measured in the following percolation period.

The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.

The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment

Formoterol inhaled as dry powder or via pressurized metered-dose inhaler in a cumulative dose-response study.

Formoterol administered by a dry-powder (DP) capsule inhaler was compared with a pressurized metered-dose inhaler (pMDI) with regard to bronchodilating and systemic effects. The study used a double-blind, crossover, double-dummy technique. Twelve patients with moderate reversible asthma in a stable phase were examined on two separate study days, and the inhalers were given in randomized order. After baseline measurements, increasing doses of formoterol were given at intervals of 75 min. FEV1 and heart rate and tremor measurements were repeated after each dose, and the doses were 12 + 12 + 24 + 48 micrograms, giving a total dose of 96 micrograms. The peak expiratory flow rate (PEFR) was recorded in the morning before the first dose, after the last dose, and then repeatedly at home until 19 h after the last dose. There was an equal increase in ventilatory capacity at each dose level, independent of inhaler device. Repeated PEFR measurements after the last dose did not reveal any differences in duration of effect. There was a slight but statistically significant increase in heart rate and tremor after the highest doses of the DP formulation compared to the pMDI. These systemic effects can probably be explained by the reduced oral deposition of the aerosol caused by using a spacer. This study indicates that the DP and pMDI formulations of formoterol are equipotent in bronchodilation.

Efficacy and tolerance of a 12-week treatment with inhaled formoterol in patients with reversible obstructive lung disease.

Formoterol, a new beta 2-agonist, and salbutamol were given as aerosols twice and four times daily, respectively, to patients with reversible obstructive lung disease. The study was controlled and double blind, and continued for 12 weeks. Ninety-nine patients from five study centers were included and 89 patients could be properly evaluated. The formoterol-treated patients used significantly less rescue medicine (salbutamol aerosol) and had higher morning PEF values. For the other efficacy variables (daytime FEV1.0, evening PEF, patient and investigator global evaluations, night sleeping time) and tolerance (side effects noted by patients, blood and urine laboratory values, ECG, patient and investigator global evaluation), there were no significant differences between the formoterol- and the salbutamol-treated groups.

Time course and duration of bronchodilatation with formoterol dry powder in patients with stable asthma.

BACKGROUND: Formoterol, a new beta 2 agonist, is long and fast acting when given as an aerosol. The aim was to determine the onset and duration of bronchodilatation with formoterol as a dry powder compared with salbutamol dry powder and with placebo. METHODS: Fifteen patients with stable asthma with a reversibility of 15% or more participated in a double blind, within patient study. On five different days the patients received formoterol 6 micrograms, 12 micrograms, or 24 micrograms, salbutamol 400 micrograms, or placebo in random order. Forced expiratory volume in one second (FEV1) was measured 10 minutes before, 30 minutes after, and then every hour for up to 12 hours after treatment. Specific airway resistance (sRaw) and specific airway conductance (sGaw) were measured immediately before and one, three, five, 10, 15, and 30 minutes after treatment. RESULTS: Formoterol 12 micrograms and 24 micrograms caused bronchodilatation as rapidly as salbutamol 400 micrograms. Peak values were not significantly different in the active treatments. The duration of action, calculated as median time with 20% or more of the maximum achieved increase in FEV1, was sustained for 9 hours and 16 minutes with salbutamol 400 micrograms, for 9 hours and 45 minutes with formoterol 6 micrograms, for 11 hours and 22 minutes with formoterol 12 micrograms, and for 11 hours and 42 minutes with formoterol 24 micrograms. CONCLUSIONS: Formoterol as a dry powder at doses of 12 micrograms and 24 micrograms produces a rapid onset of action and has a bronchodilator effect comparable with salbutamol 400 micrograms as a dry powder. The bronchodilatation was sustained for 11-12 hours. Formoterol 6 micrograms caused similar bronchodilatation but more slowly and for a shorter time.

Rapid onset of action of inhaled formoterol in asthmatic patients.

Twelve patients with stable asthma (mean age, 39 years; asthma duration, 11 years; mean forced expiratory volume in 1 s, 65 percent of predicted; and reversibility, 31 percent) were studied in a double-blind crossover trial. The patients were studied during three test days. Airway resistance and specific airway conductance (Raw and SGaw) were measured using a body plethysmograph and pulse rate, blood pressure, tremor, and subjective effects were recorded before and 1, 3, 5, 10, 15, 30, 60, and 120 min after the test doses. A baseline Raw variability of +/- 20 percent was allowed between the test days. Formoterol 12 micrograms, 24 micrograms, and terbutaline 500 micrograms were given in a spacer (Nebulator) in a randomized double-blind crossover manner as two puffs with a 30-s interval in between. The effect of formoterol 12 micrograms on Raw was significantly better than terbutaline after 3, 5, 10, 60, and 120 min. Formoterol 24 micrograms was significantly better than terbutaline as soon as 3 min after inhalation and at every point in time after that. Formoterol 24 micrograms tended to be better than formoterol 12 micrograms but the differences were not significant at any point in time. All three treatments were well-tolerated. No differences were observed for pulse rate, blood pressure, tremor, or palpitations. The overall onset of bronchodilatation after formoterol 12 and 24 micrograms was faster than after terbutaline 500 micrograms. The tolerability of formoterol was good.

Formoterol, a new long-acting beta 2 agonist, inhaled twice daily, in stable asthmatic subjects.

STUDY OBJECTIVE: To determine whether formoterol, a new beta 2 agonist with experimentally documented long duration, is clinically more effective than salbutamol in the maintenance treatment of chronic asthma. DESIGN: Randomized double-blind between-patient comparison between treatment with formoterol and with salbutamol during four weeks. SETTING: Asthma/allergy department in a university hospital. PATIENTS: Thirty-seven patients with chronic stable asthma, who during a two-week run-in period with inhaled salbutamol, 4 x 100 micrograms twice a day, used at least four additional doses (100 micrograms each) daily, were randomly assigned to use either formoterol or salbutamol. Thirty-five patients were evaluated for efficacy. One early withdrawal and one dropout were found in the salbutamol group. The groups were similar with respect to demographic data and baseline lung function. INTERVENTIONS: During the four-week study period, the patients used either formoterol (4 x 6 micrograms twice a day and as necessary, n = 19) or salbutamol (4 x 100 micrograms twice a day and as necessary, n = 16). Inhaled steroids and orally administered theophylline were allowed if doses were kept constant. MEASUREMENTS AND MAIN RESULTS: The median number of additional doses per 24 h (median of two weeks) of the test aerosols was 0 (range, 0 to 6) for formoterol and 4 (range, 0 to 14) for salbutamol (p less than 0.01). Morning and evening PEFRs were 422 (SEM = 31) and 443 (SEM = 30), respectively, for formoterol, and 335 (SEM = 30) and 360 (SEM = 26), respectively, for salbutamol (p = 0.05 for both). Formoterol was superior (p less than 0.05) to salbutamol with respect to control of asthma symptoms, estimated duration of action and patient preference. Side effects did not differ. CONCLUSIONS: Inhaled formoterol administered twice a day and as necessary was clinically more effective than the same regimen of salbutamol.

Effect of inhaled formoterol versus terbutaline on respiratory function in moderate bronchial asthma.

In a double-blind cross-over study comparing the duration of action of 12 micrograms and 24 micrograms formoterol, 500 micrograms terbutaline and placebo, lung function tests were performed in 12 never-smokers with non-allergic bronchial asthma. All the patients were hyperreactive to methacholine, had normal serum IgE level, and negative skin or RAST results. The lung function tests were carried out over an 11-h period and included measurements of lung volumes, airway resistance, dynamic spirometry, nitrogen single breath wash-out test and single breath diffusion capacity for CO. The airway resistance and maximal forced expiratory flow tests indicated a pronounced bronchodilator effect without adverse effects of 12 micrograms and 24 micrograms formoterol on both large and peripheral airways. Improved intrapulmonary gas distribution measured by the nitrogen wash-out test and more even distribution of the lung volumes indicating more homogeneous ventilation was seen for approx. 3 h after terbutaline and approx. 11 h after 24 micrograms formoterol. Measurement of the CO diffusion capacity indicates more effective gas diffusion and a better ventilation-perfusion ratio for at least 11 h, especially after inhalation of 24 micrograms formoterol.

Late asthmatic reaction decreased after pretreatment with salbutamol and formoterol, a new long-acting beta 2-agonist.

The inhibitory effect of salbutamol and formoterol, a new long-acting beta 2-agonist for inhalation, on the late asthmatic reaction (LAR), was studied in 12 patients with allergic asthma. After a single-blind, placebo-treatment control, equipotent bronchodilating doses of inhaled salbutamol (500 micrograms) and formoterol (30 micrograms) were administered 30 minutes before bronchial allergen challenge in a double-blind randomized design. The early asthmatic reaction was completely inhibited by both drugs (p less than 0.01) but not by placebo. The LAR was also significantly inhibited by both drugs (p less than 0.01); formoterol was only slightly, but significantly, more effective than salbutamol (p = 0.04). In contrast to some earlier studies, the present study indicates an inhibitory effect of beta 2-agonists on the LAR.

Inhaled formoterol during one year in asthma: a comparison with salbutamol.

Eighteen patients, who had previously taken part in a 2 wk cross-over comparison between formoterol and salbutamol, now took part in a one year double-blind study comparing salbutamol 200 micrograms b.i.d. with formoterol 12 micrograms b.i.d. Additional doses were taken when needed and were recorded. Ten patients were started on formoterol and eight on salbutamol. After one month, the patients were allowed to shift to the alternative drug. Two patients withdrew from the study. At the end of the study, 13 of 16 patients were on formoterol, thus showing a long-lasting preference for this drug. Forced expiratory volume in one second (FEV1) dose-response curves for inhaled salbutamol were repeatedly recorded during the study, and no tachyphylaxis was found. One patient stopped taking inhaled steroids but continued taking formoterol and theophylline. He deteriorated with a decreased response to salbutamol. After re-introduction of inhaled steroids his condition improved. This case indicates that effective bronchodilator therapy may mask the deterioration of asthma.

Formoterol, a new long acting beta 2 agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma.

Sixteen patients with stable chronic asthma participated in a double blind crossover study comparing the new inhaled long acting beta 2 agonist formoterol with salbutamol. Inhaled (n = 15) and oral steroid (n = 1) treatment were maintained at the same daily dose throughout the study. For four weeks the patients received either formoterol 24 micrograms twice daily or salbutamol 400 micrograms twice daily, plus additional puffs (with the same drug) when needed. Asthma symptoms, additional puffs of beta 2 agonist, peak expiratory flow (PEF), and side effects were recorded daily. During treatment with formoterol the patients used fewer additional puffs of beta 2 agonist, had better symptom scores, less disturbed sleep, more days without additional aerosol, and higher PEF both morning and evening than during salbutamol treatment. Thus formoterol 24 micrograms twice daily gave long lasting bronchodilatation and asthma symptoms were well controlled with regular twice daily administration.

Formoterol, a new long-acting bronchodilator for inhalation.

The aim of this study was to evaluate if treatment with inhaled formoterol is appreciated by asthmatics and whether it causes tachyphylaxis. Twenty stable asthmatics were included in a randomized, double-blind, crossover study. They were treated for two weeks either with formoterol or salbutamol, with one week washout inbetween. They were given 12 micrograms formoterol or 200 micrograms salbutamol twice daily and instructed to use additional spray doses on demand. On a diary card they recorded the number of doses, asthma symptoms and peak expiratory flow rate (PEFR) before every dose. Forced expiratory volume in one second (FEV1) dose-response curves for salbutamol (total dose 1.3 mg) were performed before and after each treatment period to evaluate development of tachyphylaxis. There was a significant difference in favour of formoterol concerning symptoms, PEFR recordings, spray consumption, and preference. Fifteen patients preferred formoterol and two salbutamol. The dose-response curves before formoterol and before, as well as after salbutamol were almost identical. After formoterol the curve had changed; both basal and maximum values were higher than before. Thus, no evidence of tachyphylaxis was found, compared to the ordinary beta-stimulant treatment.

Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases.

This multicentre trial was undertaken to confirm previous results indicating that long-term treatment with oral acetylcysteine reduces the exacerbation rate in patients with chronic bronchitis. Two hundred and eighty-five patients, smokers or ex-smokers, with chronic bronchitis started a pre-trial placebo-period of 1 month. After this run-in period 259 patients were included in the trial and randomized into two parallel groups. The patients were treated in a double-blind way either with acetylcysteine 200 mg b.i.d. or placebo b.i.d. for 6 months. The trial was completed by 98 patients in the acetylcysteine group and by 105 patients in the placebo group. Initially, there were no significant differences between the groups. Twice weekly, the patients filled in a diary card concerning symptoms. The number of exacerbations was assessed from these cards and at visits 2, 4 and 6 months after institution of therapy. The exacerbation rate was significantly lower in the acetylcysteine group in which 40% of the patients remained free from exacerbations compared to 19% in the placebo group. Sick-leave due to acute exacerbation was significantly less common in the acetylcysteine group. The drug was well tolerated.