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Introduction β-Blockers are known to worsen FEV 1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring β-blocker treatment Objective To determine the effects of β-blockers on AHR (provocative concentration of methacholine causing a 20% fall in FEV 1 [PC 20 ]), FEV 1 , and response to formoterol in patients with COPD Design A double-blind, placebo-controlled, randomized, cross-over study Setting An ambulatory, hospital outpatient clinic of pulmonary diseases Patients Patients with mild-to-moderate irreversible COPD and AHR Intervention Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period ≥ 3 days. On day 4 of treatment, FEV 1 and PC 20 were assessed. Immediately hereafter, formoterol (12 μg) was administered and FEV 1 was measured for up to 30 min Results PC 20 was significantly lower (p 1 deteriorated only after propranolol treatment (2.08 ± 0.31 L) [mean ± SD] compared with placebo (2.24 ± 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV 1 at 3 min, 6.7 ± 8.9%) but was unaffected by the other β-blockers (16.9 ± 9.8%, 22 ± 11.6%, and 16.9 ± 9.0% for placebo, metoprolol, and celiprolol, respectively) Conclusions Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV 1 and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of β-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a β-blocker must be weighted against the putative detrimental pulmonary effects, ie , effect on FEV 1 , AHR, and response to additional β 2 -agonists

Virtually all asthma patients use bronchodilators. Formoterol and salbutamol have a rapid onset of bronchodilating effect, whereas salmeterol acts slower. We studied the onset of improvement of dyspnoea sensation after inhalation with these bronchodilators and placebo to reverse a methacholine-induced bronchoconstriction as a model for an acute asthma attack.Seventeen patients with asthma completed this randomised, double-blind, crossover, double-dummy study. On 4 test days, forced expiratory volume in 1 s (FEV1) and Borg score were recorded and patients were challenged with methacholine until FEV1 fell with greater than or equal to 30% of baseline value. Thereafter, formoterol 12 mug via Turbuhaler(R), salbutamol 50 mug via Turbuhaler(R), salmeterol 50 mug via Diskhaler(TM), or placebo was inhaled. FEV1 and Borg scores were assessed during the following 60 min.The first sensed improvement of Borg score was significantly (P The Borg score returned significantly faster to the baseline value with formoterol, salbutamol, and salmeterol (Gmean time 13.8 (1-75), 13.4 (1-60), and 18.0 (175) min, respectively) than with placebo (33.6 (1-75 min).Formoterol and salbutamol act significantly faster than salmeterol in relieving dyspnoea induced by methacholine-induced bronchoconstriction, in patients with asthma. (C) 2004 Elsevier Ltd. All. rights reserved.

Inhalers containing corticosteroids and long-acting beta2-agonists are becoming increasingly important in asthma management. A rapid effect is important to patients, particularly during exacerbations. We compared the onset of bronchodilation and patient-perceived relief from dyspnoea following single-inhaler budesonide/formoterol or salmeterol/fluticasone in a model of acute bronchoconstriction. A randomised, double-blind, double-dummy, single-dose, crossover study included 27 outpatients with asthma (mean age 35 years; mean FEV1 90% predicted normal). Immediately following methacholine-induced bronchoconstriction (fall in FEV1or = 30%), patients inhaled budesonide/formoterol (160/4.5 microg, 1 or 2 inhalations; Symbicort Turbuhaler), salmeterol/fluticasone (50/250 microg; Seretide Diskus) or placebo on 4 study days. Lung function and Borg score were assessed for 30 min. During methacholine-induced provocation (final mean FEV1 62.5% of baseline), mean Borg score increased 10-fold (from 0.3 to 3.0 units). Hereafter, mean FEV1 at 3 min improved significantly more after budesonide/formoterol 1 and 2 inhalations (37 and 38%, respectively) than after salmeterol/fluticasone (23%; P0.001) or placebo (10%; P0.001). Median recovery times to 85% of baseline FEV1 were shorter for budesonide/formoterol (1 or 2 inhalations: 3.3 and 2.8 min, respectively) than salmeterol/fluticasone (8.9 min; P0.001) and placebo (30 min). One min after budesonide/formoterol, dyspnoea was significantly reduced (Borg score -0.86 units, both doses) compared with salmeterol/fluticasone (-0.55 units; P0.05) and placebo (-0.23 units; P0.001). Budesonide/formoterol provides immediate bronchodilation, faster than salmeterol/fluticasone, which patients can feel during acute methacholine-induced bronchoconstriction.

Salmeterol and formoterol are both long-acting beta(2)-adrenoceptor agonists (beta(2)-agonists). They both provide excellent bronchodilating and bronchoprotective effects in patients with asthma but their are some differences between these two long-acting beta(2)-agonists in vitro and in vivo. Formoterol has a greater potency and intrinsic activity than salmeterol, which can become especially apparent at higher doses than that clinically recommended, and in contracted bronchi. Long-term use of long-acting beta(2)-agonists can induce tolerance, which can be partially reversed with corticosteroids. Long-acting beta(2)-agonists have some anti-inflammatory effects in vitro, but data in vivo are less convincing. Compared with doubling the dose of inhaled corticosteroids, the addition of inhaled long-acting beta(2)-agonists to inhaled corticosteroids improves symptom control in patients with asthma and reduces both the exacerbation rate of asthma and hospital admission rate. No enhanced airway responsiveness or loss of perception of dyspnea has been observed with the use of inhaled long-acting beta(2)-agonists. Monotherapy with long-acting beta(2)-agonists is not recommended.

Background The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear. Methods The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted) who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1) after inhaling adenosine 5'-monophosphate (AMP), were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours). Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg), formoterol (4.5 μg), salbutamol (2 × 100 μg) or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day. Results In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1. Conclusions A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours after inhalation. The acute protection against subsequent bronchoconstrictor stimuli such as inhaled AMP and the rapid reversal of airway obstruction supports the use of budesonide/formoterol for both relief and prevention in the treatment of asthma. Trial Registration ClinicalTrials.gov number NCT00272753

beta-Blockers are known to worsen FEV(1) and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment.To determine the effects of beta-blockers on AHR (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]), FEV(1), and response to formoterol in patients with COPD.A double-blind, placebo-controlled, randomized, cross-over study.An ambulatory, hospital outpatient clinic of pulmonary diseases.Patients with mild-to-moderate irreversible COPD and AHR.Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period/= 3 days. On day 4 of treatment, FEV(1) and PC(20) were assessed. Immediately hereafter, formoterol (12 microg) was administered and FEV(1) was measured for up to 30 min.PC(20) was significantly lower (p0.01) with propranolol and metoprolol treatment (geometric means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL). FEV(1) deteriorated only after propranolol treatment (2.08 +/- 0.31 L) [mean +/- SD] compared with placebo (2.24 +/- 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV(1) at 3 min, 6.7 +/- 8.9%) but was unaffected by the other beta-blockers (16.9 +/- 9.8%, 22 +/- 11.6%, and 16.9 +/- 9.0% for placebo, metoprolol, and celiprolol, respectively).Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV(1) and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of beta-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a beta-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV(1), AHR, and response to additional beta(2)-agonists.

Chronic atrial fibrillation (AF) occurs often in the setting of mitral and aortic valve disease. Eventually, these patients undergo valve replacement which improves cardiac function but does not prevent AF. This study investigates which patient may benefit from additional surgery for the cure of AF performed in combination with valve surgery. Seventy-four patients were retrospectively included from our prospective database of patients referred for serial cardioversion therapy between 1986 and 1993. All these patients had chronic AF after valve replacement. After the first electrical cardioversion, patients did not receive antiarrhythmic drugs. Relapses were managed by repeated cardioversions, and then antiarrhythmic drugs were instituted. After a median follow-vp of 7 years (range 1.3 to 23), 39 patients had intractable AF. Multivariate analysis revealed that patients with a history of chronic AF before surgery (risk ratio 5.4, confidence intervals 2.5 to 11.3, p = 0.0001) had a poor arrhythmia outcome. In addition, Kaplan-Meier survival analysis demonstrated a lower success rate (p = 0.0017) in patients with mitral valve disease than in those with aortic valve disease. Congestive heart failure (41% vs 6%, p = 0.0007) and cardiovascular mortality (23% vs 9%, p = 0.09) were seen most often in patients with on unsuccessful cardioversion strategy. Thus, patients scheduled for mitral valve surgery with a history of chronic AF should be considered candidates for additional surgery for AF concomitantly performed during valve surgery. (C) 1996 by Excerpta Medica, Inc.