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Background: In Thailand, nebulized ipratropium bromide/fenoterol, is commonly used in addition to salbutamol for severe asthma exacerbation. Recently, nebulized MgSO4 is indicated in GINA 2015 as an additive treatment for severe cases. However, there is limited data showed the efficacy of both drugs in childhood severe asthma. The purpose of this study to compare efficacy and safety of nebulized MgSO4 and ipratropium bromide/fenoterol in moderate to severe asthma attacks., Methods: In this a prospective, double-blind, randomized, controlled trial study, we enrolled thirty-three children, age ranged from 2 to 15 years old, with PRAM score ≥ 4 (moderate to severe asthma exacerbation) despite 3 doses of nebulized salbutamol. Each patient was randomized to receive either three doses of nebulized MgSO4 or nebulized ipratropium bromide/fenoterol every 30 minutes. The PRAM score was measured at 0, 30, 60, 90, 120 and 240 minutes after the treatment. The adverse event and admission days were also evaluated., Results: Sixteen patients received nebulized MgSO4 and seventeen received nebulized ipratropium bromide/fenoterol. Almost patients were classified as having moderate asthmatic attack. There were no statistically significant difference between the two study groups in almost baseline characteristic, PRAM score at 0, 30, 60, 90, 120, 240 minutes. The hospital length of stay was also similar between two groups (p = 0.83). There were no serious events in both groups., Conclusions: Our double blind, randomized, controlled pilot study demonstrated non-inferior outcomes including clinical benefit and safety of nebulized MgSO4 and nebulized ipratropium bromide/fenoterol among Thai children with acute moderate asthmatic.

Purpose: β 2 -sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β 2 -sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other β 2 -mimetic tocolytic agents like fenoterol., Methods: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups., Results: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005)., Conclusions: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different β 2 -sympathomimetic tocolytic drugs.

Salbutamol is a β2 adrenergic agonist widely prescribed in patients with obstructive and restrictive lung diseases. The main side effects associated with its use are tachycardia and tremor. Myoclonus is an involuntary, irregular, abrupt, brief and sudden muscular contraction, which can be generalized, focal or multifocal. We report the case of a 61-year-old patient presenting with myoclonus difficult to treat who showed improvement only after the definitive discontinuation of the β2 adrenergic agonist. We describe the clinical findings, the interventions, and the outcomes related to the onset of myoclonus secondary to the use of salbutamol, as well as the possible genesis and importance of this adverse effect. We used the CARE guidelines to delineate the clinical case. Although myoclonus secondary to the use of different drugs has been described in the literature, as far as we know this is the fourth report of salbutamol-induced myoclonus to date.

Objective: To develop a prediction model for the chance of successful external cephalic version (ECV)., Study Design: This is a secondary analysis of a multicenter, open-label randomized controlled trial that assessed the effectiveness of atosiban compared to fenoterol as uterine relaxant during ECV in women with a singleton fetus in breech presentation with a gestational age of 36 weeks or more. Potential predictors included maternal, pregnancy, fetal, and treatment characteristics and were recorded in all participants. Multivariable logistic regression analysis with a stepwise backward selection procedure was used to construct a prediction model for the occurrence of successful ECV. Model performance was assessed using calibration and discrimination., Results: We included a total of 818 women with an overall ECV success rate of 37%. Ten predictive factors were identified with the stepwise selection procedure to be associated with a successful ECV: fenoterol as uterine relaxant, nulliparity, Caucasian ethnicity, gestational age at ECV, Amniotic Fluid Index, type of breech presentation, placental location, breech engagement, possibility to palpate the head and relaxation of the uterus. Our model showed good calibration and a good discriminative ability with a c-statistic of 0.78 (95% CI 0.75 to 0.81)., Conclusion: Prediction of success of ECV seems feasible with a model showing good performance. This can be used in clinical practice after external validation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Uterine tachysystole (more than 5 contractions per 10 minutes in 2 consecutive intervals) is common during labour, particularly with use of labour-stimulating agents. Tachysystole may reduce fetal oxygenation by interrupting maternal blood flow to the placenta during contractions. Reducing uterine contractions may improve placental blood flow, improving fetal oxygenation. This review aimed to evaluate the use of tocolytics to reduce or stop uterine contractions for improvement of the condition of the fetus in utero. This new review supersedes an earlier Cochrane Review on the same topic., Objectives: To assess the effects of the use of acute tocolysis during labour for uterine tachysystole or suspected fetal distress, or both, on fetal, maternal and neonatal outcomes., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (2 February 2018), and reference lists of retrieved studies., Selection Criteria: Randomised controlled trials (RCTs) evaluating acute tocolysis for uterine tachysystole, intrapartum fetal distress, or both., Data Collection and Analysis: We used standard methods expected by Cochrane., Main Results: We included eight studies (734 women), conducted in hospital settings, predominantly in high-income countries (USA, Austria, Uruguay). Two trials were conducted in upper and lower middle-income countries (South Africa, Sri Lanka). The hospital facilities all had the capacity to perform caesarean section. Overall, the studies had a low risk of bias, except for methods to maintain blinding. All of the trials used a selective beta 2 (ß 2 )-adrenergic agonist in one arm, however the drug used varied, as did the comparator. Limited information was available on maternal outcomes.Selective ß 2 -adrenergic agonist versus no tocolytic agent, whilst awaiting emergency deliveryThere were two stillbirths, both in the no tocolytic control group (risk ratio (RR) 0.23, 95% confidence interval (CI) 0.01 to 4.55; 2 studies, 57 women; low-quality evidence). One had gross hydrocephalus and the second occurred with vaginal delivery after waiting 55 minutes for caesarean section. The decision for caesarean section delivery was an inclusion criterion in both studies so we could not assess this as an outcome under this comparison. Abnormal fetal heart trace is probably lower with tocolytic treatment (RR 0.28, 95% CI 0.08 to 0.95; 2 studies, 43 women; moderate-quality evidence). The effects on the number of babies with Apgar score below seven were uncertain (low-quality evidence).Intravenous (IV) atosiban versus IV hexoprenaline (1 study, 26 women) One infant in the hexoprenaline group required > 24 hours in the neonatal intensive care unit (NICU) following a forceps delivery (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence). There were no fetal or neonatal mortalities and no Apgar scores below seven. There was one caesarean delivery in the IV hexoprenaline group (RR 0.33, 95% CI 0.01 to 7.50; low-quality evidence), and one case of abnormal fetal heart score in the atosiban group (RR 3.00, 95% CI 0.13 to 67.51; very low-quality evidence).IV fenoterol bromhydrate versus emergency delivery (1 study, 390 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. IV fenoterol probably increases the risk of caesarean delivery (RR 1.12, 95% CI 1.04 to 1.22; moderate-quality evidence). Fenoterol may have little or no effect on the risk of Apgar scores below seven (RR 1.28, 95% CI 0.35 to 4.68; low-quality evidence).IV hexoprenaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 37 women) No data were reported for perinatal death or severe morbidity. There were two fetal deaths in the no tocolytic control group (RR 0.23, 95% CI 0.01 to 4.55; low-quality evidence). The rate of caesarean delivery was not reported. There were two babies with Apgar scores below seven in the control group and none in the hexoprenaline group (RR 0.24, 95% CI 0.01 to 4.57; 35 women; low-quality evidence).Subcutaneous terbutaline versus IV magnesium sulphate (1 study, 46 women)No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. The decision for caesarean section was an inclusion criterion, so we could not assess this. The effects on abnormal fetal heart trace are uncertain (very low-quality evidence).Subcutaneous terbutaline with continuation of oxytocic infusion versus cessation of oxytocic infusion without tocolytic agent (1 study, 28 women) No data were reported for perinatal death, severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery in the subcutaneous terbutaline (8/15) and control groups (4/13) (RR 1.73, 95% CI 0.68 to 4.45; low-quality evidence). There were no cases of Apgar scores below seven or abnormal fetal heart trace.Subcutaneous terbutaline versus no tocolytic agent, whilst awaiting emergency delivery (1 study, 20 women) No data were reported for perinatal death or severe morbidity. There were no fetal or neonatal mortalities. The decision for caesarean section was an inclusion criterion, so we could not assess this. There were two babies with Apgar scores below seven in the control group and none in the terbutaline group (RR 0.17, 95% CI 0.01 to 3.08; low-quality evidence).IV terbutaline versus IV nitroglycerin (1 study, 110 women)No data were reported for perinatal death or severe morbidity or fetal or neonatal mortality. There may be little or no difference in the rates of caesarean delivery between the IV terbutaline (30/57) and control groups (29/53) (RR 0.96, 95% CI 0.68 to 1.36; low-quality evidence). There were no cases of Apgar scores below seven., Authors' Conclusions: There is insufficient evidence to determine the effects of tocolytics for uterine tachysystole or suspected fetal distress during labour. The clinical significance for some of the improvements in measures of fetal well-being with tocolytics is unclear. The sample sizes were too small to detect effects on neonatal morbidity, mortality or serious adverse effects. The majority of studies are from high-income countries in facilities with access to caesarean section, which may limit the generalisability of the results to lower-resource settings, or settings where caesarean section is not available.Further well-designed and adequately powered RCTs are required to evaluate clinically relevant indicators of maternal and neonatal morbidity and mortality.

Objective:  To compare the effectiveness of the oxytocin receptor antagonist atosiban with the beta mimetic fenoterol as uterine relaxants in women undergoing external cephalic version (ECV) for breech presentation., Design:  Multicentre, open label, randomised controlled trial., Setting:  Eight hospitals in the Netherlands, August 2009 to May 2014., Participants:  830 women with a singleton fetus in breech presentation and a gestational age of more than 34 weeks were randomly allocated in a 1:1 ratio to either 6.75 mg atosiban (n=416) or 40 μg fenoterol (n=414) intravenously for uterine relaxation before ECV., Main Outcome Measures:  The primary outcome measures were a fetus in cephalic position 30 minutes after the procedure and cephalic presentation at delivery. Secondary outcome measures were mode of delivery, incidence of fetal and maternal complications, and drug related adverse events. All analyses were done on an intention-to-treat basis., Results:  Cephalic position 30 minutes after ECV occurred significantly less in the atosiban group than in the fenoterol group (34% v 40%, relative risk 0.73, 95% confidence interval 0.55 to 0.93). Presentation at birth was cephalic in 35% (n=139) of the atosiban group and 40% (n=166) of the fenoterol group (0.86, 0.72 to 1.03), and caesarean delivery was performed in 60% (n=240) of women in the atosiban group and 55% (n=218) in the fenoterol group (1.09, 0.96 to 1.20). No significant differences were found in neonatal outcomes or drug related adverse events., Conclusions:  In women undergoing ECV for breech presentation, uterine relaxation with fenoterol increases the rate of cephalic presentation 30 minutes after the procedure. No statistically significant difference was found for cephalic presentation at delivery., Trial Registration:  Dutch Trial Register, NTR 1877., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Beta-agonists play an important role in tocolytic treatment. In light of recent changes in the Polish medical care system, we decided to assess the effectiveness of oral continuous treatment (in 2012) and compare it with a 3-day intravenous administration of fenoterol (in 2013). The aim of our study was to contrast cost and effectiveness of fenoterol therapy in pregnant women at risk of preterm labor during two consecutive years: 2012 - when fenoterol had been widely used (group A), and 2013 when its extensive use had been withdrawn (group B)., Material and Methods: Retrospective cohort study of 129 pregnant women: 76 treated with intravenous fenoterol, followed by continuous oral administration (November 2012; group A), and 53 treated with intravenous fenoterol only for 48-72 hours (November 2013; group B)., Results: Perinatal outcomes (based on the Apgar score and neonatal weight) were comparable in both groups. Continuous oral application of fenoterol resulted in earlier gestational age at delivery and lower cost of hospitalization among women from group A as compared to group B. Regardless, the difference was not statistically significant (37 hbd vs. 35 hbd, p = 0.626; 4334,700PLN vs. 5232,470PLN, p = 0.533)., Conclusions: A 3-day intravenous application of fenoterol is as effective as oral continuous therapy and is characterized by reduced risk of negative side effects.

Objective: The aim of this study was to investigate whether the use of fenoterol, a beta2-adrenergic agonist, was associated with multiple sclerosis (MS) risk by conducting a total population-based case-control study in Taiwan., Methods: A total of 578 patients with newly diagnosed MS who had a severely disabling disease (SDD) certificate between January 1, 2002 and December 1, 2008 comprised the case group. These cases were compared with 2890 gender-, age-, residence-, and insurance premium-matched controls. Fenoterol use was analyzed using a conditional logistic regression model that controlled for asthma, chronic obstructive pulmonary disease (COPD), salbutamol and steroid use., Results: Compared with the group of people who did not use fenoterol, the adjusted odds ratios were 0.67 (95% confidence interval (CI) = 0.48-0.93, p = 0.016) for the group prescribed fenoterol below 2.25 cumulative defined daily dose (cDDD) and 0.49 (95% CI = 0.33-0.71, p < 0.001) for the group with a cumulative fenoterol use of more than 2.25 cDDD. The dose-response relationship was similar within the non-asthma patients. The associations were similar between males and females, but differences between age groups were observed., Conclusions: The results of this study suggest that fenoterol use may reduce the risk of MS., (© The Author(s), 2014.)

Tocolysis is an important treatment in the improvement of outcome in preterm labor and preterm birth, provided that its use follows clear evidence-based recommendations. In this expert opinion, the most recent evidence about efficacy and side effects of different tocolytics is being reviewed and evidence-based recommendation about diagnosis and treatment of preterm labor is given. Further aspects such as progesterone administration or antibiotic treatment for the prevention of preterm birth are included. Our review demonstrates that an individualized choice of different tocolytics and additional treatments is necessary to improve short- and long-term neonatal outcome in preterm labor and preterm birth.

Background: Preterm birth is a major contributor to perinatal mortality and morbidity worldwide. Tocolytic agents are drugs used to inhibit uterine contractions. Betamimetics are tocolytic agents that have been widely used, especially in resource-poor countries., Objectives: To assess the effects of betamimetics given to women with preterm labour., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2013) and reference lists of retrieved studies., Selection Criteria: Randomised controlled trials of betamimetics, administered by any route or any dose, in the treatment of women in preterm labour where betamimetics were compared with other betamimetics, placebo or no treatment., Data Collection and Analysis: Two review authors assessed risk of bias and extracted the data independently., Main Results: Twenty-eight trials were assessed as eligible for inclusion in the review, but eight did not report any outcome data relevant to the review. Results are based on the 20 trials that contributed data.Twelve trials, involving 1367 women, compared betamimetics with placebo. Betamimetics decreased the number of women in preterm labour giving birth within 48 hours (average risk ratio (RR) 0.68, 95% confidence interval (CI) 0.53 to 0.88, 10 trials, 1209 women). There was a decrease in the number of births within seven days (average RR 0.80; 95% CI 0.65 to 0.98, five trials, 911 women) but there was no evidence of a reduction in preterm birth (before 37 weeks' gestation) (RR 0.95; 95% CI 0.88 to 1.03, 10 trials, 1212 women). No benefit was demonstrated for betamimetics for perinatal death (RR 0.84; 95% CI 0.46 to 1.55, 11 trials, 1332 infants), or neonatal death (RR 0.90; 95% CI 0.27 to 3.00, six trials, 1174 infants). No significant effect was demonstrated for respiratory distress syndrome (RR 0.87; 95% CI 0.71 to 1.08, eight trials, 1239 infants). A few trials reported on cerebral palsy, infant death and necrotising enterocolitis; no significant differences between groups were identified for any of these outcomes. Betamimetics were significantly associated with the following outcomes: withdrawal from treatment due to adverse effects; maternal chest pain; dyspnoea; palpitation; tremor; headaches; hypokalaemia; hyperglycaemia; nausea or vomiting; nasal stuffiness; and fetal tachycardia.Nine trials compared different types of betamimetics. Other betamimetics were compared with ritodrine in five trials (n = 948). Other comparisons were examined in single trials: hexoprenaline compared with salbutamol (n = 140), slow versus moderate release salbutamol (n = 52) and salbutamol compared with terbutaline (n = 200). Trials were small, varied, and of insufficient quality to delineate any consistent patterns of effect., Authors' Conclusions: Betamimetics help to delay birth, which may give time to allow women to be transferred to tertiary care or to complete a course of antenatal corticosteroids. However, multiple adverse effects must be considered. The data are too few to support the use of any particular betamimetic.

Purpose: To compare the efficacy of nifedipine and fenoterol in the management of threatened preterm labor (TPL)., Methods: A randomized and multicenter study assessing the tocolytic effect of nifedipine versus fenoterol in patients admitted to the participating maternity units with a diagnosis of TPL and a cost-savings study for economic assessment. For a power of 80% and an α error equal to 0.05, 132 consecutive patients were recruited during the study period; 66 patients were assigned to each group. A χ(2) analysis and a mean differences test were performed according to variable types and survival curves per intention-to-treat., Results: Demographics were similar in both groups. The latency period was similar in both groups (26.7 vs. 25.6; p = 0.3). There were no differences in the results obtained. Nifedipine failed more frequently to obtain tocolysis when used as a first-line agent (80 vs. 90%, p = 0.0001). The group treated with fenoterol showed more drug adverse events (57.8 vs. 19.0%, p = 0.0001). The economic assessment did not evidence a significant difference in terms of cost savings between groups treated with either drug., Conclusion: The present study failed to demonstrate either clinical or economic superiority of any of the two drugs used in TPL management. The highest failure percentage of nifedipine when used as a first-line agent should encourage further research., (Copyright © 2012 S. Karger AG, Basel.)

Background: Limited evidence is available on the use of budesonide inhalation suspension (BIS) for the treatment of mild to severe acute asthma exacerbations (AAE) in adults in an inpatient setting. This study was conducted to evaluate the efficacy of a five-day course of BIS compared with oral prednisolone (OP) in the management of adults with AAE., Methods: A retrospective study examined the response of 28 patients hospitalized with mild to severe acute asthma exacerbation from January 2003 to December 2003. These patients, who were steroid free ≥ 1 yr, were administered a five-day course of BIS (2 × 2 mg bid) or OP (2 × 15 mg bid). PEF, FEV(1) and asthma symptom scores were recorded daily., Results: The BIS (n = 13) and OP (n = 15) treatment groups were comparable at baseline for demographic characteristics and prebronchodilator (fenoterol) FEV(1) of 52.4% predicted normal value and 54.6% predicted normal value, respectively. Mean change of morning PEF was 152 L/min during BIS treatment and 130 L/min for OP treatment; the mean changes of morning forced expiratory volumes in 1 s (FEV(1)) were 1.0 and 0.7 L, respectively. The mean change in daytime symptom scores were -1.6 and -1.3 in the BIS and the OP groups, respectively. Improvements in PEF, FEV(1) and daytime symptom scores were significantly different between baseline and after treatment in each treatment group (p < 0.05). However, improvements in both BIS and OP groups were similar., Conclusion: Budesonide inhalation suspension may be an alternative treatment of acute asthma exacerbation in adults who are at risk for systemic corticosteroids., (Copyright © 2010. Published by Elsevier Ltd.)

Background: The addition of ipratropium, a synthetic cholinergic antagonist, to beta2-agonist therapy provides an additive improvement in adult with acute severe asthma and COPD because of increased vagal tone in the airways. We asked whether ipratropium in combination with fenoterol (Ipraterol) improved pulmonary function in comparison with original Berodual., Material and Method: In order to determine the effects of nebulized a single dose of Ipraterol, the study was conducted in a double-blind, randomized and crossover manner by comparing the effect of nebulized a single dose of Berodual on methacholine-induced bronchoconstriction. The study consisted of an 1-week run-in phase and two study visits separated by a washout period of 7 days., Patients: We studied 20 patients who ranged from 18 to 80 years of age and had mild to moderate persistent asthma., Results: Nebulized Ipraterol provided a rapid onset of bronchodilation effect similar to nebulized Berodual within 5 minutes by significantly increasing FEV, from 1.19 L to 1.73 L (p < 0.001) and from 1.19 to 1.69 L (p = 0.0001), respectively. This effect of Ipraterol lasted as long (up to 6 hours) and was similar to that of Berodual. The absolute FEV1 values at 360 min after Ipraterol treatment was still higher than the baseline values. We also found that there were no significant differences in the degree of improvement in FEV1 and hypokalemia following treatment with Ipraterol and Berodual., Conclusion: Our data suggest that nebulized Ipraterol offers a statistically significant improvement in pulmonary function without significant systemic absorption causing hypokalemia, with the improvement being comparable to that achieved with nebulized Berodual.

Background: To estimate the direct and indirect costs of severe asthma and the economic impact of its management to low-income families in Salvador, Brazil., Methods: One hundred and ninety-seven patients with severe asthma and referred to a state-funded asthma center providing free treatment were evaluated. At registration, they were asked about family cost-events in the previous year and had a baseline assessment of lung function, symptoms and quality of life. During the subsequent year, they were reassessed prospectively., Results: One hundred-eighty patients concluded a 12-month follow-up. Eighty-four percent were female patients, and the median family income was US$ 2955/year. Forty-seven percent of family members had lost their jobs because of asthma. Total cost of asthma management took 29% of family income. After proper treatment, asthma control scores improved by 50% and quality of life by 74%. The income of the families increased by US$ 711/year, as their members went back to work. The total cost of asthma to the families was reduced by a median US$ 789/family/year. Consequently, an annual surplus of US$ 1500/family became available., Conclusions: Family costs of severe asthma consumed over one-fourth of the family income of the underprivileged population in a middle-income country. Adequate management brings major economic benefit to individuals and families.

Background: Although airway obstruction, as defined by improvement of forced expiratory volume in one second (FEV1) and/or forced vital capacity (FVC), is irreversible in patients with COPD, they clearly seem to benefit from treatment with inhaled bronchodilators., Aims: To assess the response pattern of residual volume (RV) compared to FEV1 after bronchodilation in patients with reversible and irreversible airway obstruction., Methods: Changes in static lung volumes were compared with improvement in dynamic lung volumes in 396 consecutive patients undergoing reversibility testing with repeat bodyplethysmography. Reversibility was defined as improvement of FEV1 >200 ml and >12% after inhalation of fenoterol hydrobromide., Results: Irreversibility was found in 297 out of 396 patients with airway obstruction. Except for total lung capacity (TLC), all parameters (residual volume [RV], vital capacity [VC], forced inspiratory vital capacity [IVC], forced vital capacity [FVC], forced expiratory volume in one second [FEV1] and the FEV1/VC ratio) showed statistically significant changes after bronchodilation in 396 patients. The multiple linear regression model adjusted for age, sex and BMI showed a non-linear relationship between DeltaFEV1 or DeltaVC compared to DeltaRV after bronchodilation. If the increase in DeltaFEV1 is lower than 0.1 L, DeltaRV remains constant. However, if the increase in DeltaFEV1 is more than 0.1 L, DeltaRV decreases too. The same is found at an increase in VC of 0.3 L., Conclusion: In summary, in patients with irreversible airway obstruction DeltaRV cannot be predicted by DeltaFEV1 or DeltaVC after bronchodilation. Therefore, spirometric assessment should be complemented by bodyplethysmography.

We have reported therapeutic effectiveness of pharmacological stimulation of beta2 adrenoreceptors (ARs) to attenuate the cardiac remodeling and myocardial infarction (MI) expansion in a rat model of dilated cardiomyopathy (DCM) post-MI. Furthermore, the combination of beta2 AR stimulation with beta1 AR blockade exceeded the therapeutic effectiveness of beta1 AR blockade. However, these studies were relatively short (6 weeks). In this study, in the same experimental model, we compared different effects, including survival benefit, of combined therapy with the beta1 AR blocker, metoprolol, plus the beta2 AR agonist, fenoterol (beta1-beta2+), and either therapy alone (beta1- or beta2+) during the 1-year study. Therapy was started 2 weeks after permanent ligation of the left coronary artery. Cardiac remodeling, MI expansion, and left ventricular function were assessed by serial echocardiography and compared with untreated animals (nT). Sixty-seven percent mortality in nT was reduced to 33% in the beta1-beta2+ (p < 0.01). Progressive cardiac remodeling observed in nT and beta1- was significantly attenuated in beta1-beta2+ during the first 6 months of treatment. In beta1-beta2+, MI expansion was completely prevented, and functional decline was significantly attenuated during the entire year. Myocardial apoptosis was significantly reduced in both beta1-beta2+ and beta1-. A reduction of cardiac beta1 AR density and decreases in chronotropic and contractile responses to beta2 AR-specific stimulation in the absence of a reduction of beta2 AR density in nT were precluded in rats receiving combined therapy. The results demonstrate the cardioprotective and survival benefit of long-term combination therapy of beta2 AR agonists and beta1 AR blockers in a model of DCM.

Objectives: In countries with high income, tocolytic therapy with beta-mimetic agents is a cost-effective strategy compared to placebo. In our study, the cost-effectiveness of two beta-mimetic agents, ritodrine and fenoterol, used in the management of preterm labor was compared in the setting of a low-middle-income transitional country, Serbia & Montenegro., Methods: This case study was conducted at the Gynecology-Obstetrics Clinic, Clinical Center "Kragujevac," in Kragujevac, Serbia & Montenegro, between October 2004 and January 2006. In total, 235 pregnant patients with threatened preterm labor were enrolled, but 35 were lost to follow-up. Of the remaining 200 patients, 85 were given ritodrine, and 115 fenoterol. The perspective of Republic Institute for Health Insurance in Serbia was taken into account. Only direct costs were calculated; primary outcomes of the study were length of pregnancy (in weeks), time passed from the onset of uterine contractions to delivery (in weeks), and score on modified Flanagan's quality-of-life scale for chronic diseases, measured after discharge from hospital., Results: Prolongation of pregnancy was significantly longer in the fenoterol group (12.7 +/- 8.4 weeks) than in the ritodrine group (11.6 +/- 7.1 weeks). The mean duration of hospitalization was shorter in the fenoterol group (11.9 +/- 8.8 days) than in the ritodrine group (14.9 +/- 11.3 days). The treatment with fenoterol was less costly and more cost-effective than the treatment with ritodrine, but the difference in cost-effectiveness was not statistically significant. The cost of treatment per gained week of pregnancy prolongation was 3345.51 +/- 7668.04 CSD in the fenoterol group, and 4181.96 +/- 12,069.83 CSD in the ritodrine group., Conclusions: The observed differences in treatment costs and duration of hospitalization per patient did not translate into significant differences in cost-effectiveness ratios, because of low costs of hospitalization and human labor in Serbian health system. Nevertheless, fenoterol treatment still has a tendency to be more cost-effective, and its lower acquisition cost is an advantage to this treatment option.

Background: The allergen-induced release of CCL17/thymus and activation-regulated chemokine (TARC) may be crucial in asthmatic airway inflammation by recruitment of Th2 cells. In addition, it might lead to aberrant Th2 cell activity through impairment of beta2-adrenergic receptor (beta2-AR) control. We questioned how chemokine patterns change upon allergen challenge and whether treatment with the inhaled steroid ciclesonide can reduce chemokine release and subsequently prevent allergen-induced changes in Th2 cell regulation and migration., Methods: Asthma patients were double-blindly treated with placebo or 80 microg ciclesonide for 7 days. We studied allergen-induced changes in sputum chemokines, migration of peripheral blood T cells and control of beta2-agonist fenoterol over T cell migration and alpha-CD3/alpha-CD28-induced cytokine production., Results: Treatment with 80 microg ciclesonide significantly diminished the late asthmatic response. The late asthmatic response was associated with increased sputum levels of CCL17 and CCL4 (but none of the other chemokines measured) and loss of beta2-AR control over T cell migration and Th2-type cytokine production. Although ciclesonide treatment did not prevent chemokine release nor altered beta2-AR function in circulating T cells, it exerted an inhibitory effect on TARC-induced T cell migration and alpha-CD3/alpha-CD28-induced cytokine production., Conclusion: Our data support the hypothesis that CCL17 is involved in allergen-induced dysregulation of Th2 cell migration and cytokine production. Ciclesonide treatment inhibits T cell migration and cytokine production upon allergen inhalation, which is regulated independently from reducing CCL17 release, but may contribute to beneficial effects of ciclesonide on Th2-mediated airway inflammation., (2007 S. Karger AG, Basel)

Aim: To determine whether fetal intrauterine resuscitation using tocolysis and delayed delivery is better for the fetus than emergency delivery when fetal hypoxia is suspected because of a non-reassuring fetal heart-rate (FHR) pattern using conventional heart rate monitoring., Methods: This was a prospective and randomized study, conducted between 2001 and 2004 at Pereira Rossell Hospital, Montevideo, Uruguay. The population consisted of 390 fetuses, in which intrauterine distress was diagnosed using electronic FHR monitoring. Of these, 197 were randomly assigned to the emergency delivery group and 193 to the fetal intrauterine resuscitation group. The inclusion criteria were: term singleton pregnancy, in labor, cephalic presentation, and no placental accidents., Results: The time between randomization and birth was 16.9 +/- 7.6 min (mean +/- SD) for the emergency delivery group, and 34.5 +/- 11.7 min (mean +/- SD) for the resuscitation group. The relative risk (RR) of acidosis in the umbilical artery (pH < 7.1) in the emergency delivery group was 1.47 (0.95-2.27). The RR of base deficit < or =12 mEq/L in the emergency delivery group was higher than in the resuscitation group (RR = 1.48 [1.0-2.2], P = 0.04). When considering the need for admission to the neonatal care unit, the relative risk was higher in the emergency delivery group than in the resuscitation group (RR = 2.14 [1.23.3.74], P = 0.005). No maternal adverse effects were reported., Conclusion: Tocolysis and delayed delivery renders better immediate neonatal results than emergency delivery when fetal distress is suspected because of a non-reassuring fetal heart pattern. In addition, it may decrease the need for emergency delivery without increasing maternal and fetal adverse side-effects.

Preterm labor (PTL) affects up to 25% of human pregnancies in developing countries, but there are few therapeutic options. Based on the key role of oxytocin (OXT) in labor and parturition, OXT antagonists are a potentially useful class of drugs for PTL. Barusiban is a new selective, potent, and long-acting OXT receptor antagonist. In this study barusiban was given by continuous i.v. infusion to monkeys during the last 3 wk of pregnancy; the monkeys were also given daily doses of OXT to induce uterine contractions and simulate PTL. Barusiban effectively suppressed OXT-induced PTL-like contractions and prevented early delivery. In contrast, fenoterol (a beta2-adrenoceptor [beta2-AR] agonist used as a comparative control) did not inhibit uterine contractions in this model. Barusiban was particularly effective in maintaining low intrauterine pressure (IUP) near the end of pregnancy, which is when IUP in both OXT controls and fenoterol-treated females increased substantially. Although barusiban delayed the onset of labor, it did not prevent normal delivery. These data demonstrate the safety and efficacy of barusiban in reducing uterine contractility in response to repeated OXT challenge, and suggest that barusiban may be therapeutically effective in long-term treatment of PTL.

A comparative study of the data obtained from the use of forced oscillation (FO) technique, spirography (SG), flow-forced expiratory volume (F-FEC) curve recording has provided evidence that the FO technique is highly effective in assessing a drug test. The FO technique revealed changes in bronchial patency in 69.5% of patients with bronchial obstruction whereas F-FEV recording indicated this pathology only in 42.4% (p < 0.05). A concurrent use of the pooled values of viscous respiratory resistance, SG, F-FEV curve to assess the results of a broncholytic test could diagnose bronchospasm in 79.7% of patients with pulmonary tuberculosis with impaired bronchial patiency.

We derive semiparametric methods for estimating and testing treatment effects when censored recurrent event data are available over multiple periods. These methods are based on estimating functions motivated by a working "mixed-Poisson" assumption under which conditioning can eliminate subject-specific random effects. Robust pseudoscore test statistics are obtained via "sandwich" variance estimation. The relative efficiency of conditional versus marginal analyses is assessed analytically under a mixed time-homogeneous Poisson model. The robustness and empirical power of the semiparametric approach are assessed through simulation. Adaptations to handle recurrent events arising in crossover trials are described and these methods are applied to data from a two-period crossover trial of patients with bronchial asthma.

Introduction: In addition to offering favorable pharmaceutical performance, an ideal inhaler should be well accepted by patients, as this may facilitate compliance. We report a study that specifically assessed inhaler preference in patients with obstructive lung disease after treatment with ipratropium bromide/fenoterol hydrobromide (Berodual delivered via either Respimat Soft Mist Inhaler (SMI) or hydrofluoroalkane metered dose inhaler (HFA-MDI)., Methods: Patients with COPD, asthma or mixed disease were randomized to receive ipratropium bromide/fenoterol hydrobromide 20/50 microg via Respimat SMI or 40/100 microg via HFA-MDI for 7 weeks each, in a crossover design. Patients were trained in inhaler use and given < or =5 attempts to demonstrate satisfactory technique. At the end of each treatment period, patients completed a 15-item satisfaction questionnaire, and inhaler technique was re-tested. On study completion, patients were asked which inhaler they preferred and they rated their willingness to continue using each inhaler. Clinical efficacy outcomes were measured by diary card to check whether switching inhaler affected efficacy., Results: In total, 245 patients were randomized and 224 used both inhalers within their respective treatment periods. Of 201 patients expressing a preference, 162 (81%) preferred Respimat SMI and 39 (19%) preferred HFA-MDI (p < 0.001). Patients would rather continue using Respimat SMI than HFA-MDI (p < 0.001). Mean scores for 13 of the 15 satisfaction questions were significantly higher for Respimat SMI than HFA-MDI (p < 0.05); in addition, the total score was also significantly higher for Respimat SMI (p < 0.001). Most patients (217/224; 97%) were judged to have good technique with Respimat SMI after 7 weeks' use. Differences in efficacy measures between the devices were not significant., Conclusion: These data indicated that a large majority of patients preferred Respimat SMI to HFA-MDI.

Objective: The effect of short-acting inhaled beta(2)-agonists on mortality from chronic obstructive pulmonary disease (COPD) is controversial. Different observational designs were used to investigate about this topic., Study Design and Setting: A population-based case-control design was performed, by linking automated health databases from the Varese Province of Italy. Deaths of COPD generated from the cohort of 135,871 patients for whom at least one prescription for drugs used to treat COPD had been dispensed between 1997 and 1999 entered into the study as cases. Up to 20 controls were randomly selected for each case from the cohort after matching on gender, age, and date of cohort entry. Risk ratios were estimated using the case-control, case-crossover, and case-time-control approaches., Results: A total of 222 cases and 3022 controls met the inclusion criteria. Odds ratios (and corresponding 95% confidence intervals) corresponding to more than 0.5 defined-daily-doses were 2.6 (1.7, 4.0), 1.9 (1.1, 3.3), 2.1 (1.1, 4.0), and 2.3 (1.2, 4.6) by using crude and adjusted case-control, case-crossover, and case-time-control estimates, respectively., Conclusion: Evidence that higher doses of short-acting inhaled beta(2)-agonists are associated with higher mortality from COPD was consistently supplied by three observational approaches.

Background: Preterm birth is a major contributor to perinatal mortality and morbidity worldwide. Tocolytic agents are drugs used to inhibit uterine contractions. The most widely used tocolytic agents are betamimetics especially in resource-poor countries., Objectives: To assess the effects of betamimetics given to women with preterm labour., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2003) without language restrictions., Selection Criteria: Randomised controlled trials of betamimetics, administered by any route or any dose, in the treatment of women in preterm labour where betamimetics are compared with other betamimetics, placebo or no treatment., Data Collection and Analysis: Two reviewers evaluated independently methodological quality and extracted the data. We sought additional information to enable assessment of methodology and conduct intention-to-treat analyses. We present the results using the relative risk for categorical data and the weighted mean difference for continuous data., Main Results: Eleven randomised controlled trials, involving 1332 women, compared betamimetics with placebo. Betamimetics decreased the number of women in preterm labour giving birth within 48 hours (relative risk (RR) 0.63; 95% confidence interval (CI) 0.53 to 0.75) but there was no decrease in the number of births within seven days after carrying out a sensitivity analysis of studies with adequate allocation of concealment. No benefit was demonstrated for betamimetics on perinatal death (RR 0.84; 95% CI 0.46 to 1.55, 7 trials, n = 1332), or neonatal death (RR 1.00; 95% CI 0.48 to 2.09, 5 trials, n = 1174). No significant effect was demonstrated for respiratory distress syndrome (RR 0.87; 95% CI 0.71 to 1.08, 8 trials, n = 1239). A few trials reported the following outcomes, with no difference detected: cerebral palsy, infant death and necrotizing enterocolitis. Betamimetics were significantly associated with the following: withdrawal from treatment due to adverse effects; chest pain; dyspnoea; tachycardia; palpitation; tremor; headaches; hypokalemia; hyperglycemia; nausea/vomiting; and nasal stuffiness; and fetal tachycardia. Other betamimetics were compared with ritodrine in five trials (n = 948). Trials were small, varied and of insufficient quality to delineate any consistent patterns of effect., Reviewers' Conclusions: Betamimetics help to delay delivery for women transferred to tertiary care or completed a course of antenatal corticosteroids. However, multiple adverse effects must be considered. The data are too few to support the use of any particular betamimetics.

Background: Studies in isolated cardiac myocytes have demonstrated that signaling via specific beta1-adrenergic receptor subtypes (beta1ARs) promotes but that signaling via beta2ARs protects from cell death. We hypothesized that prolonged beta(2)AR stimulation or beta1AR blockade would each protect myocytes from death and thereby ameliorate cardiac remodeling in chronic heart failure., Methods and Results: A large myocardial infarction (MI) induced in rats by coronary artery ligation resulted in a dilated cardiomyopathy (DCM) characterized by infarct expansion and a progressive increase in left ventricular (LV) end-diastolic volume, accompanied by a reduction in ejection fraction (EF), as assessed by repeated echocardiography. Pressure-volume analysis at 8 weeks after ligation showed that diastolic stiffness (Eed) and arterial elastance (Ea) were increased, end-systolic elastance (Ees) was decreased, and arterioventricular (AV) coupling (Ea/Ees) had deteriorated. Apoptosis was present in both peri-infarct and remote myocardium. Chronic (6-week) administration of the beta2AR agonists fenoterol or zinterol, starting at 2 weeks after MI, reduced the extent of LV dilation, infarct expansion, and EF decline. The beta1AR blocker metoprolol did not affect the former and preserved EF to a lesser extent than did the beta2AR agonists. At 8 weeks after ligation, apoptosis was reduced by all drugs but to a greater extent by beta2AR agonists than by the beta1AR blocker. Both beta2AR agonists and the beta1AR blocker improved AV coupling, the former mainly by reducing Ea and the latter mainly by increasing Ees. Only the beta2AR agonists reduced the Eed and the MI size by reducing infarct expansion., Conclusions: These results provide proof of concept for the efficacy of chronic beta2AR stimulation in this DCM model.

Objective: To evaluate the cost of treating premature delivery with atosiban or beta-sympatomimetic drugs (fenoterol and hexoprenalin) from the perspective of health care payer--the medical insurance company., Design: A pharmaco-economic model based on the results of randomized, controlled clinical study., Setting: Hospital Pharmacy at Vitkovice Hospital of Blessed Mary Antonia, Ostrava., Methods: The study is based on the application of clinical decision-making analysis, which includes results of a randomized controlled clinical study as well as data on the cost of clinical interventions and cost of drug therapy. The pharmaco-economic model was created from the perspective of the payer of health care--the insurance company. This model presumes the administration of atosiban or beta-sympatomimetic drugs (fenoterol and hexoprenalin) for the period of 18 and 48 h and the therapy of possible untoward effects for the next 72 h after the administration of the drugs. The analysis of sensitivity of pharmacokinetic model also employs so called low and high estimate of supplementary cost for the treatment of untoward effects., Results: After the administration of the drugs for the period of 18 h the total cost of the payer of medical care was in the range of 21,914.5-21,974.4 CKr in atosiban, 19,878.7-22,661.4 CKr in fenoterol and 19,942.9-21,974.4 CKr in hexoprenalin. In the administration of the drugs for 48 h, the overall cost of the payer of medical care was in the range of 43,082.5-43,142.4 CKr in atosiban, 19,960.3-23,150.7 CKr in fenoterol and 20,131.3-23,574.0 in hexoprenalin., Conclusions: This study compared overall cost associated with hospitalization of a premature delivery from the perspective of the medical care payer, i.e. the health insurance company. The authors applied a pharmaco-economic model evaluating hospitalization for the period of 48 h and subsequent therapy of possible untoward effects for the period of up to 72 h. In case of a shorter administration of atosiban (up to 18 h) the overall cost of hospitalization for premature delivery for the period of 48 h from the point of view of medical insurance company is basically comparable with the administration of beta-sympatomimetic drugs. If atosiban is administered for more than 18 h, the overall cost of hospitalization is higher than with beta-sympatomimetic drugs, and the cost increases in relation to the duration of atosiban administration.

The beta2-adrenoceptor agonist (beta2-agonist) fenoterol has potent anabolic effects on rat skeletal muscle. We conducted an extensive dose-response study to determine the most efficacious dose of fenoterol for increasing skeletal muscle mass in adult rats and used this dose in testing the hypothesis that fenoterol may have therapeutic potential for ameliorating age-related muscle wasting and weakness. We used adult (16-month-old) rats that had completed their growth and development, and old (28-month-old) rats that exhibited characteristic muscle wasting and weakness, and treated them daily with either fenoterol (1.4 mg kg(-1), i.p), or saline vehicle, for 4 weeks. Following treatment, functional characteristics of fast-twitch extensor digitorum longus (EDL) and predominantly slow-twitch soleus muscles of the hindlimb were assessed in vitro. Untreated old rats exhibited a loss of skeletal muscle mass and a decrease in force-producing capacity, in both fast and slow muscles, compared with adult rats (P < 0.05). However, there was no age-associated decrease in skeletal muscle beta-adrenoceptor density, nor was the muscle response to chronic beta-agonist stimulation reduced with age. Thus, muscle mass and force-producing capacity of EDL and soleus muscles from old rats treated with fenoterol was equivalent to, or greater than, untreated adult rats. The increase in mass and strength was attributed to a non-selective increase in the cross-sectional area of all muscle fibre types, in both the EDL and soleus. Fenoterol treatment caused a small increase in fatiguability due to a decrease in oxidative metabolism in both EDL and soleus muscles, with some cardiac hypertrophy. Further studies are needed to fully separate the desirable effects on skeletal muscle and the undesirable effects on the heart. Nevertheless, our results demonstrate that fenoterol is a powerful anabolic agent that can restore muscle mass and strength in old rats, and provide preliminary evidence of therapeutic potential for age-related muscle wasting and weakness.

Asthma and chronic obstructive pulmonary disease (COPD) can be effectively treated by the use of bronchodilator therapies delivered by inhalation. Berodual is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and the beta2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been available for the treatment of asthma and COPD in a pressurised metered dose inhaler (MDI) [pMDI] formulation for many years. The pMDI is the most widely used device for the delivery of inhaled medications, such as IB/FEN. However, most conventional pMDIs contain chlorofluorocarbon (CFC) propellants, which are currently being withdrawn because of their detrimental effects on the environment. This has resulted in alternative methods of drug delivery being developed. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that generates a fine, slow-moving cloud (the Soft Mist) which can be easily inhaled. Scintigraphic studies have shown that this improves deposition of drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI. A clinical development programme has been conducted to compare the efficacy and safety of IB/FEN delivered via Respimat SMI with that of IB/FEN via CFC-MDI in the treatment of patients with asthma or COPD. Five clinical studies (two phase II and three phase III) investigated dosages of IB/FEN 5/12.5 microg to 320/800 microg via Respimat SMI in single and multiple dose administration regimens. Four of the trials were conducted in patients with asthma (three in adults and one in children), while one phase III trial was conducted in patients with COPD. In phase III, 2058 patients participated, with a total of 1112 patients treated with IB/FEN via Respimat SMI. In the phase III studies, each dose from Respimat SMI was given in one actuation compared with two actuations with the CFC-MDI. In the paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer device. The results of the trials demonstrated that IB/FEN via Respimat SMI allows a reduction in the nominal dose of IB/FEN, while offering similar therapeutic efficacy and safety to a CFC-MDI. In children, Respimat SMI obviates the need for a spacer.

Aim: To study the effects of nebuliser therapy with berotek on clinical symptoms, external respiration function (ERF), bronchial permeability, hemodynamics and their temporal organisation in elderly patients with chronic obstructive pulmonary disease (COPD)., Material and Methods: The study enrolled 20 COPD patients (mean age 64.9 +/- 1.9 years) with obstructive respiratory insufficiency of the second-third degree given nebuliser therapy with berotek as adjuvant to conventional treatment (the study group) and 12 COPD patients (mean age 69.7 +/- 2.5 years) given only conventional treatment (the control group). The following parameters were examined: ERF, BP, HD, AAB, OS (SaO2) in venous blood before and after treatment. Chronobiological studies of BP and HD were performed for 7 days at the beginning and end of the study., Results: Berotek efficacy manifested on the treatment day 3 as improvement in the symptoms, IRF, BP, a rise in SaO2 and PaCO2 and a fall in PaCO2 in venous blood. Circadian chronostructure of peakflowmetry, systolic and diastolic blood pressure, mean arterial pressure persisted. Circaseptal and circasemiseptal rhythms of BP and HD disappeared., Conclusion: Nebuliser therapy with berotek has a positive effect on clinical symptoms, ERF, BP, gas exchange in the lungs, SaO2, HD and their circadian chronostructure.

Objectives: Respimat (RMT) soft mist inhaler (SMI) is a novel, propellant-free alternative to chlorofluorocarbon metered-dose inhalers (CFC-MDIs). The aim of this study was to evaluate the safety and establish the equipotent dose of fenoterol delivered by RMT SMI vs. a conventional MDI., Design: Double-blind, randomized, crossover, comparative study between fenoterol inhaled via RMT (either 50 microg/actuation, RMT50; or 100 microg/actuation. RMT100) and MDI (100 microg/actuation; MDI100)., Patients and Interventions: A total of 41 asthma patients received cumulative doses of fenoterol 600 microg (RMT50) or 1200 microg (RMT100 and MDI100) on 3 test days., Measurements and Results: The bronchodilator response (forced expiratory volume in 1 second [FEV1]) was considered therapeutically equivalent (i.e., noninferior) if the 95% confidence intervals for the difference in their mean changes from baseline were within limits of +/- 0.15L. Systemic exposure was evaluated from plasma fenoterol levels. Adverse events (AEs) were recorded. RMT50 and RMT100 produced noninferior bronchodilatation to MDI100 from 30minutes after the first dose. RMT50 showed equivalent safety and tolerability to MDI100, whereas RMT100 produced a higher incidence of AEs, a significantly greater plasma potassium reduction and a significant increase in pulse rate. Fenoterol plasma levels were twice as high with RMT100 as with RMT50 or MDI100. CONCLUSIONS; The nominal dose of fenoterol administered via RMT SMI can be at least halved to achieve equivalent efficacy, safety, and tolerability to a MDI.

The aim of the present study was to assess the reproducibility of changes in forced inspiratory volumes after bronchodilator inhalation. Thirteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 32-75%pred) and 10 patients with asthma (FEV1, 43-75%pred) inhaled either 200 microg fenoterol or 200 microg oxitropium bromide or placebo, each of them on three occasions, on nine different days in a randomised, cross-over, double-blind fashion. Forced expiratory (FEV1) and inspiratory (FIV1) volumes were measured before and 30 min after inhalation. In patients with COPD, the increase in FEV1 (coefficient of variation) was 221 ml (43%) after fenoterol and 235 ml (33%) after oxitropium; changes in FIV1 were 301 ml (45%) and 360 ml (29%). In patients with asthma, FEV1 improved by 618 ml (26%) and 482 ml (25%), FIV1 by 553 ml (41%) and 475 ml (23%). In less severe COPD or asthma, the reduction in dyspnoea was associated with the improvements in both FIV1 and FEV1, but in severe COPD with the improvement in FIV1 only. The data demonstrate that, at least in terms of relative changes, the reproducibility of bronchodilator responses in terms of FIV1 is similar to that of FEV1 and they underline the assertion of FIV1 being a sensible parameter particularly in severe COPD.

Background: This study tested whether tocolysis with beta-adrenergic agonists (Fenoterol) had an effect on the frequency of cerebral lesions in preterm neonates., Patients and Methods: Head ultrasound scans of preterm neonates who were born after long-term (> 24 h) tocolysis were compared with scans of preterm neonates without preceding tocolysis. The gestational and neonatal data were analyzed retrospectively., Results: Preterm neonates after (n = 102) and without (n = 101) tocolysis were subdivided into three groups according to their gestational age (23 - 28 wk: n = 41; 29 - 33 wk: n = 66; 34 - 36 wk: n = 96). Within these groups, no significant differences were found with respect to birth weight, rate of cesarean section, or pulmonary morbidity. Preterm babies < 28 weeks of gestation from the control group had lower Apgar scores (after 1 and 5 minutes, respectively) and arterial umbilical cord pH values. Intravenous tocolysis did not lead to an increase in pseudocystic periventricular leucomalacia (PVL) or intracerebral hemorrhage (ICH) in any of the subgroups studies. However, cerebral lesions were found in preterm neonates after tocolysis who exhibited signs of infection (29 - 33 wk: PVL n = 2; 23 - 28 wk: ICH n = 1) and in preterm neonates without tocolysis who had undergone fetal hypoxia or abruptio placentae (29 - 33 wk: PVL n = 4; antenatal terminal vein bleeding n = 1; 23 - 28 wk: PVL n = 2; terminal vein bleeding n = 5; posterior cerebral artery bleeding n = 1). When compared to preterm neonates of 34 - 36 weeks of gestation, the risk of infection was increased 4-fold in neonates of 29 - 33 weeks of gestation (odds ratio 5.43, 1.10 - 26.83) and 10-fold in neonates of 23 - 28 weeks of gestation (odds ratio 20.50, 3.65 - 115.03). Chorioamnionitis also was a more common finding in preterm neonates < 28 weeks of gestation., Conclusion: Preterm neonates who were born after intravenous long-term (> 24 h) tocolysis with Fenoterol do not exhibit an increase in periventricular leucomalacia or intracranial hemorrhage. The occurrence of cerebral lesions in these patients merely depends on their degree of immaturity and on the presence or absence of perinatal infection. In preterm neonates without tocolysis, brain lesions are mainly associated with hypoxic events.

To compare the bronchodilation and adverse effects of two commercially marketed short-acting beta2-adrenergic agonists, terbutaline (Bricanyl, 5.0 mg/2ml) and fenoterol (Berotec,1.25 mg/2ml) unit dose vials (UDV), 108 acute asthmatic children, aged 5 to 14, were randomly enrolled into this study. Nebulization treatment for 10 minutes using an air compressor nebulizer was performed after measurements of baseline spirometry, SaO2, blood pressure and pulse rate. Same measurements were repeated at 0, 5, 15 and 30 minutes after the end of the nebulization treatment. The blood pressure was also monitored immediately and 30 minutes after treatment. Almost all the spirometric parameters of both treatments at various time points significantly improved. The pulse rate significantly increased at 15 and 30 min. The SaO2 significantly increased at 30 min. The systolic blood pressure significantly decreased immediately (terbutaline only) and at 30 min (fenoterol only). No significant change was found in diastolic blood pressure. When the laboratory parameters at the same time points were compared. Significant better results for fenoterol treatment were found in FEV, at 30 min (p = 0.048), PEF at 15 and 30 min (p = 0.049 and p = 0.027, respectively), FEF25-75% at 30 min (p = 0.033), mean absolute increase of PEF at 15 min (p = 0.034) and 30 min (p = 0.021), FEF25-75% at 30 min (p = 0.046), and in mean percent increase of FEF25-75% at 30 min (p = 0.047). The adverse effects for both groups were almost equal and around 21%. In conclusion, both terbutaline and fenoterol UDV nebulization treatments are effective in treating acute asthmatic children. The adverse effects are nearly equal. The fenoterol UDV nebulization treatment shows a little better result in improving pulmonary function than does terbutaline.

Aim: To study pharmacodynamics and safety of inhalatory beta-2-adrenostimulators and M-cholinolytics given via nebulizer in patients with severe exacerbation of bronchial asthma (BA)., Material and Methods: The study covered 78 patients with severe exacerbation of BA (mean age--48.6 +/- 15.0 years). The patients were randomized into 4 groups: 23, 20, 18 and 17 patients, respectively. They were treated with: ventolin nebuly (2.5 mg), berodual (0.25 mg ipratropium bromide and 0.5 mg phenoterol), atrovent (0.5 mg), berotek (1.0 mg by nebulizer Pulmo-Aide 56501). Efficiency and safety of the treatment was assessed by the data of external respiration function, arterial blood gases and ECG each 30 min for 3 hours., Results: In patients with severe exacerbation of BA pharmacodynamics of all the studied drugs was characterized by less duration and potency of the action. Salbutamol and berotek were effective for 180 min, atrovent--for 30-60 min. Inhalation broncholytics had no such serious side effects as prolongation of corrected interval Q-T or onset of arrhythmia. Berotek demonstrated longer action on heart rate than salbutamol., Conclusion: Severe complication of BA is treated more effectively with combination of beta 2-adrenomimetic with atrovent.

Aim: Comparison of acute response to nebulizer inhalation of therapeutic doses of combined broncholitic berodual and domestic bronchoselective adrenomimetic salgim in patients with bronchial asthma (BA) and chronic obstructive bronchitis (COB)., Material and Methods: The trial included 17 COB and 15 BA patients who for two consecutive days inhaled berodual and salgim solutions. Before and after the inhalations, subjective condition of the patients and parameters of the forced expiration were recorded. The sequence of the solutions use was determined randomly., Results: Nebulizer inhalations of berodual and salgim relieved respiration subjectively in 83.9 and 93.5% patients, respectively. Significant bronchodilation was registered 30 min after inhalation of each of the solutions both in BA and COB. Berodual caused no side effects, salgim provoked short-term cough in 6(19.4%) patients., Conclusion: Nebulizer therapy of berodual or salgim is clinically and cost effective in moderate and severe obstruction in BA and COB patients.

Objective: The aim of this study of multifetal pregnancies was the comparison of three-dimensional (3D) volumetry of the cervix, conventional sonographic cervical length measurement and clinical assessment., Methods: 10 mothers were investigated in an observational study between 5/1999 and 9/2000. A total of 34 consecutive 2D- and 3D-transabdominal ultrasound measurements were performed., Results: Volumetry of the cervix was possible in all 34 exams. 2D-cervical length assessment could not be obtained in 6% because the presenting fetal part obstructed the sonographic plane. Both methods allowed equal judgement of the configuration of the cervix. A significant correlation was found between mean 2D-cervical length (28.7 mm, 7.7 SD) and mean cervical volume (30.0 cm3, 16.0 SD). Parity, subjective preterm labor or need of tocolytics showed no correlation with any biometrical parameter studied., Conclusion: Volumetry was superior for the assessment of cervical biometry and conformation in women when the transabdominal 2D-plane was obstructed. When cervical length was obtainable by a conventional scan, the technically more complex 3D-imaging did not provide further information., (Copyright 2001 S. Karger AG, Basel)

A 30-year-old male truck driver, known to be asthmatic, was found dead at the roadside lying near his car. A nebulizer bottle of Berotec (fenoterol hydrobromide) was found near his hand. The anatomic cause of death was suspected to be asthma. Toxicological screening of urine using Triage demonstrated the presence of methamphetamine. The blood concentration of methamphetamine was 0.4 microg/ml, and fenoterol was not detected. Hair analysis clearly indicated chronic methamphetamine abuse and medium dependency during the 2 months before death. We conclude that death might have been induced by the interaction of fenoterol and methamphetamine.

Background: Inhaled corticosteroids are highly effective in the treatment of asthma at all ages, and their use in younger children is increasing. There are no data currently available on the treatment of infants with acute wheeze and dyspnea with nebulized budesonide., Objective: Our purpose was to assess the clinical effect of nebulized budesonide in infants with acute wheeze and dyspnea., Methods: A prospective study was performed comparing the addition of nebulized budesonide 0.25 mg every 6 hours (group A, n = 32) and nebulized ipratropium bromide 0.1 mg every 6 hours (group B, n = 39) with the normal treatment regimen with intravenous fluid, hydrocortisone, and nebulized fenoterol. A clinical score was made at admission and every 12 hours. The score included wheezing and costal retraction (0-6) and respiratory rate (counts per minute)., Results: Seventy-one infants aged 3 to 24 months were studied (42 boys). A statistically significant reduction was seen in clinical score and respiratory rate in both groups 12 hours after admission. The children who received budesonide improved significantly faster than the children who received ipratropium bromide, and the hospitalization period was significantly lower in the budesonide group (66.4 hours) compared with the ipratropium bromide group (93 hours) (P <.01). Three patients from the budesonide group and 2 from the ipratropium bromide group were readmitted within the first 4 weeks., Conclusion: Treatment of infants with acute wheeze with nebulized budesonide is associated with faster clinical improvement and reduction in hospital stay period.

We have studied the effects of a beta-agonist, fenoterol, and a cholinergic antagonist, ipratropium, on post-intubation total respiratory system resistance (Rrs) in asthmatics who developed increased Rrs after tracheal intubation. Sixteen stable asthmatics in whom Rrs increased after intubation were allocated randomly to receive either 10 puffs of fenoterol (group F) or 10 puffs of ipratropium (group IB) via a metered dose inhaler 5 min after intubation. Anaesthesia was induced and maintained with propofol i.v. Rrs was recorded before treatment and again 5, 15 and 30 min after treatment. Rrs decreased significantly from pretreatment values by mean 53 (SD 8)%, 53 (7)% and 58 (6)% at 5, 15 and 30 min, respectively, in group F, but declined by only 12 (6)%, 15 (4)% and 17 (5)% in group IB. At all times after treatment, patients in the fenoterol group had significantly lower Rrs values than those in the ipratropium group. We conclude that increased Rrs after tracheal intubation in asthmatics can be reduced effectively by treatment with fenoterol. A secondary finding of our study was that even after induction of anaesthesia with propofol, patients with a history of asthma may develop high Rrs.

We performed this study with the aims of describing the trend of asthma-related mortality in Italy between 1980 and 1994, and to evaluate the relationship between sale estimates of beta2-agonists drugs and mortality from asthma. For asthma mortality we used data provided by National Institute of Statistics, for sale estimates of beta2-agonists we used data provided by IMS HEALTH. We calculated the gender specific age-standardized incidence rates of asthma-related deaths for all ages and for age classes. We found that estimates for asthma-related mortality steadily increased between 1980 and 1987 in both sexes, and thereafter decreased. In people, aged between 34 and 64 and over 64, death rates in males were significantly higher than in females while the rates in those aged less than 34, were mostly similar in both gender. The overall exposure to beta2-agonists (alone and in combination) increased from 1980 to 1990, remained stable between 1990 and 1993, and increased steeply in 1994. We conclude that asthma-related death rates have declined since the mid-1980's. This decline has been more pronounced in males and in the older ages, while the rates in younger patients of both genders have remained nearly unchanged. Our data do not substantiate the hypothesis of an increased risk of asthma-related mortality associated to the use of inhaled beta2-agonists in general nor fenoterol or salbutamol in particular.

Aim: To determine mechanisms inducing changes in lung gas exchange after berotec inhalation in patients with bronchial asthma (BA)., Materials and Methods: A study was made of external respiration function including estimation of lung transfer factor (TLCO sbh.) and its components--transfer coefficient (KCO), membrane diffusion capacity (DM), pulmonary capillary blood volume (Vc)--by the single breath holding method on CO in 14 healthy persons and 39 patients with BA before and after berotec inhalation. The data were obtained in the absolute values and their changes after berotec inhalation were measured in percent to initial ones., Results: In healthy subjects we did not observe changes of TLCO sbh. and its components after berotec inhalation, only an insignificant decrease of VA eff. was registered (p < 0.01). After berotec inhalation a considerable improvement in Sgaw, FEV1, RPV and a decrease of TLCO sbh., KCO were observed. Changes in TLCO sbh. were caused by a decrease in DM without changes in VA eff. in BA patients with initial normal values of KCO. In patients with smaller initial values of KCO moderate improvement of bronchial permeability without changes in KCO, PaO2 were observed. These changes occurred due to a decrease of VA eff., Conclusion: Changes of the transfer factor and its components in patients with BA reflect two types of adaptation reactions in response to berotec inhalation and their role in mechanisms of compensation of gas exchange in the lungs.

Purpose: To review the literature to determine whether inhaled ipratropium bromide provides additive benefits to adults with acute asthma who are being treated with beta-agonists in an emergency department., Subjects and Methods: English-language studies, both published (1978 to 1999) and unpublished, were retrieved using Medline, Science Citation Index, Current Contents, bibliographic reviews of primary research, review articles, consultation with experts, and the register of Medical Editors' Trial Amnesty. Only randomized, double-blind, controlled trials that enrolled patients having an exacerbation of asthma were included. The main outcome measure was pulmonary function; hospital admission rate was also evaluated., Results: Ten studies including 1,483 adults with acute asthma were selected (mean age 32 +/- 13 years, 36% men). The overall effect size in SD units of pulmonary function showed a significant benefit from ipratropium (effect size 0.14, 95% confidence interval [CI]: 0.04 to 0.24, P = 0.008). Study-specific effect sizes ranged from 0.03 to 0.63. This pooled effect size was equivalent to a 10% (95% CI: 2% to 18%) increase in forced expiratory volume in 1 second (FEV1) or peak expiratory flow in the ipratropium group compared with the control group. Analysis of the four studies that included patients with extreme obstruction (FEV1 or peak flow <35% of predicted at presentation) showed substantial improvement with ipratropium therapy (effect size 0.38, 95% CI: 0.09 to 0.67). In the five trials (1,186 patients) that studied the effect of ipratropium administration on hospital admissions, pooled results revealed that ipratropium reduced admission rates significantly (odds ratio 0.62, 95% CI: 0.44 to 0.88, P = 0.007)., Conclusions: The addition of ipratropium to beta-agonist therapy offers a statistically significant, albeit modest, improvement in pulmonary function, as well as a reduction in the rate of hospital admissions.