Bronchodilating effect of terbutaline powder in acute severe bronchial obstruction.

The bronchodilating effect of terbutaline dry powder inhaled via Turbuhaler was compared with terbutaline inhaled via a conventional, chlorofluorocarbon (CFC) inhaler and Nebuhaler (750 ml spacer) in 68 consecutive patients attending the emergency department with acute severe bronchial obstruction. The study was of an open, randomized, parallel group design with one study day. Patients were treated with 2.5 mg of terbutaline 15 min apart, either as dry powder via Turbuhaler or with a CFC inhaler in conjunction with Nebuhaler. Data from 62 patients were analyzed. The mean baseline FEV1 values were 0.81 L (SD, 0.64; range, 0.14 to 2.74 L) in the Turbuhaler group (n = 33), and 0.90 L (SD, 0.90; range, 0.27 to 2.60 L) in the Nebuhaler group (n = 29). The mean increases in FEV1 from baseline were 0.40 L (SD, 0.40; range, 0.06 to 2.36 L) and 0.21 L (SD, 0.25; range, -0.05 to 0.95 L) 10 min after the last inhalation via Turbuhaler and Nebuhaler, respectively. The difference between mean values of the increase in FEV1 after terbutaline treatment with Turbuhaler and the CFC inhaler and Nebuhaler was statistically significant (p = 0.0004, ANOVA). This study showed that inhalation of terbutaline via Turbuhaler produced a significantly greater increase in FEV1 compared with the same dose of terbutaline administered via the CFC inhaler and Nebuhaler in patients attending the emergency department with acute severe bronchial obstruction.

A proposal for a practical treatment guideline designed for the initial two-hours of the management of patients with acute severe asthma and COPD using the principles of evidence-based medicine.

We have proposed a clinical treatment guideline for the management of acute, severe asthma and chronic obstructive pulmonarydisease (COPD) using the principles of evidence-based medicine. The content is based upon practical clinical issues in need of consensus. A previous study has shown that this particular area is in serious need of quality control. Based on a strict 2 h time schedule with a unified treatment plan for both asthma and COPD, it is possible to secure for the patients a well-documented medical therapy promoting decision-making and clarification of the patient within this time limit. A summary of the statements is presented in a one-page, user-friendly format in order to cope with the clinician's need of having access to published evidence quickly and easily. A website (www.phanareth.dk or a website provided by Respiratory Medicine) has been established providing regular updates. A strategy for the implementation and the evaluation process has been planned after the publication of this paper. We believe this approach to be an important step towards an increase in the quality of guidelines and also a tool to make "guideline writers" aware of the responsibility of making their recommendations work.

The role of the novel D2/beta2-agonist, Viozan (sibenadet HCl), in the treatment of symptoms of chronic obstructive pulmonary disease: results of a large-scale clinical investigation.

Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, developed specifically to treat the key symptoms of chronic obstructive pulmonary disease (COPD), breathlessness, cough and sputum. The dual sensory nerve modulation and bronchodilator effects of sibenadet have been demonstrated in initial dose-ranging studies of patients with COPD and large-scale clinical evaluation has now been completed. Sibenadet efficacy was determined by assessing symptomatic changes, as defined by the novel assessment tool, the Breathlessness, Cough and Sputum Scale (BCSS). The findings of two placebo-controlled studies are reported. These multicentre, double-blind, placebo-controlled studies recruited over 2000 patients with stable COPD, randomized to receive sibenadet (500 microg) or placebo, pressurized metered-dose inhaler (pMDI) (three times daily) for a period of 12 or 26 weeks. Diary cards were completed daily by patients throughout the study to record BCSS scores, peak expiratory flow (PEF), study drug and rescue bronchodilator usage, changes in concomitant medication and adverse events. The primary endpoints were defined as change from baseline to the final 4 weeks of the treatment period in mean BCSS total score, and forced expiratory volume in one second (FEV1) measured 1 hour after administration of the final dose of study drug and expressed as a percentage of the predicted FEV1. In addition, clinic assessments were made to determine changes in pulmonary function, health-related quality of life, perception of treatment efficacy and adverse events. Despite initial improvements in mean daily BCSS total scores in patients receiving sibenadet, the difference in the change from baseline to the final 4 weeks of the treatment period between the two treatment groups was neither statistically significant, nor considered to be of clinical importance. Although marked bronchodilator activity was seen early on with sibenadet treatment, the duration of effect diminished as the studies progressed. Sibenadet use was not associated with any safety concerns. These studies, utilizing the novel BCSS, have clearly illustrated that, despite initial symptomatic improvement with sibenadet therapy, this clinical benefit was not sustained over the course of the study.

Treatment of acute severe asthma and chronic obstructive pulmonary disease in Danish hospitals. Do national recommendations improve on the quality of the treatment?

Studies have demonstrated suboptimal treatment of acute severe asthma and chronic obstructive pulmonary disease (COPD). We examined the quality of treatment in Denmark and the effect of intervention, by publication of recommendations for standardised treatment. All 70 hospitals in Denmark with emergency facilities participated in a telephone questionnaire, examining treatment behaviours among house officers. The survey was repeated 3 years later, after publication of national recommendations for treatment of acute exacerbations of asthma and COPD. The response rate in both surveys was 100%. An insufficient handling of nebulisers, a huge variation in the delivered dose of bronchodilators and a suboptimal use of corticosteroids was found. A significant trend towards more liberate use of oxygen was seen in both asthma (3.2 l min(-1) versus 4.8 l min(-1), P<0.001) and COPD (1.5 l min(-1) versus 1.9 l min(-1), P = 0.047). Further, a huge difference in treatment behaviours was revealed from this survey The knowledge among house officers of basic principles of treatment was insufficient. Treatment behaviour was only moderately affected by national publication of detailed recommendations for treatment. This study indicates a need for implementing tools for quality control.

Clinical efficacy and safety of Turbuhaler as compared to pressurized MDIs-beta 2-agonists.

Beta 2-agonists are one of the cornerstones in the management of patients with obstructive lung diseases. The Turbuhaler containing terbutaline has been available in several countries for a few years only but has proven to have effects comparable to those of the conventional metered dose inhaler (MDI) and other powder inhalers in the treatment of obstructive lung diseases. Even in acute severe asthma, treatment with terbutaline via the Turbuhaler has proven as effective as treatment with the conventional MDI in combination with the 750ml spacer. These results indicate that the conventional MDI containing terbutaline can be exchanged by the Turbuhaler for most clinical purposes. Thereby this new method of treatment can contribute to the reduction of chlorofluorocarbon (CFC) pollution of the atmosphere. Furthermore, CFC-provoked bronchoconstriction can be avoided.

[Self-administration of adrenaline aerosol in anaphylactic reactions after insect stings]. / Selvadministrering af adrenalinaerosol ved anafylaktiske reaktioner efter insektstik.

A serious allergic reaction after an insect sting is wellknown source for concern and anxiety. Patients with known hypersensitivity to insect stings are usually equipped with an adrenaline self-injection kit by an allergologist. In Denmark a new device for self-medication of adrenaline was approved in 1994, the adrenaline aerosol spray, Adrenalin Medihaler. The article is based on former studies and experiences, related to the usage of an adrenaline aerosol spray for the treatment of anaphylactic reactions after an insect sting. We conclude that adrenaline aerosol treatment should play an important role as emergency treatment for anaphylactic reactions after insect stings, and in most cases can replace the use of adrenalin self-injection kits. Adrenaline aerosol self-treatment could have an important beneficial effect helping to avoid exacerbation of the initial symptoms after insect venom exposition, such as bronchial obstruction and laryngeal oedema.

[Allergic rhinoconjunctivitis treated with intramuscular injection of glucocorticoid]. / Allergisk rhinoconjunctivitis behandlet med intramuskulaert injiceret glukokortikoid.

Effects and side effects of injectable depot steroid in the treatment of allergic rhinoconjunctivitis (hay fever) are described. A few controlled studies have shown injectable steroids to be superior to the effect of placebo and locally applied steroid. Over a period of 10 years from 1984-95 only 26 registered side effects were reported to the central Danish register for side effects of drugs (Laegemiddelstyrelsens Bivirkningsregister). Only eight concerned subcutaneous atrophy and in two cases the cutaneous changes persisted. Based on registration of number of treatments in the county of Funen 1996, it is estimated that the use of injectable depot steroids for treatment of hay fever accounts for about 535,000 DDD (defined daily doses corresponding to about 33,000 treatments per year). We conclude that the use of injectable corticosteroids in the treatment of hay fever is common and effective and side effects are very rare. However, injectable corticosteroids should only be used when conventional treatment is not sufficient to control symptoms.

[Treatment of severe acute exacerbation of asthma and chronic obstructive lung disease. An interview study]. / Behandling af akut svaer eksacerbation af asthma og kronisk obstruktiv lungesygdom. En interviewundersøgelse.

UNLABELLED: A telephone survey was conducted of all the 71 Danish hospitals with the capacity to receive acutely ill medical patients. The purpose was to register treatment regimes used in acute asthma and exacerbations in chronic obstructive pulmonary disease (COPD). The house officer on duty was interviewed and questioned about the use of nebulizers, oxygen therapy, bronchodilators, steroids, theophyllins and monitoring of the patient's condition. The physician survey was supplemented by a smaller survey among emergency room nurses about nebulizing systems. The answers showed inadequate knowledge of nebulizing systems. There was a noticeable variation in the dosing of oxygen and in the dosing of bronchodilators and steroids. beta 2-agonist treatment by nebulizer differed with a factor 14 in dose. The majority of the physicians had no specific parameters for monitoring severity of disease. CONCLUSION: There is a need for improvement of the knowledge of nebulizing systems, including specific knowledge of the appropriate use of propellant gasflow and time of nebulizing for optimum performance of the used nebulizer. Divergent answers from the nurses and the physicians show the need for interdisciplinary instruction. The noticeable variation in treatment in this Danish survey displays a need for quality control in terms of concise guidelines for medical therapy in acute exacerbations of asthma and COPD and guidelines for monitoring of the response to the treatment. A suggestion for a treatment regime is proposed.

[Arterial puncture or pulse oximetry?]. / Arteriepunktur eller pulsoksimetri?

Arterial puncture is the general accepted standard method for monitoring oxygen therapy in critically ill patients, but this technique is painful for the patient, has the potential of complications, and does not provide immediate continuous data. Pulse oximetry is a non-invasive method used to measure arterial oxygen saturation with a clinically acceptable accuracy of +/- 2%. Despite some limitations, pulse oximetry is considered to be reliable in most cases in detecting hypoxaemia and monitoring oxygen therapy in stationary units. The pulse oximeter can reduce the number of arterial punctures, personnel's time consumption, and limit oxygen abuse. Furthermore the new transportable and hand-held pulse oximeters offer new possibilities for continuous 24 hour monitoring of oxygen saturation also out of hospitals. The pulse oximeter can optimize monitoring patients' oxygen saturation in the stationary units, however, arterial puncture will remain the most reliable method in the assessment of hypoxaemia and hypercapnia, especially in acute situations.

[Epilepsy/cardiac arrhythmia? Differential diagnostic problems]. / Epilepsi/kardial arytmi? Differentialdiagnostiske problemer.

In cases of suspected epilepsy the possibility of cardiac arrhythmias should be considered. Two case histories are presented. One patient had grand mal epilepsy combined with Wolff-Parkinson-White syndrome. In the other patient, epilepsy was suspected. However, the final diagnosis proved out to be third degree atrioventricular block. Examination must include an electrocardiogram and in case of doubt, Holter monitoring.

[Utilization of anti-asthmatic drugs among Danish children in 1998]. / Danske børns brug af asthmamedicin i 1998.

INTRODUCTION: The aim of the study was to evaluate the use of anti-asthmatics among Danish children in 1998. METHODS: Patient specific data were collected on anti-asthmatics (ATC-group R03) prescribed for children aged 0-15 years in 1998. Data included a total of 381,557 prescriptions for 139,727 individuals. RESULTS: Anti-asthmatics were prescribed for 13.9% of all Danish children on one or several occasions in 1998. The highest one-year prevalence and incidence rate of drug use was found for children aged 0-2 years. Most children were exclusively treated with either a short acting beta 2-agonist (66.7%) or an inhaled steroid (6.5%). Only 26.2% received both types of anti-asthmatics. CONCLUSION: In conclusion, anti-asthmatics were predominantly prescribed for the youngest children. Most children were exclusively treated with a short acting beta 2-agonist in 1998, which is only recommended in the case of mild intermittent asthma.

[Theophylline treatment of irreversible, chronic obstructive pulmonary disease]. / Teofyllinbehandling ved irreversibel, kronisk obstruktiv lungesygdom.

Even though the clinical efficacy is not well established, theophylline is commonly prescribed as a second or third line drug after inhaled beta 2-agonists and corticosteroids for patients with chronic obstructive pulmonary disease (COPD). The therapeutic index is narrow, and therefore theophylline is often given in a "safe standard dose", e.g. 300 mg b.i.d. We studied the long-term effect of sustained-release theophylline 300 mg b.i.d. over four weeks in 48 patients with severe irreversible COPD (FEV1: 0.99 +/- 0.45 l, FVC: 2.21 +/- 0.68 l) in a randomized, double-blind crossover study. During theophylline treatment there was significant improvements in dyspnoea score (p < 0.001) and morning peak-flow (p < 0.05). In spite of this, there was no significant change in the patients' "sense of well-being" or their daily use of inhaled beta-agonist. Spirometric tests or arterial blood gas values did not change significantly either. It is concluded that addition of theophylline in a "safe standard dose" (i.e. 300 mg b.i.d.) has only limited value in these patients.

A new inhalation technique for improved effect of aerosolized drugs in asthma. The shrug of the shoulder method.

A new, simple technique for inhalation of aerosolized drugs is described: During the breathholding period after inhalation from a pressurized aerosol the patient lifts his right and lowers his left shoulder and vice versa to "disperse" the drug as well as possible in the lungs. Twenty outpatients suffering from reversible bronchial obstruction inhaled two puffs from a pressurized terbutaline aerosol in the morning on two consecutive days using the new inhalation technique on one day and their ordinary technique on the other in this randomised, cross-over trial. Compared with the conventional method the new inhalation technique significantly improved bronchodilation as measured by forced expiratory volume in 1st s and forced vital capacity during a period of 6 h. The new method of inhalation may improve treatment with aerosolized drugs.

Evaluation of patients with only marginally abnormal arm-ankle blood pressure gradients suspected of arterial obliterative disease.

Two groups of patients with only marginally abnormal systolic blood pressure gradients from arm to ankle were studied. Group A consisted of 24 patients, who had arteriography performed for unilateral symptoms. In the non-symptomatic limbs a significant correlation was found between the severity of obliterations and the arm to ankle blood pressure gradients, which in all cases was less than 35 mmHg. In Group B consisting of 55 patients suspected of arterial obliterative disease the arm to ankle pressure gradient was measured at rest and after 2 min. of leg exercise. The diagnostic correctness of the two procedures were analysed by the direct method for evaluation of diagnostic tests using the clinical diagnosis as final diagnostic criterion. The maximal diagnostic correctness was 85 % for the gradient at rest using values between 20 and 25 mmHg as criterion for arterial obliterative disease. It equaled the maximal diagnostic correctness of 87 % of the gradient after exercise using values between 45 and 55 mmHg as criterion.