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Thomas Ringbæk,1,2 Allan Green,1 Lars Christian Laursen,2,3 Ejvind Frausing,1 Eva Brøndum,1 Charlotte Suppli Ulrik1,2 1Department of Pulmonary Medicine, Hvidovre Hospital, Hvidovre, Denmark; 2Institute of Clinical Medicine, University of Copenhagen; 3Pulmonary Unit, Department of Internal Medicine, Herlev Hospital, Herlev, Denmark Background and objective: Tele monitoring (TM) of patients with chronic obstructive pulmonary disease (COPD) has gained much interest, but studies have produced conflicting results. Our aim was to investigate the effect of TM with the option of video consultations on exacerbations and hospital admissions in patients with severe COPD.Materials and methods: Patients with severe COPD at high risk of exacerbations were eligible for the study. Of 560 eligible patients identified, 279 (50%) declined to participate. The remaining patients were equally randomized to either TM (n=141) or usual care (n=140) for the 6-month study period. TM comprised recording of symptoms, saturation, spirometry, and weekly video consultations. Algorithms generated alerts if readings breached thresholds. Both groups received standard care. The primary outcome was number of hospital admissions for exacerbation of COPD during the study period.Results: Most of the enrolled patients had severe COPD (forced expiratory volume in 1 second

Bronchodilating effects produced by increasing intravenously administered doses of enprofylline and theophylline compared to placebo were evaluated in 20 asthmatic outpatients. Three mean plasma plateaux of enprofylline of 1.5, 2.9 and 4.0 micrograms/ml produced a mean increase in forced expiratory volume in the first second (FEV1.0) as a percentage of baseline, of 12.8%, 18.8% and 30.1%, respectively. Comparable plasma plateaux of theophylline i.e. 5.5, 10.8 and 15.2 micrograms/ml produced a mean increase of FEV1.0 in percent of basal values of 12.4%, 21.6% and 28.2%, respectively. Enprofylline at plasma concentrations above 2.9 micrograms/ml induced more headache and slightly more nausea than theophylline and placebo. Theophylline infusion produced more tremor (finger oscillation) than enprofylline and placebo. Intravenously administered enprofylline produces bronchodilation comparable to theophylline in a mean dose ratio of 3.8. [ABSTRACT FROM AUTHOR]

Background: The role and impact of chronic cough in individuals with COPD have not been described in the general population. This study hypothesized that comorbid chronic cough is a marker of disease severity in individuals with COPD., Methods: This study identified individuals with COPD and chronic cough, and recorded respiratory symptoms, health-care utilizations, lung function, and inflammatory biomarkers in blood in a nested cohort of 43,271 adults from the Copenhagen General Population Study (CGPS)., Results: Among 43,271 individuals from the general population, 8,181 (19%) experienced COPD, of whom 796 (10%) had chronic cough. Individuals with COPD and chronic cough had a Leicester Cough Questionnaire median (25th-75th percentiles) total score of 17.7 (16.0-18.9), corresponding to 5.9 (5.3-6.3) for the physical domain, 5.6 (4.9-6.3) for the psychological domain, and 6.3 (5.8-6.8) for the social domain. Among individuals with COPD, those with chronic cough vs those without chronic cough more often experienced sputum production (60% vs 8%), wheezing (46% vs 14%), dyspnea (66% vs 38%), chest pain/tightness (9% vs 4%), nighttime dyspnea (8% vs 3%), episodes of acute bronchitis/pneumonias in the last 10 years (45% vs 25%), and ≥ 3 general practitioner visits in the past 12 months (53% vs 37%). Furthermore, these individuals had lower FEV 1 % predicted (81% vs 89%) and FEV 1 /FVC (0.64 vs 0.66), as well as higher levels of high-sensitivity C-reactive protein, fibrinogen, leukocytes, neutrophils, eosinophils, and IgE in blood., Conclusions: Comorbid chronic cough in individuals with COPD is associated with a more severe disease in terms of more respiratory symptoms and health-care utilizations, lower lung function, and increased inflammation in blood., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Cough is a well-recognized symptom in asthma, but the role and impact of chronic cough in individuals with asthma has not been described in the general population., Objective: We hypothesized that among individuals with asthma, those with chronic cough versus those without have a more severe disease phenotype., Methods: We identified individuals with asthma and chronic cough among 14,740 adults from the Copenhagen General Population Study, and investigated respiratory symptoms, health care utilizations, lung function, and biomarkers in blood., Results: A total of 855 (6%) individuals suffered from asthma, and 70 (8%) had chronic cough. Individuals with asthma and chronic cough had a Leicester Cough Questionnaire median total score of 16.8 (25th and 75th percentiles, 14.8-18.9), corresponding to 5.4 (4.6-6.0) for the physical domain, 5.7 (4.6-6.4) for the psychological domain, and 6.0 (5.3-6.8) for the social domain. Among individuals with asthma, those with chronic cough versus those without reported more often wheezing (70% vs 54%), dyspnea (74% vs 49%), night-time dyspnea (27% vs 11%), sputum production (59% vs 14%), chest pain/tightness (14% vs 4%), acute bronchitis/pneumonia episodes, and general practitioner visits. Furthermore, these individuals had more often FEV 1 predicted value of less than 60% (14% vs 7%) and higher levels of neutrophils, leukocytes, and fibrinogen in blood, but there were no differences with regard to levels of high-sensitive C-reactive protein, eosinophils, and IgE in blood., Conclusions: Chronic cough in individuals with asthma is associated with a more severe disease phenotype in terms of worse respiratory symptoms, greater health care utilizations, lower lung function, and higher levels of systemic inflammatory biomarkers in blood., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Risk factors for chronic cough in the general population have not been described systematically. We identified and ranked chronic cough risk factors at the individual and community level using data from 14,669 individuals from the Copenhagen General Population Study., Methods: Severity of chronic cough was assessed using the Leicester Cough Questionnaire (LCQ). We ranked chronic cough risk factors based on magnitude of age-adjusted ORs at the individual level and of the population attributable risks (PARs) at the community level., Results: Prevalence of chronic cough in the general population was 4% overall and 3% in never smokers, 4% in former smokers, and 8% in current smokers. Median score of the LCQ was 5.8 (25th-75th percentile, 5.0-6.3) for physical domain, 5.6 (25th-75th percentile, 4.6-6.3) for psychologic domain, 6.3 (25th-75th percentile, 5.5-6.8) for social domain, and 17.3 (25th- 75th percentile, 15.4-18.9) in total. At the level of the individual, age-adjusted ORs for the three top-ranked risk factors were 5.0 (95% CI, 1.4-18) for bronchiectasis, 2.6 (95% CI, 1.7-3.9) for asthma and 2.3 (95% CI, 1.5-3.4) for gastroesophageal reflux disease in never smokers, 7.1 (95% CI, 2.6-20) for bronchiectasis, 3.1 (95% CI, 2.2-4.4) for asthma and 2.2 (95% CI, 1.5-3.2) for occupational exposure to dust/fumes in former smokers, and 1.9 (95% CI, 1.3-2.9) for airflow limitation in current smokers. At the level of the community, the three top-ranked risk factors were female sex (PAR, 19%), asthma (PAR, 10%), and gastroesophageal reflux disease (PAR, 8%) in never smokers; abdominal obesity (PAR, 20%), low income (PAR, 20%), and asthma (PAR, 13%) in former smokers; and airflow limitation (PAR, 23%) in current smokers., Conclusions: Risk factors for chronic cough differ at the level of the individual and community, and by smoking status. Strategies to prevent and treat modifiable chronic cough risk factors should be tailored accordingly., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Patients with cystic fibrosis (CF) have a higher prevalence of asthma than the background population, however, it is unclear whether heterozygous CF carriers are susceptible to asthma. Given this, a meta-analysis is necessary to determine the veracity of the association of CF heterozygosity with asthma., Methods: We screened the medical literature from 1966 to 2015 and performed a meta-analysis to determine the risk of asthma in CF heterozygotes vs. non-carriers., Results: Aggregating data from 15 studies, the odds ratio for asthma in CF heterozygotes compared with non-carriers was significantly elevated at 1.61 (95% CI: 1.18-2.21). When analyzing the studies considered of high quality in which asthma was diagnosed by a physician, the patients were >18years, or study size was ≥500, the trend remained the same, that heterozygous carriers of CF had elevated risk for asthma., Conclusions: The results show that heterozygous carriers for CF have a higher risk of asthma than non-carriers., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory failure, long-term noninvasive ventilation is controversial in unstable patients with frequent exacerbations, complicated by acute hypercapnic respiratory failure. In an uncontrolled group of patients with previous episodes of acute hypercapnic respiratory failure, treated with noninvasive ventilation, we have been able to reduce mortality and the number of repeat respiratory failure and readmissions by continuing the acute noninvasive ventilatory therapy as a long-term therapy., Methods: Multi-center open label randomized controlled trial of 150 patients having survived an admission with noninvasive ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period. The primary endpoint is time to death or repeat acute hypercapnic respiratory failure; secondary endpoints are one-year mortality, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases., Discussion: Though previous studies of long-term noninvasive ventilation have shown conflicting results, we believe the treatment can reduce mortality and readmissions when applied in patients with previous need of acute ventilatory support, regardless of persistent hypercapnia., Trial Registration: clinicaltrials.org: NCT01513655 16-Jan-2012.

The purpose of this study was to explore the effect of actively constructing virtual patient (VP) cases compared with solving VP cases on knowledge gains, skills transfer and time spent on cases. Forty-five fourth-year medical students were randomized to constructing (VP-construction, n = 23) or solving (VP-solving, n = 22) four cardiopulmonary VP cases. Whereas the VP-solving group solved the cases, the VP-construction group only received the final diagnosis and had to complete the history, physical findings, and lab results. After a week, participants completed a transfer test involving two standardized patients representing cardiopulmonary cases. Performances on the transfer test were video-recorded and assessed by two blinded raters using the Reporter, Interpreter, Manager, Educator (RIME) framework. Thirty-nine participants completed the transfer test. The VP-construction group spent significantly more time on the VP cases compared with the VP-solving group, p = 0.002. There were no significant differences in RIME scores between the VP-construction group and VP-solving group, p = 0.54.In conclusion, engaging novice students in active VP case construction may be more time consuming than solving VP cases, without resulting in superior skills transfer.

Background: Telehealth interventions for patients with chronic obstructive pulmonary disease (COPD) have focused primarily on stable outpatients. Telehealth designed to handle the acute exacerbation that normally requires hospitalization could also be of interest. The aim of this study was to compare the effect of home-based telehealth hospitalization with conventional hospitalization for exacerbation in severe COPD., Materials and Methods: A two-center, noninferiority, randomized, controlled effectiveness trial was conducted between June 2010 and December 2011. Patients with severe COPD admitted because of exacerbation were randomized 1:1 either to home-based telehealth hospitalization or to continue standard treatment and care at the hospital. The primary outcome was treatment failure defined as re-admission due to exacerbation in COPD within 30 days after initial discharge. The noninferiority margin was set at 20% of the control group's risk of re-admission. Secondary outcomes were mortality, need for manual or mechanical ventilation or noninvasive ventilation, length of hospitalization, physiological parameters, health-related quality of life, user satisfaction, healthcare costs, and adverse events., Results: In total, 57 patients were randomized: 29 participants in the telehealth group and 28 participants in the control group. Testing the incidence of re-admission within 30 days after discharge could not confirm noninferiority (lower 95% confidence limit [CL], -24.8%; p=0.35). Results were also nonsignificant at 90 days (lower 95% CL, -16.2%; p=0.33) and 180 days (lower 95% CL, -16.6%; p =0.33) after discharge. Superiority testing on secondary outcomes showed nonsignificant differences between groups. Healthcare costs have not yet been evaluated., Conclusions: Whether home-based telehealth hospitalization is noninferior to conventional hospitalization requires further investigation. The results indicate that a subgroup of patients with severe COPD can be treated for acute exacerbation at home using telehealth, without the physical presence of health professionals and with a proper organizational "back-up."

Background: Recent reviews suggest that telemedicine solutions for patients with chronic obstructive pulmonary disease (COPD) may prevent hospital readmissions and emergency room visits and improve health-related quality of life. However, the studies are few and only involve COPD patients who are in a stable phase or in-patients who are ready for discharge. COPD patients hospitalized with an acute exacerbation may also benefit from telemedicine solutions. The overall aim is to investigate a telemedicine-based treatment solution for patients with acute exacerbation of COPD at home as compared to conventional hospital treatment measured according to first treatment failure, which is defined as readmission due to COPD within 30 days after discharge., Methods: COPD patients with acute exacerbation who fulfilled the eligibility criteria and were from two university hospitals in Denmark were randomized (1:1) by computer-generated tables that allocated treatments in blocks of four to receive either standard treatment at the hospital or the same standard treatment at home using telemedicine technology (that is, a video conference system with a touch screen and webcam and monitoring equipment (spirometer, thermometer, and pulse oximeter)). Patients treated in the telemedicine group were backed up by an organizational setting securing 24/7/365 online access to the hospital, as well as access to oxygen, nebulizer therapy, oral medical therapy and surveillance of vital parameters from home monitoring devices. Patients in both groups were discharged when clinically stable and when fulfilling five pre-specified discharge criteria. Follow-up was performed at 1, 3 and 6 months after discharge., Results: Enrollment of patients started in June 2010 and ended in December 2011. Follow-up ended in May 2012. Results were analyzed in 2013., Conclusions: The results may have implications on future hospital treatment modalities for patients with severe exacerbations in COPD where telemedicine may be used as an alternative to conventional admission., Trial Registration: Clinical Trials NCT01155856.

Cough is frequently a reason for seeing a doctor. Cough has a wide range of causes and the diagnosis can be difficult to make. Cough is often benign and self-limiting but can also be the first sign of malignancy. Especially chronic cough reduces the patients' quality of life. The purpose of this review was to present the most common reasons for cough, a rational method of investigation and a management protocol. Cough is a condition, which in most cases can be treated when using a systematic approach.

A systematic review of existing evidence on the efficiency of telemedicine solutions for patients with chronic obstructive pulmonary disease (COPD) was performed. A systematic literature search was conducted in five relevant databases followed by evaluation of methodology and results in selected studies. Nine RCT trials of varying quality were identified. The selected studies were mostly multimodal with telemedicine as part of a more complex intervention. Benefits of using telemedicine solutions for patients with COPD are not yet clear, but in some multimodal studies with telemedicine as part of the solution a positive effect on hospital admissions, emergency room visits and contacts to primary care may be seen. Larger studies are needed.

Introduction: Whether smoking-induced lung inflammation subsides after smoking cessation is currently a matter of debate. We used computed tomography (CT) to evaluate the effect of smoking cessation on lung density in patients with COPD., Material and Methods: Thirty-six patients quit smoking out of 254 current smokers with COPD who were followed with annual CT and lung function tests (LFT) for 2?4 years as part of a randomised placebo-controlled trial of the effect of inhaled budesonide on CT-lung density. Lung density was expressed as the 15th percentile density (PD15) and relative area of emphysema below -910 HU (RA-910). From the time-trends in the budesonide and placebo groups the expected CT-lung densities at the first visit after smoking cessation were calculated by linear regression and compared to the observed densities., Results: Following smoking cessation RA-910 increased by 2.6% (p = 0.003) and PD15 decreased by -4.9 HU (p = 0.0002). Furthermore, changes were larger in the budesonide group than the placebo group (PD15: -7.1 vs -2.8 HU. RA-910 3.7% vs 1.7%). These differences were, however, not statistically significant. The LFT parameters (FEV(1) and diffusion capacity) were not significantly influenced by smoking cessation., Conclusion: Inflammation partly masks the presence of emphysema on CT and smoking cessation results in a paradoxical fall in lung density, which resembles rapid progression of emphysema. This fall in density is probably due to an anti-inflammatory effect of smoking cessation.

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 microg bid, or placebo. COPD was defined as FEV(1) < or = 70% pred, FEV(1)/FVC < or = 60% and no reversibility to beta(2)-agonists and oral corticosteroids. The patients were followed for 2-4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15th percentile density (PD15) and the relative area of emphysema at a threshold of -910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV(1) was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was -1.12 g/L in the budesonide group and -1.81 g/L in the placebo group (p = 0.09); the annual increase in RA-910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV(1) between ICS (-54 mL) and placebo (-56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.

Food-dependent exercise-induced anaphylaxis is a relatively uncommon variation of food-allergy. In conjunction with exercise, many foods - particularly wheat - can induce erythema, generalized urticaria, angioedema, asthma and upper airway obstruction. In more severe cases hypotension and shock occur - in rare cases with fatal outcome. Neither intake of food nor exercise alone will cause anaphylaxis. However, the symptoms can be avoided by the avoidance of the specific food for a period of four hours before exercising. The diagnosis is often established late, probably because of the rare incidence of the condition.

Xolair, Omalizumab is a monoclonal antibody targeting the high-affinity receptor binding site on human immunoglobulin E (IgE). Currently, omalizumab has been approved for the treatment of persistent allergic asthma in patients who are poorly controlled with inhaled corticosteroids. However, other allergic disorders may be amenable to treatment with omalizumab because of its ability to inhibit effector functions of IgE. Treatment with omalizumab should be administered by specialists with training in diagnosis and treatment of allergic asthma. The treatment should be withheld if no positive treatment effects are observed after 4 months.

Purpose: To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms., Material and Methods: Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed., Results: The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema., Conclusion: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.

Purpose: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema., Material and Methods: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA., Results: The coefficients for volume adjustment for PD were relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema., Conclusion: Volume adjustment is mandatory in repeated CT densitometry and is more robust for PD than for RA. Therefore, PD seems more suitable for monitoring the progression of emphysema.

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.

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.

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.

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.

The importance of reversible airflow obstruction to the prognosis of asthma and chronic obstructive pulmonary disease (COPD) is not clear. We tested the hypothesis that reversibility to corticosteroid and bronchodilator is not an independent predictor of prognosis, but merely reflects a component of the maximal attainable lung function, which is the best spirometric predictor of survival. During a 6-yr period (1983-1988), 1,586 subjects with asthma or COPD underwent standardized bronchodilator and corticosteroid reversibility tests at a chest clinic in Copenhagen. The vital status was obtained by September 1997. The relationship between mortality and age, gender, smoking, FEV1, and reversibilities was examined by Cox proportional hazards analyses. Of 1,586 subjects, 850 had died before September 1997. Age, smoking, and FEV1 were significant predictors of mortality. After controlling for baseline FEV1, bronchodilator and corticosteroid reversibility were significantly associated with better survival. However, after controlling for best FEV1 all reversibilities became nonsignificant and nonpredictive. The combined use of corticosteroid and bronchodilator reversibility in survival analyses is a novel approach, and we have shown that both contribute to survival prediction to the extent that they modify FEV1. However, reversibility per se does not influence survival in subjects with moderate to severe asthma or COPD.

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.

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.

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.

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.

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.

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.

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.

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.

In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low-dose metoclopramide (LDM) (70 mg) + L (2.5 mg x 2 po) + dehydrobenzperidol (5 mg x 2 im). Among the 29 patients who completed the cross-over, HDM significantly reduced the number of vomiting episodes (p = 0.002) and the degree of nausea (p = 0.004). Seventeen patients preferred the HDM and 4 the LDM regimen (p = 0.01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low-dose metoclopramide + lorazepam + dehydrobenzperidol. Owing to the severe sedation which occurs in some patients, the dose of lorazepam should be individually adjusted.

Twenty-five asthmatic outpatients were treated for 3 one-week periods with either enprofylline slowly eroding 300 mg tablets t.i.d., theophylline 300 mg tablets (Theo-Dur) t.i.d., or placebo in a double-blind, cross-over, randomized trial. Sixteen patients were able to complete 2 or 3 one-week periods. Evaluation of bronchodilating properties by home recordings of peak expiratory flow (PEF) and side effects suggested that enprofylline was an effective antiasthmatic xanthine derivative for continuous treatment, as it improved mean morning PEF significantly. Continuous treatment with the 2 xanthine derivatives resulted in mean steady state plasma levels within therapeutic range for theophylline, and 3-4 times lower mean plasma levels for enprofylline. Enprofylline induced headache in 13 of 16 patients, theophylline in 9 of 19 patients, and placebo in 2 of 18 patients. No serious side effects were seen.

In 6 asthmatic patients, the possibility of obtaining a steady state plasma level of 5 mg/l of enprofylline by administration of two constant rate infusions was examined. The simulated plasma concentration curves, based on information from preassessment of individual pharmacokinetic parameters, were in good agreement with the plasma levels obtained. The side-effects and bronchodilatation produced by enprofylline were compared to those obtained with theophylline at a steady state level of 15 mg/l. Enprofylline and theophylline caused a mean maximal increase in FEV1.0 of 14% and 2.6% per mg/l in plasma, respectively. Side-effects, headache, nausea and vomiting, became pronounced in 2 patients in whom the plasma enprofylline level was about 6 mg/l. No other serious adverse reaction was seen. It is suggested that enprofylline should be further evaluated as a possible anti-asthmatic drug.

Twenty-two asthmatics received bambuterol solution, a terbutaline pro-drug, once every evening. The following doses were each given orally for 7 days in a double-blind cross-over study: 0.185, 0.270 and 0.400 mg/kg. Bambuterol 0.270 mg/kg was preferable regarding clinical effects and side effects. The plasma concentration of generated terbutaline showed a slow linear decrease at all doses. Tests of two methods for objective measurements of tremor in five patients did not add any new data compared with the subjective recordings.

In 23 stable asthmatic patients sensitivity to inhaled beclomethasone dipropionate (BDP) was demonstrated during single blind gradual tapering off of BDP. After a 2 week stabilization period the patients were randomly allocated to receive either 4 puffs of 50 micrograms BDP twice daily (AM/PM) or 8 puffs of 50 micrograms once daily (AM). After 4 weeks the patients were crossed over. Fifteen patients preferred the twice daily regimen, 5 preferred once daily and 3 had no preference (p less than 0.05). During the once daily dosing regimen a decrease in morning and evening peak expiratory flow (p less than 0.05) and an increase in nighttime and daytime symptom score (p less than 0.05) was found, while the number of inhaled beta 2-agonist doses did not change significantly (p = 0.05). It is concluded that a twice daily regimen controls the asthmatic symptoms significantly better than a once daily regimen.

Six patients undergoing diagnostic lumbar myelography were studied with respect to plasma and cerebrospinal fluid (CSF) concentrations of two xanthine drugs--enprofylline and theophylline. Three patients received enprofylline and three patients received theophylline, 200 mg t.i.d., and plasma and CSF were sampled on the morning of the third day of treatment. CSF plasma ratios averaged 0.095 with enprofylline (range of 0.094-0.097) and 0.36 with theophylline (range of 0.35-0.37). The different ratios of the two drugs contrast to their similar plasma protein binding, about 50%. Different lipophilicity or differences with regard to transport out of the CSF may explain the discrepancy.

A double-blind, double-dummy comparative study was made of 30 adult birch pollen-allergic outpatients with seasonal rhinoconjunctivitis. They were treated with either topically applied beclomethasone dipropionate 100 micrograms in each nostril twice daily for 4 weeks, placebo, or an injection of 2 ml of a suspension containing 5 mg betamethasone dipropionate and 2 mg betamethasone disodium phosphate per ml (Diprospan) immediately prior to the birch pollen season. Placebo- and topical steroid-treated patients experienced an increase in rhinoconjunctivitis symptoms, i.e. nasal blockage, nasal itching, rhinorrhea, sneezing and eye symptoms, and placebo-treated patients used significantly more antihistamine tablets during the pollen season. Diprospan-treated patients experienced fewer symptoms on all measured parameters. We concluded that one injection of Diprospan immediately prior to the birch pollen season produces significantly fewer rhinoconjunctivitis symptoms than does placebo and topical steroid treatment.

Fifteen asthmatic outpatients were randomly treated during two periods of 14 days each with sustained-release preparations of either enprofylline (3-propyl-xanthine) or theophylline (Theo-Dur) in a double-blind crossover study. After 4 days of treatment the mean daily doses of enprofylline and theophylline, which were 14.1 and 16.2 mg/kg/day, produced mean plasma concentrations of 4.9 and 12.7 micrograms/ml, respectively. Taking into account all the parameters used to evaluate the antiasthmatic effects, the peak expiratory flow, the number of puffs used from a beta-agonist aerosol, the asthma symptom score and the patients' preferred period, enprofylline was found to be better than theophylline. Enprofylline produced more headaches during the 1st week than theophylline did. However, during the 2nd week the score for headaches decreased to the same level as in the theophylline treatment group. Thus, enprofylline and theophylline seem to have comparable bronchodilator properties and side-effects in the long-term treatment of asthma.