[Quality assurance or research?].
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Denmark↗
Biomedical subjects
A Dirksen
Publications and source records attributed to A Dirksen.
[New treatment of emphysema--research or quality assurance?].
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Clinical Trials as Topic↗
[Prolastin in the treatment of mild emphysema in patients with alpha 1-protease inhibitor deficiency].
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Humans↗
Distribution of serum IgE in children and adolescents aged 7 to 16 years in Copenhagen, in relation to factors of importance.
The distribution of total serum-IgE and factors of importance for the level of IgE was studied in a random sample of 508 children and adolescents, aged 7-16 years, from Copenhagen. A detailed history about asthma, rhinitis, dermatitis and urticaria was obtained, and a physical examination, skin prick test with 9 common allergens, lung function test, bronchial challenge with inhaled histamine and exercise, and measurement of IgE (kU/l) were performed. The distribution of IgE among children and adolescents was found to exhibit a log normal distribution and a positive skin prick test, allergic symptoms, a family history of allergic diseases, age and smoking were found to be significantly related to an increased level of IgE. No relationship was found between increased bronchial responsiveness and IgE. The geometric mean of "normal" values of IgE (*1 SD and *2 SD) of the Danish children and adolescents was 18 kU/l (*4.7, *18.2), suggesting that normal IgE values were within 330 kU/l. Measurement of IgE as the only screening for allergic disease is unreliable, as the predictive value of an elevated IgE in population samples was found to be 50%, whereas misclassification (1-specificity) of asymptomatic subjects as allergic because of an increased IgE was low (4%). In conclusion, total IgE is highly influenced by allergen skin reactivity. Further, this study suggests that normal IgE values were within 330 kU/l, although the range was wide.
Adolescent↗
A 10 year follow up of 180 adults with bronchial asthma: factors important for the decline in lung function.
BACKGROUND: Little is known about the factors that determine outcome in asthma. The purpose of this study was to describe the relation of various factors of potential importance to the rate of decline in lung function in adults with intrinsic and extrinsic asthma. METHODS: Of 180 asthmatic patients, 143 (79%) participated in a 10 year follow up examination. At the time of enrollment all patients underwent certain tests for asthma (case history, total IgE, skinprick tests, the radioallergosorbent test (RAST), histamine release from basophil leucocytes, and specific bronchial provocations). On the basis of these tests 94 patients had intrinsic asthma and 49 extrinsic asthma. RESULTS: Patients with intrinsic asthma had an annual decline in FEV1 of 50 ml, whereas those with extrinsic asthma had a decline of 22.5 ml; the rate of decline of lung function increased with increasing age in both groups. An inverse relation between initial FEV1 and decline in FEV1 (the "horse racing effect") was found for the patients with extrinsic asthma but not for the patients with intrinsic asthma. There was no relation between rate of decline in lung function and number of cigarettes smoked. A high degree of airway variability--that is, reversibility in FEV1--at the time of enrollment was found to be associated with a steeper decline in lung function in patients with intrinsic asthma, whereas increasing degrees of obstruction (decreasing FEV1/VC ratio at enrollment) and need for treatment with corticosteroids were associated with a more pronounced decline in FEV1 in patients with extrinsic asthma. CONCLUSIONS: The rate of decline in lung function is greater in patients with intrinsic asthma than in patients with extrinsic asthma; the prognosis for intrinsic and extrinsic asthma is to some extent influenced by different factors, which suggests that the pathogenetic mechanisms underlying intrinsic and extrinsic asthma may differ.
Adult↗
Airway calibre as a confounder in interpreting bronchial responsiveness in asthma.
BACKGROUND: The relation between airway responsiveness to constrictor agents and forced expiratory volume in one second (FEV1) is important when interpreting change in airway responsiveness after an intervention. The aim of the study was to analyse the relation between FEV1 as a percentage of predicted values (% predicted) and airway responsiveness between and within asthmatic subjects. METHODS: Results of non-specific bronchial challenge tests were pooled from two randomised crossover studies comparing the effect of a non-sedative antihistamine with placebo in 35 patients with moderate asthma. The design of the two studies was similar: the provocative concentration of either histamine (first study) or methacholine (second study) resulting in a 20% decrease in ventilatory capacity (PC20) was repeated at two week intervals while patients were treated with the antihistamine or placebo. The dose of inhaled corticosteroid was gradually reduced during the study. Data were analysed with PC20 as the dependent variable in a general linear model so that the influence on PC20 of inhaled corticosteroid dose, antihistamine, and choice of bronchoconstricting agent could be separated from the influence of FEV1% predicted. RESULTS: The correlation coefficient between mean PC20 and mean prechallenge FEV1 for each patient was 0.45. In the general linear model two thirds (65%) of the variation in PC20 was due to variation between subjects. One third of the within subject variation in PC20 could be explained by variation in prechallenge FEV1% predicted (a change in FEV1 of 27% predicted was associated with one doubling or halving of PC20). Treatment with the antihistamine had no influence on PC20, except when histamine was used as the bronchoconstricting agent. The dose of inhaled corticosteroid had a small but significant effect. CONCLUSIONS: The variation in a patient's PC20 over time (several months) is related to changes in FEV1% predicted. Variation in FEV1% predicted explains less of the variation in bronchial responsiveness between subjects where a patient specific factor, which is probably related to the pathogenesis of bronchial asthma, seems to dominate.
Adrenal Cortex Hormones↗
Mortality and decline in lung function in 213 adults with bronchial asthma: a ten-year follow up.
The purpose of this longitudinal study was to describe mortality and change in lung function in adults with bronchial asthma, and furthermore to investigate a potential difference in the prognosis for patients with intrinsic and extrinsic asthma. Out of 213 asthmatics admitted to our hospital, 170 (82%) participated in a 10-year follow-up examination; according to the tests for extrinsic asthma at the first examination, the patients were divided into 117 patients with intrinsic asthma and 53 subjects with extrinsic asthma. Twenty-seven (13%) patients, 23 with intrinsic and 4 with extrinsic asthma, died during the observation period, which was almost twice the number expected in both intrinsic and extrinsic asthmatics, but because of the small number of patients with extrinsic asthma, the findings were statistically significant for the intrinsic asthmatics only (p less than 0.05). Seventeen (8.2%) died of pulmonary diseases, of whom 9 (6 patients with intrinsic asthma) died in an acute attack of bronchial asthma. After a questionnaire concerning respiratory symptoms had been answered, a lung function test was performed in all subjects in both 1976-1979 and 1988. A histamine challenge test was performed at the examination in 1988. Of the 143 subjects who were re-examined in 1988, 96% still had respiratory symptoms. The first lung function test in 1976-1979 showed no difference in FEV1 (% predicted) between the two groups, whereas the annual mean loss of FEV1 during the observation period for the intrinsic and extrinsic asthmatics was 50 ml and 22.5 ml, respectively (p less than 0.0001). Decline in FEV1 was found to be independent of smoking habits in both patient groups. We found that the decline in lung function increased with increasing age in both intrinsic and extrinsic asthmatics (p less than 0.001 and p less than 0.05, respectively). The so-called "horse-racing effect" could be demonstrated for the patients with extrinsic asthma (p less than 0.003); whereas no significant relation was found between FEV1 at the time of enrollment and decline of FEV1 for the intrinsic asthmatics. We conclude that asthmatic subjects have an excess mortality and that the prognosis for intrinsic asthma is worse than that of extrinsic asthma with regard to rate of decline in lung function.
Adolescent↗
A seven-year follow-up study of 343 adults with bronchial asthma.
A study of 343 urban adult outpatients with a history of bronchial asthma was initiated in 1981. Asthma was verified by a reversibility in airflow obstruction of at least 0.5 1 in forced expiratory volume (FEV1) (70%). The rest of the 343 patients was included because of diurnal variations of at least 100 l/min in peak expiratory flow (PEF) (22%), or because of a characteristic history of asthma (8%). In 1988, a follow-up study was performed. Two hundred-fourteen patients replied (80%), 100 women and 114 men. Fifty-four did not respond, but were known to be alive. Twenty-one had emigrated; of these, the fate of five was unknown. The mortality rate was significantly raised among the men (Standard mortality rate (SMR) = 1.55). In 19%, the cause of death was pulmonary. Seventeen percent were found dead. In these, no cause of death was obvious, and they may have died from an exacerbation of their pulmonary disease. One hundred and forty-four had non-allergic and 69 allergic asthma verified retrospectively by positive skin prick test in 1988. One was not tested and not classified. Seventy-five percent of the whole group were smokers. An annual decline of approximately 90 ml per year in FEV1 was found in both groups and was only partially explained by smoking and ageing. The remaining observed decline in lung function may be caused by asthma. Reversibility of 0.5 l in FEV1 was only maintained in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Atopy and bronchial responsiveness in random population sample of 527 children and adolescents.
The relationship between bronchial responsiveness, lung function, and results of skin prick testing was studied in 527 children and adolescents from Copenhagen. All participants completed a questionnaire concerning allergic symptoms (asthma, rhinitis, atopic dermatitis, and urticaria). Furthermore, skin prick test reactivity to nine common aeroallergens, lung function, serum IgE and bronchial responsiveness to histamine and exercise were measured. A total of 53 subjects were atopic, (skin prick 3+), 105 subjects had moderate skin reactivity (1-2+), and 366 subjects had no signs of atopic disease (prick test negative); 58% of the subjects with skin test reactivity (1-3+) were asymptomatic. Increasing degree of atopy was correlated significantly with symptoms such as asthma, rhinitis, dermatitis, and urticaria (P less than .001); increasing level of IgE (P less than .001); month of birth (P = .001); and family history of allergic diseases (P less than .05). The most important markers for the degree of bronchial responsiveness to inhaled histamine were the presence of respiratory symptoms (P less than .001), the degree of atopy (P = .001), a history of asthma in at least two first degree relatives (P less than .01), and the skin reactivity to house dust mites (P = .001), horse epithelium (P = .01), Alternaria iridis, and dog epithelium (P less than .05). In contrast, the degree of bronchial responsiveness to exercise was significantly correlated with asthma (P less than .001), the level of IgE (P less than .05), month of birth (P less than .001), and birth weight (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Assessment of the surgical risk. Is the time between myocardial infarction and a possible surgical procedure of significance for a surgical risk?].
During a five year period, 320 patients suffered from acute myocardial infarction (AMI) and within the next twelve months became candidates for surgery for either appendicitis (99 patients) or for a hip fracture (221 patients). An evaluation of the mortality at the second event (i.e. appendicitis or hip fracture) in relation to the time between AMI and second event, was done following the intention to treat principle. Appendicitis occurred with the same incidence during all 12 months following AMI. The second event mortality was independent of the time interval from AMI to second event. Age, infarction prior to index infarction and congestive heart failure were prognostically important in relation to second event mortality, but did not affect the constant second event mortality during the first year following AMI. Hip fracture occurred more often during the first months following AMI, where the second event mortality was highest. Congestive heart failure either prior to index infarction or at the index infarction was prognostically important in relation to second event mortality. The relatively high mortality in the first months after AMI could partly be explained by an association between congestive heart failure and hip fracture in the first months after AMI. We conclude that the "operative" mortality in patients with recent AMI is high. The mortality is related to congestive heart failure and not to the time between AMI and surgery.
Appendectomy↗
Spontaneous changes in bronchial responsiveness in children and adolescents: an 18-month follow-up.
The purpose of this study was to investigate spontaneous changes in bronchial responsiveness to inhaled histamine over a period of 18 months. The first measurements in 495 subjects, 7 to 16 years of age, were made in 1986. Bronchial hyperresponsiveness (BHR), i.e., PC-20 FEV1 less than or equal to 8.0 mg/mL, was found in 79 (16%) individuals, of whom 28 (35%) had symptoms of asthma. Twenty asthmatic and 42 non-asthmatic subjects who had BHR (78%) were re-examined 18 months later. The asthmatics had a modest change in BHR, while in the non-asthmatics bronchial response to inhaled histamine and exercise was significantly decreased. In twenty-two subjects (36%) bronchial response was within the normal range; of these 18 were non-asthmatic. Six asthmatics (30%) and two non-asthmatics (5%) had an increased BHR at follow-up. Two subjects (5%) developed symptoms of asthma by the time of follow-up, with an unchanged degree of BHR. Sex, age, atopic symptoms, and viral respiratory infections at the first examination were unrelated to changes in bronchial responsiveness. However, changes of BHR in the non-asthmatic subjects were significantly correlated to changes in bronchial response to exercise. Although spontaneous changes in bronchial responsiveness occur in asthmatic, as well as non-asthmatic subjects, asthmatics persistently have hyperresponsive airways. Development of asthma was found to occur among subjects with persistent BHR.
Adolescent↗
The distribution of bronchial responsiveness to histamine and exercise in 527 children and adolescents.
The aim of the study was to describe the bronchial responsiveness to inhaled histamine and exercise in a randomly selected group of 527 children and adolescents from Copenhagen, aged between 7 to 16 years. The distribution of the bronchial responsiveness was described as (1) the provoking concentration that causes a 20% reduction in FEV1 (2) the dose-response slope (DRS), that is, the linear slope of the dose-response curve, and (3) reduction in FEV1 after 6 minutes of exercise on a treadmill. The distribution of the concentration that causes a 20% reduction in FEV1 in the responsive range was not significantly different from a unimodal distribution, although the findings were skewed toward the less responsive end of the range (p greater than 0.05). The subjects with asthma represented a subgroup within the responsive distribution tail rather than a separate distribution peak. In asymptomatic individuals, the values of DRS were distributed symmetrically on a logarithmic scale. The deviation from normal was such that the standard deviation only slightly underestimated the "normal" range. The distribution of the bronchial response to exercise was found to be significantly different from a normal distribution. However, a significant relationship was found between the bronchial response to inhaled histamine and exercise (p less than 0.0001). We conclude that there is a log-normal distribution of the bronchial response to inhaled histamine in a random sample of children and adolescents.
Adolescent↗
Single-dose inhaled budesonide in subjects with chronic asthma.
In 30 stable asthmatics, a comparison was made between the changes in pulmonary function (FEV1, FVC, PEF, MEF75, MEF50 and MEF25) hourly for 9 h after a single dose of inhaled budesonide 1,600 micrograms, and placebo. All subjects used inhaled steroids daily; this medication was, however, withheld 8 days prior to the study. For all parameters of pulmonary function, a significant difference in favour of budesonide was demonstrated. The effect tended to decrease after 9 h, and had abated within 24 h. FEV1 age, sex, smoking habits, or results of an inhaled beta 2-agonist reversibility test could not be demonstrated as predictors of those subjects to react with the most pronounced responses to budesonide. In conclusion, our results demonstrate an effect 3 h after administration of an inhaled glucocorticosteroid in adult outpatients with chronic asthma. These results parallel previous findings in highly selected asthmatics and after systemic administration of glucocorticosteroids. Single-dose administration and subsequent monitoring for 8-9 h may therefore prove valuable in evaluating new prophylactic agents for the treatment of asthma.
Administration, Inhalation↗
Sensitivity and specificity of the histamine challenge test for the diagnosis of asthma in an unselected sample of children and adolescents.
The purpose of this investigation was to study factors of importance for the degree of bronchial responsiveness and, furthermore, to evaluate the sensitivity, specificity and predictive value of a bronchial challenge test with histamine for the diagnosis of asthma in 495 randomly selected children and adolescents, aged 7-16 yrs, from Copenhagen, Rigshospitalet. Detailed history about allergic symptoms, physical examination and bronchial histamine challenge tests were performed at the out-patient clinic. Asthma, atopic disease and height were found to be of great importance for the degree of bronchial responsiveness, whereas the age, sex and smoking habits were of no significance. The percentage of asthmatics with bronchial hyperresponsiveness, i.e. sensitivity to the test, increased towards 100% on inhaling increasing concentrations of histamine, but this was accompanied by a decrease in specificity and predictive values of positive test in regard to the diagnosis of asthma. However, lower concentrations of histamine may be preferable in order to distinguish between asthma and non-asthma in population samples, as inhalation of 2.4 mg.ml-1 and provocative concentration producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) provided an acceptable sensitivity (57%), specificity (98%), and predictive value of a positive test (60%). We conclude that as regards the diagnosis of asthma, a low predictive value confirms that the bronchial challenge test plays only a supplementary, but valuable, role in detecting the disease in population samples.
Adolescent↗
Bronchodilator and corticosteroid reversibility in ambulatory patients with airways obstruction.
With the aim of characterising subgroups, we analysed reversibility tests from 1,048 patients with airways obstruction (baseline FEV1 less than 60% of predicted normal (%pred), and FEV1 to FVC ratio less than 0.6). Spirometry before and after inhalation of salbutamol 0.3 mg and ipratropium bromide 0.06 mg was performed before and after one week of treatment with prednisone 30 mg daily. The changes in FEV1 after bronchodilators showed unimodal distribution (mean = 7.0 %pred, st.dev. = 6.6 %pred). The responses to corticosteroid were more spread out (mean = 6.3 %pred, st.dev. = 13.8 %pred). The correlation between bronchodilator responses before and after corticosteroid treatment was poor (r = 0.30), although highly significant (p less than 0.000,001). The responses to bronchodilators were virtually independent of the steroid reversibility. The corticosteroid response was inversely related to age (r = -0.20, p less than 0.000,001) and smoking habits (r = -0.17, p less than 0.000,001), and moderately associated with blood eosinophilia (r = 0.34, p less than 0.000,001). The frequency distribution of the bronchodilator responses and the steroid response and combinations of the responses were all unimodal, making any distinction between nosologic subgroups arbitrary. It is clear from the study that criteria other than just response to therapy must be employed for distinction of subgroups among patients with airways obstruction.
Adolescent↗
[Medical informatics].
Medical informatics is the discipline concerned with information and information streams in health care. The development of information technology has been intensified in recent years and is now influencing the international development within the health care sectors. During the coming decade, integrated hospital networks will supple communication within and between hospitals. New productivity measures useful in administrative planning are being developed. Patient data are being digitalized and stored electronically, and interactive media are implemented in education. Primarily, however, chip-based technologies find application in the evaluation of the increasing quantity of paraclinical data. Internationally product development and research are actively underway. The EEC has established development programmes specifically stimulating these activities. Is Denmark going to take an active part in this development, formalized frames are required.
Denmark↗
[New therapeutic possibilities in alpha 1-antitrypsin deficiency].
The alpha-1-antitrypsin gene is localized to chromosome 14. Numerous genetic variations may occur and some of these result in severely reduced concentration in the serum. The commonest cause of severe deficiency of alpha-1-antitrypsin is the gene-variant Z in the homozygotic form which occurs in one out of 2,000 Danes. Severe deficiency in alpha-1-antitrypsin results in liver symptoms in approximately 10% of the children. Some of these will develop cirrhosis of the liver. In adults at the ages of about 30 to 40 years, gradual development of emphysema occurs and this is earliest and most pronounced in smokers. Adults have also increased frequency of cirrhosis but this is much less pronounced than the development of emphysema. In addition to a number of theoretical therapeutic possibilities, liver transplantation is now possible and this is employed particularly in children with cirrhosis. In young persons with terminal pulmonary insufficiency with anticipated survival for less than one year, heart/lung transplantation or possibly isolated lung transplantation may be considered. An alpha-1-antitrypsin concentrate has been produced. Intravenous dosage once monthly can provide a concentration in the serum for three to four weeks which, as a rule, suffices to prevent emphysema. It is not yet known whether this treatment has any prophylactic effect in cases of developed emphysema. It is to be anticipated that treatment instituted prior to development of emphysema will prevent development of pulmonary disease but the treatment is rather expensive and must, probably, continue throughout life. No controlled investigation of the effect of treatment is available and the range of indications is not defined.
Female↗
[Pulmonary function and survival of patients with alpha 1-antitrypsin deficiency, residents of Copenhagen].
From 1976 to 1987 alpha 1-antitrypsine deficiency type PiZZ was diagnosed in 89 patients living in the Copenhagen urban area (mean age: 45 years). Spirometry was performed yearly in 66 of these patients (mean observation period was 50 months). At the time of diagnosis basic FEV1 was significantly lower in smokers and ex-smokers than in patients who had never smoked (45%, 44% and 84% of predicted normal, respectively). However, the decline in FEV1 was similar (3% per year) in all three categories of smokers. Our results indicate that both smokers and non-smokers are at risk of developing pulmonary emphysema, however, the disease usually appears later in life or not at all in non smokers.
Adult↗