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A Dirksen

Publications and source records attributed to A Dirksen.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Mathematical coupling and "regression to the mean". A statistical case history].

"Regression to the mean" (RTM) is a statistical phenomenon originating from the random variation of variables rather than a true association between the variables. RTM is closely linked to mathematical coupling; unawareness of these phenomena may lead to misinterpretation of data. A study examining intracranial pressure before and after infusion of manitol is presented, in which mathematical coupling caused a highly significant (but spurious) correlation between the analysed data. The significance of RTM and mathematical coupling is demonstrated by analysis of a data set derived from random numbers.

Data Interpretation, Statistical↗
PubMed1999

Office spirometry: temperature conversion of volumes measured by the Vitalograph-R bellows spirometer is not necessary.

The aim of the present study was to investigate the relevance of BTPS (gas at body temperature, atmospheric pressure and saturated with water vapour) conversion of volumes measured with the Vitalograph bellows spirometer. The Vitalograph bellows were tested against a MicroMedical turbine spirometer in extreme temperatures (0-37 degrees C) using a biological control to deliver expired gas at BTPS. Before testing, it was shown that the accuracy of the DairyCard turbine was stable in the relevant temperature range. In a clinical trial six patients with emphysema performed home spirometry b.i.d for 1 month using both the Vitalograph and the turbine. Both the DairyCard and the Vitalograph showed stable accuracy at extreme temperatures when results were reported without any BTPS conversion. These findings were supported by the clinical trial but the conclusions from the clinical setting were weakened by the surprising fact that domiciliary temperatures showed almost no variation. We conclude that the Vitalograph bellows, during dynamic spirometry, measures expired volume at conditions closer to BTPS (than to ATPS) gas at ambient temperature, atmospheric pressure and saturated with water vapour). The use of the BTPS correction based on ambient temperature seems unjustified at office temperatures close to 23 degrees C and at extreme temperatures the conversion of volume will introduce significant over or underestimation.

Adult↗
PubMed1999

Increasing prevalence of allergic rhinitis symptoms in an adult Danish population.

There is evidence that the prevalence of respiratory allergy is increasing. This is mainly based on studies in children and young adults. The aim of the study was to compare the prevalences of self-reported symptoms of respiratory allergy among Danish adults in two surveys 8 years apart. Identical questionnaires were mailed to two random general population samples in 1989 and 1997. The response rates were 86.1% (n = 3603) and 86.4% (n = 817), respectively. The sampling frame and sampling method were identical in both surveys. The changes in the prevalences of symptoms were expressed by sex- and age-adjusted odds ratios comparing 1997 to 1989. We found a significant increase in the prevalence of seasonal rhinitis symptoms (OR=1.6, 95% CI 1.4-1.9), rhinitis symptoms on exposure to pollen (OR =1.6, 95% CI 1.4-1.9), rhinitis symptoms on exposure to furry animals (odds ratio 1.6, 95% CI 1.3-2.0), rhinitis symptoms on exposure to house dust (OR = 1.3, 95% CI 1.1-1.6), and breathlessness on exposure to pollen (OR = 1.5, 95% CI 1.0-2.0). The observed increases were independent of sex and age. The questionnaire was validated in relation to allergen skin test reactivity in a subgroup of the responders to the 1989 survey. When the estimated associations between symptoms and skin test reactivity were considered, the results suggested an increase in allergy to pollen and animal dander. In conclusion, we found evidence of increased prevalence of allergic rhinitis symptoms associated with skin test reactivity.

Adolescent↗
PubMed1999

Transmitting genetic risk information in families: attitudes about disclosing the identity of relatives.

Attitudes about disclosing the identities of family members to a physician to ensure diffusion of genetic risk information within affected families were examined in a questionnaire study of Danish patients with alpha1-antitrypsin deficiency (A1AD), their relatives, and a control group of Danish citizens. The questionnaires were returned by 1,761 (82%) of 2,146 recipients; 1,609 (75%) agreed to participate and completed the questionnaire. Only 2.8% objected to disclosing the identity of children, 9.1% objected to disclosing the identity of parents, and 6.7% objected to disclosing the identity of siblings. When genetic tests are offered to a sister, 75.4% of screened individuals with severe A1AD (phenotype "piZ") and 66.8% of piZ probands thought that the physician should say who is ill. Important reasons for informing a sister at risk were, for 58%, the opportunity to prevent disease and, for 41% of piZ-probands, the opportunity to maintain openness in the family and to avoid uncertainty. Stepwise logistic regression of background variables showed that relatives were those for whom most respondents approved the disclosure of the parents' and siblings' identities to enable the physician to examine them for the presence of A1AD. Women were less prone to disclose the identity of siblings. The results indicate that the genetic counselor should inquire about relatives' identities, to ensure that they are properly informed about the known risk of severe genetic disorder, such as A1AD, for which disability can be prevented by a change of lifestyle or by careful management. Disease prevention is essential, but openness and avoidance of uncertainty in affected families are also important. Our findings imply that fully informing all relatives about the disorder and about who is actually ill should be the principal rule.

Attitude↗
PubMed1999

Reversible and irreversible airflow obstruction as predictor of overall mortality in asthma and chronic obstructive pulmonary disease.

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.

Asthma↗
PubMed1999

A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

Double-Blind Method↗
PubMed1998

[Risk factors for the development of asthma in children and adolescents. Results of a longitudinal study].

To investigate risk factors for the development of asthma, a population sample of children and adolescents, aged 7 to 17 yrs at enrollment, were studied twice, with a six year interval; complete data was available for 408 subjects (199 males). Obtained case history was used to assess the presence of asthma; pulmonary function, skin prick test reactivity, total serum IgE and bronchial responsiveness to inhaled histamine (BHR) were measured using standard techniques. The 12-month period prevalence of asthma increased significantly from the first to the second examination in both males (p < 0.001) and females (p < 0.001), whereas the number of subjects with a positive histamine challenge test declined in both sexes. The prevalence of a positive skin prick test was higher at the second examination (26% and 44%, respectively, p < 0.001); the proportion of subjects with a positive skin reaction to house dust mite (HDMpos) increased from 14% to 26%. Confining the analysis to subjects without a history of asthma at the first examination showed that asymptomatic BHR (Odds Ratio [OR] 3.8 [95% Confidence Interval (CI) 2.5-5.1], p = 0.0002), HDMpos (OR 2.6 [CI 1.9-3.3], p = 0.005), a history of wheezy bronchitis before the age of two yrs (OR 3.8 [CI 2.4-5.2], p = 0.006) and a history of rhinitis and/or eczema (OR 2.8 [CI 1.7-3.9], p = 0.007) at first examination were associated with an increased risk for development of symptomatic asthma at some point between the two examinations. No significant relationship could be demonstrated between smoking (passive or active) and the risk for development of asthmatic symptoms. In conclusion, this longitudinal population study showed an increase in the 12-month period prevalence of asthma with sensitization to HDM and asymptomatic BHR as important risk factors for development of asthma.

Adolescent↗
PubMed1998

Long-range correlations of serial FEV1 measurements in emphysematous patients and normal subjects.

In obstructive lung disease the annual change in lung function is usually estimated from serial measurements of forced expiratory volume in 1 s (FEV1). Frequent measurements in each patient may not improve this estimate because data are not statistically independent; i.e., the measurements are autocorrelated. The purpose of this study was to describe the correlation structure in time series of FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency (phenotype PiZ) and moderate to severe emphysema and two subjects with normal lungs were followed for several years with daily self-administered spirometry. FEV1 measurements fulfilling standard criteria were detrended, and the autocorrelation profile and the power spectrum were calculated. On average the subjects were followed for >3 yr and performed >1,000 acceptable spirometries. The autocorrelation of FEV1 measurements in the emphysematous patients was approximately 0.35 for short intervals and decreased almost exponentially with a half time of 38 days. Between 3 and 4 mo, the autocorrelation function became negative. It reached a minimum of -0.1 at approximately 8 mo and then increased toward zero over the following 12 mo. The autocorrelation function in the two normal subjects showed a similar pattern, but with a faster decay toward zero. In the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/f pattern, where f is frequency, with a slope of -0.88 at lower frequencies. We conclude that serial spirometric measurements show long-range correlations. The practical implication is that FEV1 need not be measured more often than once every 3 mo in studies of the long-term trends in lung function.

Adult↗
PubMed1997

The effect of inhaled glucocorticosteroids in emphysema due to alpha1-antitrypsin deficiency.

Despite the success of inhaled steroids in controlling asthma, the benefit in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Five subjects with moderate to severe emphysema due to alpha 1-antitrypsin deficiency (phenotype PiZ) were followed with daily home spirometry in a 2 x 8 weeks, randomized double-blind, placebo-controlled, crossover study of inhaled budesonide 0.8 mg b.i.d. In three of the five patients, there was a statistically significant increase in the mean forced expiratory volume in 1 s (FEV1), and in two of these patients, there was also a statistically significant increase in the mean forced vital capacity (FVC) during budesonide treatment. A significant diurnal variation in FEV1 and FVC was found in three and two patients, respectively, but did not change significantly during treatment. These findings emphasize the need for renewed evaluation of inhaled steroids in the treatment of patients with emphysema, and indicate that individual patients may have significant clinical improvement.

Administration, Inhalation↗
PubMed1997

Progress of emphysema in severe alpha 1-antitrypsin deficiency as assessed by annual CT.

PURPOSE: To assess serial CT as a measure of the progress of emphysema in patients with severe alpha 1-antitrypsin deficiency (phenotype PiZ). MATERIAL AND METHODS: In a randomized placebo-controlled study of alpha 1-antitrypsin augmentation therapy, 22 patients with moderate emphysema were followed for 2-4 years with an annual lung CT. The images were analysed by means of semiautomatic lung detection, and the degree of emphysema was quantitated by the density-mask and the percentile methods. The influence of lung volume was standardised by a regression model. RESULTS: A highly significant decline in Hounsfield units (HU) was found in low-density areas, corresponding to a mean (SE) annual loss of lung tissue of 2.1 (0.4) g/l lung volume. Analysis of a single slice at 5 cm below the level of the carina gave comparable results: 2.4 (0.4) g/l. CONCLUSION: Serial CT is a sensitive measure of the progress of emphysema in patients with severe alpha 1-antitrypsin deficiency.

Acute Disease↗
PubMed1997

Published models and local data can bridge the gap between reference values of lung function for children and adults.

The aim of this study was to create reference equations for pulmonary function tests (PFTs) that span the age range from childhood to young adulthood. PFT results (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), ratio of FEV1 to FVC (FEV1/FVC), total lung capacity (TLC), transfer factor) of 348 healthy 13-24 yr old Caucasian never-smokers from a local population study were compared with 13 selected sets of published reference equations. Predicted and observed PFT results differed significantly for 63 of 92 reference equations tested, and most equations accounted poorly for the increase in PFT variables which takes place during adolescence. We selected the equations with the best fit and adjusted their parameters, so that the level and variance of predicted values agreed with the local data. For subjects older than 18 yrs, we selected the European Community for Steel and Coal (ECSC) equations. For subjects younger than 18 yrs, we chose European summary equations for FVC, FEV1, and FEV1/FVC, and recent British equations for TLC and transfer factor. The customized reference equations are the best available (maximum likelihood) for analysing PFTs of patients tested in our laboratory. Our approach can be used whenever generally accepted reference equations are lacking and a local sample of normal subjects is available.

Adolescent↗
PubMed1997

Does alpha1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1-antitrypsin deficiency? Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1-AT study group.

Patients with severe hereditary alpha1-antitrypsin deficiency (alpha1-ATD) face a high risk of developing emphysema at a young age. Intravenous augmentation therapy with purified human alpha1-antitrypsin (alpha1-AT) is now available. However, a controlled trial to show its efficacy has never been carried out. The aim of this study was to compare the decline in forced expiratory volume in one second (deltaFEV1) between Danish patients who had never received augmentation therapy and German patients treated with weekly infusion of alpha1-AT. From the files of the Danish alpha1-ATD register, 97 exsmokers, with a PiZ phenotype and for whom results of at least two lung function measurements with an interval of at least 1 yr were available, were identified. From a German group of patients treated with weekly infusions of alpha1-AT, 60 mg x kg(-1) body weight, 198 exsmokers, with biannual lung function measurements were identified. The deltaFEV1 was compared between the two treatment groups by random effects modelling. The deltaFEV1 in the treated group was significantly lower than in the untreated group, with annual declines of 53 mL x yr(-1) (95% confidence interval (95% CI) 48-58 mL x yr(-1)) and 75 mL x yr(-1) (95% CI 63-87 mL x yr(-1)), respectively (p=0.02). The two groups differed with respect to gender and initial FEV1% predicted. Gender did not have any influence on the deltaFEV1. Stratification by initial FEV1% pred showed a significant effect of the treatment only in the group of patients with an initial FEV1% pred of 31-65%, and deltaFEV1 was reduced by 21 mL x yr(-1). This nonrandomized study suggests that weekly infusion of human alpha1-antitrypsin in patients with moderately reduced lung function may slow the annual decline in forced expiratory volume in one second.

Adult↗
PubMed1996

[Extrinsic and intrinsic asthma from childhood to early adult age. A 10-year follow-up].

The purpose of this study was to describe factors of potential importance for the outcome in children with intrinsic and extrinsic asthma. Of 85 consecutive children, five to 15 years of age, with asthma, 70 (82%) participated in a ten year follow up examination. At the time of referral all children underwent certain tests for asthma (case history, total IgE, skin prick tests, radioallergosorbent tests (RAST) and specific bronchial provocations). On the basis of these tests 24 children had intrinsic asthma and 46 extrinsic asthma. At the follow up examination 60 of the 70 adults (86%; 20 with intrinsic asthma) had current symptoms; 54 of the 60 (90%; 18 with intrinsic asthma) were receiving maintenance therapy. Both FEV1 %pred (from 73% +/- 19% to 92% +/- 17%) and FEV1/FVC (from 75% +/- 13% to 80% +/- 12%) increased significantly from childhood to early adulthood (p < 0.0002 and p < 0.001, respectively); a corresponding amelioration of symptoms was also observed (p < 0.0001). In children with intrinsic asthma the outcome seems to be predicted by a combination of the initial frequency of symptoms (p = 0.04), initial FEV1 (p = 0.001), active smoking (p = 0.001) and age at onset of respiratory symptoms (p = 0.001), whereas the initial FEV1 (p < 0.001) seems to be a strong predictor for the outcome in children with extrinsic asthma. These findings suggest that the pathogenetic mechanisms underlying intrinsic and extrinsic asthma in children may differ.

Adolescent↗
PubMed1996

Risk factors for development of asthma in children and adolescents: findings from a longitudinal population study.

BACKGROUND: The prevalence of asthma appears to be on the increase, and risk factors are not well established. To investigate risk factors for the development of asthma, a population sample of children and adolescents, aged 7-17 years at enrolment, were studied in 1986. Initial examinations were repeated at follow-up in 1992; complete data was available for 408 subjects (199 males). METHODS: Obtained case histories were used to assess the presence of asthma; pulmonary function, skin prick test reactivity, total serum IgE and bronchial responsiveness to inhaled histamine were measured using standard techniques. RESULTS: The 12-month period prevalence of asthma increased significantly from the first to the second examination in both males (P < 0.001) and females (P < 0.001), whereas the number of subjects with a positive histamine challenge test declined in both sexes, although this was only statistically significant in males (P < 0.001). The prevalence of a positive skin prick test was higher at the second examination (26% and 44%, respectively, P < 0.001); the proportion of subjects with a positive skin reaction to house dust mite (HDM pos) increased from 14% to 26%. Bronchial hyper-responsiveness to inhaled histamine (BHR), HDM allergy, a history of wheezy bronchitis and symptoms of asthma at first examination were more prevalent among subjects reporting asthma at the second examination than among subjects without respiratory symptoms. Confining the analysis to subjects without a history of asthma at the first examination showed that asymptomatic BHR ¿Odds ratio [OR] 3.8 [95% confidence interval (CI) 2.5-5.1], P = 0.0002¿, HDM pos [OR 2.6 (95% CI 1.9-3.3), P = 0.005], a history of wheezy bronchitis before the age of 2 years [OR 3.8 (95% CI 2.4-5.2), P = 0.006] and a history of rhinitis and/or eczema [OR 2.8 (95% CI 1.7-3.9), P = 0.007] at first examination were associated with an increased risk for development of symptomatic asthma at some point between the two examinations. No significant relationship could be demonstrated between smoking (passive or active) and the risk for development of asthmatic symptoms. CONCLUSIONS: In conclusion, this longitudinal population study showed an increase in the 12-month period prevalence of asthma with sensitization to HDM and asymptomatic BHR as important risk factors for development of asthma; the temporal relationship between sensitization to HDM and presence of airway abnormalities needs to be explored further.

Adolescent↗
PubMed1996

Classification of pulmonary lesions into central and peripheral with a template applied on chest X-ray.

To facilitate the understanding of the anatomical localization of pulmonary lesions and to optimize diagnostic evaluation, a template was designed which, on conventional chest X-rays, could be employed to discriminate between central and peripheral pulmonary lesions. The term 'central' implies that the lesion should be visible in the tracheobronchial tree through a fibre-optic bronchoscope, and the term 'peripheral' suggests that the lesion is not visible through a bronchoscope. In 20 patients examined by fibre-optic bronchoscopy, the bronchoscope was wedged into four pre-selected segmental bronchi in each lung. Using fluoroscopy, the tip of the bronchoscope was marked out on the skin with leadshot. On subsequent chest X-rays, with posterior-anterior and right lateral views, the distances and angles of the markings of the bronchi were mapped out in relation to the main carina. These data were used to design the template.

Adult↗
PubMed1996

Patient-administered sequential spirometry in healthy volunteers and patients with alpha 1-antitrypsin deficiency.

The launching of cheap, pocket-sized spirometers, with data storage capability, has made patient-administered sequential spirometry (PASS) an attractive method of monitoring ventilatory capacity. At present, little information is available on the quality of PASS, compared to laboratory spirometry. The aim of this study was to investigate whether patients could perform PASS without loss of reliability and reproducibility as compared with traditional laboratory spirometry. Ten healthy volunteers performed spirometry for 1 month and 10 emphysematous patients with alpha 1-antitrypsin deficiency (type PiZ) performed spirometry twice daily for up to 2 yr. To fulfil Good Clinical Practice criteria on full data documentation, a traditional direct recording spirometer, the Vitalograph R-model, was used. A decompression device was used for calibration and a 3.8% annual drift in volume registration was noted. This drift was largest for the first year. After training, all patients were able to perform unsupervised spirometry, producing technically correct forced expiratory curves. Reproducibility of FEV1 and FVC obtained by PASS was found to be as good as for laboratory spirometry. After adjustment for the diurnal variation, the residual variation of FEV1 was 2.5% (range 1.6-4.2%) for healthy volunteers and 5.6% (range 4.2-7.7%) for emphysematous patients. Forced vital capacity showed the same pattern. In conclusion, PASS is possible in highly motivated individuals without loss of reliability and reproducibility when compared to laboratory spirometry.

Adult↗