Bronchodilator reversibility in COPD: the roguish but harmless little brother of airway hyperresponsiveness?
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Aged↗
Biomedical subjects
E F Hansen
Publications and source records attributed to E F Hansen.
Effect of terlipressin on blood volume distribution in patients with cirrhosis.
BACKGROUND: Patients with cirrhosis and portal hypertension have an altered blood volume distribution and a hyperdynamic systemic circulation. Terlipressin is known to reduce portal pressure by decreasing splanchnic inflow, but its effect on the blood volume distribution is unknown. The aim of the study was to investigate changes in regional blood volume distribution and systemic haemodynamics after administration of terlipressin to patients with cirrhosis. METHODS: Blood volume distribution was determined in 13 patients with cirrhosis and portal hypertension by a dual-head gamma-camera technique and systemic haemodynamics was measured before and after intravenous administration of terlipressin (2 mg). RESULTS: Terlipressin increased the blood volume in the thorax region (+6.0%, P < 0.002) and the liver region (+12.2%, P < 0.002), whereas blood volume in the splanchnic region remained unchanged. Systemic vascular resistance (SVR) and mean arterial blood pressure increased after terlipressin (+34 and +21%, P < 0.001). The increase in liver blood volume correlated directly with the increase in SVR (r = 0.88. P < 0.001). CONCLUSIONS: Terlipressin ameliorates the hyperdynamic circulation, increases thorax and liver blood volumes, but produces no effect on the splanchnic blood volume. Besides decreasing the splanchnic inflow, terlipressin may affect portal pressure by causing vasodilatation of intrahepatic vessels.
Adult↗
Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis.
BACKGROUND AND AIM: Water retention is a major clinical problem in patients with liver cirrhosis. Recent research suggests that renal aquaporins may be pathophysiologically involved in this condition. The aim of the present cross sectional study of patients with liver cirrhosis was to determine if 24 hour urinary excretion of renal aquaporin 2 (AQP2) differed from that of healthy control subjects and if such excretion was related to the severity of liver disease and to the patient's water balance. RESULTS: Twenty four hour urinary excretion of AQP2 and free water clearance were measured in 33 stable cirrhosis patients on usual medication and in eight healthy subjects. AQP2 excretion, quantitated by immunoblotting, was eight times higher in cirrhosis patients than in controls (0.167 (0.270) U/day v 0.021 (0.017); p<0.05). Stratification according to clinical manifestations (Child- Pugh classes) revealed that it increased with the clinical severity of cirrhosis (class A 0.04 (0.04); class B 0.09 (0.16); class C 0.31 (0.35); p<0.05) but was not related to liver function, as measured by galactose elimination capacity. Excretion correlated inversely with free water clearance (rho=-0.57, p<0.01). It was higher in patients with oesophagogastric varices but not in those with ascites. Plasma vasopressin concentrations were not related to AQP2 excretion and there was no relation to dose or type of diuretic treatment. CONCLUSIONS: Urinary AQP2 excretion was increased in patients with cirrhosis. Moreover, urinary AQP2 excretion increased with severity of cirrhosis in parallel with impairment of free water clearance. This suggests a functional association between increased AQP2 excretion and increased renal reabsorption of water in cirrhosis.
Adult↗
Treatment of acute severe asthma and chronic obstructive pulmonary disease in Danish hospitals. Do national recommendations improve on the quality of the treatment?
Studies have demonstrated suboptimal treatment of acute severe asthma and chronic obstructive pulmonary disease (COPD). We examined the quality of treatment in Denmark and the effect of intervention, by publication of recommendations for standardised treatment. All 70 hospitals in Denmark with emergency facilities participated in a telephone questionnaire, examining treatment behaviours among house officers. The survey was repeated 3 years later, after publication of national recommendations for treatment of acute exacerbations of asthma and COPD. The response rate in both surveys was 100%. An insufficient handling of nebulisers, a huge variation in the delivered dose of bronchodilators and a suboptimal use of corticosteroids was found. A significant trend towards more liberate use of oxygen was seen in both asthma (3.2 l min(-1) versus 4.8 l min(-1), P<0.001) and COPD (1.5 l min(-1) versus 1.9 l min(-1), P = 0.047). Further, a huge difference in treatment behaviours was revealed from this survey The knowledge among house officers of basic principles of treatment was insufficient. Treatment behaviour was only moderately affected by national publication of detailed recommendations for treatment. This study indicates a need for implementing tools for quality control.
Acute Disease↗
Plasma cystatin C as a marker of renal function in patients with liver cirrhosis.
Cystatin C is a low molecular weight protein and the plasma level of cystatin C is mainly determined by glomerular filtration, making cystatin C an endogenous marker of glomerular filtration rate. The aim of the study was to elucidate the applicability of plasma cystatin C as a marker of renal function in patients with liver cirrhosis. Serum cystatin C and creatinine concentrations were compared with creatinine clearance. Thirty-six patients (14 females and 22 males aged between 33 and 81 years) with liver cirrhosis with normal to severely impaired kidney function were included. Plasma cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring Diagnostics) and plasma creatinine by an enzymatic method. Plasma levels of cystatin C and creatinine were found to increase with decreasing values of creatinine clearance. The reciprocal values of cystatin C and creatinine were compared with those for creatinine clearance revealing an r2 of 0.37 and 0.18, respectively. Comparison of the areas under the curves (AUC) of the non-parametric receiver-operating characteristic plots for plasma cystatin C (AUC=0.7364; SE=0.0929) and plasma creatinine (AUC=0.6309: SF=0.1028) revealed a significant difference between plasma cystatin C and plasma levels of creatinine (p-value=0.03). The results demonstrate that the diagnostic accuracy of plasma cystatin C was better than plasma creatinine in identifying liver cirrhotic patients with reduced glomerular filtration rate.
Adult↗
[Prevalence of asthma among young adults in Copenhagen].
INTRODUCTION: It is the general impression that the prevalence of asthma is rising. We investigated the prevalence, respiratory symptoms, smoking habits, and lung function in young adults in the City of Copenhagen at an interval of 15 years. METHODS: Men and women aged 20-35 years were sampled from the general population living in a defined area of central Copenhagen. The first examination took place from 1976 to 1978 and comprised 1,034 subjects. A second sample, comprising 1,104 subjects from the same area was examined 15 years later in 1991-1994. All the participants answered a questionnaire about respiration and a spirometry was performed, with measurement of FEV1 and FVC. RESULTS: The prevalence of self-reported asthma rose from 1.5% in the first survey to 4.8% in the second (p < 0.001). The asthmatics had, on average, poorer lung function than non-asthmatics in terms of FEV1, and this difference was more pronounced in the second survey than in the first. The number of smokers fell significantly from 62% in 1976-1978 to 45% in 1991-1994 (p < 0.001). CONCLUSION: The prevalence of self-reported asthma has risen significantly in young adults in Copenhagen over a 15-year period. The severity, as judged by the level of FEV1, has also increased. These findings cannot be explained by changes in smoking habits.
Adult↗
[Global strategy when it comes to chronic obstructive lung disease].
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Cost of Illness↗
Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation against thermodilution and assessment of pharmacological effects of terlipressin in portal hypertension.
BACKGROUND: Endoscopic ultrasound (EUS) is a new modality allowing real-time flow measurements by means of the Doppler technique. The aim of the study was to evaluate azygos blood flow measurements by endoscopic ultrasound. METHODS: Measurements of azygos blood flow by EUS and by the thermodilution technique were compared in 20 patients with portal hypertension. The ability of EUS flowmetry to detect changes in the azygos and portal venous flow after an intravenous dose of 2 mg of terlipressin was evaluated in 13 of the patients in a double-blind, randomized, placebo-controlled, cross-over design. RESULTS: The EUS Doppler and thermodilution measurements correlated significantly (R=0.81, P < 0.001). The azygos blood flow was found to be 14% higher by the EUS method than by thermodilution. The coefficient of variation of the EUS Doppler measurements of the azygos blood flow was 14.8%. After administration of terlipressin, the azygos blood flow, as measured by EUS Doppler, decreased significantly by 23% from 915 to 704 ml/min (P = 0.014) and the portal venous flow decreased by 28% from 1170 to 789 ml/min (P = 0.03). No effects of placebo were detected. CONCLUSIONS: These results show that EUS measurement of the azygos blood flow correlate strongly to the measurements by the thermodilution technique, and EUS is moreover well tolerated by the patients. The method is applicable for monitoring pharmacological effects on the superior porto-systemic collateral circulation and portal venous flow in patients with portal hypertension.
Adult↗
Peak flow as predictor of overall mortality in asthma and chronic obstructive pulmonary disease.
Lung function is a strong predictor of overall mortality in asthma and chronic obstructive pulmonary disease (COPD). FEV1 is considered to be the "gold standard," whereas peak expiratory flow (PEF) is mostly used in absence of FEV1 measurements. We compared the predictive power of PEF and FEV1, measured after maximal bronchodilation, which included a short course of oral corticosteroids. The study population comprised 491 asthmatics and 1,095 subjects with COPD. Pulmonary function tests were performed between 1983 and 1988, and survival data were obtained by September 1997, when 127 asthmatics and 723 subjects with COPD had died. Predictors of survival were examined by Cox proportional hazards analyses. After controlling for age, smoking, sex, and body mass index, we found best PEF to be at least equal to best FEV1 as predictor of overall mortality in subjects with COPD. The predictive power of best PEF was in part maintained after controlling for best FEV1. In asthma, best FEV1 seemed to be a better predictor of mortality than best PEF. Despite close correlation to FEV1, PEF apparently provides independent prognostic information in patients with COPD. This may be due to PEF and FEV1 reflecting different components of COPD, i.e., chronic bronchitis, small airways disease, and emphysema. Furthermore, extrapulmonary components such as muscle mass and general "vigour" probably affect PEF to a greater extent than they affect FEV1.
Asthma↗
Airway hyperresponsiveness and COPD mortality.
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Bronchial Hyperreactivity↗
Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients.
AIMS/BACKGROUND: Cirrhotic patients exhibit a hyperdynamic and hyporeactive circulation with central hypovolaemia which may influence the course of the disease. As terlipressin, a vasopressin analogue, may modify systemic haemodynamics in these patients, the aim of the present study was to assess the acute effects of terlipressin on central and systemic haemodynamics. METHODS: Sixteen patients with alcoholic cirrhosis and portal hypertension had their systemic, central, and splanchnic haemodynamics determined at baseline and after a blind randomised bolus infusion (2 mg) of terlipressin/placebo. RESULTS: After terlipressin, the arterial blood pressure and the systemic vascular resistance increased by 26% and 61%, respectively (both p<0.001), and the cardiac output, heart rate, and arterial compliance decreased by 18%, 11%, and 32%, respectively (all p<0.001). The central circulation time increased by 36% (p<0.001), whereas the central and arterial blood volume only increased by 4% (p= 0.07). As expected, both portal pressure and hepatic blood flow decreased (17% and 29%, both p<0.001). The decrease in portal pressure after terlipressin was significantly related to the increase in systemic vascular resistance (r=-0.52, p<0.05) and the central circulation time (r=-0.80, p<0.0001). CONCLUSIONS: Terlipressin significantly attenuates the hyperdynamic circulation in portal hypertensive patients without a further contraction of the central and arterial blood volume. The systemic haemodynamic response to terlipressin is moreover associated with the decrease in portal pressure. Terlipressin may therefore have potentially beneficial effects on the hyperdynamic circulation in cirrhosis in addition to its effects on portal pressure.
Adult↗
Gastrointestinal motor function in patients with portal hypertension.
BACKGROUND: Existing data on gastric emptying and small-intestinal transit rates in portal-hypertensive patients are scarce and contradictory, and so far, the motor function of the colon has not been assessed in these patients. In this study we evaluated the propulsive effect of all main segments of the gastrointestinal tract in patients with well-characterized portal hypertension. METHODS: Eight patients with a postsinusoidal hepatic pressure gradient of at least 13 mmHg and eight age- and sex-matched healthy controls participated in the study. Gastric emptying, small-intestinal transit, and colonic transit rates were evaluated in all subjects by means of a gamma camera technique. The technique was also used to measure the frequency of antral contractions. RESULTS: No difference was observed in gastric mean emptying time or small-intestinal mean transit time of liquid and solid markers between patients and controls. After 24 h, however, the geometric center of the liquid marker had a more caudal localization in the colon of the patient group than in the controls (P = 0.04); that is, the patients had a faster colonic transit. No difference was found in the frequency of antral contractions 45 min after the test meal between patients and controls. CONCLUSIONS: These data suggest that the colonic transit is often accelerated in patients with portal hypertension, whereas the motor function of the stomach and the small intestine is unaffected.
Adult↗
Increase in prevalence and severity of asthma in young adults in Copenhagen.
BACKGROUND: It is the general impression that the prevalence of asthma has increased during recent decades. A study was undertaken to investigate asthma prevalence, respiratory symptoms, and lung function in young adults in the City of Copenhagen 15 years apart. METHODS: Men and women aged 20-35 years were sampled from the general population living in a defined area of central Copenhagen. The first examination took place in 1976-8 and comprised 1034 subjects (response rate 67.2%). A new sample comprising 1104 subjects (response rate 62.6%) from exactly the same area was examined 15 years later in 1991-4. All participants answered a questionnaire on respiratory symptoms and diseases and performed spirometric tests with measurement of forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). RESULTS: The prevalence of self-reported asthma increased from 1.5% in the first survey to 4.8% in the second survey (p<0.001). Asthmatic subjects had, on average, poorer lung function than non-asthmatic subjects in terms of FEV(1) and this difference was more pronounced in the second survey than in the first (10.0% of predicted versus 2.4% of predicted). Smoking decreased significantly from 62% in 1976-8 to 45% in 1991-4 (p<0.001). CONCLUSIONS: The prevalence of self-reported asthma has increased significantly among young adults in Copenhagen over a 15 year period. The severity of asthma, as judged by the level of FEV(1), has also increased. These findings cannot be explained by changes in smoking habits.
Adult↗
[Efficiency of endoscopic therapy of varices. The significance of paraesophageal varices and perforating veins].
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Collateral Circulation↗
Splanchnic haemodynamics after intravenous terlipressin in anaesthetised healthy pigs.
BACKGROUND/AIMS: Terlipressin is used for the treatment of bleeding oesophageal varices. We evaluated the effects of terlipressin on hepatic haemodynamics, with special focus on the interactions between portal venous flow and hepatic arterial flow over time. Secondly, we evaluated the estimated hepatic blood flow by the ICG clearance method against direct measurements of hepatic blood flow. METHODS: Eight healthy anaesthetised pigs received terlipressin 1 mg or placebo intravenously in a randomised, blind, cross-over design. Hepatic arterial flow, portal venous flow, systemic haemodynamics, and portal vein diameter were recorded simultaneously. Portal venous flow and hepatic arterial flow were measured by transit time ultrasound flowmetry. Estimated hepatic blood flows at baseline and after terlipressin were compared with the sum of the portal venous flow and hepatic arterial flow. RESULTS: Portal venous flow decreased significantly 5 min after administration of terlipressin (p<0.05). At 30 min it had decreased by 34% (p<0.01) and the hepatic arterial flow had increased by 81% (p<0.01). The estimated hepatic blood flow and the hepatic blood flow decreased by 23% (p<0.015). At baseline the estimated hepatic blood flow and the hepatic blood flow correlated significantly (r=0.85, p<0.01), but this correlation disappeared after administration of terlipressin (r=0.06, p=ns). The hepatic blood flow was 12% higher than the estimated hepatic blood flow before and after terlipressin. CONCLUSIONS: Terlipressin decreased the portal venous flow, hepatic blood flow, and estimated hepatic blood flow significantly and was accompanied by a substantial increase in hepatic arterial flow. The estimated hepatic blood flow and hepatic blood flow were strongly correlated at baseline, but after terlipressin the correlation disappeared.
Anesthesia↗
Endoscopic ultrasound duplex scanning for measurement of portal venous flow. Validation against transit time ultrasound flowmetry in pigs.
BACKGROUND: Endoscopic ultrasound (EUS) is a new technique that makes it possible to measure portal venous flow when transabdominal ultrasound fails. As the technique has not been evaluated previously, we compared simultaneous measurements of portal venous flow using EUS Doppler with that of transit time ultrasound (TTU) in healthy pigs. The ability of EUS to detect changes in the portal venous flow after pharmacologic intervention was also investigated. METHODS: Six anaesthetized pigs were studied. Portal venous flow was measured simultaneously by EUS duplex scanning, using a Pentax FG-32UA echoendoscope connected to a Hitachi EUB 515-A ultrasound scanner, and by TTU with a Cardiomed CM 4000 flowmeter probe placed on the portal vein. Terlipressin, 1 mg, and placebo were administered in a blind, randomized, crossover design. Measurements were taken at base line and 30 min after each drug administration. RESULTS: Portal venous flow measured by EUS flowmetry and TTU flowmetry correlated significantly (R = 0.92, P < 0.001, n = 18). The limits of agreement in a Bland-Altman plot were from -0.262 l/min to +0.164 l/min. The change in portal venous flow after terlipressin measured by EUS and TTU correlated significantly (R = 0.88, P < 0.05, n = 6). All values used for analyses were the means of five repeated measurements. CONCLUSIONS: EUS measures portal venous flow with an acceptable correlation and agreement with TTU in anaesthetized pigs. The method is capable of monitoring the effects of pharmacologic intervention on the portal system.
Animals↗
Effects on plasma angiotensin-converting enzyme activity and circulating renin of lisinopril and enalapril alone and in combination with propranolol in healthy volunteers.
The effects on plasma angiotensin-converting enzyme activity and renin activity of the two long-acting angiotensin-converting enzyme inhibitors, lisinopril and enalapril, alone and in combination with propranolol were studied. In an open, randomised, cross-over design 12 healthy volunteers received orally enalapril 20 mg alone, enalapril 20 mg in combination with propranolol 80 mg, lisinopril 20 mg alone, and lisinopril 20 mg in combination with propranolol 80 mg. Plasma angiotensin-converting enzyme activity and plasma renin activity were measured for 24 h after each treatment period. Lisinopril and enalapril reduced plasma angiotensin converting enzyme activity substantially and equally at six hr (-70%, P<0.05) and 12 hr (-65%, P<0.05), irrespective of combination with propranolol. At 24 hr plasma angiotensin-converting enzyme activity remained significantly suppressed only after lisinopril (-60%, P<0.05). Plasma renin activity increased almost ten times after ingestion of both angiotensin-converting enzyme inhibitors, but the effect lasted significantly longer after lisinopril than after enalapril. Beta-Adrenergic blockade blunted the effect on the increase in plasma renin activity induced by both angiotensin-converting enzyme inhibitors. Our results show that the effect of lisinopril on plasma angiotensin-converting enzyme activity and plasma renin activity lasted longer than that of enalapril. beta-Adrenergic blockade suppressed the effect on elevated plasma renin activity, but did not influence the effect of angiotensin-converting enzyme inhibitors on plasma angiotensin-converting enzyme activity.
Adrenergic beta-Antagonists↗
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↗