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Biomedical subjects

P Ernst

Publications and source records attributed to P Ernst.

At least 73 records · Page 4Linked to original sources
PubMed1998

First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma.

BACKGROUND: Early treatment with inhaled corticosteroids appears to improve clinical symptoms in asthma. Whether a first treatment initiated in the year following the recognition of asthma can prevent major outcomes such as admission to hospital has yet to be studied. METHODS: A case-control study nested within a cohort of 13,563 newly treated asthmatic subjects selected from the databases of Saskatchewan Health (1977-1993) was undertaken to investigate the effectiveness of a first treatment with inhaled corticosteroids in preventing admissions to hospital for asthma. Study subjects were aged between five and 44 years at cohort entry. First time users of inhaled corticosteroids were compared with first time users of theophylline for a maximum of 12 months of treatment. The two treatments under study were further classified into initial and subsequent therapy to minimize selection bias and confounding by indication. Odds ratios associated with hospital admissions for asthma were estimated using conditional logistic regression. Markers of asthma severity, as well as age and sex, were considered as potential confounders. RESULTS: Three hundred and three patients admitted to hospital with asthma were identified and 2636 matched controls were selected. subjects initially treated with regular inhaled corticosteroids were 40% less likely to be admitted to hospital for asthma than regular users of theophylline (odds ratio 0.6; 95% CI 0.4 to 1.0). The odds ratio decreased to 0.2 (95% CI 0.1 to 0.5) when inhaled corticosteroids and theophylline were given subsequently. CONCLUSION: The first regular treatment with inhaled corticosteroids initiated in the year following the recognition of asthma can reduce the risk of admission to hospital for asthma by up to 80% compared with regular treatment with theophylline. This is probably due, at least in part, to reducing the likelihood of a worsening in the severity of asthma.

Administration, Inhalation↗
PubMed1998

Inhaled corticosteroids and the prevention of readmission to hospital for asthma.

Despite the proven efficacy of inhaled corticosteroids in reducing airway inflammation and their increasing use for the treatment of asthma since the mid 1980s, hospitalization for asthma has been increasing in frequency in several countries. Only few studies, reporting contradictory results, have investigated the role of inhaled corticosteroids in the prevention of hospitalizations for asthma. Using a cohort of 2,059 hospitalized asthmatic patients between 5 and 54 yr of age, we estimated the effectiveness of inhaled corticosteroids in preventing a readmission to hospital for asthma as a function of the duration of therapy. The cohort was selected from the databases of Saskatchewan Health from 1977 to 1993. The rate ratio (RR) of a readmission for asthma varied with duration of regular therapy with inhaled corticosteroids. During the first 15 d of regular therapy, users of inhaled corticosteroids were as likely as nonusers of these medications to be readmitted for asthma with a RR of 1.2 (95% CI: 0.8-1.8). Subjects treated regularly with inhaled corticosteroids for at least 16 d and as long as 6 mo were 40% less likely to be readmitted for asthma (RR = 0.6; 95% CI: 0.4-0.9), while after 6 mo of regular treatment the protective effect disappeared (RR = 1.3; 95% CI: 0.7-2.4). We conclude that regular therapy with inhaled corticosteroids can substantially reduce the risk of a readmission for asthma after only 15 d of use. Confounding by severity appears as the most likely explanation for the disappearance of the beneficial effect after 6 mo of regular therapy.

Administration, Inhalation↗
PubMed1998

Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase: effect of inhaled glucocorticoid.

Peroxynitrite is a potent oxidant formed by the rapid reaction of the free radicals nitric oxide (NO) and superoxide. It causes airway hyperresponsiveness and airway epithelial damage, enhances inflammatory cell recruitment, and inhibits pulmonary surfactant. Asthma is characterized by increased airway hyperresponsiveness, airway epithelial shedding, and inflammation. We examined the production of peroxynitrite and the expression of inducible nitric oxide synthase (iNOS) in airways of asthmatic patients compared to normal control subjects. We also performed a double-blind, crossover randomized-order, placebo-controlled study on 10 asthmatic patients to study the effects of inhaled glucocorticoid treatment (Budesonide) on the formation of peroxynitrite and NO. Fiberoptic bronchial biopsies were examined by immunohistochemistry with antiserum to nitrotyrosine, a marker of protein nitration by peroxynitrite. We also examined the expression of iNOS by immunohistochemistry and in situ hybridization, and measured exhaled NO by chemiluminescence. We correlated the airway production of peroxynitrite with pulmonary functions and airway responsiveness. In airway passages of control subjects, there was weak or no nitrotyrosine immunoreactivity. In contrast, there was strong immunoreactivity for nitrotyrosine in the airway epithelium and inflammatory cells in the airways of persons with asthma. Budesonide treatment resulted in a significant reduction in nitrotyrosine immunoreactivity. Expression of iNOS was evident in the airway pithelium of controls and asthmatic patients, but was significantly more abundant in asthmatic patients. The presence of nitrotyrosine in the airway epithelium (r=-0.841, P<0.0001; r=-0.771, P=0.0004) and inflammatory cells (r=-0.727, P=0014; r=-0.681, P=0.004) correlated inversely with methacholine PC20 and forced expiratory volume in 1 s, respectively. Asthma is associated with increased peroxynitrite formation in the airways, which is reduced after Budesonide treatment. The potent oxidant peroxynitrite may contribute to airway obstruction and hyperresponsiveness and epithelial damage in asthma.

Administration, Inhalation↗
PubMed1997

Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: The increasing costs of managing asthma are due in part to the introduction of new medications, such as leukotriene receptor antagonists. These antagonists interfere with the action of leukotrienes, which are implicated in bronchoconstriction and the formation of airway edema in patients with asthma. Leukotriene receptor antagonists must be shown to be clinically and economically effective for their clinical use to be justified. OBJECTIVE: To assess the clinical and economic effectiveness of zafirlukast, a leukotriene receptor antagonist, in patients with mild-to-moderate asthma who might benefit from regular anti-inflammatory therapy. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. SETTING: 28 outpatient clinics. PATIENTS: 146 patients with mild-to-moderate asthma who were 12 years of age or older, had not smoked cigarettes in the previous 6 months, had a smoking history of less than 10 pack-years, had an FEV1 at least 55% of the predicted value with no upper limit, had demonstrated bronchial hyperresponsiveness, and were symptomatic during the 7-day run-in period. All patients were seen every 2 to 3 weeks for 13 weeks. INTERVENTION: 103 patients received zafirlukast (20 mg twice daily), and 43 patients received placebo (twice daily). All patients received inhaled beta-agonists as needed. MEASUREMENTS: Data were obtained from medical examinations, patient questionnaires, and daily diaries. The clinical effectiveness outcomes were days per month without asthma symptoms, limitation of activity, use of beta-agonists, sleep disturbance, and episodes of asthma (the latter was a composite measure made up of the first four outcomes plus the occurrence of adverse events). The economic effectiveness outcomes were frequency and type of unscheduled health care contacts, use of beta-agonist inhalers, consumption of nonasthma medications, and days of absence from work or school. RESULTS: The zafirlukast group had 89% more days without symptoms (adjusted rates, 7.0 compared with 3.7 days per month; P = 0.03), 89% more days without use of beta-agonists (adjusted rates, 11.3 compared with 6.0 days per month; P = 0.001), and 98% more days without episodes of asthma (adjusted rates, 10.1 compared with 5.1 days per month; P = 0.003). They also had 55% (95% CI, 19% to 74%) fewer health care contacts (18.5 compared with 40.7 per 100 per month; P = 0.007) and 55% (CI, 3% to 79%) fewer days of absence from work or school (15.6 compared with 35.0 per 100 per month; P = 0.04). They used 17% fewer canisters of inhaled beta-agonists (P = 0.17) and 19% less nonasthma medication (P < 0.2). CONCLUSIONS: A daily regimen of zafirlukast added to as-needed inhaled beta-agonists is more effective than beta-agonists alone in treating mild-to-moderate asthma. The clinical and economic effectiveness of zafirlukast, a potential alternative to inhaled corticosteroids, provides further impetus to use regular "preventive" therapy in patients with mild-to-moderate asthma.

Absenteeism↗
PubMed1997

Effect of repeated dosing on the pharmacokinetics of oral fluconazole in bone marrow transplant patients.

We examined the pharmacokinetics of fluconazole in 11 bone marrow transplant patients after multiple oral daily dose of 200 mg of this drug. Blood was sampled at different intervals on day 1, day 13, and day 27. No dose was given on day 2, day 14, and day 28 to allow the concentration-time data to be collected over 48 hours. The 24 hour urine was also collected, and fluconazole was analyzed in both plasma and urine by a high performance liquid chromatography. The plasma concentration-time data were best described by the one-compartment model with first-order absorption. The overall inter-day change and the difference between day 1 and day 27 in the rate constant for absorption (ka), peak plasma concentration (Cmax), through plasma concentration (Cmin), time-to-peak (tmax), area-under-the-curve 0-24 (AUC0-24), rate constant for elimination (ka), mean residence time after oral administration (MRTor), and fraction of the dose excreted unchanged in urine 24 hours (fu24) were significant (P < or = 0.0029 and P < or = 0.01, respectively). However, the difference between day 1 and day 13 was significant (P < or = 0.05) only in ka, tmax, Cmax, Cmin, and AUC0-24, and between day 13 and day 27 was significant (P < or = 0.05) only in ka, Cmin, ka, and MRTor. There was no significant inter-day change in the renal clearance. The significant (P < or = 0.05) increases in Cmax, Cmin, and AUC0-24 after the dose given on day 13 as compared with day 1, and in Cmin on day 27 as compared with day 13 indicate that, in contrast to volunteers, the steady state condition was not reached on day 13 and possibly not on day 27 in these patients. This perhaps should be taken into account when prescribing fluconazole to seriously ill patients.

Adolescent↗
PubMed1997

Pharmacokinetics of mesna and dimesna after simultaneous intravenous bolus and infusion administration in patients undergoing bone marrow transplantation.

This study was undertaken to examine the pharmacokinetics of mesna and its dimer form, dimesna, in the plasma and urine of patients undergoing bone marrow transplantation who received 130 mg/kg of mesna divided intravenously into a 30-mg/kg bolus dose followed immediately by 100 mg/kg infused over 12 hours for uroprotection. The relationship between and urinary excretion of mesna and dimesna also was examined by comparing the data obtained in patients who developed hemorrhagic cystitis versus those who did not. Blood and urine samples were collected at different time intervals after administration, and the plasma or urine was analyzed by liquid chromatography with electrochemical detection. Dimesna was analyzed in these samples after reduction back to mesna with sodium borohydride. The concentration-time data of mesna exhibited the characteristics of the two-compartment model well, and the mean +/-SD values of the distributive phase half-life (t1/2 alpha), postdistributive phase half-life (t1/2 beta), volume of distribution of the central compartment (Vdc), volume of distribution at steady state (Vdss), volume of distribution during the postdistributive phase (Vd beta), total clearance (Cl), and mean residence time (MRT) observed were 0.12 +/- 0.15 hours, 2.12 +/- 1.61 hours, 0.324 +/- 0.336 L/kg, 1.09 +/- 1.18 L/kg, 2.09 +/- 3.0 L/kg, 0.755 +/- 0.507 L/hr.kg, and 6.77 +/- 0.72 hours, respectively. The mean +/-SD values of t1/2 and MRT of dimesna were 1.29 +/- 0.6 hours and 6.68 +/- 1.05 hours, respectively, and the ratio of the area under the concentration-time curve (AUC) of mesna to that of dimesna was 1.21 +/- 0.57. The fractions of dose excreted in urine in the form of mesna and dimesna in 20 hours (fu) were 0.361 +/- 0.15 and 0.482 +/- 0.25, and the renal clearance (ClR) values were 0.244 +/- 0.201 L/hr.kg and 0.157 +/- 0.156 L/hr.kg, respectively. The urinary excretion of mesna in these patients was higher than that required for uroprotection for the whole duration of infusion, and there was no significant difference in the pharmacokinetics of mesna between patients who developed hemorrhagic cystitis and those who did not. This was not the case with dimesna, in which patients with hemorrhagic cystitis excreted in urine less than 50% of the amount of dimesna excreted by those without hemorrhagic cystitis.

Adolescent↗
PubMed1997

Actual use of inhaled corticosteroids and risk of hospitalisation: a case-control study.

BACKGROUND: The relationship between therapy and adverse outcome in asthma is debated especially for naturally occurring situations. This is due in part to insufficient information regarding actual use of medications. OBJECTIVE: This study was conducted to clarify the relationship between actual intake of anti-asthma drugs and asthma hospitalisation, considered as an outcome. METHODS: A case-control study was performed. Patients hospitalised for an asthma exacerbation were matched to community controls identified in surrounding general practices. Patients were questioned to identify prior use of anti-asthma medications, level of use of inhaled corticosteroids and attitude towards therapy. RESULTS: Twenty-three cases and 31 matched controls were interviewed. Cases tended to have more severe asthma than controls, as judged by more frequent use of oral corticosteroids. Cases tended to make more frequent use of oral xanthines and inhaled anticholinergics, but the proportion of patients using inhaled beta 2-adrenoceptor agonists and inhaled corticosteroids was similar in both groups. Use of lower doses of inhaled corticosteroids was associated with an increased risk of hospitalisation, while higher dosage was associated with decreased risk. Cases and controls differed as to their answers to a questionnaire concerning attitudes: cases expressed less interest in optimal usage of inhaled corticosteroids than controls; they also expressed more confidence in inhaled beta 2-agonists. When both risks were combined, overconfidence in beta 2-agonists and suboptimal use of inhaled steroids, the relationship with hospitalisation was significant (OR 5.5, 95% CI 1.1; 26.1). CONCLUSION: The results suggest that patients' attitudes to inhaled corticosteroids and actual consumption of these medications are directly related to adverse outcome in asthma.

Administration, Inhalation↗
PubMed1997

Optical illusions from visual data analysis: example of the New Zealand asthma mortality epidemic.

The abundance of health-related statistics routinely collected worldwide invites their misuse from haphazard associations between secular trends of these data. This misuse is often compounded by assessing these associations simply on the basis of a visual inspection of the data. The visual approach to data analysis, known to have several pitfalls, is particularly tempting in the context of asthma where it has often been used. For example, the epidemic of asthma deaths that occurred in New Zealand during the last two decades has been imputed to fenoterol, a medication for asthma, on the basis of a visual assessment of ecological data. The simultaneity of time trends in the asthma death rate and fenoterol market share in that country formed an important part of the statistical basis of the evidence. We verified whether the results of such visual analyses are corroborated by more objective quantitative statistical methods of analysis. We reanalyzed these same data, namely the time trend data of New Zealand asthma death rates, fenoterol market share, sales of beta-agonists and inhaled corticosteroids, measured yearly for the 16-year span 1976-1991, using Poisson weighted loglinear regression. We found that the protective effect of inhaled corticosteroids (rate ratio 0.5 per canister per month; 95% confidence interval 0.4 to 0.7; p = 0.0001) was more closely associated with changes in asthma mortality than either fenoterol (RR 2.7 per canister per month; 95% CI: 0.9 to 7.5; p = 0.06) or all beta-agonists combined (RR 1.6; 95% CI: 0.8 to 3.0; p = .19). We conclude from this quantitative analysis that these ecological asthma mortality data provide evidence of a stronger association with inhaled corticosteroids, little used in New Zealand at the onset of the epidemic but used abundantly at its termination, than with fenoterol. This conclusion is diametrically opposite to that found by the visual approach. The quantitative analysis demonstrates that the visual approach to the analysis of ecological data, although seemingly convincing, can be misleading by creating an optical illusion. This purely visual approach to data analysis may thus have serious implications when the resulting scientific information is used to make vital public health and policy decisions.

Administration, Inhalation↗
PubMed1997

Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow transplant recipients.

The pharmacokinetics of fluconazole was investigated in 20 bone marrow transplant patients following oral administration of 200 mg of this drug. Blood samples were collected from each patient at different time intervals within 48 h after the first dose, and fluconazole was measured in plasma by high-performance liquid chromatography with UV detection. Urine was collected from 14 of these patients and analyzed similarly. The plasma concentration-time data exhibited the characteristics of the one-compartment model with first-order absorption quite well. The means +/- standard deviations of half-lives for absorption and elimination, peak concentration, time to peak, mean residence time, apparent volumes of distribution, area under the curve, and apparent oral clearance observed in these patients were 2.84 +/- 1.34 h, 19.94 +/- 18.7 h, 4.45 +/- 1.86 microg/ml, 8.34 +/- 5.97 h, 39.57 +/- 20.5 h, 0.874 +/- 0.48 liter/kg, 156.0 +/- 60.6 microg x h/ml, and 0.0256 +/- 0.0138 liter/h x kg, respectively. The amount of fluconazole excreted in urine in 24 h was 67.1 +/- 83 mg, which represents 33.55% +/- 41.6% of the dose administered. Patients who developed hemorrhagic cystitis excreted significantly (P < or = 0.0094) more fluconazole in 24 h than did those who did not.

Administration, Oral↗
PubMed1997

Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy.

Interleukin-12 (IL-12) and IL-13 are two recently characterized cytokines which play an important role in the induction of T helper cell type 1 (Th1-) and Th2-like cells, respectively. Using the technique of in situ hybridization, we have investigated the expression of these cytokines in bronchial biopsies from nine allergic asthmatics and nine normal control subjects. To determine the effect of steroid therapy on the expression of IL-12 and IL-13 in asthma, the numbers of cells expressing these cytokine mRNA before and after a 1-wk course of oral prednisone in six steroid-sensitive (SS) and five steroid-resistant (SR) moderately severe asthmatics were also examined. There was an increased number of IL-13, and a decreased number of IL-12 mRNA positive cells in asthmatic subjects compared with normal control subjects (p < 0.001). After steroid treatment, the increase in FEV1 values observed in SS asthmatics was accompanied by a significant decrease in cells expressing IL-13 mRNA (p < 0.05) and an increase in the numbers of cells expressing IL-12 mRNA (p < 0.05). In contrast, steroid therapy in SR asthmatics was not associated with significant changes in IL-12 and IL-13 mRNA expression. Thus, allergic asthma is associated with a downregulation of IL-12 mRNA expression and an upregulation of IL-13 mRNA expression. These results suggest an in vivo role for IL-12 and IL-13 in modulating allergic responses and support the notion that the clinical effects of glucocorticoids are at least partially mediated through the modulation of cytokine production.

Adult↗
PubMed1997

Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant.

The PARI-IS Study is a double-blind placebo-controlled randomized clinical trial to study the effect of an immunostimulating agent to prevent acute respiratory exacerbation in patients with COPD. Three hundred eighty-one ambulatory patients (190 placebo and 191 immunostimulant) were followed at home for 6 mo by experienced research nurses. The risk of having at least one episode of acute exacerbation (primary outcome) was similar in the two groups (p = 0.872). In contrast, the total number of days of hospitalization for a respiratory problem was 55% less in the group treated with OM-85 BV (287 d) than in the group treated with placebo (642 d). Patients treated with OM-85 BV spent an average of 1.5 d in hospital compared with 3.4 d for patients treated with placebo (p = 0.037). The risk of being hospitalized for a respiratory problem was 30% lower in the treated group (16.2%) than in the placebo group (23.2%); p = 0.089. Eight deaths were observed: two in patients treated with OM-85 BV and six in patients treated with placebo (p = 0.153). During the course of the study dyspnea improved slightly in patients treated with OM-85 BV, whereas it deteriorated slightly in patients receiving placebo (p = 0.028). These results suggest that this immunostimulating agent may be beneficial for patients with COPD by reducing the likelihood of severe respiratory events leading to hospitalization.

Acute Disease↗
PubMed1997

Airway function among Inuit primary school children in far northern Quebec.

The study of the prevalence and determinants of asthma and allergy in different populations may provide clues to their etiology. We describe airway function and its determinants among Inuit schoolchildren living in far Northern Quebec. We assessed the presence of airways hyperresponsiveness (AHR), defined as a 15% drop in FEV1 with exercise, airflow obstruction, as judged by a reduced FEV1/FVC, and atopy, as evidenced by skin test positivity to inhaled aeroallergens, among 509 Inuit aged mostly from 6 to 13 yr. Smoking by the children (31.9%) and their parents was common, including maternal smoking during pregnancy (79.5%). Atopy was found in only 5.3% of children. Apart from age, there were no significant associations between AHR and any of the determinants examined. Airflow obstruction was present among 7.7% of children and occurred most commonly among children with higher levels of salivary cotinine and in those with four or more lower respiratory illnesses in the first 2 yr of life. Asthma and atopy were uncommon in this population whereas evidence of chronic airflow obstruction was frequently found. Measures to reduce the spread of respiratory infection and prevention of smoking are likely to be of most benefit in improving respiratory health in these isolated communities.

Adolescent↗