Search PubMed⌕ Search

Biomedical subjects

P Ernst

Publications and source records attributed to P Ernst.

At least 91 records · Page 5Linked to original sources
PubMed1997

Increased expression of interleukin-16 in bronchial mucosa of subjects with atopic asthma.

Asthma is characterized by the presence of activated CD4+ cells in the airways. We hypothesized that the newly characterized cytokine interleukin (IL)-16 is involved in the pathogenesis of asthma through its ability to selectively induce CD4+ cell recruitment within the inflamed bronchial wall. We investigated the expression of IL-16 in bronchial biopsies obtained from subjects with mild asthma (n = 10), atopic nonasthmatic individuals (n = 6), and normal control subjects (n = 10). Cryostat sections from 4% paraformaldehyde-fixed fiberoptic bronchial biopsies were immunostained using a specific antibody that recognizes human IL-16. IL-16 mRNA expression was determined by in situ hybridization. IL-16 immunoreactivity and mRNA were demonstrated mainly in bronchial epithelial cells in all subjects. IL-16 immunoreactivity and IL-16 mRNA expression within the epithelium were significantly higher in bronchial biopsies obtained from asthmatic subjects as compared to both atopic nonasthmatic and normal controls (P < 0.001). The numbers of subepithelial IL-16 immunoreactive cells and IL-16 mRNA-positive cells were also greater in the bronchial biopsies obtained from asthmatic subjects as compared to both atopic nonasthmatic and normal controls (P < 0.001). Epithelial expression of IL-16 immunoreactivity and mRNA correlated with the CD4+ cell infiltration (r2 = 0.70, P < 0.001). There were significant associations between epithelial and subepithelial IL-16 immunoreactivity and airway responsiveness to methacholine. This study demonstates that IL-16 is expressed in airway tissues, particularly in the epithelial cells, and that up-regulation of its expression is a feature of allergic asthma. These results suggest an in vivo role for IL-16 in the pathogenesis of asthma, possibly through the recruitment of CD4+ cells, and support the increasing evidence for the participation of epithelial cells in regulating inflammatory responses.

Adult↗
PubMed1997

Eosinophil-associated TGF-beta1 mRNA expression and airways fibrosis in bronchial asthma.

The histopathology of bronchial asthma is associated with structural changes within the airways, including subepithelial fibrosis, as well as chronic eosinophilic inflammation. The mechanisms responsible for this tissue remodeling, and in particular the role of inflammatory cells, remain to be established. Transforming growth factor-beta (TGF-beta) is a potent profibrotic cytokine which may contribute to the thickening of the reticular lamina by the deposition of collagen fibers. To investigate the molecular mechanisms underlying these structural changes, we have investigated the expression of TGF-beta1 mRNA and immunoreactivity within the bronchial mucosa of mild to severe asthmatic individuals and normal control subjects using the techniques of in situ hybridization and immunocytochemistry. As eosinophils are prominent within the asthmatic airway and are known to synthesize pro-inflammatory cytokines, the presence of TGF-beta1 mRNA and immunoreactive protein in eosinophils was also examined. Asthmatic individuals exhibited a greater expression of TGF-beta1 mRNA and immunoreactivity in the airways submucosa than normal control subjects (P < 0.05), and these increases were directly related to the severity of the disorder. The extent of airways fibrosis, as detected histochemically, was also increased in asthmatics compared with normal control subjects (P < 0.005). In asthmatic subjects, the presence of subepithelial fibrosis was associated with the severity of the disease and correlated with the decline in forced expiratory volume in 1 s (r2 = 0.78; P < 0.05). Within the asthmatic airways, EG2-positive eosinophils represented the major source of TGF-beta1 mRNA and immunoreactivity. These results provide evidence that TGF-beta1 may play a role in the fibrotic changes occurring within asthmatic airways and that activated eosinophils are a major source of this cytokine.

Adult↗
PubMed1997

Assessing asthma management from interviews of patients and family physicians.

Directed self-care is recommended in asthma. Adequate patient education and follow-up are nevertheless necessary to optimize outcomes. We compared the agreement between detailed information on asthma history and management, collected from the patient and the family physician, to validate the files of physicians and to assess patients' knowledge, attitude, and behavior concerning asthma. A sample of 54 asthma patients were interviewed in detail about use of medications and self-care practice; 36 family physicians (FPs) were interviewed concerning asthma therapy, history, and attitudes of the same patients. Forty-eight percent of the patients expressed negative attitudes toward inhaled corticosteroids, for reasons of safety or lack of efficacy. Less than 20% of the patients made regular use of a peak flow meter. Eighty-three percent of the patients usually obtained prescriptions for asthma therapy from their FP, but on average, only 40% of these prescriptions were provided during visits specific to asthma. FPs were not optimally informed of actual treatments and outcomes and had poor perception of patients' attitudes toward treatment. Nonetheless, in about 30% of the patients, FPs identified risk factors for adverse outcome, such as depression and family conflicts. A majority of interviewed patients had a negative perception of anti-inflammatory therapy, specifically relating to issues of safety and efficacy. Peak flow meters were seldom used and therapy was commonly prescribed outside visits specific to asthma. Despite being centrally involved in the care of asthma patients, FP did not optimally assess therapy and outcomes. The findings suggest suboptimal education and health status in this asthma population.

Administration, Inhalation↗
PubMed1996

Confounding by indication and channeling over time: the risks of beta 2-agonists.

A previously published nested case-control study, the Saskatchewan Asthma Epidemiologic Project (SAEP) spanning 1980-1987, investigated the risk of fatal or near fatal asthma and found different risks for two inhaled beta 2-agonists, fenoterol and salbutamol. The authors assessed whether this comparison was confounded by indication because of channeling of inhaled fenoterol to more severely afflicted asthmatics. Using three subcohorts selected from a cohort of 12,301 asthmatics assembled from the computerized databases of Saskatchewan Health and followed over 7 years, the authors studied two forms of channeling and investigated whether greater asthma severity and less well-controlled disease were associated with preferential prescribing of a first prescription of inhaled fenoterol, as opposed to inhaled salbutamol, and whether they were associated with the likelihood of a switch from inhaled salbutamol to fenoterol as well as a switch from inhaled fenoterol to salbutamol. The authors found that the initial choice between fenoterol and salbutamol was independent of the severity of the asthma and disease control, but that preferential prescribing of fenoterol occurred among users of salbutamol who showed signs of increased severity or uncontrolled asthma. The switch from inhaled fenoterol to salbutamol was, however, minimally related to asthma severity. They conclude that the comparison between inhaled fenoterol and salbutamol in the SAEP may have been biased by indication. This study demonstrates that long-term information on medication use is essential to ensure that the results of such case-control studies are not biased by indication.

Administration, Inhalation↗
PubMed1996

Recommendations for reducing the effect of grain dust on the lungs. Canadian Thoracic Society Standards Committee.

OBJECTIVE: To assess the appropriateness of the current Canadian standards for exposure to grain dust in the workplace. OPTIONS: The current permissible exposure limit of 10 mg of total grain dust per cubic metre of air (expressed as mg/m3) as an 8-hour time-weighted average exposure, or a lower permissible exposure limit. OUTCOMES: Acute symptoms of grain-dust exposure, such as cough, phlegm production, wheezing and dyspnea, similar chronic symptoms, and spirometric deficits revealing obstructive or restrictive disease. EVIDENCE: Articles published from 1924 to December 1993 were identified from Index Medicus and the bibliographies of pertinent articles. Subsequent articles published from 1994 (when the recommendations were approved by the Canadian Thoracic Society Standards Committee) to June 1996 were retrieved through a search of MEDLINE, and modification of the recommendations was not found to be necessary. Studies of interest were those that linked measurements of total grain dust levels to the development of acute and chronic respiratory symptoms and changes in lung function in exposed workers. Papers on the effects of grain dust on workers in feed mills were not included because other nutrients such as animal products may have been added to the grain. Unpublished reports (e.g., to Labour Canada) were included as sources of information. VALUES: A high value was placed on minimizing the biological harm that grain dust has on the lungs of grain workers. BENEFITS, HARMS AND COSTS: A permissible exposure limit of 5 mg/m3 would control the short-term effects of exposure to grain dust on workers. Evidence is insufficient to determine what level is needed to prevent long-term effects. The economic implications of implementing a lower permissible exposure limit have not been evaluated. RECOMMENDATIONS: The current Canadian standards for grain-dust exposure should be reviewed by Labour Canada and the grain industry. A permissible exposure level of 5 mg/m3 is recommended to control short-term effects. Further measurements that link the levels of exposure to respiratory health effects in workers across Canada should be collected to establish an exposure-response relation and possible regional differences in the effects of grain dust. VALIDATION: There has been no external review of these recommendations. However, the American Conference of Governmental Industrial Hygienists has recommended an 8-hour average exposure limit of 4 mg/m3 for wheat, oats and barley.

Air Pollutants, Occupational↗
PubMed1996

Increased morbidity and mortality related to asthma among asthmatic patients who use major tranquillisers.

OBJECTIVE: To assess the potentially increased risk of death or near death from asthma in asthmatic patients with psychosis. DESIGN: Case-control study. SETTING: The computerised health databases of the Canadian province of Saskatchewan. SUBJECTS: 131 cases of death or near death from asthma identified within a cohort of asthmatic patients; 3930 matched non-cases. EXPOSURE AND OUTCOME MEASURES: The exposure of interest was the use of major tranquillisers in the period before an outcome event. Outcomes included death or near death from asthma. RESULTS: Crude analyses showed that asthmatic patients who had used major tranquillisers in the previous 12 months were at a 3.2 (95% confidence interval 1.4 to 7.5) times greater risk of death or near death from asthma than asthmatic patients who did not use major tranquillisers. Past users of major tranquillisers who had recently discontinued use were at a particularly high risk (relative risk 6.6; 2.5 to 17.6). Adjustment for use of antiasthma drugs and other confounders abolished this excess risk. CONCLUSIONS: Asthmatic patients who use major tranquillisers seem to be at an increased risk of death or near death from asthma. Physicians treating asthmatic patients with a history of use of major tranquillisers should exercise greater caution with regard to management of such patients.

Adolescent↗
PubMed1996

Effect of passive smoking on the development of respiratory symptoms in young adults: an 8-year longitudinal study.

The evidence of an association between passive smoking and occurrence of respiratory symptoms is relatively strong in children, whereas studies conducted in adult populations have provided inconsistent results. The objective of the present study was to examine the relations between exposure to environmental tobacco smoke (ETS) and development of respiratory symptoms in young adults during a study period of 8 years, with emphasis on the evaluation of potential dose-response pattern of the relations. The study population consisted of 117 "never smokers," who were 15 to 40 years of age at the time of initial examination, when they answered a standardized questionnaire on respiratory health, and who were reexamined 8 years later. ETS exposure at home and at work during the study period was recorded at the 8-year examination with a structured questionnaire. The symptoms studied as outcomes included wheezing, dyspnea, cough, and phlegm production. The relations between ETS exposure and development of respiratory symptoms were studied in multivariate logistic regression models controlling for age, gender, atopy, and the presence of other respiratory symptoms. Cumulative incidences of the respiratory symptoms, except of phlegm production, were consistently greater among subjects exposed to ETS compared with the reference group. A significant dose-related increase in the risk of developing dyspnea was observed in relation to ETS exposure, with an OR of 2.37 for an average exposure of 10 cigarettes/day (95% confidence interval, 1.25-4.51). The risk of developing other respiratory symptoms, apart from phlegm, was also related to ETS exposure, but these relations did not achieve statistical significance. The results provide evidence of adverse respiratory effects of ETS exposure in the home and office work environments in young adults. These findings emphasize the need for effective measures in the prevention of involuntary smoking during young adulthood.

Adolescent↗
PubMed1996

Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia. Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incidence at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts < 3% prior to transplant (P = n.s.). However, relapse incidence differed significantly in patients with non-T-cell-depleted transplants and high basophil counts (> 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy.

Adolescent↗
PubMed1996

A potential role for Elf-1 in terminal transferase gene regulation.

The terminal deoxynucleotidyltransferase (TdT) gene represents an attractive model for the analysis of gene regulation during an early phase of lymphocyte development. In previous studies, we identified a DNA element, termed D', which is essential for TdT promoter activity in immature lymphocytes, and two classes of D'-binding factors, Ikaros proteins and Ets proteins. Here, we report a detailed mutant analysis of the D' element which suggests that an Ets protein, rather than an Ikaros protein, activates TdT transcription. Since multiple Ets proteins are expressed in developing lymphocytes and are capable of binding to the D' element, DNA affinity chromatography was used to determine if one of the Ets proteins might bind to the D' element with a uniquely high affinity, thereby implicating that protein as a potential TdT activator. Indeed, one binding activity was greatly enriched in the high-salt eluates from a D' affinity column. Peptide microsequencing revealed that the enriched protein was Elf-1. Immunoblot analyses confirmed that in nuclear extracts, Elf-1 has a significantly higher affinity for the D' sequence than does another Ets protein, Ets-1. Transactivation and expression studies support the hypothesis that Elf-1 activates TdT transcription in immature T and B cells. Finally, a D' mutation which selectively reduces Elf-1 binding, but not the binding of other Ets proteins, was found to greatly reduce TdT promoter activity. Although Elf-1 previously had been implicated in the inducible activation of genes in mature T and B cells, our results suggest that it also plays an important role in regulating genes during an early phase of lymphocyte development.

Amino Acid Sequence↗
PubMed1996

Usual dietary salt intake and asthma in children: a case-control study.

BACKGROUND: A decline in host resistance due to an alteration in diet--primarily of salt--was recently put forward as a possible explanation for rising rates of asthma. METHODS: A case-control study was conducted in participants in a prevalence survey which included 187 children with asthma (defined by prior diagnosis and/or a decline in forced expiratory volume in one second (FEV1) of > or = 10% after exercise) and 145 age and sex matched controls. Subjects were selected from 989 children aged 5-13 years attending 18 elementary schools on the island of Montreal. Usual dietary salt intake was estimated from a food frequency questionnaire administered to the mother, and a salt intake score was used to group the children into quartiles from I (lowest) to IV (highest salt intake). Bronchial hyperresponsiveness to methacholine was assessed by Yan's method. Cases and controls were combined in one group to examine the relationship of salt intake to bronchial hyperresponsiveness to methacholine. Methacholine responsiveness was expressed as a dose-response slope and ranks of dose-response slopes were used in the analysis. RESULTS: After accounting for important confounding variables, there was no association between asthma and salt intake, while methacholine dose-response slope ranks increased with increasing salt intake and methacholine responsiveness was greater in the highest quartile than in the lowest quartile of salt intake. The median dose-response slopes in % fall in FEV1 per mumol methacholine for quartiles I, II, III, and IV were 5.4, 5.9, 7.7, and 8.7. CONCLUSIONS: No association was found between asthma or exercise-induced bronchospasm and dietary salt intake. Bronchial hyperresponsiveness to methacholine did, however, appear to increase with greater salt intake, but the relevance of this association to asthma is unclear.

Adolescent↗
PubMed1996

Socioeconomic status and lung function among primary school children in Canada.

We examined the relationship of lung function level to socioeconomic status (SES) using a cross-sectional design among 989 primary school children selected from 18 Montreal schools and studied between April 1990 and November 1992. Information on each child's health, demographics, home exposure to tobacco smoke, pets, and cooking and heating fuel used in the child's home was collected by questionnaire. Spirometry was performed at school. Parental occupation was used to establish SES. After adjusting for personal, familial, and environmental factors, in boys but not in girls, FEV1 and FVC were progressively larger in higher categories of SES (p < 0.001 for linear trend). After taking into account the effect of multiple comparisons and adjusting for personal, familial, and environmental factors, boys from families in the lowest category of SES were found to have an FEV1 lower by 8.2% (95% CI, -13.8 to -2.1) and an FVC lower by 8.1% (95% CI, -13.4 to -2.6) when compared with the most advantaged. These results provide evidence that socioeconomic status, independent of common indoor exposures, is a risk factor for lower FEV1 and FVC among boys.

Canada↗
PubMed1996

Bronchodilators and acute cardiac death.

Bronchodilators used in the treatment of airway disease have been shown to have a variety of cardiac effects that may contribute to the occurrence of life-threatening events such as cardiac arrhythmias and cardiac arrest. We investigated whether theophylline and beta-agonists were associated with cardiovascular mortality among a cohort of subjects prescribed antiasthma medications. We used a population-based cohort of 12,301 subjects aged 5 to 54 yr, formed from health-insurance data bases from Saskatchewan, Canada, and spanning the period 1978 to 1987. Within this cohort, we identified all 30 deaths from cardiovascular causes in which acute asthma did not appear to be a contributing factor. We identified all asthma and cardiovascular drugs dispensed to these subjects shortly before their deaths and compared this therapy to that dispensed to a random sample of 4,080 person-time controls. After adjustment for age and the prior use of cardiac drugs, the rate of cardiovascular death was greater in users of theophylline, with a rate ratio (RR) of 2.7 (95% Cl:1.2 to 6.1), and in users of beta-agonists taken orally or by nebulizer (RR = 2.4; 95% Cl:1.0 to 5.4), but not in users of beta-agonists administered by metered-dose inhaler (RR = 1.2; 95% Cl:0.5 to 2.7). The great majority of cardiovascular deaths occurred among subjects with clinical or pathologic evidence of potentially lethal conditions. These results suggest that the use of theophylline and of beta-agonists administered orally or by nebulization should be avoided in subjects with significant cardiac disease or at high risk for such disease, especially acute coronary insufficiency and congestive cardiomyopathy. On the other hand, the use of beta-agonists administered by metered-dose inhalers (MDIs) was not associated with an increased risk of cardiovascular death.

Adolescent↗
PubMed1996

Long-term effects of therapy on respiratory health.

Only scant information is available on the long-term consequences to respiratory health of treatment with bronchodilators and oral corticosteroids. In the present study, we aimed to gain more information about these consequences. We examined 712 men working in the Paris area, by means of a subjective assessment of whether their respiratory health worsened or improved from 1960 to 1972, the decline in forced expiratory volume in one second (FEV1) over this time-period, and mortality from 1972 to 1992, in relation to respiratory therapy dispensed during a 2 year period in 1970-1971, as recorded in social security reimbursement records. As expected, subjects with respiratory symptoms or airflow limitation were more likely to have been prescribed respiratory therapy. After accounting for the effect of lung function level and smoking, subjects dispensed inhaled beta-agonists were likely to feel their condition had worsened and had a greater decline in FEV1 from 1960 to 1972. Among subjects with airflow limitation who reported asthma or persistent wheeze, having been dispensed oral corticosteroids on an intermittent basis was associated with improved survival (relative risk (RR) 0.32; 95% confidence interval (95% CI): 0.10-0.91) after adjusting for FEV1 level and smoking category. Our results add to the evidence that regular use of beta-agonist bronchodilators may be associated with adverse effects on respiratory health, whilst intermittent use of corticosteroids may be of long-term benefit.

Adrenal Cortex Hormones↗
PubMed1996

Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation.

PURPOSE: To compare the results achieved with myeloablative therapy followed by either allogeneic bone marrow transplantation (alloBMT) or autologous bone marrow transplantation (ABMT) for patients with Hodgkin's disease (HD). PATIENTS AND METHODS: Of more than 1,200 patients with HD reported to the European Bone Marrow Transplantation (EBMT) registry, 49 underwent alloBMT. Of these, 45 with sufficient data were matched to 45 patients who underwent ABMT. The matching criteria were sex, age at time of transplantation, stage of disease at diagnosis, bone marrow involvement at diagnosis and at transplantation, year of transplantation, disease status at time of transplantation, time from diagnosis to transplantation, and conditioning regimen with or without total-body irradiation (TBI). RESULTS: The 4-year actuarial probabilities of survival, progression-free survival (PFS), relapse, and non-relapse mortality were 25%, 15%, 61%, and 48% and 37%, 24%, 61%, and 27% after alloBMT and ABMT, respectively. The toxic death rate at 4 years was significantly higher for alloBMT patients (P = .04). For patients with sensitive disease at the time of transplantation, the 4-year actuarial probability of survival was 30% after alloBMT and 64% after ABMT (P = .007). This difference is mainly due to a higher transplant-related mortality rate after alloBMT (65% v 12%, P = .005). Acute graft-versus-host disease (aGVHD) > or = grade II was associated with a significantly lower risk of relapse, but also with a lower overall survival (OS) rate. CONCLUSION: Based on this study, alloBMT from a human leukocyte antigen (HLA)-identical sibling donor does not appear to offer any advantage when compared with ABMT. A graft-versus-Hodgkin effect is associated with > or = grade II aGVHD, but its positive effect on relapse is largely offset by its toxicity. In most circumstances, alloBMT cannot be recommended for patients with HD.

Adolescent↗
PubMed1996

Interleukin-13 and interleukin-4 are coexpressed in atopic asthma.

Interleukin-4 (IL-4) is an important cytokine in the allergic inflammation associated with atopic asthma. Interleukin-13 shares many of the biological effects of IL-4, and the evidence suggests that the expression of these two cytokine genes may be coregulated. We have investigated the expression of IL-13 and IL-4 mRNA in the bronchial mucosa of nine stable atopic asthmatics and 10 normal controls, characterized the major cellular source of IL-13 mRNA, and examined the colocalization of IL-13 and IL-4 mRNA. Endobronchial biopsies were obtained and examined for IL-13 and IL-4 mRNA using radiolabeled in situ hybridization. The number of positive cells per millimeter of basement membrane for both IL-13 and IL-4 mRNA was increased significantly in the bronchial mucosa of atopic asthmatics compared to normal controls (p < .001). In the atopic asthmatics, the expression of IL-13 was significantly greater than that for IL-4 (p < .01). In these subjects, 90% of the IL-13 mRNA-positive cells were CD3-positive T cells. Furthermore, although 100% of IL-4-positive cells also expressed IL-13 mRNA, only 60% of IL-13-positive cells also expressed IL-4. These results demonstrate that, in mild atopic asthma, IL-13 and IL-4 are coexpressed and that the upregulation of IL-13 expression is greater than that of IL-4. Our data support the role of IL-13 in the allergic inflammation present in atopic asthma.

Asthma↗