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Biomedical subjects

A J Frew

Publications and source records attributed to A J Frew.

At least 91 records · Page 5Linked to original sources
PubMed1995

Type III allergy skin testing. Position statement for EAACI Subcommittee on Skin Tests and Allergen Standardization.

Immune-complex-mediated hypersensitivity has been implicated in a small number of allergic respiratory conditions. These include EAA and ABPA. In addition, there is some evidence of type IV hypersensitivity in EAA and BFL, together with activation of complement via the alternative pathway (4, 8, 26). Positive immediate skin tests are now usually regarded as an essential criterion for the diagnosis of ABPA. These reflect the presence of antigen-specific IgE, but this test is not specific for ABPA, as other atopic subjects may also be sensitized to A. fumigatus without any evidence of the parenchymal features that are required to diagnose ABPA. For FL, skin tests with currently available antigens show poor discrimination between affected patients and exposed but healthy individuals. There is little evidence that vascular deposition of immune complexes in the skin contributes to the delayed skin responses in EAA, and skin tests in FL are not specific for type III hypersensitivity. Further refinement of methodology and antigen extracts may improve the specificity of skin tests in FL, but in many cases the aetiology of EAA is multifactorial and the true causative antigens may not have been identified. Therefore, the diagnosis of EAA remains based on history and clinical findings, supported by the presence of precipitins, and sometimes by bronchial biopsy and lavage appearances (25).

Allergens↗
PubMed1995

Bronchial inflammation in occupational asthma due to western red cedar.

Bronchoalveolar lavage cells and bronchial biopsies were obtained from nine patients with red cedar asthma, six atopic asthmatics and six non-atopic, non-asthmatic control subjects. There were similar proportions of neutrophils, mast cells, lymphocytes, and macrophages in BAL samples from all three groups, but eosinophil numbers were elevated in patients with cedar asthma and atopic asthma (3.0 and 2.5% respectively versus 0.5% in control subjects; p < 0.05 for each group). In bronchial mucosal biopsies, mean numbers of T cells were elevated in both asthmatic groups (cedar asthma 9.8 times, and atopic asthma 2.6 times, control values). CD4+ cells accounted for most of the increase in T-cell numbers, while CD8+ cell numbers were elevated in biopsies from a minority of cedar asthma patients. Absolute numbers of CD25+ (IL-2 receptor-bearing) cells were increased in cedar asthma but the proportion of T cells expressing CD25, was similar in all three groups. Activated eosinophils (EG2+) were increased in both asthmatic groups, with mean numbers 2.5 times greater in the cedar asthma biopsies than in atopic asthmatics. Thus both cedar asthma and atopic asthma are associated with increased numbers of T-cells and activated eosinophils in the bronchial mucosa. There was no major histologic difference between atopic asthma and red cedar asthma.

Adult↗
PubMed1994

Persistent asthma after repeated exposure to high concentrations of gases in pulpmills.

This is a clinicopathologic study of three subjects with irritant-induced asthma. They were pulpmill workers who had a history of multiple "gassing" episodes that occurred over a period of years. Persistent symptoms of asthma and nonspecific bronchial hyperresponsiveness and/or variable airflow obstruction occurred after at least one episode of "gassing," resulting in symptoms severe enough to require emergency room treatment. One of the three subjects had normal spirometry values before he entered the pulpmill. Bronchial biopsy done on these subjects showed changes compatible with asthma, including thickened basement membrane in two and cellular infiltration with activated eosinophils and mononuclear cells in all three. The results of immunohistology of bronchial mucosal biopsy of these subjects were compared with those of patients with allergic asthma and patients with Western red cedar-induced asthma. Subjects with irritant-induced asthma had a greater density of activated eosinophils and fewer T-lymphocytes, suggesting that cell-mediated immune mechanisms are not involved in the pathogenesis of this condition.

Adult↗
PubMed1993

Injection immunotherapy. British Society for Allergy and Clinical Immunology Working Party.

A working party of the British Society for Allergy and Clinical Immunology has reviewed the role of specific allergen immunotherapy in the treatment of allergic disease and produced a position statement summarising the available evidence for efficacy and safety. The working party recommends specific allergen immunotherapy for treating summer hay fever uncontrolled by conventional medication and for wasp and bee venom hypersensitivity. It is not recommended for asthma or for allergic rhinitis due to other allergens. For the recommended indications the risk:benefit ratio is acceptable provided patients are carefully selected; in particular, patients with asthma should be excluded as they are especially vulnerable to adverse reactions. Injections should be given only by doctors experiences in this form of treatment in a clinic where full resuscitative facilities are immediately available. Provided patients remain symptom free a 60 minute observation period after injection is sufficient to detect all serious adverse reactions.

Asthma↗
PubMed1993

Lack of role for mononuclear cell-derived histamine releasing factors in occupational asthma due to western red cedar.

Occupational asthma due to Western Red Cedar (WRCA) is attributed to sensitization to plicatic acid (PA), but does not appear to be dependent on PA-specific IgE antibodies. Exposure to PA induces histamine release in vivo and in vitro, so if IgE is not important, other mechanisms of histamine release must presumably operate in WRCA. To explore the possible role of histamine-releasing factors in WRCA, peripheral blood mononuclear cells were obtained and cultured with PA, PA-albumin conjugate plicatic acid-human serum albumin (PA-HSA), grass pollen or Concanavalin A using a standard histamine releasing factor (HRF) generation protocol. Supernatants were dialysed to remove endogenous histamine and then assayed for histamine releasing activity using human basophils as targets and a Con A-induced bulk supernatant as an internal HRF standard. In contrast to some previous reports, spontaneous HRF release from the peripheral blood mononuclear cells (PBMC) of WRCA patients (n=9) and atopic asthmatic subjects (n=5) was not elevated compared with the non-asthmatic controls (n=11; five atopic and six non-atopic). Both PA and PA-HSA induced the production of small amounts of HRF by PBMC of WRCA patients, but a similar degree of HRF generation was also observed in PBMC from the atopic asthmatic, atopic nonasthmatic, and non-atopic subjects. In contrast, grass pollen induced the production of HRF by PBMC from the subjects with positive skin tests to grass pollen but not by PBMC of non-atopic subjects, confirming that our methods and assay were capable of detecting antigen-specific HRF production. Since neither PA nor PA-HSA induced significantly elevated HRF production from PBMC of WRCA patients, it seems unlikely that PA-induced HRFs play a substantial role in the pathogenesis of WRCA.

Adult↗
PubMed1993

Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses.

We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a double-blind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Th1-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance.

Adult↗
PubMed1993

Clinical pharmacology of asthma. Implications for treatment.

The past 10 years have seen three important changes in the philosophy of managing asthma. First, histological studies using fibreoptic bronchoscopy have led to the recognition that asthma is an inflammatory condition of the bronchial mucosa and is not simply caused by smooth muscle spasm. Secondly, there has been some disenchantment with the long term use of regular beta 2-adrenergic agonists as these agents do not appear to control bronchial inflammation and have been associated with deaths from asthma. Thirdly, there has been a general shift away from physician-centred management towards patient-oriented management plans. These three separate strands have led to the development of regional and international consensus documents that emphasise the use of regular anti-inflammatory treatment to control bronchial inflammation and reduce symptoms. With the emphasis on finding the minimum amount of treatment, several traditional anti-asthma medications have been downgraded in importance. The introduction of self-management plans is to be welcomed, but it is important that these new strategies for treating asthma are properly evaluated so that the benefits they confer can be ascertained and maximised.

Anti-Inflammatory Agents↗
PubMed1992

The effect of a single oral dose of prednisolone or cetirizine on inflammatory cells infiltrating allergen-induced cutaneous late-phase reactions in atopic subjects.

The effect of a single dose of prednisolone (20 mg) or cetirizine (10 mg) on the immunohistology of the cutaneous late-phase reaction was determined in a double-blind, placebo-controlled, cross-over study in 12 atopic allergic individuals. The subjects were challenged with intradermal allergen (30 BU) 2 hr after ingestion of the drugs or placebo. The magnitude of the cutaneous reactions were determined at 15 min, 6 and 24 hr, and skin biopsies performed at 24 hr. Cetirizine produced a 50% average inhibition of the immediate weal and flare response (P = 0.001) and a 27% average inhibition of the 6 hr late-phase induration (NS). Prednisolone reduced the immediate (27%, P = 0.03) and significantly inhibited the late-phase reaction (53%, P = 0.02). Prednisolone significantly inhibited infiltration of CD45+ (total leucocytes), neutrophil elastase+, EG2+ (activated eosinophils) and CD25+ (IL-2R) cells (P = 0.017, 0.005, 0.005 and 0.032 respectively). CD3, CD4, CD8 and HLA-DR expression was also inhibited but this was not significant. Cetirizine also reduced the numbers of EG2+ cells, particularly those with high counts before treatment but the overall results were not significant. No other changes in the cellular infiltrate were demonstrated when cetirizine was compared with placebo. These findings indicate a single dose of prednisolone significantly reduces leucocyte infiltration and activation as well as the magnitude of the cutaneous late-phase reaction.

Administration, Oral↗
PubMed1992

Methacholine responsiveness, smoking, and atopy as risk factors for accelerated FEV1 decline in male working populations.

Longitudinal lung function data from four occupational health surveys was used to explore the relationship between nonspecific bronchial responsiveness (NSBR) and the rate of decline of FEV1 (RDFEV) and to address other factors that may predict or influence RDFEV. Of the 1,203 subjects with baseline methacholine and lung function data, follow-up data were available for 733 individuals (61%). The data-available and data-unavailable groups were well matched with respect to baseline lung function, atopy, and smoking status. Compared with the unavailable group, those available for follow-up were younger (42.5 versus 37.7 yr; p less than 0.0001) and slightly less responsive to methacholine (p less than 0.01). Somewhat unexpectedly, RDFEV was lower in the 30 asthmatic subjects than in the nonasthmatics. Among the nonasthmatic subgroup (96% of those available for follow-up), age, occupational group, and baseline FEV1 (% predicted) were independent predictive factors for RDFEV. When these factors were included in the model, RDFEV was found to be increased among current smokers compared with never-smokers or ex-smokers. In the final regression model, a relationship was found between methacholine sensitivity (calculated as a dose-response slope) and RDFEV in nonasthmatics (p less than 0.05). Stratification by smoking status revealed that the relationship between RDFEV and bronchial responsiveness was confined to current smokers and that atopy was an additional risk factor in this subgroup only. This relationship was valid among current smokers in each of the three occupational groups studies. However, reinclusion of the 30 asthmatic subjects in the study population obscured the relationship between NSBR and RDFEV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Medical audit: the differing perspectives of managers and clinicians.

The objectives of this study were to gauge the attitudes and perceptions of managers and clinicians to medical audit, and to identify differences which might be barriers to the effective implementation of audit. A questionnaire survey of consultants and health service managers in one health district was conducted prior to the introduction of medical audit. Replies were received from 113/144 (78%) clinicians and 53/70 (76%) managers. Managers and clinicians concurred about the potential benefits of audit but had divergent opinions regarding its disadvantages. Seventy-one per cent of clinicians thought that audit would interfere with clinical work and 41% that audit would consume resources that could be better used on patient care. Only one in eight managers shared these views. Clinicians were divided on the threats to clinical autonomy and were three times more likely than managers to agree that audit would enable managers to influence medical practice. Most clinicians considered that audit would require one session a week, while 49% of responding managers thought audit could be performed within existing timetables. Although managers and clinicians are broadly in favour of the introduction of audit, they differ in their assessment of the time required and the opportunity costs. Appreciation of these differing perspectives should facilitate the effective introduction of audit.

Attitude↗