Allergy proceedings : the official journal of regional and state allergy societies最新文献

Allergic inflammation as a cause of asthma is now well recognized. New methods of identification of allergen-specific IgE including improved in vitro technologies will require optimization of the lowest threshold for the detection of allergen-specific IgE in order to maximize sensitivity without loss of specificity, thus allowing for significant enhancement in a clinical setting for determination of allergen-specific IgE levels. New concepts of allergic inflammation include the recognition that significant histologic changes may occur even in the mildest allergic patients. Thus, early intervention with antiinflammatory therapies including corticosteroids or inhaled nedrocromil sodium appears clearly warranted based on these early pathological changes occurring in asthmatic individuals. Inhaled corticosteroids have been demonstrated to prevent pathological changes that otherwise occur in asthmatic patients whose sole therapy is use of inhaled B2 agonist. Corticosteroids have also been noted to be successful in the prevention of progression of pathological changes including the development of bronchiectasis in asthmatic patients with allergic bronchopulmonary fungoses. Allergen-specific immunotherapy may be successfully used in selective asthmatic patients allergic to pollen, dust mite, or certain mold allergens including Alternaria. Immunotherapy appears to be most useful in those patients who are allergic to one rather than many allergens and whose asthma is not associated with other significant precipitating factors such as chronic rhinosinusitis or aspirin sensitivity. The risk of systemic reactions to allergen immunotherapy in the asthmatic patient is significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Early diagnosis and treatment is essential for patients afflicted with bronchopulmonary aspergillosis (ABPA). Inflammatory damage to the airways may be significantly reduced through use of corticosteroids. Without treatment, bronchiectasis causing permanent anatomic alteration of the airways may occur. ABPA should be considered in any asthmatic who requires oral corticosteroids and has recurrent pulmonary infiltrates. Evaluation should include determination of total serum IgE, which generally exceeds 1000 ng/mL in patients with ABPA. Disease categorization of ABPA patients may be made according to radiographic and clinical considerations into five stages. The treatment choice for ABPA is prednisone, although inhaled corticosteroids including beclomethasone dipropionate may also be used in long-term asthma management. Successful therapy of ABPA is typically associated with a decline in total serum IgE, subsequent exacerbations often being associated with elevation in total serum IgE. Allergen avoidance is essential for the ABPA patient, as exposure to heavy concentrations of fungi may precipitate disease exacerbation.

One of the major sources of uncertainty and controversy in allergy testing is the definition and clinical significance of a positive test result in the low assay range. Use of analytical detection limit theory can guide the diagnostic allergy laboratory director in setting a lower assay cutoff and in the evaluation of the recommended cutoff by the manufacturer of the assay. Several methods for calculating lower limit of detection are applicable to specific IgE assay methods. Receiver operating characteristic (ROC) curves illustrate the relationship between statistical sensitivity and specificity as cutoffs are adjusted, and statistical analysis of ROC curves is an invaluable aspect of the comparative performance evaluation of two or more assays relative to an independent standard such as skin testing.

Allergy skin testing for immediate hypersensitivity is affected by a number of factors, some under the control of and others not controllable by the operator. Uncontrollable factors include the patient's age, chronobiological variation, and variation in reactivity between different parts of the body. Controllable factors include medications the patient is using, the quality of the allergy extract employed, the distance between test sites, the choice of prick or intradermal technique, and in the case of percutaneous testing, the device that is used. Considering the importance of the information that is generated by skin testing, and the major therapeutic commitments often resulting, more attention should be given to the techniques employed. It is suggested that operator performance can and should be assessed by relatively simple tests.

Appreciation of the early damage that occurs to the respiratory epithelium has been limited by the use of autopsy specimens from fatally stricken asthmatics as a source of representative specimens. The use of bronchoscopy to obtain specimens from patients early in the course of their asthma has allowed a new understanding of the evolution of pathological changes that occur in asthma. Newly diagnosed, mild asthmatics have been shown to have bronchial goblet cell hyperplasia in addition to increased numbers of mast cells and eosinophils in the respiratory epithelium, and increased eosinophil granule protein deposition within the lamina propria. Endothelial gaps in postcapillary venules are greater in asthmatic airways, suggesting that increased plasma transudation may contribute to the known epithelial cell shedding characteristic of asthma attacks. Asthmatic inflammation, even early in the course of the disease, includes vascular permeability changes, inflammatory cell infiltration, epithelial cell shedding, and goblet cell hyperplasia, replacing the normal ciliated epithelium. Current investigation evaluating the effects of asthmatic inflammation on epithelial cell attachment to each other and to the extracellular matrix molecules regulated by adhesion glycoproteins will likely enhance further the understanding of the pathological changes that occur within the asthmatic airway.

The beta 2 adrenoceptor has been cloned and sequenced, and details of how agonist stimulation ultimately results in clinically evident effects are now known. Receptor desensitization by agonist is an almost universal process that can be prevented and reversed by corticosteroids. Although immunologic mechanisms appear to prevail in asthma, beta 2 receptor dysfunction may be important in some circumstances. Many receptor agonists are available for asthma therapy, including a new generation of long acting agents (such as salmeterol) with duration of action of 12 hours or more. Statistical links between beta agonist use and asthma mortality or morbidity warrant careful examination for clinical relevance, but may not be dismissed. Beta agonists are relatively safe and clearly effective in asthma, but anti-inflammatory management (including allergen avoidance and immunotherapy when appropriate) is indicated in patients who require chronic therapy.

Mast cell neutral proteases are the most precise markers of heterogeneity among human mast cells. Two types of human mast cells have been recognized. MCTC cells contain tryptase together with chymase, cathepsin-G like protease, and mast cell carboxypeptidase; MCT cells contain tryptase, but lack the other neutral proteases present in MCTC cells. All mast cells develop from hemopoietic stem cells. In vitro procedures for studying mast cell growth have been developed, using the major human mast cell growth factor, stem cell factor (SCF, also called Kit-ligand). Cultures of hemopoietic progenitor cells in the presence of SCF alone result in selective differentiation to mast cells. The same progenitor cells can be induced to differentiate into other lineages when SCF is used with various lineage-specific colony-stimulating factors such as erythropoietin for erythrocytes. Mast cell development from hematopoietic progenitors may represent a "default pathway," occurring optimally in a permissive microenvironment such as skin, bowel, and lung. The presence or absence of certain cytokines in blood and bone marrow may create a non-permissive environment, thus the absence of granulated mast cells in such locations.