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

Nedocromil sodium, a pyranoquinolone, was specifically designed as an agent to suppress allergic inflammation. Nedocromil sodium significantly affects not only the early-phase of allergen-induced responses, but also expression of late-phase inflammation, even when administered after the onset of early-phase responses. Nedocromil sodium also limits bronchoconstriction induced by nonallergic factors, including cold air and sulfur dioxide at dosages lower than required with cromolyn sodium. Nedocromil sodium is more potent than cromolyn sodium in preventing mast cell degranulation in selective animal models. In addition, nedocromil sodium limits leukotriene C4 production by calcium ionophore-stimulated eosinophils and also limits the activity of platelet activating factor to induce neutrophil generation of superoxides. Diurnal variation of peak flow rates in asthmatics and requirement for both beta 2-agonists and inhaled beclomethasone have been noted to be reduced in several trials employing nedocromil sodium, suggesting that its in vivo activity parallels its in vitro activity as an anti-inflammatory agent.

Over the last four or five years, there have been some serious attempts to look for alternatives to corticosteroids in the management of severe bronchial asthma. Rheumatologists and dermatologists long ago recognized the importance of replacing corticosteroids with other agents. Some agents such as methotrexate are now clearly established through multiple double-blind trials as being appropriate substitutes for corticosteroids, whereas other agents which have been investigated, such as cyclosporin, are very promising. Finally, a third group of agents, including troleandomycin (TAO), have been found to be totally inappropriate as possible substitutes for corticosteroids.

Occupational dermal and respiratory allergies caused by natural rubber latex (NRL) have been encountered with increasing frequency in health care workers. In order to measure the amount of airborne NRL, area and personal air sampling was performed in three hospital laboratories where workers used latex gloves. The total dust levels in laboratory air samples were lower than 0.17 mg/m3. RAST inhibition suggested that NRL antigens may exist both in the area and personal samples. Immunospot measurements, rocket immunoelectroporesis, and rocket radioimmunoelectrophoresis did not show any NRL activities in laboratory airsamples, although they were able to detect immunoactive material in positive control filter specimens. We conclude that the airborne NRL concentration was undetectable in daily hospital laboratory environment where workers used disposable NRL gloves. Airborne NRL, however, can be measured by using immunological assays.

Among the inflammatory cells involved in the pathogenesis of asthma, eosinophils have been recognized as highly significant participants in the late-phase of the inflammatory response. Bronchial challenge with allergen inducing inflammation and exacerbation of asthma results in activation of eosinophils and release of specific eosinophil mediators, including eosinophil cationic protein (ECP). Recent studies have demonstrated that activation of eosinophils and increase of their release of ECP occur in patients naturally exposed to allergen, and in patients having inflammatory exacerbations of asthma, including development of bronchial hyperreactivity. ECP is elevated during exacerbation of extrinsic and intrinsic asthma in direct relationship to concomitant decrease in pulmonary function and increasing asthma symptoms. The elevated serum levels of ECP decline subsequent to effective therapy. Monitoring modulation of ECP levels may be useful in evaluating the treatment of asthmatic patients and as a marker for the efficacy of therapy. Several investigations have strongly suggested that serial determination of ECP in asthmatics may be especially useful as an inflammatory correlate to the mechanical abnormalities assessed by determination of pulmonary function in asthmatic patients.

Increased numbers of goblet cells associated with decrease in the ciliated epithelium occur at an early stage in the patient with asthma. Recent bronchial biopsy studies have demonstrated that these changes may occur even in the mildest asthmatic patient. The protective function of the epithelium is thus compromised and secretion enhanced in early asthma. Anti-inflammatory therapy should be employed at an early stage in the asthmatic patient. Avoidance of allergen is also essential if the source of the inflammation is atopic disease. Inhaled corticosteroids not only reduce bronchial hyperresponsitivity, but also improve the diurnal variation that occurs in lung function in the asthmatic patient. Inhaled corticosteroid therapy is associated with the normalization of the ciliated to goblet cell ratio and a reduction in the inflammatory cell infiltrate, including most notably a reduction in eosinophil within the lamina propria and respiratory epithelium. These changes induced by inhaled corticosteroids are not noted when inhaled beta 2-agonists are employed alone as therapy for asthma. The use of inhaled corticosteroids may thus potentially reverse the pathologic changes that occur even in the early asthmatic patient, whereas utilization of inhaled beta 2-agonists failed to improve histologic abnormalities that occur in early asthma.

In order to characterize the profile of inhalant allergen sensitizations in patients with food hypersensitivity, we carried out a screening process using a standard panel of inhalant allergens by SPT. We screened 437 patients (mean age 5.4 years, 4.1 SD) who showed anti-allergen IgE to one or several foods, determined by both SPT and RAST. In each case in which a positive SPT to inhalant appeared, a new individualized search for these allergens was performed by both SPT and Phadezym RAST. We found sensitization to aeroallergens in 272 of the 437 children (62%) with sensitization to foods (52% of all patients were sensitized to pollens, 17% to dermatophagoides, and 26% to animal allergens). The number with sensitization to aeroallergens was proportionally increased in relation to the number of food sensitizations (p < 0.05). Sensitization to pollen allergen were found with higher frequency (p < 0.001) in patients with sensitization to fruits, legumes, and other vegetables (mainly walnuts, chestnuts, melons, or sunflower seeds) than in those sensitive to foods of animal origin. Sensitization to dermatophagoides and animal allergens did not show any special distribution relative to the kind of food sensitization. Seventeen patients with sensitization to egg showed sensitization to avian feathers. This type of sensitization did not appear in the remainder of patients evaluated.

The vital role of inflammation in the induction and perpetuation of asthmatic responses is now a widely accepted concept. Effective management of asthma requires modulation of asthmatic inflammatory responses. Eosinophils play a critical role in producing inflammation within the asthmatic lungs. Serologic assessment of the level of eosinophilic cationic protein (ECP) may be useful in assessing the degree of activation of eosinophils in asthma and the effect of pharmacotherapy on activated eosinophils. Several clinical trials have noted that ECP levels fluctuate in direct relationship to the amount of ongoing bronchospasm and asthmatic inflammation. Modulation of inflammation in asthma can occur through pharmacologic means. Nedocromil sodium has been demonstrated to significantly affect both early-phase and late-phase inflammatory events including effects on mast cell activation and effects on eosinophil function. Nedocromil sodium has also been noted to affect production and activity of cytokines that are vital to the perpetuation of the asthmatic late-phase response. Unlike cromolyn sodium, nedocromil sodium inhibits late-phase inflammation even when administered after the early phase of the allergic response and has also been demonstrated to be a steroid-sparing agent in mild-to-moderate asthmatics who require inhaled beclomethasone. Modulation of the metabolism of arachidonic acid, thereby affecting levels of prostaglandins and leukotrienes, may be extremely useful in selective asthmatic patients. Those patients having aspirin sensitivity and chronic rhinitis associated with asthma seem to be particularly responsive to arachidonic acid metabolites. In such patients, use of aspirin desensitization may be considered. Newer anti-inflammatory agents being investigated as treatments for asthma include methotrexate, hydroxychloroquin, auronifin, and sulfonylureas, among others.(ABSTRACT TRUNCATED AT 250 WORDS)

Although aspirin sensitive asthma has been recognized as a clinical entity since the beginning of this century, the mechanism for the production of this syndrome still remains obscure. Recent studies have indicated a higher than previously appreciated incidence of aspirin sensitive asthma, perhaps approaching 40% of steroid-dependent asthmatics. Challenge with both oral and bronchial instilled aspirin may be useful to identify aspirin-sensitive individuals. During aspirin-induced reactions, increased vascular permeability is noted. In addition, aspirin-sensitive individuals have altered levels of production of leukotriene E4 and enhanced sensitivity to inhaled leukotriene E4. However, nasal secretions of aspirin-sensitive individuals demonstrate enhanced leukotriene C4 concentration after aspirin challenge. It has also been noted that nonaspirin-sensitive patients have enhanced leukotriene C4 concentration. Thus, the specific defect leading to the pathogenesis of aspirin-sensitive asthma and rhinosinusitis in selected individuals remains obscure. Eosinophil activation has been noted in aspirin-sensitive rhinosinusitis patients; however, other cell types, including platelets and monocytes, have also been noted to exhibit metabolic abnormalities in this syndrome. Aspirin desensitization may be a useful option in selected patients with significant aspirin sensitive rhinosinusitis and asthma.

A 25-year-old Hispanic female with insulin dependent diabetes mellitus (IDDM) and endstage renal disease on chronic hemodialysis was hospitalized with paroxysms of fever and chills for a day. A day after starting piperacillin for presumed intravascular line infection, she developed a maculopapular dermatitis and abnormal liver function tests, at which point the drug was discontinued. However, the rash persisted for 10 days, after which it progressively worsened. She continued to have high fevers, abnormal liver function tests, and marked leukocytosis, despite multiple negative cultures and other nondiagnostic examinations. She was treated as a patient with sepsis of unknown etiology and received multiple antibiotics on an empiric basis without response. A diagnosis of Stevens-Johnson syndrome was then made based on the triad of cutaneous dermatitis, mucosal, and hepatic involvement. She received high dose corticosteroids and her fever, dermatitis, mucosal lesions, leukocytosis, and abnormal liver function tests improved dramatically.