Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma

Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma

National Asthma Education and Prevention Program.

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing "The diagnosis and Management of Rhinitis: An Updated Practice Parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.

The diagnosis and management of rhinitis: An updated practice parameter

Allergen-specific immunotherapy (SIT) has been used for almost a century as a desensitizing therapy for allergic diseases and represents the only curative and specific method of treatment. Administration of appropriate concentrations of allergen extracts has been shown to be reproducibly effective when patients are carefully selected. The mechanisms by which allergen-SIT has its effects include the modulation of T-cell and B-cell responses and related antibody isotypes as well as effector cells of allergic inflammation, such as eosinophils, basophils, and mast cells. The balance between allergen-specific T-regulatory (Treg) and T H 2 cells appears to be decisive in the development of allergic and healthy immune responses against allergens. Treg cells consistently represent the dominant subset specific for common environmental allergens in sensitized healthy individuals. In contrast, there is a high frequency of allergen-specific T H 2 cells in patients with allergy. The induction of a tolerant state in peripheral T cells represents an essential step in allergen-SIT. Peripheral T-cell tolerance is characterized mainly by generation of allergen-specific Treg cells leading to suppressed T-cell proliferation and T H 1 and T H 2 cytokine responses against the allergen. This is accompanied by a significant increase in allergen-specific IgG 4 , and also IgG 1 and IgA, and a decrease in IgE in the late stage of the disease. In addition, decreased tissue infiltration of mast cells and eosinophils and their mediator release including circulating basophils takes place. Current understanding of mechanisms of allergen-SIT, particularly the role of Treg cells in peripheral tolerance, may enable novel treatment strategies.

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Mechanisms of allergen-specific immunotherapy

Summary
Background In this study, which summarizes our last 5 years of experience, we evaluated the side-effects of ultra-rush venom immunotherapy and the possibility to define some risk factors for side-effects as age, Hymenoptera venom used for treatment, treatment phase, severity of prior insect sting reaction, concentration of skin test positivity, and level of specific IgE.

Methods In our protocol on day 1, an initial venom dose of 0.1 μg was followed by 1, 10, 20 μg at 30-min intervals and then 30 and 40 μg at 60-min intervals. Patients who completed this protocol received two booster injections of 50 μg on day 15 and one of 100 μg on day 45. Subsequently, monthly 100 μg boosters were given.

Results Fifty-one children (9.20 ± 3.41 years) and 207 adults (40.62 ± 14.00 years) underwent an ultra-rapid venom immunotherapy (ultra-RVIT). Single ultra-RVIT was administered to 195 patients: 69 with honeybee, 123 with yellow jacket and three with wasp venoms. Two venoms were injected into 59 patients: 42 with yellow jacket and wasp, 17 with yellow jacket and honeybee. Four patients received the three venoms.

The frequency of immediate systemic reactions (SR) was not significantly different between adults and children: 11.2% vs. 10.8%.

SR were experienced more frequently on day 1 (n= 33). They were uncommon on day 15 (n= 2) and on day 45 (n= 1). No late reactions have been observed. Honeybee venom induced significantly more SR (30%) vs. yellow jacket (3.2%) and wasp venom (6.1%). Among the 33 patients who experienced a SR on day 1, 24 had a reaction grade 1 or 2 and nine had a reaction grade 3 or 4. There is a significant risk for patients with a prior reaction grade 3 or 4 to experience a SR during venom immunotherapy (VIT).

The strength of positive skin tests and the level of specific IgE were not related to an increased risk of SR (P= NS).

Conclusion Treatment with honeybee extract induced more SR than the treatment with yellow jacket and wasp venom. Doses increase phase on day 1 is risk factors for SR of ultra-RVIT, as well as the severity of the prior reaction. Age, degree of positive skin tests, and specific IgE are not risk factors.

Hymenoptera ultra-rush venom immunotherapy (210 min): a safety study and risk factors.

Background
Commercially available house dust mite components may improve routine testing of allergic patients.

Objective
To establish the prevalence and serum levels of IgE to commercial Der p 1, Der p 2, Der p 10 and the carbohydrate MUXF3 in house dust-mite allergic patients. To compare individual vs. allergen microarray methods.

Methods
Prevalence and serum levels of IgE to Dermatophagoides pteronyssinus extract and components Der p 1, Der p 2, Der p 10 and MUXF3, specific IgG4 to D. pteronyssinus, total serum IgE levels, and clinical features (age, asthma, rhinitis and atopic dermatitis) were determined in 123 patients (64 children) with the ImmunoCAP® method. ImmunoCAP ISAC® was performed in 24 patients.

Results
All patients had serum IgE to D. pteronyssinus. Prevalences of serum IgE to commercial components were Der p 1 93%, Der p 2 77% (Der p 1 or Der p 2 94%), Der p 10 28% and MUXF3 25%. Levels of D. pteronyssinus IgE strongly correlated with Der p 1 and Der p 2 IgE (r = 0.89 and 0.85 respectively), but not Der p 10 and MUXF3. ImmunoCAP® and ImmunoCAP ISAC® were concordant, but the quantitative correlation was poor. No clinical implication for the prevalence, levels, or molecular IgE reactivity profile to house dust mite components was found.

Conclusions and Clinical Relevance
Commercially available Der p 1 and Der p 2 strongly correlate with IgE D. pteronyssinus. The lack of Der p 1 and Der p 2 IgE may help with differential diagnosis. Der p 10 serum IgE prevalence and levels suggest different patterns in food and mite-related tropomyosin sensitization. Serum IgE to carbohydrate MUXF3, although unexpectedly prevalent, were low and did not modify D. pteronyssinus IgE levels. Follow-up may be best carried out with individual rather than microarrayed components.

Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite allergy.

Background
Muscle relaxants (MR) are responsible for 59% of peroperative anaphylactic reactions. A major issue would be to determine whether a systematic preoperative screening in the general population should be recommended.

Objective
The purpose of the study was to evaluate the prevalence of muscle relaxant sensitivity in a sample of the general population and to assess the role of possible risk factors.

Methods
Two hundred and fifty-eight subjects, aged 20–40 years, visiting a health care centre for a check-up were evaluated. Protocol included a questionnaire (occupation, symptoms of atopy, previous surgery, history of drug allergy), skin-prick tests to four commercial muscle relaxants and measurement of specific IgE against quaternary ammonium ions. Atopy was evaluated by skin-prick tests to common inhalant allergens and by a Phadiatop test.

Results
Of the study group, 9.3% had either a positive skin test to one or more muscle relaxant or a presence of specific IgE to quaternary ammonium ions. No risk factor was identified in the studied group.

Conclusion
Since the rate of MR sensitivity is much higher than the anticipated rate of peroperative reactions due to allergy, a systematic preoperative screening for MR allergy should not be recommended for adults in a general population.

Prevalence of muscle relaxant sensitivity in a general population: implications for a preoperative screening.

To get figures of prevalence of systemic reactions (SRs) to hymenoptera sting in adults between the ages of 18 to 65 years, we performed three different surveys using the same questionnaire from 1984 to 1988. The first one was a door-to-door survey in Southeast France, which included 8271 adults and used a questionnaire. The second one, which included 2067 adults, was performed in a health care center and comprised the same questionnaire and venom skin tests in subjects reporting a history of SRs. The third survey was a national poll performed through a home-based national computer network. The percentage of SRs ranged from 0.66% in the second survey including skin tests to 3.3% in the poll survey. The higher prevalence figure in this latter survey may be related to a false-positive history. There was no urban-rural difference in prevalence of SR.

Prevalence of allergy to hymenoptera stings in different samples of the general population.

Background Venom immunotherapy (VIT) induces immune tolerance to hymenoptera venom antigens in allergic patients and is therefore a helpful model for studying modulation of allergic immune response. The objectives were to assess the early effects of ultra-rush VIT on T lymphocyte activation and regulatory profile induction, in all subjects combined and according to the four severity grades of the Mueller classification. Materials and methods Blood samples from 30 vespid-allergic patients were taken before and after the first day of treatment, and before day 15 and day 45 booster injections. IFN-gamma and IL-4 levels were assayed by ELISA, in whole-blood supernatants. IFN-gamma and IL-13-producing T cells, but also natural CD4+CD25+high regulatory T cells and acquired regulatory T cell proportions were assessed by flow cytometry. Results were analysed in the whole population and compared between patients with I-II or III-IV allergic reactions. Results During VIT, IFN-gamma increased in whole blood when IL-4 decreased. Among T cells, the percentage of CD3+IFN-gamma+ cells increased while IL-13-producing T cells decreased. Proportions of CD4+CD25+high cells and IL-10-producing T cells increased with VIT. In I-II subjects, IFN-gamma increased gradually, whereas it remained at low levels in III-IV patients. By contrast, IL-4 decrease was more pronounced in III-IV patients. Increase in CD4+CD25+high T cells occurred early in I-II patients but was delayed in III-IV patients. IL-10-producing T cells increased gradually in both groups but were in a lower proportion in III-IV patients. Conclusion A T helper type 2 (Th2)-to-Th1 switch occurs during ultra-rush VIT, in parallel with natural and acquired regulatory T cell increase. These events occur earlier and at a higher level in less severe subjects, suggesting that VIT tolerance induction is easier to achieve in these patients.

Joëlle Birnbaum

Papers

Hymenoptera ultra-rush venom immunotherapy (210 min): a safety study and risk factors.

Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1, Der p 2 and Der p 10: relevant markers for house dust mite allergy.

Prevalence of muscle relaxant sensitivity in a general population: implications for a preoperative screening.

Prevalence of allergy to hymenoptera stings in different samples of the general population.

Ultra-rush venom immunotherapy induces differential T cell activation and regulatory patterns according to the severity of allergy.