Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy.

BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.

Quality of life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with levocetirizine or desloratadine.

BACKGROUND: Persistent allergic rhinitis often impairs quality of life. OBJECTIVE: We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and levocetirizine alone or in combination improved quality of life. METHODS: A 32-week randomized, double-blind, placebo-controlled, crossover study was performed in 2 arms: 20 patients received montelukast 10 mg/d and/or desloratadine 5 mg/d or placebo; 20 patients received montelukast 10 mg/d and/or levocetirizine 5 mg/d or placebo. The treatment periods were separated by 2-week washout periods. Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Questionnaire. Sleep problems were also assessed. RESULTS: In the desloratadine plus montelukast arm, the mean (SEM) quality of life score before treatment was 3.1 (0.41). After placebo, this score was 2.16 (0.43), after desloratadine it was 1.79 (0.38), after montelukast it was 1.48 (0.37), and after montelukast plus desloratadine it was 1.59 (0.37). In the montelukast plus levocetirizine arm, the mean quality of life score before treatment was 2.58 (0.49). After placebo it was 1.78 (0.46), after levocetirizine it was 1.38 (0.42), after montelukast it was 1.36 (0.37), and after montelukast plus levocetirizine it was 1.26 (0.39). CONCLUSIONS: Placebo, montelukast, desloratadine and levocetirizine significantly improved quality of life. Combining montelukast with either levocetirizine or desloratadine gave additional benefits in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.

[Histamine releasing and immunomodulating activity of dental restorative materials].

Histamine releasing and immunomodulating activity of the following dental restorative materials (DRM) - Prizmafil, Filtek Z250, XRV Herculite Prodigy, Glasiosite, Te-Econol, Valux Plus, Polofil Supra were studied. It was shown that DRM under study as a rule did not possess the ability to release histamine (H) from human blood basophile (BB) excluding Filtek Z250 which release H from BB in patients with allergy and sound donors. The studied DRM implanted under mouse skin were able to modulate immune response to the allergen, at that some of them increased antibodies of IgE-class forming and other suppressed immune response caused by IgG-antibody forming. Received data have certain significance in the scheme of safety evaluation and individual assessment of DRM having acceptable biocompatibility for specific patient.

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN).

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 µm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician's considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal.

Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes.

OBJECTIVE: To evaluate the effect of salmeterol on asthma-specific quality of life in patients experiencing significant nocturnal symptoms. DESIGN: Randomized, double-blind, placebo-controlled, multicenter clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Nonsmokers > or = 12 years of age with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or = 15% decrease in peak expiratory flow (PEF) from baseline on nocturnal awakening at least once during screening. INTERVENTIONS: Salmeterol, 42 microg, or placebo twice daily. Patients were allowed to continue theophylline, inhaled corticosteroids, and "as-needed" albuterol. MEASUREMENTS AND RESULTS: Outcome measures included Asthma Quality of Life Questionnaire (AQLQ) global and individual domain scores, FEV1, PEF, nighttime awakenings, asthma symptoms, and supplemental albuterol use. Mean change from baseline for the global and domain AQLQ scores was significantly greater (p < or = 0.005) with salmeterol compared with placebo. At week 12, salmeterol significantly (p < 0.001 compared with placebo) increased mean change from baseline in FEV1, morning and evening PEF, percentage of symptom-free days, percentage of nights with no awakenings due to asthma, and the percentage of days and nights with no supplemental albuterol use. Significant improvements in PEF were observed after treatment with salmeterol regardless of concomitant treatment with theophylline (p < 0.05). CONCLUSIONS: These results provide evidence that validates the role of salmeterol in improving quality of life in patients with moderate persistent asthma who exhibited nocturnal asthma symptoms and supports the efficacy of salmeterol compared with that of placebo (ie, "as-needed" albuterol).

Second-generation antihistamines: the risk of ventricular arrhythmias.

Some second-generation antihistamines, notably terfenadine and astemizole, have been associated with prolongation of the QT interval and the development of torsades de pointes, a potentially fatal ventricular arrhythmia. This rare adverse event has been associated with greatly elevated blood levels of these agents, resulting from drug overdose, hepatic insufficiency (dysfunction), or interactions with other drugs that inhibit their metabolism. This paper reviews the data concerning the effects of selected second-generation antihistamines on cardiac conduction, particularly the QT interval, to evaluate whether ventricular arrhythmias are a class effect of these agents. Electrocardiographic studies indicate that terfenadine and astemizole, but not loratadine or cetirizine, prolong the QT interval in laboratory animals. In vitro studies demonstrate that terfenadine and astemizole block the cardiac K+ channels, leading to delayed ventricular repolarization and QT-interval prolongation; in contrast, neither loratadine nor its metabolite, desloratadine, significantly inhibits cardiac K+ channels at clinically achievable blood levels. Studies in human volunteers confirm the absence of electrocardiographic effects of azelastine, cetirizine, fexofenadine, and loratadine administered at several times the recommended dose or concomitantly with agents that inhibit their metabolism and elimination. In conclusion, the data indicate that the potential to cause ventricular arrhythmias is not a class effect of second-generation antihistamines and that loratadine, cetirizine, azelastine, and fexofenadine are not associated with torsades de pointes or other ventricular arrhythmias.

Randomized trial of zileuton in patients with moderate asthma: effect of reduced dosing frequency and amounts on pulmonary function and asthma symptoms. Zileuton Study Group.

This 6-month, randomized, multicenter study was designed to determine whether patients who had been treated with the leukotriene pathway inhibitor zileuton 600 mg four times daily (QID) for 2 months could be maintained at the same level of pulmonary function, symptom control, and beta-agonist use with less frequent dosing--first 600 or 800 mg three times daily (TID) and then twice daily (BID). A total of 278 patients with chronic asthma, ages 16 to 70, participated at 25 US centers. All had a 1-second forced expiratory volume (FEV1) of 35%-75%, reversible airway disease, and a nonsmoking history of 1 year. An 8-week open-label period (zileuton 600 mg QID) was followed by a 16-week double-blind period, in which patients who responded to the QID treatment were randomized to receive zileuton 600 or 800 mg TID for 8 weeks and then rerandomized to receive zileuton 600 or 800 mg BID for another 8 weeks. Primary outcomes were FEV1 and asthma symptom scores; secondary outcomes were peak expiratory flow rate, beta-agonist use, and asthma exacerbations requiring steroid rescue. Patients who showed improvements in lung function when treated with zileuton 600 mg QID demonstrated minimal decreases in FEV1 and comparable peak expiratory flow rates, symptom control, beta-agonist use, and systemic corticosteroid rescue when being treated with lower doses and/or less frequent doses of zileuton. Patients who demonstrate improved asthma control with zileuton 600 mg QID may be able to reduce their daily dosage and/or frequency while still maintaining the same level of symptom control.

Asthma: diagnosis and management of nocturnal symptoms.

An approach to asthma evaluation and treatment that seriously considers the strong nocturnal predilection for exacerbations of asthma is necessary for proper care of most asthmatics. Appreciation of the chronopharmacology of medications that may improve nocturnal asthma is essential. Controlled-release theophylline preparations, such as Uniphyl, which achieve peak blood levels 10-12 hours after dosage, should be administered immediately after the evening meal to give greatest efficacy between 3 and 6 AM when airflow reaches its nadir. Oral corticosteroids should be administered around 3 PM to achieve peak pulmonary antiinflammatory efficacy between 3 AM and 6 AM corticosteroid-induced decreases in inflammatory cell infiltration in lungs clearly being associated with improvement in lung function. Future developments of high-potency inhaled corticosteroid medications or sustained-action inhaled anticholinergic agents may add to the therapeutic armamentarium in the battle against asthma, the nocturnal affliction.

[Chemical modification of allergen leading to changes in its epitopic activity]. / Khimicheskaia modifikatsiia allergena, vedushchaia k izmeneniiu ego épitopnoi aktivnosti.

Modification of a model allergen ovalbumin (OA) with succinylation led to a decrease of its allergenicity measured by passive cutaneous anaphylaxis reaction, RAST inhibition assay and basophil histamine release. Modified OA stimulated OA-specific T-cell hybrid 3DO-548 to produce IL-2 at the same level as in case of non-modified OA. Modified OA did not induce anti-OA IgE, but did induce anti-OA IgG antibodies. This approach to chemical modification of allergen-selective blockade of B-cell epitopes while not affecting T-cell epitopes suggests new opportunities in creation of safe and effective allergovaccines.

IgE, allergic diseases, and omalizumab.

Immunoglobulin E (IgE) plays a central role in the development of allergic diseases. In sensitized individuals, IgE antibodies bind to receptors on mast cell and basophil surfaces, releasing preformed and newly generated mediators that initiate an immunologic cascade and inflammatory symptoms. Omalizumab (Xolair) is a humanized monoclonal antibody designed to bind specifically to IgE. It was approved by the United States Food and Drug Administration in 2003 for the treatment of patients with moderate-to-severe persistent asthma that is inadequately controlled with inhaled corticosteroids (ICS) and who have a positive skin test or in vitro reactivity to a perennial aeroallergen. In clinical trials in such patients, omalizumab reduced the incidence of asthma exacerbations, severe exacerbations, the use of rescue medication, and improved both symptoms and quality of life (QOL).

Differential expression of monocyte CD163 in single- and dual-asthmatic responders during allergen-induced bronchoconstriction.

BACKGROUND: Mononuclear phagocytes play an important role in modulating inflammatory reactions in response to antigen challenge. OBJECTIVE: To investigate the regulation of CD163, a marker of anti-inflammatory macrophages, during Dermatophagoides pteronyssinus (Dp)-induced bronchoconstriction. METHODS: Among 110 Dp-sensitive patients who underwent bronchial challenge with Dp, there were 51 dual responders (DR), 32 single responders (SR) and 27 non-responders (NR). Monocyte expression of CD14 and CD163 was evaluated by flow cytometry. Exhaled NO (eNO) concentration was determined on-line using a chemiluminescence analyser. In 21 DR, nine SR and 13 NR-soluble CD163 in plasma was measured by ELISA before, 1, 8 and 24 h after the challenge. RESULTS: In DR, the baseline expression of monocyte CD163 and eNO were significantly greater than in SR and NR. A pattern of (1) decreased monocyte CD163 expression, (2) unchanged sCD163 and (3) increased eNO in DR was contrasted by a pattern of (1) increased CD163 expression, (2) increased sCD163 and (3) unchanged eNO in SR. During allergen challenge, the changes in monocyte CD163 expression and sCD163 inversely correlated with the changes in eNO. CONCLUSION: Both pro-inflammatory and anti-inflammatory responses to allergen challenge are uniquely expressed among SR and DR.

Platelet activation in allergic asthma patients during allergen challenge with Dermatophagoides pteronyssinus.

BACKGROUND: Animal models of allergic asthma indicate that intravascular platelet activation is necessary for the development of allergen-induced chronic airway inflammation. OBJECTIVE: To evaluate whether the development of a late asthmatic response (LAR) in allergic asthma patients challenged with a relevant allergen is consequent to platelet activation. METHODS: Thirty-three house dust mite sensitive asthmatic patients were challenged intrabronchially with Dermatophagoides pteronyssinus (Dp) extract. Twelve non-atopic healthy subjects (HC) were used as controls. Platelet count and plasma levels of beta-thromboglobulin (beta-TG), platelet factor-4 (PF-4) and soluble P-selectin (sP-selectin) were assessed before the challenge (T(0)) and 30 min (T(EAR)), 6 h (T(LAR)) and 24 h (T(24)) after the challenge. RESULTS: Eleven patients responded to allergen challenge with an isolated early asthmatic response (single responders, SR). In 22 patients dual asthmatic response was demonstrated (dual responders, DR). At T(0) neither the platelet count nor the mean plasma level of beta-TG in DR or SR were different from HC, the mean plasma level of PF-4 in SR was significantly greater than in HC (P=0.01) or DR (P=0.001), the mean plasma level of sP-selectin was significantly greater in DR than in HC (0.0002) but not statistically different from SR (P=0.055). A significant decrease in the platelet count and increase in the plasma level of all the studied markers was seen at T(EAR), which was followed by a gradual return to the baseline values in the SR. Elevated plasma levels of platelet activation markers and decreased platelet count were seen in the DR even at T(24). Strong correlation was found between the increase in plasma concentration of beta-TG at T(EAR) and the maximum fall in forced expiratory volume in 1 s at T(LAR) (r=-0.57; P=0.0006). CONCLUSION: In allergic asthma patients development of prolonged airway inflammation after allergen challenge is associated with intravascular platelet activation.

Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine.

Nasal polyp tissue which contains mast cells and eosinophils is similar to the inflamed airway mucosa in cellular composition and mediator content. This investigation assessed the effect of desloratadine (DL), on activation of cells in nasal polyp tissue. Polyps were obtained from 22 patients with chronic rhinosinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA-tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and incubated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC4, eosinophil cationic protein (ECP) and tryptase concentrations in supernatants were measured by immunoassays. Desloratadine (1, 10 and 50 microM) inhibited calcium ionophore-induced LTC4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE-induced LTC4 release by a mean of 27%, 35% and 39% respectively. Calcium ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 microM of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47% and 66% for 1, 10 and 50 microM of DL. Desloratadine 10 microM and 50 microM inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA-sensitive patients when compared with ASA-tolerant patients released at baseline significantly more ECP (medians 120.0 microg/ml, range: 69.0-182.0 vs 63.4 microg/ml, range: 3.7-172.0; P <0.05), but similar amounts of tryptase and LTC4. This study demonstrated that DL inhibits activation of both eosinophils and mast cells derived from a site of airway mucosal inflammation.

Aspirin-triggered 15-HETE generation in peripheral blood leukocytes is a specific and sensitive Aspirin-Sensitive Patients Identification Test (ASPITest).

BACKGROUND: We have previously demonstrated that aspirin triggers specific generation of 15-hydroxyeicosateraenoic acid (15-HETE) from nasal polyp epithelial cells and peripheral blood leukocytes (PBL) from aspirin-sensitive (AS) but not aspirin-tolerant (AT) patients with asthma/rhinosinusitis. The goal of this study was to assess the diagnostic value of ASA-induced 15-HETE generation measurement to identify AS patients. METHODS: PBL were obtained from 43 AS patients with asthma and rhinosinusitis, 35 AT asthmatics and 17 healthy control (HC) subjects. PBL were incubated with 2-200 muM aspirin (ASA) and 15-HETE release was measured in cell supernatants with competitive ELISA. RESULTS: Unstimulated PBL from all three groups of patients generated similar amount of 15-HETE. Incubation with 200 microM ASA resulted in an increase in an 15-HETE generation (mean increase +421%) in AS-asthmatics but small and nonsignificant response in AT-asthmatics or control subjects. Receiver operating curve (ROC) analysis revealed that the sensitivity of the test for confirmation of ASA-sensitivity was 83% and the specificity 82%. Positive predictive value was 0.79 and negative predictive value was 0.86. Naproxen induced a significant increase in 15-HETE only in some AS-asthmatics, but not in AT-asthmatics. CONCLUSION: Our data demonstrate that ASA-induced 15-HETE generation by PBL is a specific and sensitive aspirin-sensitive patients identification test (ASPITest).

Dose-ranging comparative evaluation of cetirizine in patients with seasonal allergic rhinitis.

BACKGROUND: Cetirizine, an H1-receptor antagonist, has been studied for the relief of seasonal and perennial allergic rhinitis, one of the most common allergic disorders in the United States. Unlike newer antihistamines that can have interactions with other medications, including some macrolide antibiotics and some antifungal agents, cetirizine has not been associated with adverse events consequent to interaction with drugs that depend on hepatic enzymes for their metabolism. OBJECTIVE: The efficacy of cetirizine was compared with that of previous pharmacologic therapy in patients with allergic rhinitis. Patients were allowed to dose-titrate to achieve the optimal therapeutic response. METHOD: This was a dose-ranging, open-label, multicenter, 2-week clinical trial of 296 patients with allergic rhinitis. All patients were initially treated with 5 mg of cetirizine and allowed to dose-titrate up to 20 mg/d, depending on symptom severity. RESULTS: Symptom severity scores decreased sharply within the first 24 hours of cetirizine therapy and continued to improve. Symptoms showing the greatest immediate improvement were rhinorrhea, itching nose, sneezing, itching eyes, and watery eyes, with nasal congestion and postnasal drip improving more slowly. By study completion, 13.4% of patients remained on the initial cetirizine dose of 5 mg/d, 31.1% increased dosage to 10 mg/d, and 41.6% increased their dose to 15 or 20 mg/d. According to physician global evaluations, 82% of patients showed improvement on cetirizine, while 75% of patients indicated that cetirizine was better than or equal to previous single-agent therapy, including those who had previously used terfenadine (75%), astemizole (80%), or other antihistamines (73%), and by 58% on previous therapy with antihistamine-decongestant combination drugs. Side effects were minimal and no different from those observed in other studies of cetirizine. CONCLUSION: Dose titration of cetirizine may allow for greater efficacy and quality of life, especially for patients with refractory symptoms of allergic rhinitis in whom therapy with single-dose antihistamines has failed.

Management of inflammation in allergic asthma (IRINE symposium). Immunology Research Institute of New England.

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)

Mediator assays and modulation of inflammation in asthma: introduction.

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)

IRINE symposium; immunologic advances in the Commonwealth of Independent States(Part 1).

This symposium describes the advances in immunology that have occurred in the Commonwealth of Independent States. The worldwide difficulties of allergists and immunologists who face problems including increasing morbidity and mortality from HIV, immunoregulatory disorders, and asthma are also germane to our colleagues in Russia, Belarus, and Ukraine. The unique experiences of Dr. Petrov, who has investigated novel immunomodulators; Dr. Titov, who has studied synthetic immunogens; Dr. Babakhin, who has investigated the effects of modified allergens; and Dr. Sidorovitch, who has explored the pathogenesis and natural history of HIV infections occurring in Russia, offer interesting insights into the advances in immunology that have occurred in the Commonwealth of Independent States. Coping with the tragedies of radiation from Chernobyl and environmental pollution in Ukraine, Drs. Titov and Markov have investigated the effects of these unfortunate disruptions of the environment upon the occurrence of immunoregulatory disorders and asthma, respectively. Under the direction of Drs. Petrov and Khaitov, immunologist from the Commonwealth of Independent States, have conducted studies that are among the leading epidemiological immune investigations of our time to determine the effects of the Chernobyl radiation on the immune system.