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.
Bone marrow cells of various animal species and humans produce a group of bioregulatory peptides called myelopeptides (MPs). MPs have been isolated and purified, and their physico-chemical properties have been investigated. MPs have a wide spectrum of functional activities: immunoregulatory, differentiating, and opiate-like. A new immunocorrective drug, Myelopidum, which is used effectively in clinical practice for treating diseases accompanied by immunodeficiency, has been created on the basis of MPs. Administration of Myelopidum after surgery prevents 50% to 70% of postsurgical complications, particularly postsurgery pneumonia, and also normalizes the number and balance of T-helper cells, T-suppressor cells, and B-lymphocytes in patients with chronic pulmonary diseases, resulting in a beneficial clinical effect, including a significant prolongation of remission periods. Myelopidum is also used in veterinary medicine for prophylaxis and treatment of pneumonia and enteritis in newborn and young animals. The primary structure of several myelopeptides is established. The functional activities of two, MP-1 (Phe-Leu-Gly-Phe-Pro-Thr) and MP-2 (Leu-Val-Val-Tyr-Pro-Trp), are being investigated.
The regulation of breathing is dependent on the complex interaction of three components of the respiratory system: 1) the control centers, 2) the sensors, and 3) the effector organs. The control centers reside in the brainstem and are responsible for the automaticity of breathing. Input into these respiratory centers can be initiated from higher brain centers in order to produce voluntary breathing efforts. Afferent neural signals also come to the central control system from the respiratory sensors, which are divided into two categories: chemoreceptors and sensory receptors. The chemoreceptors respond to changes in the blood oxygen, carbon dioxide, and hydrogen ion concentration by sending impulses to the control center to alter the ventilatory pattern by affecting the effector organs--the respiratory muscles. The sensory receptors are located in the upper and lower airways, the lung, and the muscles of respiration. They also can have a marked effect on the respiratory pattern. It is believed that stimulation of these receptors is important in the initiation of hyperventilation and cough in lung diseases such as asthma. There is also recent evidence that respiratory chemoreceptor responsiveness is abnormal in patients with asthma who have a history of near-fatal attacks.
A 41-year-old woman with known food allergy to avocado was treated for anaphylaxis after eating a meal containing avocado. This prompted a study to determine the prevalence of avocado induced symptoms and skin reactivity in a group of atopic patients. One hundred consecutive atopic patients with allergic rhinitis undergoing skin testing before initiation of immunotherapy were also prick skin tested to avocado. Patients with symptoms upon avocado ingestion were also assessed for specific serum IgE antibodies to avocado. Of the 100 atopic patients not selected for avocado sensitivity, 21 had positive prick skin tests to avocado. Eight of the 21 avocado skin test positive patients reported that symptoms repeatedly followed the ingestion of avocado; two reported systemic reactions, but six noted oral symptoms only. Serum IgE antibodies to avocado were elevated in seven of the eight patients reporting symptoms after eating avocado. Seven of the eight patients also reported oral symptoms following cantaloupe ingestion. Four reported similar symptoms upon eating banana. Avocado-induced symptoms occurred in 8% of 100 consecutive atopic allergic rhinitis patients unselected for avocado reactivity. Oral, and less frequently systemic, allergy symptoms appear to be more common among the atopic population than previously appreciated.
Studies on the immediate and long-term effects of radiation on the B-system immunity of children who were affected by radiation after the Chernobyl disaster (from 1986-1992) are summarized in this paper. Complete clinical and immunological examination of more than 6000 children have been carried out. The dynamics of the immune system, with ongoing reactions of cell proliferation and differentiation, gene amplification, transcription, translation, biosynthesis and switching production of isotypes and subclasses of immunoglobulins, as well as specific and nonspecific (natural) antibodies, make it highly susceptible to the action of radiation in addition to other ecological factors. B-system of immunity (B-cel level, concentration of immunoglobulins-M, G, A, E; subclasses of IgG (IgG1-IgG4) in the serum and saliva, and the level of nonspecific heterophilic autoantibodies (RF, antithyroglobulin) were investigated in children of differing ages and sex living in the territories of the Republic of Belarus contaminated with radionuclides. Research showed decreased levels of B-cell and IgM and IgG isotopes 40-50 days after the disaster and increased levels of IgA immunoglobulins at that time. Long-term effects of low doses of radiation showed increased concentrations of IgM and IgG, correlating changes in the B-system of immunity with the level of 137Cs contamination in the territory of residence and also with the amount of 137Cs found in the children.
Serum tryptase (Tryp) and eosinophil cationic protein (ECP) and urine N-methylhistamine (N-MH) were quantitated in a group of 13 subjects who had experienced immediate allergic reactions to different drugs. Results indicated that both Tryp and N-MH were involved and the levels were related to the severity of the reaction. Results of serum ECP levels failed to provide relevant information concerning the participation of eosinophils in immediate reactions to drugs.
Asthma is the most common chronic respiratory disease of children in developed countries. It affects 10–30% of all school-age children, particularly 13–14-year-old children. This chapter focuses on childhood asthma and its diagnosis, treatment approaches, and management in detail. The quality of life of children suffering from asthma is seriously disturbed unless adequate treatment is provided. Treatment of asthma involves making the correct diagnosis, evaluating its severity, and prescribing appropriate treatment, taking into account the ability of the child and the family to comply with the management plan. The ultimate goal is to reduce the amount of disturbance caused to the everyday life of the child and the family to an acceptable level. The cost of treating children with asthma places considerable burden on health resources, especially in developed countries because of the cost of medications and hospitalizations. About two-thirds of children with asthma can grow out of their disease completely, provided there is early introduction of effective treatment that improves the prognosis.
New forms of allergen immunotherapy are proposed employing modified allergens that induce T-cell responses without associated increased IgE-related responses. Synthetic polyelectrolytes attached to an analyte amy modulate T- and B-cell function, producing effective desensitization and altering immunoglobulin production dependent on the physico-chemical nature of the carrier molecule.
Several conjugates of model allergen ovalbumin (OA) and the copolymer of N-vinyl pyrrolidone and maleic anhydride (VMA) modified with epsilon-aminocaproic acid (Acp) were prepared in different OA/Acp-VMA ratios. All conjugates were separated by ultrafiltration and analyzed by HPLC. Their compositions were determined by amino acid analysis and UV spectrometry. To detect immunogenicity, all conjugates were injected intraperitoneally into (CBAxC57BL/6)F1 mice three times in 3-week intervals in OA doses equivalent to 0.5, 10, and 100 micrograms/mouse. Only the conjugate containing 20%OA (OA(20%)-Acp-VMA) did not induce significant quantities of anti-OA IgE, but did induce anti-OA IgG antibodies in dose-dependent manner comparable to that of unmodified OA. Mixtures of OA and Acp-VMA or OA modified only with VMA without Acp activation with Acp induced dose-dependent anti-OA IgE and IgG antibody formation comparable to that of OA. Using passive cutaneous anaphylaxis, RAST inhibition and leukocyte histamine release, a significant reduction of allergenicity was noted using OA(20%)-Acp-VMA. This conjugate stimulated activation of the OA-specific T-cell hybrid 3DO-548 comparable to that of unconjugated OA. During experimental allergen-specific hyposensitization with OA(20%)-Acp-VMA, suppression of anti-OA IgE response and elevation of anti-OA IgG responses were noted when compared with unmodified OA. Selective blockade of B-cell epitopes of allergen may occur using the carrier Acp-VMA to reduce allergenicity while not affecting T-cell epitopes, thereby preserving immunogenicity. This approach of chemical modification of allergen suggests new opportunities in the creation of preparations for allergen-specific immunotherapy.
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.
