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Abstract Bronchial asthma is a common lung disease encountered in clinical practice of medicine. Mould induced asthma is considered a common type of allergic asthma due to exposure to fungal aeroallergen with type 1 hypersensitivity. After contact with a specific allergen, mast cell degranulates and induces the early phase asthma consisting of smooth muscle contraction and increased vascular permeability, followed by late phase reaction, characterised by inflammatory cellular infilterates in . the bronchial wall. These cells included mast cells, basophils, eosinophils, neutrophils, platelets, lymphocytes, macrophages and epithelial cells, all are involved in the pathogenesis of the inflammation in asthma. Late asthmatic reaction with subsequent airway inflammation is associated with increase in airway responsiveness. Eosinophils and neutrophils have been found in increased numbers in bronchoalveolar fluid. ,- The mechanism behind the enhancement of eosinophil and neutrophil activation in asthma is not known. ” SUMMARY AN.’ CIJNCWSION 132 Changes in their function and activity including aggregation, degranulation, adherence and enhanced expression of surface receptor in particular FC and complement receptors. These various properties are all potentially important in the asthmatic response for the recruitment and activation of inflammatory cells. In our work, we aimed to study some of regulatory mechanisms modulating the asthmatic process mediated by eosniophils and neutrophils via their FCy and complement receptor (CRl) expression character, and to assess their migratory response to histamine, which is one of main mediators released during early phase of asthma (i.e. histamine chemotaxis). We also extended our work to evaluate serum or plasma factors influence on eosinophil and neutrophil functions through FC and complement receptor expression and also upon their chemotactic activities toward histamine in atopic asthmatic subjects sensitive to ,~ moulds. In a period of 8 months, from August 1992 to March 1993 (out of pollen season), our study was performed and included: 1] Atopic patients with mould induced asthma selected initially by ;;. skin pri,ck test and high levels of total serum IgE ~ 100 IU/mL . as group (A). -’ -- -’ -------”-”.---- -”---’.,-- -- ._-----.----~ .._._~----- ._---------_ ...- ------ ---”’---”---’--’--- SUMMARY AND>CONCWSION 233 2] Contr~l _,~ubjects, ten apparently healthy volunteers with no respiratory tract infection, allergy, or other atopic manifestations. They had negative skin prick result and total serum IgE was below 100 IU/mL and considered group B. Both groups of subjects after questionnaire approach and good history taking, were subjected to : 1- Thorough clinical examination. 2- Radiological examinaions of head air sinuses and chest. 3- Some pulmonary (unction tests (FEV}, FVC) and ECG trace. 4- Laboratory investigations which included: a. Stool and urine analysis : three specimens were studied for parasite’S ova identification particularly intestinal and urinary bilharsiasis, and to detect renal troubles. b. Sputum examination and culture for fungi. 5- Peripheral blood studies: a. Measurement of total serum IgE by ELISA technique. b. Total white blood cell, neutrophil, eosinophil cell count. c. Immunological studies: i. Estimation of Fey receptors born on circulating eosinophils and neutrophils. SUMMARY AND CONCLUSION 234 ii. Estimation of complement receptors (CRl) bom on circulating eosinophils and neutrophils by rosette technique (Bianco technique). iii. Assessment of chemotactic properties of eosinophils and neutrophils to histamine (histamine chemotaxis) through agarsoe gel. iv. Evaluation of serum factors on modulation of FCy and complement CRI receptor expression and histamine chemotaxis in vitro. - Results were expressed as mean ± standard deviation, and the student t-test.was used for analysis. Our observations andjindings were summarized asfollows : Among 163 patients with atopic asthma, thirty asthmatics sensitive only to mould extracts were selected by skin prick method, and participated in our study. All mould sensitive asthmatics met the criteria of ~ 15% airway reversibility with FEVl% ranged from 65% to 75% of the predicted value i.e. with mild and moderate asthma. Their atopic status was further confirmed by high levels of total serum IgE antibodies, they were referred as group A. Patients III group A WHefurther subclassified into: --------------------------’ => SUMMARY AND CONCLUSION 235 1) According to phases of skin prick reactivity subgroup AI, these patients with isolated early skin response and included 13 patients, and subgroup Az, who had early as well as late skin response (dual reaction) including 17 patients. 2) According to pattern of mould allergy by skin prick method. Patients-were subdivided into subgroup A3, those asthmatic patients with single mould allergy (19 patients) and subgroup A4 patients with skin allergy to multiple moulds and constituted (11 patients) . • Mould sensitive asthmatics in group A in our study represented -t 18.4% of all atopic asthmatics in Benha area (Egypt). Group A included 16 males and 14 females their ages ranged from 12 to 45 years in comaprison to control group which included ten apparently healthy individuals, they had no respiratory tract infection or allergy other atopic manifestations, 6 males and 4 females were included, with ages ranged from 17 to 38 years and were referred as group B. • 70% of patients in group A were living in rural areas, and 30% were living in urban area. Farmers and house wives were the main subjects having mould asthma. ----,- ’-- --~- --------------- ,. SUMMARY AND CONCWSION 236 • Aspergillus species either alone or in combination with Cladosporium and Alternaria formed the main moulds inducing asthma, where Fusarium, Candida and Rhizopus species constituted the least kinds of moulds causing asthma in both sexes. • Allergic rhinitis and skin eczema were the common atopic features associated with asthma in 23% and 20% of subjects in group A while allergic conjunctivitis was absent in both sexes. • 50% of patients in group A had no accompanying atopic manifestations. The total serum IgE antibodies was significantly higher in asthmatics in relation to IgE levels in control subjects. Patients with dual skin reactivity (subgroup A2) had higher levels of total IgE in comparison to asthmatics with isolated skin response (AI). Total serum IgE levels were not significant among asthmatics in groups A3 and A<I’ • Eosinophilia was a predominant feature in all asthmatics of group A. with comparison to subjects in group B, and more observed in patients of subgroup A2 of dual skin response than patients in subgroup A] with single skin response. Eosinophilia had no much difference among patients in subgroups A3 and A.4. ,v SUMMARY ANf)”CONCWSION 237 Immunological Findings: A) Fey receptor expression: 1] Eosinophils : isolated from peripheral blood of mould induced asthma patients (group A) showed non significant expression of FCy receptors in comparison to eosinophils isolated from control group in vitro. But there was an enhancement of FCy receptor ” ”:Z expression on eosinophils in subgroup A2 than eosinophils in subgroup Ar- While FCy receptor expression on eosinophils was not significant among patients in subgroups A3 and A4. 2] Neutrophils : in asthmatic subjects showed non significant receptor expression of FCy in relation to neutrophils in group B. While enhancement of FCy receptor expression was observed in patients of dual skin response A2 and of multiple mould allergy in subgroupAa. 3] Serum factors influence on Fey receptor: Seraof asthmatics in group A had a significant suppressive effect on expression of FCy receptors on eosinophils and neutrophils, but actual suppression was not demonstrated due to priming effect. . There was non significant FCy receptor expression on eosinophils and neutrophils in subgroup Al and A2. SUMMARY AND CONCWSION 238 B) Complement receptor (CRI) expression: 1] We had found an enhancement of complement receptors CRI expression on circulating eosinophils and neutrophils in group A with co.nparison to same cells in group B. 2] Enhancement was also present on both cell types in patients of group 1\4. While CRI expression had no much difference in both cell types in subgroups A, and A2. 3] As regard, serum effect, there was a significant enhancement induced by patient sera on control eosinophils and neutrophils. While serum factors did not show any difference in complement receptor expression on both cell types of group A1 and A2· ,. C) Histamine Chemotaxis: 1] As regard eosinophil and neutrophil: Chemoattraction toward histamine, we had found that these cells in our asthmatic subjects showed positive chemotaxis toward histamine more than cells in subjects of group B. SUMMARY AND CONCLUSION 239 2] After incubation with patient and healthy sera we concluded that patient sera had made control eosinophil and neutrophil more responsive to histamine chemotaxis, while healthy sera inhibited control eosinophil and neutrophil histamine chemotaxis. Eosinophils and neutrophils in patients of dual skin response (Az) showed more chemoattraction toward histamine than cells in group ~AI, in patients of group A4 than cells in patients of group. |