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Abstract

Polymorphism in the regulatory region of MCP-1 is associated with asthmaChemokines are involved in the physiology and pathophysiology of acute and chronic inflammatory processes, by attracting and stimulating specific subsets of leukocytes. Chemokines have been identified in human asthma and related to the severity of asthmatic inflammation and reactive airway responses. Recently, polymorphisms in the MCP-1 distal gene regulatory region and in the RANTES promoter region have been found to increase the expression of these chemokines in response to inflammatory stimuli. Szalai et al (p 375) investigated whether the presence of these polymorphisms was associated with asthma or atopy and whether these alleles influenced the severity of asthma in affected individuals. In a cohort of Hungarian children (n = 614), there were associations between carrying G at –2518 of the MCP-1 gene regulatory region and the presence of asthma and between asthma severity and homozygosity for the G allele. No association was found between polymorphisms within the promoter region of RANTES and asthma. In asthmatic children, the MCP-1 –2518G allele was also associated with an increased eosinophil level. Development of therapeutic drugs for asthma specifically targeted against MCP-1 and/or its receptor, CCR2, might be a useful therapeutic strategy.Allergic inflammation enhances bacterial sinusitis in miceEthnic differences in asthma and associated phenotypesIn the Collaborative Study on the Genetics of Asthma (CSGA), a multicenter study supported by the National Heart, Lung, and Blood Institute, 2584 subjects from 314 families were characterized for asthma and allergy phenotypes. Lester et al (p 357) observed clinical heterogeneity in asthma and allergic characteristics between ethnic groups (African American, white, and Hispanic family members). The African American sibling pairs with asthma had a significantly lower baseline FEV1 percent predicted (P = .0001) and a higher rate of skin test reactivity to cockroach allergen (P = .0001). The Hispanic sibling pairs had significantly more skin reactivity overall (P = .001) and the white sibling pairs had significantly lower total serum IgE (P < .05) in comparison with the other groups. Although there was evidence of familial aggregation of asthma in these families, there were significantly more relatives with asthma among the African American families than among the white and Hispanic families (P = .001). Although variation in environmental exposures should be considered, clinical heterogeneity could be due to different genetic susceptibilities between the ethnic groups, such as suggested by published genome-wide linkage results from this study.Russian roulette at the local food marketPatients with anaphylactic sensitivity to foods are aware of the danger of hidden ingredients, such as peanut butter in chili con carne and ground-up nuts in cookies. They learn to inquire regarding ingredients and to read labels. However, are such precautions sufficient to protect them against exposure to these foods? Not always, according to a report by Altschul and colleagues in this month’s issue of the Journal (p 468). They tabulated the unsolicited reports received by the Food Allergy and Anaphylaxis Network. Over a period of 2 years, the Network received 206 reports of well-documented problems with commercial food preparations. These included cross-contamination by unlabeled allergens in 28% of cases, visible ingredient(s) not disclosed on the label in 26% of cases, and a new allergen disclosed on the label in 22% of cases. The authors conclude, “Implementation of allergen prevention plans is needed for industry to reduce the introduction of unintended allergens and to ensure accurate labeling.”Role of IL-17 in airway inflammation and remodelingFig. 2IL-17 mRNA expression from blood eosinophils in an asthmatic patient.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Risk factors for asthma in West African childrenIn this issue of the Journal, Addo-Yobo and colleagues (p 363) report on the risk factors for asthma in children 9 through 16 years of age living in Ghana in West Africa. Concentrations of house dust mite group 1 allergens were found to be very high. Levels greater than 2 μg/gram of dust were found in 79% of homes and levels greater than 10 μg/gram of dust in 59%. The levels of house dust mite allergens were approximately twice as high in the homes of the children with asthma than in the homes of control children. Skin test reactivity to mite allergen carried an odds risk of 10.4 for asthma in these children. Other significant risk factors, by multivariate analysis, were inner city residence (OR 4.8), sensitization to cockroach (OR 4.9), and being an elder child in the family (1st-4th in sibling order carried an OR of 6.3). Although 21% of the families maintained livestock in their compound, this had neither a positive nor a negative influence on occurrence of asthma. Cat and dog ownership also was without effect, perhaps because such pets were mainly kept outdoors, where they serve utilitarian purposes such as keeping watch and catching rats. In addition, soft furnishings and carpets, which might serve as reservoirs for animal dander, were uncommon. Thus the data generally support the importance of allergy in asthma in these African children, but the evidence seen in Europe for the “hygiene hypothesis” is not quite as strongly supported. Polymorphism in the regulatory region of MCP-1 is associated with asthmaChemokines are involved in the physiology and pathophysiology of acute and chronic inflammatory processes, by attracting and stimulating specific subsets of leukocytes. Chemokines have been identified in human asthma and related to the severity of asthmatic inflammation and reactive airway responses. Recently, polymorphisms in the MCP-1 distal gene regulatory region and in the RANTES promoter region have been found to increase the expression of these chemokines in response to inflammatory stimuli. Szalai et al (p 375) investigated whether the presence of these polymorphisms was associated with asthma or atopy and whether these alleles influenced the severity of asthma in affected individuals. In a cohort of Hungarian children (n = 614), there were associations between carrying G at –2518 of the MCP-1 gene regulatory region and the presence of asthma and between asthma severity and homozygosity for the G allele. No association was found between polymorphisms within the promoter region of RANTES and asthma. In asthmatic children, the MCP-1 –2518G allele was also associated with an increased eosinophil level. Development of therapeutic drugs for asthma specifically targeted against MCP-1 and/or its receptor, CCR2, might be a useful therapeutic strategy. Chemokines are involved in the physiology and pathophysiology of acute and chronic inflammatory processes, by attracting and stimulating specific subsets of leukocytes. Chemokines have been identified in human asthma and related to the severity of asthmatic inflammation and reactive airway responses. Recently, polymorphisms in the MCP-1 distal gene regulatory region and in the RANTES promoter region have been found to increase the expression of these chemokines in response to inflammatory stimuli. Szalai et al (p 375) investigated whether the presence of these polymorphisms was associated with asthma or atopy and whether these alleles influenced the severity of asthma in affected individuals. In a cohort of Hungarian children (n = 614), there were associations between carrying G at –2518 of the MCP-1 gene regulatory region and the presence of asthma and between asthma severity and homozygosity for the G allele. No association was found between polymorphisms within the promoter region of RANTES and asthma. In asthmatic children, the MCP-1 –2518G allele was also associated with an increased eosinophil level. Development of therapeutic drugs for asthma specifically targeted against MCP-1 and/or its receptor, CCR2, might be a useful therapeutic strategy. Allergic inflammation enhances bacterial sinusitis in mice Ethnic differences in asthma and associated phenotypesIn the Collaborative Study on the Genetics of Asthma (CSGA), a multicenter study supported by the National Heart, Lung, and Blood Institute, 2584 subjects from 314 families were characterized for asthma and allergy phenotypes. Lester et al (p 357) observed clinical heterogeneity in asthma and allergic characteristics between ethnic groups (African American, white, and Hispanic family members). The African American sibling pairs with asthma had a significantly lower baseline FEV1 percent predicted (P = .0001) and a higher rate of skin test reactivity to cockroach allergen (P = .0001). The Hispanic sibling pairs had significantly more skin reactivity overall (P = .001) and the white sibling pairs had significantly lower total serum IgE (P < .05) in comparison with the other groups. Although there was evidence of familial aggregation of asthma in these families, there were significantly more relatives with asthma among the African American families than among the white and Hispanic families (P = .001). Although variation in environmental exposures should be considered, clinical heterogeneity could be due to different genetic susceptibilities between the ethnic groups, such as suggested by published genome-wide linkage results from this study. In the Collaborative Study on the Genetics of Asthma (CSGA), a multicenter study supported by the National Heart, Lung, and Blood Institute, 2584 subjects from 314 families were characterized for asthma and allergy phenotypes. Lester et al (p 357) observed clinical heterogeneity in asthma and allergic characteristics between ethnic groups (African American, white, and Hispanic family members). The African American sibling pairs with asthma had a significantly lower baseline FEV1 percent predicted (P = .0001) and a higher rate of skin test reactivity to cockroach allergen (P = .0001). The Hispanic sibling pairs had significantly more skin reactivity overall (P = .001) and the white sibling pairs had significantly lower total serum IgE (P < .05) in comparison with the other groups. Although there was evidence of familial aggregation of asthma in these families, there were significantly more relatives with asthma among the African American families than among the white and Hispanic families (P = .001). Although variation in environmental exposures should be considered, clinical heterogeneity could be due to different genetic susceptibilities between the ethnic groups, such as suggested by published genome-wide linkage results from this study. Russian roulette at the local food marketPatients with anaphylactic sensitivity to foods are aware of the danger of hidden ingredients, such as peanut butter in chili con carne and ground-up nuts in cookies. They learn to inquire regarding ingredients and to read labels. However, are such precautions sufficient to protect them against exposure to these foods? Not always, according to a report by Altschul and colleagues in this month’s issue of the Journal (p 468). They tabulated the unsolicited reports received by the Food Allergy and Anaphylaxis Network. Over a period of 2 years, the Network received 206 reports of well-documented problems with commercial food preparations. These included cross-contamination by unlabeled allergens in 28% of cases, visible ingredient(s) not disclosed on the label in 26% of cases, and a new allergen disclosed on the label in 22% of cases. The authors conclude, “Implementation of allergen prevention plans is needed for industry to reduce the introduction of unintended allergens and to ensure accurate labeling.” Patients with anaphylactic sensitivity to foods are aware of the danger of hidden ingredients, such as peanut butter in chili con carne and ground-up nuts in cookies. They learn to inquire regarding ingredients and to read labels. However, are such precautions sufficient to protect them against exposure to these foods? Not always, according to a report by Altschul and colleagues in this month’s issue of the Journal (p 468). They tabulated the unsolicited reports received by the Food Allergy and Anaphylaxis Network. Over a period of 2 years, the Network received 206 reports of well-documented problems with commercial food preparations. These included cross-contamination by unlabeled allergens in 28% of cases, visible ingredient(s) not disclosed on the label in 26% of cases, and a new allergen disclosed on the label in 22% of cases. The authors conclude, “Implementation of allergen prevention plans is needed for industry to reduce the introduction of unintended allergens and to ensure accurate labeling.” Role of IL-17 in airway inflammation and remodeling Risk factors for asthma in West African childrenIn this issue of the Journal, Addo-Yobo and colleagues (p 363) report on the risk factors for asthma in children 9 through 16 years of age living in Ghana in West Africa. Concentrations of house dust mite group 1 allergens were found to be very high. Levels greater than 2 μg/gram of dust were found in 79% of homes and levels greater than 10 μg/gram of dust in 59%. The levels of house dust mite allergens were approximately twice as high in the homes of the children with asthma than in the homes of control children. Skin test reactivity to mite allergen carried an odds risk of 10.4 for asthma in these children. Other significant risk factors, by multivariate analysis, were inner city residence (OR 4.8), sensitization to cockroach (OR 4.9), and being an elder child in the family (1st-4th in sibling order carried an OR of 6.3). Although 21% of the families maintained livestock in their compound, this had neither a positive nor a negative influence on occurrence of asthma. Cat and dog ownership also was without effect, perhaps because such pets were mainly kept outdoors, where they serve utilitarian purposes such as keeping watch and catching rats. In addition, soft furnishings and carpets, which might serve as reservoirs for animal dander, were uncommon. Thus the data generally support the importance of allergy in asthma in these African children, but the evidence seen in Europe for the “hygiene hypothesis” is not quite as strongly supported. In this issue of the Journal, Addo-Yobo and colleagues (p 363) report on the risk factors for asthma in children 9 through 16 years of age living in Ghana in West Africa. Concentrations of house dust mite group 1 allergens were found to be very high. Levels greater than 2 μg/gram of dust were found in 79% of homes and levels greater than 10 μg/gram of dust in 59%. The levels of house dust mite allergens were approximately twice as high in the homes of the children with asthma than in the homes of control children. Skin test reactivity to mite allergen carried an odds risk of 10.4 for asthma in these children. Other significant risk factors, by multivariate analysis, were inner city residence (OR 4.8), sensitization to cockroach (OR 4.9), and being an elder child in the family (1st-4th in sibling order carried an OR of 6.3). Although 21% of the families maintained livestock in their compound, this had neither a positive nor a negative influence on occurrence of asthma. Cat and dog ownership also was without effect, perhaps because such pets were mainly kept outdoors, where they serve utilitarian purposes such as keeping watch and catching rats. In addition, soft furnishings and carpets, which might serve as reservoirs for animal dander, were uncommon. Thus the data generally support the importance of allergy in asthma in these African children, but the evidence seen in Europe for the “hygiene hypothesis” is not quite as strongly supported. Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severityJournal of Allergy and Clinical ImmunologyVol. 108Issue 3PreviewBackground: Chemokines play an important role in the pathophysiology of asthma and allergy. Recently, polymorphisms in the gene regulatory region of monocyte chemoattractant protein 1 (MCP-1) and in the promoter region of RANTES have been found; these polymorphisms increase the expression of the chemokines. Objective: We investigated whether the presence of the polymorphisms was associated with atopy or asthma and whether these alleles influenced the severity of asthma in affected individuals. Methods: Three groups of subjects—160 children with asthma (disease severity being classified according to the Global Initiative for Asthma guidelines, modified for children), 151 children with nonasthmatic but allergic phenotype, and 303 children without allergic or asthmatic disorders—were screened with a PCR-based assay for genotyping. Full-Text PDF Allergic inflammation enhances bacterial sinusitis in miceJournal of Allergy and Clinical ImmunologyVol. 108Issue 3PreviewBackground: Although it is not proven, one factor considered important in the development of sinusitis is allergic rhinitis. Objective: The purpose of this study was to determine whether ongoing allergic rhinitis enhances the infection and inflammation associated with Streptococcus pneumoniae acute sinus infection. Methods: BALB/c mice were sensitized to ovalbumin by intraperitoneal injection. After infection of the sinuses by S pneumoniae , either with or without concomitant administration of ovalbumin to induce allergic inflammation, mice were killed at various times and their heads were prepared for histologic evaluation of the sinuses. Full-Text PDF Ethnic differences in asthma and associated phenotypes: Collaborative Study on the Genetics of AsthmaJournal of Allergy and Clinical ImmunologyVol. 108Issue 3PreviewBackground: In the Collaborative Study on the Genetics of Asthma, 314 families with 2584 subjects were characterized for asthma and allergy. Objective: The purpose of this investigation was to examine clinical heterogeneity observed in asthma and allergic characteristics among 3 ethnic groups (African American, white, and Hispanic family members). Methods: Pulmonary function parameters and asthmaassociated phenotypes were compared among the ethnic groups. Results: In comparison with the other groups, African American sibling pairs had a significantly lower baseline FEV1 percent of predicted (P = .0001) and a higher rate of skin test reactivity to cockroach allergen (P = .0001); Hispanic sibling pairs had significantly more skin reactivity overall (P = .001); and white sibling pairs had significantly lower total serum IgE (P < .05). Full-Text PDF IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokinesJournal of Allergy and Clinical ImmunologyVol. 108Issue 3PreviewBackground: IL-17 is a cytokine that has been reported to be produced by T lymphocytes. In vitro, IL-17 activates fibro-blasts and macrophages for the secretion of GM-CSF, TNF-α, IL-1β, and IL-6. A number of these cytokines are involved in the airway remodeling that is observed within the lungs of asthmatic individuals. Objective: In this study, we investigated the expression of IL-17 in sputum and bronchoalveolar lavage specimens obtained from asthmatic subjects and from nonasthmatic control subjects. Full-Text PDF Risk factors for asthma in urban GhanaJournal of Allergy and Clinical ImmunologyVol. 108Issue 3PreviewBackground: Asthma is increasing in prevalence and severity in Africa. Previous studies have suggested that the prevalence of atopy in West Africa was low. Objective: We sought to investigate the risk factors for asthma in Ghanaian school children. Methods: Fifty children (age range, 9-16 years) with a physician diagnosis of asthma and asthma symptoms within the previous 12 months and 50 age- and sex-matched healthy control subjects were randomly selected and evaluated by means of questionnaire, skin testing, total and specific IgE measurements, and allergen level measurements from bed dust samples (mite, cat, dog, and cockroach). Full-Text PDF