News Beyond Our Pages
Authors: Marc E. Rothenberg, Harold S. Nelson
Journal: Journal of Allergy and Clinical Immunology (2008)

News…New class of leukotrienes identifiedIn anaphylaxis, more may be better: New pathway identifiedIn the January 14, 2008, New England Journal of Medicine, Vadas et al (N Engl J Med 2008;358:28-35) presented provocative results from a prospective and retrospective study of the role of platelet activating factor (PAF) acetylhydrolase in anaphylaxis. PAF is a potent inflammation mediator in anaphylaxis, secreted by mast cells and monocytes. It is inactivated by PAF acetylhydrolase. Vadas et al found that anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase and demonstrated that patients who experienced severe anaphylactic response to allergen challenge had lower than normal titers of this enzyme. They suggested that blockade of PAF receptors may be a new target for therapeutic intervention and, although their data are limited, PAF acetylhydrolase levels might be useful as a diagnostic tool to predict anaphylaxis severity risk. This article supports the findings of JACI Associate Editor Fred Finkelman, who has evidence that anaphylaxis can be mediated by macrophage-derived PAF (Finkelman et al. J Allergy Clin Immunol 115;3:449-57).We asked Scott Sicherer, MD, to comment on this article. Dr Sicherer notes, “We are constantly asked by patients ‘how severe is my food allergy?’ and since typical IgE tests do not correlate well with severity, we are often going on circumstantial risk factors data, such as presence of asthma, reaction history and amount triggering symptoms. This report may represent a strong beginning to better insight on severity assessment.”Anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Don't overtreat sinusitisNeither antibiotic nor topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Muscling-up smooth muscleView Large Image Figure ViewerDownload Hi-res image Download (PPT)Basophils: A missing linkTH2 immune responses to parasites and protein allergens are nearly identical, but the common mechanism leading to this response is still being described. Sokol et al (Nat Immunol 2007; Dec 21 [epub ahead of print]) reported the discovery of requisite basophil activation for induction of TH2 immune response to protein allergens. The authors found that basophils were a target for protease allergens and produced the necessary cytokines and chemokines to initiate TH2 response and differentiation. Sokol et al also reported that basophils were recruited to the draining lymph nodes as a first-order effect of protein allergen stimulation.We asked Donald MacGlashan, MD, to comment on this article. Dr McGlashan remarks, “This elegant and comprehensive study presents evidence that mouse basophils provide a set of signals to T cells that skews the T-cell response towards the TH2 phenotype… One of the surprising observations of these studies is that basophils can be found in correct locations in local lymph nodes to exert influence on the stimulated T cells. Unless the basophil is unique among the granulocytes, this result opens up the possibility that other granulocytes may mediate immune deviation in lymph nodes.” The full text of Dr MacGlashan's comments can be found in this article's Online Repository atwww.jacionline.org.Basophils provide a set of signals to T cells that skew the T-cell response toward the TH2 phenotype.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Wisconsin first state to screen for severe combined immunodeficiencyWisconsin babies are in the pole position when it comes to diagnostic/preventative screening. Dr Asriani Chiu, allergy/immunology faculty at the Medical College of Wisconsin, offered this report: “Through a collaboration between investigators at the Children's Hospital of Wisconsin, the Medical College of Wisconsin and the Wisconsin State Hygiene Laboratory, the state of Wisconsin has become the first state to screen all newborns for severe combined immunodeficiency, beginning January 1, 2008. The screening test, real-time PCR for T-cell receptor excision circles, is performed from DNA extracted from dried blood spots on newborn screening cards, which are obtained on all newborns. The Wisconsin group of Investigators previously performed RT-PCR for T-cell receptor excision circles on nearly 10,000 anonymized newborn screening cards before implementation of the test. Initial results on the newborn screening program will be presented at the Late Breaking Abstracts session at the upcoming American Academy of Allergy, Asthma & Immunology meeting in Philadelphia.”American Academy of Pediatrics publishes new atopy prevention guidelinesThe American Academy of Pediatrics Committee on Nutrition and Section on Allergy and Immunology published a new clinical report in Pediatrics (2008;121:183-91) that reviews issues of atopy prevention through diet. In contrast with the Committee on Nutrition guidelines published in 2000, which emphasized maternal avoidance of all nuts, eggs, milk, and fish during pregnancy and staged exposure to these foods for the child, the new report indicates there is no strong evidence for benefit of maternal exclusion diets in pregnancy or nursing (with the possible exception for atopic dermatitis regarding nursing) and there remains no convincing evidence of a significant effect regarding avoidance of specific allergens in the infant diet for various longer periods. The 2008 report supports previous recommendations on breast-feeding and introduction of solid foods. Importantly, the 2008 report indicates that the dietary advice could differ if an infant already had signs of atopic disease. Contributed by Scott H. Sicherer, MD.There remains no convincing evidence of a significant effect regarding avoidance of specific allergens in the infant diet.Translational and clinical horizonsAs part of our ongoing series highlighting ongoing and future preclinical and clinical trials related to allergy, asthma, and immunodeficiency, we asked Stanley J. Szefler, MD, from the National Institute of Allergy and Infectious Diseases (NIAID) Inner City Asthma Consortium to provide a status report on the Asthma Control Evaluation study, for which he served as lead investigator. The full text of Dr Szefler's comments can be found online at www.jacionline.org.Food allergy epidemic declared a mythAccording to an article published in Harper's Magazine (2008;316:64-5), the rising prevalence of food allergy is nothing more than mass parental hysteria and inadequate science! If you find your office packed with anxious parents holding “Everyone's Gone Nuts” by Meredith Broussard, direct them to a recent interview with Hugh Sampson, MD, on New York Public Radio where he stridently defends and skillfully clarifies the clinical science that was left out of the Harper's article. This interview is available at http://www.wnyc.org/shows/lopate/episodes/2008/01/31.The rising prevalence of food allergy is nothing more than mass parental hysteria and inadequate science.News items are written by Sherri Gabbert, PhD.Have a news item that you think other readers would be interested in? Send your ideas to the News Beyond Our Pages editors at [email protected] . Contributors will be acknowledged in these pages.Reviews…Concerns with use of long-acting β-agonists in patients with the Arg: Arg 16 β-agonist receptor genotype put to restIn 2 small 16-week studies, a reduced response to the long-acting β-agonist salmeterol was reported in subjects with asthma who had the Arg/Arg 16 genotype of the β-adrenergic receptor (BAR), compared with the response in those with the Gly/Gly 16 or Arg/Gly 16 BAR genotypes. Other studies, either with small numbers of subjects or of only 12 weeks duration, failed to confirm the report. Now, an analysis of results from 2 studies of 6 and 7 months duration, including data on 2630 subjects, 430 of whom expressed the Arg/Arg 16 BAR genotype, has been reported. In these studies, all subjects received an inhaled corticosteroid plus either formoterol or salmeterol. The principal outcome in both studies was severe asthma exacerbations, and there was no difference in this outcome by BAR genotype. Other assessments of asthma control including peak expiratory flow, FEV1, rescue inhaler use, asthma symptoms, and nighttime awakening did not differ among the 3 genotypes in either study. There was also no difference in response by haplotype. With negative data from this large number of subjects studied for 6 or 7 months, it is hoped that the issue of genetic variations at the 16th position of the β-adrenergic receptor and the response to long-acting β-agonists has finally been put to rest.(Bleecker et al. Lancet 2007;370:2118-25.)Anti–IL-5 again fails to improve patients with asthmaThere is strong support for a pivotal role of eosinophils in producing the pathophysiology of asthma. IL-5 is thought to play a major role in the accumulation of eosinophils in the airways of patients with asthma. However, preliminary studies with anti–IL-5 mAbs have failed to show any beneficial effect on allergen challenges, asthma symptoms, or pulmonary function in patients with asthma. This article reports the results of treatment for 3 months with the anti–IL-5 mAb mepolizumab in 362 patients with moderately severe asthma, still symptomatic on inhaled corticosteroids. There was prompt and sustained reduction in circulating and sputum eosinophils. However, there was no difference between treatment with placebo or low-dose or high-dose mepolizumab in pulmonary function, asthma symptoms, rescue inhaler use, or asthma quality of life. Compared with placebo and low-dose drug therapy, there was a nonsignificant reduction in asthma exacerbations with high-dose treatment (P = .065). The results, although discouraging, are not definitive. There was not a selection for patients with persisting eosinophilic inflammation in this study, nor was it powered to examine the effect on asthma exacerbations. Perhaps there will prove to be a role for anti–IL-5 therapy in selected patients with asthma.(Flood Page et al. Am J Respir Crit Care Med 2007;176:1062-71.)Ibuprofen reduces pulmonary function loss in children with cystic fibrosisHigh-dose ibuprofen was found, in a double-blind, randomized trial, to reduce the rate of decline in pulmonary function in patients with cystic fibrosis (CF). A review was undertaken to determine whether the use of ibuprofen in a less structured setting would also be effective. Data were obtained from the CF Foundation registry for the period of 1996 to 2002. Patients were included who had at least 2 consecutive years of ibuprofen use or nonuse, were 6 to 17 years of age, and had a baseline FEV1 >60% predicted. After adjusting for possible confounders, FEV1 declined less rapidly in those receiving ibuprofen. The average decline in 5 years was 7.43% for those treated compared with 9.87% in those not receiving ibuprofen. When corrected for the severity of disease, the reduction in FEV1 decline with ibuprofen was 29%. The data would appear to support the routine use of ibuprofen in children with mild to moderate CF until some better alternative anti-inflammatory agent becomes available.(Konstan et al. Am J Respir Crit Care Med 2007;176:1084-9.) News…New class of leukotrienes identifiedIn anaphylaxis, more may be better: New pathway identifiedIn the January 14, 2008, New England Journal of Medicine, Vadas et al (N Engl J Med 2008;358:28-35) presented provocative results from a prospective and retrospective study of the role of platelet activating factor (PAF) acetylhydrolase in anaphylaxis. PAF is a potent inflammation mediator in anaphylaxis, secreted by mast cells and monocytes. It is inactivated by PAF acetylhydrolase. Vadas et al found that anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase and demonstrated that patients who experienced severe anaphylactic response to allergen challenge had lower than normal titers of this enzyme. They suggested that blockade of PAF receptors may be a new target for therapeutic intervention and, although their data are limited, PAF acetylhydrolase levels might be useful as a diagnostic tool to predict anaphylaxis severity risk. This article supports the findings of JACI Associate Editor Fred Finkelman, who has evidence that anaphylaxis can be mediated by macrophage-derived PAF (Finkelman et al. J Allergy Clin Immunol 115;3:449-57).We asked Scott Sicherer, MD, to comment on this article. Dr Sicherer notes, “We are constantly asked by patients ‘how severe is my food allergy?’ and since typical IgE tests do not correlate well with severity, we are often going on circumstantial risk factors data, such as presence of asthma, reaction history and amount triggering symptoms. This report may represent a strong beginning to better insight on severity assessment.”Anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase.Don't overtreat sinusitisNeither antibiotic nor topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Muscling-up smooth muscleView Large Image Figure ViewerDownload Hi-res image Download (PPT)Basophils: A missing linkTH2 immune responses to parasites and protein allergens are nearly identical, but the common mechanism leading to this response is still being described. Sokol et al (Nat Immunol 2007; Dec 21 [epub ahead of print]) reported the discovery of requisite basophil activation for induction of TH2 immune response to protein allergens. The authors found that basophils were a target for protease allergens and produced the necessary cytokines and chemokines to initiate TH2 response and differentiation. Sokol et al also reported that basophils were recruited to the draining lymph nodes as a first-order effect of protein allergen stimulation.We asked Donald MacGlashan, MD, to comment on this article. Dr McGlashan remarks, “This elegant and comprehensive study presents evidence that mouse basophils provide a set of signals to T cells that skews the T-cell response towards the TH2 phenotype… One of the surprising observations of these studies is that basophils can be found in correct locations in local lymph nodes to exert influence on the stimulated T cells. Unless the basophil is unique among the granulocytes, this result opens up the possibility that other granulocytes may mediate immune deviation in lymph nodes.” The full text of Dr MacGlashan's comments can be found in this article's Online Repository atwww.jacionline.org.Basophils provide a set of signals to T cells that skew the T-cell response toward the TH2 phenotype.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Wisconsin first state to screen for severe combined immunodeficiencyWisconsin babies are in the pole position when it comes to diagnostic/preventative screening. Dr Asriani Chiu, allergy/immunology faculty at the Medical College of Wisconsin, offered this report: “Through a collaboration between investigators at the Children's Hospital of Wisconsin, the Medical College of Wisconsin and the Wisconsin State Hygiene Laboratory, the state of Wisconsin has become the first state to screen all newborns for severe combined immunodeficiency, beginning January 1, 2008. The screening test, real-time PCR for T-cell receptor excision circles, is performed from DNA extracted from dried blood spots on newborn screening cards, which are obtained on all newborns. The Wisconsin group of Investigators previously performed RT-PCR for T-cell receptor excision circles on nearly 10,000 anonymized newborn screening cards before implementation of the test. Initial results on the newborn screening program will be presented at the Late Breaking Abstracts session at the upcoming American Academy of Allergy, Asthma & Immunology meeting in Philadelphia.”American Academy of Pediatrics publishes new atopy prevention guidelinesThe American Academy of Pediatrics Committee on Nutrition and Section on Allergy and Immunology published a new clinical report in Pediatrics (2008;121:183-91) that reviews issues of atopy prevention through diet. In contrast with the Committee on Nutrition guidelines published in 2000, which emphasized maternal avoidance of all nuts, eggs, milk, and fish during pregnancy and staged exposure to these foods for the child, the new report indicates there is no strong evidence for benefit of maternal exclusion diets in pregnancy or nursing (with the possible exception for atopic dermatitis regarding nursing) and there remains no convincing evidence of a significant effect regarding avoidance of specific allergens in the infant diet for various longer periods. The 2008 report supports previous recommendations on breast-feeding and introduction of solid foods. Importantly, the 2008 report indicates that the dietary advice could differ if an infant already had signs of atopic disease. Contributed by Scott H. Sicherer, MD.There remains no convincing evidence of a significant effect regarding avoidance of specific allergens in the infant diet.Translational and clinical horizonsAs part of our ongoing series highlighting ongoing and future preclinical and clinical trials related to allergy, asthma, and immunodeficiency, we asked Stanley J. Szefler, MD, from the National Institute of Allergy and Infectious Diseases (NIAID) Inner City Asthma Consortium to provide a status report on the Asthma Control Evaluation study, for which he served as lead investigator. The full text of Dr Szefler's comments can be found online at www.jacionline.org.Food allergy epidemic declared a mythAccording to an article published in Harper's Magazine (2008;316:64-5), the rising prevalence of food allergy is nothing more than mass parental hysteria and inadequate science! If you find your office packed with anxious parents holding “Everyone's Gone Nuts” by Meredith Broussard, direct them to a recent interview with Hugh Sampson, MD, on New York Public Radio where he stridently defends and skillfully clarifies the clinical science that was left out of the Harper's article. This interview is available at http://www.wnyc.org/shows/lopate/episodes/2008/01/31.The rising prevalence of food allergy is nothing more than mass parental hysteria and inadequate science.News items are written by Sherri Gabbert, PhD.Have a news item that you think other readers would be interested in? Send your ideas to the News Beyond Our Pages editors at [email protected] . Contributors will be acknowledged in these pages. New class of leukotrienes identified In anaphylaxis, more may be better: New pathway identifiedIn the January 14, 2008, New England Journal of Medicine, Vadas et al (N Engl J Med 2008;358:28-35) presented provocative results from a prospective and retrospective study of the role of platelet activating factor (PAF) acetylhydrolase in anaphylaxis. PAF is a potent inflammation mediator in anaphylaxis, secreted by mast cells and monocytes. It is inactivated by PAF acetylhydrolase. Vadas et al found that anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase and demonstrated that patients who experienced severe anaphylactic response to allergen challenge had lower than normal titers of this enzyme. They suggested that blockade of PAF receptors may be a new target for therapeutic intervention and, although their data are limited, PAF acetylhydrolase levels might be useful as a diagnostic tool to predict anaphylaxis severity risk. This article supports the findings of JACI Associate Editor Fred Finkelman, who has evidence that anaphylaxis can be mediated by macrophage-derived PAF (Finkelman et al. J Allergy Clin Immunol 115;3:449-57).We asked Scott Sicherer, MD, to comment on this article. Dr Sicherer notes, “We are constantly asked by patients ‘how severe is my food allergy?’ and since typical IgE tests do not correlate well with severity, we are often going on circumstantial risk factors data, such as presence of asthma, reaction history and amount triggering symptoms. This report may represent a strong beginning to better insight on severity assessment.”Anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase. In the January 14, 2008, New England Journal of Medicine, Vadas et al (N Engl J Med 2008;358:28-35) presented provocative results from a prospective and retrospective study of the role of platelet activating factor (PAF) acetylhydrolase in anaphylaxis. PAF is a potent inflammation mediator in anaphylaxis, secreted by mast cells and monocytes. It is inactivated by PAF acetylhydrolase. Vadas et al found that anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase and demonstrated that patients who experienced severe anaphylactic response to allergen challenge had lower than normal titers of this enzyme. They suggested that blockade of PAF receptors may be a new target for therapeutic intervention and, although their data are limited, PAF acetylhydrolase levels might be useful as a diagnostic tool to predict anaphylaxis severity risk. This article supports the findings of JACI Associate Editor Fred Finkelman, who has evidence that anaphylaxis can be mediated by macrophage-derived PAF (Finkelman et al. J Allergy Clin Immunol 115;3:449-57). We asked Scott Sicherer, MD, to comment on this article. Dr Sicherer notes, “We are constantly asked by patients ‘how severe is my food allergy?’ and since typical IgE tests do not correlate well with severity, we are often going on circumstantial risk factors data, such as presence of asthma, reaction history and amount triggering symptoms. This report may represent a strong beginning to better insight on severity assessment.” Anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase. Anaphylactic severity negatively correlated to circulating levels of PAF acetylhydrolase. Don't overtreat sinusitisNeither antibiotic nor topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting. Neither antibiotic nor topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting. Neither antibiotic nor topical steroid alone or in combination was effective as a treatment for acute sinusitis in the primary care setting. Muscling-up smooth muscle Basophils: A missing linkTH2 immune responses to parasites and protein allergens are nearly identical, but the common mechanism leading to this response is still being described. Sokol et al (Nat Immunol 2007; Dec 21 [epub ahead of print]) reported the discovery of requisite basophil activation for induction of TH2 immune response to protein allergens. The authors found that basophils were a target for protease allergens and produced the necessary cytokines and chemokines to initiate TH2 response and differentiation. Sokol et al also reported that basophils were recruited to the draining lymph nodes as a first-order effect of protein allergen stimulation.We asked Donald MacGlashan, MD, to comment on this article. Dr McGlashan remarks, “This elegant and comprehensive study presents evidence that mouse basophils provide a set of signals to T cells that skews the T-cell response towards the TH2 phenotype… One of the surprising observations of these studies is that basophils can be found in correct locations in local lymph nodes to exert influence on the stimulated T cells. Unless the basophil is unique among the granulocytes, this result opens up the possibility that other granulocytes may mediate immune deviation in lymph nodes.” The full text of Dr MacGlashan's comments can be found in this article's Online Repository atwww.jacionline.org.Basophils provide a set of signals to T cells that skew the T-cell response toward the TH2 phenotype. TH2 immune responses to parasites and protein allergens are nearly identical, but the common mechanism leading to this response is still being described. Sokol et al (Nat Immunol 2007; Dec 21 [epub ahead of print]) reported the discovery of requisite basophil activation for induction of TH2 immune response to protein allergens. The authors found that basophils were a target for protease allergens and produced the necessary cytokines and chemokines to initiate TH2 response and differentiation. Sokol et al also reported that basophils were recruited to the draining lymph nodes as a first-order effect of protein allergen stimulation. We asked Donald MacGlashan, MD, to comment on this article. Dr McGlashan remarks, “This elegant and comprehensive study presents evidence that mouse basophils provide a set of signals to T cells that skews the T-cell response towards the TH2 phenotype… One of the surprising observations of these studies is that basophils can be found in correct locations in local lymph nodes to exert influence on the stimulated T cells. Unless the basophil is unique among the granulocytes, this result opens up the possibility that other granulocytes may mediate immune deviation in lymph nodes.” The full text of Dr MacGlashan's comments can be found in this article's Online Repository atwww.jacionline.org. Basophils provide a set of signals to T cells that skew the T-cell response toward the TH2 phenotype. Basophils provide a set of signals to T cells that skew the T-cell response toward the TH2 phenotype. Wisconsin first state to screen for severe combined immunodeficiencyWisconsin babies are in the pole position when it comes to diagnostic/preventative screening. Dr Asriani Chiu, allergy/immunology faculty at the Medical College of Wisconsin, offered this report: “Through a collaboration between investigators at the Children's Hospital of Wisconsin, the Medical College of Wisconsin and the Wisconsin State Hygiene Laboratory, the state of Wisconsin has become the first state to screen all newborns for severe combined immunodeficiency, beginning January 1, 2008. The screening test, real-time PCR for T-cell receptor excision circles, is performed from DNA extracted from dried blood spots on newborn screening cards, which are obtained on all newborns. The Wisconsin group of Investigators previously performed RT-PCR for T-cell receptor excision circles on nearly 10,000 anonymized newborn screening cards before implementation of the test. Initial results on the newborn screening program will be presented at the Late Breaking Abstracts session at the upcoming American Academy of Allergy, Asthma & Immunology meeting in Philadelphia.” Wisconsin babies are in the pole position when it comes to diagnostic/preventative screening. Dr Asriani Chiu, allergy/immunology faculty at the Medical College of Wisconsin, offered this report: “Through a collaboration between investigators at the Children's Hospital of Wisconsin, the Medical College of Wisconsin and the Wisconsin State Hygiene Laboratory, the state of Wisconsin has become the first state to screen all newborns for severe combined immunodeficiency, beginning January 1, 2008. The screening test, real-time PCR for T-cell receptor excision circles, is performed from DNA extracted from dried blood spots on newborn screening cards, which are obtained on all newborns. The Wisconsin group of Investigators previously performed RT-PCR for T-cell receptor excision circles on nearly 10,000 anonymized newborn screening cards before implementation of the test. Initial results on the newborn screening program will be presented at the Late Breaking Abstracts session at the upcoming American Academy of Allergy, Asthma & Immunology meeting in Philadelphia.” American Academy of Pediatrics publishes new atopy prevention guidelinesThe American Academy of Pediatrics Committee on Nutrition and Section on Allergy and Immunology published a new clinical report in Pediatrics (2008;121:183-91) that reviews issues of atopy prevention through diet. In contrast with the Committee on Nutrition guidelines published in 2000, which emphasized maternal avoidance of all nuts, eggs, milk, and fish during pregnancy and staged exposure to these foods for the child, the new report indicates there is no strong evidence for benefit of maternal exclusion diets in pregnancy or nursing (with the possible exception for atopic dermatitis regarding nursing) and there remains no convincing evidence of a significant effect regarding avoidance of specific allergens in the infant diet for various longer periods. The 2008 report supports previous recommendations on breast-feedi