Asthma Severity and Prevalence: An Ongoing Interaction between Exposure, Hygiene, and Lifestyle

Why are the prevalence and severity of asthma increasing? Platts-Mills looks at the key studies that can help to anwer this important questio

The use of machine learning to understand the relationship between IgE to specific allergens and asthma

In a study recently published in PLOS Medicine, Custovic and colleagues report an elegant analysis of the results of specific Immunoglobulin E (IgE) assays on sera from a birth cohort that they have studied in detail over the last 15 years. The IgE assays used a microchip with >100 purified allergens, and their machine learning approach used a hypothesis-free statistical approach to group children with similar allergen sensitization profiles. The primary objective was to evaluate the relationship of the results to the diagnosis of current asthma. The goal of employing a “machine learning” approach is both as a form of data reduction to avoid spuriously identified associations resulting from multiple comparisons and to identify biologically relevant groupings that may not be recognized with conventional approaches. The use of “hypothesis free” clustering methods with individual allergen components in itself is not novel. However, the authors have employed a new network analysis method, which is improved over previous methods because it can capture nonlinear relationships and does not rely on assumption of a parametric probability. As the authors show, this approach can lead to improved sensitivity and specificity. With this model, they were able to show that pairings of allergens (e.g., the cat allergen Fel d 1 and the peanut allergen Ara h 1) were more predictive of the child having asthma than individual components, although we must be cautious in the generalizability of the specific patterns identified, in this single cohort in the United Kingdom, because the pairing may represent host susceptibility to making an IgE response or common co-exposures, which could be allergens or adjuvants. Still, the concept of complicated connections between individual allergenic proteins and allergic disease are likely to apply more broadly and are important to consider in future studies

Childhood asthma and physical activity: a systematic review with meta-analysis and Graphic Appraisal Tool for Epidemiology assessment

PRISMA Items Used in Reporting in the Current Systematic Literature Review. Additional file 1 presents the PRISMA checklist items that were examined, with the draft article page numbers. (DOCX 29 kb

IgE in the diagnosis and treatment of allergic disease

Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the “allergic” disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow’s milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response

A retrospective review of α-gal syndrome complicating the management of suspected pancreatic exocrine insufficiency in one gastroenterology clinic in central Virginia

The galactose-α-1,3-galactose (α-gal) mammalian meat allergy, α-gal syndrome, often includes diarrhea, abdominal pain, and other gastrointestinal (GI) symptoms. Pancreatic exocrine insufficiency causes similar symptoms. The pancreatic replacement enzymes, referred to here as pancreatic enzymes, used to treat pancreatic insufficiency are porcine products and contain α-gal. Patients with pancreatic insufficiency who also have α-gal syndrome may be intolerant of mammalian products in their diet and of α-gal in pancreatic enzymes. In this article, we describe 40 patients from one GI clinic in central Virginia with suspected pancreatic insufficiency and increased α-gal immunoglobulin E (IgE) levels. Over 50% of these patients had some clinical improvement when mammalian products were removed from the diet. Most patients could tolerate pancreatic enzymes; 10% could not tolerate them due to suspected allergy symptoms, but none developed anaphylaxis. Understanding that α-gal syndrome can be superimposed on pancreatic exocrine insufficiency and exacerbate symptoms, and that treatment with pancreatic enzymes may increase GI and/or allergy symptoms in this group, will lead to improved medical management of this complex patient population

Allergenomics of the tick Ixodes ricinus reveal important α-Gal-carrying IgE-binding proteins in red meat allergy

Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3864]This is the peer-reviewed version of the following article: Apostolovic, D.; Mihailovic, J.; Commins, S. P.; Wijnveld, M.; Kazimirova, M.; Starkhammar, M.; Stockinger, H.; Platts-Mills, T. A. E.; Cirkovic Velickovic, T.; Hamsten, C.; et al. Allergenomics of the Tick Ixodes Ricinus Reveals Important α-Gal–Carrying IgE-Binding Proteins in Red Meat Allergy. Allergy: European Journal of Allergy and Clinical Immunology 2020, 75 (1), 217–220. [https://doi.org/10.1111/all.13978

Pain, distress, and anticipated recovery for older versus younger emergency department patients after motor vehicle collision

Abstract Background Motor vehicle collisions (MVCs) are the second most common injury mechanism resulting in emergency department (ED) visits by older adults. MVCs result in substantial pain and psychological distress among younger individuals, but little is known about the occurrence of these symptoms in older individuals. We describe the frequency of and characteristics associated with pain, distress, and anticipated time for physical and emotional recovery for older adults presenting to the ED after MVC in comparison to younger adults. Methods In-person interviews were conducted for adults presenting to one of eight EDs after MVC without an obvious fracture or injury requiring admission as part of two prospective studies. Pain severity was assessed using a 0–10 verbal scale. Distress was assessed using the Peritraumatic Distress Inventory (range 0–52). Patients were asked to estimate their expected time for physical and emotional recovery; these responses were dichotomized to <30 or ≥30 days. ED pain and distress and associations between patient and collision characteristics and ED pain and distress were examined for patients age 65 years and older and patients age 18 to 64. Results Older (n = 96) and younger (n = 943) adults had the same mean pain scores (5.5, SD 2.5 vs. 5.5, SD 2.4). Distress scores were lower in older than in younger adults (15.5, SD 9 vs. 19.2, SD 10). A higher percentage of older adults than younger adults had an anticipated time to physical recovery ≥30 days (41%, 95% confidence interval [CI] 28%-55% vs. 11%, 95% CI 9%-13%). Similarly, older adults were more likely to have an anticipated time for emotional recovery ≥30 days (45%, 95% CI 35%-55% vs. 17%, 95% CI 15%-20%). Older adults were less likely than younger adults to have moderate or severe neck pain (score ≥4) (25%, 95% CI 23% to 41% vs. 54%, 95% CI 48% to 60%) or back pain (31%, 95% CI 23% to 46% vs. 56%, 95% CI 51 to 62%) but more likely to have moderate or severe chest pain (42%, 95% CI 32% to 50% vs. 20%, 95% CI 16 to 23%). Pre-MVC depressive symptoms and pain catastrophizing were positively associated with pain and distress in both older and younger adults. Conclusions In our cohort, older adults who presented to the ED after MVC experienced similar pain severity as younger patients and less distress but were more likely to estimate their times for physical and emotional recovery to be 30 days or more. Increased emergency provider awareness of acute pain and distress symptoms among older patients experiencing MVC may improve outcomes for these patients

T Cell Epitope Immunotherapy Induces a CD4(+) T Cell Population with Regulatory Activity

BACKGROUND: Synthetic peptides, representing CD4(+) T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. METHODS AND FINDINGS: In this study we address the mechanism of action of peptide immunotherapy (PIT) in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs) after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4(+) cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4(neg) PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4(+) and CD8(+) PBMCs. CONCLUSION: This study provides evidence for the induction of a population of CD4(+) T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen