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

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

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

Galactose-α-1,3-Galactose–Specific IgE Is Associated with Anaphylaxis but Not Asthma

Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract

Anti-tumor necrosis factor-Α antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust

Background/Aims Recent studies documented that sensitization and exposure to cockroach allergens significantly increase children's asthma morbidity as well as severity, especially among inner city children. TNF-Α has been postulated to be a critical mediator directly contributing to the bronchopulmonary inflammation and airway hyper-responsiveness in asthma. This study investigated whether an anti-TNF-Α antibody would inhibit pulmonary inflammation and methacholine (Mch) hyper-responsiveness in a mouse model of asthma induced by a house dust extract containing both endotoxin and cockroach allergens. Methods A house dust sample was extracted with phosphate-buffered saline and then used for immunization and two additional pulmonary challenges of BALB/c mice. Mice were treated with an intravenous injection of anti-TNF-Α antibody or control antibody 1  h before each pulmonary challenge. Results In a kinetic study, TNF-Α levels within the bronchoalveolar lavage (BAL) fluid increased quickly peaking at 2 h while BAL levels of IL-4, IL-5, and IL-13 peaked at later time-points. Mch hyper-responsiveness was measured 24 h after the last challenge, and mice were killed 24 h later. TNF inhibition resulted in an augmentation of these Th2 cytokines. However, the allergic pulmonary inflammation was significantly reduced by anti-TNF-Α antibody treatment as demonstrated by a substantial reduction in the number of BAL eosinophils, lymphocytes, macrophages, and neutrophils compared with rat IgG-treated mice. Mch hyper-responsiveness was also significantly reduced in anti-TNF-Α antibody-treated mice and the pulmonary histology was also significantly improved. Inhibition of TNF significantly reduced eotaxin levels within the lung, suggesting a potential mechanism for the beneficial effects. These data indicate that anti-TNF-Α antibody can reduce the inflammation and pathophysiology of asthma in a murine model of asthma induced by a house dust extract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73609/1/j.1365-2222.2005.02407.x.pd

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study

Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation