Allison J. Burbank

Environmental determinants of allergy and asthma in early life

&NA; Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early‐life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a childs development is needed to identify cost‐effective interventions that reduce atopy risk in children.

Oral Immunotherapy for Food Allergy

Food allergy is a potentially life-threatening condition with no approved therapies, apart from avoidance and injectable epinephrine for acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which food-allergic patients consume gradually increasing quantities of the food to increase their threshold for allergic reaction. This therapy carries significant risk of allergic reactions. The ability of OIT to desensitize patients to particular foods is well-documented, although the ability to induce tolerance has not been established. This review focuses on recent studies for the treatment of food allergies such as cows milk, hens egg, and peanut.

A proof-of-concept clinical study examining the NRF2 activator sulforaphane against neutrophilic airway inflammation

AbstractSulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, is implicated as a possible therapy for airway inflammation via induction of the transcription factor NF-E2-related factor 2 (NRF2). In this proof-of-concept clinical study, we show that supplementation of SFN with broccoli sprout homogenate in healthy human subjects did not induce expression of antioxidant genes or protect against neutrophilic airway inflammation in an ozone-exposure model. Therefore, dietary sulforaphane supplementation is not a promising candidate for larger scale clinical trials targeting airway inflammation. Trial registration:NCT01625130. Registered 19 June, 2012.

Food specific oral immunotherapy: A potential treatment for food allergy

Food allergy is a potentially life-threatening condition affecting up to 8% of children and up to 2% of adults in westernized countries. There are currently no approved treatments for food allergy apart from avoidance. The apparent increase in incidence of food allergies over the past few decades calls attention to the need for effective, disease-modifying therapies for food allergies. Oral immunotherapy (OIT) is a promising experimental treatment in which food allergic patients consume increasing quantities of food in attempt to increase their threshold for allergic reaction. Studies are ongoing to determine whether OIT is capable of safely inducing not only desensitization but also tolerance to the allergenic foods. This article focuses on recent relevant studies of OIT for the treatment of common food allergies.

Gamma tocopherol-enriched supplement reduces sputum eosinophilia and endotoxin-induced sputum neutrophilia in volunteers with asthma

Background: We and others have shown that the gamma tocopherol (&ggr;T) isoform of vitamin E has multiple anti‐inflammatory and antioxidant actions and that &ggr;T supplementation reduces eosinophilic and endotoxin (LPS)‐induced neutrophilic airway inflammation in animal models and healthy human volunteers. Objective: We sought to determine whether &ggr;T supplementation reduces eosinophilic airway inflammation and acute neutrophilic response to inhaled LPS challenge in volunteers with asthma. Methods: Participants with mild asthma were enrolled in a double‐blinded, placebo‐controlled crossover study to assess the effect of 1200 mg of &ggr;T daily for 14 days on sputum eosinophils, mucins, and cytokines. We also assessed the effect on acute inflammatory response to inhaled LPS challenge following &ggr;T treatment, focusing on changes in sputum neutrophilia, mucins, and cytokines. Mucociliary clearance was measured using gamma scintigraphy. Results: Fifteen subjects with mild asthma completed both arms of the study. Compared with placebo, &ggr;T notably reduced pre‐LPS challenge sputum eosinophils and mucins, including mucin 5AC and reduced LPS‐induced airway neutrophil recruitment 6 and 24 hours after challenge. Mucociliary clearance was slowed 4 hours postchallenge in the placebo group but not in the &ggr;T treatment group. Total sputum mucins (but not mucin 5AC) were reduced at 24 hours postchallenge during &ggr;T treatment compared with placebo. Conclusions: When compared with placebo, &ggr;T supplementation for 14 days reduced inflammatory features of asthma, including sputum eosinophils and mucins, as well as acute airway response to inhaled LPS challenge. Larger scale clinical trials are needed to assess the efficacy of &ggr;T supplements as a complementary or steroid‐sparing treatment for asthma.

Clinically focused exome sequencing identifies an homozygous mutation that confers DOCK8 deficiency.

Live (viral and mycobacterial) vaccines are generally contraindicated in immunocompromised individuals (10). However, as rotavirus vaccination is recommended to be started at the age of 2 months, many SCID patients have already received it at the time of diagnosis (7). TREC-based NBS for SCID has been found efficient for early diagnosis of the disease and could thus prevent the administration of live vaccines to those infants (2, 3). NBS for SCID has become nationally recommended in the USA in 2010 (2). It is not yet carried out in Europe, although trials for implementing population-wide NBS for SCID are currently ongoing in several European countries (3). Delfien Bogaert; Kristof Van Schil; Tom Taghon; Victoria Bordon; Carolien Bonroy; Melissa Dullaers; Elfride De Baere & Filomeen Haerynck Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium; Department of Pediatric Immunology and Pulmonology, Ghent University Hospital, Ghent, Belgium; Center for Medical Genetics, Ghent University, Ghent University Hospital, Ghent, Belgium; Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium; Department of Pediatric Hematology and Oncology, Ghent University Hospital, Ghent, Belgium; Department of Clinical Chemistry, Microbiology and Immunology, Laboratory of Clinical Biology, Ghent University Hospital, Ghent, Belgium E-mail: filomeen.haerynck@uzgent.be DOI:10.1111/pai.12455

Low-level ozone has both respiratory and systemic effects in African American adolescents with asthma despite asthma controller therapy

In a cohort of African American adolescents with persistent asthma on guidelines-based daily controller therapies, short-term elevation of low ozone levels below the National Ambient Air Quality Standard of 70 ppb were associated with lung function decrements and elevated lipid levels.