Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy.

BACKGROUND: Anaphylaxis to egg or severe egg allergy has been considered a contraindication to receiving trivalent seasonal influenza vaccine (TIV). OBJECTIVE: To evaluate the safety of TIV among severely egg allergic children. METHODS: A 2-phase, multicenter study at 7 sites was conducted between October 2010 and March 2012. Inclusion criteria included a history of a severe reaction, including anaphylaxis, to the ingestion of egg and a positive skin test result or evidence of serum specific IgE antibody to egg. Phase 1 consisted of a randomized, prospective, double-blind, placebo controlled trial of TIV administration to egg allergic children, using a 2-step approach; group A received 0.1 mL of influenza vaccine, followed in 30 minutes if no reaction with the remainder of an age-appropriate dose, whereas group B received an injection of normal saline followed in 30 minutes if no reaction with the full 100% of the age-appropriate dose. Phase 2 was a retrospective analysis of single dose vs split-dose administration of TIV in eligible study participants who declined participation in the randomized controlled trial. RESULTS: Thirty-one study participants were prospectively evaluated in the randomized controlled trial (group A, 14; group B, 17); 45.1% had a history of anaphylaxis after egg ingestion. A total of 112 participants were retrospectively evaluated (87 with the single dose and 25 with the split dose); 77.6% of participants had a history of anaphylaxis after egg ingestion. All participants in both phases received TIV without developing an allergic reaction. CONCLUSION: TIV administration is safe even in children with histories of severe egg allergy. Use of 2-step split dosing appears unnecessary because a single dose was well tolerated.

STAT6 regulates natural helper cell proliferation during lung inflammation initiated by Alternaria.

Asthma exacerbations can be caused by a number of factors, including the fungal allergen Alternaria, which is specifically associated with severe and near-fatal attacks. The mechanisms that trigger lung responses are unclear and might vary between allergens. A comparison between Alternaria, Aspergillus, Candida, and house dust mite, all allergens in humans, showed that only Alternaria promoted immediate innate airway eosinophilia within 12 h of inhalation in nonsensitized mice. Alternaria, but not the other allergens, induced a rapid increase in airway levels of IL-33, accompanied by IL-33 receptor (IL-33R)-positive natural helper cell (NHC) production of IL-5 and IL-13. NHCs in the lung and bone marrow constitutively expressed transcription factors [GATA-3 and E26 transformation-specific sequence-1 (ETS-1)] that could allow for rapid induction of T helper type 2 (Th2) cytokines. Lung NHC numbers and proliferation (%Ki-67), but not IL-5 or GATA-3 expression, were significantly reduced in STAT6-deficient mice 3 days after one challenge with Alternaria. Alternaria induced NHC expression of the EGF receptor ligand amphiregulin (partially dependent on STAT6), as well as EGF receptor signaling in the airway epithelium. Finally, human peripheral blood NHCs (CRTH2(+)CD127(+) lineage-negative lymphocytes) from allergic individuals highly expressed GATA-3 and ETS-1, similar to lung NHCs in mice. In summary, Alternaria-induced lung NHC proliferation and expression of amphiregulin are regulated by STAT6. In addition, NHCs in mouse and humans are primed to express Th2 cytokines through constitutive expression of GATA-3 and ETS-1. Thus several transcription factor pathways (STAT6, GATA-3, and ETS-1) may contribute to NHC proliferation and Th2-type responses in Alternaria-induced asthma.

Aspirin-exacerbated respiratory disease: burden of disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by adult onset of asthma, chronic rhinosinusitis (CRS), nasal polyposis, and aspirin sensitivity. In this syndrome, each disease component has deleterious effects on the patient's health and quality of life. Latest figures from the Centers for Disease Control indicate 8.2% of the U.S. population has asthma and among adult asthmatic patients, up to 9% have AERD. Approximately 13% of the population suffers from CRS and 15% of patients with CRS with nasal polyposis have AERD. A review of the impact that each component of AERD has on patients will delineate the considerable burden of AERD, especially when considering the cumulative effects of the tetrad.

Aspirin-sensitive asthma and upper airway diseases.

BACKGROUND: Aspirin exacerbated respiratory disease (AERD) consists of nasal polyposis, rhinosinusitis, asthma, and aspirin (ASA) sensitivity. OBJECTIVE: This article details how to diagnose and treat AERD and describes the procedures associated with ASA challenge and desensitization, benefits associated with ASA desensitization, and appropriate doses for treatment. METHODS: Criteria for diagnosis of AERD as well as desensitization protocols for oral ASA challenge and combined intranasal ketorolac and oral ASA challenge, are detailed in this article based on literature review. RESULTS: AERD requires a multidimensional approach to treat the disease given the multiple conditions. With successful ASA desensitization and maintenance of ASA administration, all patients are able to achieve ASA tolerance and select patients are able to achieve improvement in clinical markers such as global scores and reduction in use of topical and systemic corticosteroids.

Smoking, environmental tobacco smoke, and aspirin-exacerbated respiratory disease.

BACKGROUND: Tobacco smoke is a widely recognized environmental pollutant and is a major public health hazard worldwide. Although environmental tobacco smoke (ETS) has a clear link with many conditions, including asthma, ear infections, and sinus cancer, evidence related to aspirin-exacerbated respiratory disease (AERD) requires further investigation. OBJECTIVE: To investigate whether active smoke or ETS exposures are associated with an increased risk of developing AERD. METHODS: A total of 260 patients with AERD were enrolled in a case-control study with their respective asymptomatic spouses serving as matched controls. Multiple logistic regression analysis was used to examine the association of AERD with active smoking and ETS, adjusted for age, sex, and location of childhood residence. RESULTS: The AERD case patients were more likely to have ever smoked actively when compared with controls (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.04-2.28). A significant association (OR, 3.46; 95% CI, 2.22-5.39) was found between childhood ETS exposure and AERD. If a patient was exposed to ETS during both childhood and adulthood, results showed an OR of 5.09 for developing AERD (95% CI, 2.75-9.43). However, no statistically significant association between AERD and ETS only during adulthood was found (OR, 1.60; 95% CI, 0.75-3.40), suggesting that the combined effect of childhood and adulthood ETS may be augmented by the prior childhood exposure. CONCLUSIONS: Active smoking and childhood ETS exposure are associated with increased odds of developing AERD. In particular, combined childhood and adulthood exposure had major effects. This study suggests that ETS is at least one contributor to the syndrome of AERD.