Absence of serum IgE antibodies indicates non-type 2 disease in young asthmatics

Abstract

Background

Atopic asthma is associated with elevated type-2 biomarkers such as fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count. However, increased type-2 markers have also been reported in traditionally-defined non-atopic asthma.

Objective

To determine a clinically useful level of IgE sensitisation for ruling out type-2 asthma.

Methods

Asthmatics (N = 408; age 10-35 years) were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP). Subjects were grouped based on IgE-antibody concentrations: ≥ 0.35 kU_A/L for at least one test (n=326) or < 0.35 kU_A/L for both tests (n=82). Τhe latter group was subsequently divided into two groups: IgE 0.10-0.34 kU_A/L (n=34) and IgE < 0.10 kU_A/L (n=48). The relationships between type-2 biomarkers, and inadequate asthma control (ACT < 20), reduced lung function (FEV₁ < 80%), recent asthma attacks, and airway hyperresponsiveness (AHR) to methacholine were determined.

Results

In univariate analyses, at least one type-2 marker related to each asthma outcome in subjects with IgE ≥ 0.35 kU_A/L. In subjects with IgE 0.10-0.34 kU_A/L, elevated FeNO related to reduced lung function (p=0.008) and B-Eos to AHR (p = 0.03). No associations were found in subjects with IgE < 0.10 kU_A/L. In multivariate analysis, a relationship between FeNO and reduced lung function remained in subjects with IgE < 0.35 kU_A/L (p = 0.03).

Conclusion and clinical relevance

Clinically relevant elevation of type-2 biomarkers was seen in young asthmatics with IgE antibodies < 0.35 kU_A/L, but not those with IgE < 0.10 kU_A/L. It seems possible to define non-type 2 asthma through sensitive IgE-antibody measurement.

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Component resolved diagnostics demonstrates that most peanut allergic individuals could potentially introduce tree nuts to their diet

Abstract

Background

Nut allergy varies from pollen cross-allergy, to primary severe allergy with life-threatening symptoms. The screening of IgE antibodies to a wide spectrum of allergens, including species-specific and cross-reactive allergens, is made possible via microarray analysis.

Objective

We sought to study the association of variable IgE sensitization profiles to clinical response in peanut-challenged children and adolescents in a birch-endemic region. In addition, we studied the avoidance of tree nuts and species-specific sensitizations.

Methods

We studied 102 peanut-sensitized patients who underwent a double-blind placebo-controlled challenge to peanut. We analyzed ISAC ImmunoCAP microarray to 112 allergens, singleplex ImmunoCAPs for hazelnut Cor a 14 and cashew Ana o 3, and performed skin prick tests to peanut, tree nuts and sesame seed. We surveyed avoidance diets with a questionnaire.

Results

Sensitization to PR-10 proteins was frequent (Bet v 1 90%), but equally high in the challenge negatives and positives. IgE to Ara h 2 and Ara h 6 discriminated peanut allergic (n=69) and tolerant (n=33) the best. Avoidance of tree nuts was common (52 to 96%), but only

6 to 44% presented species-specific sensitizations to tree nuts, so a great number could potentially introduce these species into their diet.

Conclusions and clinical relevance

PR-10-sensitizations were frequent and strong regardless of peanut allergy status. Component resolved diagnostics can be employed to demonstrate to patients that sensitization to seed storage proteins of tree nuts is uncommon. Several tree nuts could potentially be reintroduced to the diet.

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Impedance Oscillometry: Emerging Role in the Management of Chronic Respiratory Disease

Abstract

Purpose of Review

Chronic respiratory diseases affecting adults and children are widely prevalent, so lung function testing is imperative for diagnosis and management. Spirometry is the traditional standard measure of lung function; however, certain groups of patients are unable to provide accurate and reproducible exhalation maneuvers. Consequently, the impedance oscillometry system (IOS) has been developed as an effort, independent technique to assess airway function in children and the elderly. To better understand this emerging modality, the following review will compare IOS with spirometry, examine the function of the device, provide interpretation strategies, and discuss the evidence supporting its use in adults and children with chronic lung disease.

Recent Findings

In a population of symptomatic adults with suspected COPD, impedance oscillometry resistance measurements correlate with FEV₁ and lung resistance increases with the severity of airflow limitation. In patients with asthma, IOS is a sensitive measure of airway hyperresponsiveness and bronchodilator response.

Summary

Impedance oscillometry is evolving as an alternative measure to assess lung function pediatric and adult populations.

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No difference in UVB-induced changes in antigen-presenting cells and in cytokines between subjects with and without loss-of-function mutations in FLG

Abstract

Ultraviolet B (UVB) irradiation-induced skin inflammation leads to epidermal depletion of Langerhans cells (LCs), which is followed by a rapid influx of monocytes.(1) Approximately 10% of Northern Europeans carry loss-of-function mutations in the filaggrin gene (FLG) which cause partial or complete lack of epidermal filaggrin and filaggrin metabolites.(2) Deficit of the filaggrin metabolite trans-urocanic acid has been shown to cause an increased keratinocyte photosensitivity to UVB irradiation in human skin models.(3)

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A case of facial burn due to the misuse of garlic face mask for acne

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Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies—the German Cancer Consortium approach

Abstract

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

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A systematic review of pyoderma gangrenosum with pulmonmary involvement: clinical presentation, diagnosis, and management

Abstract

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that often has extracutaneous manifestations, with lung involvement being the most common (1, 2). In this systematic review we have summarized the clinical presentation, predisposing factors, and treatment of PG patients with pulmonary involvement and compared them to classic neutrophilic disorders. Using the search terms "pulmonary, lung, respiratory, bronchi, or bronchopulmonary" AND "pyoderma gangrenosum" a systematic review was conducted using PubMed and Web of Science.

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