A novel quinoline with airway relaxant effects and anti-inflammatory properties

Research - Open access

Bergwik, J., Liu, J., Padra, M. et al. Respir Res 25, 146 (2024). https://doi.org/10.1186/s12931-024-02780-8

Abstract

Background

In chronic pulmonary diseases characterized by inflammation and airway obstruction, such as asthma and COPD, there are unmet needs for improved treatment. Quinolines is a group of small heterocyclic compounds that have a broad range of pharmacological properties. Here, we investigated the airway relaxant and anti-inflammatory properties of a novel quinoline (RCD405).

Methods

The airway relaxant effect of RCD405 was examined in isolated airways from humans, dogs, rats and mice. Murine models of ovalbumin (OVA)-induced allergic asthma and LPS-induced airway inflammation were used to study the effects in vivo. RCD405 (10 mg/kg) or, for comparisons in selected studies, budesonide (3 mg/kg), were administered intratracheally 1 h prior to each challenge. Airway responsiveness was determined using methacholine provocation. Immune cell recruitment to bronchi was measured using flow cytometry and histological analyses were applied to investigate cell influx and goblet cell hyperplasia of the airways. Furthermore, production of cytokines and chemokines was measured using a multiplex immunoassay. The expression levels of asthma-related genes in murine lung tissue were determined by PCR. The involvement of NF-κB and metabolic activity was measured in the human monocytic cell line THP-1.

Results

The relaxing effect of RCD405 on human, dog, rat and mouse
isolated airway pre-contracted with CCh.

RCD405 demonstrated a relaxant effect on carbachol precontracted airways in all four species investigated (potency ranking: human = rat > dog = mouse).

Clinical Practice Guideline: Immunotherapy for Inhalant Allergy

Gurgel RK, Baroody FM, Damask CC, et al. Otolaryngol Head Neck Surg. 2024 Mar;170 Suppl 1:S1-S42. doi: 10.1002/ohn.648. 

Abstract

Objective

Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care.

Purpose

The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy.

Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma

Research - Open access

Thomas B Casale, Thomas Corbridge, Guillaume Germain, François Laliberté, Sean D MacKnight, Julien Boudreau, Mei S Duh & Arijita Deb. Allergy, Asthma & Clinical Immunology volume 20, Article number: 25 (2024)

Abstract

Background

Systemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications.

Objective

Evaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma.

Methods

This retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6–12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days).

IgE to cyclophilins in pollen allergic children: epidemiological, clinical and diagnostic relevance of a neglected panallergen

Matricardi PM, Potapova E, Panetta V et al. J Allergy Clin Immunol. 2024 Mar 19:S0091-6749(24)00235-5. doi: 10.1016/j.jaci.2024.01.030.

Abstract

Background: - Cyclophilins are ubiquitous panallergens whose epidemiological, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. The aim of this study was to investigate the epidemiological, diagnostic, and clinical relevance of cyclophilin in seasonal allergic rhinitis and its comorbidities.

Methods: - We examined a random sample (25%, n 253) of 1263 Italian children affected by seasonal allergic rhinitis from the "Panallergen in Pediatrics" (PAN-PED) cohort. Patients' disease phenotype had been already fully characterized through questionnaires (ARIA), skin prick tests (ALK), IgE tests to extracts, major and cross-reactive allergenic molecules of a comprehensive variety of allergenic pollen (immunoCAP), and carbohydrate cross-reacting determinants (CCD) (NOVEOS).

Graphical Abstract

We also performed nested studies of sensitization prevalence, correlation and allergen extract inhibition in patients (A) sensitized to birch pollen extract but lacking IgE to Bet v 1, Bet v 2, and Bet v 4, (74/1263) or with the highest serum level of IgE to Bet v 1 (26 within 1263), and (B) in patients with sensitization to extracts of ragweed (18), mugwort (18), pellitory (20), Plantago (19), and plane tree (20), but not to their respective major allergenic molecule, profilins and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7 (ImmunoCAP) and extract inhibition tests were performed with the same rBet v 7.

The role of molecular diagnosis in anaphylactic patients with dual or triple-sensitization to Hymenoptera venoms

Bemanian, M.H., Shokouhi Shoormasti, R., Arshi, S. et al.  Allergy Asthma Clin Immunol 20, 22 (2024). https://doi.org/10.1186/s13223-024-00885-9

Abstract

Background

The poly-sensitization to Hymenoptera venom makes it difficult to select genuine allergens for immunotherapy and increases patients’ costs. The objective of this study was to determine the culprit allergen in dual or triple-sensitized patients to three Hymenoptera venoms through molecular diagnosis and evaluating the results of incorporating the molecular diagnosis with skin tests.

Methods

Thirty-two patients with anaphylactic reactions and dual or triple-sensitization to Hymenoptera venoms in skin tests entered this study. IgE-sensitization to whole extracts and molecules of Apis mellifera (Api m), Vespula vulgaris (Ves v), and Polistes dominulus (Pol d) was evaluated utilizing ALEX or ImmunoCAP.

Results

A Wheal diameter of intradermal test for Hymenoptera venoms according to anaphylaxis grades. 
B The specific IgE concentration to allergenic extracts and molecules of Hymenoptera venoms
according to anaphylaxis grades

Twenty-nine patients (90.6%) were male. IgE-sensitization to at least one of the allergenic molecules related to Apis mellifera, Vespula vulgaris, and Polistes dominulus was seen in 59.4, 53.1, and 21.9%, respectively. Among 32 patients, 14 (43.8) and 8 (25%), were mono-sensitized to Api m and Ves v components in ALEX, respectively. Double sensitization to Hymenoptera was identified in 18.8% of patients in ALEX.

Navigating Food Allergies: Advances in Diagnosis and Treatment Strategies

Peddi N, Muppalla S, Sreenivasulu H, et al. Cureus 16(3): e56823. doi:10.7759/cureus.56823

Abstract

Food allergy is a major health concern worldwide, encompassing both immunologic and non-immunologic reactions. This review thoroughly examines the pathophysiology, clinical manifestations, and treatment options for various types of food allergies. Immunologic food allergies, including IgE-mediated reactions such as oral allergy syndrome and systemic anaphylaxis, pose various diagnostic and management challenges. Non-IgE-mediated reactions such as food protein-induced enterocolitis syndrome, dermatitis herpetiformis, and proctocolitis necessitate individualized patient care. In addition, mixed reactions such as eosinophilic esophagitis and atopic dermatitis complicate the clinical picture.

Lupin, a potential "hidden" food anaphylaxis allergen: An alert from the Allergy-Vigilance Network®.

Pouessel G, Sabouraud-Leclerc D, Beaumont P, Divaret-Chauveau A, Bradatan E, Dumond P, Karaca Y, Renaudin JM, Metz-Favre C, Delalande D, Correard AK, Tscheiller S, Van der Brempt X. Allergy. 2024 Mar 22. doi: 10.1111/all.16107.

To the Editor,

Lupin is a legume considered as an emerging food allergen, but the true prevalence of lupin allergy is not known.1 Due to the increasing consumption of lupin and its potential cross-reactivity with peanut, the Allergy-Vigilance Network® (AVN) aimed to report lupin-induced anaphylaxis cases and compare their main characteristics to other foods (See Data S1 for Material and Methods).

Main characteristics of 62 patients with a lupin-induced anaphylaxis
recorded by the Allergy-Vigilance Network® and comparisons by age groups

Of the 2708 cases of food-induced anaphylaxis documented by AVN (2002-2020), 62 (2.3%) cases were induced by lupin and cases are presented by time periods and according to total number of food-induced anaphylaxis cases (Figure S1). The main characteristics of these 62 cases (mean age: 32.1 years [SD: 21.4], 35% in children <18 years, 66% in females) are presented.

Current Understanding of Immune Thrombocytopenia: A Review of Pathogenesis and Treatment Options

Mititelu A, Onisâi MC, Roșca A, Vlădăreanu AM. Int J Mol Sci. 2024 Feb 10;25(4):2163. doi: 10.3390/ijms25042163. 

Abstract

Pathogenesis of immune thrombocytopenia and targets for drug action

The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP is a heterogeneous disease with an unpredictable evolution. Although the pathogenesis of ITP is currently better known and its etiology has been extensively studied, up to 75% of adult patients with ITP may develop chronicity, which represents a significant burden on patients’ quality of life. A major risk of ITP is bleeding, but knowledge on the exact relationship between the degree of thrombocytopenia and bleeding symptoms, especially at a lower platelet count, is lacking. The actual management of ITP is based on immune suppression (corticosteroids and intravenous immunoglobulins), or the use of thrombopoietin receptor agonists (TPO-RAs), rituximab, or spleen tyrosine kinase (Syk) inhibitors.