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Asthma phenotypes and IgE responses

The discovery of IgE represented a major breakthrough in allergy and asthma research, whereas the clinical interest given to IgE in asthma has been blurred until the arrival of anti-IgE biotherapy. Novel facets of the complex link between IgE and asthma have been highlighted by the effect of this treatment and by basic research. In parallel, asthma phenotyping recently evolved to the concept of endotypes, relying on identified/suspected pathobiological mechanisms to phenotype patients, but has not yet clearly positioned IgE among biomarkers of asthma.

In this review, we first summarise recent knowledge about the regulation of IgE production and its main receptor, FcRI. In addition to allergens acting as classical IgE inducers, viral infections as well as air pollution may trigger the IgE pathway, notably resetting the threshold of IgE sensitivity by regulating FcRI expression. We then analyse the place of IgE in different asthma endo/phenotypes and discuss the potential interest of IgE among biomarkers in asthma.

Recent pharmacological developments in the treatment of perennial and persistent allergic rhinitis.

Allergic rhinitis (AR) has a major negative impact on patients' quality of life (QoL) and carries a high socio-economic burden. This is particularly the case for patients who experience symptoms for extended periods of time (i.e. those with perennial (PAR) or persistent AR (PER), depending on the classification system used).

This review covers available pharmacological advances and recent developments in the treatment of PAR or PER. Areas covered: Pharmacological AR treatment is used to reduce symptom burden and help restore patients' normal daily routine. Traditionally, non-sedating antihistamines and intranasal corticosteroids (INS) were the two drug classes recommended for use first line. These, along with anti-leukotrienes, decongestants, mast cell stabilizers and anti-cholinergics, constituted the bulk of the AR treatment arsenal. MP29-02 (Dymista(®), Meda, Solna, Sweden) is the most recent addition to that arsenal. It is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) delivered in a single spray and has surpassed available therapies in terms of symptom control and treatment response. Other relatively new treatments for PAR or PER include H3 antihistamines, toll-like receptor (TLR) agonists, cellulose powders and micro-emulsions, novel biomolecular formulations and omalizumab. Each of these new additions is reviewed here.

Expert opinion: A new AR drug class has recently been introduced (i.e. RO1AD58). Currently MP29-02 is the only treatment option within this drug class. It can be estimated that combination treatments like MP29-02 will become the mainstay of PAR and PER therapy since use will result in better compliance, improved efficacy over INS and a faster response together with good levels of tolerability. The challenge is to find other equally, or more effective, combination treatments, as has been the therapeutic standard in bronchial asthma for decades. The potential of biologics, as well as TLR-agonists and other new treatment options needs to be further evaluated.

Clinical presentation, allergens, and management of wheat allergy.

IgE-mediated allergy to wheat proteins can be caused by exposure through ingestion, inhalation, or skin/mucosal contact, and can affect various populations and age groups. Respiratory allergy to wheat proteins is commonly observed in adult patients occupationally exposed to flour, whereas wheat food allergy is more common in children. Wheat allergy is of growing importance for patients with recurrent anaphylaxis, especially when exercise related. The diagnosis of wheat allergy relies on a consistent clinical history, skin prick testing with well-characterized extracts and specific IgE tests.

The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several wheat components. However, a high degree of heterogeneity has been found in the recognition pattern of allergens among patient groups with different clinical profiles, as well as within each group. Thus, oral provocation with wheat or the implicated cereal is the reference test for the definitive diagnosis of ingested wheat/cereal allergy.

Risk Factors and Comorbidities in Chronic Rhinosinusitis.

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Chronic rhinosinusitis (CRS) is a heterogeneous disorder that creates a significant burden on the healthcare system. It is caused by a combination of inflammatory, environmental, and host factors; however, the precise mechanism of how each factor leads to CRS continues to be a source of debate. Previous data regarding this topic is often inconsistent or of lower quality.

In this article, we review the recent literature on the risk factors and comorbidities in CRS. Large population-based studies have helped establish smoking as a significant risk factor for CRS. The focus has now shifted towards smoking and its effect on long-term outcomes after endoscopic sinus surgery (ESS). Ciliary dyskinesia, both primary and secondary, can affect both the sinonasal cavity and lower airways simultaneously by decreasing the beat frequency of cilia and inducing mucostasis. The effects of secondary dyskinesia may be reversible and there is some evidence to suggest the use of topical mucolytics in patients with CRS. Allergy and variants of sinonasal anatomy have been hypothesized to increase the risk of developing CRS by inducing chronic inflammation and obstructing the sinus ostia. Nevertheless, emerging data regarding these topics continue to produce inconclusive results. Inflammation of the upper and lower airways can occur simultaneously as seen in patients with asthma and aspirin sensitivity.

The connection between these pro-inflammatory disease states has been known for many years. Newer evidence include large population-based studies and studies that correlate objective tests, such as computer tomography scans to pulmonary function tests. However, the treatment of CRS and its effects on obstructive airway disease continues to be a topic of debate. More large prospective studies are needed in order to continue refining our knowledge of the disease processes in CRS.

Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations.

BACKGROUND: Management of rhinosinusitis during pregnancy requires special considerations.
OBJECTIVES: 1. Conduct a systematic literature review for acute and chronic rhinosinusitis (CRS) management during pregnancy. 2. Make evidence-based recommendations.

METHODS: The systematic review was conducted using MEDLINE and EMBASE databases and relevant search terms. Title, abstract and full manuscript review were conducted by two authors independently. A multispecialty panel with expertise in management of Rhinological disorders, Allergy-Immunology, and Obstetrics-Gynecology was invited to review the systematic review. Recommendations were sought on use of following for CRS management during pregnancy: oral corticosteroids; antibiotics; leukotrienes; topical corticosteroid spray/irrigations/drops; aspirin desensitization; elective surgery for CRS with polyps prior to planned pregnancy; vaginal birth versus planned Caesarian for skull base erosions/ prior CSF rhinorrhea.

RESULTS: Eighty-eight manuscripts underwent full review after screening 3052 abstracts. No relevant level 1, 2, or 3 studies were found. Expert panel recommendations for rhinosinusitis management during pregnancy included continuing nasal corticosteroid sprays for CRS maintenance, using pregnancy-safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspirin desensitization for aspirin exacerbated respiratory disease. The manuscript presents detailed recommendations.

CONCLUSIONS: The lack of evidence pertinent to managing rhinosinusitis during pregnancy warrants future trials. Expert recommendations constitute the current best available evidence.

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