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Monthly Archives

July 2020

Protocols for the Study of Allergic Rhinitis Therapies

Utility of Environmental Exposure Unit Challenge Protocols for the Study of Allergic Rhinitis Therapies

By Selected articles

Lubnaa Hossenbaccus, Lisa M. Steacy, Terry Walker, Anne K. Ellis.

Current Allergy and Asthma Reports (2020) 20:34. https://doi.org/10.1007/s11882-020-00922-8

Allergic rhinitis is an inflammatory disease of the nasal mucosa triggered by allergen exposure in sensitized patients. This study explores how the Environmental Exposure Unit (EEU) experimental model can be used to understand new therapies for allergic rhinitis. This study evaluated recent advances in allergic rhinitis therapies using the EEU model.

The EEU models are experimental models for the study of allergic rhinitis, including but not limited to phase 3 efficacy outpatient studies and outdoor park studies. Their use is increasing for the study of combination therapies, immunotherapies and novel AR treatments. Some examples include a combined antihistamine/corticosteroid nasal spray formulation, which was seen to have a faster onset of action relative to the therapies individually, house dust mite sublingual immunotherapy tables that have demonstrated to be safe and effective, a novel peptide-based immunotherapy approach effective in reducing grass pollen allergic rhinitis, and nasal filters that reduce seasonal AR symptoms.

The EEUs are controlled, reproducible and unique models for the study of allergic rhinitis therapies. EEUs provide valuable efficacy about the efficacy, onset and duration of action and dose-related impacts of allergic rhinitis therapies, with direct clinical relevance. Unlike phase 3 efficacy trials and park studies which rely on the natural environment, EEUs allow for the control of study variables, such as humidity, temperature, and allergen distribution. Allergic rhinitis symptoms generated in EEUs are comparable with natural pollen seasons which allows for allergen-specific research to continue even outside of the natural season.

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Transition of adolescents and young adults with allergy and asthma

EAACI Guideline on the effective transition of adolescents and young adults with allergy and asthma

By Selected articles

Graham Roberts, et al.

Allergy. 2020 Jun 19. doi: 10.1111/all.14459. Online ahead of print.

Adolescents and young adults represent a large group of patients with allergic rhinitis and/or asthma. Most times their treatment is complicated due to the biological and psychosocial changes that occur as they grow. Sometimes they have difficulty in understanding the consequences of their disease, failing to take responsibility for self-management, leading to suboptimal adherence and other negative consequences. The transitional care should address the psychological, medical, educational and vocational needs of adolescents and young adults.

The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline that provides evidence-based recommendations for healthcare professionals to support the transitional care of adolescents and young adults with allergic rhinitis and/or asthma.

This guideline includes general recommendations on operating a clinical service for these patients, which include: starting the transition as early as 11-13 years old, using a structured, multidisciplinary approach, ensuring they fully understand their condition and have resources they can access, active monitoring of adherence and discussing any implications for further education and work.

Specific allergy and asthma transition recommendations include simplifying medication regimes and using reminders, focusing on areas where these patients are not confident and involving peers in training them. Identifying and managing psychological and socioeconomic issues impacting disease control and quality of life; enrolling the family in assisting them to undertake self-management and encouraging them to let their friends know about their allergies and asthma are also recommendations of this guideline.

National healthcare systems may need to adapt these recommendations according to each culture. If optimal care is received by adolescents and young adults, they will become expert adult patients with the knowledge and skills to manage their condition throughout their lifes.

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Urticaria (angioedema) and COVID- 19 infection

Urticaria (angioedema) and COVID- 19 infection

By Selected articles

Mojgan Najafzadeh, Fanila Shahzad, Nader Ghaderi, Kaveh Ansari, Badie Jacob, Andrew Wright

J Eur Acad Dermatol Venereol . 2020 Jun 11;10.1111/jdv.16721. doi:10.1111/jdv.16721. Online ahead of print.

The relationship between urticaria and COVID-19 infection has rarely been reported, however, it has been reported that in addition to the conventional respiratory symptoms, some COVID-19 patients also have skin manifestations, such as urticaria and angioedema.

This is a case study of an elderly man who first presented with generalised pruritic hives with a diameter of 1,5 to 8,0 cm, general malaise, fatigue, temperature and sore throat. He was negative for parasitic and bacterial infections, however presented low white blood cells and lymphopenia. The CT chest showed pneumonia with bilateral and subpleural areas of ground-glass opacification, consolidation affecting the lower lobes, thus confirming the diagnosis of COVID-19.

Although the relationship between urticaria and infection has rarely been reported, literature suggests that urticaria and angioedema can be induced by viral and bacterial infections. Urticaria has been associated before with Cytomegalovirus, Herpesvirus and Epstein-Barr virus. It was also found that once the viral infection was controlled, urticaria manifestations cleared up.

One study with 88 COVID-19 patients that analysed the cutaneous involvement found that 20,4 % presented with cutaneous manifestation, 8 of them developed it at disease onset, while 10 of the, developed it after hospitalisation. The cutaneous manifestations were erythematous rash, widespread urticaria and chickenpox-like vesicles.

Urticarial skin manifestations may be used as a possible diagnostic indicator in early COVID-19 stages.

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COVID-19: organization of an allergy clinic – an EAACI/ARIA Position Paper.

COVID-19 pandemic: Practical considerations on the organization of an allergy clinic – an EAACI/ARIA Position Paper

By Selected articles

Pfaar O, Klimek L, Jutel M, Akdis CA4, Bousquet J, Breiteneder H et al.

Allergy. 2020 Jun 12;10.1111/all.14453. doi: 10.1111/all.14453. Online ahead of print..

Earlier in March 2020, the World Health Organization (WHO) declared the “corona virus disease 2019 (COVID-19)” a pandemic viral disease, transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Since the first cases were reported in China, the number of infected patients and fatalities have been increasing worldwide. Typical symptoms of COVID-19 include general malaise, fever, respiratory problems, and especially cough and shortness of breath. Specialists in the field of allergies and associated airways diseases have been in the front line, taking care of patients.

Coronaviruses may be associated with aggravation of asthma exacerbations and allergic diseases (allergic rhinitis, atopic dermatitis, urticaria and drug hypersensitivity).

This review identified studies that reported allergic diseases as co-morbidities of COVID-19 patients compared to non-allergic patients. A panel of experts have developed recommendations for the optimal management of allergic clinics during the pandemic to ensure necessary safety.

Allergic patients diagnosed with or suspect to have COVID-19 should follow the local area treatment and quarantine guidance. In general, most medications should be continued. For those unable to attend clinics, have examinations and/or receive prescriptions, e-health and telemedicine can assess the value of specialized treatments, provide educations for self-management without the risk of infection and triage patients for urgent consultations, such as diagnostic testing in drug allergy or application of medication. When biologicals are used, the decision to continue a treatment should be made on a case basis since the safety and efficacy of the mentioned biologics in COVID-19 patients are unknown. Psychological care for allergic patients during the pandemic is also essential.

Patients with allergic rhinitis and other allergies should be informed accordingly when new evidence is available, making it possible to adapt to new therapies.

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Elucidation of Inverse Agonist Activity of Bilastine

Elucidation of Inverse Agonist Activity of Bilastine

By Articles about Bilastine

Hiroyuki Mizuguchi, et al.

Pharmaceutics 2020, 12, 525; doi: 10.3390/pharmaceutics12060525.

Histamine is a chemical mediator that causes pollinosis symptoms such as a sneezing, rhinorrhoea, nasal obstruction, nasal itching, and itching of the eyes. H1-antihistamines antagonize histamine H1, preventing it from binding to the histamine H1 receptor (H1R). Bilastine is a non-sedative recently launched H1-antihistamine which has high affinity for H1R. It is one of the H1-antihistamines that most satisfies the requirements of allergic rhinitis and asthma guidelines. Inverse agonists are thought to be more potent than neutral antagonists because they supress the intrinsic histamine signalling in addition to the H1-antihistamine effect. Nevertheless, there is a lack of information regarding bilastine inverse agonist activity.

This study assessed if bilastine has inverse agonist activity or not. HeLa cells that express H1R endogenously here used, and three methods applied: time-lapse Ca2+ imaging, inositol phosphates (IPs) accumulation and H1R gene expression. Intracellular calcium concentration was measured using Fluo-8. Inositol phosphates accumulation was assayed using [3H]myo-inositol. The H1R mRNA level was measured using real-time RT-PCR.

H1R intrinsic activity was shown by Ca2+ oscillation. Also, bilastine suppressed IPs formation and basal H1R gene expression in a dose-dependent manner.

These results elucidate that bilastine has an inverse agonist activity. Taking bilastine before pollen season, the H1R gene expression level can be kept low, improving pollinosis symptoms.

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rinitis-alergica-asma

Validation of the ARIA items to assess allergic rhinitis control (ARIA-C)

By Selected articles

Valero A, Del Cuvillo A, Navarro AM, Colás C, Sastre J, Mullol J.

[published online ahead of print, 2020 May 25]. Allergy. 2020;10.1111/all.14418. doi:10.1111/all.14418.

Allergic rhinitis is a chronic disease with a high prevalence with an impact on quality of life. The original Allergic Rhinitis and Its Impact on Asthma Guideline (ARIA) severity classification uses 4 items (sleep, daily activities/sport, work/school performance and troublesome symptoms) and defines allergic rhinitis as mild (no items affected) or moderate/severe (1 to 4 items affected). A validated modified three-level ARIA (mARIA) classification was proposed to discriminate allergic rhinitis severity between moderate (1 to 3 items affected) and severe (4 items affected).

The aim of this prospective, observational, cross-sectional study was to use the 4 original ARIA items to validate a three-level evaluation of allergic rhinitis control (ARIA-C): controlled, partially controlled and not controlled, by estimating control of symptoms, impairment in activities and respiratory function.

A total of 252 adult participants with moderate-to-severe allergic rhinitis were included using both mARIA severity criteria and a reflective total nasal symptom score (rTNSS) ≥ 8. They followed their routine treatments and were interviewed twice a month. Demographic, concomitant diseases, allergic sensitization, AR severity and impact on quality of life data were collected. Additionally, participants’ control was assessed with the validated Spanish version of the Rhinitis Control Assessment Test (RCAT).

At baseline, 20 % of the participants had their allergic rhinitis controlled with the ARIA-C. At follow-up, 30 % of them were controlled and 40 % partially controlled.

Disease control was evaluated and showed that the three categories of ARIA-C can effectively discriminate between controlled, partially controlled and not controlled allergic rhinitis. Its validation shows favorable and statistically significant results for test-retest reliability, convergent validity, discrimination among groups, and responsiveness to change.

These results suggest that the ARIA-C can be used to obtain a fast screening of patients with inadequate allergic rhinitis control, or to help their communication with specialists.

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Rinitis Alergica

Validation of the MASK-air® App for Assessment of Allergic Rhinitis

By Selected articles

Sastre J, Del Cuvillo A, Colás C, et al.

Allergy. 2020 May 25. doi: 10.1111/all.14415. Online ahead of print.

A mobile application (MASK-air®) has demonstrated usefulness in assessing patient behaviour in allergic rhinitis. This app measures general, nasal, ocular and asthma symptoms with a visual scale and daily medication intake.

The objective of this study was to validate the app for allergic rhinitis, comparing it to a written questionnaire for a month.

A total of 252 participants were randomly assigned to one of two groups: participants with allergic rhinitis who used the Spanish version of the app on a daily basis and participants with allergic rhinitis who were asked to use the questionnaire at days 1, 3, 7, 14, 21 and 28 and at a final visit one week later.

The usefulness of the allergic rhinitis app was evaluated at baseline and at the end using the Rhinitis Control Assessment Tool questionnaire. Other allergic rhinitis outcomes included treatment adherence, reflective total nasal symptom score, ocular symptom score, the modified ARIA severity classification, a quality-of-life questionnaire and daily visual analogue scales for nasal, conjunctival, asthma, and global for overall allergy symptoms, and the asthma control test for asthmatic patients at baseline and at end of study. Participants and specialists’ satisfaction with the app were evaluated using a Likert scale.

Most participants in the app group (90 %) had downloaded it to their smartphone and 92 % of them used it. Most users (88 %) reported being satisfied or very satisfied with the app, with 72% of the specialists reporting that their patients were satisfied.

At the end of the study, a relevant improvement on the Rhinitis Control Assessment Tool score was observed, but with no significant or clinically relevant difference between groups. Other outcomes were not different between study groups either.

This study demonstrated that the app contributed to the improvement of allergic rhinitis as effectively as the written questionnaire. It has shown that the MASK-air® app is practical ad useful.

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urticaria angioedema hipersensibilidad

IgM and IgA in Addition to IgG Autoantibodies against FcεRIα Are Frequent and Associated with Disease Markers of Chronic Spontaneous Urticarial

By Selected articles

Altrichter S, Zampeli V, Ellrich A, Zhang K, Church MK, Maurer M.

Allergy. 2020 May 23. doi: 10.1111/all.14412. Online ahead of print.

Chronic spontaneous urticaria (CSU) is a mast cell–driven skin disease characterized by the recurrence of transient wheals, angioedema, or both for more than 6 weeks. IgG-autoantibodies against the high affinity IgE-receptor, FcεRIα, contribute to the pathogenesis of autoimmune chronic spontaneous urticaria.

The objective of this study was to develop an ELISA to assess serum levels of IgG, IgM and IgA autoantibodies against FcεRIα and to explore if their presence is linked to clinical features of CSU including the response to autologous serum skin testing (ASST).

Serum samples of 35 people with CSU and 52 healthy controls were tested using an ELISA for IgG, IgM and IgA autoantibodies to FcεRIα. 24 % of CSU patients had high serum levels of IgG-anti-FcεRIα compared to 6 % in healthy controls. IgM and IgA levels were positive for more than half of people with CSU, compared to 5 % in healthy controls. Elevated IgM, but not IgG nor IgA autoantibodies, were significantly more common in ASST-positive CSU patients (72 %) compared with ASST-negative patients (33 %). Also, elevated levels of IgM-anti-FcεRIα, but not of IgG or IgA against FcεRIα, were linked to low blood basophil and eosinophil counts.

In conclusion, people with CSU have increased serum levels of IgM-anti-FcεRIα which may relate to characteristics of autoimmune CSU.

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enfoque rinitis alergica

Local Allergic Rhinitis Revisited

By Selected articles

Vardouniotis A, Doulaptsi M, Aoi N, Karatzanis A, Kawauchi H, Prokopakis E.

Curr Allergy Asthma Rep. 2020 May 19;20(7):22. doi: 10.1007/s11882-020-00925-5.

Chronic rhinitis can be classified in allergic rhinitis and non-allergic rhinitis (NAR). Allergic rhinitis is an inflammatory disease of the nasal mucosa with symptoms such as nasal discharge, sneezing, nasal itching and congestion. It is characterized by eosinophilic inflammation as a result of IgE-sensitization to seasonal or perennial aeroallergens. NAR is a highly heterogeneous group that includes disorders characterized by either immunological or neurogenic inflammation (hormonal rhinitis, rhinitis of the elderly, gustatory rhinitis, drug-induced rhinitis and occupational rhinitis).

Local allergic rhinitis (LAR) is neither classical allergic rhinitis neither NAR. Its symptoms, duration, severity and complications are similar to those of allergic rhinitis and can affect adults and children. It is characterized by a localized nasal allergic response and the absence of systemic atopy since specific IgE antibodies are produced locally. A Th2 pattern of mucosal cell infiltration during natural exposure to aeroallergens and a positive nasal allergen provocation test (NAPT) response, with the release of inflammatory mediators such as mast cells, eosinophils, IgE, B cells, and T cells, are detected.

LAR is an underdiagnosed entity that affects a significant number of people with chronic rhinitis, mainly in Mediterranean countries. It is a chronic condition that tends to worsen and is associated with conjunctivitis and bronchial symptoms. Its diagnosis is a challenge and should be based on a detailed clinical history, the demonstration of a nasal allergic response to aeroallergens by NAPT in patients with negative skin prick test and non-detectable serum sIgE, and the exclusion of chronic rhinosinusitis with/without nasal polyps.

Oral antihistamines and intranasal corticosteroids, alone or in an intranasal formulation of fluticasone + azelastine in severe cases, are the two traditional bases of allergic rhinitis treatment. Clinical experience indicates that these drugs are similarly effective in LAR patients. Also, subcutaneous immunotherapy has shown to be effective and well tolerated in LAR. A correct early diagnosis through nasal allergen challenge enables the establishment of an etiologic treatment, improving quality of life and preventing the development of lower airway disease.

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