Telemedicine with special focus on allergic diseases and asthma-Status 2022: An EAACI position paper.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID-19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face-to-face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma.

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as a critical player in the development and progression of allergy and asthma. It is primarily produced by epithelial cells and functions as a potent immune system activator. TSLP acts through interaction with its receptor complex, composed of the TSLP receptor (TSLPR) and interleukin-7 receptor alpha chain (IL-7Rα), activating downstream complex signalling pathways. The TSLP major isoform, known as long-form TSLP (lfTSLP), is upregulated in the airway epithelium of patients with allergic diseases. More research is warranted to explore the precise mechanisms by which short-form TSLP (sfTSLP) regulates immune responses. Understanding the dynamic interplay between TSLP and the dysfunctional epithelium provides insights into the mechanisms underlying allergy and asthma pathogenesis. Targeting TSLP represents an important therapeutic strategy, as it may upstream disrupt the inflammatory cascade and alleviate symptoms associated with allergic inflammation.

Bradykinin Metabolism and Drug-Induced Angioedema.

Bradykinin (BK) metabolism and its receptors play a central role in drug-induced angioedema (AE) without urticaria through increased vascular permeability. Many cardiovascular and diabetic drugs may cause BK-mediated AE. Angiotensin-converting enzyme inhibitors (ACEIs) and neprilysin inhibitors impair BK catabolism. Dipeptidyl peptidase-IV (DPP-IV) inhibitors reduce the breakdown of BK and substance P (SP). Moreover, angiotensin receptor blockers, thrombolytic agents, and statins may also induce BK-mediated AE. Understanding pathophysiological mechanisms is crucial for preventing and treating drug-induced AE.

Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment.

Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera, and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aimed to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross-reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on available immunotherapies. Major allergens of most insects were identified, and cross-reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy.

Extracorporeal membrane oxygenation (ECMO) and beyond in near fatal asthma: A comprehensive review.

The treatment of choice in severe asthma exacerbations with respiratory failure includes ventilatory support, both invasive and/or non-invasive, along with different kinds of asthma medication. Of note, the rate of mortality of patients with asthma has decreased substantially in recent years mainly due to significant advances in pharmacological treatment and other management strategies. However, the risk of death in patients with severe asthma who require invasive mechanical ventilation has been estimated between 6.5% and 10.3%. When conventional measures fail, rescue strategies, such as extracorporeal membrane oxygenation (ECMO) or extracorporeal CO2 removal (ECCO2R) may need to be implemented. While ECMO does not constitute a definitive treatment per se, it can minimize further ventilator associated lung injury (VALI) and can enable diagnostic-therapeutic maneuvers that cannot be performed without ECMO such as bronchoscopy and transfer for diagnostic imaging. Asthma is one of the diseases that is associated with excellent outcomes for patients with refractory respiratory failure requiring ECMO support, as shown by the Extracorporeal Life Support Organization (ELSO) registry. Moreover, in such situations, the use of ECCO2R for rescue has been described and utilized in both children and adults and is more widely spread in different hospitals than ECMO. In this article, we aim to review the evidence for the usefulness of extracorporeal respiratory support measures in the management of severe asthma exacerbations that lead to respiratory failure.

Symptoms of anxiety and depression in patients with persistent asthma: a cross-sectional analysis of the INSPIRERS studies.

OBJECTIVES: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms. METHODS: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built. RESULTS: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression. CONCLUSION: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.

Optimisation of the quality of care for patients with severe asthma: ASfarMA project.

Severe asthma has an important impact on patients and healthcare resources. Recently, the new specific treatments have defined a new scenario in which person-focused care and specialist multidisciplinary teams are necessary. Our Severe Asthma Unit (SAU) started the ASfarMA project along with an external human-centered design company to understand patients' vision of their illness, treatment, and healthcare experience, and to define the ideal SAU by performing a core group session, in-depth semistructured interviews and co-creation workshop. Herein, a series of tips classified as either 'transformative solutions' or 'quick wins', according to a value versus effort matrix are presented. Successful implementation of the proposed solutions will be valuable for patients and healthcare professionals, optimising patient care and resources. These findings can also be helpful to other SAUs or other humanisation projects involving complex, chronic and multidisciplinary pathologies.

EAACI position paper on the clinical use of the bronchial allergen challenge: Unmet needs and research priorities.

Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways.

Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients.

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

Feasibility and Acceptability of an Asthma App to Monitor Medication Adherence: Mixed Methods Study.

BACKGROUND: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). METHODS: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. RESULTS: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). CONCLUSIONS: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

ß-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy.

BACKGROUND: There is controversy whether taking ß-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). METHODS: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking ß-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. RESULTS: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took ß-blockers, 11.9% ACEI, 5.0% ß-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43-1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of ß-blockers or ACEI (OR: 1.14, 95% CI: 0.89-1.46, p = 0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took ß-blockers, none an ACEI. CONCLUSIONS: This trial provides robust evidence that taking ß-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629).

The EAACI-AAAAI-WAO Junior Members' joint survey: A worldwide snapshot of Allergy and Clinical Immunology specialty.

BACKGROUND: Education and training in Allergy and Clinical Immunology (A/I) are characterized by a great variability worldwide. However, objective and worldwide data regarding this topic are lacking. METHODS: To investigate personal information, education, and involvement in scientific societies of juniors engaged in A/I field, a questionnaire was developed by representatives from the JMs' boards of the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the World Allergy Organization (WAO). RESULTS: A total of 543 questionnaires were collected from 76 regions of all continents. The geographic distribution of responders was as follows: Africa-Middle East 3.0%, Asia-Pacific 21.4%, Europe 48.2%, Latin America 12.1%, and North America 15.3%. 59.0% of responders declared that A/I is recognized as a separate specialty in their country, Europe mostly accounting for that proportion. Primary interest in the field represents the main motivation for choosing A/I specialty. Concerning involvement in scientific societies, 41.1% of responders ever attended an EAACI Congress, 20.6% an AAAAI Congress, and 20.4% a WAO Congress. According to 40.3% of responders, scientific societies do not provide enough opportunities for young members, and 96.4% believes in a more intensive cooperation between the A/I Societies. CONCLUSIONS: The survey provides the first worldwide perspective about A/I specialty. It represents the first ever example of a structured collaboration between the junior members (JMs) of the three main A/I Societies. The findings suggest the need for harmonization, at least in terms of training and formation in the field of A/I worldwide.

The role of mobile health technologies in allergy care: An EAACI position paper.

Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed.

Non-eosinophilic asthma: current perspectives.

Although non-eosinophilic asthma (NEA) is not the best known and most prevalent asthma phenotype, its importance cannot be underestimated. NEA is characterized by airway inflammation with the absence of eosinophils, subsequent to activation of non-predominant type 2 immunologic pathways. This phenotype, which possibly includes several not well-defined subphenotypes, is defined by an eosinophil count <2% in sputum. NEA has been associated with environmental and/or host factors, such as smoking cigarettes, pollution, work-related agents, infections, and obesity. These risk factors, alone or in conjunction, can activate specific cellular and molecular pathways leading to non-type 2 inflammation. The most relevant clinical trait of NEA is its poor response to standard asthma treatments, especially to inhaled corticosteroids, leading to a higher severity of disease and to difficult-to-control asthma. Indeed, NEA constitutes about 50% of severe asthma cases. Since most current and forthcoming biologic therapies specifically target type 2 asthma phenotypes, such as uncontrolled severe eosinophilic or allergic asthma, there is a dramatic lack of effective treatments for uncontrolled non-type 2 asthma. Research efforts are now focusing on elucidating the phenotypes underlying the non-type 2 asthma, and several studies are being conducted with new drugs and biologics aiming to develop effective strategies for this type of asthma, and various immunologic pathways are being scrutinized to optimize efficacy and to abolish possible adverse effects.

Management of chronic spontaneous urticaria: a worldwide perspective.

BACKGROUND: The approaches to the diagnosis and treatment of chronic spontaneous urticaria (CSU) differ in various parts of the world. We sought to determine the adherence to international and national urticaria guidelines as well as the motives to deviate from the guidelines among physicians worldwide. METHODS: A web-based questionnaire was created and launched via e-mail by the World Allergy Organization (WAO) to representatives of all WAO Member Societies, the members of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the members of the WAO Junior Members Group (JMG), regardless of the specialty, affiliation, or nationality in March 2017. RESULTS: We received 1140 completed surveys from participating physicians from 99 countries. Virtually all participants (96%) were aware of at least one urticaria guideline and reported that they follow a guideline. However, one in five physicians who follow a guideline (22%) reported to deviate from it. Reliance on own clinical experience is the most frequent reason for deviation from guidelines or not following them (44%). Young (< 40 years) and less experienced physicians more often follow a guideline and less often deviate than older and experienced ones. Physicians who follow a urticaria guideline showed higher rates of routinely ordering a complete blood count, the erythrocyte sedimentation rate, C-reactive protein, anti-thyroid antibodies, and thyroid-stimulating hormone and of performing the autologous serum skin test as compared to those who do not. Physicians who follow a urticaria guideline showed higher rates of using second generation antihistamines as their first-line treatment of CSU (p = 0.001) and more frequently observed higher efficacy of these drugs (or had more confidence that it would work, p < 0.019) as compared to those who do not follow the guidelines. CONCLUSIONS: Physicians' characteristics (e.g. age, clinical experience, and specialty) and country specifics and regional features (e.g. availability of drugs for CSU treatment) importantly influence adherence to urticaria guidelines and CSU patient care and should be addressed in more detail in future research.

'Hidden' occupational allergens such as additives.

PURPOSE OF REVIEW: With the development of innovative technologies, new agents are continually introduced to the workplace. Some of these agents can act as hidden allergens whenever they are not declared in the product labels or whenever their health hazards are unknown. This review article focuses on the identification and description of unusual and/or hidden allergens recently incriminated in occupational diseases. RECENT FINDINGS: Occupational exposure is an important global health issue that can induce respiratory and cutaneous disorders, as well as life-threatening anaphylaxis. Apart from the classic forms of occupational exposure, reports have emerged from nonconventional or newly identified allergens or additives. These compounds are substances added to another in order to alter or improve the general quality or to counteract undesirable properties, and some of them may behave as potent and frequently hidden allergens. These highly uncommon and/or hidden allergens belong to several categories: foods, spices, cosmetics, insects, enzymes, chemicals, drugs, preservatives, and coloring agents, among others. SUMMARY: A high level of suspicion and awareness about the potential hidden allergens is necessary to ascertain the allergens implicated. It is of utmost importance to identify the specific eliciting agents of the occupational diseases in order to avoid strictly further exposure to them.

Satisfaction and quality of life of allergic patients following sublingual five-grass pollen tablet immunotherapy in Spain.

BACKGROUND: Five-grass pollen tablet is an effective and well-tolerated therapy for patients with allergic rhinoconjunctivitis (ARC). This trial sought to determine the satisfaction and health-related quality of life (HRQoL) of patients undergoing this treatment. METHODS: This was a cross-sectional, multicentre, observational, naturalistic study, following a discontinuous pre- and co-seasonal five-grass pollen regimen over two seasons in Spain (2012, 2013). The HRQoL of the patients was measured with the specific Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for adults, adolescent (AdolRQLQ), or paediatric (PRQLQ) patients. Treatment satisfaction was assessed by the Satisfaction Scale for Patients Receiving Allergen Immunotherapy (ESPIA) questionnaire. Patients/investigators were surveyed on beliefs and attitudes towards the five-grass pollen tablet. ARC evolution according to allergic rhinitis and its impact on asthma (ARIA) criteria and treatment adherence were evaluated. RESULTS: Among the 591 ARC patients included, the mean (SD) HRQoL scores were 1.40 (1.1) in adults, 1.33 (1.1) in adolescents, and 1.15 (1.1) in children, indicating low levels of impairment (scale 0-6). ESPIA answers showed high levels of satisfaction, with an average score of 69.2 (scale 0-100). According to ARIA criteria, 88.2% of patients reported improvement of ARC. Moreover, this was accompanied by a reduced use of symptomatic medication. Adherence to treatment was estimated at 96.8%. In general, both patients and specialists exhibited a positive attitude towards five-grass pollen tablet treatment. CONCLUSION: ARC patients treated with five-grass pollen tablet showed favourable levels of HRQoL and treatment satisfaction, with concomitant improvements in ARC and symptomatic medication use, which translated into high levels of treatment adherence and a positive attitude towards five-grass pollen tablet.

Erratum to: Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0095-x.].