Adherence and persistence in allergen immunotherapy (APAIT): A reporting checklist for retrospective studies.

BACKGROUND: Adherence is essential for the long-term efficacy of allergen immunotherapy (AIT) and has been evaluated in numerous retrospective studies. However, there are no published guidelines for best practice in measuring and reporting adherence or persistence to AIT, which has resulted in substantial heterogeneity among existing studies. The 'adherence and persistence in AIT (APAIT)' checklist has been developed to guide the reporting, design and interpretation of retrospective studies that evaluate adherence or persistence to AIT in clinical practice. METHODS: Five existing checklists, focussing on study protocol design, the use of retrospective databases/patient registries, and the appraisal and reporting of observational studies, were identified and merged. Relevant items were selected and tailored to be specific to AIT. The content of the checklist was discussed by 11 experts from Europe, the United States and Canada, representing allergy, healthcare and life sciences, and health technology appraisal. RESULTS: The APAIT checklist presents a set of items that should either be included or at least considered, when reporting retrospective studies that assess adherence or persistence to AIT. Items are organized into four categories comprising study objective, design and methods, data analysis, and results and discussion. The checklist highlights the need for clarity and transparency in reporting and emphasizes the importance of considering potential sources of bias in retrospective studies evaluating adherence or persistence to AIT. CONCLUSIONS: The APAIT checklist provides a pragmatic guide for reporting retrospective adherence and persistence studies in AIT. Importantly, it identifies potential sources of bias and discusses how these influence outcomes.

Manifesto on united airways diseases (UAD): an Interasma (global asthma association - GAA) document.

OBJECTIVE: The large amount of evidence and the renewed interest in upper and lower airways involvement in infectious and inflammatory diseases has led Interasma (Global Asthma Association) to take a position on United Airways Diseases (UAD). METHODS: Starting from an extensive literature review, Interasma executive committee discussed and approved this Manifesto developed by Interasma scientific network (INES) members. RESULTS: The manifesto describes the evidence gathered to date and defines, states, advocates, and proposes issues on UAD (rhinitis, rhinosinusitis and nasal polyposis), and concomitant/comorbid lower airways disorders (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea) with the aim of challenging assumptions, fostering commitment, and bringing about change. UAD refers to clinical pictures characterized by the coexistence of upper and lower airways involvement, driven by a common pathophysiological mechanism, leading to a greater burden on patient's health status and requiring an integrated diagnostic and therapeutic plan. The high prevalence of UAD must be taken into account. Upper and lower airways diseases influence disease control and patient's quality of life. CONCLUSIONS: Patients with UAD need to have a timely and adequate diagnosis, treatment, and, when recommended, referral for management in a specialized center. Diagnostic testing including skin prick or serum specific IgE, lung function, fractional exhaled nitric oxide (FeNO), polysomnography, allergen-specific immunotherapies, biological therapies and home based continuous positive airway pressure (CPAP) whenever these are recommended, should be part of the management plan for UAD. Education of medical students, physicians, health professionals, patients and caregivers on the UAD is needed.

Manifesto on inhaled triple therapy in asthma: an Interasma (Global Asthma Association - GAA) document.

Objective: The optimal use of drug combinations for the management of asthma is providing significant results. This has prompted Interasma (Global Asthma Association) to take a position on inhaled triple therapy in asthma.Methods: We performed an extensive literature research to clinical trials, meta-analyses, randomized controlled trials and systematic reviews.Results: Starting from an extensive literature review, Interasma executive committee discussed and approved this Manifesto, developed by Interasma scientific network (INES) members.Conclusions: The manifesto describes the evidence gathered to date and states, advocates, and proposes issues on inhaled corticosteroid (ICS) plus long-acting beta 2 agonist (LABA) and long-acting muscarinic antagonists (LAMA) with the aim of challenging assumptions, fostering commitment, and bringing about change.

Efficacy and safety of sublingual allergen immunotherapy.

Sublingual immunotherapy (SLIT)-tablets represent a new allergen immunotherapy option for clinicians. In North America, there are five SLIT-tablets approved for the treatment of allergic rhinoconjunctivitis (ARC). No SLIT-drops products are currently approved in the United States or Canada. This work reviewed the efficacy of the timothy grass SLIT-tablet, five-grass SLIT-tablet, ragweed SLIT-tablet, house-dust mite SLIT-tablet, and tree SLIT-tablet in patients with ARC. All the SLIT-tablets showed consistent clinical efficacy for the treatment of ARC in large, double-blind, placebo-controlled trials, including for both patients who were monosensitized and those who were polysensitized. Treatment with house-dust mite SLIT-tablet has shown efficacy in patients who are pollen sensitized during their respective pollen seasons. In contrast to SLIT-tablets, efficacy studies of SLIT-drops show high heterogeneity of treatment effect. Although data are scarce, data that compared the efficacy of SLIT-tablets versus ARC pharmacotherapy generally indicated that SLIT-tablets had a greater benefit than pharmacotherapy when compared with placebo, particularly for perennial ARC. When compared with subcutaneous immunotherapy, analysis of these data indicated that SLIT-tablets had a benefit over subcutaneous immunotherapy in regard to safety but somewhat less benefit in regard to efficacy. The safety of SLIT-tablets has been well documented, and a U.S. Food and Drug Administration class label with safety considerations is present in the prescribing information for all SLIT-tablets. No new safety signals have been observed after reinitiating SLIT-tablets after a short treatment interruption.

Essentials of allergen immunotherapy: A primer for the practitioner.

It has been more than a decade since the most recent allergen immunotherapy (AIT) practice parameter was published and 5 years since a focused practice parameter on sublingual immunotherapy (SLIT) was issued. There is an unmet need, therefore, for a more up-to-date, concise summary of AIT to be published to provide allergy/immunology practitioners, allergy/immunology fellows-in-training, medical students, residents, and other health-care practitioners with the most current information available on AIT. The Allergen Immunotherapy Primer (AITP) is not intended to define a standard of care or to be inclusive of all proper methods of care, nor is it intended to replace or supplant established AIT practice parameters; rather, the goal of this AITP is to supplement the established practice parameters and to serve primarily as an updated tool for the practicing allergist/immunologist, allergy/immunology trainees, and health-care professionals seeking practical and concise information with regard to AIT. Primer topics include the history of AIT; descriptions of the mechanisms and biomarkers of subcutaneous immunotherapy (SCIT) and SLIT; the efficacy and safety of SCIT; the efficacy and safety of SLIT, pediatric SLIT, and SCIT; the long-term efficacy of SLIT and SCIT; long-term adherence strategies for AIT; the implications of real-world data for AIT; the role of AIT for asthma; patterns of cross-allergenicity among pollens; a practical implementation guide for optimized construction of AIT vaccines; standardization of allergen extracts; updated information on federal regulations about the United States Pharmacopeia and the compounding of allergenic extracts; an update on AIT venom immunotherapy; the advantages and disadvantages of accelerated immunotherapy regimens; the important role of shared decision-making in AIT and how it can be incorporated into the informed consent process; and a forecast of future directions in allergen immunotherapy.

Efficacy of sublingual immunotherapy tablets in dust mite and pollen allergy.

The latest evidence on the mechanisms, efficacy, and safety of sublingual immunotherapy (SLIT) was reviewed. Interleukin (IL) 35 and IL-35-producing regulatory T cells were assessed as new biomarkers for SLIT responsiveness. A detailed analysis of clinical studies, including timothy grass pollen, 5-grass pollen, ragweed, and house-dust mite SLIT tablets, was provided, including a comparative analysis of efficacy and safety of SLIT versus subcutaneous immunotherapy.

Shifts in allergy practice in a COVID-19 world: Implications of pre-COVID-19 national health care provider and patient surveys of treatments for nasal allergies.

Background: Most U.S. patient and health care provider surveys with regard to nasal allergy treatments were conducted before sublingual immunotherapy (SLIT)-tablets and allergy immunotherapy (AIT) shared decision-making tools were available. Objective: Patient and health care provider surveys with regard to current perceptions of nasal allergy burden, symptoms, and treatments were conducted to compare with previous surveys and provide insight into the use of SLIT-tablets and AIT shared decision-making tools. Methods: From November-December 2019, adults (N = 510) diagnosed with nasal allergies and health care providers (N = 304) who treated nasal allergies in the United States completed surveys with regard to nasal allergy management. Results: Of the patient respondents, 42% reported that their symptoms were only somewhat controlled and 48% had avoided activities because of their nasal allergies. In all, 38% were using only over-the-counter (OTC) medications for treatment, and 42%, 7%, and 8% had ever received subcutaneous immunotherapy (SCIT), sublingual allergy drops, or SLIT-tablets, respectively; 56% and 85% reported that they had never discussed SCIT or SLIT, respectively, with their health care provider. Of the health care provider respondents, 45%, 58%, and 20% were very likely to discuss OTC medications, SCIT, or SLIT, respectively. Allergists were more inclined to discuss SCIT with their patients than other health care providers (82% versus 33%, respectively). Most allergists (67%) and other health care providers (62%) reported that they did not use an AIT shared decision-making tool, primarily because of unawareness. Conclusion: The patients with nasal allergies continued to report inadequate symptom control and activity impairment. SLIT-tablets and AIT shared decision-making tools were underused. In the coronavirus disease 2019 era, social distancing may limit office visits, which impacts SCIT administration and prompts increased use of telemedicine and a possible advantage for at-home-administered SLIT-tablets over SCIT.

Allergy to oak pollen in North America.

Background: Oak pollen is an important allergen in North America. The genus Quercus (oak) belongs to the family Fagaceae under the order Fagales. Objective: The objective of this article was to narratively review the oak pollen season, clinical and epidemiologic aspects of allergy to oak pollen, oak taxonomy, and oak allergen cross-reactivity, with a focus on the North American perspective. Methods: A PubMed literature review (no limits) was conducted. Publications related to oak pollen, oak-related allergic rhinitis with or without conjunctivitis, and oak-related allergic asthma were selected for review. Results: Oak species are common throughout the United States and contribute up to 50% to overall atmospheric pollen loads. Mean peak oak pollen counts can reach >2000 grains/m³. The start of the oak pollen season generally corresponds to the seasonal shift from winter to spring based on latitude and elevation, and may begin as early as mid February. The duration of the season can last > 100 days and, in general, is longer at lower latitudes. In the United States, ∼30% of individuals with allergy are sensitized to oak. The oak pollen season correlates with increased allergic rhinitis symptom-relieving medication use and asthma-related emergency department visits or hospitalizations. Oak falls within the birch homologous group. Extensive immunologic cross-reactivity has been demonstrated between oak pollen and birch pollen allergens, and, more specifically, their major allergens Que a 1 and Bet v 1. The cross-reactivity between oak and birch has implications for allergy immunotherapy (AIT) because guidelines suggest selecting one representative allergen within a homologous group for AIT, a principle that would apply to oak. Conclusion: Allergy to oak pollen is common in North America and has a substantial clinical impact. Oak pollen allergens are cross-reactive with birch pollen allergens, which may have implications for AIT.

Association of the CD14 C159T and the Toll-like receptor 4 Asp299Gly polymorphisms with various phenotypes of asthma in adults from Crimea.

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00-2.32] and overdominant (OR 1.55 [95% CI, 1.01-2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07-0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07-0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07-0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.

Serum immunoglobulin E reactivity to cross-reacting panallergen components in north-eastern Poland patients pollen sensitized.

Background: The presence of immunoglobulin E (IgE), which cross-reacts with allergen components, such as profilins, polcalcins, and cross-reacting carbohydrate determinants (CCD), creates a problem when selecting patients for allergen immunotherapy by using conventional methods. The aim of this study was to evaluate the prevalence of sensitization to profilins, polcalcins, and CCDs in patients with seasonal pollen allergic rhinitis. Methods: The study was performed on a group of 112 patients with seasonal pollen allergic rhinitis, ages 14 to 55 years, with sensitization to at least one seasonal allergen (IgE > 0.7 kUA/L). The presence of IgE sensitization to recombinant (r) Bet v 2, rPhl p 12, rBet v 4, rPhl p 7, and CCDs, in addition to rBet v 1, rPhl p 1, rPhl p 5, was evaluated by using a multiparameter immunoblot. Results: Among the studied patients, 64.3, 80.4, and 41.1% were sensitized to birch, timothy grass, and mugwort pollen, respectively. Sensitization to profilins rBet v 2/Phl p 12 was demonstrated in 28.6%, to polcalcins Bet v 4/Phl p 7 in 8.9%, and to CCDs in 25%. In 29.3%, serum IgE reactivity to any of the cross-reactive components could be demonstrated. Serum IgE reactivity to rBet v 2 was always accompanied by IgE reactivity to rPhl p 12, and IgE reactivity to rBet v 4 was always accompanied by IgE reactivity to rPhl p 7. Among the patients with pollinosis co-sensitized to at least two allergen sources according to extract-based diagnosis, possible false-positive results due to sensitization to cross-reactive components were detected in 17.9%. Conclusion: Evaluation of sensitization to cross-reacting components may be useful in evaluation of patients with pollen allergy who are being assessed for allergen immunotherapy to optimize the constitution of their immunotherapy vaccines.

Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab.

BACKGROUND: Benralizumab is a humanized, afucosylated, monoclonal antibody that targets interleukin-5 receptor alpha and induces direct, rapid, and nearly complete depletion of eosinophils via enhanced antibody-dependent cell-mediated cytotoxicity. In the United States, benralizumab is indicated for add-on maintenance treatment of patients ≥12 years old with severe asthma and an eosinophilic phenotype. OBJECTIVE: This study evaluated the effect of benralizumab treatment on seasonal asthma exacerbation rates for patients with severe, uncontrolled asthma. METHODS: This was a post hoc analysis of pooled data from the phase III SIROCCO (ClinicalTrials.gov identifier: NCT01928771) and CALIMA (NCT01914757) trials. The primary analysis population was patients ages 12-75 years treated with high-dosage inhaled corticosteroids and long-acting beta-2 agonists who had baseline blood eosinophil counts of ≥300 cells/µL. Patients received benralizumab 30 mg subcutaneously every 4 weeks or every 8 weeks (the first three doses every 4 weeks) or placebo every 4 weeks. Crude exacerbation rates (asthma exacerbations per patient-year) were determined for each month and season. Marginal asthma exacerbation rates and exacerbation rate ratios were estimated by season or month by using a negative binomial model that included covariates for study code, treatment, region, use of maintenance oral corticosteroids, and number of exacerbations in the previous year. Hemispheric seasons were accounted for by normalizing the study site locations. RESULTS: Observed crude exacerbation rates were higher in the fall and winter than in the spring and summer for all the patients. For the patients who received placebo, benralizumab every 4 weeks, and benralizumab every 8 weeks, crude exacerbation rates were the following: fall, 1.52, 0.86, and 0.81, respectively; winter, 1.44, 0.91, and 0.82, respectively; spring, 1.11, 0.66, and 0.52, respectively; and summer, 1.02, 0.55, and 0.51, respectively. Rate reductions in seasonal marginal annual exacerbation rates were 37-50% versus placebo at each season (p < 0.001). CONCLUSION: Benralizumab significantly and consistently reduced asthma exacerbations across all seasons versus placebo for patients with severe, uncontrolled eosinophilic asthma.

In vitro impact of anti-immunoglobulin E monoclonal antibodies, including omalizumab on whole blood basophil histamine release: Assessment of direct induction of basophil histamine release and evaluation of modulation of allergen-induced basophil histamine release.

AIM: The aim of this study was to evaluate the potential of anti-immunoglobulin E (IgE) and/or anti-IgE-IgE immune complexes to release histamine from peripheral blood basophils. In addition, a potential modulating effect of anti-IgE-IgE complexes on allergen-induced peripheral blood basophil histamine release was evaluated. METHODS: Whole blood basophil histamine release (WBB-HR) tests done by using glass-fiber-based microtiter plates were performed in 62 patients with allergic rhinitis and/or asthma sensitized to perennial allergens. Evaluation of the direct effects of monoclonal anti-IgEs, including E25, E27, and QGE031, on WBB-HR, and the indirect effects of anti-IgE-serum IgE complexes on spontaneous and allergen-induced WBB-HR were conducted. The tests were performed with and without pretreatment of the basophils with interleukin 3, and the results were expressed as the fraction of total histamine content released. RESULTS: There was no difference between WBB-HR induced by any of the studied anti-IgE antibodies and that induced by isotype antibodies for all blood samples assessed, which, for each patient, was significantly less than that induced by positive anti-IgE control antibodies. Similarly, no effect of any of the studied anti-IgE-IgE complexes on spontaneous or allergen-induced WBB-HR could be demonstrated. CONCLUSION: There was no evidence that humanized, monoclonal anti-IgE antibodies E25 (omalizumab), E27, or QGE031 directly or indirectly induced histamine release from peripheral blood basophils.

A practical guide to prescribing sublingual immunotherapy tablets in North America for pediatric allergic rhinoconjunctivitis: an injection-free allergy immunotherapy option.

Allergic rhinoconjunctivitis (ARC) is a common disease that affects individuals of all ages. Pediatricians may be the first (and only) point of care for children with ARC. Sublingual immunotherapy (SLIT)-tablets are a convenient at-home, injection-free allergy immunotherapy option that can be used for the treatment of ARC. This paper provides a practical guide for pediatricians to aid in prescribing SLIT-tablets to children with ARC in North America. Topics include a summary of the available SLIT-tablets and their efficacy and safety, guidance on when SLIT-tablets are an appropriate option, and how to diagnose ARC and identify culprit allergens. Practical guidance is also provided through a proposed decision tree, a prescribing checklist and prescribing procedures, and suggested follow-up assessments.

Extrapolating Evidence-Based Medicine of AIT Into Clinical Practice in the United States.

Allergy/immunology specialists in the United States prescribing allergy immunotherapy (AIT) have placed a heavy value on practical experience and anecdotal evidence rather than research-based evidence. With the extensive research on AIT conducted in the last few decades, the time has come to better implement evidence-based medicine (EBM) for AIT. The goal of this review was to critically assess EBM for debated concepts in US AIT practice for respiratory allergies in the context and quality of today's regulatory standards. Debated topics reviewed were the efficacy and safety of AIT in various subgroups (eg, polyallergic patients, older patients, patients with asthma, and pregnant women), diagnosis topics (eg, skin prick test vs allergen-specific serum IgE, factors affecting skin prick tests, use of nasal or conjunctival allergen challenges, and telemedicine for diagnosis), and dosing topics (eg, optimal dosing for subcutaneous immunotherapy and sublingual immunotherapy tablets, US liquid allergen extract history, duration of treatment, and biomarkers of efficacy). In addition, EBM for patient-centered AIT issues (eg, adherence, use of practice guidelines, and pharmacoeconomics) and the approach to implementation of AIT EBM in future clinical practice were addressed. The EBM for each concept was briefly summarized, and when possible, a practical, concise recommendation was given.

Assessment of specific immunotherapy efficacy using a novel placebo score-based method.

BACKGROUND: In trials of allergen immunotherapy, allergen exposure is typically assessed by pollen counts, but these may misrepresent exposure if performed remotely from multiple study centers. OBJECTIVE: To assess whether symptomatology in placebo-treated patients is a better measure of local allergen burden at individual centers in such trials. METHODS: Data from a multicenter, placebo-controlled trial of preseasonal grass pollen immunotherapy were reanalyzed to identify the 4 weeks at each center in which the placebo-treated subjects had the highest combined symptom/medication scores (CSMS). The difference in CSMS between active and placebo groups was compared during the 4 peak placebo score weeks (PlSW) and the 4 peak pollen count weeks (PoCW). RESULTS: The benefit of immunotherapy over placebo in the PlSW analysis (18.5%) was greater than in the PoCW analysis (13.6%), with increased statistical significance (P = .0001, .0038, respectively). Similar improved discrimination was observed when analyzing benefits in subgroups of patients with severe symptoms, a high disease burden, and in different geographical locations. CONCLUSION: This novel PlSW analysis results in better discrimination of the effects of allergen immunotherapy compared with placebo and may be widely applicable in similar studies, both prospectively and retrospectively.

Ultrashort-specific immunotherapy successfully treats seasonal allergic rhinoconjunctivitis to grass pollen.

Specific immunotherapy is a well-established treatment for allergic rhinoconjunctivitis; conventional regimens are lengthy, however, reducing convenience and cost-effectiveness. This study evaluated the efficacy and safety of an ultrashort course (four doses) of the immunotherapy Grass Modified Allergen Tyrosine Adsorbate (Allergy Therapeutics, Worthing, U.K.) monophosphoryl lipid A (MATA MPL). Subjects were randomized to receive four injections of either Grass MATA MPL (n = 514; 300-2000 standardized units/injection) or placebo (n = 514) before the grass pollen season. They used electronic diaries to record allergy symptoms and medication use during the pollen season. The primary end point was the difference between the mean combined symptom and medication scores in the Grass MATA MPL and placebo groups during the 4 local peak pollen weeks. The injection course was completed by 95.3 and 97.7% of the Grass MATA MPL and placebo groups, respectively, and was well tolerated. Grass MATA MPL treatment afforded a 13.4% benefit over placebo in the 4 peak pollen weeks (p = 0.0038). The benefit in subjects with 28 complete diary entries during the 4 peak pollen weeks was 26.9% (p = 0.0031). Significant benefits over placebo were observed in subjects with severe symptoms (17.1%; p = 0.0023), in those who had a history of allergic rhinoconjunctivitis for up to 35 years (up to 37.2%; p = 0.0059) and at sites with a higher burden of disease (38.3%; p < 0.0001). The ultrashort course of Grass MATA MPL was well tolerated and provided a significant benefit over placebo in relieving allergy symptoms.

Dogmas, challenges, and promises in phase III allergen immunotherapy studies.

The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries. Moreover, most of these AIT products are provided on an individual patient basis as named patient products (NPP) in Europe, while individualized preparations of (mixed) allergenic extract vials for subcutaneous administration (compounding) is common practice in the US. AIT products are generally considered safe and well tolerated, but the major practical clinical development challenge is to define the optimal dose and prove the efficacy and safety of these products using state-of-the art Phase II and pivotal Phase III studies. In planning Phase II-III AIT studies, a thorough understanding of the study challenges is essential (e.g. variability and non-validated status of subjective primary endpoints, limitations of pollen season definitions) and dogmas of these products (e.g., for sublingual immunotherapy (SLIT) trials double-blinding conditions cannot be maintained, resulting in stronger placebo responses in the active treatment group and inflated treatment effects in Phase III). There is future promise for more objective biomarker endpoints (e.g. basophil activation (CD63 and CD203c), subsets of regulatory dendritic, T and B cells, IL-10-producing group 2 innate lymphoid cells; alone or in combination) to overcome several of these dogmas and challenges; innovation in AIT clinical trials can only progress with integral biomarker research to complement the traditional endpoints in Phase II-III clinical development. The aim of this paper is to provide an overview of these dogmas, challenges and recommendations based on published data, to facilitate the design of Phase III studies and improve the evidence basis of safe and effective AIT products.

Erratum to "IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper" [World Allergy Organ J 13/2 (2020) 100080].

[This corrects the article DOI: 10.1016/j.waojou.2019.100080.].

Mediator release of neuropeptides after nasal provocation in perennial allergic rhinitis patients.

BACKGROUND: Neuropeptides may play a role in allergic rhinitis including development of vasodilation and vascular leakage, which may result in rhinorrhea and congestion. While neuropeptide release during the immediate allergic response is well known, the role of neuropeptides in the late phase of allergic responses is less well defined. METHODS: Eleven subjects with dust mite allergy induced allergic rhinitis were compared to 5 healthy control subjects using nasal allergen provocation. Nasal lavage fluid was analyzed for Substance P, bradykinin, and total protein. RESULTS Both bradykinin and substance P levels increased in nasal lavage fluid immediately after dust mite allergen challenge of dust mite allergic subjects, the magnitude of increase of both neuropeptides being significantly correlated. There was a greater increase in substance P versus bradykinin 4 to 6 hours after allergen challenge, with a lack of correlation between the late phase increases of these two neuropeptides. The bradykinin increases correlated with the increase in total protein in the nasal lavages of the allergic subjects, whereas the increases in substance P did not correlate with the total protein in the nasal lavages. An increase in nasal eosinophils was only seen in the allergic subjects after allergen provocation. CONCLUSION: Both bradykinin and substance P appear in nasal lavage fluid 4 to 6 hours after allergen challenge of dust mite allergic subjects, suggesting a role for the neuropeptides in late phase allergic events.

Assessment of Google Trends terms reporting allergies and the grass pollen season in Ukraine.

BACKGROUND: Grass pollen allergy is an important trigger for the development of respiratory disorders. Defining the grass pollen season onset is critical for correct allergy diagnosis and personalized therapy. The development of a pan-European sentinel network for allergic diseases has raised the problem of translating the Google search terms into different European languages as well as defining specific pollen season characteristics in different regions. Grass pollen allergy was investigated due to high allergenicity and wide expansion of grass pollen in Europe. OBJECTIVES: The aim of this study was to examine which translations of "hay fever", "grass", and "rhinitis" could be used in the native Cyrillic languages, especially in Ukrainian and Russian, and to compare the seasonality of allergic respiratory queries in Ukraine with the grass pollen counts. METHODS: Google Trends (GT) was used to search Google queries concerning grass pollen allergy: "allergy", "hay fever", "runny nose", "grass", "asthma", and "pollen". The Cyrillic terms in Ukrainian and Russian were used. The search was done for the period from 2013 to 2017. Pollen collection from 2013 to 2016 was conducted using volumetric methods. Average daily temperatures were obtained from http://gismeteo.ua. Correlations were assessed by Spearman (R) test. RESULTS: The Ukrainian Google users searched the Cyrillic equivalents for "runny nose", "grass", and "asthma". Due to the GT queries profile, Ukraine had a "D" pattern according to the classification, developed by Bousquet J et al (2017). In Ukraine, the Poaceae pollen season generally occurred between the second ten-day period of May and the last ten-day period of July. The Poaceae pollen season started with a concentration of pollen grains of 8.0 m-3. This concentration provoked the growth of GT "grass", "allergy", "hay fever", and "asthma" queries. CONCLUSIONS: The terms "grass", "allergy", "hay fever", and "asthma" (in their Cyrillic equivalents) are required in Ukraine to account for the grass pollen exposure by GT. The study of GT may be a useful tool to make an assessment of the grass pollen season for the prevention and minimization of exposure to significant grass pollen concentrations.