Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

[Anaphylaxis and COVID-19 vaccines]. / L'anaphylaxie et les vaccins COVID-19.

Vaccines against COVID-19 are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1,000,000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. It is important to restore confidence about vaccination with COVID-19 mRNA and other vaccines and current data confirm their safety with no greater mortality than previous vaccines. Anaphylaxis is a complication that should be recognized immediately, be treated with epinephrine and which is not limiting and allows re-vaccination of some patients with pre-medication. It is important to recognize populations at risk such as women, patients with a history of allergies and anaphylaxis and to recognize the rare patients who have mast cell activating diseases. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.

Action Plan to Ensure Global Availability of Adrenaline Autoinjectors.

Adrenaline (epinephrine) is the first-line treatment for anaphylaxis and, therefore, is listed as an essential medication for the treatment of anaphylaxis by the World Health Organization (WHO). However, the availability of adrenaline autoinjectors (AAI) for use as first-aid treatment is limited to only 32% of all the world's 195 countries, most of which are high-income countries. The key issues leading to the lack of availability of AAIs include cost, national regulations, lack of regional evidence on the value of epinephrine, and limited accurate data about the epidemiology of anaphylaxis. For these reasons, regional and international allergy academies support initiatives to narrow these gaps. Our WHO Collaborating Centre is deeply involved in this process. This document aims to serve as a baseline to ensure the following: (1) adequate access to affordable autoinjectors for all patients/societies; and (2) the development of disease-/patient-specific approaches. Therefore, we propose a 5-step action plan that aims to gather accurate epidemiological data on anaphylaxis and autoinjector consumption, confirm partnerships, strengthen awareness, and include AAIs in the WHO Model List of Essential Medicines. These aspects should be considered in combination. A prioritized research agenda should encapsulate all these steps within the framework a global initiative against anaphylaxis. More than calling for universal availability of autoinjectors for optimal management of anaphylaxis, we propose an action plan as the baseline for a global initiative against anaphylaxis. We strongly believe that combined efforts will ensure a strong public health and societal approach that will lead to optimal care of allergic patients and best practices in allergology.

Epidemiological Data on Anaphylaxis in French Emergency Departments.

BACKGROUND: Although anaphylaxis has been considered a priority public health issue in the world allergy community, epidemiological data on morbidity and mortality remain suboptimal. We performed the first multicenter epidemiological study in French emergency departments (EDs). The study covered 7 EDs over a period of 1 year. The objectives were to identify areas that are amenable to change and to support ongoing national and international efforts for better diagnosis, management, and prevention of anaphylaxis. METHODS: Ours was a descriptive study based on data routinely reported to French institutional administrative databases from 7 French public health institutions in the Lorraine region between January and December 2015. Data were collected based on the anaphylaxisrelated codes of the International Classification of Diseases (ICD)-10, and cases were clinically validated as anaphylaxis. RESULTS: Of the 202 079 admissions to the EDs, 4817 had anaphylaxis-related codes; of these, 323 were clinically validated as anaphylaxis. Although 45.8% were severe, adrenaline was prescribed in only 32.4% of cases. Of the 323 cases, 57.9% were subsequently referred for an allergy work-up or evaluation (after or during hospitalization), and 17.3% were prescribed autoinjectable epinephrine. CONCLUSION: Our results highlight an urgent need for improved public health initiatives with respect to recognition and treatment of anaphylaxis. We flag key problems that should be managed in the coming years through implementation of national and international actions.

Proactive multi-modality treatment of Pancreatic Neuroendocrine Tumours (PNETs): Potential survival benefits.

BACKGROUND/OBJECTIVES: Primary and metastatic pancreatic neuroendocrine tumours (PNET) can be treated with combination of surgery, locoregional and systemic therapy. Survival benefits from individual treatments have been well reported, however, the combined outcome from multimodal treatments are not well described in the literature. We report outcomes in a cohort of PNET patients treated with proactive, multimodality therapy. METHODS: 106 patients were identified from a single tertiary referral centre prospective database. Outcomes of treatment were studied, with the primary end point being death from any cause. RESULTS: Median follow-up was 71 months and overall 5-year survival of 62%. In patients with stage I-III disease (51 patients) estimated 5-year survival was 90%. Median survival in patients with stage IV disease was 51 months with an estimated 5-year survival of 40% in this group. A total of 80 patients (75%) had surgery of which 16% suffered complications requiring intervention. There was no perioperative mortality. CONCLUSIONS: This study demonstrates that proactive multimodal treatment is safe and may confer a survival benefit to patients in this cohort compared to historical data.

What can we learn in drug allergy management from World Health Organization's international classifications?

Drug hypersensitivity reactions (DHRs) represent growing health problem worldwide, affecting more than 7% of the general population, and represent an important public health problem. However, knowledge in DHRs morbidity and mortality epidemiological data is still not optimal and international comparable standards remain poorly accessed. Institutional databases worldwide increasingly use the WHO International Classification of Diseases (ICD) system to classify diagnoses, health services utilization, and death data. The misclassification of disorders in the ICD system contributes to a lack of ascertainment and recognition of their importance for healthcare planning and resource allocation. It also hampers clinical practice and prevention actions. To further inform the allergy community and to ensure that the revision process is transparent as advised in the WHO ICD-11 revision agenda, we report the advances and use of the pioneering "Drug hypersensitivity" subsection of ICD-11 and implementation in the WHO International Classification of Health Interventions (ICHI). The new classification addressed to DHRs will enable the collection of more accurate epidemiological data to support quality management of patients with drug allergies and better facilitate healthcare planning and decision-making and public health measures to prevent and reduce the morbidity and mortality attributable to DHRs.

Validation of the MASK-rhinitis visual analogue scale on smartphone screens to assess allergic rhinitis control.

BACKGROUND: Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients. OBJECTIVE: The aim of this study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) app (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control. METHODS: Each user filled 4 different VAS measuring overall, nasal, ocular, and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity, and acceptability of the MASK-Rhinitis VAS. RESULTS: Between 1 August 2015 and 31 July 2016, the app was used 14 612 times in 15 countries. A total of 1225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test > 0.84, test-retest > 0.7), reliability (>0.9), and acceptability. In addition, the tool had a good sensitivity when users (n = 521) answered the VAS twice in less than 3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.

Decreasing the undernotification of anaphylaxis deaths in Brazil through the International Classification of Diseases (ICD)-11 revision.

BACKGROUND: In 2012, an analysis of the Brazilian mortality database demonstrated undernotification of anaphylaxis deaths due, at least in part, to difficult coding under the International Classification of Diseases (ICD)-10. This work triggered a cascade of strategic international actions supported by the Joint Allergy Academies and the ICD World Health Organization (WHO) representatives to update the classifications of allergic disorders for the ICD-11 revision. These efforts have resulted in the construction of the new 'Allergic and hypersensitivity conditions' section under the 'Disorders of the Immune system' chapter. OBJECTIVE: To analyze the capacity of the new ICD-11 revision to capture anaphylaxis deaths. METHODS: We re-estimated the anaphylaxis deaths that occurred in Brazil during the period 2008 to 2010, utilizing this new framework and the database of the Brazilian mortality information system that had initially been extracted in May 2011. However, in 2016, a manual review of each of the 3638 records was performed. RESULTS: We identified 639 anaphylaxis deaths, of which 95% were classified as 'definitive anaphylaxis deaths'. In contrast to the 2012 published data, we found a higher number of cases; moreover, all 606 definitive anaphylaxis deaths would be considered as underlying causes of death utilizing the ICD-11 revision. CONCLUSION: This study is the first example of how the new 'Allergic and hypersensitivity conditions' section of the forthcoming ICD-11 can improve the quality of official vital statistics data and the visibility of an important public health concern. This research will facilitate comprehensive, comparable population-based epidemiologic data collection on anaphylaxis.

Field-testing the new anaphylaxis' classification for the WHO International Classification of Diseases-11 revision.

BACKGROUND: To consolidate the new classification model addressed to the allergic and hypersensitivity conditions according to the International Classification of Diseases (ICD)-11 revision timeline, we here propose real-life application of quality assurance methodology to evaluate sensitivity and accuracy of the 'Anaphylaxis' subsection. METHODS: We applied field-testing methodology by analysing all the consecutive inpatients' files documented as allergies from the University Hospital of Montpellier electronic database for the period of 1 year. The files clinically validated as being anaphylaxis were manually blind-coded under ICD-10 and current ICD-11 beta draft. The correspondence of coding and the impressions regarding sensibility were evaluated. RESULTS: From all 2318 files related to allergic or hypersensitivity conditions, 673 had some of the anaphylaxis ICD-10 codes; 309 files (46%) from 209 patients had anaphylaxis and allergic or hypersensitivity comorbidities description. The correspondence between the two coders was perfect for 162 codes from all 309 entities (52.4%) (Cohen-kappa value 0.63) with the ICD-10 and for 221 codes (71.5%) (Cohen-kappa value 0.77) with the ICD-11. There was a high agreement regarding sensibility of the ICD-11 usability (Cohen-kappa value 0.75). CONCLUSION: We here propose the first attempt of real-life application to validate the new ICD-11 'Anaphylaxis' subsection. Clearer was the improvement in accuracy reaching 71.5% of agreement when ICD-11 was used. By allowing all the relevant diagnostic terms for anaphylaxis to be included into the ICD-11 framework, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, healthcare planners and other stakeholders.

Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme item (Action Plan B3 of the European Innovation Partnership on active and healthy ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a World Health Organization GARD research demonstration project.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

Optimization and simplification of the Allergic and Hypersensitivity conditions classification for the ICD-11.

BACKGROUND: Since 2013, an international collaboration of Allergy Academies, including first the World Allergy Organization (WAO), the American Academy of Allergy Asthma and Immunology (AAAAI), and the European Academy of Allergy and Clinical Immunology (EAACI), and then the American College of Allergy, Asthma and Immunology (ACAAI), the Latin American Society of Allergy, Asthma and Immunology (SLAAI), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI), has spent tremendous efforts to have a better and updated classification of allergic and hypersensitivity conditions in the forthcoming International Classification of Diseases (ICD)-11 version by providing evidences and promoting actions for the need for changes. The latest action was the implementation of a classification proposal of hypersensitivity/allergic diseases built by crowdsourcing the Allergy Academy leaderships. METHODS: Following bilateral discussions with the representatives of the ICD-11 revision, a face-to-face meeting was held at the United Nations Office in Geneva and a simplification process of the hypersensitivity/allergic disorders classification was carried out to better fit the ICD structure. RESULTS: We are here presenting the end result of what we consider to be a model of good collaboration between the World Health Organization and a specialty. CONCLUSION: We strongly believe that the outcomes of all past and future actions will impact positively the recognition of the allergy specialty as well as the quality improvement of healthcare system for allergic and hypersensitivity conditions worldwide.

Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review.

Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n = 12) and other nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 8), and IR to biologics (n = 3). We reported two genomewide association studies and four case-control studies on candidate genes validated by replication. Genes involved in IR to beta-lactams belonged to HLA type 2 antigen processing, IgE production, atopy, and inflammation, including 4 genes validated by replications, HLA-DRA, ILR4, NOD2, and LGALS3. Genes involved in NAR to aspirin belonged to arachidonic acid pathway, membrane-spanning 4A gene family, histamine production pathway, and pro-inflammatory cytokines, while those involved in NAR to all NSAIDs belonged to arachidonic acid pathway and HLA antigen processing pathway. ALOX5 was a common predictor of studies on NAR to both aspirin and NSAIDs. Although these first conclusions could be drawn, this review highlights also the lack of reliable data and the need for replicating studies in contrasted populations, taking into account worldwide allele frequencies, gene-gene interactions, and contrasted situations of environmental exposure.

Constructing a classification of hypersensitivity/allergic diseases for ICD-11 by crowdsourcing the allergist community.

The global allergy community strongly believes that the 11th revision of the International Classification of Diseases (ICD-11) offers a unique opportunity to improve the classification and coding of hypersensitivity/allergic diseases via inclusion of a specific chapter dedicated to this disease area to facilitate epidemiological studies, as well as to evaluate the true size of the allergy epidemic. In this context, an international collaboration has decided to revise the classification of hypersensitivity/allergic diseases and to validate it for ICD-11 by crowdsourcing the allergist community. After careful comparison between ICD-10 and 11 beta phase linearization codes, we identified gaps and trade-offs allowing us to construct a classification proposal, which was sent to the European Academy of Allergy and Clinical Immunology (EAACI) sections, interest groups, executive committee as well as the World Allergy Organization (WAO), and American Academy of Allergy Asthma and Immunology (AAAAI) leaderships. The crowdsourcing process produced comments from 50 of 171 members contacted by e-mail. The classification proposal has also been discussed at face-to-face meetings with experts of EAACI sections and interest groups and presented in a number of business meetings during the 2014 EAACI annual congress in Copenhagen. As a result, a high-level complex structure of classification for hypersensitivity/allergic diseases has been constructed. The model proposed has been presented to the WHO groups in charge of the ICD revision. The international collaboration of allergy experts appreciates bilateral discussion and aims to get endorsement of their proposals for the final ICD-11.

Global classification and coding of hypersensitivity diseases - An EAACI - WAO survey, strategic paper and review.

Hypersensitivity diseases are not adequately coded in the International Coding of Diseases (ICD)-10 resulting in misclassification, leading to low visibility of these conditions and general accuracy of official statistics. To call attention to the inadequacy of the ICD-10 in relation to allergic and hypersensitivity diseases and to contribute to improvements to be made in the forthcoming revision of ICD, a web-based global survey of healthcare professionals' attitudes toward allergic disorders classification was proposed to the members of European Academy of Allergy and Clinical Immunology (EAACI) (individuals) and World Allergy Organization (WAO) (representative responding on behalf of the national society), launched via internet and circulated for 6 week. As a result, we had 612 members of 144 countries from all six World Health Organization (WHO) global regions who answered the survey. ICD-10 is the most used classification worldwide, but it was not considered appropriate in clinical practice by the majority of participants. The majority indicated the EAACI-WAO classification as being easier and more accurate in the daily practice. They saw the need for a diagnostic system useful for nonallergists and endorsed the possibility of a global, cross-culturally applicable classification system of allergic disorders. This first and most broadly international survey ever conducted of health professionals' attitudes toward allergic disorders classification supports the need to update the current classifications of allergic diseases and can be useful to the WHO in improving the clinical utility of the classification and its global acceptability for the revised ICD-11.

Undernotification of anaphylaxis deaths in Brazil due to difficult coding under the ICD-10.

BACKGROUND: Undernotification is well recognized as a key challenge to the study of anaphylaxis mortality, but it is seldom mentioned that one of its reasons is the difficult coding of the condition under the tenth revision of the international classification of diseases (ICD-10), given that there are no anaphylaxis-specific ICD-10, which are considered valid for coding underlying causes-of-death, and that official mortality statistics consider exclusively the underlying and disregard the contributing causes-of-death data recorded on death certificates. Brazilian mortality data were used as a case study to call attention to the inadequacy of the ICD-10 for the measurement of anaphylaxis deaths. METHODS: Underlying and contributing causes-of-death data were used to estimate the rates of anaphylaxis deaths in the country over the years 2008-2010. RESULTS: Of 498 anaphylaxis deaths were found, of which 75% were classified as 'definite' and 25% as 'possible anaphylaxis deaths'. The average national rate for these years was 0.87 per million per year. None of these deaths would have been found had we exclusively considered information from the underlying cause-of-death field. CONCLUSION/RECOMMENDATIONS: The study of anaphylaxis mortality using secondary data requires the use of information derived from the underlying as well as from the contributing causes-of-death fields. Coding definitions should be standardized with a view of enabling trend analyses and international comparisons. The ICD-11 revision is a unique opportunity to improve the coding system so as to facilitate epidemiological studies of anaphylaxis mortality. Educational interventions targeted at improving the quality of death certificate completion are urgently needed.

Human insulin allergy: four case reports.

Insulin allergy was not uncommon in the past, but has lowered with the introduction of human recombinant insulin. Human recombinant insulin allergy is a rare condition, now reported in less than 1% of treated patients. However, it is a serious condition that requires an immediate allergological work-up. In this study, we describe 4 cases of IgE-mediated reaction to human recombinant insulin, emphasizing some practical aspects in diagnosis and treatment.