Optimization of the allergen classification of the International Classification Of Diseases, 11th Revision (ICD-11).

BACKGROUND: Accurate diagnosis of triggers or causative allergens is essential for appropriate risk assessment, providing correct advice to patients with allergy and their caregivers and personalized treatment. However, allergens have never been represented in the World Health Organization International Classification of Diseases (ICD). OBJECTIVE: In this article, we present the process of selection of allergens to better fit the ICD, 11th Revision (ICD-11) structure and the outcomes of this process. METHODS: The Logical Observation Identifiers Names and Codes database, containing 1444 allergens, was used as the basis for the selection process. Two independent experts were responsible for the first selection of the allergens according to specific technical criteria. The second step of the selection process was based on real-life relevance of the allergens according to the frequency of requests regarding each of them. RESULTS: We selected 1109 allergens (76.8%) from all 1444 present in the Logical Observation Identifiers Names and Codes database, with considerable agreement between experts (Cohen κ = 8.6). After assessment of real-life data, 297 additional relevant allergens worldwide were selected and grouped as plants (36.4%), drugs (32.6%), animal proteins (21%), mold and other microorganisms (1.5%), occupational allergens (0.4%), and miscellaneous allergens (0.5%). CONCLUSION: The stepwise approach allowed us to select the most relevant allergens in practice, which is the first step to building a classification of allergens for the WHO ICD-11. Aligned with the achievement in the construction of the pioneer section addressed to the allergic and hypersensitivity conditions in the ICD-11, the introduction of a classification for allergens can be considered timely and much needed in clinical practice.

United States Pharmacopeia guidance for compounding of allergenic extracts for allergen immunotherapy.

Patient-specific allergen-specific subcutaneous immunotherapy (SCIT) has been used as a disease modifying treatment for type 1 IgE mediated allergy to inhalants for > 100 years. Traditionally, the extracts used for a treatment set have been "mixed" under the supervision of allergists in their clinics. Until 2008, there were no specific requirements for mixing procedures. Allergenic extracts are classified as biologics by the U.S. Food and Drug Administration (FDA) and are subject to the biologics license application requirements. One of the conditions is that it must be prepared in accordance with U.S. Pharmacopeia (USP) Chapter 797, which was first published in 2008. What allergists have always considered "mixing" of allergen extracts is considered "compounding" by the FDA and other state and federal regulatory agencies. A revision of USP Chapter 797 was proposed after a series of "never events," including deaths, from compounded products. No reports of infections from SCIT have ever been reported. "Allergy" (ACAAI, AAAAI, AAOA, and other stakeholders) worked cooperatively with the USP Compounding Expert Committee to develop Section 21. "Compounding Allergenic Extracts" of what is expected to be accepted as the next version of USP Chapter 797 in mid 2022.

Global implementation of the world health organization's International Classification of Diseases (ICD)-11: The allergic and hypersensitivity conditions model.

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019, and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the subsections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients.

Changing the history of anaphylaxis mortality statistics through the World Health Organization's International Classification of Diseases-11.

We review the history of the classification and coding changes for anaphylaxis and provide current and perspective information in the field. In 2012, an analysis of Brazilian data demonstrated undernotification of anaphylaxis-related deaths because of the difficulties of coding using the International Classification of Diseases, 10th Revision. This work triggered strategic international actions supported by the Joint Allergy Academies and the International Classification of Diseases World Health Organization (WHO) leadership to update the classification of allergic disorders for the International Classification of Diseases, 11th Revision (ICD-11), which resulted in construction of the pioneer "Allergic and hypersensitivity conditions" chapter. The usability of the new framework has been tested by evaluating the same data published in 2012 from the ICD-11 perspective. Coding accuracy was much improved, reaching 95% for definite anaphylaxis. As the results were provided to the WHO Mortality Reference Group, coding rules have been changed, allowing anaphylaxis to be recorded as an underlying cause of death in official mortality statistics. The mandatory use of ICD-11 from January 2022 for documenting cause of death could have 2 immediate consequences: (1) the reported number of anaphylaxis-related deaths might increase because of more appropriate coding and (2) the cross-sectional and longitudinal mortality data generated might ultimately lead to a better understanding of anaphylaxis epidemiology and improved health policies directed at reducing anaphylaxis-related mortality.

Effect of a mobile health, sensor-driven asthma management platform on asthma control.

BACKGROUND: Asthma inflicts a significant health and economic burden in the United States. Self-management approaches to monitoring and treatment can be burdensome for patients. OBJECTIVE: To assess the effect of a digital health management program on asthma outcomes. METHODS: Residents of Louisville, Kentucky, with asthma were enrolled in a single-arm pilot study. Participants received electronic inhaler sensors that tracked the time, frequency, and location of short-acting ß-agonist (SABA) use. After a 30-day baseline period during which reference medication use was recorded by the sensors, participants received access to a digital health intervention designed to enhance self-management. Changes in outcomes, including mean daily SABA use, symptom-free days, and asthma control status, were compared among the initial 30-day baseline period and all subsequent months of the intervention using mixed-model logistic regressions and χ2 tests. RESULTS: The mean number of SABA events per participant per day was 0.44 during the control period and 0.27 after the first month of the intervention, a 39% reduction. The percentage of symptom-free days was 77% during the baseline period and 86% after the first month, a 12% improvement. Improvement was observed throughout the study; each intervention month demonstrated significantly lower SABA use and higher symptom-free days than the baseline month (P < .001). Sixty-nine percent had well-controlled asthma during the baseline period, 67% during the first month of the intervention. Each intervention month demonstrated significantly higher percentages than the baseline month (P < .001), except for month 1 (P = .80). CONCLUSION: A digital health asthma management intervention demonstrated significant reductions in SABA use, increased number of symptom-free days, and improvements in asthma control. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02162576.

International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics.

This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein.

Comparison of systemic reactions in rush, cluster, and standard-build aeroallergen immunotherapy.

BACKGROUND: Given the choice of standard, cluster, and rush build-up for aeroallergen immunotherapy, standard-build immunotherapy has generally been preferred because of a perceived high rate of systemic reactions (SRs) associated with cluster and rush immunotherapy. OBJECTIVE: To characterize the incidence of SRs during standard, cluster, and rush build-up immunotherapy in an allergy practice during a 5-year period. METHODS: A retrospective review was conducted among patients receiving standard-build, 8- to 10-step cluster, or 2-day rush immunotherapy from January 1, 2010, through December 31, 2014, at Family Allergy & Asthma clinics in Louisville, Kentucky. Investigators excluded reactions that occurred during skin prick testing, venom immunotherapy, and not-true SRs, and identified the build-up method, age, sex, date of reaction, vial concentration, and presence of asthma. Per-shot and per-patient incidence of SRs was computed from these data. RESULTS: During our review period, 2,549,643 injections were administered to 11,982 patients. Per-shot incidence of SR was 0.01%, 0.06%, and 0.33% for standard, cluster, and rush immunotherapy, respectively; per-patient incidence of SR was 2.84%, 2.52%, and 11.86% for standard, cluster, and rush immunotherapy, respectively. A total of 42% of SRs were grade 1, 43% were grade 2, 12% were grade 3, and 3% were grade 4. No fatalities were reported. A total of 70% of total SRs, 75% of cluster SR, and 55% of rush SR occurred in females, with an emergent peak in SR from May to October. CONCLUSION: Compared with previously published rates, we observed a decrease in the incidence of SR for standard, cluster, and rush immunotherapy, with peak seasonality from May to October and a female predominance.

Environmental assessment and exposure reduction of cockroaches: a practice parameter.

This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Environmental assessment and remediation: a practice parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single person, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).

Mouse allergen skin sensitization in asthmatic children of suburban, rural, and inner-city populations.

Mouse allergen (MA) exposure is a well-known risk factor for allergic sensitization and is implicated in the pathogenesis of pediatric asthma. Although previous studies report high prevalence of MA sensitization in inner-city asthmatic children, no data exist on its comparison with either suburban or rural children with asthma. We did a retrospective cohort study by chart review of all children (≤18 years of age) who underwent allergy testing during a 6-month period in a tertiary care referral center. Patients were divided geographically into suburban, rural, and inner-city groups based on their zip codes. MA was tested using the standard allergy test panel by skin prick/puncture. Positive skin test reactivity was defined as wheal diameter ≥3 mm and erythema ≥5 mm. A total of 989 patients underwent allergy testing and 349 children were tested for MA with the overall positivity rate of 18.6% (65/349). In children with asthma (mean age, 12.8 years; SD ± 3.19) who had MA testing (n = 166), the rate of positive skin test reactivity was 18% (n = 30). Inner-city asthmatic children had significantly greater MA sensitization compared with either suburban or rural children. MA sensitization is highly prevalent among children with asthma, especially in inner-city populations but also among suburban and rural children. Although most allergists do not routinely test for MA sensitization during the initial evaluation, it may be useful to include it in the allergy testing for children with asthma.

A systematic review of quality and consistency of clinical practice guidelines on the primary prevention of food allergy and atopic dermatitis.

Background and aims: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings. Methods: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022. Results: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores >70% in the "Scope and Purpose" and "Rigour of Development" domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the "Applicability" domain were generally low, and only 3 CPGs rated highly in the "Implementability" domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably. Conclusion: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders' preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe. PROSPERO registration number: CRD42021265689.

Identifying impacts of air pollution on subacute asthma symptoms using digital medication sensors.

BACKGROUND: Objective tracking of asthma medication use and exposure in real-time and space has not been feasible previously. Exposure assessments have typically been tied to residential locations, which ignore exposure within patterns of daily activities. METHODS: We investigated the associations of exposure to multiple air pollutants, derived from nearest air quality monitors, with space-time asthma rescue inhaler use captured by digital sensors, in Jefferson County, Kentucky. A generalized linear mixed model, capable of accounting for repeated measures, over-dispersion and excessive zeros, was used in our analysis. A secondary analysis was done through the random forest machine learning technique. RESULTS: The 1039 participants enrolled were 63.4% female, 77.3% adult (>18) and 46.8% White. Digital sensors monitored the time and location of over 286 980 asthma rescue medication uses and associated air pollution exposures over 193 697 patient-days, creating a rich spatiotemporal dataset of over 10 905 240 data elements. In the generalized linear mixed model, an interquartile range (IQR) increase in pollutant exposure was associated with a mean rescue medication use increase per person per day of 0.201 [95% confidence interval (CI): 0.189-0.214], 0.153 (95% CI: 0.136-0.171), 0.131 (95% CI: 0.115-0.147) and 0.113 (95% CI: 0.097-0.129), for sulphur dioxide (SO2), nitrogen dioxide (NO2), fine particulate matter (PM2.5) and ozone (O3), respectively. Similar effect sizes were identified with the random forest model. Time-lagged exposure effects of 0-3 days were observed. CONCLUSIONS: Daily exposure to multiple pollutants was associated with increases in daily asthma rescue medication use for same day and lagged exposures up to 3 days. Associations were consistent when evaluated with the random forest modelling approach.

Quality and consistency of clinical practice guidelines on the prevention of food allergy and atopic dermatitis: Systematic review protocol.

Background and aims: Allergy prevention strategies have gained significant traction as a means to attenuate the growing burden of allergic diseases over the past decade. As the evidence base for primary prevention of food allergy (FA) and atopic dermatitis (AD) is constantly advancing, clinical practice guideline (CPG) recommendations on interventions for FA and AD prevention vary in quality and consistency among professional organizations. We present a protocol for a systematic review of CPGs on primary prevention of FA and AD. Methods: We will systematically review and appraise all CPGs addressing primary prevention of FA and AD and report our findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases and manual website searches from January 2011 to March 2021 without language or geographical restrictions, and supplemented by author contact, will generate the list of potentially relevant CPGs to screen. Evaluation of the methodological quality, consistency, and global applicability of shortlisted CPGs will be performed by members of the Allergy Prevention Work Group of the World Allergy Organization (WAO) using the Appraisal of Guidelines for Research and Evaluation (AGREE) II and AGREE-REX (Recommendations EXcellence). instruments. Guideline contents, consistency, and quality of the recommendations will be summarised in tabular and narrative formats. We aim to present consolidated recommendations from international guidelines of the highest methodological quality and applicability, as determined by AGREE II and AGREE-REX. Dissemination: This systematic review will provide a succinct overview of the quality and consistency of recommendations across all existing CPGs for FA and AD prevention, as well as crucial perspectives on applicability of individual recommendations in different geographical contexts. Results from this systematic review will be reported in a peer-reviewed journal. It will also inform a position statement by WAO to provide a practical framework to guide the development of future guidelines for allergy prevention worldwide. Prospero registration number: CRD42021265689.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.