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.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides three separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum Guidelines for the Prevention of Peanut Allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-Sponsored Expert Panel.

BACKGROUND: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. OBJECTIVES: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. RESULTS: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. CONCLUSIONS: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Consensus Communication on Early Peanut Introduction and Prevention of Peanut Allergy in High-Risk Infants.

The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants.

The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants.

The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology.

Home dust microbiota is disordered in homes of low-income asthmatic children.

OBJECTIVE: Exposure to microorganisms has repeatedly been found to influence development of atopic diseases, such as asthma. Innovative techniques have been developed that can comprehensively characterize microbial communities. The objective of this study was to characterize the home microbiota of asthmatic children utilizing 16S rRNA-based phylogenetic analysis by microarray. METHODS: In this cross-sectional study, DNA was extracted from home dust and bacterial 16S rRNA genes amplified. Bacterial products were hybridized to the PhyloChip Array and scanned using a GeneArray scanner (Affymetrix, Santa Clara, CA). The Adonis test was used to determine significant differences in the whole microbiome. Welch's t-test was used to determine significant abundance differences and genus-level richness differences. RESULTS: Nineteen homes were included in the analysis (14 asthma and five no asthma). About 1741 operational taxonomic units (OTUs) were found in at least one sample. Bacterial genus richness did not differ in the homes of asthmatics and non-asthmatics (p = 0.09). The microbial profile was significantly different between the two groups (p = 0.025). All the top 12 OTUs with significant abundance differences were increased in homes of asthmatics and belonged to one of the five phyla (p = 0.001 to p = 7.2 × 10(-6)). Nearly half of significant abundance differences belonged to the phylum Cyanobacteria or Proteobacteria. CONCLUSIONS: These results suggest that home dust has a characteristic microbiota which is disturbed in the homes of asthmatics, resulting in a particular abundance of Cyanobacteria and Proteobacteria. Further investigations are needed which utilize high-throughput technology to further clarify how home microbial exposures influence human health and disease.

FCER2 (CD23) asthma-related single nucleotide polymorphisms yields increased IgE binding and Egr-1 expression in human B cells.

CD23 is the low-affinity Fc receptor for IgE. When expressed on B cells, CD23 appears to play a role in regulation of IgE synthesis. Polymorphisms within FCER2, the gene encoding CD23, have been associated with atopy, increased risk of exacerbations in patients with asthma, and high serum IgE levels. A single-nucleotide polymorphism (rs2228137) present in exon 4 of FCER2 encodes a nonsynonymous amino acid change (R62W) and is the subject of the present analysis. Human B cell stable transfectants were established to characterize the functional relevance of the R62W SNP. We demonstrate that CD23b-R62W-expressing human B cells bind IgE with greater affinity than wild-type cells and display differences in kinetics of CD23-mediated ERK1/2 activation that may be responsible for the increased levels of Egr-1 mRNA observed after stimulation through CD23. Finally, the R62W SNP seems to alter the tertiary or quaternary structure of CD23 because in the absence of N-glycosylation the CD23b-R62W-expressing cells appear to be less sensitive to endogenous proteases. These observations may have implications in mechanisms responsible for the atopic phenotypes observed in patients with asthma who possess this genotype.

Secondhand tobacco smoke exposure in low-income children and its association with asthma.

Secondhand tobacco smoke (SHS) is a common indoor environmental exposure that is particularly prevalent in low-income families. It has been found to be associated with asthma in some studies; however, across all relevant studies, results have been conflicting. This study aimed to determine the prevalence of SHS exposure in the home environment in a low-income, minority population and to determine the association of exposure with childhood asthma, wheeze, and oral corticosteroids use. This retrospective study analyzed self-reported data collected as part of the Kansas City Safe and Healthy Homes Partnership to determine prevalence of SHS exposure. A logistic regression model was then used to assess the association between exposure and asthma, oral steroid use, and wheeze. Overall, 40% of children lived with at least one smoker and 15% of children lived with at least one smoker who smoked inside the house. No significant association was found between asthma or oral corticosteroid use and SHS exposure. Children who lived with a smoker had a 1.54 increased odds of wheeze in the past year. A large percentage of low-income children in the Kansas City area continue to suffer the adverse effects of SHS. These data support the need for innovative public policy to protect children from such exposure in their home environment.

Homes of low-income minority families with asthmatic children have increased condition issues.

The home is increasingly associated with asthma. It acts both as a reservoir of asthma triggers and as a refuge from seasonal outdoor allergen exposure. Racial/ethnic minority families with low incomes tend to reside in neighborhoods with low housing quality. These families also have higher rates of asthma. This study explores the hypothesis that black and Latino urban households with asthmatic children experienced more home mechanical, structural condition-related areas of concern than white households with asthmatic children. Participant families (n = 140) took part in the Kansas City Safe and Healthy Homes Program, had at least one asthmatic child, and met income qualifications of no more than 80% of local median income; many were below 50%. Families self-identified their race. Homes were assessed by environmental health professionals using a standard set of criteria and a specific set of on-site and laboratory sampling and analyses. Homes were given a score for areas of concern between 0 (best) and 53 (worst). The study population self-identified as black (46%), non-Latino white (26%), Latino (14.3%), and other (12.9%). Mean number of areas of concern were 18.7 in Latino homes, 17.8 in black homes, 13.3 in other homes, and 13.2 in white homes. Latino and black homes had significantly more areas of concern. White families were also more likely to be in the upper portion of the income. In this set of 140 low-income homes with an asthmatic child, households of minority individuals had more areas of condition concerns and generally lower income than other families.

Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes.

BACKGROUND: Hypereosinophilic syndromes (HESs) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid refractory or develop corticosteroid toxicity. Mepolizumab, a humanized monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HESs. OBJECTIVE: We evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES. METHODS: MHE100901 is an open-label extension study. The primary end point was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of antimepolizumab antibodies were also explored. RESULTS: Seventy-eight subjects received 1 to 66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 9 to 12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including 1 death, were reported by the investigator as possibly due to mepolizumab in 3 subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone free without other HES medications for ≥ 12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew before study completion for death (n = 4), lack of efficacy (n = 6), or other reasons. CONCLUSION: Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES.

Detecting gene expression in buccal mucosa in subjects with asthma versus subjects without asthma.

BACKGROUND: Differences in mRNA expression for inflammatory markers have been observed between subjects with asthma vs. controls and in relation to corticosteroid response. However, these studies utilized methods (e.g., bronchoscopy) that are too invasive to be used routinely in children and in the clinic. The primary purpose of this study was to determine the feasibility of obtaining RNA of adequate quantity and quality from buccal mucosa of children and adults for gene expression studies. Secondly, this study aimed to determine whether gene expression patterns in buccal mucosa are similar to those that have been observed in respiratory epithelium. METHODS: We enrolled 94 subjects with and without asthma between 5 and 54 years of age. Relative gene expression in buccal mucosa was determined with quantitative RT-PCR for the following genes: CCL2, EDN1, FKBP5, IL8, IFNAR2, NFKB1, RELA, SERPINB2, DENND1B, HRH1, ICAM1, ORMDL3, NR3C1, CLCA1, CRHR1, MUC5B, FCER2, POSTN, GAPDH, PPIA. RESULTS: mRNA Expression of the following genes was detected in buccal mucosa: CCL2, EDN1, FKBP5, IL8, IFNAR2, NFKB1, RELA, SERPINB2, DENND1B, HRH1, ICAM1, ORMDL3, NR3C1, GAPDH, PPIA. HRH1 was differentially expressed in adults with asthma vs. controls (p = 0.04), and EDN1 was differentially expressed in children with asthma vs. controls 12-18 years old (p = 0.03). A similar trend for HRH1 was observed in children 12-18 years old. CONCLUSIONS: Buccal mucosa sampling is a reliable method for detecting changes in gene expression in patients with asthma. This non-invasive technique may serve as a valuable tool for diagnosing asthma and evaluating therapeutic response.

Association of tobacco smoke exposure and atopic sensitization.

BACKGROUND: Forty million children are regularly exposed to environmental tobacco smoke (ETS) each year, increasing their risk for premature death and middle ear and acute respiratory infections. Early life exposure to ETS also is clearly associated with wheezing. However, there is no clear understanding of the influence of ETS on the development of allergic sensitization. OBJECTIVE: To determine the association of combined exposure to ETS and indoor allergens on IgE sensitization to aeroallergens in children. METHODS: This case-control study enrolled 116 cases and 121 controls from low-income families from Kansas City, Missouri. The adjusted odds ratio was calculated using a logistic model to assess the association between ETS and allergic sensitization using dust allergen levels as a covariate. RESULTS: Thirty-six percent of atopic children and 39% of controls were exposed to ETS (P < .05). Unadjusted analyses showed no significant influence of ETS on IgE sensitization to indoor allergens. Logistic regression analyses also showed no significant influence of ETS on sensitization when adjusted for levels of allergens in the home dust and family history of allergic rhinitis. CONCLUSION: These data suggest that ETS exposure was not associated with IgE sensitization to indoor allergens, even when home allergen levels were taken into consideration. Further understanding of how components of tobacco smoke influence the immune response is necessary to interpret the disparate findings across studies.

Genetic variation in the TNFA promoter region and TNFA gene expression in subjects with asthma.

OBJECTIVE: Asthma is a chronic disease that affects millions of people. Messenger RNA (mRNA) expression of specific inflammatory markers has been associated with asthma and corticosteroid response. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, has been shown to have increased expression in airways of asthmatics and may be related to corticosteroid sensitivity. The purpose of this study was to determine how genetic variants within the promoter region of the TNFA gene differ between subjects with asthma and controls. We also investigated how genetic variation affects gene expression. METHODS: We enrolled 94 subjects between 5 to 54 years of age who met the inclusion and exclusion criteria. TNFA mRNA expression was determined by qRT-PCR on total RNA isolated from the buccal mucosa. Genotyping was performed for TNFA-1031T/C, -857C/T, and -308G/A on genomic DNA isolated from blood with commercially available assays. Gene expression was log-2 transformed and corrected with 2 normalization genes. General linear model, Chi-square test, Fisher's exact test, and Cochran-Mantel-Haenszel test were performed with p < .05. RESULTS: The TNFA-857C/T polymorphism is associated with asthma in this cohort. The TNFA-857 T allele is underrepresented in pediatric subjects with asthma relative to those without asthma (3% and 29% of individuals, respectively, p = .01). Furthermore, a TNFA haplotype combination containing -1031T/-857C/-308G and -1031T/-857T/-308G is associated with lower expression of TNF-α mRNA (p = .01) in pediatric subjects. CONCLUSIONS: Presence of the TNFA-857T allele may be protective in the development of asthma and a haplotype combination that contains the TNFA-857T allele is associated with TNFA expression.