Epithelial overexpression of IL-33 induces eosinophilic esophagitis dependent on IL-13.

BACKGROUND: Eosinophilic esophagitis (EoE) is an increasingly common inflammatory condition of the esophagus; however, the underlying immunologic mechanisms remain poorly understood. The epithelium-derived cytokine IL-33 is associated with type 2 immune responses and elevated in esophageal biopsy specimens from patients with EoE. OBJECTIVE: We hypothesized that overexpression of IL-33 by the esophageal epithelium would promote the immunopathology of EoE. METHODS: We evaluated the functional consequences of esophageal epithelial overexpression of a secreted and active form of IL-33 in a novel transgenic mouse, EoE33. EoE33 mice were analyzed for clinical and immunologic phenotypes. Esophageal contractility was assessed. Epithelial cytokine responses were analyzed in three-dimensional organoids. EoE33 phenotypes were further characterized in ST2-/-, eosinophil-deficient, and IL-13-/- mice. Finally, EoE33 mice were treated with dexamethasone. RESULTS: EoE33 mice displayed ST2-dependent, EoE-like pathology and failed to thrive. Esophageal tissue remodeling and inflammation included basal zone hyperplasia, eosinophilia, mast cells, and TH2 cells. Marked increases in levels of type 2 cytokines, including IL-13, and molecules associated with immune responses and tissue remodeling were observed. Esophageal organoids suggested reactive epithelial changes. Genetic deletion of IL-13 in EoE33 mice abrogated pathologic changes in vivo. EoE33 mice were responsive to steroids. CONCLUSIONS: IL-33 overexpression by the esophageal epithelium generated immunopathology and clinical phenotypes resembling human EoE. IL-33 may play a pivotal role in the etiology of EoE by activating the IL-13 pathway. EoE33 mice are a robust experimental platform for mechanistic investigation and translational discovery.

Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Atopic dermatitis (eczema) guidelines: 2023 American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters GRADE- and Institute of Medicine-based recommendations.

BACKGROUND: Guidance addressing atopic dermatitis (AD) management, last issued in 2012 by the American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force, requires updating as a result of new treatments and improved guideline and evidence synthesis methodology. OBJECTIVE: To produce evidence-based guidelines that support patients, clinicians, and other decision-makers in the optimal treatment of AD. METHODS: A multidisciplinary guideline panel consisting of patients and caregivers, AD experts (dermatology and allergy/immunology), primary care practitioners (family medicine, pediatrics, internal medicine), and allied health professionals (psychology, pharmacy, nursing) convened, prioritized equity, diversity, and inclusiveness, and implemented management strategies to minimize influence of conflicts of interest. The Evidence in Allergy Group supported guideline development by performing systematic evidence reviews, facilitating guideline processes, and holding focus groups with patient and family partners. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed rating the certainty of evidence and strength of recommendations. Evidence-to-decision frameworks, subjected to public comment, translated evidence to recommendations using trustworthy guideline principles. RESULTS: The panel agreed on 25 recommendations to gain and maintain control of AD for patients with mild, moderate, and severe AD. The eAppendix provides practical information and implementation considerations in 1-2 page patient-friendly handouts. CONCLUSION: These evidence-based recommendations address optimal use of (1) topical treatments (barrier moisturization devices, corticosteroids, calcineurin inhibitors, PDE4 inhibitors [crisaborole], topical JAK inhibitors, occlusive [wet wrap] therapy, adjunctive antimicrobials, application frequency, maintenance therapy), (2) dilute bleach baths, (3) dietary avoidance/elimination, (4) allergen immunotherapy, and (5) systemic treatments (biologics/monoclonal antibodies, small molecule immunosuppressants [cyclosporine, methotrexate, azathioprine, mycophenolate, JAK inhibitors], and systemic corticosteroids) and UV phototherapy (light therapy).

Incidence of and risk factors for paediatric perioperative anaphylaxis in the USA.

BACKGROUND: Perioperative anaphylaxis is a serious and often life-threatening immediate hypersensitivity reaction. There are few published data on paediatric perioperative anaphylaxis (pPOA). We evaluated the incidence of and risk factors involved in the occurrence of pPOA within a large US national database. METHODS: Deidentified data from the US Nationwide Inpatient Sample from 2005 to 2014 were used to identify pPOA cases and to conduct a retrospective multivariate analysis of preselected independent variables. RESULTS: Among 3,601,180 surgeries and procedures in children aged 0-18 yr, 297 pPOA cases were identified for an incidence of one in 12,125 surgeries and procedures. Compared with controls, pPOA cases had an increased median length of stay (6 vs 2 days; P<0.001) and median hospital cost ($54 719 vs $5109; P<0.0001). The age groups between 6 and 12 yr (odds ratio [OR] 7.1; 95% confidence interval [CI] 3.9-12.9; P<0.001) and 13 and 17 yr (OR 8.5; 95% CI 4.7-15.2; P<0.001) were associated with increased odds of pPOA. Transplant (OR 46.3; 95% CI 20.8-102.9; P<0.001), cardiac (OR 16.4; 95% CI 7.5-35.9; P<0.001), and vascular (OR 15.2; 95% CI 7.5-30.7; P<0.001) procedures posed the highest risk for pPOA. Chronic pulmonary disease, coagulopathy, and fluid and electrolyte disorders were also associated with pPOA (OR 2.2; 95% CI 1.5-3.3; P<0.001). CONCLUSIONS: The incidence of pPOA was one in 12,125 cases. Risk factors included age, procedure type, and comorbidities.

Eosinophils promote effector functions of lung group 2 innate lymphoid cells in allergic airway inflammation in mice.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia associated with allergen provocation. Although ILC2s have been shown to promote eosinophil activities, the role of eosinophils in group 2 innate lymphoid cell (ILC2) responses is less well defined. OBJECTIVE: We sought to investigate the role of eosinophils in activation of ILC2s in models of allergic asthma and in vitro. METHODS: Inducible eosinophil-deficient mice were exposed to allergic respiratory inflammation models of asthma, such as ovalbumin or house dust mite challenge, or to innate models of type 2 airway inflammation, such as inhalation of IL-33. Eosinophil-specific IL-4/13-deficient mice were used to address the specific roles for eosinophil-derived cytokines. Direct cell interactions between ILC2s and eosinophils were assessed by in vitro culture experiments. RESULTS: Targeted depletion of eosinophils resulted in significant reductions of total and IL-5+ and IL-13+ lung ILC2s in all models of respiratory inflammation. This correlated with reductions in IL-13 levels and mucus in the airway. Eosinophil-derived IL-4/13 was necessary for both eosinophil and ILC2 accumulation in lung in allergen models. In vitro, eosinophils released soluble mediators that induced ILC2 proliferation and G protein-coupled receptor-dependent chemotaxis of ILC2s. Coculture of ILC2s and IL-33-activated eosinophils resulted in transcriptome changes in both ILC2s and eosinophils, suggesting potential novel reciprocal interactions. CONCLUSION: These studies demonstrate that eosinophils play a reciprocal role in ILC2 effector functions as part of both adaptive and innate type 2 pulmonary inflammatory events.

The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.

Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic allergic disease associated with type 2 inflammation and epithelial barrier dysfunction. The etiology is unknown, however, genetic heritability studies suggest environmental factors play a key role in pathogenesis. Detergents, such as sodium dodecyl sulfate (SDS), are common ingredients in household products such as dish soap and toothpaste. We hypothesized detergent exposure decreases epithelial barrier function and induces esophageal inflammation. METHODS: Immortalized esophageal epithelial cells (EPC2) were cultured in air-liquid interface (ALI) and exposed to SDS. Barrier function/activity was assessed by transepithelial electrical resistance (TEER), FITC-dextran flux, and RT-PCR. Additionally, SDS-treated mouse esophageal organoids were evaluated for morphology. To investigate the effects of SDS in vivo, mice were treated with 0.5% SDS in drinking water for 14 days. Esophagi were assessed by gross morphology, histopathology, protein expression, and bulk RNA sequencing. RESULTS: When EPC2 cells were exposed to SDS (5 µg/ml) for 96 h, TEER decreased (p = 0.03), and FITC-dextran flux increased (p = 0.0002). mRNA expression of IL-33 increased 4.5-fold (p = 0.02) at 6 h and DSG1 decreased (p < 0.0001) by 72 h. Disrupted epithelial integrity was noted in SDS-treated esophageal organoids. When mice were exposed to SDS, they showed increased esophageal width, chemokine, and metalloprotease levels. Mice treated with SDS also showed increased IL-33 protein expression, basal zone hyperplasia, CD4+ cell infiltration, and esophageal eosinophilia. RNA sequencing revealed upregulation of immune response pathway genes. CONCLUSION: Exposure to SDS decreases esophageal barrier integrity, stimulates IL-33 production, and promotes epithelial hyperplasia and tissue eosinophilia. Detergents may be a key environmental trigger in EoE pathogenesis.

The chronic rhinosinusitis practice parameter.

The Allergy-Immunology Joint Task Force on Practice Parameters has published the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines for the medical management of chronic rhinosinusitis with nasal polyposis (CRSwNP). The practice parameter provides evidence-based guidelines on the use of intranasal corticosteroids (INCS) and biologics for CRSwNP, and aspirin therapy after desensitization (ATAD) for the management of aspirin-exacerbated respiratory disease (AERD). Evidence on surgery was not assessed. Overall, the guidelines suggest INCS rather than no INCS (conditional recommendation, low certainty of evidence), biologics rather than no biologics (conditional recommendation, moderate certainty of evidence), and ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). Patient-important outcomes are compared across the various INCS delivery modalities and across the different biologics and ATAD. Specific consideration points for shared decision making with patients are detailed in the guideline. These include delivery method and small treatment effect sizes for INCS, disease burden at presentation, variability in efficacy among biologics, cost issues for biologics, and adverse effects of aspirin and risks related to desensitization for ATAD. The guidelines also identify a need for randomized control trials directly comparing treatment modalities and further investigation into which outcomes are important for patients.

A prediction model for asthma exacerbations after stopping asthma biologics.

BACKGROUND: Little is known regarding the prediction of the risks of asthma exacerbation after stopping asthma biologics. OBJECTIVE: To develop and validate a predictive model for the risk of asthma exacerbations after stopping asthma biologics using machine learning models. METHODS: We identified 3057 people with asthma who stopped asthma biologics in the OptumLabs Database Warehouse and considered a wide range of demographic and clinical risk factors to predict subsequent outcomes. The primary outcome used to assess success after stopping was having no exacerbations in the 6 months after stopping the biologic. Elastic-net logistic regression (GLMnet), random forest, and gradient boosting machine models were used with 10-fold cross-validation within a development (80%) cohort and validation cohort (20%). RESULTS: The mean age of the total cohort was 47.1 (SD, 17.1) years, 1859 (60.8%) were women, 2261 (74.0%) were White, and 1475 (48.3%) were in the Southern region of the United States. The elastic-net logistic regression model yielded an area under the curve (AUC) of 0.75 (95% confidence interval [CI], 0.71-0.78) in the development and an AUC of 0.72 in the validation cohort. The random forest model yielded an AUC of 0.75 (95% CI, 0.68-0.79) in the development cohort and an AUC of 0.72 in the validation cohort. The gradient boosting machine model yielded an AUC of 0.76 (95% CI, 0.72-0.80) in the development cohort and an AUC of 0.74 in the validation cohort. CONCLUSION: Outcomes after stopping asthma biologics can be predicted with moderate accuracy using machine learning methods.

Allergies Come Clean: The Role of Detergents in Epithelial Barrier Dysfunction.

PURPOSE OF REVIEW: The prevalence and incidence of allergic disease have been rising in Westernized countries since the twentieth century. Increasingly, evidence suggests that damage to the epithelium initiates and shapes innate and adaptive immune responses to external antigens. The objective of this review is to examine the role of detergents as a potential risk factor for developing allergic disease. RECENT FINDINGS: Herein, we identify key sources of human detergent exposure. We summarize the evidence suggesting a possible role for detergents and related chemicals in initiating epithelial barrier dysfunction and allergic inflammation. We primarily focus on experimental models of atopic dermatitis, asthma, and eosinophilic esophagitis, which show compelling associations between allergic disease and detergent exposure. Mechanistic studies suggest that detergents disrupt epithelial barrier integrity through their effects on tight junction or adhesion molecules and promote inflammation through epithelial alarmin release. Environmental exposures that disrupt or damage the epithelium may account for the increasing rates of allergic disease in genetically susceptible individuals. Detergents and related chemical compounds represent possible modifiable risk factors for the development or exacerbation of atopy.

Meteorological and environmental factors that impact pollen counts, allergenicity, and thresholds: A scoping review.

Background: Pollen is a key source of aeroallergens responsible for allergic rhinitis, conjunctivitis, and asthma. Objective: The goal of this scoping review was to summarize current available literature on the factors that affect pollen counts, allergenicity, and thresholds that induce symptoms in individuals who were sensitized. Methods: Several databases showed no published articles with a similar scope as of January 2022. A search of these data bases yielded 373 articles for assessment. These were then reviewed for relevance, and articles were selected to demonstrate the breadth of available data on pollen counts, allergenicity, and thresholds that induce symptoms in individuals who were sensitized. Additional articles were identified through examination of bibliographies of search-identified articles. Results: Several environmental factors have shown a correlation with pollen counts and allergen load, including the distance from the source, wind characteristics, pollen size, terrain, urban environments, air composition (particulate matter, CO2 levels, ozone, NO2), and weather conditions (humidity, thunderstorms, precipitation). Pollen thresholds at which symptoms were induced varied by study, pollen type, symptom, disease, and location. In addition, there was heterogeneity in study designs, threshold definition, and outcome measures. Conclusion: This scoping review demonstrates the plethora of variables that influence the relationship between pollen and the symptoms of allergic diseases. Analysis of the available data sheds light on the complex interaction between environmental and biologic factors that affect pollen's role in allergic diseases and provides guidance on multiple areas for further investigation.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). CONCLUSIONS: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Asthma biologic trial eligibility and real-world outcomes in the United States.

OBJECTIVE: To compare the outcomes of real-world patients who would have been eligible for asthma biologics to those who would not have been eligible. METHODS: We used data from the OptumLabs Data Warehouse (OLDW) to categorize patients into eligible and ineligible groups based on clinical trials (n = 19 trials) used for Food and Drug Administration (FDA) approval. We then compared the change in the number of asthma exacerbations before and after biological initiation between the two groups. RESULTS: The percentage of people who would have been eligible for asthma biologic clinical trials ranged from 0-10.2%. The eligible group had a greater reduction in number of asthma exacerbations compared to the ineligible group based on eligibility criteria from 1 omalizumab trial (1.52, 95% CI 1.25, 1.8 in eligible vs. 0.47, 95% CI 0.43, 0.52 in ineligible) and from 1 dupilumab trial (1.6, 95% CI 0.92, 2.28 in eligible vs. 0.52, 95% CI 0.38, 0.65 ineligible). Notably, 15 of the 19 trials had fewer than 11 eligible people, limiting additional comparisons. CONCLUSIONS: Fewer than 1 in 10 people in the United States treated with asthma biologics would have been eligible to participate in the trial for the biologic they used. Where comparisons could be made, trial eligible people have a greater reduction in exacerbations.Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2010749 .

Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy.

Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy.

BACKGROUND & AIMS: Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time. METHODS: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis. RESULTS: At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia. CONCLUSIONS: In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov no: NCT02103270.

Persistence of asthma biologic use in a US claims database.

BACKGROUND: Little is known on the persistence of asthma biologic use in clinical practice. OBJECTIVE: To evaluate the persistence of asthma biologic use and time to clinical response in clinical practice. METHODS: A cohort of people with asthma who used at least 1 asthma biologic was constructed using data from 2003 to 2019 in the OptumLabs Data Warehouse. Treatment persistence was defined by the length of time that a person continuously used an asthma biologic, allowing for a lapse in use up to 4 months before confirming that a person stopped. Clinical response to treatment (defined as a decline in asthma exacerbations of at least 50% compared with the 6 months before starting an asthma biologic) was described over time and in relation to biologic persistence. RESULTS: There were 9575 people who had at least 1 episode of asthma biologic use. There were 5319 people (64%, 95% confidence interval, 63%-65%) who completed 6 months or more on an asthma biologic and 3284 (45%, 95% confidence interval, 44%-46%) who completed 12 months or more. Of people with 1 or more asthma exacerbation 6 months before index biologic use, 63%, 76%, 80%, and 81% realized a 50% or more reduction in postindex asthma exacerbations in the first 6 months, 6 to 12 months, 12 to 18 months, and 18 to 24 months, respectively. CONCLUSION: Between 48% and 64% of people remained on an asthma biologic for 6 months or more after first use. Most people who achieved a reduction in asthma exacerbations did so in the first 6 months of treatment.

Incidence of and risk factors for perioperative or periprocedural anaphylaxis in the United States from 2005 to 2014.

BACKGROUND: The estimated worldwide incidence of perioperative or periprocedural anaphylaxis (PA) is between 1 in 1250 and 1 in 20,000 procedures. OBJECTIVE: To evaluate the incidence of PA in the United States and compare patient characteristics and underlying risk factors using a large national database. METHODS: Using deidentified data from the nationwide inpatient sample from 2005 to 2014, we identified cases of PA through the International Classification of Diseases, Ninth Revision, Clinical Modification codes and conducted a retrospective analysis. RESULTS: Among 35,647,347 surgeries and procedures, there were 5458 (0.015%) PA cases identified. The incidence of PA was 15.3 cases per 100,000 procedures. When compared with controls, PA cases had an increased mortality (3.4% vs 1.4%; P < .001), median length of stay (5 vs 3 days; P < .001), and median hospital cost ($45,155 vs $24,734; P < .001). The age group between 18 and 34 years (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.13-1.58; P < .001) and female sex (OR, 1.40; 95% CI, 1.31-1.49; P < .001) were associated with increased odds of PA. Transplant (OR, 3.35; 95% CI, 2.59-4.34; P < .001), hematologic (OR, 1.63; 95% CI, 1.30-2.05; P < .001), vascular (OR, 1.49; 95% CI, 1.30-1.67; P < .001), and cardiac (OR, 1.47; 95% CI, 1.30-1.67; P < .001) procedures were at increased risk for PA. Several comorbidities were associated with PA including chronic pulmonary disease (OR, 1.41; 95% CI, 1.31-1.51; P < .001). CONCLUSION: The incidence of PA is 1 in 6531 procedures, with a mortality of 1 in 191,652 procedures. PA has worsening outcomes compared with controls. The risk factors of PA include age, sex, procedure type, and comorbidities.

Incidence and risk factors for near-fatal and fatal outcomes after perioperative and periprocedural anaphylaxis in the USA, 2005-2014.

BACKGROUND: The incidence of fatal and near-fatal outcomes after perioperative anaphylaxis is unknown in the USA. Previously identified risk factors of neuromuscular-blocker-induced fatal perioperative anaphylaxis include male sex, obesity, and use of beta blockers. We examined the incidence of fatal and near-fatal outcomes after perioperative anaphylaxis in the USA and the underlying risk factors using a large national database. METHODS: Using the Nationwide Inpatient Sample from 2005 to 2014, we identified cases of fatal and near-fatal perioperative anaphylaxis, defined as perioperative anaphylaxis cases complicated by respiratory or cardiac arrest, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. RESULTS: Amongst 5223 perioperative anaphylaxis cases, the proportion of near-fatal or fatal cases attributable to perioperative anaphylaxis was 7.0% (95% confidence interval [CI]: 6.2-7.7), with near-fatal perioperative anaphylaxis cases accounting for 5.0% (95% CI: 4.4-5.6%) and fatal cases accounting for 2.0% (95% CI: 1.5-2.5%) of cases overall. Thus, the incidence of fatal or near-fatal perioperative anaphylaxis is 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal perioperative anaphylaxis include age (≥65 yr); undergoing a cardiac procedure; and comorbid conditions of weight loss, non-metastatic solid tumours, metastatic cancer, paralysis, coagulopathy, renal failure, congestive heart failure, fluid and electrolyte disorder, and neurological disorders. Individuals with near-fatal or fatal perioperative anaphylaxis reactions had increased lengths of stay and hospital costs compared with controls. CONCLUSIONS: The incidence of fatal or near-fatal perioperative anaphylaxis in the USA was 1.26 in 100 000 procedures. Risk factors for fatal or near-fatal outcomes include older age, cardiac procedures, and specific comorbidities.

Image Analysis of Eosinophil Peroxidase Immunohistochemistry for Diagnosis of Eosinophilic Esophagitis.

BACKGROUND: Diagnosis of eosinophilic esophagitis (EoE) requires manual quantification of tissue eosinophils. Eosinophil peroxidase (EPX) is an eosinophil-specific, cytoplasmic granule protein released during degranulation. AIMS: The objective of this study was to evaluate image analysis of EPX immunohistochemistry as an automated method for histologic diagnosis of EoE. METHODS: We performed a secondary analysis of prospectively collected esophageal biopsies obtained from adult subjects with EoE and controls. Tissue sections were stained with hematoxylin and eosin (H&E) and evaluated for peak eosinophils per high power field (eos/hpf). The same slides were de-stained and re-stained to detect EPX for direct comparison. Slides were digitized, and EPX staining area/mm2 was quantified using image analysis. Paired samples were compared for changes in EPX staining in treatment responders and non-responders. RESULTS: Thirty-eight EoE cases and 49 controls were analyzed. Among EoE subjects, matched post-treatment biopsies were available for 21 responders and 10 non-responders. Baseline EPX/mm2 was significantly increased in EoE subjects and decreased in treatment responders. EPX quantification correlated strongly with eos/hpf (r = 0.84, p < 0.0001) and identified EoE subjects with high diagnostic accuracy (AUC 0.95, p < 0.0001). The optimal diagnostic EPX-positive pixel/area threshold was 17,379 EPX/mm2. Several controls (5/49) with < 15 eos/hpf on H&E staining exceeded this cutoff. CONCLUSIONS: EPX/mm2 correlates strongly with eos/hpf, accurately identifies subjects with EoE, and decreases in treatment responders. Automated quantification of intact eosinophils and their degranulation products may enhance pathologic assessment. Future studies are needed to correlate EPX/mm2 with symptoms, endoscopic findings, and esophageal distensibility.

Peanut allergy diagnosis: A 2020 practice parameter update, systematic review, and GRADE analysis.

Given the burden of disease and the consequences of a diagnosis of peanut allergy, it is important that peanut allergy be accurately diagnosed so that an appropriate treatment plan can be developed. However, a test that indicates there is peanut sensitization present (eg, a "positive" test) is not always associated with clinical reactivity. This practice parameter addresses the diagnosis of IgE-mediated peanut allergy, both in children and adults, as pertaining to 3 fundamental questions, and based on the systematic reviews and meta-analyses, makes recommendations for the clinician who is evaluating a patient for peanut allergy. These questions relate to when diagnostic tests should be completed, which diagnostic tests to utilize, and the utility (or lack thereof) of diagnostic testing to predict the severity of a future allergic reaction to peanut.