Publications by authors named "Matthew Rank"

96 Publications

Which people with asthma are most likely to be hospitalized with COVID-19 in the United States?

J Allergy Clin Immunol Pract 2021 Mar 5. Epub 2021 Mar 5.

Division of Health Care Delivery Research, Mayo Clinic, Rochester, Minn.

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http://dx.doi.org/10.1016/j.jaip.2021.02.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934792PMC
March 2021

Asthma Patients Who Stop Asthma Biologics Have a Similar Risk of Asthma Exacerbations as Those Who Continue Asthma Biologics.

J Allergy Clin Immunol Pract 2021 Feb 27. Epub 2021 Feb 27.

Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minn; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, Ariz; Division of Pulmonology, Phoenix Children's Hospital, Phoenix, Ariz. Electronic address:

Background: There is limited information about outcomes associated with stopping asthma biologics.

Objective: To compare outcomes in people who stopped or continued asthma biologics.

Methods: We identified a cohort of people with asthma who stopped or continued asthma biologics in the Optum Labs Database Warehouse, using a propensity matching method for case and control groups with the variables of age, sex, race, region, insurance, income, specialist access, Charlson comorbidity, specific medical conditions, pre-index exacerbation count, pre-index rescue inhaler pharmacy fills, and pre-index inhaled corticosteroid with or without long-acting β-agonist pharmacy fills. Primary outcome used to assess failure of stopping was an increase of 50% or more in the asthma exacerbation rate in the 6 months after discontinuing the biologic compared with the 6-month period before biologic initiation.

Results: Among a cohort of 4960 asthma biologic users, 1249 were observed to stop use after 6 to 12 months of use. We identified a matched cohort of 1247 stoppers and 1247 people who continued biologic use for at least 18 months. In the first 6 months after stopping or sham stopping, 10.2% of stoppers and 9.5% of continuers had an increase of 50% or more in asthma exacerbations. We found a similar adjusted odds of failing among stoppers and continuers (odds ratio = 1.085; 95% confidence interval, 0.833-1.413).

Conclusions: An increase in asthma exacerbations is infrequently observed in people who stopped asthma biologics and was observed at similar rates as in matched controls who continued asthma biologics.
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http://dx.doi.org/10.1016/j.jaip.2021.02.031DOI Listing
February 2021

Adherence to Asthma Biologics: Implications for Patient Selection, Step Therapy, and Outcomes.

Chest 2021 Mar 24;159(3):924-932. Epub 2020 Oct 24.

Division of Pulmonology, Phoenix Children's Hospital, Phoenix, AZ; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, AZ. Electronic address:

Background: Little is known about adherence to asthma biologics.

Research Question: Is adherence to inhaled corticosteroid (ICS) associated with subsequent asthma biologic adherence?

Study Design And Methods: We analyzed individuals with asthma who started asthma biologics in the OptumLab Data Warehouse and used that data until October 2019. We calculated proportion days covered (PDC) for ICS ± long-acting β-agonists in the 6 months before and after asthma biologics were started and asthma biologic PDC for the first 6 months of use. We performed a multivariable analysis to identify factors associated with asthma biologic PDC ≥0.75, ICS PDC ≥0.75 during the 6-month period after asthma biologic were started, and achievement of a ≥50% reduction in asthma exacerbations during the first 6 months of asthma biologic use.

Results: We identified 5,319 people who started asthma biologics. The mean PDC for asthma biologics was 0.76 (95% CI, 0.75-0.77) in the first 6 months after starting, higher than the mean PDCs for ICS in the 6 months before (0.44 [95% CI, 0.43-0.45]) and after (0.40 [95% CI, 0.39-0.40]) starting the asthma biologic. PDC ≥0.75 for ICS 6 months before index biologic use is associated with PDC for asthma biologics ≥0.75 (OR, 1.25; 95% CI, 1.10-1.43) and for ICS during the first 6 months of biologic use (OR, 9.93; 95% CI, 8.55-11.53). Neither ICS PDC ≥0.75 (OR, 0.92; 95% CI, 0.74-1.14) nor asthma biologic PDC ≥0.75 (OR, 1.15; 95% CI, 0.97-1.36) is associated with a statistically significant reduction in asthma exacerbations during the first 6 months of asthma biologic use among people with any exacerbation in the 6 months before first use.

Interpretation: Adherence to asthma biologic is higher than to ICS and is associated with different factors.
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http://dx.doi.org/10.1016/j.chest.2020.10.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965652PMC
March 2021

Benefits of biologic therapy administered for asthma on co-existent chronic rhinosinusitis: A real-world study.

Int Forum Allergy Rhinol 2021 Feb 1. Epub 2021 Feb 1.

Department of Otorhinolaryngology, Mayo Clinic, Phoenix, AZ.

Background: Asthma and some chronic rhinosinusitis (CRS) subtypes are mediated by similar pathophysiologic mechanisms. The purpose of this study was to evaluate the effects of biologic therapy for asthma on co-existent CRS in the "real-world" setting.

Methods: A review of electronic health records (2016-2019) at Mayo Clinic was conducted to identify asthma patients treated with biologics who had co-existent CRS. Matched-pair analyses compared pretherapy and posttherapy Lund-Mackay computed tomography (CT) scores and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Performance of endoscopic sinus surgery (ESS) after initiating biologics was studied.

Results: We identified 247 patients who received anti-asthma biologic therapy and had co-existent CRS. Of these, 181 patients (73.3%) had CRS with nasal polyposis (CRSwNP) and 66 (26.7%) had CRS without nasal polyposis (CRSsNP). The biologics utilized were omalizumab (51.0%), mepolizumab (46.6%), benralizumab (10.5%), reslizumab (1.6%), and dupilumab (2.4%). Anti-interleukin-5 (anti-IL-5) intervention was associated with significant improvement in CT scores (CRS overall, CRSwNP subgroup, CRSsNP subgroup) and SNOT-22 scores (CRS overall, CRSwNP subgroup). Patients on omalizumab had a decrease in CT scores, but not SNOT-22 scores. ESS was performed in 206 patients (84.1%); 55 (22.3%) underwent surgery post-biologic intervention (anti-IL-5: 16.5%; omalizumab 27.8% of patients).

Conclusion: Anti-IL-5 agents were associated with improved CT and SNOT-22 scores in the overall CRS group and in CRSwNP subgroup; CRSsNP patients showed improved CT scores only. Omalizumab improved CT but not SNOT-22 scores. ESS was performed in 22% of patients after initiating biologics. These real-world results may influence future trial designs and clinical applications of biologics for CRS. ©2021 ARSAAOA, LLC.
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http://dx.doi.org/10.1002/alr.22774DOI Listing
February 2021

Effectiveness of Physical Distancing: Staying 6 Feet Over to Put Respiratory Viruses 6 Feet Under.

Mayo Clin Proc 2021 01;96(1):148-151

Division of Allergy, Asthma and Immunology, Mayo Clinic, Scottsdale, AZ.

Community transmission of severe acute respiratory illness Coronavirus-2 (SARS-CoV-2) in Arizona was noted in March 2020. It was our hypothesis that the associated implementation of physical distancing and masking led to a decline in circulation and detection of common respiratory viruses. Nasopharyngeal swabs processed with the Biofire, Film Array respiratory panel at Mayo Clinic Arizona were reviewed from January 1, 2017, to July 31, 2020. A total of 13,324 nasopharyngeal swabs were analyzed. Between April and July 2017- 2019 (Period A) a mean of 262 tests were performed monthly, falling to 128 for the corresponding months of 2020 (Period B). A reduction in the monthly mean number of positive tests (Period A 71.5; Period B 2.8) and mean positivity rate (Period A 25.04%; Period B 2.07%) was observed. Rhinovirus/enterovirus was the most prevalent virus, with a monthly mean of 21.6 cases (30.2% of positives) for Period A and 2 cases (72.7% of positives) for Period B. Positivity for a second virus occurred in a mean of 2.1 positive tests (3.3%) in Period A but was absent in Period B. Implementation of distancing and masking coincides with a marked reduction in respiratory virus detection and likely circulation. Data from the fall/winter of 2020 will help clarify the potential role for distancing and masking as a mitigation strategy, not only for SARS-CoV-2 but also in the seasonal battle against common respiratory viruses.
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http://dx.doi.org/10.1016/j.mayocp.2020.10.040DOI Listing
January 2021

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

Ann Allergy Asthma Immunol 2021 02 14;126(2):180-186.e3. Epub 2020 Oct 14.

Department of Allergic Diseases, Mayo Clinic, Rochester, Minnesota.

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.
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http://dx.doi.org/10.1016/j.anai.2020.10.001DOI Listing
February 2021

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

J Allergy Clin Immunol 2020 12 15;146(6):1302-1334. Epub 2020 Aug 15.

Nova Southeastern University College of Allopathic Medicine, Fort Lauderdale, Fla.

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.
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http://dx.doi.org/10.1016/j.jaci.2020.07.031DOI Listing
December 2020

Rhinitis 2020: A practice parameter update.

J Allergy Clin Immunol 2020 10 22;146(4):721-767. Epub 2020 Jul 22.

Division of Allergy and Immunology, Department of Pediatrics, The Elliot and Roslyn Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.
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http://dx.doi.org/10.1016/j.jaci.2020.07.007DOI Listing
October 2020

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

Clin Gastroenterol Hepatol 2020 May 17. Epub 2020 May 17.

Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cgh.2020.05.019DOI Listing
May 2020

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

Gastroenterology 2020 05;158(6):1789-1810.e15

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

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.
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http://dx.doi.org/10.1053/j.gastro.2020.02.039DOI Listing
May 2020

AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis.

Gastroenterology 2020 05;158(6):1776-1786

Division of Gastroenterology and Hepatology, Veterans Affairs Northeast Ohio Healthcare System, Case Western Reserve University School of Medicine, Cleveland, Ohio.

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http://dx.doi.org/10.1053/j.gastro.2020.02.038DOI Listing
May 2020

Technical review on the management of eosinophilic esophagitis: a report from the AGA institute and the joint task force on allergy-immunology practice parameters.

Ann Allergy Asthma Immunol 2020 05;124(5):424-440.e17

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

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.
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http://dx.doi.org/10.1016/j.anai.2020.03.021DOI Listing
May 2020

AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis.

Ann Allergy Asthma Immunol 2020 05;124(5):416-423

Division of Gastroenterology and Hepatology, Veterans Affairs Northeast Ohio Healthcare System, Case Western Reserve University School of Medicine, Cleveland, Ohio.

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http://dx.doi.org/10.1016/j.anai.2020.03.020DOI Listing
May 2020

Spotlight: Treatment of Eosinophilic Esophagitis (EoE).

Gastroenterology 2020 05 6;158(6):1788. Epub 2020 Apr 6.

Section of Allergy/Immunology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.

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http://dx.doi.org/10.1053/j.gastro.2020.03.069DOI Listing
May 2020

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

Dig Dis Sci 2021 Mar 4;66(3):775-783. Epub 2020 Apr 4.

Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, 4140 Bioinformatics Building, Campus Box 7080, Chapel Hill, NC, 27599, USA.

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/mm 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/mm 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/mm. Several controls (5/49) with < 15 eos/hpf on H&E staining exceeded this cutoff.

Conclusions: EPX/mm 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/mm with symptoms, endoscopic findings, and esophageal distensibility.
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http://dx.doi.org/10.1007/s10620-020-06230-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541435PMC
March 2021

Making the GRADE in anaphylaxis management: Toward recommendations integrating values, preferences, context, and shared decision making.

Ann Allergy Asthma Immunol 2020 06 19;124(6):526-535.e2. Epub 2020 Mar 19.

Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, New York.

Objective: To review GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methods and discuss the clinical application of conditional recommendations in clinical guidelines, specifically in the context of anaphylaxis.

Data Sources: Articles that described GRADE, evidence synthesis, evidence to recommendation frameworks, and shared decision making were used to discuss conditional recommendations of the 2020 Anaphylaxis GRADE guideline.

Study Selections: A narrative review detailing concepts of GRADE and approaches to translate conditional recommendations to individualized and contextualized patient care.

Results: GRADE methods encourage a nuanced relationship between certainty of evidence and strength of recommendations. Strength of recommendation must incorporate key factors, including the balance between benefits and harms, patient values and preferences, and resource allocation (costs), with equity, feasibility, and acceptability also often included as considerations. GRADE guidelines provide recommendations that are characterized by directionality (for or against) and strength (strong or conditional). A conditional recommendation is tailored to context and primarily applied through a lens of patient preferences related to the likelihood of outcomes of importance and a shared decision-making approach. Although the 2020 Anaphylaxis GRADE guideline better informs the practice of anaphylaxis prevention through (1) identification and mitigation of risk factors for biphasic anaphylaxis and (2) evaluation of the use of glucocorticoid and/or antihistamine pretreatment, all GRADE recommendations, although directional, are conditional and as such should not be universally applied to every circumstance.

Conclusion: Clinical guidelines provide an important opportunity to critically appraise evidence and translate evidence to practice. Patients, practitioners, and policy makers should appreciate the strength of recommendation and certainty of evidence and understand how this affects guideline applicability and implementation.
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http://dx.doi.org/10.1016/j.anai.2020.03.009DOI Listing
June 2020

The Rationale for Multidisciplinary Management of Chronic Rhinosinusitis with Nasal Polyposis.

J Allergy Clin Immunol Pract 2020 05 12;8(5):1565-1566. Epub 2020 Mar 12.

Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, AZ. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.03.001DOI Listing
May 2020

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

J Allergy Clin Immunol 2020 04 28;145(4):1082-1123. Epub 2020 Jan 28.

Office of Evidence-Based Practice, Children's Mercy Hospital, Kansas City, Mo.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.
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http://dx.doi.org/10.1016/j.jaci.2020.01.017DOI Listing
April 2020

Trends and Disparities in Asthma Biologic Use in the United States.

J Allergy Clin Immunol Pract 2020 02 28;8(2):549-554.e1. Epub 2019 Aug 28.

Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minn; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, Ariz; Division of Pulmonology, Phoenix Children's Hospital, Phoenix, Ariz. Electronic address:

Background: From 2003 to 2015, only 1 biologic was approved for the treatment of moderate to severe asthma in the United States. Since 2015, 4 new asthma biologics were approved by the US Food and Drug Administration.

Objective: To describe trends and disparities of asthma biologic use in the United States from 2003 to 2018.

Methods: We conducted a retrospective analysis using a cohort developed from the OptumLabs Data Warehouse. Prevalent and incident asthma biologic users were identified, and characteristics of users and nonusers were analyzed using regression analysis. Clinician prescribing behavior was described.

Results: Use of biologic medications remains uncommon among individuals with asthma, with prevalence peaking in 2006 at 3 in 1000 individuals with asthma. Several factors are associated with a higher likelihood of asthma biologic use: middle age, higher income, commercial insurance, and access to a specialist. Most clinicians (65%) in the cohort prescribed only 1 biologic.

Conclusions: We report low overall use of asthma biologics and evidence of disparities in access to asthma biologics.
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http://dx.doi.org/10.1016/j.jaip.2019.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012665PMC
February 2020

Inhaled corticosteroids prescriptions increased in the ED for recurrent asthma exacerbations by automated electronic reminders in the ED.

J Asthma 2020 10 8;57(10):1140-1144. Epub 2019 Jul 8.

Pediatric Pulmonology, Phoenix Children's Hospital, Phoenix, AZ, USA.

The objective of this study was to evaluate the impact of an electronic alert on the prescription rate of inhaled corticosteroids (ICS) by ED providers for poorly controlled persistent asthmatic children. Study subjects included asthmatic patients age 4-18 presenting to the ED at Phenix Children's Hospital between February 9, 2018 and December 4, 2018, with a history of at least two previous ED visits for acute exacerbation of asthma within 365 days, no active ICS prescription within 90 days, and free from developmental delay, bronchopulmonary dysplasia due to prematurity, cystic fibrosis, sickle cell disease, and/or interstitial ling disease. Patients meeting these criteria triggered an electronic alert prompting the medical provider to prescribe ICS or indicate reason for not prescribing. Instruction on the alert was provided to ED attending physicians and residents by email and through several educational sessions held prior to the implementation. Among 62 patients without prior ICS who were discharged home from the ED, ICS was prescribed for 48 (77%). No statistically significant differences were detected in baseline characteristics between patients discharged home from the ED with and without ICS prescription. While ICS was prescribed by a larger proportion of physicians (56%) compared to residents (42%), statistical significance was not reached. For the 14 (33%) patients who were discharged home without ICS, no reason was provided to indicate why ICS were not prescribed.: An electronic alert incorporated into the ED workflow to populate a discharge order set is effective to initiate asthma controller medication for poorly controlled pediatric patients. Additional data describing reasons for not prescribing ICS can further refine recommendations for ICS prescriptions, and provide a comprehensive strategy to support clinical decision for pediatric asthma control in acute care settings.
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http://dx.doi.org/10.1080/02770903.2019.1635152DOI Listing
October 2020

Eosinophil peroxidase, GATA3, and T-bet as tissue biomarkers in chronic rhinosinusitis.

J Allergy Clin Immunol 2019 06 8;143(6):2284-2287.e6. Epub 2019 Feb 8.

Department of Otolaryngology, Mayo Clinic, Phoenix, Ariz; Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, Ariz; Division of Pulmonology, Phoenix Children's Hospital, Phoenix, Ariz. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2019.01.038DOI Listing
June 2019

Eosinophil-derived IL-13 promotes emphysema.

Eur Respir J 2019 05 30;53(5). Epub 2019 May 30.

Division of Pulmonary Medicine, Dept of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, USA.

The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, , that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.
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http://dx.doi.org/10.1183/13993003.01291-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313423PMC
May 2019

Asthma biologics: Underuse, overuse, and best use?

Ann Allergy Asthma Immunol 2019 04 19;122(4):358-359. Epub 2018 Dec 19.

Department of Medicine, Rutgers New Jersey Medical School, Morristown, New Jersey.

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http://dx.doi.org/10.1016/j.anai.2018.12.016DOI Listing
April 2019

The Asthma Controller Step-down Yardstick.

Ann Allergy Asthma Immunol 2019 03 12;122(3):241-262.e4. Epub 2018 Dec 12.

Kaiser Permanente Southern California Region, Department of Allergy and Research and Evaluation, San Diego and Pasadena, California.

Asthma guidelines recommend a control-based approach to disease management in which the assessment of impairment and risk is linked to step-based therapy. Using this model, controller treatment is adjusted-upward or downward-according to a patient's level of asthma control over time. Strategies for stepping up controller therapy are well described, and the adult and pediatric Asthma Yardsticks provide operational recommendations based on patient profiles. Strategies for stepping down controller treatment are less clear, although stepping down to the minimum effective therapy is important and should be considered when a patient's asthma has been well controlled for an adequate period as defined by risk and impairment. This Yardstick presents recommendations for when and how to step down asthma controller therapy according to guideline-defined control levels. The objective is to provide clinicians who treat patients with asthma with a practical and clinically relevant framework for implementing a step-down in controller therapy.
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http://dx.doi.org/10.1016/j.anai.2018.12.004DOI Listing
March 2019

Baseline Gastrointestinal Eosinophilia Is Common in Oral Immunotherapy Subjects With IgE-Mediated Peanut Allergy.

Front Immunol 2018 22;9:2624. Epub 2018 Nov 22.

Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, CA, United States.

Oral immunotherapy (OIT) is an emerging treatment for food allergy. While desensitization is achieved in most subjects, many experience gastrointestinal symptoms and few develop eosinophilic gastrointestinal disease. It is unclear whether these subjects have subclinical gastrointestinal eosinophilia (GE) at baseline. We aimed to evaluate the presence of GE in subjects with food allergy before peanut OIT. We performed baseline esophagogastroduodenoscopies on 21 adults before undergoing peanut OIT. Subjects completed a detailed gastrointestinal symptom questionnaire. Endoscopic findings were assessed using the Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) and biopsies were obtained from the esophagus, gastric antrum, and duodenum. Esophageal biopsies were evaluated using the EoE Histologic Scoring System. Immunohistochemical staining for eosinophil peroxidase (EPX) was also performed. Hematoxylin and eosin and EPX stains of each biopsy were assessed for eosinophil density and EPX/mm was quantified using automated image analysis. All subjects were asymptomatic. Pre-existing esophageal eosinophilia (>5 eosinophils per high-power field [eos/hpf]) was present in five participants (24%), three (14%) of whom had >15 eos/hpf associated with mild endoscopic findings (edema, linear furrowing, or rings; median EREFS = 0, IQR 0-0.25). Some subjects also demonstrated basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis. Increased eosinophils were noted in the gastric antrum (>12 eos/hpf) or duodenum (>26 eos/hpf) in 9 subjects (43%). EPX/mm correlated strongly with eosinophil counts ( = 0.71, < 0.0001). Pre-existing GE is common in adults with IgE-mediated peanut allergy. Eosinophilic inflammation (EI) in these subjects may be accompanied by mild endoscopic and histologic findings. Longitudinal data collection during OIT is ongoing.
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http://dx.doi.org/10.3389/fimmu.2018.02624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261984PMC
October 2019

Science of Health Care Delivery: An Innovation in Undergraduate Medical Education to Meet Society's Needs.

Mayo Clin Proc Innov Qual Outcomes 2017 Sep 2;1(2):117-129. Epub 2017 Aug 2.

Department of Radiology, Mayo Clinic, Scottsdale, AZ.

The purpose of this special article is to describe a new, 4-year Science of Health Care Delivery curriculum at Mayo Clinic School of Medicine, including curricular content and structure, methods for instruction, partnership with Arizona State University, and implementation challenges. This curriculum is intended to ensure that graduating medical students enter residency prepared to train and eventually practice within person-centered, community- and population-oriented, science-driven, collaborative care teams delivering high-value care. A Science of Health Care Delivery curriculum in undergraduate medical education is necessary to successfully prepare physicians so as to ensure the best clinical outcomes and patient experience of care, at the lowest cost.
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http://dx.doi.org/10.1016/j.mayocpiqo.2017.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135021PMC
September 2017

Revision endoscopic sinus surgery rates by chronic rhinosinusitis subtype.

Int Forum Allergy Rhinol 2018 09 31;8(9):1047-1051. Epub 2018 May 31.

Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic in Arizona, Phoenix, AZ.

Background: Revision surgery rates following endoscopic sinus surgery (ESS) range between 7% and 50% and are influenced by many factors. This study investigates ESS outcomes for chronic rhinosinusitis (CRS) subtypes.

Methods: Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010-2015) was conducted. Outcomes were analyzed by CRS subtypes.

Results: ESS was performed in 424 CRS patients (CRS with nasal polyps [CRSwNP], n = 170; CRS without polyps [CRSsNP], n = 254). Most patients (309; 72.9%) could not be specifically subtyped; 115 (27.1%) were subtyped as follows: aspirin-exacerbated respiratory disease (AERD), n = 47 (11.1%); allergic fungal sinusitis (AFS), n = 39 (9.2%); immunodeficiency, n = 21 (5.0%); granulomatosis with polyangiitis (GPA), n = 5 (1.2%); and eosinophilic granulomatosis with polyangiitis (EGPA), n = 3 (0.7%). All subgroups experienced clinically meaningful reduction in postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores. At median follow-up of 28 months (interquartile range [IQR], 10-47 months), 19 patients (4%) underwent revision ESS (CRSwNP, n = 6; CRSsNP, n = 13). Revision ESS rates were 3.5% and 5.1% for CRSwNP and CRSsNP, respectively. Revision ESS rate for subtypes were: AERD 2%; AFS 2%; immunodeficiency 14%; GPA 40%; EGPA 0%; and "all other CRS" 4% at median follow-up duration of 36, 28, 41, 37, 44, and 26 months, respectively.

Conclusion: All CRS subtypes demonstrated clinically meaningful improvement in postoperative SNOT-22 scores following ESS. Our overall revision ESS rate was 4% (3.5% in CRSwNP). AFS, AERD, and EGPA groups demonstrated low revision rates, while immunodeficiency and GPA patients required more revision surgery. A contemporary understanding of CRSwNP subtypes facilitated surgical and medical strategies in improving outcomes for AERD, AFS, and EGPA patients. CRSsNP subtypes with immunodeficiency and GPA merit further investigation to optimize outcomes.
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http://dx.doi.org/10.1002/alr.22146DOI Listing
September 2018

Minimally invasive biomarker studies in eosinophilic esophagitis: A systematic review.

Ann Allergy Asthma Immunol 2018 08 16;121(2):218-228. Epub 2018 May 16.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

Background: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus that currently requires repeated endoscopic biopsies for diagnosis and monitoring because no reliable noninvasive markers have been identified.

Objective: To identify promising minimally invasive EoE biomarkers and remaining gaps in biomarker validation.

Methods: We performed a systematic review of EMBASE, Ovid MEDLINE, PubMed, and Web of Science from inception to June 6, 2017. Studies were included if patients met the 2007 consensus criteria for EoE diagnosis, a minimally invasive biomarker was assessed, and the study included at least 1 control for comparison.

Results: The search identified 2094 studies, with 234 reviewed at full-text level, and 49 included in the analysis (20 adult, 19 pediatric, 7 pediatric and adult, and 3 not stated). Most (26 of 49) were published after 2014. Thirty-five studies included healthy controls, 9 analyzed atopic controls, and 29 compared samples from patients with active and inactive EoE. Minimally invasive biomarkers were obtained from peripheral blood (n = 41 studies), sponge or string samples (n = 3), oral or throat swab secretions (n = 2), breath condensate (n = 2), stool (n = 2), and urine (n = 2). The most commonly reported biomarkers were peripheral blood eosinophils (n = 16), blood and string eosinophil granule proteins (n = 14), and eosinophil surface or intracellular markers (n = 12). EoE biomarkers distinguished active EoE from healthy controls in 23 studies, atopic controls in 2 studies, and inactive EoE controls in 20 studies.

Conclusion: Several promising minimally invasive biomarkers for EoE have emerged; however, few are able to differentiate EoE from other atopic diseases.
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http://dx.doi.org/10.1016/j.anai.2018.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104633PMC
August 2018

Use of Asthma APGAR Tools in Primary Care Practices: A Cluster-Randomized Controlled Trial.

Ann Fam Med 2018 03;16(2):100-110

National Research Network, American Academy of Family Physicians, Leawood, Kansas.

Purpose: The purpose of this study was to assess patient and practice outcomes after introducing the Asthma APGAR (Activities, Persistent, triGGers, Asthma medications, Response to therapy) tools into primary care practices.

Methods: We used a pragmatic cluster-randomized controlled design in 18 US family medicine and pediatric practices to compare outcomes in patients with persistent asthma aged 5 to 45 years after introduction of the Asthma APGAR tools vs usual care. Patient outcomes included asthma control, quality of life, and emergency department (ED), urgent care, and inpatient hospital visits. The practice outcome was adherence to asthma guidelines.

Results: We enrolled 1,066 patients: 245 children, 174 adolescents, and 647 adults. Sixty-five percent (692 patients) completed both baseline and 12-month questionnaires, allowing analysis for patient-reported outcomes. Electronic health record data were available for 1,063 patients (99.7%) for practice outcomes. The proportion of patients reporting an asthma-related ED, urgent care, or hospital visit in the final 6 months of the study was lower in the APGAR practices vs usual care practices (10.6% vs 20.9%, = .004). The percentage of patients with "in control" asthma increased more between baseline and 1 year in the APGAR group vs usual care group (13.5% vs 3.4%, =.0001 vs =.86) with a trend toward better control scores and asthma-related quality of life in the former at 1 year ( ≤.06 and = .06, respectively). APGAR practices improved their adherence to 3 or more guideline elements compared with usual care practices (20.7% increase vs 1.9% decrease, = .001).

Conclusions: Introduction of the Asthma APGAR tools improves rates of asthma control; reduces asthma-related ED, urgent care, and hospital visits; and increases practices' adherence to asthma management guidelines.
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http://dx.doi.org/10.1370/afm.2179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847347PMC
March 2018