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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.We systematically synthesized the evidence addressing INCS for CRSwNP.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.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).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.

There are many definitions of anaphylaxis in the medical literature. The authors propose a modified definition of anaphylaxis to be used for clinical decision making that promotes the early utilization of intramuscular epinephrine. Anaphylaxis can be a result of an allergic or nonallergic mechanism. In general, allergic reactions are more severe; however, any type of anaphylaxis can result in death and improve with IM epinephrine. The World Allergy Organization's Grading Criteria for allergic systemic reactions are adapted as a guide to identify manifestations that may progress to anaphylaxis. The intent is to promote and encourage the use of IM epinephrine in the health care setting before the progression of manifestations and the onset of life-threatening respiratory or cardiovascular dysfunction generally recognized as meeting the definition of anaphylaxis.

The concept of atopy was initially developed in the first quarter of the 20th century on the basis of clinical observations without any knowledge of pathogenic mechanisms. Atopy involves a collection of comorbidities that share pathogenic features, and atopic comorbidities affect outcomes of concomitant conditions rather than existing synchronously. The clinical importance of understanding the relationship of these conditions is necessary because the treatment of one condition influences the others, and the development of one leads to or precedes the development of another. Environmental influences and multigenetic predispositions result in complex relationships among the atopic conditions sharing a type 2 pathogenesis. The specialty of Allergy and Immunology is devoted to managing the comorbidities of atopy, and better understanding of their connections can improve patient care.

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. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) 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.

Background: Asthma is a complex disorder with variable clinical expression. Recognizable clinical and laboratory features define phenotypes, and specific biologic pathways define endotypes. Identifying the specific pathway responsible for persistent asthma would enable the clinician to select the optimal inhibitors, which currently are biologic therapies. Objective: To provide an up-to-date review of the current clinical status of endotype and phenotype characterizations of asthma and discuss these categories in relation to the available, or likely available, biologic therapies for asthma. Methods: The medical literature was reviewed based on the search terms: asthma biologics, severe asthma, uncontrolled asthma, corticosteroid-dependent asthma, phenotype, endotype, and type 2. We also used our knowledge of the literature and current research. Results: All of the current biologics, including the recently approved tezepelumab, were most effective with increased type 2 biomarkers, which identify exacerbation-prone asthma. Current biomarkers do not permit consistent identification of specific endotypes to facilitate informed selection of the optimal therapy for an individual patient. Thus, empiricism and the art of care continue to play major roles in treatment selection. Conclusion: Current biologic therapies for asthma and those likely to be U.S. Food and Drug Administration approved within the near future work best in subjects with strong type 2 signatures. Available biomarkers and observable characteristics do not enable clinicians to recognize specific endotypes, but rather subphenotypes or overlapping endotypes. The goal of identifying the optimal patient for a specific therapy remains elusive, but worthy of pursuit. In the interim, the availability of an increasing number of treatment options allows the clinician to help most of his or her patients.

Wendy C Moore,1 Dennis K Ledford,2 Donna D Carstens,3 Christopher S Ambrose4 1Wake Forest School of Medicine Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC, USA; 2Morsani College of Medicine, University of South Florida, and James A. Haley Veterans’ Hospital, Tampa, FL, USA; 3BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA; 4BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USACorrespondence: Wendy C Moore, Wake Forest School of Medicine Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Medical Center Boulevard, Winston-Salem, NC, 27157, USA, Tel +1 336-716-7765, Fax +1 336-716-7277, Email wmoore@wakehealth.eduPurpose: Patients with severe asthma (SA) are at an increased risk of asthma-related hospitalizations and exacerbations. Despite concerns that COVID-19 circulation would increase exacerbations of SA, anecdotal reports suggest that social distancing and exposure avoidance may have led to reduced exacerbations.Patients and methods: CHRONICLE is an ongoing noninterventional observational study of 3100 subspecialist-treated patients with SA. Eligible adults (≥ 18 years of age) have (1) current use of monoclonal antibody (ie, biologic) therapy for SA, (2) use of maintenance systemic corticosteroids (mSCS) or other systemic immunosuppressants for ≥ 50% of the prior 12 months for SA, or (3) persistently uncontrolled asthma while treated with high-dosage inhaled corticosteroids with additional controllers. For enrolled patients, electronic medical records were reviewed to record all exacerbations and asthma-related hospitalizations. Descriptive analyses were conducted of the monthly incidence of exacerbations, exacerbation-related visits to the emergency department (ED), and asthma hospitalizations from July 2018 through July 2021.Results: Exacerbations, exacerbation-related ED visits, and hospitalizations decreased since April 2020. Exacerbations in 2020 were 20% to 52% lower in April through August relative to the same months in 2019. Exacerbations remained lower than the prior year through May 2021. Similar results were observed by United States (US) census region, with an earlier decrease in exacerbation rates in the western US versus other regions. Across all months, exacerbation rates were lower among biologic recipients.Conclusion: In a clinical cohort of subspecialist-treated patients with SA, there was a meaningful reduction in exacerbations, exacerbation-related ED visits, and asthma hospitalizations following COVID-19–related stay-at-home orders and social distancing recommendations. Reasons for these reductions are likely multifactorial, including reduced viral infections due to less social contact and altered patient behavior.Keywords: management/control, healthcare resource use

Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States.To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA.CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described.Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (gt; 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both Plt; .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E.Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes.ClinicalTrials.gov identifier: NCT03373045.

Non-type 2 inflammation (Non-T2)-mediated asthma is difficult to define due to lack of signature biomarkers. It exists in the absence of T2-high or eosinophilic inflammation and includes neutrophilic and paucigranulocytic subtypes. Several cell types and cytokines, including Th1, Th17, IL-6, and IL-17, contribute to mechanisms of non-T2 asthma. Neutrophil extracellular traps (NETs) and inflammasome activation likely play a role in severe neutrophilic asthma. Several mechanisms lead to uncoupling of airway hyperresponsiveness and remodeling from airway inflammation in paucigranulocytic asthma. Recent research on transcriptomics and proteomics in non-T2 asthma is discussed in this review. Investigations of specific drug therapies for non-T2 asthma have been disappointing, and remain an important area for future clinical studies.

Background Approximately 5-10% of patients with asthma have severe disease. High-quality real-world studies are needed to identify areas for improved management. Objective Aligned with the International Severe Asthma Registry, the CHRONICLE study (ClinicalTrials.gov: NCT03373045) was developed to address this need in the US. Study design Learnings from prior studies were applied to develop a real-world, prospective, noninterventional study of US patients with confirmed severe asthma who are treated by subspecialist physicians and require biologic or maintenance systemic immunosuppressant therapy or who are uncontrolled by high-dosage inhaled corticosteroids and additional controllers. Target enrollment is 4000 patients, with patient observation for ≥3 years. A geographically diverse sample of allergist/immunologist and pulmonologist sites approach all eligible patients under their care and report patient characteristics, treatment, and health outcomes every 6 months. Patients complete online surveys every 1-6 months. Initial results From February 2018 to February 2019, 102 sites screened 1428 eligible patients; 936 patients enrolled. Study sites (40% allergist/immunologist, 42% pulmonologist, 18% both) were similar to other US asthma subspecialist samples. Enrolled patients were 67% female with median ages at enrollment and diagnosis of 55 (range: 18-89) and 26 (0-80) years, respectively. Median body mass index was 31 kg/m2; 3% and 29% were current or former smokers, respectively, and >60% reported ≥1 exacerbation in the prior year and suboptimal symptom control. Conclusion CHRONICLE will provide high-quality provider- and patient-reported data from a large, real-world cohort of US adults with subspecialist-treated severe asthma.

Chronic rhinosinusitis, historically, has been considered to be caused by upper airway anatomical abnormalities. However, today that concept has changed, for it is now recognized as an inflammatory disorder of the nasal and sinus mucosa. Acute rhinosinusitis is usually caused by a viral infection, whereas chronic rhinosinusitis is a persistent and heterogeneous inflammatory disorder with increased expression of type 1, 2, or 17 cytokines in the nasal and sinus mucosa, similar to that which occurs in asthma. Exacerbations are caused by aeroallergens in the allergic individual and irritants, pollutants, and viral/bacterial infections in all subjects. It may be categorized by phenotypes, examples of which include chronic rhinosinusitis with nasal polyps or chronic rhinosinusitis without nasal polyps. Defined endotypes are based on underlying pathophysiological mechanisms. Knowledge of chronic rhinosinusitis endotypes will optimize management by employing targeted medical therapies. Understanding that rhinosinusitis is a heterogeneous inflammatory disease has led to the identification of a variety of different predisposing conditions, new medical treatment options, and the concept that rhinosinusitis is primarily a medical problem.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. Acurrent challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.

There are many definitions of anaphylaxis in the medical literature. The authors propose a modified definition of anaphylaxis to be used for clinical decision making that promotes the early utilization of intramuscular epinephrine. Anaphylaxis can be a result of an allergic or nonallergic mechanism. In general, allergic reactions are more severe; however, any type of anaphylaxis can result in death and improve with IM epinephrine. The World Allergy Organization's Grading Criteria for allergic systemic reactions are adapted as a guide to identify manifestations that may progress to anaphylaxis. The intent is to promote and encourage the use of IM epinephrine in the health care setting before the progression of manifestations and the onset of life-threatening respiratory or cardiovascular dysfunction generally recognized as meeting the definition of anaphylaxis.

RATIONALE: The impact of the COVID-19 pandemic on disease control in patients with severe asthma (SA) has not been described. Anecdotal reports suggest that social distancing, exposure avoidance, and restrictions on travel may have impacted the incidence of asthma exacerbations. Methods: CHRONICLE is an observational study of specialist-treated US adults (aged ≥18 years) with SA. At enrollment, patients must be: (1) receiving FDAapproved monoclonal antibody therapy for SA;(2) receiving systemic corticosteroids (SCS) or other systemic immunosuppressants for ≥50% of the prior 12 months;or (3) persistently uncontrolled while treated with highdosage inhaled corticosteroids and additional controllers. Specialists report all exacerbations and asthma hospitalizations for enrolled patients from 12 months prior to enrollment, with updates provided every 6 months. To describe the effect of the COVID-19 pandemic, we calculated the incidence of these events by month from July 2018 to May 2020 (latest month with complete data) among patients enrolled through November 2020. Results: Among enrolled patients (N=2633), specialist-reported exacerbations and asthma hospitalizations declined significantly in April and May 2020, following varying state/local COVID-19-related stay-at-home orders and social distancing recommendations. Relative to the average rates from July 2018 to March 2020, exacerbations (Figure panel A) and asthma hospitalizations (Figure panel B) were 47% and 57% lower, respectively, in April 2020 and 72% and 74% lower, respectively, in May 2020. Relative to the same months in 2019, exacerbations and asthma hospitalizations were 49% and 58% lower, respectively, in April 2020 and 67% and 74% lower, respectively, in May 2020. Conclusions: There was a notable decline in exacerbations and asthma hospitalizations among US patients with SA coincident with COVID-19-related stay-at-home orders and social distancing recommendations. Reasons for these declines are likely multifactorial and may be explained by reduced viral infections due to reduced social contact, altered patient behavior, and possibly reduced access to care. Rates in later months will be evaluated as data become available.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Tang, Mimi/0000-0002-3839-5293; Romano, Antonino/0000-0001-9742-9898; Zuberbier, Torsten/0000-0002-1466-8875; Thong, Bernard/0000-0002-6338-8482; EBO, Didier/0000-0003-0672-7529; Scala, Enrico/0000-0002-9391-9168; Monge Ortega, Olga Patricia/0000-0002-6195-417X WOS:000523267300003 PubMed: 32128023 Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen. WAO Board of Directors The authors wish to thank the allergy societies from the membership of the World Allergy Organization who provided critical review of the draft and the WAO Board of Directors for supporting this work.

Objective Hepatitis B (HBV) is a viral illness that chronically infects 240 million people worldwide, leads to cirrhotic liver disease, and increases risk of hepatocellular carcinoma. The HBV vaccine has decreased HBV infection and along with human papilloma virus (HPV) vaccine are the only vaccines that prevent cancer. Despite the effectiveness of HBV vaccine, some populations do not develop protective responses. The risk groups for poor response include those with immunosuppression or dialysis-dependent, end-stage renal disease. Five percent of normal people do not respond. These subjects are deemed HBV "non-responders". Multiple strategies to improve the immunogenicity of the HBV vaccine are currently being pursued, including vaccine adjuvants, recombinant vaccines, and immune enhancement via up-regulation of dendritic cells. Data Sources PubMed was searched for peer-reviewed publications published from January 1980 to September 2017. Study Selections: Studies retrieved for inclusion summarized potential mechanisms behind HBV vaccine non-responsiveness and potential solutions. Results The mechanisms behind HBV vaccine non-responsiveness vary between each subject population. There are many current and future strategies that may provide protective immunity against HBV in each of these populations. Conclusion This review will provide a background on the immunology of HBV infection, the possible immunologic mechanisms to explain HBV vaccine non-responsiveness, current research aimed at improving vaccine effectiveness, and possible future approaches for providing non-responders protection from HBV.

Unaware of the natural history of large local reactions caused by Hymenoptera stings, patients and clinicians are often concerned when faced with these reactions. These concerns include the difficulty in avoiding stings, the local discomfort, and the fear that the local reaction portends systemic, potentially life-threatening subsequent reactions. This review presents the historical studies that have assessed the natural history of large local reactions caused by Hymenoptera stings and, in doing so, provides rationale for the current consensus guidelines for the management of these reactions. Retrospective and prospective studies in both adult and pediatric populations have provided insight into the natural history of large local reactions caused by Hymenoptera stings dating back to the 1980s. Each of these studies has demonstrated a low risk of future systemic allergic reactions or anaphylaxis in patients with a history of large local reactions. No clinical biomarker exists to determine the severity of future Hymenoptera sting reactions. Without a reliable clinical biomarker to identify those at risk for systemic allergic reactions or anaphylaxis, recommendations on the management of Hymenoptera sting reactions are derived from retrospective and prospective studies reviewed in this article. These studies provide strong evidence describing a low risk of future systemic allergic reactions or anaphylaxis in patients who have a history of large local reactions. Referral to an allergy specialist can provide reassurance for the referring clinicians and patients with a history of large local reactions. Treatment of large local reactions involves symptom relief with cold compresses, over-the-counter analgesics, oral antihistamines, and occasionally topical or oral glucocorticoids, usually reserved for very large, protracted reactions. Given the low risk of systemic allergic reactions and anaphylaxis, venom or imported fire ant whole body extract immunotherapy is not recommended for patients with a history of large local reactions. However, there may be some cases where the clinician considers providing an epinephrine autoinjector and/or venom or imported fire ant whole body extract immunotherapy for reasons other than future systemic allergic reactions or anaphylaxis risk. In any case, shared decision-making between the patient and clinician should take place with appropriate documentation of the risks and benefits.

Nasal and ocular challenges facilitate the evaluation of subjective and objective responses to defined allergen or irritant exposure. Nasal and ocular allergen challenges are the gold standard to diagnose allergic rhinitis and conjunctivitis, respectively, and aid in the evaluation of novel therapies in clinical trials. Additionally, nasal and ocular allergen challenges might help identify medically relevant allergens in clinical practice. Nonspecific or irritant challenges evaluate mucosal hyperreactivity. Direct mucosal challenges, which can be performed in an office or research setting, expose the participant to higher allergen doses than common in the natural environment. Park studies and environmental chambers, which are most practical in clinical trials, more closely simulate natural allergen exposure. International consensus guidelines for nasal and ocular challenges do not exist. Therefore the positivity criteria, methodologies, and extract or allergen preparations used in challenges vary in the literature. Regardless of these limitations, nasal and ocular challenges are helpful clinical and research tools for nasal and ocular diseases.

The publisher regrets we have been made aware of the below errors: 1) In Table 15, row NOVEOS chemiluminescent assay is written “utilizes 40 μL (0.04 ml) of sample per result”. The correct value would be “4 μL (0.004 ml)" of sample per result.2) In Table 16, is written “NOVEOS menu has 79 available allergens, consisting of 69 extracts and 10 molecular allergens”. It should say “NOVEOS menu continues to increase and it has 152 total allergens with 108 extracts and 44 components".3) In Table 15, row “Euroimmun”, column “Patient's serum”, is written “1000 ml”. The correct value would be “0.1 ml (-0.4 ml)”.The publisher would like to apologise for any inconvenience caused.

Poor adherence to asthma medication and inadequate communication are critical problems in asthma care in older adults. They contribute to morbidity and mortality through poor asthma control, frequent asthma exacerbations, acute care visits, and oral corticosteroid usage in this particularly vulnerable population. The objective of this chapter is to discuss evidence-based, time-efficient strategies that can be adopted by healthcare professionals (HCPs) to increase patient adherence and promote optimal asthma outcomes. Authors will use asthma management guidelines in older patients and other key publications to enhance discussion. Findings include that establishing patient-centered, collaborative care in older asthmatic adults facilitates effective patient–provider communication that likely will improve adherence, thus leading to improved asthma outcomes. One critical strategy is shared decision-making (SDM), in which the older adult patient and the HCP share relevant information, discuss risks versus benefits of various treatment options, express treatment preferences, deliberate the options, and agree on treatment. Asthma self-management education in older adults, which emphasizes self-efficacy, is also essential. Special attention must be paid to the health literacy of the individual as well as the cultural and social issues for each patient. In order to increase patient adherence in older asthmatic adult, clinicians need to consider a variety of factors and implement strategies directly targeting underlying issues that may be specific for older adults. Strategies may include customizing and simplifying learning and intervention regimes, identifying barriers to adherence and addressing them, ensuring patient support structures are in place, and improving self-efficacy and health literacy.

Background Treatments for patients with chronic idiopathic urticaria (CIU)chronic spontaneous urticaria (CSU) who were unresponsive to antihistamines include oral corticosteroids (OCS). Risks of OCS-related side effects in these patients have not been described quantitatively. Objective To investigate the relationship between OCS use and the risk of developing side effects possibly attributable to OCS and associated health care costs in privately insured patients with CIU/CSU. Methods This retrospective cohort study analyzed a commercial claims data base from January 1, 2008, to December 31, 2012. Patients with CIU/CSU were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes via a validated algorithm. Possible OCS-related side effects included the following: diabetes mellitus, hypertension, lipid disorders, cataracts, depression or mania, osteoporosis or fractures, and infectious diseases. A time-dependent Cox regression (adjusted for age, sex, Charlson Comorbidity Index, and immunomodulator use) was used to separately model cumulative oral prednisone-equivalent exposure and the risk of side effects. Incremental total adjusted health care costs were compared in patients with versus patients without possible OCS-related side effects. Results Among 12,647 patients with CIU/CSU, 55.4% used OCS. An additional 1 g of prednisone-equivalent exposure was associated with a 7% increase in the likelihood of developing a possible side effect (hazard ratio, 1.07 [95% confidence interval, 1.051.08]). From the period before to the period after OCS initiation, the total mean adjusted annual health care costs increased by 1833 in users of OCS with new possible side effects and decreased by 2183 in patients without new possible side effects (p 0.001). Conclusion Patients with CIU/CSU who were treated with OCS had an increased risk of possible OCS-related side effects and higher total health care costs than their counterparts not treated with OCS.

Patients who have had an anaphylactic reaction to stinging insect should be educated on the potential of fatality from venom allergy. These patients should be referred to an allergist/immunologist, a specialist with training in the diagnosis and management of stinging insect allergy. The three tenets of treatment for stinging insect allergy are insect avoidance measures, proper use of epinephrine, and insect immunotherapy. Avoidance is ideal but not always practical. Intramuscular epinephrine is the only effective therapy for anaphylaxis. Insect immunotherapy is proven to reduce the probability of anaphylaxis with repeat stings from approximately 60 % to less than 5 %. This reduction is not only potentially life-saving but also improves quality of life and reduces anxiety. Before starting immunotherapy, clinicians should have a discussion with patients regarding their goals of care, disease-specific anxiety level, comorbid conditions, and possible compliance issues.

Aspirin (ASA)-exacerbated respiratory disease (AERD) is characterized by upper airway congestion due to eosinophilic inflammation of the nasal and sinus membranes and nasal polyposis, associated with increased leukotriene production that is further accentuated by ASA or other nonsteroidal anti-inflammatory drug (NSAID) ingestion. It occurs in 5% to 10% of subjects with chronic rhinosinusitis (CRS) and in 15% to 40% of those with nasal polyposis. Although AERD with CRS is usually associated with asthma, this is not always the case. The eosinophilic airway inflammation and symptoms precede clinical reactions to ASA or other NSAIDs, but ultimately affected subjects experience worsening of symptoms with ingestion of ASA/NSAIDs. The endotypic mechanism for this worsening is related to a chronic increase in leukotriene and a decrease in prostaglandin production, particularly prostaglandin E2, that is further aggravated by the inhibition of cycloxgenase I. IgE does not likely play a role in the pathogenesis of the disease although nasal and sinus staphylococcal infection increases local IgE level and may increase total IgE and specific IgE levels. Genetic studies suggest that multiple genes may be involved, but the genetic abnormalities may differ in affected subjects from different ethnicities and candidate genes have not been confirmed in multiple studies. Genome-wide association studies have not been revealing. The phenotype is recognized by the mucosal inflammation and worsening of symptoms acutely with ASA/NSAID. There is clinical improvement with ASA desensitization followed by regular ingestion of ASA or other NSAIDs. Further understanding of this unique phenotype and endotype of CRS will likely improve the understanding of other eosinophilic airway diseases.

Background Severe asthma (SA) often requires subspecialist management and treatment with biologic therapies or maintenance systemic corticosteroids (mSCS). Objective To describe contemporary, real-world biologic and mSCS use among US subspecialist-treated patients with SA. Methods CHRONICLE is an ongoing, noninterventional study of US adults with SA treated by allergists/immunologists or pulmonologists. Eligible patients are receiving biologics or mSCS or are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Biologic and mSCS use patterns and patient characteristics were summarized for patients enrolled between February 2018 and February 2019. Results Among protocol-eligible patients, 58% and 12% were receiving biologics and mSCS, respectively, with 7% receiving both. Among 796 enrolled, most were women (67%), non-Hispanic white (71%), of suburban residence (50%), and had elevated body mass index (median: 31). Respiratory and nonrespiratory comorbidities were highly prevalent. With biologics (n = 557), 51% were anti–immunoglobulin E and 48% were anti–interleukin (IL)-5/IL-5Rα; from May 2018, 76% of initiations were anti–IL-5/IL-5Rα. In patients receiving mSCS, median prednisone-equivalent daily dose was 10 mg. Multivariate logistic regression found that patients of hospital clinics, sites with fewer nonphysician staff, and with a recorded concurrent chronic obstructive pulmonary disease diagnosis were less likely to receive biologics and more likely to receive mSCS. Conclusion In this real-world sample of US subspecialist-treated patients with SA not controlled by high-dosage inhaled corticosteroids with additional controllers, mSCS use was infrequent and biologic use was common, with similar prevalence of anti–immunoglobulin E and anti–IL-5/IL-5Rα biologics. Treatment differences associated with patient and site characteristics should be investigated to ensure equitable access to biologics and minimize mSCS use. Trial Registration ClinicalTrials.gov Identifier: NCT03373045 .

An elevation of serum inflammatory biomarkers in achalasia patients compared with controls recently was demonstrated. It has not been determined whether the elevation of inflammatory cytokines is unique to achalasia or occurs with other diseases involving the esophagus. The primary aim of our study was to compare the differences in plasma immunological profiles (TNF- α receptor, IL-6, IFN-γ, IL-12, IL-17, IL-22, and IL-23) of patients with achalasia, eosinophilic esophagitis (EoE), and gastroesophageal reflux disease (GERD). A secondary aim of this study was to classify these same plasma cytokine profiles in the three achalasia subtypes. Methods Plasma from 53 patients with achalasia, 22 with EoE, and 20 with GERD (symptoms plus esophagitis or + reflux study) were analyzed. Exclusion criteria: malignancy, autoimmune condition, immunodeficiency disorder, and treatment with steroids/immune modulating drugs. Cytokine levels were assayed via multiplex enzyme-linked immunosorbent assay (ELISA). Results Our key finding revealed significant elevations in IL- 6 (p = 0.0158) in achalasia patients compared with EoE patients. Overall, plasma inflammatory biomarker patterns were not different in the three subtypes of achalasia. Conclusion There were no differences between the cytokine levels of any of the measured biomarkers between the achalasia and GERD groups suggesting that luminal stasis does increase biomarker levels for any of the cytokines examined in our study. While these results are an early first step towards clarifying some aspects of the pathogenesis of achalasia, they bring about many more questions that require further investigation and expansion. Further investigation with a larger cohort and a broader panel of biomarkers is needed.

Asthma is a heterogeneous syndrome with numerous underlining molecular and inflammatory mechanisms contributing to the wide spectrum of clinical phenotypes. Multiple therapies targeting severe asthma with type 2 (T2) high inflammation are or soon will be available. T2 high inflammation is defined as inflammation associated with atopy or eosinophilia or an increase in cytokines associated with T-helper 2 lymphocytes. Omalizumab is a humanized anti-IgE monoclonal antibody and the first biologic therapy approved for moderate-severe allergic asthma. Despite the specificity of biologic therapies like omalizumab, clinical response is variable, with approximately 50% of treated patients achieving the primary outcome. A prior identification of the ideal candidate for therapy would improve patient outcomes and optimize the use of health care resources. As the number of biologic therapies for asthma increases, the goal is identification of biomarkers or clinical phenotypes likely to respond to a specific therapy. This review focuses on potential biomarkers and clinical history that may identify responders to omalizumab therapy for asthma.

ObjectiveTo assess birth outcomes in primiparous women with diagnosis of non-asthmatic atopy (NAA). Researchers hypothesised that women with NAA would have reduced the risk of adverse birth outcomes compared with women without NAA. NAA is defined as having allergic rhinitis and/or atopic dermatitis.SettingWomen were mostly treated in primary care settings in South Carolina, USA.ParticipantsThis is a retrospective cohort study in which participants were identified using a Medicaid database. Participants were primiparous women aged 19 to 25. Births occurring between 2004 and 2014 were identified using the South Carolina’s Vital Statistics (VS) records of live births. Incomplete records (ie, information on plural birth, gestational age at birth or birth weight missing), plural births or infants born before completing 24 weeks of gestation were excluded. This provided 65 650 complete maternal–infant dyads, representing 97.6% of the maternal records and 96.9% of the VS records. Women previously diagnosed with NAA were frequency matched 1:4 to non–atopic controls for a total of 9965 maternal–infant dyads used in the statistical analysis.Primary outcome measuresLow birth weight, small for gestational age and preterm birth.ResultsLinear tests for trend were statistically significant (pConclusionA diagnosis of NAA among women living in the southeastern region of the USA does not reduce the risk of adverse birth outcomes nor does it elevate the risk of same. Additional studies with more rigorous designs are warranted to confirm the findings in this study.

Several biologics are currently FDA approved for asthma that target Th2 high patients. Unfortunately, 50% of patients with severe asthma do not fit this phenotype of disease and have fewer effective therapeutic options. In the clinical setting, total IgE, FeNO and peripheral blood eosinophils are important tools in defining Th2 high patients with asthma. However, precise biomarkers to predict better response to one specific Th2 high asthma therapy versus another is lacking. It is important to recognize that none of the current medications targeting the Th2 pathway induces persistent immunomodulation or remission.

Introduction Allergic fungal rhinosinusitis (AFRS) is a noninvasive fungal disease of the sinuses arising from local fungal hypersensitivity and is a subtype of chronic rhinosinusitis (CRS). Typical signs and symptoms of AFRS may be similar to allergic rhinitis, CRS with/without nasal polyposis, or an acute bacterial exacerbation of CRS which can delay proper diagnosis and management. Case Description A 46-year-old immunocompetent Caucasian male from Florida with a history of allergic rhinitis and CRS presented with nasal congestion, anosmia, yellow-green nasal discharge, and post-nasal drip for 1 year despite daily use of intranasal fluticasone. Symptoms persisted despite the addition of intranasal azelastine, nasal saline irrigation, and a 14-day course of oral amoxicillin-clavulanate. Labs revealed an eosinophil count of 450 cells/mm3, total IgE of 127 KU/L, and specific IgE to dust mites, grasses, weeds, and molds (Alternaria, Aspergillus, Cladosporium, Curvularia). Rhinoscopy revealed bilateral, thick, mucopurulent discharge from the middle meatus and a left middle turbinate polyp. Oral clindamycin with a prednisone taper also did not improve his symptoms. CT sinus revealed complete opacification of the right maxillary sinus and left ethmoid air cells containing hyperdense material. He was referred to otolaryngology. Endoscopic sinus surgery revealed multiple nasal polyps, mucin with eosinophils, Charcot-Leyden crystals, and noninvasive fungal elements confirming AFRS. Oral prednisone and intranasal fluticasone were given post-operatively to reduce allergic inflammation and prevent disease recurrence. Discussion This case illustrates the importance of considering AFRS in patients with difficult to treat CRS with nasal polyposis, particularly those with IgE-mediated hypersensitivity to fungi.

Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1-antihistamines along with 1 or more add-on therapies.We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H₁-antihistamines at up to 4 times the approved dose plus H₂-antihistamines, leukotriene receptor antagonists, or both.In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24.The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was -8.6 (95% CI, -9.3 to -7.8) in the omalizumab group compared with -4.0 (95% CI, -5.3 to -2.7) in the placebo group (P.001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24.Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H₁-antihistamines (up to 4 times the approved dose) plus H₂-antihistamines, leukotriene receptor antagonists, or both.

Chronic rhinosinusitis (CRS) is a complex disease consisting of several disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of CRS and improving treatment. It is generally agreed that there are clinically relevant CRS phenotypes defined by an observable characteristic or trait, such as the presence or absence of nasal polyps. Defining the phenotype of the patient is useful in making therapeutic decisions. However, clinical phenotypes do not provide full insight into all underlying cellular and molecular pathophysiologic mechanisms of CRS. Recognition of the heterogeneity of CRS has promoted the concept that CRS consists of multiple groups of biological subtypes, or "endotypes," which are defined by distinct pathophysiologic mechanisms that might be identified by corresponding biomarkers. Different CRS endotypes can be characterized by differences in responsiveness to different treatments, including topical intranasal corticosteroids and biological agents, such as anti-IL-5 and anti-IgE mAb, and can be based on different biomarkers that are linked to underlying mechanisms. CRS has been regarded as a single disease entity in clinical and genetic studies in the past, which can explain the failure to identify consistent genetic and environmental correlations. In addition, better identification of endotypes might permit individualization of therapy that can be targeted against the pathophysiologic processes of a patient's endotype, with potential for more effective treatment and better patient outcomes.

Allan T Luskin,1 Evgeniya N Antonova,2 Michael S Broder,3 Eunice Y Chang,3 Theodore A Omachi,2 Dennis K Ledford4 1HealthyAirways, Madison, WI, 2Genentech, Inc., South San Francisco, 3Partnership for Health Analytic Research, LLC, Beverly Hills, CA, 4Division of Allergy and Immunology, Department of Medicine, James A. Haley Veterans’ Hospital, Morsani College of Medicine, University of South Florida, Tampa, FL, USA Background: The objective of this study was to estimate the prevalence of possible oral corticosteroid (OCS)-related side effects and health care resource use and costs in patients with asthma.Methods: This was a cross-sectional, matched-cohort, retrospective study using a commercial claims database. Adults with asthma diagnosis codes and evidence of asthma medication use were studied. Patients with high OCS use (≥30 days of OCS annually) were divided into those who did versus those who did not experience OCS-related possible side effects. Their health care resource use and costs were compared using linear regression or negative binomial regression models, adjusting for age, sex, geographic region, Charlson Comorbidity Index score, and chronic obstructive pulmonary disease status.Results: After adjustment, high OCS users with possible side effects were more likely to have office visits (23.0 vs 19.6; P