Showing papers in "Annals of Allergy Asthma & Immunology in 2020"

The role of filaggrin in atopic dermatitis and allergic disease.

Abstract: Objective To provide an overview of filaggrin biology and the role of filaggrin variants in atopic dermatitis (AD) and allergic disease. Data Sources We performed a PubMed literature review consisting mainly of studies relating to filaggrin in the last 5 years. Study Selections We selected articles that were found in PubMed using the search terms filaggrin, atopic dermatitis, skin barrier, and atopy. Results Filaggrin plays an important role in the development of AD and allergic disease. Novel methods in measuring filaggrin expression and identifying filaggrin mutations aid in stratifying this patient cohort. We review new insights into understanding the role of filaggrin in AD and allergic disease. Conclusion Filaggrin remains a very important player in the pathogenesis of atopic dermatitis and allergic disease. This review looks at recent studies that aid our understanding of this crucial epidermal protein.

New treatments for atopic dermatitis targeting beyond IL-4/IL-13 cytokines

Abstract: Objective Atopic dermatitis (AD) is an increasingly common inflammatory skin disease undergoing significant revolution in recent years. New data on disease pathogenesis advanced the developments of novel therapeutics, mainly for patients with moderate to severe conditions, for whom treatment options have been largely insufficient for many years. Data Sources Review of recent studies investigating systemic treatments for AD. Study Selections Relevant literature concerning novel therapeutics for AD beyond targeted monoclonal antibodies antagonizing selectively interleukin (IL)-4 or IL-13 was obtained from a PubMed and clinicaltrials.gov search and summarized. Results Multiple clinical trials of both nonspecific as well as specific agents revealed favorable outcomes in AD, including JAK inhibitors, a dual JAK/SYK inhibitor, a histamine H4R antagonist, antagonists of the TSLP/OX40L axis, an IL-22 inhibitor, and IL-33 and IL-17C antagonists. Importantly, negative trials were published as well (eg, phosphodiesterase 4 inhibitor, apremilast). Conclusion In this rapidly evolving field of AD treatments, a completely new treatment paradigm will be available in the near future.

New treatments for chronic urticaria

Abstract: Objective Chronic urticaria (CU) is a common, heterogeneous, and debilitating disease. Antihistamines and omalizumab are the mainstay therapies of CU. Additional treatment options are needed. Here, we review the off and beyond label use of licensed drugs, novel treatments that are currently under development, and promising new targets. Data Sources MEDLINE was searched for recent reports of the successful use of treatments in CU and promising targets for the development of novel treatment options. We also searched ClinicalTrials.gov for recent and ongoing randomized clinical trials in CU. Study Selections Relevant articles were selected and reviewed. Results Omalizumab, the treatment of choice in patients with antihistamine-resistant chronic spontaneous urticaria (CSU), should be explored for use in chronic inducible urticaria in children younger than 12 years with CSU and at higher doses. The off-label use of dupilumab, reslizumab, mepolizumab, and benralizumab can be effective in CU. Ligelizumab and UB-221, 2 novel anti-IgE monoclonal antibodies, are in clinical trials for CU. Other promising drugs that are currently under development for CU are a chemoattractant receptor–homologous molecule expressed on TH2 cell antagonist, a monoclonal antibody to Siglec-8 (AK002), Bruton tyrosine kinase inhibitors (fenebrutinib and Lou064), a spleen tyrosine kinase inhibitor, and dupilumab. Promising targets of future therapies include the Mas-related G-protein–coupled receptor X2; the histamine4 receptor; C5a and its receptor; inhibitory mast cell receptors other than Siglec-8; interleukin 33, interleukin 25, and thymic stromal lymphopoietin, and stem cell factor. Conclusion Novel and better treatments for CU are very much needed. Some agents are in clinical trials already (eg, ligelizumab), and additional ones should be developed, making use of the many promising targets recently identified and characterized.

Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis

Abstract: Objective With the advent of new treatment options for Chronic Rhinosinusitis (CRS) comes the ability for physicians to provide more individualized patient care. Physicians are now tasked with identifying who may be the best candidate for a particular therapy. In this review, existing biomarkers and potentially new methods that could guide treatment choices in CRS patients will be discussed. Data Sources Published literature obtained through PubMed searches. Study Selection Studies relevant to inflammatory endotypes, phenotypes, and biomarkers in CRS were included. Results Currently, there are no clinically validated tools that determine the best therapeutic modality for CRS patients with or without nasal polyps (CRSwNP or CRSsNP). Patients with CRS can be classified into three endotypes based on the presence of type 1, type 2, or type 3 inflammation. CRS endotypes can be influenced by age and geographic location. Clinical application however may be limited since endotyping current requires basic research laboratory support. Clinical symptoms may also predict inflammatory endotypes with smell loss being indicative of type 2 inflammation. Numbers of tissue and/or peripheral eosinophils as well as levels of IgE may predict disease severity in CRSwNP but not necessarily treatment responses. Unique clinical phenotypes or biomarkers are especially lacking that predict type 1 or type 3 inflammation in CRSwNP or type 1, type 2, or type 3 inflammation in CRSsNP. Conclusion While significant progress has been made in characterizing endotypes, phenotypes, and biomarkers in CRS, additional studies are needed to determine if and how these factors could assist physicians in providing more individualized clinical care.

ICON: Diagnosis and management of allergic conjunctivitis.

Abstract: Ocular allergy (OA), interchangeably known as allergic conjunctivitis, is a common immunological hypersensitivity disorder affecting up to 40% of the population. Ocular allergy has been increasing in frequency, with symptoms of itching, redness, and swelling that significantly impacts an individual's quality of life (QOL). Ocular allergy is an often underdiagnosed and undertreated health problem, because only 10% of patients with OA symptoms seek medical attention, whereas most patients manage with over-the-counter medications and complementary nonpharmacological remedies. The clinical course, duration, severity, and co-morbidities are varied and depend, in part, on the specific ocular tissues that are affected and on immunologic mechanism(s) involved, both local and systemic. It is frequently associated with allergic rhinitis (commonly recognized as allergic rhino conjunctivitis), and with other allergic comorbidities. The predominance of self-management increases the risk of suboptimal therapy that leads to recurrent exacerbations and the potential for development of more chronic conditions that can lead to corneal complications and interference with the visual axis. Multiple, often co-existing causes are seen, and a broad differential diagnosis for OA, increasing the difficulty of arriving at the correct diagnosis(es). Ocular allergy commonly overlaps with other anterior ocular disease disorders, including infectious disorders and dry eye syndromes. Therefore, successful management includes overcoming the challenges of underdiagnosis and even misdiagnosis by a better understanding of the subtleties of an in-depth patient history, ophthalmologic examination techniques, and diagnostic procedures, which are of paramount importance in making an accurate diagnosis of OA. Appropriate cross-referral between specialists (allergists and eyecare specialists) would maximize patient care and outcomes. This would significantly improve OA management and overcome the unmet needs in global health.

The journey to a respiratory syncytial virus vaccine

Abstract: Objective The high burden associated with respiratory syncytial virus (RSV) has made the development of RSV vaccine(s) a global health high priority. This review summarizes the journey to an RSV vaccine, the different strategies and challenges associated with the development of preventive strategies for RSV, and the diverse products that are undergoing clinical testing. Data Sources Studies on RSV biology, immunology, epidemiology, and monoclonal antibodies (mAbs) and vaccines were searched using MEDLINE. We also searched PATH.org and ClinicalTrials.gov for updated information regarding the status of RSV vaccines and mAbs undergoing clinical trials. Study Selections We selected relevant studies conducted in infants and young children, pregnant women, and elderly population for the prevention of RSV infection. Results Identification of a safe and immunogenic vaccine has been an important but elusive initiative for more than 60 years for different reasons, including the legacy of formalin-inactivated vaccine, our limited understanding of the immune response to RSV and how it relates to clinical disease severity, or the need for different end points according to the different vaccine platforms. Nevertheless, there are currently 39 vaccines and mAbs under development and 19 undergoing clinical trials. Conclusion Over the past decade, there have been significant advances in our knowledge of RSV molecular and structural biology and in understanding the human immune response to RSV. Despite the barriers, there are several promising mAbs and RSV vaccines undergoing clinical trials that hope to offer protection to the most vulnerable populations.

Asthma biologics: Comparing trial designs, patient cohorts and study results

Abstract: Objective Five biologic therapies have FDA-approved indications for difficult-to-control asthma. The clinical trials that proved the efficacy and safety of these biologics were often similar in their inclusion criteria, study designs, and endpoints. Many of these trials have been reanalyzed post hoc to identify subsets of subjects considered to be enhanced responders. As a result, keeping up with the literature and deciding on the most appropriate biologic for our patients has become increasingly difficult. This review summarizes and compares trial designs, patient cohorts, and study results of the major trials involving these therapies. Data Sources Included are basic science articles, online Food and Drug Administration (FDA) applications, and all the published reports of phase II and phase III clinical trials for FDA-approved asthma biologics. Study Selections Included are the major phase II and phase III clinical trials of 5 asthma biologics. Results Because of variations in inclusion criteria and natural variations in enrolled cohorts, the baseline clinical traits and severity of study populations in asthma biologic trials differed significantly, which is important because baseline annualized exacerbation rates and blood eosinophilia are both strong predictors of a biologic's success. Notwithstanding, the trial results, when considered together, can help guide care providers in choosing the most appropriate biologic for our patients. Conclusion Understanding the details and differences in asthma biologic trial designs, patient cohorts, and in study results will help care providers make more informed decisions when choosing a biologic. We are hopeful this review will serve as a reference to care providers for this purpose.

Biologics in chronic rhinosinusitis with nasal polyposis.

Abstract: Objective Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory condition, for which the drivers of the underlying inflammation are not yet fully understood. The use of biologic therapies to target specifically relevant effector cells or cytokines in CRSwNP is a growing field of interest. The objectives of this review are to provide an update on the existing studies of biologics in CRSwNP and to identify potential future areas for further research. Data Sources An initial literature review of biologic therapies in CRS was performed through publications gathered from a PubMed search for title/abstract containing “biologic” and “chronic rhinosinusitis”. Further manuscripts describing scientific premise for each biologic were then reviewed. Study Selections A detailed review of all studies describing biologic therapies targeting inflammation in CRSwNP was performed. Results Biologic therapies targeting IL-4Ra, IL-5, IL-5Ra, IL-33, IgE, and TSLP have all been developed and have been investigated for treatment in CRSwNP or current research suggests that they may have utility in this area. Thus far only dupilumab, which inhibits IL-4Ra, has gained FDA approval for the treatment of adults with inadequately controlled CRSwNP. Conclusion Recent advances in our understanding of the fundamental drivers of the chronic respiratory inflammation in CRSwNP has led to the identification of several potential therapeutic targets for this disease. Future clinical success will rely on the availability of biomarker-based endotyping and responder analyses so that clinicians can precisely match each patient to the appropriate biologic, thereby optimizing the proper treatment strategy.

Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States.

Abstract: Background Hereditary angioedema (HAE) with C1-inhibitor deficiency is associated with painful, potentially fatal attacks affecting subcutaneous or submucosal tissues. Objective To evaluate HAE burden from the patients’ perspective. Methods This was a noninterventional survey of patients with HAE in the United States, conducted from March 17 to April 28, 2017. Patients were recruited through the US Hereditary Angioedema Association. Key eligibility criteria included the following: (1) aged 18 years and older, (2) self-reported physician diagnosis of HAE type I or II, (3) 1 or more HAE attacks or prodromal symptoms within the last year, and (4) receipt of HAE medication for an attack within the last 2 years. Descriptive analyses were conducted. Results A total of 445 patients completed the survey. Most patients (92.8%) were aged 18 to 64 years with HAE type I (78.4%) and had a positive family history (78.4%). Mean (SD) ages at symptom onset and diagnosis were 12.5 (9.1) and 20.1 (13.7) years, respectively. Most patients (78.7%) experienced an attack within the past month. The abdomen (58.0%) and extremities (46.1%) were commonly affected sites; pain (73.9%) and abdominal (57.0%) and nonabdominal (55.1%) swelling were frequently reported symptoms. Most patients (68.5%) had received or were currently receiving long-term prophylaxis. Most patients (88.8%) reported visiting allergists or immunologists, whereas 9.2% visited emergency departments or urgent care clinics. Per the Hospital Anxiety and Depression Scale, 49.9% and 24.0% of respondents had anxiety and depression, respectively. Mean Hereditary Angioedema-Quality of Life scores were generally lower with higher attack frequency. General health was “poor” or “fair” for 24.8% of patients. Mean (SD) percentage impairments were 5.9% (14.1%) for absenteeism, 23.0% (25.8%) for presenteeism, 25.4% (28.1%) for work productivity loss, and 31.8% (29.7%) for activity impairment. Conclusion Despite treatment advances, patients with HAE in the United States continue to have a high burden of illness.

Increased cardiovascular and atherosclerosis markers in blood of older patients with atopic dermatitis

Abstract: Background Atopic dermatitis (AD) is associated with increased systemic inflammation and cardiovascular risk. Although previous studies have found increased inflammatory proteins in the blood of patients with AD, detailed comparison among patients with AD of different ages is unavailable. Objective To characterize the blood proteomic signature of patients with AD as a function of age. Methods We used the OLINK high-throughput proteomic assay to measure serum inflammatory and cardiovascular risk proteins in 71 patients with moderate to severe AD from 3 age groups (18-40 years old [n = 26], 41-60 years old [n = 24], and >60 years old [n = 21]) compared with 37 age-matched controls. Total and allergen-specific serum IgEs were also measured. Results When we compared patients with AD from 3 different age groups with their respective controls, we identified a total of 172 differentially expressed proteins. TH2 chemokines (CCL13, CCL17) were consistently elevated in patients with AD across all ages (P 60 years old) exhibited striking upregulation of key proinflammatory proteins, including markers of atherosclerosis (CCL4, CCL7, SORT1), cardiovascular risk (GDF15, MPO, ST2), cell adhesion (CDH3), and apoptosis (FAS; all P Conclusion Elderly patients with AD had increased levels of systemic inflammatory markers, including those associated with cardiovascular and atherosclerosis risk, which may explain their increased incidence of cardiovascular disease. This finding suggests that older patients with AD may benefit from cardiovascular disease screening and prevention.

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

Abstract: 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.

Children with reported penicillin allergy: Public health impact and safety of delabeling.

Abstract: Objective To review the relevant literature related to children with reported penicillin allergy and highlight the different ways in which children could be delabeled and to evaluate the public health impact that a penicillin allergy has for children. Data Sources Data for this review were obtained via PubMed searches and then retrieval of articles from their respective journals for further review. Study Selections Studies regarding the safety of different ways to evaluate penicillin allergy in children were identified via PubMed searches. Any study that reported different ways of testing (3-tier, direct oral challenge, 5-day oral challenges) were included. This same format was used when selecting relevant articg:les related to the costs, prescription patterns, and stewardship trends associated with a penicillin allergy label. Results This review found that penicillin allergy testing is a safe and effective way to delabel those with reported allergy. In children with low-risk allergy symptoms, a direct oral challenge approach may be optimal. In those children with a history of high-risk allergy symptoms, a 3-tiered approach is ideal. The review also found that there is a significant cost associated with reported penicillin allergy and that there are increased negative health benefits to those children with reported allergy. Conclusion Penicillin allergy is overdiagnosed, often incorrectly, and the label is frequently first applied during childhood. Targeting children for the removal of the incorrect penicillin allergy label provides a mechanism to reduce the use of broader-spectrum and less effective antibiotics.

Prevalence and natural history of tree nut allergy

Abstract: Objective Tree nuts are common causes of food-related allergic reactions and anaphylaxis. Resolution of tree nut allergy is thought to be low, yet studies of the natural history of tree nut allergy are limited. This review summarizes the available literature regarding tree nut allergy prevalence and natural history and discusses emerging diagnostic and prognostic developments that will inform clinical management of tree nut allergy. Data Sources A comprehensive literature search using PubMed was performed. Study Selections Peer-reviewed publications relating to tree nut allergy prevalence, resolution, and diagnosis were selected, and findings were summarized using a narrative approach. Results Tree nut allergy prevalence varies by age, region, and food allergy definition, and ranges from less than 1% to approximately 3% worldwide. Reports on the natural history of tree nut allergy data are limited to retrospective clinical data or cross-sectional survey data of self-reported food allergy, with reported resolution ranging from 9% to 14%. Component-resolved diagnostics and basophil activation testing offer the potential to improve the diagnostic accuracy and predicted prognosis of specific tree nut allergy, but studies are limited. Conclusion Tree nut allergy remains an understudied area of food allergy research with limited region-specific studies based on robust food allergy measures in population cohorts with longitudinal follow-up. This currently limits our understanding of tree nut allergy prognosis.

Key steps in vaccine development.

Abstract: Objective The goal of a vaccine is to prime the immune response so the immune memory can facilitate a rapid response to adequately control the pathogen on natural infection and prevent disease manifestation. This article reviews the main elements that provide for the development of safe and effective vaccines. Data Sources Literature covering target pathogen epidemiology, the key aspects of the functioning immune response underwriting target antigen selection, optimal vaccine formulation, preclinical and clinical trial studies necessary to deliver safe and efficacious immunization. Study Selections Whole live, inactivated, attenuated, or partial fractionated organism-based vaccines are discussed in respect of the balance of reactogenicity and immunogenicity. The use of adjuvants to compensate for reduced immunogenicity is described. The requirements from preclinical studies, including establishing a proof of principle in animal models, the design of clinical trials with healthy volunteers that lead to licensure and beyond are reviewed. Results The 3 vaccine development phases, preclinical, clinical, and post-licensure, integrate the requirements to ensure safety, immunogenicity, and efficacy in the final licensed product. Continuing monitoring of efficacy and safety in the immunized populations is essential to sustain confidence in vaccination programs. Conclusion In an era of increasing vaccine hesitancy, the need for a better and widespread understanding of how immunization acts to counteract the continuing and changing risks from the pathogenic world is required. This demands a societal responsibility for obligate education on the benefits of vaccination, which as a medical intervention has saved more lives than any other procedure.

The impact of psychological stress on mast cells.

Abstract: Objective Atopic diseases worsen with psychological stress, but how stress contributes to their pathogenesis is still not clear. We review the evidence supporting the premise that stress contributes to allergic and inflammatory processes through stimulation of mast cells (MCs) by neuroimmune stimuli. Data Sources PubMed was searched between 1950 and 2019 using the following terms: allergies, atopic diseases, corticotropin-releasing hormone, inflammation, hypothalamic-pituitary-adrenal axis, mast cells, mastocytosis, neuropeptides, psychological stress, neurotensin, and substance P. Study Selections Only articles published in English were selected based on their relevance to stress and MCs, especially those that discussed potential mechanisms of action. Results Psychological stress worsens many diseases, especially asthma, atopic dermatitis, and mastocytosis. This effect is mediated through MCs stimulated by neuropeptides, especially corticotropin-releasing hormone, neurotensin, and substance P, a process augmented by interleukin-33. Conclusion Understanding how stress stimulates MCs to release proinflammatory mediators is important in advancing treatments for diseases that worsen with stress.

Phenotypes and endotypes in eosinophilic esophagitis.

Abstract: Objective To improve understanding of the heterogeneous presentation of eosinophilic esophagitis (EoE), and its different potential phenotypes and endotypes. Data Sources We reviewed studies addressing EoE genetics, risks, natural history, treatment, phenotype, or endotype to assess data relating to differences in the presentation of EoE in children and adults. This review was restricted to articles in the English language. Study Selections Data source abstracts, pertinent articles, and book chapters meeting the objectives were critically reviewed. Results Data to support differing phenotypes and endotypes in EoE are emerging, but findings are based on multiple studies and therefore sometimes incomparable. Like other atopic disorders EoE is a complex disease with diverse clinical presentations (phenotypes) based on response to therapy, natural history, and association with atopic comorbidities. Different pathogenetic mechanisms (endotypes) may drive the multiple phenotypes. T Helper type 2 inflammation, epithelial barrier defects, enhanced fibrosis, and association with rare monogenetic diseases are the most described endotypes in EoE. Conclusion Eosinophilic esophagitis is an atopic disorder that is increasing in prevalence and can be difficult to treat. Better understanding of phenotypes and endotypes in EoE may enable future care to be individualized more effectively, resulting in shorter time to remission and fewer endoscopies.

Effect of omalizumab on lung function and eosinophil levels in adolescents with moderate-to-severe allergic asthma.

Abstract: Background Omalizumab improves clinical outcomes in patients with asthma. Several studies have shown lung function improvements with omalizumab; however, this has not been examined exclusively in adolescents. Objective To assess the effect of omalizumab on lung function and eosinophil counts in adolescents with uncontrolled moderate-to-severe allergic asthma. Methods In this post hoc analysis, data from adolescents aged 12 to 17 years from 8 randomized trials of omalizumab were pooled (studies 008, 009, and 011, and SOLAR, INNOVATE, ALTO, ETOPA, and EXTRA). Changes from baseline to end of study in forced expiratory volume in 1 second (FEV1), percent predicted FEV1 (ppFEV1), forced vital capacity (FVC), and blood eosinophil counts were assessed by fitting an analysis of covariance model and calculating least squares mean (LSM) difference for omalizumab vs placebo. Results A total of 340 adolescents were identified (omalizumab, n = 203 [59.7%]; placebo, n = 137 [40.3%]). Omalizumab increased all baseline lung function variables more than placebo by end of study: LSM treatment differences (95% confidence interval) were 3.0% (0.2%-5.7%; P = .035), 120.9 mL (30.6-211.2 mL; P = .009), and 101.5 mL (8.3-194.6 mL; P = .033) for ppFEV1, absolute FEV1, and FVC, respectively. The LSM difference demonstrated a greater reduction in eosinophil counts for omalizumab vs placebo: −85.9 cells/μL (−137.1 to −34.6 cells/μL; P = .001). Conclusion Omalizumab was associated with lung function improvements and circulating eosinophil counts reductions in adolescents with moderate-to-severe uncontrolled asthma. Findings emphasize the effect of omalizumab in young patients and the need to optimize treatment early in the disease course. https://clinicaltrials.gov/: NCT00314574, NCT00046748, NCT00401596

Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis.

Abstract: Background Comorbid perennial allergic rhinitis (PAR) or year-round aeroallergen sensitivity substantially contributes to disease burden in patients with asthma. Dupilumab blocks the shared receptor for interleukin (IL) 4 and IL-13, key drivers of type 2 inflammation that play important roles in asthma and PAR. In the LIBERTY ASTHMA QUEST trial ( NCT02414854 ), dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline (blood eosinophils and fractional exhaled nitric oxide). Objective To assess dupilumab efficacy in LIBERTY ASTHMA QUEST patients with comorbid PAR. Methods Severe asthma exacerbation rates, FEV1, asthma control (5-item Asthma Control Questionnaire), rhinoconjunctivitis-specific health-related quality of life (Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores), and type 2 inflammatory biomarkers during the 52-week treatment period were assessed. Results A total of 814 of the 1902 patients (42.8%) had comorbid PAR (defined as an allergic rhinitis history and ≥1 perennial aeroallergen specific immunoglobulin E (IgE) level ≥0.35 kU/L at baseline). Dupilumab, 200 and 300 mg every 2 weeks, vs placebo reduced severe exacerbations rates by 32.2% and 34.6% (P Conclusion Dupilumab improved key asthma-related outcomes, asthma control, and rhinoconjunctivitis-specific health-related quality of life while suppressing type 2 inflammatory biomarkers and perennial allergen-specific IgE in patients with moderate-to-severe asthma and comorbid PAR, highlighting its dual inhibitory effects on IL-4 and IL-13 and its role in managing asthma and PAR.

Reaction phenotypes in IgE-mediated food allergy and anaphylaxis.

Abstract: Objective Food allergy encompasses a range of food hypersensitivities. Different clinical phenotypes for food allergy likely exist in much the same way as endotype discovery is now a major research theme in asthma. We discuss the emerging evidence for different reaction phenotypes (ie, symptoms experienced after allergen exposure in food allergic individuals) and their relevance for clinical practice. Data Sources Published and unpublished literature relating to reaction phenotypes in food allergy. Study Selections Authors assessment of the available data. Results Food anaphylaxis may be pathophysiologically different than anaphylaxis caused by nonfood triggers. Currently, there are no robust, clinically useful predictors of severity in food allergy. It is likely that patient-specific reaction phenotypes exist in food allergy, which may affect the risk of severe anaphylaxis. Allergen immunotherapy may modulate these phenotypes. Conclusion Data are emerging to confirm our clinical experience that many food allergic patients experience stereotypical symptoms after allergen exposure, both in the community and at supervised oral food challenge, in a manner that varies among patients. Integrating data sets from different cohorts and applying unbiased machine-based learning analyses may demonstrate specific food allergy endotypes in a similar way to asthma. Whether this results in improvements in patient management (eg, through facilitating risk stratification or affecting the decision to prescribe an epinephrine autoinjector and, perhaps, the number of devices) remains to be determined, but given our current inability to predict which patients are most at risk of severe food allergic reactions, this will clearly be an important area of research in the future.

Development and acceptability of a shared decision-making tool for commercial peanut allergy therapies.

Abstract: Background Shared decision making (SDM) is the process through which patients and their medical provider mutually explore therapy goals, risk/benefit, and treatment options regarding medical care. Decision aids are tools that aid in the process of values clarification and help assess decisional needs and potential decisional conflicts. Objective To develop and assess acceptability of a decision aid for commercial peanut allergy therapies. Methods The creation of this decision aid occurred in 3 stages, including a qualitative study to assess decisional needs, development of a draft decision aid through multiple iterations in accordance with international guidelines and decision aid experts, and assessment of decisional acceptability, decisional conflict, and decisional self-efficacy related to using the decision aid. Results The decision aid went through 9 iterations, resulting in a 4-page aid with 7 parts, explaining the therapies, key risks and benefits of therapy choices, relative importance of key attributes of the therapies, and a self-check assessment regarding informational adequacy and how to take the next steps. A total of 24 subjects assessed the decision aid, noting it had good acceptability, high decisional self-efficacy (mean score 91.9/100), and low decisional conflict (mean score 20.2/100). Respondents rated the information content as adequate and sufficient and the information regarding the therapy choices as fair and balanced without a clear bias or presenting a “best choice.” Conclusion We have developed this decision aid as a tool to help caregivers navigate the complexity of decision making for peanut allergy treatment options. The decision aid was noted to have good acceptability, with scores reflective of the instrument enhancing decisional self-efficacy and reducing decisional conflict.

Efficacy and safety of twice-daily and once-daily olopatadine-mometasone combination nasal spray for seasonal allergic rhinitis

Abstract: Background GSP301 is an investigational fixed-dose combination nasal spray of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). Objective To evaluate efficacy and safety of GSP301 in patients with seasonal AR (SAR). Methods In this phase 2, double-blind, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to twice-daily GSP301 (olopatadine 665 μg and mometasone 25 μg), once-daily GSP301 (olopatadine 665 μg and mometasone 50 μg), twice-daily or once-daily olopatadine monotherapy (665 μg), mometasone monotherapy (twice-daily 25 μg or once-daily 50 μg), or placebo for 14 days. The primary endpoint—mean change from baseline in morning and evening reflective Total Nasal Symptom Score (rTNSS)—was analyzed using analysis of covariance (ANCOVA; P Results A total of 1111 patients were randomized. Twice-daily GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (P Conclusion Twice-daily GSP301 treatment was efficacious and well tolerated, providing statistically significant and clinically meaningful improvements in rTNSS (primary endpoint) vs placebo and both monotherapies. Trial Registration Clinicaltrials.gov Identifier NCT02318303

Chronic stress and asthma in adolescents.

Abstract: Objective First, to review and critically discuss published evidence on psychosocial stressors, stress, and asthma in adolescents and, then, discuss potential future directions in this field. Data Sources The data source is the National Library of Medicine (PubMed database). Study Selections A literature search was conducted for human studies on stressors or stress and asthma between 2000 and 2020. Studies that were published in English, contained a full text, and included adolescents were considered for inclusion in this review. Results Compared with the available body of evidence in children and adults, relatively few studies have been published in adolescents. Current evidence suggests that exposure to stressors (at the individual, family, and community levels) or stress (acute and chronic) is associated with asthma and worse asthma outcomes, but such evidence must be cautiously interpreted owing to limitations in the design or the analytical approach of the published studies. Conclusion Future large studies with a prospective design should determine whether and how stressors or stress causes or worsens asthma in adolescents. At present, clinicians should assess exposure to stressors (eg, violence or abuse) and screen for anxiety and depressive disorders when caring for adolescents with asthma in addition to providing referrals to social workers or mental health professionals when appropriate. Public health policies are needed to reduce psychosocial stressors, such as gun violence and racism, in adolescents.