Background: Group 2 innate lymphoid cells (ILC2s) play a critical role in asthma pathogenesis. Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is associated with reduced signaling via EP2, a receptor for prostaglandin E 2 (PGE 2). However, the respective roles for the PGE 2 receptors EP2 and EP4 (both share same downstream signaling) in the regulation of lung ILC2 responses has yet been deciphered. Methods: The roles of PGE 2 receptors EP2 and EP4 on ILC2-mediated lung inflammation were investigated using genetically modified mouse lines and pharmacological approaches in IL-33- and Alternaria alternata (A.A.)-induced lung allergy models. The effects of PGE 2 receptors and downstream signals on ILC2 metabolic activation and effector function were examined using in vitro cell cultures. Results: Deficiency of EP2 rather than EP4 augments IL-33-induced lung ILC2 responses and eosinophilic inflammation in vivo. In contrast, exogenous agonism of EP4 but not EP2 markedly restricts IL-33- and Alternaria alternata-induced lung ILC2 responses and eosinophilic inflammation. Mechanistically, PGE 2 directly suppresses IL-33-dependent ILC2 activation through the EP2/EP4-cAMP pathway, which downregulates STAT5 and MYC pathway gene expression and ILC2 energy metabolism. Blocking glycolysis diminishes IL-33-dependent ILC2 responses in mice lacking endogenous PG synthesis but not in PG-competent mice. Conclusion: We have defined a mechanism for optimal suppression of lung ILC2 responses by endogenous PGE 2-EP2 signaling which underpins the clinical findings of defective EP2 signaling in patients with NERD. Our findings also indicate that exogenously targeting the PGE 2-EP4-cAMP and energy metabolic pathways may provide novel opportunities for treating ILC2-initiated lung inflammation in asthma and NERD.
Background: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, avidity) and cellular (spike-induced T cell interferon‑γ release) immune responses in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Results: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared to BNT162b2 (70±114 vs. 226±279 BAU/ml, p<0.01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387±1627 and homologous BNT162b2 3202±2184 vs. homologous ChAdOx1 nCoV-19 413±461 BAU/ml, both p<0.001; spike-induced T cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069±6733 and homologous BNT162b2 4880±7570 vs. homologous ChAdOx1 nCoV-19 1152±2243 mIU/ml, both p<0.001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses.
Title:Comparative assessment of allergic reactions to COVID-19 vaccines in Europe and the United StatesTo the EditorCOVID-19 vaccines are safe and effective at preventing severe disease. Among the rare complications that may compromise vaccine acceptance are allergic reactions.1-3 Recently we demonstrated that anaphylaxis rates associated with COVID-19 vaccines are comparable to those of traditional vaccines.4 Herein, we aimed to comparatively assess the incidence and potential underlying causes of the most common allergic reactions post COVID-19 vaccination in Europe and the United States (US).Allergic reactions data following COVID-19 vaccination reported from week 52/2020 to week 39/2021 were collected from EudraVigilance for the European Economic Area (EEA) and from Vaccine Adverse Event Reporting System (VAERS) for the US and analyzed for all licensed vaccines. These included mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), AD26.COV2.S (Janssen/Johnson & Johnson), and the not yet licensed in the US ChAdOx1-S (Oxford/AstraZeneca). Incidence rates were calculated using the corresponding administered vaccine doses as denominators. Vaccine composition was examined to identify potential allergic triggers.The most common allergic reactions after COVID-19 vaccination were anaphylactic reactions, with an overall incidence of 9.91/million doses (EEA: 13.69/million/US: 4.44/million, Fig.1). Anaphylactic shock followed, with much lower rates (overall incidence: 1.36/million, EEA: 2.01/million/US: 0.41/million).The incidence of anaphylactic reactions reported in EudraVigilance varied considerably by vaccine and was 3- to 4-fold higher for BNT162b2 or mRNA-1273 compared to VAERS. AD26.COV2.S-associated anaphylaxis did not differ between databases. The very low incidence of anaphylactic shock also varied by vaccine, particularly as captured in EudraVigilance.Considering vaccine platforms, the incidence of anaphylactic reactions post adenovirus-vectored vaccination was higher compared to mRNA-based vaccines (EudraVigilance: 15.62/ vs . 13.36/million, VAERS: 6.79/vs . 4.34/million doses). Anaphylactic shock incidence rates were also higher for vectored compared to mRNA vaccines (EudraVigilance: 3.14/ vs . 1.81/million, VAERS: 1.20/ vs . 0.38).Detailed demographic data and outcomes of anaphylactic reaction and anaphylactic shock cases post-COVID-19 vaccination are presented in Tables S1 and S2, respectively. The vast majority of cases affected females (82% of anaphylactic reaction/75% of anaphylactic shock reports). With regard to age, different patterns are evident. In EudraVigilance, both types of anaphylaxis were more common among working age (18-64 years) and older individuals; in VAERS, anaphylactic reactions were more frequent among subjects aged 30-59 years (69%), while the very rare anaphylactic shock cases were distributed across age groups.Regarding outcome, the vast majority of cases were resolved or resolving (90.0% of anaphylactic reaction/81.7% of anaphylactic shock cases as captured in EudraVigilance, Table S1). The disease course was complicated (life threatening or leading to permanent disability) in 25.5% of anaphylactic reaction and 31.3% of anaphylactic shock cases as captured in VAERS (Table S2). Fatalities from allergic reactions post COVID-19 vaccination were extremely rare and 2- to 6-fold higher for vectored than mRNA vaccines in both databases (Table 1).The cause(s) that may trigger allergic reactions after vaccination remain elusive.2 Potential contributing factors include: i) components of the final pharmaceutical product [i.e., the active ingredient (antigen) and excipients]; ii) impurities or “related materials” unintentionally present in the final formula;1 iii) the packaging material, especially the rubber stopper.2Cross-reactivity has been reported upon exposure between two of the main excipients of mRNA and vectored vaccines (polyethylene glycol 2000 and polysorbate 80, respectively).5 If true, should we anticipate increased anaphylaxis rates following first time or booster vaccination with vaccines of different platforms according to the so-called heterologous vaccination (mix-and-match) approach?Our study revealed differences in anaphylaxis rates as captured in two of the world’s largest pharmacovigilance databases between Europe and the US, as well as between vaccines and vaccine platforms. Understanding the reasons behind true differences could lead to the further optimization of COVID-19 vaccines.
Microbial metabolism of specific dietary components, such as fiber, contribute to the sophisticated inter-kingdom dialogue in the gut that maintains a stable environment with important beneficial physiological, metabolic, and immunological effects on the host. Historical changes in fiber intake may be contributing to the increase of allergic and hypersensitivity disorders as fiber-derived metabolites are evolutionarily hardwired into the molecular circuitry governing immune cell decision making processes. In this review, we highlight the importance of fiber as a dietary ingredient, its effects on the microbiome, its effects on immune regulation, and potential mechanisms for dietary fibers in the prevention and management of allergic diseases. In addition, we review the human studies examining fiber or prebiotic interventions on asthma and respiratory outcomes, allergic rhinitis, atopic dermatitis, and overall risk of atopic disorders. While exposures, interventions and outcomes were too heterogeneous for meta-analysis, there is significant potential for using fiber in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health.
Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarises currently available knowledge, novel discoveries and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarise the major knowledge gaps and unmet needs in current eicosanoid research.
Background: Type 2-high asthma is characterized by elevated levels of circulating Th2 cells and eosinophils, cells that express chemoattractant-homologous receptor expressed on Th2 cells (CRTh2). Severe asthma is more common in women than men; however, the underlying mechanism(s) remain elusive. Here we examined whether the relationship between severe asthma and type 2 inflammation differs by sex and if estrogen influences Th2 cell response to glucocorticoid (GC). Methods: Type 2 inflammation and the proportion of blood Th2 cells (CD4 +CRTh2 +) were assessed in whole blood from subjects with asthma (n = 66). The effects of GC and estrogen receptor alpha (ERα) agonist on in vitro differentiated Th2 cells were examined. Expression of CRTh2, type 2 cytokines and degree of apoptosis (Annexin V +, 7-AAD) were determined by flow cytometry, qRT-PCR, western blot and ELISA. Results: In severe asthma, the proportion of circulating Th2 cells and hospitalizations were higher in women than men. Women with severe asthma also had more Th2 cells and serum IL-13 than women with mild/moderate asthma. Th2 cells, eosinophils and CRTh2 mRNA correlated with clinical characteristics associated with asthma control in women but not men. In vitro, GC and ERα agonist treated Th2 cells exhibited less apoptosis, more CRTh2 as well as IL-5 and IL-13 following CRTh2 activation than Th2 cells treated with GC alone. Conclusion: Women with severe asthma had higher levels of circulating Th2 cells than men, which may be due to estrogen modifying the effects of GC, enhancing Th2 cell survival and type 2 cytokine production. (249)
Background There is substantial interest in allergen-specific immunotherapy in food allergy. We systematically reviewed its efficacy and safety. Methods We searched six bibliographic databases from 1946 to 30 April 2021 for randomised controlled trials about immunotherapy alone or with biologicals in IgE-mediated food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis. Results We included 36 trials with 2,126 participants, mainly children. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5. to 21.4, high certainty); cow’s milk (RR 5.7, 1.9 to 16.7, moderate certainty) and hen’s egg allergy (RR 8.9, 4.4 to 18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300mg or 1000mg peanut protein was 2. In peanut allergy, oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0 to 1.2, low certainty) or severe reactions (RR 1,6, 0.7 to 3.5, low certainty). It may increase adverse reactions in cow’s milk (RR 3.9, 2.1 to 7.5, low certainty) and hen’s egg allergy (RR 7.0, 2.4 to 19.8, moderate certainty), but reactions tended to be mild and gastrointestinal. Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8 to 3.8, moderate certainty). Results were unclear for other allergies and administration routes. Conclusions Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow’s milk and hen’s egg allergy. However, our review found little about whether this improves quality of life, is sustained or cost-effective.
Predicting reaction threshold and severity are important to improve the management of food allergy, however the determinants of, and relationship between, these parameters are significant knowledge gaps. Identifying robust predictors could enable the reliable risk-stratification of food-allergic individuals. In this series of young people with CM-allergy undergoing DBPCFC – the largest reported in the literature – we did identify any baseline marker which predicted the occurrence of anaphylaxis at challenge, consistent with existing data. 1 There is one report of IgE-sensitisation being predictive of severity in CM-allergy, 5 however the authors included non-reactive patients in their analysis which significantly skewed the analyses, resulting in misleading conclusions. 6 IgE-sensitisation in our cohort, particularly to casein, was predictive of LOAEL. Including an assessment of casein IgE may therefore be of clinical utility when evaluating patients with CM-allergy in the clinical setting.
Most patients presenting with allergies are first seen by primary care health professionals. The perceived knowledge gaps and educational needs were recently assessed in response to which the LOGOGRAM Task Force was established with the remit of constructing pragmatic flow-diagrams for common allergic conditions in line with an earlier EAACI proposal to develop simplified pathways for the diagnosis and management of allergic diseases in primary care. To address the lack of accessible and pragmatic guidance, we designed flow-diagrams for five major clinical allergy conditions: asthma, anaphylaxis, food allergy, drug allergy and urticaria. Existing established allergy guidelines were collected and iteratively distilled to produce five pragmatic and accessible tools to aid diagnosis and management of these common allergic problems. Ultimately, they should now be validated prospectively in primary care settings.
Background It has been hypothesized that epigenomic modifications such as genomic methylation changes are an intermediate step linking environmental exposures with allergic disease development. Associations between individual DNA methylation CpG sites and allergic diseases have been reported, but they have not been assessed regarding their joint predictive capability. Methods Data were obtained from 240 children of the German LISA cohort. Blood-based DNA methylation was measured at six and ten years. Aeroallergen sensitization, at least RAST class 1, was measured in blood at six, ten and 15 years. We calculated six methylation risk scores (MRS) for allergy-related phenotypes based on available publications and assessed their performance both cross-sectionally and prospectively. Dose-response associations between aeroallergen sensitization and MRS, their correlation and mapping of common hits were evaluated. Results All six atopy-related MRS were highly correlated (r>0.86) and seven CpGs were included in more than one MRS. Cross-sectionally, we observed an 80% increased risk for aeroallergen sensitization at six years with an increased risk score by one standard deviation (best MRS: relative risk = 1.81, 95% confidence interval = [1.43; 2.27]). Significant associations were also seen at ten years and in prospective models, though the effect of the latter was attenuated when only including participants not sensitized at baseline. A clear dose-response relationship with RAST classes of aeroallergen sensitization could be established cross-sectionally, but not prospectively. Conclusion We found good classification and prediction capabilities of calculated allergy-related MRS, particularly cross-sectionally for the allergy prevalence, underlining the relevance of altered gene-regulation in allergic diseases.
World Health Organization Global Air Quality Guideline Recommendations: Executive SummaryAnna Goshua1, Cezmi Akdis2, Kari C. Nadeau3,4 1Stanford School of Medicine, Stanford, CA, USA2Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, Switzerland3Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, USA4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USACorresponding Author: Kari C. Nadeau, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Email: email@example.comConflict of Interest: Dr Cezmi Akdis reports research grants from Allergopharma, Idorsia, Swiss National Science Foundation, Christine Kühne-Center for Allergy Research and Education, European Commission’s Horison’s 2020 Framework Programme “Cure”, Novartis Research Institutes, Astra Zeneca, research grants and advisory board from Glaxo Smith-Kline, Sanofi/Regeneron, Scibase, Novartis, and is Editor-in-Chief of Allergy. All other authors declare no conflict of interest.Text Word Count: 1243Abstract Word Count: 147Figure/Table Count: 2Reference Count: 9
There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) impacts of climate change depending on their vulnerability (i.e., diseases) on an international, economic, political and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.
Initial guidelines advised that sensitization to PEG should be taken into consideration in suspected subjects before a recommendation on the administration of vaccines for COVID-19 containing PEG or its cross-reactive analogues. 3 However, PEG shows an important variability in terms of molecular weights and conjugation forms. In that sense, although it is known that PEG-2000 (MW: 2000g/mol) conjugated with lipids is the form contained in the vaccines for COVID-19, there has been great variability in the PEG molecules used in allergy tests to evaluate sensitization of suspected subjects in the context of the current COVID-19 vaccination campaigns. 4 In this context, recent findings have shed light on the specific form of PEG that could be responsible of the hypersensitivity reactions to the mRNA vaccines for COVID-19.
Addressing Beta-lactam Allergy: A Time for actionElizabeth J. Phillips, MD, FIDSA, FAAAAI, Pascal Demoly, MD, PhD, Maria J Torres, MD, PhD1 Department of Medicine, Center for Drug Safety and Immunology, Vanderbilt University Medical Center, Nashville Tennessee USA, 2Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch Australia, 3Division of Allergy, Department of Pulmonology, University Hospital of Montepellier, and IDESP, Univ. Montpellier – Inserm, Montpellier France,4Allergy Unit, Hospital Regional Universitario de Malaga-IBIMA-BIONAND-ARADyAL, and Departmento de Medicina, Universidad de Malaga, Malaga, SpainCorrespondence:Elizabeth J. Phillips, MD, FIDSA, FAAAAICenter for Drug Safety and ImmunologyVanderbilt University Medical Center1161 – 21st Avenue SouthNashville, TN 37232(615) 322-9174 (tel)Elizabeth.firstname.lastname@example.orgIt is now 93 years since the discovery of penicillins, and over 75 years since the first use of penicillin. We have entered yet another wave of challenges plagued with antibiotic resistance accelerating at a rate that well exceeds that of new antibiotic development. In the face of these uphill battles, 8-15% of a global population who has had access to care is labeled as penicillin allergic.1 In the United States (US) there are at maximum 6000 specialists who practice allergy out of a total of 700,000 practicing physicians, and not all allergists are proficient in and practice drug allergy. Conservatively out of 30,000,000 who are labeled as penicillin allergic at any one time in the US, this would mean that each allergist would need to delabel a minimum of 6000 patients. In Europe and the United Kingdom, the figures are proportionately identical, with some differences between countries. Even if all patients had equal access to care, this type of scalability remains impossible. This overwhelming burden that threatens to negatively impact healthcare through delays in treatment, higher healthcare utilization and cost, less effective treatment and increased antibiotic resistance and Clostridioides difficile infection, demands a risk-based approach that simplifies the penicillin allergy delabeling process and establishes bridges with non-allergists.1, 2What have we learned that now makes the population level goal of penicillin delabeling achievable? First off, prevention is better than cure. We should critically examine pediatric populations for antibiotic use to address over-prescription of antibiotics including penicillins for viral infections. We should avoid labeling children with benign delayed exanthems that occur in the setting of a likely viral infection as penicillin allergic. When continued treatment is necessary we should in fact encourage “treating through” such reactions. When a label of penicillin allergy seems inevitable in a child we should address this label early and pay particular attention to antibiotic stewardship. New data on serum sickness-like reaction suggests that many of these are likely virally mediated and do not reproduce on ingestion challenge.3 Community based education programs can help disseminate timely information on penicillin allergy to dispel myths and alleviate fears. A label of penicillin allergy should be both viewed and approached as a threat to both individual and public health. On a public health level addressing penicillin allergy should be seen as a broad stewardship tool that provides a level of herd protectiveness against antibiotic resistance. On an individual level a label of penicillin allergy should be approached with the same routineness as any other preventative health check, and primary care physicians and providers should be trained to understand and manage low-risk penicillin allergy labels.4 Patients should regularly discuss their drug allergy passport with their healthcare providers such as pharmacists and physicians. Allergy passports should enable interoperability, high traceability and time-stamped information solving the problem of frequent unavailability and inaccuracy of drug allergy information.5 Risk stratification should occur and if in a low-risk category a patient should be given the option of direct oral challenge and delabeling. Risk stratification to identify by clinical history the low-risk penicillin allergic patients who would be appropriate for simple procedures is key. Several mechanisms now exist to risk stratify those labeled as penicillin allergic in routine clinical practice. These clinical prediction rules provide an evidence base to identify the majority of low-risk penicillin allergy labeled patients who are at low risk for rechallenge reactions.6, 7 In current practice it is likely that less than 1% of such low-risk patients will be at risk for a reaction on ingestion challenge.1, 8To make widespread penicillin allergy delabeling an achievable and scalable goal we must be convinced of the safety of direct ingestion challenges. A randomized study allocated children 5 years or older with low-risk cutaneous reaction to penicillin skin testing followed by amoxicillin challenge versus 2 step direct oral challenge with amoxicillin with tolerance of amoxicillin of 96% of those with direct challenge and only minor reactions in the remainder.9These results have recently been confirmed in an European population of children.10 Aside from the inconvenience and potential need for specialty assessment, for very low-risk patients, the use of skin testing would be expected to perform poorly considering their low pre-test probability of a reaction. Several other studies have demonstrated that a single or two-step direct ingestion challenge with penicillins such as amoxicillin is a safe and practical strategy to remove a label of penicillin allergy.11 Although there is evidence to support the use of risk stratification tools to delabel penicillin allergy under allergist guidance, we require an educational program on drug allergy for primary care physicians as well validation of these risk stratification tools, to show that low-risk penicillin delabeling can be achieved in this setting.Even in the face of risk stratification and safety of direct ingestion challenge, populations are not equal in terms of their medical risk or antibiotic needs. Intuitively populations that serve to benefit from penicillins and other beta lactams have been shown to have inferior outcomes when labeled as penicillin allergic that would benefit from a delabeling intervention. This includes the association of penicillin allergy label and use of an alternative antibiotic with post-operative surgical site infections.12 Other settings where research has shown feasibility in delabeling include children in the emergency department, critically ill populations with high antibiotic needs, and pregnant women where the high rates of surgical delivery and group B Streptococcal colonization in pregnancy create a high demand for penicillin and cephalosporins as safe firstline drugs.1, 13, 14 Increasingly, assessment of unverified penicillin allergy has been recognized as an antibiotic stewardship intervention in immunocompromised states such as transplant and cancer where populations have much to gain by being delabeled.15There is a “time for action” for removal of penicillin allergy labels on a population level but how do we achieve widespread implementation (Figure 1)? Policy changes should be driven by collaboration with Infectious diseases specialists and allergists who should join forces to pair antibiotic allergy management with antibiotic stewardship. In the community we need to educate parents and pediatricians to make them aware of the hazards of both unnecessary antibiotics and penicillin allergy labels for mild rashes that are often related to a viral infection and unlikely to recur. Primary healthcare providers should be given greater incentives to delabel penicillin allergic patients at the point-of-care and armed with decision support tools to facilitate risk stratification. For those whose history is not consistent with allergy this could include direct delabeling without testing. In the future, evidence may support that routine direct ingestion challenge with a penicillin and delabeling is safe in the primary care setting. Finally, by off-loading low-risk reactions to primary care providers we can then prioritize care of the patients with a higher-risk allergy and/or medical history by engagement with specialists who can provide more in-depth assessments and give them the best antibiotic options.Figure 1: Addressing Beta-lactam Allergy: An Implementation Roadmap: There are currently many missed opportunities for community members and healthcare providers to take action forward on the “penicillin allergy delabeling” movement. This includes not only active measures to delabel patients by history and direct oral challenge and to identify high risk patients for prioritized penicillin allergy delabeling but also preventive measures to avoid unnecessary use and exposure to antibiotics and avoidance of unnecessary labeling in those with mild rashes of likely viral origin.
Disrupted epithelial barrier in nasal polyps characterizes aspirin exacerbated respiratory disease Anand Kumar Andiappan1*, Mohammad Asad2, Celine Chua3, Esha Sehanobish2 , Zhen Ren4, Xue Ying Chan1, Josephine Lum1, Nicholas Ang1, Duan Kaibo1, Adam Gersten2, Waleed M. Abuzeid5, Nadeem Akbar2, Marc Gibber2, Shanshan Howland1, Bernett Lee1, Olaf Rotzschke1, Steven A. Porcelli2, Elina Jerschow2*1 Singapore Immunology Network, Agency for Science, Technology and Research2 Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA3 Department of Biological Science, National University of Singapore4 Division of Allergy and Immunology, Department of Medicine, Washington University Schoolf of Medicine, St Louis, MO, USA5Rhinology and Endoscopic Skull Base Surgery, Department of Otolaryngology – Head and Neck Surgery, University of Washington, Seattle, WA, USA*Correspondence: EJERSCHO@montefiore.org; email@example.com