The field of allergy and immunology (A/I) has transformed modern medicine with the development of diagnostic and therapeutic advances in all areas of health. This Work Group Report from the Division Directors Committee of the American Academy of Allergy, Asthma & Immunology describes the current state of 5 mission areas (clinical, educational, research, equity, and advocacy) within the A/I divisions/subdivisions of academic medical centers (AMCs) in the United States. The current states of the clinical and educational mission areas in AMCs in A/I are strong, with an increasing prevalence of atopic/immunologic disorders and novel therapeutics, solid trainee interest, and tremendous potential for research, equity, and advocacy efforts. The interest in the field of A/I has outpaced the creation of new positions, leading to an increase in unmatched applicants yearly. Weaknesses and threats include decreasing federal research and educational funding, changing health care insurance policies, the dynamic legislative environment, and the negative impact of the business focus in academic institutions. The future of A/I will depend on the preservation of a strong academic foundation with improved recruitment to academic positions, increased training positions, and greater incentives for development of career opportunities in research and education, utilizing artificial intelligence tools and strong advocacy strategies.

Introduction Integrative medicine includes a holistic approach, consisting of a combination of conventional treatment and complementary and alternative medicine (CAM). Our objective is to identify if patients with allergic and immunologic (AI) conditions in our academic allergy clinic are currently using or interested in future CAM to supplement their conventional allergy treatment. Methods A cross-sectional questionnaire was administered (n=200) in our allergy clinic. This included past use and future interest in CAM for AI conditions. Results 27.1% participants had used CAM while 72.5% participants had not used CAM for AI conditions. 52.5% participants would be interested in future CAM. Acupuncture (35%), relaxation (34.7%), and herbs (31.7%) were the most common interested CAM techniques. Females (81%) were more interested in CAM use relative to males (19%). Asthma (35), urticaria, (21%), and allergic rhinitis (54%) were the most frequent diagnoses associated with future CAM interest. The most common reason for CAM non-interest was “unfamiliar” (23.1%). Conclusion We show that 47.5% of participants had used CAM for any condition, consistent with current studies. However, we found only 27.1% participants had used CAM previously for AI conditions. More than half (52.5%) participants are interested in future CAM to supplement current AI treatments. Our findings show that our AI patients desire to implement CAM into treatment plans, and that patients in our clinic have an interest in CAM, but many patients are unfamiliar. More work is needed to create CAM standardized intake forms, and education and services to offer CAM is needed to be more accessible for patients and clinicians.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) consists of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). Asthma is associated with increased risk of atherosclerotic cardiovascular diseases (ASCVD). However, there is lack of data on association between AERD and ASCVD. OBJECTIVE: To investigate the relationship between AERD and subsequent risk of ASCVD. METHODS: An algorithm to find patients with AERD was generated and validated through chart review at our home institution. This algorithm was applied to a national insurance claims database to obtain data for a retrospective cohort study. Demographic and comorbidity data were obtained for propensity matching. Several methods of analysis were performed on the data. RESULTS: A total of 571 patients met criteria for AERD; 3909 met criteria for asthma, CRSwNP, and no allergy to aspirin or NSAIDs (group 1); and 75,050 met criteria for asthma, CRS without nasal polyps, and no allergy to aspirin or NSAIDs (group 2). After covariate adjustment, AERD was significantly associated with ASCVD, including severe ASCVD, over groups 1 and 2 regardless of asthma severity. CONCLUSION: Patients with AERD are at higher risk of ASCVD than patients with asthma and CRSwNP or CRS without nasal polyps, underscoring the need for early ASCVD screening and a consideration for aspirin desensitization or use of a nonaspirin antiplatelet agent in the setting of AERD and comorbid ASCVD. (c) 2023 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:3445-53)

Introduction: Staging of non-small cell lung cancer is crucial in predicting patient prognosis and more importantly, determining cancer management. In patients without driver mutations, PD-L1 tumor proportion score evaluation becomes vital in dictating treatment, as immunotherapy can be recommended. These agents have been shown to lead to excellent outcomes, even in patients with late-stage disease. Case Report: A 69-year-old male with a history of chronic obstructive pulmonary disease (COPD) presented with worsening dyspnea found to have lung collapse from a large hilar soft tissue mass causing obstruction of the left mainstem bronchus. After malignancy workup, the patient was diagnosed with non-small cell lung cancer clinically staged as IIIB. An incidental finding of microsatellite instability colon cancer was also found during workup. Pembrolizumab treatment was initiated and led to near resolution of both tumors. Conclusion: Stage IIIB non-small cell lung cancer has an overall poor prognosis. Biomarker testing in our case prior to starting concurrent chemoradiation revealed the malignancy to have a 100% tumor proportion score for PD-L1, the fundamental reason why our patient’s treatment was successful. Based on our findings, we advocate for all patients with non-small cell lung cancer regardless of stage to undergo biomarker testing prior to therapy initiation. Furthermore, the resolution of PD-L1 negative microsatellite instability stable colon cancer after pembrolizumab therapy supports further investigation of the utility and mechanism of PD-1/PD-L1-based therapy in PD-L1 negative colon cancer.

Since the introduction of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines, much attention has been paid to adverse reactions. Numerous cutaneous reactions are described in the literature, but less so about chronic spontaneous urticaria (CSU). CSU is described as recurrent hives with no identifiable trigger, with or without angioedema, which persists for more than 6 weeks. It can be a frustrating diagnosis for physicians and patients alike because of the difficulty in identification and management. The mainstay of CSU treatment is antihistaminergic therapy. In this case, we describe a 35-year-old woman who was newly diagnosed with CSU after receiving the Pfizer-BioNTech COVID-19 mRNA vaccine.

Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction, triggered by variable allergic and nonallergic exposures. 1 Adkinson NF, Bochner BS, Burks AW, et al. Middleton's Allergy: Principles and Practice: Eighth Edition.2013. Available at: https://research.monash.edu/en/publications/middletons-allergy-principles-and-practice-eighth-edition. Accessed July 1, 2021. Google Scholar Here, we report a case of recurrent anaphylaxis coinciding with flares of chronic cholecystitis. We hypothesize that in rare cases, inflammatory mediators released during episodes of cholecystitis can trigger anaphylaxis.

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This JAMA Insights Clinical Update reviews recent evidence favoring use of inhaled corticosteroids (ICS)in all patients with asthma, regardless of frequency, and summarizes the SMART (single maintenance and reliever therapy) treatment approach, which uses an inhaler combining ICS and formoterol for control and relief of symptoms, and differences between SMART and symptom-driven therapy.

Purpose of review Asthma is a chronic, inflammatory disorder of the airways caused by a complex interplay of various biologic mechanisms. Several monoclonal antibody therapies targeting interleukin (IL)-4/IL-13 and IL-5 cytokine pathways have been developed for the treatment of severe eosinophilic asthma. As individuals can display biomarkers and clinical features characteristic of several asthma phenotypes, selection of anoptimal biologic can be difficult. Recent findings Dupilumab, a monoclonal antibody that binds to the α subunit of the IL-4 receptor (IL-4Rα) and has been approved for the treatment of adults with severe atopic dermatitis, has been shown in recent phase 3 trials to also have significant clinical benefits in the asthmatic population irrespective of baseline eosinophil counts. Summary As monoclonal antibodies targeting either IL-4 or IL-13 cytokines individually have failed to demonstrate significant clinical benefits, biologics that target cytokine receptors may be more efficacious compared to those that target cytokines. Furthermore, inhibition of the IL-4/IL-13 signaling cascades may disrupt a broader Th2 inflammatory response compared to a more selective impairment of eosinophil proliferation and activity via blockage of the IL-5 pathway. Future research with independently funded, head-to-head trials of approved biologics is needed to elucidate a favorable therapeutic option.

Cell activation stimulates Topoisomerase-dependent formation of DNA double strand breaks in the promoters of early-response genes. These breaks are sufficient to induce the expression of these of early-response genes. Here we hypothesized that improving the genomic integrity of Topoisomerase 2a (Top2a) in the lungs of mice that are being subjected to K. pneumoniae-induced ARDS augments innate immune response. To improve the genomic integrity of Top2a, recombinant rNEIL2, a DNA repair enzyme that initiates excision of oxidized DNA lesion via the DNA-base excision repair (DNA-BER) pathway, was transfected into the lungs of mice. In a control group, heat-inactivated rNEIL2 was transfected. These transfected mice were intranasally infected with 5 x 105 PFU of K. pneumoniae. Six hours post-infection, the lung genomic DNA was extracted and subjected to a high-sensitivity long-run real-time PCR technique for DNA-damage quantification (LORD-Q) of Top2a. Innate lung inflammation was quantified by performing BAL cell counts 48 hrs post infection. Stimulating oxidative DNA-BER by transfecting the lungs with rNEIL2 prior to K. pneumoniae infection increased neutrophil recruitment by about 10-fold compared to mice transfected with heat-inactivated rNEIL2. K. pneumoniae infection induced 76.46 +/- 6.8 detected lesions in Top2a gene per 10Kb lung genomic DNA in mice transfected with heat-inactivated rNEIL2. By contrast, in mice transfected with active rNEIL2, the infection induced only 54.74 +/- 8.1 detected lesions in Top2a gene per 10Kb, p<0.04. Stimulating oxidative DNA-BER in mice being subjected to K. pneumoniae-induced ARDS improves the genomic integrity of Topoisomerase 2a and augments innate immune response.

Fortilin, a molecule also known as histamine-releasing factor (HRF), has demonstrated histamine-release activity and been implicated in various allergic diseases. While mast cell release of histamine is thought to play a role in chronic idiopathic urticaria (CIU), the pathogenesis remains unclear, as does reliable serologic testing. A potential role of fortilin in CIU has not yet been reported. Twenty adult subjects with CIU, defined as the presence of hives with itching for more than 6 consecutive weeks without clear etiology were recruited for this study. The CIU group consisted of 5 males and 15 females with a mean age of 43.3 years. Thirty-five control patients without CIU were also recruited, consisting of 8 males and 27 females with a mean age of 41.4 years. Serum samples were obtained from all enrolled subjects and fortilin levels examined using ELISA. Unpaired two-tailed t-tests using GraphPad Prism software were performed for analysis. Compared to non-CIU patients (mean 6.7ng/mL ± SEM 1.3), subjects with CIU demonstrated elevated serum levels of fortilin (12.33ng/mL ± 2.7; p<0.05). The newly-developed fortilin assay enabled accurate quantification of serum fortilin levels. CIU subjects demonstrated almost double the serum fortilin levels present in non-CIU subjects. Elevated fortilin levels have been reported in BAL fluid of asthmatics and in nasal lavage fluid from subjects with allergic rhinitis, with fortilin inhibition able to alleviate mast cell-mediated airway inflammation. Fortilin may contribute to the pathophysiology of CIU by stimulating mast cell degranulation, and provide a potential therapeutic target for the treatment of CIU.

Allergic rhinitis is a prevalent condition that has a significant impact on the quality of life of many patients. When initial therapy fails to control the symptoms, allergen immunotherapy (AIT) has been suggested as an option by the Joint Task Force on Practice Parameters. The 2 main forms of AIT are via subcutaneous and sublingual routes, called subcutaneous immunotherapy and sublingual immunotherapy, respectively. There is debate about which is the better option for patients with each method offering its own pros and cons. We present 2 patients with allergic rhinitisAR that were deemed good candidates for AIT and explore current evidence for both subcutaneous immunotherapy and sublingual immunotherapy. The advantages and disadvantages of each method are discussed with the goal of providing a framework for the physician when deciding on AIT for their patients. In addition, we explore the use of AIT in patients with asthma and atopic dermatitis as potential patient populations that may benefit from the treatment. We use the discussion to provide recommendations regarding which method of AIT is best suited for both our patients.

Repair of oxidatively-induced DNA base lesions can stimulate innate and allergic airway inflammation. Specific allergenic extracts like ragweed pollen extract and cat dander extract (CDE) induce TLR4-dependent oxidative stress and DNA damage. These studies suggest that stimulation of an innate receptor/adaptor by allergenic extracts initiates excision of a set of DNA-base lesions. The extent of DNA damage in the genome of nasal epithelial cells of human subjects has not been reported. Wild-type (WT) and Myd88KO naïve mice were intranasally challenged once with CDE, and oxidatively-induced DNA base lesions in lung genomic DNA was quantified by GC-MS/MS Genomic DNA was isolated from Rhinoprobe nasal curettes samples collected from eight human subjects with asymptomatic allergic rhinitis (AAR) and four healthy human nonallergic control subjects (NC), and long-run real-time PCR technique for DNA-damage quantification (LORD-Q) assay was performed to quantify total damage to genomic DNA in these samples. CDE challenge stimulated MyD88-dependent excision of DNA base lesions 5-OH-Cyt, FapyAde and FapyGua from the lung genome of mice and innate and allergic airway inflammation. The level of DNA damage in nasal epithelial cells was lower in AAR human subjects compared to NC human subjects. These data suggest that repair and reduction of DNA base lesions in genomic DNA is associated with increased airway inflammation, whereas low levels of DNA damage is associated with an asymptomatic state in human subjects with allergic rhinitis.

Chronic obstructive pulmonary disease (COPD) is common worldwide. The predominant cause in most COPD is environmental exposure to toxicants. The inflammatory processes in COPD are multifactorial, complex, and interacting, leading to many potential therapeutic targets. Although most typically associated with neutrophilic/macrophagic inflammation (type 1), it is now known that COPD can also be associated with eosinophilic inflammation (type 2), particularly in exacerbations. Accordingly, there is an active program of investigation of highly selective biologic therapeutic agents in the management of COPD. This review summarizes clinical trials of the use of these novel agents in the management of COPD.

Purpose of review Asthma and COPD represent heterogeneous disorders with broad ranging impact on patients and health systems. This review focuses on evidence for early attempts at understanding their pathogenesis by the British and Dutch hypotheses. It also addresses the role of eosinophils, IL-5, and biologics targeting these pathways in asthma and COPD. Recent findings Among asthma and COPD patients, clusters exist based on phenotypic and biologic markers allowing for further understanding of endotypes. Recent studies suggest the role of eosinophils and optimal therapies for each condition may be different. Summary Although patients with ACOS or overlap symptoms may be an exception, overall there appears to be more evidence supporting that asthma and COPD are distinct processes. Targeting eosinophils with anti-IL-5 therapy appears to be an exciting pathway in the properly selected patient with asthma and recent data also supports its use in COPD.

Purpose of reviewCurrent asthma management relies on inhaled corticosteroids, but some asthma is not well controlled with inhaled steroids alone or in combination with long-acting bronchodilators or leukotriene pathway inhibitors. The field of biologic therapy has grown dramatically in the past two decades, with current availability of three molecules, with two distinct and highly selective approaches to interfering with the allergic and eosinophilic airway inflammation common to most asthma. This review summarizes current and future options for incorporating biologic therapy into the overall management of asthma.Recent findingsTwo new biologic agents have been recently introduced in the United States market, supported by well controlled, randomized clinical trials. These trials have provided insight into the types of patients who are most likely to benefit from these novel agents.SummaryIn asthma patients with frequent exacerbations, the addition of a biologic agent targeting the interleukin-5 pathway, or immunoglobulin E, can significantly reduce exacerbations and improve asthma control. The clinical predictors of utility of specific agents overlap with one another, highlighting the importance of clinical judgment in the overall management of this complex disorder.

Fortilin, also known as histamine-releasing factor [HRF] and translationally controlled tumor protein, has been studied as a HRF and implicated as a mediator in late phase allergic reactions. It has a proinflammatory role in murine asthma and skin immediate hypersensitivity. However, the ability of allergen challenge to modulate the levels of fortilin in the nasal secretion of subjects with allergic rhinitis has not been reported. Nine adult subjects with allergic rhinitis and positive skin prick testing to ragweed pollen extract (RWPE) were recruited for this study. The mean age of the subjects was 41.6 years. Intranasal challenge with saline and provoking doses of RWPE solution were performed on two different days. During nasal challenge, symptom scores were recorded at baseline, 30 min, and hourly for a total of 6 hours. Nasal lavage was performed at baseline, 30 min and 5 hours post-challenge, and the collected nasal fluid was analyzed for fortilin levels by ELISA. Compared to saline challenge, RWPE challenge rapidly increased congestion, drainage, sneezing, and total symptom scores at 30 min post-challenge (p<0.05). These scores decreased 2 hours post-challenge. Compared to saline challenge, ragweed extract increased the level of fortilin 5 hours after challenge (p<0.05), but not at 30 min post challenge. Exposure to ragweed pollen induces a delayed secretion of fortilin in the nasal airway of ragweed-IgE skin test positive subjects with allergic rhinitis. Fortilin may play a role in the pathophysiology of allergic rhinitis.

In addition to the well-known signs of methotrexate toxicity, rare cutaneous side effects have been described. These cutaneous signs may provide a diagnostic clue into the diagnosis of toxicity as well as facilitate early and aggressive therapy. We describe the case of a 37-year-old male, with a diagnosis of psoriasis, who developed characteristic signs and symptoms of acute methotrexate toxicity after receiving an unknown amount of intravenous methotrexate. The patient experienced a distinct change in the morphology of his existing psoriatic plaques, which became ulcerated and necrotic in the week following the methotrexate injection. Shortly after the development of cutaneous erosions, the patient developed pancytopenia, which ultimately led to his death. Ulceration and necrosis of cutaneous psoriasis plaques may serve as a herald for the impending development of life-threatening pancytopenia in patients with acute methotrexate toxicity.