Nasal allergen challenge (NAC): Practical aspects and applications from an EU/US perspective-a Work Group Report of the AAAAI Rhinitis, Rhinosinusitis and Ocular Allergy Committee.

Nasal allergen challenge (NAC) is applied in a variety of settings (research centers, specialty clinics, and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, and occupational rhinitis; to design the composition of allergen immunotherapy in patients who are polysensitized; and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time- and resource-consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (eg, local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.

Antibody and T-cell responses to coronavirus disease 2019 vaccination in common variable immunodeficiency and specific antibody deficiency.

BACKGROUND: Clinical trials of the mRNA coronavirus disease 2019 (COVID-19) vaccines excluded individuals with primary antibody deficiencies. OBJECTIVE: To evaluate whether antibody and T-cell responses to mRNA COVID-19 vaccination in patients with common variable immunodeficiency (CVID) and specific antibody deficiency (SAD) were comparable to those in healthy controls. METHODS: We measured antibody responses against the spike glycoprotein and the receptor-binding domain (RBD) in addition to severe acute respiratory syndrome coronavirus 2 specific T-cell responses using peripheral blood mononuclear cells 2 to 8 weeks after the subjects completed the primary 2-dose vaccine series. RESULTS: The study comprised 12 patients with CVID, 7 patients with SAD, and 10 controls. Individuals with CVID had lower immunoglobulin (Ig) G and Ig A levels against spike glycoprotein than did both individuals with SAD (P = .27 and P = .01, respectively) and controls (P = .01 and P = .004, respectively). The CVID group developed lower IgG titers against the RBD epitope than did the control group (P = .01). Participants with CVID had lower neutralizing titers than did the control group (P = .002). All participants with SAD developed neutralizing titers. All 3 groups (SAD, CVID, and control) developed antigen-specific CD4+ and CD8+ T-cell responses after vaccination. CONCLUSION: Our results suggest that patients with CVID may have impaired antibody responses to COVID-19 vaccination but intact T-cell responses, whereas patients with SAD would be expected to have both intact antibody and T-cell responses to vaccination.

The Use and Teaching of Telemedicine in Allergy/Immunology Training Programs.

PURPOSE OF REVIEW: The use of telemedicine has greatly increased since the onset of the coronavirus disease 2019 (COVID-19) pandemic. This review discusses the types of telemedicine, current telehealth curricula in medical education, and benefits and disadvantages of incorporation of telemedicine into Allergy/Immunology training programs. RECENT FINDINGS: The majority of Allergists/Immunologists use telemedicine in their clinical practice with leaders in graduate medical education recommending inclusion of telemedicine in training. Fellows-in-training reported that use of telemedicine in Allergy/Immunology training during the pandemic mitigated some concerns for lack of adequate clinical experience. Still, no standardized curriculum for telemedicine training in Allergy/Immunology exists, although curricula from internal medicine and primary care residencies can provide a framework for incorporation of telemedicine training into fellowship. Benefits of telemedicine in Allergy/Immunology training include enhanced immunology training, home environment monitoring, and flexibility to reduce physician burnout while disadvantages include limited physical examination skill building and lack of a standardized curriculum. As telemedicine has been widely accepted in medicine with high patient satisfaction, it is necessary to incorporate a standardized telehealth curriculum in Allergy/Immunology fellowship training, both as a tool for patient care as well as trainee education.

The role of aspirin desensitization followed by oral aspirin therapy in managing patients with aspirin-exacerbated respiratory disease: A Work Group Report from the Rhinitis, Rhinosinusitis and Ocular Allergy Committee of the American Academy of Allergy, Asthma & Immunology.

Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and an intolerance to medications that inhibit the cycloxgenase-1 enzyme. Patients with AERD on average have more severe respiratory disease compared with patients with chronic rhinosinusitis with nasal polyps and/or asthma alone. Although patients with AERD traditionally develop significant upper and lower respiratory tract symptoms on ingestion of cycloxgenase-1 inhibitors, most of these same patients report clinical benefit when desensitized to aspirin and maintained on daily aspirin therapy. This Work Group Report provides a comprehensive review of aspirin challenges, aspirin desensitizations, and maintenance aspirin therapy in patients with AERD. Identification of appropriate candidates, indications and contraindications, medical and surgical optimization strategies, protocols, medical management during the desensitization, and recommendations for maintenance aspirin therapy following desensitization are reviewed. Also included is a summary of studies evaluating the clinical efficacy of aspirin therapy after desensitization as well as a discussion on the possible cellular and molecular mechanisms explaining how this therapy provides unique benefit to patients with AERD.

Robust Antibody and T Cell Responses to SARS-CoV-2 in Patients with Antibody Deficiency.

Immunocompromised patients, including those with inborn errors of immunity (IEI), may be at increased risk for severe or prolonged infections with SARS-CoV-2 (Zhu et al. N Engl J Med. 382:727-33, 2020; Guan et al. 2020; Minotti et al. J Infect. 81:e61-6, 2020). While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity has not yet been characterized in patients with antibody deficiency (Grifoni et al. Cell. 181:1489-1501 e1415, 2020; Burbelo et al. 2020; Long et al. Nat Med. 26:845-8, 2020; Braun et al. 2020). Herein, we describe the clinical course, antibody, and T cell responses to SARS-CoV-2 structural proteins in a cohort of adult and pediatric patients with antibody deficiencies (n = 5) and controls (related and unrelated) infected with SARS-CoV-2. Five patients within the same family (3 with antibody deficiency, 2 immunocompetent controls) showed antibody responses to nucleocapsid and spike proteins, as well as SARS-CoV-2 specific T cell immunity at days 65-84 from onset of symptoms. No significant difference was identified between immunocompromised patients and controls. Two additional unrelated, adult patients with common variable immune deficiency were assessed. One did not show antibody response, but both demonstrated SARS-CoV-2-specific T cell immunity when evaluated 33 and 76 days, respectively, following SARS-CoV-2 diagnosis. This report is the first to show robust T cell activity and humoral immunity against SARS-CoV-2 structural proteins in some patients with antibody deficiency. Given the reliance on spike protein in most candidate vaccines (Folegatti et al. Lancet. 396:467-78, 2020; Jackson et al. N Engl J Med. 383:1920-31, 2020), the responses are encouraging. Additional studies will be needed to further define the timing of onset of immunity, longevity of the immune response, and variability of response in immunocompromised patients.

The Impact of Social Determinants and Air Pollution on Healthcare Disparities in Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND/OBJECTIVE: Multiple factors affect healthcare disparities in chronic rhinosinusitis (CRS) with and without nasal polyps. These factors include access to care, economic burdens to treatment, and differences in air pollution and air quality. In this paper, we will discuss how socioeconomic status, race, and air pollution burden influence healthcare disparities in the diagnosis and treatment outcomes of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: A literature search was performed via PubMed for articles related to CRSwNP, healthcare disparities, race, socioeconomic status, and air pollution in September 2022. Original studies from 2016 to 2022, landmark articles, and systematic reviews were included. We summarized these articles to cohesively discuss factors contributing to healthcare disparities in CRSwNP. RESULTS: Literary search produced 35 articles. Individual factors such as socioeconomic status, race, and air pollution influence CRSwNP severity and treatment outcomes. Correlations were noted with socioeconomic status, race, and air pollution exposure and CRS severity and post-surgical outcomes. Air pollution exposure was also associated with histopathologic changes in CRSwNP. Lack of access to care was a notable contributor to healthcare disparities in CRS. CONCLUSION: Healthcare disparities in the diagnosis and treatment of CRSwNP differentially affect racial minorities and individuals of lower socioeconomic status. Increased air pollution exposure in areas of lower socioeconomic status is a compounding factor. Clinician advocacy for greater healthcare access and reductions in environmental exposures for patients, among other societal changes, may help improve disparities.

Biologics for Nasal Polyps: Synthesizing Current Recommendations into a Practical Clinical Algorithm.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) has been traditionally managed with a combination of topical and systemic medical therapy as well as endoscopic sinus surgery. The emergence of biologic therapies that target specific aspects of the inflammatory cascade has ushered in a potentially new paradigm in the management options available for CRSwNP. PURPOSE: To summarize the current literature and recommendations supporting the use of available biologic therapies for CRSwNP and to develop an algorithm to aid clinical decision-making regarding treatment selection. METHODS: A review of available literature and studies that demonstrated the clinical efficacy of biologic agents for the treatment of CRSwNP informing current CRSwNP consensus algorithms. RESULTS: Current biologic medications target immunoglobulin E, interleukins, or interleukin receptors implicated in the Th2 inflammatory cascade. Institution of biologic therapy is now an option for patients who have disease refractory to topical medical therapy and endoscopic sinus surgery, those who cannot tolerate surgery, or patients with other comorbid Th2 diseases. Response to treatment should be monitored at 4-6 months and 1 year after initiating therapy. Across multiple indirect comparisons, dupilumab appears to have the largest therapeutic benefit across multiple subjective and objective outcomes. The choice of therapeutic agent also depends on drug availability, patient tolerance, presence of comorbid illnesses, and cost. CONCLUSIONS: Biologics are emerging as an important option in the management of patients with CRSwNP. While more data is required to fully inform indications, treatment selection, and health economics related to their use, biologics may offer robust symptom relief to patients who have failed other interventions.

Lymphomatosis cerebri presenting with orthostatic hypotension, anorexia, and paraparesis.

To increase awareness about lymphomatosis cerebri by describing a patient with a unique presentation Case report a 58 year old woman presented with progressive lower extremity weakness, postural hypotension, and 90 pound weight loss over 3 months a brain magnetic resonance image revealed multiple non-enhancing foci of T2 hyperintensity in the periventricular white matter despite treatment with corticosteroids, she expired autopsy demonstrated normal gross appearance of the brain and spinal cord microscopic inspection revealed diffuse infiltration of the central nervous system (CNS) parenchyma and white matter by large atypical B cells, consistent with a diagnosis of lymphomatosis cerebri lymphomatosis cerebri is a primary CNS lymphoma variant that is poorly recognized and often misdiagnosed it commonly presents as a rapidly progressive dementia, although patients may present with neurologic dysfunction without dementia diagnosis requires a pathological examination treatment with intravenous high-dose methotrexate based chemotherapy should be considered in appropriate patients.

Health and Clinical Impacts of Air Pollution and Linkages with Climate Change.

Air Pollution Impacts and Climate Change LinksAs part of the NEJM Group series on climate change, Keswani and colleagues review the linkages between climate change and air pollution and suggest strategies that clinicians may use to mitigate the adverse health impacts of air pollution.

A Framework for Augmented Intelligence in Allergy and Immunology Practice and Research-A Work Group Report of the AAAAI Health Informatics, Technology, and Education Committee.

Artificial and augmented intelligence (AI) and machine learning (ML) methods are expanding into the health care space. Big data are increasingly used in patient care applications, diagnostics, and treatment decisions in allergy and immunology. How these technologies will be evaluated, approved, and assessed for their impact is an important consideration for researchers and practitioners alike. With the potential of ML, deep learning, natural language processing, and other assistive methods to redefine health care usage, a scaffold for the impact of AI technology on research and patient care in allergy and immunology is needed. An American Academy of Asthma Allergy and Immunology Health Information Technology and Education subcommittee workgroup was convened to perform a scoping review of AI within health care as well as the specialty of allergy and immunology to address impacts on allergy and immunology practice and research as well as potential challenges including education, AI governance, ethical and equity considerations, and potential opportunities for the specialty. There are numerous potential clinical applications of AI in allergy and immunology that range from disease diagnosis to multidimensional data reduction in electronic health records or immunologic datasets. For appropriate application and interpretation of AI, specialists should be involved in the design, validation, and implementation of AI in allergy and immunology. Challenges include incorporation of data science and bioinformatics into training of future allergists-immunologists.

The Future of Telehealth in Allergy and Immunology Training.

With emerging interest in the use of telemedicine, allergy-immunology should be at the forefront of adoption and implementation of these services. Patients report a greater desire for telemedicine services as well as satisfaction with video-based visits with their providers. Interim virtual visits can accommodate overscheduled clinics, reduce burdens of travel to distant sites, improve access to subspecialty care, and increase adherence during monitoring of chronic allergic conditions. The outpatient nature of allergy-immunology coupled with the ease of conducting many aspects of a routine visit via telemedicine makes the incorporation of telehealth training into fellowship programs highly desirable. The short-term closure of hospital-affiliated clinics, in particular, for vulnerable or immunodeficient patients, in the setting of a global pandemic demonstrates the timeliness of this topic. A framework for implementing telemedicine into the allergy-immunology curriculum, training faculty on appropriate supervision, providing elective clinical experience in the form of continuity clinics, and simulating telemedicine delivery is discussed. Proposed telemedicine competencies desired for the independent practice of telemedicine are suggested.

Hypoxia inducible factor-alpha activation in lymphoma and relationship to the thioredoxin family.

Hypoxia inducible factors (HIFs) activate oncogenic pathways, while thioredoxins (Trx), including Trx1 and Trx reductases-1 and -2 (TrxR1 and TrxR2), promote HIF-alpha stabilization. In immunoblotting studies in lymphoma cell lines we found that Raji and SUDHL4 cells exhibited normoxic HIF-2alpha protein stabilization. Five cell lines showed increased TrxR1 expression, while only Namalwa, HF1 and SUDHL4 had Trx1 and TrxR2 activation. Tissue microarrays in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) identified different HIF expression among histological subgroups (e.g. 44% DLBCL vs. 11% of FL cases with moderate-to-high expression of HIF-1alpha and HIF-2alpha, P = 0.0017). These data demonstrate that HIF and the thioredoxin family are abnormally activated in lymphoma.