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 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.

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.

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.

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.

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.

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 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.

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.

The Eyes Have It: Eyelid Swelling and Rash in a 79-year-old Woman With Macular Degeneration.

INTRODUCTION: A 79-year-old woman with macular degeneration was referred to the Allergy/Immunology clinic for the evaluation of a potential allergy to anti-vascular endothelial growth factor (anti-VEGF) treatments. The patient developed urticaria and eyelid swelling immediately following a retinal injection of aflibercept, which she had previously tolerated. She previously had allergic reactions following ranibizumab and bevacizumab injections. Injections of anti-VEGF treatments were discontinued given concern for allergy with progression of the patient's disease. OBJECTIVE: To assess the culprit medication(s) responsible for hypersensitivity reactions following anti-VEGF injections for macular degeneration. METHODS: Medication records were reviewed for each retinal injection. All medications used in each procedure, including the anti-VEGF therapy (aflibercept), topical anesthetics (tetracaine and proparacaine hydrochloride), and antiseptic (povidine), were evaluated with skin testing. She was additionally tested for alternative anti-VEGF therapies (ranibizumab and bevacizumab) as she was thought to have allergies to these agents by prior history. A test dose challenge was completed for aflibercept, ranibizumab, and bevacizumab. RESULTS: Skin prick and intradermal testing were negative to aflibercept, ranibizumab, bevacizumab, and povidine. Intradermal testing was positive to tetracaine and proparacaine hydrochloride. The patient passed test dose challenges to aflibercept, ranibizumab, and bevacizumab. Due to her positive hypersensitivity testing to 2 ester anesthetics, the patient underwent skin prick and intradermal testing to the amide anesthetic, lidocaine. This was negative and the patient tolerated a graded challenge to lidocaine. She was deemed to have an immunoglobulin E (IgE)-mediated hypersensitivity to ester-type local anesthetics. She successfully resumed anti-VEGF therapy with an amide local anesthetic. CONCLUSIONS: The reason for this consult was the concern for hypersensitivity to a biologic anti-VEGF medication. The culprit allergen, the local anesthetic, could have been overlooked without an assessment of all medications used during the procedure. This case highlights the importance of a thorough allergy evaluation of all medications used during procedures to determine the causative agent.Chief Complaint: Eyelid swelling and rash after ophthalmic procedures for macular degeneration.

The Clinical Significance of Specific Antibody Deficiency (SAD) Severity in Chronic Rhinosinusitis (CRS).

BACKGROUND: Despite the increased identification of specific antibody deficiency (SAD) in chronic rhinosinusitis (CRS), little is known about the relationship between SAD severity and the severity and comorbidities of CRS. The prevalence of an impaired antibody response in the general population is also unknown. OBJECTIVE: The objective of this study was to determine if the SAD severity stratification applies to real-life data of patients with CRS. METHODS: An electronic health record database was used to identify patients with CRS evaluated for humoral immunodeficiency with quantitative immunoglobulins and Streptococcus pneumoniae antibody titers before and after pneumococcal vaccine. SAD severity was defined, according to the guidelines, based on the numbers of titers ≥1.3 µg/dL after vaccination: severe (≤2 serotypes), moderate (3-6 serotypes), and mild (7-10 serotypes). Comorbidities and therapeutic response were assessed. The prevalence of an impaired antibody response in a normal population was assessed. RESULTS: Twenty-four percent of the patients with CRS evaluated for immunodeficiency had SAD, whereas 11% of a normal population had an impaired immune response to polysaccharide vaccination (P < .05). When evaluated by the practice parameter definition, 239 of 595 (40%) met the definition of SAD. Twenty-four (10%) had severe SAD, 120 (50%) had moderate SAD, and 95 (40%) had mild SAD. Patients with moderate-to-severe SAD had worse asthma, a greater likelihood of pneumonia, and more antibiotic courses in the 2 years after vaccination than patients with mild SAD. CONCLUSIONS: This study provides real world data supporting stratification of SAD by severity, demonstrating a significant increase in the comorbid severity of asthma and infections in CRS patients with moderate-to-severe SAD compared with those with mild SAD and those without SAD.

Sinusitis in patients on tumor necrosis factor alpha inhibitors.

BACKGROUND: Tumor necrosis factor alpha (TNF-α) inhibitors have revolutionized treatment of many inflammatory diseases. Sinusitis after initiation of TNF-α inhibitors has been observed, but has not been well described in the literature. We aim to characterize the clinical features of sinusitis in patients on anti-TNF-α therapy. METHODS: This is a retrospective chart review of 28 patients on a TNF-α inhibitor diagnosed with sinusitis by otolaryngologists at Duke University. Patient demographics, sinusitis characteristics, and treatment course were studied by chart review. RESULTS: The prevalence of sinusitis diagnosed and treated by an otolaryngologist was less than 1%. Of the 28 patients studied, 12 (42.9%) had a history of preexisting sinusitis and 16 (57.1%) had new-onset sinusitis. 71.4% were diagnosed with chronic rhinosinusitis without polyps (CRSsNP), with disease mainly involving the maxillary and ethmoid sinuses. No patients had major extrasinus complications or required hospital admission or intravenous (IV) antibiotics. 35.7% (n = 10), including 44% (7/16) of new-onset patients required a surgical intervention after initiating anti-TNF therapy. 14.3% (n = 4) of the cohort had improvement in sinonasal symptoms after stopping, changing, or holding doses of the TNF-α inhibitor. CONCLUSION: Anti-TNF-α therapy can be associated with new-onset sinusitis, mainly CRSsNP. Overall, the percentage of patients on a TNF-α inhibitor seeking consultation from an otolaryngologist is low. While some patients with new-onset sinusitis will require surgery, modification of anti-TNF-α therapy should be considered as an option in the medical management of these patients.