COVID-19 Vaccination in Patients with Inborn Errors of Immunity Reduces Hospitalization and Critical Care Needs Related to COVID-19: a USIDNET Report.

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission. CONCLUSION: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity.

Ensuring equitable access to guideline-based asthma care across the lifespan: Tips and future directions to the successful implementation of the new NAEPP 2020 guidelines, a Work Group Report of the AAAAI Asthma, Cough, Diagnosis, and Treatment Committee.

The most recent recommendations from the 2020 National Asthma Education and Prevention Program Update and Global Initiative for Asthma 2021 guide evidence-based clinical decision making. However, given the present state of health disparities by age, income, and race, the equitable implementation and dissemination of these guidelines will be unlikely without further guidance. This work group report reviews the current state of the new asthma guideline implementation; presents updated evidence-based therapeutic options with attention to specific patient populations; and addresses barriers to the implementation of these guidelines in minoritized, historically marginalized, and underresourced communities. Allergists and immunologists can use practical ways to accomplish the goals of improved asthma care access and advanced asthma care across the life span, with specific considerations to historically marginalized populations. Modifiable barriers to guideline implementation include financial barriers, environmental factors, and allergy subspecialty access and care coordination. Various programs to improve access to guideline-based asthma care include community programs, school-based asthma programs, and digital health solutions, with an emphasis on reducing disparities by race.

American College of Allergy, Asthma and Immunology members' preferred steps 1 to 3 asthma maintenance and reliever therapy and incomplete insurance coverage indicated as main practice hurdle.

BACKGROUND: New asthma guidelines (GINA, 2022; NAEPP EPR-4, 2020) include considerable changes in treatment recommendations, specifically regarding anti-inflammatory rescue and Single MAintenance and Reliever Therapy (SMART). OBJECTIVE: To explore American College of Allergy, Asthma and Immunology members' preferred treatment and perceived hurdles. METHODS: A survey (SurveyMonkey) regarding steps 1 to 3 asthma therapy was e-mailed to American College of Allergy, Asthma and Immunology members. RESULTS: The allergists completed 147 surveys (46% with >20 years of experience; 98% from United States; 29% academic, 75% [also] private practice). In addition, 69% follow the National Asthma Education and Prevention Program and 81% the Global Initiative for Asthma recommendations. Of 147 allergists, 117 (80%) indicated correctly what SMART strategy is; 21%/36%/50%/39% would use SMART in step 3 treatment of a below 5-year-old/5- to 11-year-old/12- to 65-year-old/above 65-year-old patient, respectively. In this group, 11% to 14% incorrectly chose inhaled corticosteroid (ICS) plus salmeterol and 9% ICS plus vilanterol for SMART. In a 4-year-old needing step 1 therapy (N = 129), 55% of the respondents would add anti-inflammatory therapy; for step 2 treatment, most would prescribe ICS 100 to 200 µg budesonide equivalent daily; in step 3, 49% would prescribe ICS plus long-acting beta-agonist (LABA). In a 7-year-old needing step 1 treatment (N = 134), 40% would prescribe only short-acting beta-agonist; in step 3, 45% would institute SMART strategy, but only 8 of 135 (6%) chose very-low dose ICS plus formoterol (as recommended in Global Initiative for Asthma); most (39%) use low-dose ICS plus formoterol. As for rescue therapy, 59% is now instituting some form of anti-inflammatory rescue. Finally, in a 25-year-old patient (N = 144): in step 1, 39% would prescribe exclusively short-acting beta-agonist; in step 2, 4% only anti-inflammatory rescue and the rest prescribes ICS maintenance; one-third begins SMART strategy at step 2 and 50% in step 3. Major hurdles for prescribing one's preferred strategy included incomplete insurance coverage, insurance not approving more than one canister of ICS-formoterol per month, and cost. CONCLUSION: Asthma therapy varies among physicians, with respondents suggesting underutilization of the recommended anti-inflammatory rescue and SMART therapy. A major hurdle is lack of insurance coverage of medication in line with the guidelines.

Asthma guidelines: comparison of the National Heart, Lung, and Blood Institute Expert Panel Report 4 with Global Initiative for Asthma 2021.

PURPOSE OF REVIEW: Asthma continues to be a prevalent respiratory disease that affects lives within the United States and worldwide. Clinical asthma guidelines based on scientific evidence on testing and therapeutic interventions are needed to control this disease better. To meet this need, the NAEPP (National Asthma Education and Prevention Program) and GINA (Global Initiative for Asthma) were formed to assist with best practice diagnosis and treatments for asthma. This paper reviews the subtle differences and similarities between the most recent recommendations put forth by NAEPP 2020 and GINA 2021, mainly examining the six selected topics, as well as methodology, guidance on emerging topics, and implementation. RECENT FINDINGS: In December 2020, the National Asthma Education and Prevention Program Coordinating Committee released their focused update on fraction of exhaled nitric oxide, indoor allergen mitigation, inhaled corticosteroids, long-acting muscarinic antagonists, allergen immunotherapy, and bronchial thermoplasty. The Global Initiative for Asthma comprehensive document is published annually as a framework for all nations. Therefore, it is timely to consider the National Asthma Education and Prevention Program Coordinating Committee 2020 in relation to the GINA 2021. SUMMARY: The comparison provides a better understanding of evidence-based recommendations for asthma. The NAEPP 2020 and GINA 2021 will equip providers with the knowledge to provide their patients with the best and most updated asthma care.

Clinical use of biologics for asthma treatment by allergy specialists: A questionnaire survey.

BACKGROUND: Asthma is a heterogeneous disease with emerging phenotypes and endotypes. At present, 5 distinct biologics are Food and Drug Administration-approved as an add-on therapy for difficult-to-control type 2-high asthma. Because allergy specialists manage a spectrum of diseases for which biologics may be appropriate, it is important to understand their prescribing patterns. OBJECTIVE: To elucidate the allergist's use of biologics in the treatment of asthma, including barriers, preferences, indications for prescribing, measures to determine effectiveness, and cost-effectiveness. METHODS: A survey was performed among allergists using a semistructured 10-item self-administered web-based questionnaire and the responses were analyzed using one-way frequencies and multiple logistic regression. RESULTS: The response rate was approximately 9%. Omalizumab was the most prescribed biologic for asthma (98%), and "uncontrolled asthma despite adherence to controller medication" was the most common reason. The common selection criteria among the biologics included elevated peripheral eosinophil count, asthma with nasal polyps, and asthma type (type 1; type 2; nonallergic). A decreased exacerbation frequency was the best standard to determine the efficacy among biologics. Benralizumab was considered the most cost-effective. CONCLUSION: This study represents one of the largest surveys among allergy specialists regarding the real-world use of asthma biologics. It seems that there has been reasonably good dissemination and application of current guidelines among allergists based on prescribing patterns. However, their responses reflect the need for the continued modification of asthma guidelines that incorporate novel biologics and other pathway-specific agents into step therapy. As clinical phenotypes and predictive biomarkers develop, allergy specialists will be better prepared to practice precision medicine that optimizes the use of asthma biologics.

Diagnosis of 22q11.2 deletion syndrome and artemis deficiency in two children with T-B-NK+ immunodeficiency.

Two infants are described who presented with 22q11.2 deletion and a T(-)B(-)NK(+) immune phenotype. For both infants, the initial diagnosis was athymia secondary to complete DiGeorge anomaly. The first infant underwent thymus transplantation but 6 months after transplantation had circulating thymus donor T cells; the patient did not develop recipient naïve T cells. Genetic analyses revealed that both patients had Artemis deficiency, a rare form of severe combined immunodeficiency (SCID). Both infants have subsequently undergone bone marrow transplantation. These cases illustrate the importance and paradox of differentiating SCID from complete DiGeorge anomaly because hematopoietic stem cell transplantation (HSCT) is the preferred treatment for SCID but is ineffective for complete DiGeorge anomaly. However, if the thymus is completely absent, donor stem cells from a HSCT would not be able to be educated.

PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma model.

Dysregulation of matrix metalloproteinases (MMPs) and ineffective fibrinolysis are associated with the deposition of extracellular matrix (ECM). We hypothesized that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis. Degree of airway inflammation was similar in PAI-1(-/-) and wild type (WT) mice after ovalbumin (OVA) challenge. PAI-1 production, deposition of collagen and fibrin, and MMP-9 activity in the lung tissue or airways were greater after OVA challenge compared with saline challenge. However, in PAI-1(-/-) mice, collagen deposition was 2-fold less, fibrin deposition was 4-fold less, and MMP-9 activity was 3-fold higher. This is the first direct evidence that the plasmin system regulates ECM deposition in the airways of a murine asthma model, independently of the effect of PAI-1 on inflammatory cells. The results suggest that the PAI-1-dependent inhibition of MMP-9 activity and fibrinolysis is a major mechanism by which ECM deposition occurs.