Randomized trial of pharmacokinetic and pharmacodynamic effects of 13.2 mg intranasal epinephrine treatment in congestion.

BACKGROUND: Nasal congestion could affect the absorption of an epinephrine nasal spray (ENS). OBJECTIVE: To compare the pharmacokinetics of 13.2 mg ENS with nasal congestion vs without congestion and vs intramuscular (IM) treatments. METHODS: This phase I, open-label, 4-period randomized crossover study enrolled 51 healthy adults with seasonal allergies into cohorts that received a single dose of 13.2 mg ENS (NDS1C; Bryn Pharma, Lebanon, New Jersey) administered as 2 consecutive sprays in either opposite nostrils (cohort 1) or the same nostril (cohort 2). Both cohorts received 13.2 mg ENS with and without nasal allergen challenge (NAC), 0.3 mg IM epinephrine by autoinjector, and 0.5 mg IM epinephrine by manual syringe (MS). RESULTS: The ENS after NAC resulted in higher extent and peak exposures and more rapid time to maximum plasma concentration vs ENS without NAC and IM treatments. In cohort 1, the maximum observed baseline-adjusted epinephrine plasma concentration (pg/mL) of ENS with NAC, IM autoinjector, IM MS, or ENS without NAC was 458.0, 279.0, 364.2, and 270.1, respectively, and in cohort 2 was 436.3, 228.2, 322.3, and 250.8, respectively. The maximum observed baseline-adjusted epinephrine plasma concentration geometric mean ratio (90% CI) for ENS with NAC vs without NAC in cohort 1 was 170% (123%-234%), and in cohort 2 was 174% (115%-263%). In cohort 1, the time to maximum plasma concentration was 15, 21, 45, and 25 minutes, respectively, and in cohort 2 was 18, 20, 45, and 20 minutes, respectively (P < .01 for ENS with NAC vs IM MS). The postdose mean heart rate and blood pressure remained stable and relatively similar to predose values regardless of plasma epinephrine concentration. Mild nausea and headache were the most common adverse events with ENS. CONCLUSION: The 13.2 mg ENS with congestion exhibited enhanced absorption vs IM treatments and ENS without congestion and seemed to be well tolerated. There was no clinically impactful relationship between pharmacodynamic effects and plasma epinephrine concentration.

The Art of Dosing for Subcutaneous Immunotherapy in North America.

Subcutaneous immunotherapy (SCIT) is a long-established treatment option for allergic rhinoconjunctivitis. Proper dosing of the allergens is critical for the efficacy and safety of SCIT. Of the hundreds of liquid allergen extracts in the United States, effective and well-tolerated SCIT dosing has only been established for a small number. Thus, SCIT dosing remains largely empiric and continues to be, by necessity, an art. To highlight the complexity of SCIT dosing, this review summarizes the historical and current landscape of U.S. allergen extracts, differences among U.S. and European allergen extracts, allergen selection for SCIT, considerations for compounding of allergen extract mixtures, and recommended dosing. As of 2021, 18 standardized allergen extracts are available in the United States; all other extracts remain unstandardized without characterization of allergen content or potency. U.S. allergen extracts differ from European extracts in formulation and potency characterization. There is no standardized methodology for SCIT allergen selection, and interpretation of allergen sensitization is not straightforward. Compounding of SCIT mixtures requires consideration of potential dilution effects, allergen cross-reactivity, proteolytic activity, and additives. Probable effective dose ranges for SCIT are recommended in U.S. allergy immunotherapy practice parameters, although there are few studies using U.S. extracts supporting these doses as therapeutic. In contrast, optimized doses of sublingual immunotherapy tablets have been confirmed in North American phase 3 trials. The SCIT dosing for each patient remains an art that requires clinical experience and consideration of polysensitization, tolerability, compounding of allergen extract mixtures, and the range of recommended doses within the context of extract potency variability.

A practical guide to prescribing sublingual immunotherapy tablets in North America for pediatric allergic rhinoconjunctivitis: an injection-free allergy immunotherapy option.

Allergic rhinoconjunctivitis (ARC) is a common disease that affects individuals of all ages. Pediatricians may be the first (and only) point of care for children with ARC. Sublingual immunotherapy (SLIT)-tablets are a convenient at-home, injection-free allergy immunotherapy option that can be used for the treatment of ARC. This paper provides a practical guide for pediatricians to aid in prescribing SLIT-tablets to children with ARC in North America. Topics include a summary of the available SLIT-tablets and their efficacy and safety, guidance on when SLIT-tablets are an appropriate option, and how to diagnose ARC and identify culprit allergens. Practical guidance is also provided through a proposed decision tree, a prescribing checklist and prescribing procedures, and suggested follow-up assessments.

Extrapolating Evidence-Based Medicine of AIT Into Clinical Practice in the United States.

Allergy/immunology specialists in the United States prescribing allergy immunotherapy (AIT) have placed a heavy value on practical experience and anecdotal evidence rather than research-based evidence. With the extensive research on AIT conducted in the last few decades, the time has come to better implement evidence-based medicine (EBM) for AIT. The goal of this review was to critically assess EBM for debated concepts in US AIT practice for respiratory allergies in the context and quality of today's regulatory standards. Debated topics reviewed were the efficacy and safety of AIT in various subgroups (eg, polyallergic patients, older patients, patients with asthma, and pregnant women), diagnosis topics (eg, skin prick test vs allergen-specific serum IgE, factors affecting skin prick tests, use of nasal or conjunctival allergen challenges, and telemedicine for diagnosis), and dosing topics (eg, optimal dosing for subcutaneous immunotherapy and sublingual immunotherapy tablets, US liquid allergen extract history, duration of treatment, and biomarkers of efficacy). In addition, EBM for patient-centered AIT issues (eg, adherence, use of practice guidelines, and pharmacoeconomics) and the approach to implementation of AIT EBM in future clinical practice were addressed. The EBM for each concept was briefly summarized, and when possible, a practical, concise recommendation was given.

Shifts in allergy practice in a COVID-19 world: Implications of pre-COVID-19 national health care provider and patient surveys of treatments for nasal allergies.

Background: Most U.S. patient and health care provider surveys with regard to nasal allergy treatments were conducted before sublingual immunotherapy (SLIT)-tablets and allergy immunotherapy (AIT) shared decision-making tools were available. Objective: Patient and health care provider surveys with regard to current perceptions of nasal allergy burden, symptoms, and treatments were conducted to compare with previous surveys and provide insight into the use of SLIT-tablets and AIT shared decision-making tools. Methods: From November-December 2019, adults (N = 510) diagnosed with nasal allergies and health care providers (N = 304) who treated nasal allergies in the United States completed surveys with regard to nasal allergy management. Results: Of the patient respondents, 42% reported that their symptoms were only somewhat controlled and 48% had avoided activities because of their nasal allergies. In all, 38% were using only over-the-counter (OTC) medications for treatment, and 42%, 7%, and 8% had ever received subcutaneous immunotherapy (SCIT), sublingual allergy drops, or SLIT-tablets, respectively; 56% and 85% reported that they had never discussed SCIT or SLIT, respectively, with their health care provider. Of the health care provider respondents, 45%, 58%, and 20% were very likely to discuss OTC medications, SCIT, or SLIT, respectively. Allergists were more inclined to discuss SCIT with their patients than other health care providers (82% versus 33%, respectively). Most allergists (67%) and other health care providers (62%) reported that they did not use an AIT shared decision-making tool, primarily because of unawareness. Conclusion: The patients with nasal allergies continued to report inadequate symptom control and activity impairment. SLIT-tablets and AIT shared decision-making tools were underused. In the coronavirus disease 2019 era, social distancing may limit office visits, which impacts SCIT administration and prompts increased use of telemedicine and a possible advantage for at-home-administered SLIT-tablets over SCIT.

Real-world evidence costs of allergic rhinitis and allergy immunotherapy in the commercially insured United States population.

OBJECTIVE: To assess total and allergic rhinitis (AR)-related healthcare costs among AR patients residing in the United States with a focus on patients persisting with AIT. METHODS: AR patients were identified in the IBM MarketScan database between 1 January 2014 to 31 March 2017. Patients receiving allergy immunotherapy (AIT) were identified with relevant billing codes (earliest AIT claim = index date); non-AIT patients were identified with claims containing a diagnosis code for AR (earliest AR claim = index date). AIT patients reaching 25+ injection claims were analyzed as a separate maintenance cohort. All patients were required to have continuous enrollment for 12 months preceding and following index. RESULTS: A total of 2,334,530 AR patients were included; 103,207 had at least 1 AIT claim, with 45,279 (43.9%) of these patients reaching maintenance, and 24,640 AIT patients (23.9%) never presenting a single injection claim. Compared to non-AIT patients, patients initiating AIT presented higher rates of baseline comorbidities, including asthma (30.1% vs. 7.5%) and conjunctivitis (21.7% vs. 4.4%). During the follow-up period, patients reaching the maintenance phase of AIT incurred lower total costs than the overall AIT cohort ($10,431±$16,606 vs. $11,612±$24,797), and also presented lower follow-up hospitalization costs ($698±$7,248 vs. $1,281±$12,991) and total medical costs ($7950±$13,844 vs. $8989±$22,019). CONCLUSIONS: Continued efforts are needed to increase patient awareness of available options and adherence to AIT, along with reducing wastage. Despite AIT patients presenting fairly progressed disease at the time of treatment initiation, this therapy remains an economical treatment option, as it was not accompanied by substantial increases in overall healthcare expenditure, and may promote positive societal impacts beyond the direct medical costs.What is known on this topicThe prevalence of allergic diseases has increased over the past 50 years and affects between 10-30% of the world population.Allergic rhinitis (AR) poses a significant economic burden in the form of both direct and indirect costsAllergy immunotherapy (AIT) is the only treatment option able to modify the underlying course of the disease.What this study addsSpecific all-cause and AR-related healthcare costs decreased following the initiation of AIT among patients diagnosed with AR, with the largest decreases observed among AIT patients reaching the maintenance phase of treatment, while non-AIT patients showed increases in all categories assessed over a similar follow-up period.Cost decreases among AIT patients were observed despite increased levels of comorbidities compared to non-AIT patients, as the AIT cohort presented elevated rates of atopic dermatitis (7.1% vs. 2.7%), conjunctivitis (21.7% vs. 4.4%), asthma (30.1% vs. 7.5%), and chronic sinusitis (22.6% vs. 4.9%).An analysis of patients' index subcutaneous AIT consultation revealed substantial variability in the initial treatment costs, with nearly 20% of paid amounts exceeding $1,000; given nearly 1 in 4 AIT patients who get AIT mixed never came back for their first injection, this highlights an opportunity to target frontloaded billing practices and the timing of mixing/injection as an area to minimize healthcare waste.

Real-world mapping of allergy immunotherapy in the United States: The argument for improving adherence.

Background: There is a dearth of real-world evidence studies focused on allergy immunotherapy (AIT) use among patients with allergic rhinitis (AR). Objective: This study examined claims data of AR patients residing in the United States to assess patient characteristics and health outcomes. Methods: AR patients were identified in the IBM MarketScan database between January 1, 2014, and March 31, 2017. Patients receiving AIT were identified with relevant billing codes (earliest AIT claim for vaccine as the index date); patients without AIT were identified with claims that contained a diagnosis code for AR (earliest AR claim as the index date). All the patients were required to have continuous enrollment 12 months prior to and following their index date. AIT patients reaching 25+ injection claims were analyzed as a separate maintenance cohort. Patients were assessed for demographic characteristics, comorbid conditions, and health care utilization. Results: A total of 2,334,530 AR patients were included; 103,207 had at least one AIT claim, with 45,279 (43.9%) of these patients reaching maintenance. Patients who reached AIT maintenance presented higher rates of baseline comorbidities than both the full AIT cohort and the patients with no AIT claims, including asthma (34.6% versus 30.1% versus 7.5%) and upper respiratory tract infections (63.1% versus 60.3% versus 34.2%). From baseline to follow-up, maintenance AIT patients demonstrated reductions in all AR-related comorbidities assessed, along with reductions in all-cause and AR-related service utilization. Conclusion: Patients initiating AIT presented the greatest need for therapeutic intervention, as evidenced by higher allergy-related comorbidities; those who reached maintenance demonstrated improved outcomes following the initiation of therapy. Continued efforts to increase patient awareness and adherence to AIT are needed.

National standards for asthma self-management education.

BACKGROUND: Asthma education reimbursement continues to be an issue in the United States. Among the greatest barriers is the lack of a standardized curriculum for asthma self-management education recognized by a physician society, non-physician health care professional society or association, or other appropriate source. The applicable Current Procedural Terminology codes for self-management education and training are 98960 through 98962, stating that "if a practitioner has created a training curriculum for educating patients on management of their medical condition, he or she may employ a non-physician health care professional to provide education using a standardized curriculum for patients with that disease." Without a standardized curriculum, reimbursement from payers is beyond reach. OBJECTIVE: Representatives from the Joint Council of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; American Academy of Allergy, Asthma, and Immunology; American Lung Association; American Thoracic Society; National Asthma Educator Certification Board; American College of Chest Physicians; and Association of Asthma Educators gathered to write a standardized curriculum as a guideline for payer reimbursement. METHODS: The Task Force began with a review of the American Lung Association and American Thoracic Society's Operational Standards for Asthma Education. Board members of the National Asthma Educator Certification Board incorporated comments, rationale, and references into the document. RESULTS: This document is the result of final reviews of the standards completed by the Task Force and national health care professional organizations in September 2014. CONCLUSION: This document meets the requirements of Current Procedural Terminology codes 98960 through 98962 and establishes the minimum standard for asthma self-management education when teaching patients or caregivers how to effectively manage asthma in conjunction with the professional health care team.

A Health-Related Quality of Life Measure for Older Adolescents With Asthma: Child Health Survey for Asthma-T (Teen Version).

BACKGROUND: Although adolescent substance use can have direct effects on asthma symptoms and interact with medications used to treat asthma, no validated health-related quality of life (HRQL) instrument exists for adolescents 17 to 19 years of age with asthma. PURPOSE: The American Academy of Pediatric's HRQL instrument, the Child Health Survey for Asthma (CHSA)-Child version, was modified with a substance use subscale to address outcomes specific to adolescents ages 17 to 19 years with asthma. METHODS: Two cohorts (N = 70) were recruited for instrument testing at pediatric primary care practices and two university clinics. A small methodological study with 24 adolescents was conducted to obtain initial support of the psychometric properties for the CHSA-Teen version at baseline, day 14, and day 16. A follow-up study included 46 teens to provide further support. RESULTS: The psychometric properties of the CHSA-Teen version were good and comparable with the CHSA-Child version for feasibility, reliability, and validity. CONCLUSIONS: Health care providers need to be aware of each adolescent's substance use to personalize counseling related to asthma medications.

The emerging role of Vitamin D in asthma management.

PURPOSE: Vitamin D deficiency and asthma share risk factors. Epidemiologists suggest that the U.S. prevalence of Vitamin D deficiency has increased as a result of the Westernization of culture and less time spent outdoors. Numerous studies support a patient's Vitamin D deficiency as a contributing cause to increased asthma symptoms, lower lung function levels, increased airway reactivity, and worsening asthma control. The purpose of the review article is to discuss the emerging role of Vitamin D in asthma management. DATA SOURCES: A review of original research identified through MEDLINE and CINAHL and published in English was performed. CONCLUSIONS: Research suggests promising benefits of Vitamin D supplementation in asthma patients with low (<30 ng/mL) Vitamin D levels. Evidence supports several possible mechanisms, including downregulation of allergen sensitivity and enhanced steroid responsiveness. Studies demonstrate that Vitamin D modifies airway hyperresponsiveness by minimizing airway inflammation. Ongoing studies seek to further evaluate the effects of Vitamin D supplementation on asthma and asthma morbidity. IMPLICATIONS FOR PRACTICE: While there is no consensus on the use of Vitamin D as a mainstay in asthma treatment, research supports its consideration for use in asthma patients with low Vitamin D levels. Current evidence reinforces the need to measure Vitamin D levels for all asthma patients.

Managing asthma during pregnancy.

PURPOSE: Pregnant women with asthma have many concerns about their respiratory health, as well as the health of their baby. A woman's respiratory system experiences many physiological changes during pregnancy and when a diagnosis of asthma is present, the clinical effect of pregnancy on asthma is variable. Regardless of disease years, when asthma patients become pregnant, both patients and healthcare providers want to know how pregnancy affects asthma and how asthma may affect pregnancy outcomes. This article will review how to optimally manage asthma during pregnancy using an evidence-based approach that recognizes the patient's changing needs. DATA SOURCES: Literature collected from sources identified through searches of PubMed and CINAHL covering the periods from 1996 to 2012. CONCLUSION: With the implementation of evidence-based management and treatment, pregnant patients who have asthma can be positioned to better control their symptoms and avoid unwanted complications that may affect the health of their baby. IMPLICATIONS FOR PRACTICE: Pregnant patients with asthma may be cared for in a variety of healthcare settings ranging from primary care to specialty care to the emergency department. Consequently, it is imperative that healthcare providers across the array of clinical venues be proficient on how to optimize the asthma outcomes of their pregnant patients.

National Asthma Education Prevention Program: survey of nurse practitioners' knowledge, attitudes, and behaviors.

INTRODUCTION: Much has been written regarding poor physician adherence to the National Asthma Education, Prevention Program (NAEPP) guidelines, but no data are available regarding nurse practitioners (NP) adherence. This descriptive study compared NP adherence to figures reported for medical doctors (MDs) in the 2001 and 2007 analyses by Cabana and colleagues. METHOD: A national, cross-sectional survey approach was used to assess NP knowledge, attitudes, and behaviors regarding the NAEPP guidelines. The survey was adapted from Cabana's 48-item questionnaire. RESULTS: NPs provided more prescriptions of inhaled corticosteroids (ICSs) to patients with daily symptoms than did physicians (NPs, 79%; MDs, 54%). Overall, compared with MDs, NPs reported higher adherence on three of the four NAEPP guideline components surveyed, two of which were statistically significant. DISCUSSION: This survey suggests that NPs have greater adherence to prescribing ICSs than do MDs. However, improved adherence still needs to be a goal for all providers because prescription of ICSs is the cornerstone of management of persistent asthma.

Update on asthma management in primary care.

Asthma, a chronic inflammatory lung disease, is one of the most common and costly diseases in the United States, affecting people of all ages and all ethnic groups. While there is no cure for asthma, optimal disease control and quality of life are possible with proper management and treatment.

Managing asthma in Black children.

Black children bear a disproportionate burden of asthma when compared to other segments of the population. This study assessed the role of symptom scores, spirometry testing, and serum-specific immunoglobulin E in the primary care management of asthma in Black children.

Helping patients attain and maintain asthma control: reviewing the role of the nurse practitioner.

Nurse practitioners (NPs) have a unique opportunity as frontline caregivers and patient educators to recognize, assess, and effectively treat the widespread problem of uncontrolled asthma. This review provides a perspective on the role of the NP in implementing the revised National Asthma Education and Prevention Program (NAEPP) Guidelines put forth by the National Heart, Lung, and Blood Institute, thereby helping patients achieve and maintain asthma control. A literature search of PubMed was performed using the terms asthma, nurse practitioner, asthma control, burden, impact, morbidity, mortality, productivity, quality of life, uncontrolled asthma, NAEPP guidelines, assessment, pharmacotherapy, safety. Despite the increased morbidity and mortality and impaired quality of life attributable to uncontrolled asthma, the 2007 NAEPP asthma guidelines are greatly underused. NPs have an opportunity to identify patients at risk and provide enhanced care and education for asthma control. Often, NPs can prescribe medication for and manage these patients, but it is necessary to be able to discern which patients require referral to a specialist.

Improving asthma care for African American children by increasing national asthma guideline adherence.

INTRODUCTION: Children, particularly African American children, bear a disproportionate burden of asthma and are at highest risk for associated morbidity and mortality. The under-utilization of the National Asthma Education and Prevention Program (NAEPP) guidelines across all demographics and the under use of inhaled corticosteroids (ICS) as controller therapy in these children are well-documented. The primary aim of this study was to increase health care provider (HCP) adherence to the NAEPP guidelines by means of a guideline reminder tool, the Multi-colored Simplified Asthma Guideline Reminder, consequently increasing the prescription of ICS in this population. METHOD: This study had a pre-experimental design with descriptive analysis. RESULTS: The Multi-colored Simplified Asthma Guideline Reminder was effective in increasing HCP adherence to the NAEPP guidelines as evidenced by increased use of ICS as controller therapy. DISCUSSION: Despite the increasing prevalence and burden of asthma in African American children, the associated prescriptive use of ICS has not increased substantially in the past decade. The greatest obstacle in the scope of improving asthma outcomes is the underuse of ICS by HCPs.

Profile of a primary care practice asthma program: improved patient outcomes in a high-risk population.

Asthma touches all of our lives. Asthma is a disease entity of huge proportions nationally and locally. It is the most common cause of school absences from a chronic disease and a common reason for parents and caregivers to miss work. The purpose of this article is to provide pediatric nurse practitioners with an understanding of the impact of asthma on children, their families, and on clinical practice. It will examine an asthma program created in a pediatric primary care setting to treat a high-risk population that proved very successful. The discussion of these issues incorporates results from a 2-year clinical project that focused on the reduction of asthma-related emergency department visits, asthma-related hospitalizations, and asthma-related missed school days.