Sublingual grass and ragweed immunotherapy: Clinical considerations-a PRACTALL consensus report.

Sublingual allergen immunotherapy provides a new option for patients with allergic rhinitis in the United States. The efficacy of these sublingual immunotherapy tablets in the treatment of allergic rhinitis has been firmly established in large multicenter clinical trials. In addition, the clinical benefits of sublingual immunotherapy might persist after treatment is discontinued. Local reactions, such as gastrointestinal or oropharyngeal symptoms, are common. However, severe anaphylaxis is rare, and therefore the immunotherapy tablets can be administered at home. Sublingual immunotherapy for allergic rhinitis has been used successfully for years in Europe, and these products might be appropriate for patients who do not do well with standard drug therapy or for those who prefer a disease-modifying approach.

Appropriateness of epinephrine use in ED patients with anaphylaxis.

BACKGROUND: Studies have demonstrated low rates of emergency department (ED) epinephrine administration for anaphylaxis patients, suggestive of ED undertreatment of anaphylaxis. Our study assessed the appropriateness of ED epinephrine administration in anaphylaxis management. METHODS: A prospective observational study was conducted involving ED patients presenting with possible allergic reactions. Patients and ED providers completed questionnaires regarding the suspected trigger, signs and symptoms, and prehospital treatment. Two board-certified allergists-immunologists independently reviewed the questionnaires, as well as electronic health records, to determine whether the cases represented anaphylaxis and whether ED epinephrine administration was appropriate. RESULTS: Among 174 patients enrolled in the study, 61 (35%) were confirmed to have anaphylaxis. Overall, 47 anaphylaxis patients (77%) received epinephrine either before ED arrival or in the ED. In the latter situation, 24 anaphylaxis patients (39%) received epinephrine and 37 (61%) did not. Of the patients who received ED epinephrine, the allergists-immunologists determined that its administration was appropriate in all cases (95% confidence interval [CI], 83%-100%). Among the 37 patients who did not receive ED epinephrine, the allergists-immunologists determined that nonadministration of epinephrine was appropriate in 36 patients (97%; 95% CI, 84%-100%). The allergists-immunologists determined that overall, ED management was appropriate for 60 (98%) of 61 patients with anaphylaxis (95% CI, 90%-100%). CONCLUSIONS: Although more than 60% of anaphylaxis patients did not receive epinephrine in the ED, the allergists-immunologists deemed ED management appropriate in 98% of total cases. Previous retrospective studies may underestimate the appropriateness of ED anaphylaxis management, particularly when prehospital epinephrine administration is not reported.

Burden of chronic obstructive pulmonary disease: healthcare costs and beyond.

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating respiratory condition that leads to significant burden, both medically and financially. It affects millions of people worldwide and causes significant morbidity and mortality. Most detailed information related to its prevalence, morbidity, and mortality comes from high-income countries, but 90% of COPD-related deaths occur in low- and middle-income countries. Cigarette smoking is the main risk factor for developing COPD, but other risk factors do exist and need to be recognized. A majority of morbidity and mortality as well as health care costs occur from acute exacerbations of COPD with a known phenotype of patients being "frequent exacerbators." Health care costs for COPD are not only from treatment of exacerbations, such as hospitalization, but also medication costs for maintenance therapy and outpatient treatment. COPD has been linked with many comorbidities leading to significant burden of disease. The goal of this review is to evaluate the overall burden of disease including prevalence, morbidity, mortality, health care costs, and economic costs.

Stepping down from inhaled corticosteroids with leukotriene inhibitors in asthma: a systematic review and meta-analysis.

BACKGROUND: The risks of using leukotriene receptor antagonists (LTRA) as part of a strategy for stepping down inhaled corticosteroid (ICS) are not well known. OBJECTIVE: To estimate the risk of asthma exacerbation in individuals with stable asthma who start LTRA when stopping ICS or reducing ICS dose. METHODS: We identified articles from a systematic review of English and non-English articles by using a number of data bases. We included randomized controlled trials with a stable asthma run-in period of 4 weeks or more and a follow-up period of at least 3 months. We included studies of individuals with stable asthma who stopped ICS and substituted LTRA (versus continuing ICS) and who reduced ICS while starting LTRA (versus placebo). RESULTS: The search strategy identified 1132 potential articles, of which 52 were reviewed at the full-text level, and four met criteria for inclusion. The single article that met the inclusion criteria for substitution of LTRA for ICS as a step-down strategy found a statistically increased risk of treatment failure of 30.3% for substituting LTRA compared with 20.2% for continuing ICS. The three articles that met the inclusion criteria for comparing LTRA versus placebo in patients with stable asthma who reduce ICS found a modestly decreased risk ratio that favored LTRA of 0.57 (95% confidence interval, 0.36-0.90; I(2) = 0%) in studies that only included individuals >15 years old. CONCLUSION: Only one study addressed the risk of substitution of LTRA for ICS in stable asthma, which limited any strong conclusions about this step-down strategy.

Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis.

BACKGROUND: Risk factors for increased anaphylaxis severity are poorly understood. Angiotensin-converting enzyme (ACE) inhibitors have been associated with severe anaphylactic reactions in patients with hymenoptera venom allergy. Studies evaluating the association between beta-blockers and severe anaphylaxis have been conflicting. OBJECTIVE: To evaluate the association between antihypertensive medication use and increased anaphylaxis severity. METHODS: We included emergency department anaphylaxis patients aged 18 years and older. Markers of severe anaphylaxis were defined as (1) syncope, hypotension, or hypoxia; (2) signs and symptoms involving 3 or more organ systems; and (3) hospitalization. Antihypertensive medications evaluated included beta-blockers, ACE inhibitors, calcium channel blockers, angiotensin receptor blockers, and diuretics. Simple and multiple logistic regression analyses were conducted to estimate the association between antihypertensive medication use and markers of increased anaphylaxis severity. RESULTS: Among 302 patients with anaphylaxis, 55 (18%) had syncope, hypoxia, or hypotension, 57 (19%) required hospitalization, and 139 (46%) had 3 or more organ system involvement. After adjusting for age, gender, suspected trigger, and preexisting lung disease, beta-blocker, ACE-inhibitor, diuretic, or antihypertensive medication use in aggregate remained associated with both 3 or more organ system involvement and need for hospital admission. The adjusted associations between antihypertensive medication use in aggregate and 3 or more organ system involvement yielded an odds ratio of 2.8 (95% CI, 1.5-5.2; P=.0008) and with hospitalization an odds ratio of 4.0 (95% CI, 1.9-8.4; P=.0001). CONCLUSIONS: In emergency department anaphylaxis patients, antihypertensive medication use is associated with increased organ system involvement and increased odds of hospital admission, independent of age, gender, suspected trigger, or preexisting lung disease.

Exercise-induced bronchoconstriction.

OBJECTIVE: To review the literature regarding the pathophysiology of exercise-induced bronchoconstriction (EIB). DATA SOURCES: The databases of PubMed, Ovid MEDLINE, and Scopus were searched for articles using the subject headings and/or keywords asthma, exercise-induced/etiology, exercise, mechanism, pathogenesis, and bronchoconstriction. STUDY SELECTIONS: Articles were selected based on their relevance to the focus of this review, with emphasis on the specific pathophysiologic mechanisms of EIB. RESULTS: EIB occurs in response to the loss of water from the lower airways that results from heating and humidifying large volumes of air in a short period. The resulting hyperosmolar environment activates various cellular mechanisms to release mediators from mast cells, eosinophils, epithelial cells, and sensory nerves. These mediators, in turn, lead to airway smooth muscle contraction and bronchoconstriction. Airway hyperresponsiveness in elite athletes may develop from a process of airway injury and changes in the contractile properties of airway smooth muscle. CONCLUSION: EIB commonly affects individuals with and without clinically recognized asthma, especially those who participate in competitive athletics. Through years of research, the pathophysiology of EIB is now better understood and involves a complex interaction between several different cell types and mediators. Continued research to improve the knowledge regarding the mechanisms of EIB should aid the identification, diagnosis, and treatment of this common condition.

Anaphylaxis: diagnostic criteria and epidemiology.

Evaluation of anaphylaxis is a common reason for emergency department referral to an allergist. Establishing unified diagnostic criteria has been an evolving process with the most recent definition proposed by the Second Symposium on the Definition and Management of Anaphylaxis convened by the National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network. Proper identification of these patients in the emergency department allows for the opportunity to dispense potentially life-saving epinephrine autoinjectors, provide education, and allergist referral. Future epidemiological studies are likely to be impacted as the definition of anaphylaxis becomes more unified.

Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients.

BACKGROUND: Diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis convened by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN). Validation is needed before these criteria can be widely adapted into clinical practice. OBJECTIVE: Our aim was to retrospectively assess the diagnostic accuracy of the NIAID/FAAN criteria for the diagnosis of anaphylaxis in emergency department (ED) patients. METHODS: A retrospective cohort study of ED patients presenting from April to October 2008 was conducted. Patients given a diagnosis of an allergic reaction or anaphylaxis and a subset of patients with related diagnoses were included. Electronic medical records were reviewed and data were abstracted to determine whether the NIAID/FAAN criteria were met. Records were also independently reviewed in a blinded fashion by 2 experienced attending allergists. Final diagnosis by allergists was considered the reference standard. RESULTS: Of 214 patients, 86 (40.2%) met the NIAID/FAAN criteria for anaphylaxis. Allergists gave 61 (28.5%) patients diagnoses of anaphylaxis, 59 (96.7%) of whom satisfied the NIAID/FAAN criteria. The interrater agreement between allergists was substantial (κ = 0.77). The test characteristics of the NIAID/FAAN criteria were as follows: sensitivity, 96.7% (95% CI, 88.8% to 99.1%); specificity, 82.4% (95% CI, 75.5% to 87.6%); positive predictive value, 68.6% (95% CI, 58.2% to 77.4%); negative predictive value, 98.4% (95% CI, 94.5% to 99.6%); positive likelihood ratio, 5.48; and negative likelihood ratio, 0.04. CONCLUSIONS: These results suggest that the NIAID/FAAN criteria are highly sensitive but less specific and are likely to be useful in the ED for the diagnosis of anaphylaxis.

Risks and safety of biologics: A practical guide for allergists.

Biologic agents are a rapidly expanding class of medications, and several options are now available for the management of allergic and immunologic disorders. The risks of biologic therapy need to be understood in order to adequately counsel patients and appropriately monitor for potential adverse events. We sought to provide a comprehensive review of the risks and adverse effects reported for the current FDA-approved biologics used in management of allergic and immunologic disorders, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab and tralokinumab. Our review focuses on the risk of hypersensitivity reactions, pregnancy-specific considerations, risk of infection and risk of malignancy. We also highlight drug-specific adverse events and unique safety issues identified in case reports.

Development of a machine learning algorithm based on administrative claims data for identification of ED anaphylaxis patient visits.

Background: Epidemiologic studies of anaphylaxis commonly rely on International Classification of Diseases (ICD) codes to identify anaphylaxis cases, which may lead to suboptimal epidemiologic classification. Objective: We sought to develop and assess the accuracy of a machine learning algorithm using ICD codes and other administrative data compared with ICD code-only algorithms to identify emergency department (ED) anaphylaxis visits. Methods: We conducted a retrospective review of ED visits from January 2013 to September 2017. Potential ED anaphylaxis visits were identified using 3 methods: anaphylaxis ICD diagnostic codes (method 1), ICD symptom-based codes with or without a code indicating an allergic trigger (method 2), and ICD codes indicating a potential allergic reaction only (method 3). A machine learning algorithm was developed from administrative data, and test characteristics were compared with ICD code-only algorithms. Results: A total of 699 of 2191 (31.9%) potential ED anaphylaxis visits were classified as anaphylaxis. The sensitivity and specificity of method 1 were 49.1% and 87.5%, respectively. Method 1 used in combination with method 2 resulted in a sensitivity of 53.9% and a specificity of 68.7%. Method 1 used in combination with method 3 resulted in a sensitivity of 98.4% and a specificity of 15.1%. The sensitivity and specificity of the machine learning algorithm were 87.3% and 79.1%, respectively. Conclusions: ICD coding alone demonstrated poor sensitivity in identifying cases of anaphylaxis, with venom-related anaphylaxis missing 96% of cases. The machine learning algorithm resulted in a better balance of sensitivity and specificity and improves upon previous strategies to identify ED anaphylaxis visits.

Effectiveness of trivalent inactivated influenza vaccine in influenza-related hospitalization in children: a case-control study.

Influenza is known to be associated with asthma exacerbation but the effectiveness of the trivalent inactivated flu vaccine (TIV) in children, especially children with asthma, in preventing hospitalization is unknown. We assessed the effectiveness of the TIV in all children and especially children with asthma to prevent hospitalization with influenza. We conducted a nested case control study of all pediatric subjects (6 months to 18 years old) who were evaluated at the Mayo Clinic, Rochester, MN, who had laboratory-confirmed influenza during each flu season from 1999 to 2006 to evaluate the efficacy of TIV in preventing hospitalization. A case-control analysis was performed with the cases and the controls being the subjects who did and did not required hospitalization with the influenza illness, respectively. There were 261 subjects with laboratory-confirmed influenza from 1996 to 2006. There was an overall trend toward higher rates of hospitalization in subjects who got the TIV when compared with the ones who did not get the TIV (odds ratio [OR], 3.67; CI, 1.6, 8.4). Using the Cochran-Mantel-Haenszel test for asthma status stratification, there was a significant association between hospitalization in asthmatic subjects and TIV (p = 0.001). TIV did not provide any protection against hospitalization in pediatric subjects, especially children with asthma. On the contrary, we found a threefold increased risk of hospitalization in subjects who did get the TIV vaccine. This may be a reflection not only of vaccine effectiveness but also the population of children who are more likely to get the vaccine.

Anaphylaxis: Epidemiology and Differential Diagnosis.

Anaphylaxis-related emergency department (ED) visits and hospitalizations are increasing. Triggers for anaphylaxis include food, medications, and stinging insects. Idiopathic anaphylaxis accounts for 30% to 60% of cases of anaphylaxis in adults and up to 10% of cases in children with novel allergens such as galactose-α-1,3 galactose reclassifying these cases. Recent practice guidelines have recommended against the routine use of systemic corticosteroids and antihistamines for the prevention of biphasic reactions and recommend an extended observation, up to 6 hours, for those with risk factors for biphasic anaphylaxis and those with lack of access to epinephrine and to emergency medical services.

Elevating Health Disparities Education Among Trainees and Physicians.

Health disparities disproportionately affect patients in racial and ethnic minority groups, and these disparities are linked to economic, environmental, and social disadvantage. It is widely known that health disparities impact patients with allergic and immunologic conditions, yet universal and comprehensive training in health disparities is lacking. More robust educational opportunities are needed to fully equip trainees with tools to recognize and develop effective strategies to reduce the burden of health disparities. Also, there are no universal standards or requirements for professional medical boards in their respective maintenance of certification programs that will ensure ongoing training for practicing providers that will help them identify and manage individual or societal issues such as social determinants that contribute to health disparities. Further, the long-term impact of systematic discrimination, implicit and overt bias, and medical mistrust among populations most often affected by disparities compounds the complexity of the methods and types of training that is desperately needed to overcome health disparities. We provide a commentary on important topics that should be addressed during allergy and immunology training and beyond. We further highlight strategies and tools that should be used to tackle this important issue affecting millions of patients under our specialty care. It is past time for us to go beyond the bedside and comprehensively integrate health disparities training in our fellowship programs and in our practices.

Current and emerging biologic therapies targeting eosinophilic disorders.

Eosinophilic disorders include a wide array of conditions in which eosinophils play a primary pathophysiologic role. While historically treated with corticosteroids and immunosuppressants, knowledge of eosinophil biology has led to the development of several biologics targeting eosinophils. In this review, we discuss the current US Food and Drug Administration (FDA) approved eosinophil-specific biologics targeting IL-5 (mepolizumab and reslizumab) and IL-5R (benralizumab) along with biologics under investigation targeting siglec-8 (lirentelimab). We discuss efficacy and safety data from trials of these medications in conditions including eosinophilic asthma, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), and eosinophilic gastrointestinal disease (EGID). Additionally, we discuss case reports utilizing these medications in conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic pneumonia, among others. While eosinophilic targeting biologic therapy has been successful in eosinophilic asthma, HES, EGPA, and CRSwNP leading to FDA approval for these conditions, trials treating EoE and EGID have been disappointing to date. Given the increasing number of trials utilizing these biologics, it will be imperative for the allergist-immunologist to stay up to date on the latest treatment options to provide the most optimal care for eosinophilic disorders.

Collaboration between allergists and pharmacists increases ß-lactam antibiotic prescriptions in patients with a history of penicillin allergy.

BACKGROUND: Over 90% of patients with a history of penicillin allergy have negative penicillin skin tests. Pharmacists are trained to identify and resolve medication-related problems. We hypothesized that collaboration between allergists and pharmacists to identify and evaluate patients with a history of penicillin allergy would increase ß-lactam antibiotic prescription. METHODS: We conducted a prospective observational study in which patients with a history of penicillin allergy were identified and educated at the pharmacy about penicillin allergy and offered an allergist consultation with a penicillin skin test. All patients were followed up to determine which antibiotics were subsequently prescribed. RESULTS: A total of 503 patients were enrolled, and 71 (14%) were evaluated by an allergist. Sixty-seven of these 71 patients (94%) had a negative penicillin skin test. Twenty-nine patients evaluated by an allergist and 205 patients not evaluated were prescribed antibiotics. Patients prescribed antibiotics and evaluated by an allergist were compared to those not evaluated by an allergist, with the following results: 19 of 29 patients (66%) were prescribed a ß-lactam antibiotic compared to 54 of 205 (26%; p < 0.0001); 8 of 29 patients (28%) were prescribed penicillin compared to 7 of 205 (3%; p < 0.0001); 15 of 29 patients (52%) were prescribed a cephalosporin compared to 48 of 205 (23%; p < 0.01), and 10 of 29 patients (34%) were prescribed a non-ß-lactam antibiotic compared with 177 of 205 (86%; p < 0.0001). CONCLUSION: A collaborative effort between allergists and pharmacists can increase ß-lactam antibiotic prescriptions and decrease non-ß-lactam prescriptions in patients with a history of penicillin allergy.

Prescriptions for self-injectable epinephrine in emergency department angioedema management.

BACKGROUND: Angioedema is often treated in the emergency department (ED). Few studies have evaluated self-injectable epinephrine (SIE) prescribing patterns for angioedema. OBJECTIVES: To describe presentation and management of ED patients with angioedema and determine factors associated with epinephrine administration, hospital admission and SIE prescription. METHODS: We conducted a retrospective cohort study of all ED patients with angioedema between January 2005 and December 2006. RESULTS: Of 63 patients, 39 (61.9%) were female. Median age was 49 years. Precipitating factors were identified in 36 (57.1%) patients. History of other allergic conditions was seen in 37 (58.7%) patients. Seventeen (27.0%) patients received epinephrine, 55 (87.3%) received antihistamines, and 51 (81.0%) received steroids. Epinephrine was administered more commonly in patients with edema of the tongue (risk ratio [RR], 5.28, 95% confidence interval [CI] 1.95-14.33, P = .0003), tightness/fullness of throat (RR, 3.31, 95% CI 1.62-6.76, P = .006), and dyspnea/wheeze (RR, 3.04, 95% CI 1.41-6.59, P = .005). Hospitalization was more common in patients with dyspnea/wheeze (P = .028) and allergic history (P = .006). Thirteen patients (22.0%) were discharged with SIE. An SIE prescription was associated with younger patients (median age, 26 years [interquartile range (IQR) 15-50] vs a median age 57.5 years [IQR 43-68], P = .004) and patients with throat tightness/fullness (RR, 4.2, 95% CI 1.8-9.8, P = .005). CONCLUSION: Patients with respiratory symptoms and allergic history were likely to be admitted. Epinephrine use was more frequent in patients with signs and symptoms of oropharyngeal edema. Younger patients and those with tightness/fullness of throat were likely to be prescribed SIE. Further studies are needed to determine who would benefit from epinephrine use and SIE prescription.