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Purpose: Younger age of asthma onset (AAO) has been associated with an allergic phenotype, whereas eosinophilic phenotypes have been associated with older AAO. In randomized trials, biologic efficacy among adults with severe asthma (SA) has varied by age at asthma onset. To determine whether these associations observed in trials apply to real-world outcomes, this study examined biologic effectiveness by AAO and biologic class in a large, real-world cohort. Patients and methods: CHRONICLE is an ongoing, real-world study of US adults with subspecialist-treated SA receiving biologics, maintenance corticosteroids, or who are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled between February 2018 and February 2022 who initiated a biologic for SA and had complete data for analysis were included. A locally estimated scatterplot smoothing (LOESS) analysis was used to plot the relationship between percentage exacerbation rate reduction and AAO by biologic class. Results: Of 578 patients with complete data, 198, 149, and 231 were diagnosed with asthma at age < 18, 18– 39, and ≥ 40 years, respectively. Across subgroups, patients were predominantly White (72– 78%), female (67– 73%), and commercially insured (54– 71%). In the LOESS analysis, exacerbation rate reductions were similar for anti-IgE and anti–IL-5/5R and anti–IL-4R subgroups with younger AAO, but the exacerbation rate reduction diminished for patients with older AAO receiving anti-IgE therapy, particularly with asthma onset age ≥ 40 years. Conclusion: Clinicians should consider age of onset in biologic treatment decisions, given reduced effectiveness of omalizumab in patients with asthma onset at age ≥ 40 years. Clinicaltrials.gov Identifier: NCT03373045. [ABSTRACT FROM AUTHOR]

For patients with severe asthma (SA), overestimation of asthma control may lead to poorer outcomes. The objective of this study was to assess concurrent patient and specialist assessments of asthma control and treatment effectiveness among a large US cohort of SA patients. CHRONICLE is an ongoing observational study of patients with SA treated by US subspecialists. Asthma control was assessed using the patient-completed Asthma Control Test™ (ACT™) and specialist clinical assessment of control. Treatment effectiveness was measured using the Global Evaluation of Treatment Effectiveness (GETE) completed by patients and specialists. 1109 patients who completed online surveys at enrollment were included. 14%, 28%, 25%, and 33% of patients had ACT™ scores of 5–9, 10–15, 16–19, and 20–25, respectively. Compared with 67% of patients with uncontrolled asthma by ACT™, 44% were uncontrolled by specialist assessment. 54% of patients who were uncontrolled according to the ACT™ were rated as controlled by specialists, demonstrating overestimation of asthma control. Based on ACT™ score, asthma control was more frequent among patients treated with biologics compared to other treatments. Using the GETE, 90% of patients reported treatment effectiveness compared with 71% of specialists. Patient and specialist treatment effectiveness categorizations agreed 73% of the time. Specialists commonly overestimated asthma control relative to ACT™ scores. Patients reported treatment effectiveness more frequently than specialists. These findings emphasize the importance of validated instruments to assess asthma control and reduce potential treatment gaps associated with patient-specialist discordance. ClinicalTrials.gov Identifier: NCT03373045. [ABSTRACT FROM AUTHOR]

An attempt was made to describe a case series of acute eosinophilic pneumonia (AEP), illustrating the clinical features of this syndrome, and reporting the results of an epidemiologic investigation among US military personnel deployed in or near Iraq. It was found that AEP occurred at an increased rate among this deployed military population and resulted in two deaths, thus patients can present with fulminant respiratory failure or have less-severe forms of the disease, both of which can mimic community-acquired pneumonia.

Allergic conjunctivitis (AC) affects an estimated 20% of the population in the Western world, with a large fraction suffering due to seasonal or perennial allergen exposures. Bepotastine besilate ophthalmic solution (BBOS) 1.5%, a dual-acting histamine (H1) receptor antagonist and mast cell stabilizer, is indicated for itching associated with AC. This study was designed to evaluate the efficacy and safety of BBOS 1.5% for reducing ocular itching associated with AC in subjects enrolled in a natural exposure trial. Eligible subjects in a multicenter, double-masked, randomized, parallel-group, placebo-controlled, natural exposure clinical trial were randomly assigned to either BBOS 1.5% or placebo eyedrops on a 1:1 basis and instilled 1 drop of the test agent into both eyes twice daily for 2 weeks. The mean change from baseline in instantaneous and reflective ocular itching scores at the end of 2 weeks of treatment were evaluated based on subject-assessed severity of instantaneous and reflective itching. Subject-reported adverse events (AEs) were also recorded for safety. Treatment with BBOS 1.5% significantly reduced instantaneous and reflective ocular itching scores from baseline compared with placebo over the 2-week study period (p = 0.007 and p = 0.005, respectively). BBOS 1.5% was well tolerated, and AEs were generally transient and mild. This clinical study indicates BBOS 1.5% effectively and safely treated ocular itching in a natural exposure allergy study and is a useful treatment option for the management of ocular itching associated with AC. (ClinicalTrials.gov identifier number: NCT01174823.) [ABSTRACT FROM AUTHOR]

Given the potential differences in performance of skin test devices, the purpose of this study was to prospectively assess the performance of two single-headed and two multiheaded devices for allergy skin testing in terms of wheal size, sensitivity, specificity, intradevice variability, and pain level. Two single-headed devices (Greer Pick, Duotip-Test) and two multiheaded devices (Multi-Test II, OMNI) were tested in 15 subjects in a prospective partially blind fashion looking at wheal reactions and pain using histamine and glycerol-saline on the arms and back. Differences among devices in wheal size and pain were noted. Sensitivity, specificity, and intradevice variability were calculated. Differences between corner and interior heads in multiheaded devices were analyzed. No significant differences were observed in wheal size between Greer Pick (7.1 ± 1.4 mm) and Duotip-Test (7.2 ± 1.6 mm). Multiheaded devices were significantly different in wheal size compared with each other and to the single-headed devices (Multi-Test II, 5.4 ± 1.7 mm; OMNI, 3.3 ± 1.2 mm). Single-headed devices were more sensitive (100% each, 95% CI of 92–100%) than the multiheaded devices. Multi-Test II was significantly more sensitive (83%, 95% CI of 78–87%) than OMNI (57%, 95% CI of 51–62%). There was significant intradevice variability for the multiheaded devices with corner heads being significantly more sensitive than interior heads. Specificities for all devices were equally good (≥97%). Pain was greater for multiheaded devices than single-headed devices but was generally mild. In conclusion, this study supports the idea that single-headed devices may be more sensitive and consistent than multiheaded devices. Multi-Test II is more sensitive than OMNI. In multiheaded devices, corner heads are more sensitive than interior heads. [ABSTRACT FROM AUTHOR]

A case of idiopathic chronic urticaria (CU) is described briefly. The clinical characteristics, pathogenesis, diagnosis, and management of this disease are discussed followed by clinical pearls and pitfalls for the practicing allergist as well as the immunologist. CU, defined as recurring attacks of hives lasting for >6 weeks, is a common disorder for which the cause is determined in <20% of patients. Although the pathogenesis of idiopathic CU is not certain, the immune dysregulation/ disruption causing autoimmunity is blamed. The diagnosis is based principally on the patient's history. Autologous serum skin test possibly should be performed in older children as a screening test for idiopathic autoimmune CU. This test shows the availability of serum IgG autoantibodies directed against the α-chain of FcεRI. However, basophil mediator release assay still is accepted as a gold standard. Treatment is aimed first at avoiding underlying causative factors. Medications varying from H1-antihistamines to plasmapheresis as well as immunosuppressive therapies should be considered depending on clinical improvement. Spontaneous resolution of the disease is probable also. [ABSTRACT FROM AUTHOR]

Allergy skin testing is the primary modality used in the diagnosis of allergic diseases and guides development of treatment and avoidance plans. The goal of the Allergist is to skin test the appropriate population with a device and technique that minimizes pain while maximizing sensitivity and specificity. The debate involving the use of intradermal versus skin-prick testing in the diagnosis of aeroallergy has been long lasting. Past and present medical literature will be reviewed, establishing the lack of diagnostic use of intradermal testing in the setting of aeroallergy. New skin devices continue to be developed with a trend toward production of multidevices. Performance characteristics of various skin test devices will be reviewed with an emphasis on sensitivity, specificity, and variability of skin-prick testing devices. Significant statistical differences exist between all devices tested and reported in the literature. Whether these statistical differences equate to clinical differences is not known. With this review the practicing allergist should carefully evaluate multiple different devices and choose a device that suits their practice needs. In addition, allergists must ensure that technicians are sufficiently trained on the correct use of their device and should conduct continuing education to ensure that proper skin testing techniques are being used in their practice. Finally, the use of skin testing in pediatrics will be reviewed with a focus on safety. Care should be taken when skin testing infants ≤6 months of age, especially in the setting of eczema and a family history of atopy. [ABSTRACT FROM AUTHOR]

A 34-year-old man with peripheral eosinophilia, chronic pruritus, and colonic eosinophilic infiltration is presented as a patient-oriented problem-solving case report to show the important aspects of differential and specific diagnosis, treatment, prognosis, and caveats in the approach to the workup of the patient with eosinophilia. Allergic rhinitis, asthma, atopy, and drug-induced eosinophilia should come to mind in the initial differential diagnosis of any patient with peripheral eosinophilia. Also included in the differential after allergic disease processes would be the general categories of infectious, neoplastic, and the various forms of organ-specific eosinophilic infiltration and idiopathic syndromes. The importance of ruling out infectious causes for eosinophilia is paramount, especially given the dangers of immunosuppressive treatments often used to treat other conditions associated with eosinophilia. [ABSTRACT FROM AUTHOR]

A case of interferon-gamma (IFN-γ)/interleukin-12 (IL-12) pathway defect is presented. Pathophysiology, clinical characteristics, diagnostic test, and case management are reviewed. Clinical Pearls and Pitfalls include: (1) A high probability of a defect in the IFN-γ/IL-12 cascade exists in patients with disseminated or recurrent infection due to poorly pathogenic mycobacteria or systemic infections caused by non-typhi Salmonella species that are persistent and recurrent despite antibiotic therapy. (2) Although less frequent, patients with impaired IFN-γ/IL-12 mediated immunity are more susceptible to cytomegalovirus, human herpesvirus 8, herpes simplex virus, Listeria monocytogenes, and Histoplasma capsulatum. [ABSTRACT FROM AUTHOR]

Epinephrine is the only definitive treatment of anaphylaxis, and recent evidence suggests that the intramuscular route has superior pharmacokinetics to subcutaneous administration. There is little data regarding what route is commonly used in clinical practice. The objective of this article is to determine the rate of epinephrine use in cases of anaphylaxis and route of administration utilized. A retrospective review was made of 220 medical records with the primary diagnosis of urticaria, angioedema, or anaphylaxis over a 28-month period at a military medical center Twenty-four cases of anaphylaxis identified in the records. Demographics, along with signs and symptoms of those experiencing anaphylaxis, were similar to other published reports. Epinephrine was given in only 50% of cases and largely by the subcutaneous route. No intramuscular epinephrine was administered. H1 blockers and steroids were the most commonly administered treatments. H2 blockers were given at the same rate as epinephrine. An autoinjector was prescribed in 29% of cases with instruction on its use documented in 13%. An allergy referral was made in 29% of cases. Greater educational efforts and collaboration are needed between the allergy community and other providers regarding the importance of administering epinephrine intramuscularly, prescribing autoinjectors, and referring to an allergist in cases of anaphylaxis. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Trial Registration Peanut allergy is a common, life‐threatening food allergy in children. We evaluated whether dupilumab, which blocks the activity of interleukin (IL)‐4/IL‐13, enhances the efficacy of oral immunotherapy (OIT) AR101 in pediatric patients with peanut allergy.A Phase II, multicenter, randomized, double‐blind study was conducted in the USA (NCT03682770) in pediatric patients (6–≤ 17 years old) with confirmed peanut allergy. Patients were randomized 2:1 to receive dupilumab + OIT or placebo + OIT during a 28–40‐week up‐dosing period. Patients in the dupilumab + OIT group were re‐randomized 1:1 and received dupilumab + OIT or placebo + OIT during 24‐week OIT maintenance, undergoing a 2044 mg (cumulative) of peanut protein double‐blind, placebo‐controlled food challenge (DBPCFC) following up‐dosing, maintenance, and at 12‐week post‐treatment follow‐up.The study enrolled 148 patients, 123 of whom were included in the modified full analysis set, with a mean age of 11.1 years. Dupilumab + OIT treatment (n = 84) led to a 20.2% increase (p < 0.05) in the number of patients who passed a DBPCFC to 2044 mg (cumulative) of peanut protein following the up‐dosing period versus placebo (OIT alone, n = 39). Following the OIT maintenance period, continuous dupilumab treatment improved the number of patients who passed a DBPCFC to 2044 mg (cumulative) of peanut protein versus patients continuously on OIT alone (16.6% difference [95% CI −9.7, 42.8], p = 0.2123). Safety was consistent with known dupilumab safety profile.Dupilumab provided a modest increase efficacy of OIT in children and adolescents with peanut allergy, though it did not provide protection against OIT‐related anaphylaxis.ClinicalTrials.gov identifier: NCT03793608 [ABSTRACT FROM AUTHOR]

A case of atrophic rhinitis complicated by nasal septum perforation is presented, followed by a discussion of the clinical characteristics, pathophysiology, diagnosis, and management of this disease process. Clinical pearls and pitfalls are emphasized for the use of the practicing allergist and fellow in-training. The diagnosis of atrophic rhinitis is guided by a careful clinical history and evaluation to exclude other possible etiologies for the patient's symptoms and physical findings. Because atrophic rhinitis is a poorly understood process, it is surrounded by considerable contention in the literature and its management is not well defined. Atrophic rhinitis often carries significant morbidity and is best addressed by a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

A case of pediatric peanut allergy is presented. Pathophysiology, clinical characteristics, diagnostic test, case management, and natural history are reviewed. Clinical Pearls and Pitfalls include: (1) About 20% of young infants will outgrow peanut allergy, especially if IgE levels measured by ImmunoC4P RAST are less than 5kU/L. (2) Cases of resensitization have been documented after negative peanut oral challenges. (3) Only a negative food challenge can provide convincing evidence that the patient has outgrown his or her peanut allergy. [ABSTRACT FROM AUTHOR]

A case of Oral Allergy syndrome or Pollen-Food Allergy Syndrome is briefly discussed. The clinical characteristics, diagnosis, pathogenesis, and management of this syndrome are discussed followed by clinical pearls and pitfalls for the practicing allergist Symptoms generally occur with the ingestion of raw fruits/vegetables and nuts; cooked foods are not a problem. Symptoms are caused by a heat-labile protein in fruits, vegetables, and nuts that cross-reacts with proteins in aeroallergens. Cross-reactive proteins share homologous epitopes, and several groups with similar homologous proteins have been identified; many of these groups are referred to as pathogenesis-related proteins. [ABSTRACT FROM AUTHOR]