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Background: Sublingual immunotherapy (SLIT) using food extracts is safe and effective in desensitizing patients with food allergy, yet not often used in clinical practice., Objectives: To propose a cost-effective, expedited SLIT protocol using real food., Methods: Patients with food allergy aged 5 to 50 years (median, 11 years) initiated food SLIT in a single-clinic setting. The daily maintenance dose was 4 to 11 mg protein in 0.1 to 0.5 mL volume, depending on the food. Some foods were available in liquid form at the local grocery (milk, egg white liquid, and cashew/walnut/sunflower/hazelnut milk), whereas others were prepared in the office using flour and 50% glycerin saline (peanut/sesame/wheat). The first cohort of 20 patients began dosing at a 1:1000 dilution, the next 30 patients at 1:100 dilution. An exercise challenge was performed in a subset of patients on maintenance dosing to evaluate the need for a predose or postdose rest period., Results: The 1:1000 and 1:100 cohorts both completed day 1 without adverse reactions beyond itchy mouth. There were no systemic reactions requiring epinephrine throughout the study period and 88% reached their maintenance dose. Skin testing of 6-month-old peanut flour solution was not diminished from fresh solution and similar to food extract. Exercise challenge test results in 12 patients were negative., Conclusions: Allergen extract food SLIT as used in published trials has limitations of cost and multiple office visits. Inexpensive real food, at the same or slightly higher protein dose, was well tolerated in 4 updose visits, a minimum of a week apart. Unlike food oral immunotherapy, a predose or postdose rest period may not be necessary., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process., Objective: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form., Methods: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed., Results: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form., Conclusion: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Approximately one-third of patients who present for oral immunotherapy (OIT) will be allergic to more than one food. Those patients with more than one food allergy have the option of sequential courses of single-food OIT or, in the right situation, combining several foods as part of multifood OIT. The time and cost savings can be substantial. Treatment protocols used with multiple foods are basically the same as with single-food courses, so clinics proficient with single-food OIT can easily transition to multifood OIT. Outcomes have been shown to be similar between the two approaches, so patients should be offered the opportunity to address their food allergies in one, more convenient OIT course., (Copyright © 2022, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Oral immunotherapy (OIT) provides an active treatment option for patients with food allergies. OIT may improve quality of life and raise the threshold at which a patient with food allergy may react to an allergen, but it is a rigorous therapy that requires a high degree of commitment by the clinician, patients, and families. Recent guidelines from the Canadian Society for Allergy and Clinical Immunology have provided a framework for the ethical, evidence-based, and patient-oriented clinical practice of OIT, and the European Academy of Allergy, Asthma, and Immunology guidelines have also recommended that OIT can be used as a potential treatment. The recent Food and Drug Administration approval of an OIT pharmaceutical has accelerated the adoption of OIT. This review provides a summary of the recent Canadian Society for Allergy and Clinical Immunology guidelines and a consensus of practical experience of clinicians across the United States and Canada related to patient selection, office and staff preparation, the general OIT process, OIT-related reaction management, and treatment outcomes., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions., Methods: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms., Results: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older., Conclusions: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

Objectives: Specific recommendations for administering the influenza vaccine to patients with egg allergy are based on limited scientific data. The objectives of this investigation were to determine the safety of a 2-dose administration of an influenza vaccine to patients with egg allergy and to evaluate the usefulness of skin testing with the influenza vaccine before administration., Study Design: In this multicenter clinical trial, clinical histories of egg allergy were confirmed by skin testing with egg and, if possible, by oral challenges with egg. Subjects with egg allergy received the vaccine in 2 doses, 30 minutes apart; the first dose was one tenth and the second dose nine tenths of the recommended dose as determined by age. Subjects without egg allergy were recruited as control subjects and received 1 age-determined dose of the vaccine. Skin prick tests with the influenza vaccine were performed on all subjects., Results: From 1994 to 1997, 83 subjects with egg allergy and 124 control subjects were evaluated. The content of ovalbumin/ovomucoid was 0.1, 1.2, and 0.02 micrograms/mL, respectively in the 1994-95, 1995-96, and 1996-97 influenza vaccines. Results of vaccine skin prick tests were positive in 4 subjects with egg allergy and in 1 control subject. All patients with egg allergy tolerated the vaccination protocol without any significant allergic reactions., Conclusions: These results demonstrate that patients with egg allergy, even those with significant allergic reactions after egg ingestion, can safely receive an influenza vaccine in a 2-dose protocol when the vaccine preparation contains no more than 1.2 micrograms/mL egg protein.

Purpose: To determine the patterns of chronic outpatient management in urban patients with moderate and severe asthma, and to assess medical practice adherence to the Guidelines for the Diagnosis and Management of Asthma from the National Asthma Education Program (NAEP)., Patients and Methods: This is a cross-sectional survey of adult patients with asthma admitted to the general medical services at the Johns Hopkins Medical Institutes (Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center) Baltimore, Maryland. Subjects were 101 adults admitted with an asthma exacerbation from February 1992 through January 1993. Using a validated questionnaire, these subjects were surveyed within 48 hours of admission concerning their chronic outpatient medical management and the measures patients or their physicians took to alleviate symptoms during the asthma exacerbation leading to hospitalization., Results: The average asthma admission rate in the past year for this group of patients was 2.5, indicative of moderate to severe disease. Less than half of these patients had been prescribed inhaled anti-inflammatory therapy. Of the patients who had previously been shown the metered dose inhaler technique by a health care professional, 11% could perform all components of this technique correctly. Only 28% of patients had been given an action plan by their physician in the event of an acute exacerbation. Sixty percent of patients who contacted their physician during the exacerbation that preceded admission had no changes made in their treatment regimen. In those whose exacerbation lasted at least 24 hours, the average beta-agonist metered dose inhaler use during the 24 hour prior to admission was 44.8 +/- 7.8 puffs (mean +/- standard error of the mean). Older age, (current smoking, and race (black) were the most significant correlates of inhaled beta-agonist use during this period., Conclusions: This is the first documentation of multiple problems in conforming with the standards of care delineated by the NAEP as they relate to the outpatient management of inner-city patients with moderate to severe asthma in the United States. In this population of patients with asthma, management was characterized by underutilization of anti-inflammatory therapy, inability to use inhalation devices properly, inadequate communication between patient and physician of an action plan to be utilized in the event of an acute exacerbation and inadequate physician intervention during the acute stages of the exacerbation. There was also overutilization of inhaled beta-agonists during exacerbations. It is imperative that these aspects of management, for which the NAEP has set standards of care, are addressed as part of the effort to reduce asthma morbidity in the urban United States.

To investigate the pathogenic role of cell-mediated immunity (CMI) in acute severe asthma, 10 patients with acute asthma requiring admission to hospital had measurements of serum and urine absolute neopterin and neopterin/creatinine ratios. Serum was collected upon entry to hospital, 24 hr later and at 2 weeks; and urine at 24 hr and at 2 weeks after admission. Comparisons were made with 12 stable asthmatic patients, healthy control subjects, and six renal transplant patients undergoing transplant rejection. In contrast to the renal transplant patients who demonstrated T-lymphocyte-macrophage activation, neopterin concentrations and neopterin/creatinine ratios in both acute and stable asthmatic patients were not elevated. We have not found functional evidence that CMI participates in the pathogenesis of acute severe asthma.

In order to investigate the pharmacodynamic selectivity of a number of beta-receptor agonists currently used in asthma, we compared the pulmonary and extrapulmonary effects of repeated inhalations of epinephrine, fenoterol, isoproterenol, and metaproterenol in 12 patients with asthma in a randomized double-blind crossover study. The drugs were administered from metered-dose inhalers at 15-min intervals for five doses (total dose, 10 puffs of each compound). Measurements of heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval, plasma potassium, and FEV1 were made 5 min after each dose and 30 min after the final dose. Fenoterol and metaproterenol had significantly greater inotropic, electrocardiographic, chronotropic, and hypokalemic effects than did both isoproterenol and epinephrine. There was no difference in the bronchodilating effect of metaproterenol, fenoterol, or isoproterenol although these agents caused a significantly greater increase in FEV1 than did epinephrine. The concept of increasing beta-2 selectivity for metaproterenol and fenoterol compared with isoproterenol are not supported in the clinical setting.

The cardiovascular, respiratory, and hypokalemic effects of repeated inhalation of fenoterol, albuterol, and isoproterenol were compared in 12 subjects with stable asthma according to a double-blind, crossover design. Ipratropium bromide served as a control providing bronchodilatation without extrapulmonary effects. Subjects inhaled the beta-agonists on an equal-weight basis (400 micrograms) at 0, 30, 40, and 45 minutes. Measurements of heart rate, blood pressure, total electromechanical systole (measure of inotropic activity), preejection period, QTc interval, plasma potassium levels, and forced expiratory volume in 1 second were made 5 minutes after each dose and again at 60 and 75 minutes. There were no differences in the bronchodilating effect between the beta-agonists. However, both fenoterol and isoproterenol resulted in greater positive inotropic stimulation than did albuterol, and fenoterol caused a greater fall in plasma potassium levels than did the other beta-agonists.

Interviews were conducted with 101 consecutive adult patients admitted to Wellington Hospital with a diagnosis of asthma to assess the extent to which beta agonist drugs are self-administered by asthmatic patients during severe asthma. The 99 patients prescribed an inhaled beta agonist were subdivided into two groups: group A comprising 79 patients prescribed a beta agonist for inhalation via an inhaler (metered dose aerosol or dry powder device) alone; group B comprising 20 patients prescribed beta agonist for inhalation via both an inhaler and nebuliser. In group A, the attacks of asthma lasted greater than 24 hours in 64/79 patients, and 22% of these patients reported taking more than 60 doses of their inhaler, and 52% more than 30 doses during the 24 hr period prior to admission. In group B, the attacks of asthma lasted greater than 24 h in 17/20 patients, and 35% of these patients self-administered their nebuliser more than six times, and 76% more than four times during the 24 h period prior to admission. In addition to their nebuliser use, these patients also took a median 23 doses of their inhaler during this 24 h period. This use of inhaled beta agonist contrasts with the recommended practice in both the USA and Europe, where most physicians recommend no more than 15 doses of a beta agonist as the maximal dose per day. We conclude that asthmatic patients in New Zealand self-administer high doses of inhaled beta 2 agonist drugs during severe exacerbations of asthma.

A young man with focal glomerulosclerosis and severe steroid resistant nephrotic syndrome was treated with oral cyclosporin for six months without histological evidence of drug induced nephrotoxicity. A marked and sustained partial remission of the degree of proteinuria one year following cessation of treatment was not accompanied by a deterioration in renal function. Cyclosporin may have a role, as yet not fully defined, in the treatment of steroid-resistant or dependent nephrotic syndrome.