Patient-Reported Outcomes in Asthma.

The FDA's Center for Drug Evaluation and Research defines patient-reported outcomes (PROs) as "any report of the status of a patient's health condition, health behavior, or experience with healthcare that comes directly form the patient, without interpretation of the patient's response by a clinician or anyone else". Validated PRO measures are used extensively in pediatric and adult asthma across clinical and research settings to assess the impact of treatments on patient outcomes over time. This work aims to review some of the most commonly used asthma PROs across the following criteria: validity, reliability, responsiveness, time to complete, ease of administration, target population, recall period, scoring method, availability in different languages, use in clinical practice or research settings, licensing requirements, and cost of use.

Digital inhalers for asthma management.

PURPOSE OF REVIEW: Although digital inhaler systems for asthma management have been commercially available for over a decade, their current use in clinical practice is limited. This review outlines barriers and offers potential solutions to their implementation. RECENT FINDINGS: Digital inhaler systems demonstrate increased controller medication adherence, decreased quick-relief medication use, and improved asthma control. SUMMARY: Use of digital inhaler systems is supported by data from large clinical trials demonstrating improved asthma outcomes. Navigating telemedicine during the coronavirus disease 2019 pandemic has led to advances clearing the path for increased adoption of digital inhaler systems. Progress in areas including patient education and onboarding, clinical management, coding and billing, privacy and security have facilitated implementation in clinical practice.

Social Determinants of Health and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected disadvantaged populations. Many of the factors related to the disproportionate impact on underserved communities are related to social determinants of health, defined by the World Health Organization as the nonmedical factors that influence health outcomes. They include the wider set of forces and systems shaping the conditions of daily life. This work explores the interrelationships between social determinants of health and access to care, health care professional and supply shortages, social and environmental factors, health behaviors, vaccine uptake, and treatment options on COVID-19 health outcomes. Increased awareness of inequities, learning from failures, and leveraging new opportunities to partner with key stakeholders in underserved communities create empowerment and preparedness to face new challenges.

Towards an FDA-cleared basophil activation test.

Food allergy is a global health problem affecting up to 10% of the world population. Accurate diagnosis of food allergies, however, is still a major challenge in medical offices and for patients seeking alternative avenues of diagnosis. A flawless test to confirm or rule out a food allergy does not exist. The lack of optimum testing methods to establish precise clinical correlations remains a major obstacle to effective treatment. Certain IgE measurement methods, including component testing, have received FDA clearance, but they have been used primarily as an analytical tool and not to establish clinical correlations. Most allergy tests are still carried out within the laboratory, and skin tests outside a laboratory setting that are used for food allergy diagnosis rely on non-standardized allergens, according to the FDA definition. Epitope mapping and basophil activation test (BAT) have recently been proposed as a means of establishing better clinical correlations. Yet neither have received FDA clearance for widespread distribution. Of the two methods, the BAT has the advantage of being a functional assay. Over the past few years, several large private practice groups in the United States, have developed BAT as a clinical assay and have started using it in patient care. Given this clinical experience, the vast number of papers published on BAT (more than 1,400 as of 2022) and the trend toward increasing FDA regulation, it is essential to understand the roadmap for regulatory clearance of this assay.

Validation of inducible basophil biomarkers: Time, temperature and transportation.

BACKGROUND: The short stability window of several hours from blood collection to measuring basophil activation has limited the use of flow cytometry-based basophil activation assays in clinical settings. We examine if it is possible to extend this window to 1 day allowing for shipment of samples between laboratories. Several options exist for reporting the results including reporting all the measured values directly, calculating ratios and reporting a single value covering all measured results. Each of these options have different stability and value to the physician. METHODS: Whole blood samples from peanut allergic patients were stimulated with four different peanut concentrations at Day 0, Day 1, and Day 2. Samples were stored under temperature-controlled conditions. Flow cytometry was used to analyze the samples. The basophil activation and degranulation were measured as percentage of positive CD63 basophils and CD203c MFI fold change. Shipped samples were transported under ambient conditions. RESULTS: The results show that CD63 is a stable marker at Day 1. The CD203c ratio decreases significantly at Day 1. Calculating the CD63/IgE ratio proves to be more stable than CD63 alone. The most stable readouts are the semi-quantitative results and the trajectory of the dose response curve. Finally, we confirmed that the stability can be extended to samples shipped overnight to the laboratory. CONCLUSIONS: It is possible to extend the stability of the basophil activation assay to 1 day for samples stored at 18-25°C as well as samples shipped under ambient conditions as long as the temperature is within the 2-37°C range.

Marked enhancement of the immune response to BioThrax® (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers.

Immunization with BioThrax(®) (Anthrax Vaccine Adsorbed) is a safe and effective means of preventing anthrax. Animal studies have demonstrated that the addition of CpG DNA adjuvants to BioThrax can markedly increase the immunogenicity of the vaccine, increasing both serum anti-protective antigen (PA) antibody and anthrax toxin-neutralizing antibody (TNA) concentrations. The immune response to CpG-adjuvanted BioThrax in animals was not only stronger, but was also more rapid and led to higher levels of protection in spore challenge models. The B-class CpG DNA adjuvant CPG 7909, a 24-base synthetic, single-strand oligodeoxynucleotide, was evaluated for its safety profile and adjuvant properties in a Phase 1 clinical trial. A double-blind study was performed in which 69 healthy subjects, age 18-45 years, were randomized to receive three doses of either: (1) BioThrax alone, (2) 1 mg of CPG 7909 alone or (3) BioThrax plus 1 mg of CPG 7909, all given intramuscularly on study days 0, 14 and 28. Subjects were monitored for IgG to PA by ELISA and for TNA titers through study day 56 and for safety through month 6. CPG 7909 increased the antibody response by 6-8-fold at peak, and accelerated the response by 3 weeks compared to the response seen in subjects vaccinated with BioThrax alone. No serious adverse events related to study agents were reported, and the combination was considered to be reasonably well tolerated. The marked acceleration and enhancement of the immune response seen by combining BioThrax and CPG 7909 offers the potential to shorten the course of immunization and reduce the time to protection, and may be particularly useful in the setting of post-exposure prophylaxis.

Dust-mite avoidance measures in patients on immunotherapy.

The compliance of dust-mite (DM) allergic patients receiving immunotherapy (IT) with environmental avoidance measures has not been reported. To investigate patient practices, a questionnaire was distributed to patients receiving IT for indoor allergens. Ninety-three of 200 patients (46%) with indoor allergies completed the questionnaire. Of the 93 patients, 69% were allergic to DMs, 45% were allergic to pets, 17% were allergic to mold, and 3% were allergic to cockroaches. Of 64 patients allergic to DMs, 53% reported use of mattress covers, 61% reported use of pillow covers, 81% reduced moisture in their homes, 83% washed their bed linens in water that was >130 degrees F, 77% vacuumed or dusted weekly, and 21% replaced carpets with polished flooring. Fifty-two percent of patients who did not use covers and 49% who did not replace their carpets cited cost as the most common reason. Education about the use of DM covers was reported by 97% of patients allergic to DMs, predominantly by physicians. In conclusion, many patients on IT for DM allergy do not use avoidance measures for decreasing allergen exposure. Cost appears to influence compliance with several measures including protective mattress and pillow covers. It may be unreasonable to require most patients to use such avoidance measures before being candidates for IT.

Anaphylaxis from the influenza virus vaccine.

BACKGROUND: Allergic reactions to the influenza vaccine are uncommon and usually associated with sensitivity to egg or gelatin. The aim of this study was to report the case of anaphylaxis to the influenza vaccine. METHODS: Allergy percutaneous skin testing, serum specific IgE testing and IgE immunoblotting were performed to the influenza vaccine, egg, and gelatin. RESULTS: Percutaneous skin testing to the influenza vaccine and gelatin were positive and egg (white, whole, and yolk) was negative. Immunocap serum-specific IgE testing to egg (white, whole, and yolk) and gelatin were negative (<0.35 kU/l). IgE immunoblots were performed with 2 cord blood serums and the patient's serum at a 1:20 dilution against 10 microg of the Fluzone influenza vaccine. The patient's IgE immunoblot showed a protein band at 100 kDa which is similar to the molecular weight of gelatin protein, a 68-kDa protein which is similar to the molecular weight of hemagglutinin protein from the influenza vaccine, and a 45-kDa protein band that is similar to the molecular weight of ovalbumin protein from chicken embryo/egg. CONCLUSION: Based on clinical symptoms, skin testing, Immunocap testing and immunoblot evaluation, we feel that our patient is allergic to the infectious agent in the influenza vaccine as well as gelatin and ovalbumin in egg.

Seal and whale meat: two newly recognized food allergies.

BACKGROUND: Alaska's marine mammals compose a large portion of the diet of indigenous coastal Alaskan people. Bowhead whales (Balaena mysticetus) and bearded seals (Erignathus barbatus), inhabitants of the Bering and Beaufort seas along Alaska's western and northern coasts, are 2 of the most important subsistence species, serving as major food sources to the native population. OBJECTIVE: To describe an Inupiaq boy with symptoms consistent with an IgE-mediated food allergy after ingestion of bowhead whale and bearded seal meat. METHODS: Extracts of cooked bowhead whale and bearded seal were prepared, lyophilized, and evaluated for protein content. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed for each extract, followed by transfer to nitrocellulose and IgE immunoblots. Skin prick testing was conducted using reconstituted extracts of 1:10 wt/vol dilution. RESULTS: Immunoblots revealed serum specific IgE binding with the extracts of bowhead whale and bearded seal meat. Protein bands of approximately 25, 40, 50, and 90 kDa were found in the seal meat. Protein bands of 55 and 90 kDa were found in the whale meat. Skin prick test results were positive to whale and seal extracts with appropriate positive and negative controls. Ten control subjects had negative reactions to both extracts. CONCLUSION: A patient with moderate anaphylaxis to bowhead whale and bearded seal meat demonstrated serum specific IgE by means of immunoblot and positive skin prick test results. This is the first known reported case of specific IgE to these species.

Effect of imported fire ant extract on the degradation of mountain cedar pollen allergen.

BACKGROUND: Dust mite, cockroach, and mold extracts have been shown to contain proteases capable of degrading the proteins in other extracts. Loss of potency of allergens has been reported in mixtures containing cockroach and fungal extracts. Fire ant venoms consist of 90% to 95% n-alkyl and n-alkenyl piperidine alkaloids, which are not allergenic. No studies are available addressing the mixture of imported fire ant (IFA) whole-body extract with other allergens or the presence of proteolytic activity in the venom extract. OBJECTIVES: To evaluate the stability of mountain cedar pollen extract mixed with IFA whole-body extract and to qualitatively analyze the extract mixture for degradation of mountain cedar protein. METHODS: One milliliter each of mountain cedar and IFA whole-body extracts at a concentration of 500 microg/mL were combined and stored at 4 degrees C for 1, 3, 6, 15, 30, 60, 90, and 180 days. Separate mixtures of 1 mL of mountain cedar and IFA with 1 mL of human serum albumin were used as controls. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was performed, and protein bands were qualitatively analyzed for degradation. RESULTS: We detected 3 distinct IFA protein bands and 1 mountain cedar protein band. With respect to these bands, no protein degradation was observed during 6 months of study in the extract mixture compared with the controls. CONCLUSIONS: Imported fire ant whole-body extract does not seem to degrade mountain cedar protein. Mixtures of allergenic extracts may be able to include IFA whole-body extract.

Intraoperative anaphylaxis to bacitracin during pacemaker change and laser lead extraction.

BACKGROUND: Bacitracin is widely used in operating rooms to soak implants, irrigate compound fractures, and apply to surgical incisions. However, bacitracin is a known sensitizer and causes not only allergic contact dermatitis but also anaphylaxis. OBJECTIVE: To describe a 72-year-old woman with anaphylaxis after irrigation and packing of an infected pacemaker pocket with a bacitracin solution. METHODS: Skin prick testing to bacitracin and latex; serum tryptase, serum histamine, serum IgE to latex, and serial cardiac enzyme measurements; blood cultures, transthoracic echocardiograms, and venograms were performed to characterize the reaction. RESULTS: Six hours after the anaphylactic event, the patient had an elevated serum tryptase level of 49 ng/mL (reference range, 2-10 ng/mL), which normalized the next morning. She had immediate-type skin prick test reactions to full-strength bacitracin ointment (500 U/g) and bacitracin solution (150 U/mL). Serum IgE level to latex was undetectable, and results of skin testing to latex were negative. CONCLUSIONS: To our knowledge, this is the first case report of anaphylaxis to bacitracin during pacemaker surgery. This case illustrates that intraoperative anaphylaxis to bacitracin can be life-threatening.

Patient knowledge of immunotherapy before and after an educational intervention: a comparison of 2 methods.

BACKGROUND: Immunotherapy is an invaluable therapy for allergic asthma, allergic rhinitis, and hymenoptera hypersensitivity. It is, however, not without risks. OBJECTIVES: To examine patient knowledge regarding immunotherapy and to determine the most effective educational method to improve their knowledge by answering the following questions: Before educational intervention, what is the current knowledge level regarding allergy vaccinations of patients receiving immunotherapy? What effect does an educational encounter have on that level of knowledge? Which educational intervention--a one-on-one session vs a handout--if either, increases patient knowledge more? METHODS: An original, self-administered patient questionnaire was distributed to all patients receiving immunotherapy. Patients were randomly assigned to a control group, an intervention group that received an educational handout monthly for 2 months, or an intervention group that had a one-on-one educational session with a physician or nurse practitioner. After 3 months, all patients completed an identical follow-up questionnaire. Pretest and posttest scores were compared for each group and among the different groups to determine which method was more effective. Repeated-measures analysis of variance was used to determine the effect of instruction type on differences in pretest and posttest scores. RESULTS: All 3 groups significantly improved their mean overall questionnaire scores (P < .001). The amount of change was greater in the intervention groups than in the control group, but it did not reach statistical significance (P = .59). CONCLUSIONS: Baseline immunotherapy knowledge of allergy vaccination patients was better than expected, and further educational interventions did not significantly improve this knowledge.