Allergy, asthma, and proteomics: opportunities with immediate impact.

Allergy is widely discussed by researchers due to its complex mechanism that leads to disorders and injuries, but the reason behind the allergic status remains unclear. Current treatments are insufficient to improve the patient's quality of life significantly. New technologies in scientific and technological development are emerging. For instance, the union between allergy and peptidomics and bioinformatics tools may help fill the gaps in this field, diagnosis, and treatment. In this review, we look at peptidomics and address some findings, such as target proteins or biomarkers that help better understand mechanisms that lead to inflammation, organ damage, and, consequently, poor quality of life or even death.

A Prospective Study of Costs Associated With the Evaluation of Allergic Reactions to Radiological Contrast Media.

BACKGROUND AND OBJECTIVE: The prevalence of hypersensitivity reactions to radiological contrast media (RCM) is increasing owing to the improved performance of diagnostic and therapeutic tests that require RCMs. Objective: We carried out a year-long real-life observational study to prospectively evaluate patients referred to the allergy department from primary care, the emergency department, and other specialties with suspected moderate-to-severe RCM hypersensitivity reactions. METHODS: To study the costs of evaluating RCM hypersensitivity reactions, we systematically recorded direct and indirect costs. RESULTS: Sixty-nine patients with previous reactions to RCM were evaluated in the allergy department from June 1, 2017, to May 31, 2018.Total direct health care costs were €10 715.84, with a mean (SD) cost per patient of €155.30 (77.08). Specifically, direct non-health care costs reached €1605.42 (mean, €23.27 [41.14]), and indirect costs were €6490.85 (mean, €94.07 [110.61]). In summary, the total cost was €18 812.11, that is, a mean cost of €272.64 (164.77). CONCLUSION: Our study shows that the costs of an elective evaluation of hypersensitivity reactions to RCM are low, thus confirming that correct and safe management of affected patients are cost-effective. Therefore, our efforts should be directed toward ensuring the necessary logistics.

Fellows in Training Wellness in Allergy and Immunology: AAAAI Workgroup Report.

Physician health and wellness can be negatively affected by burnout, which in turn can lead to multiple potential professional and personal issues. Burnout issues can start in medical school and progress during residency and fellowship, and throughout a physician's career. A previous survey of allergists and immunologists reported a burnout rate of 35%. However, there are currently few data regarding health and wellness specifically for fellows-in-training (FIT) in allergy and immunology. This workgroup report was developed to assess health and wellness among FIT in our specialty. The American Academy of Allergy, Asthma & Immunology electronically distributed an anonymous questionnaire using the validated mini-Z survey to a total of 388 allergy and immunology FIT. In addition to the mini-Z items, the survey queried personal and professional demographic characteristics and included open-ended wellness questions. A total of 82 FIT completed the survey, yielding a 24% response rate. The burnout rate was 39%, which is lower than the national average among US physicians. Overall job satisfaction was 82%, and 72% reported satisfactory or better control over workload. Our results identify FIT-specific concerns in our specialty that can be used to develop tailored interventions to improve wellness and minimize burnout among this group. However, future surveys are needed to continue to address allergy and immunology FIT-specific wellness challenges.

Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records.

BACKGROUND: Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby's umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown. OBJECTIVES: We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section. DESIGN: This was a controlled interrupted time series study. SETTING: The study took place in primary and secondary care. PARTICIPANTS: Children born in the UK during 2006-18 delivered by caesarean section were compared with a control cohort delivered vaginally. INTERVENTIONS: In-utero exposure to antibiotics immediately prior to birth. MAIN OUTCOME MEASURES: Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed. DATA SOURCES: The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN-CPRD data set. RESULTS: In the THIN-CPRD and HES data sets, records of 515,945 and 3,945,351 mother-baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively. LIMITATIONS: It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years. CONCLUSIONS: There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006-18 had an impact on the incidence of asthma and eczema in early childhood in the UK. FUTURE WORK: There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children. STUDY REGISTRATION: This study is registered as researchregistry3736. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.

WHAT WAS THE QUESTION?: Women giving birth by caesarean section are at risk of developing infections (such as wound infections) and are offered antibiotics at the time of their operation to reduce this risk. In 2011, the national guidelines changed from recommending antibiotics after cord clamping to giving them before the operation to further reduce the risk of maternal infection. During birth, the newborn gut is colonised by microbes. Antibiotics given to the mother before caesarean section can reach the baby through the placenta and disrupt the normal microbes that colonise the gut. These microbes are believed to play a role in the development of the immune system and altering the normal development of these microbes has been linked to children developing allergic conditions, such as asthma and eczema. This study investigated whether or not giving antibiotics before the caesarean section had a longer-term impact on children's health. WHAT DID WE DO?: We used routine NHS information already collected by hospitals and general practitioners about women who gave birth in the UK between 2006 and 2018, and their children. We compared the risk of asthma, eczema and other health conditions in the first 5 years after birth in children born by caesarean section before and after the change in hospital policies. We also compared their health with children born vaginally. WHAT DID WE FIND?: We found that there was no increased risk of asthma or eczema for children born by caesarean section after the policy decision in 2011 to give the mother antibiotics before the operation. WHAT DOES THIS MEAN?: The study findings provide further evidence for the current recommendation to give preventative antibiotics to women shortly before the caesarean section to reduce the overall risk of infections after birth.

Immune-related conditions and cancer-specific mortality among older adults with cancer in the United States.

Immunity may play a role in preventing cancer progression. We studied associations of immune-related conditions with cancer-specific mortality among older adults in the United States. We evaluated 1 229 443 patients diagnosed with 20 common cancer types (age 67-99, years 1993-2013) using Surveillance Epidemiology and End Results-Medicare data. With Medicare claims, we ascertained immune-related medical conditions diagnosed before cancer diagnosis (4 immunosuppressive conditions [n = 3380 affected cases], 32 autoimmune conditions [n = 155 766], 3 allergic conditions [n = 101 366]). For each cancer site, we estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer-specific mortality associated with each condition, applying a Bonferroni cutoff for significance (P < 5.1 × 10-5 ). Bayesian metaanalysis methods were used to detect patterns across groups of conditions and cancers. We observed 21 associations with cancer-specific mortality at the Bonferroni threshold. Increased cancer-specific mortality was observed with rheumatoid arthritis for patients with melanoma (aHR 1.51, 95% CI 1.31-1.75) and breast cancer (1.24, 1.15-1.33)), and with hemolytic anemia for bladder cancer (2.54, 1.68-3.82). Significant inverse associations with cancer-specific mortality were observed for allergic rhinitis (range of aHRs: 0.84-0.94) and asthma (0.83-0.95) for cancers of the lung, breast, and prostate. Cancer-specific mortality was nominally elevated in patients with immunosuppressive conditions for eight cancer types (aHR range: 1.27-2.36; P-value range: 7.5 × 10-5 to 3.1 × 10-2 ) and was strongly associated with grouped immunosuppressive conditions using Bayesian metaanalyses methods. For older patients with several cancer types, certain immunosuppressive and autoimmune conditions were associated with increased cancer-specific mortality. In contrast, inverse associations with allergic conditions may reflect enhanced immune control of cancer.

Cost assessment of allergy procedures to improve high-value care implementation.

Background: Oral challenges and desensitizations are regularly performed by allergy/immunology physicians. However, there is limited research that has evaluated their cost-effectiveness and overall health-care-related value. Objective: The objective was to analyze the costs of oral challenges and desensitizations by clinician type (including allergy/immunology physicians, other physicians, and certified registered nurse practitioners [CRNP] and physician assistants [PA]), and by geographic distribution in the United States. Methods: By using a de-identified commercial database of medical encounters, we identified all claims for outpatient oral challenges and desensitizations in 2017 and grouped them separately by clinician type and by U.S. Census region. We used analysis of variance to test for cost differences between these two groupings. Results: Allergy/immunology physicians performed the majority of oral challenges (74.36%) with a mean cost of $161, significantly less than that of other physicians ($280). Allergy/immunology physicians also performed the majority of desensitizations (84.48%) with a mean cost of $335, significantly higher than that of CRNPs/PAs ($280); other physicians were reimbursed significantly more than both groups ($410). By geographic region, the mean costs of oral challenges in the Northeast ($212) and the West ($210) were significantly higher than those of other regions, whereas the mean cost of desensitizations was significantly highest in the West ($381). Conclusion: Allergy/immunology physicians and CRNPs/PAs cost the least with respect to oral challenges, whereas CRNPs/PAs cost the least with respect to desensitizations. The Northeast and the West regions provided the highest cost for oral challenges, whereas the West was most expensive in terms of desensitizations. Further knowledge and examination of these reimbursement patterns are crucial in understanding their relative value and the impact on delivery of high-value care.

Evaluation and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens using a new multiplex assay: a real-life experience on an Italian population.

Summary: Background. House dust mites (HDM) are among the most important allergen sources worldwide, representing a major cause of perennial allergic rhinitis and asthma. Aim. To evaluate the prevalence of IgE responses towards a comprehensive panel of HDM allergens and to evaluate the implications of molecular sensitization profiles on respiratory symptoms. Methods. 155 consecutive HDM-allergic patients (mean age: 27.5 years; range: 1-62; female: 63), 86 affected by rhinitis and 68 by asthma, were enrolled. Specific IgE reactivity to Der f 1, Der p 1, Der f 2, Der p 2, Der p 5, Der p 7, Der p 10, Der p 11, Der p 20, Der p 21 and Der p 23 was tested in patients' sera using the last version of the multiparametric assay Allergy Explorer (ALEX). Results. In all, major and minor allergens were positive, respectively, in 96.8% and 50.9% of the patients. Prevalence and IgE levels of Der f 1, Der f 2, Der p 1 and Der p 20 were significantly higher in asthmatic patients (p less than 0.05), whereas subjects negative for minor allergens resulted more frequently suffering from rhinitis (p = 0.0001). Asthmatic patients had IgE reactivity to a larger number of HDM allergens (mean 5.4; SD ± 2.3) than patients with only rhinitis (mean 4.2; SD ± 2.5) (p = 0.003), whereas no differences in the number of HDM positive molecules and in the specific IgE levels were found among different ages. Conclusions. This study confirms that the assessment of IgE to a comprehensive panel of HDM allergens defines different serological reactivity profiles that seem associated with different clinical presentations.

Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System.

Importance: As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported. Objective: To characterize the immunologic mechanisms underlying allergic reactions to these vaccines. Design, Setting, and Participants: This case series included 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines between December 18, 2020, and January 27, 2021, at a large regional health care network. Participants were individuals who received at least 1 of the following International Statistical Classification of Diseases and Related Health Problems, Tenth Revision anaphylaxis codes: T78.2XXA, T80.52XA, T78.2XXD, or E949.9, with documentation of COVID-19 vaccination. Suspected allergy cases were identified and invited for follow-up allergy testing. Exposures: FDA-authorized mRNA COVID-19 vaccines. Main Outcomes and Measures: Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and polysorbate 80 (P80). Histamine (1 mg/mL) and filtered saline (negative control) were used for internal validation. Basophil activation testing after stimulation for 30 minutes at 37 °C was also conducted. Concentrations of immunoglobulin (Ig) G and IgE antibodies to PEG were obtained to determine possible mechanisms. Results: Of 22 patients (20 [91%] women; mean [SD] age, 40.9 [10.3] years; 15 [68%] with clinical allergy history), 17 (77%) met Brighton anaphylaxis criteria. All reactions fully resolved. Of patients who underwent skin prick tests, 0 of 11 tested positive to PEG, 0 of 11 tested positive to P80, and 1 of 10 (10%) tested positive to the same brand of mRNA vaccine used to vaccinate that individual. Among these same participants, 10 of 11 (91%) had positive basophil activation test results to PEG and 11 of 11 (100%) had positive basophil activation test results to their administered mRNA vaccine. No PEG IgE was detected; instead, PEG IgG was found in tested individuals who had an allergy to the vaccine. Conclusions and Relevance: Based on this case series, women and those with a history of allergic reactions appear at have an elevated risk of mRNA vaccine allergy. Immunological testing suggests non-IgE-mediated immune responses to PEG may be responsible in most individuals.

Clinical and immunological allergy assessment in cancer patients.

Cancer is associated with immunodeficiency, while allergies result from immune system hyperactivity mediated by cytokines and immunoglobulins. The purpose of this study was to determine the relationship between immune environment of specific cancers and allergies, emphasizing cytokines related to Th1 and Th2 responses associated with IgE. 80 adults were distributed into two groups: control (n = 20) and cancer (n = 60), distributed in three subgroups (n = 20), head and neck, stomach, and prostate cancers. This study compared Th1 (IL-2) and Th2 (IL-4) parameters, anti-inflammatory, pro-inflammatory, or regulatory profile regarding both IgE levels and reported allergies, by means of clinical manifestations and IgE, IL-1ß, IL-2, IL-4, IL-17, and TGF-ß serum concentration. Clinically allergies were observed in 50% of the control group and in 20% of the cancer group (p = 0.009). IL-2 cytokine and TGF-ß concentrations were higher in the patients with cancer as compared to the control (p < 0.005). However, there were IL-4, IL-17, and IL-1ß decreases in the patients with cancer (p < 0.05). No correlation was observed between the cytokines studied and IgE and clinically proven allergies in both investigated groups. There was an inverse association between cancer and clinical allergy manifestations. In head and neck, stomach, and prostate cancers, an immunosuppressive serum tumor environment was predominant. There was no difference in cytokines related to Th1 and Th2 parameters in relation to IgE. No correlation was found between clinically proved allergies and immunity markers related to the same allergens.

[Evaluation of the effectiveness of a procedure for identifying patients with allergy in paediatric emergency rooms]. / Evaluación de la efectividad de un procedimiento de identificación de pacientes con alergia en urgencias pediátricas.

INTRODUCTION: Correct identification of the patient with an allergy is critical for patient safety, since it involves a potential risk of a serious adverse event (AE). Our Emergency Pediatric department has an integrated quality management and risk management system focused on the continuous improvement of patient care quality and safety, which incident reporting system could identified a potential risk arising from the registration of allergies in new computer softwares. As a safety barrier, an allergy identification procedure was implemented, using a sticker placed on the identification bracelet (RED: allergy; WHITE: non-allergies). MATERIALS AND METHODS: A descriptive study was conducted to evaluate, by direct observation, the correct identification of patients with allergy using this new protocol. The reports of incidents related to this procedure were analyzed. RESULTS: Of the 342 patients included, 327 (95.6% (95%:93.4-97.8%)) were correctly identified. Identification errors were most common in the group of patients with allergies [10 of 45; 22.2% (95%:10.1-34.4%) than in the non-allergic group: 5 of 297; 1.7% (95%:0.2-3.2); p<0.001)]. No AEs were reported. 2 quasi-incidents detected before reaching the patient were reported thanks of the protocol application. CONCLUSIONS: This procedure is a useful safety barrier and can be easily exported to other units. Further work is needed to promote the professional's adherence to the protocol and improve the correct identification of the patient with allergy.

Houston hurricane Harvey health (Houston-3H) study: assessment of allergic symptoms and stress after hurricane Harvey flooding.

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall. METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 unique participants from four sites across Harris County at two times: within approximately 1-month of Harvey (T1, n = 206) and approximately 12-months after Harvey (T2, n = 266), including 125 individuals who participated at both time points. Using a self-administered questionnaire, participants reported details on demographics, flood-related exposures, and health outcomes, including allergic symptoms and stress. RESULTS: The majority of participants reported hurricane-related flooding in their homes at T1 (79.1%) and T2 (87.2%) and experienced at least one allergic symptom after the hurricane (79.4% at T1 and 68.4% at T2). In general, flood-exposed individuals were at increased risk of upper respiratory tract allergic symptoms, reported at both the T1 and T2 time points, with exposures to dirty water and mold associated with increased risk of multiple allergic symptoms. The mean stress score of study participants at T1 was 8.0 ± 2.1 and at T2, 5.1 ± 3.2, on a 0-10 scale. Participants who experienced specific flood-related exposures reported higher stress scores when compared with their counterparts, especially 1 year after Harvey. Also, a supplementary paired-samples analysis showed that reports of wheezing, shortness of breath, and skin rash did not change between T1 and T2, though other conditions were less commonly reported at T2. CONCLUSION: These initial Houston-3H findings demonstrate that flooding experiences that occurred as a consequence of Hurricane Harvey had lasting impacts on the health of Houstonians up to 1 year after the hurricane.

The relationship between malnutrition and TH 2 immune markers: a study in school-aged children of different socio-economic backgrounds in Makassar, Indonesia.

OBJECTIVE: The burden of underweight remains a major problem in Indonesia, and at the same time, the prevalence of overweight is increasing. Malnutrition is a major determinant of health and has been linked to allergic disorders in children. We examined the relationship between malnutrition and TH 2 immune markers in school-aged children in Makassar, Indonesia. METHODS: A cross-sectional study was performed in five schools where socio-demographic characteristics were recorded. Children's standardised z-scores of body mass index (z-BMI) and age-standardised z-scores of height (z-HA) were assessed using WHO child growth standards. Skin prick test (SPT) reactivity was determined to house dust mite allergens. Helminth infection status, (growth) hormones including insulin-like growth factor (IGF-1) and TH 2 immune markers were measured. RESULTS: In total, 954 children were included of whom 21.6% were underweight and 14.8% overweight. After controlling for confounders, overweight was positively associated with leptin (GMR 3.55, 95% CI: 2.99-4.23) and IGF-1 (GMR 1.45, 95% CI: 1.15-1.82), whereas underweight was negatively associated (respectively GMR 0.57, 95% CI: 0.49-0.66 and GMR 0.78, 95% CI: 0.63-0.97). Underweight was associated with a lower eosinophil count (GMR 0.79, 95% CI: 0.64-0.97) but not with total IgE levels or SPT reactivity. Overweight was positively associated with SPT reactivity (adjusted OR 2.68, 95% CI: 1.50-4.78) but no relationship was found with the other TH 2 immune markers. CONCLUSION: Malnutrition is prominent in school-aged children in Makassar, with overweight associated with increased SPT reactivity. Therefore, interventions should focus on undernutrition, but also on overweight to prevent the increase of allergic disorders in Indonesia.

OBJECTIF: La charge de l'insuffisance pondérale reste un problème majeur en Indonésie et parallèlement, la prévalence du surpoids augmente. La malnutrition est un déterminant majeur de la santé et a été associée à des troubles allergiques chez les enfants. Nous avons examiné la relation entre la malnutrition et les marqueurs immunitaires TH 2 chez les enfants d'âge scolaire à Makassar, en Indonésie. MÉTHODES: Etude transversale dans cinq écoles où les caractéristiques sociodémographiques ont été enregistrées. Les scores z standardisés de l'indice de masse corporelle (z-IMC) et les scores z standardisés pour l'âge de la taille (z-HA) pour les enfants ont été évalués en utilisant les normes de croissance de l'enfant de l'OMS. La réactivité du test cutané (SPT) a été déterminée pour les allergènes d'acariens. L'état de l'infection par les helminthes, les hormones (de croissance), y compris le facteur de croissance analogue à l'insuline (IGF-1) et les marqueurs immunitaires TH 2 ont été mesurés. RÉSULTATS: Au total, 954 enfants ont été inclus, dont 21,6% en insuffisance pondérale et 14,8% en surpoids. Après contrôle des facteurs de confusion, le surpoids était positivement associé à la leptine (GMR 3,55, IC95%: 2,99-4,23) et à l'IGF-1 (GMR 1,45 ; IC95%: 1,15-1,82), tandis que l'insuffisance pondérale était associée négativement (respectivement GMR 0,57 ; IC95%: 0,49-0,66 et GMR 0,78 ; IC95%: 0,63-0,97). L'insuffisance pondérale était associée à un nombre plus faible d'éosinophiles (GMR 0,79 ; IC95%: 0,64-0,97) mais pas aux taux d'IgE totaux ou à la réactivité du SPT. Le surpoids était positivement associé à la réactivité du SPT (OR ajusté 2,68 ; IC95%: 1,50-4,78) mais aucune relation n'a été trouvée avec les autres marqueurs immunitaires T H 2. CONCLUSION: La malnutrition est importante chez les enfants d'âge scolaire à Makassar, avec un surpoids associé à une réactivité accrue du SPT. Par conséquent, les interventions devraient se concentrer sur la dénutrition, mais aussi sur le surpoids pour prévenir l'augmentation des troubles allergiques en Indonésie.