Allergy Group Research Articles

Immunocompromised Children and Young People Are at No Increased Risk of Severe COVID-19

Background: The risk of SARS-CoV-2 infection to immunocompromised children and young people remains of concern to parents and clinicians despite little data suggesting increased morbidity or mortality. We aimed to prospectively describe the incidence and clinical spectrum of SARS-CoV-2 infection in immunocompromised paediatric patients in the UK.Methods: From March 2020 – 2021 weekly questionnaires were sent to immunocompromised paediatric patients or their parents. Information, including symptom presentation and SARS-CoV-2 PCR test results, was collected from 1527 participants from 46 hospitals. Cross-sectional serology was investigated in February and March 2021.Findings: Until the end of September 2020 no cases were reported. From September 28th 2020 through March 2021 a total of 38 PCR-detected SARS-CoV-2 infections were reported. Of these, four children were admitted to hospital but none had acute severe COVID-19. Increasing age in association with immunodeficiency increased reporting of SARS-CoV-2 infection. Worsening of fever, cough, and sore throat were associated with participants reporting SARS-CoV-2 infection.Serology data included 452 unvaccinated participants. In those reporting prior positive SARS-CoV-2 PCR, there were detectable antibodies in 9 of 18 (50%). In those with no prior report of infection, antibodies were detected in 32 of 434 (7·4%).Interpretation: This study shows SARS-CoV-2 infections have occurred in immunocompromised children and young people with no increased risk of severe disease. No children died. Funding Information: British Paediatric Allergy, Immunity and Infection Group. Southampton Rheumatology Trust. NIHR Senior Investigator award to SNF.Declaration of Interests: All authors have completed ICMJE disclosure forms. HdG received grant funding from the BPAIIG for the submitted work; there are no other relationships or activities that could appear to have influenced the submitted work. Ethics Approval Statement: The study gained ethical approval from the Yorkshire and the Humber – Leeds West NHS Research Ethics Committee (IRAS 281544).

Prevalence of confirmed immunoglobulin E-mediated food allergy among adult Egyptian patients

Food allergy (FA) represents an increasing social and economic health problem. Prevalence of food allergy differs from one country to another depending on genetic and environmental as well as feeding habits of each country. Estimate the prevalence of confirmed immunoglobulin E-mediated food allergy (FA) among adult Egyptian patients and identify its possible risk factors. A total of 2081 adult subjects were randomly selected from the Allergy outpatient clinic at Ain Shams university hospitals. Patients who disclosed food adverse complaints (probable food allergy group) were further subjected to a detailed questionnaire, complete blood cell count, total immunoglobulin E level, skin prick test and /or specific immunoglobulin E test for common food allergens, and oral food challenge with the culprit food. Patients were classified into confirmed food allergy and no food allergy groups depending on the results of oral food challenge test. Out of the 2081 adults, 100 subjects had self-reported food adverse complaints, and of them, 45 (45%) had confirmed diagnosis of FA. Thirty four (75.6%) confirmed FA patients were females with mean age ± SD of (38.02 ± 13.08) years, five patients (11.1%) had persistent childhood FA, 11 (24.4 %) had family history of atopy, five (11.1%) had associated atopic diseases and 24 (53.3%) were polysensitized. Female gender, young age and exercise were found to be risk factors for confirmed FA (OR: 1.766, 1.4, and 1.9 respectively). Cutaneous manifestations were the most common presentation of confirmed FA patients in the form of urticaria 40/45 (88.9%) and angioedema 18/45 (40%). The most common food allergen was milk, banana, fish, tomato, strawberry and eggs. In conclusion, IgE mediated food allergy is a noticeable health problem among adult Egyptians, particularly adult females and young age groups.

Perioperative anaphylaxis: A five-year review in a tertiary paediatric hospital.

Making a diagnosis of perioperative anaphylaxis and identifying culprit drugs are diagnostic challenges. The aim of this study is to describe the perioperative presentation of anaphylaxis and results of patients who underwent allergy evaluation. This is a retrospective review of perioperative anaphylaxis of severity Grade 2 and above based on the Australian and New Zealand Anaesthetic Allergy Group criteria from 2015 to 2019 in a tertiary paediatric hospital. Data collected were demographics, clinical features, investigations and management. Of the 35,361 cases of paediatric anaesthesia, there were 15 cases of perioperative anaphylaxis, giving an incidence of four in 10,000. The median age was seven years (interquartile range four-15 years) with a male predominance of 86.7% (13/15). The severity of anaphylaxis was Grade 2 in 33.3% (5/15) and Grade 3 in 66.7% (10/15). The commonest presenting feature was hypotension (13/15, 86.7%) while the earliest symptom was respiratory change (9/15, 60.0%). Dynamic tryptase was raised in 75% (6/8) of the patients with adequate tryptase samples. Eight patients (53.3%) completed allergy testing, of whom five patients (62.5%) had IgE-mediated anaphylaxis with skin test positive to cefazolin (n = 3), atracurium (n = 1) and rocuronium (n = 1). Three patients (25.0%) had non-IgE-mediated reactions with negative skin tests. Although only half the patients completed allergy evaluation, a culprit drug could be identified in 62.5%, with antibiotics being the commonest. This emphasises the need for appropriate evaluation in cases of suspected perioperative anaphylaxis.

1153. Characterization of Invasive Mold Infections in Acute Leukemia and Hematopoietic Stem Cell Transplant Recipient Patients and Risk Factors for Mortality - a Single Center Experience

BackgroundInvasive mold infections (IMIs) remain a significant cause of morbidity and mortality in patients with acute leukemia (AL) and those undergoing hematopoietic stem cell transplantation (HSCT). We describe the epidemiology of IMIs, the incidence of IMI in patients with acute myelogenous Leukemia (AML) post HSCT, and risk factors for mortality.MethodsPatients were identified using ICD9 and ICD10 codes using a University of Kansas internal database from 2009-2019, microbiology records, and an AML HSCT database and were followed through May 1st, 2020. Patients’ electronic medical records were reviewed for inclusion. IMI was defined as proven or probable using the 2009 National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) guidelines. Incidence was calculated as IMI cases/100-person-years. Risk factors for overall mortality were evaluated using a Cox regression model.ResultsWe included 138 patients: 79 developed IMI after HSCT (8 autologous, 71 allogeneic) and 59 developed IMI after AL diagnosis. Seventeen of the AL patients underwent HSCT after IMI diagnosis (12 within 100 days of IMI). Proven IMI occurred in 45 (32.6%) and probable IMI occurred in 93 (67.4%) patients. The most common prophylactic agent prior to IMI diagnosis was fluconazole (31.2%), with 21.0% receiving none. Aspergillus was the most commonly identified mold with 91 (65.9%) cases. The average treatment duration was 101 (range 0 - 799) days. The incidence of IMI in patients with AML who underwent HSCT was 2.35 cases/100 person-years. All-cause mortality among patients with AL or HSCT who developed IMI was 23.1% at 6 weeks, 34.1% at 12 weeks, and 61.2% at 1 year. On univariate Cox model, Karnofsky performance status > 70 was associated with lower mortality (hazard ratio (HR) 0.317, 95% confidence interval (CI) [0.110, 0.914]) among HSCT recipients. ICU admission within 7 days prior to IMI diagnosis (HR 6.469, 95% CI [1.779, 23.530]) and each one point increase in BMI (HR 1.051, CI [1.001, 1.103]) were associated with increased mortality in the AL group.Figure 1 - Invasive mold infections by pathogen in HSCT-recipients and acute leukemia patients from 2009-2019. Figure 2 - Antifungal prophylactic agents prescribed for at least one week at time of IMI diagnosis Table 1 - Univariate survival analysis calculated using a Cox proportional-hazards regression model among patients who developed IMI after HSCT and patients who developed IMI after acute leukemia diagnosis ConclusionIMIs are associated with significant mortality in HSCT recipients and AL patients; patients at higher risk for mortality include those with lower baseline Karnofsky scores, recent ICU admissions, and higher BMI at time of IMI diagnosis.Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

742. Breakthrough Invasive Fungal Infections with Isavuconazonium Sulfate versus Voriconazole as Primary Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia (AML) who Received Induction Chemotherapy

BackgroundFungal infections in patients with hematologic malignancies are associated with high mortality. Primary antifungal prophylaxis has been shown to be a more effective strategy than treating a documented infection. This retrospective analysis aims to compare the rates of breakthrough invasive fungal infections in patients with acute myeloid leukemia (AML) who received induction chemotherapy and were prescribed voriconazole (Vori) or isavuconazonium (Isv) for primary antifungal prophylaxis.The European Organization for Research and Treatment of Cancer/ Invasive Fungal Infection Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to categorize incidence of breakthrough invasive fungal infections bIFI into ‘possible’, ‘probable’ or ‘definite’ groups who required treatment with liposomal amphotericin B, echinocandin, and/or different triazole.MethodsThis is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML. These patients received either Vori or Isv sulfate as the primary antifungal prophylaxis at Moffitt Cancer Center between July 2017 and June 2019. Patients who were over 18 years old and received at least 10 days of uninterrupted primary antifungal prophylaxis with either Vori or Isv sulfate were included in the study. Patients with a history of stem cell or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or who received systematic antifungal, other than fluconazole, therapy within 30 days to induction chemotherapy were excluded.Results250 patients were screened for the study and out of which 118 patients met the above criteria. There was a 20.2% (18/89) break through rate of fungal infections in the Vori arm and 17.2% (5/29) in the Isv arm. In the Vori arm there were 15 possible bIFIs, 3 probable bIFIs and 0 definite bIFIs. In the Isv arm there are 2 possible bIFIs, 2 probable bIFIs and 1 definite bIFIs.ConclusionThere is no significant statistical difference (Using the Fisher Exact test statistic p=1) between the Isv and Vori in patients who received these agents for primary fungal prophylaxis for induction chemotherapy for AML at Moffitt Cancer Center between July 2017 - June 2019.Disclosures Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)

Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature.

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug–drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. ‘Breakthrough’ invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3–4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one ‘probable’ and one ‘possible’. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.

Prevalence, concomitant reactions, and factors associated with fragrance allergy in Thailand.

Fragrances are the most common cause of cosmetic contact allergy. Up-to-date information on contact allergy frequencies and relevance aids primary and secondary preventive measures. To determine the prevalence, associated factors, and concomitant reactions in fragrance allergy among Thais. This retrospective study collected data from 2012 to 2019. The patient characteristics of fragrance and nonfragrance allergy groups were compared. Concurrent positive reactions to fragrance allergens (fragrance mix [FM] I, FM II, Myroxylon pereirae resin and hydroxyisohexyl 3-cyclohexene carboxaldehyde) and other baseline-series allergens were analysed. Of 1032 patients, 175 (17.0%) had fragrance allergy, with 57.7% of clinical relevance. FM I showed the highest prevalence (9.4%). The associated factors were being elderly, lesions on the extremities, metal allergy history, and long dermatitis duration. Contact allergies to epoxy resin and Compositae plants were significantly associated with fragrance allergy with an odds ratio of 5.95 (95% confidence interval [CI]: 5.21-6.80) and an odds ratio of 4.42 (95% CI: 1.58-12.36), respectively. No significant associations between colophonium (previously proposed as a fragrance marker) and fragrance allergens were found. The prevalence of fragrance contact allergy remains high and should be considered in old patients presenting with long-standing eczema on the extremities. Unlike reports from other countries, varied, significant, concomitant reactions were observed.

Invasive Fungal Infections in Pediatric Patients with High-Risk Acute Lymphoblastic Leukemia during Initial Phases of Therapy: A Retrospective Evaluation

BACKGROUND Patients with newly diagnosed acute lymphoblastic leukemia (ALL) are at increased risk of infection. While previously published guidelines recommend primary antifungal prophylaxis in patients with T-cell ALL, we sought to determine the pattern of invasive fungal disease (IFI) at our center so as to assess risk factors for IFI, beyond the diagnosis of T-ALL, with the administration of dexamethasone and an anthracycline during induction. The current practice at Children's Health Children's Medical Center Dallas is to provide primary antifungal prophylaxis with micafungin during induction therapy for hospitalized patients with T-cell ALL and those with Down Syndrome. Additionally, we recently decided to provide primary antifungal prophylaxis to patients with HR B-ALL with hyperglycemia who remain hospitalized during induction. The primary objective of this study was to capture the institution-specific five-year incidence of IFI prior to the start of delayed intensification (DI) phase chemotherapy among pediatric patients with ALL. Secondary objectives were to identify potential IFI risk factors specifically amongst pediatric patients with HR ALL. METHODS This retrospective chart review included patients younger than 21 years with newly diagnosed ALL between July 1, 2014 and June 30, 2019. Patients with secondary leukemia, infantile leukemia, or those receiving treatment for a fungal infection at presentation were excluded. The primary outcome was the development of probable or proven IFI, as defined by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria, prior to the start of the DI phase of therapy. Statistical methods included Chi-square test, t-test, and Wilcoxon Rank Sum test, as appropriate to the variable's level of measurement and distribution. Time series analyses were used to assess overall and seasonal trends of IFI incidence over the study period. RESULTS Of 220 included patients, there were 13 cases of IFI diagnosed during the induction and consolidation phases of therapy during the five-year period. IFI occurred in 15.3% of the HR group (11/72), 5.9% of the T-cell ALL group (1/17), and 0.8% of the standard risk (SR) group (1/131). Among individuals with HR ALL, the majority of cases occurred in the absence of primary antifungal prophylaxis (90.9%). The most common sites of IFI included the lungs (n=6) and sinuses (n=4). Implicated fungal pathogens included Aspergillus, Candida, Curvularia, Exserohilum, and Bipolaris. Univariate analysis of the potential IFI risk factors in HR ALL patients did not identify any significant differences between those patients that did or did not develop IFI, with respect to pre-existing comorbidities, body mass index, laboratory results at diagnosis, or hospital exposures during induction including length of stay, intensive care admissions, and receipt of systemic antibiotics (Table). Race and ethnicity was significantly different likely due to the skewed distribution of IFI among patients who identified as Asian (p = 0.03; 8/8 identified as Asian and did not develop IFI). With respect to seasonality of ALL diagnosis, the percent of patients in each group (winter, spring, summer, and fall) that developed IFI were 7.4%, 18.2%, 20%, and 31.2%, respectively. However, time series analysis did not show an association between seasonality of diagnosis and development of IFI (p=0.89). During the induction phase of therapy, hyperglycemia, defined as blood glucose 140-200 mg/dL for ≥ 2 days or >200 mg/dL for 1 day, was present in 100% of the HR patients that developed IFI and 74% of the HR patients that did not develop IFI (p=0.12). CONCLUSION In this pediatric population, patients with HR B-ALL developed more fungal infections during the early phases of therapy then those with SR disease (15.6% versus 0.8%). In analysis of potential risk factors, there were no significant differences between HR ALL groups that did or did not develop IFI. Larger-scale studies are needed in order to identify potential risk factors that will guide decisions on the routine use of primary antifungal prophylaxis in patients with HR ALL during induction therapy. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Micafungin use for primary antifungal prophylaxis during induction phase of therapy.

Correlation between exhaled nitric oxide and carbon monoxide and allergic rhinitis

Objective:In this study, the level of nasal nitric oxide（nNO）, exhaled nitric oxide（eNO）, and exhaled carbon monoxide（eCO） in patients with allergic rhinitis（AR） were tested, to explore the correlation between nNO, eNO, eCO and AR. Method:A total of 60 AR patientswere enrolled as the allergy group and then divided into mild, medium and severe subgroups according to symptom scores. 30 healthy volunteers were recruited as control group. The levels of nNO, eNO and eCO were detected in AR group, AR subgroups and control group. Result:The levels of nNO, eNO and eCO in AR group were higher than those in control group（P<0.05）. nNO, eNO and eCO levels were positively correlated with symptom scores（P<0.05）.Pairwise comparison was used between mild, moderate and severe subgroups. The difference of both nNO and eNO levels between mild, moderate and severe AR subgroups was statistically significant, severe>and moderate>were mild（P<0.05）, but there was no significant difference in eNO levels between the mild AR subgroup and the control group（P>0.05）. Level of eCO in severe AR subgroup was higher than those in moderate and mild AR subgroups（P<0.05）, but there was no significant difference between mild, moderate AR subgroups and control group（P>0.05）. nNO, eNO and eCO levels were used as indicators to evaluate the severity of AR, and the receiver operating characteristic（ROC） curves were plotted. The area under curve（AUC） was 0.978, 0.786 and 0.577, respectively. Taking eCO level as the indicator for disease assessment of severe AR, the AUC was 0.728. It showed that nNO had a high accuracy in evaluating the severity of AR, eNO had a certain accuracy in evaluating the severity of AR, and eCO had a certain accuracy in the assessment of severe AR. Conclusion:The detection of nNO, eNO and eCO levels can be used as an objective assessment method of the severity of AR.

Analysis of the immunoglobin E molecular sensitization profile in children with allergic asthma and predictive factors for the efficacy of allergy immunotherapy.

BackgroundAs the incidence of allergic asthma in children increases, the immunoglobin E (IgE) molecular sensitization profile of allergic asthma remains underreported while the level of total IgE (tIgE) and sIgE/tIgE have not been studied as predictors of efficacy of allergen immunotherapy (AIT) for allergic asthma, specifically in children.MethodsStarting from August 2018 to March 2019 in the Respiratory Department of the Children’s Hospital of Chongqing Medical University, asthmatic children, with positive skin prick tests to Der p or Der f, were enrolled in this study. Total IgE, allergen serum-specific IgE (sIgE) of Der p, Der f, Blomia tropicalis (Blo t), cat dander, dog dander, egg white, milk, cockroach, shrimp, and crab, along with Der p allergen components, Der p1 and Der p2, were measured by ImmunoCAP™ assay.ResultsA total of 142 children with allergic asthma were enrolled, all of whom showed positive IgE for Der p, Der p1, Der p2, and Der f; meanwhile, the positive rates of Blo t, cat dander, dog dander, egg white, milk, cockroach, shrimp, and crab were 91.84%, 10.96%, 7.32%, 9.15%, 11.58%, 17.03%, 18.90%, and 18.28% respectively. A significantly high correlation was found between total IgE and the sIgE of Der f, Der p, Der p 1, and Der p 2. Asthmatic children with a family history of allergy displayed higher total IgE and unknown IgE levels than those patients without a family history of allergy. The ratios of Der f sIgE/tIgE and Der p sIgE/tIgE were higher in the negative family history of allergy group than in the positive family history of allergy group. Furthermore, total IgE and unknown IgE were higher in the polysensitized group than in the in monosensitized group. The ratios of Der f sIgE/tIgE and Der p sIgE/tIgE were higher in the monosensitized group than in the polysensitized group.ConclusionsFrom this study, we noticed that dust mites are the main cause of asthma in children investigated. Our findings indicate patients with no family history of allergy and monosensitized patients have a higher ratio of sIgE/tIgE, and those patients may benefit more from AIT.

Microbial signature in IgE-mediated food allergies

BackgroundMultiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state.MethodsTo characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31).ResultsThe gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs.ConclusionsOur results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.

Opportunistic Invasive Fungal Infections Mimicking Progression of Non–Small-Cell Lung Cancer

BackgroundMany studies have shown that invasive pulmonary aspergillosis, cryptococcosis, and mucormycosis can mimic radiographic and clinical features of primary lung cancer. However, more research surveying the incidence and outcomes of these fungal infections among patients with a history of lung cancer is needed. The aim of this study was to describe the occurrence and clinical outcomes of opportunistic invasive fungal infections that can mimic tumors in non–small-cell lung cancer patients. Patients and MethodsPatients seen at Stanford University Medical Center from January 1, 2007, to May 1, 2020, with pulmonary aspergillosis, cryptococcosis, or mucormycosis after non–small-cell lung cancer (NSCLC) diagnosis were reviewed. The European Organization for Research and Treatment of Cancer National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to classify patients with evidence of proven or probable invasive fungal infection within our cohort. ResultsA total of 12 patients with proven or probable invasive mold infection (including 8 cases of aspergillosis) and 1 patient with proven cryptococcosis were identified, without any cases of mucormycosis. Of this cohort, 6 patients (46%) showed radiographic findings that were found to be most consistent with lung cancer by radiologists. Eight cases (62%) were suspected of cancer recurrence or progression by the treatment team on the basis of additional considerations of medical history and clinical symptoms. Most patients had active NSCLC or had a history of recurrence without active NSCLC at the time of fungal discovery (11 patients; 85%). Most patients died without full recovery (7 patients; 54%). ConclusionsInvasive pulmonary aspergillosis and cryptococcosis can often be mistaken as cancer recurrence or progression in patients with a history of NSCLC because of mimicking radiographic and clinical characteristics.

Lasmiditan in patients with common migraine comorbidities: a post hoc efficacy and safety analysis of two phase 3 randomized clinical trials

Objective Determine whether common migraine comorbidities affect the efficacy and safety of lasmiditan, a 5-HT1F receptor agonist approved in the United States for the acute treatment of migraine. Methods In SPARTAN and SAMURAI (double-blind Phase 3 clinical trials), patients with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100mg, 200 mg, or placebo. Lasmiditan increased the proportion of pain-free and most bothersome symptom (MBS)-free patients at 2 h after dose compared with placebo. Most common treatment-emergent adverse events (TEAEs) were dizziness, paraesthesia, somnolence, fatigue, nausea, muscular weakness, and hypoesthesia. Based upon literature review of common migraine comorbidities, Anxiety, Allergy, Bronchial, Cardiac, Depression, Fatigue, Gastrointestinal, Hormonal, Musculoskeletal/Pain, Neurological, Obesity, Sleep, and Vascular Comorbidity Groups were created. Using pooled results, efficacy and TEAEs were assessed to compare patients with or without a given common migraine comorbidity. To compare treatment groups, p-values were calculated for treatment-by-subgroup interaction, based on logistic regression with treatment-by-comorbidity condition status (Yes/No) as the interaction term; study, treatment group, and comorbidity condition status (Yes/No) were covariates. Differential treatment effect based upon comorbidity status was also examined. Trial registration at clinicaltrials.gov: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). Results Across all the Comorbidity Groups, with the potential exception of fatigue, treatment-by-subgroup interaction analyses did not provide evidence of a lasmiditan-driven lasmiditan versus placebo differential treatment effect dependent on Yes versus No comorbidity subgroup for either efficacy or TEAE assessments. Conclusions The efficacy and safety of lasmiditan for treatment of individual migraine attacks appear to be independent of comorbid conditions.

The Clinical and Radiological Characterizations of the Allergic Phenotype of Chronic Rhinosinusitis with Nasal Polyps.

PurposeThe allergic phenotype of chronic rhinosinusitis (CRS) and central compartment atopic disease (CCAD) have been described. The CCAD is a radiological phenotype in patients with CRS that presents as a central mucosal disease due to allergy. The subset of patients having chronic rhinosinusitis with nasal polyps (CRSwNP) has not been well characterized. We aim to describe the clinical and radiological characterizations of patients presenting with the allergic phenotype of CRSwNP.Patients and MethodsA cross-sectional study at a tertiary hospital was performed. Adult patients diagnosed with CRSwNP who had both allergology and radiological assessments were enrolled. The symptoms of allergic rhinitis, Lund–Kennedy (LK) endoscopic scoring, Lund–Mackay (LM) computed tomography scan of paranasal sinuses (CTPNS) scoring, CCAD features, skin prick test (SPT) and level of specific IgE were assessed. All the patients underwent SPT for house dust mites.ResultsA total of 38 patients were enrolled. Symptoms, endoscopic and CTPNS scores were higher in the allergy and CCAD groups compared to the nonallergy and nonCCAD groups. The symptom of “need to blow nose” was statistically significant in allergy vs nonallergy (p=0.01) and CCAD vs nonCCAD (p=0.02). There were significant differences in the endoscopic scores in both allergy and CCAD (allergy vs nonallergy, p=0.01; CCAD vs nonCCAD, p=0.03), and CT scores in both allergy and CCAD (allergy vs nonallergy, p=0.02; CCAD vs nonCCAD, p=0.02). All patients with CCAD have worse scoring than nonCCAD (LK score, p=0.03; LM score, p=0.02). Patients with allergy have more polypoidal involvement of the middle turbinates (left middle turbinate, p=0.141; right middle turbinate, p=0.074) and CCAD (left middle turbinate, p=0.017; right middle turbinate, p=0.009) than nonallergy and nonCCAD patients.ConclusionAllergic phenotype of CRSwNP has a worse clinical and radiological disease burden. Optimal treatment of allergy is essential for a better outcome.

Human Rhinovirus Infection Enhances the Th2 Environment in Allergic and Non-allergic Patients with Chronic Rhinosinusitis.

Objectives. This study was conducted to determine whether patients with allergic rhinitis might be more susceptible to human rhinovirus (HRV) infection and whether the effects of infection on the elicited immune responses are different in allergic and non-allergic patients with chronic rhinosinusitis (CRS).Methods. Uncinate process tissues were obtained from 61 CRS patients (of whom 39 had allergies and 22 did not) and were infected with HRV-16 using an air-liquid interface organ culture system. The expression levels of programmed cell death-ligand (PD-L)1, PD-L2, intracellular adhesion molecule 1, interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, and IL-10 were evaluated in the infected nasal mucosa.Results. The HRV infection rates were not significantly different between the allergy (74.4%) and non-allergy (72.7%) groups. In the allergy group, the expression of PD-L1 (P=0.013) and IL-10 (P=0.040) was significantly elevated in the HRV-infected tissues, and there was a strong correlation between PD-L1 and IL-10 (r=0.868, P<0.001). In contrast, infected tissues from the non-allergy group displayed increased levels of IL-4 (P=0.039), IL-5 (P=0.023), and IFN-γ (P=0.031), as well as an increased IL-4/IFN-γ ratio, after HRV infection (P=0.043).Conclusion. This study showed that HRV infection rates were similar in the nasal mucosa of patients with CRS regardless of the presence of allergic rhinitis. HRV infection enhanced the Th2 environment by modulating PD-L1 and PD-L2 expression levels in allergic mucosa and by increasing the IL-4/IFN-γ ratio in non-allergic mucosa.

Pentraxin-3 polymorphisms and pulmonary fungal disease in non-neutropenic patients.

BackgroundPentraxin 3 (PTX3) plays a non-redundant role in innate immunity against fungal diseases. Although single nucleotide polymorphisms (SNPs) of PTX3 are associated with a higher risk of invasive aspergillosis among the immunosuppressed population and chronic obstructive pulmonary disease patients, it is unknown whether PTX3 genetic variants influence the risk of pulmonary fungal disease in immunocompetent patients.MethodsTo investigate the association between PTX3 gene polymorphisms and pulmonary mycosis in non-neutropenic patients, we conducted a case-control study in a tertiary hospital department. Forty-five patients were identified using the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) and enrolled in the case group. Of these patients, 15 had allergic bronchopulmonary aspergillosis (ABPA), 10 had invasive pulmonary aspergillosis (IPA), 18 had pulmonary cryptococcosis, and 2 had other types of pulmonary mycosis. One hundred and twenty-two non-neutropenic inpatients not infected by fungal disease were randomly selected as the control group. We detected three SNPs (rs2305619, rs3816527, and rs1840680) within the PTX3 gene using polymerase chain reaction sequencing and compared their associations with different types of pulmonary fungal disease.ResultsThree SNPs were consistent with Hardy-Weinberg equilibrium (HWE). SNP rs2305619 was in linkage disequilibrium with rs3816527 (D’=0.85) and rs1840680 (D’=0.85), respectively. There was no difference in the genotypic distribution and haplotype frequency of the SNPs between the case group and the control group. When we focused on invasive mold infections as a subgroup, we found that the SNP rs3816527 CC homozygote was associated with a higher risk of IPA (OR, 7.37; 95% CI, 0.93–44.44; P=0.033), while the rs3816527 AA homozygote might lower the risk of pulmonary cryptococcosis (OR, 0.35; 95% CI, 0.11–0.96; P=0.047). No genotypic distribution differences were observed for the other two SNPs (rs2305619 and rs1840680). When it came to the comparison between ABPA subgroup and control group, no difference in single nucleotide polymorphism was observed.ConclusionsThis study showed that the SNP rs3816527 is associated with IPA in non-neutropenic patients. Further investigations in large populations are needed to validate this genetic predisposition. Functional studies are also required.

A survey of anesthetists’ experience and perspectives of perioperative anaphylaxis at an Australian tertiary hospital

Background : Anaphylaxis is a life-threatening emergency that requires prompt recognition and institution of life-saving therapy. Perioperative Anaphylaxis Management Guidelines have been developed by the Australian and New Zealand College of Anaesthetists and Australian and New Zealand Anaesthetic Allergy Group and anesthetic societies worldwide to facilitate diagnosis and management of this rare, but severe complication. Objectives : To perform a cross-sectional survey of the anesthetists’ experience of perioperative anaphylaxis at a single centre and its effect on their practice. Design : Survey questionnaire constructed in Survey Monkey® and sent via e-mail link to all anesthetists. This questionnaire included qualitative and quantitative questions. Setting : Royal Brisbane and Women’s Hospital, a tertiary referral hospital in Queensland. Methods : Anesthetic specialists and provisional fellows at The Royal Brisbane and Women’s Hospital were surveyed using an online platform regarding their experiences of managing anaphylaxis, referral for testing, formal incident reporting and knowledge of existing departmental protocol. We also asked if their experience of anaphylaxis modified their clinical practice. Results : Forty-five out of 102 (44%) of the specialists and provisional fellows surveyed responded. Of these, 17 (38%) had been involved as primary anesthetist and 20 (44.5%) indirectly in at least one suspected case of perioperative anaphylaxis in the past 12-months. Most anesthetists were aware of the resources available in this crisis and appropriate referral for testing had occurred. There was poor local and national reporting of anaphylaxis as a critical incident. Conclusion : A large percentage of the anesthetists surveyed had seen a case of perioperative anaphylaxis in the past year. Managing this life-threatening event has led to practice change for many anesthetists. There is a requirement for further education around incident reporting.

The prescription practices of adrenaline auto-injector for children at risk of anaphylaxis

Background: Guidelines on indications for adrenaline auto-injector (AAI) exist. There is no consensus on the prescription criteria of AAI. However, the European Academy of Allergy and Clinical Immunology (EAACI) and the United Kingdom (UK) resuscitation council provide guidances on prescription practices. Objectives: This study aims to investigate prescription practices of AAIs prescribed by members of four regional pediatric allergy groups (PAGs) in the UK. Materials and Methods: An online questionnaire was e-mailed to the PAGs members. Scenarios of absolute and relative indications for AAI prescriptions (as per the EAACI guidelines) were presented to clinicians to establish whether they would prescribe an AAI. Results: One hundred and seventeen responses from members of PAGs working in four different regions were received. Practices were similar in scenarios of absolute indications for AAI. Intraregional (variations within the regions) as well as interregional (variations between the regions) variations were observed. There were statistically significant interregional differences in scenarios of relative indications for AAIs. For mild reaction to peanut (PN)/tree nut (TN), AAI would be prescribed more often by doctors from Wessex clinicians (67%) than those from Midlands (31%), London (24%), and Northern (20%) (P &lt; 0.05). Whereas for a previous mild reaction to trace of PN/TN, Northern clinicians (47%) would prescribe AAI less often than those from the Midlands (78%), Wessex (82%) and London (79%) (P &lt; 0.05). Intraregional differences were also observed. Conclusions: There is a consensus with absolute indications for AAI prescriptions across and within regions. There are intraregional and interregional differences in prescribing practices in scenarios where there is a relative indications for an AAI. Better intra- and interregional work could improve consistency or practice across the country are explain differences in practice.

UK allergy and immunology in a post‐COVID‐19 era

UK allergy and immunology in a post‐COVID‐19 era

Relationship between gene polymorphism at rs2228055 locus in the exon region of interleukin-10 receptor A and susceptibility to food allergy in children

Objective: To investigate the relationship between gene polymorphism of rs2228055 locus in the exon region of interleukin-10 receptor A (IL-10RA) and susceptibility to food allergy in children. Methods: This was a case-control study. The food allergy group had 150 children who were diagnosed with food allergy in the Pediatric Food Allergy Clinic of Peking University Third Hospital from August 1, 2017 to November 30, 2018. Another 150 healthy children attended Child Health and Development Center in the same hospital were selected as control group. The genotypes of rs2228055 locus in both groups were detected by PCR re-sequencing. And the genotypes and allele frequencies of rs2228055 locus were compared between these two groups, as well as between food allergy children with positive and negative allergen specific IgE, and between those with and without involvement of different organs. Using the computer virtual mutation to stimulate the changes of amino acid caused by change of rs2228055 locus allele, to analyze the effect of amino acid changes on the structure of IL-10RA. The chi-square test was used for comparison between groups. Results: (1) There were 92 males and 58 females in food allergy group, and 86 males and 64 females in control group, without any statistically significant difference (χ(2)=0.497, P=0.481). The ages of the two groups were 4.2 (0.1-15.0) and 8.0 (0.1-14.0) years old, respectively, the difference was statistically significant (Z=-6.109, P<0.01). (2) The genotype frequencies of rs2228055 locus in the food allergy group and the control group were as follows: AA accounted for 73 (48.7%) and 98 (65.3%), AG accounted for 62 (41.3%) and 42 (28.0%), and GG accounted for 15 (10.0%) and 10 (6.7%), respectively. The allele frequencies in the two groups were as follows: 208 (69.3%) and 238 (79.3%) for A, 92 (30.7%) and 62 (20.7%) for G, respectively. AG and GG genotype frequency and the allele G frequency in food allergy group were significantly higher than that in control group (χ(2)=8.501 and 7.862, P=0.014 and 0.005, respectively). (3) There were no significant differences in genotype frequencies and allele frequencies of rs2228055 locus of allergen-specific IgE-positive and negative food allergy children (all P>0.05). (4) There were no significant differences in genotype frequencies and allele frequencies of rs2228055 locus in the manifestations of skin, digestive system and respiratory system in food allergy children (all P>0.05). (5) The computer virtual mutation showed that the mutation energy was -0.08 without any increase in the stability of IL-10RA when the amino acid encoded by rs2228055 locus was changed from isoleucine to valine. Conclusions: The frequencies of genotype AG, GG and allele G of rs2228055 locus in the IL-10RA exon region in food allergy children are higher than that in non-allergic children, and those with the G allele are more likely to develop food allergy.