Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology最新文献

Background: Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA.

Case presentation: Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly.

Conclusions: These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner's attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing.

Background: Asthma is an important non-communicable disease worldwide. DNA methylation is associated with the occurrence and development of asthma. We are aimed at assuring differential expressed genes (DEGs) modified by aberrantly methylated genes (DMGs) and pathways related to asthma by integrating bioinformatics analysis.

Methods: One mRNA dataset (GSE64913) and one gene methylation dataset (GSE137716) were selected from the Gene Expression Omnibus (GEO) database. Functional enrichment analysis was performed using GeneCodies 4.0 database. All gene expression matrices were analyzed by Gene set enrichment analysis (GSEA) software. STRING was applied to construct a protein-protein interaction (PPI) network to find the hub genes. Then, electronic validation was performed to verify the hub genes, followed by the evaluation of diagnostic value. Eventually, quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of hub genes.

Results: In total, 14 hypomethylated/high-expression genes and 10 hypermethylated/low-expression genes were obtained in asthma. Among them, 10 hub genes were identified in the PPI network. Functional analysis demonstrated that the differentially methylated/expressed genes were primarily associated with the lung development, cytosol and protein binding. Notably, HLA-DOA was enriched in asthma. FKBP5, WNT5A, TM4SF1, PDK4, EPAS1 and GMPR had potential diagnostic value for asthma.

Conclusion: The project explored the pathogenesis of asthma, which may provide a research basis for the prediction and the drug development of asthma.

Background: IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing.

Case presentation: Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127-/CD4+/CD25+/FOXP3+-396 cells-63%) and a pathogenic mutation in FOXP3 gene (c.1150G>A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome.

Conclusions: IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.

Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin's lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin's lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

Background: The antigen avoidance has been used in the diagnosis and treatment of hypersensitivity pneumonitis (HP); however, its usefulness in stable fibrotic HP is controversial.

Objective: To investigate the usefulness of the antigen avoidance test in patients with fibrotic HP in stable phase.

Methods: The antigen avoidance test was conducted during a 2-week hospitalization comparing clinical parameters at admission and before discharge. A retrospective review of patients who underwent surgical lung biopsy or transbronchial lung cryobiopsy, who were diagnosed with fibrotic HP by multi-disciplinary discussion, and whose disease progression was stable for more than two months before the antigen avoidance test was done.

Results: Between 2016 and 2021, 40 patients met the criteria, and 17 (43%) patients had a positive antigen avoidance test. The patients with positive in the antigen avoidance test had significantly greater annual forced vital capacity (FVC) decline than those with negative before the test (- 6.5% vs. - 0.3%, p = 0.045). The patients with positive antigen avoidance test had less annual FVC decline than those with negative in the year following the test (0.8% vs. - 5.0%, p = 0.048). The differences in annual improvement were found for serum Krebs von den Lungen-6 between the positive and negative patients in the year following the test (- 27% vs. - 5%, p = 0.049). In multivariate Cox hazard regression analysis, a negative result of the antigen avoidance test was a risk factor for death or acute exacerbation of fibrotic HP (HR = 0.26 [95% CI: 0.07-0.90], p = 0.034).

Conclusions: In fibrotic HP patients in stable phase, the antigen avoidance test under a 2-week hospitalization was valuable in predicting prognosis.

Background: To date, little consideration has been given to access to allergy-related care, despite the fact that food allergy affects a considerable proportion of children. As such, the current study aimed to describe access to food allergy-related services in Canada and the United States (US).

Methods: Participants were recruited via social media from March-July 2021 and were asked to complete an online survey focused on food allergy-related medical care. Participants were Canadian and US residents who live with a child < 18 years old, with ≥ 1 food allergy. A series of logistic regressions were used to assess the associations between country of residence and type of allergy testing utilized during diagnosis.

Results: Fifty-nine participants were included in the analysis (Canadian: 32/59; 54.2%; US residents: 27/59; 45.8%). Relative to Canadian participants, US respondents were less likely to be diagnosed using an oral food challenge (OFC; OR 0.16; 95% CI 0.04; 0.75: p < 0.05). Compared to children diagnosed by age 2 years, those diagnosed at age 3 years and older were less likely to have been diagnosed using an OFC (OR 0.12; 95% CI 0.01; 1.01; p = 0.05).

Conclusions: Access to food allergy-related services, varies between Canada and the US. We speculate that this variation may reflect differences in clinical practice and types of insurance coverage. Findings also underscore the need for more research centered on food allergy-related health care, specifically diagnostic testing, among larger and more diverse samples.

Background: In anaphylaxis, the dosing of injectable epinephrine in medical settings has been arbitrarily recommended to be 0.01 mg/kg of body weight. For ethical reasons, there have been no dose-response studies or double-blind studies performed on patients with active anaphylaxis. Intramuscular delivery of epinephrine has been the standard. Auto-injectors for use in the treatment of anaphylaxis are available in four strengths (0.1, 0.15, 0.3, and 0.5 mg). However, in many countries, only the 0.15 and 0.3 mg strengths are available. Consequently, many adult, heavy patients are prescribed the 0.3 mg dose, which may result in only one-fifth to one-third of the recommended weight-based dose being administered in heavy patients experiencing anaphylaxis. Underdosing may have therefore contributed to mortality in anaphylaxis.

Objective: To review the doses of epinephrine recommended for the treatment of anaphylaxis in the community, and assess whether recommendations should be made to increase dosing for heavy adult patients in hopes of avoiding future deaths from anaphylaxis.

Methods: We reviewed multiple national and international recommendations for the dosing of epinephrine. We also reviewed the literature on adverse drug reactions from epinephrine, lethal doses of epinephrine, and epinephrine dose-finding studies.

Results: The majority of national and regional professional societies and authorities recommend epinephrine delivered by auto-injectors at doses far lower than the generally accepted therapeutic dose of 0.01 mg/kg body weight. Furthermore, we found that the recommendations vary even within regions themselves.

Conclusions: We suggest prescribing more appropriate doses of epinephrine auto-injectors based on weight-based recommendations. There may be some exceptions, such as for patients with heart disease. We hypothesize that these recommendations will lead to improved outcomes of anaphylaxis.

Background: Long non-coding RNAs (lncRNAs) have been extensively reported to play critical roles in the pathogenesis of various disease, especially in cancer. However, little is known about the role of lncRNAs in the pathogenesis of pediatric allergic asthma.

Methods: High-throughput sequencing analysis was performed to identify differentially expressed mRNAs and lncRNAs in peripheral blood mononuclear cells (PBMCs) from 3 children with allergic asthma and 3 matched healthy controls. Bioinformatics analysis was used to select candidate lncRNAs and mRNAs that may be involved in the pathogenesis of asthma. Candidate lncRNAs were validated in a larger size of asthma patients and healthy controls. Finally, lncRNAs and molecular pathways associated with the pathogenesis of allergic asthma were identified by competing endogenous RNA (ceRNA) analysis.

Results: Five differentially expressed lncRNAs were identified after high-throughput sequencing and verified by real-time PCR. LncRNAs ENST0000631797, TCONS_00004989 and ENST00000499459 were verified to be differentially expressed in allergic asthma. Besides, ENST00000499459/DIXDC1 axis was identified to play a crucial role in allergic asthma after comprehensive ceRNA network analysis.

Conclusion: ENST00000499459 and TCONS_00004989 are potential biomarkers for house dust mite-induced allergic asthma.

Background: Sensitization to Ara h 2 has been proposed as a promising biological marker for the severity of peanut allergy and may reduce the need for oral food challenges. This study aimed to evaluate whether peanut oral food challenge is still a useful diagnostic tool for children with suspected peanut allergy and an elevated level of Ara h 2-specific IgE. Additionally, we assessed whether well-controlled asthma is an additional risk for severe reactions.

Methods: A retrospective analysis of 107 children with sensitization to Ara h 2-specific IgE (> 0.35 kU/l) undergoing open peanut challenges during 2012-2018 in the Tampere University Hospital Allergy Centre, Finland.

Results: Of the 107 challenges, 82 (77%) were positive. Serum levels of Ara h 2 -sIgE were higher in subjects with a positive challenge than in those who remained negative (median 32.9 (IQR 6.7-99.8) vs. 2.1 (IQR 1.0-4.9) kU/l), p < 0.001) but were not significantly different between subjects with and without anaphylaxis. No correlation was observed between the serum level of Ara h 2-sIgE and reaction severity grading. Well-controlled asthma did not affect the challenge outcome.

Conclusions: Elevated levels of Ara h 2-specific IgE are associated with a positive outcome in peanut challenges but not a reliable predictor of reaction severity. Additionally, well-controlled asthma is not a risk factor for severe reactions in peanut challenges in children with sensitization to Ara h 2.

Background: Self-administered subcutaneous immunoglobulin G (SCIg) reduces nursing time and eliminates the need for treatment at ambulatory care clinics, as compared with clinic-based intravenously administered IgG (IVIg), and are therapeutically equivalent. Estimating the economic impact of self-administered SCIg versus clinic-administered IVIg therapy may guide treatment recommendations.

Methods: A retrospective population-based cohort study using administrative data from Alberta was performed; those treated with IgG between April 1, 2012 and March 31, 2019 were included. Costs for medical laboratory staff and nursing time, as well as ambulatory care visits were considered. Univariate generalized linear model regression with gamma distribution and log link was used to compare cost ($CDN 2020) between SCIg and IVIg administration. Stratified analysis by age (≥ 18-years; < 18-years) was performed.

Results: Among 7,890 (6,148 adults; 1,742 children) individuals who received IgG, the average administration cost per patient-year of self-administered SCIg was $5,386 (95% confidence interval [CI] $5,039, $5,734) lower than clinic-administered IVIg; per patient-year cost of self-administered SCIg was $817 (95% CI $723, $912) versus $6,204 (95% CI $6,100, $6,308) for clinic-administered IVIg. The per patient-year cost of self-administered SCIg was $5,931 (95% CI $5,543, $6,319) lower among adults and $3,177 (95% CI $2,473, $3,882) lower among children compared with clinic-administered IVIg. An estimated $31.0 million (95% CI $29.0, $33.0) in cost savings to the health system would be realised if 80% of individuals switched from clinic-administered IVIg to self-administered SCIg.

Conclusions: Self-administered SCIg is substantially less costly from a health care payer perspective in Canada. Within this type of health system, switching to self-administered SCIg has the potential to reduce overall health care costs, lessen nursing burden, and may increase clinic-based capacity for others.