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

Background: The Cystic Fibrosis Foundation Patient Registry (CFFPR) reports a high prevalence of asthma (34.6%) in people with Cystic Fibrosis (PwCF). While our current understanding of this relationship is limited, a type 2 inflammatory (T2) phenotype has often been identified in CF patients.

Research question: This study aimed to evaluate the relationship between the eosinophilic CF T2 inflammatory phenotype and CF-related pulmonary outcomes and microbiological data.

Study design and methods: We conducted a retrospective chart review of adult patients with CF (18 and older; n = 93) receiving their care at University of Virginia Medical Center adult program from January, 2013 through December, 2018. Data collected included demographic data, CFTR (CF transmembrane conductance regulator) mutation, CF comorbidities, medications, Absolute Eosinophil Counts (AEC) in cells/µL and Immunoglobulin E (IgE) levels in IU/mL.

Results: Of 93 patients screened for study eligibility, 74 were included in the final analysis; 19 patients were excluded due to lack of longitudinal data across the study timeline. Lung function decline correlated with increased AEC (p < 0.001) and IgE (p < 0.001) even when adjusting for covariates: age, gender, presence of Pseudomonas spp., MRSA, other bacterial spp., Aspergillus spp., and other fungi (p < 0.001). Univariate analysis demonstrated that people with CF who experienced more than 2 exacerbations requiring hospitalizations and/or intravenous antibiotics a year were more likely to have high AEC (p = 0.018). Logistic regression showed that as AEC increases, the probability that the measurement was taken during a CF exacerbation increases (p = 0.0039). A linear mixed model showed that each additional annual exacerbation event increased on average the log IgE by 0.04. (p = 0.015). This finding remained stable in a multivariate model (p = 0.0145). When adjusted for atopy, log IgE increases as the number of exacerbation events increases (p = 0.022). There was no association between AEC and IgE and microbiological colonization.

Interpretation: This study has shown that in CF patients, T2 inflammation based on serum AEC and IgE correlated with pulmonary exacerbations requiring hospitalizations and/or intravenous antibiotics, independent of bacterial airway colonization. In addition, lung function decline correlated with increased IgE and AEC. Further studies are needed to explore these correlations and potential impact on treatment.

Background: There is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population.

Objective: To report the prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian patient population diagnosed with chronic urticaria.

Methods: A retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records.

Results: Seventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Vitamin B12 (cobalamin) deficiency, defined as serum vitamin B12 level ≤ 250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and vitamin B12, 68% reported gastrointestinal symptoms.

Conclusions: This is the first study to provide data on the high prevalence of gastrointestinal symptoms and vitamin B12 (cobalamin) deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients. Trial registration Not applicable.

Background: DCLRE1C gene mutation leads to Artemis deficiency, a severe form of combined immunodeficiency (SCID). Impaired DNA repair and block in early adaptive immunity maturation results in T-B-NK+ immunodeficiency associated with radiosensitivity. Recurrent infections early in life are the main characteristic of Artemis patients.

Method: Among 5373 registered patients, 9 Iranian patients (33.3% female) with confirmed DCLRE1C mutation were identified since 1999-2022. The demographic, clinical, immunological and genetic features were collected through retrospective investigation of medical records and using next generation sequencing.

Results: Seven patients were born in a consanguineous family (77.8%). The median age of onset was 6.0 (5.0-17.0) months. Severe combined immunodeficiency (SCID) was clinically detected at a median (IQR) age of 7.0 (6.0-20.5) months, following a median diagnostic delay of 2.0 (1.0-3.5) months The most typical first presentation was pneumonia (44.4%) and otitis media (3.33%), followed by BCG lymphadenitis (22.2%) and gastroenteritis (11.1%). The most prevalent manifestations were respiratory tract infections (including otitis media) (66.6%) and chronic diarrhea (66.6%). In addition, juvenile idiopathic arthritis (P5) and celiac disease and idiopathic thrombocytopenic purpura (P9) as autoimmune disorders were reported in 2 patients. All patients had reduced B CD19+ and CD4+ cell counts. IgA deficiency occurred in 77.8% of individuals.

Conclusion: Recurrent infections particulary respiratory tract infection and chronic diarrhea during the first months of life in patients born to consanguineous parents should raise the suspicion for inborn errors of immunity, even in the presence of normal growth and development.

Background: In Canada, severe asthma affects an estimated 5-10% of people with asthma and is associated with frequent exacerbations, poor symptom control and significant morbidity from the disease itself, as well as the high dose inhaled, and systemic steroids used to treat it. Significant heterogeneity exists in service structure and patient access to severe asthma care, including access to biologic treatments. There appears to be over-reliance on short-acting beta agonists and frequent oral corticosteroid use, two indicators of uncontrolled asthma which can indicate undiagnosed or suboptimally treated severe asthma. The objective of this modified Delphi consensus project was to define standards of care for severe asthma in Canada, in areas where the evidence is lacking through patient and healthcare professional consensus, to complement forthcoming guidelines.

Methods: The steering group of asthma experts identified 43 statements formed from eight key themes. An online 4-point Likert scale questionnaire was sent to healthcare professionals working in asthma across Canada to assess agreement (consensus) with these statements. Consensus was defined as high if ≥ 75% and very high if ≥ 90% of respondents agreed with a statement.

Results: A total of 150 responses were received from HCPs including certified respiratory educators, respirologists, allergists, general practitioners/family physicians, nurses, pharmacists, and respiratory therapists. Consensus amongst respondents was very high in 37 (86%) statements, high in 4 (9%) statements and was not achieved in 2 (5%) statements. Based on the consensus scores, ten key recommendations were proposed. These focus on referrals from primary and secondary care, accessing specialist asthma services, homecare provision for severe asthma patients and outcome measures.

Conclusions: Implementation of these recommendations across the severe asthma care pathway in Canada has the potential to improve outcomes for patients through earlier detection of undiagnosed severe asthma, reduction in time to severe asthma diagnosis, and initiation of advanced phenotype specific therapies.

Background: Angioedema with eosinophilia (AE) is a rare allergic disease classified as episodic or nonepisodic. AE is characterized by angioedema, urticaria, fever, weight gain, and eosinophilia, but its etiology and pathogenesis have not yet been clarified.

Case presentations: We present a 70-year-old woman presented with generalized edema and urticaria after Moderna COVID-19 vaccination. Peripheral blood eosinophil count was marked elevated and echocardiography and Doppler ultrasonography of both the upper and lower extremities were unremarkable. Her symptoms and peripheral blood eosinophil count were improved after systemic steroid therapy, but she failed to respond to steroid tapering. Reslizumab (anti-interluekin-5) was administered intravenously, and she remained symptom free with a normal eosinophil count during 8 months of reslizumab treatment without steroids.

Conclusions: We report a case of nonepisodic AE after COVID-19 vaccination that was successfully treated with reslizumab.

Background: High-fidelity simulations based on real-life clinical scenarios have frequently been used to improve patient care, knowledge and teamwork in the acute care setting. Still, they are seldom included in the allergy-immunology curriculum or continuous medical education. Our main goal was to assess if critical care simulations in allergy improved performance in the clinical setting.

Methods: Advanced anaphylaxis scenarios were designed by a panel of emergency, intensive care unit, anesthesiology and allergy-immunology specialists and then adapted for the adult allergy clinic setting. This simulation activity included a first part in the high-fidelity simulation-training laboratory and a second at the adult allergy clinic involving actors and a high-fidelity mannequin. Participants filled out a questionnaire, and qualitative interviews were performed with staff after they had managed cases of refractory anaphylaxis.

Results: Four nurses, seven allergy-immunology fellows and six allergy/immunologists underwent the simulation. Questionnaires showed a perceived improvement in aspects of crisis and anaphylaxis management. The in-situ simulation revealed gaps in the process, which were subsequently resolved. Qualitative interviews with participants revealed a more rapid and orderly response and improved confidence in their abilities and that of their colleagues to manage anaphylaxis.

Conclusion: High-fidelity simulations can improve the management of anaphylaxis in the allergy clinic and team confidence. This activity was instrumental in reducing staff reluctance to perform high-risk challenges in the ambulatory setting, thus lifting a critical barrier for implementing oral immunotherapy at our adult center.

Background: Chronic obstructive pulmonary disease (COPD) affects up to 10% of Canadians. Patients with COPD may present with secondary humoral immunodeficiency as a result of chronic disease, poor nutrition or frequent courses of oral corticosteroids; decreased humoral immunity may predispose these patients to mucosal infections. We hypothesized that decreased serum immunoglobulin (Ig) levels was associated with the severity of an acute COPD exacerbations (AECOPD).

Methods: A prospective study to examine cardiovascular risks in patients hospitalized for AECOPD, recruited patients on the day of hospital admission and collected data on length of hospital stay at index admission, subsequent emergency department visits and hospital readmissions. Immunoglobulin levels were measured in serum collected prospectively at recruitment.

Results: Among the 51 patients recruited during an admission for AECOPD, 14 (27.5%) had low IgG, 1 (2.0%) low IgA and 16 (31.4%) low IgM; in total, 24 (47.1%) had at least one immunoglobulin below the normal range. Patients with low IgM had longer hospital stay during the index admission compared to patients with normal IgM levels (6.0 vs. 3.0 days, p = 0.003), but no difference in other clinical outcomes. In the whole cohort, there was a negative correlation between serum IgM levels and length of hospital stay (R = - 0.317, p = 0.024). There was no difference in clinical outcomes between subjects with normal and low IgG levels.

Conclusion: In patients presenting with AECOPD, low IgM is associated with longer hospital stay and may indicate a patient phenotype that would benefit from efforts to prevent respiratory infections. Trial registration statement: Retrospectively registered.

Background: House dust mite (HDM) induces greater responses than other allergens during allergen bronchoprovocation (ABP) testing. The two standardized methods for reporting results of ABP tests are the maximal percent fall in forced expiratory volume in one second (FEV_{1, max}; %) and the area under the FEV₁ vs time curve (AUC; %FEV₁ x min). The relationship between these methods has not been previously investigated.

Aims: We aimed to measure the correlation between FEV_{1, max} and AUC during the early asthmatic response (EAR) and the late asthmatic response (LAR), and to determine if the EAR recovery period for HDM would be longer than other allergens (cat, grass, horse, and ragweed).

Methods: We retrospectively calculated the AUC and correlation between FEV_{1, max} and AUC during the EAR_(0-2 h) and LAR_(3-7 h) for each allergen. We compared EAR_(0-3 h) and LAR_(3-7 h) FEV_{1, max}, AUC and absolute difference in FEV_{1, max} to the most recovered FEV₁ (FEV_{1, min}). We performed pairwise comparisons of correlation and slope values using Fischer's r to z transformation and t-tests, respectively. AUC and absolute differences in FEV_{1, max} and FEV_{1, min} were compared using a one-way ANOVA test, followed by a post-hoc Scheffe test.

Results: Correlation between the FEV_{1, max} and AUC during the EAR_(0-2 h) (n = 221) was 0.807, and was 0.798 during the LAR_(3-7 h) (n = 157 of 221), (difference p = 0.408). The EAR_(0-3 h) AUC and FEV_{1, max} did differ between allergens (both p < 0.0001) but the LAR_(3-7 h) AUC and FEV_{1, max} did not (p = 0.548 and 0.824, respectively). HDM did not have a larger AUC or FEV_{1, max}, than all other allergens during the EAR_(0-3 h) or the LAR_(3-7 h). The absolute difference between the FEV_{1, max} and FEV_{1, min} during the EAR_(0-3 h) did not differ between allergens (p = 0.180).

Conclusion: The FEV_{1, max} and AUC for both the EAR_(0-2 h) and LAR_(3-7 h) had excellent correlation, with no significant difference. Thus, significant bronchoconstriction will likely result in a longer recovery period. There was no evidence of delayed EAR_(0-3 h) recovery following HDM challenges, so HDM did not induce a larger response compared to all the other allergens examined.

Registration: Not registered. This is not a clinical trial. (This study is a retrospective analysis of data collected during several registered trials.).

Background: The diagnosis of food allergy is based on a history of immediate allergic reaction following food ingestion, and skin prick test (SPT) demonstrating sensitization with commercial extracts (CE) or fresh food (FF). For most food allergens, the SPT with FF is considered more accurate and predictive. Regarding cow's milk, the results are inconclusive. This retrospective study aimed to evaluate the accuracy of SPT with fresh milk compared to CE (cow's milk and casein) for evaluation of cow's milk allergy (CMA).

Methods: This study summarized the medical records of children, diagnosed with CMA. The data include demographics, skin tests and oral food challenge results, as well as atopic comorbidities.

Results: Records of 698 patients with the diagnosis of CMA were reviewed, 388 fulfilled the inclusion criteria. Overall, 134 patients (34.54%) had an additional atopic disease. The SPT wheal size with fresh milk was significantly larger than with CE (cow's milk and casein) at first evaluation or before oral food challenge (OFC). Combination of SPT results (CE and FF) gave the maximal odds ratio for reaction during OFC and SPT with fresh milk alone gave the minimal OR (34.18 and 4.74, respectively).

Conclusions: SPT with CE for CMA evaluation is more reliable than SPT performed with fresh milk. In patients suspected of having IgE-mediated CMA, before deciding on performing OFC, it is advised to perform SPT with at least two different extracts, and always include casein. Fresh milk can serve as a backup if commercial extracts are not available. In cases that the SPT with fresh milk is 3 mm or less, there is 93.3% chance that the OFC will pass without reaction. Trial registration This study protocol was reviewed and approved by the Ethics Committee of Meir Medical Center, IRB Number 0083-18 MMC.

Background: Allergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex^®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC.

Methods: A cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes.

Results: Over the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios.

Conclusions: In this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA.