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

Background: Canada has high immunoglobulin (IG) product utilization, raising concerns about appropriate utilization, cost and risk of shortages. Currently, there is no national set of standardized IG guidelines, and considerable variations exist among the existing provincial guidelines. The aims of this study were: (1) to compare the existing Canadian provincial guidelines on the use of IG products to identify their consistencies and differences and (2) to examine the existing research in Canada on IG supply and utilization following the establishment of IG guidelines to understand the scope of research and pinpoint the gaps.

Methods: A comparative analysis accounted for the differences across provincial IG guidelines. We highlighted similarities and differences in recommendations for medical conditions. A scoping review of citations from MEDLINE, PubMed, Scopus and Embase databases was conducted for studies published from January 01, 2014, to April 12, 2023.

Results: While provincial guidelines represented a considerable overlap in the medical conditions delineated and relatively uniform dose calculations, numerous differences were observed, including in recommendation categories, provision of pediatric dosing, and divergent recommendations for identical conditions based on patient demographics. The scoping review identified 29 studies that focused on the use of IG in Canada. The themes of the studies included: IVIG utilization and audits, the switch from IVIG to SCIG, patient satisfaction with IVIG and/or SCIG, the economic impact of self-administered SCIG versus clinically administered IVIG therapy, and the efficacy and cost-effectiveness of alternative medications to IG treatment.

Conclusion: The differences in guidelines across provinces and the factors influencing IVIG/SCIG use, patient satisfaction, and cost savings are highlighted. Future research may focus on clarifying costs and comparative effectiveness, exploring factors influencing guideline adherence, and evaluating the impact of updated guidelines on IG use and patient outcomes.

Background: Idiopathic Anaphylaxis (IA) is the most common anaphylactic syndrome in adults. Mental health problems associated with IA are not well recognised. We aimed to assess if patients diagnosed with IA were more likely to experience mental health problems compared to a normative Australian population. We additionally hypothesised that the number of anaphylactic episodes would correlate with symptoms of anxiety.

Methods: A total of 34 patients with at least one episode of IA were recruited from an adult immunology clinic. Patients were recruited as part of a separate study evaluating alternative aetiologies in IA. Mental health problems were measured using the Depression, Anxiety and Stress Scale (DASS-21). An extension of the survey included questions specifically focused on the psychological impact of IA.

Results: Compared to population norms, those with IA had significantly higher levels of mental health problems. Statistically significant DASS-21 scores were identified for depression 4.24 vs. 2.57 (p < 0.001), anxiety 4.76 vs. 1.74 (p < 0.012), stress 7.35 vs. 3.95 (p < 0.001) and total score 16.35 vs. 8.00 (p < 0.001). There was no association between two or more episodes of anaphylaxis and increased anxiety levels (β = 0.52, CI -2.59-3.62, p = 0.74).

Conclusions: This is the first paper to demonstrate that patients living with idiopathic anaphylaxis are more symptomatic for mental illness than those in the community. Screening for mental illness and referral for psychological support should be undertaken in people with IA.

Background: To investigate the role of combined impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) in the diagnosis of cough variant asthma (CVA) in preschool children.

Methods: A total of 197 preschool-aged children with chronic cough were selected from the paediatric outpatient clinic. Allergy histories were collected for all children along with IOS and FeNO. Paediatric respiratory specialists divided the children into a CVA group (n = 90) and a noncough variant asthma (nCVA) group (n = 107) according to the diagnostic criteria for CVA After diagnostic treatment, the correlation between the FeNO and IOS values and the diagnosis in the two groups was analysed, and the area under the curve (AUC) of each index was calculated.

Results: (1) X5 was significantly different between the CVA group and the nCVA group (- 4.22 vs. - 3.64, p < 0.001), as was the FeNO value (29.07 vs. 16.64, p < 0.001). (2) Receiver operating characteristic (ROC) analysis showed that the AUCs of FeNO alone and X5 alone were 0.779 and 0.657, respectively, while the AUC of FeNO (cut-off value of 18 ppb) plus X5 (cut-off value of -4.15 cmH2O/(l/s)) reached 0.809.

Conclusions: Children with CVA may have small airway dysfunction at an early stage. For preschool children with chronic cough, the combination of FeNO and X5 can better identify those with CVA.

Trial registration number: This trial was registered with and approved by the Chinese Clinical Trial Registry, with registration number ChiCTRcRRC-17011738, and was reviewed and approved by the Ethics Committee of Southwest Hospital.

Background: Anaphylaxis is an acute, potentially life-threatening allergic reaction that typically occurs after exposure to a trigger, while idiopathic anaphylaxis (IA) occurs in the absence of a trigger. Acute management of both triggered anaphylaxis and IA relies on the use of epinephrine. In some patients with recurrent IA, glucocorticoid prophylaxis with prednisone can be effective. While there is currently no high quality evidence for the use of other prophylactic options to prevent recurrent IA, evolving data exists to support the consideration of biologics that target IgE or the Th2 pathway.

Case presentation: We present the case of a 28 year old female with no atopic or autoimmune history with recurrent episodes of IA since childhood occurring up to twice weekly. There was improvement in acute symptoms with administration of first or second generation antihistamines and/or intramuscular epinephrine. Without an identifiable trigger, she was diagnosed with IA and frequent idiopathic urticaria and omalizumab was added to her treatment regimen with improvement in symptom frequency. After being lost to follow up, she had recurrence of symptom frequency and severity without omalizumab therapy and subsequently presented to our institution. Her workup at this point was negative for food allergy, alpha gal syndrome, systemic mastocytosis, hereditary alpha tryptasemia, carcinoid syndrome, and pheochromocytoma, and she was trialed on dupilumab with near resolution of her symptom frequency over a six month time period.

Conclusion: Recurrent IA is a diagnosis of exclusion that is associated with high morbidity. Prophylaxis remains an area of uncertainty, although prednisone has been effective in some cases. When prednisone is contraindicated or ineffective for the prevention of IA, biologic therapies that target IgE or the Th2 pathway may present a reasonable consideration. This case adds support to the suggestion that dupilumab may be a logical off-label consideration for prophylaxis of recurrent IA. The data for dupilumab in this clinical scenario is still very limited, and further research is required before any recommendation can be made.

Background: The prevalence of eosinophilic asthma in Lebanon, one of the most severe phenotypes among severe asthma, is not known. This study aimed at determining the prevalence of the eosinophilic phenotype defined as an eosinophil count ≥ 300 cells/mm³ among severe asthma patients in Lebanon.

Methods: The Lebanese Chapter of the PREPARE study was a national, multicenter, cross-sectional observational study. Patients aged ≥ 12 years with severe asthma were identified and prospectively enrolled during clinic visits and completed the Global Initiative for Asthma (GINA) assessment of asthma control questionnaire. Patients' health characteristics were collected from medical records and blood samples were obtained for measurement of serum IgE levels and blood eosinophils count.

Results: Overall, 101 patients (with mean age of 46.3 ± 17.0 years and 73.27% females) with severe asthma were included and, among them, 37% had eosinophilic phenotype, 67.3% had atopic phenotype with IgE > 100 IU/mL and 25.7% patients had overlapping atopic and eosinophilic phenotypes. Close to 80% had late-onset asthma, beyond 12 years of age, and around 85% had at least one severe exacerbation in the 12 months prior to study enrolment. The majority of participants [64.4%] had uncontrolled asthma, 24.7% had partially controlled symptoms and 10.9% had controlled symptoms. 19.8% of participants were on chronic oral corticosteroids, 78.2% had short course treatment of corticosteroids and all were prescribed a combination of inhaled corticosteroids and long-acting beta-agonist.

Conclusions: The majority of patients with severe asthma were uncontrolled of which 37% present with an eosinophilic phenotype, which should be taken into consideration for better management of these patients in view of the novel phenotype-specific therapeutic options.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used classes of medications, and are among the leading causes of drug hypersensitivity. NSAIDs hypersensitivity reactions are classified by symptom involvement and NSAIDs subclass cross-reactivity. Reactions varying from cutaneous involvement to respiratory symptoms can be triggered by multiple NSAIDs subclasses. Anaphylaxis, while rare, can be induced by a single NSAID, with tolerability of other structurally unrelated subclasses. Reactions that fall outside of these traditional categories are deemed "blended reactions". We report a unique case of possible anaphylaxis to acetylsalicylic acid (ASA) and ibuprofen, two structurally dissimilar NSAIDs, indicating a severe blended reaction outside of the typical NSAIDs hypersensitivity reaction categories.

Case presentation: An otherwise healthy 45 year old woman was referred to the Allergy and Immunology clinic after developing acute onset dyspnea, lip swelling, and generalized urticaria with ibuprofen use requiring treatment with intramuscular epinephrine in the emergency department. She previously tolerated ibuprofen, naproxen, and acetaminophen and had no history of urticaria, angioedema, asthma, or nasal polyps. She underwent an oral challenge to ASA whereby she developed urticaria and throat irritation with rebound symptoms requiring 2 doses of intramuscular epinephrine. On subsequent visits she passed treatment dose acetaminophen and celecoxib challenges. She was counseled to avoid all other NSAIDs and ASA desensitization was offered should this medication be clinically indicated in the future.

Conclusions: NSAIDs hypersensitivity reactions can be triggered by individual NSAIDs with tolerance of other subclasses or by multiple structurally unrelated NSAIDs due to COX-1 inhibition. Determining the type of reaction (NERD, NECD, NIUA, SNIUAA, or SNIDHR) allows for appropriate oral challenges and safe alternative therapy recommendations. However, not all clinical reactions fit perfectly into these categories. Patients may also develop blended reactions. Our case highlights a severe blended reaction to multiple unrelated NSAIDs, including likely anaphylaxis to ASA. We note the utility of drug provocation tests (DPTs) to identify safe alternative medication options, as well as the importance of performing DPTs in settings properly equipped to assess and manage severe hypersensitivity reactions including anaphylaxis.

Background: Interleukin (IL)-36 family cytokines have received increasing attention, especially in the fields of inflammation and immunity research. However, whether IL-36 family cytokine levels are correlated with the results of the assessment of allergic rhinitis (AR) and affect the severity of AR remains unknown. Therefore, this study aimed to investigate the correlations between IL-36 family cytokine levels and subjective and objective assessment results and to further analyze the possible mechanisms of IL-36 family cytokines in the development of AR.

Methods: An enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of the IL-36 family cytokines IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 in the peripheral blood of patients with AR. The condition of patients with AR was assessed by 22-item sino-nasal outcome test (SNOT-22) score, visual analogue scale (VAS) scores for disease severity, and serum inhalant allergen immunoglobulin E (IgE) detection. Correlations between IL-36 family cytokine levels and subjective and objective assessment results in patients with AR were analyzed.

Results: The concentration of IL-36α in the peripheral blood of patients with AR was the highest, and the concentration of IL-36β was the lowest. The concentration of IL-36α was higher in juvenile patients than in adult patients, and there was a difference in the IL-36Ra level between the perennial allergen group and the seasonal allergen group. There was a positive correlation between IL-36α level and IL-36γ level, IL-36γ level and IL-36Ra level, and IL-36Ra level and IL-38 level, and IL-36β level was positively correlated with IL-36Ra and IL-38 levels, respectively. IL-36α level was positively correlated with VAS score for nasal congestion symptom. IL-36β level was positively correlated with the total VAS score for ocular symptoms and VAS scores for ocular itching and eye pain symptoms. However, there was no correlation between the levels of all cytokines in IL-36 family and SNOT-22 score, the number of positive inhaled allergens, or the highest positive intensity of allergen specific immunoglobulin E (sIgE).

Conclusion: Peripheral blood IL-36 family cytokines play an important role in AR, and the concentrations of IL-36α and IL-36β were related to the severity of symptoms in patients with AR.

Background: While both the AAAAI/ACAAI and the EAACI/GA²LEN/EuroGuiDerm/APAAACI guidelines recommend starting cyclosporine for patients with chronic urticaria who have had an inadequate response to omalizumab, many clinicians are hesitant to initiate cyclosporine due to paucity of clinical data. The objective of this study was to report real-life clinical outcomes in adult patients with chronic urticaria who had an inadequate response to omalizumab and were switched from omalizumab to cyclosporine. Medical records of adult patients with chronic urticaria who had an inadequate response with omalizumab and were later treated with cyclosporine were reviewed retrospectively. Data pertaining to treatment method, clinical response, and adverse effects were recorded.

Results/presentation of cases: Five patients with omalizumab-refractory chronic urticaria, three of whom also had angioedema and one with an inducible urticaria, were treated with low doses of oral cyclosporine (1-3 mg/kg/d). Four of five patients in this case series had complete resolution of symptoms with oral cyclosporine, while continuing other standard therapies. Systemic side effects occurred in three patients which prompted drug discontinuation in two patients.

Discussion: Cyclosporine alone was effective in inducing urticaria control in adult patients with chronic urticaria who had an inadequate response to omalizumab, though the impact of cyclosporine was limited by reversible adverse effects. Adverse effects were associated with pre-existing medical conditions. As novel chronic urticaria therapies are being investigated, this experience highlights the importance of uncovering chronic urticaria subtypes which tend to respond to cyclosporine, while providing alternative treatments with better tolerability.

Background: Autophagy protein 5 (ATG5) regulates airway epithelial cell autophagy, immune response, and inflammation, which is involved in asthma progression. This study aimed to evaluate ATG5 levels and its clinical roles in adult asthma patients.

Methods: Totally, 200 adult asthma patients and 100 healthy controls (HCs) were enrolled in this case-control study. Subsequently, serum ATG5 was measured by enzyme-linked immunosorbent assay.

Results: ATG5 was increased in asthma patients compared with HCs [median (interquartile range): 44.2 (31.7-77.8) vs. 23.2 (16.7-39.2) ng/mL] (P < 0.001). In asthma patients, ATG5 was positively related to male gender (P = 0.022), a family history of asthma (P = 0.035), eosinophil count (P < 0.001), and immune globulin E (P < 0.001), while it was negatively correlated with forced expiratory volume in 1 s (FEV₁)/forced vital capacity (P < 0.001) and FEV₁ (Predicted) (P < 0.001). Meanwhile, ATG5 was inversely associated with T helper (Th) 1 cells (P = 0.008), while it was positively linked with Th2 cells (P < 0.001), Th2/Th1 ratio (P < 0.001), interleukin (IL)-4 (P = 0.002), and IL-4/interferon-γ ratio (P = 0.015). Additionally, ATG5 was positively correlated with tumor necrosis factor-α (P < 0.001), IL-1β (P = 0.001), IL-6 (P = 0.003), and IL-17 (P = 0.029). Notably, ATG5 was elevated in asthma patients at exacerbation compared to those at remission [median (interquartile range): 53.6 (37.6-90.0) vs. 35.6 (28.2-51.5) ng/mL] (P < 0.001). It was also noteworthy that ATG5 was positively linked with exacerbation severity in asthma patients (P = 0.005).

Conclusion: Serum ATG5 is related to increased Th2/Th1 ratio, inflammation, exacerbation risk and severity in adult asthma patients, which serves as a candidate marker for the management of asthma. However, further validation is still needed.

Background: Respiratory conditions, such as asthma, are infrequently associated with auto-inflammatory diseases. We describe five patients with uncontrolled respiratory symptoms that were seen at St. Joesph's Healthcare in Hamilton for severe asthma management diagnosed with rare autoinflammatory conditions using genetic molecular analysis.

Case presentation: Five patients are included in this case series. Gene mutations associated with familial Mediterranean fever, Yao syndrome, Cryopyrin-associated periodic syndrome, and Majeed syndrome were considered to explain partly the patient's clinical manifestation after comprehensive clinical, biochemical, hematological investigations ruled out other disorders such as parasitosis, Allergic Bronchopulmonary Fungosis, Eosinophilic Granulomatosis with Poly Angitis, IgG4 disease, and Hypereosinophilia syndrome.

Conclusions: Complex patients initially presenting with respiratory conditions in addition to unexplained autoinflammatory conditions are a diagnostic challenge. Genetic molecular testing provides healthcare practitioners with useful information that may diagnose underlying auto-inflammatory diseases in undifferentiated patients. Role of inflammasome-activation in asthma and eosinophilia needs further investigation.