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Medical Journal Review

September 2021

WAO Reviews – Editors’ Choice

Articles are selected for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases by Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor.

Asthma and Coronavirus Disease 2019 risk: A systematic review and meta-analysis
Sunjaya AP, Allida SM, Di Tanna GL, Jenkins CR
European Respiratory Journal 2021; 58(3): Published online ahead of print (24 August)

Thus far, case series and cohort studies have reported conflicting results regarding the vulnerability to and risk of mortality of people with asthma from COVID-19. In this study, Sunjaya and colleagues examined whether people with asthma are at a higher risk of being infected, being hospitalized, or having poorer clinical outcomes from COVID-19. They do this through exploring a systematic review and meta-analysis based on five main databases, which included the World Health Organization (WHO) COVID-19 database, between 1 December 2019 to 11 July 2021, and involved studies with a control (non-asthma) group. They found 51 studies with an 8.08% (95% CI 6.87-9.30) pooled prevalence of people with asthma among COVID-19 positive cases. Overall, they reported that the risk of being infected with SARS-CoV-2 was reduced compared to the non-asthma group. No statistically significant differences in hospitalization, ICU admission, and ventilator use were found between groups. Subgroup analyses showed significant differences in outcomes from COVID-19 between America, Europe, and Asia. The authors suggested that additional studies are required to confirm this risk profile, particularly in Africa and South America where few studies originate.

Four subtypes of childhood allergic rhinitis identified by latent class analysis
Yavuz ST, Oksel Karakus C, Custovic A, Kalayci O
Pediatric Allergy and Immunology 2021; Published online ahead of print (26 July)

Childhood allergic rhinitis (AR) is clinically heterogenous. To better understand, the authors utilized data-driven techniques to ascertain their association with patterns of symptoms, allergic sensitization, and comorbidities in attempt to identify distinct phenotypes in children with AR. They recruited 510 children with physician-diagnosed AR, of whom 205 (40%) had asthma. Latent class analysis (LCA) was performed to identify latent structure within the data set using 17 variables (allergic conjunctivitis, eczema, asthma, family history of asthma, family history of allergic rhinitis, skin sensitization to 8 common allergens, tonsillectomy, and adenoidectomy). They found 4 latent classes: (1) AR with grass mono-sensitization and conjunctivitis (n = 361, 70.8%); (2) AR with house dust mite sensitization and asthma (n = 75, 14.7%); (3) AR with pet and grass polysensitization and conjunctivitis (n = 35, 6.9%); and (4) AR among children with tonsils and adenoids removed (n = 39, 7.6%). Perennial AR was significantly more common among children in Class 2 (OR 5.83, 95% CI 3.42– 9.94, p < .001) and Class 3 (OR 2.88, 95% CI 1.36–6.13, p = .006). Mild and intermittent AR symptoms were significantly more common in children in Class 2 compared to those in Class 1. AR was more severe in Class 1 compared to other 3 classes, indicating that upper respiratory symptoms are more severe among children with isolated seasonal rhinitis, than in those with rhinitis and coexisting asthma.

Presence of IgE autoantibodies against eosinophil peroxidase and eosinophil cationic protein in severe chronic spontaneous urticarial and atopic dermatitis
Sánchez J, Sánchez A, Munera M et al
Allergy Asthma & Immunology Research 2021;13(5):746-761

Eosinophils are frequently found in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU), and they release eosinophil peroxidase (EPX) and eosinophil cationic protein (ECP). Some suggest that exposure to these proteins could trigger an autoimmune response which may contribute to the pathogenesis and severity of skin inflammation. In this study, Sánchez and colleagues investigated the immunoglobulin E (IgE) response against eosinophil proteins in CSU and AD via studying patients with severe AD and severe CSU and healthy subjects, examining the presence of IgE autoantibodies and cross-reactivity against EPX, ECP, and thyroid peroxidase (TPO). They found the frequency of anti-EPX IgE (28.8%) and anti-ECP IgE (26.6%) were higher in the AD group, and anti-TPO IgE was higher in the CSU group (27.2%). In the CSU group, there was a correlation between the anti-EPX IgE and anti-TPO IgE levels (r = 0.542, P < 0.001); TPO inhibited 42% of IgE binding to EPX, while EPX inhibited 59% of IgE binding to TPO, suggesting a cross-reactivity with EPX as a primary sensitizer. Furthermore, they found greater inhibition when using pooled sera from patients with CSU and AD, TPO inhibited 52% of IgE binding to EPX, while EPX inhibited 78% of IgE binding to TPO. They also found cross-reactivity between EPX and TPO could explain thyroid problems in patients with CSU. Overall, this study suggests that IgE against eosinophil proteins may contribute to chronic inflammation in AD and CSU.

Asthma phenotyping in primary care: Applying the International Severe Asthma Registry eosinophil phenotype algorithm across all asthma severities
Kerkhof M, Tran TN, Allehebi R et al
Journal of Allergy and Clinical Immunology: In Practice 2021; Published online ahead of print (14 September)

In this study, Kerkhof and colleagues apply an inflammatory algorithm in a UK primary care asthma cohort, specifically quantifying the eosinophilic phenotype, exploring the relationship between likelihood of eosinophilic phenotype and asthma severity/healthcare resource utilization (HCRU). Patients (≥13 years old) with active asthma and ≥1 blood eosinophil count included from the Optimum Patient Care Research Database and the Clinical Practice Research Datalink were categorized according to the likelihood of eosinophilic phenotype using the ISAR gradient eosinophilic algorithm. Patient demographic, clinical, and HCRU characteristics were described for each phenotype, finding of 241,006 patients, 50.3%, 22.2% and 21.9% “most likely” (Grade 3), “likely” (Grade 2), and 115 “least likely” (Grade 1) had an eosinophilic phenotype respectively, and 5.6% had a non-eosinophilic phenotype (Grade 0). Compared to patients with non-eosinophilic asthma, those “most likely” to have an eosinophilic phenotype tended to have more co-morbidities (% with Charlson co-morbidity index ≥2: 28.2% vs 6.9%) and experienced more asthma attacks (% with ≥1 attack: 24.8% vs 15.3%). These patients were also more likely to have difficult-to-treat asthma (31.1% vs 18.3%), receive more intensive treatment (% on GINA (2020) Step 4 or 5: 44.2% vs 27.5%), and greater HCRU (e.g. 10.8 vs 121 7.9 GP all-cause consultations/year). Overall this reinforces that the eosinophilic asthma phenotype predominates in primary care and is associated with greater asthma severity and HCRU. The authors conclude that these patients may benefit from earlier and targeted asthma therapy

IgE-recognition of the house dust mite allergen Der p 37 is associated with asthma
Huang JH, Resch-Marat Y, Casset A et al
Journal of Allergy and Clinical Immunology 2021; Published online ahead of print (19 August)

The intent of this study was to identify, characterize, and evaluate the diagnostic utility of a new house dust mite (HDM) allergen, by performing cDNA coding for a new Dp allergen. Der p 37, was isolated from a Dp expression library with allergic patients IgE antibodies. Recombinant Der p 37 expressed in Escherichia coli was purified, characterized (by mass spectrometry, circular dichroism, and IgE reactivity by ImmunoCAP ISAC technology) with sera from clinically defined HDM-allergic patients (n=111). The allergenic activity of rDer p 37 was studied by basophil activation and CD4+ T cell responses by CFSE dilution assays. Specific antibodies raised against rDer p 37 were used for the ultrastructural localization of Der p 37 in mites by immunogold-transmission electron microscopy. The found that Der p 37, a 26 kDa allergen with homology to chitin-binding proteins is immunologically distinct from Der p 15, 18, 23. It is located in the peritrophic membrane of fecal pellets. Der p 37 reacted with IgE antibodies from a third of HDM allergic patients and induced specific basophil- and CD4+ T cell activation. Der p 37-IgE positive patients had significantly higher IgE levels to major HDM allergens, reacted with more HDM allergens, and had a higher risk (OR=3.1) of asthma as compared to Der p 67 37-negative patients. The results indicate that this newly defined Dp allergen (Der p 37), is recognized by one-third of HDM allergic patients and may serve as a surrogate marker for severe HDM-sensitization and asthma.

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