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Medical Journal Review

May 2020

WAO Reviews – Editors' Choice

The Editors’ Choice comes to you from Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD, FACAAI, FAAAAI. They select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible, for their accessibility to everyone.

Handling of allergen immunotherapy in the COVID-19 pandemic: An ARIA-EAACI Statement
Klimek L, Jutel M, Akdis C, Bousquet J, Akdis M et al.
Allergy 2020; Published online ahead of print (24 April)
https://doi.org/10.1111/all.14336

This EAACI expert panel regarding use of allergen immunotherapy (AIT) during the COVID-19 pandemic suggest the possibility that expanding injection intervals in the continuation phase may be beneficial. They recommend that confirmed cases should discontinue AIT, both subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT), independent of disease severity until the symptoms have completely resolved and/or an adequate quarantine has been performed. In patients, who recovered from COVID-19 or who are found to have a sufficient SARS-CoV-2 antibody response after (asymptomatic) disease, AIT can be started or continued as planned. AIT also can be continued as usual in patients without clinical symptoms and signs of COVID-19 or other infections and without a history of exposure to SARS-CoV-2 or contact to COVID-19 confirmed individuals within the past 14 days. Finally, they note that SLIT offers the possibility of taking immunotherapy at home, thus avoiding the need to travel to or stay in an allergy clinic or doctor’s office, which would be associated with a risk of infection.

Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure
Besedovsky L, Benischke M, Fischer J, Yazdi AS, Born J
PNAS 2020;117(20):10983-10988.
https://doi.org/10.1073/pnas.1920564117

In this provocative article by Besedovsky et al., the authors provide evidence that allergic responses can be conditioned to contextual information alone, even after only a single trial conditioning procedure, and that sleep is necessary to consolidate this rapidly acquired maladaptive response. The results unravel a mechanism that could explain part of the strong psychological impact on allergic responses.

Different expression levels of interleukin-35 in asthma phenotypes
Li W, Gao R, Xin T, Gao P
Respiratory Research 2020;21(1):89
https://doi.org/10.1186/s12931-020-01356-6

Interleukin (IL)-35 is a newly discovered inhibitory cytokine, which is produced by regulatory B and T lymphocytes and belongs to the IL-12 family. It has been shown to play a suppressive role in human inflammatory diseases; however, its role in asthma phenotypes is unclear. In this study by Li and colleagues, the authors examine the sputum IL-35 level in patients and investigate different airway inflammation capacities of sputum IL-35 in patients with different asthma phenotypes. To do so, sputum samples were collected from patients with clinical asthma remission (n = 89, 37 males, age 52.24 ± 13.32 years) and a healthy control group (n = 19, 9 males, age 44.58 ± 16.3 years). All subjects underwent sputum induction, which was then assessed for inflammatory cell count, and sputum levels of IL-35 and other cytokines by ELISA and Cytometric Bead Array, respectively. They found that sputum IL-35 (median [q1, q3]) levels showed no significant difference between asthma patients (4.89 ng/ mL [2.97, 22.75]) and healthy controls (6.01 ng/mL [4.09, 30.47]). However, sputum IL-35 levels were significantly reduced in patients with eosinophilic asthma (EA) (3.95 ng/mL [2.80, 11.00]) compared to patients with neutrophilic asthma (NA) (40.59 ng/mL [20.59, 65.06], p = 0.002), paucigranulocytic asthma (PA) (6.25 ng/mL [3.10, 24.60], p = 0.012), and mixed granulocytic asthma (MA) (22.54 ng/mL [2.58, 52.45], p = 0.026). IL-35 levels in sputum showed a positive correlation with sputum neutrophil cells and a negative correlation with FeNO, FEV1% predicted, and FVC predicted. Furthermore, sputum IL-35 had a significant positive association with Th1-related factors and a negative correlation with Th2-related factors. NA and EA and exerts different effects in asthma phenotypes.

Antibody responses to SARS-CoV-2 in patients with COVID-19
Long QX, Liu BZ, Deng HJ, Wu GC, Deng K et al.
Nature Medicine 2020; Published online ahead of print (29 April)
https://doi.org/10.1038/s41591-020-0897-1

In this paper by Long and colleagues, the authors examine acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. The authors note that serological testing may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.

Anaphylaxis – A 2020 Practice Parameter Update, Systematic Review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Analysis
Shaker MS, Wallace DV, Golden DBK, Oppenheimer J, Bernstein JA et al.
Journal of Allergy and Clinical Immunology 2020;145(4):1082-1123.
https://doi.org/10.1016/j.jaci.2020.01.017

In this document from the Joint Task force of Practice Parameters, Shaker et al., explore 5 questions regarding anaphylaxis using the GRADE format.

Question 1. What risk factors should clinicians take into consideration in determining the likelihood of biphasic anaphylaxis?

Recommendation 1. Suggest that a clinician incorporate severity of anaphylaxis presentation and/or the administration of >1 dose of epinephrine for the treatment of initial anaphylaxis as a guide to determining a patient’s risk for developing biphasic anaphylaxis.

Recommendation 2. Suggest extended clinical observation in a setting capable of managing anaphylaxis (to detect a biphasic reaction) for patients with resolved severe anaphylaxis and/or those who need >1 dose of epinephrine.

Question 2. Should antihistamines or glucocorticoids be used to prevent biphasic anaphylaxis?

Recommendation. Suggest against administering glucocorticoids or antihistamines as an intervention to prevent biphasic anaphylaxis. Giving both recommendations a conditional recommendation, with a certainty rating of evidence of very low.

Question 3. Should antihistamine and/or glucocorticoid premedication be used to prevent index hypersensitivity/infusion reactions to chemotherapy?

Recommendation. Suggest in favor of administering glucocorticoids and/or antihistamines to prevent anaphylaxis or infusion-related reactions when indicated for specific agents in chemotherapy protocols.

Question 4. Should antihistamine and/or glucocorticoid premedication be used to prevent recurrent HSRs to RCM?

Recommendation. Suggest against routinely administering glucocorticoids and/or antihistamines to prevent anaphylaxis in patients with prior radiocontrast HSRs when re-administration of a low- or iso-osmolar, nonionic RCM agent is required.

Question 5. Should antihistamine and/or glucocorticoid premedication be used to prevent HSRs to allergen immunotherapy or other agents?

Recommendation. Suggest the administration of glucocorticoids and/or antihistamines as an intervention to prevent anaphylaxis in patients undergoing aeroallergen rush immunotherapy (RIT).

All recommendations were conditional recommendation, with a certainty rating of evidence of very low.

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