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Medical Journal Review

November 2020

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. 

Non-allergic severe asthma: Is it really always non-allergic? The IDENTIFY project.
Koschel D, Mailänder, C, Schwab Sauerbeck I, Schreiber J
Allergy, Asthma & Clinical Immunology 2020;16:92

When stratifying asthma into allergic vs non-allergic, the classification of the allergic phenotype is typically based upon proof of sensitization to allergens. In Germany, the number of specific allergen tests is limited and non-standardized (across clinicians and laboratories), with the potential for false negative diagnoses. This study by Koschel et al examined retesting in patients with severe asthma who had initially tested negative to a panel of perennial aeroallergens, via a single visit, non-randomized, non-interventional study conducted in 87 centers across Germany.

The only inclusion criteria were that patients had to be adults (at least 18 years of age) with a diagnosis of severe asthma (receiving at least Global Initiative for Asthma Step IV therapy) and had to previously test negative to a panel of perennial aeroallergens. Patients were then re-tested for sensitization to a panel of 35 perennial aeroallergens, with positive sensitization indicated by CAP ≥ 0.35 kU/L. Of 588 patients recruited, 454 completed the evaluation with 43.6% of the analyzed patients demonstrating a positive response to at least one of the included aeroallergens, with 18.7% testing positive for 3 or more, and 4.2% positive for more than 10. The 5 most common sensitizations were to Staphylococcus aureus enterotoxin B, Aspergillus fumigatus, Candida albicans, Dermatophagoides farinae, and Rhizopus nigricans. This study reinforces the importance of using sensitive testing procedures. It is important to note, however, that with added sensitivity comes an increase false positive response.

Anaphylaxis refractory to intramuscular adrenaline during in-hospital food challenges: A case series and proposed management
Alviani C, Burrell S, Macleod A, Edees S, Roberts G et al
Clinical & Experimental Allergy 2020; Published online ahead of print (30 September)

In this paper, the authors present 4 patients who experienced severe life-threatening anaphylaxis, refractory to intramuscular adrenaline treatment, during supervised oral food challenges finding that all did respond to treatment with low-dose intravenous adrenaline, with no reported adverse effects. The authors conclude that this demonstrates the need for clinicians undertaking higher risk allergen challenges to be able to manage cases of severe anaphylaxis refractory to intramuscular adrenaline, and to consider a framework for managing these reactions, including IV adrenaline.

Sputum macrophage diversity and activation in asthma: Role of severity and inflammatory phenotype
Tiotiu A, Zounemat Kermani N, Badi Y, Pavlidis S, Hansbro PM et al
Allergy 2020; Published online ahead of print (1 August)

While we know that macrophages control innate as well as acquired immunity, their role in severe asthma remains ill-defined. In this study, Tiotiu and colleagues investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U-BIOPRED cohort. Forty-nine gene signatures (modules) for differentially stimulated macrophages, 1 to assess lung tissue-resident cells (TR-Mφ) and 2 for their polarization (classically and alternatively activated macrophages: M1 and M2, respectively) were studied using gene set variation analysis. From this, they calculated enrichment scores (ES) across severity and previously identified asthma transcriptome-associated clusters (TACs).

They found that macrophage numbers were significantly decreased in severe asthma compared to mild-moderate asthma or healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll-like receptors via NF-κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all P < .01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (P < .001) and in TAC2 for the inflammasome and interferon signaling pathways (P < .001).  Overall, these data indicate that macrophage activation is attenuated in severe asthma highlighting defective innate immunity, except for specific subsets characterized by distinct inflammatory pathways.

Are there pulmonary sequelae in patients recovering from COVID-19?
Rogliani P, Calzetta L, Coppola A, Puxeddu E, Sergiacomi G et al
Respiratory Research 2020; 21:286

It has been hypothesized recently that infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to fibrotic sequelae in patients recovering from coronavirus disease 2019 (COVID-19). In this observational study, Rogliani and colleagues examined hospitalized patients with COVID-19, performing high-resolution computed tomography (HRCT) of the chest to detect the extension of fibrotic abnormalities via Hounsfield Units (HU). At follow-up, the lung density significantly improved in both lungs and in each lobe of all patients, being in the normal range (− 950 to − 700 HU). Thankfully, this study provides preliminary evidence that hospitalized patients with mild-to-moderate forms of COVID-19 are not at risk of developing pulmonary fibrosis. Certainly, further study is needed with larger numbers, across diverse strata of disease severity.

What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2
Hodgson SH, Mansatta K, Mallett G, Harris V, Emary KRW, Pollard AJ
The Lancet Infectious Diseases 2020; Published online ahead of print (27 October)

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 1 million deaths in the first 6 months of the pandemic and huge economic and social upheaval internationally. An effective vaccine is essential to prevent further morbidity and mortality. Although some countries might deploy COVID-19 vaccines based solely on the strength of safety and immunogenicity data, the ultimate goal of vaccine development is to demonstrate vaccine efficacy in protecting humans against SARS-CoV-2 infection and COVID-19. A candidate vaccine against SARS-CoV-2 might act against infection, disease, or transmission, and a vaccine capable of reducing any of these elements could contribute to disease control. However, the most important efficacy endpoint, protection against severe disease and death, is difficult to assess in phase 3 clinical trials. In this review, the authors examine the challenges in assessing the efficacy of candidate SARS-CoV-2 vaccines, discuss the issues needed to interpret reported efficacy endpoints, and provide insight into answering the trillion-dollar question, “Does this COVID-19 vaccine work?”’


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