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Medical Journal Review

May 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.

A rich meconium metabolome in infants is associated with early-life gut microbiota composition and reduced allergic sensitization
Petersen C, Dai DLY, Boutin RCT et al
Cell Reports Medicine 2021;2(5):100260 (29 April)

Microbiota maturation and immune development have been implicated in the development of allergic diseases, and research has begun to demonstrate the importance of prenatal influencers on both. In this study by Petersen and colleagues, the authors investigated the meconium metabolome, which is a critical link between prenatal exposures and both early microbiota and immune development. Their aim was to identify components of the neonatal gut niche that may contribute to allergic sensitization, finding that newborns who develop IgE-mediated allergic sensitization by 1 year of age have a less-diverse gut metabolome at birth, and specific metabolic clusters appear to be associated with both protection against atopy and the abundance of key taxa driving microbiota maturation. These metabolic signatures, when coupled with early-life microbiota and clinical factors, increase our ability to predict accurately whether infants will develop atopy. Overall, the findings indicate that trajectory of both microbiota colonization and immune development are significantly affected by metabolites present in the neonatal gut at birth.

High-dimensional characterization of post-acute sequelae of COVID-19
Al-Aly Z, Xie Y, and Bowe B
Nature 2021 (22 April)

While the acute clinical manifestations of COVID-19 have been well characterized, the post-acute sequalae have not been comprehensively described. To understand better the post-acute consequences of COVID-19, the authors of this paper examined the national healthcare databases of the US Department of Veterans Affairs to identify systematically 6-month incident sequalae including diagnoses, medication use, and laboratory abnormalities in 30-day survivors of COVID-19. They found that beyond the first 30 days of illness, people with COVID-19 exhibit higher risk of death and health resource utilization. They specifically identified incident sequalae in the respiratory system and several others including nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain, and anemia, with increased incident use of several therapeutics including pain medications (opioids and non-opioids), antidepressants, anxiolytics, antihypertensives, and oral hypoglycemics and evidence of laboratory abnormalities in multiple organ systems. Analysis of an array of pre-specified outcomes revealed a risk gradient that increased across severity of the acute COVID-19 infection (non-hospitalized, hospitalized, and admitted to intensive care). Overall, this study demonstrates that beyond the acute illness, substantial burden of health loss — spanning pulmonary and several extrapulmonary organ systems — is experienced by COVID-19 survivors and provides a roadmap to inform health system planning and development of multidisciplinary care strategies to reduce chronic health loss among COVID-19 survivors.

Systemic corticosteroids in coronavirus disease 2019 (COVID-19)-related smell dysfunction: an international view
Huart C, Philpott CM, Altundag A et al
International Forum of Allergy and Rhinology 2021; Published online ahead of print (16 March)

With the development of hyposmia as a consequence of COVID-19, many have recommended the use of systemic corticosteroids as a treatment option. This multinational expert panel however suggests caution using this treatment in early COVID-19–related olfactory dysfunction because: (1) evidence supporting its usefulness is weak; (2) the rate of spontaneous recovery of COVID-19–related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. They stress the need for randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize early institution of smell training, which is supported by a robust evidence base and has no known side effects.

Tregitopes improve asthma by promoting highly suppressive and antigen-specific Tregs
Dembele M, Tao S, Massoud AH et al
Frontiers in Immunology 2021 (19 April)

Tregitopes (T regulatory epitopes) are IgG-derived peptides with high affinity to major histocompatibility complex class II (MHCII) that promote tolerance by activating T regulatory cell (Treg) activity. In this study by Dembele and colleagues, the authors explore the effect of IgG Tregitopes in a murine model of allergic asthma, demonstrating in vivo antigen-specific tolerance via adoptive transfer of Tregitope-and-allergen-activated Tregs. Asthma is a heterogeneous chronic inflammatory condition affecting the airways and impacting over 300 million individuals worldwide. Treatment is suppressive, and no current therapy addresses immune regulation in severely affected asthmatics. Although high dose intra-venous immunoglobulin (IVIG) is not commonly used in the asthma clinic setting, it has been shown to improve severe asthma in children and in adults. Previous work by this group has demonstrated that IVIG abrogates airway hyperresponsiveness (AHR) in a murine model of asthma and induces suppressive antigen-specific T-regulatory cells. To prove that IgG-derived Tregitopes would modulate allergic airway disease by inducing highly suppressive antigen-specific Tregs capable of diminishing T effector cell responses and establishing antigen-specific tolerance, the authors utilized ovalbumin (OVA-) and ragweed-driven murine models of allergic airway disease for characterizing the immunoregulatory properties of Tregitopes and performed Treg adoptive transfer to OVA- and ragweed-allergic mice to test for allergen specificity. They found that treatment with Tregitopes attenuated allergen-induced airway hyperresponsiveness and lung inflammation and Tregitopes induced highly suppressive allergen-specific Tregs. The tolerogenic action of IgG Tregitopes in this model is very similar to that of IVIG.  The authors conclude that IgG Tregitopes could potentially replace steroid-based treatment and can offer a synthetic alternative to IVIG in a range of inflammatory and allergic conditions.

A skin-conformable wireless sensor to objectively quantify symptoms of pruritus
Chun KS, Kang YJ, Lee JY et al
Science Advances 2021; 7(18):eabf9405

Itch is a common clinical symptom and major driver of disease-related morbidity across a wide range of medical conditions. A substantial unmet need is for objective, accurate measurements of itch. In this article, Chun et al present a noninvasive technology for objective quantification of scratching behavior via the use of a soft, flexible, and wireless sensor that captures the acousto-mechanic signatures of scratching from the dorsum of the hand. A machine learning algorithm validated data collected from healthy subjects (n = 10), indicating excellent performance relative to alternative smartwatch-based approaches. Clinical validation in a cohort of a largely pediatric cohort (n = 11) with moderate to severe atopic dermatitis included 46 sleep-nights totaling 378.4 hours. The data indicate an accuracy of 99.0% (84.3% sensitivity, 99.3% specificity) against visual observation. The authors suggest that this technology has broad capabilities, including assessing the efficacy of drugs for conditions that cause itch to monitoring disease severity and treatment response.

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