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Medical Journal Review

December 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. 

Cold urticaria – what we know and what we do not know
Maltseva N, Borzova E, Fomina D, Bizjak M, Terhorst-Molawi et al
Allergy 2020; Published online ahead of print (28 November)
https://doi.org/10.1111/all.14674

 Recent research regarding cold urticaria (ColdU) has advanced our understanding and management of this illness. Presently, its pathophysiology is thought to involve the cold-induced formation of auto-allergens and IgE to these auto-allergens, which provoke a release of pro-inflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop upon rewarming of the skin and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient’s history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be performed if indicated by the patient’s history. The management of ColdU includes cold avoidance, the regular use of non-sedating antihistamines, and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered.

Bacterial lysate therapy for the prevention of wheezing episodes and asthma exacerbations: a systematic review and meta-analysis
de Boer GM, Żółkiewicz J,  Strzelec KP, Ruszczyński M, Hendriks RW et al
European Respiratory Review 2020;29(158):190175
https://doi.org/10.1183/16000617.0175-2019

Wheezing and asthma are a growing cause of morbidity in children and adults. Treatment is aimed at prevention of disease exacerbations and preservation of lung function. Respiratory viruses are involved in ∼40–60% of exacerbations. Bacterial lysates prevent recurrent respiratory tract infections and might reduce exacerbations, with immunomodulatory effects observed in human studies. In this study the authors explored the effects of bacterial lysate therapy on preschool wheezing episodes and asthma exacerbation frequency by performing a systematic literature and a meta-analysis using Cochrane Review Manager. Out of 2016 retrieved articles, 22 studies were included, of which five provided sufficient data for a meta-analysis. They found that the use of bacterial lysates showed a decrease of both wheezing episodes (mean difference −2.35(−3.03–−1.67), p<0.001) and asthma exacerbations in children (mean difference −0.90 (−1.23–−0.57), p<0.001). Additionally, antibiotic use was reduced, and the duration of wheezing episodes was also decreased. They found no current data for adults with asthma. The immunomodulatory effect seems to be dependent on increased T-helper (Th)1-cell activation and Th2-cell suppression. The authors conclude that the effects of bacterial lysates show promise as add-on therapy in preschool wheezing and childhood asthma.

2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group
Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC); Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T et al
Journal of Allergy and Clinical Immunology 2020;146(6):1217-1270
https://doi.org/10.1016/j.jaci.2020.10.003

The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group addresses six priority topic areas, including: Fractional Exhaled Nitric Oxide Testing, Indoor Allergen Mitigation, Intermittent Inhaled Corticosteroids, Long-Acting Muscarinic Antagonists, Immunotherapy in the Treatment of Allergic Asthma, and Bronchial Thermoplasty. This is a must read for the allergy community.

The Impact of COVID-19 on Patients with Asthma
Izquierdo JL, Almonacid C, González Y, Del Rio-Bermúdez C, Ancochea J et al
European Respiratory Journal 2020; Published online ahead of print (5 November)
https://doi.org/10.1183/13993003.03142-2020

There is tremendous controversy in the literature regarding the impact of COVID-19 on asthma. This study by Izquierdo and colleagues was conducted to understand the impact of COVID-19 in patients with asthma through big data analytics and artificial examination of clinical data from patients with asthma from January 1 to May 10, 2020. They found that out of 71,182 patients with asthma, 1,006 (1.41%) suffered from COVID-19. Compared to asthmatic individuals without COVID-19, patients with asthma and COVID-19 were significantly older (55 vs. 42 years), predominantly female (66% vs. 59%), smoked more frequently, and had higher prevalence of hypertension, dyslipidemias, diabetes, and obesity. Allergy-related factors such as rhinitis and eczema were less common in asthmatic patients with COVID-19 (P < .001). Higher prevalence of these comorbidities was also observed in patients with COVID-19 who required hospital admission. The use of inhaled corticosteroids (ICS) was lower in patients who required hospitalization due to COVID-19, as compared to non-hospitalized patients (48.3% vs. 61.5%; OR: 0.58: 95% CI 0.44 - 0.77). Although patients treated with biologics (n = 865; 1.21%) showed increased severity and more comorbidities at the ENT level, COVID-19-related hospitalizations in these patients were relatively low (0.23%). Overall, they found that patients with asthma and COVID-19 were older and at increased risk due to comorbidity-related factors. The authors conclude that ICS and biologics are generally safe and may actually be associated with a protective effect against severe COVID-19 infection.  More research on this topic is sure to follow.

Cytokine storm
Faigenbaum DC and June CH
New England Journal of Medicine 2020;383:2255-2273
https://doi.org/10.1056/NEJMra2026131

In this article, the authors provide a great review of cytokine storm.  As they note, mild, secondary organ dysfunction during an inflammatory response is evolutionarily acceptable if it allows the host to overcome the infection and survive. If, however, the inflammatory response causes excessive organ dysfunction that puts host survival and reproductive fitness at risk, then it is pathologic. Extensive regulatory mechanisms exist that modulate the immune response and prevent cytokine storm, but still it can occur due to iatrogenic causes, pathogens, cancers, autoimmunity, and autoinflammatory mechanisms. Distinguishing between protective inflammatory responses and pathologic cytokine storm has important implications for treatment, but is quite challenging. The authors highlight that no agreed upon definition of cytokine storm exists, and there is much disagreement regarding what the definition should be and whether specific conditions such as Covid-19 should be included in the spectrum of cytokine storm disorders. In this article, the authors propose a unifying definition for cytokine storm that is based on the following criteria: elevated circulating cytokine levels, acute systemic inflammatory symptoms, and secondary organ dysfunction beyond that which could be attributed to a normal response to a pathogen, if a pathogen is present. Targeted therapeutic approaches to cytokine storm have been utilized in idiopathic multicentric Castleman’s disease, hemophagocytic lymphohistiocytosis, as well as CAR T-cell therapy and have turned deadly conditions into often reversible states. The authors conclude that with advances in “multi-omic” profiling and therapeutic modulation of the immune system, they expect to see continued improvements in outcomes.

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