The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses
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REVIEW
The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses Kaori Uchiumi Davis1,2 and M. Katie Sheats
1,2,3
(Received July 29, 2020; accepted October 12, 2020)
Received July 29, 2020; revised October 7, 2020; accepted October 12, 2020
Abstract— Asthma is a common and debilitating chronic airway disease that affects people
and horses of all ages worldwide. While asthma in humans most commonly involves an excessive type 2 immune response and eosinophilic inflammation, neutrophils have also been recognized as key players in the pathophysiology of asthma, including in the severe asthma phenotype where neutrophilic inflammation predominates. Severe equine asthma syndrome (sEAS) features prominent neutrophilic inflammation and has been increasingly used as a naturally occurring animal model for the study of human neutrophilic asthma. This comparative review examines the recent literature in order to explore the role of neutrophil inflammatory functions in the pathophysiology and immunology of asthma in humans and horses. KEY WORDS: asthma; neutrophils; noneosinophilic asthma; equine asthma syndrome; nonallergic asthma; horses.
OVERVIEW OF ASTHMA Asthma Phenotypes and Endotypes Asthma is a common, chronic airway disease that is naturally occurring in both humans and horses. According to the Global Asthma Report published in 2018, more than 300 million people suffer from asthma worldwide [1]. Survey data from Great Britain suggests that 10–20% of adult horses in the northern hemisphere, and other 1
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr., Raleigh, NC 27607, USA 2 Center for Comparative Medicine and Translational Research, North Carolina State University, 1060 William Moore Dr, Raleigh, NC 27607, USA 3 To whom correspondence should be addressed at Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr., Raleigh, NC 27607, USA.
temperate climates, have severe Equine Asthma Syndrome (sEAS) [2]. In both humans and horses, the clinical symptoms of asthma are caused by bronchoconstriction, airway hyper responsiveness, excess mucus, and airway remodeling, resulting in cough, shortness of breath, wheeze, and chest tightness. Common treatments for both humans and horses include avoidance of airway triggers, steroids, and bronchodilators. In humans with asthma, there is remarkable variability in the severity, underlying mechanisms, and responsiveness to treatment in individuals with asthma. A long-standing approach to address this heterogeneity of asthma in humans has been to group patients based on “phenotypes,” which represent observable clinical characteristics such as exacerbating factors (e.g., allergens, exercise and infections), age of onset (early vs late onset), comorbidities (e.g., obesity), and response to treatment (e.g., steroid resistant vs steroid sensitive) [3]. Phenotypes have also been used to describe EAS. Currently in horses,
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