Understanding the role of neutrophils in chronic inflammatory airway disease

Abstract

Airway neutrophilia is a common feature of many chronic inflammatory lung diseases and is associated with disease progression, often regardless of the initiating cause. Neutrophils and their products are thought to be key mediators of the inflammatory changes in the airways of patients with chronic obstructive pulmonary disease (COPD) and have been shown to cause many of the pathological features associated with disease, including emphysema and mucus hypersecretion. Patients with COPD also have high rates of bacterial colonisation and recurrent infective exacerbations, suggesting that neutrophil host defence mechanisms are impaired, a concept supported by studies showing alterations to neutrophil migration, degranulation and reactive oxygen species production in cells isolated from patients with COPD. Although the role of neutrophils is best described in COPD, many of the pathological features of this disease are not unique to COPD and also feature in other chronic inflammatory airway diseases, including asthma, cystic fibrosis, alpha-1 anti-trypsin deficiency, and bronchiectasis. There is increasing evidence for immune cell dysfunction contributing to inflammation in many of these diseases, focusing interest on the neutrophil as a key driver of pulmonary inflammation and a potential therapeutic target than spans diseases. This review discusses the evidence for neutrophilic involvement in COPD and also considers their roles in alpha-1 anti-trypsin deficiency, bronchiectasis, asthma, and cystic fibrosis. We provide an in-depth assessment of the role of the neutrophil in each of these conditions, exploring recent advances in understanding, and finally discussing the possibility of common mechanisms across diseases.

Subphenotypes of nonsteroidal antiinflammatory disease‐exacerbated respiratory disease identified by latent class analysis

“…Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper Th2 cell‐derived cytokines. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild‐to‐moderate to severe disease and are associated with worse control and disease exacerbations . More severe disease is frequently accompanied by mixed patterns of inflammation including both eosinophils and neutrophils.…”

Mechanisms and Points of Control in the Spread of Inflammation: A Mathematical Investigation

“…The role of neutrophil migration in many different inflammation-related pathologies is of increasing interest (Brubaker et al 2013;Cecchi et al 2018); there is strong evidence in the biological literature that a reduction in the rate of neutrophil chemotaxis occurs under trauma and ageing and results in an otherwise healthy inflammatory response being pushed into a persistent inflammatory response (Sapey et al 2014). Indeed, neutrophil migration is now thought to be an attractive therapeutic target for diseases such as chronic obstructive pulmonary disease, a chronic lung disease characterised by aberrant neutrophil migration (Sapey et al 2011;Jasper et al 2019).…”

“…The balance between the cellular components of inflammation is orchestrated via a variety of pro-and anti-inflammatory mediators that, combined with the interactions between neutrophils and macrophages, control the progression of inflammation to healthy resolution or a chronic, self-perpetuating condition. Diseases characterised by chronic inflammation may be linked to the inability of acute inflammation to resolve, and specific pro-resolution pathways are now seen as alternative therapeutic targets (Fullerton and Gilroy 2016;Sugimoto et al 2016); however, in addition, there is growing experimental evidence that the inflammatory response is characterised by spatial changes and that mechanisms such as cell motility are key in identifying how inflammatory conditions progress (Luster et al 2005;Eming et al 2007;Nourshargh et al 2016;Jasper et al 2019). There is a growing need to elucidate the mechanisms that control the interactions between the distinct cell types that drive the resolution of inflammation and, in particular, how spatial effects such as cell motility effect inflammatory outcomes, since the potential to actively manipulate these aspects of the inflammatory response exhibits great scope for development of new drugs and treatments (Libby 2007;Hunter 2012).…”

Granulocyte-targeted therapies for airway diseases

“…Several airway diseases including COPD, bronchiolitis, pneumonia, asthma and acute lung injury are characterized by neutrophil infiltration of the airway wall [31]. Both clinical and experimental data have shown an association between neutrophil numbers and the severity and progression of these airway diseases [32][33][34]. This dual "face" of neutrophils is further evidenced by the different phenotypes of these cells (N1 versus N2) that can either promote or inhibit lung cancer [35].…”