Understanding the role of neutrophils in chronic inflammatory airway disease

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.