Inflammatory endotypes in COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is largely corticosteroid-resistant in most patients. Although rare genetic endotypes of COPD have been recognized, despite the clinical heterogeneity of COPD, it has proved difficult to identify distinct inflammatory endotypes.Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs.However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL-5 has been detected, anti-IL-5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines. K E Y W O R D Sasthma-COPD overlap, eosinophil, exacerbations, interleukin-5, macrophage, neutrophil

Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis

“…Among these categories, the most important BPs included inflammatory response, immune response and response to lipopolysaccharide; the most important MFs included receptor activity and RAGE receptor binding; and the most important CCs included extracellular region and space, integral component of plasma membrane, plasma membrane and external side of plasma membrane. This finding accords with the knowledge that COPD is characterized by chronic inflammation in the lung and airways [28,29]; immune response mediates the development of COPD caused by the harmful stimuli [30][31][32]; lipopolysaccharide may lead to increased airway and systemic inflammation, and contribute to the progressive deterioration of lung function [33,34]; and RAGE is a 'driving force' for cigarette smoke (CS)-induced airway inflammation in COPD [35]. KEGG pathway analysis indicated that 48 pathways corresponded to these DEGs associated with COPD.…”

Alterations of multiple alveolar macrophage states in chronic obstructive pulmonary disease

“…Lung inflammation in COPD is characterized by alterations in the number and function of immune cells, whereby macrophages and neutrophils gained much attention (Barnes, 2019). Elevated cell numbers in COPD have also been described for eosinophils (Berg and Wright, 2016;Saha and Brightling, 2006), CD8 + T cells (O'Shaughnessy et al, 1997) and innate lymphoid cells (ILCs) (De Grove et al, 2016).…”

Nitrosative stress in patients with asthma−chronic obstructive pulmonary disease overlap

“…These patients might have greater reversibility, more frequent exacerbations, and a better response to corticosteroids in reducing COPD exacerbations. 2 It is likely that these patients would also have an increase in 3-NT levels in sputum cells, as reported in patients with COPD. 8 Increased oxidative stress in the lungs might play a key role in driving the chronic inflammation, corticosteroid resistance, and cellular senescence seen in patients with COPD.…”

“…However, the relatively poor response to anti-IL-5 therapies in patients with COPD might indicate that different mechanisms of eosinophilia are at play. 2 More is understood about the mechanisms of smoking asthma, where smoking-induced neutrophilic inflammation is imposed on T2 inflammation with eosinophils, resulting in fixed airway obstruction and reduced responsiveness to corticosteroids. 3 Various airway and blood biomarkers of neutrophilic and eosinophilic inflammation might distinguish the different phenotypes of ACO.…”