Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

Abstract

Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD.

Eosinophilic phenotype was associated with better early clinical remission in elderly patients but not middle‐aged patients with acute exacerbations of COPD

“…Subsequent infiltration of eosinophils in the airways of COPD patients regulates an immunoglobulin E (IgE)dependent mechanism, which is considered an important part of Th2 cell cytokine production process, resulting in an imbalanced production of Th2 cells that may cause an irregular Th1/Th2 ratio and interleukin-17/IgE ratio. [36][37][38] We also observed a lower medical cost in eosinophilic AECOPD patients. These findings are consistent with those of previous studies despite different clinical settings, enrolment criteria, and definitions of disease severity and exacerbation.…”

“…Moreover, in this study, similar difference of LOS was observed in the subgroup analysis of elderly patients but not middle‐aged patients. A potential explanation for this difference between the eosinophilic and non‐eosinophilic group is that high eosinophil counts are associated with high levels of T‐helper cell type 2 (Th2) inflammation, which implies more eosinophilic airway inflammation but less bacterial inflammation 36 . Increasing evidence in recent years has shown that eosinophilic airway inflammation might play an important role in pathogenesis of COPD 37 .…”

“…Eosinophilic exacerbation has been proven to be associated with eosinophilic airway inflammation related to Th2 inflammation. Subsequent infiltration of eosinophils in the airways of COPD patients regulates an immunoglobulin E (IgE)‐dependent mechanism, which is considered an important part of Th2 cell cytokine production process, resulting in an imbalanced production of Th2 cells that may cause an irregular Th1/Th2 ratio and interleukin‐17/IgE ratio 36‐38 …”

“…A potential explanation for this difference between the eosinophilic and non-eosinophilic group is that high eosinophil counts are associated with high levels of T-helper cell type 2 (Th2) inflammation, which implies more eosinophilic airway inflammation but less bacterial inflammation. 36 Increasing evidence in recent years has shown that eosinophilic airway inflammation might play an important role in pathogenesis of COPD. 37 Eosinophilic exacerbation has been proven to be associated with eosinophilic airway inflammation related to Th2 inflammation.…”

Clinical Utility of Central and Peripheral Airway Nitric Oxide in Aging Patients with Stable and Acute Exacerbated Chronic Obstructive Pulmonary Disease

“… 3 In recent years, there have been a large number of studies on the role of type 2 biomarkers in COPD, including eosinophils, IgE and FeNO 50. 4 Nitric oxide (NO) is biosynthesized from L-arginine and oxygen by the enzyme NO synthase (NOS) endogenously, fractional concentration of exhaled nitric oxide at a flow rate of 50mL/s (FeNO 50 ) is a known marker of airway inflammation. As a noninvasive, convenient and highly reproducible method for assessing airway inflammation, FeNO measurement has been used to evaluate type 2 inflammation of asthma and guide anti-inflammatory treatment.…”