Leukocyte Function in COPD: Clinical Relevance and Potential for Drug Therapy

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive lung condition affecting 10% of the global population over 45 years. Currently, there are no disease-modifying treatments, with current therapies treating only the symptoms of the disease. COPD is an inflammatory disease, with a high infiltration of leukocytes being found within the lung of COPD patients. These leukocytes, if not kept in check, damage the lung, leading to the pathophysiology associated with the disease. In this review, we focus on the main leukocytes found within the COPD lung, describing how the release of chemokines from the damaged epithelial lining recruits these cells into the lung. Once present, these cells become active and may be driven towards a more pro-inflammatory phenotype. These cells release their own subtypes of inflammatory mediators, growth factors and proteases which can all lead to airway remodeling, mucus hypersecretion and emphysema. Finally, we describe some of the current therapies and potential new targets that could be utilized to target aberrant leukocyte function in the COPD lung. Here, we focus on old therapies such as statins and corticosteroids, but also look at the emerging field of biologics describing those which have been tested in COPD already and potential new monoclonal antibodies which are under review.

Serum YKL-40 Levels, Leukocyte Profiles, and Acute Exacerbations of Advanced COPD

“…Another drawback is the fact that this investigation did not assess the number and frequency of different types of leukocytes in the sputum or lungs of COPD patients during exacerbation episodes. These individuals often exhibit altered leukocyte profiles in these body matrices [52], and as a consequence, such measurements may help confirm and explain the differences noticed here in different YKL-40 strata. The diagnosis of COPD relied on spirometric measurements, but we were not able to show these values given the lack of electronic database of spirometry.…”

Prognostic value of lymphocyte count for in-hospital mortality in patients with severe AECOPD

“…In addition, the lymphopenia group had longer hospital stay (median [IQR] 16 days [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] vs. 14 days [10][11][12][13][14][15][16][17][18][19][20],…”

“…Lymphocytes are one of the inflammatory markers, and different subpopulations of lymphocytes are involved in different stages of COPD development [ 18 ]. COPD leads to the activation of the adaptive immune system of the body, causing lymphocytes to infiltrate the small airways of the lungs [ 9 ], which may cause fewer circulating lymphocytes.…”

“…Compared to patients with normal lymphocyte counts, those with low counts were older (79.2 ± 7.4 vs. 77.5 ± 8.6 years, p = 0.036), had lower activities of daily living scores on admission (35.9 ± 27.6 vs. 47.5 ± 17.1, p < 0.001), and had a greater need for home oxygen therapy (84.6 vs. 72.1%, p = 0.002). Patients with low lymphocytes had higher mortality rates during hospitalization (17.1 vs. 7.1%, p = 0.001), longer hospital stay (median [IQR] 16 days [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] vs. 14 days [10][11][12][13][14][15][16][17][18][19][20], p = 0.002) and longer time on mechanical ventilation (median [IQR] 11.…”

An Overview of the Safety and Efficacy of Monoclonal Antibodies for the Chronic Obstructive Pulmonary Disease

“… 43 It has been suggested that targeting IL-17 in COPD may therefore be therapeutically useful if it is aimed at well-characterised neutrophilic patients who may respond well to these drugs, possibly identified by nasal sampling performed to detect those with high IL-17 levels. 44 However, it must be highlighted that secukinumab was unable to inhibit ozone-induced acute neutrophilic airway inflammation in healthy volunteers. 45 Furthermore, targeting the IL-17 pathway may increase the risk of AECOPD by diminishing host defense.…”