Review
Post ScreenEmerging trends in the therapy of COPD: novel anti-inflammatory agents in clinical development
Post Screen
Introduction
As discussed in the accompanying article [1], COPD is a disorder that is characterized by airflow obstruction that is progressive and relatively insensitive to treatment with bronchodilators, which provide mainly symptomatic relief. The lung pathology of COPD is complex and heterogeneous, comprising pulmonary inflammation, small airway remodelling, emphysema and mucous hypersecretion. The characteristic features of inflammation in COPD are described in Table 1.
Inflammation in the lungs of patients with COPD occurs in both small and large airways and is thought to be crucial to the development of the disease pathology: the severity of inflammation is associated with disease severity as measured by spirometry [2]. Key contributors to the progression of airway obstruction in COPD are an increase in the volume of tissue in the small-airway wall, accumulation of mucous exudates and infiltration of the airway wall by cells of the innate and adaptive immune responses 3, 4. Emphysema is defined as dilation and destruction of lung tissue beyond the terminal bronchiole, and its development contributes to a reduction in lung function by decreasing the elastic recoil of the lung. This reduces maximum expiratory flow, which leads to trapping of gas within the lung [5]. Up to 40% of heavy smokers develop emphysema and increased CD8+ lymphocytes 2, 6, eosinophils, CD4+ lymphocytes and macrophages are associated with the presence of emphysema [7].
Recent literature indicates that antigen-driven cellular-mediated immunity is involved in severe COPD, and that this might be responsible for the persistent inflammation that is characteristic of severe emphysema [8]. The role of the B-cell follicles, which are present in increasing numbers in the small airways as COPD progresses in severity, in the development of a specific antigenic response is under investigation. Studies in emphysema patients and mice exposed to tobacco smoke (TS) show the presence of B-cell follicles that undergo antigen-specific proliferation. The specific antigens involved in this proliferative response are unknown but might include bacteria, viruses, components of TS and, potentially, the breakdown products of the extracellular matrix 9, 10.
Section snippets
Aims of therapy
The aim of therapy in COPD is to prevent and control symptoms, reduce the frequency and severity of exacerbations, improve health status, improve exercise tolerance and, ultimately, prevent the accelerated decline in lung function that might reduce mortality. Reducing the frequency and severity of exacerbations is an increasingly important target therapy because the prognosis for patients following exacerbations is poor. Current therapy focuses mainly on reducing symptoms using short-acting and
New anti-inflammatory agents in clinical development
COPD is a chronic inflammatory disorder, thus, a key question is whether novel anti-inflammatory agents can halt or slow the decline in lung function that does not appear to be modified by currently prescribed therapies. A schematic of the airway inflammation in COPD and the approaches that are being developed clinically is outlined in Box 1.
Our current understanding of the relationship between inflammatory biomarkers measured in sputum, bronchoalveolar lavage (BAL) and bronchial biopsies, and
Conclusions and future perspectives
Several anti-inflammatory mechanisms are being investigated clinically in COPD patients and data generated in the next 5 years should indicate whether significant anti-inflammatory activity can be achieved in COPD patients and whether this leads to improved clinical outcomes. Orally administered drugs have the advantage of improving compliance compared to inhaled medications and might reduce the chronic systemic inflammation that occurs in COPD as well as reducing the inflammation within the
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