Recent advances in chronic obstructive pulmonary disease pathogenesis: from disease mechanisms to precision medicine

Abstract

Chronic obstructive pulmonary disease (COPD) is a devastating lung disease with a high personal and societal burden. Exposure to toxic particles and gases, including cigarette smoke, is the main risk factor for COPD. Together with smoking cessation, current treatment strategies of COPD aim to improve symptoms and prevent exacerbations, but there is no disease-modifying treatment. The biggest drawback of today's COPD treatment regimen is the 'one size fits all' pharmacological intervention, mainly based on disease severity and symptoms and not the individual's disease pathology. To halt the worrying increase in the burden of COPD, disease management needs to be advanced with a focus on personalized treatment. The main pathological feature of COPD includes a chronic and abnormal inflammatory response within the lungs, which results in airway and alveolar changes in the lung as reflected by (small) airways disease and emphysema. Here we discuss recent developments related to the abnormal inflammatory response, ECM and age-related changes, structural changes in the small airways and the role of sex-related differences, which are all relevant to explain the individual differences in the disease pathology of COPD and improve disease endotyping. Furthermore, we will discuss the most recent developments of new treatment strategies using biologicals to target specific pathological features or disease endotypes of COPD. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Keywords: CELSR1; COPD; ECM; aging; biologics; genome-wide association study; inflammation; personalized treatment; precision imaging; sex differences; small airways.

Figure 1

(A) COPD lung tissue with severe emphysema showing a small airway with extensive loss of alveolar attachments. (B) Comparable image of normal lung tissue with a small airway with normal parenchymal surroundings and attachments.

Figure 2

Relationship between mean packs per day and annual change in FEV₁ in men and women: greater smoking‐related lung function decline in women compared with men with airflow obstruction. Reproduced from Downs et al 96 © 2005 Downs et al; Licensed under Creative Commons Attribution 4.0 International Public License (https://creativecommons.org/licenses/by/4.0/legalcode).

Figure 3

From key contributors to the individual's disease pathology to disease endotyping and personalized treatment in COPD.