Advances in Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder with significant morbidity and mortality. Despite its prevalence, COPD is underdiagnosed, and many patients do not receive a diagnosis until the disease is clinically advanced. Recent basic science and clinical research have focused on the early physiologic and pathobiologic changes in COPD with the hopes of improving diagnosis, providing targets for disease-modifying therapy, and identifying patients most likely to benefit from early intervention. Available treatments for COPD have grown substantially in the past 20 years with the introduction of new oral and inhaled medications as well as novel surgical and bronchoscopic procedures. This article summarizes some of the recent advances in our understanding of disease pathogenesis and treatment paradigms.

Keywords: COPD; chronic bronchitis; emphysema; lung function.

Figure 1

Distribution of participants in the Framingham Offspring Cohort (FOC) and the Copenhagen City Heart Study (CCHS) grouped into four lung function trajectories (TR1 to TR4) according to baseline FEV₁ (below or above 80% predicted value) and presence or absence of GOLD grade ≥ 2 COPD at the final examination. Solid lines represent the natural history of FEV₁ for the age range of the study while dotted lines represent hypothetical trajectories. Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in one second; GOLD, Global Initiative for Obstructive Lung Disease. Copyright © 2015 Massachusetts Medical Society. Figure adapted with permission from Massachusetts Medical Society (5).

Figure 2

Small airway damage induced by epigenetic changes in chronic obstructive pulmonary disease (COPD). (a) Normal distal respiratory epithelium. Its self-renewing basal cells differentiate into ciliated and mucus-producing goblet cells, which are joined by tight junctions forming an impermeable barrier. Mucus is separated from the epithelial surface by an aqueous periciliary layer. (b) Smoking-related abnormalities: basal and goblet cell hyperplasia, squamous metaplasia, loss of ciliated cells, decrease in the periciliary layer with ciliary damage and crowding, and junctional barrier loss. (c) In normal small airways, dimeric IgA (structure shown in inset) is transcytosed by the polymeric Ig receptor (pIgR) into the mucosal lumen. Liberation of secretory IgA after pIgR cleavage at the luminal surface prevents bacterial invasion. (d) Expression of pIgR is reduced by smoking, which leads to a localized secretory IgA deficiency in small airways and allows bacteria to invade and induce sustained airway inflammation. Abbreviations: Ig, immunoglobulin; NF-κB, nuclear factor-κB. (Figure adapted with permission from Reference . Copyright © 2020 American Thoracic Society. All rights reserved. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society. Readers are encouraged to read the entire article for the correct context at https://doi.org/10.1164/rccm.201710-2028PP. The authors, editors, and The American Thoracic Society are not responsible for errors or omissions in adaptations.)