COPD in the 21st Century

This chapter aims to capture the patient's perspective on living with COPD, and their hopes for future research and care. The review combines data from the published literature, and insights from a group discussion with people affected by COPD and patient organisations from Europe. COPD can impact every aspect of a person's life, including their physical health, psychological wellbeing, personal relationships and overall quality of life. Patients’ experiences of diagnosis and COPD care are often negative, and they would like to have access to empathic and supportive services that encompass treatment for physical symptoms of COPD, psychological impacts, self-management support, patient education and palliative care. The patients’ priorities for future research include striving to find a cure and better treatment options, understanding how to best meet the changing needs of people with COPD from different demographic backgrounds, and understanding the impacts of air quality on the development and course of COPD.

Cite as: Senek M, Badyda A, Barbaglia S, et al. The patients’ perspective on living with COPD and their priorities for future research and care. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 1–15 [https://doi.org/10.1183/2312508X.10006123].

Agreeing a definition of COPD fit for the 21st century is a challenge. This chapter addresses key questions about defining COPD. Are there characteristic clinico-pathological features that can be used to identify COPD? At what point is it possible to distinguish COPD from non-COPD? What tests should be used? What is the threshold for defining COPD? Can we define a state or states of pre-COPD that either define healthy people at significant risk of developing COPD or people with clinico-pathological features that do not yet meet the threshold for diagnosis, and is this necessary or useful? On the basis of the available evidence, the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) definition appears the best way of defining COPD in the 21st century.

Cite as: Halpin DMG. Defining COPD in the 21st century. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 30–44 [https://doi.org/10.1183/2312508X.10007123].

COPD is an important cause of morbidity, mortality and healthcare expenditure globally. Epidemiological studies allow us to determine the burden of disease, identify modifiable factors responsible for development and progression of disease, and distinguish effective interventions from ineffective ones. This information helps guide public health efforts and areas for investment and further research. In this chapter, we will discuss the historic view of COPD, examine current epidemiological data, and consider future directions in the epidemiology of COPD.

Cite as: Khan MI, Khan MMKS, Mannino DM. The new epidemiology of COPD. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 63–80 [https://doi.org/10.1183/2312508X.10006323].

COPD is a common respiratory condition characterised by airway limitation and changes in airway structure. There is currently no curative treatment for COPD and there is an urgent unmet need for new therapeutics that could modify the course of the disease. The mechanisms underlying COPD pathology are complex and are composed of chronic inflammatory processes, oxidative stress induced by continued exposure of the lungs to harmful particles and accelerated ageing due to an increased number of senescent cells within the airways. The main challenge of current studies is to explore how these underlying mechanisms coalesce to drive disease pathophysiology. This chapter aims to describe recent developments in our understanding of COPD mechanisms, from the inflammatory response to the induction of cellular senescence in the lung. Understanding these mechanisms may result in the development of new therapeutics that could be effective for COPD but also for other age-related diseases.

Cite as: Devulder JV, Donnelly LE. Mechanisms and mediators of disease. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 100–117 [https://doi.org/10.1183/2312508X.10006423].

Chronic bronchitis refers to symptoms of sputum production across the preceding 2 years. The meaning of this term has changed across the last century, and how best to define this symptomatic state is still debated. Active smoking is a major, but not the only, cause of chronic bronchitis. Chronic bronchitis increasingly emerges with adult ageing, and may remit and relapse over time. This dynamic symptom pattern often mirrors changing smoking behaviour and reflects the rate of lung function loss. In mid-life, these symptoms appear predictive of future COPD development. Among those with already established COPD, chronic bronchitis predicts poorer quality of life, poorer physical function, accelerated decline in FEV₁ and higher mortality. The role of chronic bronchitis in COPD development and progression suggests that it may reflect an underlying pathological process and identifies it as a major potential target for therapy.

Cite as: Allinson JP. Chronic bronchitis revisited. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 135–148 [https://doi.org/10.1183/2312508X.10006723].

COPD diagnosis and quantification of its severity is traditionally based on spirometric measurements. Recent advances in lung imaging have provided new insight into the pathogenesis of COPD at the airway, lung parenchyma and vascular levels. In this chapter, we describe how CT has advanced our knowledge of the disease using visual assessment but mainly using automated quantitative methods. Quantitative measurements have made possible the indirect characterisation of small airways disease as well regional assessment of ventilation/perfusion relationships. In addition to advances in CT methods, we introduce the role of magnetic resonance imaging that provides dynamic characterisation of the lung including a measure of gas exchange at the alveolar–capillary interface. These quantitative methods are transformative in regard to the future clinical management of COPD.

Cite as: Fortis S, Comellas AP, Hoffman EA. Advances in the characterisation of COPD using quantitative imaging. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 168–184 [https://doi.org/10.1183/2312508X.10006523].

In recent years, many guideline documents have used high-level methodology but addressed only a few and very specific questions, with the consequence that their applicability in clinical routine may be limited. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document uses a different approach by covering all relevant aspects of COPD. This document, which was first published in 2001 and revised annually, has evolved over time. Initially the level of airflow limitation served as a basis for treatment recommendations. This was replaced by an assessment scheme tailored to the patient's symptoms and risk of exacerbations. Additionally, a more specific exacerbation definition and an assessment building on signs and symptoms have been introduced. In parallel, the evidence base has become much better, with high-quality clinical trials. Future guidelines will need to address the complexities of multimorbidity.

Cite as: Vestbo J, Vogelmeier C. Guidelines and strategies of management. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 204–211 [https://doi.org/10.1183/2312508X.10007423].

There are multiple areas of pharmacotherapy currently in development for the management of COPD. These range from new inhaled bronchodilators that may simplify management to the more distant future of lung-regeneration therapies. Modulating type 2 cell inflammation in relevant patients via monoclonal antibodies has been shown to reduce exacerbations, improve lung function and enhance quality of life. Other anti-inflammatory approaches such as p38 mitogen-activated protein kinase inhibitors and phosphoinositide 3-kinase-δ inhibitors remain under development. New combined phosphodiesterase 3/4 (PDE3/4) inhibitors may be beneficial, while attenuating the side-effects that limit use with PDE4 inhibitors. The advent of “multi-omics” methods of characterising endotypes will allow us to treat patients with greater precision and identify phenotypes earlier. This may facilitate treatments that can modify the disease course, preventing significant structural lung disease and irreversible airflow obstruction. We may be on the brink of a “paradigm shift” in COPD management with biomarker-guided care and early intervention becoming standard, allowing better care for all.

Cite as: Flynn CA, Aung H, Greening NJ, et al. The future drug treatment of COPD. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 233–254 [https://doi.org/10.1183/2312508X.10016423].

Exacerbations are the main cause of death and hospitalisation from COPD. Exacerbation risk increases with disease severity, delayed diagnosis and multimorbidity. As the burden of COPD continues to increase in LMICs, more research is urgently needed to understand exacerbation epidemiology and pathogenesis in these areas in order to develop effective prevention strategies. Respiratory viruses and airway microbiome dysbiosis are common triggers for exacerbations. Exacerbations are associated with both neutrophilic and eosinophilic airway inflammation, as well as mucus hypersecretion. Air pollution is increasingly recognised as a potential trigger of COPD exacerbations. However, further work is needed to understand the relationship between air pollution, airway inflammation and exacerbation risk.

Cite as: Finney LJ, MacLeod M, Wedzicha JA. New insights into the pathophysiology and epidemiology of COPD exacerbations. In: Wedzicha JA, Allinson J, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 267–282 [https://doi.org/10.1183/2312508X.10007923].

COPD is characterised by damage of the alveolar and vascular structures and peripheral airways. These characteristics are associated with a loss of gas-exchange surface, heterogeneous distribution of ventilation over the lungs, an increase in ventilation–perfusion mismatch, lung hyperinflation and increased work of breathing. Therapeutic approaches to address hypoxic failure include oxygen supply and positive end-expiratory pressure. Hyperinflation with a flattened diaphragm and a horizontal course of the ribs reduces the efficiency of the respiratory muscles. The work of breathing may overcharge the capability of the ventilatory system. The treatment of choice for hypercapnic failure is noninvasive ventilation (NIV), which can be used to avoid invasive ventilation, prevent ventilatory failure after extubation and improve long-term outcome in chronic respiratory failure. The efficacy of NIV depends crucially on optimal adaptation of the interface, precise selection and setting of the machine, and training and education of the patient and relatives. Evidence has shown that NIV improves the long-term survival of COPD patients with chronic hypercapnic failure.

Cite as: Herkenrath S, Matthes S, Randerath W. Noninvasive ventilation in COPD. In: Wedzicha JA, Allinson JP, Calverley PMA, eds. COPD in the 21st Century (ERS Monograph). Sheffield, European Respiratory Society, 2024; pp. 297–312 [https://doi.org/10.1183/2312508X.10008123].