Elsevier

The Lancet

Volume 400, Issue 10356, 17–23 September 2022, Pages 921-972
The Lancet

The Lancet Commissions
Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission

https://doi.org/10.1016/S0140-6736(22)01273-9Get rights and content

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Executive summary

Despite substantial progress in reducing the global impact of many non-communicable diseases, including heart disease and cancer, morbidity and mortality due to chronic respiratory disease continues to increase. This increase is driven primarily by the growing burden of chronic obstructive pulmonary disease (COPD), and has occurred despite the identification of cigarette smoking as the major risk factor for the disease more than 50 years ago. Many factors have contributed to what must now be

COPD: a global health crisis

COPD has become a global health crisis partly as a result of the failure of governmental, medical, and scientific agencies, as well as private enterprises, to eliminate active cigarette smoking and to recognise and eliminate other environmental exposures. This Commission9 aims to change the course of this global emergency by demanding urgent action targeting the factors most responsible for the uncontrolled burden of COPD. We will focus on the greatest difficulties to overcome, which lie in

COPD: beyond tobacco smoking

Real-world observations call into question Fletcher and Peto's traditional conceptual definition of COPD as a self-inflicted disease caused by tobacco smoking that is associated with accelerated loss of lung function and eventually results in persistent respiratory symptoms.49 This definition, which was formulated in 1976, has increasingly been undermined by evidence of risk factors for COPD other than smoking.8 These risk factors can have distinct pathophysiological mechanisms and clinical

Type 1: genetically determined COPD

Genome-wide association studies focusing on disease phenotypes defined by spirometry suggest that the genetic heritability of COPD is moderate.56 Although about 40% of the variability in airflow limitation and up to 60% of the risk for COPD related to smoking is attributable to genetics,57 α1 antitrypsin deficiency and telomerase reverse transcriptase mutation are the only two monogenetic variants that have been clearly shown to have a causative role in the disease. The role of epigenetic

Prematurity

Around 10–12% of all deliveries are premature births,69 resulting in approximately 15 million premature infants worldwide yearly, some born as early as 23 or 24 weeks' gestation. Prematurity is associated with low birthweight, nutritional problems, susceptibility to respiratory infections, and poor lung function early in life. Together with insults such as exposure to tobacco smoke in the second half of pregnancy, prematurity can cause substantial impairment in alveolar, vascular, and airway

Type 3: infection-related COPD

Pulmonary and systemic infections are among the most important non-smoking related risk factors for chronic lung disease and COPD, especially in LMICs.4, 7, 8 An estimated 10–42% of people with early-life pneumonia, tuberculosis, or HIV develop COPD.83, 84, 85

Type 4: COPD related to smoking or vaping

The clinical and radiographic characteristics associated with tobacco smoking are well known and account for most knowledge about COPD. Maternal smoking, second-hand and third-hand smoking (ie, exposure to pollutants that settle on surfaces when tobacco is smoked indoors), and vaping or e-cigarette smoking also have substantial implications for lifelong lung health.

Type 5: environmental exposure-related COPD

Environmental exposure encompasses exposure to particles and gases from indoor fuel use, wildfire smoke, air pollution or smog, and occupational exposure. Emerging data suggest that different environmental exposures can lead to differing pathological processes leading to COPD (table 3).

Why revisit the diagnostic criteria for COPD?

It is well accepted that COPD is a complex and heterogeneous disease: complex in that the disease has several distinct components and is driven by both genetic and environmental factors that dynamically interact over time, heterogeneous in that all components are not present in all individuals at any given timepoint and can vary in severity over time.143 Diagnostic criteria for COPD capture none of this complexity nor the variation in underlying pathophysiology. Rather, they rely exclusively on

A proposal for diagnosis of COPD

As discussed, diagnostic guidelines do not account for the heterogeneity of the pathophysiological processes underlying COPD, which are in turn driven by the genetic determinants and cumulative lifelong environmental exposures leading to the disease. The elimination of COPD will require both prevention of new cases and cure for those with existing disease. Thus, a novel approach to diagnosis that moves beyond spirometric criteria alone (which identifies disease only after irreversible airway

Diagnostics in symptomatic people with COPD types

Extensive efforts have been made to drive the uptake of spirometry in diagnosis of COPD. Use of spirometry is common practice, and guidelines recommend spirometric measurements of lung function before and after administration of a short-acting bronchodilator to diagnose COPD (based on the post-bronchodilator measurement). However, use of post-bronchodilator testing to establish the presence of airflow limitation adds little predictive utility beyond the information gained from

A crucial moment in COPD: revisiting exacerbations

Exacerbations of COPD are a major cause of morbidity, and account for more than 1 million hospitalisations annually in Europe.201 Reducing and ultimately eliminating exacerbations is thus a crucial step on the pathway to elimination of COPD. Substantial progress in understanding of exacerbations has been made in the past few decades, but therapeutic approaches have not advanced in tandem. We aim to offer a new way forward to catalyse progress.

How can COPD therapy be more effective?

Currently, COPD care starts after the presence of persistent airflow limitation is spirometrically confirmed in a person with dyspnoea, exercise limitation, cough, or sputum production. Available pharmacological therapies focus on symptom relief, improvement of lung function, and reduction of the risk and frequency of exacerbations. Some data suggest that pharmacological treatments are associated with improvements in survival, but only in subsets of patients with severe disease—and even then

What is required to achieve COPD control?

For maximum effect and to ultimately eliminate the disease, new COPD therapies must be precise and target the specific molecular pathways or endotypes responsible for disease expression. These therapies might be more effective versions of the inhaled or orally administered small molecules that are already available, but could also include stem-cell or other regenerative approaches, nanotechnology delivery systems, or gene therapy. The prospects for the development of these treatments (and the

Towards the elimination of COPD

Advocacy efforts in COPD have largely focused on raising public awareness of the disease. Such efforts include World COPD Day, which has occurred since 2002 and is typically the third Thursday in November. World COPD Day has been highly successful in mobilising COPD organisations and helping patients to find their voice. However, to prevent and eliminate COPD, fundamental changes in approaches to advocacy are required.

The Commission's proposal to classify COPD on the basis of the primary risk

Appreciation of overlapping and interacting risk factors

A major barrier to the advancement of COPD care is the underappreciation of important risk factors beyond smoking. Targeted efforts to reduce these risk factors and to increase knowledge and understanding of the effects of these exposures on lung growth, disease initiation, and lung function decline will pave the way to innovative treatment strategies and perhaps the possibility to eliminate COPD. Many of these risk factors for COPD are closely linked to poverty, and although beyond the remit

Increased treatment efficacy and effectiveness and cure

In a survey316 of 1102 US patients with COPD, 82% were satisfied with their treatment plan, but only 12% stated that their disease was completely controlled. Further surveys by the COPD Foundation have suggested that most patients desire treatments that have a greater effect on their symptoms or that halt disease progression.317 The drug pipeline needs to be more robust, and there needs to be a shift of focus from blockbuster drugs aimed at most or all patients with moderate to severe disease

Conclusions and recommendations

It is quite possible that the elimination of COPD is not achievable, much as it might be impossible to eliminate other highly complex diseases with high morbidity and mortality, such as cancer, heart disease, and diabetes. However, our approach to date has lacked clarity, focus, and urgency and the global burden of COPD continues to increase. Although the decline in tobacco smoking in high-income countries is welcome, failure to control other risk factors jeopardises the gains that might

Declaration of interests

DS reports a grant from the Swiss National Foundation (SNF 320030_189280), and unrestricted grants from Curetis, AstraZeneca, and Boston Scientifics (paid to their institution); honoraria for participation in data safety monitoring or advisory boards or talks for CSL Behring, Berlin-Chemie Menarini, Novartis, GlaxoSmithKline, AstraZeneca, Vifor, Merck, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, and Chiesi; and is the current Global Initiative for Chronic Obstructive Lung Disease (GOLD)

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