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

Abstract

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 considered a public health emergency: failure to limit the sale and consumption of tobacco products, unchecked exposure to environmental pollutants across the life course, and the ageing of the global population (partly as a result of improved outcomes for other conditions). Additionally, despite the heterogeneity of COPD, diagnostic approaches have not changed in decades and rely almost exclusively on post-bronchodilator spirometry, which is insensitive for early pathological changes, underused, often misinterpreted, and not predictive of symptoms. Furthermore, guidelines recommend only simplistic disease classification strategies, resulting in the same therapeutic approach for patients with widely differing conditions that are almost certainly driven by variable pathophysiological mechanisms. And, compared with other diseases with similar or less morbidity and mortality, the investment of financial and intellectual resources from both the public and private sector to advance understanding of COPD, reduce exposure to known risks, and develop new therapeutics has been woefully inadequate.

Figure 1:. DALYs (A) and years of life lost (B) to COPD

In 2019, COPD was the seventh leading cause of DALYs globally and the eighth leading cause of years of life lost. DALYs=disability-adjusted life-years. COPD=chronic obstructive pulmonary disease.

Figure 2:. The importance of early diagnosis to eliminate COPD

(A) Currently, COPD is diagnosed at a stage when pathological changes are irreversible. This late diagnosis is due to a combination of factors, including the lack of predictive biomarkers, under-recognised clinical symptoms, a long period of disease activity associated with no or minimal symptoms, and reliance on spirometry, an insensitive diagnostic tool. (B) Implementation of a more inclusive diagnosis of COPD allows for the detection of early disease before irreversible pathological changes have occurred and could lead to disease interception. COPD=chronic obstructive pulmonary disease. RCT=randomised controlled trial.

Figure 3:. Proportion of global population with access to spirometry (A), chest CT (B), and chest radiography (C) for diagnosis of chronic obstructive pulmonary disease

Data were obtained from the survey done by the Commission (appendix pp 1–5).

Figure 4:. Availability of pharmacological therapies (A) and non-pharmacological therapies (B) for chronic obstructive pulmonary disease in lower-middle-income, upper-middle-income, and high-income countries

LAMA=long-acting muscarinic antagonist. LABA=long-acting β agonist. SAMA=short-acting muscarinic antagonist. SABA=short-acting β agonist.

Figure 5:. Research expenditure per death by the US National Institutes of Health, by disease, 2020

The bars depict the deaths per year per disease in the USA. In terms of US dollars committed per death from each disease, chronic obstructive pulmonary disease receives the lowest funding.^,

Figure 6:. Proposed classification of COPD according to major risk factors

The five proposed types are related to genetics, early-life events, infections, exposure to tobacco smoke, and environmental exposures. We remain cognisant, however, that individuals are prone to multiple exposures throughout life, which could cause additive or interactive damage to lung health. COPD=chronic obstructive pulmonary disease.

Figure 7:. Thoracic CT of a 72-year-old patient with α₁ antitrypsin deficiency

The arrows show emphysematous areas in the lung. The patient is an ex-smoker with a 40-pack-year history of tobacco use, a COPD assessment test score of 21 (range 0–40; higher scores suggest greater disease effects), and a modified medical research council dyspnoea score of 3 (0–4; higher scores suggest greater dyspnoea). COPD=chronic obstructive pulmonary disease.

Figure 8:. Thoracic CT of a patient aged 56 years diagnosed with HIV in 1995

At the time of the CT, the patient was an active smoker and had a diffusing capacity of the lungs for carbon monoxide of 32·2% of predicted, severe pulmonary hypertension, and cachexia (body-mass index 18·9 kg/m²).

Figure 9:

Lung function trajectories across the lifecourse (A) and environmental and individual risk factors that affect lung function trajectories and lung health from before conception to old age (B)

Figure 10:. Comparison of physiology between healthy lungs and lungs affected by COPD

COPD=chronic obstructive pulmonary disease.

Figure 11:. Proposed diagnostic algorithm for COPD

COPD=chronic obstructive pulmonary disease. mMRC=modified medical research council scale. CAT=COPD assessment test. FEV₁=forced expiratory volume in 1 s. FVC=forced vital capacity.

Figure 12:. Receiver operating characteristic curves (A) and calibration curves (B) for prediction of exacerbations of chronic obstructive pulmonary disease

Analyses that include lung function use pre-bronchodilator measurements. Higher AUC indicates better discrimination, whereas lower ICI indicates better calibration. For more information, see the appendix (p 6). AUC=area under the receiver operating curve. ICI=integrated calibration index.

Figure 13:. Association between proposed COPD types, endotypes, and phenotypes

The proposed COPD types probably result from varying molecular mechanisms (endotypes) that in turn result in the observable phenotypes of the disease. COPD=chronic obstructive pulmonary disease

Figure 14:. Specific effective airway resistance in patients with COPD with and without airflow limitation (A); and in current and former smokers vs never smokers without airflow limitation (B) and with airflow limitation (C)

Specific effective airway resistance is pathological if it is ≥1·2 kPa per s, which is further classified as mild (1·2–2·0 kPa per s), moderate (2·1–4·0 kPa per s), or severe (>4·0 kPa per s). It is higher in current or former smokers than in non-smokers, irrespective of the presence or absence of spirometrically determined airflow limitation. COPD=chronic obstructive pulmonary disease.

Figure 15:. Maps of the incidence of moderate or severe exacerbations (A) and pneumonia (B) in patients with chronic obstructive pulmonary disease

Data sourced from the IMPACT study. This figure is redrawn with permission from GlaxoSmithKline.

Figure 16:. Flowchart to assess the status of patients with chronic obstructive pulmonary disease with new or worsening respiratory symptoms who contact medical personnel by telephone

*Concerning symptoms. †Alarming symptoms. ‡Mandatory diagnostics include respiratory rate, oxygen saturation, chest image, full blood count, and measurement of C-reactive protein and D-dimer.

Figure 17:. Timeline of medications entering the market for COPD vs cardiovascular disease

COPD=chronic obstructive pulmonary disease. SABA=short-acting β agonist. SAMA=short-acting muscarinic antagonist. LABA=long-acting β agonist. LAMA=long-acting muscarinic antagonist. PDE4=phosphodiesterase-4. ACEI=angiotensin-converting enzyme inhibitor. ARB=angiotensin receptor blocker. MRA=mineralcorticoid receptor antagonists. ARNI=angiotensin receptor–neprilysin inhibitor. SGLT2I=sodium-glucose linked transporter 2 inhibitor. CRT=cardiac resynchronisation therapy. ICD=implantable cardioverter defibrillator. CABG=coronary artery bypass graft. LVAD=left-ventricular assisted device. CRT-P=cardiac resynchronisation therapy pacemaker. CRT-D=cardiac resynchronisation therapy defibrillator..

Figure 18:. Estimation of the number of deaths avoided (A), years lived with disability avoided (B), and years of life gained (C) after the implementation of more stringent tobacco control policies

Such policies include increased cigarette prices, protections from environmental tobacco smoke, health warnings, and bans on tobacco advertising, promotion, and sponsorship. Data are broken down by WHO region. The appendix (pp 7–8) contains full details on the methods.