Medical Health Cluster

6 septiembre, 2022

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

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 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.

In this Lancet Commission on COPD, our objective is to set the course to eliminate the disease by challenging accepted dogma and generating debate. We recognise that many of our recommendations could not be used as the foundation for evidenced-based guidelines. However, that is not our goal. We believe that a wholesale rethinking of COPD is needed. In general, we believe that the traditional incremental approach to advancing understanding of disease and developing new methods for diagnosis and treatment has failed. In particular, we advocate for: broader understanding of risk factors (including the devastating effects of global poverty) and the preventive measures necessary to avoid future cases of COPD, disruptive approaches to diagnosis that are not solely based on spirometric airflow limitation but also involve identification of early pathological changes that are more amenable to reversal, classification of the disease into types that share pathophysiological similarities and could lead to novel preventive and therapeutic approaches, and a new approach to the diagnosis and assessment of exacerbations of COPD that focuses on disease mechanisms. We also advocate for a coordinated plan to combat the disease through increased financial investment, broad public policy initiatives, regulatory reform, and the alignment of health-care systems, which will enable a path towards prevention and cure rather than crisis management.

The most efficient way to reduce the burden of COPD is to ban cigarette smoking in all its forms. We strongly advocate for this ban, and support the associated financial, technological, and retraining investments that would be necessary to prevent economic disaster among people dependent on the tobacco industry for their livelihood. However, risk factors unrelated to tobacco are increasingly responsible for the burden of COPD, and are likely to surpass the risk attributable to smoking within the next two decades. These risks include many underappreciated factors that span the life course, from in-utero exposures to maternal factors leading to preterm birth or low birthweight, early-life infections, and indoor and outdoor pollution. Poverty increases the prevalence of these risk factors but decreases societal efforts to control them. Messaging targeted at medical professionals, government officials, private corporations, and the general public should emphasise these risk factors and drive preventive strategies. Otherwise the tobacco-related COPD crisis will be replaced by a COPD crisis driven by one or more of the other factors.

The definition of COPD requires the presence of spirometric airflow limitation, which all but eliminates the possibility that the disease could be cured or eliminated globally because the pathological changes required for airflow limitation are almost certainly permanent. We advocate for a broader definition of COPD that includes people with airflow limitation detected by more sensitive pulmonary function tests or pathological changes detected by imaging techniques. This broader definition will enable detection of patients with earlier pathological changes, which would enhance the possibility of understanding the mechanistic pathways driving disease inception and could thus lead to the development of effective treatments to interrupt and reverse the course of COPD. In low-income settings, we also advocate for the use of risks and symptoms to identify a population with probable COPD, in whom preventive measures and low risk non-pharmacological and pharmacological treatments could be beneficial. Throughout the Commission, we have provided similar options for alternative approaches when technology, the health-care system, or the personnel available limit the implementation of our recommendations.

Closely tied to the inadequacy of current diagnostic criteria is the failure to classify COPD in a way that could help to identify new approaches to prevention and treatment. We recommend that COPD be classified into types based on five main risk factors: genetics, early-life events, pulmonary infections, tobacco smoke exposure, and pollution. This approach mirrors that developed for pulmonary hypertension in the 1970s, which has revolutionised understanding of the disease and led to numerous novel therapeutics targeting individual classes of the disorder. We recognise that the risks factors leading to airflow limitation are numerous, and that many patients are affected by more than one. However, this is also true for patients with pulmonary hypertension, who can have more than one mechanism driving their disease (eg, heart failure and coexistent lung disease). Our proposal is not perfect and, like the WHO classification of pulmonary hypertension, will require iterative refinement, but it is far more likely to yield new therapeutics than a system that relies solely on the presence of spirometric airflow limitation and a patient’s level of dyspnoea and exacerbation frequency (the extent of current attempts to classify COPD).

An acute worsening of COPD is termed an exacerbation, and such episodes account for a substantial proportion of the attributable cost of the disease and are associated with accelerated lung function loss, prolonged impairments in quality of life, and similar prognosis to many stage III or IV solid organ malignancies. Yet exacerbations tend to be imprecisely defined, and their severity is judged according to the site of treatment rather than the extent of underlying physiological derangement. Few exacerbations are thoroughly investigated to establish the underlying trigger (despite the availability of many diagnostic tools). Reflexive treatment with corticosteroids or antibiotics, or both, is prescribed in almost all cases—a therapeutic approach that has not changed in more than 30 years and in some cases is almost certainly harmful. We call for an objective definition of COPD exacerbations, a standardised assessment, and a precision approach to treatment (such a treatment approach will take time, because the development of new therapeutics will be contingent on the implementation of the new definition).

In the almost 4 years since this Commission was formed, the devastating COVID-19 pandemic has led to unprecedented efforts to align health authorities, regulatory agencies, private corporations, and the public in the fight against the disease. Although many parts of the world do not yet have access to the vaccines and treatments that were rapidly developed to combat COVID-19, the availability of these therapeutics in many high-income countries has shown that barriers preventing a coordinated response to a global crisis can be overcome and that a rapid response is possible. We argue that such a response is needed for the many chronic diseases that cause far greater yearly morbidity and mortality than COVID-19, including COPD. This response will require substantially increased investment in public health policies to prevent exposure to risk factors, implementation of our proposals to capture COPD earlier and enable phenotyping of patients, and research and development of precision therapeutics.

Créditos: Comité científico Covid

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