Elsevier

Clinics in Chest Medicine

Volume 41, Issue 3, September 2020, Pages 307-314
Clinics in Chest Medicine

Chronic Obstructive Pulmonary Disease Pathogenesis

https://doi.org/10.1016/j.ccm.2020.05.001Get rights and content

Section snippets

Key points

  • Tobacco smoking is the main, but not the sole risk factor for COPD.

  • COPD can start early in life. About 4% to 12% of individuals in the general population never achieve normal peak lung function in early adulthood and are at risk for developing COPD (and other concomitant diseases) later in life, and of dying prematurely.

  • The pathogenesis of COPD involves a series of dynamic, cumulative, environment-host interactions that occur throughout life and determine lung development, repair, and aging,

The traditional understanding of chronic obstructive pulmonary disease: a self-inflicted disease caused by tobacco smoking (in males)

In 1976, Fletcher and coworkers4 published the classic book The Natural History of Chronic Bronchitis and Emphysema. It details the results of a study in a stratified, relatively small (n = 792), random sample of men (no females were included in the study) aged 30 to 59 working in West London, who were followed the next 8 years.4 Results were summarized 1 year later.1 Fig. 1 here and in that review became, until recently,2 the holy grail of the understanding of the pathogenesis of COPD. It

Some observations do not fit this traditional pathogenic paradigm

The following recent epidemiologic and clinical observations do not fit this traditional paradigm and, overall, partially challenge its validity.

A new pathogenic understanding of chronic obstructive pulmonary disease: a balanced lung development and aging process determines lifelong lung function trajectories

As summarized graphically in Fig. 3, and discussed in detail next, we propose that COPD should be considered the end result of several dynamic, cumulative, and lifelong gene-environment interactions that modulate the intensity and interaction of two key biologic phenomena3: organ development, maintenance, and repair; and cumulative tissue injury and aging. The interaction of these two mechanisms determines the trajectory followed by lung function throughout life (Figs. 4 and 5), and by doing

Implications

This new pathogenic understanding of COPD has numerous implications that clearly open new opportunities for its prevention and early therapy.

Summary

The understanding of the pathogenesis of COPD has changed significantly in recent years. Although tobacco smoking continues to be a key environmental risk factor for the development of the disease in some smokers, it is now recognized that there are many other risk factors that can significantly affect lung development and lung aging, both of which are key pathogenic mechanisms of the disease (see Fig. 3).3 Eventually, it is the dynamic and cumulative interaction of environment and host factors

Disclosure

Supported, in part, by FIS (PI17/00369, PI18/01008)CIBERES and SEPAR. RF is a recipient of a Miguel Servet Research Contract supported by FEDER funds (CP16/00039).

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    Present address: CIBERES, C/Casanova 143, Cellex, P2A, Barcelona 08036, Spain.

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