There is not much doubt that cigarette smoking is the main trigger for the development of chronic obstructive pulmonary disease (COPD). However, the mechanisms by which cigarettes produce the disease have been elusive. The consideration of new ideas could bring new insights. The paper by Di Stefano et al. 1 in this issue of the European Respiratory Journal invites me to revisit a previously stated hypothesis 2–4, that the T‐cell and autoimmunity may be the key in the mechanisms leading to COPD, since Di Stefano et al. 1 provide another piece of evidence in favour of this paradigm.
Let's look at the autoimmune hypothesis with open eyes. Concepts evolve as new evidence settles in. Who would have believed 20 or even 10 yrs ago that peptic ulcer is an infectious disease, now treated with antibiotics, or that arteriosclerosis is an autoimmune disease, triggered by epitopes generated in the process of atherogenesis, such as oxidised low-density lipoproteins 5, 6? Therefore, why not consider COPD as an autoimmune disease triggered by smoking? But why should we consider such as scenario? I will explain and, in doing so, how the Di Stefano et al. 1 paper fits into this paradigm.
For years, the inflammatory reaction in COPD was focused on neutrophils and their elastase, and macrophages and their metalloproteinases: the protease–antiprotease paradigm; an important mechanism, but probably only one step in the complex pathogenesis of COPD. Then, Finkelstein et al. 7 introduced the T‐cell as an important inflammatory component in the lungs of smokers, expanding the field of investigation of the inflammatory reaction in COPD to include the T‐cells. For years, it was believed that because neutrophils and macrophages were increased in smokers, they were involved in the pathogenesis of the disease. T‐cells are also increased in smokers' lungs, …
