Immune response in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a major public health problem because of its high prevalence, rising incidence and associated socio-economic cost. The inhalation of toxic particles and gases, mostly tobacco smoke, is the main risk factor for COPD. Yet, not all smokers are equally susceptible to these toxic effects and only a percentage of them develop the disease (so-called ‘susceptible smokers’). This, in combination with the observation that COPD shows familial aggregation, suggests that the genetic background of the smoker is a key element in the pathogenesis of the disease. On the other hand, it is well established that ‘susceptible’ smokers exhibit an enhanced inflammatory response of the lung parenchyma as compared with ‘resistant’ smokers (i.e., those who manage to maintain lung function within the normal age range despite their habit). Importantly, in COPD patients this inflammatory response does not resolve after quitting smoking, again at variance with resistant smokers. All in all, these observations suggest that the pathogenesis of COPD may involve, in some patients, an autoimmune component which contributes to the enhanced and persistent inflammatory response that characterizes the disease. Here we: i) review briefly the pathobiology of COPD; ii) present the available scientific evidence supporting a potential role for autoimmunity in COPD; iii) propose a three-step pathogenic hypothesis in the transition from smoking to COPD; and iv) discuss potential implications for the diagnosis and treatment of this frequent, growing, devastating and costly disease.

Keywords::

• autoimmunity
• chronic obstructive pulmonary disease
• emphysema
• inflammation
• repair

Financial & competing interests disclosure

The authors were supported in part by FIS PI10/00523 and FIS PI12/01117, Mutua Madrileña PI041966/2012, Beca Fucap 2012, SEPAR 133/2011. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Only a proportion of smokers (20–30%) develop chronic obstructive pulmonary disease (COPD).

• • Those smokers who develop COPD appear to have an enhanced inflammatory response that does not resolve after the initiating event (smoking) disappears.

• • In last few years, direct, indirect and circumstantial evidences have been found that support that the pathogenesis of COPD may involve an autoimmune component (particularly in COPD patients with emphysema and/or severe disease).

• • These evidences include the existence of an inflammatory response in the lung of COPD patients characterized by T- and B-lymphocyte infiltrates and the identification of several auto-antigens recognized by these cells, such as collagen and elastin.

• • A model of disease progression is proposed from available scientific evidence that involves both the innate and the acquired immune system. So far, there are no direct implications of these observations for the diagnosis and/or treatment of COPD, but in the future they may be useful for a better phenotypic characterization (and, eventually, treatment) of patients with COPD.