Hypothesis: Does COPD have an autoimmune component?

Chronic obstructive pulmonary disease (COPD) is a major public health problem because: (1) it causes significant morbidity and mortality which is expected to increase worldwide in the near future;1 (2) it jeopardises the quality of life of the patients suffering from this devastating disease (particularly during exacerbations);2,3 and (3) it imposes an enormous global healthcare cost.1 However, because the pathogenesis of COPD is poorly understood, treatment is mostly symptomatic and new therapeutic strategies are limited.4 In this paper we propose a new hypothesis that considers the largely unexplored role of the immune system in the pathogenesis of COPD. If true, this hypothesis will generate new therapeutic opportunities in COPD.

THE CURRENT VIEW

The Global initiative for the diagnosis, management, and prevention of Obstructive Lung Disease (GOLD) defines COPD as a “disease state which is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases”.5 Many studies have attempted to characterise this abnormal inflammatory response. However, this issue is far from resolved because the results of these studies vary according to the severity of the disease (mild, moderate, or severe), the type of controls studied (never smokers, smokers with normal lung function, patients with stable COPD compared with those studied during exacerbations of the disease), the compartment of the lung sampled (central airways, peripheral airways, alveolar space), and/or the bias of the study towards the role of a given cell type.6 A critical review of this literature7 indicates the following salient features: (1) all smokers develop airway inflammation; (2) this is amplified in patients with COPD, particularly during exacerbations …