The pathogenesis of COPD and IPF: distinct horns of the same devil?

Abstract

New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences. There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema). The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD).

Figure 1

Pathogenic scheme of IPF and COPD. Summation of genetic and environmental factors underlay the abnormal renewal of either epithelial (left) or mesenchymal (right) alveolar components leading to parenchymal fibrotic obliteration and remodeling in IPF, or emphysematous changes and airway inflammation in COPD. The genetic background can be either hereditary (fully consistent with a "telomere dysfunction" as observed in familial IPF), or can variably provide a genetic susceptibility.

Figure 2

Pathogenic scheme of IPF and COPD. The complex effects of either epithelial (left), or mesenchymal (right) insufficiency on derangements of various signaling pathways in IPF and COPD as hypothesized in this review is summarized.