2.6. Evolving theory of the pathogenesis of idiopathic UIP

One of the major aims of the research on pulmonary fibrosis is to define the mechanisms that lead to persistence of fibroblast foci and thus to irreversible fibrosis and interstitial remodeling in UIP. The reason for this is that idiopathic UIP is a progressive and usually fatal lung disease still without efficient treatment (Bjoraker et al. 1998, Katzenstein & Myers 1998). UIP responds to corticosteroids much more poorly than the other histopathologic subgroups of interstitial pneumonias, except for acute interstitial pneumonia (Bjoraker et al. 1998, Daniil et al. 1999, Nicholson et al. 2000). Mainly because of this the prevailing hypothesis of UIP as an inflammatory disease is being questioned. Parallel with the classification of idiopathic interstitial pneumonias represented by Katzenstein & Myers (1998), it became evident that part of the cases included in earlier studies as UIP actually represented other subgroups of interstitial pneumonias with different histological characteristics and different clinical behavior. In fact, in UIP the inflammatory component is usually mild, occurs mainly in areas of collagen deposition of honeycomb change, and rarely involves otherwise unaltered alveolar septa (Katzenstein & Myers 1998). On the other hand, interstitial lung diseases in which inflammation is a prominent feature of early disease, for example desquamative interstitial pneumonia and hypersensitivity pneumonitis, often do not progress to end-stage fibrosis (Katzenstein & Myers 1998). Adamson et al. showed in 1988 that epithelial injury in the absence of ongoing inflammation is adequate to stimulate the development of fibrosis. In recent years a few animal model studies have been published also suggesting that it is possible to dissociate the inflammatory response from the fibrotic response (Huaux et al. 1998, Munger et al. 1999, Sime et al. 1997). In histologic tissue samples, the extent of cellularity or alveolar space cellularity (i.e. amount of inflammatory cells) did not affect survival. Instead, the only histologic finding with prognostic significance was the number of fibroblast foci, which had an adverse correlation with survival (King et al. 2001). However, both the number of fibroblast foci and the amount of interstitial mononuclear cells have been shown to correlate with pulmonary function (Nicholson et al. 2002).

In 2001, Selman et al. published a review presenting a theory of an abnormal wound healing model for UIP. According to this theory, fibrosis in UIP is suspected to result from a failure of re-epithelialization of injured areas combined with prolonged survival of active myofibroblasts and deficient vascularization of fibroblast foci. The authors have compared morphological changes of fibroblast foci of UIP to those seen in normal wound healing model in skin and in Masson bodies of BOOP (Selman et al. 2001). In the present study an analogous approach has been applied to the subject by comparing vascularization, apoptosis and re-epithelialization of intraluminal fibrosis in UIP and BOOP.