Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is a poorly understood respiratory disease of humans. Affecting approximately 11 male and 8 female patients, respectively, per 100,000 individuals per year, it is one of the more prevalent interstitial lung diseases. Confounding these many cases is the lack of efficacy of most therapeutics for the disease; this lack of therapeutic options is associated with a 5-year mortality between 50% and 70%. The indolent nature of the disease, with the high mortality, unknown cause(s), and poorly understood pathogenesis makes the identification of appropriate animal models extremely important and challenging. The National Heart, Lung, and Blood Institute of the National Institutes of Health convened a workshop to identify critical future research areas directed toward a better understanding of IPF. Identification/development of an animal model of IPF was deemed critical toward any future progress in filling gaps in understanding of the disease and the testing of future therapeutic modalities. Unfortunately, there is not currently an animal model that recapitulates the progression of the disease, nor develops remodeling within the lungs typical of IPF.
Historically, there has been confusion as to the variety of morphologic presentations of IPF; no less than four distinct entities were classified under the rubric of IPF, including acute interstitial pneumonia (Hamman-Rich syndrome), usual interstitial pneumonia (UIP), desquamative interstitial pneumonia, and nonspecific interstitial pneumonia (NSIP). In 2000, an international consensus statement was issued by the American Thoracic Society and the European Respiratory Society that defines the criteria for diagnosis of IPF in humans. This statement eliminated all but UIP from the definition of IPF, leaving the other three as separate, distinct entities. The salient histologic features of UIP lungs are as follows: temporal heterogeneity of lung remodeling, with the primary changes involved being interstitial fibrosis and ongoing fibroblast/myofibroblast proliferation, “honeycomb” change (enlarged airspaces lined by prominent variable epithelium), and scant inflammation. The histologic complexity is complicated by the finding of Flaherty et al; data presented show that there is abundant interlobar variability in patients with idiopathic interstitial pneumonia, with significant numbers of patients having changes consistent with both UIP and NSIP.