Idiopathic pulmonary fibrosis: New insights into classification and pathogenesis usher in a new era in therapeutic approaches

PW Noble - American journal of respiratory cell and molecular …, 2003 - search.proquest.com
PW Noble
American journal of respiratory cell and molecular biology, 2003search.proquest.com
Idiopathic pulmonary fibrosis (IPF) is a fascinating and poorly understood disease with
devastating consequences to those afflicted that has undergone several revisions in the last
30 yr. IPF is a clinical, physiologic, radiographic, and pathologic entity that has been difficult
to characterize as a homogenous" disease"(1). A major reason for the difficulty in defining
IPF has been the lack of a gold standard in the diagnosis. Unlike cancer, infection, or
pulmonary embolism, in which it is possible to unequivocally obtain documentation of …
Idiopathic pulmonary fibrosis (IPF) is a fascinating and poorly understood disease with devastating consequences to those afflicted that has undergone several revisions in the last 30 yr. IPF is a clinical, physiologic, radiographic, and pathologic entity that has been difficult to characterize as a homogenous" disease"(1). A major reason for the difficulty in defining IPF has been the lack of a gold standard in the diagnosis. Unlike cancer, infection, or pulmonary embolism, in which it is possible to unequivocally obtain documentation of disease, it has been debated whether lung biopsy provides a gold standard in IPF. There are (at least) three major reasons for this ambiguity:(i) not all patients with radiographic suspicion of pulmonary fibrosis have a lung biopsy performed,(ii) the lung biopsy only samples small regions of the lung, and (iii) pathologists have differed in their description of the pathologic findings in IPF. The pathologic description of IPF was originally delineated by Leibow and colleagues, and termed" usual interstitial pneumonia (UIP)"(2). Over the last 30 yr, there has been a refinement in the pathologic description of Idiopathic Interstitial Pneumonias, and the most recent classification represents a consensus of leading experts in the field (2). The major refinement has been that the mere presence of fibrosis in the lung biopsy does not necessary mean that the patient has IPF. What has been reproducible in several large retrospective series of patients with presumed IPF is that the mean survival after recognition is between 2 and 5 yr, with the most recent studies suggesting a mean of 2.8 yr (3). UIP has been recognized as a distinct pathological entity characterized by the presence of (i) patchy chronic interstitial inflammation;(ii) oldest disease (fibrosis) is peripheral in the lung acinus or lobule;(iii) transitions to uninvolved lung in the biopsy, ie, temporal heterogeneity; and (iv) a leading edge of fibroblastic foci and microscopic honeycombing. In studies in which this description has been identified by skilled observers in lung biopsies from patients with the clinical, physiologic, and radiographic findings characteristic of IPF, the majority of patients have demonstrated progressive disease and died despite treatment with high doses of corticosteroids and/or potent cytotoxic immunosuppressants such as cyclophosphamide and azathioprine. This is in contrast to patients that have distinct pathologic descriptions as well as distinguishing clinical, physiologic, and radiographic features that allow for the characterization of nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RBILD), or acute interstitial pneumonia (AIP). NSIP has been subdivided into cellular and fibrotic forms that differ in prognosis (4). With the exception of AIP, the other idiopathic interstitial pneumonias (IIPs) have a better prognosis and improve with corticosteroid/immunosuppressive more frequently than observed with UIP. Important observations from Flaherty and colleagues have suggested that patients with IIP may have both UIP and NSIP-fibrotic patterns in different regions of the lung (5). However, the presence of UIP appears to be dominant in terms of clinical outcome. That is, patients with both NSIP-fibrotic and UIP patterns on biopsy have a poor prognosis relative to those with only NSIP-fibrotic (5). This work raises the interesting question as to the relationship between NSIP and UIP. Future studies will be needed to determine if these are a continuum or distinct pathologic and clinical entities.
The combination of the unique pathologic features of UIP on biopsy, the inexorable progression to death …
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