Chest

Chest

Volume 127, Issue 1, January 2005, Pages 275-283
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Reviews
Idiopathic Pulmonary Fibrosis

https://doi.org/10.1378/chest.18.4.330Get rights and content

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and typically fatal interstitial lung disease. Besides its grave natural history and prognosis, three aspects of IPF challenge clinicians and investigators: (1) recent changes in the conceptual framework and definition of IPF complicate interpretation of prior clinical investigations; (2) while most patients with suspected IPF do not undergo open-lung biopsy, clinical definitions that do not include biopsy criteria have not been validated prospectively; and (3) available treatments have not been shown to be effective. To optimize clinical care and facilitate clinical investigation, a major goal of IPF research should be to develop validated sets of clinical diagnostic and prognostic criteria. Studies have shown the diagnostic value of high-resolution CT scans and identified important prognostic variables; many of these observations await prospective validation. While previous therapeutic studies have been limited by small sample sizes, lack of a placebo control group, and insufficient attention to patient-centered outcomes, the recent study of interferon γ-1b demonstrated the feasibility of a large-scale, multicenter clinical trial in IPF. In this article, we discuss how overcoming challenges in IPF research will enable future investigators to conduct well-designed observational studies and clinical trials, whose meaningful results will advance our understanding of IPF, its management, and its impact on patients’ lives.

Section snippets

Challenges Related to Nomenclature

A potentially confusing and ever-changing nomenclature makes it difficult to interpret prior studies and hinders effective communication about patients with IPF. IPF belongs to a group of related but distinct interstitial lung diseases (IIP). While most of the IIPs can present similarly, each has a unique pathologic pattern that forms the basis for their current classification.2

An international multidisciplinary consensus committee2 has proposed this standardized classification system, which

Challenges Related to the Discovery of NSIP

One reason that classification schemes have become outdated is the discovery of NSIP. The presence of NSIP complicates the design of new studies and, like nomenclature, creates challenges to interpreting previous studies of patients with IPF. Katzenstein and Fiorelli4 described NSIP in 1994 as a “nonspecific” pattern of lung injury, consisting of varying degrees of inflammation and fibrosis that do not satisfy criteria for the histologic pattern of any other IIP. According to the most recent

Surgical Biopsy: the Current “Gold Standard”

In IPF clinical research, the first step should be to ensure that all study subjects have IPF. Many studies141516 have used the finding of a UIP pattern in the appropriate clinical setting as the diagnostic reference test. Even though the characteristic features of a UIP pattern have been outlined in several important articles,2317 it is often difficult for less experienced pathologists to make this histologic diagnosis. Sometimes even experts cannot agree on the presence of a UIP pattern. For

Challenges Related to Studies of Prognosis

Practical, validated prediction rules can provide concrete and reliable information about prognosis for patients and their family members. They facilitate communication between physicians and, in the case of IPF, such models can provide valuable information about the optimal timing of referral for lung transplantation. When used in drug trials, prognostic models serve three purposes: (1) permitting baseline comparisons between patients assigned to placebo and those assigned to active treatment;

Challenges Related to Studies of Treatment

Recent pathologic and clinical data suggest inflammation does not play a prominent role in the pathophysiology of IPF. This observation, combined with evidence from in vitro studies demonstrating alveolar epithelial injury may directly induce fibrosis,33 provide impetus for the hypothesis that IPF is an “epithelial-fibroblastic disease.”1

Nevertheless, widely used management strategies for IPF have included anti-inflammatory and immunosuppressive medications in the form of glucocorticoids and

Future Trials

What should be the design of future IPF therapeutic trials? Small, single-center trials enable testing of a wide range of novel therapeutic agents, and they sometimes generate hypotheses for future studies. Because patient numbers at any one center are small, such trials must be designed to look for large differences in the effects of treatment between groups (as opposed to large trials, which have greater statistical power and are able to look for smaller effects). For IPF, large,

Conclusions

IPF is a debilitating and typically fatal form of IIP. Treatments are commonly offered for IPF, but no regimen has been proven effective. The updated nomenclature of IIP and new conceptual framework, including the recent discovery and addition of NSIP, have reshaped perspectives on IPF. However, caution must be exercised when interpreting past IPF clinical studies because of evolution in the disease case definition. Future IPF clinical research should utilize precise nomenclature in reference

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    Dr. Swigris received support from an National Institutes of Health institutional training grant (T32 HL07948–01A1).

    Dr. Gould received an Advanced Research Career Development Award from the VA Health Services Research and Development Service.

    The views presented in this article are those of the authors and are not necessarily the views of the Department of Veterans Affairs.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]).

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    Copyright © 2005 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.