Semin Respir Crit Care Med 2006; 27(6): 567-568
DOI: 10.1055/s-2006-957327
PREFACE

Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Idiopathic Pulmonary Fibrosis

Victor J. Thannickal1  Guest Editor 
  • 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan
Further Information

Publication History

Publication Date:
29 December 2006 (online)

In this issue of Seminars, we have assembled an internationally renowned group of clinicians and scientists to discuss current controversies and evolving concepts in idiopathic pulmonary fibrosis (IPF). Over the past 5 years, the implementation of an improved classification system of the idiopathic interstitial pneumonias (IIPs) has helped to define subgroups of non-IPF patients who carry more favorable prognoses and are more likely to respond to currently available therapies.[1] IPF, the most common of the IIPs, remains enigmatic and no effective therapies currently exist. Our panel of experts outlines current concepts and controversies regarding pathogenesis, diagnosis, and management of patients with IPF.

First, I provide a clinicopathological perspective of the diffuse IIPs; the concept that lungs of affected patients respond to an unknown injury (or injuries), which results in varied histopathological patterns (host responses/tissue reactions), ranging from more inflammatory to more fibrotic, is proposed. The importance of the natural history of the disease notwithstanding, patients who present with more fibrotic disease, by histopathology or high-resolution computed tomography (HRCT), are less likely to respond to conventional antiinflammatory/immunosuppressive therapy. In their discussion on “Host-Environment Interactions in Pulmonary Fibrosis,” Drs. Garantziotis and Schwartz advance the concept that host susceptibility, both genetic and nongenetic, interacts with repetitive environmental injury that results in the phenotypic expression of IPF. Such complex interactions between multiple genes and potentially multiple environmental triggers/stimulants may explain why there has been difficulty in defining a single etiology and elucidating a clear-cut pathogenetic schema. This notion is further reinforced in the treatise on “Genetic Factors in Pulmonary Fibrotic Disorders” by Dr. du Bois. He cautions that a strategy of assigning relative contributions from different genes together with environmental interactions to the expression of the disease will be a difficult one, but one that he feels may be accomplished with a concerted internationally coordinated effort.

In their article on “Inflammation and Angiogenesis in Fibrotic Lung Disease,” Drs. Keane, Strieter, Lynch, and Belperio address the controversy regarding the role of inflammation and vascular remodeling in IPF. They advocate that mechanisms of inflammation in IPF pathogenesis should not be discounted altogether, solely based on the observed lack of efficacy to currently available antiinflammatory agents, and that a better understanding of the “type” of inflammation present in IPF lungs is required. On the subject of vascular remodeling, they point out that, although the precise role of this aberrant vasculature is the subject of ongoing investigation, alterations in the vasculature likely contribute to the heterogeneous fibroproliferation, refractory hypoxemia, and pulmonary hypertension that are seen in IPF. The complexity of the lung injury/repair process is further highlighted in the article on “Epithelial-Mesenchymal Interactions in Pulmonary Fibrosis” by Drs. Horowitz and Thannickal. The emergence of abnormal epithelial and mesenchymal cell phenotypes seen in IPF/usual interstitial pneumonia (UIP) by the formation and maintenance of dysregulated interactions (autocrine and paracrine signaling) between these cell types is discussed. Drs. Lai, Wallace, and Fishbein review the histopathology of the major interstitial lung diseases, including the idiopathic interstitial pneumonias and pulmonary fibrotic disorders associated with collagen vascular diseases and smoking in the article entitled, “Histopathology of Pulmonary Fibrotic Disorders.” They warn that interpretation of lung biopsy findings is often difficult, with surprisingly significant interobserver variability, even among experienced pathologists, and emphasize that correct classification of these complex disorders requires integration of clinical, radiological, and pathological findings.

Drs. Suh and Goldin, in their article on “High-Resolution Computed Tomography of Interstitial Pulmonary Fibrosis,” provide the reader with an appreciation of recent advances in imaging for diffuse lung diseases and the increasing role of HRCT in the diagnosis of IPF. Drs. Lynch, Saggar, Weigt, Zisman, and White discuss the current approach to the clinical diagnosis of the most progressive and severe form of the IIPs, IPF, as well as prognostication based on variabilities in the natural history of the disease in their article on “Usual Interstitial Pneumonia.” Significant variability in prognosis and treatment responsiveness also exists in nonspecific interstitial pneumonia (NSIP), as discussed by Drs. Flaherty and Martinez (under “Nonspecific Interstitial Pneumonia”). They emphasize that NSIP is a “provisional” diagnosis that should be reserved for true “idiopathic” cases in which no causative factors, including immunodeficiency, drug or environmental exposures, and connective tissue diseases, are identified. In “Acute Interstitial Pneumonia and Acute Exacerbations of Idiopathic Pulmonary Fibrosis,” Drs. Swigris and Brown provide information on the emerging role of acute exacerbations in the natural history of IPF with clinical and pathological features that resemble acute interstitial pneumonia (AIP). They call for more research to identify clinical predictors of disease occurrence, pathogenetic mechanisms, and effective therapies for these devastating disorders.

In the last article by Drs. Daniels and Ryu on “Treatment of Idiopathic Pulmonary Fibrosis,” a balanced and pragmatic approach to management of IPF patients is presented. It is acknowledged that no proven drug therapies exist and that patients should be encouraged to enroll in clinical trials. I would like to emphasize this latter point because large, well-controlled trials are lacking-it is not inconceivable that “placebo” may be a better option to the pharmacotherapeutic agents that are currently available, particularly when significant side-effects of these agents are weighed against their limited efficacy. Thus every effort should be made to keep patients enrolled in such trials for the duration of the trial even if the perception (on the part of the patient or physician) is that they are receiving placebo. Often, the desire to “treat”-with something-results in significant harm caused by unproven drug therapies and, at the same time, retards progress in gaining new knowledge regarding the potential benefits/risks of more novel therapeutic agents.

I would like to thank all the authors for their excellent contributions to this issue of Seminars in Respiratory and Critical Care Medicine. We hope that the articles in this issue will provide the practitioner with a fresh perspective on a most challenging group of patients with respiratory disorders. As we continue to make progress in understanding disease pathogenesis, improving classification and diagnostic accuracy, we hope that more acceptable and beneficial treatment regimens for our patients with fibrotic lung diseases will follow.

REFERENCE

  • 1 American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias . This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001.  Am J Respir Crit Care Med. 2002;  165 277-304

Victor J ThannickalM.D. 

Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center

6301 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI 48109

Email: vjt@umich.edu

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