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Introduction

San Francisco General Hospital, San Francisco, California

Moisés Selman, M.D.

Instituto Nacional de Enfermedades Respiratorias, México DF, México

When Hamman and Rich described their four cases of interstitial lung diseases—now recognized as fulminant cases of idiopathic acute interstitial pneumonia—they likely did not realize that they were opening the door to one of the most fascinating lung mysteries (1). Over the last half century, remarkable advances have been made in understanding the classification, epidemiology, diagnosis, and pathogenesis of the interstitial lung diseases. However, although it became clear that a variety of identifiable exposures and diseases were able to provoke an interstitial lung disease, a number of disorders remain shrouded under a confusing array of clinical, radiologic, and pathologic classification schemes and overlapping terminology (Figure 1). It is only in the last decade that these idiopathic lung disorders, defined primarily based on their morphology and radiologic appearance, have revealed their subtle but important differences and emerged as complex but probably distinct interstitial lung diseases (2). (Figure 2).

View larger version (20K): [in this window] [in a new window]   Figure 1. Historical progression of the classification of the idiopathic interstitial pneumonias. Reprinted with permission from Reference 6. AIP = acute interstitial pneumonia; BOOP = bronchiolitis obliterans organizing pneumonia; COP = cryptogenic organizing pneumonia; DAD = diffuse alveolar damage; DIP = desquamative interstitial pneumonia; GIP = giant cell interstitial pneumonia; IPF = idiopathic pulmonary fibrosis; LIP = lymphocytic interstitial pneumonia; NSIP = nonspecific interstitial pneumonia; RB-ILD = respiratory bronchiolitis interstitial lung disease; UIP = usual interstitial pneumonia.

View larger version (16K): [in this window] [in a new window]   Figure 2. Diffuse parenchymal lung diseases (DPLDs) consist of disorders of known causes (collagen vascular disease, environmental or drug related) as well as disorders of unknown cause. The latter include idiopathic interstitial pneumonias (IIPs), granulomatous lung disorders (e.g., sarcoidosis), and other forms of interstitial lung disease including lymphangioleiomyomatosis (LAM), pulmonary Langerhans' cell histiocytosis/histiocytosis X (HX), and eosinophilic pneumonia. The most important distinction among the idiopathic interstitial pneumonias is that between idiopathic pulmonary fibrosis (characterized by usual interstitial pneumonia on lung biopsy) and the other interstitial pneumonias, which include nonspecific interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, acute interstitial pneumonia, cryptogenic organizing pneumonia, and lymphocytic interstitial pneumonia. Reprinted with permission from Reference 2.

Idiopathic pulmonary fibrosis (IPF) is the most common of the IIPs and carries the worst prognosis (3). This disorder constitutes a challenge for clinicians primarily because no preventive approach, early biomarker, or successful treatment is available. Most patients with IPF die within a few years of diagnosis. IPF is also a challenge for researchers. To date, the genes and environmental factors involved in its pathogenesis are unknown, and the pathologic processes responsible for the structural changes of the lung parenchyma microenvironment are still poorly understood. Recently, it has been proposed that an abnormal communication between epithelial and mesenchymal cells (rather than lung inflammation) is a key mechanism in the pathogenesis of IPF (4).

The recognition of idiopathic nonspecific interstitial pneumonia— a pattern of lung injury that can be seen in many settings, in particular, hypersensitivity pneumonitis, collagen-vascular diseases, and drug-induced interstitial lung disease—has drawn a lot of attention from clinical investigators (5). It is often confused with IPF; however, it has a markedly better long term outcome than does IPF. Consequently, greater understanding of this entity may be critical to our understanding of the key features that control reversible or less progressive lung fibrosis.

This virtual symposium was designed in two complementary sections. The first section focuses on a clinical perspective. It includes discussions of the role of environmental exposures and smoking in the development of IIP. In addition, several papers review the latest information on chest imaging, functional testing, and morphological evaluation of these entities. The authors emphasize the importance of a dynamic, integrated process among clinicians, radiologists, and pathologists (when a surgical lung biopsy is available) in arriving at a final diagnosis. Also, the current state of the management of the IIPs, in particular idiopathic pulmonary fibrosis, is discussed. In the second section, the recent advances in our understanding of the pathogenesis of lung fibrosis, including genetic susceptibility and genomics are explored.

FOOTNOTES

Conflict of Interest Statement: T.E.K. has served on Advisory Boards for Actelion (compensation in 2003 = $11,725; 2004 = $9,940; 2005 = $15,000); for InterMune (2003 = $21,000; 2004 = $15,000; 2005 = $20,000); for GlaxoSmithKline (2004 = $12,625; 2005 = $10,000); and served as a consultant for Nektar, Alexza, AstraZeneca, Biogen, Centocor, Fibrogen, Genzyme, Human Genome Sciences, Merck, and CoTherix, and for none of these did compensation exceed $10,000 per company per year in any of the preceding 3 yr. M.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Hamman L, Rich AR. Acute diffuse interstitial fibrosis of the lungs. Bull Johns Hopkins Hosp 1944;74:177–212.
2. American Thoracic Society/European Respiratory Society. ATS/ERS International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med 2002;165:277–304.[Free Full Text]
3. King TE Jr, Tooze JA, Schwarz MI, Brown K, Cherniack RM. Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. Am J Respir Crit Care Med 2001;164:1171–1181.[Abstract/Free Full Text]
4. Selman M, King TE Jr, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 2001;134:136–151.[Abstract/Free Full Text]
5. Selman M, Pardo A, Barrera L, Estrada A, Watson SR, Wilson K, Aziz N, Kaminski N, Zlotnik A. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. Am J Respir Crit Care Med 2006;173:188–198.[Abstract/Free Full Text]
6. King TE Jr. Clinical advances in the diagnosis and therapy of the interstitial lung diseases. Am J Respir Crit Care Med 2005;172:268–279.[Abstract/Free Full Text]

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