Idiopathic Interstitial Pneumonia: A Clinicopathological Perspective

ABSTRACT

Idiopathic interstitial pneumonia (IIP) represents a diverse group of lung disorders with variable prognoses and responses to therapy. As the name implies, the etiology is unknown. In the more severe forms of IIP, such as idiopathic pulmonary fibrosis and acute interstitial pneumonia, no effective therapies have been identified. In this perspective, the spatiotemporal variability in the histopathology of these disorders is discussed. It is proposed that common etiologies or injurious agents may produce variable histopathological “reactions” in the lung due to complex interactions between the host (genetic/epigenetic factors, age) and environmental factors. Accurate clinical and biological phenotyping may be necessary to stratify or group patients who are most likely to respond to specific modes of therapy.

KEYWORDS

Pulmonary fibrosis - inflammation - therapeutics - phenotype - histopathology - pathophysiology

REFERENCES

• 1 Hamman L, Rich A. Acute diffuse interstitial fibrosis of the lungs.  Bull Johns Hopkins Hosp. 1944;  74 177-212
• 2 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
• 3 Leibow A A, Carrington C B. The interstitial pneumonias. In: Simon M, Potchen EJ, LeMay M Frontiers of Pulmonary Radiology. 1st ed. New York; Grune and Stratton 1969: 102-141
• 4 Muller N L, Colby T V. Idiopathic interstitial pneumonias: high-resolution CT and histological findings.  Radiographics. 1997;  17 1016-1022
• 5 Katzenstein A L, Myers J L. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification.  Am J Respir Crit Care Med. 1998;  157(4 Pt 1) 1301-1315
• 6 Liebow A A. Definition and classification of interstitial pneumonia in human pathology.  Prog Respir Res. 1975;  8 1-31
• 7 Flaherty K R, King Jr T E, Raghu G et al.. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis?.  Am J Respir Crit Care Med. 2004;  170 904-910
• 8 Flaherty K R, Mumford J A, Murray S et al.. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia.  Am J Respir Crit Care Med. 2003;  168 543-548
• 9 Latsi P I, du Bois R M, Nicholson A G et al.. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends.  Am J Respir Crit Care Med. 2003;  168 531-537
• 10 Collard H R, King Jr T E, Bartelson B B, Vourlekis J S, Schwarz M I, Brown K K. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med. 2003;  168 538-542
• 11 Raghu G, Brown K K, Bradford W Z et al.. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis.  N Engl J Med. 2004;  350 125-133
• 12 Demedts M, Behr J, Buhl R et al.. High-dose acetylcysteine in idiopathic pulmonary fibrosis.  N Engl J Med. 2005;  353 2229-2242
• 13 Bjoraker J A, Ryu J H, Edwin M K et al.. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med. 1998;  157 199-203
• 14 Flaherty K R, Toews G B, Travis W D et al.. Clinical significance of histological classification of idiopathic interstitial pneumonia.  Eur Respir J. 2002;  19 275-283
• 15 Flaherty K R, Thwaite E L, Kazerooni E A et al.. Radiological versus histological diagnosis in UIP and NSIP: survival implications.  Thorax. 2003;  58 143-148
• 16 King Jr T E, Schwarz M I, Brown K et al.. Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality.  Am J Respir Crit Care Med. 2001;  164 1025-1032
• 17 Nicholson A G, Fulford L G, Colby T V, du Bois R M, Hansell D M, Wells A U. The relationship between individual histologic features and disease progression in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med. 2002;  166 173-177
• 18 Selman M, King T E, Pardo A. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy.  Ann Intern Med. 2001;  134 136-151
• 19 Thannickal V J, Toews G B, White E S, Lynch J P, Martinez F J. Mechanisms of pulmonary fibrosis.  Annu Rev Med. 2004;  55 395-417
• 20 Flaherty K R, Travis W D, Colby T V et al.. Histopathologic variability in usual and nonspecific interstitial pneumonias.  Am J Respir Crit Care Med. 2001;  164 1722-1727
• 21 Katzenstein A L, Zisman D A, Litzky L A, Nguyen B T, Kotloff R M. Usual interstitial pneumonia: histologic study of biopsy and explant specimens.  Am J Surg Pathol. 2002;  26 1567-1577
• 22 Tansey D, Wells A U, Colby T V et al.. Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis.  Histopathology. 2004;  44 585-596
• 23 Lee H K, Kim D S, Yoo B et al.. Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease.  Chest. 2005;  127 2019-2027
• 24 Thomas A Q, Lane K, Phillips III J et al.. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred.  Am J Respir Crit Care Med. 2002;  165 1322-1328
• 25 Steele M P, Speer M C, Loyd J E et al.. Clinical and pathologic features of familial interstitial pneumonia.  Am J Respir Crit Care Med. 2005;  172 1146-1152
• 26 Thannickal V J, Lee D Y, White E S et al.. Myofibroblast differentiation by transforming growth factor-beta1 is dependent on cell adhesion and integrin signaling via focal adhesion kinase.  J Biol Chem. 2003;  278 12384-12389
• 27 Horowitz J C, Lee D Y, Waghray M et al.. Activation of the pro-survival phosphatidylinositol 3-kinase/AKT pathway by transforming growth factor-beta1 in mesenchymal cells is mediated by p38 MAPK-dependent induction of an autocrine growth factor.  J Biol Chem. 2004;  279 1359-1367
• 28 Selman M, Pardo A, Barrera L et al.. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis.  Am J Respir Crit Care Med. 2005;  173 188-198
• 29 Thannickal V J, Wells A U. Classification of interstitial pneumonias: what do gene expression profiles tell us?.  Am J Respir Crit Care Med. 2006;  173 141-142