Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Idiopathic interstitial pneumonias: Clinical manifestations and pathology

Carlyne D Cool, MD
Section Editors
Talmadge E King, Jr, MD
Andrew Nicholson, MD
Deputy Editor
Helen Hollingsworth, MD


"Diffuse interstitial lung disease" (ILD) is a generic term encompassing a broad range of largely unrelated conditions that share the propensity to cause breathlessness and/or cough associated with bilateral abnormal opacities of various types on conventional chest radiographs or computed tomographic (CT) scans (algorithm 1).

The idiopathic interstitial pneumonias are a subset of diffuse interstitial lung diseases of unknown etiology characterized by expansion of the interstitial compartment (ie, that portion of the lung parenchyma sandwiched between the epithelial and endothelial basement membranes) with an infiltrate of inflammatory cells. The inflammatory infiltrate is sometimes accompanied by fibrosis, either in the form of abnormal collagen deposition or proliferation of fibroblasts capable of collagen synthesis.

Our understanding of the idiopathic interstitial pneumonias has been plagued by our inability to clearly define the extent to which these represent distinct entities, as opposed to variations on the same fundamental theme. "Lumpers" have maintained that all are appropriately captured beneath the venerable umbrella of idiopathic pulmonary fibrosis (IPF, also referred to as cryptogenic fibrosing alveolitis [CFA]), and that morphologic separations are misguided attempts to segregate what are in fact highly related points on the same continuum of fibrosing lung disease. "Splitters" respond that failure to control for histologic subtypes has impeded our efforts to explain or predict the seemingly capricious behavior of a family of similar but separable interstitial lung diseases.

The pathologic classification of idiopathic interstitial pneumonias is reviewed here. In additional, clinical features of each type of idiopathic interstitial pneumonia are discussed. The diagnostic approach to patients with interstitial lung disease is presented elsewhere. (See "Approach to the adult with interstitial lung disease: Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing".)


Averill Liebow pioneered the notion that morphologic characteristics are useful in separating idiopathic interstitial pneumonias into clinically and histologically distinct groups [1]. These categories of usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP) have persisted as important histologic groups, while bronchiolitis obliterans with classical interstitial pneumonia (BIP) and giant cell interstitial pneumonia (GIP) have disappeared from subsequent classification schemes (table 1) [2]. The system outlined in the joint American Thoracic Society and European Respiratory Society statement on the histopathologic classification of idiopathic interstitial pneumonias further refines this terminology (table 2 and table 3) [3-5].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Apr 1, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Liebow, A. Definition and classification of interstitial pneumonias in human pathology. Prog Respir Res 1975; 8:1.
  2. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med 1998; 157:1301.
  3. American Thoracic Society, European Respiratory Society. 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.
  4. Nicholson AG. Classification of idiopathic interstitial pneumonias: making sense of the alphabet soup. Histopathology 2002; 41:381.
  5. Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013; 188:733.
  6. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183:788.
  7. Gruden JF, Panse PM, Leslie KO, et al. UIP diagnosed at surgical lung biopsy, 2000-2009: HRCT patterns and proposed classification system. AJR Am J Roentgenol 2013; 200:W458.
  8. Hodnett PA, Naidich DP. Fibrosing interstitial lung disease. A practical high-resolution computed tomography-based approach to diagnosis and management and a review of the literature. Am J Respir Crit Care Med 2013; 188:141.
  9. Cool CD, Groshong SD, Rai PR, et al. Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast reticulum. Am J Respir Crit Care Med 2006; 174:654.
  10. Kondoh Y, Taniguchi H, Kawabata Y, et al. Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases. Chest 1993; 103:1808.
  11. Daniels CE, Yi ES, Ryu JH. Autopsy findings in 42 consecutive patients with idiopathic pulmonary fibrosis. Eur Respir J 2008; 32:170.
  12. Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998; 157:199.
  13. Gay SE, Kazerooni EA, Toews GB, et al. Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med 1998; 157:1063.
  14. Flaherty KR, Toews GB, Travis WD, et al. Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J 2002; 19:275.
  15. King TE Jr, Schwarz MI, Brown K, et al. Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality. Am J Respir Crit Care Med 2001; 164:1025.
  16. Lee HL, Ryu JH, Wittmer MH, et al. Familial idiopathic pulmonary fibrosis: clinical features and outcome. Chest 2005; 127:2034.
  17. Vij R, Noth I, Strek ME. Autoimmune-featured interstitial lung disease: a distinct entity. Chest 2011; 140:1292.
  18. Suzuki T, Li W, Zhang Q, et al. Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene. Nat Genet 2002; 30:321.
  19. Sahin H, Brown KK, Curran-Everett D, et al. Chronic hypersensitivity pneumonitis: CT features comparison with pathologic evidence of fibrosis and survival. Radiology 2007; 244:591.
  20. King TE Jr, Schwarz MI. Chronic diffuse parenchymal lung disease. In: Medical management of pulmonary diseases, Davis G (Ed), Marcel Decker, New York 1999. p.487.
  21. Carrington CB, Gaensler EA, Coutu RE, et al. Natural history and treated course of usual and desquamative interstitial pneumonia. N Engl J Med 1978; 298:801.
  22. Myers JL, Veal CF Jr, Shin MS, Katzenstein AL. Respiratory bronchiolitis causing interstitial lung disease. A clinicopathologic study of six cases. Am Rev Respir Dis 1987; 135:880.
  23. Akira M, Yamamoto S, Hara H, et al. Serial computed tomographic evaluation in desquamative interstitial pneumonia. Thorax 1997; 52:333.
  24. Hartman TE, Primack SL, Kang EY, et al. Disease progression in usual interstitial pneumonia compared with desquamative interstitial pneumonia. Assessment with serial CT. Chest 1996; 110:378.
  25. Moon J, du Bois RM, Colby TV, et al. Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease. Thorax 1999; 54:1009.
  26. Yousem SA, Colby TV, Gaensler EA. Respiratory bronchiolitis-associated interstitial lung disease and its relationship to desquamative interstitial pneumonia. Mayo Clin Proc 1989; 64:1373.
  27. Ryu JH, Myers JL, Capizzi SA, et al. Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease. Chest 2005; 127:178.
  28. Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 Suppl 5:v1.
  29. Myers, JL. Respiratory bronchiolitis-associated interstitial lung disease. In: Diseases of the Bronchioles, Epler, G (Eds), Raven Press, New York 1994. p.297.
  30. Fraig M, Shreesha U, Savici D, Katzenstein AL. Respiratory bronchiolitis: a clinicopathologic study in current smokers, ex-smokers, and never-smokers. Am J Surg Pathol 2002; 26:647.
  31. Portnoy J, Veraldi KL, Schwarz MI, et al. Respiratory bronchiolitis-interstitial lung disease: long-term outcome. Chest 2007; 131:664.
  32. Washko GR, Hunninghake GM, Fernandez IE, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med 2011; 364:897.
  33. Cottin V, Reix P, Khouatra C, et al. Combined pulmonary fibrosis and emphysema syndrome associated with familial SFTPC mutation. Thorax 2011; 66:918.
  34. Jankowich MD, Rounds S. Combined pulmonary fibrosis and emphysema alters physiology but has similar mortality to pulmonary fibrosis without emphysema. Lung 2010; 188:365.
  35. Lederer DJ, Enright PL, Kawut SM, et al. Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study. Am J Respir Crit Care Med 2009; 180:407.
  36. Tsushima K, Sone S, Yoshikawa S, et al. The radiological patterns of interstitial change at an early phase: over a 4-year follow-up. Respir Med 2010; 104:1712.
  37. Doyle TJ, Washko GR, Fernandez IE, et al. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med 2012; 185:756.
  38. Katzenstein AL, Mukhopadhyay S, Zanardi C, Dexter E. Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. Hum Pathol 2010; 41:316.
  39. Kawabata Y, Hoshi E, Murai K, et al. Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course. Histopathology 2008; 53:707.
  40. Schmidt SL, Nambiar AM, Tayob N, et al. Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema. Eur Respir J 2011; 38:176.
  41. Jankowich MD, Rounds SI. Combined pulmonary fibrosis and emphysema syndrome: a review. Chest 2012; 141:222.
  42. Inomata M, Ikushima S, Awano N, et al. An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features. BMC Pulm Med 2014; 14:104.
  43. The definition of emphysema. Report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases workshop. Am Rev Respir Dis 1985; 132:182.
  44. Churg A, Müller NL, Wright JL. Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. Arch Pathol Lab Med 2010; 134:27.
  45. Yousem SA. Respiratory bronchiolitis-associated interstitial lung disease with fibrosis is a lesion distinct from fibrotic nonspecific interstitial pneumonia: a proposal. Mod Pathol 2006; 19:1474.
  46. Olson J, Colby TV, Elliott CG. Hamman-Rich syndrome revisited. Mayo Clin Proc 1990; 65:1538.
  47. Katzenstein AL, Myers JL, Mazur MT. Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study. Am J Surg Pathol 1986; 10:256.
  48. Flaherty KR, Travis WD, Colby TV, et al. Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001; 164:1722.
  49. Cottin V, Donsbeck AV, Revel D, et al. Nonspecific interstitial pneumonia. Individualization of a clinicopathologic entity in a series of 12 patients. Am J Respir Crit Care Med 1998; 158:1286.
  50. Katzenstein AL, Myers JL. Nonspecific interstitial pneumonia and the other idiopathic interstitial pneumonias: classification and diagnostic criteria. Am J Surg Pathol 2000; 24:1.
  51. Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance. Am J Surg Pathol 1994; 18:136.
  52. Nicholson AG, Colby TV, du Bois RM, et al. The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 2000; 162:2213.
  53. Travis WD, Matsui K, Moss J, Ferrans VJ. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol 2000; 24:19.
  54. Daniil ZD, Gilchrist FC, Nicholson AG, et al. A histologic pattern of nonspecific interstitial pneumonia is associated with a better prognosis than usual interstitial pneumonia in patients with cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 1999; 160:899.
  55. Katzenstein AL, Zisman DA, Litzky LA, et al. Usual interstitial pneumonia: histologic study of biopsy and explant specimens. Am J Surg Pathol 2002; 26:1567.