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Idiopathic Pulmonary Fibrosis

  • Author: Amanda M K Godfrey, MD; Chief Editor: Ryland P Byrd, Jr, MD  more...
 
Updated: Aug 11, 2015
 

Practice Essentials

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, primarily occurring in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP).[1]

Signs and symptoms

The clinical symptoms of idiopathic pulmonary fibrosis are nonspecific and can be shared with many pulmonary and cardiac diseases. Most patients present with a gradual onset (often >6 mo) of exertional dyspnea and/or a nonproductive cough. Approximately 5% of patients have no presenting symptoms when idiopathic pulmonary fibrosis is serendipitously diagnosed.

Associated systemic symptoms that can occur but are not common in idiopathic pulmonary fibrosis include the following:

  • Weight loss
  • Low-grade fevers
  • Fatigue
  • Arthralgias
  • Myalgias

See Clinical Presentation for more detail.

Diagnosis

It is critical to obtain a complete history, including medication history, drug use, social history, occupational, recreational, and environmental respiratory exposure history, risks for the human immunodeficiency virus, and review of systems, to ensure other causes of interstitial lung disease are excluded. The diagnosis of idiopathic pulmonary fibrosis relies on the clinician to integrate and correlate the clinical, laboratory, radiologic, and/or pathologic data.[5]

Physical examination in patients with idiopathic pulmonary fibrosis may reveal the following:

  • Fine bibasilar inspiratory crackles (Velcro crackles): Noted in most patients
  • Digital clubbing (25-50%)
  • Pulmonary hypertension at rest (20-40%) [6] : Loud P2 component of the second heart sound, a fixed split S2, a holosystolic tricuspid regurgitation murmur, pedal edema

Laboratory testing

Results from routine laboratory studies are nonspecific for the diagnosis of idiopathic pulmonary fibrosis. Some tests that may be helpful to exclude other causes of interstitial lung disease include the following:

  • Antinuclear antibodies or rheumatoid factor titers: Positive results in about 30% of patients with IPF, but the titers are generally not high [7] . The presence of high titers may suggest a connective tissue disease
  • C-reactive protein level and erythrocyte sedimentation rate: Elevated but nondiagnostic in idiopathic pulmonary fibrosis
  • Complete blood cell count: polycythemia (rare)
  • Arterial blood gas analysis: chronic hypoxemia (common)
  • Pulmonary function studies: Nonspecific findings of a restrictive ventilatory defect and reduced diffusion capacity for carbon monoxide (DL CO) [8]

A 6-minute walk test (6MWT) is often used in the initial and longitudinal clinical assessment of patients with idiopathic pulmonary fibrosis. In patients who desaturate to less than 88% during a 6MWT, a progressive decline in the DLCO (>15% after 6 mo) is a strong predictor of increased mortality.[9]

Imaging studies

  • High-resolution computed tomography (HRCT) scanning: Sensitive, specific, and essential for the diagnosis of idiopathic pulmonary fibrosis. Demonstrates patchy, peripheral, subpleural, and bibasilar reticular opacities.
  • Chest radiography: Abnormal findings but lacks diagnostic specificity. Demonstrate peripheral reticular opacities (netlike linear and curvilinear densities) predominantly at the lung bases, honeycombing (coarse reticular pattern), and lower lobe volume loss [10] (see the image below)
    Chest radiograph of a patient with idiopathic pulm Chest radiograph of a patient with idiopathic pulmonary fibrosis showing bilateral lower lobe reticular opacities (red circles).
  • Transthoracic echocardiography: Detects pulmonary hypertension well but has variable performance in patients with idiopathic pulmonary hypertension and other chronic lung disease [6]

Procedures

  • Bronchoscopy: Absence of lymphocytosis in bronchoalveolar lavage fluid may be important for the diagnosis (increased neutrophils [70-90% of patients] and eosinophils [40-60% of all patients]). This procedure may be used to exclude alternative diagnoses.
  • Surgical lung biopsy (via open lung biopsy or video-assisted thoracoscopic surgery [VATS] [preferred]): Best sample for distinguishing usual interstitial pneumonia from other idiopathic interstitial pneumonias.

See Workup for more detail.

Management

The optimal medical therapy for the treatment of idiopathic pulmonary fibrosis has yet to be identified. Treatment strategies for idiopathic pulmonary fibrosis include the assessment and management of comorbid conditions according to current practice guidelines, including chronic obstructive pulmonary disease, obstructive sleep apnea, gastroesophageal reflux disease, and coronary artery disease.

Other management strategies include the following:

  • Encourage tobacco users to quit and offer pharmacotherapy as needed.
  • Prescribe oxygen therapy in patients with hypoxemia at rest or with exercise (partial pressure of oxygen [PaO 2] < 55 mmHg or an oxygen saturation by pulse oximetry [SpO 2] < 88%). The goal is to maintain an oxygen saturation of at least 90% at rest, with sleep, and with exertion.
  • Vaccinate patients against influenza and pneumococcal infection.

Surgery

  • Lung transplantation: Refer all patients with diagnosed or probable idiopathic pulmonary fibrosis for lung transplantation evaluation regardless of the vital capacity, unless there are contraindications. [11]

Pharmacotherapy

  • Systemic corticosteroids (eg, prednisone)
  • Immunosuppressant agents (eg, azathioprine, cyclophosphamide)
  • Tyrosine kinase inhibitors (eg, nintedanib)
  • Antifibrotic agents (eg, pirfenidone)

See Treatment and Medication for more detail.

Next

Background

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, primarily occurring in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP).[1]

Of the seven listed idiopathic interstitial pneumonias in the American Thoracic Society/European Respiratory Society consensus statement (ie, idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial pneumonia, lymphoid interstitial pneumonia), idiopathic pulmonary fibrosis is the most common.[12] Idiopathic pulmonary fibrosis portends a poor prognosis, and, to date, no proven effective therapies are available for the treatment of idiopathic pulmonary fibrosis beyond lung transplantation.[5]

Most patients with idiopathic pulmonary fibrosis present with a gradual onset, often greater than six months, of dyspnea and/or a nonproductive cough. The symptoms often precede the diagnosis by a median of one to two years.[13] A chest radiograph typically reveals diffuse reticular opacities. However, it lacks diagnostic specificity.[14] High-resolution computed tomography (HRCT) findings are significantly more sensitive and specific for the diagnosis of idiopathic pulmonary fibrosis. On HRCT images, usual interstitial pneumonia is characterized by the presence of reticular opacities often associated with traction bronchiectasis. As idiopathic pulmonary fibrosis progresses, honeycombing becomes more prominent.[10] Pulmonary function tests often reveal restrictive impairment and reduced diffusing capacity for carbon monoxide.[14]

Available data suggest that no single etiologic agent serves as a common inciting event in the pathogenesis of idiopathic pulmonary fibrosis. During the past 15 years, the pathogenesis theory of generalized inflammation progressing to widespread parenchymal fibrosis has become less popular.[14] Rather, it is now believed that epithelial injury and activation in fibroblast foci are crucial early events that trigger a cascade of changes leading to reorganization of pulmonary tissue compartments.[15]

As mentioned above, idiopathic pulmonary fibrosis is an idiopathic interstitial pneumonitis characterized by usual interstitial pneumonia on histopathology. The hallmark pathologic feature of usual interstitial pneumonia is a heterogeneous, variegated appearance with alternating areas of healthy lung, interstitial inflammation, fibrosis, and honeycomb change. Fibrosis predominates over inflammation.[15]

The diagnosis of idiopathic pulmonary fibrosis relies on the clinician integrating the clinical, laboratory, radiologic, and/or pathologic data to make a clinical-radiologic-pathologic correlation that supports the diagnosis of idiopathic pulmonary fibrosis.[5]

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Pathophysiology

The previous theory regarding the pathogenesis of idiopathic pulmonary fibrosis (IPF) was that generalized inflammation progressed to widespread parenchymal fibrosis. However, anti-inflammatory agents and immune modulators have proved to be minimally effective in modifying the natural course of the disease. It is currently believed that idiopathic pulmonary fibrosis (IPF) is an epithelial-fibroblastic disease, in which unknown endogenous or environmental stimuli disrupt the homeostasis of alveolar epithelial cells, resulting in diffuse epithelial cell activation and aberrant epithelial cell repair.[16]

In the current hypothesis regarding the pathogenesis of idiopathic pulmonary fibrosis, exposure to an inciting agent (eg, smoke, environmental pollutants, environmental dust, viral infections, gastroesophageal reflux disease, chronic aspiration) in a susceptible host may lead to the initial alveolar epithelial damage.[17] Reestablishing an intact epithelium following injury is a key component of normal wound healing. In idiopathic pulmonary fibrosis, it is believed that after injury, aberrant activation of alveolar epithelial cells provokes the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic/myofibroblastic foci, leading to the exaggerated accumulation of extracellular matrix with the irreversible destruction of the lung parenchyma.[17]

Activated alveolar epithelial cells release potent fibrogenic cytokines and growth factors. These include, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), platelet-derived growth factor, insulin-like growth factor-1, and endothelin-1 (ET-1).[15, 17] These cytokines and growth factors are involved in the migration and proliferation of fibroblasts and the transformation of fibroblasts into myofibroblasts. Fibroblasts and myofibroblasts are key effector cells in fibrogenesis, and myofibroblasts secrete extracellular matrix proteins.[17]

For normal wound healing to occur, wound myofibroblasts must undergo apoptosis. Failure of apoptosis leads to myofibroblast accumulation, exuberant extracellular matrix protein production, persistent tissue contraction, and pathologic scar formation.[17] TGF-β has been shown to promote an antiapoptotic phenotype in fibroblasts.[17] Additionally, myofibroblasts in fibroblastic foci of idiopathic pulmonary fibrosis have been reported to undergo less apoptotic activity in comparison to myofibroblasts in the fibromyxoid lesions of bronchiolitis obliterans organizing pneumonia.[18]

Excess alveolar epithelial cell apoptosis and fibroblast resistance to apoptosis are also believed to contribute to fibroproliferation in idiopathic pulmonary fibrosis. Research has demonstrated that prostaglandin E2 deficiency, in lung tissue of patients with pulmonary fibrosis, results in increased sensitivity of alveolar epithelial cells to FAS-ligand induced apoptosis but induces fibroblast resistance to Fas-ligand induced apoptosis.[19] Therefore, apoptosis resistance in the fibroblasts and myofibroblasts participating in the repair of the alveolar epithelium may contribute to the persistent and/or progressive fibrosis in idiopathic pulmonary fibrosis.

Evidence for a genetic basis for idiopathic pulmonary fibrosis is accumulating. It has been described that mutant telomerase is associated with familial idiopathic pulmonary fibrosis.[20] Telomerase is a specialized polymerase that adds telomere repeats to the ends of chromosomes. This helps to offset shortening that occurs during DNA replication. TGF-β negatively regulates telomerase activity.[17] It is proposed that pulmonary fibrosis in patients with short telomeres is provoked by a loss of alveolar epithelial cells. Telomere shortening also occurs with aging, and it can also be acquired. This telomere shortening could promote the loss of alveolar epithelial cells, resulting in aberrant epithelial cell repair, and therefore should be considered as another potential contributor to the pathogenesis of idiopathic pulmonary fibrosis.[20]

Additionally, a common variant in the putative promoter of the gene that encodes mucin 5B (MUC5B) has been associated with the development of both familial interstitial pneumonia and sporadic pulmonary fibrosis. MUC5B expression in the lung was reported to be 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not. Therefore, dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis.[21]

Finally, caveolin-1 has been proposed as a protective regulator of pulmonary fibrosis. Caveolin-1 limits TGF-β–induced production of extracellular matrix proteins and restores the alveolar epithelial-repair process.[17] It has been observed that the expression of caveolin-1 is reduced in lung tissue from patients with idiopathic pulmonary fibrosis and that fibroblasts, the key cellular component of fibrosis, have low levels of caveolin-1 expression in patients with idiopathic pulmonary fibrosis.[22]

The recognition of the above-mentioned factors as contributors to the pathogenesis of idiopathic pulmonary fibrosis has led to the development of novel approaches to treat idiopathic pulmonary fibrosis.

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Frequency

United States

No large-scale studies of the incidence or prevalence of idiopathic pulmonary fibrosis are available on which to base formal estimates.

A population-based cohort study was completed in Olmsted County, Minnesota, between 1997 and 2005, with the intention of updating and describing the incidence and prevalence of idiopathic pulmonary fibrosis. Narrow-criteria idiopathic pulmonary fibrosis was defined by usual interstitial pneumonia on a surgical lung biopsy specimen or a definite usual interstitial pneumonia pattern on an HRCT image. Broad-criteria idiopathic pulmonary fibrosis was defined by usual interstitial pneumonia on a surgical lung biopsy specimen or a definite or possible usual interstitial pneumonia pattern on an HRCT image.[23] These criteria were obtained from the 2002 American Thoracic Society/European Thoracic Society consensus statement.[12]

The age-adjusted and sex-adjusted incidence rate of idiopathic pulmonary fibrosis among residents aged 50 years or older ranges from 8.8 cases per 100,000 person-years (narrow-case criteria) to 17.4 cases per 100,000 person-years (broad-case criteria).[23]

The age-adjusted and sex-adjusted prevalence among residents aged 50 years or older ranges from 27.9 cases per 100,000 persons (narrow-case criteria) to 63 cases per 100,000 persons (broad-case criteria).[23]

Whether the incidence and prevalence of idiopathic pulmonary fibrosis are influenced by geographic, ethnic, cultural, or racial factors is unclear.[1]

International

Worldwide, the incidence of idiopathic pulmonary fibrosis is estimated to be 10.7 cases per 100,000 person-years for males and 7.4 cases per 100,000 person years for females. The prevalence of idiopathic pulmonary fibrosis is estimated to be 20 cases per 100,000 persons for males and 13 cases per 100,000 persons for females.[14]

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Mortality/Morbidity

Idiopathic pulmonary fibrosis portends a poor prognosis, with an estimated mean survival of 2-5 years from the time of diagnosis.[5] Estimated mortality rates are 64.3 deaths per million in men and 58.4 deaths per million in women.[24]

Death rates in patients with idiopathic pulmonary fibrosis increase with increasing age, are consistently higher in men than women, and experience seasonal variation, with the highest death rates occurring in the winter, even when infectious causes are excluded.[13]

Estimates are that 60% of patients with idiopathic pulmonary fibrosis die from their idiopathic pulmonary fibrosis, as opposed to dying with their idiopathic pulmonary fibrosis. Of those patients who die with idiopathic pulmonary fibrosis, most commonly it is after an acute exacerbation of idiopathic pulmonary fibrosis. When an acute exacerbation of idiopathic pulmonary fibrosis is not the cause of death, an increased cardiovascular risk and an increased venous thromboembolic disease risk contribute to the cause of death. The most common causes of death in patients with idiopathic pulmonary fibrosis include acute exacerbations of idiopathic pulmonary fibrosis, acute coronary syndromes, congestive heart failure, lung cancer, infectious causes, and venous thromboembolic disease.[5]

Race

Epidemiologic data from large, geographically diverse populations are limited, and, therefore this data cannot be used to accurately determine the existence of a racial predilection for idiopathic pulmonary fibrosis.

Sex

Using data obtained from a large US healthcare claims database, the incidence and prevalence of idiopathic pulmonary fibrosis is higher in men aged 55 years or older, compared with women of the same age.[25]

Age

Idiopathic pulmonary fibrosis mainly affects persons aged 50 years or older. Approximately two thirds of persons diagnosed with idiopathic pulmonary fibrosis are aged 60 years or older at the time of diagnosis. Using data obtained from a large US healthcare claims database, the incidence of idiopathic pulmonary fibrosis was estimated to range from 0.4-1.2 cases per 100,000 person-years for persons aged 18-34 years. However, the estimated incidence of idiopathic pulmonary fibrosis in persons aged 75 years or older was significantly higher and ranged from 27.1-76.4 cases per 100,000 person-years.[25]

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Contributor Information and Disclosures
Author

Amanda M K Godfrey, MD Associate Staff, Department of Internal Medicine, IHA Pulmonary, Critical Care, and Sleep Consultants; Associate Staff, Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, St Joseph Mercy Ann Arbor

Amanda M K Godfrey, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Michigan State Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Chair of the Clinical Competency Committee, Pulmonary and Critical Care Fellowship Program, Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Health System; Chair, Guideline Oversight Committee, American College of Chest Physicians

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, Society of Critical Care Medicine, American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Chair of the Clinical Competency Committee, Pulmonary and Critical Care Fellowship Program, Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Health System; Chair, Guideline Oversight Committee, American College of Chest Physicians

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, Society of Critical Care Medicine, American Thoracic Society

Disclosure: Nothing to disclose.

Chief Editor

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Thomas H Davis Chair in Pulmonary Medicine, Chief, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Professor of Internal Medicine, Pediatrics, and Translational Science, Associate Director, Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine; Executive Director of the Respiratory Service Line, Wake Forest Baptist Medical Center

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, Sigma Xi

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Integrity CE, Merck<br/>Received income in an amount equal to or greater than $250 from: – Array Biopharma, AstraZeneca, Aerocrine, Airsonett AB, Boehringer-Ingelheim, Experts in Asthma, Gilead, GlaxoSmithKline, Merck, Novartis, Ono Pharmaceuticals, Pfizer, PPD Development, Quintiles, Sunovion, Saatchi & Saatichi, Targacept, TEVA, Theron.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Rajesh G. Patel, MD, and Javier I. Diaz, MD, to the development and writing of this article.

References
  1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. 2011 Mar 15. 183(6):788-824. [Medline].

  2. Hand L. FDA Approves Ofev and Esbriet for Idiopathic Pulmonary Fibrosis. Medscape Medical News. Available at http://www.medscape.com/viewarticle/833307. Accessed: October 15, 2014.

  3. FDA approves Ofev to treat idiopathic pulmonary fibrosis. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418994.htm. Accessed: October 15, 2014.

  4. FDA approves Esbriet to treat idiopathic pulmonary fibrosis. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418991.htm. Accessed: October 15, 2014.

  5. Frankel SK, Schwarz MI. Update in idiopathic pulmonary fibrosis. Curr Opin Pulm Med. 2009 Sep. 15(5):463-9. [Medline].

  6. Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. 2007 Sep. 132(3):998-1006. [Medline].

  7. Fishman A, Elias J, Fishman J, Grippi M, Senior R, Pack A. Idiopathic Pulmonary Fibrosis. Fishman AP. Fishman's Pulmonary Diseases and Disorders. 4th ed. The McGraw-Hill Companies, Inc.; 2008. Vol 1: 1143-60.

  8. Martinez FJ, Flaherty K. Pulmonary function testing in idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun. 3(4):315-21. [Medline]. [Full Text].

  9. Flaherty KR, Andrei AC, Murray S, et al. Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test. Am J Respir Crit Care Med. 2006 Oct 1. 174(7):803-9. [Medline]. [Full Text].

  10. Misumi S, Lynch DA. Idiopathic pulmonary fibrosis/usual interstitial pneumonia: imaging diagnosis, spectrum of abnormalities, and temporal progression. Proc Am Thorac Soc. 2006 Jun. 3(4):307-14. [Medline].

  11. Orens JB, Estenne M, Arcasoy S, et al. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006 Jul. 25(7):745-55. [Medline].

  12. 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 Jan 15. 165(2):277-304. [Medline].

  13. Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Feb 15. 183(4):431-40. [Medline].

  14. Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun. 3(4):285-92. [Medline]. [Full Text].

  15. Visscher DW, Myers JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun. 3(4):322-9. [Medline].

  16. Verma S, Slutsky AS. Idiopathic pulmonary fibrosis--new insights. N Engl J Med. 2007 Mar 29. 356(13):1370-2. [Medline].

  17. Harari S, Caminati A. IPF: new insight on pathogenesis and treatment. Allergy. 2010 May. 65(5):537-53. [Medline].

  18. Thannickal VJ, Horowitz JC. Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proc Am Thorac Soc. 2006 Jun. 3(4):350-6. [Medline]. [Full Text].

  19. Maher TM, Evans IC, Bottoms SE, Mercer PF, Thorley AJ, Nicholson AG. Diminished prostaglandin E2 contributes to the apoptosis paradox in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010 Jul 1. 182(1):73-82. [Medline].

  20. Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29. 356(13):1317-26. [Medline].

  21. Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011 Apr 21. 364(16):1503-12. [Medline].

  22. Wang XM, Zhang Y, Kim HP, et al. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med. 2006 Dec 25. 203(13):2895-906. [Medline]. [Full Text].

  23. Fernandez Perez ER, Daniels CE, Schroeder DR, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010 Jan. 137(1):129-37. [Medline]. [Full Text].

  24. Olson AL, Swigris JJ, Lezotte DC, Norris JM, Wilson CG, Brown KK. Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003. Am J Respir Crit Care Med. 2007 Aug 1. 176(3):277-84. [Medline].

  25. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006 Oct 1. 174(7):810-6. [Medline].

  26. Antoniou KM, Hansell DM, Rubens MB, et al. Idiopathic pulmonary fibrosis: outcome in relation to smoking status. Am J Respir Crit Care Med. 2008 Jan 15. 177(2):190-4. [Medline].

  27. Lancaster LH, Mason WR, Parnell JA, et al. Obstructive sleep apnea is common in idiopathic pulmonary fibrosis. Chest. 2009 Sep. 136(3):772-8. [Medline]. [Full Text].

  28. Lawson WE, Loyd JE. The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease?. Proc Am Thorac Soc. 2006 Jun. 3(4):345-9. [Medline]. [Full Text].

  29. Wootton SC, Kim DS, Kondoh Y, et al. Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Jun 15. 183(12):1698-702. [Medline]. [Full Text].

  30. Flaherty KR, Thwaite EL, Kazerooni EA, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax. 2003 Feb. 58(2):143-8. [Medline]. [Full Text].

  31. Tzilas V, Koti A, Papandrinopoulou D, Tsoukalas G. Prognostic factors in idiopathic pulmonary fibrosis. Am J Med Sci. 2009 Dec. 338(6):481-5. [Medline].

  32. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011 Dec 15. 184(12):1382-9. [Medline].

  33. Swigris JJ, Swick J, Wamboldt FS, et al. Heart rate recovery after 6-min walk test predicts survival in patients with idiopathic pulmonary fibrosis. Chest. 2009 Sep. 136(3):841-8. [Medline]. [Full Text].

  34. Bois RM, Weycker D, Albera C, et al. Six-minute-walk test in idiopathic pulmonary fibrosis: test validation and minimal clinically important difference. Am J Respir Crit Care Med. 2011 May 1. 183(9):1231-7. [Medline].

  35. Ohshimo S, Bonella F, Cui A, et al. Significance of bronchoalveolar lavage for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2009 Jun 1. 179(11):1043-7. [Medline].

  36. Kinder BW, Brown KK, Schwarz MI, Ix JH, Kervitsky A, King TE Jr. Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest. 2008 Jan. 133(1):226-32. [Medline].

  37. Lee JS, Ryu JH, Elicker BM, Lydell CP, Jones KD, Wolters PJ, et al. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Dec 15. 184(12):1390-4. [Medline].

  38. [Guideline] Pullen LC. Idiopathic pulmonary fibrosis: new guidelines released. Medscape Medical News. WebMD Inc. Available at http://www.medscape.com/viewarticle/848220. July 17,2015;

  39. Raghu G, Rochwerg B, Zhang Y, Garcia CA, Azuma A, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Am J Respir Crit Care Med. 2015 Jul 15. 192 (2):e3-e19. [Medline].

  40. Kozower BD, Meyers BF, Smith MA, et al. The impact of the lung allocation score on short-term transplantation outcomes: a multicenter study. J Thorac Cardiovasc Surg. 2008 Jan. 135(1):166-71. [Medline].

  41. Weiss ES, Allen JG, Merlo CA, Conte JV, Shah AS. Survival after single versus bilateral lung transplantation for high-risk patients with pulmonary fibrosis. Ann Thorac Surg. 2009 Nov. 88(5):1616-25; discussion 1625-6. [Medline].

  42. Behr J, Kolb M, Cox G. Treating IPF--all or nothing? A PRO-CON debate. Respirology. 2009 Nov. 14(8):1072-81. [Medline].

  43. Demedts M, Behr J, Buhl R, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005 Nov 24. 353(21):2229-42. [Medline].

  44. Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. N Engl J Med. 2012 May 20. [Medline].

  45. National Heart, Lung, and Blood Institute. Clinical Alert: Commonly Used Three-Drug Regimen for Pulmonary Fibrosis Found Harmful. NIH Stops One Treatment Arm of Trial; Other Two Treatments to Continue. National Institutes of Health. October 21, 2011. Available at http://www.nlm.nih.gov/databases/alerts/2011_nhlbi_ifp.html.

  46. Raghu G, Brown KK, Bradford WZ, et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2004 Jan 8. 350(2):125-33. [Medline].

  47. Raghu G, Brown KK, Costabel U, et al. Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am J Respir Crit Care Med. 2008 Nov 1. 178(9):948-55. [Medline].

  48. King TE Jr, Albera C, Bradford WZ, et al. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. Lancet. 2009 Jul 18. 374(9685):222-8. [Medline].

  49. King TE Jr, Behr J, Brown KK, et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Jan 1. 177(1):75-81. [Medline].

  50. The Idiopathic Pulmonary Fibrosis Clinical Research Network, Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010 Aug 12. 363(7):620-8. [Medline].

  51. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29. 370(22):2071-82. [Medline].

  52. Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 365:1079-1087.

  53. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011 May 21. 377(9779):1760-9. [Medline].

  54. King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29. 370(22):2083-92. [Medline].

  55. Azuma A, Nukiwa T, Tsuboi E, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2005 May 1. 171(9):1040-7. [Medline].

  56. Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010 Apr. 35(4):821-9. [Medline].

  57. Esbriet® (pirfenidone). InterMune. Available at http://www.intermune.com/pirfenidone. Accessed: May 3, 2014.

  58. Hyzy R, Huang S, Myers J, Flaherty K, Martinez F. Acute exacerbation of idiopathic pulmonary fibrosis. Chest. 2007 Nov. 132(5):1652-8. [Medline].

  59. Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011 Feb. 37(2):356-63. [Medline].

  60. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, et al. Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Aug 15. 184(4):459-66. [Medline].

  61. Ley B, Ryerson CJ, Vittinghoff E, et al. A Multidimensional Index and Staging System for Idiopathic Pulmonary Fibrosis. Annals of Internal Medicine. 2012/05. 156:684-691.

  62. Fang A, Studer S, Kawut SM, Ahya VN, Lee J, Wille K. Elevated Pulmonary Artery Pressure Is a Risk Factor for Primary Graft Dysfunction Following Lung Transplantation for Idiopathic Pulmonary Fibrosis. Chest. 2011 Apr. 139(4):782-787. [Medline].

  63. Kinder BW, Brown KK, McCormack FX, et al. Serum surfactant protein-A is a strong predictor of early mortality in idiopathic pulmonary fibrosis. Chest. 2009 Jun. 135(6):1557-63. [Medline]. [Full Text].

  64. Daniels CE, Lasky JA, Limper AH, Mieras K, Gabor E, Schroeder DR. Imatinib treatment for idiopathic pulmonary fibrosis: Randomized placebo-controlled trial results. Am J Respir Crit Care Med. 2010 Mar 15. 181(6):604-10. [Medline].

  65. Noth I, Anstrom KJ, Calvert SB, de Andrade J, Flaherty KR, Glazer C. A Placebo-Controlled Randomized Trial of Warfarin in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2012 Jul 1. 186(1):88-95. [Medline].

  66. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. 2000 Feb. 161(2 Pt 1):646-64. [Medline].

  67. Henderson D. High-resolution CT can identify IPF without lung biopsy. Medscape Medical News. February 19, 2014. Available at http://www.medscape.com/viewarticle/820810. Accessed: February 24, 2014.

  68. Patel AS, Siegert RJ, Brignall K, Gordon P, Steer S, Desai SR. The development and validation of the King's Brief Interstitial Lung Disease (K-BILD) health status questionnaire. Thorax. 2012 May 3. [Medline].

  69. Raghu G, Lynch D, Godwin JD, et al. Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial. Lancet Respir Med. 2014 Feb.

 
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Chest radiograph of a patient with idiopathic pulmonary fibrosis showing bilateral lower lobe reticular opacities (red circles).
Classic subpleural honeycombing (red circle) in a patient with a diagnosis of idiopathic pulmonary fibrosis.
A patient with IPF and a confirmed histologic diagnosis of usual interstitial pneumonia. Note the reticular opacities (red circle) distributed in both lung bases and the minimal ground-glass opacities (blue circle).
A patient with nonspecific interstitial pneumonia. Note the predominance of ground-glass opacities (blue circles) and a few reticular lines (red arrow).
Patchwork distribution of abnormalities in a classic example of usual interstitial pneumonia (low-magnification photomicrograph; hematoxylin and eosin stain; original magnification, X4). Courtesy of Chad Stone, MD.
Table 1. Scoring for mortality risk in IPF.
  Predictor Points
Sex Female 0
Male 1
Age (years) ≥60 0
61-65 1
>65 2
FVC (% predicted) >75 0
50-75 1
< 50 2
DLCO (% predicted) >55 0
36-55 1
≤35 2
Cannot perform 3
Table 2. Staging and mortality risk for IPF.
Stage I II III
Points 0-3 4-5 6-8
Mortality      
1-year 5.6 16.2 39.2
2-year 10.9 29.9 62.1
3-year 16.3 42.1 76.8
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