eMedicine Specialties > Pulmonology > Interstitial Lung Diseases
Pulmonary Fibrosis, Idiopathic
Updated: Jun 30, 2009
Introduction
Background
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease of unknown etiology characterized by a poor prognosis and no proven effective treatment.
Idiopathic pulmonary fibrosis is the most common of the 7 idiopathic interstitial pneumonias classified by the American Thoracic Society/European Respiratory Society (ATS/ERS) consensus in 2002. Its pathogenesis remains unknown, but disordered fibroproliferation and alveolar epithelial cell function has been identified. The most common histologic pattern found in surgical lung biopsy specimens from patients with idiopathic pulmonary fibrosis is called usual interstitial pneumonia (UIP), making idiopathic pulmonary fibrosis and UIP interchangeable terms in most patients. See Table 1 below.
Clinical features consist of progressive dyspnea and/or nonproductive cough, diffuse interstitial infiltrates on chest radiographs, honeycombing on high-resolution CT (HRCT) scans, and a restrictive impairment with reduced gas exchange on pulmonary function test results.
The definitive diagnosis should be made after a clinical, radiological, and pathological evaluation of the patient, and only after excluding other causes of interstitial lung disease.
Treatment with systemic corticosteroids, other immunosuppressants, or both may benefit patients with idiopathic pulmonary fibrosis. However, lung transplantation is the therapy with the most data supporting survival benefit.
Table 1. Classification of Idiopathic Interstitial Pneumonias From the ATS/ERS 2002 Consensus
Open table in new window
Table
Clinical Diagnosis | Pathological Diagnosis |
| Idiopathic pulmonary fibrosis | Usual interstitial pneumonia |
| Nonspecific interstitial pneumonia | Nonspecific interstitial pneumonia |
| Desquamative interstitial pneumonia | Desquamative interstitial pneumonia |
| Respiratory bronchiolitis interstitial lung disease | Respiratory bronchiolitis interstitial lung disease |
| Acute interstitial pneumonia | Diffuse alveolar damage |
| Cryptogenic organizing pneumonia | Organizing pneumonia |
| Lymphoid interstitial pneumonia | Lymphoid interstitial pneumonia |
Clinical Diagnosis | Pathological Diagnosis |
| Idiopathic pulmonary fibrosis | Usual interstitial pneumonia |
| Nonspecific interstitial pneumonia | Nonspecific interstitial pneumonia |
| Desquamative interstitial pneumonia | Desquamative interstitial pneumonia |
| Respiratory bronchiolitis interstitial lung disease | Respiratory bronchiolitis interstitial lung disease |
| Acute interstitial pneumonia | Diffuse alveolar damage |
| Cryptogenic organizing pneumonia | Organizing pneumonia |
| Lymphoid interstitial pneumonia | Lymphoid interstitial pneumonia |
Pathophysiology
The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unknown. Intra-alveolar inflammation was believed to play a big role; however, anti-inflammatory agents and immune modulators have proven to be minimally effective in the treatment of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis is characterized by diffuse interstitial fibrosis with only mild inflammation, honeycomb cysts, and fibroblastic foci (areas of accumulation of fibroblasts and connective tissue).
A disruption in the homeostasis of alveolar epithelial cells caused by unknown endogenous or environmental stimuli is thought to occur. Some of the factors associated with idiopathic pulmonary fibrosis include cigarette smoking, infections, environmental pollutants, gastroesophageal reflux disease, and drugs.
This disruption in the homeostasis results in diffuse epithelial cell activation and aberrant epithelial repair, in which cytokines (eg, tumor necrosis factor-alpha, transforming growth factor beta-1) and dysfunctional apoptosis are involved1 This process leads to the overproduction of collagen and fibronectin by fibroblasts. A vicious cycle of injury and abnormal epithelial healing sets the stage for progressive fibrosis and architectural distortion of the lung parenchyma.
Frequency
United States
The prevalence of idiopathic pulmonary fibrosis ranges from 14-42.7 cases per 100,000 persons depending on the criteria used for diagnosis. Meanwhile, the incidence ranges from 6.8-16.3 cases per 100,000 persons based on recent estimates.2
International
Worldwide, the reported prevalence and incidence are estimated at 10-20 and 7-10 cases per 100,000 persons, respectively.
Mortality/Morbidity
From 1992-2003, the average age- and sex-adjusted mortality rate associated with idiopathic pulmonary fibrosis was estimated at 50.8 deaths per million persons.3 Mortality increases with age, and rates are higher in men than in women. Median survival is 2-4 years once the diagnosis is made, and the 5-year survival rate ranges from 20-40%. The most common cause of death in patients with idiopathic pulmonary fibrosis is the disease itself.3 New evidence suggests that pulmonary hypertension and gastroesophageal reflux disease contribute to morbidity and mortality in idiopathic pulmonary fibrosis.4,5
Race
Not enough data have shown any particular racial predilection for idiopathic pulmonary fibrosis.
Sex
The prevalence of idiopathic pulmonary fibrosis is higher in men than in women, predominantly those older than 55 years.
Age
Idiopathic pulmonary fibrosis mainly affects elderly persons, with more than two thirds of patients being older than 60 years at the time of presentation. A US study estimated the prevalence at 4 cases per 100,000 persons aged 18-34 years and 227.2 cases per 100,000 persons older than 75 years.2
Clinical
History
Clinical features of idiopathic pulmonary fibrosis (IPF) are variable. Onset is insidious, and the condition follows a progressive course. The median duration of symptoms before the diagnosis of idiopathic pulmonary fibrosis is 1-2 years. Among asymptomatic patients with idiopathic pulmonary fibrosis (diagnosed by radiographic abnormalities found on routine chest radiographs and after lung biopsy specimens show UIP), symptoms developed approximately 1000 days after the recognition of the radiologic abnormality.6
Dyspnea upon exertion is the most common symptom. Most patients have a nonproductive cough in the early part of the disease. Approximately 5% have no presenting symptoms when idiopathic pulmonary fibrosis is diagnosed. Patients become disabled with dyspnea and are oxygen-dependent. Some patients stabilize after initially declining.
Acute exacerbation of idiopathic pulmonary fibrosis (defined most often by worsening dyspnea, new radiologic pulmonary infiltrates, deterioration in pulmonary function measurements or gas exchange, and the absence of an identifiable cause) is an indicator of disease progression.7 Extrapulmonary (eg, articular, muscular, skin) involvement may indicate a collagen-vascular disease with pulmonary fibrosis. In addition, fever and wheezing are not features of idiopathic pulmonary fibrosis.
A thorough history of occupational (eg, silica, asbestos, heavy metals, moldy foliage), environmental (eg, pigeon breeding, contaminated ventilation system), and drug (eg, amiodarone) exposure is essential to exclude other causes of diffuse interstitial disease.
Physical
End-inspiratory velcrolike rales can be heard at the lung bases. Clubbing of the fingers is noted in 20-50% of patients. Signs of pulmonary hypertension and right-sided heart failure (eg, a loud second heart sound, right ventricular heave, pedal edema) may be observed as the disease progresses.4
Causes
The etiology of idiopathic pulmonary fibrosis remains undefined. Familial pulmonary fibrosis represents 20% of all cases of idiopathic pulmonary fibrosis.8 Only one genetic mutation, which involves surfactant protein C, has been clearly associated with idiopathic pulmonary fibrosis.9
Cigarette smoking has been associated with increased severity and mortality in persons with idiopathic pulmonary fibrosis.10 Wood and metal dust exposure are more common in patients with idiopathic pulmonary fibrosis than in age-matched control subjects. The risk of developing idiopathic pulmonary fibrosis increases with the number of work-years of exposure. Chronic aspiration secondary to gastroesophageal reflux disease has been implicated in the development of pulmonary fibrosis.
More on Pulmonary Fibrosis, Idiopathic |
 Overview: Pulmonary Fibrosis, Idiopathic |
| Differential Diagnoses & Workup: Pulmonary Fibrosis, Idiopathic |
| Treatment & Medication: Pulmonary Fibrosis, Idiopathic |
| Follow-up: Pulmonary Fibrosis, Idiopathic |
| Multimedia: Pulmonary Fibrosis, Idiopathic |
| References |
| Next Page » |
References
Verma S, Slutsky AS. Idiopathic pulmonary fibrosis--new insights. N Engl J Med. Mar 29 2007;356(13):1370-2. [Medline].
Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. Oct 1 2006;174(7):810-6. [Medline].
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. Aug 1 2007;176(3):277-84. [Medline].
Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. Sep 2007;132(3):998-1006. [Medline].
Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C, Hayes J, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. Jan 2006;27(1):136-42. [Medline].
Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. Jun 2006;3(4):285-92. [Medline].
Hyzy R, Huang S, Myers J, Flaherty K, Martinez F. Acute exacerbation of idiopathic pulmonary fibrosis. Chest. Nov 2007;132(5):1652-8. [Medline].
Loyd JE. Pulmonary fibrosis in families. Am J Respir Cell Mol Biol. Sep 2003;29(3 Suppl):S47-50. [Medline].
Lawson WE, Loyd JE. The genetic approach in pulmonary fibrosis: can it provide clues to this complex disease?. Proc Am Thorac Soc. Jun 2006;3(4):345-9. [Medline].
Antoniou KM, Hansell DM, Rubens MB, Marten K, Desai SR, Siafakas NM, et al. Idiopathic pulmonary fibrosis: outcome in relation to smoking status. Am J Respir Crit Care Med. Jan 15 2008;177(2):190-4. [Medline].
Silva CI, Müller NL, Lynch DA, Curran-Everett D, Brown KK, Lee KS, et al. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology. Jan 2008;246(1):288-97. [Medline].
Misumi S, Lynch DA. Idiopathic pulmonary fibrosis/usual interstitial pneumonia: imaging diagnosis, spectrum of abnormalities, and temporal progression. Proc Am Thorac Soc. Jun 2006;3(4):307-14. [Medline].
Thannickal VJ, Horowitz JC. Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proc Am Thorac Soc. Jun 2006;3(4):350-6. [Medline].
Flaherty KR, Thwaite EL, Kazerooni EA, Gross BH, Toews GB, Colby TV, et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax. Feb 2003;58(2):143-8. [Medline].
Erbes R, Schaberg T, Loddenkemper R. Lung function tests in patients with idiopathic pulmonary fibrosis. Are they helpful for predicting outcome?. Chest. Jan 1997;111(1):51-7. [Medline].
Jegal Y, Kim DS, Shim TS, Lim CM, Do Lee S, Koh Y, et al. Physiology is a stronger predictor of survival than pathology in fibrotic interstitial pneumonia. Am J Respir Crit Care Med. Mar 15 2005;171(6):639-44. [Medline].
Martinez FJ, Flaherty K. Pulmonary function testing in idiopathic interstitial pneumonias. Proc Am Thorac Soc. Jun 2006;3(4):315-21. [Medline].
Kinder BW, Brown KK, Schwarz MI, Ix JH, Kervitsky A, King TE Jr. Baseline BAL neutrophilia predicts early mortality in idiopathic pulmonary fibrosis. Chest. Jan 2008;133(1):226-32. [Medline].
Raghu G, Brown KK, Bradford WZ, Starko K, Noble PW, Schwartz DA, et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med. Jan 8 2004;350(2):125-33. [Medline].
[Best Evidence] King TE, 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. Jun 2009;[Full Text].
Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, et al. Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. May 1 2005;171(9):1040-7. [Medline].
Demedts M, Behr J, Buhl R, Costabel U, Dekhuijzen R, Jansen HM, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. Nov 24 2005;353(21):2229-42. [Medline].
Orens JB, Estenne M, Arcasoy S, Conte JV, Corris P, Egan JJ, 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. Jul 2006;25(7):745-55. [Medline].
Daniels CE, Ryu JH. Treatment of idiopathic pulmonary fibrosis. Semin Respir Crit Care Med. Dec 2006;27(6):668-76. [Medline].
Flaherty KR, Andrei AC, King TE Jr, Raghu G, Colby TV, Wells A, et al. Idiopathic interstitial pneumonia: do community and academic physicians agree on diagnosis?. Am J Respir Crit Care Med. May 15 2007;175(10):1054-60. [Medline].
Gay SE, Kazerooni EA, Toews GB, Lynch JP 3rd, Gross BH, Cascade PN, et al. Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med. Apr 1998;157(4 Pt 1):1063-72. [Medline].
Gharaee-Kermani M, Gyetko MR, Hu B, Phan SH. New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: a potential role for stem cells in the lung parenchyma and implications for therapy. Pharm Res. May 2007;24(5):819-41. [Medline].
Hunninghake GW, Kalica AR. Approaches to the treatment of pulmonary fibrosis. Am J Respir Crit Care Med. Mar 1995;151(3 Pt 1):915-8. [Medline].
Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med. Apr 1998;157(4 Pt 1):1301-15. [Medline].
King TE Jr. Idiopathic pulmonary fibrosis. In: Schwarz MI, King TE Jr, eds. Interstitial Lung Disease. St. Louis, Mo: Mosby; 1993:367-403.
Martinez FJ, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, et al. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med. Jun 21 2005;142(12 Pt 1):963-7. [Medline].
Noth I, Martinez FJ. Recent advances in idiopathic pulmonary fibrosis. Chest. Aug 2007;132(2):637-50. [Medline].
Visscher DW, Myers JL. Histologic spectrum of idiopathic interstitial pneumonias. Proc Am Thorac Soc. Jun 2006;3(4):322-9. [Medline].
Further Reading
Keywords
IPF, cryptogenic fibrosing alveolitis, usual interstitial pneumonitis, UIP, interstitial disease, intersitial lung disease, desquamative interstitial pneumonitis, DIP, cor pulmonale, pneumothorax, thromboembolism disease, thromboembolic disease, chronic fibrosing alveolitis, fibrosing alveolitis, Hamman-Rich syndrome, collagen-vascular disease, collagen vascular disease, alveolar injuries, alveolar injury, inflammation of the lung parenchyma, fibrosis of the lung parenchyma, Ebstein-Barr virus, chronic aspiration secondary to gastroesophageal reflux
