Clinical manifestations and diagnosis of idiopathic pulmonary fibrosis
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), previously known as cryptogenic fibrosing alveolitis (CFA) in Europe, is the most common type of idiopathic interstitial pneumonia (IIP). IIPs are spontaneously occurring (ie, idiopathic) diffuse parenchymal lung diseases. An American Thoracic Society (ATS) consensus statement defined IPF as a spontaneously occurring (idiopathic) specific form of chronic fibrosing interstitial pneumonia limited to the lung and associated with a pattern of UIP on high resolution computed tomography or histologic appearance on surgical (thoracoscopic or open) lung biopsy [1,2].
The other IIPs include nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis associated interstitial lung disease (RB-ILD), acute interstitial pneumonia (AIP), lymphocytic interstitial pneumonia (LIP), and cryptogenic organizing pneumonia (COP).
The clinical manifestations, evaluation, and diagnosis of IPF will be reviewed here. The evaluation of interstitial lung disease in general, the diagnosis and management of the other IIPs, and the treatment of IPF are discussed separately. (See "Approach to the adult with interstitial lung disease: Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing" and "Idiopathic interstitial pneumonias: Clinical manifestations and pathology" and "Acute interstitial pneumonia (Hamman-Rich syndrome)" and "Treatment and prognosis of nonspecific interstitial pneumonia" and "Cryptogenic organizing pneumonia" and "Respiratory bronchiolitis-associated interstitial lung disease" and "Lymphoid interstitial pneumonia in adults".)
Reported prevalence and incidence data for idiopathic pulmonary fibrosis (IPF) vary and depend on ascertainment and reporting methods and also the age and geographic location of the population. Both prevalence and incidence increase with advancing age, with presentation commonly occurring in the sixth and seventh decades; rarely is IPF seen in patients aged less than 50 years [1,2]. The prevalence and incidence are higher in men than women .
In a systematic review, the prevalence of IPF ranged from 0.5 to 27.9/100,000 and the incidence ranged from 0.22 to 8.8/100,000 . In the United States, IPF incidence estimates range from 7 to 16 cases per 100,000 overall . In contrast, among a random sample of Medicare beneficiaries (largely ≥65 years old), the prevalence of IPF was 494 cases per 100,000, and the incidence was 94 cases per 100,000 person years . In the United Kingdom, the IPF incidence in 2008 was 7.4 per 100,000 person-years . In Europe, IPF prevalence ranged from 1.25 to 23.4 cases per 100,000 population, and the annual incidence ranged between 0.22 and 7.4 per 100,000 population . Overall, the incidence of IPF is increasing worldwide and conservative estimates of the incidence range from 3 to 9 cases per 100,000 per year for Europe and North America .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- 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.
- 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; 161:646.
- Esposito DB, Lanes S, Donneyong M, et al. Idiopathic Pulmonary Fibrosis in United States Automated Claims. Incidence, Prevalence, and Algorithm Validation. Am J Respir Crit Care Med 2015; 192:1200.
- Kaunisto J, Salomaa ER, Hodgson U, et al. Idiopathic pulmonary fibrosis--a systematic review on methodology for the collection of epidemiological data. BMC Pulm Med 2013; 13:53.
- Raghu G, Weycker D, Edelsberg J, et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006; 174:810.
- Raghu G, Chen SY, Yeh WS, et al. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001-11. Lancet Respir Med 2014; 2:566.
- Navaratnam V, Fleming KM, West J, et al. The rising incidence of idiopathic pulmonary fibrosis in the U.K. Thorax 2011; 66:462.
- Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D. Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev 2012; 21:355.
- Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J 2015; 46:795.
- Bennett D, Mazzei MA, Squitieri NC, et al. Familial pulmonary fibrosis: Clinical and radiological characteristics and progression analysis in different high resolution-CT patterns. Respir Med 2017; 126:75.
- van Moorsel CH, Ten Klooster L, van Oosterhout MF, et al. SFTPA2 Mutations in Familial and Sporadic Idiopathic Interstitial Pneumonia. Am J Respir Crit Care Med 2015; 192:1249.
- 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.
- Vicary GW, Vergne Y, Santiago-Cornier A, et al. Pulmonary Fibrosis in Hermansky-Pudlak Syndrome. Ann Am Thorac Soc 2016; 13:1839.
- Snetselaar R, van Moorsel CH, Kazemier KM, et al. Telomere length in interstitial lung diseases. Chest 2015; 148:1011.
- Armanios M, Blackburn EH. The telomere syndromes. Nat Rev Genet 2012; 13:693.
- George G, Rosas IO, Cui Y, et al. Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease. Chest 2015; 147:1549.
- Calado RT, Regal JA, Kleiner DE, et al. A spectrum of severe familial liver disorders associate with telomerase mutations. PLoS One 2009; 4:e7926.
- Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med 2007; 356:1317.
- Petrovski S, Todd JL, Durheim MT, et al. An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis. Am J Respir Crit Care Med 2017; 196:82.
- Lee JS, Collard HR, Raghu G, et al. Does chronic microaspiration cause idiopathic pulmonary fibrosis? Am J Med 2010; 123:304.
- Lee JS. The Role of Gastroesophageal Reflux and Microaspiration in Idiopathic Pulmonary Fibrosis. Clin Pulm Med 2014; 21:81.
- King TE, Jr. Idiopathic pulmonary fibrosis. In: Interstitial Lung Disease, 5th, Schwarz MI, King TE, Jr (Eds), People's Medical Publishing House-USA, Shelton, CT 2011. p.895.
- Wells AU. Managing diagnostic procedures in idiopathic pulmonary fibrosis. Eur Respir Rev 2013; 22:158.
- Flaherty KR, King TE Jr, 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.
- Pezzuto G, Claroni G, Puxeddu E, et al. Structured multidisciplinary discussion of HRCT scans for IPF/UIP diagnosis may result in indefinite outcomes. Sarcoidosis Vasc Diffuse Lung Dis 2015; 32:32.
- Chung JH, Lynch DA. The Value of a Multidisciplinary Approach to the Diagnosis of Usual Interstitial Pneumonitis and Idiopathic Pulmonary Fibrosis: Radiology, Pathology, and Clinical Correlation. AJR Am J Roentgenol 2016; 206:463.
- Moua T, Maldonado F, Decker PA, et al. Frequency and implication of autoimmune serologies in idiopathic pulmonary fibrosis. Mayo Clin Proc 2014; 89:319.
- Lee JS, Kim EJ, Lynch KL, et al. Prevalence and clinical significance of circulating autoantibodies in idiopathic pulmonary fibrosis. Respir Med 2013; 107:249.
- Lynch DA, Godwin JD, Safrin S, et al. High-resolution computed tomography in idiopathic pulmonary fibrosis: diagnosis and prognosis. Am J Respir Crit Care Med 2005; 172:488.
- Quadrelli S, Molinari L, Ciallella L, et al. Radiological versus histopathological diagnosis of usual interstitial pneumonia in the clinical practice: does it have any survival difference? Respiration 2010; 79:32.
- Fell CD, Martinez FJ, Liu LX, et al. Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2010; 181:832.
- 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.
- 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.
- Søyseth V, Aaløkken TM, Mynarek G, et al. Diagnosis of biopsy verified usual interstitial pneumonia by computed tomography. Respir Med 2015; 109:897.
- Gruden JF, Panse PM, Gotway MB, et al. Diagnosis of Usual Interstitial Pneumonitis in the Absence of Honeycombing: Evaluation of Specific CT Criteria With Clinical Follow-Up in 38 Patients. AJR Am J Roentgenol 2016; 206:472.
- Brownell R, Moua T, Henry TS, et al. The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia. Thorax 2017; 72:424.
- Sumikawa H, Johkoh T, Colby TV, et al. Computed tomography findings in pathological usual interstitial pneumonia: relationship to survival. Am J Respir Crit Care Med 2008; 177:433.
- Oda T, Ogura T, Kitamura H, et al. Distinct characteristics of pleuroparenchymal fibroelastosis with usual interstitial pneumonia compared with idiopathic pulmonary fibrosis. Chest 2014; 146:1248.
- 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; 179:1043.
- Casoni GL, Tomassetti S, Cavazza A, et al. Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. PLoS One 2014; 9:e86716.
- Tomassetti S, Wells AU, Costabel U, et al. Bronchoscopic Lung Cryobiopsy Increases Diagnostic Confidence in the Multidisciplinary Diagnosis of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2016; 193:745.
- Salisbury ML, Xia M, Murray S, et al. Predictors of idiopathic pulmonary fibrosis in absence of radiologic honeycombing: A cross sectional analysis in ILD patients undergoing lung tissue sampling. Respir Med 2016; 118:88.
- Yagihashi K, Huckleberry J, Colby TV, et al. Radiologic-pathologic discordance in biopsy-proven usual interstitial pneumonia. Eur Respir J 2016; 47:1189.
- 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.
- Lee HL, Ryu JH, Wittmer MH, et al. Familial idiopathic pulmonary fibrosis: clinical features and outcome. Chest 2005; 127:2034.
- Vij R, Noth I, Strek ME. Autoimmune-featured interstitial lung disease: a distinct entity. Chest 2011; 140:1292.
- Pneumotox. http://www.pneumotox.com/pattern/index/ (Accessed on October 20, 2015).
- Jankowich MD, Rounds SI. Combined pulmonary fibrosis and emphysema syndrome: a review. Chest 2012; 141:222.
- 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.
- POTENTIAL RISK FACTORS
- CLINICAL MANIFESTATIONS
- Pulmonary function tests
- Chest imaging
- Bronchoalveolar lavage
- Lung biopsy
- Diagnosis without lung biopsy
- Diagnosis with lung biopsy
- Post-diagnostic evaluation
- DIFFERENTIAL DIAGNOSIS
- SUMMARY AND RECOMMENDATIONS