Diagnosis and treatment of interstitial lung disease: focusing on idiopathic pulmonary fibrosis
Article information
J Korean Med Assoc. 2020;63(3):159-168
Publication date (electronic) : 2020 March 17
doi :
https://doi.org/10.5124/jkma.2020.63.3.159
Revised 2020 February 07; Accepted 2020 March 03.
Abstract
Abstract
Interstitial lung disease (ILD) is a rare condition characterized by extensive inflammation and fibrosis mainly involving the pulmonary interstitium or alveoli. Usually, patients with ILD clinically present with chronic cough and exertional dyspnea. ILD is classified into subtypes based on clinical characteristics, detailed history obtained from patients, and radiological, and/or histopathological features. The most common type of idiopathic interstitial pneumonia is idiopathic pulmonary fibrosis (IPF). IPF is a chronic progressive fibrosing ILD and is associated with poor prognosis. An exclusive diagnosis of IPF requires no known condition causing ILD and typical radiological and/or histopathological features of lung fibrosis. Fibrosis observed in this condition is attributable to repetitive epithelial injury with consequent abnormal wound healing in genetically susceptible and elderly individuals. Currently, pirfenidone and nintedanib are useful disease-modifying agents available to treat IPF. In this article, we review the concept, diagnosis, clinical course, and treatment of ILD.
Keywords: Interstitial lung diseases; Idiopathic interstitial pneumonias; Idiopathic pulmonary fibrosis
Classification of interstitial lung diseases (ILDs). IIP, interstitial idiopathic pneumonia.
Pathophysiology of idiopathic pulmonary fibrosis (IPF). (A) Normal lung and (B) IPF lung. Drawn by authors.
Typical usual interstitial pneumonia pattern of chest X-ray and high-resolution computed tomography of patient with idiopathic pulmonary fibrosis. Increased extent of diffuse subpleural reticular opacities, traction bronchiectasis and honeycombing in both lungs showing a basilar predominancy, consistent with usual interstitial pneumonia pattern. (A) Chest posteroanterior and (B) high-resolution computed tomography. The patient provided written informed consent for the publication.
Diagnostic algorithm for idiopathic pulmonary fibrosis (IPF). HRCT, high-resolution computed tomography; IIP, idiopathic interstitial pneumonia; CTD, connective tissue disease; ILD, interstitial lung disease; UIP, usual interstitial pneumonia; BAL, bronchoalveolar lavage; MDD, multidisciplinary discussion.
References
1. Flaherty KR, Brown KK, Wells AU, Clerisme-Beaty E, Collard HR, Cottin V, Devaraj A, Inoue Y, Le Maulf F, Richeldi L, Schmidt H, Walsh S, Mezzanotte W, Schlenker-Herceg R. Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res 2017;4:e000212.
2. Jin GY, Lynch D, Chawla A, Garg K, Tammemagi MC, Sahin H, Misumi S, Kwon KS. Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology 2013;268:563–571.
3. Rosas IO, Dellaripa PF, Lederer DJ, Khanna D, Young LR, Martinez FJ. Interstitial lung disease: NHLBI Workshop on the primary prevention of chronic lung diseases. Ann Am Thorac Soc 2014;11(Suppl 3)S169-S177.
4. Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med 1994;150:967–972.
5. Demedts M, Wells AU, Antó JM, Costabel U, Hubbard R, Cullinan P, Slabbynck H, Rizzato G, Poletti V, Verbeken EK, Thomeer MJ, Kokkarinen J, Dalphin JC, Taylor AN. Interstitial lung diseases: an epidemiological overview. Eur Respir J Suppl 2001;32:2s–16s.
6. Stoller JK. Murray & Nadelʼs Textbook of Respiratory Medicine, 6th Edition. Ann Am Thorac Soc 2015;12:1257–1258.
7. Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med 2018;378:1811–1823.
8. Cottin V, Hirani NA, Hotchkin DL, Nambiar AM, Ogura T, Otaola M, Skowasch D, Park JS, Poonyagariyagorn HK, Wuyts W, Wells AU. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 2018;27:180076.
9. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D. ATS/ERS Committee on Idiopathic Interstitial Pneumonias. 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;188:733–748.
10. De Sadeleer LJ, Meert C, Yserbyt J, Slabbynck H, Verschakelen JA, Verbeken EK, Weynand B, De Langhe E, Lenaerts JL, Nemery B, Van Raemdonck D, Verleden GM, Wells AU, Wuyts WA. Diagnostic ability of a dynamic multidisciplinary discussion in interstitial lung diseases: a retrospective observational study of 938 cases. Chest 2018;153:1416–1423.
11. Meyer KC, Raghu G, Baughman RP, Brown KK, Costabel U, du Bois RM, Drent M, Haslam PL, Kim DS, Nagai S, Rottoli P, Saltini C, Selman M, Strange C, Wood B. American Thoracic Society Committee on BAL in Interstitial Lung Disease. An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med 2012;185:1004–1014.
12. Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, Richeldi L, Kolb M, Tetzlaff K, Stowasser S, Coeck C, Clerisme-Beaty E, Rosenstock B, Quaresma M, Haeufel T, Goeldner RG, Schlenker-Herceg R, Brown KK. INBUILD Trial Investigators. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med 2019;381:1718–1727.
13. Gjonbrataj J, Choi WI, Bahn YE, Rho BH, Lee JJ, Lee CW. Incidence of idiopathic pulmonary fibrosis in Korea based on the 2011 ATS/ERS/JRS/ALAT statement. Int J Tuberc Lung Dis 2015;19:742–746.
14. Awadalla NJ, Hegazy A, Elmetwally RA, Wahby I. Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Egypt: a multicenter case-control study. Int J Occup Environ Med 2012;3:107–116.
15. Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res 2018;19:32.
16. Wolters PJ, Collard HR, Jones KD. Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol 2014;9:157–179.
17. Selman M, King TE, Pardo A. American Thoracic Society; European Respiratory Society; American College of Chest Physicians. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med 2001;134:136–151.
18. Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet 2017;389:1941–1952.
19. Martinez FJ, Collard HR, Pardo A, Raghu G, Richeldi L, Selman M, Swigris JJ, Taniguchi H, Wells AU. Idiopathic pulmonary fibrosis. Nat Rev Dis Primers 2017;3:17074.
20. Bagnato G, Harari S. Cellular interactions in the pathogenesis of interstitial lung diseases. Eur Respir Rev 2015;24:102–114.
21. Raghu G, Lynch D, Godwin JD, Webb R, Colby TV, Leslie KO, Behr J, Brown KK, Egan JJ, Flaherty KR, Martinez FJ, Wells AU, Shao L, Zhou H, Pedersen PS, Sood R, Montgomery AB, O'Riordan TG. 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;2:277–284.
22. Nishimura K, Kitaichi M, Izumi T, Nagai S, Kanaoka M, Itoh H. Usual interstitial pneumonia: histologic correlation with high-resolution CT. Radiology 1992;182:337–342.
23. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, Flaherty KR, Wells A, Martinez FJ, Azuma A, Bice TJ, Bouros D, Brown KK, Collard HR, Duggal A, Galvin L, Inoue Y, Jenkins RG, Johkoh T, Kazerooni EA, Kitaichi M, Knight SL, Mansour G, Nicholson AG, Pipavath SNJ, Buendía-Roldán I, Selman M, Travis WD, Walsh S, Wilson KC. American Thoracic Society; European Respiratory Society; Japanese Respiratory Society; Latin American Thoracic Society. Diagnosis of idiopathic pulmonary fibrosis: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2018;198:e44–e68.
24. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M, Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser S, Schlenker-Herceg R, Disse B, Collard HR. INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2071–2082.
25. King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW. ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2083–2092.
26. Ley B, Swigris J, Day BM, Stauffer JL, Raimundo K, Chou W, Collard HR. Pirfenidone reduces respiratory-related hospitalizations in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2017;196:756–761.
27. Costabel U, Inoue Y, Richeldi L, Collard HR, Tschoepe I, Stowasser S, Azuma A. Efficacy of nintedanib in idiopathic pulmonary fibrosis across prespecified subgroups in INPULSIS. Am J Respir Crit Care Med 2016;193:178–185.
28. Nathan SD, Albera C, Bradford WZ, Costabel U, Glaspole I, Glassberg MK, Kardatzke DR, Daigl M, Kirchgaessler KU, Lancaster LH, Lederer DJ, Pereira CA, Swigris JJ, Valeyre D, Noble PW. Effect of pirfenidone on mortality: pooled analyses and metaanalyses of clinical trials in idiopathic pulmonary fibrosis. Lancet Respir Med 2017;5:33–41.
29. Torrisi SE, Pavone M, Vancheri A, Vancheri C. When to start and when to stop antifibrotic therapies. Eur Respir Rev 2017;26:170053.
30. Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, Behr J, Brown KK, Cottin V, Flaherty KR, Fukuoka J, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kolb M, Lynch DA, Myers JL, Raghu G, Richeldi L, Taniguchi H, Martinez FJ. Acute exacerbation of idiopathic pulmonary fibrosis. An international working group report. Am J Respir Crit Care Med 2016;194:265–275.
31. Atkins CP, Loke YK, Wilson AM. Outcomes in idiopathic pulmonary fibrosis: a metaanalysis from placebo controlled trials. Respir Med 2014;108:376–387.
32. 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;37:356–363.
33. Collard HR, Yow E, Richeldi L, Anstrom KJ, Glazer C. IPFnet investigators. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials. Respir Res 2013;14:73.
34. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Müller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schünemann HJ. ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence- based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788–824.
35. Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;183:431–440.
36. King TE Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet 2011;378:1949–1961.
37. du Bois RM, Nathan SD, Richeldi L, Schwarz MI, Noble PW. Idiopathic pulmonary fibrosis: lung function is a clinically meaningful endpoint for phase III trials. Am J Respir Crit Care Med 2012;186:712–715.
38. Flaherty KR, Mumford JA, Murray S, Kazerooni EA, Gross BH, Colby TV, Travis WD, Flint A, Toews GB, Lynch JP 3rd, Martinez FJ. Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia. Am J Respir Crit Care Med 2003;168:543–548.
39. Ballester B, Milara J, Cortijo J. idiopathic pulmonary fibrosis and lung cancer: mechanisms and molecular targets. Int J Mol Sci 2019;20:593.
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