Future directions in idiopathic pulmonary fibrosis research an NHLBI workshop report

American Journal of Respiratory and Critical Care Medicine

Volumn 189, Issue 2, 2014, Pages 214-222

  Blackwell, Timothy S ^a   Tager, Andrew M ^b   Borok, Zea ^c   Moore, Bethany B ^d   Schwartz, David A ^e   Anstrom, Kevin J ^f   Bar Joseph, Ziv ^g   Bitterman, Peter ^h   Blackburn, Michael R ⁱ   Bradford, William ^j   Brown, Kevin K ^e   Chapman, Harold A ^k   Collard, Harold R ^k   Cosgrove, Gregory P ^e   Deterding, Robin ^e   Doyle, Ramona ^l   Flaherty, Kevin R ^d   Garcia, Christine Kim ^m   Hagood, James S ⁿ   Henke, Craig A ^h   Herzog, Erica ^o   Hogaboam, Cory M ^d   Horowitz, Jeffrey C ^d   King Jr , Talmadge E ^k   Loyd, James E ^a   Lawson, William E ^a   Marsh, Clay B ^p   Noble, Paul W ^q   Noth, Imre ^r   Sheppard, Dean ^k   Olsson, Julie ^l   Ortiz, Luis A ^s   O'Riordan, Thomas G ^t   Oury, Tim D ^s   Raghu, Ganesh ^u   Roman, Jesse ^v   Sime, Patricia J ^w   Sisson, Thomas H ^d   Tschumperlin, Daniel ^x   Violette, Shelia M ^y   Weaver, Timothy E ^z   Wells, Rebecca G ^aa   White, Eric S ^d   Kaminski, Naftali ^g   Martinez, Fernando J ^d   Wynn, Thomas A ^ab   Thannickal, Victor J ^ac   Eu, Jerry P ^ad   more..

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^d UNIVERSITY OF MICHIGAN   (United States)

^e UNIVERSITY OF COLORADO   (United States)

^f DUKE CLINICAL RESEARCH INSTITUTE   (United States)

^g CARNEGIE MELLON UNIVERSITY   (United States)

^h UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

ⁱ UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^j InterMune Inc   (United States)

^k UNIVERSITY OF CALIFORNIA   (United States)

^l GENENTECH INC   (United States)

^m UNIVERSITY OF TEXAS AT DALLAS   (United States)

ⁿ UNIVERSITY OF CALIFORNIA   (United States)

^o YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^p OHIO STATE UNIVERSITY   (United States)

^q CEDARS SINAI MEDICAL CENTER   (United States)

^r UNIVERSITY OF CHICAGO   (United States)

^s UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^t GILEAD SCIENCES   (United States)

^u UNIVERSITY OF WASHINGTON   (United States)

^v UNIVERSITY OF LOUISVILLE   (United States)

^w UNIVERSITY OF ROCHESTER   (United States)

^x HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^y BIOGEN   (United States)

^z CINCINNATI CHILDREN S HOSPITAL RESEARCH FOUNDATION   (United States)

^aa UNIVERSITY OF PENNSYLVANIA   (United States)

^ab NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^ac UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^ad NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

more..

Author keywords

Alveolar epithelial cells; Extracellular matrix; Idiopathic pulmonary fibrosis; Inflammation; Interstitial lung disease

Indexed keywords

ADVANCED GLYCATION END PRODUCT RECEPTOR; BIOLOGICAL MARKER; BLEOMYCIN; IMMUNOSUPPRESSIVE AGENT; MICRORNA; MUCIN 5B; PROTEOME; RELAXIN;

BASIC RESEARCH; CELL TYPE; CLINICAL ASSESSMENT; CLINICAL PROTOCOL; CLINICAL RESEARCH; CLINICAL TRIAL (TOPIC); COHORT ANALYSIS; CONFERENCE PAPER; DRUG EFFICACY; DRUG INDUSTRY; ENVIRONMENTAL FACTOR; EPIGENETICS; EXTRACELLULAR MATRIX; FIBROSING ALVEOLITIS; FOOD AND DRUG ADMINISTRATION; GENOMICS; HEREDITY; HUMAN; IMMUNITY; IMMUNOCOMPETENT CELL; IMMUNOPATHOGENESIS; INFLAMMATION; INFLAMMATORY CELL; LUNG ALVEOLUS EPITHELIUM; LUNG FIBROSIS; LUNG INJURY; MACROPHAGE; MEDIATOR; MESENCHYME CELL; MOLECULAR BIOLOGY; MOLECULAR DYNAMICS; MYOFIBROBLAST; NONHUMAN; PATIENT ADVOCACY; PHENOTYPE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; STRATEGIC PLANNING; TRANSLATIONAL RESEARCH;

ANIMALS; BIOMEDICAL RESEARCH; DISEASE MODELS, ANIMAL; EXTRACELLULAR MATRIX; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IDIOPATHIC PULMONARY FIBROSIS; INFLAMMATION; MICE; PULMONARY ALVEOLI; RESPIRATORY MUCOSA;

EID: 84892643019     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201306-1141WS     Document Type: Conference Paper

References (114)

1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al.; 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.
2. Crystal RG, Bitterman PB, Mossman B, Schwarz MI, Sheppard D, Almasy L, Chapman HA, Friedman SL, King TE Jr, Leinwand LA, et al. Future research directions in idiopathic pulmonary fibrosis: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med 2002;166:236-246.
3. Moore B, Lawson W, Oury T, Sisson T, Raghavendran K, Hogaboam C. Animal models of fibrotic lung disease. Am J Respir Cell Mol Biol 2013;49:167-179.
4. Sakai N, Tager AM. Fibrosis of two: epithelial cell-fibroblast interactions in pulmonary fibrosis. Biochim Biophys Acta.
5. Selman M, Pardo A. Role of epithelial cells in idiopathic pulmonary fibrosis: from innocent targets to serial killers. Proc Am Thorac Soc 2006;3:364-372.
6. Tanjore H, Lawson WE, Blackwell TS. Endoplasmic reticulum stress as a pro-fibrotic stimulus. Biochim Biophys Acta 2013;1832:911-921.
7. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 2010;328:1662-1668.
8. Scotton CJ, Chambers RC. Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest 2007;132:1311-1321.
9. Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast: one function, multiple origins. Am J Pathol 2007;170:1807-1816.
10. Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M, Kalluri R. Fibroblasts in kidney fibrosis emerge via endothelial-tomesenchymal transition. J Am Soc Nephrol 2008;19:2282-2287.
11. Zeisberg M, Kalluri R. Fibroblasts emerge via epithelial-mesenchymal transition in chronic kidney fibrosis. Front Biosci 2008;13:6991-6998.
12. Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, Sheppard D, Chapman HA. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA 2006;103:13180-13185.
13. Humphreys BD, Lin SL, Kobayashi A, Hudson TE, Nowlin BT, Bonventre JV, Valerius MT, McMahon AP, Duffield JS. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 2010;176:85-97.
14. Rock JR, Barkauskas CE, Cronce MJ, Xue Y, Harris JR, Liang J, Noble PW, Hogan BL. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci USA 2011;108:E1475-E1483.
15. Beers MF, Morrisey EE. The three R's of lung health and disease: repair, remodeling, and regeneration. J Clin Invest 2011;121:2065-2073.
16. Rock JR, Hogan BL. Epithelial progenitor cells in lung development, maintenance, repair, and disease. Annu Rev Cell Dev Biol 2011;27:493-512.
17. Kotton DN. Next-generation regeneration: the hope and hype of lung stem cell research. Am J Respir Crit Care Med 2012;185:1255-1260.
18. Hynes RO, Naba A. Overview of the matrisome-an inventory of extracellular matrix constituents and functions. Cold Spring Harb Perspect Biol 2012;4:a004903.
19. Kliment CR, Englert JM, Gochuico BR, Yu G, Kaminski N, Rosas I, Oury TD. Oxidative stress alters syndecan-1 distribution in lungs with pulmonary fibrosis. J Biol Chem 2009;284:3537-3545.
20. Naik PK, Bozyk PD, Bentley JK, Popova AP, Birch CM, Wilke CA, Fry CD, White ES, Sisson TH, Tayob N, et al.; COMET Investigators. Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2012;303:L1046-L1056.
21. Teder P, Vandivier RW, Jiang D, Liang J, Cohn L, Puré E, Henson PM, Noble PW. Resolution of lung inflammation by CD44. Science 2002;296:155-158.
22. Okamoto M, Hoshino T, Kitasato Y, Sakazaki Y, Kawayama T, Fujimoto K, Ohshima K, Shiraishi H, Uchida M, Ono J, et al. Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias. Eur Respir J 2011;37:1119-1127.
23. Olsen AL, Sackey BK, Marcinkiewicz C, Boettiger D, Wells RG. Fibronectin extra domain-A promotes hepatic stellate cell motility but not differentiation into myofibroblasts. Gastroenterology 2012;142:928-937.e3.
24. Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factorbeta1. J Cell Biol 1998;142:873-881.
25. Gao F, Koenitzer JR, Tobolewski JM, Jiang D, Liang J, Noble PW, Oury TD. Extracellular superoxide dismutase inhibits inflammation by preventing oxidative fragmentation of hyaluronan. J Biol Chem 2008;283:6058-6066.
26. Sera T, Fujioka H, Yokota H, Makinouchi A, Himeno R, Schroter RC, Tanishita K. Localized compliance of small airways in excised rat lungs using microfocal X-ray computed tomography. J Appl Physiol (1985) 2004;96:1665-1673.
27. McGee KP, Hubmayr RD, Ehman RL. MR elastography of the lung with hyperpolarized 3He. Magn Reson Med 2008;59:14-18.
28. Li Z, Dranoff JA, Chan EP, Uemura M, Sé vigny J, Wells RG. Transforming growth factor-beta and substrate stiffness regulate portal fibroblast activation in culture. Hepatology 2007;46:1246-1256.
29. Liu F, Mih JD, Shea BS, Kho AT, Sharif AS, Tager AM, Tschumperlin DJ. Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression. J Cell Biol 2010;190:693-706.
30. Balestrini JL, Chaudhry S, Sarrazy V, Koehler A, Hinz B. The mechanical memory of lung myofibroblasts. Integr Biol (Camb) 2012;4:410-421.
31. Huang X, Yang N, Fiore VF, Barker TH, Sun Y, Morris SW, Ding Q, Thannickal VJ, Zhou Y. Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic mechanotransduction. Am J Respir Cell Mol Biol 2012;47:340-348.
32. Wipff PJ, Rifkin DB, Meister JJ, Hinz B. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol 2007;179:1311-1323.
33. Goldmann WH. Mechanotransduction and focal adhesions. Cell Biol Int 2012;36:649-652.
34. Duffield JS, Lupher M, Thannickal VJ, Wynn TA. Host responses in tissue repair and fibrosis. Annu Rev Pathol 2013. 24:241-276.
35. Henderson NC, Iredale JP. Liver fibrosis: cellular mechanisms of progression and resolution. Clin Sci (Lond) 2007;112:265-280.
36. Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 1998;102:538-549.
37. Georges PC, Hui JJ, Gombos Z, McCormick ME, Wang AY, Uemura M, Mick R, Janmey PA, Furth EE, Wells RG. Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis. Am J Physiol Gastrointest Liver Physiol 2007;293:G1147-G1154.
38. Wells RG. The role of matrix stiffness in hepatic stellate cell activation and liver fibrosis. J Clin Gastroenterol 2005;39:S158-S161.
39. Tschumperlin DJ, Dai G, Maly IV, Kikuchi T, Laiho LH, McVittie AK, Haley KJ, Lilly CM, So PT, Lauffenburger DA, et al. Mechanotransduction through growth-factor shedding into the extracellular space. Nature 2004;429:83-86.
40. Booth AJ, Hadley R, Cornett AM, Dreffs AA, Matthes SA, Tsui JL, Weiss K, Horowitz JC, Fiore VF, Barker TH, et al. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am J Respir Crit Care Med 2012;186:866-876.
41. Peng R, Sridhar S, Tyagi G, Phillips JE, Garrido R, Harris P, Burns L, Renteria L, Woods J, Chen L, et al. Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease. PLoS ONE 2013;8:e59348.
42. Baughman RP, Lower EE, Miller MA, Bejarano PA, Heffelfinger SC. Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 1999;16:57-61.
43. Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovectormediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest 1997;100:768-776.
44. Lee CG, Cho SJ, Kang MJ, Chapoval SP, Lee PJ, Noble PW, Yehualaeshet T, Lu B, Flavell RA, Milbrandt J, et al. Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary fibrosis. J Exp Med 2004;200:377-389.
45. Fernandez IE, Eickelberg O. The impact of TGF-[5 on lung fibrosis: from targeting to biomarkers. Proc Am Thorac Soc 2012;9:111-116.
46. Thomas AQ, Lane K, Phillips J III, Prince M, Markin C, Speer M, Schwartz DA, Gaddipati R, Marney A, Johnson J, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med 2002;165:1322-1328.
47. Lawson WE, Grant SW, Ambrosini V, Womble KE, Dawson EP, Lane KB, Markin C, Renzoni E, Lympany P, Thomas AQ, et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax 2004;59:977-980.
48. Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet 2009;84:52-59.
49. Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, Lawson WE, Xie M, Vulto I, Phillips JA III, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med 2007;356:1317-1326.
50. Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, Rosenblatt RL, Shay JW, Garcia CK. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci USA 2007;104:7552-7557.
51. Lawson WE, Polosukhin VV, Stathopoulos GT, Zoia O, Han W, Lane KB, Li B, Donnelly EF, Holburn GE, Lewis KG, et al. Increased and prolonged pulmonary fibrosis in surfactant protein C-deficient mice following intratracheal bleomycin. Am J Pathol 2005;167:1267-1277.
52. Lawson WE, Cheng DS, Degryse AL, Tanjore H, Polosukhin VV, Xu XC, Newcomb DC, Jones BR, Roldan J, Lane KB, et al. Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs. Proc Natl Acad Sci USA 2011;108:10562-10567.
53. Degryse AL, Xu XC, Newman JL, Mitchell DB, Tanjore H, Polosukhin VV, Jones BR, McMahon FB, Gleaves LA, Phillips JA, 3rd, et al. Telomerase deficiency does not alter bleomycin-induced fibrosis in mice. Exp Lung Res 2012;38:124-134.
54. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International concensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000;161:646-664.
55. Englert JM, Hanford LE, Kaminski N, Tobolewski JM, Tan RJ, Fattman CL, Ramsgaard L, Richards TJ, Loutaev I, Nawroth PP, et al. A role for the receptor for advanced glycation end products in idiopathic pulmonary fibrosis. Am J Pathol 2008;172:583-591.
56. Naik P, Horowitz JC, Moore TA, Wilke CA, Toews GB, Moore BB. Pulmonary fibrosis induced by γ-herpesvirus in aged mice is associated with increased fibroblast responsiveness to transforming growth factor-β. J Gerontol A Biol Sci Med Sci 2012;67:714-725.
57. Samuel CS, Zhao C, Bathgate RA, Bond CP, Burton MD, Parry LJ, Summers RJ, Tang ML, Amento EP, Tregear GW. Relaxin deficiency in mice is associated with an age-related progression of pulmonary fibrosis. FASEB J 2003;17:121-123.
58. Torres-González E, Bueno M, Tanaka A, Krug LT, Cheng DS, Polosukhin VV, Sorescu D, Lawson WE, Blackwell TS, Rojas M, et al. Role of endoplasmic reticulum stress in age-related susceptibility to lung fibrosis. Am J Respir Cell Mol Biol 2012;46:748-756.
59. Pierce EM, Carpenter K, Jakubzick C, Kunkel SL, Flaherty KR, Martinez FJ, Hogaboam CM. Therapeutic targeting of CC ligand 21 or CC chemokine receptor 7 abrogates pulmonary fibrosis induced by the adoptive transfer of human pulmonary fibroblasts to immunodeficient mice. Am J Pathol 2007;170:1152-1164.
60. Trujillo G, Meneghin A, Flaherty KR, Sholl LM, Myers JL, Kazerooni EA, Gross BH, Oak SR, Coelho AL, Evanoff H, et al. TLR9 differentiates rapidly from slowly progressing forms of idiopathic pulmonary fibrosis. Sci Transl Med 2010;2:57ra82.
61. 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.
62. Gilani SR, Vuga LJ, Lindell KO, Gibson KF, Xue J, Kaminski N, Valentine VG, Lindsay EK, George MP, Steele C, et al. CD28 down-regulation on circulating CD4 T-cells is associated with poor prognoses of patients with idiopathic pulmonary fibrosis. PLoS ONE 2010;5:e8959.
63. 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.
64. Wilson MS, Elnekave E, Mentink-Kane MM, Hodges MG, Pesce JT, Ramalingam TR, Thompson RW, Kamanaka M, Flavell RA, Keane-Myers A, et al. IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. J Clin Invest 2007;117:2941-2951.
65. Wilson MS, Madala SK, Ramalingam TR, Gochuico BR, Rosas IO, Cheever AW, Wynn TA. Bleomycin and IL-1beta-mediated pulmonary fibrosis is IL-17A dependent. J Exp Med 2010;207:535-552.
66. Wynn TA. Fibrotic disease and the T (h) 1/T (h) 2 paradigm. Nat Rev Immunol 2004;4:583-594.
67. Reilkoff RA, Bucala R, Herzog EL. Fibrocytes: emerging effector cells in chronic inflammation. Nat Rev Immunol 2011;11:427-435.
68. Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1994;1:71-81.
69. Peng X, Mathai SK, Murray LA, Russell T, Reilkoff R, Chen Q, Gulati M, Elias JA, Bucala R, Gan Y, et al. Local apoptosis promotes collagen production by monocyte-derived cells in transforming growth factor β1-induced lung fibrosis. Fibrogenesis Tissue Repair 2011;4:12.
70. Moeller A, Gilpin SE, Ask K, Cox G, Cook D, Gauldie J, Margetts PJ, Farkas L, Dobranowski J, Boylan C, et al. Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;179:588-594.
71. Moore BB, Murray L, Das A, Wilke CA, Herrygers AB, Toews GB. The role of CCL12 in the recruitment of fibrocytes and lung fibrosis. Am J Respir Cell Mol Biol 2006;35:175-181.
72. Murray LA, Chen Q, Kramer MS, Hesson DP, Argentieri RL, Peng X, Gulati M, Homer RJ, Russell T, van Rooijen N, et al. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. Int J Biochem Cell Biol 2011;43:154-162.
73. Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY, Belperio JA, Keane MP, Strieter RM. Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 2004;114:438-446.
74. Mehrad B, Burdick MD, Strieter RM. Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis. Int J Biochem Cell Biol 2009;41:1708-1718.
75. Song E, Ouyang N, Hörbelt M, Antus B, Wang M, Exton MS. Influence of alternatively and classically activated macrophages on fibrogenic activities of human fibroblasts. Cell Immunol 2000;204:19-28.
76. Atabai K, Jame S, Azhar N, Kuo A, Lam M, McKleroy W, Dehart G, Rahman S, Xia DD, Melton AC, et al. Mfge8 diminishes the severity of tissue fibrosis in mice by binding and targeting collagen for uptake by macrophages. J Clin Invest 2009;119:3713-3722.
77. Wynn TA, Barron L. Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 2010;30:245-257.
78. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011;11:723-737.
79. Murray LA, Rosada R, Moreira AP, Joshi A, Kramer MS, Hesson DP, Argentieri RL, Mathai S, Gulati M, Herzog EL, et al. Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PLoS ONE 2010;5:e9683.
80. Gibbons MA, MacKinnon AC, Ramachandran P, Dhaliwal K, Duffin R, Phythian-Adams AT, van Rooijen N, Haslett C, Howie SE, Simpson AJ, et al. Ly6Chi monocytes direct alternatively activated profibrotic macrophage regulation of lung fibrosis. Am J Respir Crit Care Med 2011;184:569-581.
81. Richards TJ, Kaminski N, Baribaud F, Flavin S, Brodmerkel C, Horowitz D, Li K, Choi J, Vuga LJ, Lindell KO, et al. Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2012;185:67-76.
82. Prasse A, Probst C, Bargagli E, Zissel G, Toews GB, Flaherty KR, Olschewski M, Rottoli P, Müller-Quernheim J. Serum CC-chemokine ligand 18 concentration predicts outcome in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;179:717-723.
83. Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 2012;18:1028-1040.
84. Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011;364:1503-1512.
85. Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 2013;45:613-620.
86. Noth I, Zhang Y, Ma S-F, Flores C, Barber M, Huang Y, Broderick SM, Wade MS, Hysi P, Scuirba J, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genomewide association study. Lancet Respir Med 2013;1:309-317.
87. Peljto AL, Zhang Y, Fingerlin TE, Ma SF, Garcia JG, Richards TJ, Silveira LJ, Lindell KO, Steele MP, Loyd JE, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA 2013;309:2232-2239.
88. Hunninghake GM, Hatabu H, Okajima Y, Gao W, Dupuis J, Latourelle JC, Nishino M, Araki T, Zazueta OE, Kurugol S, et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med 2013;368:2192-2200.
89. Maitra M, Cano CA, Garcia CK. Mutant surfactant A2 proteins associated with familial pulmonary fibrosis and lung cancer induce TGF-β1 secretion. Proc Natl Acad Sci USA 2012;109:21064-21069.
90. Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, Rosenblatt RL, Shay JW, Garcia CK. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci USA 2007;104:7552-7557.
91. Yang IV, Schwartz DA. The next generation of complex lung genetic studies. Am J Respir Crit Care Med 2012;186:1087-1094.
92. Konishi K, Gibson KF, Lindell KO, Richards TJ, Zhang Y, Dhir R, Bisceglia M, Gilbert S, Yousem SA, Song JW, et al. Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;180:167-175.
93. Yang IV, Burch LH, Steele MP, Savov JD, Hollingsworth JW, McElvania-Tekippe E, Berman KG, Speer MC, Sporn TA, Brown KK, et al. Gene expression profiling of familial and sporadic interstitial pneumonia. Am J Respir Crit Care Med 2007;175:45-54.
94. Yang IV, Luna LG, Cotter J, Talbert J, Leach SM, Kidd R, Turner J, Kummer N, Kervitsky D, Brown KK, et al. The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis. PLoS ONE 2012;7:e37708.
95. Zuo F, Kaminski N, Eugui E, Allard J, Yakhini Z, Ben-Dor A, Lollini L, Morris D, Kim Y, DeLustro B, et al. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proc Natl Acad Sci USA 2002;99:6292-6297.
96. Oak SR, Murray L, Herath A, Sleeman M, Anderson I, Joshi AD, Coelho AL, Flaherty KR, Toews GB, Knight D, et al. A micro RNA processing defect in rapidly progressing idiopathic pulmonary fibrosis. PLoS ONE 2011;6:e21253.
97. Pandit KV, Milosevic J, Kaminski N. MicroRNAs in idiopathic pulmonary fibrosis. Transl Res 2011;157:191-199.
98. Milosevic J, Pandit K, Magister M, Rabinovich E, Ellwanger DC, Yu G, Vuga LJ, Weksler B, Benos PV, Gibson KF, et al. Profibrotic role of miR-154 in pulmonary fibrosis. Am J Respir Cell Mol Biol 2012;47:879-887.
99. Sanders YY, Tollefsbol TO, Varisco BM, Hagood JS. Epigenetic regulation of thy-1 by histone deacetylase inhibitor in rat lung fibroblasts. Am J Respir Cell Mol Biol 2011;45:16-23.
100. Rabinovich EI, Kapetanaki MG, Steinfeld I, Gibson KF, Pandit KV, Yu G, Yakhini Z, Kaminski N. Global methylation patterns in idiopathic pulmonary fibrosis. PLoS ONE 2012;7:e33770.
101. du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, Lancaster L, Noble PW, Raghu G, Sahn SA, et al. Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;184:459-466.
102. Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, Poletti V, Buccioli M, Elicker BM, Jones KD, et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med 2012;156:684-691.
103. Wynn TA. Integrating mechanisms of pulmonary fibrosis. J Exp Med 2011;208:1339-1350.
104. Vij R, Noth I. Peripheral blood biomarkers in idiopathic pulmonary fibrosis. Transl Res 2012;159:218-227.
105. Zhang Y, Kaminski N. Biomarkers in idiopathic pulmonary fibrosis. Curr Opin Pulm Med 2012;18:441-446.
106. Lee JS, Ryu JH, Elicker BM, Lydell CP, Jones KD, Wolters PJ, King TE Jr, Collard HR. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;184:1390-1394.
107. Kahloon RA, Xue J, Bhargava A, Csizmadia E, Otterbein L, Kass DJ, Bon J, Soejima M, Levesque MC, Lindell KO, et al. Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. Am J Respir Crit Care Med 2013;187:768-775.
108. Selman M, Carrillo G, Estrada A, Mejia M, Becerril C, Cisneros J, Gaxiola M, Perez-Padilla R, Navarro C, Richards T, et al. Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern. PLoS ONE 2007;2:e482.
109. Micheel C, Ball J, editors. Evaluation of biomarkers and surrogate endpoints in chronic disease. Washington, DC: The National Academic Press; 2010.
110. Swigris JJ, Fairclough D. Patient-reported outcomes in idiopathic pulmonary fibrosis research. Chest 2012;142:291-297.
111. Raghu G, Collard HR, Anstrom KJ, Flaherty KR, Fleming TR, King TE Jr, Martinez FJ, Brown KK. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Respir Crit Care Med 2012;185:1044-1048.
112. 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.
113. Olson AL, Swigris JJ, Brown KK. Clinical trials and tribulations-lessons from pulmonary fibrosis. QJM 2012;105:1043-1047.
114. Wells AU. Forced vital capacity as a primary end point in idiopathic pulmonary fibrosis treatment trials: making a silk purse from a sow's ear. Thorax 2013;68:309-310.