Are newly launched pharmacotherapies efficacious in treating idiopathic pulmonary fibrosis? Or is there still more work to be done?

References

• Raghu G, Rochwerg B, Zhang Y, 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;192(2):e3–19.
   PubMed Web of Science ®Google Scholar
• Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet. 2017;389(10082):1941–1952.
   Google Scholar
• Knudsen L, Ruppert C, Ochs M. Tissue remodelling in pulmonary fibrosis. Cell Tissue Res. 2017;367(3):607–626.
   PubMed Web of Science ®Google Scholar
• Wollin L, Maillet I, Quesniaux VV, et al. Anti-fibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor, nintedanib, in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014;349(2):209–220.
   PubMed Web of Science ®Google Scholar
• Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079–1087.
   PubMed Web of Science ®Google Scholar
• Richeldi L, Du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Eng J Med. 2014;370(22):2071–2082.
   PubMed Web of Science ®Google Scholar
• Azuma A. Pirfenidone treatment of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2012;6(2):107–114.
   PubMed Web of Science ®Google Scholar
• Conte E, Gili E, Fagone E, et al. Effect of pirfenidone on proliferation, TGF-β-induced myofibroblast differentiation and fibrogenic activity of primary human lung fibroblasts. Eur J Pharm Sci. 2014;58:13–19.
   PubMed Web of Science ®Google Scholar
• Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;377:1760–1769.
   PubMed Web of Science ®Google Scholar
• King TE, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–2092.
   PubMed Web of Science ®Google Scholar
• Nathan SD, Albera C, Bradford WZ, et al. Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis. Lancet Respir Med. 2017;5(1):33–41.
   PubMed Web of Science ®Google Scholar
• Tomos IP, Tzouvelekis A, Aidinis V, et al. Extracellular matrix remodeling in idiopathic pulmonary fibrosis. It is the “bed” that counts and not “the sleepers. Expert Rev Respir Med. 2017;2(2):1–11.
   Google Scholar
• Cong X, Hubmayr RD, Li C, et al. Plasma membrane wounding and repair in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol. 2017;312(3):L371–L391.
   PubMedGoogle Scholar
• Canestaro WJ, Forrester SH, Raghu G, et al. Drug treatment of idiopathic pulmonary fibrosis systematic review and network meta-analysis. Chest. 2016;149(3):756–766.
   PubMed Web of Science ®Google Scholar
• Lehtonen ST, Veijola A, Karvonen H, et al. Pirfenidone and nintedanib modulate properties of fibroblasts and myofibroblasts in idiopathic pulmonary fibrosis. Respir Res. 2016;17(1):14.
   PubMed Web of Science ®Google Scholar
• Knüppel L, Ishikawa Y, Aichler M, et al. A novel antifibrotic mechanism of nintedanib and pirfenidone: inhibition of collagen fibril assembly. Am J Respir Cell Mol Biol. 2017;153(Pt9):2817–2822.
   Google Scholar
• Ogura T, Taniguchi H, Azuma A, et al. Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1382–1392.
   PubMed Web of Science ®Google Scholar
• Jia G, Chandriani S, Abbas AR, et al. CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis. Thorax. 2017;30(1):281–288.
   Google Scholar
• Izumi S, Iikura M, Hirano S. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;367(9):870.
   PubMed Web of Science ®Google Scholar
• Leask A, Parapuram SK, Shi-Wen X, et al. Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease?. J Cell Commun Signal. 2009;3(2):89–94.
   PubMed Web of Science ®Google Scholar
• Allen JT, Knight RA, Bloor CA, et al. Enhanced insulin-like growth factor binding protein–related protein 2 (connective tissue growth factor) expression in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Cell Mol Biol. 1999;21(6):693–700.
   PubMed Web of Science ®Google Scholar
• Wang X, Wu G, Gou L, et al. A novel single-chain-Fv antibody against connective tissue growth factor attenuates bleomycin-induced pulmonary fibrosis in mice. Respirology. 2011;16(3):500–507.
   PubMed Web of Science ®Google Scholar
• Tremblay M, Grouix B, Sarra-Bournet F, et al. Pbi-4050, a novel first-in-class anti-fibrotic compound, inhibits ctgf and collagen i production in human alveolar epithelial cells and fibroblasts, and reduces lung fibrosis in the bleomycin-induced lung fibrosis model. Am J Respir Crit Care Med. 2014;189:A1998.
   Web of Science ®Google Scholar
• Cui Y, Osorio J, Risquez C, et al. Transforming growth factor-β1 downregulates vascular endothelial growth factor-D expression in human lung fibroblasts via the Jun NH2-terminal kinase signaling pathway. Mol Med. 2014;20(1):1.
   PubMed Web of Science ®Google Scholar
• Neidlinger NA, Larkin SK, Bhagat A, et al. Hydrolysis of phosphatidylserine-exposing red blood cells by secretory phospholipase A2 generates lysophosphatidic acid and results in vascular dysfunction. J Biol Chem. 2006;281(2):775–781.
   PubMed Web of Science ®Google Scholar
• Oikonomou N, Mouratis M-A, Tzouvelekis A, et al. Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol. 2012;47(5):566–574.
   PubMed Web of Science ®Google Scholar
• Watterson KR, Lanning DA, Diegelmann RF, et al. Regulation of fibroblast functions by lysophospholipid mediators: potential roles in wound healing. Wound Repair Regen. 2007;15(5):607–616.
   PubMed Web of Science ®Google Scholar
• Swaney J, Chapman C, Correa L, et al. A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010;160(7):1699–1713.
   PubMed Web of Science ®Google Scholar
• Wygrecka M, Zakrzewicz D, Taborski B, et al. TGF-β1 induces tissue factor expression in human lung fibroblasts in a PI3K/JNK/Akt-dependent and AP-1–dependent manner. Am J Respir Cell Mol Biol. 2012;47(5):614–627.
   PubMed Web of Science ®Google Scholar
• Conte E, Gili E, Fruciano M, et al. PI3K p110γ overexpression in idiopathic pulmonary fibrosis lung tissue and fibroblast cells: in vitro effects of its inhibition. Lab Invest. 2013;93(5):566–576.
   PubMed Web of Science ®Google Scholar
• Conte E, Fruciano M, Fagone E, et al. Inhibition of PI3K prevents the proliferation and differentiation of human lung fibroblasts into myofibroblasts: the role of class I P110 isoforms. PLoS One. 2011;6(10):e24663.
   PubMed Web of Science ®Google Scholar
• Königshoff M, Rojas M. Galectin-3: the bridge over troubled waters. Am J Respir Crit Care Med. 2012;185(5):473–475.
   PubMed Web of Science ®Google Scholar
• Mackinnon AC, Gibbons MA, Farnworth SL, et al. Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3. Am J Respir Crit Care Med. 2012;185(5):537–546.
   PubMed Web of Science ®Google Scholar
• Goodwin A, Jenkins G. Role of integrin-mediated TGFβ activation in the pathogenesis of pulmonary fibrosis. Biochem Soc Trans. 2009;37(4):849–854.
   PubMed Web of Science ®Google Scholar
• Saini G, Porte J, Weinreb PH, et al. αvβ6 integrin may be a potential prognostic biomarker in interstitial lung disease. Eur Respir J. 2015;46(2):486–494.
   PubMed Web of Science ®Google Scholar
• Horan GS, Wood S, Ona V, et al. Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation. Am J Respir Crit Care Med. 2008;177(1):56–65.
   PubMed Web of Science ®Google Scholar
• Mercer PF, Woodcock HV, Eley JD, et al. Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF. Thorax. 2016;71(8):701–711.
   PubMed Web of Science ®Google Scholar
• Street CA, Bryan BA. Rho kinase proteins–pleiotropic modulators of cell survival and apoptosis. Anticancer Res. 2011;31(11):3645–3657.
   PubMed Web of Science ®Google Scholar
• Le -T-T-T, Karmouty-Quintana H, Melicoff E, et al. Blockade of IL-6 trans signaling attenuates pulmonary fibrosis. J Immunol. 2014;193:3755–3768.
   PubMed Web of Science ®Google Scholar
• Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, et al. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci U S A. 2014;111(47):16814–16819.
   PubMed Web of Science ®Google Scholar
• Hinz B. Mechanical aspects of lung fibrosis: a spotlight on the myofibroblast. Proc Am Thorac Soc. 2012;9(3):137–147.
   PubMedGoogle Scholar
• Wipff PJ, Rifkin DB, Meister JJ, et al. Myofibroblast contraction activates latent TGF-beta1 from the extracellular matrix. J Cell Biol. 2007;179(6):1311–1323.
   PubMed Web of Science ®Google Scholar
• Park S-W-W, Ahn M-H-H, Jang HK, et al. Interleukin-13 and its receptors in idiopathic interstitial pneumonia: clinical implications for lung function. J Korean Med Sci. 2009;24(4):614–620.
   PubMed Web of Science ®Google Scholar
• Lee CG, Homer RJ, Zhu Z, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med. 2001;194(6):809–821.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Pascual F, Slatter DA. Collagen cross-linking: insights on the evolution of metazoan extracellular matrix. Sci Rep. 2016;6:37374.
   PubMed Web of Science ®Google Scholar
• Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase–like-2 impedes the development of a pathologic microenvironment. Nat Med. 2010;16(9):1009–1017.
   PubMed Web of Science ®Google Scholar
• Chien JW, Richards TJ, Gibson KF, et al. Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J. 2014;43(5):1430–1438.
   PubMed Web of Science ®Google Scholar
• Raghu G, Brown KK, Collard HR, et al. Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial. Lancet Respir Med. 2017;5(1):22–32.
   PubMed Web of Science ®Google Scholar
• Kahloon RA, Xue J, Bhargava A, 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(7):768–775.
   PubMed Web of Science ®Google Scholar
• Duffield JS, Lupher ML. PRM-151 (recombinant human serum amyloid P/pentraxin 2) for the treatment of fibrosis. Drug News Perspect. 2010;23(5):305–315.
   PubMedGoogle Scholar
• Peters-Golden M, Henderson WR. Leukotrienes. N Engl J Med. 2007;357(18):1841–1854.
   PubMed Web of Science ®Google Scholar
• Wilborn J, Bailie M, Coffey M, et al. Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis. J Clin Invest. 1996;97(8):1827–1836.
   PubMed Web of Science ®Google Scholar
• Izumo T, Kondo M, Nagai A. Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis. Eur Respir J. 2009;34(6):1444–1451.
   PubMed Web of Science ®Google Scholar
• May RD, Fung M. Strategies targeting the IL-4/IL-13 axes in disease. Cytokine. 2015;75(1):89–116.
   PubMed Web of Science ®Google Scholar
• Batra V, Musani AI, Hastie AT, et al. Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin (IL)-4 and IL-13 after segmental allergen challenge and their effects on alpha-smooth muscle actin and collagen III synthesis by primary human lung fibroblasts. Clin Exp Allergy. 2004;34(3):437–444.
   PubMed Web of Science ®Google Scholar
• Pilling D, Roife D, Wang M, et al. Reduction of bleomycin-induced pulmonary fibrosis by serum amyloid P. J Immunol. 2007;179(6):4035–4044.
   PubMed Web of Science ®Google Scholar
• Castaño AP, Lin S-L, Surowy T, et al. Serum amyloid P inhibits fibrosis through Fc gamma R-dependent monocyte-macrophage regulation in vivo. Sci Transl Med. 2009;1(5):5ra13.
   PubMed Web of Science ®Google Scholar
• Murray LA, Rosada R, Moreira AP, et al. Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PLoS One. 2010;5(3).
   Web of Science ®Google Scholar
• Dillingh MRR, Van Den Blink B, Moerland M, et al. Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis. Pulm Pharmacol Ther. 2013;26(6):672–676.
   PubMed Web of Science ®Google Scholar
• Van Den Blink B, Dillingh MR, Ginns LC, et al. Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy. Eur Respir J. 2016;47(3):889–897.
   PubMed Web of Science ®Google Scholar
• Burlingham WJ, Love RB, Jankowska-Gan E, et al. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest. 2007;117(11):3498–3506.
   PubMed Web of Science ®Google Scholar
• Vittal R, Mickler EA, Fisher AJ, et al. Type V collagen induced tolerance suppresses collagen deposition, TGF-beta and associated transcripts in pulmonary fibrosis. PLoS One. 2013;8(10):e76451.
   PubMed Web of Science ®Google Scholar
• Wilkes DS, Chew T, Flaherty KR, et al. Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis. Eur Respir J. 2015;45(5):1393–1402.
   PubMed Web of Science ®Google Scholar
• Feghali-Bostwick CA, Tsai CG, Valentine VG, et al. Cellular and humoral autoreactivity in idiopathic pulmonary fibrosis. J Immunol. 2007;179(4):2592–2599.
   PubMed Web of Science ®Google Scholar
• Roskoski R. Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol Res. 2015;94(1):9–25.
   PubMed Web of Science ®Google Scholar
• Yilmaz O, Oztay F, Kayalar O. Dasatinib attenuated bleomycin-induced pulmonary fibrosis in mice. Growth Factors. 2015;33(5–6):366–375.
   PubMed Web of Science ®Google Scholar
• Cruz FF, Horta LFB, De Albuquerque Maia L, et al. Dasatinib reduces lung inflammation and fibrosis in acute experimental silicosis. PLoS One. 2016;11(1):1–17.
   Web of Science ®Google Scholar
• Spagnolo P, Sverzellati N, Rossi G, et al. Idiopathic pulmonary fibrosis: an update. Ann Med. 2015;47(1):15–27.
   PubMed Web of Science ®Google Scholar
• Tzouvelekis A, Bonella F, Spagnolo P. Update on therapeutic management of idiopathic pulmonary fibrosis. Ther Clin Risk Manag. 2015;11:359–370.
   PubMed Web of Science ®Google Scholar
• Barczyk M, Schmidt M, Mattoli S. Stem cell-based therapy in idiopathic pulmonary fibrosis. Stem Cell Rev Reports. 2015;11(4):598–620.
   PubMed Web of Science ®Google Scholar
• Toonkel RL, Hare JM, Matthay MA, et al. Mesenchymal stem cells and idiopathic pulmonary fibrosis potential for clinical testing. Am J Respir Crit Care Med. 2013;188(2):133–140.
   PubMed Web of Science ®Google Scholar
• Chambers DC, Enever D, Ilic N, et al. A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology. 2014;19(7):1013–1018.
   PubMed Web of Science ®Google Scholar
• Tzouvelekis A, Paspaliaris V, Koliakos G, et al. A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis. J Transl Med. 2013;11(1):171.
   PubMed Web of Science ®Google Scholar
• Glassberg MK, Minkiewicz J, Toonkel RL, et al. Allogeneic human mesenchymal stem cells in patients with idiopathic pulmonary fibrosis via intravenous delivery (AETHER): a phase I, safety, clinical trial. Chest. 2017;151(5):971–981.
   PubMed Web of Science ®Google Scholar
• Molyneaux PL, Maher TM, Maher TM. The role of infection in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir Rev. 2013;22(129):376–381.
   PubMedGoogle Scholar
• Tang Y-W, Johnson JE, Browning PJ, et al. Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis. J Clin Microbiol. 2003;41(6):2633–2640.
   PubMed Web of Science ®Google Scholar
• Egan JJ, Adamali HI, Lok SS, et al. Ganciclovir antiviral therapy in advanced idiopathic pulmonary fibrosis: an open pilot study. Pulm Med. 2011;2011:240805. doi: 10.1155/2011/240805.
   PubMedGoogle Scholar
• Moore BB, Moore TA. Viruses in idiopathic pulmonary fibrosis etiology and exacerbation. Ann Am Thorac Soc. 2015;12(Suppl 2):S186–192.
   PubMedGoogle Scholar
• Vergnon JM, Vincent M, De Thé G, et al. Cryptogenic fibrosing alveolitis and Epstein-Barr virus: an association?. Lancet. 1984;2(8406):768–771.
   PubMed Web of Science ®Google Scholar
• Yonemaru M, Kasuga I, Kusumoto H, et al. Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis. Eur Respir J. 1997;10(9):2040–2045.
   PubMed Web of Science ®Google Scholar
• Manika K, Alexiou-Daniel S, Papakosta D, et al. Epstein-Barr virus DNA in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffus Lung Dis. 2007;24(2):134–140.
   PubMed Web of Science ®Google Scholar
• Kropski JA, Pritchett JM, Zoz DF, et al. Extensive phenotyping of individuals at risk for familial interstitial pneumonia reveals clues to the pathogenesis of interstitial lung disease. Am J Respir Crit Care Med. 2015;191(4):417–426.
   PubMed Web of Science ®Google Scholar
• Molyneaux PL, Cox MJ, Willis-Owen SAG, et al. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014;190(8):906–913.
   PubMed Web of Science ®Google Scholar
• Han MLK, Zhou Y, Murray S, et al. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study. Lancet Respir Med. 2014;2(7):548–556.
   PubMed Web of Science ®Google Scholar
• Shulgina L, Cahn AP, Chilvers ER, et al. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial. Thorax. 2013;68(9):884–885.
   PubMed Web of Science ®Google Scholar
• Selman M, Pardo A. Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. An integral model. Am J Respir Crit Care Med. 2014;189(10):1161–1172.
   PubMed Web of Science ®Google Scholar
• Wolters PJ, Collard HR, Jones KD. Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol. 2014;9:157–179.
   PubMed Web of Science ®Google Scholar
• 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;171(9):1040–1047.
   PubMed Web of Science ®Google Scholar
• Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):821–829.
   PubMed Web of Science ®Google Scholar
• Spagnolo P, Del Giovane C, Luppi F, et al. Non-steroid agents for idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2010;16(9):CD003134.
   Google Scholar
• Ahluwalia N, Shea BS, Tager AM. New therapeutic targets in idiopathic pulmonary fibrosis aiming to rein in runaway wound-healing responses. Am J Respir Crit Care Med. 2014;190(8):867–878.
   PubMed Web of Science ®Google Scholar
• Betensley A, Sharif R, Karamichos D. A systematic review of the role of dysfunctional wound healing in the pathogenesis and treatment of idiopathic pulmonary fibrosis. J Clin Med. 2016;6(1):2.
   PubMed Web of Science ®Google Scholar
• Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis. AJP Lung Cell Mol Physiol. 2007;294(2):L152–L160.
   Google Scholar
• Vancheri C, Failla M, Crimi N, et al. Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology. Eur Respir J. 2010;35(3):496–504.
   PubMed Web of Science ®Google Scholar
• Kreuter M, Ehlers-Tenenbaum S, Palmowski K, et al. Impact of comorbidities on mortality in patients with idiopathic pulmonary fibrosis. PLoS One. 2016;11(3):1–18.
   Web of Science ®Google Scholar
• Collard HR, Bradford WZ, Cottin V, et al. A new era in idiopathic pulmonary fibrosis: considerations for future clinical trials. Eur Respir J. 2015;46(1):243–249.
   PubMed Web of Science ®Google Scholar
• Raghu G, Collard HR, Anstrom KJ, et al. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Respir Crit Care Med. 2012;185(10):1044–1048.
   PubMed Web of Science ®Google Scholar
• Wells AU, Behr J, Costabel U, et al. Hot of the breath: mortality as a primary end-point in IPF treatment trials: the best is the enemy of the good. Thorax. 2012;67(11):938–940.
   PubMed Web of Science ®Google Scholar
• Ryerson CJ. Risk prediction and end-points in idiopathic pulmonary fibrosis: one step at a time. Eur Respir J. 2014;43(5):1237–1239.
   PubMed Web of Science ®Google Scholar
• Fernandez IE, Amarie OV, Mutze K, et al. Systematic phenotyping and correlation of biomarkers with lung function and histology in lung fibrosis. Am J Physiol Lung Cell Mol Physiol. 2016;310(10):L919–927.
   PubMed Web of Science ®Google Scholar
• Gonzalez De Castro D, Clarke PA, Al-Lazikani B, et al. Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance. Clin Pharmacol Ther. 2013;93(3):252–259.
   PubMed Web of Science ®Google Scholar
• Pathak RR, Davé V. Integrating omics technologies to study pulmonary physiology and pathology at the systems level. Cell Physiol Biochem. 2014;33(5):1239–1260.
   PubMed Web of Science ®Google Scholar
• Wilson JW, Du Bois RM, King TE. Challenges in pulmonary fibrosis: 8–the need for an international registry for idiopathic pulmonary fibrosis. Thorax. 2008;63(3):285–287.
   PubMed Web of Science ®Google Scholar
• Ryerson CJ, Corte TJ, Collard HR, et al. A global registry for idiopathic pulmonary fibrosis: the time is now. Eur Respir J. 2014;44(2):273–276.
   PubMed Web of Science ®Google Scholar