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;161:646–64.
Raghu G, Collard HR, Egan JJ, et al. Idiopathic pulmonary fibrosis: evidence based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788–824.
Spagnolo P, Sverzellati N, Rossi G, et al. Idiopathic pulmonary fibrosis: an update. Ann Med. 2015;47:15–27.
Johkoh T, Muller NL, Cartier Y, et al. Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients. Radiology. 1999;211:555–60.
Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner society: glossary of terms for thoracic imaging. Radiology. 2008;246:697–722.
Wuyts WA, Cavazza A, Rossi G, Bonella F, Sverzellati N, Spagnolo P. Differential diagnosis of usual interstitial pneumonia: when is it truly idiopathic? Eur Respir Rev 2014; 23:308–319. Erratum in: Eur Respir Rev 2014; 23:537.
Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174:810–6.
Raghu G, Chen S-Y, Yeh W-S, et al. Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence and survival, 2001–2011. Lancet Respir Med. 2014;2:566–72.
Iwai K, Mori T, Yamada N, Yamaguchi M, Hosoda Y. Idiopathic pulmonary fibrosis: epidemiologic approaches to occupational exposure. Am J Respir Crit Care Med. 1994;150:670–5.
Olson AL, Swigris JJ. Idiopathic pulmonary fibrosis: diagnosis and epidemiology. Clin Chest Med. 2012;33:41–50.
Spagnolo P, Grunewald J, du Bois RM. Genetic determinants of pulmonary fibrosis: evolving concepts. Lancet Respir Med. 2014;2:416–28.
Bellaye PS, Kolb M. Why do patients get idiopathic pulmonary fibrosis? Current concepts in the pathogenesis of pulmonary fibrosis. BMC Med. 2015;13:176.
Behr J, Kreuter M, Hoeper MH, et al. Management of patients with idiopathic pulmonary fibrosis in clinical practice: INSIGHTS-IPF registry. Eur Respir J. 2015;46:186–96.
Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;157:199–203.
Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183:431–40.
Johannson KA, Ley B, Collard HR. Models of disease behavior in idiopathic pulmonary fibrosis. BMC Med. 2015;13:165.
Selman M, Carrillo G, Estrada A, et al. Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern. PLoS ONE. 2007;2:e482.
du Bois RM. Strategies for treating idiopathic pulmonary fibrosis. Nat Rev Discov. 2010;9:129–40.
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;134:136–51.
Wolters PJ, Collard HR, Jones KD. Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol. 2014;9:157–79.
Spagnolo P, Rossi G, Cavazza A. Pathogenesis of idiopathic pulmonary fibrosis and its clinical implications. Expert Rev Clin Immunol. 2014;10:1005–17.
Maher TM. Idiopathic pulmonary fibrosis: pathobiology and novel approaches to treatment. Clin Chest Med. 2012;33:69–83.
King TE Jr, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083–92.
Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071–82.
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:e3–19.
Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401–6.
Andrews JC, Schünemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation’s direction and strength. J Clin Epidemiol. 2013;66:726–35.
Kim ES, Keating GM. Pirfenidone: a review of its use in idiopathic pulmonary fibrosis. Drugs. 2015;75:219–30.
Di Sario A, Bendia E, Svegliati Baroni G, et al. Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production. J Hepatol. 2002;37:584–91.
Schaefer CJ, Ruhrmund DW, Pan L, Seiwert SD, Kossen K. Antifibrotic activities of pirfenidone in animal models. Eur Respir Rev. 2011;20:85–97.
Nakayama S, Mukae H, Sakamoto N, et al. Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts. Life Sci. 2008;82:210–7.
Oku H, Nakazato H, Horikawa T, Tsuruta Y, Suzuki R. Pirfenidone suppresses tumor necrosis factor-alpha, enhances interleukin-10 and protects mice from endotoxic shock. Eur J Pharmacol. 2002;446:167–76.
Raghu G, Johnson WC, Lockhart D, Mageto Y. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label Phase II study. Am J Respir Crit Care Med. 1999;159:1061–9.
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;171:1040–7.
Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35:821–9.
Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011;77:1760–9.
Spagnolo P, Del Giovane C, Luppi F. Non-steroid agents for idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2010;9:CD003134.
Lederer DJ, Bradford WZ, Fagan EA, et al. Sensitivity analyses of the change in FVC in a phase 3 trial of pirfenidone for idiopathic pulmonary fibrosis. Chest. 2015;148:196–201.
Costabel U, Bendstrup E, Cottin V, et al. Pirfenidone in idiopathic pulmonary fibrosis: expert panel discussion on the management of drug-related adverse events. Adv Ther 2014;31:375–391. Erratum in: Adv Ther 2014;31:575–576.
Oltmanns U, Kahn N, Wenz H, et al. Pirfenidone in idiopathic pulmonary fibrosis—real life experience from a German tertiary referral center for interstitial lung diseases. Respiration. 2014;88:199–207.
Cottin V, Maher T. Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis. Eur Respir Rev. 2015;24:58–64.
Costabel U, Albera C, Bradford WZ, et al. Analysis of lung function and survival in RECAP: an open-label extension study of pirfenidone in patients with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis. 2014;31:198–205.
Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774–82.
Wollin L, Wex E, Pautsch A, et al. Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015;45:1434–45.
Keating GM. Nintedanib: a review of its use in patients with idiopathic pulmonary fibrosis. Drugs. 2015;75:1131–40.
Rangarajan S, Kurundkar A, Kurundkar D et al. Novel mechanisms for the anti-fibrotic action of nintedanib. Am J Respir Cell Mol Biol 2015 Jun 13. [Epub ahead of print].
Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365:1079–87.
Costabel U, Inoue Y, Richeldi L, et al. Efficacy of nintedanib in idiopathic pulmonary fibrosis across pre-specified subgroups in INPULSIS®. Am J Respir Crit Care Med 2015 Sep 22 [epub ahead of print].
Corte T, Bonella F, Crestani B, et al. Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis. Respir Res. 2015;16:116.
Raghu G, Freudenberger TD, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J. 2006;27:136–42.
Raghu G, Amatto VC, Behr J, Stowasser S. Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review. Eur Respir J. 2015;46:1113–30.
Savarino E, Carbone R, Marabotto E, et al. Gastro-oesophageal reflux and gastric aspiration in idiopathic pulmonary fibrosis patients. Eur Respir J. 2013;42:1322–31.
Lozo Vukovac E, Lozo M, Mise K, et al. Bronchoalveolar pH and inflammatory biomarkers in newly diagnosed IPF and GERD patients: a case-control study. Med Sci Monit. 2014;20:255–61.
Lee JS, Ryu JH, Elicker BM, et al. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;184:1390–4.
Lee JS, Collard HR, Anstrom KJ, et al. Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lancet Resp Med. 2013;1:369–76.
Kreuter M, Wuyts W, Renzoni E, et al. Presented at the 25th European Respiratory Society annual meeting, Amsterdam, the Netherlands, September 2015.
Spagnolo P, du Bois RM, Cottin V. Rare lung disease and orphan drug development. Lancet Respir Med. 2013;1:479–87.
Van Den Blink B, Burggraaf J, Morrison LD, et al. A phase I study of Prm-151 in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2013;187:A5707.
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;187:768–75.
Sumpter TL, Wilkes DS. Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection. Am J Physiol Lung Cell Mol Physiol. 2004;286:L1129–39.
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:e76451.
Parra ER, Teodoro WR, Velosa AP, et al. Interstitial and vascular type V collagen morphologic disorganization in usual interstitial pneumonia. J Histochem Cytochem. 2006;54:1315–25.
Wilkes DS, Chew T, Flaherty KR, et al. Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis. Eur Respir J. 2015;45:1393–402.
Nishi Y, Sano H, Kawashima T, et al. Role of galectin-3 in human pulmonary fibrosis. Allergol Int. 2007;56:57–65.
Watterson KR, Lanning DA, Diegelmann RF, Spiegel S. Regulation of fibroblast functions by lysophospholipid mediators: potential roles in wound healing. Wound Repair Regen. 2007;15:607–16.
Tager AM, LaCamera P, Shea BS, et al. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat Med. 2008;14:45–54.
Raghu G, Scholand MB, De Andrade J, et al. Safety and efficacy of anti-CTGF monoclonal antibody FG-3019 for treatment of idiopathic pulmonary fibrosis (IPF): results of phase 2 clinical trial two years after initiation. Am J Respir Crit Care Med. 2014;189:A1426.
Hancock A, Armstrong L, Gama R, Millar A. Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol. 1998;18:60–5.
Belperio JA, Dy M, Burdick MD, et al. Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2002;27:419–27.
Murray LA, Zhang H, Oak SR, et al. Targeting interleukin-13 with tralokinumab attenuates lung fibrosis and epithelial damage in a humanized SCID idiopathic pulmonary fibrosis model. Am J Respir Cell Mol Biol. 2014;50:985–94.
Jakubzick C, Kunkel SL, Puri RK, et al. Therapeutic targeting of IL-4- and IL-13-responsive cells in pulmonary fibrosis. Immunol Res. 2004;30:339–49.
Jakubzick C, Choi ES, Carpenter KJ, et al. Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia. Am J Pathol. 2004;164:1989–2001.
Soubrane C, Lin Y, Delfolie A, et al. Presented at the 18th international colloquium on lung and airway fibrosis (ICLAF). Quebec: Mont Tremblant; 2014.
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;16:1009–17.
Chien JW, Richards TJ, Gibson KF, et al. Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J. 2014;43:1430–8.
Akhurst RJ, Hata A. Targeting the TGFβ signalling pathway in disease. Nat Rev Drug Discov. 2012;11:790–811.
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;177:56–65.