Acute exacerbations in patients with idiopathic pulmonary fibrosis

Respiratory Research

Dong Soon Kim¹ 

[1] Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea

关键词: Treatment;    Prevention;    Management;    Impact;    Idiopathic pulmonary fibrosis (IPF);    Acute exacerbation;   

Others  :  792889
DOI  :  10.1186/1465-9921-14-86

 received in 2013-05-16, accepted in 2013-08-21,  发布年份 2013

【 摘 要 】

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung disease that primarily affects older adults. Median survival after diagnosis is 2–3 years. The clinical course of IPF may include periods of acute deterioration in respiratory function, which are termed acute exacerbations of IPF (AEx-IPF) when a cause cannot be identified. AEx-IPF may represent a sudden acceleration of the underlying disease process of IPF, or a biologically distinct pathological process that is clinically undiagnosed. An AEx-IPF can occur at any time during the course of IPF and may be the presenting manifestation. The incidence of AEx-IPF is hard to establish due to variation in the methodology used to assess AEx-IPF in different studies, but AEx-IPF are believed to occur in between 5 and 10% of patients with IPF every year. Risk factors for AEx-IPF are unclear, but there is evidence that poorer lung function increases the risk of an AEx-IPF and reduces the chances of a patient surviving an AEx-IPF. The presence of comorbidities such as gastroesophageal reflux disease (GERD) and pulmonary hypertension may also increase the risk of an AEx-IPF. AEx-IPF are associated with high morbidity and mortality. Patients who experience an AEx-IPF show a worsened prognosis and AEx-IPF are believed to reflect disease progression in IPF. Current treatments for AEx-IPF have only limited data to support their effectiveness. The latest international treatment guidelines state that supportive care remains the mainstay of treatment for AEx-IPF, but also give a weak recommendation for the treatment of the majority of patients with AEx-IPF with corticosteroids. There is emerging evidence from clinical trials of investigational therapies that chronic treatment of IPF may reduce the incidence of AEx-IPF. Additional clinical trials investigating this are underway.

【 授权许可】

   
2013 Kim; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]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.
• [2]Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D: Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev 2012, 21:355-361.
• [3]Mura M, Porretta MA, Bargagli E, Sergiacomi G, Zompatori M, Sverzellati N, Taglieri A, Mezzasalma F, Rottoli P, Saltini C, Rogliani P: Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study. Eur Respir J 2012, 40:101-109.
• [4]Martinez FJ, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, Flaherty KR, Schwartz DA, Noble PW, Raghu G, Brown KK, IPF Study Group: The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med 2005, 142:963-967.
• [5]Kim DS, Collard HR, King TE Jr: Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc 2006, 3:285-292.
• [6]Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE Jr, Lasky JA, Loyd JE, Noth I, Olman MA, Raghu G, Roman J, Ryu JH, Zisman DA, Hunninghake GW, Colby TV, Egan JJ, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kondoh Y, Lynch DA, Müller-Quernheim J, Myers JL, Nicholson AG, Selman M, Toews GB, Wells AU, Martinez FJ, Idiopathic Pulmonary Fibrosis Clinical Research Network Investigators: Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2007, 176:636-643.
• [7]Abe S, Azuma A, Mukae H, Ogura T, Taniguchi H, Bando M, Sugiyama Y: Polymyxin B-immobilized fiber column (PMX) treatment for idiopathic pulmonary fibrosis with acute exacerbation: a multicenter retrospective analysis. Intern Med 2012, 51:1487-1491.
• [8]Akira M, Hamada H, Sakatani M, Kobayashi C, Nishioka M, Yamamoto S: CT findings during phase of accelerated deterioration in patients with idiopathic pulmonary fibrosis. AJR Am J Roentgenol 1997, 168:79-83.
• [9]Ambrosini V, Cancellieri A, Chilosi M, Zompatori M, Trisolini R, Saragoni L, Poletti V: Acute exacerbation of idiopathic pulmonary fibrosis: report of a series. Eur Respir J 2003, 22:821-826.
• [10]Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, Taguchi Y, Nagai S, Itoh H, Ohi M, Sato A, Kudoh S: Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005, 171:1040-1047.
• [11]Kim DS, Park JH, Park BK, Lee JS, Nicholson AG, Colby T: Acute exacerbation of idiopathic pulmonary fibrosis: frequency and clinical features. Eur Respir J 2006, 27:143-150.
• [12]Kondoh Y, Taniguchi H, Kawabata Y, Yokoi T, Suzuki K, Takagi K: Acute exacerbation in idiopathic pulmonary fibrosis. Analysis of clinical and pathologic findings in three cases. Chest 1993, 103:1808-1812.
• [13]Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, King TE Jr, Lancaster L, Sahn SA, Szwarcberg J, Valeyre D, Du Bois RM, CAPACITY Study Group: Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011, 377:1760-1769.
• [14]Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Klueglich M, Du Bois RM: Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 2011, 365:1079-1087.
• [15]Bando M, Hosono T, Mato N, Nakaya T, Yamasawa H, Ohno S, Sugiyama Y: Long-term efficacy of inhaled N-acetylcysteine in patients with idiopathic pulmonary fibrosis. Intern Med 2010, 49:2289-2296.
• [16]Lee JS, Collard HR, Raghu G, Sweet MP, Hays SR, Campos GM, Golden JA, King TE Jr: Does chronic microaspiration cause idiopathic pulmonary fibrosis? Am J Med 2010, 123:304-311.
• [17]Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ: Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 2012, 366:1968-1977.
• [18]Simon-Blancal V, Freynet O, Nunes H, Bouvry D, Naggara N, Brillet PY, Denis D, Cohen Y, Vincent F, Valeyre D, Naccache JM: Acute exacerbation of idiopathic pulmonary fibrosis: outcome and prognostic factors. Respiration 2012, 83:28-35.
• [19]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.
• [20]Hyzy R, Huang S, Myers J, Flaherty K, Martinez F: Acute exacerbation of idiopathic pulmonary fibrosis. Chest 2007, 132:1652-1658.
• [21]Kim DS: Acute exacerbation of idiopathic pulmonary fibrosis. Clin Chest Med 2012, 33:59-68.
• [22]Churg A, Muller NL, Silva CI, Wright JL: Acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. Am J Surg Pathol 2007, 31:277-284.
• [23]Parambil JG, Myers JL, Ryu JH: Histopathologic features and outcome of patients with acute exacerbation of idiopathic pulmonary fibrosis undergoing surgical lung biopsy. Chest 2005, 128:3310-3315.
• [24]Rice AJ, Wells AU, Bouros D, Du Bois RM, Hansell DM, Polychronopoulos V, Vassilakis D, Kerr JR, Evans TW, Nicholson AG: Terminal diffuse alveolar damage in relation to interstitial pneumonias. An autopsy study. Am J Clin Pathol 2003, 119:709-714.
• [25]Vannella KM, Moore BB: Viruses as co-factors for the initiation or exacerbation of lung fibrosis. Fibrogenesis Tissue Repair 2008, 1:2. BioMed Central Full Text
• [26]Yoshizawa Y: Idiopathic pulmonary fibrosis: acute exacerbation and lung cancer associated with pulmonary fibrosis. Jpn Med Assoc J 2003, 46:490-496.
• [27]Wootton SC, Kim DS, Kondoh Y, Chen E, Lee JS, Song JW, Huh JW, Taniguchi H, Chiu C, Boushey H, Lancaster LH, Wolters PJ, DeRisi J, Ganem D, Collard HR: Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011, 183:1698-1702.
• [28]Agarwal R, Jindal SK: Acute exacerbation of idiopathic pulmonary fibrosis: a systematic review. Eur J Intern Med 2008, 19:227-235.
• [29]Mukae H, Liboshi H, Nakazato M, Hiratsuka T, Tokojima M, Abe K, Ashitani J, Kadota J, Matsukura S, Kohno S: Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis. Thorax 2002, 57:623-628.
• [30]Collard HR, Calfee CS, Wolters PJ, Song JW, Hong SB, Brady S, Ishizaka A, Jones KD, King TE Jr, Matthay MA, Kim DS: Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2010, 299:L3-L7.
• [31]Ebina M, Taniguchi H, Miyasho T, Yamada S, Shibata N, Ohta H, Hisata S, Ohkouchi S, Tamada T, Nishimura H, Ishizaka A, Maruyama I, Okada Y, Takashi K, Nukiwa T: Gradual increase of high mobility group protein b1 in the lungs after the onset of acute exacerbation of idiopathic pulmonary fibrosis. Pulm Med 2011, 2011:916486.
• [32]Iwata Y, Okamoto M, Hoshino T, Kitasato Y, Sakazaki Y, Tajiri M, Matsunaga K, Azuma K, Kawayama T, Kinoshita T, Imaoka H, Fujimoto K, Kato S, Yano H, Aizawa H: Elevated levels of thioredoxin 1 in the lungs and sera of idiopathic pulmonary fibrosis, non-specific interstitial pneumonia and cryptogenic organizing pneumonia. Intern Med 2010, 49:2393-2400.
• [33]Konishi K, Gibson KF, Lindell KO, Richards TJ, Zhang Y, Dhir R, Bisceglia M, Gilbert S, Yousem SA, Song JW, Kim DS, Kaminski N: Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009, 180:167-175.
• [34]Suga M, Iyonaga K, Okamoto T, Gushima Y, Miyakawa H, Akaike T, Ando M: Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2000, 162:1949-1956.
• [35]Willis BC, Borok Z: TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol 2007, 293:L525-L534.
• [36]Mackinnon AC, Gibbons MA, Farnworth SL, Leffler H, Nilsson UJ, Delaine T, Simpson AJ, Forbes SJ, Hirani N, Gauldie J, Sethi T: Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3. Am J Respir Crit Care Med 2012, 185:537-546.
• [37]Mehrad B, Burdick MD, Zisman DA, Keane MP, Belperio JA, Strieter RM: Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease. Biochem Biophys Res Commun 2007, 353:104-108.
• [38]Moeller A, Gilpin SE, Ask K, Cox G, Cook D, Gauldie J, Margetts PJ, Farkas L, Dobranowski J, Boylan C, O’Byrne PM, Strieter RM, Kolb M: Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009, 179:588-594.
• [39]Sakamoto K, Taniguchi H, Kondoh Y, Ono K, Hasegawa Y, Kitaichi M: Acute exacerbation of idiopathic pulmonary fibrosis as the initial presentation of the disease. Eur Respir Rev 2009, 18:129-132.
• [40]Kondoh Y, Taniguchi H, Katsuta T, Kataoka K, Kimura T, Nishiyama O, Sakamoto K, Johkoh T, Nishimura M, Ono K, Kitaichi M: Risk factors of acute exacerbation of idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2010, 27:103-110.
• [41]Taniguchi H, Ebina M, Kondoh Y, Ogura T, Azuma A, Suga M, Taguchi Y, Takahashi H, Nakata K, Sato A, Takeuchi M, Raghu G, Kudoh S, Nukiwa T: Pirfenidone Clinical Study Group in Japan: Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J 2010, 35:821-829.
• [42]Suzuki H, Sekine Y, Yoshida S, Suzuki M, Shibuya K, Yonemori Y, Hiroshima K, Nakatani Y, Mizuno S, Takiguchi Y, Yoshino I: Risk of acute exacerbation of interstitial pneumonia after pulmonary resection for lung cancer in patients with idiopathic pulmonary fibrosis based on preoperative high-resolution computed tomography. Surg Today 2011, 41:914-921.
• [43]Judge EP, Fabre A, Adamali HI, Egan JJ: Acute exacerbations and pulmonary hypertension in advanced idiopathic pulmonary fibrosis. Eur Respir J 2012, 40:93-100.
• [44]Hiwatari N, Shimura S, Takishima T, Shirato K: Bronchoalveolar lavage as a possible cause of acute exacerbation in idiopathic pulmonary fibrosis patients. Tohoku J Exp Med 1994, 174:379-386.
• [45]Sakamoto K, Taniguchi H, Kondoh Y, Wakai K, Kimura T, Kataoka K, Hashimoto N, Nishiyama O, Hasegawa Y: Acute exacerbation of IPF following diagnostic bronchoalveolar lavage procedures. Respir Med 2012, 106:436-442.
• [46]Kaarteenaho R: The current position of surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis. Respir Res 2013, 14:43. BioMed Central Full Text
• [47]Lee JS, Song JW, Wolters PJ, Elicker BM, King TE Jr, Kim DS, Collard HR: Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 2012, 39:352-358.
• [48]Tobin RW, Pope CE, Pellegrini CA, Emond MJ, Sillery J, Raghu G: Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998, 158:1804-1808.
• [49]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.
• [50]Raghu G, Yang ST, Spada C, Hayes J, Pellegrini CA: Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Chest 2006, 129:794-800.
• [51]Kubo H, Nakayama K, Yanai M, Suzuki T, Yamaya M, Watanabe M, Sasaki H: Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 2005, 128:1475-1482.
• [52]Daniels CE, Yi ES, Ryu JH: Autopsy findings in 42 consecutive patients with idiopathic pulmonary fibrosis. Eur Respir J 2008, 32:170-174.
• [53]Al-Hameed FM, Sharma S: Outcome of patients admitted to the intensive care unit for acute exacerbation of idiopathic pulmonary fibrosis. Can Respir J 2004, 11:117-122.
• [54]Morawiec E, Tillie-Leblond I, Pansini V, Salleron J, Remy-Jardin M, Wallaert B: Exacerbations of idiopathic pulmonary fibrosis treated with corticosteroids and cyclophosphamide pulses. Eur Respir J 2011, 38:1487-1489.
• [55]Inase N, Sawada M, Ohtani Y, Miyake S, Isogai S, Sakashita H, Miyazaki Y, Yoshizawa Y: Cyclosporin A followed by the treatment of acute exacerbation of idiopathic pulmonary fibrosis with corticosteroid. Intern Med 2003, 42:565-570.
• [56]Sakamoto S, Homma S, Miyamoto A, Kurosaki A, Fujii T, Yoshimura K: Cyclosporin A in the treatment of acute exacerbation of idiopathic pulmonary fibrosis. Intern Med 2010, 49:109-115.
• [57]Noth I, Anstrom KJ, Calvert SB, De Andrade J, Flaherty KR, Glazer C, Kaner RJ, Olman MA, Idiopathic Pulmonary Fibrosis Clinical Research Network (IPFnet): A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2012, 186:88-95.
• [58]Yokoyama T, Kondoh Y, Taniguchi H, Kataoka K, Kato K, Nishiyama O, Kimura T, Hasegawa R, Kubo K: Noninvasive ventilation in acute exacerbation of idiopathic pulmonary fibrosis. Intern Med 2010, 49:1509-1514.
• [59]Seo Y, Abe S, Kurahara M, Okada D, Saito Y, Usuki J, Azuma A, Koizumi K, Kudoh S: Beneficial effect of polymyxin B-immobilized fiber column (PMX) hemoperfusion treatment on acute exacerbation of idiopathic pulmonary fibrosis. Intern Med 2006, 45:1033-1038.
• [60]Horita N, Akahane M, Okada Y, Kobayashi Y, Arai T, Amano I, Takezawa T, To M, To Y: Tacrolimus and steroid treatment for acute exacerbation of idiopathic pulmonary fibrosis. Intern Med 2011, 50:189-195.
• [61]Zisman DA, Schwarz M, Anstrom KJ, Collard HR, Flaherty KR, Hunninghake GW: A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med 2010, 363:620-628.
• [62]Daniels CE, Lasky JA, Limper AH, Mieras K, Gabor E, Schroeder DR: Imatinib treatment for idiopathic pulmonary fibrosis: randomized placebo-controlled trial results. Am J Respir Crit Care Med 2010, 181:604-610.
• [63]King TE Jr, Brown KK, Raghu G, Du Bois RM, Lynch DA, Martinez F, Valeyre D, Leconte I, Morganti A, Roux S, Behr J: BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011, 184:92-99.
• [64]King TE Jr, Albera C, Bradford WZ, Costabel U, Hormel P, Lancaster L, Noble PW, Sahn SA, Szwarcberg J, Thomeer M, Valeyre D, Du Bois RM, INSPIRE Study Group: Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. Lancet 2009, 374:222-228.
• [65]Hilberg F, Roth GJ, Krssak M, Kautschitsch S, Sommergruber W, Tontsch-Grunt U, Garin-Chesa P, Bader G, Zoephel A, Quant J, Heckel A, Rettig WJ: BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res 2008, 68:4774-4782.
• [66]Hostettler KE, Papakonstantinou E, Klagas I, Karakiulakis G, Zhong J, Tamm M, Lardinois D, Roth M: Anti-fibrotic effects of nintedanib (BIBF 1120) in primary human lung fibroblasts derived from patients with idiopathic pulmonary fibrosis and from non-fibrotic controls. Am J Respir Crit Care Med 2013, 187:A3374.
• [67]Wollin L, Neugebauer J, Ostermann A, Holweg A, Wex E, Ehinger K, Maertens M, Gantner F: Sustained inactivation of human lung fibroblasts by nintedanib. Am J Respir Crit Care Med 2013, 187:A3378.
• [68]Lee JS, Collard HR, Anstrom KJ, Martinez FJ, Noth I, Roberts RS, Yow E, Raghu G: Anti-acid treatment and disease progression in idiopathic pulmonary fibrosis: an analysis of data from three randomised controlled trials. Lancet Respir Med 2013, 1:369-376.