Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis

Respiratory Research

Hiroshi Mukae¹  Shigeru Kohno⁶  Kentaro Watanabe²  Jun-ichi Kadota⁷  Masamitsu Nakazato⁵  Kazuhiro Yatera¹  Keisuke Naito¹  Nobuhiro Matsumoto⁵  Yuji Ishimatsu⁶  Tatsuhiko Harada⁶  Tomotoshi Imanaga³  Hiroshi Ishii²  Hisako Kushima⁷  Sohsuke Yamada⁴  Hiroshi Ishimoto¹  Keishi Oda¹ 

[1] Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City 807-8555, Fukuoka, Japan;Department of Respiratory Medicine, Fukuoka University School of Medicine, 7-45-1, Nakakuma, Jonanku 814-0180, Fukuoka, Japan;Department of Respiratory Medicine, Steel Memorial Yawata Hospital, 1-1-1, Harunomachi, Yahatahigashiku, Kitakyushu City 805-8508, Fukuoka, Japan;Department of Pathology and Cell Biology, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu City 807-8555, Fukuoka, Japan;Neurology, Respirology, Endocrinology and Metabolism, Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, 889-1692, Japan;Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan;Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan

关键词: Diffuse alveolar damage;    Autopsy;    Idiopathic pulmonary fibrosis;    Acute exacerbation;   

Others  :  1146244
DOI  :  10.1186/s12931-014-0109-y

 received in 2014-07-14, accepted in 2014-08-26,  发布年份 2014

【 摘 要 】

Background

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. However, few studies have so far reviewed analyses of autopsy findings in patients with AE-IPF.

Methods

We retrospectively reviewed 52 consecutive patients with AE-IPF who underwent autopsies at five university hospitals and one municipal hospital between 1999 and 2013. The following variables were abstracted from the medical records: demographic and clinical data, autopsy findings and complications during the clinical course until death.

Results

The median age at autopsy was 71 years (range 47–86 years), and the subjects included 38 (73.1%) males. High-dose corticosteroid therapy was initiated in 45 (86.5%) patients after AE-IPF. The underling fibrotic lesion was classified as having the usual interstitial pneumonia (UIP) pattern in all cases. Furthermore, 41 (78.8%) patients had diffuse alveolar damage (DAD), 15 (28.8%) exhibited pulmonary hemorrhage, nine (17.3%) developed pulmonary thromboembolism and six (11.5%) were diagnosed with lung carcinoma. In addition, six (11.5%) patients developed pneumothorax prior to death and 26 (53.1%) developed diabetes that required insulin treatment after the administration of high-dose corticosteroid therapy. In addition, 15 (28.8%) patients presented with bronchopneumonia during their clinical course and/or until death, including fungal (seven, 13.5%), cytomegalovirus (six, 11.5%) and bacterial (five, 9.6%) infections.

Conclusions

The pathological findings in patients with AE-IPF represent not only DAD, but also a variety of pathological conditions. Therefore, making a diagnosis of AE-IPF is often difficult, and the use of cautious diagnostic approaches is required for appropriate treatment.

【 授权许可】

   
2014 Oda et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, Offord KP: Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998, 157:199-203.
• [2]Flaherty KR, Toews GB, Travis WD, Colby TV, Kazerooni EA, Gross BH, Jain A, Strawderman RL, Paine R, Flint A, Lynch JP, Martinez FJ: Clinical significance of histological classification of idiopathic interstitial pneumonia. Eur Respir J 2002, 19:275-283.
• [3]Nicholson AG, Colby TV, du Bois RM, Hansell DM, Wells AU: The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 2000, 162:2213-2217.
• [4]Rudd RM, Prescott RJ, Chalmers JC, Johnston ID: British Thoracic Society Study on cryptogenic fibrosing alveolitis: Response to treatment and survival. Thorax 2007, 62:62-66.
• [5]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.
• [6]Ley B, Collard HR, King TE: Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011, 183:431-440.
• [7]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.
• [8]Society AT, Society ER: American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002, 165:277-304.
• [9]Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE, 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: Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2007, 176:636-643.
• [10]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, et al.: 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.
• [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]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.
• [13]Churg A, Müller 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.
• [14]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.
• [15]Katzenstein AL, Bloor CM, Leibow AA: Diffuse alveolar damage–the role of oxygen, shock, and related factors. A review. Am J Pathol 1976, 85:209-228.
• [16]Sulavik SB: The concept of “organizing pneumonia”. Chest 1989, 96:967-969.
• [17]Forman MB, Wilson BH, Sheller JR, Kopelman HA, Vaughn WK, Virmani R, Friesinger GC: Right ventricular hypertrophy is an important determinant of right ventricular infarction complicating acute inferior left ventricular infarction. J Am Coll Cardiol 1987, 10:1180-1187.
• [18]Nadrous HF, Pellikka PA, Krowka MJ, Swanson KL, Chaowalit N, Decker PA, Ryu JH: Pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Chest 2005, 128:2393-2399.
• [19]Sawabe M, Saito M, Naka M, Kasahara I, Saito Y, Arai T, Hamamatsu A, Shirasawa T: Standard organ weights among elderly Japanese who died in hospital, including 50 centenarians. Pathol Int 2006, 56:315-323.
• [20]Husari A, Beydoun A, Sheik Ammar A, Maakaron JE, Taher A: The untold story of Dabigatran etexilate: alveolar hemorrhage in an elderly patient with interstitial pulmonary fibrosis. J Thromb Thrombolysis 2013, 35:81-82.
• [21]Perri D, Cole DE, Friedman O, Piliotis E, Mintz S, Adhikari NK: Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase. Eur Respir J 2007, 30:1014-1017.
• [22]Birnbaum J, Danoff S, Askin FB, Stone JH: Microscopic polyangiitis presenting as a “pulmonary-muscle” syndrome: is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis? Arthritis Rheum 2007, 56:2065-2071.
• [23]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.
• [24]Sprunger DB, Olson AL, Huie TJ, Fernandez-Perez ER, Fischer A, Solomon JJ, Brown KK, Swigris JJ: Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease. Eur Respir J 2012, 39:125-132.
• [25]Patel SR, Karmpaliotis D, Ayas NT, Mark EJ, Wain J, Thompson BT, Malhotra A: The role of open-lung biopsy in ARDS. Chest 2004, 125:197-202.
• [26]Esteban A, Fernández-Segoviano P, Frutos-Vivar F, Aramburu JA, Nájera L, Ferguson ND, Alía I, Gordo F, Ríos F: Comparison of clinical criteria for the acute respiratory distress syndrome with autopsy findings. Ann Intern Med 2004, 141:440-445.
• [27]Beasley MB, Franks TJ, Galvin JR, Gochuico B, Travis WD: Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002, 126:1064-1070.
• [28]Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, Winton TL, Rutledge F, Todd TJ, Roy P: Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994, 330:377-381.
• [29]Hernández-Díaz S, Rodríguez LA: Steroids and risk of upper gastrointestinal complications. Am J Epidemiol 2001, 153:1089-1093.
• [30]Lettieri CJ, Nathan SD, Barnett SD, Ahmad S, Shorr AF: Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis. Chest 2006, 129:746-752.
• [31]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.
• [32]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.
• [33]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.
• [34]Kim DS, Collard HR, King TE: Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc 2006, 3:285-292.
• [35]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.
• [36]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.
• [37]Stuck AE, Minder CE, Frey FJ: Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis 1989, 11:954-963.
• [38]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.
• [39]Collard HR, Yow E, Richeldi L, Anstrom KJ, Glazer C: Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials. Respir Res 2013, 14:73. BioMed Central Full Text