Tuberculosis and Respiratory Diseases

  • 제85권2호
  • /
  • Pages.122-136
  • /
  • 2022
  • /
  • 1738-3536(pISSN)
  • /
  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
권호 표지
DOI QR코드

DOI QR Code

Chronic Obstructive Pulmonary Disease Combined with Interstitial Lung Disease

  • Choi, Joon Young (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Song, Jin Woo (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Rhee, Chin Kook (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • 투고 : 2021.09.23
  • 심사 : 2022.01.25
  • 발행 : 2022.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.

키워드

참고문헌

  1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, 2021 report [Internet]. Global Initiative for Chronic Obstructive Lung Disease; 2021 [cited 2020 Dec 23]. Available from: https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf.
  2. Liu Z, Shi F, Liu JX, Gao CL, Pei MM, Li J, et al. Effect of the emphysema subtypes of patients with chronic obstructive pulmonary disease on airway inflammation and COTE index. Exp Ther Med 2018;16:4745-52.
  3. Broaddus VC, Mason RJ, Ernst JD, King TE Jr, Lazarus SC, Murray JF, et al. Murray and Nadel's testbook of respiratory medicine. 6th ed. Philadelphia: Elsevier; 2016.
  4. Huie TJ, Solomon JJ. Emphysema and pulmonary fibrosis: coincidence or conspiracy? Respirology 2013;18:1163-4. https://doi.org/10.1111/resp.12187
  5. Hage R, Gautschi F, Steinack C, Schuurmans MM. Combined pulmonary fibrosis and emphysema (CPFE) clinical features and management. Int J Chron Obstruct Pulmon Dis 2021;16:167-77. https://doi.org/10.2147/COPD.S286360
  6. Selman M, Martinez FJ, Pardo A. Why does an aging smoker's lung develop idiopathic pulmonary fibrosis and not chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2019;199:279-85. https://doi.org/10.1164/rccm.201806-1166pp
  7. Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med 2018;378:1811-23. https://doi.org/10.1056/NEJMra1705751
  8. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, 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. https://doi.org/10.1164/rccm.2009-040GL
  9. Cottin V, Nunes H, Brillet PY, Delaval P, Devouassoux G, Tillie-Leblond I, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J 2005;26:586-93. https://doi.org/10.1183/09031936.05.00021005
  10. Alsumrain M, De Giacomi F, Nasim F, Koo CW, Bartholmai BJ, Levin DL, et al. Combined pulmonary fibrosis and emphysema as a clinicoradiologic entity: characterization of presenting lung fibrosis and implications for survival. Respir Med 2019;146:106-12. https://doi.org/10.1016/j.rmed.2018.12.003
  11. Cottin V, Nunes H, Mouthon L, Gamondes D, Lazor R, Hachulla E, et al. Combined pulmonary fibrosis and emphysema syndrome in connective tissue disease. Arthritis Rheum 2011;63:295-304. https://doi.org/10.1002/art.30077
  12. Koo BS, Park KY, Lee HJ, Kim HJ, Ahn HS, Yim SY, et al. Effect of combined pulmonary fibrosis and emphysema on patients with connective tissue diseases and systemic sclerosis: a systematic review and meta-analysis. Arthritis Res Ther 2021;23:100. https://doi.org/10.1186/s13075-021-02494-y
  13. Antoniou KM, Margaritopoulos GA, Goh NS, Karagiannis K, Desai SR, Nicholson AG, et al. Combined pulmonary fibrosis and emphysema in scleroderma-related lung disease has a major confounding effect on lung physiology and screening for pulmonary hypertension. Arthritis Rheumatol 2016;68:1004-12. https://doi.org/10.1002/art.39528
  14. Ariani A, Silva M, Bravi E, Parisi S, Saracco M, De Gennaro F, et al. Overall mortality in combined pulmonary fibrosis and emphysema related to systemic sclerosis. RMD Open 2019;5:e000820. https://doi.org/10.1136/rmdopen-2018-000820
  15. Champtiaux N, Cottin V, Chassagnon G, Chaigne B, Valeyre D, Nunes H, et al. Combined pulmonary fibrosis and emphysema in systemic sclerosis: a syndrome associated with heavy morbidity and mortality. Semin Arthritis Rheum 2019;49:98-104. https://doi.org/10.1016/j.semarthrit.2018.10.011
  16. Lee SH, Park JS, Kim SY, Kim DS, Kim YW, Chung MP, et al. Clinical features and prognosis of patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Int J Tuberc Lung Dis 2019;23:678-84. https://doi.org/10.5588/ijtld.18.0194
  17. Ryerson CJ, Hartman T, Elicker BM, Ley B, Lee JS, Abbritti M, et al. Clinical features and outcomes in combined pulmonary fibrosis and emphysema in idiopathic pulmonary fibrosis. Chest 2013;144:234-40. https://doi.org/10.1378/chest.12-2403
  18. Yoon HY, Kim TH, Seo JB, Lee SM, Lim S, Lee HN, et al. Effects of emphysema on physiological and prognostic characteristics of lung function in idiopathic pulmonary fibrosis. Respirology 2019;24:55-62. https://doi.org/10.1111/resp.13387
  19. Jacob J, Song JW, Yoon HY, Cross G, Barnett J, Woo WL, et al. Prevalence and effects of emphysema in never-smokers with rheumatoid arthritis interstitial lung disease. EBioMedicine 2018;28:303-10. https://doi.org/10.1016/j.ebiom.2018.01.038
  20. Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA 2016;315:672-81. https://doi.org/10.1001/jama.2016.0518
  21. Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med 2011;364:897-906. https://doi.org/10.1056/NEJMoa1007285
  22. Ash SY, Harmouche R, Ross JC, Diaz AA, Rahaghi FN, Vegas Sanchez-Ferrero G, et al. Interstitial features at chest CT enhance the deleterious effects of emphysema in the COPDGene Cohort. Radiology 2018;288:600-9. https://doi.org/10.1148/radiol.2018172688
  23. Ohgiya M, Matsui H, Tamura A, Kato T, Akagawa S, Ohta K. The evaluation of interstitial abnormalities in group B of the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of chronic obstructive pulmonary disease (COPD). Intern Med 2017;56:2711-7. https://doi.org/10.2169/internalmedicine.8406-16
  24. Amariei DE, Dodia N, Deepak J, Hines SE, Galvin JR, Atamas SP, et al. Combined pulmonary fibrosis and emphysema: pulmonary function testing and a pathophysiology perspective. Medicina (Kaunas) 2019;55:580. https://doi.org/10.3390/medicina55090580
  25. Bedard Methot D, Leblanc E, Lacasse Y. Meta-analysis of gastroesophageal reflux disease and idiopathic pulmonary fibrosis. Chest 2019;155:33-43. https://doi.org/10.1016/j.chest.2018.07.038
  26. Tzouvelekis A, Zacharis G, Oikonomou A, Mikroulis D, Margaritopoulos G, Koutsopoulos A, et al. Increased incidence of autoimmune markers in patients with combined pulmonary fibrosis and emphysema. BMC Pulm Med 2013;13:31. https://doi.org/10.1186/1471-2466-13-31
  27. Hanaoka M, Ito M, Droma Y, Ushiki A, Kitaguchi Y, Yasuo M, et al. Comparison of gene expression profiling between lung fibrotic and emphysematous tissues sampled from patients with combined pulmonary fibrosis and emphysema. Fibrogenesis Tissue Repair 2012;5:17. https://doi.org/10.1186/1755-1536-5-17
  28. Papaioannou AI, Kostikas K, Manali ED, Papadaki G, Roussou A, Kolilekas L, et al. Combined pulmonary fibrosis and emphysema: the many aspects of a cohabitation contract. Respir Med 2016;117:14-26. https://doi.org/10.1016/j.rmed.2016.05.005
  29. Ding Y, Li Q, Wu C, Wang W, Zhao J, Feng Q, et al. TERT gene polymorphisms are associated with chronic obstructive pulmonary disease risk in the Chinese Li population. Mol Genet Genomic Med 2019;7:e773.
  30. Hirano C, Ohshimo S, Horimasu Y, Iwamoto H, Fujitaka K, Hamada H, et al. FAM13A polymorphism as a prognostic factor in patients with idiopathic pulmonary fibrosis. Respir Med 2017;123:105-9. https://doi.org/10.1016/j.rmed.2016.12.007
  31. Wang B, Liang B, Yang J, Xiao J, Ma C, Xu S, et al. Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese. Clin Biochem 2013;46:1683-8. https://doi.org/10.1016/j.clinbiochem.2013.07.013
  32. Wang H, Zhuang Y, Peng H, Cao M, Li Y, Xu Q, et al. The relationship between MUC5B promoter, TERT polymorphisms and telomere lengths with radiographic extent and survival in a Chinese IPF cohort. Sci Rep 2019;9:15307. https://doi.org/10.1038/s41598-019-51902-6
  33. Guzman-Vargas J, Ambrocio-Ortiz E, Perez-Rubio G, Ponce-Gallegos MA, Hernandez-Zenteno RJ, Mejia M, et al. Differential genomic profile in TERT, DSP, and FAM13A between COPD patients with emphysema, IPF, and CPFE syndrome. Front Med (Lausanne) 2021;8:725144.
  34. Cottin V, Reix P, Khouatra C, Thivolet-Bejui F, Feldmann D, Cordier JF. Combined pulmonary fibrosis and emphysema syndrome associated with familial SFTPC mutation. Thorax 2011;66:918-9. https://doi.org/10.1136/thx.2010.151407
  35. Epaud R, Delestrain C, Louha M, Simon S, Fanen P, Tazi A. Combined pulmonary fibrosis and emphysema syndrome associated with ABCA3 mutations. Eur Respir J 2014;43:638-41. https://doi.org/10.1183/09031936.00145213
  36. Kinjo T, Kitaguchi Y, Droma Y, Yasuo M, Wada Y, Ueno F, et al. The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients. Sci Rep 2020;10:12811. https://doi.org/10.1038/s41598-020-69184-8
  37. Cornwell WD, Kim C, Lastra AC, Dass C, Bolla S, Wang H, et al. Inflammatory signature in lung tissues in patients with combined pulmonary fibrosis and emphysema. Biomarkers 2019;24:232-9. https://doi.org/10.1080/1354750x.2018.1542458
  38. Xu L, Bian W, Gu XH, Shen C. Differing expression of cytokines and tumor markers in combined pulmonary fibrosis and emphysema compared to emphysema and pulmonary fibrosis. COPD 2017;14:245-50. https://doi.org/10.1080/15412555.2017.1278753
  39. Papaioannou AI, Kostikas K, Manali ED, Papadaki G, Roussou A, Spathis A, et al. Serum levels of surfactant proteins in patients with combined pulmonary fibrosis and emphysema (CPFE). PLoS One 2016;11:e0157789. https://doi.org/10.1371/journal.pone.0157789
  40. Tasaka S, Mizoguchi K, Funatsu Y, Namkoong H, Yamasawa W, Ishii M, et al. Cytokine profile of bronchoalveolar lavage fluid in patients with combined pulmonary fibrosis and emphysema. Respirology 2012;17:814-20. https://doi.org/10.1111/j.1440-1843.2012.02182.x
  41. Chiba S, Ohta H, Abe K, Hisata S, Ohkouchi S, Hoshikawa Y, et al. The diagnostic value of the interstitial biomarkers KL-6 and SP-D for the degree of fibrosis in combined pulmonary fibrosis and emphysema. Pulm Med 2012;2012:492960. https://doi.org/10.1155/2012/492960
  42. Jiang Y, Luo Q, Han Q, Huang J, Ou Y, Chen M, et al. Sequential changes of serum KL-6 predict the progression of interstitial lung disease. J Thorac Dis 2018;10:4705-14. https://doi.org/10.21037/jtd.2018.07.76
  43. Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, et al. Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology 2006;11:164-8. https://doi.org/10.1111/j.1440-1843.2006.00834.x
  44. Satoh H, Kurishima K, Ishikawa H, Ohtsuka M. Increased levels of KL-6 and subsequent mortality in patients with interstitial lung diseases. J Intern Med 2006;260:429-34. https://doi.org/10.1111/j.1365-2796.2006.01704.x
  45. Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M. New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. Chest 1989;96:68-73. https://doi.org/10.1378/chest.96.1.68
  46. Chiba S, Tsuchiya K, Nukui Y, Sema M, Tamaoka M, Sumi Y, et al. Interstitial changes in asthma-COPD overlap syndrome. Clin Respir J 2017;11:1024-31. https://doi.org/10.1111/crj.12461
  47. Kishaba T, Shimaoka Y, Fukuyama H, Yoshida K, Tanaka M, Yamashiro S, et al. A cohort study of mortality predictors and characteristics of patients with combined pulmonary fibrosis and emphysema. BMJ Open 2012;2:e000988. https://doi.org/10.1136/bmjopen-2012-000988
  48. Ohshimo S, Ishikawa N, Horimasu Y, Hattori N, Hirohashi N, Tanigawa K, et al. Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med 2014;108:1031-9. https://doi.org/10.1016/j.rmed.2014.04.009
  49. Wong AW, Liang J, Cottin V, Ryerson CJ. Diagnostic features in combined pulmonary fibrosis and emphysema: a systematic review. Ann Am Thorac Soc 2020;17:1333-6. https://doi.org/10.1513/annalsats.202002-122rl
  50. Lee CH, Kim HJ, Park CM, Lim KY, Lee JY, Kim DJ, et al. The impact of combined pulmonary fibrosis and emphysema on mortality. Int J Tuberc Lung Dis 2011;15:1111-6. https://doi.org/10.5588/ijtld.10.0491
  51. Suzuki M, Kawata N, Abe M, Yokota H, Anazawa R, Matsuura Y, et al. Objective quantitative multidetector computed tomography assessments in patients with combined pulmonary fibrosis with emphysema: Relationship with pulmonary function and clinical events. PLoS One 2020;15:e0239066. https://doi.org/10.1371/journal.pone.0239066
  52. Cottin V. The impact of emphysema in pulmonary fibrosis. Eur Respir Rev 2013;22:153-7. https://doi.org/10.1183/09059180.00000813
  53. Matsuoka S, Yamashiro T, Matsushita S, Fujikawa A, Kotoku A, Yagihashi K, et al. Morphological disease progression of combined pulmonary fibrosis and emphysema: comparison with emphysema alone and pulmonary fibrosis alone. J Comput Assist Tomogr 2015;39:153-9. https://doi.org/10.1097/RCT.0000000000000184
  54. Kitaguchi Y, Fujimoto K, Hanaoka M, Kawakami S, Honda T, Kubo K. Clinical characteristics of combined pulmonary fibrosis and emphysema. Respirology 2010;15:265-71. https://doi.org/10.1111/j.1440-1843.2009.01676.x
  55. Inomata M, Ikushima S, Awano N, Kondoh K, Satake K, Masuo M, et al. An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features. BMC Pulm Med 2014;14:104. https://doi.org/10.1186/1471-2466-14-104
  56. Sugino K, Ishida F, Kikuchi N, Hirota N, Sano G, Sato K, et al. Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone. Respirology 2014;19:239-45. https://doi.org/10.1111/resp.12207
  57. Jankowich MD, Polsky M, Klein M, Rounds S. Heterogeneity in combined pulmonary fibrosis and emphysema. Respiration 2008;75:411-7. https://doi.org/10.1159/000107048
  58. Brillet PY, Cottin V, Letoumelin P, Landino F, Brauner MW, Valeyre D, et al. Combined apical emphysema and basal fibrosis syndrome (emphysema/fibrosis syndrome): CT imaging features and pulmonary function tests. J Radiol 2009;90:43-51. https://doi.org/10.1016/S0221-0363(09)70077-0
  59. Sakai F, Tominaga J, Kaga A, Usui Y, Kanazawa M, Ogura T, et al. Imaging diagnosis of interstitial pneumonia with emphysema (combined pulmonary fibrosis and emphysema). Pulm Med 2012;2012:816541. https://doi.org/10.1155/2012/816541
  60. Abi Khalil S, Gourdier AL, Aoun N, Nedelcu C, El Rai S, Moubarak E, et al. Cystic and cavitary lesions of the lung: imaging characteristics and differential diagnosis. J Radiol 2010;91:465-73. https://doi.org/10.1016/s0221-0363(10)70061-5
  61. Swigris JJ. Towards a refined definition of combined pulmonary fibrosis and emphysema. Respirology 2019;24:9-10. https://doi.org/10.1111/resp.13426
  62. Jiang CG, Fu Q, Zheng CM. Prognosis of combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis alone. Ther Adv Respir Dis 2019;13:1753466619888119.
  63. Jankowich MD, Rounds S. Combined pulmonary fibrosis and emphysema alters physiology but has similar mortality to pulmonary fibrosis without emphysema. Lung 2010;188:365-73. https://doi.org/10.1007/s00408-010-9251-6
  64. Jacob J, Bartholmai BJ, Rajagopalan S, Kokosi M, Maher TM, Nair A, et al. Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis. Eur Respir J 2017;50:1700379. https://doi.org/10.1183/13993003.00379-2017
  65. Mejia M, Carrillo G, Rojas-Serrano J, Estrada A, Suarez T, Alonso D, et al. Idiopathic pulmonary fibrosis and emphysema: decreased survival associated with severe pulmonary arterial hypertension. Chest 2009;136:10-5. https://doi.org/10.1378/chest.08-2306
  66. Zhang L, Zhang C, Dong F, Song Q, Chi F, Liu L, et al. Combined pulmonary fibrosis and emphysema: a retrospective analysis of clinical characteristics, treatment and prognosis. BMC Pulm Med 2016;16:137. https://doi.org/10.1186/s12890-016-0300-7
  67. Kohashi Y, Arai T, Sugimoto C, Tachibana K, Akira M, Kitaichi M, et al. Clinical impact of emphysema evaluated by high-resolution computed tomography on idiopathic pulmonary fibrosis diagnosed by surgical lung biopsy. Respiration 2016;92:220-8. https://doi.org/10.1159/000448118
  68. Choi SH, Lee HY, Lee KS, Chung MP, Kwon OJ, Han J, et al. The value of CT for disease detection and prognosis determination in combined pulmonary fibrosis and emphysema (CPFE). PLoS One 2014;9:e107476. https://doi.org/10.1371/journal.pone.0107476
  69. Todd NW, Jeudy J, Lavania S, Franks TJ, Galvin JR, Deepak J, et al. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival. Fibrogenesis Tissue Repair 2011;4:6. https://doi.org/10.1186/1755-1536-4-6
  70. Kurashima K, Takayanagi N, Tsuchiya N, Kanauchi T, Ueda M, Hoshi T, et al. The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis. Respirology 2010;15:843-8. https://doi.org/10.1111/j.1440-1843.2010.01778.x
  71. Jacob J, Bartholmai BJ, Rajagopalan S, Karwoski R, Nair A, Walsh SLF, et al. Likelihood of pulmonary hypertension in patients with idiopathic pulmonary fibrosis and emphysema. Respirology 2018;23:593-9. https://doi.org/10.1111/resp.13231
  72. Lin H, Jiang S. Combined pulmonary fibrosis and emphysema (CPFE): an entity different from emphysema or pulmonary fibrosis alone. J Thorac Dis 2015;7:767-79. https://doi.org/10.3978/j.issn.2072-1439.2015.04.17
  73. Ikuyama Y, Ushiki A, Kosaka M, Akahane J, Mukai Y, Araki T, et al. Prognosis of patients with acute exacerbation of combined pulmonary fibrosis and emphysema: a retrospective single-centre study. BMC Pulm Med 2020;20:144. https://doi.org/10.1186/s12890-020-01185-9
  74. Zantah M, Dotan Y, Dass C, Zhao H, Marchetti N, Criner GJ. Acute exacerbations of COPD versus IPF in patients with combined pulmonary fibrosis and emphysema. Respir Res 2020;21:164. https://doi.org/10.1186/s12931-020-01432-x
  75. Cottin V, Le Pavec J, Prevot G, Mal H, Humbert M, Simonneau G, et al. Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. Eur Respir J 2010;35:105-11. https://doi.org/10.1183/09031936.00038709
  76. Malli F, Papakosta D, Antoniou K, Dimadi M, Polychronopoulos V, Malagari K, et al. Combined pulmonary fibrosis and emphysema characteristics in a Greek cohort. ERJ Open Res 2019;5:00014-2018.
  77. Jankowich MD, Rounds SI. Combined pulmonary fibrosis and emphysema syndrome: a review. Chest 2012;141:222-31. https://doi.org/10.1378/chest.11-1062
  78. Kwak N, Park CM, Lee J, Park YS, Lee SM, Yim JJ, et al. Lung cancer risk among patients with combined pulmonary fibrosis and emphysema. Respir Med 2014;108:524-30. https://doi.org/10.1016/j.rmed.2013.11.013
  79. Oh JY, Lee YS, Min KH, Hur GY, Lee SY, Kang KH, et al. Presence of lung cancer and high gender, age, and physiology score as predictors of acute exacerbation in combined pulmonary fibrosis and emphysema: A retrospective study. Medicine (Baltimore) 2018;97:e11683. https://doi.org/10.1097/MD.0000000000011683
  80. Moon SW, Park MS, Kim YS, Jang J, Lee JH, Lee CT, et al. Combined pulmonary fibrosis and emphysema and idiopathic pulmonary fibrosis in non-small cell lung cancer: impact on survival and acute exacerbation. BMC Pulm Med 2019;19:177. https://doi.org/10.1186/s12890-019-0951-2
  81. Usui K, Tanai C, Tanaka Y, Noda H, Ishihara T. The prevalence of pulmonary fibrosis combined with emphysema in patients with lung cancer. Respirology 2011;16:326-31. https://doi.org/10.1111/j.1440-1843.2010.01907.x
  82. Nemoto M, Nei Y, Bartholmai B, Yoshida K, Matsui H, Nakashita T, et al. Automated computed tomography quantification of fibrosis predicts prognosis in combined pulmonary fibrosis and emphysema in a real-world setting: a single-centre, retrospective study. Respir Res 2020;21:275. https://doi.org/10.1186/s12931-020-01545-3
  83. Bolaki M, Antoniou KM. Combined pulmonary fibrosis and emphysema. Semin Respir Crit Care Med 2020;41:177-83. https://doi.org/10.1055/s-0040-1708058
  84. Ono M, Kobayashi S, Hanagama M, Ishida M, Sato H, Makiguchi T, et al. Clinical characteristics of Japanese patients with chronic obstructive pulmonary disease (COPD) with comorbid interstitial lung abnormalities: a cross-sectional study. PLoS One 2020;15:e0239764. https://doi.org/10.1371/journal.pone.0239764
  85. Jacob J, Bartholmai BJ, Rajagopalan S, van Moorsel CH, van Es HW, van Beek FT, et al. Predicting outcomes in idiopathic pulmonary fibrosis using automated computed tomographic analysis. Am J Respir Crit Care Med 2018;198:767-76. https://doi.org/10.1164/rccm.201711-2174oc
  86. Fleming H, Clifford SM, Haughey A, MacDermott R, McVeigh N, Healy GM, et al. Differentiating combined pulmonary fibrosis and emphysema from pure emphysema: utility of late gadolinium-enhanced MRI. Eur Radiol Exp 2020;4:61. https://doi.org/10.1186/s41747-020-00187-w
  87. Araki T, Putman RK, Hatabu H, Gao W, Dupuis J, Latourelle JC, et al. Development and progression of interstitial lung abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med 2016;194:1514-22. https://doi.org/10.1164/rccm.201512-2523oc
  88. Hunninghake GM. Interstitial lung abnormalities: erecting fences in the path towards advanced pulmonary fibrosis. Thorax 2019;74:506-11. https://doi.org/10.1136/thoraxjnl-2018-212446
  89. Hobbs BD, Putman RK, Araki T, Nishino M, Gudmundsson G, Gudnason V, et al. Overlap of genetic risk between interstitial lung abnormalities and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2019;200:1402-13. https://doi.org/10.1164/rccm.201903-0511oc
  90. Feldhaus FW, Theilig DC, Hubner RH, Kuhnigk JM, Neumann K, Doellinger F. Quantitative CT analysis in patients with pulmonary emphysema: is lung function influenced by concomitant unspecific pulmonary fibrosis? Int J Chron Obstruct Pulmon Dis 2019;14:1583-93. https://doi.org/10.2147/COPD.S204007
  91. WHO coronavirus (COVID-19) dashboard [Internet]. Geneva: World Health Orgniazation; 2020 [cited 2020 Dec 23]. Available from: https://covid19.who.int/.
  92. Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis 2020;94:91-5. https://doi.org/10.1016/j.ijid.2020.03.017
  93. Information note on COVID-19 and NCDs [Internet]. Geneva: World Health Orgniazation; 2020 [cited 2020 Dec 23]. Available from: https://www.who.int/publications/m/item/covid-19-and-ncds.
  94. Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ 2020;369:m1985.
  95. Sanchez-Ramirez DC, Mackey D. Underlying respiratory diseases, specifically COPD, and smoking are associated with severe COVID-19 outcomes: a systematic review and meta-analysis. Respir Med 2020;171:106096. https://doi.org/10.1016/j.rmed.2020.106096
  96. Drake TM, Docherty AB, Harrison EM, Quint JK, Adamali H, Agnew S, et al. Outcome of hospitalization for COVID-19 in patients with interstitial lung disease: an international multicenter study. Am J Respir Crit Care Med 2020;202:1656-65. https://doi.org/10.1164/rccm.202007-2794oc
  97. Esposito AJ, Menon AA, Ghosh AJ, Putman RK, Fredenburgh LE, El-Chemaly SY, et al. Increased odds of death for patients with interstitial lung disease and COVID-19: a casecontrol study. Am J Respir Crit Care Med 2020;202:1710-3. https://doi.org/10.1164/rccm.202006-2441LE
  98. Gallay L, Uzunhan Y, Borie R, Lazor R, Rigaud P, Marchand-Adam S, et al. Risk factors for mortality after COVID-19 in patients with preexisting interstitial lung disease. Am J Respir Crit Care Med 2021;203:245-9. https://doi.org/10.1164/rccm.202007-2638LE
  99. Graziani D, Soriano JB, Del Rio-Bermudez C, Morena D, Diaz T, Castillo M, et al. Characteristics and prognosis of COVID-19 in patients with COPD. J Clin Med 2020;9:3259. https://doi.org/10.3390/jcm9103259
  100. Clift AK, Coupland CA, Keogh RH, Diaz-Ordaz K, Williamson E, Harrison EM, et al. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ 2020;371:m3731.
  101. Hippisley-Cox J, Young D, Coupland C, Channon KM, Tan PS, Harrison DA, et al. Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people. Heart 2020;106:1503-11. https://doi.org/10.1136/heartjnl-2020-317393
  102. Calmes D, Graff S, Maes N, Frix AN, Thys M, Bonhomme O, et al. Asthma and COPD are not risk factors for ICU stay and death in case of SARS-CoV2 infection. J Allergy Clin Immunol Pract 2021;9:160-9. https://doi.org/10.1016/j.jaip.2020.09.044
  103. Gupta S, Hayek SS, Wang W, Chan L, Mathews KS, Melamed ML, et al. Factors associated with death in critically ill patients with coronavirus disease 2019 in the US. JAMA Intern Med 2020;180:1436-47. https://doi.org/10.1001/jamainternmed.2020.3596
  104. Ioannou GN, Locke E, Green P, Berry K, O'Hare AM, Shah JA, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open 2020;3:e2022310. https://doi.org/10.1001/jamanetworkopen.2020.22310
  105. Chae KJ, Jin GY, Han YM, Kim YS, Chon SB, Lee YS, et al. Prevalence and progression of combined pulmonary fibrosis and emphysema in asymptomatic smokers: a casecontrol study. Eur Radiol 2015;25:2326-34. https://doi.org/10.1007/s00330-015-3617-3
  106. Tashkin DP. Smoking cessation in chronic obstructive pulmonary disease. Semin Respir Crit Care Med 2015;36:491-507. https://doi.org/10.1055/s-0035-1555610
  107. Aduen JF, Zisman DA, Mobin SI, Venegas C, Alvarez F, Biewend M, et al. Retrospective study of pulmonary function tests in patients presenting with isolated reduction in single-breath diffusion capacity: implications for the diagnosis of combined obstructive and restrictive lung disease. Mayo Clin Proc 2007;82:48-54. https://doi.org/10.4065/82.1.48
  108. Ando K, Sekiya M, Tobino K, Takahashi K. Relationship between quantitative CT metrics and pulmonary function in combined pulmonary fibrosis and emphysema. Lung 2013;191:585-91. https://doi.org/10.1007/s00408-013-9513-1
  109. Kitaguchi Y, Fujimoto K, Hayashi R, Hanaoka M, Honda T, Kubo K. Annual changes in pulmonary function in combined pulmonary fibrosis and emphysema: over a 5-year follow-up. Respir Med 2013;107:1986-92. https://doi.org/10.1016/j.rmed.2013.06.015
  110. Tzilas V, Bouros D. Combined pulmonary fibrosis and emphysema, a clinical review. COPD Res Pract 2016;2:2. https://doi.org/10.1186/s40749-016-0018-1
  111. Schmidt SL, Nambiar AM, Tayob N, Sundaram B, Han MK, Gross BH, et al. Pulmonary function measures predict mortality differently in IPF versus combined pulmonary fibrosis and emphysema. Eur Respir J 2011;38:176-83. https://doi.org/10.1183/09031936.00114010
  112. Young KA, Strand M, Ragland MF, Kinney GL, Austin EE, Regan EA, et al. Pulmonary subtypes exhibit differential global initiative for chronic obstructive lung disease spirometry stage progression: the COPDGene(R) study. Chronic Obstr Pulm Dis 2019;6:414-29.
  113. Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013;188:e13-64. https://doi.org/10.1164/rccm.201309-1634ST
  114. Zeng Y, Jiang F, Chen Y, Chen P, Cai S. Exercise assessments and trainings of pulmonary rehabilitation in COPD: a literature review. Int J Chron Obstruct Pulmon Dis 2018;13:2013-23. https://doi.org/10.2147/COPD.S167098
  115. Holland AE, Hill CJ, Conron M, Munro P, McDonald CF. Short term improvement in exercise capacity and symptoms following exercise training in interstitial lung disease. Thorax 2008;63:549-54. https://doi.org/10.1136/thx.2007.088070
  116. Nishiyama O, Kondoh Y, Kimura T, Kato K, Kataoka K, Ogawa T, et al. Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis. Respirology 2008;13:394-9. https://doi.org/10.1111/j.1440-1843.2007.01205.x
  117. Kozu R, Senjyu H, Jenkins SC, Mukae H, Sakamoto N, Kohno S. Differences in response to pulmonary rehabilitation in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Respiration 2011;81:196-205. https://doi.org/10.1159/000315475
  118. Holland A, Hill C. Physical training for interstitial lung disease. Cochrane Database Syst Rev 2008;(4):CD006322.
  119. Huppmann P, Sczepanski B, Boensch M, Winterkamp S, Schonheit-Kenn U, Neurohr C, et al. Effects of inpatient pulmonary rehabilitation in patients with interstitial lung disease. Eur Respir J 2013;42:444-53. https://doi.org/10.1183/09031936.00081512
  120. Tomioka H, Mamesaya N, Yamashita S, Kida Y, Kaneko M, Sakai H. Combined pulmonary fibrosis and emphysema: effect of pulmonary rehabilitation in comparison with chronic obstructive pulmonary disease. BMJ Open Respir Res 2016;3:e000099. https://doi.org/10.1136/bmjresp-2015-000099
  121. Dong F, Zhang Y, Chi F, Song Q, Zhang L, Wang Y, et al. Clinical efficacy and safety of ICS/LABA in patients with combined idiopathic pulmonary fibrosis and emphysema. Int J Clin Exp Med 2015;8:8617-25.
  122. Cottin V, Crestani B, Valeyre D, Wallaert B, Cadranel J, Dalphin JC, et al. Diagnosis and management of idiopathic pulmonary fibrosis: French practical guidelines. Eur Respir Rev 2014;23:193-214. https://doi.org/10.1183/09059180.00001814
  123. Hu PW, Ko HK, Su KC, Feng JY, Su WJ, Hsiao YH, et al. Functional parameters of small airways can guide bronchodilator use in idiopathic pulmonary fibrosis. Sci Rep 2020;10:18633. https://doi.org/10.1038/s41598-020-75597-2
  124. Bickel S, Popler J, Lesnick B, Eid N. Impulse oscillometry: interpretation and practical applications. Chest 2014;146:841-7. https://doi.org/10.1378/chest.13-1875
  125. Choi JY, Rhee CK. Diagnosis and treatment of early chronic obstructive lung disease (COPD). J Clin Med 2020;9:3426. https://doi.org/10.3390/jcm9113426
  126. Kitaguchi Y, Fujimoto K, Hanaoka M, Honda T, Hotta J, Hirayama J. Pulmonary function impairment in patients with combined pulmonary fibrosis and emphysema with and without airflow obstruction. Int J Chron Obstruct Pulmon Dis 2014;9:805-11. https://doi.org/10.2147/COPD.S65621
  127. King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2083-92. https://doi.org/10.1056/NEJMoa1402582
  128. Noble PW, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J 2016;47:243-53. https://doi.org/10.1183/13993003.00026-2015
  129. Noble PW, Albera C, Bradford WZ, Costabel U, Glassberg MK, Kardatzke D, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet 2011;377:1760-9. https://doi.org/10.1016/S0140-6736(11)60405-4
  130. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2071-82. https://doi.org/10.1056/NEJMoa1402584
  131. Cottin V, Azuma A, Raghu G, Stansen W, Stowasser S, Schlenker-Herceg R, et al. Therapeutic effects of nintedanib are not influenced by emphysema in the INPULSIS trials. Eur Respir J 2019;53:1801655. https://doi.org/10.1183/13993003.01655-2018
  132. Vacchi C, Sebastiani M, Cassone G, Cerri S, Della Casa G, Salvarani C, et al. Therapeutic options for the treatment of interstitial lung disease related to connective tissue diseases: a narrative review. J Clin Med 2020;9:407. https://doi.org/10.3390/jcm9020407
  133. Wijsenbeek M, Cottin V. Spectrum of fibrotic lung diseases. N Engl J Med 2020;383:958-68. https://doi.org/10.1056/NEJMra2005230
  134. Homma S, Bando M, Azuma A, Sakamoto S, Sugino K, Ishii Y, et al. Japanese guideline for the treatment of idiopathic pulmonary fibrosis. Respir Investig 2018;56:268-91. https://doi.org/10.1016/j.resinv.2018.03.003
  135. Higginson IJ, Bausewein C, Reilly CC, Gao W, Gysels M, Dzingina M, et al. An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respir Med 2014;2:979-87. https://doi.org/10.1016/S2213-2600(14)70226-7
  136. Brighton LJ, Miller S, Farquhar M, Booth S, Yi D, Gao W, et al. Holistic services for people with advanced disease and chronic breathlessness: a systematic review and meta-analysis. Thorax 2019;74:270-81. https://doi.org/10.1136/thoraxjnl-2018-211589
  137. Simon ST, Higginson IJ, Booth S, Harding R, Weingartner V, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev 2016;10:CD007354.
  138. Ekstrom M, Bajwah S, Bland JM, Currow DC, Hussain J, Johnson MJ. One evidence base; three stories: do opioids relieve chronic breathlessness? Thorax 2018;73:88-90. https://doi.org/10.1136/thoraxjnl-2016-209868
  139. Ekstrom M, Nilsson F, Abernethy AA, Currow DC. Effects of opioids on breathlessness and exercise capacity in chronic obstructive pulmonary disease: a systematic review. Ann Am Thorac Soc 2015;12:1079-92. https://doi.org/10.1513/AnnalsATS.201501-034OC
  140. Higginson IJ, Wilcock A, Johnson MJ, Bajwah S, Lovell N, Yi D, et al. Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility). Thorax 2020;75:176-9.
  141. Smoller JW, Pollack MH, Systrom D, Kradin RL. Sertraline effects on dyspnea in patients with obstructive airways disease. Psychosomatics 1998;39:24-9. https://doi.org/10.1016/S0033-3182(98)71377-5
  142. Lacasse Y, Beaudoin L, Rousseau L, Maltais F. Randomized trial of paroxetine in end-stage COPD. Monaldi Arch Chest Dis 2004;61:140-7.
  143. Eiser N, Harte R, Spiros K, Phillips C, Isaac MT. Effect of treating depression on quality-of-life and exercise tolerance in severe COPD. COPD 2005;2:233-41. https://doi.org/10.1081/COPD-57596
  144. Currow DC, Ekstrom M, Louw S, Hill J, Fazekas B, Clark K, et al. Sertraline in symptomatic chronic breathlessness: a double blind, randomised trial. Eur Respir J 2019;53:1801270. https://doi.org/10.1183/13993003.01270-2018
  145. Nathan SD, Barbera JA, Gaine SP, Harari S, Martinez FJ, Olschewski H, et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J 2019;53:180914.
  146. Kusaka K, Morio Y, Kimura Y, Takeda K, Kawashima M, Masuda K, et al. Improvement of pulmonary arterial compliance by pulmonary vasodilator in pulmonary hypertension from combined pulmonary fibrosis and emphysema. Respir Med Case Rep 2019;28:100940.
  147. Straub G, Caviezel C, Frauenfelder T, Bloch KE, Franzen D. Successful lung volume reduction surgery in combined pulmonary emphysema and fibrosis without body-plethysmographic hyperinflation-a case report. J Thorac Dis 2018;10(Suppl 23):S2830-4. https://doi.org/10.21037/jtd.2018.06.60
  148. Takahashi T, Terada Y, Pasque MK, Liu J, Byers DE, Witt CA, et al. Clinical features and outcomes of combined pulmonary fibrosis and emphysema after lung transplantation. Chest 2021;160:1743-50. https://doi.org/10.1016/j.chest.2021.06.036