慢性阻塞性肺疾病肺气肿表型影像学特征与发生机制研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

陈臻平 , 赵海金 ,  蔡绍曦

南方医科大学南方医院呼吸与危重症医学科（广东广州 510515）;

Corresponding author：

蔡绍曦, Email: hxkcai@126.com

Keywords：

DOI：

10.7507/1671-6205.202201035

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Citation： 陈臻平, 赵海金, 蔡绍曦. 慢性阻塞性肺疾病肺气肿表型影像学特征与发生机制研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(5): 363-369. doi: 10.7507/1671-6205.202201035 Copy

1.	Burrows B, Fletcher CM, Heard BE, et al. The emphysematous and bronchial types of chronic airways obstruction. A clinicopathological study of patients in London and Chicago. Lancet, 1966, 1(7442): 830-835.
2.	Dornhorst AC. Respiratory insufficiency. Lancet, 1955, 268(6876): 1185-1187.
3.	Jones NL, Burrows B, Fletcher CM. Serial studies of 100 patients with chronic airway obstruction in London and Chicago. Thorax, 1967, 22(4): 327-335.
4.	Miravitlles M, Vogelmeier C, Roche N, et al. A review of national guidelines for management of COPD in Europe. Eur Respir J, 2016, 47(2): 625-637.
5.	Lynch DA, Austin JH, Hogg JC, et al. CT-definable subtypes of chronic obstructive pulmonary disease: a statement of the Fleischner Society. Radiology, 2015, 277(1): 192-205.
6.	Lynch DA, Moore CM, Wilson C, et al. CT-based visual classification of emphysema: association with mortality in the COPDGene Study. Radiology, 2018, 288(3): 859-866.
7.	Goddard PR, Nicholson EM, Laszlo G, et al. Computed tomography in pulmonary emphysema. Clin Radiol, 1982, 33(4): 379-387.
8.	Crossley D, Renton M, Khan M, et al. CT densitometry in emphysema: a systematic review of its clinical utility. Int J Chron Obstruct Pulmon Dis, 2018, 13: 547-563.
9.	Humphries SM, Notary AM, Centeno JP, et al. Deep learning enables automatic classification of emphysema pattern at CT. Radiology, 2020, 294(2): 434-444.
10.	Orting SN, Petersen J, Thomsen LH, et al. Learning to quantify emphysema extent: what labels do we need?. IEEE J Biomed Health Inform, 2020, 24(4): 1149-1159.
11.	Lin X, Li YJ, Gong L, et al. Tempo-spatial regulation of the Wnt pathway by FAM13A modulates the stemness of alveolar epithelial progenitors. Ebiomedicine, 2021, 69: 103463.
12.	Gazourian L, Thedinger WB, Regis SM, et al. Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study. Respir Med, 2021, 176: 106245.
13.	Dong WG, Zhu YQ, Du Y, et al. Association between features of COPD and risk of venous thromboembolism. Clin Respir J, 2019, 13(8): 499-504.
14.	El Kaddouri B, Strand MJ, Baraghoshi D, et al. Fleischner Society visual emphysema CT patterns help predict progression of emphysema in current and former smokers: results from the COPDGene Study. Radiology, 2021, 298(2): 441-449.
15.	Park J, Hobbs BD, Crapo JD, et al. Subtyping COPD by using visual and quantitative CT imaging features. Chest, 2020, 157(1): 47-60.
16.	González J, Henschke CI, Yankelevitz DF, et al. Emphysema phenotypes and lung cancer risk. Plos One, 2019, 14(7): e219187.
17.	Mouronte-Roibás C, Fernández-Villar A, Ruano-Raviñaña A, et al. Influence of the type of emphysema in the relationship between COPD and lung cancer. Int J Chron Obstruct Pulmon Dis, 2018, 13: 3563-3570.
18.	Pompe E, Strand M, van Rikxoort EM, et al. Five-year progression of emphysema and air trapping at CT in smokers with and those without chronic obstructive pulmonary disease: results from the COPDGene Study. Radiology, 2020, 295(1): 218-226.
19.	Labaki WW, Gu T, Murray S, et al. Reprint of: voxel-wise longitudinal parametric response mapping analysis of chest computed tomography in smokers. Acad Radiol, 2019, 26(3): 306-312.
20.	Subramanian DR, Gupta S, Burggraf D, et al. Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography. Eur Respir J, 2016, 48(1): 92-103.
21.	李然, 白澎, 孙永昌, 等. 慢性阻塞性肺疾病肺气肿表型的临床与病理生理特征分析. 中华结核和呼吸杂志, 2011, 34(11): 857-858.
22.	Lim JU, Kim EK, Lim SY, et al. Mixed phenotype of emphysema and airway wall thickening is associated with frequent exacerbation in chronic obstructive pulmonary disease patients. Int J Chron Obstruct Pulmon Dis, 2019, 14: 3035-3042.
23.	Kim YW, Lee CH, Hwang HG, et al. Resting hyperinflation and emphysema on the clinical course of COPD. Sci Rep, 2019, 9(1): 3764.
24.	Ash SY, San JER, Fain SB, et al. Relationship between emphysema progression at CT and mortality in ever-smokers: results from the COPDGene and ECLIPSE cohorts. Radiology, 2021, 299(1): 222-231.
25.	Celli B, Locantore N, Yates JC, et al. Markers of disease activity in COPD: an 8-year mortality study in the ECLIPSE cohort. Eur Respir J, 2021, 57(3): 2001339.
26.	Lee KS, Park HY. Progression of emphysema at CT in smokers and its relationship to mortality. Radiology, 2021, 299(1): 232-233.
27.	Boueiz A, Chang Y, Cho MH, et al. Lobar emphysema distribution is associated with 5-year radiological disease progression. Chest, 2018, 153(1): 65-76.
28.	Al-Kassimi FA, Alhamad EH, Al-Hajjaj MS, et al. Can computed tomography and carbon monoxide transfer coefficient diagnose an asthma-like phenotype in COPD?. Respirology, 2017, 22(2): 322-328.
29.	Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med, 2003, 348(21): 2059-2073.
30.	Ahmad S, Taneja A, Kurman J, et al. National trends in lung volume reduction surgery in the United States: 2000 to 2010. Chest, 2014, 146(6): e228-e229.
31.	Welling J, Hartman JE, Augustijn S, et al. Patient selection for bronchoscopic lung volume reduction. Int J Chron Obstruct Pulmon Dis, 2020, 15: 871-881.
32.	Kotecha S, Williams TJ. Endobronchial coils for emphysema: Do they work and why?. Respirology, 2020, 25(11): 1116-1118.
33.	Gompelmann D, Benjamin N, Bischoff E, et al. Survival after endoscopic valve therapy in patients with severe emphysema. Respiration, 2019, 97(2): 145-152.
34.	Turan D, Dogan D, Cortuk M, et al. Does bronchoscopic lung volume reduction reduce mortality in patients with severe emphysema?. J Coll Physicians Surg Pak, 2021, 31(1): 60-64.
35.	Slebos DJ, Cicenia J, Sciurba FC, et al. Predictors of response to endobronchial coil therapy in patients with advanced emphysema. Chest, 2019, 155(5): 928-937.
36.	Hartman JE, Klooster K, Augustijn S, et al. Identifying responders and exploring mechanisms of action of the endobronchial coil treatment for emphysema. Respiration, 2021, 100(5): 443-451.
37.	Biener L, Skowasch D, Hollmann S, et al. Endoscopic lung volume reduction in COPD: the impact of coil implantation on patients' physical activity. Respiration, 2020, 99(2): 177-180.
38.	Garner JL, Kemp SV, Srikanthan K, et al. 5-Year survival after endobronchial coil implantation: secondary analysis of the first randomised controlled trial, RESET. Respiration, 2020, 99(2): 154-162.
39.	Hartman JE, Shah PL, Sciurba F, et al. Endobronchial coils for emphysema: Dual mechanism of action on lobar residual volume reduction. Respirology, 2020, 25(11): 1160-1166.
40.	Amaza IP, O'Shea AMJ, Fortis S, et al. Discordant quantitative and visual CT assessments in the diagnosis of emphysema. Int J Chron Obstruct Pulmon Dis, 2021, 16: 1231-1242.
41.	Vikgren J, Khalil M, Cederlund K, et al. Visual and quantitative evaluation of emphysema: a case-control study of 1111 participants in the Pilot Swedish CArdioPulmonary BioImage Study (SCAPIS). Acad Radiol, 2020, 27(5): 636-643.
42.	Grenier PA. Emphysema at CT in smokers with normal spirometry: why it is clinically significant. Radiology, 2020, 296(3): 650-651.
43.	Lowe KE, Regan EA, Anzueto A, et al. COPDGene(®) 2019: redefining the diagnosis of chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis, 2019, 6(5): 384-399.
44.	Coxson HO, Dirksen A, Edwards LD, et al. The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study. Lancet Respir Med, 2013, 1(2): 129-136.
45.	Fischer BM, Voynow JA, Ghio AJ. COPD: balancing oxidants and antioxidants. Int J Chron Obstruct Pulmon Dis, 2015, 10: 261-276.
46.	Hadzic S, Wu CY, Avdeev S, et al. Lung epithelium damage in COPD - An unstoppable pathological event?. Cell Signal, 2020, 68: 109540.
47.	Kirkham PA, Caramori G, Casolari P, et al. Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2011, 184(7): 796-802.
48.	Fratta Pasini AM, Stranieri C, Ferrari M, et al. Oxidative stress and Nrf2 expression in peripheral blood mononuclear cells derived from COPD patients: an observational longitudinal study. Resp Res, 2020, 21(1): 37.
49.	Sugitani A, Asai K, Watanabe T, et al. A polymorphism rs6726395 in Nrf2 contributes to the development of emphysema-associated age in smokers without COPD. Lung, 2019, 197(5): 559-564.
50.	Chamitava L, Cazzoletti L, Ferrari M, et al. Biomarkers of oxidative stress and inflammation in chronic airway diseases. Int J Mol Sci, 2020, 21(12): 4339.
51.	Basil MC, Katzen J, Engler AE, et al. The Cellular and physiological basis for lung repair and regeneration: past, present, and future. Cell Stem Cell, 2020, 26(4): 482-502.
52.	Kosmider B, Lin CR, Karim L, et al. Mitochondrial dysfunction in human primary alveolar type Ⅱ cells in emphysema. Ebiomedicine, 2019, 46: 305-316.
53.	Zhao KS, Dong R, Yu YF, et al. Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway. Aging (Albany NY), 2020, 12(10): 9125-9138.
54.	Xiong Y, Gao SH, Luo GW, et al. Increased circulating autoantibodies levels of IgG, IgA, IgM against cytokeratin 18 and cytokeratin 19 in chronic obstructive pulmonary disease. Arch Med Res, 2017, 48(1): 79-87.
55.	Cass SP, Dvorkin-Gheva A, Yang Y, et al. Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol, 2021, 320(6): L1169-L1182.
56.	Kim WD, Chi HS, Choe KH, et al. The role of granzyme B containing cells in the progression of chronic obstructive pulmonary disease. Tuberc Respir Dis (Seoul), 2020, 83(Suppl 1): S25-S33.
57.	Wang YJ, Xu JY, Meng YQ, et al. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis, 2018, 13: 3341-3348.
58.	Carp H, Janoff A. Possible mechanisms of emphysema in smokers. In vitro suppression of serum elastase-inhibitory capacity by fresh cigarette smoke and its prevention by antioxidants. Am Rev Respir Dis, 1978, 118(3): 617-621.
59.	Overbeek SA, Braber S, Koelink PJ, et al. Cigarette smoke-induced collagen destruction; key to chronic neutrophilic airway inflammation?. PLoS One, 2013, 8(1): e55612.
60.	Houghton AM, Quintero PA, Perkins DL, et al. Elastin fragments drive disease progression in a murine model of emphysema. J Clin Invest, 2006, 116(3): 753-759.
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1. Burrows B, Fletcher CM, Heard BE, et al. The emphysematous and bronchial types of chronic airways obstruction. A clinicopathological study of patients in London and Chicago. Lancet, 1966, 1(7442): 830-835.
2. Dornhorst AC. Respiratory insufficiency. Lancet, 1955, 268(6876): 1185-1187.
3. Jones NL, Burrows B, Fletcher CM. Serial studies of 100 patients with chronic airway obstruction in London and Chicago. Thorax, 1967, 22(4): 327-335.
4. Miravitlles M, Vogelmeier C, Roche N, et al. A review of national guidelines for management of COPD in Europe. Eur Respir J, 2016, 47(2): 625-637.
5. Lynch DA, Austin JH, Hogg JC, et al. CT-definable subtypes of chronic obstructive pulmonary disease: a statement of the Fleischner Society. Radiology, 2015, 277(1): 192-205.
6. Lynch DA, Moore CM, Wilson C, et al. CT-based visual classification of emphysema: association with mortality in the COPDGene Study. Radiology, 2018, 288(3): 859-866.
7. Goddard PR, Nicholson EM, Laszlo G, et al. Computed tomography in pulmonary emphysema. Clin Radiol, 1982, 33(4): 379-387.
8. Crossley D, Renton M, Khan M, et al. CT densitometry in emphysema: a systematic review of its clinical utility. Int J Chron Obstruct Pulmon Dis, 2018, 13: 547-563.
9. Humphries SM, Notary AM, Centeno JP, et al. Deep learning enables automatic classification of emphysema pattern at CT. Radiology, 2020, 294(2): 434-444.
10. Orting SN, Petersen J, Thomsen LH, et al. Learning to quantify emphysema extent: what labels do we need?. IEEE J Biomed Health Inform, 2020, 24(4): 1149-1159.
11. Lin X, Li YJ, Gong L, et al. Tempo-spatial regulation of the Wnt pathway by FAM13A modulates the stemness of alveolar epithelial progenitors. Ebiomedicine, 2021, 69: 103463.
12. Gazourian L, Thedinger WB, Regis SM, et al. Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study. Respir Med, 2021, 176: 106245.
13. Dong WG, Zhu YQ, Du Y, et al. Association between features of COPD and risk of venous thromboembolism. Clin Respir J, 2019, 13(8): 499-504.
14. El Kaddouri B, Strand MJ, Baraghoshi D, et al. Fleischner Society visual emphysema CT patterns help predict progression of emphysema in current and former smokers: results from the COPDGene Study. Radiology, 2021, 298(2): 441-449.
15. Park J, Hobbs BD, Crapo JD, et al. Subtyping COPD by using visual and quantitative CT imaging features. Chest, 2020, 157(1): 47-60.
16. González J, Henschke CI, Yankelevitz DF, et al. Emphysema phenotypes and lung cancer risk. Plos One, 2019, 14(7): e219187.
17. Mouronte-Roibás C, Fernández-Villar A, Ruano-Raviñaña A, et al. Influence of the type of emphysema in the relationship between COPD and lung cancer. Int J Chron Obstruct Pulmon Dis, 2018, 13: 3563-3570.
18. Pompe E, Strand M, van Rikxoort EM, et al. Five-year progression of emphysema and air trapping at CT in smokers with and those without chronic obstructive pulmonary disease: results from the COPDGene Study. Radiology, 2020, 295(1): 218-226.
19. Labaki WW, Gu T, Murray S, et al. Reprint of: voxel-wise longitudinal parametric response mapping analysis of chest computed tomography in smokers. Acad Radiol, 2019, 26(3): 306-312.
20. Subramanian DR, Gupta S, Burggraf D, et al. Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography. Eur Respir J, 2016, 48(1): 92-103.
21. 李然, 白澎, 孙永昌, 等. 慢性阻塞性肺疾病肺气肿表型的临床与病理生理特征分析. 中华结核和呼吸杂志, 2011, 34(11): 857-858.
22. Lim JU, Kim EK, Lim SY, et al. Mixed phenotype of emphysema and airway wall thickening is associated with frequent exacerbation in chronic obstructive pulmonary disease patients. Int J Chron Obstruct Pulmon Dis, 2019, 14: 3035-3042.
23. Kim YW, Lee CH, Hwang HG, et al. Resting hyperinflation and emphysema on the clinical course of COPD. Sci Rep, 2019, 9(1): 3764.
24. Ash SY, San JER, Fain SB, et al. Relationship between emphysema progression at CT and mortality in ever-smokers: results from the COPDGene and ECLIPSE cohorts. Radiology, 2021, 299(1): 222-231.
25. Celli B, Locantore N, Yates JC, et al. Markers of disease activity in COPD: an 8-year mortality study in the ECLIPSE cohort. Eur Respir J, 2021, 57(3): 2001339.
26. Lee KS, Park HY. Progression of emphysema at CT in smokers and its relationship to mortality. Radiology, 2021, 299(1): 232-233.
27. Boueiz A, Chang Y, Cho MH, et al. Lobar emphysema distribution is associated with 5-year radiological disease progression. Chest, 2018, 153(1): 65-76.
28. Al-Kassimi FA, Alhamad EH, Al-Hajjaj MS, et al. Can computed tomography and carbon monoxide transfer coefficient diagnose an asthma-like phenotype in COPD?. Respirology, 2017, 22(2): 322-328.
29. Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med, 2003, 348(21): 2059-2073.
30. Ahmad S, Taneja A, Kurman J, et al. National trends in lung volume reduction surgery in the United States: 2000 to 2010. Chest, 2014, 146(6): e228-e229.
31. Welling J, Hartman JE, Augustijn S, et al. Patient selection for bronchoscopic lung volume reduction. Int J Chron Obstruct Pulmon Dis, 2020, 15: 871-881.
32. Kotecha S, Williams TJ. Endobronchial coils for emphysema: Do they work and why?. Respirology, 2020, 25(11): 1116-1118.
33. Gompelmann D, Benjamin N, Bischoff E, et al. Survival after endoscopic valve therapy in patients with severe emphysema. Respiration, 2019, 97(2): 145-152.
34. Turan D, Dogan D, Cortuk M, et al. Does bronchoscopic lung volume reduction reduce mortality in patients with severe emphysema?. J Coll Physicians Surg Pak, 2021, 31(1): 60-64.
35. Slebos DJ, Cicenia J, Sciurba FC, et al. Predictors of response to endobronchial coil therapy in patients with advanced emphysema. Chest, 2019, 155(5): 928-937.
36. Hartman JE, Klooster K, Augustijn S, et al. Identifying responders and exploring mechanisms of action of the endobronchial coil treatment for emphysema. Respiration, 2021, 100(5): 443-451.
37. Biener L, Skowasch D, Hollmann S, et al. Endoscopic lung volume reduction in COPD: the impact of coil implantation on patients' physical activity. Respiration, 2020, 99(2): 177-180.
38. Garner JL, Kemp SV, Srikanthan K, et al. 5-Year survival after endobronchial coil implantation: secondary analysis of the first randomised controlled trial, RESET. Respiration, 2020, 99(2): 154-162.
39. Hartman JE, Shah PL, Sciurba F, et al. Endobronchial coils for emphysema: Dual mechanism of action on lobar residual volume reduction. Respirology, 2020, 25(11): 1160-1166.
40. Amaza IP, O'Shea AMJ, Fortis S, et al. Discordant quantitative and visual CT assessments in the diagnosis of emphysema. Int J Chron Obstruct Pulmon Dis, 2021, 16: 1231-1242.
41. Vikgren J, Khalil M, Cederlund K, et al. Visual and quantitative evaluation of emphysema: a case-control study of 1111 participants in the Pilot Swedish CArdioPulmonary BioImage Study (SCAPIS). Acad Radiol, 2020, 27(5): 636-643.
42. Grenier PA. Emphysema at CT in smokers with normal spirometry: why it is clinically significant. Radiology, 2020, 296(3): 650-651.
43. Lowe KE, Regan EA, Anzueto A, et al. COPDGene(®) 2019: redefining the diagnosis of chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis, 2019, 6(5): 384-399.
44. Coxson HO, Dirksen A, Edwards LD, et al. The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression: a prospective analysis from the ECLIPSE study. Lancet Respir Med, 2013, 1(2): 129-136.
45. Fischer BM, Voynow JA, Ghio AJ. COPD: balancing oxidants and antioxidants. Int J Chron Obstruct Pulmon Dis, 2015, 10: 261-276.
46. Hadzic S, Wu CY, Avdeev S, et al. Lung epithelium damage in COPD - An unstoppable pathological event?. Cell Signal, 2020, 68: 109540.
47. Kirkham PA, Caramori G, Casolari P, et al. Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2011, 184(7): 796-802.
48. Fratta Pasini AM, Stranieri C, Ferrari M, et al. Oxidative stress and Nrf2 expression in peripheral blood mononuclear cells derived from COPD patients: an observational longitudinal study. Resp Res, 2020, 21(1): 37.
49. Sugitani A, Asai K, Watanabe T, et al. A polymorphism rs6726395 in Nrf2 contributes to the development of emphysema-associated age in smokers without COPD. Lung, 2019, 197(5): 559-564.
50. Chamitava L, Cazzoletti L, Ferrari M, et al. Biomarkers of oxidative stress and inflammation in chronic airway diseases. Int J Mol Sci, 2020, 21(12): 4339.
51. Basil MC, Katzen J, Engler AE, et al. The Cellular and physiological basis for lung repair and regeneration: past, present, and future. Cell Stem Cell, 2020, 26(4): 482-502.
52. Kosmider B, Lin CR, Karim L, et al. Mitochondrial dysfunction in human primary alveolar type Ⅱ cells in emphysema. Ebiomedicine, 2019, 46: 305-316.
53. Zhao KS, Dong R, Yu YF, et al. Cigarette smoke-induced lung inflammation in COPD mediated via CCR1/JAK/STAT /NF-κB pathway. Aging (Albany NY), 2020, 12(10): 9125-9138.
54. Xiong Y, Gao SH, Luo GW, et al. Increased circulating autoantibodies levels of IgG, IgA, IgM against cytokeratin 18 and cytokeratin 19 in chronic obstructive pulmonary disease. Arch Med Res, 2017, 48(1): 79-87.
55. Cass SP, Dvorkin-Gheva A, Yang Y, et al. Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol, 2021, 320(6): L1169-L1182.
56. Kim WD, Chi HS, Choe KH, et al. The role of granzyme B containing cells in the progression of chronic obstructive pulmonary disease. Tuberc Respir Dis (Seoul), 2020, 83(Suppl 1): S25-S33.
57. Wang YJ, Xu JY, Meng YQ, et al. Role of inflammatory cells in airway remodeling in COPD. Int J Chron Obstruct Pulmon Dis, 2018, 13: 3341-3348.
58. Carp H, Janoff A. Possible mechanisms of emphysema in smokers. In vitro suppression of serum elastase-inhibitory capacity by fresh cigarette smoke and its prevention by antioxidants. Am Rev Respir Dis, 1978, 118(3): 617-621.
59. Overbeek SA, Braber S, Koelink PJ, et al. Cigarette smoke-induced collagen destruction; key to chronic neutrophilic airway inflammation?. PLoS One, 2013, 8(1): e55612.
60. Houghton AM, Quintero PA, Perkins DL, et al. Elastin fragments drive disease progression in a murine model of emphysema. J Clin Invest, 2006, 116(3): 753-759.
61. Zacharias WJ, Frank DB, Zepp JA, et al. Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor. Nature (London), 2018, 555(7695): 251-255.
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