Longitudinal changes in structural lung abnormalities using MDCT in chronic obstructive pulmonary disease with asthma-like features

Autoři: Rie Anazawa aff001;  Naoko Kawata aff001;  Yukiko Matsuura aff001;  Jun Ikari aff001;  Yuji Tada aff001;  Masaki Suzuki aff001;  Shin Takayanagi aff001;  Shin Matsuoka aff002;  Shoichiro Matsushita aff002;  Koichiro Tatsumi aff001
Působiště autorů: Department of Respirology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba-shi, Chiba, Japan aff001;  Department of Radiology, St. Marianna University School of Medicine, Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa, Japan aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0227141



Some patients with chronic obstructive pulmonary disease (COPD) have asthma-like features. However, there have been few reports on the structural lung abnormalities found in this patient population. Multi-detector computed tomography (MDCT) can detect emphysematous low-attenuation areas (LAA) within the lung, airway thickness (wall area percentage, WA%), and the loss of pulmonary vasculature as the percentage of small pulmonary vessels with cross-sectional area (CSA) less than 5 mm2 (%CSA<5). We analyzed differences in structural lung changes over time between patients with COPD and those with COPD with asthma-like features using these CT parameters.

Material and methods

We performed pulmonary function tests (PFTs), MDCT, and a COPD assessment test (CAT) in 50 patients with COPD and 29 patients with COPD with asthma-like features at the time of enrollment and two years later. We analyzed changes in clinical parameters and CT indices over time and evaluated differences in structural changes between groups.


The CAT score and FEV1 did not significantly change during the follow-up period in either group. Emphysematous LAA regions significantly increased in both groups. The %CSA<5 showed a small but significant increase in COPD patients, but a significant decrease in patients with COPD with asthma-like features. The WA% at the distal bronchi was significantly decreased in COPD, but did not significantly change in COPD with asthma -like features.


Emphysematous LAA increased in patients with COPD with and without asthma-like features. The %CSA<5 and WA% at the distal bronchi did not change in parallel with LAA. Furthermore, changes in %CSA<5 were significantly different between patients with COPD and those with COPD with asthma-like features. Patients with COPD with asthma-like features may have different longitudinal structural changes than those seen in COPD patients.

Klíčová slova:

Asthma – Bronchi – Computed axial tomography – Emphysema – Chronic obstructive pulmonary disease – Pulmonary function – Smoking habits – Bronchodilators


1. Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Eur Respir J. 2017;49(3). doi: 10.1183/13993003.00214–2017 28182564.

2. The top 10 causes of death, World Health Organization 2017. Available from: http://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death.

3. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit Care Med. 1995;152(5 Pt 2):S77–121. 7582322.

4. Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128–38. doi: 10.1056/NEJMoa0909883 20843247.

5. Asthma COPD and Ashtma-COPD Overlap Syndrome (ACOS). Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease 2015. Available from: https://goldcopd.org/asthma-copd-asthma-copd-overlap-syndrome/.

6. Tho NV, Park HY, Nakano Y. Asthma-COPD overlap syndrome (ACOS): A diagnostic challenge. Respirology. 2016;21(3):410–8. doi: 10.1111/resp.12653 26450153.

7. Soler-Cataluna JJ, Cosio B, Izquierdo JL, Lopez-Campos JL, Marin JM, Aguero R, et al. Consensus document on the overlap phenotype COPD-asthma in COPD. Arch Bronconeumol. 2012;48(9):331–7. doi: 10.1016/j.arbres.2011.12.009 22341911.

8. Cosio BG, Soriano JB, Lopez-Campos JL, Calle-Rubio M, Soler-Cataluna JJ, de-Torres JP, et al. Defining the Asthma-COPD Overlap Syndrome in a COPD Cohort. Chest. 2016;149(1):45–52. doi: 10.1378/chest.15-1055 26291753.

9. Suzuki M, Makita H, Konno S, Shimizu K, Kimura H, Kimura H, et al. Asthma-like Features and Clinical Course of Chronic Obstructive Pulmonary Disease. An Analysis from the Hokkaido COPD Cohort Study. Am J Respir Crit Care Med. 2016;194(11):1358–65. doi: 10.1164/rccm.201602-0353OC 27224255.

10. Leigh R, Pizzichini MM, Morris MM, Maltais F, Hargreave FE, Pizzichini E. Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment. Eur Respir J. 2006;27(5):964–71. doi: 10.1183/09031936.06.00072105 16446316.

11. Fattahi F, ten Hacken NH, Lofdahl CG, Hylkema MN, Timens W, Postma DS, et al. Atopy is a risk factor for respiratory symptoms in COPD patients: results from the EUROSCOP study. Respir Res. 2013;14:10. doi: 10.1186/1465-9921-14-10 23356508; PubMed Central PMCID: PMC3599617.

12. Gevenois PA, de Maertelaer V, De Vuyst P, Zanen J, Yernault JC. Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1995;152(2):653–7. doi: 10.1164/ajrccm.152.2.7633722 7633722.

13. Mishima M, Hirai T, Itoh H, Nakano Y, Sakai H, Muro S, et al. Complexity of terminal airspace geometry assessed by lung computed tomography in normal subjects and patients with chronic obstructive pulmonary disease. Proc Natl Acad Sci U S A. 1999;96(16):8829–34. doi: 10.1073/pnas.96.16.8829 10430855; PubMed Central PMCID: PMC17692.

14. Haruna A, Muro S, Nakano Y, Ohara T, Hoshino Y, Ogawa E, et al. CT scan findings of emphysema predict mortality in COPD. Chest. 2010;138(3):635–40. doi: 10.1378/chest.09-2836 20382712.

15. Nakano Y, Muro S, Sakai H, Hirai T, Chin K, Tsukino M, et al. Computed tomographic measurements of airway dimensions and emphysema in smokers. Correlation with lung function. Am J Respir Crit Care Med. 2000;162(3 Pt 1):1102–8. doi: 10.1164/ajrccm.162.3.9907120 10988137.

16. Hasegawa M, Nasuhara Y, Onodera Y, Makita H, Nagai K, Fuke S, et al. Airflow limitation and airway dimensions in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173(12):1309–15. doi: 10.1164/rccm.200601-037OC 16556695.

17. Xie X, Dijkstra AE, Vonk JM, Oudkerk M, Vliegenthart R, Groen HJ. Chronic respiratory symptoms associated with airway wall thickening measured by thin-slice low-dose CT. AJR Am J Roentgenol. 2014;203(4):W383–90. doi: 10.2214/AJR.13.11536 25247967.

18. Matsuoka S, Washko GR, Dransfield MT, Yamashiro T, San Jose Estepar R, Diaz A, et al. Quantitative CT measurement of cross-sectional area of small pulmonary vessel in COPD: correlations with emphysema and airflow limitation. Acad Radiol. 2010;17(1):93–9. doi: 10.1016/j.acra.2009.07.022 19796970; PubMed Central PMCID: PMC2790546.

19. Matsuoka S, Washko GR, Yamashiro T, Estepar RS, Diaz A, Silverman EK, et al. Pulmonary hypertension and computed tomography measurement of small pulmonary vessels in severe emphysema. Am J Respir Crit Care Med. 2010;181(3):218–25. doi: 10.1164/rccm.200908-1189OC 19875683; PubMed Central PMCID: PMC2817812.

20. Jones PW, Anderson JA, Calverley PM, Celli BR, Ferguson GT, Jenkins C, et al. Health status in the TORCH study of COPD: treatment efficacy and other determinants of change. Respir Res. 2011;12:71. doi: 10.1186/1465-9921-12-71 21627828; PubMed Central PMCID: PMC3117702.

21. Soejima K, Yamaguchi K, Kohda E, Takeshita K, Ito Y, Mastubara H, et al. Longitudinal follow-up study of smoking-induced lung density changes by high-resolution computed tomography. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1264–73. doi: 10.1164/ajrccm.161.4.9905040 10764322.

22. Tanabe N, Muro S, Hirai T, Oguma T, Terada K, Marumo S, et al. Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183(12):1653–9. doi: 10.1164/rccm.201009-1535OC 21471102.

23. Ohara T, Hirai T, Sato S, Terada K, Kinose D, Haruna A, et al. Longitudinal study of airway dimensions in chronic obstructive pulmonary disease using computed tomography. Respirology. 2008;13(3):372–8. doi: 10.1111/j.1440-1843.2008.01269.x 18399859.

24. Saruya S, Matsuoka S, Yamashiro T, Matsushita S, Fujikawa A, Yagihashi K, et al. Quantitative CT measurements of small pulmonary vessels in chronic obstructive pulmonary disease: do they change on follow-up scans? Clin Physiol Funct Imaging. 2016;36(3):211–7. doi: 10.1111/cpf.12215 25393655.

25. Hardin M, Cho M, McDonald ML, Beaty T, Ramsdell J, Bhatt S, et al. The clinical and genetic features of COPD-asthma overlap syndrome. Eur Respir J. 2014;44(2):341–50. doi: 10.1183/09031936.00216013 24876173; PubMed Central PMCID: PMC4154588.

26. Takayanagi S, Kawata N, Tada Y, Ikari J, Matsuura Y, Matsuoka S, et al. Longitudinal changes in structural abnormalities using MDCT in COPD: do the CT measurements of airway wall thickness and small pulmonary vessels change in parallel with emphysematous progression? Int J Chron Obstruct Pulmon Dis. 2017;12:551–60. doi: 10.2147/COPD.S121405 28243075; PubMed Central PMCID: PMC5315203.

27. Celli BR, MacNee W, Force AET. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932–46. doi: 10.1183/09031936.04.00014304 15219010

28. Committee of Pulmonary Physiology, The Japanese Respiratory Society, Guidelines for pulmonary function tests: spirometry, flow-volume curve, diffusion capacity of the lung. 1st ed. Nihon Kokyuki Gakkai Zasshi. 2004;(Suppl):1–56.

29. Yamashiro T, Matsuoka S, Estepar RS, Dransfield MT, Diaz A, Reilly JJ, et al. Quantitative assessment of bronchial wall attenuation with thin-section CT: An indicator of airflow limitation in chronic obstructive pulmonary disease. AJR Am J Roentgenol. 2010;195(2):363–9. doi: 10.2214/AJR.09.3653 20651191.

30. Tanabe N, Muro S, Sato S, Tanaka S, Oguma T, Kiyokawa H, et al. Longitudinal study of spatially heterogeneous emphysema progression in current smokers with chronic obstructive pulmonary disease. PLoS One. 2012;7(9):e44993. doi: 10.1371/journal.pone.0044993 23028728; PubMed Central PMCID: PMC3445600.

31. Kitaguchi Y, Yasuo M, Hanaoka M. Comparison of pulmonary function in patients with COPD, asthma-COPD overlap syndrome, and asthma with airflow limitation. Int J Chron Obstruct Pulmon Dis. 2016;11:991–7. doi: 10.2147/COPD.S105988 27274220; PubMed Central PMCID: PMC4869610.

32. Hardin M, Silverman EK, Barr RG, Hansel NN, Schroeder JD, Make BJ, et al. The clinical features of the overlap between COPD and asthma. Respir Res. 2011;12:127. doi: 10.1186/1465-9921-12-127 21951550; PubMed Central PMCID: PMC3204243.

33. Stockley RA, Mannino D, Barnes PJ. Burden and pathogenesis of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2009;6(6):524–6. doi: 10.1513/pats.200904-016DS 19741261.

34. Ind PW. COPD disease progression and airway inflammation: uncoupled by smoking cessation. Eur Respir J. 2005;26(5):764–6. doi: 10.1183/09031936.05.00102805 16264034.

35. Suzuki T, Tada Y, Kawata N, Matsuura Y, Ikari J, Kasahara Y, et al. Clinical, physiological, and radiological features of asthma-chronic obstructive pulmonary disease overlap syndrome. Int J Chron Obstruct Pulmon Dis. 2015;10:947–54. doi: 10.2147/COPD.S80022 26028967; PubMed Central PMCID: PMC4440433.

36. Kanazawa H. Role of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease. Med Sci Monit. 2007;13(11):RA189–95. 17968307.

37. Kasahara Y, Tuder RM, Cool CD, Lynch DA, Flores SC, Voelkel NF. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med. 2001;163(3 Pt 1):737–44. doi: 10.1164/ajrccm.163.3.2002117 11254533.

38. Li X, Wilson JW. Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med. 1997;156(1):229–33. doi: 10.1164/ajrccm.156.1.9607066 9230753.

39. Menezes AMB, Montes de Oca M, Perez-Padilla R, Nadeau G, Wehrmeister FC, Lopez-Varela MV, et al. Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma. Chest. 2014;145(2):297–304. doi: 10.1378/chest.13-0622 24114498.

40. Shimizu K, Hasegawa M, Makita H, Nasuhara Y, Konno S, Nishimura M. Comparison of airway remodelling assessed by computed tomography in asthma and COPD. Respir Med. 2011;105(9):1275–83. doi: 10.1016/j.rmed.2011.04.007 21646007.

41. Kosciuch J, Krenke R, Gorska K, Zukowska M, Maskey-Warzechowska M, Chazan R. Airway dimensions in asthma and COPD in high resolution computed tomography: can we see the difference? Respir Care. 2013;58(8):1335–42. doi: 10.4187/respcare.02175 23307823.

42. Niimi A, Matsumoto H, Amitani R, Nakano Y, Sakai H, Takemura M, et al. Effect of short-term treatment with inhaled corticosteroid on airway wall thickening in asthma. Am J Med. 2004;116(11):725–31. doi: 10.1016/j.amjmed.2003.11.026 15144908.

43. Hasegawa M, Makita H, Nasuhara Y, Odajima N, Nagai K, Ito Y, et al. Relationship between improved airflow limitation and changes in airway calibre induced by inhaled anticholinergic agents in COPD. Thorax. 2009;64(4):332–8. doi: 10.1136/thx.2008.103671 19074932.

44. Baarnes CB, Kjeldgaard P, Nielsen M, Miravitlles M, Ulrik CS. Identifying possible asthma-COPD overlap syndrome in patients with a new diagnosis of COPD in primary care. NPJ Prim Care Respir Med. 2017;27:16084. doi: 10.1038/npjpcrm.2016.84 28055002; PubMed Central PMCID: PMC5214698.

45. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Global Initiative for Chronic Obstructive Lung Disease 2019. Available from: https://goldcopd.org/gold-reports/.

Článok vyšiel v časopise


2019 Číslo 12