Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지
DOI QR코드

DOI QR Code

The Relationship between Airway Inflammation and Exacerbation in Chronic Obstructive Pulmonary Disease

  • Perng, Diahn-Warng (Department of Chest Medicine, Taipei Veterans General Hospital) ;
  • Chen, Pei-Ku (Department of Chest Medicine, Taipei Veterans General Hospital)
  • Received : 2017.07.25
  • Accepted : 2017.07.31
  • Published : 2017.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory response and airflow limitation. Acute exacerbation involves increased inflammatory burden leading to worsening respiratory symptoms, including dyspnea and sputum production. Some COPD patients have frequent exacerbations (two or more exacerbations per year). A substantial proportion of COPD patients may remain stable without exacerbation. Bacterial and viral infections are the most common causative factors that breach airway stability and lead to exacerbation. The increasing prevalence of exacerbation is associated with deteriorating lung function, hospitalization, and risk of death. In this review, we summarize the mechanisms of airway inflammation in COPD and discuss how bacterial or viral infection, temperature, air pollution, eosinophilic inflammation, and concomitant chronic diseases increase airway inflammation and the risk of exacerbation.

Keywords

References

  1. National Institutes of Health; National Heart, Lung, and Blood Institute. Global Initiative for Chronic Obstructive Lung Disease: global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO workshop report, publication No. 2701. Bethesda, MD: National Institutes of Health; National Heart, Lung, and Blood Institute; 2001.
  2. Fujimoto K, Yasuo M, Urushibata K, Hanaoka M, Koizumi T, Kubo K. Airway inflammation during stable and acutely exacerbated chronic obstructive pulmonary disease. Eur Respir J 2005;25:640-6. https://doi.org/10.1183/09031936.05.00047504
  3. Sapey E, Stockley RA. COPD exacerbations. 2: aetiology. Thorax 2006;61:250-8. https://doi.org/10.1136/thx.2005.041822
  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;363:1128-38. https://doi.org/10.1056/NEJMoa0909883
  5. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645-53. https://doi.org/10.1056/NEJMoa032158
  6. Balzano G, Stefanelli F, Iorio C, De Felice A, Melillo EM, Martucci M, et al. Eosinophilic inflammation in stable chronic obstructive pulmonary disease: relationship with neutrophils and airway function. Am J Respir Crit Care Med 1999;160(5 Pt 1):1486-92. https://doi.org/10.1164/ajrccm.160.5.9810105
  7. Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a doubleblind, placebo-controlled biopsy study. Am J Respir Crit Care Med 2002;165:1592-6. https://doi.org/10.1164/rccm.2105025
  8. Lacoste JY, Bousquet J, Chanez P, Van Vyve T, Simony-Lafontaine J, Lequeu N, et al. Eosinophilic and neutrophilic inflammation in asthma, chronic bronchitis, and chronic obstructive pulmonary disease. J Allergy Clin Immunol 1993;92:537-48. https://doi.org/10.1016/0091-6749(93)90078-T
  9. Peleman RA, Rytila PH, Kips JC, Joos GF, Pauwels RA. The cellular composition of induced sputum in chronic obstructive pulmonary disease. Eur Respir J 1999;13:839-43. https://doi.org/10.1034/j.1399-3003.1999.13d24.x
  10. Stanescu D, Sanna A, Veriter C, Kostianev S, Calcagni PG, Fabbri LM, et al. Airways obstruction, chronic expectoration, and rapid decline of $FEV_1$ in smokers are associated with increased levels of sputum neutrophils. Thorax 1996;51:267-71. https://doi.org/10.1136/thx.51.3.267
  11. Perng DW, Huang HY, Chen HM, Lee YC, Perng RP. Characteristics of airway inflammation and bronchodilator reversibility in COPD: a potential guide to treatment. Chest 2004;126:375-81. https://doi.org/10.1378/chest.126.2.375
  12. Di Stefano A, Capelli A, Lusuardi M, Balbo P, Vecchio C, Maestrelli P, et al. Severity of airflow limitation is associated with severity of airway inflammation in smokers. Am J Respir Crit Care Med 1998;158:1277-85. https://doi.org/10.1164/ajrccm.158.4.9802078
  13. Finkelstein R, Fraser RS, Ghezzo H, Cosio MG. Alveolar inflammation and its relation to emphysema in smokers. Am J Respir Crit Care Med 1995;152(5 Pt 1):1666-72. https://doi.org/10.1164/ajrccm.152.5.7582312
  14. Vernooy JH, Lindeman JH, Jacobs JA, Hanemaaijer R, Wouters EF. Increased activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in induced sputum from patients with COPD. Chest 2004;126:1802-10. https://doi.org/10.1378/chest.126.6.1802
  15. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smokeinduced emphysema in mice. Science 1997;277:2002-4. https://doi.org/10.1126/science.277.5334.2002
  16. Churg A, Wang RD, Tai H, Wang X, Xie C, Dai J, et al. Macrophage metalloelastase mediates acute cigarette smokeinduced inflammation via tumor necrosis factor-alpha release. Am J Respir Crit Care Med 2003;167:1083-9. https://doi.org/10.1164/rccm.200212-1396OC
  17. Chou KT, Su KC, Huang SF, Hsiao YH, Tseng CM, Su VY, et al. Exhaled nitric oxide predicts eosinophilic airway inflam mation in COPD. Lung 2014;192:499-504. https://doi.org/10.1007/s00408-014-9591-8
  18. Dippolito R, Foresi A, Chetta A, Castagnaro A, Malorgio R, Marangio E, et al. Eosinophils in induced sputum from asymptomatic smokers with normal lung function. Respir Med 2001;95:969-74. https://doi.org/10.1053/rmed.2001.1191
  19. Chou KT, Su KC, Hsiao YH, Huang SF, Ko HK, Tseng CM, et al. Post-bronchodilator reversibility of $FEV_1$ and eosinophilic airway inflammation in COPD. Arch Bronconeumol 2017 Apr 21 [Epub]. https://doi.org/10.1016/j.arbres.2017.01.014.
  20. Chanez P, Vignola AM, O'Shaugnessy T, Enander I, Li D, Jeffery PK, et al. Corticosteroid reversibility in COPD is related to features of asthma. Am J Respir Crit Care Med 1997;155:1529-34. https://doi.org/10.1164/ajrccm.155.5.9154853
  21. Fujimoto K, Kubo K, Yamamoto H, Yamaguchi S, Matsuzawa Y. Eosinophilic inflammation in the airway is related to glucocorticoid reversibility in patients with pulmonary emphysema. Chest 1999;115:697-702. https://doi.org/10.1378/chest.115.3.697
  22. Brightling CE, Monteiro W, Ward R, Parker D, Morgan MD, Wardlaw AJ, et al. Sputum eosinophilia and shortterm response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2000;356:1480-5. https://doi.org/10.1016/S0140-6736(00)02872-5
  23. Brightling CE, McKenna S, Hargadon B, Birring S, Green R, Siva R, et al. Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease. Thorax 2005;60:193-8. https://doi.org/10.1136/thx.2004.032516
  24. Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE, et al. CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157(3 Pt 1):822-6. https://doi.org/10.1164/ajrccm.157.3.9709027
  25. Majo J, Ghezzo H, Cosio MG. Lymphocyte population and apoptosis in the lungs of smokers and their relation to emphysema. Eur Respir J 2001;17:946-53. https://doi.org/10.1183/09031936.01.17509460
  26. O'Shaughnessy TC, Ansari TW, Barnes NC, Jeffery PK. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with $FEV_1$. Am J Respir Crit Care Med 1997;155:852-7. https://doi.org/10.1164/ajrccm.155.3.9117016
  27. Chrysofakis G, Tzanakis N, Kyriakoy D, Tsoumakidou M, Tsiligianni I, Klimathianaki M, et al. Perforin expression and cytotoxic activity of sputum CD8+ lymphocytes in patients with COPD. Chest 2004;125:71-6. https://doi.org/10.1378/chest.125.1.71
  28. Liu AN, Mohammed AZ, Rice WR, Fiedeldey DT, Liebermann JS, Whitsett JA, et al. Perforin-independent CD8(+) T-cell-mediated cytotoxicity of alveolar epithelial cells is preferentially mediated by tumor necrosis factor-alpha: relative insensitivity to Fas ligand. Am J Respir Cell Mol Biol 1999;20:849-58. https://doi.org/10.1165/ajrcmb.20.5.3585
  29. Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-31. https://doi.org/10.1136/thx.2005.040527
  30. Jones PW, Willits LR, Burge PS, Calverley PM; Inhaled Steroids in Obstructive Lung Disease in Europe Study Investigators. Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations. Eur Respir J 2003;21:68-73. https://doi.org/10.1183/09031936.03.00013303
  31. Wei YF, Kuo PH, Tsai YH, Tao CW, Cheng SL, Lee CH, et al. Factors associated with the prescription of inhaled corticosteroids in GOLD group A and B patients with COPD: subgroup analysis of the Taiwan obstructive lung disease cohort. Int J Chron Obstruct Pulmon Dis 2015;10:1951-6.
  32. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med 2011;184:662-71. https://doi.org/10.1164/rccm.201104-0597OC
  33. Sethi S, Murphy TF. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev 2001;14:336-63. https://doi.org/10.1128/CMR.14.2.336-363.2001
  34. Wedzicha JA. Role of viruses in exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2004;1:115-20. https://doi.org/10.1513/pats.2306030
  35. Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006;173:1114-21. https://doi.org/10.1164/rccm.200506-859OC
  36. Gomez MI, Prince A. Airway epithelial cell signaling in response to bacterial pathogens. Pediatr Pulmonol 2008;43:11-9. https://doi.org/10.1002/ppul.20735
  37. Gomez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A, et al. Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med 2004;10:842-8. https://doi.org/10.1038/nm1079
  38. Adamo R, Sokol S, Soong G, Gomez MI, Prince A. Pseudomonas aeruginosa flagella activate airway epithelial cells through asialoGM1 and toll-like receptor 2 as well as tolllike receptor 5. Am J Respir Cell Mol Biol 2004;30:627-34. https://doi.org/10.1165/rcmb.2003-0260OC
  39. Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002;57:759-64. https://doi.org/10.1136/thorax.57.9.759
  40. Subauste MC, Jacoby DB, Richards SM, Proud D. Infection of a human respiratory epithelial cell line with rhinovirus: induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. J Clin Invest 1995;96:549-57. https://doi.org/10.1172/JCI118067
  41. Buchweitz JP, Harkema JR, Kaminski NE. Time-dependent airway epithelial and inflammatory cell responses induced by influenza virus A/PR/8/34 in C57BL/6 mice. Toxicol Pathol 2007;35:424-35. https://doi.org/10.1080/01926230701302558
  42. Ko FW, Hui DS. Air pollution and chronic obstructive pulmonary disease. Respirology 2012;17:395-401. https://doi.org/10.1111/j.1440-1843.2011.02112.x
  43. Persinger RL, Blay WM, Heintz NH, Hemenway DR, Janssen-Heininger YM. Nitrogen dioxide induces death in lung epithelial cells in a density-dependent manner. Am J Respir Cell Mol Biol 2001;24:583-90. https://doi.org/10.1165/ajrcmb.24.5.4340
  44. Devalia JL, Campbell AM, Sapsford RJ, Rusznak C, Quint D, Godard P, et al. Effect of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro . Am J Respir Cell Mol Biol 1993;9:271-8. https://doi.org/10.1165/ajrcmb/9.3.271
  45. Wagner U, Staats P, Fehmann HC, Fischer A, Welte T, Groneberg DA. Analysis of airway secretions in a model of sulfur dioxide induced chronic obstructive pulmonary disease (COPD). J Occup Med Toxicol 2006;1:12. https://doi.org/10.1186/1745-6673-1-12
  46. Medina-Ramon M, Zanobetti A, Schwartz J. The effect of ozone and PM10 on hospital admissions for pneumonia and chronic obstructive pulmonary disease: a national multicity study. Am J Epidemiol 2006;163:579-88. https://doi.org/10.1093/aje/kwj078
  47. Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, et al. Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 2006;295:1127-34. https://doi.org/10.1001/jama.295.10.1127
  48. Ghozikali MG, Mosaferi M, Safari GH, Jaafari J. Effect of exposure to $O_3$ , $NO_2$, and $SO_2$ on chronic obstructive pulmonary disease hospitalizations in Tabriz, Iran. Environ Sci Pollut Res Int 2015;22:2817-23. https://doi.org/10.1007/s11356-014-3512-5
  49. Tseng CM, Chen YT, Ou SM, Hsiao YH, Li SY, Wang SJ, et al. The effect of cold temperature on increased exacerbation of chronic obstructive pulmonary disease: a nationwide study. PLoS One 2013;8:e57066. https://doi.org/10.1371/journal.pone.0057066
  50. Koskela HO, Koskela AK, Tukiaineu HO. Bronchoconstriction due to cold weather in COPD. The roles of direct airway effects and cutaneous reflex mechanisms. Chest 1996;110:632-6. https://doi.org/10.1378/chest.110.3.632
  51. Takada K, Matsumoto S, Kojima E, Iwata S, Okachi S, Ninomiya K, et al. Prospective evaluation of the relationship between acute exacerbations of COPD and gastroesophageal reflux disease diagnosed by questionnaire. Respir Med 2011;105:1531-6. https://doi.org/10.1016/j.rmed.2011.03.009
  52. Casanova C, Baudet JS, del Valle Velasco M, Martin JM, Aguirre-Jaime A, de Torres JP, et al. Increased gastro-oesophageal reflux disease in patients with severe COPD. Eur Respir J 2004;23:841-5. https://doi.org/10.1183/09031936.04.00107004
  53. Rascon-Aguilar IE, Pamer M, Wludyka P, Cury J, Coultas D, Lambiase LR, et al. Role of gastroesophageal reflux symptoms in exacerbations of COPD. Chest 2006;130:1096-101. https://doi.org/10.1378/chest.130.4.1096
  54. Perng DW, Chang KT, Su KC, Wu YC, Wu MT, Hsu WH, et al. Exposure of airway epithelium to bile acids associated with gastroesophageal reflux symptoms: a relation to transforming growth factor-beta1 production and fibroblast proliferation. Chest 2007;132:1548-56. https://doi.org/10.1378/chest.07-1373
  55. Su KC, Wu YC, Chen CS, Hung MH, Hsiao YH, Tseng CM, et al. Bile acids increase alveolar epithelial permeability via mitogen-activated protein kinase, cytosolic phospholipase A2, cyclooxygenase-2, prostaglandin E2 and junctional proteins. Respirology 2013;18:848-56. https://doi.org/10.1111/resp.12086
  56. Perng DW, Wu YC, Tsai CC, Su KC, Liu LY, Hsu WH, et al. Bile acids induce CCN2 production through p38 MAP kinase activation in human bronchial epithelial cells: a factor contributing to airway fibrosis. Respirology 2008;13:983-9.
  57. Wu YC, Hsu PK, Su KC, Liu LY, Tsai CC, Tsai SH, et al. Bile acid aspiration in suspected ventilator-associated pneumonia. Chest 2009;136:118-24. https://doi.org/10.1378/chest.08-2668
  58. Patel IS, Vlahos I, Wilkinson TM, Lloyd-Owen SJ, Donaldson GC, Wilks M, et al. Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:400-7. https://doi.org/10.1164/rccm.200305-648OC
  59. Martinez-Garcia MA, Soler-Cataluna JJ, Donat Sanz Y, Catalan Serra P, Agramunt Lerma M, Ballestin Vicente J, et al. Factors associated with bronchiectasis in patients with COPD. Chest 2011;140:1130-7. https://doi.org/10.1378/chest.10-1758
  60. Martinez-Garcia MA, de la Rosa Carrillo D, Soler-Cataluna JJ, Donat-Sanz Y, Serra PC, Lerma MA, et al. Prognostic value of bronchiectasis in patients with moderate-to-severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013;187:823-31. https://doi.org/10.1164/rccm.201208-1518OC
  61. Menezes AM, 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;145:297-304. https://doi.org/10.1378/chest.13-0622
  62. 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. https://doi.org/10.1186/1465-9921-12-127
  63. Siva R, Green RH, Brightling CE, Shelley M, Hargadon B, McKenna S, et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J 2007;29:906-13. https://doi.org/10.1183/09031936.00146306
  64. Perng DW, Wu CC, Su KC, Lee YC, Perng RP, Tao CW. Inhaled fluticasone and salmeterol suppress eosinophilic airway inflammation in chronic obstructive pulmonary disease: relations with lung function and bronchodilator reversibility. Lung 2006;184:217-22. https://doi.org/10.1007/s00408-005-2586-8
  65. Pizzichini E, Pizzichini MM, Gibson P, Parameswaran K, Gleich GJ, Berman L, et al. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Respir Crit Care Med 1998;158(5 Pt 1):1511-7. https://doi.org/10.1164/ajrccm.158.5.9804028
  66. Hang LW, Hsu JY, Chang CJ, Wang HC, Cheng SL, Lin CH, et al. Predictive factors warrant screening for obstructive sleep apnea in COPD: a Taiwan National Survey. Int J Chron Obstruct Pulmon Dis 2016;11:665-73.
  67. Soler X, Gaio E, Powell FL, Ramsdell JW, Loredo JS, Malhotra A, et al. High prevalence of obstructive sleep apnea in patients with moderate to severe chronic obstructive pulmonary disease. Ann Am Thorac Soc 2015;12:1219-25.
  68. Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med 2010;182:325-31. https://doi.org/10.1164/rccm.200912-1869OC
  69. Wang Y, Hu K, Liu K, Li Z, Yang J, Dong Y, et al. Obstructive sleep apnea exacerbates airway inflammation in patients with chronic obstructive pulmonary disease. Sleep Med 2015;16:1123-30. https://doi.org/10.1016/j.sleep.2015.04.019
  70. Hanania NA, Donohue JF. Pharmacologic interventions in chronic obstructive pulmonary disease: bronchodilators. Proc Am Thorac Soc 2007;4:526-34. https://doi.org/10.1513/pats.200701-016FM
  71. Montuschi P. Drugs for chronic obstructive pulmonary disease. Curr Med Chem 2013;20:1461-3. https://doi.org/10.2174/0929867311320120001
  72. Bourbeau J, Christodoulopoulos P, Maltais F, Yamauchi Y, Olivenstein R, Hamid Q. Effect of salmeterol/fluticasone propionate on airway inflammation in COPD: a randomised controlled trial. Thorax 2007;62:938-43. https://doi.org/10.1136/thx.2006.071068
  73. Barnes NC, Qiu YS, Pavord ID, Parker D, Davis PA, Zhu J, et al. Antiinflammatory effects of salmeterol/fluticasone propionate in chronic obstructive lung disease. Am J Respir Crit Care Med 2006;173:736-43. https://doi.org/10.1164/rccm.200508-1321OC
  74. Perng DW, Tao CW, Su KC, Tsai CC, Liu LY, Lee YC. Antiinflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD. Eur Respir J 2009;33:778-84. https://doi.org/10.1183/09031936.00115308
  75. Pera T, Zuidhof A, Valadas J, Smit M, Schoemaker RG, Gosens R, et al. Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J 2011;38:789-96. https://doi.org/10.1183/09031936.00146610
  76. Wollin L, Pieper MP. Tiotropium bromide exerts anti-inflammatory activity in a cigarette smoke mouse model of COPD. Pulm Pharmacol Ther 2010;23:345-54. https://doi.org/10.1016/j.pupt.2010.03.008
  77. Rice KL, Kunisaki KM, Niewoehner DE. Role of tiotropium in the treatment of COPD. Int J Chron Obstruct Pulmon Dis 2007;2:95-105.
  78. Anderson R, Theron AJ, Steel HC, Durandt C, Tintinger GR, Feldman C. The beta-2-adrenoreceptor agonists, formoterol and indacaterol, but not salbutamol, effectively suppress the reactivity of human neutrophils in vitro. Mediators Inflamm 2014;2014:105420.
  79. Decramer ML, Chapman KR, Dahl R, Frith P, Devouassoux G, Fritscher C, et al. Once-daily indacaterol versus tiotropium for patients with severe chronic obstructive pulmonary disease (INVIGORATE): a randomised, blinded, parallelgroup study. Lancet Respir Med 2013;1:524-33. https://doi.org/10.1016/S2213-2600(13)70158-9
  80. Wedzicha JA, Decramer M, Ficker JH, Niewoehner DE, Sandstrom T, Taylor AF, et al. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respir Med 2013;1:199-209. https://doi.org/10.1016/S2213-2600(13)70052-3
  81. Miravitlles M, D'Urzo A, Singh D, Koblizek V. Pharmacological strategies to reduce exacerbation risk in COPD: a narrative review. Respir Res 2016;17:112. https://doi.org/10.1186/s12931-016-0425-5
  82. Chong J, Leung B, Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013;(11):CD002309.
  83. Walters JA, Tang JN, Poole P, Wood-Baker R. Pneumococcal vaccines for preventing pneumonia in chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2017;1:CD001390.
  84. Sehatzadeh S. Influenza and pneumococcal vaccinations for patients with chronic obstructive pulmonary disease (COPD): an evidence-based review. Ont Health Technol Assess Ser 2012;12:1-64.
  85. Qian Y, Willeke K, Grinshpun SA, Donnelly J, Coffey CC. Performance of N95 respirators: filtration efficiency for airborne microbial and inert particles. Am Ind Hyg Assoc J 1998;59:128-32. https://doi.org/10.1080/15428119891010389
  86. Ingebrigtsen TS, Marott JL, Vestbo J, Nordestgaard BG, Hallas J, Lange P. Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease. Respirology 2015;20:101-7. https://doi.org/10.1111/resp.12420
  87. Kiljander TO, Harding SM, Field SK, Stein MR, Nelson HS, Ekelund J, et al. Effects of esomeprazole 40 mg twice daily on asthma: a randomized placebo-controlled trial. Am J Respir Crit Care Med 2006;173:1091-7. https://doi.org/10.1164/rccm.200507-1167OC
  88. Angrill J, Agusti C, de Celis R, Rano A, Gonzalez J, Sole T, et al. Bacterial colonisation in patients with bronchiectasis: microbiological pattern and risk factors. Thorax 2002;57:15-9. https://doi.org/10.1136/thorax.57.1.15
  89. Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med 2011;365:689-98. https://doi.org/10.1056/NEJMoa1104623
  90. Uzun S, Djamin RS, Kluytmans JA, Mulder PG, van't Veer NE, Ermens AA, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2014;2:361-8. https://doi.org/10.1016/S2213-2600(14)70019-0
  91. Dal Negro R, Micheletto C, Tognella S, Visconti M, Turati C. Tobramycin nebulizer solution in severe COPD patients colonized with Pseudomonas aeruginosa : effects on bronchial inflammation. Adv Ther 2008;25:1019-30. https://doi.org/10.1007/s12325-008-0105-2
  92. Zanini A, Cherubino F, Zampogna E, Croce S, Pignatti P, Spanevello A. Bronchial hyperresponsiveness, airway inflammation, and reversibility in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2015;10:1155-61.
  93. Jin J, Liu X, Sun Y. The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function. Respir Res 2014;15:130. https://doi.org/10.1186/s12931-014-0130-1
  94. Singh B, Arora S, Khanna V. Association of severity of COPD with IgE and interleukin-1 beta. Monaldi Arch Chest Dis 2010;73:86-7.
  95. Kobayashi S, Hanagama M, Yamanda S, Ishida M, Yanai M. Inflammatory biomarkers in asthma-COPD overlap syndrome. Int J Chron Obstruct Pulmon Dis 2016;11:2117-23. https://doi.org/10.2147/COPD.S113647
  96. Negewo NA, McDonald VM, Baines KJ, Wark PA, Simpson JL, Jones PW, et al. Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD. Int J Chron Obstruct Pulmon Dis 2016;11:1495-504. https://doi.org/10.2147/COPD.S100338
  97. Barnes NC, Sharma R, Lettis S, Calverley PM. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Respir J 2016;47:1374-82. https://doi.org/10.1183/13993003.01370-2015
  98. Pavord ID, Lettis S, Locantore N, Pascoe S, Jones PW, Wedzicha JA, et al. Blood eosinophils and inhaled corticosteroid/long-acting beta-2 agonist efficacy in COPD. Thorax 2016;71:118-25. https://doi.org/10.1136/thoraxjnl-2015-207021
  99. Hernandez C, Abreu J, Abreu P, Colino R, Jimenez A. Effects of nasal positive airway pressure treatment on oxidative stress in patients with sleep apnea-hypopnea syndrome. Arch Bronconeumol 2006;42:125-9.
  100. Pinto P, Barbara C, Montserrat JM, Patarrao RS, Guarino MP, Carmo MM, et al. Effects of CPAP on nitrate and norepinephrine levels in severe and mild-moderate sleep apnea. BMC Pulm Med 2013;13:13. https://doi.org/10.1186/1471-2466-13-13

Cited by

  1. Plantamajoside Inhibits Lipopolysaccharide-Induced MUC5AC Expression and Inflammation through Suppressing the PI3K/Akt and NF-κB Signaling Pathways in Human Airway Epithelial Cells vol.41, pp.3, 2017, https://doi.org/10.1007/s10753-018-0733-7
  2. Independent factors associate with hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease requiring intensive care unit admission: Focusing on the eosinophil-t vol.14, pp.7, 2017, https://doi.org/10.1371/journal.pone.0218932
  3. Effects of High-Dose Vitamin D Replacement on the Serum Levels of Systemic Inflammatory Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease vol.16, pp.3, 2017, https://doi.org/10.1080/15412555.2019.1666812
  4. Elastases and elastokines: elastin degradation and its significance in health and disease vol.55, pp.3, 2017, https://doi.org/10.1080/10409238.2020.1768208
  5. The role of air pollution (PM and NO2) in COVID-19 spread and lethality: A systematic review vol.191, pp.None, 2017, https://doi.org/10.1016/j.envres.2020.110129
  6. Gallic acid ameliorates COPD-associated exacerbation in mice vol.476, pp.1, 2017, https://doi.org/10.1007/s11010-020-03905-5