氣道黏液栓在慢性阻塞性肺疾病中的研究進展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

吳方燕 ¹ , 吳繁 ^1,2 , 夏亭亭 ³ , 周坤寧 ¹ ,  周玉民 ^1,2

1. ;
2. ;
3. ;

Corresponding?author：

周玉民, Email: zhouyumin410@126.com

Keywords：

DOI：

10.7507/1671-6205.202502041

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Abstract Full text Figures/Tables Video References Cited by

1.	Dunican EM, Elicker BM, Henry T, et al. Mucus plugs and emphysema in the pathophysiology of airflow obstruction and hypoxemia in smokers. Am J Respir Crit Care Med, 2021, 203(8): 957-968.
2.	Okajima Y, Come CE, Nardelli P, et al. Luminal plugging on chest ct scan: association with lung function, quality of life, and COPD clinical phenotypes. Chest, 2020, 158(1): 121-130.
3.	Diaz AA, Orejas JL, Grumley S, et al. Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease. JAMA, 2023, 329(21): 1832-1839.
4.	Tamura K, Shirai T, Hirai K, et al. Mucus plugs and small airway dysfunction in asthma, COPD, and asthma-COPD overlap. Allergy Asthma Immunol Res, 2022, 14(2): 196-209.
5.	Tanabe N, Shimizu K, Shima H, et al. Computed tomography mucus plugs and airway tree structure in patients with chronic obstructive pulmonary disease: Associations with airflow limitation, health-related independence and mortality. Respirology, 2024, 29(11): 951-961.
6.	Mettler SK, Nath HP, Grumley S, et al. Silent airway mucus plugs in COPD and clinical implications. Chest, 2024, 166(5): 1010-1019.
7.	Jin KN, Lee HJ, Park H, et al. Mucus plugs as precursors to exacerbation and lung function decline in COPD patients. Arch Bronconeumol, 2025, 61(3): 138-146.
8.	Wan E, Yen AA, Elalami R, et al. Airway mucus plugs on chest computed tomography are associated with exacerbations in COPD. Am J Respir Crit Care Med, 2025, 211(5): 814-822.
9.	Chassagnon G, Burgel PR. Mucus plugs in medium-sized airways: A novel imaging biomarker for phenotyping chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2021, 203(8): 932-934.
10.	Kirby M, Parraga G. CT evidence of airway luminal plugging in COPD: a new plug for targeted treatment?. Chest, 2020, 158(1): 7-8.
11.	Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J, 2016, 47(2): 410-419.
12.	Koo M, Kirby M. Mucus plugs: A treatable trait for preventing COPD exacerbations. Am J Respir Crit Care Med, 2025, 211(5): 685-686.
13.	Dunican EM, Elicker BM, Gierada DS, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest, 2018, 128(3): 997-1009.
14.	Abdalla M, Elalami R, Cho MH, et al. Airway mucus plugs in community-living adults: a study protocol. J Clin Exp Pathol, 2024, 14(3): 492.
15.	Tang M, Elicker BM, Henry T, et al. Mucus plugs persist in asthma, and changes in mucus plugs associate with changes in airflow over time. Am J Respir Crit Care Med, 2022, 205(9): 1036-1045.
16.	Boucher RC. Muco-obstructive lung diseases. N Engl J Med, 2019, 380(20): 1941-1953.
17.	Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev, 2006, 86(1): 245-278.
18.	Leith DE. Cough. Phys Ther, 1968, 48(5): 439-447.
19.	Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med, 2010, 363(23): 2233-2247.
20.	Kesimer M, Ford AA, Ceppe A, et al. Airway mucin concentration as a marker of chronic bronchitis. N Engl J Med, 2017, 377(10): 911-922.
21.	Button B, Goodell HP, Atieh E, et al. Roles of mucus adhesion and cohesion in cough clearance. Proc Natl Acad Sci U S A, 2018, 115(49): 12501-12506.
22.	Worlitzsch D, Tarran R, Ulrich M, et al. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest, 2002, 109(3): 317-325.
23.	Cowley ES, Kopf SH, LaRiviere A, et al. Pediatric cystic fibrosis sputum can be chemically dynamic, anoxic, and extremely reduced due to hydrogen sulfide formation. mBio, 2015, 6(4): e767.
24.	Button B, Cai LH, Ehre C, et al. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science, 2012, 337(6097): 937-941.
25.	Tanabe N, Matsumoto H, Morimoto C, et al. Mucus plugging on computed tomography and the sputum microbiome in patients with asthma, chronic obstructive pulmonary disease, and asthma-COPD overlap. Allergol Int, 2024, 73(4): 515-523.
26.	Audousset C, Swaleh S, Olivenstein R, et al. Mucus plugs in the airways of asthmatic subjects and smoking status. Respir Res, 2024, 25(1): 52.
27.	Tran C, Singh GV, Haider E, et al. Luminal mucus plugs are spatially associated with airway wall thickening in severe COPD and asthma: a single-centered, retrospective, observational study. Respir Med, 2022, 202: 106982.
28.	Kooner HK, Serajeddini H, Eddy RL, et al. Airway mucus in older people without chronic respiratory illness. Chest, 2024, 166(3): 429-432.
29.	Agustí A, Celli BR, Criner GJ, et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J, 2023, 61(4): 2300239.
30.	Mullen JB, Wright JL, Wiggs BR, et al. Reassessment of inflammation of airways in chronic bronchitis. Br Med J (Clin Res Ed), 1985, 291(6504): 1235-1239.
31.	Nadel JA. Mucous hypersecretion and relationship to cough. Pulm Pharmacol Ther, 2013, 26(5): 510-513.
32.	Vestbo J, Prescott E, Lange P. Association of chronic mucus hypersecretion with FEV₁ decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group . Am J Respir Crit Care Med, 1996, 153(5): 1530-1535.
33.	Prescott E, Lange P, Vestbo J. Chronic mucus hypersecretion in COPD and death from pulmonary infection. Eur Respir J, 1995, 8(8): 1333-1338.
34.	Melton L. Does mucus hypersecretion matter in airway disease?. Lancet, 2002, 359(9321): 1924.
35.	Kim V, Dolliver WR, Nath HP, et al. Mucus plugging on computed tomography and chronic bronchitis in chronic obstructive pulmonary disease. Respir Res, 2021, 22(1): 110.
36.	Widdicombe J. Airway receptors. Respir Physiol, 2001, 125(1-2): 3-15.
37.	McGarvey L, Rubin BK, Ebihara S, et al. Global physiology and pathophysiology of cough: Part 2. Demographic and clinical considerations: Chest expert panel report. Chest, 2021, 160(4): 1413-1423.
38.	Calzetta L, Ritondo BL, Zappa MC, et al. The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review. Eur Respir Rev, 2022, 31(164): 210196.
39.	Yang IA, Clarke MS, Sim EH, et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2012, 2012(7): D2991.
40.	Montuschi P, Macagno F, Valente S, et al. Inhaled muscarinic acetylcholine receptor antagonists for treatment of COPD. Curr Med Chem, 2013, 20(12): 1464-1476.
41.	Hogg JC, Chu FS, Tan WC, et al. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med, 2007, 176(5): 454-459.
42.	Huang BK, Elicker BM, Henry TS, et al. Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma. JCI Insight, 2024, 9(3): e174124.
43.	Kim V, Evans CM, Dickey BF. Dawn of a new era in the diagnosis and treatment of airway mucus dysfunction. Am J Respir Crit Care Med, 2019, 199(2): 133-134.
44.	Svenningsen S, Nair P. Persistent airway plugs: a call for clinical recognition and novel therapies. Am J Respir Crit Care Med, 2022, 205(9): 977-978.
45.	McIntosh MJ, Kooner HK, Eddy RL, et al. CT mucus score and (129)Xe MRI ventilation defects after 2. 5 years' anti-IL-5Rα in eosinophilic asthma. Chest, 2023, 164(1): 27-38.
46.	Svenningsen S, Haider EA, Eddy RL, et al. Normalisation of MRI ventilation heterogeneity in severe asthma by dupilumab. Thorax, 2019, 74(11): 1087-1088.
47.	Anai M, Yoshida C, Izumi H, et al. Successful treatment with dupilumab for mucus plugs in severe asthma. Respirol Case Rep, 2023, 11(1): e1074.
48.	Hearn AP, Mak MS, Budaj I, et al. The prevalence of mucus plugging in severe eosinophilic asthma and its relationship to clinical efficacy of anti-IL-5R treatment. J Allergy Clin Immunol Pract, 2022, 10(4): 1102-1103.
49.	Castro M, Papi A, Porsbjerg C, et al. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med, 2025, 13(3): 208-220.

1. Dunican EM, Elicker BM, Henry T, et al. Mucus plugs and emphysema in the pathophysiology of airflow obstruction and hypoxemia in smokers. Am J Respir Crit Care Med, 2021, 203(8): 957-968.
2. Okajima Y, Come CE, Nardelli P, et al. Luminal plugging on chest ct scan: association with lung function, quality of life, and COPD clinical phenotypes. Chest, 2020, 158(1): 121-130.
3. Diaz AA, Orejas JL, Grumley S, et al. Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease. JAMA, 2023, 329(21): 1832-1839.
4. Tamura K, Shirai T, Hirai K, et al. Mucus plugs and small airway dysfunction in asthma, COPD, and asthma-COPD overlap. Allergy Asthma Immunol Res, 2022, 14(2): 196-209.
5. Tanabe N, Shimizu K, Shima H, et al. Computed tomography mucus plugs and airway tree structure in patients with chronic obstructive pulmonary disease: Associations with airflow limitation, health-related independence and mortality. Respirology, 2024, 29(11): 951-961.
6. Mettler SK, Nath HP, Grumley S, et al. Silent airway mucus plugs in COPD and clinical implications. Chest, 2024, 166(5): 1010-1019.
7. Jin KN, Lee HJ, Park H, et al. Mucus plugs as precursors to exacerbation and lung function decline in COPD patients. Arch Bronconeumol, 2025, 61(3): 138-146.
8. Wan E, Yen AA, Elalami R, et al. Airway mucus plugs on chest computed tomography are associated with exacerbations in COPD. Am J Respir Crit Care Med, 2025, 211(5): 814-822.
9. Chassagnon G, Burgel PR. Mucus plugs in medium-sized airways: A novel imaging biomarker for phenotyping chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2021, 203(8): 932-934.
10. Kirby M, Parraga G. CT evidence of airway luminal plugging in COPD: a new plug for targeted treatment?. Chest, 2020, 158(1): 7-8.
11. Agusti A, Bel E, Thomas M, et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J, 2016, 47(2): 410-419.
12. Koo M, Kirby M. Mucus plugs: A treatable trait for preventing COPD exacerbations. Am J Respir Crit Care Med, 2025, 211(5): 685-686.
13. Dunican EM, Elicker BM, Gierada DS, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest, 2018, 128(3): 997-1009.
14. Abdalla M, Elalami R, Cho MH, et al. Airway mucus plugs in community-living adults: a study protocol. J Clin Exp Pathol, 2024, 14(3): 492.
15. Tang M, Elicker BM, Henry T, et al. Mucus plugs persist in asthma, and changes in mucus plugs associate with changes in airflow over time. Am J Respir Crit Care Med, 2022, 205(9): 1036-1045.
16. Boucher RC. Muco-obstructive lung diseases. N Engl J Med, 2019, 380(20): 1941-1953.
17. Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev, 2006, 86(1): 245-278.
18. Leith DE. Cough. Phys Ther, 1968, 48(5): 439-447.
19. Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med, 2010, 363(23): 2233-2247.
20. Kesimer M, Ford AA, Ceppe A, et al. Airway mucin concentration as a marker of chronic bronchitis. N Engl J Med, 2017, 377(10): 911-922.
21. Button B, Goodell HP, Atieh E, et al. Roles of mucus adhesion and cohesion in cough clearance. Proc Natl Acad Sci U S A, 2018, 115(49): 12501-12506.
22. Worlitzsch D, Tarran R, Ulrich M, et al. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J Clin Invest, 2002, 109(3): 317-325.
23. Cowley ES, Kopf SH, LaRiviere A, et al. Pediatric cystic fibrosis sputum can be chemically dynamic, anoxic, and extremely reduced due to hydrogen sulfide formation. mBio, 2015, 6(4): e767.
24. Button B, Cai LH, Ehre C, et al. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science, 2012, 337(6097): 937-941.
25. Tanabe N, Matsumoto H, Morimoto C, et al. Mucus plugging on computed tomography and the sputum microbiome in patients with asthma, chronic obstructive pulmonary disease, and asthma-COPD overlap. Allergol Int, 2024, 73(4): 515-523.
26. Audousset C, Swaleh S, Olivenstein R, et al. Mucus plugs in the airways of asthmatic subjects and smoking status. Respir Res, 2024, 25(1): 52.
27. Tran C, Singh GV, Haider E, et al. Luminal mucus plugs are spatially associated with airway wall thickening in severe COPD and asthma: a single-centered, retrospective, observational study. Respir Med, 2022, 202: 106982.
28. Kooner HK, Serajeddini H, Eddy RL, et al. Airway mucus in older people without chronic respiratory illness. Chest, 2024, 166(3): 429-432.
29. Agustí A, Celli BR, Criner GJ, et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J, 2023, 61(4): 2300239.
30. Mullen JB, Wright JL, Wiggs BR, et al. Reassessment of inflammation of airways in chronic bronchitis. Br Med J (Clin Res Ed), 1985, 291(6504): 1235-1239.
31. Nadel JA. Mucous hypersecretion and relationship to cough. Pulm Pharmacol Ther, 2013, 26(5): 510-513.
32. Vestbo J, Prescott E, Lange P. Association of chronic mucus hypersecretion with FEV₁ decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group . Am J Respir Crit Care Med, 1996, 153(5): 1530-1535.
33. Prescott E, Lange P, Vestbo J. Chronic mucus hypersecretion in COPD and death from pulmonary infection. Eur Respir J, 1995, 8(8): 1333-1338.
34. Melton L. Does mucus hypersecretion matter in airway disease?. Lancet, 2002, 359(9321): 1924.
35. Kim V, Dolliver WR, Nath HP, et al. Mucus plugging on computed tomography and chronic bronchitis in chronic obstructive pulmonary disease. Respir Res, 2021, 22(1): 110.
36. Widdicombe J. Airway receptors. Respir Physiol, 2001, 125(1-2): 3-15.
37. McGarvey L, Rubin BK, Ebihara S, et al. Global physiology and pathophysiology of cough: Part 2. Demographic and clinical considerations: Chest expert panel report. Chest, 2021, 160(4): 1413-1423.
38. Calzetta L, Ritondo BL, Zappa MC, et al. The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review. Eur Respir Rev, 2022, 31(164): 210196.
39. Yang IA, Clarke MS, Sim EH, et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2012, 2012(7): D2991.
40. Montuschi P, Macagno F, Valente S, et al. Inhaled muscarinic acetylcholine receptor antagonists for treatment of COPD. Curr Med Chem, 2013, 20(12): 1464-1476.
41. Hogg JC, Chu FS, Tan WC, et al. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med, 2007, 176(5): 454-459.
42. Huang BK, Elicker BM, Henry TS, et al. Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma. JCI Insight, 2024, 9(3): e174124.
43. Kim V, Evans CM, Dickey BF. Dawn of a new era in the diagnosis and treatment of airway mucus dysfunction. Am J Respir Crit Care Med, 2019, 199(2): 133-134.
44. Svenningsen S, Nair P. Persistent airway plugs: a call for clinical recognition and novel therapies. Am J Respir Crit Care Med, 2022, 205(9): 977-978.
45. McIntosh MJ, Kooner HK, Eddy RL, et al. CT mucus score and (129)Xe MRI ventilation defects after 2. 5 years' anti-IL-5Rα in eosinophilic asthma. Chest, 2023, 164(1): 27-38.
46. Svenningsen S, Haider EA, Eddy RL, et al. Normalisation of MRI ventilation heterogeneity in severe asthma by dupilumab. Thorax, 2019, 74(11): 1087-1088.
47. Anai M, Yoshida C, Izumi H, et al. Successful treatment with dupilumab for mucus plugs in severe asthma. Respirol Case Rep, 2023, 11(1): e1074.
48. Hearn AP, Mak MS, Budaj I, et al. The prevalence of mucus plugging in severe eosinophilic asthma and its relationship to clinical efficacy of anti-IL-5R treatment. J Allergy Clin Immunol Pract, 2022, 10(4): 1102-1103.
49. Castro M, Papi A, Porsbjerg C, et al. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med, 2025, 13(3): 208-220.

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