pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2011-0-4-118-124pulmo-368Research ArticleОБЗОРЫREVIEWЗначение мукоактивных препаратов в терапии хронической обструктивной болезни легкихRole of mucoactive drugs in treatment of chronic obstructive pulmonary diseaseАвдеевС. Н.AvdeevS. N.

д. м. н., проф., руководитель клинического отдела 

105077, Москва, ул. 11-я Парковая, 32, корп. 4. Тел. / факс: 8 (495) 465-52-64.

serg_avdeev@list.ruФГУ "НИИ пульмонологии" ФМБА РоссииРоссия20112808201104118124Copyright © Авдеев С.Н., 20112011Авдеев С.Н.Avdeev S.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/368

Значение мукоактивных препаратов в терапии хронической обструктивной болезни легких.

Role of mucoactive drugs in treatment of chronic obstructive pulmonary disease.

хроническая обструктивная болезнь легкиххронический бронхитмукоактивная терапияамброксолchronic obstructive pulmonary diseasechronic bronchitismucoactive therapyambroxolReferencesGlobal Initiative for Chronic Obstructive Lung Diseas (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI / WHO workshop report. The 2010 report is available on www.goldcopd.comGlobal Initiative for Chronic Obstructive Lung Diseas (GOLD). Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI / WHO workshop report. The 2010 report is available on www.goldcopd.comTashkin D.P., Celli B., Senn S. et al. for the UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N. Engl. J. Med. 2008; 359: 1543–1554.Tashkin D.P., Celli B., Senn S. et al. for the UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N. Engl. J. Med. 2008; 359: 1543–1554.Rogers D.F. Mucoactive agents for airway mucus hypersecretory diseases. Respir. Care 2007; 52: 1176–1193.Rogers D.F. Mucoactive agents for airway mucus hypersecretory diseases. Respir. Care 2007; 52: 1176–1193.Openshaw P.J., Turner)Warwick M. Observations on sputum production in patients with variable airflow obstruction; implications for the diagnosis of asthma and chronic bronchitis. Respir. Med. 1989; 83: 25–31.Openshaw P.J., Turner)Warwick M. Observations on sputum production in patients with variable airflow obstruction; implications for the diagnosis of asthma and chronic bronchitis. Respir. Med. 1989; 83: 25–31.Turner-Warwick M., Openshaw P. Sputum in asthma. Postgrad. Med. J. 1987; 63 (Suppl. 1): 79–82.Turner-Warwick M., Openshaw P. Sputum in asthma. Postgrad. Med. J. 1987; 63 (Suppl. 1): 79–82.Rogers D.F., Barnes P.J. Treatment of airway mucus hypersecretion. Ann. Med. 2006; 38: 116–125.Rogers D.F., Barnes P.J. Treatment of airway mucus hypersecretion. Ann. Med. 2006; 38: 116–125.Speizer F.E., Fay M.E., Dockery D.W. et al. Chronic obstructive pulmonary disease mortality in six U.S. cities. Am. Rev. Respir. Dis. 1989; 140 (Suppl. 3): S49–S55.Speizer F.E., Fay M.E., Dockery D.W. et al. Chronic obstructive pulmonary disease mortality in six U.S. cities. Am. Rev. Respir. Dis. 1989; 140 (Suppl. 3): S49–S55.Prescott E., Lange P., Vestbo J. Chronic mucus hypersecretion in COPD and death from pulmonary infection. Eur. Respir. J. 1995; 8: 1333–1338.Prescott E., Lange P., Vestbo J. Chronic mucus hypersecretion in COPD and death from pulmonary infection. Eur. Respir. J. 1995; 8: 1333–1338.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: 1530–1535.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: 1530–1535.Burgel P.-R., Nesme)Meyer P., Chanez P. et al. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009; 135: 975–982.Burgel P.-R., Nesme)Meyer P., Chanez P. et al. Cough and sputum production are associated with frequent exacerbations and hospitalizations in COPD subjects. Chest 2009; 135: 975–982.De Marco R., Accordini S., Cerveri I. et al. Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm. Am. J. Respir. Crit. Care Med. 2007; 175: 32–39.De Marco R., Accordini S., Cerveri I. et al. Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm. Am. J. Respir. Crit. Care Med. 2007; 175: 32–39.Kohansal R., Martinez)Camblor P., Agusti A. et al. The natural history of chronic air flow obstruction revisited: an analysis of the Framingham offspring cohort. Am. J. Respir. Crit. Care Med. 2009; 180: 3–10.Kohansal R., Martinez)Camblor P., Agusti A. et al. The natural history of chronic air flow obstruction revisited: an analysis of the Framingham offspring cohort. Am. J. Respir. Crit. Care Med. 2009; 180: 3–10.Hogg J.C., Chu F.S., Tan W.C. et al. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airways pathology. Am. J. Respir. Crit. Care Med. 2007; 176: 454–459.Hogg J.C., Chu F.S., Tan W.C. et al. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airways pathology. Am. J. Respir. Crit. Care Med. 2007; 176: 454–459.Vestbo J. Epidemiological studies in mucus hypersecretion. In: Chadwick D.J., Goode J.A., eds. Novartis foundation symposium 248: mucus hypersecration in respiratory disease. Malden: Wiley; 2002. 277–282.Vestbo J. Epidemiological studies in mucus hypersecretion. In: Chadwick D.J., Goode J.A., eds. Novartis foundation symposium 248: mucus hypersecration in respiratory disease. Malden: Wiley; 2002. 277–282.Burgel P.R., Nadel J.A. Epidermal growth factor receptormediated innate immune responses and their roles in airway diseases. Eur. Respir. J. 2008; 32: 1068–1081.Burgel P.R., Nadel J.A. Epidermal growth factor receptormediated innate immune responses and their roles in airway diseases. Eur. Respir. J. 2008; 32: 1068–1081.Randell S.H., Boucher R.C. Effective mucus clearance is essential for respiratory health. Am. J. Respir. Cell. Mol. Biol. 2006; 35: 20–28.Randell S.H., Boucher R.C. Effective mucus clearance is essential for respiratory health. Am. J. Respir. Cell. Mol. Biol. 2006; 35: 20–28.Innes A.L., Carrington S.D., Thornton D.J. et al. Ex vivo sputum analysis reveals impairment of protease-dependent mucus degradation by plasma proteins in acute asthma. Am. J. Respir. Crit. Care Med. 2009; 180: 203–210.Innes A.L., Carrington S.D., Thornton D.J. et al. Ex vivo sputum analysis reveals impairment of protease-dependent mucus degradation by plasma proteins in acute asthma. Am. J. Respir. Crit. Care Med. 2009; 180: 203–210.Lethem M.I., James S.L., Marriott C., Burke J.F. The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum. Eur. Respir. J. 1990; 3: 19–23.Lethem M.I., James S.L., Marriott C., Burke J.F. The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum. Eur. Respir. J. 1990; 3: 19–23.Tomkiewicz R.P., Kishioka C., Freeman J., Rubin B.K. DNA and actin filament ultrastructure in cystic fibrosis sputum. In: Baum G.L., Priel Z., Roth Y. et al., eds. Cilia, mucus, and mucociliary interactions. New York: Dekker; 1998. 333–341.Tomkiewicz R.P., Kishioka C., Freeman J., Rubin B.K. DNA and actin filament ultrastructure in cystic fibrosis sputum. In: Baum G.L., Priel Z., Roth Y. et al., eds. Cilia, mucus, and mucociliary interactions. New York: Dekker; 1998. 333–341.Shah S.A., Santago P., Rubin B.K. Quantification of biopolymer filament structure. Ultramicroscopy 2005; 104: 244–254.Shah S.A., Santago P., Rubin B.K. Quantification of biopolymer filament structure. Ultramicroscopy 2005; 104: 244–254.Hogg J.C., Chu F., Utokaparch S. et al. The nature of smallairway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350: 2645–2653.Hogg J.C., Chu F., Utokaparch S. et al. The nature of smallairway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350: 2645–2653.James A.L., Wenzel S. Clinical relevance of airway remodelling in airway diseases. Eur. Respir. J. 2007; 30: 134–155.James A.L., Wenzel S. Clinical relevance of airway remodelling in airway diseases. Eur. Respir. J. 2007; 30: 134–155.Macklem P.T., Proctor D.F., Hogg J.C. The stability of peripheral airways. Respir. Physiol. 1970; 8: 191–203.Macklem P.T., Proctor D.F., Hogg J.C. The stability of peripheral airways. Respir. Physiol. 1970; 8: 191–203.van der Vliet A., O'Neill C.A., Cross C.E. et al. Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids. Am. J. Physiol. 1999; 276: L289– L296.van der Vliet A., O'Neill C.A., Cross C.E. et al. Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids. Am. J. Physiol. 1999; 276: L289– L296.Rahman I., Adcock I.M. Oxidative stress and redox regulation of lung inflammation in COPD. Eur. Respir. J. 2006; 28: 219–242.Rahman I., Adcock I.M. Oxidative stress and redox regulation of lung inflammation in COPD. Eur. Respir. J. 2006; 28: 219–242.Ricevuti G., Mazzone A., Uccelli E. et al. Influence of erdosteine, a mucolytic agent, on amoxycillin penetration into sputum in patients with an infective exacerbation of chronic bronchitis. Thorax 1988; 43: 585–590.Ricevuti G., Mazzone A., Uccelli E. et al. Influence of erdosteine, a mucolytic agent, on amoxycillin penetration into sputum in patients with an infective exacerbation of chronic bronchitis. Thorax 1988; 43: 585–590.Moldeus P., Cotgreave I.A., Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 1986; 50: 31–42.Moldeus P., Cotgreave I.A., Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 1986; 50: 31–42.Gillissen A. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir. Med. 1998; 92: 609–623.Gillissen A. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir. Med. 1998; 92: 609–623.Curran D.R., Cohn L. Advances in mucous cell metaplasia: a plug for mucus as a therapeutic focus in chronic airway disease. Am. J. Respir. Cell. Mol. Biol. 2010; 42: 268–275.Curran D.R., Cohn L. Advances in mucous cell metaplasia: a plug for mucus as a therapeutic focus in chronic airway disease. Am. J. Respir. Cell. Mol. Biol. 2010; 42: 268–275.Woodruff P.G., Wolff M., Hohlfeld J.M. et al. Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2010; 181: 438–445.Woodruff P.G., Wolff M., Hohlfeld J.M. et al. Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2010; 181: 438–445.Singer M., Martin L.D., Vargaftig B.B. et al. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nature Med. 2004; 10: 193–196.Singer M., Martin L.D., Vargaftig B.B. et al. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nature Med. 2004; 10: 193–196.Zheng J.P., Kang J., Huang S.G. et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE study): a randomised placebo-controlled study. Lancet 2008; 371: 2013–2018.Zheng J.P., Kang J., Huang S.G. et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE study): a randomised placebo-controlled study. Lancet 2008; 371: 2013–2018.Poole P.J., Black P.N. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. Br. Med. J. 2001; 322: 1271–1274.Poole P.J., Black P.N. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. Br. Med. J. 2001; 322: 1271–1274.Poole P., Black P.N. Mucolytic agents for chronic bronchitis and chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2006; 19 (3): JulCD001287.Poole P., Black P.N. Mucolytic agents for chronic bronchitis and chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2006; 19 (3): JulCD001287.Rensch H., Seefeld H. Surfatant-mucus interaction. In: Robertson B., Van Golde L.M., Batenburg J.J., eds. Pulmonary surfactant. Amsterdam: Elsevier; 1984. 203–214.Rensch H., Seefeld H. Surfatant-mucus interaction. In: Robertson B., Van Golde L.M., Batenburg J.J., eds. Pulmonary surfactant. Amsterdam: Elsevier; 1984. 203–214.Haagsman H.P., Van Golde L.M. Lung surfactant and pulmonary toxicytology. Lung 1985; 163: 275–303.Haagsman H.P., Van Golde L.M. Lung surfactant and pulmonary toxicytology. Lung 1985; 163: 275–303.Jarstrand C. Role of surfactant in the pulmonary defence system. In: Robertson B., Van Golde L.M., Batenburg J.J., eds. Pulmonary surfactant. Amsterdam: Elsevier; 1984. 188–201.Jarstrand C. Role of surfactant in the pulmonary defence system. In: Robertson B., Van Golde L.M., Batenburg J.J., eds. Pulmonary surfactant. Amsterdam: Elsevier; 1984. 188–201.Disse B.G. The pharmacology of ambroxol-review and new results. Eur. J. Respir. Dis. 1987; Suppl.153: 255–262.Disse B.G. The pharmacology of ambroxol-review and new results. Eur. J. Respir. Dis. 1987; Suppl.153: 255–262.Beeh K.M., Beier J., Esperester A., Paul L.D. Antiinflammatory properties of ambroxol. Eur. J. Med. Res. 2008; 13: 557–562.Beeh K.M., Beier J., Esperester A., Paul L.D. Antiinflammatory properties of ambroxol. Eur. J. Med. Res. 2008; 13: 557–562.Фархутдинов У.Р., Петряков В.В., Фархутдинов Ш.У. Эффективность амброксола (ЛазолванаR) у больных хронической обструктивной болезнью легких. Пульмонология 2009; 1: 73–76.Фархутдинов У.Р., Петряков В.В., Фархутдинов Ш.У. Эффективность амброксола (ЛазолванаR) у больных хронической обструктивной болезнью легких. Пульмонология 2009; 1: 73–76.Фархутдинов У.Р., Фархутдинов Р.Р., Петряков В.В. и др. Влияние муколитической терапии на продукцию активных форм кислорода в крови у больных с обострением хронической обструктивной болезни легких. Тер. арх. 2010; 3: 29–32.Фархутдинов У.Р., Фархутдинов Р.Р., Петряков В.В. и др. Влияние муколитической терапии на продукцию активных форм кислорода в крови у больных с обострением хронической обструктивной болезни легких. Тер. арх. 2010; 3: 29–32.Ottonello L., Arduino N., Bertolotto M. et al. In vitro inhibition of human neutrophil histotoxicity by ambroxol: Evidence for a multistep mechanism. Br. J. Pharmacol. 2003; 140: 736–742.Ottonello L., Arduino N., Bertolotto M. et al. In vitro inhibition of human neutrophil histotoxicity by ambroxol: Evidence for a multistep mechanism. Br. J. Pharmacol. 2003; 140: 736–742.Li F., Wang W., Hu L. et al. Effect of ambroxol on pneumonia caused by pseudomonas aeruginosa with biofilm formation in an endotracheal intubation rat model. Chemotherapy 2011; 57: 173–180.Li F., Wang W., Hu L. et al. Effect of ambroxol on pneumonia caused by pseudomonas aeruginosa with biofilm formation in an endotracheal intubation rat model. Chemotherapy 2011; 57: 173–180.Lu Q., Yu J., Yang X. et al. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. Int. J. Antimicrob. Agents. 2010; 36: 211–215.Lu Q., Yu J., Yang X. et al. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. Int. J. Antimicrob. Agents. 2010; 36: 211–215.Xia D.-H., Xi L., Xv C. et al. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor β1 and tumor necrosis factor α. Med. Oncol. 2010; 27: 697–701.Xia D.-H., Xi L., Xv C. et al. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor β1 and tumor necrosis factor α. Med. Oncol. 2010; 27: 697–701.Olivieri D., Zavattini G., Tomasini G. et al. Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial. Protective effect of ambroxol against winter semester exacerbations: a double-blind study versus placebo. Respiration 1987; 51 (Suppl. 1): 42–51.Olivieri D., Zavattini G., Tomasini G. et al. Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial. Protective effect of ambroxol against winter semester exacerbations: a double-blind study versus placebo. Respiration 1987; 51 (Suppl. 1): 42–51.Puscinska E., Radwan L., Zielinski J. Effect of intravenous ambroxol hydrochloride on lung function and exercise capacity in patients with severe chronic obstructive pulmonary disease. Pneumonol. Alergol. Pol. 1994; 62: 246–249.Puscinska E., Radwan L., Zielinski J. Effect of intravenous ambroxol hydrochloride on lung function and exercise capacity in patients with severe chronic obstructive pulmonary disease. Pneumonol. Alergol. Pol. 1994; 62: 246–249.Malerba M., Ponticiello A., Radaeli A. et al. Effect of twelvemonths therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial). Pulm. Pharmacol. Ther. 2004; 17: 27–34.Malerba M., Ponticiello A., Radaeli A. et al. Effect of twelvemonths therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial). Pulm. Pharmacol. Ther. 2004; 17: 27–34.

The authors declare that there are no conflicts of interest present.