Biofilm-dependent airway infections: A role for ambroxol?

Pulmonary Pharmacology and Therapeutics

Volumn 28, Issue 2, 2014, Pages 98-108

  Cataldi, M ^a   Sblendorio, V ^a   Leo, A ^b   Piazza, O ^c  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^c UNIVERSITY OF SALERNO   (Italy)

Author keywords

Ambroxol; Ambroxol hydrochloride (PubChem CID: 108013); Biofilm; Bronchiectasis; Chronic obstructive pulmonary disease; Cystic fibrosis; Ventilator associated pneumonia

Indexed keywords

AMBROXOL; ANTIBIOTIC AGENT; AQUAPORIN; BICARBONATE; ION CHANNEL; SODIUM POTASSIUM CHLORIDE COTRANSPORTER; ANTIINFLAMMATORY AGENT; EXPECTORANT AGENT;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ARTIFICIAL VENTILATION; BACTERIAL COLONIZATION; BIOFILM; BIOFILM DEPENDENT AIRWAY INFECTION; BRONCHIECTASIS; CHRONIC OBSTRUCTIVE LUNG DISEASE; CYSTIC FIBROSIS; DRUG EFFECT; HUMAN; MUCOCILIARY CLEARANCE; NEUTROPHIL; OPPORTUNISTIC INFECTION; PRIORITY JOURNAL; QUORUM SENSING; RESPIRATORY EPITHELIUM; RESPIRATORY TRACT DISEASE; RESPIRATORY TRACT INFECTION; TREATMENT RESPONSE; VENTILATOR ASSOCIATED PNEUMONIA; ANIMAL; DRUG EFFECTS; METABOLISM; MICROBIOLOGY; RESPIRATORY TRACT INFECTIONS;

AMBROXOL; ANIMALS; ANTI-INFLAMMATORY AGENTS; BIOFILMS; DRUG RESISTANCE, MICROBIAL; EXPECTORANTS; HUMANS; MUCOCILIARY CLEARANCE; NEUTROPHILS; RESPIRATORY TRACT INFECTIONS;

EID: 84904091578     PISSN: 10945539     EISSN: 15229629     Source Type: Journal    
DOI: 10.1016/j.pupt.2013.11.002     Document Type: Article

References (169)

1. Houtmeyers E., Gosselink R., Gayan-Ramirez G., Decramer M. Effects of drugs on mucus clearance. Eur Respir J 1999, 14:452-467.
2. Malerba M., Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol 2008, 4:1119-1129.
3. Hall-Stoodley L., Costerton J.W., Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2004 Feb, 2(2):95-108.
4. Høiby N., Ciofu O., Johansen H.K., Song Z.J., Moser C., Jensen P.Ø., et al. The clinical impact of bacterial biofilms. Int J Oral Sci 2011, 3:55-65.
5. Li Y.H., Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel) 2012, 12:2519-2538.
6. O'Toole G., Kaplan H.B., Kolter R. Biofilm formation as microbial development. Annu Rev Microbiol 2000, 54:49-79.
7. Bhardwaj A.K., Vinothkumar K., Rajpara N. Bacterial quorum sensing inhibitors: attractive alternatives for control of infectious pathogens showing multiple drug resistance. Recent Pat Antiinfect Drug Discov 2013, 8:68-83.
8. Schuster M., Sexton D.J., Diggle S.P., Greenberg E.P. Acyl-homoserine lactone quorum sensing: from evolution to application. Annu Rev Microbiol 2013, 67:43-63.
9. Davies J.C., Bilton D. Bugs, biofilms, and resistance in cystic fibrosis. Respir Care 2009, 54:628-640.
10. Wiener-Kronish J.P., Dorr H.I. Ventilator-associated pneumonia: problems with diagnosis and therapy. Best Pract Res Clin Anaesthesiol 2008, 22:437-449.
11. Di Bonito M., Caiazzo S., Iannazzone M., Miccichè V., De Marco G., De Robertis E., et al. Prognostic differences between VAP caused by Acinetobacter baumannii and VAP caused by other microorganisms. Transl Med UniSa 2012, 3:15-21.
12. Barbier F., Andremont A., Wolff M., Bouadma L. Hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. Curr Opin Pulm Med 2013, 19:216-228.
13. Chastre J., Fagon J.Y. Ventilator-associated pneumonia. Am J Respir Crit Care Med 2002, 165:867-903.
14. Timsit J.F., Zahar J.R., Chevret S. Attributable mortality of ventilator-associated pneumonia. Curr Opin Crit Care 2011, 17:464-471.
15. Safdar N., Dezfulian C., Collard H.R., Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 2005, 33:2184-2193.
16. Sottile F.D., Marrie T.J., Prough D.S., Hobgood C.D., Gower D.J., Webb L.X., et al. Nosocomial pulmonary infection: possible etiologic significance of bacterial adhesion to endotracheal tubes. Crit Care Med 1986, 14:265-270.
17. Gil-Perotin S., Ramirez P., Marti V., Sahuquillo J.M., Gonzalez E., Calleja I., et al. Implications of endotracheal tube biofilm in ventilator-associated pneumonia response: a state of concept. Crit Care 2012 May 23, 16(3):R93.
18. Lambiase A., Rossano F., Piazza O., Del Pezzo M., Catania M.R., Tufano R. Typing of Pseudomonas aeruginosa isolated from patients with VAP in an intensive care unit. New Microbiol 2009, 32:277-283.
19. Rello J., Torres A., Ricart M., Valles J., Gonzalez J., Artigas A., et al. Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes. Am J Respir Crit Care Med 1994, 150:1545-1549.
20. Adair C.G., Gorman S.P., Feron B.M., Byers L.M., Jones D.S., Goldsmith C.E., et al. Implications of endotracheal tube biofilm for ventilator-associated pneumonia. Intensive Care Med 1999, 25:1072-1076.
21. Safdar N., Crnich C.J., Maki D.G. The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention. Respir Care 2005, 50:725-739.
22. Estes R.J., Meduri G.U. The pathogenesis of ventilator-associated pneumonia: I. Mechanisms of bacterial transcolonization and airway inoculation. Intensive Care Med 1995, 21:365-383.
23. Pneumatikos I.A., Dragoumanis C.K., Bouros D.E. Ventilator-associated pneumonia or endotracheal tube-associated pneumonia? An approach to the pathogenesis and preventive strategies emphasizing the importance of endotracheal tube. Anesthesiology 2009, 110:673-680.
24. Branson R.D. The ventilator circuit and ventilator-associated pneumonia. Respir Care 2005, 50:774-785.
25. Restrepo R.D., Brown J.M., Hughes J.M. AARC clinical practice guidelines. Endotracheal suctioning of mechanically ventilated patients with artificial airways 2010. Respir Care 2010, 55:758-764. American Association for Respiratory Care.
26. Mietto C., Pinciroli R., Patel N., Berra L. Ventilator associated pneumonia: evolving definitions and preventive strategies. Respir Care 2013, 58:990-1007.
27. Kobayashi H., Kobayashi O., Kawai S. Pathogenesis and clinical manifestations of chronic colonization by Pseudomonas aeruginosa and its biofilms in the airway tract. JInfect Chemother 2009, 15:125-142.
28. Moreau-Marquis S., Stanton B.A., O'Toole G.A. Pseudomonas aeruginosa biofilm formation in the cystic fibrosis airway. Pulm Pharmacol Ther 2008, 21:595-599.
29. O'Sullivan B.P., Freedman S.D. Cystic fibrosis. Lancet 2009, 373:1891-1904.
30. Ratjen F., Döring G. Cystic fibrosis. Lancet 2003, 361:681-689.
31. Flume P.A. Pulmonary complications of cystic fibrosis. Respir Care 2009, 54:618-627.
32. Lyczak J.B., Cannon C.L., Pier G.B. Lung infections associated with cystic fibrosis. Clin Microbiol Rev 2002, 15:194-222.
33. Singh P.K., Schaefer A.L., Parsek M.R., Moninger T.O., Welsh M.J., Greenberg E.P. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 2000, 407:762-764.
34. Wagner V.E., Iglewski B.H. P.aeruginosa biofilms in CF Infection. Clinic Rev Allergy Immunol 2008, 35:124-134.
35. Ratjen F.A. Cystic fibrosis: pathogenesis and future treatment strategies. Respir Care 2009, 54:595-602.
36. Boucher R.C. New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J 2004, 23:146-158.
37. Mannino D.M. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest 2002, 121(Suppl.5):121S-126S.
38. Buist A.S., McBurnie M.A., Vollmer W.M., Gillespie S., Burney P., Mannino D.M., et al. International variation in the prevalence of COPD (the BOLD study): a population-based prevalence study. Lancet 2007, 370:741-750.
39. Lozano R., Naghavi M., Foreman K., Lim S., Shibuya K., Aboyans V., et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380:2095-2128.
40. Sethi S., Sethi R., Eschberger K., Lobbins P., Cai X., Grant B.J., et al. Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007, 176:356-361.
41. Eldika N., Sethi S. Role of nontypeable Haemophilus influenzae in exacerbations and progression of chronic obstructive pulmonary disease. Curr Opin Pulm Med 2006, 12:118-124.
42. Brusselle G.G., Joos G.F., Bracke K.R. New insights into the immunology of chronic obstructive pulmonary disease. Lancet 2011, 378:1015-1026.
43. Rovina N., Koutsoukou A., Koulouris N.G. Inflammation and immune response in COPD: where do we stand?. Mediators Inflamm 2013, 2013:413735.
44. Dancer R., Sansom D.M. Regulatory T cells and COPD. Thorax 2013, 68:1176-1178.
45. Drago L., Mattina R., Legnani D., Romano C.L., Vianello E., Ricci C., et al. Modulation of biofilm of strains isolated from patients with chronic obstructive pulmonary disease by levofloxacin, moxifloxacin, ciprofloxacin, amoxicillin/clavulanic acid and ceftriaxone. Int J Immunopathol Pharmacol 2011, 24:1027-1035.
46. Murphy T.F., Kirkham C. Biofilm formation by nontypeable Haemophilus influenzae: strain variability, outer membrane antigen expression and role of pili. BMC Microbiol 2002, 2:7.
47. Roveta S., Schito A.M., Marchese A., Schito G.C. Activity of moxifloxacin on biofilms produced invitro by bacterial pathogens involved in acute exacerbations of chronic bronchitis. Int J Antimicrob Agents 2007, 30:415-421.
48. Vandevelde N.M., Diaz Iglesias Y., Tulkens P.M., Rodriguez-Villalobos H., Liistro G., Boel A., et al. Relationship between antibiotic susceptibility to β-lactams (BL), clarithromycin (CLR), and fluoroquinolones (FQ) of Streptococcus pneumoniae (Sp) isolated from COPD patients and the ability to produce mature biofilm in an invitro model. Abstract of the 53rd interscience conference on antimicrobial agents and chemotherapy 2013.
49. Murphy T.F., Kirkham C., Sethi S., Lesse A.J. Expression of a peroxiredoxin-glutaredoxin by Haemophilus influenzae in biofilms and during human respiratory tract infection. FEMS Immunol Med Microbiol 2005, 44:81-89.
50. Pang B., Hong W., West-Barnette S.L., Kock N.D., Swords W.E. Diminished ICAM-1 expression and impaired pulmonary clearance of nontypeable Haemophilus influenzae in a mouse model of chronic obstructive pulmonary disease/emphysema. Infect Immun 2008, 76:4959-4967.
51. Sethi S., Murphy T.F. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev 2001, 14:336-363.
52. Sethi S., Evans N., Grant B.J., Murphy T.F. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. NEngl J Med 2002, 347:465-471.
53. Martínez-Solano L., Macia M.D., Fajardo A., Oliver A., Martinez J.L. Chronic Pseudomonas aeruginosa infection in chronic obstructive pulmonary disease. Clin Infect Dis 2008, 47:1526-1533.
54. Chalmers J.D., Hill A.T. Mechanisms of immune dysfunction and bacterial persistence in non-cystic fibrosis bronchiectasis. Mol Immunol 2013, 55:27-34.
55. Martínez-García M.Á., Soler-Cataluña J.J., Donat Sanz Y., Catalán Serra P., Agramunt Lerma M., Ballestín Vicente J., et al. Factors associated with bronchiectasis in patients with COPD. Chest 2011, 140:1130-1137.
56. Martínez-García M.A., de la Rosa Carrillo D., Soler-Cataluña J.J., Donat-Sanz Y., Serra P.C., Lerma M.A., et al. Prognostic value of bronchiectasis in patients with moderate-to-severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013, 187:823-831.
57. McShane P.J., Naureckas E.T., Tino G., Strek M.E. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2013, 188:647-656.
58. Stockley R.A. Bronchiectasis with chronic obstructive pulmonary disease: association or a further phenotype?. Am J Respir Crit Care Med 2013, 187:786-788.
59. McNabe M., Tennant R., Danelishvili L., Young L., Bermudez L.E. Mycobacterium avium ssp. hominissuis biofilm is composed of distinct phenotypes and influenced by the presence of antimicrobials. Clin Microbiol Infect 2011, 17:697-703.
60. Mirsaeidi M., Hadid W., Ericsoussi B., Rodgers D., Sadikot R.T. Non-tuberculous mycobacterial disease is common in patients with non-cystic fibrosis bronchiectasis. Int J Infect Dis 2013 Nov, 17(11):e1000-e1004.
61. Mah T.-F.C., O'Toole G.A. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 2001, 9:34-39.
62. Høiby N., Bjarnsholt T., Givskov M., Molin S., Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 2010, 35:322-332.
63. Vuong C., Voyich J.M., Fischer E.R., Braughton K.R., Whitney A.R., DeLeo F.R., et al. Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system. Cell Microbiol 2004, 6:269-275.
64. Jesaitis A.J., Franklin M.J., Berglund D., Sasaki M., Lord C.I., Bleazardet J.B., et al. Compromised host defense on Pseudomonas aeruginosa biofilms: characterization of neutrophil and biofilm interactions. JImmunol 2003, 171:4329-4339.
65. Johnson G.M., Lee D.A., Regelmann W.E., Gray E.D., Peters G., Quie P.G. Interference with granulocyte function by Staphylococcus epidermidis slime. Infect Immun 1986, 54:13-20.
66. Xie Z., Thompson A., Sobue T., Kashleva H., Xu H., Vasilakos J., et al. Candida albicans biofilms do not trigger reactive oxygen species and evade neutrophil killing. JInfect Dis 2012, 206:1936-1945.
67. Lu X., Roe F., Jesaitis A., Lewandowski Z., Liu X. Resistance of biofilms to the catalase inhibitor 3-amino-1,2,4-triazole. Biotechnol Bioeng 1998, 59:156-162.
68. Cerca N., Jefferson K.K., Oliveira R., Pier G.B., Azeredo J. Comparative antibody-mediated phagocytosis of Staphylococcus epidermidis cells grown in a biofilm or in the planktonic state. Infect Immun 2006, 74:4849-4855.
69. Kristian S.A., Birkenstock T.A., Sauder U., Mack D., Götz F., Landmann R. Biofilm formation induces C3a release and protects Staphylococcus epidermidis from IgG and complement deposition and from neutrophil-dependent killing. JInfect Dis 2008, 197:1028-1035.
70. Garcin F., Leone M., Antonini F., Charvet A., Albanèse J., Martin C. Non-adherence to guidelines: an avoidable cause of failure of empirical antimicrobial therapy in the presence of difficult-to-treat bacteria. Intensive Care Med 2010, 36:75-82.
71. Wilke M.H., Grube R.F., Bodmann K.F. Guideline-adherent initial intravenous antibiotic therapy for hospital-acquired/ventilator-associated pneumonia is clinically superior, saves lives and is cheaper than non guideline adherent therapy. Eur J Med Res 2011, 16:315-323.
72. El Solh A.A., Akinnusi M.E., Wiener-Kronish J.P., Lynch S.V., Pineda L.A., Szarpa K. Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia. Am J Respir Crit Care Med 2008, 178:513-519.
73. Coffin S.E., Klompas M., Classen D., Arias K.M., Podgorny K., Anderson D.J., et al. Practice recommendation of Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA): strategies to prevent ventilator-associated pneumonia in acute care hospitals. Infect Control Hosp Epidemiol 2008, 29:S31-S40.
74. Masterton R.G., Galloway A., French G., Street M., Armstrong J., Brown E., et al. Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy. JAntimicrob Chemother 2008, 62:5-34.
75. Muscedere J., Dodek P., Keenan S., Fowler R., Cook D., Heyland D., et al. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: prevention. JCrit Care 2008, 23:126-137.
76. Torres A., Ewig S., Lode H., Carlet J., European HAP working group Defining, treating and preventing hospital acquired pneumonia: European perspective. Intensive Care Med 2009, 35:9-29.
77. Reeve J.C. Instillation of normal saline before suctioning reduces the incidence of pneumonia in intubated and ventilated adults. Aust J Physiother 2009, 55:136.
78. Mogayzel P.J., Naureckas E.T., Robinson K.A., Mueller G., Hadjiliadis D., Hoag J.B., et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2013, 187:680-689.
79. Li F., Yu J., Yang H., Wan Z., Bai D. Effects of ambroxol on alginate of mature Pseudomonas aeruginosa biofilms. Curr Microbiol 2008, 57:1-7.
80. Riise G.C., Qvarfordt I., Larsson S., Eliasson V., Andersson B.A. Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells invitro. Respiration 2000, 67:552-558.
81. Hafez M.M., Aboulwafa M.M., Yassien M.A., Hassouna N.A. Activity of some mucolytics against bacterial adherence to mammalian cells. Appl Biochem Biotechnol 2009, 158:97-112.
82. Ndour C.T., Ahmed K., Nakagawa T., Nakano Y., Ichinose A., Tarhan G., et al. Modulating effects of mucoregulating drugs on the attachment of Haemophilus influenzae. Microb Pathog 2001, 30:121-127.
83. Lu Q., Yu J., Yang X., Wang J., Wang L., Lin Y., et al. Ambroxol interferes with Pseudomonas aeruginosa quorum sensing. Int J Antimicrob Agents 2010, 36:211-215.
84. Pulcrano G., Panellis D., De Domenico G., Rossano F., Catania M.R. Ambroxol influences voriconazole resistance of Candida parapsilosis biofilm. FEMS Yeast Res 2012, 12:430-438.
85. Paganin F., Bouvet O., Chanez P., Fabre D., Galtier M., Godard P., et al. Evaluation of the effects of ambroxol on the ofloxacin concentrations in bronchial tissues in COPD patients with infectious exacerbation. Biopharm Drug Dispos 1995, 16:393-401.
86. Gené R., Poderoso J.J., Corazza C., Lasala M.B., Wiemeyer J.C., Fernández M., et al. Influence of ambroxol on amoxicillin levels in bronchoalveolar lavage fluid. Arzneimittelforschung 1987, 37:967-968.
87. Spatola J., Poderoso J.J., Wiemeyer J.C., Fernandez M., Guerreiro R.B., Corazza C. Influence of ambroxol on lung tissue penetration of amoxicillin. Arzneimittelforschung 1987, 37:965-966.
88. Wiemeyer J.C. Influence of ambroxol on the bronchopulmonary level of antibiotics. Arzneimittelforschung 1981, 31:974-976.
89. Li F., Wang W., Hu L., Li L., Yu J. Effect of ambroxol on pneumonia caused by Pseudomonas aeruginosa with biofilm formation in an endotracheal intubation rat model. Chemotherapy 2011, 57:173-180.
90. Gao X., Huang Y., Han Y., Bai C.X., Wang G. The protective effects of ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats. Arch Med Sci 2011, 7:405-413.
91. Rubin B.K. An invitro comparison of the mucoactive properties of guaifenesin, iodinated glycerol, surfactant, and albuterol. Chest 1999, 116:195-200.
92. + absorption by canine airway epithelial cells in culture. JPharm Pharmacol 1991, 43:841-843.
93. + ion transport pathway in airways. Pol J Pharmacol 1998, 50:31-38.
94. Tyrakowski T., Sedlaczek A., Greczko I., Bartlomowicz M., Wojciechowska M. Ambroxol effect on transepithelial electrical potential difference of isolated tracheal wall. Pol J Pharmacol 1997, 49:53-58.
95. Verkman A.S., Song Y., Thiagarajah J.R. Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. Am J Physiol Cell Physiol 2003 Jan, 284(1):C2-C15.
96. Krane C.M., Fortner C.N., Hand A.R., McGraw D.W., Lorenz J.N., Wert S.E., et al. Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation. Proc Natl Acad Sci U S A 2001, 98(24):14114-14119.
97. Krane C.M., Deng B., Mutyam V., McDonald C.A., Pazdziorko S., Mason L., et al. Altered regulation of aquaporin gene expression in allergen and IL-13-induced mouse models of asthma. Cytokine 2009, 46:111-118.
98. Donaldson S.H., Bennett W.D., Zeman K.L., Knowles M.R., Tarran R., Boucher R.C. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. NEngl J Med 2006, 354:241-250.
99. Berdiev B.K., Qadri Y.J., Benos D.J. Assessment of the CFTR and ENaC association. Mol Biosyst 2009, 5:123-127.
100. Hasegawa I., Niisato N., Iwasaki Y., Marunaka Y. Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia. Biochem Biophys Res Commun 2006, 343:475-482.
101. Engelhardt J.F., Yankaskas J.R., Ernst S.A., Yang Y., Marino C.R., Boucher R.C., et al. Submucosal glands are the predominant site of CFTR expression in the human bronchus. Nat Genet 1992, 2:240-248.
102. Varelogianni G., Hussain R., Strid H., Oliynyk I., Roomans G.M., Johannesson M. Effect of ambroxol on chloride transport, CFTR and ENaC in cystic fibrosis airway epithelial cells. Cell Biol Int 2013 Jun 14, 10.1002/cbin.
103. Ben Y., Chen J., Zhu R., Gao L., Bai C. Upregulation of AQP3 and AQP5 induced by dexamethasone and ambroxol in A549 cells. Respir Physiol Neurobiol 2008, 161:111-118.
104. Dong C., Wang G., Li B., Xiao K., Ma Z., Huang H., et al. Anti-asthmatic agents alleviate pulmonary edema by upregulating AQP1 and AQP5 expression in the lungs of mice with OVA-induced asthma. Respir Physiol Neurobiol 2012, 181:21-28.
105. Snowden J.N., Beaver M., Smeltzer M.S., Kielian T. Biofilm-infected intracerebroventricular shunts elicit inflammation within the central nervous system. Infect Immun 2012, 80:3206-3214.
106. Clunes M.T., Boucher R.C. Introduction to section I: overview of approaches to study cystic fibrosis pathophysiology. Methods Mol Biol 2011, 742:3-14.
107. Su X., Wang L., Song Y., Bai C. Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide. Intensive Care Med 2004, 30:133-140.
108. Nawrocka A., Papierz W., Bialasiewicz P., Stolarek R., Komos J., Nowak D. N-acetylcysteine and ambroxol inhibit endotoxin-induced phagocyte accumulation in rat lungs. Pulm Pharmacol Ther 1999, 12:369-375.
109. Bianchi M., Mantovani A., Erroi A., Dinarello C.A., Ghezzi P. Ambroxol inhibits interleukin 1 and tumor necrosis factor production in human mononuclear cells. Agents Actions 1990, 31:275-279.
110. Pfeifer S., Zissel G., Kienast K., Muller-Quernheim J. Reduction of cytokine release of blood and bronchoalveolar mononuclear cells by ambroxol. Eur J Med Res 1997, 24:129-132.
111. Stokley R.A., Shaw J., Burnett D. Effect of ambroxol on neutrophil chemotaxis invitro. Agents Actions 1988, 24:292-296.
112. Nemery B., Vanlommel S., Verbeken E.K., Lauweryns J.M., Demedts M. Lung injury induced by paraquat, hyperoxia and cobalt chloride: effects of ambroxol. Pulm Pharmacol 1992, 5:53-60.
113. Stettner S., Ledwozyw A. The effect of ambroxol on bleomycin-induced changes in phospholipid composition of rat lung surfactant. Acta Physiol Hung 1995, 83:181-187.
114. Kim Y.K., Jang Y.Y., Han E.S., Lee C.S. Depressant effect of ambroxol on stimulated functional responses and cell death in rat alveolar macrophages exposed to silica invitro. JPharmacol Exp Ther 2002, 300:629-637.
115. Perin L., Donnini M., Diomede L., Romano M., Tacconi M.T., Luisetti M., et al. Protection against acute paraquat toxicity by ambroxol. Cytotechnology 1991, 5:S25-S27.
116. Zhi Q.M., Yang L.T., Sun H.C. Protective effect of ambroxol against paraquat-induced pulmonary fibrosis in rats. Intern Med 2011, 50:1879-1887.
117. Xia D.H., Xi L., Xv C., Mao W.D., Shen W.S., Shu Z.Q., et al. The protective effects of ambroxol on radiation lung injury and influence on production of transforming growth factor beta1 and tumor necrosis factor alpha. Med Oncol 2010, 27:697-701.
118. Ware L.B., Matthay M.A. The acute respiratory distress syndrome. NEngl J Med 2000, 342:1334-1349.
119. De Rose V. Mechanisms and markers of airway inflammation in cystic fibrosis. Eur Respir J 2002, 19:333-340.
120. Clark R.A., Stone P.J., El Hag A., Calore J.D., Franzblau C. Myeloperoxidase-catalyzed inactivation of alpha 1-protease inhibitor by human neutrophils. Biol Chem J 1981, 256:3348-3353.
121. Ossanna P.J., Test S.T., Matheson N.R., Regiani S., Weiss S.J. Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions. JClin Invest 1986, 77:1936-1951.
122. Felix K., Pairet M., Zimmermann R. The antioxidative activity of the mucoregulatory agents: ambroxol, bromhexine and N-acetyl-L-cysteine. A pulse radiolysis study. Life Sci 1996, 59:1141-1147.
123. Gillissen A., Bartling A., Schoen S., Schultze-Werninghause G. Antioxidant function of ambroxol in mononuclear and polymorphonuclear cellsinvitro. Lung 1997, 175:235-242.
124. Gillissen A., Scharling B., Jaworska M., Bartling A., Raske K., Schultze-Werninghause G. Oxidant scavenger function of ambroxol invitro: a comparison with N-acetylcysteine. Res Exp Med 1997, 196:389-398.
125. Gillissen A., Nowak D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir Med 1998, 92:609-623.
126. Lapenna D., de Gioia S., Ciofani G., Cuccurullo F. Ambroxol is a scavenger of hypochlorous acid and monochloramine. Pharmacology 1994, 49:132-135.
127. Nowak D., Antczak A., Pietras T., Bialasiewicz P., Krol M. Protective effect of ambroxol against heat- and hydrogen peroxide-induced damage to lung lipids in mice. Eur Respir J 1994, 7:1629-1634.
128. Koh J.Y., Han E.S., Lee C.S. Protective action of ambroxol on the oxidative damage of lipid, hyaluronic acid and collagen. JAppl Pharmacol 1998, 6:111-118.
129. Cho Y., Jang Y.Y., Han E.S., Lee C.S. The inhibitory effect of ambroxol on hypochlorous acid-induced tissue damage and respiratory burst of phagocytic cells. Eur J Pharmacol 1999, 383:83-91.
130. Ottonello L., Arduino N., Bertolotto M., Dapino P., Mancini M., Dallegri F. Invitro inhibition of human neutrophil histotoxicity by ambroxol: evidence for a multistep mechanism. Br J Pharmacol 2003, 140:736-742.
131. Gibbs B.F., Schmutzler W., Vollrath I.B., Brosthardt P., Braam U., Wolff H.H., et al. Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells. Inflamm Res 1999, 48:86-93.
132. Gibbs B.F., Wolff H.H., Grabbe J. Ambroxol inhibits IgE-dependent mediator secretion from human skin mast cells. Inflamm Res 2000, 49(Suppl.1):S17-S18.
133. 2+ change in degraded immunoglobulin G-activated neutrophils. Pharmacol Toxicol 1999, 84:81-87.
134. Lee C.S., Jang Y.Y., Song J.S., Song J.H., Han E.S. Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells. Pharmacol Toxicol 2002, 91:140-149.
135. Severina I.S., Bussygina O.G., Pyatakova N.V., Khropov Y.V., Krasnoperov R.A. Ambroxol as an inhibitor of nitric oxide-dependent activation of soluble guanylate cyclase. Eur J Pharmacol 2000, 407:61-64.
136. Ricciardolo F.L., Di Stefano A., Sabatini F., Folkerts G. Reactive nitrogen species in the respiratory tract. Eur J Pharmacol 2006, 533:240-252.
137. Andreadis A.A., Hazen S.L., Comhair S.A., Erzurum S.C. Oxidative and nitrosative events in asthma. Free Radic Biol Med 2003, 35:213-225.
138. Kharitonov S.A., Barnes P.J. Nitric oxide, nitrotyrosine, and nitric oxide modulators in asthma and chronic obstructive pulmonary disease. Curr Allergy Asthma Rep 2003, 3:121-129.
139. Lang J.D., McArdle P.J., O'Reilly P.J., Matalon S. Oxidant-antioxidant balance in acute lung injury. Chest 2002, 122(Suppl.6):314S-320S.
140. Morán J.M., Ortiz-Ortiz M.A., Ruiz-Mesa L.M., Fuentes J.M. Nitric oxide in paraquat-mediated toxicity: a review. JBiochem Mol Toxicol 2010, 24:402-409.
141. Ricciardolo F.L., Caramori G., Ito K., Capelli A., Brun P., Abatangelo G., et al. Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease. JAllergy Clin Immunol 2005, 116:1028-1035.
142. Hallman M., Glumoff V., Rämet M. Surfactant in respiratory distress syndrome and lung injury. Comp Biochem Physiol A Mol Integr Physiol 2001, 129:287-294.
143. Putman E., van Golde L.M., Haagsman H.P. Toxic oxidant species and their impact on the pulmonary surfactant system. Lung 1997, 175:75-103.
144. Rahman I. Oxidative stress in pathogenesis of chronic obstructive pulmonary disease: cellular and molecular mechanisms. Cell Biochem Biophys 2005, 43:167-188.
145. Gil J., Thurnheer U. Morphometric evaluation of ultrastructural changes in type II alveolar cells of rat lung produced by bromhexine. Respiration 1971, 28:438-456.
146. Cerutti P., Kapanci Y. Effects of metabolite VIII of bromexine (Na-872) on type II epithelium of the lung: an experimental and morphological study with reference to surfactant secretion. Respiration 1979, 37:241-251.
147. von Wichert P., Bavendamm U., von Teichmann M., Muller G., Thalheim E., Wilke A., et al. Increased incorporation of fatty acids into phospholipids of lungs and livers of rabbits under the influence of bromhexine and ambroxol. Naunyn Schmiedebergs Arch Pharmacol 1977, 297:269-273.
148. Wirtz H.R. Effect of ambroxol on surfactant secretion and synthesis in isolated type II alveolar cells. Pneumologie 2000, 54:278-283.
149. Seifart C., Clostermann U., Seifart U., Muller B., Vogelmeier C., von Wichert P., et al. Cell-specific modulation of surfactant proteins by ambroxol treatment. Toxicol Appl Pharmacol 2005, 203:27-35.
150. Tokieda K., Iwamoto H.S., Bachurski C., Wert S.E., Hull W.M., Ikeda K., et al. Surfactant protein-B-deficient mice are susceptible to hyperoxic lung injury. Am J Respir Cell Mol Biol 1999, 21:463-472.
151. Sepulveda J., Velasquez B.J. Study on the influence of NA-872 (ambroxol) and dexamethasone on the differentiation of Clara cells in albino mice. Respiration 1982, 43:363-388.
152. Kostakioti M., Hadjifrangiskou M., Hultgren S.J. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med 2013, 3:a010306.
153. Kollef M.H., Afessa B., Anzueto A., Veremakis C., Kerr K.M., Margolis B.D., et al. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAm Med Assoc 2008, 300:805-813.
154. Machado M.C., Tarquinio K.M., Webster T.J. Decreased Staphylococcus aureus biofilm formation on nanomodified endotracheal tubes: a dynamic airway model. Int J Nanomed 2012, 7:3741-3750.
155. Berra L., Coppadoro A., Bittner E.A., Kolobow T., Laquerriere P., Pohlmann J.R., et al. Aclinical assessment of the Mucus Shaver: a device to keep the endotracheal tube free from secretions. Crit Care Med 2012, 40:119-124.
156. Biel M.A., Sievert C., Usacheva M., Teichert M., Wedell E., Loebel N., et al. Reduction of endotracheal tube biofilms using antimicrobial photodynamic therapy. Lasers Surg Med 2011, 43:586-590.
157. Li Q., Yao G., Zhu X. High-dose ambroxol reduces pulmonary complications in patients with acute cervical spinal cord injury after surgery. Neurocrit Care 2012, 16:267-272.
158. Ulas M.M., Hizarci M., Kunt A., Ergun K., Kocabeyoglu S.S., Korkmaz K., et al. Protective effect of ambroxol on pulmonary function after cardiopulmonary bypass. JCardiovasc Pharmacol 2008, 52:518-523.
159. Marcatili S., Guarino C., Giannattasio A., Marcatili A., Festa M., Cautiero V., et al. Alterations of the endoalveolar surfactant after surgery with extracorporeal circulation. Respiration 1990, 57:233-238.
160. Refai M., Brunelli A., Xiumé F., Salati M., Sciarra V., Socci L., et al. Short-term perioperative treatment with ambroxol reduces pulmonary complications and hospital costs after pulmonary lobectomy: a randomized trial. Eur J Cardiothorac Surg 2009, 35:469-473.
161. Romanini B.M., Sandri M.G., Tosi M., Mezzetti M., Mazzetti A. Ambroxol for prophylaxis and treatment of bronchopulmonary complications after chest surgery. Int J Clin Pharmacol Res 1986, 6:123-127.
162. Fegiz G. Prevention by ambroxol of bronchopulmonary complications after upper abdominal surgery: double-blind Italian multicenter clinical study versus placebo. Lung 1991, 169:69-76.
163. Kranicke R. Results of a clinical trial with ambroxol as to postoperative therapy of bronchitis. Arzneimittelforschung 1978, 28:934-935.
164. Caramia G., Gagliardini R., Ruffini E., Osimani P., Nobilini A. The management of cystic fibrosis with carbocysteine lysine salt: single-blind comparative study with ambroxol hydrochloride. JInt Med Res 1995, 23:284-293.
165. Derelle J., Bertolo-Houriez E., Marchal F., Weber M., Virion J.M., Vidailhet M. Respiratory evolution of patient with mucoviscidosis treated with mucolytic agents plus domase alfa. Arch Pediatr 1998, 5:371-377.
166. Ratjen F., Wönne R., Posselt H.G., Stöver B., Hofmann D., Bender S.W. Adouble-blind placebo controlled trial with oral ambroxol and N-acetylcysteine for mucolytic treatment in cystic fibrosis. Eur J Pediatr 1985, 144:374-378.
167. Nash E.F., Stephenson A., Ratjen F., Tullis E. Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis. Cochrane Database Syst Rev 2009, 1:CD007168.
168. Poole P., Black P.N., Cates C.J. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012, 8:CD001287.
169. Malerba M., Ponticiello A., Radaeli A., Bensi G., Grassi V. Effect of twelve-months 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.