메뉴 건너뛰기




Volumn 34, Issue 3, 2015, Pages 421-429

Role of biofilm in children with recurrent upper respiratory tract infections

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; BACTERIUM ADHERENCE; BIOFILM; CELLULAR IMMUNITY; CHILDHOOD DISEASE; DNA TRANSFER; FEASIBILITY STUDY; HUMAN; HUMORAL IMMUNITY; INFECTION CONTROL; NONHUMAN; PRIORITY JOURNAL; QUORUM SENSING; RECURRENT INFECTION; REVIEW; UPPER RESPIRATORY TRACT INFECTION; ANIMAL; BACTERIAL INFECTIONS; CHILD; DRUG TOLERANCE; GROWTH, DEVELOPMENT AND AGING; IMMUNE EVASION; IMMUNOLOGY; INFANT; MICROBIOLOGY; PRESCHOOL CHILD; RECURRENT DISEASE; RESPIRATORY TRACT INFECTIONS;

EID: 84943014296     PISSN: 09349723     EISSN: 14354373     Source Type: Journal    
DOI: 10.1007/s10096-014-2261-1     Document Type: Review
Times cited : (42)

References (102)
  • 1
    • 0037298897 scopus 로고    scopus 로고
    • Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides
    • COI: 1:CAS:528:DC%2BD3sXjsVWntrc%3D, PID: 12678415
    • Principi N, Esposito S, Cavagna R, Bosis S, Droghetti R, Faelli N, Tosi S, Begliatti E; Snoopy Study Group (2003) Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides. J Chemother 15:53–59
    • (2003) J Chemother , vol.15 , pp. 53-59
    • Principi, N.1    Esposito, S.2    Cavagna, R.3    Bosis, S.4    Droghetti, R.5    Faelli, N.6    Tosi, S.7    Begliatti, E.8
  • 3
    • 44849111010 scopus 로고    scopus 로고
    • Guidelines for the diagnosis and treatment of acute and subacute rhinosinusitis in children
    • Italian Society of Pediatrics; Italian Society of Pediatric Infectivology; Italian Society of Pediatric Allergology and Immunology; Italian Society of Pediatric Respiratory Diseases; Italian Society of Preventive and Social Pediatrics; Italian Society of Otorhinolaryngology; Italian Society of Chemotherapy; Italian Society of Microbiology, COI: 1:CAS:528:DC%2BD1cXnvVaguro%3D, PID: 18467238
    • Esposito S, Principi N; Italian Society of Pediatrics; Italian Society of Pediatric Infectivology; Italian Society of Pediatric Allergology and Immunology; Italian Society of Pediatric Respiratory Diseases; Italian Society of Preventive and Social Pediatrics; Italian Society of Otorhinolaryngology; Italian Society of Chemotherapy; Italian Society of Microbiology (2008) Guidelines for the diagnosis and treatment of acute and subacute rhinosinusitis in children. J Chemother 20:147–157
    • (2008) J Chemother , vol.20 , pp. 147-157
    • Esposito, S.1    Principi, N.2
  • 5
    • 84891588635 scopus 로고    scopus 로고
    • Immunostimulants and prevention of recurrent respiratory tract infections
    • COI: 1:CAS:528:DC%2BC3sXhsl2htrnK, PID: 24152832
    • Esposito S, Musio A (2013) Immunostimulants and prevention of recurrent respiratory tract infections. J Biol Regul Homeost Agents 27:627–636
    • (2013) J Biol Regul Homeost Agents , vol.27 , pp. 627-636
    • Esposito, S.1    Musio, A.2
  • 6
    • 0037529295 scopus 로고    scopus 로고
    • Effectiveness of influenza vaccination of children with recurrent respiratory tract infections in reducing respiratory-related morbidity within the households
    • PID: 12804844
    • Esposito S, Marchisio P, Cavagna R, Gironi S, Bosis S, Lambertini L, Droghetti R, Principi N (2003) Effectiveness of influenza vaccination of children with recurrent respiratory tract infections in reducing respiratory-related morbidity within the households. Vaccine 21:3162–3168
    • (2003) Vaccine , vol.21 , pp. 3162-3168
    • Esposito, S.1    Marchisio, P.2    Cavagna, R.3    Gironi, S.4    Bosis, S.5    Lambertini, L.6    Droghetti, R.7    Principi, N.8
  • 7
    • 34548357281 scopus 로고    scopus 로고
    • The child with recurrent respiratory infections: normal or not?
    • PID: 17767600
    • de Martino M, Ballotti S (2007) The child with recurrent respiratory infections: normal or not? Pediatr Allergy Immunol 18(Suppl 18):13–18
    • (2007) Pediatr Allergy Immunol , vol.18 , pp. 13-18
    • de Martino, M.1    Ballotti, S.2
  • 8
    • 0033591467 scopus 로고    scopus 로고
    • Bacterial biofilms: a common cause of persistent infections
    • COI: 1:CAS:528:DyaK1MXjs1Squ78%3D, PID: 10334980
    • Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: a common cause of persistent infections. Science 284:1318–1322
    • (1999) Science , vol.284 , pp. 1318-1322
    • Costerton, J.W.1    Stewart, P.S.2    Greenberg, E.P.3
  • 9
    • 0037313237 scopus 로고    scopus 로고
    • Understanding biofilm resistance to antibacterial agents
    • COI: 1:CAS:528:DC%2BD3sXot12lsg%3D%3D, PID: 12563302
    • Davies D (2003) Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2:114–122
    • (2003) Nat Rev Drug Discov , vol.2 , pp. 114-122
    • Davies, D.1
  • 12
    • 84883319452 scopus 로고    scopus 로고
    • Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease
    • PID: 23882016
    • Marks LR, Davidson BA, Knight PR, Hakansson AP (2013) Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. MBio 4:e00438-13
    • (2013) MBio , vol.4
    • Marks, L.R.1    Davidson, B.A.2    Knight, P.R.3    Hakansson, A.P.4
  • 13
    • 84896399845 scopus 로고    scopus 로고
    • The co-pathogenesis of influenza viruses with bacteria in the lung
    • COI: 1:CAS:528:DC%2BC2cXjtlylsLw%3D, PID: 24590244, Epub 2014 Mar 3
    • McCullers JA (2014) The co-pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Microbiol 12:252–262. doi:10.1038/nrmicro3231. Epub 2014 Mar 3
    • (2014) Nat Rev Microbiol , vol.12 , pp. 252-262
    • McCullers, J.A.1
  • 14
    • 70350144846 scopus 로고    scopus 로고
    • Biofilms in pediatric respiratory and related infections
    • COI: 1:CAS:528:DC%2BD1cXhsFCltL%2FM, PID: 19814917
    • Liu YC, Post JC (2009) Biofilms in pediatric respiratory and related infections. Curr Allergy Asthma Rep 9:449–455
    • (2009) Curr Allergy Asthma Rep , vol.9 , pp. 449-455
    • Liu, Y.C.1    Post, J.C.2
  • 15
    • 80051738044 scopus 로고    scopus 로고
    • Diagnostic accuracy of nasopharyngeal swabs in detecting biofilm-producing bacteria in chronic adenoiditis: a preliminary study
    • PID: 21493370
    • Torretta S, Drago L, Marchisio P, Mattina R, Clemente IA, Pignataro L (2011) Diagnostic accuracy of nasopharyngeal swabs in detecting biofilm-producing bacteria in chronic adenoiditis: a preliminary study. Otolaryngol Head Neck Surg 144:784–788
    • (2011) Otolaryngol Head Neck Surg , vol.144 , pp. 784-788
    • Torretta, S.1    Drago, L.2    Marchisio, P.3    Mattina, R.4    Clemente, I.A.5    Pignataro, L.6
  • 16
    • 73649133262 scopus 로고    scopus 로고
    • Visualization of adherent micro-organisms using different techniques
    • COI: 1:CAS:528:DC%2BC3cXhsVyquro%3D, PID: 19815663
    • Hannig C, Follo M, Hellwig E, Al-Ahmad A (2010) Visualization of adherent micro-organisms using different techniques. J Med Microbiol 59(Pt 1):1–7
    • (2010) J Med Microbiol , vol.59 , pp. 1-7
    • Hannig, C.1    Follo, M.2    Hellwig, E.3    Al-Ahmad, A.4
  • 19
    • 80054727563 scopus 로고    scopus 로고
    • Nasal cytology: the “infectious spot”, an expression of a morphological-chromatic biofilm
    • COI: 1:STN:280:DC%2BC3MjmtlKjsA%3D%3D, PID: 21359623
    • Gelardi M, Passalacqua G, Fiorella ML, Mosca A, Quaranta N (2011) Nasal cytology: the “infectious spot”, an expression of a morphological-chromatic biofilm. Eur J Clin Microbiol Infect Dis 30:1105–1109
    • (2011) Eur J Clin Microbiol Infect Dis , vol.30 , pp. 1105-1109
    • Gelardi, M.1    Passalacqua, G.2    Fiorella, M.L.3    Mosca, A.4    Quaranta, N.5
  • 23
  • 24
    • 69549108598 scopus 로고    scopus 로고
    • Morphological evidence of biofilm formation in Greenlanders with chronic suppurative otitis media
    • PID: 19283404
    • Homøe P, Bjarnsholt T, Wessman M, Sørensen HC, Johansen HK (2009) Morphological evidence of biofilm formation in Greenlanders with chronic suppurative otitis media. Eur Arch Otorhinolaryngol 266:1533–1538
    • (2009) Eur Arch Otorhinolaryngol , vol.266 , pp. 1533-1538
    • Homøe, P.1    Bjarnsholt, T.2    Wessman, M.3    Sørensen, H.C.4    Johansen, H.K.5
  • 26
    • 84862672886 scopus 로고    scopus 로고
    • Bacterial biofilms in the upper airway—evidence for role in pathology and implications for treatment of otitis media
    • PID: 22726871
    • Bakaletz LO (2012) Bacterial biofilms in the upper airway—evidence for role in pathology and implications for treatment of otitis media. Paediatr Respir Rev 13:154–159
    • (2012) Paediatr Respir Rev , vol.13 , pp. 154-159
    • Bakaletz, L.O.1
  • 27
    • 84881315175 scopus 로고    scopus 로고
    • Role of adenoid biofilm in chronic otitis media with effusion in children
    • PID: 23179928
    • Saafan ME, Ibrahim WS, Tomoum MO (2013) Role of adenoid biofilm in chronic otitis media with effusion in children. Eur Arch Otorhinolaryngol 270:2417–2425
    • (2013) Eur Arch Otorhinolaryngol , vol.270 , pp. 2417-2425
    • Saafan, M.E.1    Ibrahim, W.S.2    Tomoum, M.O.3
  • 28
    • 0032573876 scopus 로고    scopus 로고
    • Evidence of bacterial metabolic activity in culture-negative otitis media with effusion
    • COI: 1:CAS:528:DyaK1cXovFWquw%3D%3D, PID: 9450714
    • Rayner MG, Zhang Y, Gorry MC, Chen Y, Post JC, Ehrlich GD (1998) Evidence of bacterial metabolic activity in culture-negative otitis media with effusion. JAMA 279:296–299
    • (1998) JAMA , vol.279 , pp. 296-299
    • Rayner, M.G.1    Zhang, Y.2    Gorry, M.C.3    Chen, Y.4    Post, J.C.5    Ehrlich, G.D.6
  • 29
    • 66249124592 scopus 로고    scopus 로고
    • Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media
    • PID: 19462851
    • Hoa M, Syamal M, Sachdeva L, Berk R, Coticchia J (2009) Demonstration of nasopharyngeal and middle ear mucosal biofilms in an animal model of acute otitis media. Ann Otol Rhinol Laryngol 118:292–298
    • (2009) Ann Otol Rhinol Laryngol , vol.118 , pp. 292-298
    • Hoa, M.1    Syamal, M.2    Sachdeva, L.3    Berk, R.4    Coticchia, J.5
  • 30
    • 68749119639 scopus 로고    scopus 로고
    • Formation of biofilm by Haemophilus influenzae isolated from pediatric intractable otitis media
    • PID: 19135325
    • Moriyama S, Hotomi M, Shimada J, Billal DS, Fujihara K, Yamanaka N (2009) Formation of biofilm by Haemophilus influenzae isolated from pediatric intractable otitis media. Auris Nasus Larynx 36:525–531
    • (2009) Auris Nasus Larynx , vol.36 , pp. 525-531
    • Moriyama, S.1    Hotomi, M.2    Shimada, J.3    Billal, D.S.4    Fujihara, K.5    Yamanaka, N.6
  • 31
  • 33
    • 84905980027 scopus 로고    scopus 로고
    • Frequent carriage of resistance mechanisms to β-lactams and biofilm formation in Haemophilus influenzae causing treatment failure and recurrent otitis media in young children
    • PID: 24891432
    • García-Cobos S, Moscoso M, Pumarola F, Arroyo M, Lara N, Pérez-Vázquez M, Aracil B, Oteo J, García E, Campos J (2014) Frequent carriage of resistance mechanisms to β-lactams and biofilm formation in Haemophilus influenzae causing treatment failure and recurrent otitis media in young children. J Antimicrob Chemother 69:2394–2399
    • (2014) J Antimicrob Chemother , vol.69 , pp. 2394-2399
    • García-Cobos, S.1    Moscoso, M.2    Pumarola, F.3    Arroyo, M.4    Lara, N.5    Pérez-Vázquez, M.6    Aracil, B.7    Oteo, J.8    García, E.9    Campos, J.10
  • 36
    • 77953881179 scopus 로고    scopus 로고
    • Association of adenoid surface biofilm formation and chronic otitis media with effusion
    • PID: 20566904
    • Saylam G, Tatar EC, Tatar I, Ozdek A, Korkmaz H (2010) Association of adenoid surface biofilm formation and chronic otitis media with effusion. Arch Otolaryngol Head Neck Surg 136:550–555
    • (2010) Arch Otolaryngol Head Neck Surg , vol.136 , pp. 550-555
    • Saylam, G.1    Tatar, E.C.2    Tatar, I.3    Ozdek, A.4    Korkmaz, H.5
  • 37
    • 84873642275 scopus 로고    scopus 로고
    • Topographic distribution of biofilm-producing bacteria in adenoid subsites of children with chronic or recurrent middle ear infections
    • PID: 23534125
    • Torretta S, Drago L, Marchisio P, Gaffuri M, Clemente IA, Pignataro L (2013) Topographic distribution of biofilm-producing bacteria in adenoid subsites of children with chronic or recurrent middle ear infections. Ann Otol Rhinol Laryngol 122:109–113
    • (2013) Ann Otol Rhinol Laryngol , vol.122 , pp. 109-113
    • Torretta, S.1    Drago, L.2    Marchisio, P.3    Gaffuri, M.4    Clemente, I.A.5    Pignataro, L.6
  • 38
    • 0037904430 scopus 로고    scopus 로고
    • Anatomical evidence of microbial biofilms in tonsillar tissues: a possible mechanism to explain chronicity
    • PID: 12810467
    • Chole RA, Faddis BT (2003) Anatomical evidence of microbial biofilms in tonsillar tissues: a possible mechanism to explain chronicity. Arch Otolaryngol Head Neck Surg 129:634–636
    • (2003) Arch Otolaryngol Head Neck Surg , vol.129 , pp. 634-636
    • Chole, R.A.1    Faddis, B.T.2
  • 39
    • 35148891556 scopus 로고    scopus 로고
    • Biofilm formation by Haemophilus influenzae isolated from adeno-tonsil tissue samples, and its role in recurrent adenotonsillitis
    • COI: 1:STN:280:DC%2BD2srmsVGnsA%3D%3D, PID: 17883191
    • Galli J, Calò L, Ardito F, Imperiali M, Bassotti E, Fadda G, Paludetti G (2007) Biofilm formation by Haemophilus influenzae isolated from adeno-tonsil tissue samples, and its role in recurrent adenotonsillitis. Acta Otorhinolaryngol Ital 27:134–138
    • (2007) Acta Otorhinolaryngol Ital , vol.27 , pp. 134-138
    • Galli, J.1    Calò, L.2    Ardito, F.3    Imperiali, M.4    Bassotti, E.5    Fadda, G.6    Paludetti, G.7
  • 41
    • 84903204020 scopus 로고    scopus 로고
    • Streptococcus pyogenes biofilm growth in vitro and in vivo and its role in colonization, virulence, and genetic exchange
    • PID: 24465015
    • Marks LR, Mashburn-Warren L, Federle MJ, Hakansson AP (2014) Streptococcus pyogenes biofilm growth in vitro and in vivo and its role in colonization, virulence, and genetic exchange. J Infect Dis 210:25–34
    • (2014) J Infect Dis , vol.210 , pp. 25-34
    • Marks, L.R.1    Mashburn-Warren, L.2    Federle, M.J.3    Hakansson, A.P.4
  • 42
    • 84855480364 scopus 로고    scopus 로고
    • Detection of group A Streptococcus in tonsils from pediatric patients reveals high rate of asymptomatic streptococcal carriage
    • PID: 22230361
    • Roberts AL, Connolly KL, Kirse DJ, Evans AK, Poehling KA, Peters TR, Reid SD (2012) Detection of group A Streptococcus in tonsils from pediatric patients reveals high rate of asymptomatic streptococcal carriage. BMC Pediatr 12:3
    • (2012) BMC Pediatr , vol.12 , pp. 3
    • Roberts, A.L.1    Connolly, K.L.2    Kirse, D.J.3    Evans, A.K.4    Poehling, K.A.5    Peters, T.R.6    Reid, S.D.7
  • 43
    • 79955589530 scopus 로고    scopus 로고
    • Biofilm formation or internalization into epithelial cells enable Streptococcus pyogenes to evade antibiotic eradication in patients with pharyngitis
    • COI: 1:CAS:528:DC%2BC3MXlvFWis7g%3D, PID: 21443942
    • Ogawa T, Terao Y, Okuni H, Ninomiya K, Sakata H, Ikebe K, Maeda Y, Kawabata S (2011) Biofilm formation or internalization into epithelial cells enable Streptococcus pyogenes to evade antibiotic eradication in patients with pharyngitis. Microb Pathog 51:58–68
    • (2011) Microb Pathog , vol.51 , pp. 58-68
    • Ogawa, T.1    Terao, Y.2    Okuni, H.3    Ninomiya, K.4    Sakata, H.5    Ikebe, K.6    Maeda, Y.7    Kawabata, S.8
  • 44
    • 0024508448 scopus 로고
    • Naso- and oropharyngeal dimensions in children with obstructive sleep apnea
    • COI: 1:STN:280:DyaL1M3htlWktA%3D%3D, PID: 2707973
    • Brodsky L, Adler E, Stanievich JF (1989) Naso- and oropharyngeal dimensions in children with obstructive sleep apnea. Int J Pediatr Otorhinolaryngol 17:1–11
    • (1989) Int J Pediatr Otorhinolaryngol , vol.17 , pp. 1-11
    • Brodsky, L.1    Adler, E.2    Stanievich, J.F.3
  • 45
    • 84872604935 scopus 로고    scopus 로고
    • Recurrences in chronic tonsillitis substained by tonsillar biofilm-producing bacteria in children. Relationship with the grade of tonsillar hyperplasy
    • PID: 23137856
    • Torretta S, Drago L, Marchisio P, Cappadona M, Rinaldi V, Nazzari E, Pignataro L (2013) Recurrences in chronic tonsillitis substained by tonsillar biofilm-producing bacteria in children. Relationship with the grade of tonsillar hyperplasy. Int J Pediatr Otorhinolaryngol 77:200–204
    • (2013) Int J Pediatr Otorhinolaryngol , vol.77 , pp. 200-204
    • Torretta, S.1    Drago, L.2    Marchisio, P.3    Cappadona, M.4    Rinaldi, V.5    Nazzari, E.6    Pignataro, L.7
  • 46
    • 33745757955 scopus 로고    scopus 로고
    • Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis
    • PID: 16675778
    • Starner TD, Zhang N, Kim G, Apicella MA, McCray PB Jr (2006) Haemophilus influenzae forms biofilms on airway epithelia: implications in cystic fibrosis. Am J Respir Crit Care Med 174:213–220
    • (2006) Am J Respir Crit Care Med , vol.174 , pp. 213-220
    • Starner, T.D.1    Zhang, N.2    Kim, G.3    Apicella, M.A.4    McCray, P.B.5
  • 47
    • 77957159654 scopus 로고    scopus 로고
    • Effect of tonsillectomy on the level of exhaled nitric oxide (NO) in patients with recurrent tonsillitis
    • COI: 1:STN:280:DC%2BC3cfkvVKjtQ%3D%3D, PID: 20729049
    • Kasperska-Zajac A, Czecior E, Namyslowski G (2010) Effect of tonsillectomy on the level of exhaled nitric oxide (NO) in patients with recurrent tonsillitis. Respir Med 104:1757–1759
    • (2010) Respir Med , vol.104 , pp. 1757-1759
    • Kasperska-Zajac, A.1    Czecior, E.2    Namyslowski, G.3
  • 49
    • 79956225765 scopus 로고    scopus 로고
    • The role of nitric-oxide-synthase-derived nitric oxide in multicellular traits of Bacillus subtilis 3610: biofilm formation, swarming, and dispersal
    • COI: 1:CAS:528:DC%2BC3MXmslClur8%3D, PID: 21599925
    • Schreiber F, Beutler M, Enning D, Lamprecht-Grandio M, Zafra O, González-Pastor JE, de Beer D (2011) The role of nitric-oxide-synthase-derived nitric oxide in multicellular traits of Bacillus subtilis 3610: biofilm formation, swarming, and dispersal. BMC Microbiol 11:111
    • (2011) BMC Microbiol , vol.11 , pp. 111
    • Schreiber, F.1    Beutler, M.2    Enning, D.3    Lamprecht-Grandio, M.4    Zafra, O.5    González-Pastor, J.E.6    de Beer, D.7
  • 50
    • 72249092095 scopus 로고    scopus 로고
    • Nitric oxide signaling in Pseudomonas aeruginosa biofilms mediates phosphodiesterase activity, decreased cyclic di-GMP levels, and enhanced dispersal
    • COI: 1:CAS:528:DC%2BD1MXhsVyrtrbP, PID: 19801410
    • Barraud N, Schleheck D, Klebensberger J, Webb JS, Hassett DJ, Rice SA, Kjelleberg S (2009) Nitric oxide signaling in Pseudomonas aeruginosa biofilms mediates phosphodiesterase activity, decreased cyclic di-GMP levels, and enhanced dispersal. J Bacteriol 191:7333–7342
    • (2009) J Bacteriol , vol.191 , pp. 7333-7342
    • Barraud, N.1    Schleheck, D.2    Klebensberger, J.3    Webb, J.S.4    Hassett, D.J.5    Rice, S.A.6    Kjelleberg, S.7
  • 51
    • 77951250543 scopus 로고    scopus 로고
    • Anaerobic metabolism occurs in the substratum of gonococcal biofilms and may be sustained in part by nitric oxide
    • COI: 1:CAS:528:DC%2BC3cXlsFKnsLk%3D, PID: 20231417
    • Falsetta ML, McEwan AG, Jennings MP, Apicella MA (2010) Anaerobic metabolism occurs in the substratum of gonococcal biofilms and may be sustained in part by nitric oxide. Infect Immun 78:2320–2328
    • (2010) Infect Immun , vol.78 , pp. 2320-2328
    • Falsetta, M.L.1    McEwan, A.G.2    Jennings, M.P.3    Apicella, M.A.4
  • 52
    • 84861380355 scopus 로고    scopus 로고
    • The effects of nitric oxide on Staphylococcus aureus biofilm growth and its implications in chronic rhinosinusitis
    • PID: 22144052
    • Jardeleza C, Foreman A, Baker L, Paramasivan S, Field J, Tan LW, Wormald PJ (2011) The effects of nitric oxide on Staphylococcus aureus biofilm growth and its implications in chronic rhinosinusitis. Int Forum Allergy Rhinol 1:438–444
    • (2011) Int Forum Allergy Rhinol , vol.1 , pp. 438-444
    • Jardeleza, C.1    Foreman, A.2    Baker, L.3    Paramasivan, S.4    Field, J.5    Tan, L.W.6    Wormald, P.J.7
  • 53
    • 65449164321 scopus 로고    scopus 로고
    • Bacterial nitric oxide synthases: what are they good for?
    • COI: 1:CAS:528:DC%2BD1MXls12htr0%3D, PID: 19375324
    • Sudhamsu J, Crane BR (2009) Bacterial nitric oxide synthases: what are they good for? Trends Microbiol 17:212–218
    • (2009) Trends Microbiol , vol.17 , pp. 212-218
    • Sudhamsu, J.1    Crane, B.R.2
  • 56
    • 79957680030 scopus 로고    scopus 로고
    • Pediatric chronic rhinosinusitis: the old, the new, and the reasonable
    • PID: 21485998
    • Silviu-Dan F (2011) Pediatric chronic rhinosinusitis: the old, the new, and the reasonable. Pediatr Ann 40:213–220
    • (2011) Pediatr Ann , vol.40 , pp. 213-220
    • Silviu-Dan, F.1
  • 57
    • 84878538890 scopus 로고    scopus 로고
    • Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology
    • PID: 23587334
    • Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM, Schleimer RP, Ledford D (2013) Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 131:1479–1490
    • (2013) J Allergy Clin Immunol , vol.131 , pp. 1479-1490
    • Akdis, C.A.1    Bachert, C.2    Cingi, C.3    Dykewicz, M.S.4    Hellings, P.W.5    Naclerio, R.M.6    Schleimer, R.P.7    Ledford, D.8
  • 58
    • 15944375877 scopus 로고    scopus 로고
    • Evidence of bacterial biofilms in a rabbit model of sinusitis
    • PID: 15794067
    • Perloff JR, Palmer JN (2005) Evidence of bacterial biofilms in a rabbit model of sinusitis. Am J Rhinol 19:1–6
    • (2005) Am J Rhinol , vol.19 , pp. 1-6
    • Perloff, J.R.1    Palmer, J.N.2
  • 59
    • 17244381820 scopus 로고    scopus 로고
    • Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis
    • PID: 15805862
    • Sanclement JA, Webster P, Thomas J, Ramadan HH (2005) Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis. Laryngoscope 115:578–582
    • (2005) Laryngoscope , vol.115 , pp. 578-582
    • Sanclement, J.A.1    Webster, P.2    Thomas, J.3    Ramadan, H.H.4
  • 60
    • 43549121706 scopus 로고    scopus 로고
    • The relationship of biofilms to chronic rhinosinusitis
    • PID: 18475078
    • Hunsaker DH, Leid JG (2008) The relationship of biofilms to chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg 16:237–241
    • (2008) Curr Opin Otolaryngol Head Neck Surg , vol.16 , pp. 237-241
    • Hunsaker, D.H.1    Leid, J.G.2
  • 62
    • 84861712913 scopus 로고    scopus 로고
    • Prevalence of biofilms and their response to medical treatment in chronic rhinosinusitis without polyps
    • PID: 22241786
    • Tatar EÇ, Tatar I, Ocal B, Korkmaz H, Saylam G, Ozdek A, Celik HH (2012) Prevalence of biofilms and their response to medical treatment in chronic rhinosinusitis without polyps. Otolaryngol Head Neck Surg 146:669–675
    • (2012) Otolaryngol Head Neck Surg , vol.146 , pp. 669-675
    • Tatar, E.Ç.1    Tatar, I.2    Ocal, B.3    Korkmaz, H.4    Saylam, G.5    Ozdek, A.6    Celik, H.H.7
  • 63
    • 84856735514 scopus 로고    scopus 로고
    • Bacterial biofilms in chronic rhinosinusitis and their relationship with inflammation severity
    • COI: 1:STN:280:DC%2BC387ntleitA%3D%3D, PID: 21641137
    • Chen HH, Liu X, Ni C, Lu YP, Xiong GY, Lu YY, Wang SQ (2012) Bacterial biofilms in chronic rhinosinusitis and their relationship with inflammation severity. Auris Nasus Larynx 39:169–174
    • (2012) Auris Nasus Larynx , vol.39 , pp. 169-174
    • Chen, H.H.1    Liu, X.2    Ni, C.3    Lu, Y.P.4    Xiong, G.Y.5    Lu, Y.Y.6    Wang, S.Q.7
  • 64
    • 84857048543 scopus 로고    scopus 로고
    • Evaluation of bacterial adherence and biofilm arrangements as new targets in treatment of chronic rhinosinusitis
    • PID: 21814734
    • Ragab A, Essa N, El-Raghy N, Zahran W, El Borolsy A (2012) Evaluation of bacterial adherence and biofilm arrangements as new targets in treatment of chronic rhinosinusitis. Eur Arch Otorhinolaryngol 269:537–544
    • (2012) Eur Arch Otorhinolaryngol , vol.269 , pp. 537-544
    • Ragab, A.1    Essa, N.2    El-Raghy, N.3    Zahran, W.4    El Borolsy, A.5
  • 65
    • 84861231286 scopus 로고    scopus 로고
    • Role of bacterial and fungal biofilms in chronic rhinosinusitis
    • PID: 22322439
    • Foreman A, Boase S, Psaltis A, Wormald PJ (2012) Role of bacterial and fungal biofilms in chronic rhinosinusitis. Curr Allergy Asthma Rep 12:127–135
    • (2012) Curr Allergy Asthma Rep , vol.12 , pp. 127-135
    • Foreman, A.1    Boase, S.2    Psaltis, A.3    Wormald, P.J.4
  • 66
    • 33747189512 scopus 로고    scopus 로고
    • Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis
    • PID: 16826045
    • Sanderson AR, Leid JG, Hunsaker D (2006) Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis. Laryngoscope 116:1121–1126
    • (2006) Laryngoscope , vol.116 , pp. 1121-1126
    • Sanderson, A.R.1    Leid, J.G.2    Hunsaker, D.3
  • 68
    • 77950880153 scopus 로고    scopus 로고
    • A biofilm exists on healthy mucosa of the paranasal sinuses: a prospectively performed, blinded, scanning electron microscope study
    • COI: 1:STN:280:DC%2BC3czmtlaksQ%3D%3D, PID: 20500579
    • Mladina R, Skitarelić N, Musić S, Ristić M (2010) A biofilm exists on healthy mucosa of the paranasal sinuses: a prospectively performed, blinded, scanning electron microscope study. Clin Otolaryngol 35:104–110
    • (2010) Clin Otolaryngol , vol.35 , pp. 104-110
    • Mladina, R.1    Skitarelić, N.2    Musić, S.3    Ristić, M.4
  • 69
    • 84857038299 scopus 로고    scopus 로고
    • Relationship between bacterial biofilm and clinical features of patients with chronic rhinosinusitis
    • PID: 21739098
    • Li H, Wang D, Sun X, Hu L, Yu H, Wang J (2012) Relationship between bacterial biofilm and clinical features of patients with chronic rhinosinusitis. Eur Arch Otorhinolaryngol 269:155–163
    • (2012) Eur Arch Otorhinolaryngol , vol.269 , pp. 155-163
    • Li, H.1    Wang, D.2    Sun, X.3    Hu, L.4    Yu, H.5    Wang, J.6
  • 70
    • 33646795659 scopus 로고    scopus 로고
    • Biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa is associated with an unfavorable evolution after surgery for chronic sinusitis and nasal polyposis
    • PID: 16730544
    • Bendouah Z, Barbeau J, Hamad WA, Desrosiers M (2006) Biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa is associated with an unfavorable evolution after surgery for chronic sinusitis and nasal polyposis. Otolaryngol Head Neck Surg 134:991–996
    • (2006) Otolaryngol Head Neck Surg , vol.134 , pp. 991-996
    • Bendouah, Z.1    Barbeau, J.2    Hamad, W.A.3    Desrosiers, M.4
  • 71
    • 77953634744 scopus 로고    scopus 로고
    • The impact of biofilms on outcomes after endoscopic sinus surgery
    • PID: 20537281
    • Singhal D, Psaltis AJ, Foreman A, Wormald PJ (2010) The impact of biofilms on outcomes after endoscopic sinus surgery. Am J Rhinol Allergy 24:169–174
    • (2010) Am J Rhinol Allergy , vol.24 , pp. 169-174
    • Singhal, D.1    Psaltis, A.J.2    Foreman, A.3    Wormald, P.J.4
  • 72
    • 34347359806 scopus 로고    scopus 로고
    • Confocal scanning laser microscopy evidence of biofilms in patients with chronic rhinosinusitis
    • PID: 17603329
    • Psaltis AJ, Ha KR, Beule AG, Tan LW, Wormald PJ (2007) Confocal scanning laser microscopy evidence of biofilms in patients with chronic rhinosinusitis. Laryngoscope 117:1302–1306
    • (2007) Laryngoscope , vol.117 , pp. 1302-1306
    • Psaltis, A.J.1    Ha, K.R.2    Beule, A.G.3    Tan, L.W.4    Wormald, P.J.5
  • 76
    • 82955188788 scopus 로고    scopus 로고
    • Streptococcus pneumoniae in biofilms are unable to cause invasive disease due to altered virulence determinant production
    • COI: 1:CAS:528:DC%2BC3MXhs1yjsr3O, PID: 22174882
    • Sanchez CJ, Kumar N, Lizcano A, Shivshankar P, Dunning Hotopp JC, Jorgensen JH, Tettelin H, Orihuela CJ (2011) Streptococcus pneumoniae in biofilms are unable to cause invasive disease due to altered virulence determinant production. PLoS One 6:e28738
    • (2011) PLoS One , vol.6 , pp. 28738
    • Sanchez, C.J.1    Kumar, N.2    Lizcano, A.3    Shivshankar, P.4    Dunning Hotopp, J.C.5    Jorgensen, J.H.6    Tettelin, H.7    Orihuela, C.J.8
  • 77
    • 77956911922 scopus 로고    scopus 로고
    • Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease
    • PID: 20715928
    • Weimer KE, Armbruster CE, Juneau RA, Hong W, Pang B, Swords WE (2010) Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease. J Infect Dis 202:1068–1075
    • (2010) J Infect Dis , vol.202 , pp. 1068-1075
    • Weimer, K.E.1    Armbruster, C.E.2    Juneau, R.A.3    Hong, W.4    Pang, B.5    Swords, W.E.6
  • 78
    • 27944501527 scopus 로고    scopus 로고
    • Demonstration of biofilm in human bacterial chronic rhinosinusitis
    • PID: 16270598
    • Ferguson BJ, Stolz DB (2005) Demonstration of biofilm in human bacterial chronic rhinosinusitis. Am J Rhinol 19:452–457
    • (2005) Am J Rhinol , vol.19 , pp. 452-457
    • Ferguson, B.J.1    Stolz, D.B.2
  • 79
    • 78650810250 scopus 로고    scopus 로고
    • Bacterial biofilms and the pathophysiology of chronic rhinosinusitis
    • PID: 21150431
    • Al-Mutairi D, Kilty SJ (2011) Bacterial biofilms and the pathophysiology of chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 11:18–23
    • (2011) Curr Opin Allergy Clin Immunol , vol.11 , pp. 18-23
    • Al-Mutairi, D.1    Kilty, S.J.2
  • 80
    • 84871715708 scopus 로고    scopus 로고
    • Low-frequency ultrasound for biofilm disruption in chronic rhinosinusitis with nasal polyposis: in vitro pilot study
    • PID: 22893599
    • Karosi T, Sziklai I, Csomor P (2013) Low-frequency ultrasound for biofilm disruption in chronic rhinosinusitis with nasal polyposis: in vitro pilot study. Laryngoscope 123:17–23
    • (2013) Laryngoscope , vol.123 , pp. 17-23
    • Karosi, T.1    Sziklai, I.2    Csomor, P.3
  • 81
    • 84859967583 scopus 로고    scopus 로고
    • Biofilm formation by bacteria isolated from upper respiratory tract before and after adenotonsillectomy
    • PID: 22515296
    • Drago L, De Vecchi E, Torretta S, Mattina R, Marchisio P, Pignataro L (2012) Biofilm formation by bacteria isolated from upper respiratory tract before and after adenotonsillectomy. APMIS 120:410–416
    • (2012) APMIS , vol.120 , pp. 410-416
    • Drago, L.1    De Vecchi, E.2    Torretta, S.3    Mattina, R.4    Marchisio, P.5    Pignataro, L.6
  • 82
    • 84911959184 scopus 로고    scopus 로고
    • Biophysics of biofilm infection
    • COI: 1:CAS:528:DC%2BC2cXlvVSgtLo%3D, PID: 24376149
    • Stewart PS (2014) Biophysics of biofilm infection. Pathog Dis 70:212–218
    • (2014) Pathog Dis , vol.70 , pp. 212-218
    • Stewart, P.S.1
  • 83
    • 84913621695 scopus 로고    scopus 로고
    • (2014) Antimicrobial susceptibility testing in biofilm-growing bacteria. Clin Microbiol Infect
    • Macià MD, Rojo-Molinero E, Oliver A (2014) Antimicrobial susceptibility testing in biofilm-growing bacteria. Clin Microbiol Infect. Epub 2014 Apr 26
    • (2014) Epub , pp. 26
    • Macià, M.D.1    Rojo-Molinero, E.2    Oliver, A.3
  • 84
    • 79959797242 scopus 로고    scopus 로고
    • Eradicating chronic ear, nose, and throat infections: a systematically conducted literature review of advances in biofilm treatment
    • PID: 21493193
    • Smith A, Buchinsky FJ, Post JC (2011) Eradicating chronic ear, nose, and throat infections: a systematically conducted literature review of advances in biofilm treatment. Otolaryngol Head Neck Surg 144:338–347
    • (2011) Otolaryngol Head Neck Surg , vol.144 , pp. 338-347
    • Smith, A.1    Buchinsky, F.J.2    Post, J.C.3
  • 85
    • 34249782013 scopus 로고    scopus 로고
    • Effectiveness of topical antibiotics on Staphylococcus aureus biofilm in vitro
    • PID: 17424869
    • Desrosiers M, Bendouah Z, Barbeau J (2007) Effectiveness of topical antibiotics on Staphylococcus aureus biofilm in vitro. Am J Rhinol 21:149–153
    • (2007) Am J Rhinol , vol.21 , pp. 149-153
    • Desrosiers, M.1    Bendouah, Z.2    Barbeau, J.3
  • 86
    • 33646107379 scopus 로고    scopus 로고
    • Treatment of chronic rhinosinusitis exacerbations due to methicillin-resistant Staphylococcus aureus with mupirocin irrigations
    • COI: 1:CAS:528:DC%2BD28XktVeitbk%3D, PID: 16647979
    • Solares CA, Batra PS, Hall GS, Citardi MJ (2006) Treatment of chronic rhinosinusitis exacerbations due to methicillin-resistant Staphylococcus aureus with mupirocin irrigations. Am J Otolaryngol 27:161–165
    • (2006) Am J Otolaryngol , vol.27 , pp. 161-165
    • Solares, C.A.1    Batra, P.S.2    Hall, G.S.3    Citardi, M.J.4
  • 87
    • 34848857359 scopus 로고    scopus 로고
    • Effect of ototopical medications on tympanostomy tube biofilms
    • COI: 1:CAS:528:DC%2BD2sXhtFSntrvI, PID: 17690613
    • Oxley KS, Thomas JG, Ramadan HH (2007) Effect of ototopical medications on tympanostomy tube biofilms. Laryngoscope 117:1819–1824
    • (2007) Laryngoscope , vol.117 , pp. 1819-1824
    • Oxley, K.S.1    Thomas, J.G.2    Ramadan, H.H.3
  • 89
    • 84867736189 scopus 로고    scopus 로고
    • Effect of furanone on experimentally induced Pseudomonas aeruginosa biofilm formation: in vitro study
    • PID: 22884365
    • Kim SG, Yoon YH, Choi JW, Rha KS, Park YH (2012) Effect of furanone on experimentally induced Pseudomonas aeruginosa biofilm formation: in vitro study. Int J Pediatr Otorhinolaryngol 76:1575–1578
    • (2012) Int J Pediatr Otorhinolaryngol , vol.76 , pp. 1575-1578
    • Kim, S.G.1    Yoon, Y.H.2    Choi, J.W.3    Rha, K.S.4    Park, Y.H.5
  • 90
    • 84863690101 scopus 로고    scopus 로고
    • Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics
    • PID: 22778497
    • Steel HC, Theron AJ, Cockeran R, Anderson R, Feldman C (2012) Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics. Mediators Inflamm 2012:584262
    • (2012) Mediators Inflamm , vol.2012 , pp. 584262
    • Steel, H.C.1    Theron, A.J.2    Cockeran, R.3    Anderson, R.4    Feldman, C.5
  • 93
    • 84873084205 scopus 로고    scopus 로고
    • Low dose macrolide administration for long term is effective for otitis media with effusion in children
    • PID: 22673738
    • Chen K, Wu X, Jiang G, Du J, Jiang H (2013) Low dose macrolide administration for long term is effective for otitis media with effusion in children. Auris Nasus Larynx 40:46–50
    • (2013) Auris Nasus Larynx , vol.40 , pp. 46-50
    • Chen, K.1    Wu, X.2    Jiang, G.3    Du, J.4    Jiang, H.5
  • 94
    • 84861357166 scopus 로고    scopus 로고
    • Methylglyoxal: (active agent of manuka honey) in vitro activity against bacterial biofilms
    • PID: 22287464
    • Kilty SJ, Duval M, Chan FT, Ferris W, Slinger R (2011) Methylglyoxal: (active agent of manuka honey) in vitro activity against bacterial biofilms. Int Forum Allergy Rhinol 1:348–350
    • (2011) Int Forum Allergy Rhinol , vol.1 , pp. 348-350
    • Kilty, S.J.1    Duval, M.2    Chan, F.T.3    Ferris, W.4    Slinger, R.5
  • 95
    • 84908354413 scopus 로고    scopus 로고
    • Antiadhesive and antibiofilm activity of hyaluronic acid against bacteria responsible for respiratory tract infections
    • COI: 1:CAS:528:DC%2BC2cXhsFyjurbL, PID: 24698341
    • Drago L, Cappelletti L, De Vecchi E, Pignataro L, Torretta S, Mattina R (2014) Antiadhesive and antibiofilm activity of hyaluronic acid against bacteria responsible for respiratory tract infections. APMIS 122:1013–1019
    • (2014) APMIS , vol.122 , pp. 1013-1019
    • Drago, L.1    Cappelletti, L.2    De Vecchi, E.3    Pignataro, L.4    Torretta, S.5    Mattina, R.6
  • 96
    • 0033768954 scopus 로고    scopus 로고
    • Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro
    • COI: 1:CAS:528:DC%2BD3cXosFSitbg%3D, PID: 11070462
    • Riise GC, Qvarfordt I, Larsson S, Eliasson V, Andersson BA (2000) Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro. Respiration 67:552–558
    • (2000) Respiration , vol.67 , pp. 552-558
    • Riise, G.C.1    Qvarfordt, I.2    Larsson, S.3    Eliasson, V.4    Andersson, B.A.5
  • 97
    • 77951984143 scopus 로고    scopus 로고
    • N-acetylcysteine inhibit biofilms produced by Pseudomonas aeruginosa
    • COI: 1:CAS:528:DC%2BC3cXnsFCku7c%3D, PID: 20462423
    • Zhao T, Liu Y (2010) N-acetylcysteine inhibit biofilms produced by Pseudomonas aeruginosa. BMC Microbiol 10:140
    • (2010) BMC Microbiol , vol.10 , pp. 140
    • Zhao, T.1    Liu, Y.2
  • 98
    • 77955936850 scopus 로고    scopus 로고
    • Biofilms and infections of the upper respiratory tract
    • COI: 1:STN:280:DC%2BC3cjkvVelsg%3D%3D, PID: 20707288
    • Pintucci JP, Corno S, Garotta M (2010) Biofilms and infections of the upper respiratory tract. Eur Rev Med Pharmacol Sci 14:683–690
    • (2010) Eur Rev Med Pharmacol Sci , vol.14 , pp. 683-690
    • Pintucci, J.P.1    Corno, S.2    Garotta, M.3
  • 99
    • 0036969666 scopus 로고    scopus 로고
    • In vitro activity of thiamphenicol against multiresistant Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Italy
    • COI: 1:CAS:528:DC%2BD3sXhtVWht7s%3D, PID: 12583545
    • Marchese A, Debbia EA, Tonoli E, Gualco L, Schito AM (2002) In vitro activity of thiamphenicol against multiresistant Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Italy. J Chemother 14:554–561
    • (2002) J Chemother , vol.14 , pp. 554-561
    • Marchese, A.1    Debbia, E.A.2    Tonoli, E.3    Gualco, L.4    Schito, A.M.5
  • 100
    • 33751197878 scopus 로고    scopus 로고
    • Efficacy of N-acetyl-cysteine in combination with thiamphenicol in sequential (intramuscular/aerosol) therapy of upper respiratory tract infections even when sustained by bacterial biofilms
    • COI: 1:CAS:528:DC%2BD28XhtlWhur%2FO, PID: 17127228
    • Macchi A, Ardito F, Marchese A, Schito GC, Fadda G (2006) Efficacy of N-acetyl-cysteine in combination with thiamphenicol in sequential (intramuscular/aerosol) therapy of upper respiratory tract infections even when sustained by bacterial biofilms. J Chemother 18:507–513
    • (2006) J Chemother , vol.18 , pp. 507-513
    • Macchi, A.1    Ardito, F.2    Marchese, A.3    Schito, G.C.4    Fadda, G.5
  • 101
    • 67650469808 scopus 로고    scopus 로고
    • Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery
    • COI: 1:STN:280:DC%2BD1MvntVWqtA%3D%3D, PID: 19505384
    • Macchi A, Castelnuovo P (2009) Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery. Int J Immunopathol Pharmacol 22:303–310
    • (2009) Int J Immunopathol Pharmacol , vol.22 , pp. 303-310
    • Macchi, A.1    Castelnuovo, P.2
  • 102
    • 53749106586 scopus 로고    scopus 로고
    • Inhaled thiamphenicol and acetylcysteine in children with acute bacterial rhinopharyngitis
    • COI: 1:CAS:528:DC%2BD1cXht1ygs73M, PID: 18831930
    • Varricchio A, Capasso M, Di Gioacchino M, Ciprandi G (2008) Inhaled thiamphenicol and acetylcysteine in children with acute bacterial rhinopharyngitis. Int J Immunopathol Pharmacol 21:625–629
    • (2008) Int J Immunopathol Pharmacol , vol.21 , pp. 625-629
    • Varricchio, A.1    Capasso, M.2    Di Gioacchino, M.3    Ciprandi, G.4


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.