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04.07.2016 | Original Investigation

Colonization of CF patients’ upper airways with S. aureus contributes more decisively to upper airway inflammation than P. aeruginosa

verfasst von: Wibke Katharina Janhsen, Christin Arnold, Julia Hentschel, Thomas Lehmann, Wolfgang Pfister, Michael Baier, Klas Böer, Kerstin Hünniger, Oliver Kurzai, Uta-Christina Hipler, Jochen Georg Mainz

Erschienen in: Medical Microbiology and Immunology | Ausgabe 5/2016

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Abstract

In cystic fibrosis (CF) patients’ airways, inflammatory processes decisively contribute to remodeling and pulmonary destruction. The aims of this study were to compare upper airway (UAW) inflammation in the context of Staphylococcus aureus and Pseudomonas aeruginosa colonization in a longitudinal setting, and to examine further factors influencing UAW inflammation. Therefore, we analyzed soluble inflammatory mediators in noninvasively obtained nasal lavage (NL) of CF patients together with microbiology, medication, and relevant clinical parameters. NL, applying 10 mL of isotonic saline per nostril, was serially performed in 74 CF patients (326 samples). Concentrations of the inflammatory mediators’ interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-9, and its anti-protease TIMP-1 were quantified by bead-based multiplexed assay, neutrophil elastase (NE) via ELISA. Culture-based microbiology of the upper and lower airways (LAW), as well as serological and clinical findings, were compiled. Our results indicate that UAW colonization with S. aureus significantly impacts the concentration of all measured inflammatory mediators in NL fluid except TIMP-1, whereas these effects were not significant for P. aeruginosa. Patients with S. aureus colonization of both the UAW and LAW showed significantly increased concentrations of IL-1β, IL-6, IL-8, MMP-9, and slightly elevated concentrations of NE in NL fluid compared to non-colonized patients. This work elaborates a survey on S. aureus’ virulence factors that may contribute to this underestimated pathology. Serial assessment of epithelial lining fluid by NL reveals that colonization of the UAW with S. aureus contributes more to CF airway inflammatory processes than hitherto expected.

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Stoltz DA, Meyerholz DK, Welsh MJ (2015) Origins of cystic fibrosis lung disease. New Eng J Med 372(4):351–362. doi:10.1056/NEJMra1300109 PubMedPubMedCentralCrossRef

Mall MA, Hartl D (2014) CFTR: cystic fibrosis and beyond. Eur Respir J. doi:10.1183/09031936.00228013 PubMed

Folkesson A, Jelsbak L, Yang L, Johansen HK, Ciofu O, Hoiby N, Molin S (2012) Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective. Nat Rev Microbiol 10(12):841–851. doi:10.1038/nrmicro2907 PubMedCrossRef

Hansen SK, Rau MH, Johansen HK, Ciofu O, Jelsbak L, Yang L, Folkesson A, Jarmer HO, Aanaes K, von Buchwald C, Hoiby N, Molin S (2012) Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection. ISME J 6(1):31–45. doi:10.1038/ismej.2011.83 PubMedCrossRef

Johansen HK, Aanaes K, Pressler T, Nielsen KG, Fisker J, Skov M, Hoiby N, von Buchwald C (2012) Colonisation and infection of the paranasal sinuses in cystic fibrosis patients is accompanied by a reduced PMN response. J Cyst Fibros 11(6):525–531. doi:10.1016/j.jcf.2012.04.011 PubMedCrossRef

Gysin C, Alothman GA, Papsin BC (2000) Sinonasal disease in cystic fibrosis: clinical characteristics, diagnosis, and management. Pediatr Pulmonol 30(6):481–489PubMedCrossRef

Roby BB, McNamara J, Finkelstein M, Sidman J (2008) Sinus surgery in cystic fibrosis patients: comparison of sinus and lower airway cultures. Int J Pediatr Otorhinolaryngol 72(9):1365–1369. doi:10.1016/j.ijporl.2008.05.011 PubMedCrossRef

Bonestroo HJ, de Winter-de Groot KM, van der Ent CK, Arets HG (2010) Upper and lower airway cultures in children with cystic fibrosis: do not neglect the upper airways. J Cyst Fibros 9(2):130–134. doi:10.1016/j.jcf.2010.01.001 PubMedCrossRef

Mainz JG, Hentschel J, Schien C, Cramer N, Pfister W, Beck JF, Tummler B (2012) Sinonasal persistence of Pseudomonas aeruginosa after lung transplantation. J Cyst Fibros 11(2):158–161. doi:10.1016/j.jcf.2011.10.009 PubMedCrossRef

10.

Dickson RP, Erb-Downward JR, Huffnagle GB (2014) Towards an ecology of the lung: new conceptual models of pulmonary microbiology and pneumonia pathogenesis. Lancet Respir Med 2(3):238–246. doi:10.1016/s2213-2600(14)70028-1 PubMedPubMedCentralCrossRef

11.

Ciofu O, Johansen HK, Aanaes K, Wassermann T, Alhede M, von Buchwald C, Hoiby N (2013) P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs. J Cyst Fibros 12(6):729–736. doi:10.1016/j.jcf.2013.02.004 PubMedCrossRef

12.

Aanaes K (2013) Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis. J Cyst Fibros 12(Suppl 2):S1–S20. doi:10.1016/s1569-1993(13)00150-1 PubMedCrossRef

13.

Mainz JG, Naehrlich L, Schien M, Kading M, Schiller I, Mayr S, Schneider G, Wiedemann B, Wiehlmann L, Cramer N, Pfister W, Kahl BC, Beck JF, Tummler B (2009) Concordant genotype of upper and lower airways P. aeruginosa and S. aureus isolates in cystic fibrosis. Thorax 64(6):535–540. doi:10.1136/thx.2008.104711 CrossRef

14.

Martin C, Hamard C, Kanaan R, Boussaud V, Grenet D, Abely M, Hubert D, Munck A, Lemonnier L, Burgel PR (2015) Causes of death in French cystic fibrosis patients: the need for improvement in transplantation referral strategies! J Cyst Fibros. doi:10.1016/j.jcf.2015.09.002

15.

Cystic Fibrosis Foundation (2014) 2013 Annual Data Report to the Center Directors. https://www.cff.org/2013_CFF_Annual_Data_Report_to_the_Center_Directors.pdf. Accessed 14 May 2016

16.

Fischer N, Hentschel J, Markert UR, Keller PM, Pletz MW, Mainz JG (2014) Non-invasive assessment of upper and lower airway infection and inflammation in CF patients. Pediatr Pulmonol. doi:10.1002/ppul.22982

17.

Hentschel J, Fischer N, Janhsen WK, Markert UR, Lehmann T, Sonnemann J, Boer K, Pfister W, Hipler UC, Mainz JG (2014) Protease-antiprotease imbalances differ between cystic fibrosis patients’ upper and lower airway secretions. J Cyst Fibros. doi:10.1016/j.jcf.2014.09.003 PubMed

18.

Ahlgren HG, Benedetti A, Landry JS, Bernier J, Matouk E, Radzioch D, Lands LC, Rousseau S, Nguyen D (2015) Clinical outcomes associated with Staphylococcus aureus and Pseudomonas aeruginosa airway infections in adult cystic fibrosis patients. BMC Pulm Med 15:67. doi:10.1186/s12890-015-0062-7 PubMedPubMedCentralCrossRef

19.

Sagel SD, Gibson RL, Emerson J, McNamara S, Burns JL, Wagener JS, Ramsey BW (2009) Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical status in young children with cystic fibrosis. J Pediatr 154(2):183–188. doi:10.1016/j.jpeds.2008.08.001 PubMedCrossRef

20.

Pillarisetti N, Williamson E, Linnane B, Skoric B, Robertson CF, Robinson P, Massie J, Hall GL, Sly P, Stick S, Ranganathan S (2011) Infection, inflammation, and lung function decline in infants with cystic fibrosis. Am J Respir Crit Care Med 184(1):75–81. doi:10.1164/rccm.201011-1892OC PubMedCrossRef

21.

Gangell C, Gard S, Douglas T, Park J, de Klerk N, Keil T, Brennan S, Ranganathan S, Robins-Browne R, Sly PD (2011) Inflammatory responses to individual microorganisms in the lungs of children with cystic fibrosis. Clin Infect Dis 53(5):425–432. doi:10.1093/cid/cir399 PubMedCrossRef

22.

Andersen DH (1949) Therapy and prognosis of fibrocystic disease of the pancreas. Pediatrics 3(4):406–417PubMed

23.

Wong JK, Ranganathan SC, Hart E (2013) Staphylococcus aureus in early cystic fibrosis lung disease. Pediatr Pulmonol 48(12):1151–1159. doi:10.1002/ppul.22863 PubMedCrossRef

24.

Kahl BC (2010) Impact of Staphylococcus aureus on the pathogenesis of chronic cystic fibrosis lung disease. Int J Med Microbiol 300(8):514–519. doi:10.1016/j.ijmm.2010.08.002 PubMedCrossRef

25.

Wang JH, Kwon HJ, Jang YJ (2010) Staphylococcus aureus increases cytokine and matrix metalloproteinase expression in nasal mucosae of patients with chronic rhinosinusitis and nasal polyps. Am J Rhinol Allergy 24(6):422–427. doi:10.2500/ajra.2010.24.3509 PubMedCrossRef

26.

Ou J, Wang J, Xu Y, Tao ZZ, Kong YG, Chen SM, Shi WD (2014) Staphylococcus aureus superantigens are associated with chronic rhinosinusitis with nasal polyps: a meta-analysis. Eur Arch Otorhinolaryngol 271(10):2729–2736. doi:10.1007/s00405-014-2955-0 PubMedCrossRef

27.

Alexis NE (2014) Biomarker sampling of the airways in asthma. Curr Opin Pulm Med 20(1):46–52. doi:10.1097/MCP.0000000000000010 PubMedCrossRef

28.

Araujo E, Palombini BC, Cantarelli V, Pereira A, Mariante A (2003) Microbiology of middle meatus in chronic rhinosinusitis. Am J Rhinol 17(1):9–15PubMed

29.

Mauch H, Podbielski A, Herrmann M, Kniehl E (2007) Qualitätsstandards EM-I. MIQ: Qualitätsstandards in der mikrobiologischinfektiologischen Diagnostik. Urban & Fischer Verlag/Elsevier GmbH, München und Jena

30.

Lee TW, Brownlee KG, Conway SP, Denton M, Littlewood JM (2003) Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2(1):29–34. doi:10.1016/s1569-1993(02)00141-8 PubMedCrossRef

31.

Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ (2012) EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 50(1):1–12. doi:10.4193/Rhino50E2 PubMed

32.

Huvenne W, Hellings PW, Bachert C (2013) Role of staphylococcal superantigens in airway disease. Int Arch Allergy Immunol 161(4):304–314. doi:10.1159/000350329 PubMedCrossRef

33.

Foster TJ, Geoghegan JA, Ganesh VK, Hook M (2014) Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat Rev Microbiol 12(1):49–62. doi:10.1038/nrmicro3161 PubMedCrossRef

34.

Gomez MI, Lee A, Reddy B, Muir A, Soong G, Pitt A, Cheung A, Prince A (2004) Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1. Nat Med 10(8):842–848. doi:10.1038/nm1079 PubMedCrossRef

35.

Tsuchiya M, Kumar P, Bhattacharyya S, Chattoraj S, Srivastava M, Pollard HB, Biswas R (2013) Differential regulation of inflammation by inflammatory mediators in cystic fibrosis lung epithelial cells. J Interferon Cytokine Res 33(3):121–129. doi:10.1089/jir.2012.0074 PubMedCrossRef

36.

Bhattacharyya S, Balakathiresan NS, Dalgard C, Gutti U, Armistead D, Jozwik C, Srivastava M, Pollard HB, Biswas R (2011) Elevated miR-155 promotes inflammation in cystic fibrosis by driving hyperexpression of interleukin-8. J Biol Chem 286(13):11604–11615. doi:10.1074/jbc.M110.198390 PubMedPubMedCentralCrossRef

37.

Rao R, Nagarkatti P, Nagarkatti M (2015) Role of miRNA in the regulation of inflammatory genes in staphylococcal enterotoxin B-induced acute inflammatory lung injury and mortality. Toxicol Sci 144(2):284–297. doi:10.1093/toxsci/kfu315 PubMedPubMedCentralCrossRef

38.

Dilda F, Gioia G, Pisani L, Restelli L, Lecchi C, Albonico F, Bronzo V, Mortarino M, Ceciliani F (2012) Escherichia coli lipopolysaccharides and Staphylococcus aureus enterotoxin B differentially modulate inflammatory microRNAs in bovine monocytes. Vet J 192(3):514–516. doi:10.1016/j.tvjl.2011.08.018 PubMedCrossRef

39.

Voynow JA, Fischer BM, Zheng S (2008) Proteases and cystic fibrosis. Int J Biochem Cell Biol 40(6–7):1238–1245. doi:10.1016/j.biocel.2008.03.003 PubMedCentralCrossRef

40.

Weldon S, McNally P, McElvaney NG, Elborn JS, McAuley DF, Wartelle J, Belaaouaj A, Levine RL, Taggart CC (2009) Decreased levels of secretory leucoprotease inhibitor in the Pseudomonas-infected cystic fibrosis lung are due to neutrophil elastase degradation. J Immunol 183(12):8148–8156. doi:10.4049/jimmunol.0901716 PubMedPubMedCentralCrossRef

41.

Weathington NM, van Houwelingen AH, Noerager BD, Jackson PL, Kraneveld AD, Galin FS, Folkerts G, Nijkamp FP, Blalock JE (2006) A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med 12(3):317–323. doi:10.1038/nm1361 PubMedCrossRef

42.

Halverson TW, Wilton M, Poon KK, Petri B, Lewenza S (2015) DNA is an antimicrobial component of neutrophil extracellular traps. PLoS Pathog 11(1):e1004593. doi:10.1371/journal.ppat.1004593 PubMedPubMedCentralCrossRef

43.

Weidenmaier C, Goerke C, Wolz C (2012) Staphylococcus aureus determinants for nasal colonization. Trends Microbiol 20(5):243–250. doi:10.1016/j.tim.2012.03.004 PubMedCrossRef

44.

Giai C, Gonzalez C, Ledo C, Garofalo A, Di Genaro MS, Sordelli DO, Gomez MI (2013) Shedding of tumor necrosis factor receptor 1 induced by protein A decreases tumor necrosis factor alpha availability and inflammation during systemic Staphylococcus aureus infection. Infect Immun 81(11):4200–4207. doi:10.1128/iai.00593-13 PubMedPubMedCentralCrossRef

45.

Michl RK, Hentschel J, Fischer C, Beck JF, Mainz JG (2013) Reduced nasal nitric oxide production in cystic fibrosis patients with elevated systemic inflammation markers. PLoS ONE 8(11):e79141. doi:10.1371/journal.pone.0079141 PubMedPubMedCentralCrossRef

46.

Tang AC, Turvey SE, Alves MP, Regamey N, Tummler B, Hartl D (2014) Current concepts: host-pathogen interactions in cystic fibrosis airways disease. Eur Respir Rev 23(133):320–332. doi:10.1183/09059180.00006113 PubMedCrossRef

47.

Cohen TS, Prince A (2012) Cystic fibrosis: a mucosal immunodeficiency syndrome. Nat Med 18(4):509–519. doi:10.1038/nm.2715 PubMedPubMedCentralCrossRef

48.

Gifford AM, Chalmers JD (2014) The role of neutrophils in cystic fibrosis. Curr Opin Hematol 21(1):16–22. doi:10.1097/MOH.0000000000000009 PubMedCrossRef

49.

Cohen-Cymberknoh M, Kerem E, Ferkol T, Elizur A (2013) Airway inflammation in cystic fibrosis: molecular mechanisms and clinical implications. Thorax 68(12):1157–1162. doi:10.1136/thoraxjnl-2013-203204 PubMedCrossRef

50.

Hirschhausen N, Block D, Bianconi I, Bragonzi A, Birtel J, Lee JC, Dubbers A, Kuster P, Kahl J, Peters G, Kahl BC (2013) Extended Staphylococcus aureus persistence in cystic fibrosis is associated with bacterial adaptation. Int J Med Microbiol 303(8):685–692. doi:10.1016/j.ijmm.2013.09.012 PubMedCrossRef

51.

Goerke C, Wolz C (2010) Adaptation of Staphylococcus aureus to the cystic fibrosis lung. Int J Med Microbiol 300(8):520–525. doi:10.1016/j.ijmm.2010.08.003 PubMedCrossRef

52.

Windmuller N, Witten A, Block D, Bunk B, Sproer C, Kahl BC, Mellmann A (2015) Transcriptional adaptations during long-term persistence of Staphylococcus aureus in the airways of a cystic fibrosis patient. Int J Med Microbiol 305(1):38–46. doi:10.1016/j.ijmm.2014.10.005 PubMedCrossRef

53.

Frederiksen B, Pressler T, Hansen A, Koch C, Hoiby N (2006) Effect of aerosolized rhDNase (Pulmozyme) on pulmonary colonization in patients with cystic fibrosis. Acta Paediatr 95(9):1070–1074. doi:10.1080/08035250600752466 PubMedCrossRef

54.

Bonestroo HJ, Slieker MG, Arets HG (2010) No positive effect of rhdnase on the pulmonary colonization in children with cystic fibrosis. Monaldi Arch Chest Dis 73(1):12–17PubMed

55.

Meng W, Paunel-Gorgulu A, Flohe S, Hoffmann A, Witte I, MacKenzie C, Baldus SE, Windolf J, Logters TT (2012) Depletion of neutrophil extracellular traps in vivo results in hypersusceptibility to polymicrobial sepsis in mice. Crit Care 16(4):R137. doi:10.1186/cc11442 PubMedPubMedCentralCrossRef

56.

Moskowitz SM, Ernst RK (2010) The role of Pseudomonas lipopolysaccharide in cystic fibrosis airway infection. Subcell Biochem 53:241–253. doi:10.1007/978-90-481-9078-2_11 PubMedPubMedCentralCrossRef

57.

Hector A, Schafer H, Poschel S, Fischer A, Fritzsching B, Ralhan A, Carevic M, Oz H, Zundel S, Hogardt M, Bakele M, Rieber N, Riethmueller J, Graepler-Mainka U, Stahl M, Bender A, Frick JS, Mall M, Hartl D (2015) Regulatory T cell impairment in cystic fibrosis patients with chronic Pseudomonas infection. Am J Respir Crit Care Med. doi:10.1164/rccm.201407-1381OC PubMed

58.

Hogardt M, Heesemann J (2010) Adaptation of Pseudomonas aeruginosa during persistence in the cystic fibrosis lung. Int J Med Microbiol 300(8):557–562. doi:10.1016/j.ijmm.2010.08.008 PubMedCrossRef

59.

Baldan R, Cigana C, Testa F, Bianconi I, De Simone M, Pellin D, Di Serio C, Bragonzi A, Cirillo DM (2014) Adaptation of Pseudomonas aeruginosa in cystic fibrosis airways influences virulence of Staphylococcus aureus in vitro and murine models of co-infection. PLoS ONE 9(3):e89614. doi:10.1371/journal.pone.0089614 PubMedPubMedCentralCrossRef

60.

Wolter J, Seeney S, Bell S, Bowler S, Masel P, McCormack J (2002) Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Thorax 57(3):212–216PubMedPubMedCentralCrossRef

61.

Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S, Anstead M (2012) Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest 142(5):1259–1266. doi:10.1378/chest.12-0628 PubMedPubMedCentralCrossRef

62.

Cameron EJ, McSharry C, Chaudhuri R, Farrow S, Thomson NC (2012) Long-term macrolide treatment of chronic inflammatory airway diseases: risks, benefits and future developments. Clin Exp Allergy 42(9):1302–1312. doi:10.1111/j.1365-2222.2012.03979.x PubMedCrossRef

63.

Gavilanes X, Huaux F, Meyer M, Lebecque P, Marbaix E, Lison D, Scholte B, Wallemacq P, Leal T (2009) Azithromycin fails to reduce increased expression of neutrophil-related cytokines in primary-cultured epithelial cells from cystic fibrosis mice. J Cyst Fibros 8(3):203–210. doi:10.1016/j.jcf.2009.03.003 PubMedCrossRef

64.

Saint-Criq V, Ruffin M, Rebeyrol C, Guillot L, Jacquot J, Clement A, Tabary O (2012) Azithromycin fails to reduce inflammation in cystic fibrosis airway epithelial cells. Eur J Pharmacol 674(1):1–6. doi:10.1016/j.ejphar.2011.10.027 PubMedCrossRef

65.

Hentschel J, Jager M, Beiersdorf N, Fischer N, Doht F, Michl RK, Lehmann T, Markert UR, Boer K, Keller PM, Pletz MW, Mainz JG (2014) Dynamics of soluble and cellular inflammatory markers in nasal lavage obtained from cystic fibrosis patients during intravenous antibiotic treatment. BMC Pulm Med 14(1):82. doi:10.1186/1471-2466-14-82 PubMedPubMedCentralCrossRef

66.

Beigelman A, Isaacson-Schmid M, Sajol G, Baty J, Rodriguez OM, Leege E, Lyons K, Schweiger TL, Zheng J, Schechtman KB, Castro M, Bacharier LB (2015) Randomized trial to evaluate azithromycin’s effects on serum and upper airway IL-8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis. J Allergy Clin Immunol 135(5):1171–1178.e1. doi:10.1016/j.jaci.2014.10.001 PubMedCrossRef

67.

Yamada T, Fujieda S, Mori S, Yamamoto H, Saito H (2000) Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal lavage. Am J Rhinol 14(3):143–148PubMedCrossRef

68.

Biswas L, Biswas R, Schlag M, Bertram R, Gotz F (2009) Small-colony variant selection as a survival strategy for Staphylococcus aureus in the presence of Pseudomonas aeruginosa. Appl Environ Microbiol 75(21):6910–6912. doi:10.1128/aem.01211-09 PubMedPubMedCentralCrossRef

69.

Zhang YJ, Luroe S, Schieber F, Kelsey J, Nabbie F, Rizzi G, Richards P, Weiner R, Rhyne PW (2009) Immunoassay-based measurement of clinical biomarkers for monitoring changes in nasal cavity. J Pharm Biomed Anal 50(5):823–830. doi:10.1016/j.jpba.2009.06.043 PubMedCrossRef

70.

Hentschel J, Muller U, Doht F, Fischer N, Boer K, Sonnemann J, Hipler C, Hunniger K, Kurzai O, Markert UR, Mainz JG (2013) Influences of nasal lavage collection-, processing-and storage methods on inflammatory markers—evaluation of a method for non-invasive sampling of epithelial lining fluid in cystic fibrosis and other respiratory diseases. J Immunol Methods. doi:10.1016/j.jim.2013.12.003 PubMed

71.

Doring G, Hoiby N (2004) Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. J Cyst Fibros 3(2):67–91. doi:10.1016/j.jcf.2004.03.008 PubMedCrossRef

72.

Dalboge CS, Pressler T, Hoiby N, Nielsen KG, Johansen HK (2013) A cohort study of the Copenhagen CF centre eradication strategy against Staphylococcus aureus in patients with CF. J Cyst Fibros 12(1):42–48. doi:10.1016/j.jcf.2012.06.005 PubMedCrossRef

73.

Smyth AR, Walters S (2014) Prophylactic anti-staphylococcal antibiotics for cystic fibrosis. Cochrane Database Syst Rev 11:Cd001912. doi:10.1002/14651858.CD001912.pub3 PubMed

74.

UK Cystic Fibrosis Trust AWG (2009) Antibiotic treatment for cystic fibrosis. Report of the UK Cystic Fibrosis Trust Antibiotic Working Group. 3rd Edition. https://www.cysticfibrosis.org.uk/~/media/documents/life-with-cf/care-and-treatment/cd_antibiotic_treatment_for_cf_may_09.ashx?la=en. Accessed 14 May 2016

Titel: Colonization of CF patients’ upper airways with S. aureus contributes more decisively to upper airway inflammation than P. aeruginosa
verfasst von: Wibke Katharina Janhsen
Christin Arnold
Julia Hentschel
Thomas Lehmann
Wolfgang Pfister
Michael Baier
Klas Böer
Kerstin Hünniger
Oliver Kurzai
Uta-Christina Hipler
Jochen Georg Mainz
Publikationsdatum: 04.07.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Medical Microbiology and Immunology / Ausgabe 5/2016
Print ISSN: 0300-8584
Elektronische ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-016-0463-0

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