Portal de Periódicos da CAPES

Pathogenesis of Early Lung Disease in Cystic Fibrosis: A Window of Opportunity To Eradicate Bacteria

2005; American College of Physicians; Volume: 143; Issue: 11 Linguagem: Inglês

10.7326/0003-4819-143-11-200512060-00010

1539-3704

Timothy D. Starner, Paul B. McCray,

Tracheal and airway disorders

Reviews6 December 2005Pathogenesis of Early Lung Disease in Cystic Fibrosis: A Window of Opportunity To Eradicate BacteriaTimothy D. Starner, MD and Paul B. McCray Jr., MDTimothy D. Starner, MDFrom University of Iowa, Iowa City, Iowa. and Paul B. McCray Jr., MDFrom University of Iowa, Iowa City, Iowa.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-11-200512060-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesEarly lung disease in patients with cystic fibrosis may be clinically silent.Bacterial colonization, inflammation, or both can be detected before other signs or symptoms of lung disease develop.Pathophysiologic PrinciplesThe early pathophysiology of lung disease in patients with cystic fibrosis has several interconnected deleterious cycles leading to impaired innate immunity.Patients with cystic fibrosis typically experience transition from sterile lower airways, to transient infections (with organisms including nontypeable Haemophilius influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa), to chronic nonmucoid P. aeruginosa infection, to mucoid biofilm P. aeruginosa infection.The time before chronic colonization with P. aeruginosa represents a window of opportunity to eradicate ...References1. Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, et al. Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR Recomm Rep. 2004;53:1-36. [PMID: 15483524] MedlineGoogle Scholar2. Chow CW, Landau LI, Taussig LM. Bronchial mucous glands in the newborn with cystic fibrosis. Eur J Pediatr. 1982;139:240-3. [PMID: 7182186] CrossrefMedlineGoogle Scholar3. Farrell PM, Li Z, Kosorok MR, Laxova A, Green CG, Collins J, et al. Longitudinal evaluation of bronchopulmonary disease in children with cystic fibrosis. Pediatr Pulmonol. 2003;36:230-40. [PMID: 12910585] CrossrefMedlineGoogle Scholar4. Armstrong DS, Grimwood K, Carlin JB, Carzino R, Gutièrrez JP, Hull J, et al. Lower airway inflammation in infants and young children with cystic fibrosis. Am J Respir Crit Care Med. 1997;156:1197-204. [PMID: 9351622] CrossrefMedlineGoogle Scholar5. Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995;151:1075-82. [PMID: 7697234] MedlineGoogle Scholar6. Balough K, McCubbin M, Weinberger M, Smits W, Ahrens R, Fick R. The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis. Pediatr Pulmonol. 1995;20:63-70. [PMID: 8570304] CrossrefMedlineGoogle Scholar7. Armstrong DS, Hook SM, Jamsen KM, Nixon GM, Carzino R, Carlin JB, et al. Lower airway inflammation in infants with cystic fibrosis detected by newborn screening. Pediatr Pulmonol. 2005;40:500-10. [PMID: 16208679] CrossrefMedlineGoogle Scholar8. Meyer KC, Sharma A. Regional variability of lung inflammation in cystic fibrosis. Am J Respir Crit Care Med. 1997;156:1536-40. [PMID: 9372672] CrossrefMedlineGoogle Scholar9. Gutierrez JP, Grimwood K, Armstrong DS, Carlin JB, Carzino R, Olinsky A, et al. Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis. Eur Respir J. 2001;17:281-6. [PMID: 11334132] CrossrefMedlineGoogle Scholar10. Rosenfeld M, Gibson RL, McNamara S, Emerson J, Burns JL, Castile R, et al. Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr Pulmonol. 2001;32:356-66. [PMID: 11596160] CrossrefMedlineGoogle Scholar11. Cystic Fibrosis Foundation Registry Data Annual Report. Cystic Fibrosis Foundation National Cystic Fibrosis Patient Registry 2001. Annual Data Report. Bethesda, MD: Cystic Fibrosis Foundation; 2002. Google Scholar12. Valerius NH, Koch C, Høiby N. Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet. 1991;338:725-6. [PMID: 1679870] CrossrefMedlineGoogle Scholar13. Frederiksen B, Koch C, Høiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol. 1997;23:330-5. [PMID: 9168506] CrossrefMedlineGoogle Scholar14. Burns JL, Gibson RL, McNamara S, Yim D, Emerson J, Rosenfeld M, et al. Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis. 2001;183:444-52. [PMID: 11133376] CrossrefMedlineGoogle Scholar15. Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol. 2002;34:91-100. [PMID: 12112774] CrossrefMedlineGoogle Scholar16. Schaedel C, de Monestrol, Hjelte L, Johannesson M, Kornfält R, Lindblad A, et al. Predictors of deterioration of lung function in cystic fibrosis. Pediatr Pulmonol. 2002;33:483-91. [PMID: 12001283] CrossrefMedlineGoogle Scholar17. Li Z, Kosorok MR, Farrell PM, Laxova A, West SE, Green CG, et al. Longitudinal development of mucoid Pseudomonas aeruginosa infection and lung disease progression in children with cystic fibrosis. JAMA. 2005;293:581-8. [PMID: 15687313] CrossrefMedlineGoogle Scholar18. Demko CA, Byard PJ, Davis PB. Gender differences in cystic fibrosis: Pseudomonas aeruginosa infection. J Clin Epidemiol. 1995;48:1041-9. [PMID: 7775991] CrossrefMedlineGoogle Scholar19. Parad RB, Gerard CJ, Zurakowski D, Nichols DP, Pier GB. Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype. Infect Immun. 1999;67:4744-50. [PMID: 10456926] CrossrefMedlineGoogle Scholar20. Hentzer M, Teitzel GM, Balzer GJ, Heydorn A, Molin S, Givskov M, et al. Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function. J Bacteriol. 2001;183:5395-401. [PMID: 11514525] CrossrefMedlineGoogle Scholar21. Høiby N. Prospects for the prevention and control of pseudomonal infection in children with cystic fibrosis. Paediatr Drugs. 2000;2:451-63. [PMID: 11127845] CrossrefMedlineGoogle Scholar22. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284:1318-22. [PMID: 10334980] CrossrefMedlineGoogle Scholar23. Parsek MR, Singh PK. Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol. 2003;57:677-701. [PMID: 14527295] CrossrefMedlineGoogle Scholar24. Prince AS. Biofilms, antimicrobial resistance, and airway infection. N Engl J Med. 2002;347:1110-1. [PMID: 12362015] CrossrefMedlineGoogle Scholar25. Jesaitis AJ, Franklin MJ, Berglund D, Sasaki M, Lord CI, Bleazard JB, et al. Compromised host defense on Pseudomonas aeruginosa biofilms: characterization of neutrophil and biofilm interactions. J Immunol. 2003;171:4329-39. [PMID: 14530358] CrossrefMedlineGoogle Scholar26. Høiby N. Understanding bacterial biofilms in patients with cystic fibrosis: current and innovative approaches to potential therapies. J Cyst Fibros. 2002;1:249-54. [PMID: 15463822] CrossrefMedlineGoogle Scholar27. Singh PK, Schaefer AL, Parsek MR, Moninger TO, Welsh MJ, Greenberg EP. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature. 2000;407:762-4. [PMID: 11048725] CrossrefMedlineGoogle Scholar28. Poschet JF, Boucher JC, Tatterson L, Skidmore J, Van Dyke RW, Deretic V. Molecular basis for defective glycosylation and Pseudomonas pathogenesis in cystic fibrosis lung. Proc Natl Acad Sci U S A. 2001;98:13972-7. [PMID: 11717455] CrossrefMedlineGoogle Scholar29. Imundo L, Barasch J, Prince A, Al-Awqati Q. Cystic fibrosis epithelial cells have a receptor for pathogenic bacteria on their apical surface. Proc Natl Acad Sci U S A. 1995;92:3019-23. [PMID: 7708767] CrossrefMedlineGoogle Scholar30. Bryan R, Kube D, Perez A, Davis P, Prince A. Overproduction of the CFTR R domain leads to increased levels of asialoGM1 and increased Pseudomonas aeruginosa binding by epithelial cells. Am J Respir Cell Mol Biol. 1998;19:269-77. [PMID: 9698599] CrossrefMedlineGoogle Scholar31. Matsui H, Grubb BR, Tarran R, Randell SH, Gatzy JT, Davis CW, et al. Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell. 1998;95:1005-15. [PMID: 9875854] CrossrefMedlineGoogle Scholar32. Sturgess J, Imrie J. Quantitative evaluation of the development of tracheal submucosal glands in infants with cystic fibrosis and control infants. Am J Pathol. 1982;106:303-11. [PMID: 7065115] MedlineGoogle Scholar33. Bonfield TL, Konstan MW, Berger M. Altered respiratory epithelial cell cytokine production in cystic fibrosis. J Allergy Clin Immunol. 1999;104:72-8. [PMID: 10400842] CrossrefMedlineGoogle Scholar34. Joseph T, Look D, Ferkol T. NF-kappaB activation and sustained IL-8 gene expression in primary cultures of cystic fibrosis airway epithelial cells stimulated with Pseudomonas aeruginosa. Am J Physiol Lung Cell Mol Physiol. 2005;288:L471-9. [PMID: 15516493] CrossrefMedlineGoogle Scholar35. DiMango E, Zar HJ, Bryan R, Prince A. Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8. J Clin Invest. 1995;96:2204-10. [PMID: 7593606] CrossrefMedlineGoogle Scholar36. Chmiel JF, Konstan MW, Knesebeck JE, Hilliard JB, Bonfield TL, Dawson DV, et al. IL-10 attenuates excessive inflammation in chronic Pseudomonas infection in mice. Am J Respir Crit Care Med. 1999;160:2040-7. [PMID: 10588626] CrossrefMedlineGoogle Scholar37. Heeckeren A, Walenga R, Konstan MW, Bonfield T, Davis PB, Ferkol T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa. J Clin Invest. 1997;100:2810-5. [PMID: 9389746] CrossrefMedlineGoogle Scholar38. Tirouvanziam R, de Bentzmann S, Hubeau C, Hinnrasky J, Jacquot J, Péault B, et al. Inflammation and infection in naive human cystic fibrosis airway grafts. Am J Respir Cell Mol Biol. 2000;23:121-7. [PMID: 10919974] CrossrefMedlineGoogle Scholar39. Aldallal N, McNaughton EE, Manzel LJ, Richards AM, Zabner J, Ferkol TW, et al. Inflammatory response in airway epithelial cells isolated from patients with cystic fibrosis. Am J Respir Crit Care Med. 2002;166:1248-56. [PMID: 12403695] CrossrefMedlineGoogle Scholar40. Becker MN, Sauer MS, Muhlebach MS, Hirsh AJ, Wu Q, Verghese MW, et al. Cytokine secretion by cystic fibrosis airway epithelial cells. Am J Respir Crit Care Med. 2004;169:645-53. [PMID: 14670800] CrossrefMedlineGoogle Scholar41. Velsor LW, van Heeckeren A, Day BJ. Antioxidant imbalance in the lungs of cystic fibrosis transmembrane conductance regulator protein mutant mice. Am J Physiol Lung Cell Mol Physiol. 2001;281:L31-8. [PMID: 11404242] CrossrefMedlineGoogle Scholar42. Day BJ, van Heeckeren AM, Min E, Velsor LW. Role for cystic fibrosis transmembrane conductance regulator protein in a glutathione response to bronchopulmonary pseudomonas infection. Infect Immun. 2004;72:2045-51. [PMID: 15039325] CrossrefMedlineGoogle Scholar43. Noah TL, Black HR, Cheng PW, Wood RE, Leigh MW. Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis. J Infect Dis. 1997;175:638-47. [PMID: 9041336] CrossrefMedlineGoogle Scholar44. Hiatt PW, Grace SC, Kozinetz CA, Raboudi SH, Treece DG, Taber LH, et al. Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis. Pediatrics. 1999;103:619-26. [PMID: 10049966] CrossrefMedlineGoogle Scholar45. Pier GB, Grout M, Zaidi TS, Olsen JC, Johnson LG, Yankaskas JR, et al. Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science. 1996;271:64-7. [PMID: 8539601] CrossrefMedlineGoogle Scholar46. Smith JJ, Travis SM, Greenberg EP, Welsh MJ. Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell. 1996;85:229-36. [PMID: 8612275] CrossrefMedlineGoogle Scholar47. Kelley TJ, Drumm ML. Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells. J Clin Invest. 1998;102:1200-7. [PMID: 9739054] CrossrefMedlineGoogle Scholar48. Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM. Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell. 1997;88:553-60. [PMID: 9038346] CrossrefMedlineGoogle Scholar49. Abman SH, Ogle JW, Harbeck RJ, Butler-Simon N, Hammond KB, Accurso FJ. Early bacteriologic, immunologic, and clinical courses of young infants with cystic fibrosis identified by neonatal screening. J Pediatr. 1991;119:211-7. [PMID: 1907318] CrossrefMedlineGoogle Scholar50. Muhlebach MS, Stewart PW, Leigh MW, Noah TL. Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients. Am J Respir Crit Care Med. 1999;160:186-91. [PMID: 10390398] CrossrefMedlineGoogle Scholar51. Johansen HK, Høiby N. Seasonal onset of initial colonisation and chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis in Denmark. Thorax. 1992;47:109-11. [PMID: 1549817] CrossrefMedlineGoogle Scholar52. Kanthakumar K, Taylor GW, Cundell DR, Dowling RB, Johnson M, Cole PJ, et al. The effect of bacterial toxins on levels of intracellular adenosine nucleotides and human ciliary beat frequency. Pulm Pharmacol. 1996;9:223-30. [PMID: 9160410] CrossrefMedlineGoogle Scholar53. Munro NC, Barker A, Rutman A, Taylor G, Watson D, McDonald-Gibson WJ, et al. Effect of pyocyanin and 1-hydroxyphenazine on in vivo tracheal mucus velocity. J Appl Physiol. 1989;67:316-23. [PMID: 2759959] CrossrefMedlineGoogle Scholar54. Del Donno M, Bittesnich D, Chetta A, Olivieri D, Lopez-Vidriero MT. The effect of inflammation on mucociliary clearance in asthma: an overview. Chest. 2000;118:1142-9. [PMID: 11035690] CrossrefMedlineGoogle Scholar55. Amitani R, Wilson R, Rutman A, Read R, Ward C, Burnett D, et al. Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium. Am J Respir Cell Mol Biol. 1991;4:26-32. [PMID: 1898852] CrossrefMedlineGoogle Scholar56. Svartengren M, Mossberg B, Philipson K, Camner P. Mucociliary clearance in relation to clinical features in patients with bronchiectasis. Eur J Respir Dis. 1986;68:267-78. [PMID: 3732423] MedlineGoogle Scholar57. McShane D, Davies JC, Wodehouse T, Bush A, Geddes D, Alton EW. Normal nasal mucociliary clearance in CF children: evidence against a CFTR-related defect. Eur Respir J. 2004;24:95-100. [PMID: 15293610] CrossrefMedlineGoogle Scholar58. Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol. 2002;33:293-306. [PMID: 11921459] CrossrefMedlineGoogle Scholar59. Saba S, Soong G, Greenberg S, Prince A. Bacterial stimulation of epithelial G-CSF and GM-CSF expression promotes PMN survival in CF airways. Am J Respir Cell Mol Biol. 2002;27:561-7. [PMID: 12397015] CrossrefMedlineGoogle Scholar60. Bonfield TL, Panuska JR, Konstan MW, Hilliard KA, Hilliard JB, Ghnaim H, et al. Inflammatory cytokines in cystic fibrosis lungs. Am J Respir Crit Care Med. 1995;152:2111-8. [PMID: 8520783] CrossrefMedlineGoogle Scholar61. Venaille TJ, Ryan G, Robinson BW. Epithelial cell damage is induced by neutrophil-derived, not pseudomonas-derived, proteases in cystic fibrosis sputum. Respir Med. 1998;92:233-40. [PMID: 9616518] CrossrefMedlineGoogle Scholar62. Birrer P, McElvaney NG, Rüdeberg A, Sommer CW, Liechti-Gallati S, Kraemer R, et al. Protease-antiprotease imbalance in the lungs of children with cystic fibrosis. Am J Respir Crit Care Med. 1994;150:207-13. [PMID: 7912987] CrossrefMedlineGoogle Scholar63. Britigan BE, Edeker BL. Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation. J Clin Invest. 1991;88:1092-102. [PMID: 1655825] CrossrefMedlineGoogle Scholar64. Hull J, Vervaart P, Grimwood K, Phelan P. Pulmonary oxidative stress response in young children with cystic fibrosis. Thorax. 1997;52:557-60. [PMID: 9227724] CrossrefMedlineGoogle Scholar65. Tosi MF, Zakem H, Berger M. Neutrophil elastase cleaves C3bi on opsonized pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. J Clin Invest. 1990;86:300-8. [PMID: 2164045] CrossrefMedlineGoogle Scholar66. Fick RB, Naegel GP, Squier SU, Wood RE, Gee JB, Reynolds HY. Proteins of the cystic fibrosis respiratory tract. Fragmented immunoglobulin G opsonic antibody causing defective opsonophagocytosis. J Clin Invest. 1984;74:236-48. [PMID: 6429195] CrossrefMedlineGoogle Scholar67. Alcorn JF, Wright JR. Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function. J Biol Chem. 2004;279:30871-9. [PMID: 15123664] CrossrefMedlineGoogle Scholar68. Britigan BE, Hayek MB, Doebbeling BN, Fick RB. Transferrin and lactoferrin undergo proteolytic cleavage in the Pseudomonas aeruginosa-infected lungs of patients with cystic fibrosis. Infect Immun. 1993;61:5049-55. [PMID: 8225581] CrossrefMedlineGoogle Scholar69. Taggart CC, Lowe GJ, Greene CM, Mulgrew AT, O'Neill SJ, Levine RL, et al. Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. J Biol Chem. 2001;276:33345-52. [PMID: 11435427] CrossrefMedlineGoogle Scholar70. Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB, O'Neill S, et al. Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol. 2003;171:931-7. [PMID: 12847264] CrossrefMedlineGoogle Scholar71. Schuster A, Fahy JV, Ueki I, Nadel JA. Cystic fibrosis sputum induces a secretory response from airway gland serous cells that can be prevented by neutrophil protease inhibitors. Eur Respir J. 1995;8:10-4. [PMID: 7744174] CrossrefMedlineGoogle Scholar72. Nakamura H, Yoshimura K, McElvaney NG, Crystal RG. Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest. 1992;89:1478-84. [PMID: 1569186] CrossrefMedlineGoogle Scholar73. Carnoy C, Scharfman A, Van Brussel E, Lamblin G, Ramphal R, Roussel P. Pseudomonas aeruginosa outer membrane adhesins for human respiratory mucus glycoproteins. Infect Immun. 1994;62:1896-900. [PMID: 8168955] CrossrefMedlineGoogle Scholar74. Dakin CJ, Numa AH, Wang H, Morton JR, Vertzyas CC, Henry RL. Inflammation, infection, and pulmonary function in infants and young children with cystic fibrosis. Am J Respir Crit Care Med. 2002;165:904-10. [PMID: 11934712] CrossrefMedlineGoogle Scholar75. Ernst RK, Yi EC, Guo L, Lim KB, Burns JL, Hackett M, et al. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science. 1999;286:1561-5. [PMID: 10567263] CrossrefMedlineGoogle Scholar76. Oliver A, Cantón R, Campo P, Baquero F, Blázquez J. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science. 2000;288:1251-4. [PMID: 10818002] CrossrefMedlineGoogle Scholar77. Koch C. Early infection and progression of cystic fibrosis lung disease. Pediatr Pulmonol. 2002;34:232-6. [PMID: 12203855] CrossrefMedlineGoogle Scholar78. Wiesemann HG, Steinkamp G, Ratjen F, Bauernfeind A, Przyklenk B, Döring G, et al. Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis. Pediatr Pulmonol. 1998;25:88-92. [PMID: 9516091] CrossrefMedlineGoogle Scholar79. Ratjen F, Döring G, Nikolaizik WH. Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis [Letter]. Lancet. 2001;358:983-4. [PMID: 11583754] CrossrefMedlineGoogle Scholar80. Munck A, Bonacorsi S, Mariani-Kurkdjian P, Lebourgeois M, Gérardin M, Brahimi N, et al. Genotypic characterization of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonization. Pediatr Pulmonol. 2001;32:288-92. [PMID: 11568989] CrossrefMedlineGoogle Scholar81. Nixon GM, Armstrong DS, Carzino R, Carlin JB, Olinsky A, Robertson CF, et al. Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis. J Pediatr. 2001;138:699-704. [PMID: 11343046] CrossrefMedlineGoogle Scholar82. Griese M, Müller I, Reinhardt D. Eradication of initial Pseudomonas aeruginosa colonization in patients with cystic fibrosis. Eur J Med Res. 2002;7:79-80. [PMID: 11891148] MedlineGoogle Scholar83. Gibson RL, Emerson J, McNamara S, Burns JL, Rosenfeld M, Yunker A, et al. Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am J Respir Crit Care Med. 2003;167:841-9. [PMID: 12480612] CrossrefMedlineGoogle Scholar84. Lee TW, Brownlee KG, Denton M, Littlewood JM, Conway SP. Reduction in prevalence of chronic Pseudomonas aeruginosa infection at a regional pediatric cystic fibrosis center. Pediatr Pulmonol. 2004;37:104-10. [PMID: 14730654] CrossrefMedlineGoogle Scholar85. Rosenfeld M, Ramsey BW, Gibson RL. Pseudomonas acquisition in young patients with cystic fibrosis: pathophysiology, diagnosis, and management. Curr Opin Pulm Med. 2003;9:492-7. [PMID: 14534401] CrossrefMedlineGoogle Scholar86. Early Pseudomonas Infection Control (EPIC) Trial. National Heart, Lung, and Blood Institute (NHLBI). Accessed at www.clinicaltrials.gov/ct/gui/show/NCT00097773 on 18 October 2005. Google Scholar87. Chiron-Corporation. Chiron Announces Launch of ELITE Trial. Accessed at phx.corporate-ir.net/phoenix.zhtml?c=105850&p=irol-newsArticle&ID=552967&highlight= on 18 October 2005. Google Scholar88. Frederiksen B, Koch C, Høiby N. Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974–1995). Pediatr Pulmonol. 1999;28:159-66. [PMID: 10495331] CrossrefMedlineGoogle Scholar89. Johansen HK, Nørregaard L, Gøtzsche PC, Pressler T, Koch C, Høiby N. Antibody response to Pseudomonas aeruginosa in cystic fibrosis patients: a marker of therapeutic success? A 30-year cohort study of survival in Danish CF patients after onset of chronic P. aeruginosa lung infection. Pediatr Pulmonol. 2004;37:427-32. [PMID: 15095326] CrossrefMedlineGoogle Scholar90. Høiby N, Frederiksen B, Pressler T. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros. 2005;4 Suppl 2 49-54. [PMID: 16023416] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Timothy D. Starner, MD; Paul B. McCrayJr., MDAffiliations: From University of Iowa, Iowa City, Iowa.Grant Support: None.Disclosures: None disclosed.Corresponding Author: Paul B. McCray Jr., MD, or Timothy D. Starner, MD, Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242.Current Author Addresses: Drs. Starner and McCray: Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe use of tobramycin for Pseudomonas aeruginosa: a reviewTobramycin safety and efficacy review articleNontypeable Haemophilus influenzae Infection Impedes Pseudomonas aeruginosa Colonization and Persistence in Mouse Respiratory TractMucoid Pseudomonas aeruginosa and regional inflammation in the cystic fibrosis lungDuration of intravenous antibiotic therapy in people with cystic fibrosisRapid detection of the bacterial biomarker pyocyanin in artificial sputum using a SERS-active silicon nanowire matrix covered by bimetallic noble metal nanoparticlesCystic Fibrosis and Pseudomonas aeruginosa: the Host-Microbe InterfaceCystic Fibrosis: Advancing Along the ContinuumCystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95)Recent Advances in Molecular Diagnosis of Pseudomonasaeruginosa Infection by State-of-the-Art Genotyping TechniquesOne time quantitative PCR detection of Pseudomonas aeruginosa to discriminate intermittent from chronic infection in cystic fibrosisStructure‐Function Relationships of Rhamnolipid and Exopolysacharide Biosurfactants of Pseudomonas aeruginosa as Therapeutic Targets in Cystic Fibrosis Lung InfectionsEvaluation of quantitative PCR for early diagnosis of Pseudomonas aeruginosa infection in cystic fibrosis: a prospective cohort studyNanoformulations for the Therapy of Pulmonary InfectionsDuration of intravenous antibiotic therapy in people with cystic fibrosisChronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolutionAirway clearance techniques used by people with cystic fibrosis in the UKAirflow limitation following cardiopulmonary exercise testing and heavy-intensity intermittent exercise in children with cystic fibrosisOpen label study of inhaled aztreonam for Pseudomonas eradication in children with cystic fibrosis: The ALPINE studyHost Antimicrobial Peptides in Bacterial Homeostasis and Pathogenesis of DiseaseSerology as a diagnostic tool for predicting initialPseudomonas aeruginosa acquisition in childrenwith cystic fibrosisDuration of intravenous antibiotic therapy in people with cystic fibrosisAdenoviral Gene Transfer Corrects the Ion Transport Defect in the Sinus Epithelia of a Porcine CF ModelLongitudinal Cystic Fibrosis CareChallenges with current inhaled treatments for chronic Pseudomonas aeruginosa infection in patients with cystic fibrosisPseudomonas aeruginosa: A Persistent Pathogen in Cystic Fibrosis and Hospital-Associated InfectionsCreeping baselines and adaptive resistance to antibioticsDuration of intravenous antibiotic therapy in people with cystic fibrosisClinical Significance of Microbial Infection and Adaptation in Cystic FibrosisEmerging Issues in Pulmonary Infections of Cystic FibrosisLentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expressionDuration of intravenous antibiotic therapy in people with cystic fibrosisCirculating and airway neutrophils in cystic fibrosis display different TLR expression and responsiveness to interleukin-10Pseudomonas aeruginosa : résistance et options thérapeutiques à l'aube du deuxième millénaireInfections in Chronic Lung DiseasesDuration of intravenous antibiotic therapy in people with cystic fibrosisPseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millenniumAdvances in cystic fibrosis therapies 6 December 2005Volume 143, Issue 11 Page: 816-822 Keywords Antibiotics Bacteria Bacterial diseases Bronchoalveolar lavage Cystic fibrosis Inflammation Lungs Neutrophils Pathogens Pneumonia ePublished: 6 December 2005 Issue Published: 6 December 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...