Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

Expert Review of Molecular Diagnostics

Volumn 11, Issue 2, 2011, Pages 197-206

  Rogers, Geraint B ^a   Hoffman, Lucas R ^b   Johnson, Matt W ^c   Mayer Hamblett, Nicole ^b,d   Schwarze, Jürgen ^e   Carroll, Mary P ^f   Bruce, Kenneth D ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c ST MARK S HOSPITAL   (United Kingdom)

^d SEATTLE CHILDREN S RESEARCH INSTITUTE   (United States)

^e UNIVERSITY OF EDINBURGH   (United Kingdom)

^f UNIVERSITY HOSPITAL SOUTHAMPTON NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

biomarkers; cystic fibrosis; exhaled breath; inflammation; molecular diagnostics; predictive biomarkers; proteomics; pulmonary exacerbation; quantitative PCR; sputum; trace metals

Indexed keywords

8 ISOPROSTANE; ALKALINE PROTEINASE; BACTERIAL TOXIN; BIOLOGICAL MARKER; ELASTASE; GAMMA INTERFERON; HYDROGEN PEROXIDE; INTERLEUKIN 8; LEUKOCYTE ELASTASE; MYELOPEROXIDASE; NITRATE; NITRIC OXIDE; NITRITE;

BACTERIUM; BLOOD; CYSTIC FIBROSIS; DISEASE EXACERBATION; ENZYME LINKED IMMUNOSORBENT ASSAY; EXHALATION; HUMAN; LUNG CYSTIC FIBROSIS; MICROBIAL COMMUNITY; MOLECULAR DIAGNOSIS; NONHUMAN; POLYMERASE CHAIN REACTION; PREDICTION; PSEUDOMONAS AERUGINOSA; REAL TIME POLYMERASE CHAIN REACTION; REVIEW; SALIVA; SPUTUM; URINE;

BACTERIA; BACTERIAL INFECTIONS; BIOLOGICAL MARKERS; CYSTIC FIBROSIS; HUMANS; RESPIRATORY FUNCTION TESTS;

EID: 79952972412     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/erm.10.117     Document Type: Review

References (132)

1. Ramsey BW. Management of pulmonary disease in patients with cystic fibrosis. N. Engl. J. Med. 335(Suppl. 3), 179-188 (1996). (Pubitemid 26249456)
2. Konstan MW, Berger M. Current understanding of the inflammatory process in cystic fibrosis: Onset and etiology. Pediatr. Pulmonol. 24(Suppl. 2), 137-142; discussion 159-161 (1997). (Pubitemid 27450731)
3. Balfour-Lynn IA, Elborn JS. Respiratory disease: Infection. In:Cystic Fibrosis (3rd Edition). Hodson M, Geddes D, Bush A (Eds). Hodder Arnold, London, UK, 137-158 (2007).
4. Sanders DB, Bittner RCL, Rosenfeld M, Hoffman LR, Redding GJ, Goss CH. Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am. J. Respir. Crit. Care Med. 182, 627-632 (2010).
5. Sanders DB, Bittner RCL, Rosenfeld M, Redding GJ, Goss CH. Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis. Ped. Pulmonol. DOI: 10.1002/ppul.21374 (2010) (Epub ahead of print).
6. Bradley J, McAlister O, Elborn S. Pulmonary function, inflammation, exercise capacity and quality of life in cystic fibrosis. Eur. Respir. J. 17(Suppl. 4), 712-715 (2001). (Pubitemid 32492561)
7. Orenstein DM, Pattishall EN, Nixon PA et al. Quality of well-being before and after antibiotic treatment of pulmonary exacerbation in patients with cystic fibrosis. Chest 98(Suppl. 5), 1081-1084 (1990). (Pubitemid 20381265)
8. Britto MT, Kotagal UR, Hornung RW et al. Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis. Chest 121(Suppl. 1), 64-72 (2002). (Pubitemid 34114229)
9. Yi MS, Tsevat J, Wilmott RW et al. The impact of treatment of pulmonary exacerbations on the health-related quality of life of patients with cystic fibrosis: Does hospitalization make a difference? J. Pediatr. 144(Suppl. 6), 711-718 (2004). (Pubitemid 38858085)
10. Liou TG, Adler FR, Fitzsimmons SC et al. Predictive 5-year survivorship model of cystic fibrosis. Am. J. Epidemiol. 153(Suppl. 4), 345-352 (2001). (Pubitemid 32144560)
11. Emerson J, Rosenfeld M, McNamara S et al. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr. Pulmonol. 34(Suppl. 2), 91-100 (2002). (Pubitemid 34809519)
12. Ellaffi M, Vinsonneau C, Coste J et al. One-year outcome after severe pulmonary exacerbation in adults with cystic fibrosis. Am. J. Respir. Crit. Care Med. 171(Suppl. 2), 158-164 (2005). (Pubitemid 40105415)
13. Mayer-Hamblett N, Rosenfeld M, Emerson J et al. Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am. J. Respir. Crit. Care Med. 166(Suppl. 12, Pt 1), 1550-1555 (2002). (Pubitemid 36015948)
14. Ramsey BW, Boat TF. Outcome measures for clinical trials in cystic fibrosis. Summary of a Cystic Fibrosis Foundation consensus conference. J. Pediatr. 124(Suppl. 2), 177-192 (1994). (Pubitemid 24057781)
15. Goss CH, Burns JL. Exacerbations in cystic fibrosis. 1: Epidemiology and pathogenesis. Thorax 62(Suppl. 4), 360-367 (2007). (Pubitemid 46580580)
16. Bush A. Treatment of cystic fibrosis: Time for a new paradigm? Chest 136(Suppl. 5), 1197-1199 (2009).
17. Dakin C, Henry RL, Field P et al. Defining an exacerbation of pulmonary disease in cystic fibrosis. Pediatr. Pulmonol. 31(Suppl. 6), 436-442 (2001).Examination of the basis of cystic fibrosis pulmonary exacerbation (CFPE) diagnosis. (Pubitemid 32523636)
18. Amsden GW. Anti-inflammatory effects of macrolides-an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J. Antimicrob. Chemother. 55(Suppl. 1), 10-21 (2005). (Pubitemid 40192609)
19. Mallon P, Murphy P, Elborn S. Fever associated with intravenous antibiotics in adults with cystic fibrosis. Lancet 350(9092), 1676-1677 (1997). (Pubitemid 28036832)
20. Lopez-Boado YS, Rubin BK. Macrolides as immunomodulatory medications for the therapy of chronic lung diseases. Curr. Opin. Pharmacol. 8(Suppl. 3), 286-291 (2008).
21. Kabra SK, Pawaiya R, Lodha R et al. Long-term daily high and low doses of azithromycin in children with cystic fibrosis: A randomized controlled trial. J. Cyst. Fibros. 9(Suppl. 1), 17-23 (2010).
22. Florescu DF, Murphy PJ, Kalil AC. Effects of prolonged use of azithromycin in patients with cystic fibrosis: A metaanalysis. Pulm. Pharmacol. Ther. 22(Suppl. 6), 467-472 (2009).
23. Rosenfeld M, Emerson J, Williams-Warren J et al. Defining a pulmonary exacerbation in cystic fibrosis. J. Pediatr. 139(Suppl. 3), 359-365 (2001). (Pubitemid 32889511)
24. Rabin HR, Butler SM, Wohl ME et al. Pulmonary exacerbations in cystic fibrosis. Pediatr. Pulmonol. 37(Suppl. 5), 400-406 (2004). (Pubitemid 38620061)
25. Meyer KB, Clayton KA. Measurement and analysis of patient-reported outcomes. Methods Mol. Biol. 473, 155-169 (2009).
26. Christ-Crain M, Muller B. Biomarkers in respiratory tract infections: Diagnostic guides to antibiotic prescription, prognostic markers and mediators. Eur. Respir. J. 30(Suppl. 3), 556-573 (2007). (Pubitemid 351182082)
27. Marshall JC, Reinhart K. International Sepsis Forum. Biomarkers of sepsis. Crit. Care Med. 37(Suppl. 7), 2290-2298 (2009).
28. Pierrakos C, Vincent JL. Sepsis biomarkers: A review. Crit. Care 14(Suppl. 1), R15 (2010).
29. Aaron SD, Ramotar K, Ferris W et al. Adult cystic fibrosis exacerbations and new strains of Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med. 169(Suppl. 7), 811-815 (2004). (Pubitemid 38402456)
30. VanDevanter DR, Van Dalfsen JM. How much do Pseudomonas biofilms contribute to symptoms of pulmonary exacerbation in cystic fibrosis? Pediatr. Pulmonol. 39(Suppl. 6), 504-506 (2005). (Pubitemid 40696320)
31. Jaffar-Bandjee MC, Lazdunski A, Bally M et al. Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa. J. Clin. Microbiol. 33(Suppl. 4), 924-929. (1995)Analysis of Pseudomonas aeruginosa exoprotein concentrations in cystic fibrosis (CF) sputum over the course of treatment for CFPE.
32. Hiatt PW, Grace SC, Kozinetz CA et al. Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis. Pediatrics 103(Suppl. 3), 619-626 (1999). (Pubitemid 29274510)
33. de Almeida MB, Zerbinati RM, Tateno AF et al. Rhinovirus C and respiratory exacerbations in children with cystic fibrosis. Emerg. Infect. Dis. 16(Suppl. 6), 996-999 (2010).
34. Goss CH, Newsom SA, Schildcrout JS et al. Effect of ambient air pollution on pulmonary exacerbations and lung function in cystic fibrosis. Am. J. Respir. Crit. Care Med. 169(Suppl. 7), 816-821 (2004). (Pubitemid 38402457)
35. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am. J. Respir. Crit. Care Med. 168(Suppl. 8), 918-951 (2003). (Pubitemid 37267172)
36. Konstan MW, Hilliard KA, Norvell TM et al. Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am. J. Respir. Crit. Care Med. 150(Suppl. 2), 448-454 (1994). (Pubitemid 24252357)
37. Bonfield TL, Panuska JR, Konstan MW et al. Inflammatory cytokines in cystic fibrosis lungs. Am. J. Respir. Crit. Care Med. 152(Suppl. 6 Pt 1), 2111-2118 (1995).
38. Sagel SD, Kapsner R, Osberg I et al. Airway inflammation in children with cystic fibrosis and healthy children assessed by sputum induction. Am. J. Respir. Crit. Care Med. 164(Suppl. 8 Pt 1), 1425-1431 (2001). (Pubitemid 33124021)
39. Ordonez CL, Henig NR, Mayer-Hamblett N et al. Inflammatory and microbiologic markers in induced sputum after intravenous antibiotics in cystic fibrosis. Am. J. Respir. Crit. Care Med. 168(Suppl. 12), 1471-1475 (2003).Assessment of the usefulness of microbiologic and inflammatory markers in CF-induced sputum as outcome measures. (Pubitemid 38037331)
40. Colombo C, Costantini D, Rocchi A et al. Cytokine levels in sputum of cystic fibrosis patients before and after antibiotic therapy. Pediatr. Pulmonol. 40(Suppl. 1), 15-21 (2005).Assessment of changes in cytokine levels in CF sputum in response to antibiotic therapy. (Pubitemid 40917903)
41. Chmiel JF, Berger M, Konstan MW. The role of inflammation in the pathophysiology of CF lung disease. Clin. Rev. Allergy Immunol. 23(Suppl. 1), 5-27 (2002). (Pubitemid 34785780)
42. Pfeffer KD, Huecksteadt TP, Hoidal JR. Expression and regulation of tumor necrosis factor in macrophages from cystic fibrosis patients. Am. J. Respir. Cell Mol. Biol. 9(Suppl. 5), 511-519 (1993). (Pubitemid 2007498)
43. Muhlebach MS, Stewart PW, Leigh MW et al. Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients. Am. J. Respir. Crit. Care Med. 160(Suppl. 1), 186-191 (1999).Evidence of an increased inflammatory response in CF patients. (Pubitemid 29326086)
44. Noah TL, Black HR, Cheng PW et al. Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis. J. Infect. Dis. 175(Suppl. 3), 638-647 (1997). (Pubitemid 27086168)
45. Shak S, Capon DJ, Hellmiss R et al. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Proc. Natl Acad. Sci. USA 87(Suppl. 23), 9188-9192 (1990). (Pubitemid 120030590)
46. Berger M. Inflammation in the lung in cystic fibrosis. A vicious cycle that does more harm than good? Clin. Rev. Allergy 9(Suppl. 1-2), 119-142 (1991).
47. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69(Suppl. 3), 89-95 (2001).
48. Moriates C, Maisel A. The utility of biomarkers in sorting out the complex patient. Am. J. Med. 123(Suppl. 5), 393-399 (2010).
49. Anderson R, Schmidt R. Clinical biomarkers in sepsis. Front. Biosci. (Elite Ed.) 2, 504-520 (2010).
50. Duffy MJ, Crown J. A personalized approach to cancer treatment: How biomarkers can help. Clin. Chem. 54(Suppl. 11), 1770-1779 (2008).
51. Bucher H, Guyatt G, Cook D et al. Surrogate outcomes. In:The Users' Guide to the Medical Literature: A Manual for Evidence-based Clinical Practice Guyatt G, Rennie D (Eds). AMA Publications, IL, USA (2002).
52. Wittes J, Lakatos E, Probstfield J. Surrogate endpoints in clinical trials: Cardiovascular diseases. Stat. Med. 8(Suppl. 4), 415-425 (1989). (Pubitemid 19105889)
53. Mayer-Hamblett N, Aitken ML, Accurso FJ et al. Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am. J. Respir. Crit. Care Med. 175(Suppl. 8), 822-828 (2007).Correlation between expectorate sputum biomarkers and lung function. (Pubitemid 46631794)
54. Sagel SD, Chmiel JF, Konstan MW. Sputum biomarkers of inflammation in cystic fibrosis lung disease. Proc. Am. Thorac. Soc. 4(Suppl. 4), 406-417 (2007).Review of biomarkers of inflammation in CF lung disease. (Pubitemid 47330878)
55. Laguna TA, Wagner BD, Luckey HK et al. Sputum desmosine during hospital admission for pulmonary exacerbation in cystic fibrosis. Chest 136, 1561-1568 (2009).
56. Ferkol T, Rosenfeld M, Milla CE. Cystic fibrosis pulmonary exacerbations. J. Pediatr. 148(Suppl. 2), 259-264 (2006). (Pubitemid 43286770)
57. Thomassen MJ, Klinger JD, Badger SJ et al. Cultures of thoracotomy specimens confirm usefulness of sputum cultures in cystic fibrosis. J. Pediatr. 104(Suppl. 3), 352-356 (1984). (Pubitemid 14160458)
58. Aaron SD, Kottachchi D, Ferris WJ et al. Sputum versus bronchoscopy for diagnosis of Pseudomonas aeruginosa biofilms in cystic fibrosis. Eur. Respir. J. 24(Suppl. 4), 631-637 (2004). (Pubitemid 39406137)
59. Gilljam H, Malmborg AS, Strandvik B. Conformity of bacterial growth in sputum and contamination free endobronchial samples in patients with cystic fibrosis. Thorax 41(Suppl. 8), 641-646 (1986). (Pubitemid 16039657)
60. Rubin BK. Mucus structure and properties in cystic fibrosis. Paediatr. Respir. Rev. 8(Suppl. 1), 4-7 (2007). (Pubitemid 46523785)
61. Rogers GB, Skelton S, Serisier DJ et al. Determining CF lung microbiology: A comparison of spontaneous and serially induced sputum samples using T-RFLP profiling. J. Clin. Microbiol. 48(1), 78-86. (2009).
62. Kharitonov SA, Barnes PJ. Exhaled biomarkers. Chest 130, 1541-1546 (2006). (Pubitemid 44786751)
63. Barnes PJ, Chowdhury B, Kharitonov SA et al. Pulmonary biomarkers in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 174, 6-14 (2006). (Pubitemid 43955238)
64. Keen C, Gustafsson P, Lindblad A, Wennergren G, Olin A-C. Low levels of exhaled nitric oxide are associated with impaired lung function in cystic fibrosis. Ped. Pulmonol. 45, 241-248 (2010).
65. Barnes PJ, Dweik RA, Gelb AF et al. Exhaled nitric oxide in pulmonary diseases: A comprehensive review. Chest 138, 682-692 (2010).
66. Hofer M, Mueller L, Rechsteiner T, Benden C, Boehler A. Extended nitric oxide measurements in exhaled air of cystic fibrosis and healthy adults. Lung 187, 307-313 (2009).
67. Robroeks CMHHT, Roozeboom MH, de Jong PA et al. Structural lung changes, lung function, and non-invasive inflammatory markers in cystic fibrosis. Pediatr. Allergy Immunol. 21, 493-500 (2010).
68. Tirelli AS, Colombo C, Torresani E, Cariani L, Arnaboldi E, Conese M. Validation of an automated immunoassay for quantification of cytokines in the sputum of cystic fibrosis patients. Clin. Chem. Lab. Med. 45, 108-111 (2007). (Pubitemid 46155571)
69. Saiman L, Marshall BC, Mayer-Hamblett N et al. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: A randomized controlled trial. JAMA 290(Suppl. 13), 1749-1756 (2003). (Pubitemid 37430625)
70. Ordonez CL, Kartashov AI, Wohl ME. Variability of markers of inflammation and infection in induced sputum in children with cystic fibrosis. J. Pediatr. 145(Suppl. 5), 689-692 (2004).Analysis of the reproducibility of inflammatory marker concentrations in induced sputum. (Pubitemid 39440951)
71. Sagel SD, Sontag MK, Wagener JS et al. Induced sputum inflammatory measures correlate with lung function in children with cystic fibrosis. J. Pediatr. 141(Suppl. 6), 811-817 (2002). (Pubitemid 35471643)
72. Gray RD, Imrie M, Boyd AC et al. Sputum and serum calprotectin are useful biomarkers during CF exacerbation. J. Cyst. Fibros. 9(3), 193-198 (2010).
73. Salva PS, Doyle NA, Graham L et al. TNF-a, IL-8, soluble ICAM-1, and neutrophils in sputum of cystic fibrosis patients. Pediatr Pulmonol. 21(Suppl. 1), 11-19 (1996).
74. Henig NR, Tonelli MR, Pier MV et al. Sputum induction as a research tool for sampling the airways of subjects with cystic fibrosis. Thorax 56(Suppl. 4), 306-311 (2001). (Pubitemid 32269812)
75. McGarvey LP, Dunbar K, Martin SL et al. Cytokine concentrations and neutrophil elastase activity in bronchoalveolar lavage and induced sputum from patients with cystic fibrosis, mild asthma and healthy volunteers. J. Cyst. Fibros. 1(Suppl. 4), 269-275 (2002).
76. Downey DG, Martin SL, Dempster M et al. The relationship of clinical and inflammatory markers to outcome in stable patients with cystic fibrosis. Pediatr. Pulmonol. 42(Suppl. 3), 216-220 (2007). (Pubitemid 46417692)
77. Gray RD, MacGregor G, Noble D et al. Sputum proteomics in inflammatory and suppurative respiratory diseases. Am. J. Respir. Crit. Care Med. 178(Suppl. 5), 444-452 (2008).
78. Sloane AJ, Lindner RA, Prasad SS et al. Proteomic analysis of sputum from adults and children with cystic fibrosis and from control subjects. Am. J. Respir. Crit. Care Med. 172(Suppl. 11), 1416-1426 (2005).Proteomic analysis of biomarkers of inflammation relating to CFPE. (Pubitemid 43069815)
79. Regelmann WE, Siefferman CM, Herron JM et al. Sputum peroxidase activity correlates with the severity of lung disease in cystic fibrosis. Pediatr. Pulmonol. 19(Suppl. 1), 1-9 (1995).
80. Meyer KC. Neutrophils, myeloperoxidase, and bronchiectasis in cystic fibrosis: Green is not good. J. Lab. Clin. Med. 144(Suppl. 3), 124-126 (2004). (Pubitemid 39349032)
81. Sagel SD, Kapsner RK, Osberg I. Induced sputum matrix metalloproteinase-9 correlates with lung function and airway inflammation in children with cystic fibrosis. Pediatr. Pulmonol. 39(Suppl. 3), 224-232 (2005). (Pubitemid 40460690)
82. Klein M, Cohen-Cymberknoh M, Armoni S et al. 18F-fluorodeoxyglucose- PET/CT imaging of lungs in patients with cystic fibrosis. Chest 136(Suppl. 5), 1220-1228 (2009).
83. Wat D, Gelder C, Hibbitts S et al. The role of respiratory viruses in cystic fibrosis. J. Cyst. Fibros. 7(Suppl. 4), 320-328 (2008).
84. van Ewijk BE, van der Zalm MM, Wolfs TF et al. Viral respiratory infections in cystic fibrosis. J. Cyst. Fibros. 4(Suppl. 2), 31-36 (2005). (Pubitemid 41131326)
85. Wang EE, Prober CG, Manson B et al. Association of respiratory viral infections with pulmonary deterioration in patients with cystic fibrosis. N. Engl. J. Med. 311(Suppl. 26), 1653-1658 (1984). (Pubitemid 15183995)
86. Collinson J, Nicholson KG, Cancio E et al. Effects of upper respiratory tract infections in patients with cystic fibrosis. Thorax 51(Suppl. 11), 1115-1122 (1996). (Pubitemid 26402824)
87. Kalu SU, Loeffelholz M, Beck E et al. Persistence of adenovirus nucleic acids in nasopharyngeal secretions: A diagnostic conundrum. Pediatr. Infect. Dis. J. 29, 746-750 (2010).
88. Sikkel MB, Quint JK, Mallia P et al. Respiratory syncytial virus persistence in chronic obstructive pulmonary disease. Pediatr. Infect. Dis. J. 27, S63-S70 (2008).
89. Arens MQ, Buller RS, Rankin A et al. Comparison of the eragen multi-code respiratory virus panel with conventional viral testing and real-time multiplex pcr assays for respiratory viruses. J. Clin. Microbiol. 48(7), 2387-2395 (2010).
90. Gadsby NJ, Hardie A, Claas EC et al. Comparison of the Luminex RVP Fast assay with in-house real-time PCR for respiratory viral diagnosis. J. Clin. Microbiol. 48(6), 2213-2216 (2010).
91. Lassauniere R, Kresfelder T, Venter M. A novel multiplex real-time RT-PCR assay with FRET hybridization probes for the detection and quantitation of 13 respiratory viruses. J. Virol. Methods 165(Suppl. 2), 254-260 (2010).
92. Willner D, Furlan M, Haynes M et al. Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals. PLoS One 4(Suppl. 10), e7370 (2009).
93. Rogers GB, Stressmann FA, Walker AW et al. Lung infections in cystic fibrosis: Deriving clinical insight from microbial complexity. Expert Rev. Mol. Diagn. 10(2), 187-196 (2010).
94. Rogers GB, Carroll MP, Bruce KD. Studying bacterial infections through culture-independent approaches. J. Med. Microbiol. 58(Suppl. Pt 11), 1401-1418 (2009).
95. Proctor RA, von Eiff C, Kahl BC et al. Small colony variants: A pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat. Rev. Microbiol. 4(Suppl. 4), 295-305 (2006).
96. Schneider M, Muhlemann K, Droz S et al. Clinical characteristics associated with isolation of small-colony variants of Staphylococcus aureus and Pseudomonas aeruginosa from respiratory secretions of patients with cystic fibrosis. J. Clin. Microbiol. 46(Suppl. 5), 1832-1834 (2008). (Pubitemid 351657236)
97. Colwell RR. Viable but nonculturable bacteria: A survival strategy. J. Infect. Chemother. 6(Suppl. 2), 121-125 (2000). (Pubitemid 30480310)
98. Anderson M, Bollinger D, Hagler A et al. Viable but nonculturable bacteria are present in mouse and human urine specimens. J. Clin. Microbiol. 42(Suppl. 2), 753-758 (2004). (Pubitemid 38222658)
99. Rogers GB, Daniels TT, Tuck A et al. Studying bacteria in respiratory specimens by using conventional and molecular microbiological approaches. BMC Pulm. Med. 9(Suppl. 1), 14 (2009).
100. Bittar F, Richet H, Dubus JC et al. Molecular detection of multiple emerging pathogens in sputa from cystic fibrosis patients. PLoS One 3(Suppl. 8), e2908 (2008).
101. Fenollar F, Raoult D. Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria. Int. J. Antimicrob. Agents 30(Suppl. 1), S7-S15 (2007).
102. Nadkarni MA, Martin FE, Jacques NA et al. Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. Microbiology 148(Suppl. Pt 1), 257-266 (2002). (Pubitemid 34083204)
103. Espy MJ, Uhl JR, Sloan LM et al. Real-time PCR in clinical microbiology: Applications for routine laboratory testing. Clin. Microbiol. Rev. 19(Suppl. 1), 165-256 (2006). (Pubitemid 43158452)
104. Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr. Pulmonol. 33(Suppl. 4), 293-306 (2002). (Pubitemid 34273340)
105. Boucher RC. Evidence for airway surface dehydration as the initiating event in CF airway disease. J. Intern. Med. 261(Suppl. 1), 5-16 (2007). (Pubitemid 46046468)
106. Nocker A, Sossa KE, Camper AK. Molecular monitoring of disinfection efficacy using propidium monoazide in combination with quantitative PCR. J. Microbiol. Methods 70(Suppl. 2), 252-260 (2007). (Pubitemid 47198131)
107. Rogers GB, Stressmann FA, Koller G et al. Assessing the diagnostic importance of nonviable bacterial cells in respiratory infections. Diagn. Microbiol. Infect. Dis. 62(Suppl. 2), 133-141 (2008).
108. Rogers GB, Marsh P, Stressmann AF et al. The exclusion of dead bacterial cells is essential for accurate molecular analysis of clinical samples. Clin. Microbiol. Infect. 16(11), 1656-1658 (2010).
109. da Silva Filho LV, Tateno AF, Velloso Lde F et al. Identification of Pseudomonas aeruginosa, Burkholderia cepacia complex, and Stenotrophomonas maltophilia in respiratory samples from cystic fibrosis patients using multiplex PCR. Pediatr. Pulmonol. 37(Suppl. 6), 537-547 (2004). (Pubitemid 38680121)
110. da Silva Filho LV, Tateno AF, Martins KM et al. The combination of PCR and serology increases the diagnosis of Pseudomonas aeruginosa colonization/ infection in cystic fibrosis. Pediatr. Pulmonol. 42(Suppl. 10), 938-944 (2007). (Pubitemid 47549801)
111. Qin X, Emerson J, Stapp J et al. Use of real-time PCR with multiple targets to identify Pseudomonas aeruginosa and other nonfermenting gram-negative bacilli from patients with cystic fibrosis. J. Clin. Microbiol. 41(Suppl. 9), 4312-4317 (2003). (Pubitemid 37099701)
112. Singh PK, Parsek MR, Greenberg EP et al. A component of innate immunity prevents bacterial biofilm development. Nature 417(6888), 552-555 (2002). (Pubitemid 34595922)
113. Bjarnsholt T, Jensen PO, Fiandaca MJ et al. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr. Pulmonol. 44(Suppl. 6), 547-558 (2009).
114. Pizzichini E, Pizzichini MM, Efthimiadis A et al. Indices of airway inflammation in induced sputum: Reproducibility and validity of cell and fluid-phase measurements. Am. J. Respir. Crit. Care Med. 154(Suppl. 2 Pt 1), 308-317 (1996). (Pubitemid 26269096)
115. MacGregor G, Gray RD, Hilliard TN et al. Biomarkers for cystic fibrosis lung disease: Application of SELDI-TOF mass spectrometry to BAL fluid. J. Cyst. Fibros. 7(Suppl. 5), 352-358 (2008).
116. Sagel SD, Sontag MK, Accurso FJ. Relationship between antimicrobial proteins and airway inflammation and infection in cystic fibrosis. Pediatr. Pulmonol. 44(Suppl. 4), 402-409 (2009).Analysis of antimicrobial proteins in CF airway secretions, with correlation to airway inflammation and infection.
117. Cummings DM, King DE, Mainous AG et al. Combining serum biomarkers: The association of C-reactive protein, insulin sensitivity, and homocysteine with cardiovascular disease history in the general US population. Eur. J. Cardiovasc. Prev. Rehabil. 13(Suppl. 2), 180-185 (2006). (Pubitemid 44097721)
118. Sabatine MS, Morrow DA, de Lemos JA et al. Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: Simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation 105(Suppl. 15), 1760-1763 (2002). (Pubitemid 34408881)
119. Robin X, Turck N, Hainard A et al. Bioinformatics for protein biomarker panel classification: What is needed to bring biomarker panels into in vitro diagnostics? Expert Rev. Proteomics 6(Suppl. 6), 675-689 (2009).
120. Sibley CD, Parkins MD, Rabin HR et al. A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients. Proc. Natl Acad. Sci. USA 105(Suppl. 39), 15070-15075 (2008).
121. Bouchara JP, Hsieh HY, Croquefer S et al. Development of an oligonucleotide array for direct detection of fungi in sputum samples from patients with cystic fibrosis. J. Clin. Microbiol. 47(Suppl. 1), 142-152 (2009).
122. Ramsey MM, Whiteley M. Polymicrobial interactions stimulate resistance to host innate immunity through metabolite perception. Proc. Natl Acad. Sci. USA 106(Suppl. 5), 1578-1583 (2009).
123. Sibley CD, Duan K, Fischer C et al. Discerning the complexity of community interactions using a Drosophila model of polymicrobial infections. PLoS Pathog. 4(10), e1000184 (2008).
124. Aaron SD, Ramotar K, Ferris W et al. Adult cystic fibrosis exacerbations and new strains of Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med. 169(Suppl. 7), 811-815 (2004). (Pubitemid 38402456)
125. Regelmann WE, Elliott GR, Warwick WJ et al. Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone. Am. Rev. Respir. Dis. 141(Suppl. 4 Pt 1), 914-921 (1990). (Pubitemid 20157719)
126. Rogers GB, Hoffman LR, Whiteley M et al. Revealing the dynamics of polymicrobial infections: Implications for antibiotic therapy. Trends Microbiol. 18, 357-364 (2010).
127. Smyth A, Elborn JS. Exacerbations in cystic fibrosis: 3-management. Thorax 63(Suppl. 2), 180-184 (2008).
128. Hiatt PW, Grace SC, Kozinetz CA et al. Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis. Pediatrics 103(Suppl. 3), 619-626 (1999). (Pubitemid 29274510)
129. Wat D, Doull I. Respiratory virus infections in cystic fibrosis. Paediatr. Respir. Rev. 4(Suppl. 3), 172-177 (2003). (Pubitemid 36987173)
130. Scheithauer S, Haase G, Hausler M et al. Association between respiratory and herpes viruses on pulmonary exacerbations in cystic fibrosis patients. J. Cyst. Fibros. 9(3), 234-236 2010).
131. Griffard EA, Guajardo JR, Cooperstock MS et al. Isolation of Exophiala dermatitidis from pigmented sputum in a cystic fibrosis patient. Pediatr. Pulmonol. 45(Suppl. 5), 508-510 (2010).
132. Chotirmall SH, O'Donoghue E, Bennett K et al. Sputum Candida albicans presages FEV decline and hospital-treated exacerbations in cystic fibrosis Chest 138, 1186-1195 (2010).