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Am. J. Respir. Crit. Care Med., Volume 160, Number 1, July 1999, 186-191

Quantitation of Inflammatory Responses to Bacteria in Young Cystic Fibrosis and Control Patients

MARIANNE S. MUHLEBACH, PAUL W. STEWART, MARGARET W. LEIGH, and TERRY L. NOAH

Division of Pulmonary Medicine and Allergy, Department of Pediatrics, Department of Biostatistics, and Center for Environmental Medicine and Lung Biology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina

Recent studies suggest that inflammation plays a role in the pathogenesis of lung disease in cystic fibrosis (CF). The goal of the present study was to quantitatively compare bronchoalveolar lavage fluid (BALF) inflammation and its relation to bacterial infection, between children with CF and children with other chronic respiratory problems. Differential cell counts, immunoreactive interleukin 8 (IL-8), and quantitative bacterial cultures were done in BALF from 54 CF (median age 1.8 yr) and 55 control patients (median age 1.0 yr) who underwent bronchoscopy for clinical indications. Among infected CF patients, those with Pseudomonas aeruginosa did not have more inflammation than those without P. aeruginosa. The ratio of neutrophils or of IL-8 to bacteria in BALF was significantly greater for CF patients compared with control subjects, regardless of pathogen. Calculation of linear regression for either neutrophils or IL-8, as a function of bacterial quantity, yielded positive slopes for both CF and control patients, but with significant elevations for CF. We conclude that the inflammatory response to bacterial infection is increased or prolonged in CF compared with control patients, and that this increase is not necessarily due to pathogens specific for CF (e.g., P. aeruginosa). These data may provide further rationale for anti-inflammatory therapy early in CF.




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T. Jungas, I. Motta, F. Duffieux, P. Fanen, V. Stoven, and D. M. Ojcius
Glutathione Levels and BAX Activation during Apoptosis Due to Oxidative Stress in Cells Expressing Wild-type and Mutant Cystic Fibrosis Transmembrane Conductance Regulator
J. Biol. Chem., July 26, 2002; 277(31): 27912 - 27918.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. Berger
Lung Inflammation Early in Cystic Fibrosis . Bugs Are Indicted, But the Defense Is Guilty
Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 857 - 858.
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 Am. J. Respir. Crit. Care Med.Home page
C. J. DAKIN, A. H. NUMA, H. WANG, J. R. MORTON, C. C. VERTZYAS, and R. L. HENRY
Inflammation, Infection, and Pulmonary Function in Infants and Young Children with Cystic Fibrosis
Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 904 - 910.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. S. Muhlebach and T. L. Noah
Endotoxin Activity and Inflammatory Markers in the Airways of Young Patients with Cystic Fibrosis
Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 911 - 915.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
J. Soltys, T. Bonfield, J. Chmiel, and M. Berger
Functional IL-10 Deficiency in the Lung of Cystic Fibrosis (cftr-/-) and IL-10 Knockout Mice Causes Increased Expression and Function of B7 Costimulatory Molecules on Alveolar Macrophages
J. Immunol., February 15, 2002; 168(4): 1903 - 1910.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
V. De Rose
Mechanisms and markers of airway inflammation in cystic fibrosis
Eur. Respir. J., February 1, 2002; 19(2): 333 - 340.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
M.Y. Kazachkov, M.S. Muhlebach, C.A. Livasy, and T.L. Noah
Lipid-laden macrophage index and inflammation in bronchoalveolar lavage fluids in children
Eur. Respir. J., November 1, 2001; 18(5): 790 - 795.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
J. ANGRILL, C. AGUSTI, R. DE CELIS, X. FILELLA, A. RANO, M. ELENA, J. P. DE LA BELLACASA, A. XAUBET, and A. TORRES
Bronchial Inflammation and Colonization in Patients with Clinically Stable Bronchiectasis
Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1628 - 1632.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S. D. SAGEL, R. KAPSNER, I. OSBERG, M. K. SONTAG, and F. J. ACCURSO
Airway Inflammation in Children with Cystic Fibrosis and Healthy Children Assessed by Sputum Induction
Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1425 - 1431.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
H. Yeger, J. Pan, X. W. Fu, C. Bear, and E. Cutz
Expression of CFTR and Cl{-} conductances in cells of pulmonary neuroepithelial bodies
Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L713 - L721.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
B. J. McMorran, J. S. Palmer, D. P. Lunn, D. Oceandy, E. O. Costelloe, G. R. Thomas, D. A. Hume, and B. J. Wainwright
G551D CF mice display an abnormal host response and have impaired clearance of Pseudomonas lung disease
Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L740 - L747.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. J. Weber, G. Soong, R. Bryan, S. Saba, and A. Prince
Activation of NF-{kappa}B in airway epithelial cells is dependent on CFTR trafficking and Cl{-} channel function
Am J Physiol Lung Cell Mol Physiol, July 1, 2001; 281(1): L71 - L78.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
R. S. Smith, E. R. Fedyk, T. A. Springer, N. Mukaida, B. H. Iglewski, and R. P. Phipps
IL-8 Production in Human Lung Fibroblasts and Epithelial Cells Activated by the Pseudomonas Autoinducer N-3-Oxododecanoyl Homoserine Lactone Is Transcriptionally Regulated by NF-{{kappa}}B and Activator Protein-2
J. Immunol., July 1, 2001; 167(1): 366 - 374.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. Kube, U. Sontich, D. Fletcher, and P. B. Davis
Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithelial cell lines
Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L493 - L502.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
J.P. Gutierrez, K. Grimwood, D.S. Armstrong, J.B. Carlin, R. Carzino, A. Olinsky, C.F. Robertson, and P.D. Phelan
Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis
Eur. Respir. J., February 1, 2001; 17(2): 281 - 286.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
S. D. Freedman, D. Weinstein, P. G. Blanco, P. Martinez-Clark, S. Urman, M. Zaman, J. D. Morrow, and J. G. Alvarez
Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid
J Appl Physiol, May 1, 2002; 92(5): 2169 - 2176.
[Abstract] [Full Text] [PDF]


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