Inflammation of the airways

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Airways in cystic fibrosis are acidified: detection by exhaled breath

condensate

S Tate, G MacGregor, M , J A Innes and A P Greening

ish Adult Cystic Fibrosis Service, Respiratory Medicine Unit,

Western General Hospital and Medical Genetics Section, University of

Edinburgh, Edinburgh, EH4 2XU, UK

Correspondence to:

Dr S Tate, Respiratory Medicine, Ward 54, Anne Ferguson Building,

Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK;

steve.tate@...

Background: The loss of cystic fibrosis transmembrane conductance

regulator (CFTR) mediated chloride conductance does not fully explain

the diverse pathologies evident in patients with cystic fibrosis

(CF). Bicarbonate (HCO3-) secretion is also impaired in CFTR

expressing tissues and CFTR is thought to regulate HCO3- secretion at

the apical membrane of epithelial cells. We hypothesised that the

epithelial lining fluid (ELF) of patients with CF would be acidified

and that this may be worsened during an infective exacerbation due to

the increased inflammatory burden.

Methods: pH and nitrite levels in exhaled breath condensate (EBC)

from 12 healthy non-smoking controls and 30 patients with CF (11 of

whom were in an infective exacerbation) were measured. A further nine

patients were studied before and after intravenous antibiotic

treatment for an exacerbation of CF.

Results: The pH of EBC was significantly lower in patients with

stable CF than in controls (5.88 (0.32) v 6.15 (0.16), p=0.017), and

was further reduced in CF patients with an exacerbation (5.32 (0.38),

p=0.001) compared with stable CF patients. EBC pH increased

significantly following antibiotic treatment from 5.27 (0.42) to 5.71

(0.42), p=0.049). Nitrite levels in EBC were increased in CF patients

with an exacerbation compared with control subjects (4.4 (4.0) µm v

1.6 (1.6) µm p=0.047). No correlation was found between EBC pH and

nitrite levels.

Conclusions: These findings support the hypothesis that airway

acidification occurs in CF. This acidity is in part a function of

inflammation as the pH of the EBC of patients increased significantly

with treatment of an exacerbation, although not to control levels.

Acidic pH of the ELF may play a role in the pathophysiology of CF

lung disease and requires further investigation.

Inflammatory Response in Airway Epithelial Cells Isolated from

Patients with Cystic Fibrosis

Nada Aldallal, E. McNaughton, Lori J. Manzel, Autumn M.

s, ph Zabner, W. Ferkol and Dwight C. Look

Departments of Pediatrics and Internal Medicine, Washington

University School of Medicine, St. Louis, Missouri; and Department of

Internal Medicine, University of Iowa College of Medicine, Iowa City,

Iowa

Correspondence: Correspondence and requests for reprints should be

addressed to Dwight Look, M.D., University of Iowa College of

Medicine, Department of Internal Medicine, C33A-GH, 200 Hawkins

Drive, Iowa City, IA 52242. E-mail: dwight-look@...

The concept that inflammatory gene expression is dysregulated in

airway epithelial cells from patients with cystic fibrosis (CF) is

controversial. To examine this possibility systematically, responses

to inflammatory stimuli were compared in CF airway epithelial cell

lines without versus with wild-type CF transmembrane conductance

regulator (CFTR) complementation and in tracheobronchial epithelial

cells from patients with versus without CF. Epithelial cell

expression of the leukocyte adhesion glycoprotein intercellular

adhesion molecule-1 (ICAM-1) and release of the neutrophil

chemoattractant interleukin (IL)-8 were determined under basal

conditions or after exposure to stimuli important in CF airway

inflammatory responses. We found that uncorrected CF airway

epithelial cell lines inconsistently expressed higher ICAM-1 and IL-8

levels. Human CF tracheobronchial epithelial cells in primary culture

released moderately increased IL-8 only after exposure to Pseudomonas

aeruginosa. In CF cells with higher IL-8 release, transient

expression of wild-type CFTR using an adenoviral vector did not

specifically affect cytokine levels. The results indicate that there

is considerable variability in airway epithelial cell responses to

inflammatory stimuli among different individuals and cell models

systems. Although increased ICAM-1 and IL-8 expression are observed

in some CF airway epithelial cell models, many CF cells do not

exhibit significant dysregulation of these important inflammatory

genes