K.G. Nielsen

Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

BACKGROUND Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine concentrations in CF patients with and without chronic infection were compared to healthy controls. METHODS Cytokines in serum and sputum were measured using multiplex bead based immunoassay. RESULTS Sixty CF patients, 11 with A. xylosoxidans, 11 with Bcc, 21 with P. aeruginosa and 17 non-infected CF patients were compared to 11 healthy controls. A. xylosoxidans patients were younger, but had a FEV(1) decline similar to P. aeruginosa patients. Bcc patients had the steepest decline in FEV(1). Serum levels of G-CSF, IL-6 and TNF-alpha were significantly higher in CF patients compared to healthy controls. Chronically infected CF patients had significantly higher serum levels of IFN-gamma and IL-6 compared to non-infected CF patients. Bcc patients had significantly lower serum G-CSF and A. xylosoxidans patients had significantly higher sputum TNF-alpha compared to the other groups of chronically infected patients. CONCLUSION A. xylosoxidans can cause a level of inflammation similar to P. aeruginosa in chronically infected CF patients. A. xylosoxidans is a clinically important pathogen in CF and should be treated accordingly.

Colonisation and infection of the paranasal sinuses in cystic fibrosis patients is accompanied by a reduced PMN response

BACKGROUND We studied whether the sinuses might be foci for Pseudomonas aeruginosa lung infection. METHODS Endoscopic Sinus Surgery was performed in 78 CF patients; PFGE was used for bacterial genotyping. Material from sinuses and lungs were Gram-stained to detect biofilms. Immunoglobulins were measured in serum and saliva. RESULTS When P. aeruginosa was cultured simultaneously from the sinuses and the lungs they were genetically identical in 38 of the 40 patients (95%). In the sinuses, P. aeruginosa formed biofilms with minimal cellular inflammation, probably because of a significantly higher local production of secretory IgA compared with IgG (p<0.001). CONCLUSIONS We have shown that P. aeruginosa form biofilm in the sinuses, which constitute an important bacterial reservoir for subsequent lung infection. The high amount of IgA in the upper airways probably protects P. aeruginosa from the inflammatory immune system, and they can proceed unnoticed into a permanent infectious focus that cannot be eradicated with antibiotics.

WS14.1 Day-time variability and short term effect of chest physiotherapy on multiple breath nitrogen washout in children with cystic fibrosis

WS14.1 Day-time variability and short term effect of chest physiotherapy on multiple breath nitrogen washout in children with cystic fibrosis C. Voldby1, K. Green1, T. Kongstad1, L. Philipsen1, F.F. Buchvald1, M. Skov1, T. Pressler1, P. Gustafsson2, K.G. Nielsen1. 1Copenhagen University Hospital, Rigshospitalet, CF-Center Copenhagen, Pediatric Pulmonary Service, Copenhagen, Denmark; 2Central Hospital Skovde, Department of Pediatrics, Skovde, Sweden

82 Increasing levels of precipitating antibodies to Achromobacter xylosoxidans and Burkholderia multivorans reflect more aggressive pulmonary disease in chronically infected Cystic Fibrosis patients

Introduction; Absolute level and rapidly increasing levels of precipitating antibodies to Pseudomonas aeruginosa (PA) in chronic pulmonary infection in cystic fibrosis (CF) are correlated with degree of lung inflammation, tissue damage and poor prognosis. Precipitating antibodies to other Gram-negative bacteria may exhibit similar properties. Aims; To assess the correlation between levels of precipitins to Achromobacter xylosoxidans (AX), and Burkholderia multivorans iBM) and lung function in chronically infected CF patients. Methods: All patients with a diagnosis of chronic infection with either AX or BM as per 2005 were included. The correlation between level of precipitating antibodies and FEV1% predicted was assessed. Results; 14 patients with chronic AX had median (range) FEV1% predicted of 66% (23 to 111%) and precipitin levels of 25 (3 to 40) showing statistically significant, but weak, negative correlation (r2 0.24, p < 0.05). Correspondingly, in 12 patients with chronic BM a statistically significant negative correlation (r2 0.65, p < 0.05) was shown between lung function: 63% (40 to 110%) and precipitin levels: 17 (8 to 25). Conclusion: Chronic infection with AX or BM, like PA, induces increasing levels of precipitins as markers of enhanced tissue damage as reflected in declining lung function. Precipitins to other Gram-negative bacteria than PA may function as markers of infection severity, treatment success or failure. S19