Non-invasive assessment of upper and lower airway infection and inflammation in CF patients.
BACKGROUND
The upper (UAW) and lower (LAW) airways of patients with cystic fibrosis (CF) have the same ion-channel defects, but little is known about similarities and differences in host immunological responses at the two levels.


OBJECTIVE
Identification and comparison of both levels' pathogen colonization and resulting immunological host responses.


METHODS
The UAW and LAW of 40 CF patients were non-invasively assessed by nasal lavage and induced sputum. Pathogen colonization, cytology, and the concentrations of inflammatory mediators (TNF-α, MPO, matrix metalloprotease (MMP)-9, tissue inhibitor of metalloprotease (TIMP)-1, regulated upon activation, normal T-cell expressed and presumably secreted (RANTES), and interleukin (IL)-1β, -5, -6, -8, and -10) were measured.


RESULTS
Inflammatory responses were more pronounced in the LAW than the UAW. Pseudomonas aeruginosa LAW colonization is accompanied by a significantly enhanced neutrophil (PMN)-dominated response (P = 0.041) and IL-8 concentration (P = 0.01) not observed in P. aeruginosa UAW colonization. In contrast, sinonasal P. aeruginosa colonization resulted in elevated RANTES (P = 0.039) and reduced MMP-9 (P = 0.023) and TIMP-1 (P = 0.035) concentrations. Interestingly, LAW P. aeruginosa colonization was associated with reduced sinonasal concentrations of MMP-9 (P = 0.01) and TIMP-1 (P = 0.02), a finding independent of UAW colonization for MMP-9.


CONCLUSIONS
CF UAW and LAW show distinct inflammatory profiles and differentiated responses upon P. aeruginosa colonization. Assessment of UAW colonization and MMP-9 are predictive of chronic pulmonary colonization with P. aeruginosa. Thus, this linkage between CF UAW and LAW can provide new clinical and scientific implications.
Department of Paediatrics, Cystic Fibrosis Centre, Jena University Hospital, Jena, Germany.
Nele
N
Fischer
Julia
J
Hentschel
Udo R
UR
Markert
Peter M
PM
Keller
Mathias W
MW
Pletz
Jochen G
JG
Mainz
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008168:Lung; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D055556:Nasal Lavage; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D013183:Sputum / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D009195:Peroxidase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Pseudomonas aeruginosa; cystic fibrosis; cytokines; nasal lavage; upper airways