Nitric oxide in airway inflammation

Exhaled breath condensate (EBC) is a non-invasive method of investigating airway inflammation associated with nitric oxide (NO) and the metabolites nitrite/nitrates (NOx) in diseases such as chronic obstructive pulmonary disease (COPD), but some of the variables affecting the results are unknown. It was hypothesised that 1) EBC would be influenced by lung volumes and the type of EBC collection device; 2) fractional exhaled NO (FENO) and EBC NOx in COPD patients would be altered by smoking and glucocorticosteroids (GCS); 3) cigarette smoke could contribute to the EBC NOx concentration while it may also decrease FENO indirectly by converting airway NO to NOx.It was found that EBC volume was significantly correlated with both tidal volume and minute volume. Comparing four EBC collection devices demonstrated greater efficiency with the ECoScreen® than siliconised glass tubes or RTube® but it gave factitiously high NOx levels. Total EBC protein levels over a 10-minute collection were significantly higher using the ECoScreen® than either glass or RTube® devices. A cross-sectional study of 96 COPD patients and 80 age-matched control subjects demonstrated that FENO levels in COPD patients were significantly higher than normal subjects when comparing either the combined groups or appropriate two subgroups: ex-smokers and smokers. GCS treatment demonstrated no significant effect on either FENO levels or EBC NOx, but EBC NOx was elevated in smokers. In vitro, cigarette smoke extract (CSE) induced significantly higher NOx and asymmetric dimethylarginine (ADMA) levels in A549 cells when compared with control media. The anti-oxidant, NAC pre-treatment partially reversed the elevated NOx levels but not the ADMA levels. This thesis is the first to report FENO and EBC NOx in COPD patients in an appropriate sample size to be able to evaluate each subgroup, and the increased EBC NOx levels found in smokers in vivo was consistent with the elevated NOx level in response to CSE observed in vitro. These data indicate that smoking-related airway inflammation and activation of the NO pathway are complex with both an increase in ADMA, NO, NOx and may be regulated by oxidative stress rather than the nitric oxide synthase (NOS) pathway..

Medienart:	E-Book

Erscheinungsjahr:	2009
Erschienen:	Erscheinungsort nicht ermittelbar: University of New South Wales. Clinical School - Prince of Wales Hospital ; 2009

Sprache:	Englisch

Beteiligte Personen:	Liu, Jia [VerfasserIn]
Hochschulschrift:	Dissertation, University of New South Wales. Clinical School - Prince of Wales Hospital, 2009

Links:	handle.unsw.edu.au [kostenfrei]

Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1803296321