View - ResearchSpace@Auckland - The University of Auckland

high in the alveolar compartment which correlated with severity and progression regardless of
the patient's smoking habit or current treatment (Tsoukias and George 1998; Kharitonov and
Barnes 2004; Brindicci, Ito et al. 2005). As well, No metabolites of nitrite and nitrate have
been higher in induced sputum in COPD patients compared to normals (Kanazawa, Shoji et
al. 199g). Lung biopsies from patients with severe COPD had higher iNOS seen than those
that had more mild disease and normal controls (Maestrelli, Paska et al. 2003).
COpD patients having frequent exacerbations had higher levels of exhaled NO than stable
current smokers and ex-smokers with COPD or chronic bronchitis (Agusti, Villaverde et al.
1999; Silkoff, Martin et al. 2001). Similarly during admission, the level of exhaled NO was
high and remained elevated at discharge despite intravenous steroid therapy, but when the
patients were once again clinically stable it had reduced to levels similar to control subjects
(Agusti, Villaverde et al. lggg). The NO levels correlated to the drop in FEV1 during
exacerbation in one study (Silkoff, Martin et al. 2001), but did not relate to FEVr or other
variables such as FVC, lung volumes, diffusing capacity or pulmonary gas exchange at the
time of discharge in another study (Agusti, Villaverde et al. 1999). Assessing the effect of
pollution; an association between exhaled NO and particulate matter when measured in a
cross section of the population was significantly greater in subjects who had a doctor
diagnosis of coPD (Adamkiewicz, Ebelt et al. 2004). Exhaled No levels measured
seasonally and during exacerbations in 79 COPD outpatients showed higher levels during
winter months, as well as being higher during the 68 exacerbations seen in 38 of these
patients. The degree of elevation, however, was noted to be lower in those more severely
affected (Bhowmik, Seemungal et al. 2005). Elevated No levels decreased significantly in 47
patients commencing IHCS therapy but there were no changes in FEVr (Zietkowski'
Kucharewi cz et a:.2005). Two studies showed higher exhaled No levels that positively
correlated with post-bronchodilator FEVr suggesting NO may be a marker for inflammation'
responsive to bronchodilator treatment similar to asthmatics, although these COPD patients
were not known to be atopic (Papi, Romagnoli et al. 2000; Zietkowski, Kucharewicz et al'
2005). Both exhaled No and co levels were low in 19 individuals with alpha-l antitrypsin
deficiency compared to both controls and coPD patients (Machado, Stoller et al' 2002)'
9.14 Nitric oxide levels in smokers
NO is known to be contained within cigarettes as previously discussed (see Section 2'2'3)'
Exact concentrations between brands differ, but cigarettes produced in France and the United
States exceeded the NO content of those produced in the UK up to 3-5 fold with no other
247