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differences noted based on filter, design, tar, nicotine or CO yield. This research was done in<br />

the 1980s and the relationship to what is made and sold now here in New Zealand has not<br />

been studied. Many studies have demonstrated that both peak and plateau NO is lower in<br />

smokers than non-smokers who are otherwise 'healthy' with normal lung function (Persson,<br />

Zetterstrom et al. 1994; Schilling, Holzer et al. 1994; Kharitonov, Robbins et al. 1995;<br />

Robbins, Millatmal et al. 1997; Verleden, Dupont et al. 1999; Balint, Donnelly et al. 2001;<br />

Mazzone, Cusa et al. 2001; Hogman, Holmkvist et ^1.200.2; Horvath, Donnelly et al.2O04).<br />

In mild asthmatics, smokers also had a lower level <strong>of</strong> exhaled NO when compared to non-<br />

smokers (Persson, Zetterstrom et al. 1994; Verleden, Dupont et al. 1999; Horvath, Donnelly et<br />

al. 2ffi4; McSharry, McKay et al. 2005). Nasal NO measurements in 'healthy' normal and<br />

asthmatic smokers compared with their non-smoking counterparts were also reduced<br />

(Robbins, Millatmal et al. 1997; Olin, Hellgren et al. 1998). This reduction <strong>of</strong> NO was<br />

correlated with 'pack years' in current (McSharry, McKay et al. 2005) and ex-smokers<br />

(Corradi, Majori et al. 1999). Two studies also found significant reductions in levels <strong>of</strong><br />

exhaled NO and NO output in a total <strong>of</strong> ll8 healthy infants exposed to pre-natal cigarette<br />

smoke compared to the non-exposed (Hall, Reinmann et al.2OO2; Frey, Kuehni et al. 2OO4).<br />

<strong>The</strong> effects <strong>of</strong> a single cigarette have also been studied. A transient reduction in peak exhaled<br />

NO occurs immediately (Kharitonov, Robbins et al. 1995) and at 50 minutes with a co-<br />

incident rise in HzOz (Horvath, Donnelly et al. 2OO4). However another study found an<br />

increase level <strong>of</strong> NO at one and ten minutes (Chambers, Tunnicliffe et al. 1998) while a fourth<br />

found no change in the levels <strong>of</strong> exhaled NO, S-nitrosothiol or nitrotyrosine at 30 and 90<br />

minutes, although nitrite and nitrate levels were significantly increased (Balint, Donnelly et al.<br />

2001). A decrease in plasma nitrate and nitrite concentrations were seen after smoking a<br />

single 'real' cigarette compared to a sham cigarette (Tsuchiya, Asada et al.2002). Passive<br />

exposure and active smoking in usual non-smokers resulted in a reduction in the level <strong>of</strong><br />

exhaled NO when measured every 15 minutes to one hour (Yates, Breen et al. 2001).<br />

Recently a murine model showed that cigarette smoke caused a reduction <strong>of</strong> NO by<br />

decreasing iNOS mRNA transcription but did not alter the iNOS mRNA half life once already<br />

developed (Hoyt, Robbins et al.20O3). It may be that the NO in the cigarettes operates as a<br />

negative feedback mechanism, resulting in reduction <strong>of</strong> activity <strong>of</strong> the NOS enzymes.<br />

<strong>The</strong> effect <strong>of</strong> quitting smoking on the subsequent levels <strong>of</strong> NO has also been examined. In 20<br />

smokers, nine that were able to refrain from smoking for four weeks resulted in increased<br />

levels <strong>of</strong> exhaled NO, which was no longer significantly lower than controls (Hogman,<br />

Holmkvist et al.20O2). Fourteen smokers had an increase in their exhaled NO compared to<br />

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