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screening, diagnostic and monitoring purposes. Initially cross sectional studies were carried
out with comparisons to the traditional inflammatory and clinical markers used in asthma (see
Chapter 1). Research then graduated to the use of longitudinal studies to assess the predictive
value of NO for presence, severity and to denote exacerbations of asthma' Longitudinal
studies have also been used to assess treatment effects in standard and new therapies' The
relationships between NO and asthmatic inflammatory markers, lung function testing'
bronchodilator responsiveness and airway challenges have all been studied. I have grouped
the studies presented here under headings of the hypotheses that the studies were devised to
address.
g.g.l Does nitric oxide correlate with other asthmatic inflammatory markers?
Exhaled NO was found to correlate with sputum eosinophil numbers in asthmatics and
healthy controls in adults (Jatakanon, Lim et al. 1998; Berlyne, Parameswaran et al' 2000;
Tsujino, Nishimura et al. 2000; Reid, Johns et al. 2003; silkoff, Ifnt et al' 2005; Fujimoto'
Yamaguchi et al. 2006; Zietkowski, Bodzenta-Lukaszyk et al' 2006) and in children
(Piacentini, Bodini et al. L999; Little, Chalmers et al. 2000; Warke, Fitch et al' 2002; Sacco'
sale et al. 2003; Mahut, Delclaux et a:.2004: Thomas, Gibson et al. 2005; Li, Tsang et al'
2006). while these have been demonstrated in asthmatics whether on or off a range of
medications, the correlations are strongest for steroid naive patients. These findings have been
consistent across the studies that used variable expiratory flows, and were confirmed in one
study that compared results in these subject groups across a range of flows (Beny, shaw et al'
2005). A positive correlation has also been demonstrated between exhaled No and serum
eosinophil cell counts in adults and children (Tsujino, Nishimura et al' 2000; Reid' Johns et
al.Z}o3:Silvestri, sabatini et al. 2003; Strunk, Szefler et al. 2003; Irhtimaki' Kankaanranta
et al. 2005; Zietkowski, Bodzenta-Lukaszyk et al' 2006). Correlations have been described
between NO and sputum ECP levels (Piacentini, Bodini et al. 1999; Warke, Fitch et al' 2002;
Thomas, Gibson et al. 2005), as well as No and lerum ECP levels (Aziz, wilson et al' 2000;
Dal Negro, Micheletto et al. 2003; Strunk, Szefler et al' 2003; Mahut, Delclaux et al' 200,4i
Zietkowski, Bodzenta-Lukaszyk et al. 2006). Perhaps unsurprisingly, in studies that compared
both, it was sputum rather than serum markers that had stronger correlations with exhaled NO
levels. A positive correlation was also shown with the leukotriene group of inflammatory
markers - leukotriene%,leukotriene B4 and 8-isoprostane (Mondino, Ciabattoni et al' 2W4)'
and a negative correlation with the anti-inflammatory cytokines IL-4 and IL-13 (Shome'
Starnes et al. 2006).
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