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While these cross-sectional and the longitudinal studies described below (see Section 9.8.5)
have confirmed these findings, it has not been universal. For example, in 58 asthmatic
children no association between NO and eosinophils or ECP from sputum or serum was
shown (Wilson, James et al. 2001). Other studies did not demonstrate a relation between one
specific parameter such as NO with serum eosinophils (Turktas, Oguzulgen et al. 2003), with
serum ECP (del Giudice, Brunese et al. 2004) or with sputum leukotriene levels (Strunk,
Szefler et al. 2003), although they confirmed other associations. Iooking at these studies,
there is no apparent difference in methodology compared to others with positive findings,
although they are more often heterogeneous groups of asthmatics on a wide range of
medications, with smaller numbers of subjects and tended to be 'doctor diagnosed' asthmatics
rather than those diagnosed with specific testing when in clinic which was also conducting the
research.
Direct comparisons of NO with bronchial biopsy results have also been studied. One goup
found a correlation between exhaled NO and each of the eosinophil, lymphocyte and mast cell
components (Silkoffl lrnt et al. 2005), while another study found that NO was only related to
the total number of inflammatory cells present (Turktas, Oguzulgen et al. 2003). In 31
children with difficult asthma, there was a relationship between exhaled NO and the
eosinophil score in seven of 2l children for whom biopsies and NO were obtained. The
strongest relationship was an exhaled NO >7ppb and raised eosinophils at baseline in children
who had persistent symptoms despite high dose prednisolone for two weeks (Payne,
McKenzie et al. 2001). Exhaled NO was also shown to correlate with the degree of airway re-
modeling on biopsy samples in a group of 28 children (Mahut, Delclaux et al.2004) and the
degree of bronchial wall thickening seen on a CT scan in nine asthmatic children (Ketai,
Harkins et al. 2005).
9.8.2 Does nitric oxide correlate with lung function and bronchial hyper-responsiveness?
Comparisons of exhaled NO with lung function parameters have produced variable results.
While many have shown a significant negative correlation, particularly to FEV1, in adults (de
Gouw, Hendriks et al. 1998; Ho, Wood et al. 2000; Dal Negro, Micheletto et al. 2003;
Nogami, Shoji et al. 2003) and children (Colon-Semidey, Marshik et al. 2000; Piacentini,
Bodini et al. 2000; Spallarossa, Battistini et al. 2001; Beck-Ripp, Griese et al. 2002;
Malmberg, Pelkonen et al. 2003; del Giudice, Brunese et al. 2004; Saito, Inoue et al. 2004)
others were not able to demonstrate this (al-Ali, Eames et al. 1998; Silkoff, McClean et al.
1998; Piacentini, Bodini et al. 1999; Ho, Wood et al. 2000; Silvestri, Spallarossa et al. 2000;
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