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89Vo for PCD, and above that excluded PCD with 1007o certainty (Corbelli, Bringolf-Isler et
al. 2004). Reviews now recommend the use of nasal NO to screen for PCD, usually with the
250ppb cut-off (Silkoff 2004; Stehling, Roll et al. 2006).
Nebulised L-arginine given to ten patients with PCD and ten healthy individuals increased
ciliary beat frequency (Inukides, Kharitonov et al. 1998). L-arginine given intravenously
resulted in an increase of nasal and exhaled NO in both PCD and CF subjects, although the
mean concentrations were still significantly lower than normals (Grasemann, Gartig et al.
1999). Neither study showed that the increase in NO translated into other clinical effects or
improvements.
The mechanism behind the low nasal NO in PCD is not yet determined. In other diseases
where low levels are obtained such as CF @alfour-Lynn, Laverty et al. 1996; Dotsch,
Demirakca et al. 1996; Lundberg, Nordvall et al. 1996), diffuse panbronchiolitis (Nakano, Ide
et al. 2000), paranasal sinus inflammatory disease (Arnal, Flores et al. 1999), chronic sinusitis
(Lindberg, Cervin et al. 1997; Deja, Busch et al. 2003) (described in sections below), it is
thought to be secondary to thickened secretions and/or obstruction of the ostea preventing NO
diffusion. However, in clinically stable PCD patients with low NO, their ostea were noted to
be open (Wodehouse, Kharitonov et al. 2003) and sinuses clear (Amal, Flores et al. 1999).
NO has been implicated in control of ciliary function. In our own study (conducted after the
data presented in this thesis), we found no correlation between exhaled NO levels and ciliary
beat frequency in 135 children of European, Maori and Pacific ethnicities. However, we did
find an increase in the percentage of ciliary structural defects, three times that reported in
previous control groups (Edwards, Douglas et al. 2005). Endothelial NOS is located at the
basal micro-tubular membrane in ciliated epithelium (Xue, Botkin et al. 1996) with a
suggestion that NO acts as an intermediate messenger @uner and Lindberg 1999) and TNFc
or ILI can up-regulate ciliary motility seeming to act through NO via induction of NOS (Jain,
Rubinstein et al. 1993). Further research is needed in this area for an adequate explanation of
this phenomenon of low NO levels in this condition.
9.10 Nitric oxide levels in cystic fibrosis
Studies of NO in subjects with cystic fibrosis (CF) have resulted in conflicting data.
Contributing factors are likely to be the different techniques used for measurement when these
studies began in the late 1990s, as well as the variation in age of the patients, co-morbidities
and treatments, not always specified. Cross-sectional studies in children have shown no
difference in levels of oral exhaled NO across CF, asthmatics on IHCS and healthy groups,
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