Inducible Nitric Oxide Synthetase (iNOS) is the principal enzyme responsible for Nitric oxide (NO) production and
is expressed by many cells including respiratory epithelial cells. Both exhaled NO (eNO) and epithelial iNOS are
low in Cystic Fibrosis (CF). The low levels observed may be due to low constitutional expression of iNOS in CF or
may be secondary to the effects of thick pulmonary mucus and chronic bacterial infection on iNOS and NO release
from epithelial cells. The proposed study will be the first to study eNO and epithelial expression of the NOS
isoenzymes in infants with CF before the onset of chronic lung infection.
10 infants with CF will be identified by the Western Australie CF screening program. As a control group, 10
infants, that require a bronchoscopic evaluation for upper airway abnormalities will be included. eNO will be
collected using a tidal breathing method, where the exhaled air of the infants is sampled in a PVC-bag. ENO will
be measured using a chemoluminiscence analyser. During bronchoscopy, tracheal brushing and bronchoalveolar
lavage will be carried out. To ensure that any differences observed between the two groups are not secondary to
inflammation, BAL fluid will be assayed for the presence of 3 potential markers of inflammation - IL8, TNF-alpha
and neutrophil elastase. NOS-activity will be measured in respiratory epithelial cells using the PCR-method. In the
statistical evaluations, differences between the two groups concerning eNO and NOS-expression will be
compared.The findings of the proposed study may have significant therapeutic implications. If NO is
constitutionally low in CF, it may be possible to reduce rates of bacterial infection in infancy through the use of
therapies that increase NO levels in the lung. Likewise, if eNO is low in CF secondary to infection, this would
support the early aggressive treatment of CF with antibiotics.