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Shoji, S., H. Kanazawa, et al. (1998). "Clinical implication of protein levels of IL-5 in induced sputum in asthmatic patients." Journal of Asthma 35(3): 243-9' Shome, G. p., J. D. Starnes, 3rd, et al. (2006). "Exhaled nitric oxide in asthma: variability' relation to asthma severity, and peripheral blood lymphocyte cytokine expression." Journal of Asthma 43(2):95-9. SIGN tZOOSlr gritish Guidelines on the Management of Asthma; A national clinical guideiine. Edinburgh, Scotland., British Thoracic Society, Scottish Intercollegiate buidelines Networli, Guideline No. 63. www.sign.ac.uk/guidelines: I -94' Sigurs, N., R.Bjarnason, et al. (2000). "Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7." American Journal of Respiratory & Critical Care Medicine 161(5): 1501-7' Silber, G,- D. prouO, tt ut. (t$g). "In vivo release of inflammatory mediators by . hyperosmolar solutions." American Review of Respiratory Disgase 137(3): 606-L2. Silkoff, F. g. IZOO4). "Nasal nitric oxide: clue to a diagnosis of ciliary dyskinesia." @! D6Q):1013-4. Silkoff, p. E. (2005). "Exhaled nitric oxide and asthma." New England Journal of Medicine 353(7): 732-3; author tePlY 732-3. silkofl p. E., c. A. Bates, et-ai. (2004). "single-breath exhaled nitric oxide in preschool children facilitated by a servo-controlled device maintaining constant flow." Pediatric Pulmonology 37 (6): 554-8. SilkoffF E., J. Chatkin, et al. (1999). "Nasal nitric oxide: a comparison of measurement techniques." American Journal of Rhinology 13(3): 169-78' Silkoff, p. E.; S. t
Silvestri, M., F. Sabatini, et al. (2003). "Correlations between exhaled nitric oxide levels, blood eosinophilia, and airway obstruction reversibility in childhood asthma are detectable only in atopic individuals." Pediatric Pulmonology 35(5): 353-63. Silvestri, M., D. Spallarossa, et al. (2000). "Dissociation between exhaled nitric oxide and hyperresponsiveness in children with mild intermittent asthma." Thorax 55(6): 484-8. Silvestri, M., D. Spallarossa, et al. (1999). "Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma." Eur Respir J 13(2): 321-6. Simons, F. E. (1997). "A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group." New England Journal of Medicine 337(23):1659-65. Simons, F. E., M. P. Persaud, et al. (1993). "Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids." Lancet 342(8874):776-8. Simpson, A., A. Custovic, et al. (1999). "Exhaled nitric oxide, sensitization, and exposure to allergens in patients with asthma who are not taking inhaled steroids." American Journal of Respiratory & Critical Care Medicine 160(l): 45-9. Sin, A., E. Terzioglu, et al. (1998). "Serum eosinophil cationic protein (ECP) levels in patients with seasonal allergic rhinitis and allergic asthma." Allergy & Asthma Proceedin gs l9(2): 69 -7 3. Singel, D. J. and J. R. Lancaster (1996). Electron paramagnetic resonance spectroscopy and nitric oxide biology. Methods in Nitric Oxide Research. M. F. J. S. Stamler. Sussex, England., John Wiley & Sons Ltd.: 341-356. Singh, S. and T. W. Evans (1997). "Nitric oxide, the biological mediator of the decade: fact or fiction?. [Review] [112 refs]." European Respiratory Journal. Mar:10(3):699-707. Sipahi, 8.,2. S. Ercan, et al. (1998). "Nitric oxide-mediated relaxation induced by bradykinin in the isolated mouse trachea." European Journal of Pharmacology 352(2-3):263-8. Sippel, J. M., W. E. Holden, et al. (2000). "Exhaled nitric oxide levels correlate with measures of disease control in asthma." Journal of Allergy & Clinical Immunology 106(a): 6a5- 50. Sirsjo, A., P. Soderkvist, et al. (1994). "Different induction mechanisms of mRNA for inducible nitric oxide synthase in rat smooth muscle cells in culture and in aortic strips." FEBS Irtters 33E(2): 191-6. Skinner, K. A., C. R. White, et al. (1998). "Nitrosation of uric acid by peroxynitrite. Formation of a vasoactive nitric oxide donor." Journal of Biological Chemistry 273(38):24491-7. Slivka, A., R. Chuttani, et al. (1994). "Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N-acetylcysteine in rabbits and humans." Joumal of Clinical Investigation 94(5): 1792-8. Sly, P. D. and A. A. Hutchison (1980). "Validity of sputum eosinophilia in diagnosing coexistent asthma in children with cystic fibrosis." Australian Paediatric Journal 16(3): 205-6. Sly, P. D., L. I. Landau, et al. (1985). "Home recording of peak expiratory flow rates and perception of asthma." American Journal of Diseases of Children 139(5): 479-82. Sly, P. D., R. Tepper, et al. (2000). "Tidal forced expirations. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society." European Respiratory Journal 16(4):741-8. Smiddy, J. F., W. E. Ruth, et al. (1971). "Flexible fiberoptic bronchoscope." Annals of Internal Medicine 75(6): 971-2. Smith, A. D., J. O. Cowan, et al. (2005). "Exhaled nitric oxide: a predictor of steroid response." American Journal of Respiratory & Critical Care Medicine 172@):453-9. Smith, A. D., J. O. Cowan, et al. (2005). "Use of exhaled nitric oxide measurements to guide treatment in chronic asthma." New England Journal of Medicine 352(21):2L63-73.
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UNIVERSITV OF AUCKI'AND Abstract -
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There was no significant difference
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This is Dedicated: Dedication To th
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New Zealand The Paediatric Departme
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Contents Abstract ........tr Dedica
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6.5.4 The subjects............... .
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XIV
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List of Figures Figure l.l: Top l0
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List of Abbreviations ABPA allergic
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LADA N*N* dimethyl L-arginine LFA1
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t}ryem(eNoS)Typeltrendothelialnifti
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area, some of it has been expanded
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In addition, both of these groups a
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studies conducted throughout the Un
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Video clips of infants with a varie
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the Paediatric Society of New 7*ala
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inhaled anti-cholinergic agents and
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ecommended to monitor asthma at hom
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improvement to 70Vo PEF would have
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Furthermore, investigators have als
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poorer predictor of a diagnosis of
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Bronsky et al. 1998), and a long-te
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SIGN guideline (SIGN 2005) stated "
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In brief, the human airway can be d
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The ability to biopsy has led to st
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small proportion of cells recovered
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methodology of sputum induction and
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et al. 1999; Giannini, Di Franco et
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over a six month treatment prograrn
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There are other studies suggesting
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So is induced sputum in adults and
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asymptomatic patients independent o
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onchial hyper-responsiveness (Reich
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led to research which looked for le
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analyser machines. This thesis pres
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The pollution of the 'great smog of
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adults greater than 65 years (Ostro
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levels compared to those children l
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More recently 'Air Quality Indexes'
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acetylcholine. These were known to
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cyclase does not produce significan
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Garthwaite l99l), and the non adren
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significant complication, this trea
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locus for the enzyme is a susceptib
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NO synthesis and in so doing blocke
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3.1 Chapter 3: The synthesis, react
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BHa = tetrahyrobiopterin, FAD = fla
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(Knowles, McWeeny et al. 1974) and
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more potent at low oxygen tensions
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toxic products such as isoprostanes
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Figure 3.3: The nitric oxide syntha
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providing NO as a neurotransmitter
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The enzyme of this second pathway -
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inappropriate production from comme
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Nicotinamide adenosine dinucleotide
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enzyme and are competitively revers
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4.1 Introduction Chapter 4: Methods
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4.4 Nitrite and nitrate The measure
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insensitive (Braker and Mossman 197
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A group of instruments have been de
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The original group demonstrated tha
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equired it. For example, there was
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helium for 30 minutes to remove Oz.
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(Postlethwait and Bidani 1990; Post
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is set at 5ppm (AIHA 1966) based on
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5.1 Chapter 5: Methodological asses
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wanted to compare the patterns of e
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in different colours that became th
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an advisor for this work and main s
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Delay time: the time between turnin
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led to an increased water content t
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Chapter 6: Methodological studies o
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pulmonary circulation appeared to c
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al found levels of 10.3ppb compared
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Authors and Pap€r Sublect numbers
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only those measured by mouth or low
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6. Check that the pens work. Fill w
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keys but it is currently in the mid
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Calibration pressures: the test por
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T-piece: tO The first figure shows
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the rotameter. Tracings of each par
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Figure 6.6: Mean exhaled NO levels
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NO and COz results from single exha
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6.6.4 (iii) Comparison of exhaled n
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Figure 6.11b: COz levels at peak NO
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I also considered whether the diffe
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the direct to the indirect method l
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need for methodological experiments
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The exhalations were carried out in
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Figure 7.2: Example of the tracing
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7.4.4 Results There was an increase
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Table 7.3: NO, COz and duration of
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The second set of exhalations invol
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Figure 7.6: Photographs of the chan
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Table 7.5: Exhaled NO results with
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the NO concentrations taken pre and
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Figure 7.10: Hyperbolic relationshi
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pressure over the likely range enco
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subjects with respiratory disease,
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8.1 Chapter 8: Exhaled nitric oxide
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standard error of the mean (SEM), s
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T-piece sampling system to analyser
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Figure 8.2a: Comparison of peak exh
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if yes who? if yes who? if yes who?
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There are limitations with regard t
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significantly between research grou
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controls. Kharitinov et al reported
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direct method in asthmatic children
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Figure 8.4a: The eftect of commenci
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had last used her p2 agonist inhale
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higher level of exhaled NO at 4.9pp
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9.1 Introduction Chapter 9: Exhaled
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For the oral measurements options i
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Table 9.1: The recommended standard
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taken from the available literature
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compartment correlated with the ser
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measurement with variable expirator
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to settle. We may have been measuri
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9.5 Off-line measurement NO determi
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(Hyde, Geigel et al. 1997; Tsoukias
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9.6 Nasal nitric oxide measurement
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measured over two 24 hour periods,
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women who coincidently experienced
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While these cross-sectional and the
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symptoms. Steroid response was sign
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'difficult asthma' also had higher
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season and then reduced down to bas
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of cross sectional studies with a t
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Ciabattoni et al. 2004; Petersen, A
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FEV9.5, symptom score and airways r
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Indomethacin - This medication alte
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89Vo for PCD, and above that exclud
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This low NO occurs despite higher t
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patients were followed through one
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differences noted based on filter,
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9.L6 Nitric oxide levels in exercis
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another study of 111 school childre
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Almost all studies used sedation, w
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peak exhaled NO production in the f
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flow and to minimize nasal contamin
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ecruit blood vessels in the lung. S
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Chapter 10: Reflections The outcome
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and I enrolled 52 asthmatic childre
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Edwards EA, Douglas C, Broome S, Je
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o Cass Byrnes & Nicky Holt. "Drugs
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o Byrnes CA. Paediatric fibreoptic
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Appendix 2: Questionnaire for enrol
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Al-Ali, M. K. and P. H. Howarth (20
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Archer, S. L., P. J. Shultz, et al.
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Baraldi, E., N. M. Azzolin, et al.
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Belda, J., P. Hussack, et al. (2001
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Bongers, T. and B. R. ODriscoll (20
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Brown, G. C. and C. E. Cooper (1994
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Castro-Rodriguez, J. A., C. J. Holb
Page 311 and 312: Cockcroft, D. W., D. N. Killian, et
Page 313 and 314: de Blic, J., V. Marchac, et al. (20
Page 315 and 316: Donaldson, S. H., W. D. Bennett, et
Page 317 and 318: Emi-Miwa, M., A. Okitani, et al. (1
Page 319 and 320: Frey, U., J. Stocks, et al. (2000).
Page 321 and 322: Gershman, N. H., H. Liu, et al. (19
Page 323 and 324: Grasemann, H., E. Michler, et al. (
Page 325 and 326: Hashimoto, T., K. Minoguchi, et al.
Page 327 and 328: Holgate, S. T., D. E. Davies, et al
Page 329 and 330: Iriso, R., P. M. Mudido, et al. (20
Page 331 and 332: Jones, A. W., M. Fransson, et al. (
Page 333 and 334: Kercsmar, C. M. (2006). Wheezing in
Page 335 and 336: Kleinert, H., T. Wallerath, et al.
Page 337 and 338: Lamblin, C., P. Gosset, et al. (199
Page 339 and 340: Li, X. and J. W. Wilson (1997). "In
Page 341 and 342: Lymar, S. V. and J. K. Hurst (1996)
Page 343 and 344: Massaro, A. F., S. Mehta, et al. (1
Page 345 and 346: Miyabara, Y., R. Yanagisawa, et al.
Page 347 and 348: contribute to impaired endothelium-
Page 349 and 350: ODell, T. J., R. D. Hawkins, et al.
Page 351 and 352: Panza, J. A., C. E. Garcia, et al.
Page 353 and 354: Peters, S. P. (2006). "Safety of in
Page 355 and 356: Prieto, L., L. Bruno, et al. (2003)
Page 357 and 358: Ribbons, K. A., X. J. Zhang, et al.
Page 359 and 360: Sacco, O., R. Sale, et al. (2003).
Page 361: Sessa, W. C., K. Pritchard, et al.
Page 365 and 366: Stamler, J. S. (1994). "Redox signa
Page 367 and 368: Stuehr, D. J., N. S. Kwon, et al. (
Page 369 and 370: Tierney, W. M., J. F. Roesner, et a
Page 371 and 372: Upchurch, G. R., G. N. Welch, et al
Page 373 and 374: Wadsworth, R., E. Stankevicius, et
Page 375 and 376: Williams, O., R. Y. Bhat, et al. (2
Page 377 and 378: Yates, D. H., S. A. Kharitonov, et
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