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Niimi, A., H. Matsumoto, et al. (2000). "Airway remodelling in cough-variant asthma'" Lancet 356(9229): 564-5. Nikasinovic, L., I. Momas, et al. (2003). "Nasal epithelial and inflammatory response to -u ;;;;p;rut i""iew of laboratory-based studies published since 1985." JWI of Toxicologv & Environmental tlealm raIT rr' unusar ,=.,vr.'wD 6(5):521-68. v\Jr. J' NIOSH (ZOOS)r N1FH r""o.-endations for occupational safety and health standards' Nishida, K., D. G. Harrison, et al. (Igg2). "Molicular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase." Journal of Clinical Investi gation 90(5): 2092-6. Nitta, H., T. Sato, et al. (1993). "Respiratory health exhaust. I. Results of cross-sectional studies Environmental Health 48(l): 53-8. associated with exposure to automobile in 1979, 1982, and 1983." Archives of Noack, 8., D. Kubitzek, et al. (Lgg2). "oxyhemoglobin assay for nitric oxide"' Neuroprotocols t(2): 133-139. Noble, V., M. tvtunal, et al. (1997). "Respiratory status and allergy nine to l0 years after acute bronchiolitis." Archives of Disease in Childhood 76(1-):315-9' Nocker, R. E., T. A. out, et al. (2000;. "Induced sputum and bronchoalveolar lavage as tools for evaluating the effects of inhaled corticosteroids in patients with asthma." Journal Nog*i of Laboratori & Clinical Medicine 136(1): 39-49' aled nitric oxide as a simple assessment of airway hyperresponJiu.n"r, in bronchial asthma and chronic cough patients." Journal of Asthma 40(6): 653-9. Nogu-i, n, n. Umeno, et al. (1998). "Effect of nitric oxide synthase inhibitor on allergenand hyperventilation-induced bronchoconstriction in guinea-pigs"' Eurooean Respiratory Journal 12(6): l3l8-21' Nolan, S., E. Tolffi d.'(tggg). 'Peak expiratory flow associated with change in positioning oi the instrument: comparison of iive peak flow meters'" Journal of Asthma 36(3): 29I-4. Nootheti, S. and I-. iietory (2006). "Risk of cataracts and glaucoma -with inhaled steroid use in children." Compiehensive Ophthalmology Update 7(1): 31-9. Nordvall,S.L.,C.Janson,"tut.(zoos@-iit'iioxideinapopulation-basedstudyof asthma and allergy in schoolchildren." Allergy 60(a): 469-75. Norman, v. and c. H. Keith (1965). "Nitrogen o*ides in tobacco smoke." Nature 205: 915- 916. Norzila, M.2., K. Fakes, et al. (2000). "Interleukin-8 secretion and neutrophil recruitment accompanies induced ,puiu. eosinophil activation in children with acute asthma'" Amarinqn rnrrrnnl of Resniratorv & Critical Care Medicine 161(3 Pt 1): 769-74. NRC (19SS). e."6ry una *tin;""r *p"sire guidance levels for selected airborne contaminants] Wastrington DC, National Academy Press, Committee on Toxicology' Board on Toxicolog/ and Environmental Health Hazards, Commission on Life Sciences, National Research Council': Vol4 page 8395' Nunn, A. J. and I. Gregg (1989). "New regression iquations for predicting peak expiratory flow in adults." BMJ 298(6680): 1068-70' Nunokawa, Y., N. Ishida, et al. (1994). "Promoter analysis of human inducible nitric oxide synthase gene associated with cardiovascular homeostasis." Biochemical & B ioph ysical Research Communic ations 200(2) : 802-7' Nussbaum,E.(200@ronchoscopy:Clinicalexperiencewith2,836 bronchoscopies." Pediatric critical care Mediciqe 3(2): t7l-176' Nussler, A. K., T. R. gilli., "t uf. tfgg4)t 'Coinduction of nitric oxide synthase and argininosuccinate synthetase in a murine macrophage cell.line- Implicationl lgr regulation of nitric oxide production." Journal of Biological Chemistry 269(2): 1257- 61. 325
ODell, T. J., R. D. Hawkins, et al. (1991). "Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger." Proceedings of the Nation my of Sciences of the United States of America E8(24): I 1285-9. ODonnell, V. B., P. H. Chumley, et al. (1997). "Nitric oxide inhibition of lipid peroxidation: kinetics of reaction with lipid peroxyl radicals and comparison with alpha-tocopherol." Biochemistry 36@9): | 5216-23. O'Sullivan, S., A. Roquet, et al. (1998). "Urinary excretion of inflammatory mediators during allergen-induced early and late phase asthmatic reactions." Clinical & Experimental Allergy 28(1 1): 1332-9. Obase, Y., T. Shimoda, et al. (2001). "Correlation between airway hyperresponsiveness and airway inflammation in a young adult population: eosinophil, ECP, and cytokine levels in induced sputum." Annals of Allergy. Asthma. & Immunology 86(3): 304-10. Obata, H., M. Dittrick, et al. (1999). "Sputum eosinophils and exhaled nitric oxide during late asthmatic reaction in patients with western red cedar asthma." European Respiratory Journal 13(3): 489-95. Ochoa, J. B., A. O. Udekwu, et al. (1991). "Nitrogen oxide levels in patients after trauma and during sepsis." Annals of Surgery 214(5):621-6. Oguzulgen, I. K., H. Turktas, et al. (2N2). "Airway inflammation in premenstrual asthma." Journal of Asthma 39(6): 517-22. Oh, J. W., H. B. Ire, et al. (1999). "Analysis of induced sputum to examine the effects of inhaled corticosteroid on airway inflammation in children with asthma." 1\nng!so[ Allergy. Asthma. & Immunology E2(5): 491-6. Oh, J. W., S. A. Shin, et al. (2005). "Urine leukotriene E and eosinophil cationic protein in nasopharyngeal aspiration from young wheezy children." Pediatric Allergy & Immunology 16(5): 416-21. Ohnishi, T., S. Sur, et al. (1993). "Eosinophil survival activity identified as interleukin-S is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge." Journal of Allergy & Clinical Immunology 92(|): 607- I 5. Ohshima, H., M. Friesen, et al. (1990). "Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins." Food & Chemical Toxicology 28(9): 647-52. Ohta, K., N. Araki, et al. (1994). "A novel in vivo assay system for consecutive measurement of brain nitric oxide production combined with the microdialysis technique." Neuroscience I-etters 17 6(2): 165-8. Olin, A. C., A. Aldenbratt, et al. (2001). "Increased nitric oxide in exhaled air after intake of a nitrate-rich meal. " Respiratory Medicine 95(2): 1 53-8. Olin, A. C., K. Alving, et al. (2004). "Exhaled nitric oxide: relation to sensitization and respiratory symptoms." 34(2):221-6. Olin, A. C., J. Hellgren, et al. (1998). "Nasal nitric oxide and its relationship to nasal symptoms, smoking and nasal nitrate." Rhinology 36(3): II7-2L. Olin, A. C., G. Ljungkvist, et al. (1999). "Exhaled nitric oxide among pulpmill workers reporting gassing incidents involving ozone and chlorine dioxide." European Respiratory Journal M(0: 828-3L. Olivieri, D., A. Chetta, et al. (1997). "Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study." American Journal of Respiratory & Critical Care Medicine 155(6): 1864-7r. Olivieri, M., G. Talamini, et al. (2006). "Reference values for exhaled nitric oxide (reveno) study." Respiratory Research 7:94. 326
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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
Page 297 and 298: Al-Ali, M. K. and P. H. Howarth (20
Page 299 and 300: Archer, S. L., P. J. Shultz, et al.
Page 301 and 302: Baraldi, E., N. M. Azzolin, et al.
Page 303 and 304: Belda, J., P. Hussack, et al. (2001
Page 305 and 306: Bongers, T. and B. R. ODriscoll (20
Page 307 and 308: Brown, G. C. and C. E. Cooper (1994
Page 309 and 310: 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: contribute to impaired endothelium-
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 and 362: Sessa, W. C., K. Pritchard, et al.
Page 363 and 364: Silvestri, M., F. Sabatini, 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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