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Gryglewski, R. J., R. M. Palmer, et al. (1986). "Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor." Nature 320(606t): 454- 6. Guilbert, T. W., W. J. Morgan, et al. (2006). "L,ong-term inhaled corticosteroids in preschggl children at high risk-for asrhma." New England Jgurnal of Medicinq 354(19): 1985-97 ' Gundersen, y., C. O. Corso, et at. (tgt7). 'U; of selective and nonselective nitric oxide synthase inhibitors in rat endotoxemia: effects on hepatic morphology and function'" Shock 8(5): 368-72. Gupta, n.;. N. Aggarwal, et al. (2000). "Reducing the number of daily measurements results in poJr-estimation of diurnal variability of peak expiratory flow in healthy individuals. " Journal of Posteraduate Medicine 46(4): 262-4. Gustafsson, L. 8., n. U. frone, ei uf. ffqgtD Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans." -giochemicat & Bioph Communications. Dec 16(181): 852-7 ' Gutierrez,H.H.,n-.Ni,no,"tal.(1996).''Nitricoxideregulationofsuperoxide-dependent lung injury: oxidant-protective actions of endogenously produced and exogenously adminisrered nitric o*id"." Free Radical Biology & Medicine 21(1): 43-52' Gutierrez, v., L. Prieto, et al. (l-998). "P"ak flow uatiauitity and sputum. eosinophilia in allergic rhinitis." Annals of Allergy. Asthm,a. & Immunologv 81(2): 143-50' Haight, J. S., W. Qian, tt .1. (2000) 'Hyp"-* dep-resses nitric oxide output in the human nasal airways." Laryngoscope 110(3 Pt 1): 429-33' Hajat, S., H. n. nnO"*oi,lt ut. (2002). "Effects of air pollution on..general practitioner consultations for upper respiiatory diseases in London'" Occupational & Environmental Medicine 59(5): 294-9' Hakim, T. s., K. s.rg--ueimo-ti, "t ul. (iqqq. "Half-life of nitric oxide in aqueous solutions with andwithoutliaemoglobin.".Ph)'siologicalMe lT(4):267-77'., Hall,C.B.(200l).,,Respiratory'yffiunaparainfluenzavirus.''NewEngland Journal of Medicine 344(25): L9L7-28' Hall, G. L., B. Reinmann, et al. (2002). 'Tidal exhaled nitric oxide in healthy' unsedated newborn infants with prenatal tobacco exposure." Journal of Applied Physiology 92(r):59-66. Halliwell, B., M. L. Hu, et al. (1992). "Interaction of nitrogen dioxide with human plasma' Antioxidant depletion and oxidative damage." FEBS lrtters 3t3(l):62-6' Hamid, Q., D. R. Springall, et al. (1993). "Induction of nitric oxide synthase in asthma'" Lancet. Dec 18-25:342(8886-8881:: 1510-3' Hamid, Q., M. K. Turt., "t ul- (2003)r Tnflammatory cells in asthma: mechanisms and implications for therapy." Journal of Allergy & Clinical Immunology 111(1 Suppl): S5-S12; discussion SL2-7 . Hampl, V., C. L. Walters, et al. (1996). Determination of teh nitric oxide by the chemiluminescence reaction *iti, orone. Methods in Nitric Oxide Research' M' F' J' J' Stamler. Sussex, England., John Wiley & Sons Ltd.: 310-318. Hamzaoui, A., M. B. Braf,im, et al. (2000). "Inflammatory respoxse.in induced sputum mononuclear cells from patients with acute exacerbation of asthma'" Md@f Infl ammation 9(3-4): 147 -53. Hanssen, H., T. M. Brunini, et al. (1993). "Increased L-arginine transport in human erythrocytes in chronic heart failure." Clinical Science 94(l): 43-8' Hara, J., M. Fujimura, et al. (2006). "Eosinophilic inflammation, remodeling of lower airway' bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy.i' International Archi;es of Aue{gy & hmunologl/ 140(a): 327-33' Harkins, M. S., K. L. Fiato, et al. (2002). 'G[ul"d ttifiitoxide predicts asthma exacerbation"' Journal of Asthma 4t(4): 47I-6. 301
Hashimoto, T., K. Minoguchi, et al. (1999). "Correlation between respiratory function and airway inflammation in asthma." International Archives of Allergy & Immunology 120 Suppl l:82-5. Haslam, P. L. and R. P. Baughman (1999). "Report of ERS Task Force: guidelines for measurement of acellular components and standardization of BAL." European Respiratory Journal l4(2): 245-8. Hattori, R., K. Kosuga, et al. (1993). "Stabilization of inducible nitric oxide synthase by monoclonal antibodies. " Hybridoma l2(7 63 -7 7 0). Hattori, Y., E. B. Campbell, et al. (1994). "Argininosuccinate synthetase mRNA and activity are induced by immunostimulants in vascular smooth muscle. Role in the regeneration or arginine for nitric oxide synthesis." Journal of Biological Chemistry 269(13):9405- 8. Hecker, M., W. C. Sessa, et al. (1990). "The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine." of the United States of America 87(21):8612-6. Henriksen, A. H., T. L. Holmen, et al. (2001). "Sensitization and exposure to pet allergens in asthmatics versus non-asthmatics with allergic rhinitis." Respiratory Medicine 95(2): 122-9. Henriksen, A. H., T. Lingaas-Holmen, et al. (2000). "Combined use of exhaled nitric oxide and airway hyperresponsiveness in characterizing asthma in a large population survey." European Respiratory Journal 15(5): 849-55. Henry, Y., C. Ducrocq, et al. (1991). "Nitric oxide, a biological effector. Electron paramagnetic resonance detection of nitrosyl-iron-protein complexes in whole cells." European Biophysics Journal 20(l): 1-15. Henry, Y., M. Lepoivre, et al. (1993). "EPR characterization of molecular targets for NO in mammalian cells and organelles." EASELI@! 7(12): ll24-34. Hernandez-Garduno, E., J. Perez-Neria, et al. (1997). "Air pollution and respiratory health in Mexico City." Journal of Occupational & Environmental Medicine 39(a): 299-307. Herulf, M., T. Ljung, et al. (1998). "Increased luminal nitric oxide in inflammatory bowel disease as shown with a novel minimally invasive method." Scandinavian Journal of Gastroenterology 33(2): 164-9. Hetzel, M. R. (1981). "The pulmonary clock." Thorax 36(7):481-6. Hetzel, M. R. and T. J. Clark (1980). "Comparison of normal and asthmatic circadian rhythms in peak expiratory flow rate." Thorax 35(10): 732-8. Hevel, J. M. and M. A. Marletta (1992). "Macrophage nitric oxide synthase: relationship between enzyme-bound tetrahydrobiopterin and synthase activity." Biochemistry 31(31):7160-5. Heymann, P. W., H. T. Carper, et al. (2004). "Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing." Journal of Allergy & Clinical Immunology ll4(2): 239-47 . Hibbs, J. 8., Jr. (1991). "Synthesis of nitric oxide from L-arginine: a recently discovered pathway induced by cyokines with antitumour and antimicrobial activity." Research in Immunology 142(7): 565-9; discussion 596-8. Hibbs, J. B., Jr., R. R. Taintor, et al. (1990). Synthesis of nitric oxide from a guanidino nitrogen of L-arginine: a molecular mechanism that targets intracellular iron. Nitric Oxide from L-arginine: A Bioregulatory System. S. Moncada and A. Higgs. Elsevier, Amsterdamz L89 -223. Hibbs, J. 8., Jr., R. R. Taintor, et al. (1987). "Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite." Science 235(4787):473-6. 302
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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,
Page 273 and 274: 9.L6 Nitric oxide levels in exercis
Page 275 and 276: another study of 111 school childre
Page 277 and 278: Almost all studies used sedation, w
Page 279 and 280: peak exhaled NO production in the f
Page 281 and 282: flow and to minimize nasal contamin
Page 283 and 284: ecruit blood vessels in the lung. S
Page 285 and 286: Chapter 10: Reflections The outcome
Page 287 and 288: and I enrolled 52 asthmatic childre
Page 289 and 290: Edwards EA, Douglas C, Broome S, Je
Page 291 and 292: o Cass Byrnes & Nicky Holt. "Drugs
Page 293 and 294: o Byrnes CA. Paediatric fibreoptic
Page 295 and 296: 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: Grasemann, H., E. Michler, 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 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
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Williams, O., R. Y. Bhat, et al. (2
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Yates, D. H., S. A. Kharitonov, et
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