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Karadag, 8., A. J. James, et al. (1999). "Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia." European Respiratory Journal 13(6): 1402- 5. Kariyawasam, H. H. and D. S. Robinson (2005). "Airway remodelling in asthma: models and ' supennodels?[comment]." clinical & Experimental Allergy 35(2): ll7-2I' Karjalainen, E. M., A. Lindqvist, et al. (2003). "Airway inflammation and basement membrane tenascin in newly diagnosed atopic and nonatopic asthma"' @ir3!ry Medicine 97 (9): 1045-5 1. Katrlik, J. and p. Zaiesakova (2002). "Nitric oxide determination by amperometric carbon fiber microelectrode. " Bi oelectrochemi stry 56(L -2): 7 3 -6' Kavuru, M. S., R. A. Dweik, et al. (1999). 'Role of bronchoscopy in asthma research." Clinics in Chest Medicine 20(1): 153-89' Kawai, N, D B. Bloch, et al. (1995). "Constitutive endothelial nitric oxide synthase gene expression is regulated during lung development." American Journal of Physiology 268(4 Pt 1): L589-95. Keatings, v. M., D. J. Evans, et al. (1997). "Cellular profiles in asthmatic airways: a -comparison of induced sputum, bronchial washings, and bronchoalveolar lavage fluid." Thorax 52(\: 372-4. Kelch, H. and c. rruttei (1gg0). "clinical guidelines and indications for bronchoalveolar lavage(BAl): Report of the European-society of Pneumology Task Group on BAL." European Respiratory Journal (3): 937 -97 4' Kelly,ffi88).''RelationbetweenFEV1andpeakexpiratoryflowin patients with chronic airflow obstruction." :rhorax 43(a): 335-6. Kelly, g., N. S. Shah, et al. (1997). "Physiologic and-molecular characterization of the role of nitric oxide in hemorrhagic shoik: evidence that type tr nitric oxide synthase does not regulate vascular decompensation." Shock 7 (3): 157 -63' Kelly, r.j. (zOo:). "Oxidative stress: its role in air pollution and adverse health effects'" Occupational & Environmental Medicine 60(8): 612-6' Kelly, f. l. una T'. Sunart otn (2004). eit pottution, oxidative stress, and allergic response." Lancet 363(9403): 95-6. Kelly, p. I unA T. D. Tetley (lgg7). "Nitrogen dioxide depletes uric acid and ascorbic acid but not glutathione fiom lung lining fluid." Biocher-nical Journal32S(Pt 1): 95-9' Kelly, M. M., V. Keatings, et al. (2002;. "Analysis of fluid-phase mediators." EuroDean Respiratory Journal 20(Suppl 37): 24s-39s' Kelly, N., S. Ct"., "t ury1995). "Bioactive tumor necrosis factor in the sputa of cystic fibrosis ' patients." Clinicai & Diagnostic Laboratory Immunology 2(4): 499-502' Kelm, M., R. putt*nn, "t ut. (t997). The nitric oxide/superoxide Tl?y: Insights into the biological chemistry of the NO/O-2. interaction." Journal of Biological Chemistry 272(15):9922-32. Kelm, M., M. Feelisch, et al. (1988). "Quantitative and kinetic chuacteization of nitric oxide and EDRF released from cultirred endothelial cells." Biochemical & Biophysical Research Communications 154(l): 236-44' Kemp, f. una N. p"*"" Ogg;4 "The decline in asthma hospitalisations in persons aged 0-34 years in New T-ealLand." Australian & New Zealand Journal of Medicine ?il(5):578-81' Kendrick, A. H., c. M. Higgs, et al. (rqgrl. "Accuracy of perception of severity of asthma: patients treated in general practice." BMJ 307(690I):422-4. Kennebeck, M., Jr., R. WJtheringion, et al. (1963). "Toxic Hazards Evaluation of Titan Ii Test Firings: Methods and Results of Laboratory and Field Investigations." AMRLTR: l- 70. Kepley, C. L., P. J. McFeeley, et al. (2001). basophils in postmortem cases of fatal Critical Care Medicine 164(6): 1053-8. 309 "Immunohistochemical detection of human asthma." American Journal of Respiratory &
Kercsmar, C. M. (2006). Wheezing in Older Children: Asthma. Kendig's Disorders of the Respiratory Tract in Children. T. F. B. Victor Chernick, Robert W. Wilmott & Andrew Bush. Philadelphia, USA, Saunders, Elsevier. Seventh edition.: 810-838. Kerstjens, H. A., P. L. Brand, et al. (1994). "Influence of treatment on peak expiratory flow and its relation to airway hyperresponsiveness and symptoms. The Dutch CNSLD Study Group." Thorax 49(11): 1109-15. Ketai, L., M. Harkins, et al. (2005). "Exhaled nitric oxide and bronchial wall thickening in asthmatics during and after acute exacerbation: evidence of bronchial wall remodeling." Journalot|:\s]lhmg 42(8): 667 -7 l. Khamapirad, T. and W. P. Glezen (1987). "Clinical and radiographic assessment of acute lower respiratory tract disease in infants and children." Seminars in Respiratory Infections 2(2): 130-M. Khan, M. T. and R. F. Furchgott (1987). Additional evidence that endothelium-derived relaxing factor is nitric oxide. Pharmacology. M. J. Rand and R. C. Amsterdam, Elsevier: 341-344. Kharitonov, S., K. Alving, et al. (1997). "Exhaled and nasal nitric oxide measurements: recorlmendations. The European Respiratory Society Task Force." Egr&lpilJ 10(7): 1683-93. Kharitonov, S. A. and P. J. Barnes (1997). "Nasal contribution to exhaled nitric oxide during exhalation against resistance or during breath holding." Thorax 52(6): 540-4. Kharitonov, S. A. and P. J. Barnes (2N4). "Effects of corticosteroids on noninvasive biomarkers of inflammation in asthma and chronic obstructive pulmonary disease." Proceedings of the American Thoracic Society 1(3): 191-9. Kharitonov, S. A., K. F. Chung, et al. (1996). "Increased exhaled nitric oxide in asthma is mainly derived from the lower respiratory tract." American Journal of Respiratory & Critical Care Medicine. Jun 153(6 Pt 1): t773-80. Kharitonov, S. A., L. E. Donnelly, et d. (2002). "Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma." Thorax 57(10): 889-96. Kharitonov, S. A., F. Gonio, et al. (2003). "Reproducibility of exhaled nitric oxide measurementsinhealthyandasthmaticadultsandchildren.''@ Journal 2l(3):433-8. Kharitonov, S. A., R. B. Logan-Sinclair, et al. (1994). "Peak expiratory nitric oxide differences in men and women: relation to the menstrual cycle." British Heart Journal. Sep:0: 72(3):243-5. Kharitonov, S. A., B. J. O'Connor, et al. (1995). "Allergen-induced late asthmatic reactions are associated with elevation of exhaled nitric oxide." American Journal of Respiratory & Critical Care Medicine. Jun 151(6): 1894-9. Kharitonov, S. A., K. Rajakulasingam, et al. (1997). "Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids." Journal of Allergy & Clinical Immunology 99(1 Pt 1): 58-64. Kharitonov, S. A., R. A. Robbins, et al. (1995). "Acute and chronic effects of cigarette smoking on exhaled nitric oxide." Medicine. Aug:O: 152(2): 609-12. Kharitonov, S. A., M. A. Sapienza, et al. (1998). "Prostaglandins E2 and F2alpha reduce exhaled nitric oxide in normal and asthmatic subjects irrespective of airway caliber changes." American Journal of Respiratory & Critical Care Medicine 158(5 Pt 1): 1374-8. Kharitonov, S. A., L. Walker, et al. (2005). "Repeatability of standardised nasal nitric oxide measurements in healthy and asthmatic adults and children." Respiratory Medicine 99(9): 1105-14. 310
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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
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 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: Jones, A. W., M. Fransson, et al. (
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
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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