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(see Figure 8.1). The following assessments used peak exhaled NO levels in keeping with our work in adults. The mean level of NO measured by direct exhalation into the analyser was 49.6 ppb' (SD 37.8, range lt.s-lgl.2ppb). The mean level of No measured via the t-piece system was29'7 ppb, (SD 2'7.1, range 5.I-t4l.2ppb). The reduction of the exhaled NO peak seen between the two systems with the higher flow required for the t-piece measurement was consistent in all subjects and consistent with the results in the adult experiments (see Figure 8'1)' Figure 8.1: Peak exhaled NO results in healthy children .o CL o. .E o .9 o zE.e6gxUJ 150 100 comparison of the peak exhaled No results in the direct to analyser and the t-piece sampling system in 39 healthy children with each data point being a mean of five exhalations' There was no significant difference between the direct mean NO levels in boys at 43'lppb (SD 40.5, range ll.5-lg7.2ppb) and girls with mean NO of 55.2 ppb (SD 35'4, runge 17 '7- 124.gppb, p=0.43). There was also no significant difference between the t-piece mean NO levels in boys at 25.6ppb (SD 2g.z,range 7.3-L4l.2ppb) and girls with mean NO 33'8ppb (SD 25.l,range 5'l-g4'3 PPb, p=0'11)' (see Figure 8'2a and 8'2b)' 183
Figure 8.2a: Comparison of peak exhaled NO in boys and girls measured by the direct system o 200 ft reo .s 160 p rco g t2o ! roo 880 E60 fi40 20 0 No difference was seen when comparing the peak exhaled NO results between 23 girls and 16 boys aged 9-11 years in the direct to analyser sampling system with each data point being a mean of five exhalations. Figure 8.2b: Comparison of peak exhaled NO in boys and girls measured by the t-piece system 200 o 180 B reo E reo o a 120 o 100 =80 fi60 fi40 20 0 A t I Boys Glrls No difference was seen when comparing the peak exhaled NO results between 23 girls and 16 boys aged 9-11 years in the t-piece sampling system with each data point being a mean of five exhalations. There was no significant difference between the mean COz levels by direct and t-piece measurements. The mean COz was 5.4Vo (SD 0.66, range 3.8-6.2Vo) direct compared to 5.52Vo (SD 0.66, range 3.9-6.3Vo) via t-piece measurements (p=0.44). Duration of the exhalation had 184 A A a I T
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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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Page 157 and 158: keys but it is currently in the mid
Page 159 and 160: Calibration pressures: the test por
Page 161 and 162: T-piece: tO The first figure shows
Page 163 and 164: the rotameter. Tracings of each par
Page 165 and 166: Figure 6.6: Mean exhaled NO levels
Page 167 and 168: NO and COz results from single exha
Page 169 and 170: 6.6.4 (iii) Comparison of exhaled n
Page 171 and 172: Figure 6.11b: COz levels at peak NO
Page 173 and 174: I also considered whether the diffe
Page 175 and 176: the direct to the indirect method l
Page 177 and 178: need for methodological experiments
Page 179 and 180: The exhalations were carried out in
Page 181 and 182: Figure 7.2: Example of the tracing
Page 183 and 184: 7.4.4 Results There was an increase
Page 185 and 186: Table 7.3: NO, COz and duration of
Page 187 and 188: The second set of exhalations invol
Page 189 and 190: Figure 7.6: Photographs of the chan
Page 191 and 192: Table 7.5: Exhaled NO results with
Page 193 and 194: the NO concentrations taken pre and
Page 195 and 196: Figure 7.10: Hyperbolic relationshi
Page 197 and 198: pressure over the likely range enco
Page 199 and 200: subjects with respiratory disease,
Page 201 and 202: 8.1 Chapter 8: Exhaled nitric oxide
Page 203 and 204: standard error of the mean (SEM), s
Page 205: T-piece sampling system to analyser
Page 209 and 210: if yes who? if yes who? if yes who?
Page 211 and 212: There are limitations with regard t
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Page 215 and 216: controls. Kharitinov et al reported
Page 217 and 218: direct method in asthmatic children
Page 219 and 220: Figure 8.4a: The eftect of commenci
Page 221 and 222: had last used her p2 agonist inhale
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Page 225 and 226: 9.1 Introduction Chapter 9: Exhaled
Page 227 and 228: For the oral measurements options i
Page 229 and 230: Table 9.1: The recommended standard
Page 231 and 232: taken from the available literature
Page 233 and 234: compartment correlated with the ser
Page 235 and 236: measurement with variable expirator
Page 237 and 238: to settle. We may have been measuri
Page 239 and 240: 9.5 Off-line measurement NO determi
Page 241 and 242: (Hyde, Geigel et al. 1997; Tsoukias
Page 243 and 244: 9.6 Nasal nitric oxide measurement
Page 245 and 246: measured over two 24 hour periods,
Page 247 and 248: women who coincidently experienced
Page 249 and 250: While these cross-sectional and the
Page 251 and 252: symptoms. Steroid response was sign
Page 253 and 254: 'difficult asthma' also had higher
Page 255 and 256: 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
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Cockcroft, D. W., D. N. Killian, et
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de Blic, J., V. Marchac, et al. (20
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Donaldson, S. H., W. D. Bennett, et
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Emi-Miwa, M., A. Okitani, et al. (1
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Frey, U., J. Stocks, et al. (2000).
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Gershman, N. H., H. Liu, et al. (19
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Grasemann, H., E. Michler, et al. (
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Hashimoto, T., K. Minoguchi, et al.
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Holgate, S. T., D. E. Davies, et al
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Iriso, R., P. M. Mudido, et al. (20
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Jones, A. W., M. Fransson, et al. (
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Kercsmar, C. M. (2006). Wheezing in
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Kleinert, H., T. Wallerath, et al.
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Lamblin, C., P. Gosset, et al. (199
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Li, X. and J. W. Wilson (1997). "In
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Lymar, S. V. and J. K. Hurst (1996)
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Massaro, A. F., S. Mehta, et al. (1
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Miyabara, Y., R. Yanagisawa, et al.
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contribute to impaired endothelium-
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ODell, T. J., R. D. Hawkins, et al.
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Panza, J. A., C. E. Garcia, et al.
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Peters, S. P. (2006). "Safety of in
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Prieto, L., L. Bruno, et al. (2003)
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Ribbons, K. A., X. J. Zhang, et al.
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Sacco, O., R. Sale, et al. (2003).
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Sessa, W. C., K. Pritchard, et al.
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Silvestri, M., F. Sabatini, et al.
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Stamler, J. S. (1994). "Redox signa
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Stuehr, D. J., N. S. Kwon, et al. (
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Tierney, W. M., J. F. Roesner, et a
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Upchurch, G. R., G. N. Welch, et al
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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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