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etween these researchers were documented in the literature for other subject groups such as those with asthma, bronchiectasis, hypertension and smokers. The measurement of NO in these studies did vary between mean peak exhaled NO, mean plateau exhaled NO and NO measured during tidal breathing. This led me to the suspicion that the technique of measurement critically affected the No levels obtained. In the first methodological study in twelve healthy adults (Byrnes, Dinarevic et al. 1997), I demonstrated that the concentration of NO obtained could be halved depending on whether the subject was breathing directly into the No analyser (mean 84.Sppb) or breathing through a t-piece system (mean 41.2ppb)' The main difference between these two methods was a change in flow from 440 mls/min to 665 mls/min. The methodology experiments detailed in this chapter were therefore designed to determine what factors altered the concentration of exhaled No obtained. In the second methodological study, changing the expiratory flow rate significantly altered the mean concentration of NO obtained. The higher the expiratory flow' the lower the concentrations recorded, with a mean decrease of 35ppb when moving from 25omls/min to 1100mls/min in ten subjects (see Figure 7.1). Most of the literature at the time in the cross sectional studies had usually mentioned the samplin g rate of the machine only, or measured tidal volumes over a L-2 minute time periods with none specifically noting a standard expiratory flow. Alving et al reported that if the airflow was increased in 12 healthy controls from2umin-l to 5 Umin-l a slight increase in the levels of No was noted - the data were not shown and the increase was noted to be insignificant. This proved a different finding from most others (Alving 1993). Imada et al showed a hyperbolic relationship between the NO concentration and the sampling flow rate (see Figure 7'10) with a marked reduction of exhaled No when increasing flow in one subject (Imada 1996). t7r
Figure 7.10: Hyperbolic relationship between exhaled NO and sampling flow rate 800 e 800 5' e 400 200 0 305*(x-0.07) r=0.995, p
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http://researchspace.auckland.ac.nz
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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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Page 145 and 146: Chapter 6: Methodological studies o
Page 147 and 148: pulmonary circulation appeared to c
Page 149 and 150: al found levels of 10.3ppb compared
Page 151 and 152: Authors and Pap€r Sublect numbers
Page 153 and 154: only those measured by mouth or low
Page 155 and 156: 6. Check that the pens work. Fill w
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: the NO concentrations taken pre and
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 and 206: T-piece sampling system to analyser
Page 207 and 208: Figure 8.2a: Comparison of peak exh
Page 209 and 210: if yes who? if yes who? if yes who?
Page 211 and 212: There are limitations with regard t
Page 213 and 214: significantly between research grou
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
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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
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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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