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individual subjects (see Figure 7 .2 for an example of the recording on one subject)' The mean decrease in exhaled NO was 35ppb (957o C| 25.7,43.4) from the expiratory flow rate of 25omls/min to ll0omls/min. There were no significant differences in the mean CO2 levels, mean mouth pressure (controlled) or mean duration of exhalation in the measurements made at the differing flow rates. There was no difference between the first baseline and repeated baseline of NO when the expiratory flow was the same (p-0.9 95Vo CI -16'9, 17'0), excluding an order effect (see Table 7.2). Table 7.1: NO, COz and duration of each exhalation at different expiratory flows NO is measured as peak NO in parts per billion, COz is measured as peak aq the percentage of QOz total gases, duration is measured in seconds. Lach result is the mean of five exhalations for every subject. a. Duratn = duration of exhalation. Figure 7.1: Exhaled NO results with increasing expiratory flows 160 og rao .E 120 $ 1oo o80 =60 *40 t ,i 20 0 250 mls/mln 500 mlr/mln 750 mle/mln 1100 mlr/mln Sublect Gender Age NO COz Durtn' NO COz Durtn NO COz Durtn NO COr Durtn 1 Female 32 23 4.7 57 17 4.5 59 23 4.5 55 4.5 50 2 Male 33 102 7.2 52 89 7.0 55.0 73 6.3 55 TI 6.2 51 3 Male 37 78 6.0 56 68 6.1 56 60 5.9 62 51 5.9 62 4 Male 49 85 6.4 66 70 5.7 59 79 5.8 62 70 6.0 61 c Female 43 31 6.2 55 23 6.2 54 19 5.8 54 17 6.0 54 6 Female 32 147 6.2 63 115 6.1 64 100 6.2 68 92 6.1 63 7 Female 37 83 5.7 50 86 5.8 52 82 5.9 47 76 6.0 44 8 Female 35 143 6.4 71 127 6,2 7',| 95 5.2 67 85 6.2 69 9 Male 43 67 6.7 84 60 6.9 72.1 43 2.0 71.0 38 7.0 71 10 Female 36 30 6.1 58 24 6.0 57 18 5.9 55 15 5.8 50 L __ F.-f 2g 500 7s0 Explratory flows In mls/mln Mean peak exhaled No levels at different expiratory flows for ten individuals (six females). Each point is the mean of five exhalations. t57 ------ a 11(n
Figure 7.2: Example of the tracing in one subject at two different expiratory flows 7 .4 Methodological experiment three - 7.4.1 Hypotheses effect of pressure l. The levels of NO will alter with different pressure. 2. The levels of NO measured in exhaled air will be different with changes in expiratory mouth pressure. 7.4.2 Aim 1. To compare NO levels measured using a calibration gas delivered to the NO analyser at different pressures. 2. To compare NO levels measured at different expiratory mouth pressures. 7.4.3 Procedure (i) A calibration gas of 110ppb was applied to the NO analyser as measured via the direct system and was delivered to the analyser at pressures from 4 to 4OmmHg in increasing increments of 4mmHg determined by the pressure gauge, and the NO level recorded. 158
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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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Page 131 and 132: is set at 5ppm (AIHA 1966) based on
Page 133 and 134: 5.1 Chapter 5: Methodological asses
Page 135 and 136: wanted to compare the patterns of e
Page 137 and 138: in different colours that became th
Page 139 and 140: an advisor for this work and main s
Page 141 and 142: Delay time: the time between turnin
Page 143 and 144: led to an increased water content t
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: The exhalations were carried out in
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
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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
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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
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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
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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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