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o There was a signed consent form and a questionnaire filled out by their parent/s' o The child was willing to be part of the study' o The child had a doctor diagnosis of asthma' o The child was on either bronchodilator therapy only or bronchodilator therapy and long term IHCS therapy. No child studied was on any other asthma medications (such as long acting p2 agonist therapy, theophylline or oral steroids). some of the children were on topical treatments for eczema' o There had been no change in their asthma treatment in the last six weeks' o There was no current or recent upper or lower respiratory tract infection for at least four weeks. o The child had recorded no other respiratory, cardiac or other major chronic disease' The ethical consent obtained for the study and the statistical analysis have been documented previously in Section 8.2. 8.5.3 Protocol The protocols for the asthmatic subjects were identical to those used the control subjects and are listed in Section g.3.3 above. The two techniques of measurement were used: the direct to analysers method and the t-piece sampling method' The children did one set of five exhalations under each condition and continued until five sets of measurable exhalations were made, or it became obvious that either the procedure was too difficult or it was exacerbating their asthma. As the children were enrolled from either the morning clinics or the school (as previously organised) all the children were measured at the same time during the day - late morning between 1000 hours and 1300 hours' 8.5.4 Results In total 31 asthmatic children were recruited for the studies of exhaled NO in asthma: fifteen were on bronchodilator treatment only and 16 on regular IHCS therapy. The children with asthma on bronchodilator treatment only had an FVC of 92Vo (SD 14.5) and FEVr of 78Vo (sD 10.4) percent predicted by the Polgar reference equation @olgar and Promadh^t I97I)' The children with asthma on regular IHCS had a mean FVC of 987o (SD 18.5) and FEVr of g6qo (SD 17.5). The mean peak No level measured by the direct method in asthmatic children on bronchodilator treatment only was 126.1ppb (SD 77.1, range L4.4-36l.lppb) which was significantly higher than compared to the healthy children (mean 49'6ppb, SD 37'4' range n.s-lgl.2ppb see previous results, p
direct method in asthmatic children on regular IHCS therapy was 48.7ppb (SD 43.3, range 8.6-106.4ppb) which was significantly lower than the asthmatic children on bronchodilator treatment only (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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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
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 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: controls. Kharitinov et al reported
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
Page 257 and 258: of cross sectional studies with a t
Page 259 and 260: Ciabattoni et al. 2004; Petersen, A
Page 261 and 262: FEV9.5, symptom score and airways r
Page 263 and 264: Indomethacin - This medication alte
Page 265 and 266: 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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