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Figure 6.10b: Time to peak NO and peak COz measured by the t'piece system 80 70 a :60 o E50 o .s 40 .g 30 F20 10 0 Tlmeto NO peak Tlme to Duraton of CO2 pak total exhalatbn Comparisons of the time in seconds taken to reach peak NO,.taken to reach peak COz with the total time for exhalation in measurements by the t-piece system (n=12, each mean of 5 exhalations)' I also marked the coz level at the time of No peak to compare the difference between the coz level at this time and at the time of co2 peak, which occurred later in the exhalation. For the direct measurements, the COz level measured at peak NO was 4.88Vo (SEM 0'14) which was significantly lower than the peak CO2 at 5.8lVo (SEM 0'21,p
Figure 6.11b: COz levels at peak NO and at peak CO2 measured by the t-piece system 88 o !g'I ot E6 F5 g4 4 t! E3 E2 {r 8o GOrat NO peak PeakCO, : Comparisons of the COz conc€Dtrations in percent of total expired gases at the time of peak NO and at peak COz in measurements by the direct system (n=12, each mean of 5 exhalations). 6.7 Discussion: The origin of the exhaled nitric oxide The study demonstrated that NO from a single exhalation could be measured by two methods; either by direct connection to the NO analyser or by using a t-piece side arm sampling system. However the results of NO were significantly different with an approximate halving of the peak levels from the direct to t-piece technique, while there was no difference seen in the COz results. These methods gave similar individual coefficients of variation as other groups (Kharitonov, Yates et al. 1994; Monis, Caroll et al. 1995; Jilma, Kastner et al. 1996; Massaro, Mehta et al, 1996; Hogman, Stromberg et al. 1997). The NO results from the female subjects showed greater variability, and this has been noted previously as possibly being an effect of the menstrual cycle in one (Kharitonov, lngan-Sinclair et al. 1994) but not a second paper (Jilma, Kastner et al. 1996). Our subjects were chosen to minimise any other confounding factors most notably being non atopic, non-asthmatic and having normal lung function. As noted in the total group of subjects from which all the studies were done, there were two smokers (two cigarettes per day) which was not ideal but I believed controlling for atopy was more important when excluding subjects. As it happened, neither subject took part in this direct versus t-piece experiment but were involved in later experiments. Previous researchers had been unable to agree whether NO was of alveolar or airway origin (Alving, Weitzberg et al. 1993; Borland, Cox et al. 1993; Persson, Wiklund et al. 1993). It is known that the vast bulk of COz is of alveolar origin, having diffused across the alveolar:capillary membrane from the pulmonary circulation. If COz and NO were both of alveolar origin, the time to reach their respective peaks and the ratio of peak NO to COz would remain the same even if measurement conditions were varied. I thus measured exhaled 148
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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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Page 121 and 122: A group of instruments have been de
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Page 127 and 128: 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
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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: 6.6.4 (iii) Comparison of exhaled n
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
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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
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Page 207 and 208: Figure 8.2a: Comparison of peak exh
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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
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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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