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the rest of the respiratory tracr (Kimberly, Nejadnik et al. 1996). Higher levels still were demonstrated in the paranasal sinuses with an age-dependent increase in keeping with sinus pneumatisation (Kimberly, Nejadnik et al. 1996). It was postulated that the sinus production of NO diffusing into the nasal spaces gave the high levels of NO then measured in the nasal cavity. Gerlach et al measured NO concentrations in the nasopharynx and trachea showing higher levels during inspiration than expiration (Gerlach, Rossaint et al. 1993). This led to the suggestion that there may be absorption of NO by the lower respiratory tract (giving a concept of auto-inhalation). However they could not exclude an exhaled component coming from pulmonary synthesis of NO. The variation in NO levels obtained made it difficult to comparc results presented by different groups (see Table 6.1). Table 6.1: The published results of exhaled nitric oxide in adults Authors and PaPer Subject numbers Method of measurement Borland et al, 1993 (Borland, Cox et al. 1 ss3) Schedin et al, 1995 (Schedin, Frostellet al. 1995) Gerlach et al 1994 (Gerlach, Rossaint et al. 1994) Kimberly et al, 1996 (Kimberly, Nejadnik et al. 1996) I controls 5 controls 11 conlrols 10 controls 10 smokers 5 controls 8 controls single exhalation tidal breathing mouth breathing tracheostomy breathing tidal breathing via nose tidalbreathing via mouth following intubation Soontaneous breathing: trachea controlled ventilation trachea controlled ventilation Bronchoscooe sampling: at epiglottis, nose breathing at epiglottis, mouth breathing in trachea, nose breathing in trachea, mouth breathing Tidal breathino over 2 minutes: during nasalbreathing during oral breathing Sinole exhalations: exhalation after 30s breath-hold r27 Results in controls Results In dieease 8.1ppb 14.7ppb 16ppb 4.6ppb 64ppb 1 Sppb 0.3ppb 89ppb (insP) 42ppb (ep) 2ppb (insp) 63ppb (exP) 72ppb (insp) 31ppb (exp) 2ppb (insp) 49ppb (exp) 22ppb 9ppb 18ppb 9ppb
Authors and Pap€r Sublect numbers Method of measurement Jilma et al, 1996 (Jilma, Kastner et al. 1996) Persson et al, 1993 (Persson, Wiklund et al. 1993) Sato et al, 1996 (Sato, Sakamaki et al. 1996) Morris et al, 1996 (Morris, Sooranna et al. 1996) Kharitonov et al, 1994 (Kharitonov, Logansinclair et al. 1994) Trolin et al, 1994 (Trolin, Anden et al. 1 994) Robbins et al, 1996 (Robbins, Floreaniet al. 1996) lwamoto et al, 1994 (lwamoto, Pendergast et al. 1994) Martin el al, 1996 (Martin, Bryden et al. 1 996) Alving et al 1993 (Alving, Weitzberg et al. 1993) 22male controls 21 female controls 10 controls 5 controls single exhalations 34ppb tidal breathing following brealh-hold of 60s during hyperventilation pre-exercise exercise at 50 and 100 watts 16 controls reservoir collection no breath-hold breath-hold for 10 seconds breath-hold for 60 seconds 5 female controls single exhalations daily for one month 40 male controls 19 female controls 7 females through a menstrual cycle 27 controls 8 with exercise 91 controls 18 asthmatics 23 smokers I controls with exercise 18 controls 32 allergic rhinitis 18 conlrols 32 allergic rhinitis 18 controls 32 allergic rhinitis 12 controls 8 asthmatics single e;fialations gg single exhalation total output over one minute single exhalation total output single exhalation reservoir collection single exhalation reservoir collection single exhalation reservoir collection single exhalation at rest one minute collection: at rest exercise hyperventilation single exhalation following breath-hold of 10s following breath-hold of :::,,,, Tidalbreathing: nasal inhalation oralinhalation with URTI oral inhalation 128 Results In controls Results ln dlsease 20ppb 3.2Sppb 100.25ppb 4.75ppb 9ppb 5-6ppb (numbers from graph) 't2ppb 14ppb 1Sppb 51 ng g-1 No varialion across the month 75ppb 70ppb midcycle 150ppb menstruation 59ppb 8.6ppb 90.9ppb 2.8ppb 171.2ppb 105.5ppb 14.Sppb 26.3ppb 9.Sppb graphs for individuals 4.8ppb 1 1.1ppb 15.6ppb 32.1ppb 23ppb 9ppb 32ppb 'l74.2ppb 27.2ppb 39.6ppb 7.3ppb 16.3ppb 34.Oppb 62.Oppb 1 lppb
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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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Page 101 and 102: toxic products such as isoprostanes
Page 103 and 104: Figure 3.3: The nitric oxide syntha
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Page 107 and 108: The enzyme of this second pathway -
Page 109 and 110: inappropriate production from comme
Page 111 and 112: Nicotinamide adenosine dinucleotide
Page 113 and 114: enzyme and are competitively revers
Page 115 and 116: 4.1 Introduction Chapter 4: Methods
Page 117 and 118: 4.4 Nitrite and nitrate The measure
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Page 121 and 122: A group of instruments have been de
Page 123 and 124: The original group demonstrated tha
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Page 127 and 128: helium for 30 minutes to remove Oz.
Page 129 and 130: (Postlethwait and Bidani 1990; Post
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: al found levels of 10.3ppb compared
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 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,
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8.1 Chapter 8: Exhaled nitric oxide
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standard error of the mean (SEM), s
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T-piece sampling system to analyser
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Figure 8.2a: Comparison of peak exh
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if yes who? if yes who? if yes who?
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There are limitations with regard t
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significantly between research grou
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controls. Kharitinov et al reported
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direct method in asthmatic children
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Figure 8.4a: The eftect of commenci
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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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