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Table 9.2: The recommended standards for single breath and tidal breathing otf-line NO measurement The current recommended technique for single exhalation collection into a reservoir is: r inhale through the mouth from NO free air (
9.6 Nasal nitric oxide measurement For completion, I am going to briefly cover nasal NO although I did not measure this parameter as part of my research. Presentation of standard techniques for this measurement commenced in 1999 (American Thoracic Society and Association. 1999), with minor amendments in 2002 and 2005 (Baraldi, de Jongste et al.2N2; American Thoracic Society and European Respiratory Society 2005). The NO concentration is far greater in the nose than the lower respiratory tract and is measured in parts per million as opposed to parts per billion (Alving, Weitzberg et al. 1993; Gerlach, Rossaint et al. 1994; Lundberg, Farkas-Szallasi et al. 1995). NO concentration is even higher in the para-nasal sinuses (Lundberg, Rinder et al. 1994; Lundberg, Farkas-Szallasi et al. 1995; Haight, Qian et al. 2000). Table 9.3: The recommended standard for nasal NO measurement The current recommended technique for measurement of nasal NO is: o tho subject is seated o two nasalolives are placed with a central lumen in the nares. o these must be of sufficient size to occlude the nostril. o d sdlTrple is aspirated continuously at a constant rate from one narus. o gas is entrained via the other narus giving a trans-nasal flow in series. o a target sampling airflow of 0.25 to O.3Umin is recommended. . oropharyngeal and lower airway contamination is prevented by one of the methods suggested (see paragraph below). . mean NO values are calculated for a stable plateau of greater than ten seconds or five breaths (Silkotf, Chatkin et al. 1999; Ratjen, Kavuk et al. 2000). o the higher flow rate (compared to exhaled oral sampling) at 0.25-3Umin allows a steady plateau levelof NO concentration in subjects within 20-30 seconds. This trans-nasal flow reflects the most cornmon method of measurement. An alternative is to have continual aspiration of both nares; one to discard and one to measure. Velum closure can be achieved in a number of ways; the most common is to slowly exhale orally against a resistance similar to the exhaled NO recommendation (Arnal, Didier et al. 1997; Kharitonov, Rajakulasingam et al. 1997; Silkofl McClean et al. 1997; Dubois, Douglas et al. 1998; Silkoff, Chatkin et al. 1999). Other options that have also been effective are purse-lip breathing via the mouth (Rodenstein and Stanescu 1983), breath-holding with the velum closed (Kimberly, Nejadnik et al. 1996) or voluntary elevation of the soft palate by a trained subject (Giraud, Nejadnik et al. 1998). Of note for nasal NO measurements, healthy adults have significantly better repeatability than healthy children (Kharitonov, Walker et al. 2005). 220
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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
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Figure 6.6: Mean exhaled NO levels
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NO and COz results from single exha
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6.6.4 (iii) Comparison of exhaled n
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Figure 6.11b: COz levels at peak NO
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I also considered whether the diffe
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the direct to the indirect method l
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need for methodological experiments
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The exhalations were carried out in
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Figure 7.2: Example of the tracing
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7.4.4 Results There was an increase
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Table 7.3: NO, COz and duration of
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The second set of exhalations invol
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Figure 7.6: Photographs of the chan
Page 191 and 192: Table 7.5: Exhaled NO results with
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Page 195 and 196: Figure 7.10: Hyperbolic relationshi
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Page 201 and 202: 8.1 Chapter 8: Exhaled nitric oxide
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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
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Page 215 and 216: controls. Kharitinov et al reported
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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: (Hyde, Geigel et al. 1997; Tsoukias
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
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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
Page 267 and 268: This low NO occurs despite higher t
Page 269 and 270: patients were followed through one
Page 271 and 272: differences noted based on filter,
Page 273 and 274: 9.L6 Nitric oxide levels in exercis
Page 275 and 276: another study of 111 school childre
Page 277 and 278: Almost all studies used sedation, w
Page 279 and 280: peak exhaled NO production in the f
Page 281 and 282: flow and to minimize nasal contamin
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Page 285 and 286: Chapter 10: Reflections The outcome
Page 287 and 288: and I enrolled 52 asthmatic childre
Page 289 and 290: Edwards EA, Douglas C, Broome S, Je
Page 291 and 292: 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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