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payne, D. N., A. V. Rogers, et al. (2003). "Early thickening of the reticular basement membrane in chilJren with difficult asthma." American Journal of Respiratory & Critical Care Medicine 167(l): 78-82. payne, WJJ. L G.tt, "t .1. (1996). Use of mass spectrometry for detection of nitrogen oxides. Methods in Nitric Oxide Research. M. F. J. J. Stamler. Susexx, England., John Wiley & Sons Ltd. Peat, J. K., C. M. Salome, et al. (1989). "A prospective -strldy of bronchial hyperresponsiveness and respiratory symptoms in a population of Australian sihoolchildren." Clinical & Experimental Allergy 19(3): 299-306. peat, J. K., R. H. van d"" Brrg, "Changing prevalence of asthma in Australian "t ^1.-(-19%). children." BMJ 30E(6944): 159l-6. Pedroletti, c., w. Zetterquist, et al. (2002). "Evaluation of exhaled nitric oxide in schoolchildren at difierent exhalation flow rates." Pediatric Research 52(3):393-8. Peebles, R. S., Jr., R. G. Hamilton, et al. (2001). "Antigen-specific IgE an{ IgA antibodies in bronchoalveolar lavage fluid are associated with stronger antigen-induced late phase reactions." clinical & Experimental Allergy 31(2): 239-48. Pendergast,D.R.,@9;.'Effectsofimmersionincoolwateronlungexhaled nitric oxide at rlst and during exercise." Respiration Physiology 115(1): 73- 81. pepe, C., S. Foley, et al. (2005). "Differences in airway remodeling between subjects with severe and moderate asthma." Journal of Allergy & Clinical Immunology tl6(3):544- 9. pepke-Zaba, J., T. W. Higenbottam, et al. (1991). "Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension." @! 33E(8776): lI73-4. perez,c. R. ana-R. E. Wood (1994). "Updatl on pediatric flexible bronchoscopy." Pediatric Clinics of North America 4l(2):385-400. peroni, D., A. nodni, a ut. (2005). "Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens." Allergy 60(2): 206-10. perrella, M. A., C. Patterson, et al. (1996). "suppression of interleukin-lbeta-induced nitricoxide synthase promoter/enhancer activity by transforming growth factor-betal in vascular smooth muscle cells. Evidence for mechanisms other than NF-kappaB." Journal of Biological Chemistry 27L(23): t3776-80' e".rhug"n, G, n nyfuna"r, rt uf. (19t5). "Air pollution involving nitrogen dioxide exposure and wheezing bronchitis in children." international Journal of Epidemiology 24(6): rr47-53. persson, M. G., B. Cederqvist, et al. (1994). "Ethanol causes decrements in airway excretion of endogenous nitric oxide in humans." European Journal of Pharmacology. Aug 3;270@\273-8. persson, M. G. unJ I g. Gustafsson (1993). "Allergen-induced airway obstruction in guineapigs is associated with changes in nitric oxide levels in exhaled air." @s!91@ Scandinavica 149 (4): 46 L -6. Persson, M. G., N. P. Wiklund, et al. (1993). and the change during exercise." Nov:148(5):1210-4. "Endogenous nitric oxide in single exhalations American Review of Respiratory Disease' persson, M. G., O. Z"tto.trom, et al. (1994). "Single-breath nitric oxide measurements in asthmatic patients and smokers." Lancet. Jan 15:343(8890):146-7 peters, A., D. W. bockery, et al. (2001). "Increased particulate air pollution and the triggering of myocardial infarction." Circulalion 103(23): 2810-5' peters, A., E. Liu, et at. (ZOOO). "eFpollution and incidence of cardiac arrhythmia." Epidemiology 11(1): I 1-7. Peters, S. P. (2003t "Heterogeneity in the pathology and treatment of asthma." @ Journal of Medicine 115 Suppl 3A: 49S-54S' 329
Peters, S. P. (2006). "Safety of inhaled corticosteroids in the treatment of persistent asthma." Journal of the National Medical Association 98(6): 851-61. Petersen, R., L. Agertoft, et al. (2004). "Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma." European Respiratory Journal 24(6):932-7. Petros, A., G. Lamb, et al. (1994). "Effects of a nitric oxide synthase inhibitor in humans with septic shock. " Cardiovascular Research 28(l): 34-9. Pfaff, J. K. and W. J. Morgan (1994). "Pulmonary function in infants and children." !9gfu11jg Clinics of North America 4l(2):40t-23. Pfeiffer, S., A. C. Gorren, et al. (1997). "Metabolic fate of peroxynitrite in aqueous solution. Reaction with nitric oxide and pH-dependent decomposition to nitrite and oxygen in a 2:1 stoichiometry." Journal of Biological Chemistry 272(6):3465-70. Phillips, C. R., G. D. Giraud, et al. (1996). "Exhaled nitric oxide during exercise: site of release and modulation by ventilation and blood flow." Journal of Applied Physiology 80(6): 1865-71. Phillips, M. L., T. A. Hall, et al. (1999). "Assessment of medical personnel exposure to nitrogen oxides during inhaled nitric oxide treatment of neonatal and pediatric patients." Pediatrics 104(5 Pt l): 1095-100. Piacentini, G. L., A. Bodini, et al. (2000). 'Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children." European Respiratory Journal 15(5): 839- 43. Piacentini, G. L., A. Bodini, et al. (1999). "Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children." Eur Respir J 13(6): 1386-90. Piacentini, G. L., A. Bodini, et al. (2000). "Exhaled nitric oxide in asthmatic children exposed torelevantallergens:effectofflunisolide.''15(4):730- 4. Pietropaoli, A. P., I. B. Perillo, et al. (1999). "Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans." Journal of Applied Physiology 87(a): 1532-42. Pijnenburg,M. W., E. M. Bakker, et al. (2005). "Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial." American Journal of Respiratory & Critical Care Medicine 172(7):831-6. Pijnenburg, M. W., W. Hoftruis, et al. (2005). "Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission." Thorax 60(3): 215-8. Pijnenburg, M. W., E. T. Lissenberg, et al. (2002). "Exhaled nitric oxide measurements with dynamic flow restriction in children aged 4-8 yrs." 2O(4):919-24. Pilz, R. B., M. Suhasini, et al. (1995). "Nitric oxide and cGMP analogs activate transcription from AP-l-responsive promoters in mammalian cells." FASEB Journal 9(7):552-8. Pin, I., A. P. Freitag, et al. (1992). "Changes in the cellular profile of induced sputum after allergen-induced asthmatic responses." American Review of Respiratory Disease 145(6): 1265-9. Pin, I., P. G. Gibson, et al. (1992). "Use of induced sputum cell counts to investigate ainvay inflammation in asthma." @. Pizzichini, E., M. M. Pizzichini, et al. (1996). "Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements." American Journal of Respiratory & Critical Care Medicine 154(2 Pt l): 308-17. Pizzichini, E., M. M. Pizzichini, et al. (1996). "Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination." European Respiratory Journal 9(6): 1174-80. 330
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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
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Table 7.5: Exhaled NO results with
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the NO concentrations taken pre and
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Figure 7.10: Hyperbolic relationshi
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pressure over the likely range enco
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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.
Page 301 and 302: Baraldi, E., N. M. Azzolin, et al.
Page 303 and 304: Belda, J., P. Hussack, et al. (2001
Page 305 and 306: Bongers, T. and B. R. ODriscoll (20
Page 307 and 308: Brown, G. C. and C. E. Cooper (1994
Page 309 and 310: Castro-Rodriguez, J. A., C. J. Holb
Page 311 and 312: Cockcroft, D. W., D. N. Killian, et
Page 313 and 314: de Blic, J., V. Marchac, et al. (20
Page 315 and 316: Donaldson, S. H., W. D. Bennett, et
Page 317 and 318: Emi-Miwa, M., A. Okitani, et al. (1
Page 319 and 320: Frey, U., J. Stocks, et al. (2000).
Page 321 and 322: Gershman, N. H., H. Liu, et al. (19
Page 323 and 324: Grasemann, H., E. Michler, et al. (
Page 325 and 326: Hashimoto, T., K. Minoguchi, et al.
Page 327 and 328: Holgate, S. T., D. E. Davies, et al
Page 329 and 330: Iriso, R., P. M. Mudido, et al. (20
Page 331 and 332: Jones, A. W., M. Fransson, et al. (
Page 333 and 334: Kercsmar, C. M. (2006). Wheezing in
Page 335 and 336: Kleinert, H., T. Wallerath, et al.
Page 337 and 338: Lamblin, C., P. Gosset, et al. (199
Page 339 and 340: Li, X. and J. W. Wilson (1997). "In
Page 341 and 342: Lymar, S. V. and J. K. Hurst (1996)
Page 343 and 344: Massaro, A. F., S. Mehta, et al. (1
Page 345 and 346: Miyabara, Y., R. Yanagisawa, et al.
Page 347 and 348: contribute to impaired endothelium-
Page 349 and 350: ODell, T. J., R. D. Hawkins, et al.
Page 351: Panza, J. A., C. E. Garcia, et al.
Page 355 and 356: Prieto, L., L. Bruno, et al. (2003)
Page 357 and 358: Ribbons, K. A., X. J. Zhang, et al.
Page 359 and 360: Sacco, O., R. Sale, et al. (2003).
Page 361 and 362: Sessa, W. C., K. Pritchard, et al.
Page 363 and 364: Silvestri, M., F. Sabatini, et al.
Page 365 and 366: Stamler, J. S. (1994). "Redox signa
Page 367 and 368: Stuehr, D. J., N. S. Kwon, et al. (
Page 369 and 370: Tierney, W. M., J. F. Roesner, et a
Page 371 and 372: Upchurch, G. R., G. N. Welch, et al
Page 373 and 374: Wadsworth, R., E. Stankevicius, et
Page 375 and 376: Williams, O., R. Y. Bhat, et al. (2
Page 377 and 378: Yates, D. H., S. A. Kharitonov, et
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