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Malmberg, L. P. (2004). "Exhaled nitric oxide in childhood asthma--time to use inflammometry rather than spirometry?" Journal of Asthma 41(5): 5ll-20. Malmberg, L. P., A. S. Pelkonen, et al. (2003). "Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma." Thorax 58(6): 494-9. Maniscalco, M., L. Grieco, et al. (2004). "Increase in exhaled nitric oxide in shoe and leather workers at the end of the work-shift." Occupational Medicine (Oxford) 54(6): 404-7. Manning, P. J., J. Rokach, et al. (1990). "Urinary leukotriene Bl levels during early and late asthmatic responses." Journal of Allergy & Clinical Immunology 86(2): 2lt-20. Manning, P. J., R. M. Watson, et al. (1993). "Exercise-induced refractoriness in asthmatic subjects involves leukotriene and prostaglandin interdependent mechanisms." American Review of Respiratory Disease 148(4 Pt l): 950-4. Mappa, L., F. Cardinale, et al. (2005). "Exaled nitric oxide and air trapping correlation in asthmatic children." Allergy 60(11): 1436-9. Marguet, C., T. P. Dean, et al. (2001). "Eosinophil cationic protein and interleukin-8 levels in bronchial lavage fluid from children with asthma and infantile wheeze." Pediatric Allergy & Immunology l2(L):27-33. Markhorst, D. G., T. Leenhoven, et al. (1996). "Occupational exposure during nitric oxide inhalational therapy in a pediatric intensive care setting." Intensive Care Medicine 22(9):954-8. Marletta, M. A., M. A. Tayeh, et al. (1990). "Unraveling the biological significance of nitric oxide. " Biofactors 2(4): 219 -25. Maroun, M. J., S. Mehta, et al. (1995). "Effects of physical conditioning on endogenous nitric oxide output during exercise." Journal of Applied Physiology 79(4): I2L9-25. Marsden, P. A., H. H. Heng, et al. (1994). "Localization of the human gene for inducible nitric oxide synthase (NOS2) to chromosome l7q1I.2-q12," Genomics 19(1): 183-5. Marsden, P. A., H. H. Heng, et al. (1993). "Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene." Journal of Biological Chemistry. : 26E(23): I 7478-88. Marsden, P. A., K. T. Schappert, et al. (1992). "Molecular cloning and characterization of human endothelial nitric oxide synthase." FEBS Letters 307(3): 287-93. Martin, J. H. and S. W. Edwards (1993). "Changes in mechanisms of monocyte/macrophagemediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing." Journal of Immunology 150(8 Pt 1): 3478-86. Martin, R. J., L. C. Cicutto, et al. (1991). "Airways inflammation in nocturnal asthma." American Review of Respiratory Disease 143(2): 351-7. Martin, U., K. Bryden, et al. (1996). "Increased levels of exhaled nitric oxide during nasal and oralbreathinginsubjectswithseasonalrhinitis.'' Immunology 97 (3): 7 68-7 2. Martinez, F. D. (2002). "What have we learned from the Tucson Children's Respiratory Study?" Paediatric Respiratory Reviews 3(3): 193-7. Martinez, F. D., A. L. Wright, et al. (1995). "Asthma and wheezing in the first six years of life. The Group Health Medical Associates." 332(3):133-8. Martinez, T., A. Weist, et al. (2003). "Assessment of exhaled nitric oxide kinetics in healthy infants." Journal of Applied Physiology 94(6):2384-90. Massaro, A. F., B. Gaston, et al. (1995). "Expired nitric oxide levels during treatment of acute asthma." American Journal of Respiratory & Critical Care Medicine. Aug:152(2):800- 3.. 319
Massaro, A. F., S. Mehta, et al. (1996). "Elevated nitric oxide concentrations in isolated lower airway gas of asthmatic subjects." American Journal of Respiratory & Critical Care Medicine. May:153(5): l5 10-4. Matsumoto, H., A. Niimi, et al. (2006). "Prognosis of cough variant asthma: a retrospective analysis." Journal of Asthma 43(2): 131-5. Matsumoto, I., S. Walker, et al. (1996). "The influence of breathhold on peak expiratory flow in normal and asthmatic children." European Respiratory Journal 9(7): 1363-7. Mattes, J., K. Storm van's Gravesande, et al. (2002). "Circadian variation of exhaled nitric oxide and urinary eosinophil protein X in asthmatic and healthy children." Pediatric Research 5l(2):190-4. Mattoli, S., V. L. Mattoso, et al. (1991). "Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic nonallergic asthma." Journal of Allergy & Clinical Immunology 87 (4): 7 94-802. Maziak, W., S. Loukides, et al. (1998). "Exhaled nitric oxide in chronic obstructive pulmonary disease." American Journal of Respiratory & Critical Care Medicine 157(3 ft l):998-1002. Mazumdar, S., H. Schimmel, et al. (1982). "Relation of daily mortality to air pollution: an analysis of 14 l-ondon winters, 1958159-1971172." Archives of Environmental Health 37(4):213-20. Mazzone, A., C. Cusa, et al. (2001). "Cigarette smoking and hypertension influence nitric oxide release and plasma levels of adhesion molecules." Clinical Chemistry & Laboratory Medicine 39(9): 822-6. McCall, T. B., R. M. Palmer, et al. (1992). "Interleukin-8 inhibits the induction of nitric oxide synthase in rat peritoneal neutrophils." Biochemical & Biophlsical Research Communications 186(2): 680-5. McDougall, C. M. and P. J. Helms (2006). "Neutrophil airway inflammation in childhood asthma." Thorax 61(9): 739-4I. McIntosh,K.(2002).''Community-acquiredpneumoniainchildren.''@ Medicine 346(6): 429-37 . McKean, M. and F. Ducharme "Inhaled steroids for episodic viral wheeze of childhood [Systematic Review]." Cochrane Database of Systematic Reviews 2007:(2). McMullen, A. H., H. L. Yoos, et al. (2002). "Peak flow meters in childhood asthma: parent reportofuseandperceivedusefulness.''|6(2):67-72. McSharry, C. P., I. C. McKay, et al. (2005). "Short and longterm effects of cigarette smoking independently influence exhaled nitric oxide concentration in asthma." Journal of Allergy & Clinical Immunology 116(1): 88-93. Mehta, J. L., L. Y. Chen, et al. (1995). "Identification of constitutive and inducible forms of nitric oxide synthase in human platelets." Journal of Laboratory & Clinical Medicine 125(3):370-7. Meijer, G. G., D. S. Postma, et al. (1996). "Seasonal variations in house dust mite influence the circadian peak expiratory flow amplitude." American Journal of Respiratory & Critical Care Medicine 154(4 ft l): 881-4. Meijer, R. J., H. A. Kerstjens, et al. (1996). "Exhaled nitric oxide concentration is influenced byalcoholcontainingdisinfectants.''9(5):1111. Meldrum, B. and J. Garthwaite (1990). "Excitatory amino acid neurotoxicity and neurodegenerative disease." Trends in Pharmacological Sciences f 1(9): 379-87. Menon, N., A. Wolf, et al. (1989). "An improved chemiluminescence assay suggest non nitric oxide-mediated action of lysophosphatidylcholine ad acetylcholine." Proceedings of the Society for Biology and Experimental Medicine 191: 316-319. Mercer, R. 8., D. L. Costa, et al. (1995). "Effects of prolonged exposure to low doses of nitric oxide or nitrogen dioxide on the alveolar septa of the adult rat lung." Laboratory Investi gation 73(l): 20-26. 320
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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
Page 291 and 292: o Cass Byrnes & Nicky Holt. "Drugs
Page 293 and 294: o Byrnes CA. Paediatric fibreoptic
Page 295 and 296: Appendix 2: Questionnaire for enrol
Page 297 and 298: Al-Ali, M. K. and P. H. Howarth (20
Page 299 and 300: 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: Lymar, S. V. and J. K. Hurst (1996)
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 and 352: Panza, J. A., C. E. Garcia, et al.
Page 353 and 354: Peters, S. P. (2006). "Safety of in
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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