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Krug, N., T. Tschernig, et al. (2001). "ComPlement bronchoalveolar lavage fluid after segmental asthma." factors C3a and C5a are increased in allergen provocation in subjects with 164(10 ft 1): 1841-3. Kuhn, H., J. Belkner, et al. (lgg4). "Involvement of l5-lipoxygenase in early stages of atherogenesis. " Journal of Experimental Medicine 17 9(6): 1903- I l' Kuhn, H., D. Heydeck, et al. (1992;. 'ttt uiuo attlon of l5Jipoxygenase ln early stages of human atherogenesis." Journal of Clinical Investigation 99(5): 888-93. Kulkarni, N., N. Pieie, "t ut. (ZOOO)t 'C*bon in airway macrophages and lung function in children." New England Journal of Medicine 355(1): 2l-30. Kumar, S. M., D. M. Pott.tfitld, tt al. (200D. "Nerve injury induces a lpid efflux of nitric oxide (NO) detected with a novel NO microsensor." Journal of Neuroscience 21(1): 2t5-20. Kumlin, M. and B. Dahlen (2000). "The challenge procedure influences the extent of allergen-induced urinary excretion of leukotriene E4." Clinical & Experimental Allerey 30(a): 585-9. Ku.tinJnt, g. Dahlen, et al. (1992). "Urinary excretion of leukotrieneF/ and ll-dehydrothromboxan e B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4, and hisiamine in asthmatics." American Review of Respiratory Disease 146(1): 96-103. Kunrli, N., g. Z. Siua,et al. (1999). "Peak flow variability in the SAPALDIA study and its validity in screening for asthma-related conditions. The SPALDIA Team." American Journal of Respiratory & Critical Care Medicine 160(2): 427-34. Kwon, N. s, c. r.-Nutnu-n, "t al. (1990). "L-citrulline productign frgm L-arginine by macrophage nitric oxide synthase. The ureido oxygen derives from dioxygen." J@ of Biological Chemistry 265(23): 13442-5. Kwon, N. S., C. F. Nathan, et al. (1939). "Reduced biopterin as a cofactor in the generation of nitrogen oxides by murine macrophages." Journal of Biological Chemistry 264Q4):. 20496-501. Kwon, N. S., D. J. Stuehr, et al. (1991). "Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide." Journal of Experimental Medicine 174@):76I-7 ' Kyllonen, H., P. Malmberg, et al. (2006). "Respiratory symptoms, bronchial hyperresponsiveness, and elosinophilic ainvay inflammation in patients with moderate-to- ,"n.r" atopic dermatitis." ciinical & Experimental Allergy 36(2):192-7 ' Labbe, A., B. Aublet-Cuvelier, et af.?OOt). "Prospective longitudinal study of urinary eosinophil protein X in children with asthma and chronic cough." Pediatric Pulmonology 31(5): 354-62. Lai, C. H., S. H. Liou, et al. (2005). "Exposure to traffic exhausts and oxidative DNA damage. " occupational & Environmental Medicine 62(4: 216-22. Laitinen,A.,A.Alt@scinisincreasedinairwaybasementmembraneof asthmatics uni d"rr"used by an inhaled steroid." American Journal of Respiratory & Critical Care Medicine 156(3 Pt 1): 951-8' Laitinen, A., E. tvt. fqdainen, et ai. (2000). "Histopathologic ft-lrly of early and progressive asthmal" Joumal of Allergy & Clini-cal Immunology 105(2 Pt2): 5509-13' Laitinen, L. A., M. Heino, et at. lteaS;. Oarnage of the airway epithelium and bronchial reactivity in patients with asthma." Ameriian Review of Respirator)' Disease 131(a): 599-606. Laitinen, L. A., A. Laitinen, et al. (1996). "Bronchial biopsy findings in l]lrlnmttent or "early" asthma.,' Journal of Allergy & ilinical Immunology 98(5 Pt 2): 53-6; discussion S33- 40. 313
Lamblin, C., P. Gosset, et al. (1998). "Bronchial neutrophilia in patients with noninfectious status asthmaticus." American Journal of Respiratory & Critical Care Medicine 157(2):394-402. Lamkhioued, 8., P. M. Renzi, et al. (1997). "Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation." Journal of Immunology 159(9): 4593-60I. Lammers, J. W., P. J. Barnes, et al. (L992). "Nonadrenergic, noncholinergic airway inhibitory nerves. [Review] [85 refs]." Euro[pan Respiratory Journal. 5(2):239-46. Lancaster, J. R. (1992). "Nitric oxide in cells: This simple molecule plays Janus-faced roles in thebody,actingasbothmesSengeranddestroyer.''@'80:248.259. Lancaster, J. R., Jr., J. M. Langrehr, et al. (1992). "EPR detection of heme and nonheme ironcontaining protein nitrosylation by nitric oxide during rejection of rat heart allograft." Journal of Biological Chemistry 267 (16): 10994-8. Langley, S. J., S. Goldthorpe, et al. (2003). "Exposure and sensitization to indoor allergens: association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma." Journal of Allergy & Clinical Immunology ll2(2):362-8. Langley, S. J., S. Goldthorpe, et al. (2003). "Relationship among pulmonary function, bronchial reactivity, and exhaled nitric oxide in a large goup of asthmatic patients." Annals of Allergy. Asthma. & Immunology 91(4): 398-404. Lanz, M. J., D. Y. Leung, et al. (1997). "Comparison of exhaled nitric oxide, serum eosinophilic cationic protein, and soluble interleukin-2 receptor in exacerbations of pediatric asthma. " Pediatric Pulmonology 7A(5): 305- I 1. Lanz, M. J., D. Y. Irung, et al. (1999). "Comparison of exhaled nitric oxide to spirometry during emergency treatment of asthma exacerbations with glucocorticoids in children." Annals of Allergy. Asthma. & Immunology. 82(2): L6l-4. Larsen,G.L.andP.G.Holt(2000).''Theconceptofairwayinflammation.'.@aI of Respiratory & Critical Care Medicine 162(2 Pt 2): 52-6. Latzin, P., J. Beck, et al. (2002). "Exhaled nitric oxide in healthy children: variability and a lack of correlation with atopy." 13(1): 3746. Lauer, T., M. Preik, et al. (2001). "Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action." Proceedings of the National Academ), of Sciences of the United States of America 98(22): r28r4-9. Laufs, U. and J. K. Liao (1998). "Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase." Journal of Biological Chemistry 273(37): 24266-71. Lazarus, R., B. A. Raby, et al. (20M). "TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples." American Journal of Respiratory & Critical Care Medicine 170(6): 594-600. lravey, J. F., R. L. Dubin, et al. (2004). "Silo-Filler's disease, the acute respiratory distress syndrome, and oxides of nitrogen." @ 141(5):410-1. I-ee, D. K., T. C. Fardon, et al. (2005). "Airway and systemic effects of hydrofluoroalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma." Chest 127(3):851-60. ke, D. K., C. M. Jackson, et al. (2003). "Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma." British Journal of Clinical Pharmacolog], 56(5): 494-500. Lee, M. H., J. H. I-ee, et al. (1997). "Serum eosinophil cationic protein levels and bronchodilator responses at acute asthma exacerbation." Annals of Allergy. Asthma. & Immunology 79@): 363-9. Ire, M. Y., Y. S. Lai, et al. (2005). "Effects of montelukast on symptoms and eNO in children with mild to moderate asthma." Pediatrics International 47(6):622-6. 314
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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
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
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: Kleinert, H., T. Wallerath, et al.
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 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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