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Chirpaz-Oddou, M. F., A. Favre-Juvin, et al. (1997). "Nitric oxide response in exhaled air duringanincrementalexhaustiveexercise.''82(4): 1311-8. Chlumsky, J., I. Striz, et al. (2006). "Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma." Journal of International Medical Research 34(2): L29 -39. Cho, S. H., J. Y. Seo, et al. (1996). "Pathological changes according to the severity of asthma." Clinical & Experimental Allergy 26(10): l2l0-9. Choi, D. W. (1988). "Glutamate neurotoxicity and diseases of the nervous system." Neuron l(8):623-34. Chow, C. K. and C. B. Hong (2002). "Dietary vitamin E and selenium and toxicity of nitrite and nitrate." Tox]gqlggy 1E0(2): 195-207. Chowienczyk, P.J., D. H. Parkin, et al. (1994). "Do asthmatic patients correctly record home spirometry measurements?" Elvlf 309(6969): 1 6 1 8. Chung, E., D. Curtis, et al. (1996). "Genetic evidence for the neuronal nitric oxide synthase gene (NOSI) as a susceptibility locus for infantile pyloric stenosis." American Joumal of Human Genetics 58(2): 363-70. Chung, K. F. and P. J. Barnes (1999). "Cyokines in asthma." Thorax 54(9): 825-57. Chung, S. and H. Fung (1990). "Identification of the subcellular site for nitroglycerin metabolisim to nitric oxide in bovine coronary smooth muscle cells." Journal of Pharmacolo gical & Experimental Therapeutics 253: 614-619. Claman, D. M., H. A. Boushey, et al. (1994). "Analysis of induced sputum to examine the effects of prednisone on airway inflammation in asthmatic subjects." Journal of Allergy & Clinical Immunology 94(5): 861-9. Clean Air Act (1990). Unites States Environmental Protection Agency. Available at: www.epa. g ov I airl caal. California. Cleeter, M. W., J. M. Cooper, et al. (1994). "Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases." FEBS Letters 345(1): 50-4. Clini, E., L. Bianchi, et al. (2001). "Effect of pulmonary rehabilitation on exhaled nitric oxide in patients with chronic obstructive pulmonary disease." Thorax 56(7):519-23. Clini, E., L. Bianchi, et al. (2002). "Exhaled nitric oxide and exercise tolerance in severe COPD patients." Respiratory Medicine 96(5): 312-6. Clini, E., L. Bianchi, et al. (1998). "Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease." I@.53(10): 881-3. Clini, E., L. Bianchi, et al. (2000). "Exhaled nitric oxide and exercise in stable COPD patients." Chest ll7 (3): 702-7 . Closs, E. I., J. S. Scheld, et al. (2000). "Substrate supply for nitric-oxide synthase in macrophages and endothelial cells: role of cationic amino acid transporters." Molecular Pharmacology 57(1): 68-7 4. Clough, J. B. (1996). "Recommendations for peak flow monitoring in children. British Thoracic Society." Respiratory Medicine 90(8): 459-61. Clough, J. B., K. A. Keeping, et al. (1999). "Can we predict which wheezy infants will continue to wheeze?" American Journal of Respirator)' & critical care Medicine 160(5 Pt l): 1473-80. Clutton-Brock, J. (1967). "Two cases of poisoning by contamination of nitrous oxide with higheroxidesofnitrogenduringanaesthesia.''39(5): 388-92. Clyne, M. A. A., B. A. Thrush, et al. (1964). "Kinetics of the chemiluminscent reaction between nitric oxide and ozone." Trans. Faraday Soceity ffi:359-370. Cochran, D. (1998). "Diagnosing and treating chesty infants. A short trial of inhaled corticosteroid is probably the best approach." BMJ 316(7lM): 1546-7. 287
Cockcroft, D. W., D. N. Killian, et al. (1977). "Bronchial reactivity to inhaled histamine: a method and clinical survey." Clinical Allergy 7(3):235-43. Cockcroft, D. W., K. Y. Murdock, et al. (1992). "Sensitivity and specificity of histamine PC20 determination in a random selection of young college students." Journal of Allergy & Clinical Immunology 89(l Pt l):23-30. Cohen, R. I., S. Huberfeld, et d. (1996). 'A comparison between the acute effects of nitric oxide synthase inhibition and fluid resuscitation on myocardial function and metabolism in entotoxemic dogs." Journal of Critical Care 11(1): 27-36. Cokugras, H., N. Akcakaya, et al. (2001). "Ultrastructural examination of bronchial biopsy specimens from children with moderate asthma." Thorax 56(l):25-9. Colasanti, M., L. Gradoni, et al. (2N2). "Molecular bases for the anti-parasitic effect of NO @eview)." International Journal of Molecular Medicine 9(2): l3l-4. Colavita, A. M., A. J. Reinach, et al. (2000). "Contributing factors to the pathobiology of asthma. The Thl/Th2 paradigm." @ 2l(2):263-77. Colnaghi, M., V. Condo, et al. (2003). "Endogenous nitric oxide production in the airways of preterm and term infants." Biology of the Neonate 83(2): 113-6. Colon-Semidey, A. J., P. Marshik, et al. (2000). "Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma." Pediatric Pulmonology 30(5): 385-92. Colt, H. G. and T. Matsuo (2001). "Hospital charges attributable to bronchoscopy-related complications in outpatients. " Respiration 68( I ): 67 -7 2. Connelly, L., M. Palacios-Callender, et al. (2001). "Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide." Journal of Immunology 166(6): 3873-81. Connett, G. J. (2000). "Bronchoalveolar lavage." Paediatric Respiratory Reviews l(L):52-6. Connolly,C.K.(|979),''Diurnalrhythmsinairwayobstruction.''@ of the Chest B@):357-66. Conrad, K. P., G. M. Joffe, et al. (1993). "Identification of increased nitric oxide biosynthesis during pregnancy in rats." FASEB Journal 7(6):566-71. Conrad, K. P., M. Vill, et al. (1993). "Expression of nitric oxide synthase by syncytiotrophoblast in human placental villi." FASEB Journal T(13): 1269-76. Corbelli, R., B. Bringolf-Isler, et al. (2004). "Nasal nitric oxide measurements to screen children for primary ciliary dyskinesia." h! 126(4): 1054-9. Corradi, M., M. Majori, et al. (1999). "Increased exhaled nitric oxide in patients with stable chronic obstructive pulmonary disease. " Thorax 54(7): 57 2-5. Corson, M. A., N. L. James, et al. (1996). "Phosphorylation of endothelial nitric oxide synthaseinresponsetofluidshearstress.''@79(5):984-9|. Cortas, N. K. and N. W. Wakid (1990). "Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method." Clinical Chemistry 36(8 Pt 1): 1440-3. Cosentino, F., S. Patton, et al. (1998). "Tetrahydrobiopterin alters superoxide and nitric oxide releaseinprehypertensiverats.''101(7):1530-7. Cottin, V., P. Deviller, et al. (1998). "Urinary eosinophil-derived neurotoxin/protein X: a simple method for assessing eosinophil degranulation in vivo." Journal of Allergy & Clinical Immunology 101(1 Pt 1): 116-23. Covar, R. A., J. D. Spahn, et al. (2004)."Safety and application of induced sputum analysis in childhood asthma." Journal of Allergy & Clinical Immunology 114(3): 575-82. Covar, R. A., S. J. Szefler, et al. (2003). "Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma." Journal of Pediatrics 142(5): 469-75. Cowie, R. L., S. G. Revitt, et al. (1997). "The effect of a peak flow-based action plan in the prevention of exacerbations of asthma." Chest 112(6): 1534-8. 288
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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
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
Page 283 and 284: 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: Castro-Rodriguez, J. A., C. J. Holb
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 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).
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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. (
Page 369 and 370:
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
Page 375 and 376:
Williams, O., R. Y. Bhat, et al. (2
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Yates, D. H., S. A. Kharitonov, et
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