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Crane, J., N. Pearce, et al. (1995). "End of New Zealand asthma epidemic'" @! 345(8955): 984-5. crane, J., N. Pearce, et al. (1989). "Prescribed fenoterol and death from asthma in New 7-ealand, 1 98 I -83 : case-control study. " Lancet 1 (8644) : 9 l7 -22. Craven, P. and L. J. Ignarro (1996). Purification of soluble guanylylcyclase-and modulation of enzymatic ictivity. Methods tn Nttnc Ox . M. F' J' S' Stamler' Sussex' England, John Wiley & Sons Ltdz 209-220' Crawley, b. n., S. F. Liu, et al. (1990). "Inhibitory role of endothelium-derived relaxing factor in rat and human pulmonary arteries." iritish Journal of Pharmacolog]' 101(1): 166-70. Crimi, E., M. Chiaramondia, et al. (1991).''Increasednumbersofmastcellsinbronchial asthmatic response to allergen." American Review of mucosa after the late-Phase Respiratory Disease 144(6): 1282-6. al. (1981). "Ozone toxicity as a model of lung fibrosis'" Cross, C. E., T. W. Hesterberg, et Chest 80(1 SuPPI): 52-4. cserey, A. and M.'Giatzl (2001). "Stationary-state oxidized platinum microsensor for selectiveandonJinemonitoringofnitric-oxideinbiologicalpreparations.''@ Chemistry 73(16): 3965-7 4. Csoma, 2., A.Bush, et al. (2003). "Nitric oxide metabolites are not reduced in exhaled breath condensate of patients wiitr primary ciliary dyskinesia." ehes! 124(2):633-8' Cunha, F. Q., S. Moncada, et al. (lgg2). "interleukin-lg (L-10) inhibits the induction of nitric oxide synthase by interferon-galnma !n muril-e macrophages"' Biochemical & Bioph),sical Research Communications 182(3): 1 1 55-9' curran, R. D., F. K. F"rruti, "t ar. trggll. "Nitric oxide and nitric oxide-generating 'compounds inhibit hepatocyte protein synthesis." FASEB Journal 5(7):2085-92' Currie, G. p., D. K. fue, et al. (2003). "Effetts of montelukast on surrogate inflammatory markers in corticosteroid+reated patients with asthma." American Journal of Respiratory & Critical Care Medicine 167(9): L232-8' currie, G. p., N. J. Syme-Grant, et ai-. (2003;. ;Effects of low dose fluticasone/salmeterol combination on ,urrogate inflammatory markers in moderate persistent asthma.l' Allergy 58(7): 602-7. Cvtz, E., H. Irvison, et al. (1978). "Ultrastructure of airways in children with asthma'" Histopathology 2(Q: aol -21. D'Alonzo, G. 8., V. W. Steinijans, et al. (1995)' "Measurements of morning and evening airflow grossly underestimate the circadian variability of FEVI and peak expiratory flow rate in asthma." 152(3): rO97-9. Dahlqvist, M., E. A. Eisen, et al. (1993). "Reproducibility of peak expiratory flow measurements. " Occupational Medicine 8(2): 29 5 -302' Dal Negro, R., C. Vtlct et"tto, et .ol- (2003). 'Assessment of inhaled BDP-dose dependency. of exhaled nitric oxide and local and serum eosinophilic markers in steroids-naive nonatopic asthmatics. " Allglgy 58( 1 0) : l0l8-22' Davies, H. D., E. E. Wang, "t;1. (166;.;'Reliability of the chest radiograph in the diagnosis of lower respirator:y infections in young chil&en." Pediatric Infectious Disease Journal 15(7): 600-4. Dawson, T. M., V. L. Dawson, et al. (1992). "A nOVel neuronal messenggr molecule in brain: the free radical, nitric oxide." Annals of Neurology 32(3): 297 -3Il' Dawson, v. L. and r. M. Dawson (rggs)' 'Nltric oxide in neurodegeneration"' b€EgS Brain Research ll8: 2L5-29. de Blay, F., A. puro-hit, et al. (1998). "Serum eosinophil cationic protein measurements in the management oi perennial and periodic asthma: a prospective study'" @ Respiratory Journal 11(3): 594-8. 289
de Blic, J., V. Marchac, et al. (2002). "Complications of flexible bronchoscopy in children: prospectivestudyof|,328procedures.''20(5):|27|-6. de Blic, J. and P. Scheinmann (2000). "Early use of corticosteroids in infancy." Paediatric Respiratory Reviews l: 368-37 L de Blic, J., I. Tillie-Leblond, et al. (2005). "High-resolution computed tomography scan and airway remodeling in children with severe asthma." Journal of Allergy & Clinical Immunology 116(4): 7 50-4. de Blic, J., I. Tillie-Leblond, et al. (2004). "Difficult asthma in children: an analysis of airway inflammation." 113(1):94-100. De Diego, A., E. Martinez, et al. (2005). "Airway inflammation and cough sensitivity in cough-variant asthma." Allgrgy 60( I I ): 1407 -Ll. de Gouw, H. W., K. Grunberg, et al. (1998). "Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects." European Respiratory Journal 11(1): L26-32. de Gouw, H. W., J. Hendriks, et al. (1998). "Exhaled nitric oxide (NO) is reduced shortly after bronchoconstriction to direct and indirect stimuli in asthma." American Journal of Respiratory & Critical Care Medicine 15E(l): 315-9. de la Fuente, P. T., M. Romagnoli, et al. (1998). "Safety of inducing sputum in patients with asthma of varying severity." American Journal of Respiratory & Critical Care Medicine 157(4 Pt 1): tL27-3O. de Medeiros Matsushita, M., L. F. da Silva, et al. (2005). "Airway proteoglycans are differentially altered in fatal asthma." Journal of Pathology 207(l): 102-10. Dehaut, P., A. Rachiele, et al. (1983). "Histamine dose-response curves in asthma: reproducibility and sensitivity of different indices to assess response." Thorax 38(7): 516-22. Deja, M., T. Busch, et al. (2003). "Reduced nitric oxide in sinus epithelium of patients with radiologic maxillary sinusitis and sepsis." Care Medicine 168(3): 28I-6. del Giudice, M. M., F. P. Brunese, et al. (2004). "Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naive atopic asthmatic children." Journal of Asthma 4l(7):759-65. Delgado-Corcoran, C., N. Kissoon, et al. (2004). "Exhaled nitric oxide reflects asthma severity and asthma control." Pediatric Critical Care Medicine 5(l): 48-52. Demple, B. (2004). "Protection from the dark side of NO: signaling and cellular defenses against nitric oxide toxicity." IUBMB Life 56(2):59-64. den Otter, J. J., G. M. Reijnen, et al. (1997). "Testing bronchial hyper-responsiveness: provocation or peak expiratory flow variability?" British Journal of General Practice 47(421):487-92. Devalia, J. L., H. Bayram, et al. (1997). "Mechanisms of pollution-iduced airway disease: in vitro studies in the upper and lower airways." Allergy. 52((38 Suppl)): 45-52. Devalia, J. L., C. Rusznak, et al. (1996). "Effect of nitrogen dioxide and sulphur dioxide on airway response of mild asthmatic patients to allergen inhalation." Lancet 344(8938): 1688-1671. Devalia, J. L., C. Rusznak, et al. (1996). "Air pollutants and respiratory hypersensitivity." Toxicology ktters 86(2-3): 169-17 6. Deykin, A., O. Halpern, et al. (1998). "Expired nitric oxide after bronchoprovocation and repeated spirometry in patients with asthma." American Journal of Respiratory & Critical Care Medicine 157(3 ft l): 769-75. Deykin, A., S. C. Lazarus, et al. (2005). "Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids." Journal of Allergy & Clinical Immunology 115(4): 720-7 . 290
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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
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 and 310: Castro-Rodriguez, J. A., C. J. Holb
Page 311: Cockcroft, D. W., D. N. Killian, et
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).
Page 361 and 362: 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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