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Aziz,I.,A. M. Wilson, et al. (2000). "Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults"' Chest 118(a): 1049-58. Azzawi, M., B. Bradley, et al. (1990). "Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma." American Review of Respiratory Disease 142(6 Pt 1): t407-t3' Baba, K., K. yornid-ut. (1998). i'Effects of prostaglandin E2 on nitric oxide-mediated nonadrenergic noncholinergic relaxations in the guinea-pig tracheal muscle'" Arzneimittel-Forschung 4E(1): 47 -51' Bacci,E.,S.ciun.hffiQo0i2).''Inducedsputumisareproducible-methodtoassess ' airway inflammation in asthma." Mediators of Inflammation 11(5): 293-8' Bacci, E., S. Cianchetti, et al. (1998;. "C patison b.twe:n eosinophilic markers in induced sputum and blood in asthmatic patients." Clinical & Experimental Allerey 28(10): 1237-43. Backer, v., A. Dirksen, et al. (1991). "The distribution of bronchial responsiveness. to histamine and exercis e in 527 children and adolescents." Journal of Allergy & Clinical Immunology 88(1): 68-7 6. Backer, V., S. Groih, ef al. (1991). "Sensitivity and specificity of the histamine challenge test for the diagnosis of asthma in an unselected sample of children and adolescents'" European Respiratory Journal4(9): 1093-100' random sample Backer, V. and C. S. Ulrik (1992). "Bronchial responsiveness to exerose ln a ' of 494 children and adolescents from Copenhagen." Clinical & Experimental Allergy 22(8):74r-7. Bagetta, G., M. Iannone, et al. (1993)' of the electrocortical arousal "Inhibition by N omega-nitro-L-arginine methyl ester response in iats." British Journal of Pharmacology 108(a): 858-60. Bagg, L. R. and D. T. Hughes (1980). "Diurnal variation in peak expiratory flow in asthmatics. " European iournal of Respiratory Diseases 61(5): 298-302' Bakke, P. S., V. Baste, et al. (1991). "B;;iiul t"tponsiveness in a Norwegian community'" American Review of Respirator)' Disease 143(2):3L7-22' Balfour-Lynn, L UJ.-hurrty, .Gl.@f'Reduced upper airway nitric oxide in cystic fibrosis." Arch Dis Child 75($):3t9-22' Balfour_Lynn, L. (1gg5). "childhood asthma and puberty." Archives of Disease in childhood 60(3):23t-s. Balint, B., L.E. Donnelly, et al. (2001). "Increased nitric oxide metabolites in exhaled breath condensate after exposure to tobacco smoke." Thorax 56(6): 456-61' Balzar, S., S. E. Wenzel, et al. (2002). "Transbron.t'iut tiopty as a tool to evaluate small airways in asthma." European Respiratory Journal 20(2):254-9. Bancalari, L., I. Conti, et al. (1999). 'E.tty tt-"^e in urinary leukotriel" E4 (LTB[) is dependent on allergen dose inhaled during bronchial challenge in asthmatic subjects'" Allergy 54(12): 127 8-85. Bannenberg, G., J. Xue, et al. (1995). "Characterization of bronchodilator effects and fate of S-nitrosothiols in the isolated perfused and ventilated guinea pig lung'" Journal of Pharmacolo gy & Experimental Therapeutics 27 2(3): 1238-45. Baraldi,E.,N.r"r.fantibiotictherapyonnasalnitricoxide concentration in children with acute sinusitis." American Journal of Respiratory & Critical Care Medicine. 155(5): 1680-3' Baraldi,E.,N'rrr.affil.(1999).''Referencevaluesofexhalednitricoxideforhealthy children 6-15 years old." Pediatric Pulmonology.-: 27(D:5a-8. Baraldi, E., N. M. izzolin, et al- (1998). "Eff".t of atmospheric nitric oxide (NO) on measurements of exhaled NO in asthmatic children." Pediatric Pulmonology' 26(l): 30-4. 277
Baraldi, E., N. M. Azzolin, et al. (1997). "Corticosteroids decrease exhaled nitric oxide in children with acute asthma." Journal of Pediatrics f31(3):381-5. Baraldi, E., N. M. Azzolin, et al. (1997). "Corticosteroids decrease exhaled nitric oxide in children with acute asthma.[see comment]." Journal of Pediatrics. Sep 131(3): 381-5. Baraldi, E., S. Carra, et al. (1999). "Effect of natural grass pollen exposure on exhaled nitric oxide in asthmatic children." American Journal of Respiratory & Critical Care Medicine 159(1): 262-6. Baraldi, E., C. Dario, et al. (1999). "Exhaled nitric oxide concentrations during treatment of wheezing exacerbation in infants and young children." American Journal of Respiratory & Critical Care Medicine. 159(4 Pt 1): 1284-8. Baraldi, E., J. C. de Jongste, et al. (2002). "Measurement of exhaled nitric oxide in children, 200L." European Respiratory Journal 20(1): 223-37. Baraldi, 8., M. F. Pasquale, et al. (2004). "Nasal nitric oxide is low early in life: case study of twoinfantswithprimaryciliarydyskinesia.''A(5): 881-3. Baraldi, E., M. Scollo, et al. (2000). "A simple flow-driven method for online measurement of exhaled NO starting at the age of 4 to 5 years." American Journal of Respiratory & Critical Care Medicine 162(5): 1828-32. Barbato, A., C. Panizzolo, et al. (2001). "Bronchoalveolar lavage in asthmatic children: evidence of neutrophil activation in mild+o-moderate persistent asthma." Pediatric Allergy & Immunology t2(2):73-7. Barbier, A. J. and R. A. I-efebvre (1994). "Influence of S-nitrosothiols and nitrate tolerance in the rat gastric fundus." British Journal of Pharmacology 111(a): 1280-6. Barck, C., J. Lundahl, et al. (2005). "Total eosinophil cationic protein levels in induced sputum as a marker of changes in eosinophilic inflammation in a patient with allergic asthma." Annals of Allergy. Asthma. & Immunology 95(1): 86-92. Barnes, N. C., C. M. Burke, et al. (2000). "The anti-inflammatory profile of inhaled corticosteroids: biopsy studies in asthmatic patients." Respiratory Medicine 94 Suppl F: 516-21. Barnes, P. J. (1993). "Nitric oxide and airways.[comment]." European Respiratory Journal. Feb:O: 6(2):163-5. Barnes,P.J.(l994).''Airpollutionandasthma.''7o(823):3L9- 25. Barnes, P. J. and M. G. Belvisi (1993). "Nitric oxide and lung disease. [Review] [145 refs]." Thorax. oct:o: 48(10): 103443. Barnes, P. J. and S. A. Kharitonov (1996). "Exhaled nitric oxide: a new lung function test. [Review] [73 refs]." Thorax. Mar:O: 51(3): 233-7. Bames, P. J., S. Pedersen, et al. (1998). "Efficacy and safety of inhaled corticosteroids. New developments." American Journal of Respiratory & Critical Care Medicine 157(3 Pt 2): S1-53. Barreto, M., M. P. Villa, et al. (2001). "Off-line exhaled nitric oxide measurements in chi ldren. " Pediatric Pulmonolo gy 32(2) : I 59 -67 . Barreto, M., M. P. Villa, et al. (2001). "Exhaled nitric oxide in asthmatic and non-asthmatic children: influence of type of allergen sensitization and exposure to tobacco smoke." Pediatric Allergy & lmmunology l2(5):247-56. Barreto, M., M. P. Villa, et al. (2005). "Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms." Pediatric Allergy & Immunology 16(l): 52-8. Barrios, R. J., F. Kheradmand, et al. (2006). "Asthma: pathology and pathophysiology." Archives of Pathology & Laboratory Medicine 130(4): 447-51. 278
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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
Page 249 and 250: While these cross-sectional and the
Page 251 and 252: symptoms. Steroid response was sign
Page 253 and 254: 'difficult asthma' also had higher
Page 255 and 256: season and then reduced down to bas
Page 257 and 258: 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: Archer, S. L., P. J. Shultz, 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.
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Panza, J. A., C. E. Garcia, et al.
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Peters, S. P. (2006). "Safety of in
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Prieto, L., L. Bruno, et al. (2003)
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Ribbons, K. A., X. J. Zhang, et al.
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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. (
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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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