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Bussotti, M., D. Andreini, et al. (2004). "Exercise-induced changes in exhaled nitric oxide in heart failure." European Journal of Heart Failure 6(5): 551-4. Butler,A'R.,F.w.Foniumions,nitroxideions,nitrosothiols and iron-nitrosyls in biology: a chemist's perspective." Trends in Pharmacological Sciences 16(1): 18-22. By-"r,EJ. Bush, et al. (1996). "Measuring expiratory nitric oxide in humans. [Review] lztrefsl." Methods in Enzymology' :: 269:459-73' Byrnes, C. A., A. Buth, .t ul. (1990 VteitroOs to Measure ExpiratoryNitric-Oxide in People' ' L' Packeter' Academic Press Incorporated' Byrn"., cA, s. Din-orir, "t uL trqgD 'ts nitric oxide in exhaled air produced at airway or alveolar level?" European Respiratory Journal. May:(): 10(5): I02l-5. Byrnes, C. A., S. Uin'.*i.Jt A. (t997). 'Eff""t "f measurement conditions on measured levelsofpeakexhalednitricoxide."]]@52(8):697-701' Byrnes, c. A., s. Dinarevic, et al. (lgg7). "E*ttl,td nitric oxide measurements in normal and asthmatic children. " Pediatric Pulmonology. Nov:O: 24(5): 312-8' Byrnes,C.A.,A.M.vog.t@zeandChestInfectioninInfantsunderone year. Best Practice-Evidence Based Guideline. A. M. V. V. C' C A Byrnes' Auckland' Nr* Z.dunl.-pn"diutrir Society of New Zealand.t l-53, www.paediatrics.org.nz' Cai, y., K. Carty, et al. (1998). "Plrsistence of sputum eosinophilia in children with controlled asthma when compared with healthy children." European Respiratory Journal 11(4): 848-53. Call, R. S., T. F. Smith, et al. (lgg2). "Risk factors for asthma in inner city children'" J9@ of Pediatrics 12l(6): 862-6. Calpin, C., C. Nfacarthur, et al. (1997). "Effectiveness of prophylactic^inhaled steroids in childhood asthma: a systemic rwiew of the literature." Journal of Allergy & Clinical Immunology 100(4): 452-7 . c^tu"rt"yJLut-E s. iurge, et al. (2003). "Bronchodilator reversibility testing in chronic o-bstructive pulmonary disease." Thorax 5E(8): 659-64' Canady, R. G., T. Platts-Mills, et al. (1999). "Vital capacity reservoir and g{^ine measurement of childhood nitrosopneu ar" iin"*iy related. Clinical implications." American Journal of Respiratory & Critical Care Medicine 159(1): 3Il-4' Cane,R.S.andSF"K"nzie(2001).''Parents'interpretati9n9o{c!i.tdren'srespiratory symptoms on video." Archives of Disease in Qhildhood 84(1): 3I-34' Cane, R. S., S. C. Ranganathun, "What do parents of wheezy children "-i12000;. understand by "wieeze"?[see comment].'j Archives of Disease in Childhood 82(4): 327-32. Cardinale, F., F.M. de Benedictis, et al. (2005). "Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis." Pediatric Allergy & Immunology 16(3): 236-42. C-roll, N., C. C*1", (Lgg7). "The distribution of eosinophils and lymphocytes in the large and small airways "t'ul. of asthmatics." European RespiratoryJourrlal 10(2): 292-300' Carson, J. L., A. M. Collier, et al. (1993). 'nff..t of niirogen dioxide on human nasal epithelium." American Journal ;f Respiratorv Cell & Molecular Biology 9(3):264-7O' carson, T. R., M. S. Ror"nholtr, at. og6z). "The responses of animals inhaling nitrogen "t dioxide for single, short-term exposures." American Industrial Hygiene Association Journal 23:457-62. Castagnaro, A., A. Chetta, et al. (1999). "Effect of sputum induction on spirometric measurements and arterial oxygen saturation in asthmatic Patients, smokers, and healthy subjects." Chest 116(a): 941-5. Castillejos, M., p.-R. Gold, et al. (1992). "Effects of ambient ozone on respiratory function and symptoms in Mexico City schoolchildren." American Review of Resoiratory Disease t45(2 Pt l): 276-82. 285
Castro-Rodriguez, J. A., C. J. Holberg, et al. (1999). "Association of radiologically ascertained pneumonia before age 3 yr with asthma like symptoms and pulmonary function during childhood: a prospective study." American Journal of Respiratory & Critical Care Medicine 159(6): l89l-1897. Castro-Rodriguez, J. A., C. J. Holberg, et al. (2000). "A clinical index to define risk of asthma in young children with recurrent wheezing." American Journal of Respiratory & Critical Care Medicine 162(4 Pt 1): 1403-6. Castro, L., M. Rodriguez, et al. (1994). "Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide." Journal of Biological Chemistry 269(47):29409-15. Cech, P. and R. I. Lehrer (1984). "Phagolysosomal pH of human neutrophils." B!99d 63(1): 88-95. Chambers, D. C. and J. G. Ayres (2001). "Effect of nebulised L and D-arginine on exhaled nitric oxide in steroid naive asthma." Thorax 56(8): 602-6. Chambers, D. C., W. S. Tunnicliffe, et al. (1998). "Acute inhalation of cigarette smoke increases lower respiratory tract nitric oxide concentrations." Thorax. Aug:0: 53(8): 677-9. Chan-Yeung, M., H. Obata, et al. (1999). "Airway inflammation, exhaled nitric oxide, and severity of asthma in patients with western red cedar asthma." American Journal of Respiratory & Critical Care Medicine 159(5 ft l): 1434-8. Chancellor, M. B. and N. Yoshimura (2N4). "Treatment of interstitial cystitis." Urology 63(3 Suppl l): 85-92. Chang, A. B., V. A. Harrhy, et al. (2002). "Cough, airway inflammation, and mild asthma exacerbation." E6(a): 270'5. Chang, A. 8., L. I. Landau, et al. (2006). "Cough in children: definitions and clinical evaluation." @ 184(8): 398-403. Chang, A. B., M. McKean, et al. (20fJ.4)."Inhaled anti-cholinergics for prolonged non-specific cough in children." (1): CD004358. Chang, A. B. and C. V. Powell (1998). "Non-specific cough in children: diagnosis and treatment." Hospital Medicine 0,ondon) 59(9): 680-4. Chang, L. Y., R. R. Mercer, et al. (1988). "Effects of low levels of NO2 on terminal bronchiolar cells and its relative toxicity compared to O3." Toxicology & Applied Pharmacology 96(3): 451-&. Charlton, I., G. Charlton, et al. (1990). "Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice." BMJ 301(6765): 1355-9. Chartrain, N. A., D. A. Geller, et al. (1994). "Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide synthase gene." Journal of Biological Chemistry 269(9): 67 65 -7 2. Chauhan, A. J., M. T. Krishna, et al. (1998). "Exposure to nitrogen dioxide (NO2) and respiratory disease risk." Reviews on Environmental Health l3(L-2):73-90. Chen, F. H., K. T. Samson, et al. (2N4). "Airway remodeling: a comparison between fatal and nonfatal asthma." Journal of Asthma 41(6): 631-8. Chen, Z.P,,K. I. Mitchelhill, et al. (1999). "AMP-activated protein kinase phosphorylation of endothelial NO synthase. " EEE!.LIrtters M3(3): 285 -9 . Cheney, F. W. and J. Butler (1970). "The effects of ultrasonic aerosols on the total respiratory resistance of the intubated patient." Anesthesiology 32(5): 456-8. Chetta, A., A. Foresi, et al. (1997). "Ainvays remodeling is a distinctive feature of asthma and is related to severity of disease." Chest 111(a): 852-7. Chilton, F. H., F. J. Averill, et al. (1996). "Antigen-induced generation of lyso-phospholipids in human airways." Journal of Experimental Medicine 1E3(5): 2235-45. Chinn, S., P. Burney, et al. (1997). "Variation in bronchial responsiveness in the European Community Respiratory Health Survey (ECRHS)." European Respiratory Journal 10(1 l): 2495-501. 286
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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
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 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: Brown, G. C. and C. E. Cooper (1994
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.
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.
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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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