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References Aalbers, R., H. F. Kauffman, et al. (1993). "Allergen-induced recruitment of inflammatory cells in lavage 3 and 24hafter challenge in allergic asthmatic lungs." Chest 103(a): I 178-84. Aaron, s. D., F. Valenza, et al. (1993). "Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation." critical care Medicine 26(2):309-14' Abbey, D. 8., B. L. Hwang, et al. (1995). "Estimated long-telm ambient-concentrations of pMl0 and develop--"nt of respiratory symptomJ in a nonsmoking population"' Archives of Environmental Health 50(2): 139-52' Abelsohn, A., D. Stieb, et al. (2002). "Identifying and managing adverse environmental health effects: 2. ouidoor air pollution." 'clriAJ canadian Medical Association Journal 166(9): 116I-7. Ackerman, V., M. Marini, et al. (1994). "Detection of cytokinel and their cell sources in bronchial biopsy specimens from asthmatic patients. Relationship to atopic status, symptoms, una t.u"t of airway hyperresponsiven^ess." Chest 105(3): 687-96' Ackermann-Liebrich, u., P. I-euen-berger, et al. (1997). "Lung function and long term exposure to ui, poilutants in Swi6erland. Study on Air Pollution and Lung Diseases in Adults (SAPAiDIA) Team." American Journal of Respiratory & Cfitical Care Medicine 155(1): 122-9. Adamkiewicz, G., S. Ebelt, et al. (2004). "Association between air pollution exposure and exhaled nitric oxide in an elderly population." @ 59(3): 204-9' Adams, R. J., K. Boath, et al. (2001). ;e ranaomized trial of peak-flow and-symptom-based action plans in adults with moderate-to-severe asthma." Respirolog)' 6(4):297-304' Adelroth, E., F. E. Hargreave, et al. (1986). "Do physicians need objective measurements to diagnose asthmi?" American Review of Respiratory Diseas.e t34(4):704-7 ' Agertoft, L. and s. P"d"rs.n 11991. "Short-t.rrn knemometry and urine- cortisol excretion in children treated with fluticasone propionate and budesonide: a dose response study'" European Respiratory Journal 10(7): 1507-12' eg"nor''Bonemineraldensityinchildrenwithasthmareceiving long-term treatment with inhaled budesonide." American Journal of Respiratory & Critical Care Medicine 157(1): 178-83' Agertoft,L'andsTp"o",,,,,(2000).''Effectoflong-termtreatmentwithinhaledbudesonide on adult height in children with asthma." New England Journal of Medicine 343(15): 1064-9. Aggarwal, A. N., D. Gupta, et al. (2002). "Assessment of diurnal variability of peak expiratory flow in siable asthmatics." Journal of Asthma 39(6): 487-91' Agostoni, p. and M. Bussotti (2003). "Exhalecl nitric oxide and exercise performance in heart failure." Archives of Ph)'siology & Biochemistry 111(4): 293-6' Agusti, A. G., J. M. Villu*td", "t uil@ Soiut measurements of exhaled nitric oxide during exacerbations of chronic obstructive pulmonary disease." European Respiratory Journal 14(3): 523-8. AIHA (tg66),. 'Ozone." American Industrial and Hygiene,Association 27: L96198' Aikawa, T., S. Shimura, et al. tfg92). \'Iarked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack." Chest 101(4): 9r6-2t. Akinbami, L. J. and K. c. schoendorf (2002). "Trends in childhood asthma: prevalence' health care utilization, and mortality." Pediatrics ll0(2 Pt 1): 315-22' Akiyama, H., S. Barger, et al. (2000). ''Infiammati.on and Alzheimer's disease.'' Neurobiology of Agin g 2l(3): 383 -421. al-Ali, M. K., C. Eames, et al. (1998). "Exhaled nitric oxide; relationship to clinicophysiological markers of asihma severity." Respiratory Medicine 92(7):908-13' 273
Al-Ali, M. K. and P. H. Howarth (2001). "Exhaled nitric oxide levels in exacerbations of asthma, chronic obstructive pulmonary disease and pneumonia." Saudi Medical Journal 22(3):249-53. Albertini, M., S. Politano, et al. (1989). "Variation in peak expiratory flow of normal and asymptomatic asthmatic children. " Pediatric Pulmonology 7 (3): 1404. Aldridge, R. 8., R. J. Hancox, et al. (2002). "Fosinophils and eosinophilic cationic protein in induced sputum and blood: effects of budesonide and terbutaline treatment." Annals of Allergy. Asthma. & tmmunology E9(5): 492-7. Alican, I. and P. Kubes (1996). "A critical role for nitric oxide in intestinal barrier function and dysfunction." American Journal of Physiology 270(2 Pt 1): G225-37. Allen, D. 8., E. A. Bronsky, et al. (1998). "Growth in asthmatic children treated with fluticasone propionate. Fluticasone Propionate Asthma Study Group." Journal of Pediatrics 132(3 Pt l):472-7. Allen, H. D., I. G. Thong, et al. (2000). "Effects of high-dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma." Pediatric Pulmonology 29(3): 188- 93. Alvarez, 8., H. Rubbo, et al. (1996). "Peroxynitrite-dependent tryptophan nitration." Chemical Research in Toxicolog), 9(2):390-6. Alvarez, M. J., J. M. Olaguibel, et al. (2000). "Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients." Allergy 55(6): 531-9. Alving, K., E. Weitzberg, et al. (1993). "Increased amount of nitric oxide in exhaled air of asthmatics." 6(9): 1368-70. Ambalavanan, N., G. Mariani, et al. (1999). "Role of nitric oxide in regulating neonatal porcine pulmonary artery smooth muscle cell proliferation." Biology of the Neonate 76(5):29r-300. American Thoracic Society (1990). "Clinical role of bronchoalvoelar lavage in pulmonary disease." American Review of Respiratory Disease 142:481486. American Thoracic Society (2000). "Guidelines for methacholine and exercise challenge testing -1999." American Journal of Respiratory & Critical Care Medicine 161: 309- 329. American Thoracic Society and M. S. o. t. A. L. Association. (1994). "Standardization of spirometry. Update." American Journal of Respiratory & Critical Care Medicine 152: ttoT-1136. American Thoracic Society and M. S. o. t. A. L. Association. (1999). "Recommendations for standarized procedures for the online and offline measurement of exhaled lower respiratory tract nitric oxide and nasal nitric oxide in adults and children - 1999." American Journal of Respiratory and Critical Care Medicine 160:2104-2117 . American Thoracic Society and European Respiratory Society (2005). "ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2W5." American Journal of Respiratory & Critical Care Medicine 171(8): 912-30. Amin, A. R., P. E. Di Cesare, et al. (1995). "The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase." Journal of Experimental Medicine 182(6):2097-102. Amin, K., D. Ludviksdottir, et al. (2000). "Inflammation and structural changes in the airways of patients with atopic and nonatopic asthma. BHR Group." American Journal of Respiratory & Critical Care Medicine 162(6):2295-301. Anderson, H. R., P. Bailey, et al. (1980). "Trends in the hospital care of acute childhood asthma 1970-8: a regional study." British Medical Journal 281(6249): lI9I-4. Anderson, H. R., A. Ponce de I-eon, et al. (1998). "Air pollution, pollens, and daily admissions for asthma in London 1987-92." Thorax 53(10): 842-8. 274
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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
Page 245 and 246: measured over two 24 hour periods,
Page 247 and 248: 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: Appendix 2: Questionnaire for enrol
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 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.
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contribute to impaired endothelium-
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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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