Non-invasive assessment of airway inflammation in asthma : a thesis by publications presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Public Health, Massey University, Wellington, New Zealand

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Massey University
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Inflammation is a central feature in current definitions of asthma. Despite this, airway inflammation remains infrequently assessed in either population-based studies or clinical practice. In this thesis, conventional and novel non-invasive methods (based on exhaled nitric oxide (FENO) measurement and sputum induction) were used to assess airway inflammation and examine the presence, characteristics and stability of inflammatory asthma phenotypes in a general population sample, which included very young and very old individuals. It was shown that FENO measurement could be easily and cost-effectively conducted, and that flow cytometric analysis of sputum leukocyte populations is a feasible alternative to conventional manual cell counts. In particular, flow cytometric analysis was shown to be well suited to the detection of rare cell populations, and provided data suggesting that airway invariant natural killer T cells may not be a key player in asthma pathophysiology and that basophils may be a useful indicator of allergic airway inflammation in asthma. When examining inflammatory asthma phenotypes, it was shown that less than 50% of asthmatics (both children and adults) had evidence of eosinophilic inflammation, although in one small study, altered treatment resulted in phenotype changes in more than 50% of asthmatics studied. Neutrophilic airway inflammation was rare, and was statistically significantly associated with age. Approximately half of all the asthmatics studied had no detectable evidence of airway inflammation at the time of assessment. In conclusion, the methods developed and validated for the non-invasive assessment of airway inflammation allow more detailed investigations of asthma aetiology in populationbased studies. However, a single assessment of airway inflammation may not be adequate for valid identification of inflammatory asthma phenotypes. The results of the studies described in this thesis suggest that 50% of asthmatics may have eosinophilic airway inflammation, with the remainder having no airway inflammation. Further investigations of noninflammatory mechanisms are therefore warranted, as a better understanding of the mechanisms and the associated environmental exposures involved may guide the development of more effective therapies and control measures for this common phenotype.
The following articles were removed due to copyright restrictions: Brooks C.R., Brogan S.B., van Dalen C.J., Lampshire P.K., Crane J., Douwes J. (2011) Measurement of Exhaled Nitric Oxide in a General Population Sample: A Comparison of the Medisoft HypAir FE(NO) and Aerocrine NIOX Analyzers. Journal of Asthma,48(4), 324-8; Brooks C.R., van Dalen C.J., Hermans I.F., Douwes J. (2013) Identifying leukocyte populations in fresh and cryopreserved sputum using flow cytometry, Cytometry B Clinical Cytometry, 84(2), 104-13; Brooks C.R., Gibson P.G., Douwes J., Van Dalen C.J., Simpson J.L (2013) Relationship between airway neutrophilia and aging in asthmatics and non-asthmatics, Respirology, 18,856-866.
Asthma, Airway inflammation, Sputum, Flow cytometry, Sputum leukocyte populations, Asthma pathophysiology