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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Date
2013
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Massey University
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Abstract
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.
Description
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.
Keywords
Asthma, Airway inflammation, Sputum, Flow cytometry, Sputum leukocyte populations, Asthma pathophysiology