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SIGN guideline (SIGN 2005) stated "the smallest dose of inhaled steroids compatible with
maintaining disease control should be used. At higher doses add on agents for example long
acting p-2 agonists should be actively considered". In the NzpAG @aediatric
Society of New
7*,aland2005) again the recommendation is to "titrate the dose of inhaled corticosteroids to
the lowest dose at which effective control of asthma is maintained". The difficulty here is how
to measure what the appropriate low dose is and whether control has been achieved.
Ultimately, treating the pathological changes rather than being guided by symptoms alone
might well be useful. In the next section, I will present that data suggesting that asthma is an
to measure, non invasive, marker of airway
inflammatory disease, and whY an easY
inflammation might be of great value'
1.6
During the last decades there has been a gradual move from the concept of asthma as a
disease of bronchoconstriction to that of an inflammatory disorder, and from the concept of
complete reversibility to accepting that some irreversible airway damage can occur' The
current definition of asthma proposed by the GINA committee is "Asthma is a chronic
inflammatory disorder of the airway in which many cells play a role, in particular mast cells'
eosinophils, and T lymphocytes" (GINA 2005). In the following sections, I will briefly
summarise findings from autopsy studies, then biopsy and lavage' induced sputum' blood and
urine samples in asthmatic patients compared to normal subjects. while a full description of
the research that has resulted in these two major premise alterations is beyond the scope of
this thesis, the purpose of the next sections are two-fold; to background the concept of asthma
as an inflammatory disease and to show that many of these samples are difficult to obtain.
This makes them more appropriate for single or pre and post intervention determinations
rather than repeated longitudinal or population assessments. I have also concentrated on what
was known at the time of my research commencing but have included how this is viewed to
date. NO will be discussed in the next chapter'
1.6.1 What has been leamtfrom autopsy studies?
The hint that asthma was an inflammatory disease occurred early. In the late 19ft century
Charcot-I-eyden crystals (crystalline structures shaped as double nalrow pyramids)'
curschmanns spirals (coiled fibrils of mucus) and eosinophilia in sputum were recognised
during severe exacerbations of asthma (ossler rg92). This was followed early and mid last
century by autopsy studies of adults dying from asthma (Huber and Koessler 1922; Bullen
1952;Dunnill 1960) and much later by autopsy studies in children (cutz, Irvison et al' 1978)'
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