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In brief, the human airway can be divided into three layers; the inner wall (epithelium,
basement membrane and the submucosa), the outer wall (loose connective tissue), and the
smooth muscle layer (Bergeron and Boulet 2006). All layers have shown some alterations in
obstructive respiratory disease compared to normal lung. with regard to the presence of
inflammation, biopsy studies have shown increases in eosinophils, eosinophilic proteins, T
lymphocytes (Foresi, Bertorelli et al. 1990; Poston, chanez et al. 1992: Laitinen, Laitinen et
al. 1gg6; carrou, cooke et al. lggT) and certain cytokines (or their messenger ribonucleic
acid (mRNA)) such as interleukin 2 (n-2), interleukin 3 (IL3), IL5, granulocyte macrophage
colony stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF0) and rantes when
compared to both normal subjects and patients with other respiratory diseases (Azzawi'
Bradley et al. 1990; Ackerman, Marini er al. 1994; Humbert, Durham et al' 1996; Powell'
Humbert et al. 1996; Vrugt, Wilson et al. lggg). The presence of inflammation was confirmed
even in mild asthma @easley,
Burgess et al. 1993; Laitinen, Laitinen et al' 1996;
Grootendorst, Sont et al. t997; Laitinen, Karjalainen et al. 2000; ward, Reid et al' 2005) and
in patients during disease remission (Foresi, Bertorelli et al. 1990). A positive correlation with
each of these parameters to the severity of asthma has been demonstrated by some studies
(Beasley, Burgess et al. 1993; Carroll, cooke et al. 1997; Vrugt, wilson et al' 1999; Amin'
Ludviksdottir et al. 2000; Barnes, Burke et al. 2000; Benayoun, Druilhe et al' 2003)' In
addition, some markers more commonly associated with infective diseases, such as
interleukin g (ILg) and eotaxin, have also been demonstrated to be positively conelated with
asthma severity (Lamkhioued, Renzi et al. 1997; Pepe, Foley et al' 2005)' However' the
correlations of these markers with severity have not been unanimous @enayoun,
Druilhe et
al.2oI3;shahana, Bjornsson et al. 2005) and overall no unique inflammatory profile has been
demonstrated for all asthmatic patients (Kavuru, Dweik et al. 1999)'
In addition to the increase in inflammation demonstrated in asthma, there have also been
increases noted in the airway wall components. These include airway smooth muscle' mucus
glands, and submucosal and extra-cellular matrix tissue which have also been related to
symptom severity and bronchial hyper-responsiveness
(Saetta, Di Stefano et al' 1991; Chetta'
Foresi et al. 1997;Benayoun, Druilhe et al. 2003; chen, samson et al'20o4; Pepe' Foley et al'
2005). The presence of high numbers of fibroblasts has been the most consistent feature
demonstrated to relate to severity of disease and poor response to treatment (wenzel'
Schwartz et ar. lggg; Boulet, Turcotte et al. 2000). In the last decade, these findings have
taken on new importance as to their relevance to possible remodelling of the airway resulting
in irreversible changes occurring (Jeffery, Laitinen et al' 2000; wilson and Bamford 2001;
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