View - ResearchSpace@Auckland - The University of Auckland

Black and Johnson 2002; Jeffery 2004; Kariyawasam and Robinson 2005: ward and walters
2005). This airway remodelling in asthma has been found in both large and small airways
(Saetta, Di Stefano et al. l99l; James, Maxwell et al. 2OO2) and the changes are the same
regardless of the asthma being atopic, occupational or intrinsic (Homer and Elias 2000). The
inner wall components include loss of epithelial integrity (Naylor 1962; Laitinen, Heino et al.
1985; Jeffery, Wardlaw et al. 1989) and hyperplasia of the globlet cells in the sub-epithelium
(Aikawa, Shimura et al. 1992: Ordonez, Khashayar et al. 2001). While rhickening of the
basement membrane was also described in the original autopsy and other studies above, it
now appears that the true basement membrane (the 'lamina rare' and 'lamina densa') is not
grossly altered (Roche, Beasley et al. 1989; Homer and Elias 2000) with the actual fibril
content of the membrane found to be similar in asthmatic and control groups (Saglani,
Molyneux et al. 2006). It is the area that sits immediately below the true basement membrane,
'the lamina reticularis' that is increased and this has been termed 'subepithelial fibrosis' or
'reticular or sub-basement membrane thickening' (Boulet, Laviolette et al. 1997;Elias, Zhu et
al. 1999; Beckett and Howarth 2OO3). Here, enhanced collagen deposition has been
demonstrated with subtypes I, III and IV, fibronectin, tenascin, Iumican and biglycan @oche,
Beasley et al. 1989; Laitinen, Laitinen et al. 1996; Laitinen, Altraja et al. 1997;Wilson and Li
1997 Huang, Olivenstein et al. t999; Benayoun, Druilhe et al. 2003; Karjalainen, Lindqvist
et al. 2O03). Myofibroblasts are specialized cells that have features of both myocytes and
fibroblasts and are sources of interstitial collagens so are likely contributing to this deposition
(Homer and Elias 2000). Myofibroblast number has been demonstrated to correlate directly to
the thickness of this layer (Brewster, Howarth et al. 1990; Hoshino, Nakamura et al. l99g).
However, it is the increased thickness of the smooth muscle layer that contributes most to the
overall thickness of the airway. This has variably been described as due to hypertrophy and/or
hyperplasia (Hossain 1973; Ebina, Takahashi et al. 1993; Cho, Seo et al. 1996;James lggT).
The smooth muscle contraction has been shown to particularly narrow the airway where the
entire lumen is surrounded as in the smaller bronchi prior to respiratory bronchioles. This is
consistent with computer modeling of ainvay function, showing that the smaller airways are
the site of the greatest increase in airway resistance in asthma (Hogg lggT). Finally, changes
have also been described in the airway vasculature with an increase in both size and number
of vessels and this angiogenesis also contributes to airway oedema seen (Li and Wilson 1997;
Tanaka, Yamada et al.20O3). Given the variable nature of the findings it is difficult to show
the exact nature of the progression, and this is the subject of ongoing research (Boulet 2000).
27