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<strong>The</strong> ability to biopsy has led to studies <strong>of</strong> the early (Gonzalez,Diaz et al. 1987; Georas, Liu et<br />

al. 1992) and late asthma reactions (Robertson, Kerigan et al. 1974; Crimi, Chiaramondia et<br />

al. 1991) and a comparison <strong>of</strong> both (Metzger, Richerson et al. 1986; Metzger, Richerson et al.<br />

1986; Aalbers, Kauffman et al. 1993) in response to deliberate allergy provocation. <strong>The</strong>se<br />

demonstrated an influx <strong>of</strong> neutrophils at 6-8 hours followed by an influx <strong>of</strong> eosinophils at24-<br />

48 hours which continued more than a week but seemed to resolve by day 16. An increase in<br />

the cellular expression <strong>of</strong> the mRNA <strong>of</strong> IL5 and GM-CSF occurred at 18 to 48 hours<br />

(Ohnishi, Sur et al. 1993; Tang, Rolland et al. 1997) with an increase in total proteins and<br />

ainvay permeability also in the late phase (Taylor, Hill et al.1996; Teeter and Bleecker 1996).<br />

In assessing response to treatment in asthmatic patients treated with moderate to high doses <strong>of</strong><br />

IHCS (400mcg to l600mcdday beclomethasone equivalent) for between two weeks and up 5-<br />

l0 years, most studies have reported a decrease in T-lymphocytes, eosinophils, and mast cell<br />

numbers in the airway wall (Lundgren, Soderberg et al. 1988; Burke, Power et al. 1992;<br />

Booth, Richmond et al. 1995; Djukanovic, Homeyard et al. 1997; Olivieri, Chetta et al. L997i<br />

Barnes, Burke et al. 2000). As well, decreased dendritic cell number @urke, Power et al.<br />

1992; Trigg, Manolitsas et al. 1994; Bentley, Hamid et al. 1996) and reduced inflammatory<br />

cell activation measured as less gmnule secretory production and less cell membrane<br />

activation markers have also been noted @entley, Hamid et al. 1996; Olivieri, Chetta et al.<br />

1997; Barnes, Burke et al. 2000; Ward, Reid et al. 2005). <strong>The</strong> expression <strong>of</strong> mRNA for nA,<br />

IL5 and GM-CSF within cells also decreased with steroid treatment (Sousa, Poston et al.<br />

1993; Bentley, Hamid et al. 1996). Interestingly, the effects have been more marked in the<br />

biopsy samples than the corresponding lavage studies (Booth, Richmond et al. 1995;<br />

Thompson, Teschler et al. 1996: Djukanovic, Homeyard et al. 1997; Olivieri, Chetta et al.<br />

1997). <strong>The</strong> effect <strong>of</strong> steroids on the thickness <strong>of</strong> the epithelium and basement membrane have<br />

been less conclusive; some studies showing improvement (Olivieri, Chetta et al. 1997; Ward<br />

and Walters 2005) that has not been demonstrated in others even after years <strong>of</strong> treatment<br />

(Lundgren, Soderberg et al. 1988; Wenzel, Szefler et al. 1997; Wenzel, Schwartz et al. 1999;<br />

Barnes, Burke et al. 2000).<br />

Paediatric studies have been more recent, in keeping with the later technical bronchoscopy<br />

development and the additional concerns regarding safety in this group. <strong>The</strong>se have shown<br />

similar findings to the adult asthma studies with eosinophilic and lymphocytic inflammation,<br />

and an increase in the same cytokines (interleukin 4 (IL+), IL5, rantes) (de Blic, Tillie-<br />

Irblond et al. 2OO4; Payne, Qiu et al. 2O04; Pohunek, Warner et al. 2005). <strong>The</strong> findings<br />

associated with airway remodeling (smooth muscle hypertrophy and reticular basement<br />

28

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