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membrane thickening) were present early in a study in children with an age range down to 1.2<br />

years (Pohunek, Warner et al. 2005) and did not show differences between those with few<br />

symptoms compared to those with persistent symptoms or 'difficult to control' asthma<br />

(cokugras, Akcakaya et al. 2001; Jenkins, cool et aL.2003; payne, Rogers et al.29613; de<br />

Blic, Tillie-kblond et al. 2004; Fedorov, Wilson et al. 2005). In addition, the findings were<br />

not associated with age, length <strong>of</strong> symptoms, lung function or bronchial reactivity (payne,<br />

Rogers et al. 2003). Bronchial wall thickening on high resolution computerized tomography<br />

(HRCT) scan was shown to correlate with eosinophils numbers, ECp and sub-basement<br />

membrane thickening (de Blic, Tillie-Irblond et al. 2005).<br />

1.6.3 studies <strong>of</strong> inflammation using bronchoalveolar lavage<br />

In adults the standard bronchoscope wedges between the 4th and 6ft order bronchus<br />

(Hunninghake, Gadek et al. 1979) typically localising a lung zone with 106 alveoli or a<br />

volume <strong>of</strong> l65ml at total lung capacity and 45ml at residual volume. In the 1960s, two studies<br />

initially started using catheters to do small volume bronchopulmonary lavage for assessment<br />

<strong>of</strong> disease @nley, Swenson et al. 1967; pratt, Finley et al. 1969). standard guidelines for<br />

clinical, diagnostic and research practices have been developed for use in adults (Klech and<br />

Pohl 1989; American Thoracic Society 1990; Rennard, Aalbers et al. 1998; Reynolds 2000),<br />

and more recently for use in children (ERS 2000; Midulla, de Blic et al. 2003). Lavage studies<br />

have confirmed many <strong>of</strong> the biopsy study findings in asthmatics when compared to normal<br />

subjects. Increases are seen in eosinophils, T-lymphocytes, eosinophilic proteins and<br />

cytokines such as n-4,L5, rantes and chemo-attractant factors with excellent recent reviews<br />

detailing these findings (Barrios, Kheradmand et aL.2006; Graham 2006: Tulic and Hamid<br />

2006). An antigenic or exercise challenge resulted in an observed increase in eosinophils<br />

(Kirby, Hargreave et al. 1987; Wardlaw, Dunnette et al. 1988; Bousquet, Van Vyve et al.<br />

1993; Krug, Tschernig et al. 2001), T cell lymphocytes (Virchow, Walker et al. 1995;<br />

Schuster, Tschernig et al. 2000), mast cells (Kirby, Hargreave et al. 1987; Bousquet, Van<br />

Vyve et al. 1993; Olsson, Rak et al. 2000), basophils and neutrophils (Kirby, Hargreave et al.<br />

1987; Mattoli, Mattoso et al. 1991; Bousquet, Van Vyve et al. 1993), complement factors<br />

C3A and C5 (Krug, Erpenbeck et al. 2001) and eosinophilic proteins (Wardlaw, Dunnette et<br />

al. 1988).<br />

Many more proteins can be measured in lavage fluid and this can demonstrat e the effect <strong>of</strong><br />

cells' even if the latter are not as visible. For example, mast cells account for up to 20Vo <strong>of</strong> the<br />

inflammatory cells and basophils are also prominent in biopsy studies, but both are only a<br />

29

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