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led to research which looked for less invasive methods <strong>of</strong> assessing the inflammatory<br />

component <strong>of</strong> asthma and bronchoalveolar lavage and this led to the development <strong>of</strong> the<br />

ability to induce sputum using nebulised hypertonic saline. <strong>The</strong>se samples allowed increasing<br />

measurement not only <strong>of</strong> the cellular component, but also <strong>of</strong> the proteins that formed the<br />

asthmatic inflammation. <strong>The</strong>se measurements could be done repeatedly so parameters were<br />

followed longitudinally to determine what happened during acute exacerbations <strong>of</strong> asthma, in<br />

response to treatment and over longer periods <strong>of</strong> time during chronic asthma. Studies were<br />

also undertaken using blood and urine samples. In the main there has been a recognition that<br />

the majority <strong>of</strong> asthma and other allergic diseases have an increased allergic inflammatory<br />

pr<strong>of</strong>ile with an eosiniphilic dominant pattern, raised levels <strong>of</strong> eosinophilic proteins @CP,<br />

EPO, EDN and MBP), and cytokines (IL3, nA,n-5, rantes). While over the last decades this<br />

was thought to be an imbalance between T lymphocyte classes, between the T helper type 2<br />

(Ts2) and T helper type I (Tnl), (Colavita, Reinach et al. 2000; Holgate, Davies et al. 2000;<br />

Busse and Irmanske 2001; Peters 2003), very recently it has been thought there may be<br />

upregulation <strong>of</strong> both classes with a third type, the T lymphocyte regulatory cells playing a<br />

pivotal role (Lazarus, Raby et al.2004; Goldman 2007). Certainly some asthma is known to<br />

have a neutrophil dominant or neutrophil present pattern, with the markers more commonly<br />

associated with infective conditions. This is seen more <strong>of</strong>ten in severe persistent asthma<br />

(Wenzel, Szefler et al. 1997i Jatakanon, Uasuf et al. 1999), associated with a poor response to<br />

treatment (McDougall and Helms 2006; Wenzel 2006), has been demonstrated in some acute<br />

exacerbations (Martin, Cicutto et al. 1991; Fahy, Kim et al. 1995; Ordonez, Shaughnessy et<br />

al. 2000), and in sudden fatal asthma (Sur, Crotty et al. 1993). While the eosinophils and<br />

neutrophils themselves and the proteins they release have shown the best association with<br />

asthma exacerbations and response to treatment - neither have been completely consistent. In<br />

addition, obtaining the appropriate samples can be difficult.<br />

So, while contributing enonnously to our understanding <strong>of</strong> asthma, the use <strong>of</strong> bronchoscopy,<br />

biopsy and BAL, induced sputum, blood and urine testing all have their disadvantages,<br />

particularly when assessing disease in children. <strong>The</strong> first three options remain invasive,<br />

require anaesthesia in children and are associated with risks and side effects, especially in<br />

children with respiratory disease, and therefore cannot be done frequently. <strong>The</strong>y also require<br />

specialised personnel in terms <strong>of</strong> theatre and bronchoscopy staff. Induced sputum results in<br />

less satisfactory sample success in children than in adults, although successful samples can be<br />

obtained in up to 757o <strong>of</strong> control children. It also can be associated with side effects, as<br />

nebulised hypertonic saline is also used as an airway challenge. This test also requires<br />

46

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