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et al. 1999; Giannini, Di Franco et al. 2000; Jatakanon, Lim et al. 2000; Green, Brightling et<br />

al. 2002). <strong>The</strong> results seen across all the studies suggest that the inflammation measured in<br />

this way reflects current asthma control rather than grading chronicity or severity per se.<br />

As indicated in the biopsy and lavage studies above, increased neutrophil counts may also be<br />

a marker for poorly responsive disease. In severe asthmatics, there were more neutrophils and<br />

less eosinophils compared to mild asthmatics (Loh, Kanabar et al. 2005) and neutrophilic<br />

inflammation was dominant in the minority <strong>of</strong> subjects from over 250 adult asthmatics who<br />

demonstrated less corticosteroid response (Green, Brightling et al. 2002). Both eosinophilic<br />

inflammation and neutrophilic inflammation were found to independently contribute to<br />

abnormalities <strong>of</strong> FEVr in 205 adult asthmatics (Woodrufl Khashayar et d. 2001). Treating<br />

the neutrophil count resulted in better control than monitoring lung function or symptoms<br />

(Chlumsky, Striz et al.20O6). Neutrophils were also increased acutely, making up more than<br />

757o <strong>of</strong> the sputum cells in 10 <strong>of</strong> 18 adult subjects during acute asthma while eosinophils<br />

made up more thanT1Vo <strong>of</strong> the cells in only three subjects (Fahy, Kim et al. 1995).<br />

1.6.4 (ii) Induced sputum in children<br />

Sputum induction in children developed more recently and therefore in some <strong>of</strong> the studies<br />

from the 2000s it has been combined with NO measurement. As this will be covered in depth<br />

in later parts <strong>of</strong> the thesis, I will only discuss the cell and cytokine inflammatory markers<br />

from induced sputum in this section. <strong>The</strong> technique has been used for getting bacterial, viral,<br />

fungal and tuberculosis cultures to determine infective aetiology (Merrick, Sepkowitz et al.<br />

L997; Utsunomiya, Ahmed et al. 1998; Ordonez, Henig et al. 2003; kiso, Mudido et al. 2005;<br />

Ratjen 2W6). Using induced sputum to assess inflammatory disease was first described in<br />

1980 when presence <strong>of</strong> an eosinophilia was used to diagnose co-existent asthma in children<br />

with CF was investigated (Sly and Hutchison 1980). In 1995 sputum and nasal smears taken<br />

from I 11 young children presenting acutely with wheeze showed increased eosinophils,<br />

neutrophils and basophils in those deemed 'asthmatic' compared to those who were wheezy<br />

but unresponsive to asthma treatment (Twaddell, Gibson et al. 1996). Increased eosinophils at<br />

3.8Vo and epithelial cells at tl.S%o were seen in 16 children with uncontrolled asthma<br />

compared to 15 with controlled asthma at 2.5Vo and lO.SVo and 72 healthy non-asthmatic<br />

children at0.3Vo and l.5Vo respectively (Cai, Carty et al. 1998). Mast cells, prominent in adult<br />

asthma studies, were found in only 4 <strong>of</strong> the 42 asthmatic children (Cai, Carty et al. 1998). An<br />

increase in eosinophil percentage and ECP was seen in 50 asthmatic children compared to<br />

fifteen children with chronic bronchitis (CB) and 25 healthy children (Yazicioglu, Ones et al.<br />

34

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