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poorer predictor of a diagnosis of asthma than responses to the question 'has your child had
wheezing in the past 12 months' on written questionnaires @attemore, Asher et al. 1990). In
495 children aged 7-16 years, the subjects with asthma represented a subgroup within the
responsive end when inhaling increasing concentrations of histamine rather than the asthma
and the 'normals' having separate distribution peaks. Selecting a low dose of 2.4mglrnl-r as
the cut off point gave a specificity of 98Vo for asthma, but a positive predictive value of only
6OVo and a sensitivity of only 57Vo (Backer, Groth et al. l99l).
Using indirect challenges is a more recent phenomenon from the late 1980s and eady 1990s
(Manning, Watson et al. 1993; Joos, O'Connor et al. 2003). These are termed indirect as the
triggers act on cells, which then release mediators or cytokines to cause a secondary
bronchoconstriction and airflow limitation. They include physical stimuli such as exercise,
osmotic stimuli such as hypertonic saline or mannitol, or pharmacological stimuli such as
adenosine or bradykinin. These challenges are thought to be a better reflection of the active
airway inflammation as observed in asthma (Joos, O'Connor et al. 2003). Also IHCS reduce
responsiveness to these indirect challenges, as in asthma, while in contrast they only have a
small effect on histamine and methacholine challenges. The indirect challenges have
demonstrated less sensitivity but more specificity in differentiating asthmatics from 'normals'
(Vasar, Braback et al. 1996; Godfrey, Springer et al. 1999; Joos, O'Connor et al. 2003). In
addition in children, an exercise challenge has also been shown to be better at distinguishing
asthma from other chronic airway disorders such as CF, bronchiolitis obliterans, ciliary
dyskinesia and bronchiectasis (Avital, Springer et al. 1995; Godfrey, Springer et al. 1999).
There is a statistical, albeit weak, correlation between the methods; however there are
individuals who have positive exercise challenges and negative histamine or methacholine
challenges. A hypertonic saline challenge in adults has been shown to identify exercise
induced asthma (Belcher, I-ee et al. 1989; Boulet, Turcotte et al. 1989; Smith and Anderson
1990; Brannan, Koskela et al. 1998). The possibility of having exercise induced asthma and
not responding to hypertonic saline or mannitol challenges occurs, but only in those with very
mild asthma @rannan, Koskela et al. 1998). In children, those with a history of current
wheeze were seven times more likely to have a positive response to hypertonic saline than
asymptomatic children (Riedler, Reade et al. 1994). However the use of osmotic challenges to
date have been seen more frequently as a treatment to improve mucociliary clearance and
lung function, predominantly in children with CF (Eng, Morton et al. 1996; Rodwell and
Anderson 1996; Robinson, Daviskas et al. 1999).
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