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sensitive and to have good negative predictive value in getting a response in asthmatics who
have recent or current symptoms. This comes at the cost of being less specific and having less
positive predictive value or being useful for population screening for asthma (Cockcroft,
Murdock et al. 1992). As part of the ECRHS, bronchial hyper-reactivity using standardised
methacholine challenges was tested in over 13,000 adult subjects in 35 centres from 16
countries showing considerable variation in incidence (Chinn, Burney et al. 1997). In some
this mirrored their known rates of asthma disease, such as being high in New Zealand, Great
Britain, Australia and the USA, and low in Iceland and Switzerland. There was less of an
obvious connection in others, for example showing high rates of hyper-reactivity in Denmark
which has far lower documented asthma prevalence than, for example, Italy, Spain or Sweden
which all had low reactivity rates. In an early study of 307 adults, bronchial reactivity was
noted in 3Vo of normal subjects, l00vo of symptomatic asthmatics, 69Vo of currently
asymptomatic asthmatics (Cockcroft, Killian et al. 1977). In other studies, the proportion of
individuals with bronchial hyper-responsiveness was only about 40-60Vo of those reporting
current wheeze (Backer, Dirksen et al. 1991; Backer, Groth et al. l99l; Backer and Ulrik
1992; GINA 2005).
As well as some 'normals' responding in what is deemed the asthmatic range (Cockcroft,
Killian et al. 1977; Cockcroft, Murdock et al. 1992). the direct airway challenges are also non-
specific, as subjects with other respiratory diseases also react, most notably cough (Brooke,
Lambert et al. 1998), chronic obstructive pulmonary disease (COPD) and/or chronic
bronchitis (CB) (Ramsdell, Nachtwey et al. 1982; Ramsdale, Roberts et al. 1985; Calverley,
Burge et al. 2003).
Direct airway challenges in children are limited to older age groups. In over 2000 children
aged 7-10 years tested with a cumulative dose of 3.9;rmol of histamine, only 5BVo of the
children with asthma and current symptoms responded. While 52Vo of those diagnosed with
asthma responded overall, 53Vo of subjects demonstrating bronchial hyperactivity had no
asthma diagnosis (Pattemore, Asher et al. 1990). In three regions with similar asthma
admissions (Auckland, inland New South Wales and coastal New South Wales) between 700
to over l'000 children were tested at each centre and while two groups had similar rates of
bronchial hyper-reactivity to methacholine challenges, the third had a much lower rate (Asher,
Pattemore et al. 1988). The hyper-reactivity to direct airway challenge has a similar sensitivity
and specificity profile for asthma diagnosis as questionnaire data (Asher, pattemore et al.
1988; Backer, Dirksen et al. I99l; Bakke, Baste et al. l99l; Backer and LJlrik 1992; Joos,
O'Connor et al. 2003). In one of these studies, the level of bronchial hyper-reactivity was a
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