Classifying disease activity in
asthma relies on clinical and physiological variables, but these variables do not capture all aspects of
asthma that distinguish levels of disease activity. We used data from two pivotal trials of
montelukast in
asthma to classify disease activity as "high" or "low". We performed a principal component analysis (PCA) of disease activity using 21 efficacy outcome variables, including several novel derived outcome variables reflecting clinical and
airway obstruction lability. Then we performed discriminant analysis (DA) based on disease activity classification. PCA revealed 6 factors (daytime
asthma control, nighttime-predominant
asthma control, airway obstruction, exacerbations, clinical lability,
airway obstruction lability) that explained 76% of the variance between outcome variables. Although
airway obstruction lability (comprising both diurnal variability in peak expiratory flow and diurnal variability in β-agonist use) accounted for only 6% of the explained variance in PCA, in DA it was more accurate (canonical coefficient 0.75) than traditional measures of
asthma severity such as obstruction (-0.54) and daytime control (-0.56) in distinguishing between high and low disease activity. We conclude that
airway obstruction lability, a parameter not typically captured in clinical trials, may contribute to more complete assessment of
asthma disease activity and may define an emerging clinical target of future
therapy.