Airway obstruction lability helps distinguish levels of disease activity in asthma.
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.
Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA. steven_greenberg@merck.com
Steven
S
Greenberg
Nancy
N
Liu
Amarjot
A
Kaur
Mani
M
Lakshminarayanan
Yijie
Y
Zhou
Linda M
LM
Nelsen
Steven S
SS
Smugar
Gertrude
G
Noonan
Theodore F
TF
Reiss
Barbara A
BA
Knorr
D000085:Acetates / Q000627:therapeutic use*; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000502:physiology; D017326:Clinical Trials, Phase III as Topic; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D013440:Sulfides; D016896:Treatment Outcome; D055815:Young Adult
D000085:Acetates; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D001507:Beclomethasone; C093875:montelukast