Respiratory Medicine
Volume 106, Issue 4 , Pages 500-507, April 2012

Airway obstruction lability helps distinguish levels of disease activity in asthma

  • Steven Greenberg

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
    • Department of Medicine, Columbia University, 630 West 168th St., New York, NY 10032, USA
    • Corresponding Author InformationCorresponding author. Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA. Tel.: +1 908 740 7306; fax: +1 908 740 2169.
  • ,
  • Nancy Liu

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
  • ,
  • Amarjot Kaur

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
  • ,
  • Mani Lakshminarayanan

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
  • ,
  • Yijie Zhou

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
  • ,
  • Linda M. Nelsen

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
  • ,
  • Steven S. Smugar

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
  • ,
  • Gertrude Noonan

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
  • ,
  • Theodore F. Reiss

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA
    • Current address: Allergy, Pulmonary and Critical Care Division, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • ,
  • Barbara A. Knorr

      Affiliations

    • Merck Sharp & Dohme Corp., 1 Merck Drive, Whitehouse Station, NJ 08889, USA

Received 12 July 2011; accepted 19 December 2011. published online 02 February 2012.

Summary 

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.

Keywords: Asthma, Airway obstruction lability, Diurnal variability, Discriminant analysis, Outcome variables

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PII: S0954-6111(12)00023-6

doi:10.1016/j.rmed.2011.12.013

Respiratory Medicine
Volume 106, Issue 4 , Pages 500-507, April 2012