David A Kaminsky1, Lucy L Wang2, Jason H T Bates1, Cindy Thamrin3, David M Shade4, Anne E Dixon1, Robert A Wise4, Stephen Peters5, Charles G Irvin1. 1. 1 Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, Vermont. 2. 2 Department of Biomedical Informatics and Medical Education, University of Washington School of Medicine, Seattle, Washington. 3. 3 Woolcock Institute of Medical Research, Syndey, New South Wales, Australia. 4. 4 Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland; and. 5. 5 Pulmonary and Critical Care Wake Forest School of Medicine, Winston-Salem, North Carolina.
Abstract
RATIONALE: Temporal fluctuations have been demonstrated in lung function and asthma control, but the effect of controller therapy on these fluctuations is unknown. OBJECTIVES: To determine if fluctuations in peak expiratory flow (PEF) are predictive of subsequent treatment failure and may be modified by controller therapy. METHODS: We applied detrended fluctuation analysis to once-daily PEF data from 493 participants in theLOCCS (Leukotriene Modifier Corticosteroid or Corticosteroid-Salmeterol) trial of the American Lung Association Airways Clinical Research Centers. We evaluated the coefficient of variation of PEF (CVpef) and the scaling exponent α, reflecting self-similarity of PEF, in relation to treatment failure from the run-in period of open-label inhaled fluticasone, and the treatment periods for subjects randomized to (1) continued twice daily fluticasone (F), (2) once daily fluticasone plus salmeterol (F + S), or (3) once daily oral montelukast (M). MEASUREMENTS AND MAIN RESULTS: The CVpef was higher in those with treatment failure in the F and F + S groups in the run-in phase, and all three groups in the treatment phase. α was similar between those with and without treatment failure in all three groups during the run-in phase but was higher among those with treatment failure in the F and F + S groups during the treatment phase. Participants in all three groups showed variable patterns of change in α leading up to treatment failure. CONCLUSIONS: We conclude that increased temporal self-similarity (α) of more variable lung function (CVpef) is associated with treatment failure, but the pattern of change in self-similarity leading up to treatment failure is variable across individuals.
RCT Entities:
RATIONALE: Temporal fluctuations have been demonstrated in lung function and asthma control, but the effect of controller therapy on these fluctuations is unknown. OBJECTIVES: To determine if fluctuations in peak expiratory flow (PEF) are predictive of subsequent treatment failure and may be modified by controller therapy. METHODS: We applied detrended fluctuation analysis to once-daily PEF data from 493 participants in the LOCCS (Leukotriene Modifier Corticosteroid or Corticosteroid-Salmeterol) trial of the American Lung Association Airways Clinical Research Centers. We evaluated the coefficient of variation of PEF (CVpef) and the scaling exponent α, reflecting self-similarity of PEF, in relation to treatment failure from the run-in period of open-label inhaled fluticasone, and the treatment periods for subjects randomized to (1) continued twice daily fluticasone (F), (2) once daily fluticasone plus salmeterol (F + S), or (3) once daily oral montelukast (M). MEASUREMENTS AND MAIN RESULTS: The CVpef was higher in those with treatment failure in the F and F + S groups in the run-in phase, and all three groups in the treatment phase. α was similar between those with and without treatment failure in all three groups during the run-in phase but was higher among those with treatment failure in the F and F + S groups during the treatment phase. Participants in all three groups showed variable patterns of change in α leading up to treatment failure. CONCLUSIONS: We conclude that increased temporal self-similarity (α) of more variable lung function (CVpef) is associated with treatment failure, but the pattern of change in self-similarity leading up to treatment failure is variable across individuals.
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