Fluctuation Analysis of Peak Expiratory Flow and Its Association with Treatment Failure in Asthma.
BACKGROUND
Temporal fluctuations have been demonstrated in lung function and asthma control, but the effect of controller therapy on these fluctuations is unknown.


OBJECTIVE
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).


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.
1 Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, Vermont.
David A
DA
Kaminsky
2 Department of Biomedical Informatics and Medical Education, University of Washington School of Medicine, Seattle, Washington.
Lucy L
LL
Wang
1 Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, Vermont.
Jason H T
JH
Bates
3 Woolcock Institute of Medical Research, Syndey, New South Wales, Australia.
Cindy
C
Thamrin
4 Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland; and.
David M
DM
Shade
1 Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, Vermont.
Anne E
AE
Dixon
4 Pulmonary and Critical Care, Johns Hopkins University, Baltimore, Maryland; and.
Robert A
RA
Wise
5 Pulmonary and Critical Care Wake Forest School of Medicine, Winston-Salem, North Carolina.
Stephen
S
Peters
1 Pulmonary and Critical Care, University of Vermont College of Medicine, Burlington, Vermont.
Charles G
CG
Irvin
D000085:Acetates / Q000494:pharmacology*; D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D000068299:Salmeterol Xinafoate / Q000494:pharmacology*; D013440:Sulfides; D017211:Treatment Failure
D000085:Acetates; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; C093875:montelukast
asthma; fluctuation analysis; lung function variability; peak expiratory flow; treatment failure