Fluctuation Analysis of Peak Expiratory Flow and Its Association with Treatment Failure in Asthma

Am J Respir Crit Care Med. 2017 Apr 15;195(8):993-999. doi: 10.1164/rccm.201601-0076OC.


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.

Keywords: asthma; fluctuation analysis; lung function variability; peak expiratory flow; treatment failure.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetates / pharmacology*
  • Administration, Inhalation
  • Adult
  • Anti-Asthmatic Agents / pharmacology*
  • Asthma / drug therapy*
  • Bronchodilator Agents / pharmacology*
  • Drug Therapy, Combination
  • Female
  • Fluticasone / pharmacology*
  • Humans
  • Male
  • Peak Expiratory Flow Rate / drug effects
  • Quinolines / pharmacology*
  • Salmeterol Xinafoate / pharmacology*
  • Treatment Failure


  • Acetates
  • Anti-Asthmatic Agents
  • Bronchodilator Agents
  • Quinolines
  • Salmeterol Xinafoate
  • Fluticasone
  • montelukast