Risk of severe asthma episodes predicted from fluctuation analysis of airway function

Nature. 2005 Dec 1;438(7068):667-70. doi: 10.1038/nature04176.


Asthma is an increasing health problem worldwide, but the long-term temporal pattern of clinical symptoms is not understood and predicting asthma episodes is not generally possible. We analyse the time series of peak expiratory flows, a standard measurement of airway function that has been assessed twice daily in a large asthmatic population during a long-term crossover clinical trial. Here we introduce an approach to predict the risk of worsening airflow obstruction by calculating the conditional probability that, given the current airway condition, a severe obstruction will occur within 30 days. We find that, compared with a placebo, a regular long-acting bronchodilator (salmeterol) that is widely used to improve asthma control decreases the risk of airway obstruction. Unexpectedly, however, a regular short-acting beta2-agonist bronchodilator (albuterol) increases this risk. Furthermore, we find that the time series of peak expiratory flows show long-range correlations that change significantly with disease severity, approaching a random process with increased variability in the most severe cases. Using a nonlinear stochastic model, we show that both the increased variability and the loss of correlations augment the risk of unstable airway function. The characterization of fluctuations in airway function provides a quantitative basis for objective risk prediction of asthma episodes and for evaluating the effectiveness of therapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Albuterol / administration & dosage
  • Albuterol / analogs & derivatives
  • Albuterol / pharmacology
  • Albuterol / therapeutic use
  • Asthma / drug therapy
  • Asthma / physiopathology*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacology
  • Bronchodilator Agents / therapeutic use
  • Humans
  • Middle Aged
  • Placebos
  • Probability
  • Random Allocation
  • Respiratory System / drug effects
  • Respiratory System / physiopathology*
  • Risk
  • Salmeterol Xinafoate
  • Stochastic Processes


  • Bronchodilator Agents
  • Placebos
  • Salmeterol Xinafoate
  • Albuterol