Risk of severe asthma episodes predicted from fluctuation analysis of airway function.
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.
Frey
Urs
U
Paediatric Respiratory Medicine, Department of Paediatrics, University Hospital of Berne, Inselspital 3010 Berne, Switzerland. urs.frey@insel.ch
Brodbeck
Tanja
T
Majumdar
Arnab
A
Taylor
D Robin
DR
Town
G Ian
GI
Silverman
Michael
M
Suki
Béla
B
D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D011336:Probability; D011897:Random Allocation; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology*; D012306:Risk; D000068299:Salmeterol Xinafoate; D013269:Stochastic Processes
D001993:Bronchodilator Agents; D010919:Placebos; D000068299:Salmeterol Xinafoate; D000420:Albuterol