Asthma and lower airway disease
Predicting future risk of asthma exacerbations using individual conditional probabilities

https://doi.org/10.1016/j.jaci.2011.01.018Get rights and content

Background

Determination of future risk of exacerbations is a key issue in the management of asthma. We previously developed a method to calculate conditional probabilities (π) of future decreases in lung function by using the daily fluctuations in peak expiratory flow (PEF).

Objective

We aimed to extend calculation of π values to individual patients, validated by using electronically recorded data from 2 past clinical trials.

Methods

Twice-daily PEF data were analyzed from 78 patients with severe (study A) and 61 patients with poorly controlled (study B) asthma. For each patient, the π value was calculated from 5000 PEF data points simulated based on the correlation and distribution properties of observed PEF. Given an initial PEF, the π value was defined as the probability of a decrease in PEF to less than 80% of predicted value on 2 consecutive days within a month. These probabilities were then compared with actual occurrences of such events and clinically defined exacerbations within the following month.

Results

π Values were related to actual occurrences of decreases in PEF (adjusted R2 > 0.800 for both studies). Every increase of 10% in π value was associated with an odds ratio of having a future exacerbation of 1.24 (95% CI, 1.07-1.43) for study A and 1.13 (95% CI, 1.02-1.26) for study B, with better sensitivity and specificity than clinic-measured FEV1.

Conclusion

These results from 2 independent datasets with differing asthmatic populations and differing exacerbation criteria provide support that clinically relevant quantification of individual future risk of exacerbations is possible.

Section snippets

Methods

The following represents a summarized version of the methodology. Detailed methods can be found in this article’s Online Repository at www.jacionline.org.

Results

Subjects’ demographics and baseline characteristics can be found in Table II. In summary, 35 of 78 patients in study A (with severe persistent asthma uncontrolled by high-dose inhaled [± oral] corticosteroid and long-acting β2-agonist treatment) and 34 of 61 patients in study B (with uncontrolled asthma and not necessarily taking any inhaled corticosteroids at entry [maximum dose, 1200 μg/d]) had sufficient data for analysis satisfying the quality control criterion.

The mean ± SD number of

Summary of results

We found good association between our novel method (ICP) of quantifying individual risk of future exacerbation and the number of actual events of a decrease in PEF based on data from 2 different populations of asthmatic patients studied by using 2 different time windows of observation and 2 different thresholds for defining a PEF decrease. The probabilities calculated by using this method were also well associated with whether future decreases in PEF and clinically defined exacerbations

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    C.T. was funded by a Allen & Hanburys/Thoracic Society of Australia and New Zealand Respiratory Research Fellowship. R.A.W. and S.F. are employed by Johnson & Johnson. Centocor R&D, a fully-owned subsidiary of Johnson & Johnson, is the owner of the dataset of study A, whereas AstraZeneca Pty Ltd is the owner of the dataset study B. R.A.W. and S.F. assisted with interpretation of the original datasets but did not influence the aims and analyses of this study.

    Disclosure of potential conflict of interest: P. Chanez has consultant arrangements with AstraZeneca and Centocor, and receives grant support from Centocor. S. E. Wenzel has had consultant arrangements with Centocor and has received research support from Centocor. H. K. Reddel has participated on advisory boards for, received speaker's honoraria, and received research funding from AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

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