Asthma and lower airway disease
Development and validation of a novel risk score for asthma exacerbations: The risk score for exacerbations

https://doi.org/10.1016/j.jaci.2014.08.015Get rights and content

Background

Identifying patients at risk of future severe asthma exacerbations, those whose asthma might be less treatment responsive, or both might guide treatment selection.

Objective

We sought to investigate predictors for failure to achieve Global Initiative for Asthma (GINA)–defined good current asthma control and severe exacerbations on treatment and to develop a simple risk score for exacerbations (RSE) for clinical use.

Methods

A large data set from 3 studies comparing budesonide/formoterol maintenance and reliever therapy with fixed-dose inhaled corticosteroid/long-acting β2-agonist therapy was analyzed. Baseline patient characteristics were investigated to determine dominant predictors for uncontrolled asthma at 3 months and for severe asthma exacerbations within 12 months of commencing treatment. The RSE, right censored at 6 months to include all 3 studies, was based on the dominant predictors for exacerbations in two thirds of the data set and validated in one third.

Results

Patients (n = 7446) whose symptoms were not controlled on GINA treatment steps 3 and 4 and with 1 or more exacerbations (as judged by a clinician based on patient records, history, or both) in the previous year were included. On multivariate analysis, GINA step, reliever use, postbronchodilator FEV1, and 5-item Asthma Control Questionnaire score were dominant (all P < .001) predictors for both the risk of uncontrolled asthma and severe exacerbations. Additional dominant predictors for uncontrolled asthma were smoking status and asthma symptom scores and an additional predictor for severe exacerbation was body mass index. An exponential increase in risk was observed with increments in RSE based on 5 selected predictors for exacerbations.

Conclusion

Risk of uncontrolled asthma at 3 months and a severe exacerbation within 12 months can be estimated from simple clinical assessments. Prospective validation of these predictive factors and the RSE is required. Use of these models might guide the management of asthmatic patients.

Section snippets

Studies

This retrospective analysis included data from 3 double-blind, randomized, parallel-group clinical studies15, 16, 17 of 6 or 12 months' duration for which several candidate predictors were available. The detailed methodologies of the studies are summarized in Table E1 in this article's Online Repository at www.jacionline.org. The studies investigated the efficacy of BUD/FORM MRT compared with the following fixed-dose comparator therapies: (1) the same maintenance dose of inhaled corticosteroid

Study populations and baseline demographics

Demographic and baseline data were similar between the 2 treatment groups (BUD/FORM MRT, n = 3172; fixed-dose ICS/LABA, n = 4274); mean age was 39.5 years, 59% were female, mean time since asthma diagnosis was 14.6 years, and 79% of patients had never smoked. The mean prebronchodilator FEV1 was 72.0%, and the mean ACQ-5 score at randomization was 1.9 (Table I).

Predictors for uncontrolled asthma after 3 months

The univariate analysis of baseline predictors for the risk of uncontrolled asthma at 3 months showed that 8 of the 16 baseline

Discussion

In this analysis of data pooled from several similarly designed studies, we have identified clinical factors that are associated with not achieving a satisfactory level of current asthma control (defined by GINA as uncontrolled asthma). Similarly, we have identified clinical factors associated with increased risk for severe exacerbations requiring treatment with oral corticosteroids, emergency department treatment/hospitalization, or both. By examining factors associated with increased risk of

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    The analysis was sponsored by AstraZeneca. E.D.B. has served as a consultant to ALK-Abelló, Almirall, Cephalon, Hoffman La Roche, ICON, and MS Consulting Group; been involved with advisory boards for Almirall, AstraZeneca, Boehringer Ingelheim, Elevation Pharma, Forest, GlaxoSmithKline, Merck, Napp, Novartis, and Nycomed; and received lecture fees from ALK-Abelló, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Takeda; his institution has received remuneration for participation in clinical trials sponsored by Actelion, Aeras, Almirall, AstraZeneca, Boehringer Ingelheim, Forest, GlaxoSmithKline, Hoffman La Roche, Merck, Novartis, Takeda, and TEVA. S.P. and G.E. were employees of AstraZeneca at the time this analysis was conducted. The analysis was funded by AstraZeneca AB, Mölndal, Sweden.

    Disclosure of potential conflict of interest: E. D. Bateman has received consulting fees from AstraZeneca for participation in a working group that performed analyses of databases that led to this paper; has received compensation for board membership from Almirall, AstraZeneca, Boehringer Ingelheim, Elevation Pharma, Forest, GlaxoSmithKline, Merck, Napp, Novartis, and Nycomed; has received consultancy fees from ALK-Abelló, Almirall, Cephalon, ICON, and MS Consulting Group; has received or has grants pending from Actelion, Aeras, Almirall, AstraZeneca, Boehringer Ingelheim, Forest, GlaxoSmithKline, Roche/Genentech, Merck, Novartis, Takeda, TEVA, and Cephalon; and has received payment for delivering lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, and Takeda, as well as from Novartis for the development of education presentations. R. Buhl has received compensation for board membership from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, and Roche; has received or has grants pending from Boehringer Ingelheim, Novartis, and Roche; and has received compensation for delivering lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, Grifols, GlaxoSmithKline, Novartis, Roche, and Takeda. P. M. O'Byrne has received compensation for board membership from the Joint Oversight Board for an LABA safety study, and has received consultancy fees from AstraZeneca, GlaxoSmithKline, Merck, Boehringer, and Novartis and has received or has grants pending from AstraZeneca, Amgen, Genentech, Axikin, and Novartis. M. Humbert has received consultancy fees from AstraZeneca, GlaxoSmithKline, TEVA, Novartis, and Roche. H. K. Reddel has received consultancy fees from AstraZeneca for a face-to-face meeting at which this manuscript and other studies were discussed; has received compensation for board membership from AstraZeneca, GlaxoSmithKline, Merck, and Novartis; has received consultancy fees from AstraZeneca, Mundipharma, and Novartis; has received or has grants pending from GlaxoSmithKline and AstraZeneca; and has received payment for delivering lectures from AstraZeneca, GlaxoSmithKline, and Novartis. C. Jenkins has received consultancy fees from AstraZeneca, as well as support for travel and other meeting-related expenses; has received compensation for board membership from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Novartis, and Mundipharma; has also received consultancy fees from GlaxoSmithKline, Boehringer Ingelheim, Novartis, and Mundipharma; has received payment for delivering lectures from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Novartis, and Mundipharma and payment for the development of educational presentations from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Novartis, Mundipharma; and has also been paid an hourly rate for face-to-face individual consultations and for offering advice on regulatory issues for airways disease medications from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Novartis, and Mundipharma. T. W. Harrison has received compensation for being a member of the NAPP advisory board; his institution has received or has grants pending from AstraZeneca; he has received payment from AstraZeneca, GlaxoSmithKline, and Chiesi for delivering lectures; and he has received compensation for travel and other meeting-related expenses from Boehringer Ingelheim. S. Quirce has received payment for delivering lectures from GlaxoSmithKline, AstraZeneca, Chiesi, Boehringer Ingelheim, and MSD (Merck). S. Peterson is employed by AstraZeneca and has received compensation for employment from Novo Nordisk A/S and StatMind AB. G. Eriksson was previously employed by AstraZeneca, from which he also received stock/stock options, and has received consultancy fees from GErik Medical Consulting AB.

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