Overall asthma control: The relationship between current control and future risk

doi:10.1016/j.jaci.2009.11.033

Journal of Allergy and Clinical Immunology

Volume 125, Issue 3, March 2010, Pages 600-608.e6

https://doi.org/10.1016/j.jaci.2009.11.033 Get rights and content

Background

Asthma guidelines emphasize both maintaining current control and reducing future risk, but the relationship between these 2 targets is not well understood.

Objective

This retrospective analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler^∗) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations.

Methods

The percentage of patients with Global Initiative for Asthma–defined controlled asthma over time was assessed for budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting β₂-agonist (LABA), and higher dose ICS/LABA plus short-acting β₂-agonist. The relationship between baseline ACQ-5 and exacerbations was investigated. A Markov analysis examined the transitional probability of change in control status throughout the studies.

Results

The percentage of patients achieving asthma control increased with time, irrespective of treatment; the percentage Controlled/Partly Controlled at study end was at least similar to budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies: higher dose ICS (56% vs 45%), same dose ICS/LABA (56% vs 53%), and higher dose ICS/LABA (54% vs 54%). Baseline ACQ-5 score correlated positively with exacerbation rates. A Controlled or Partly Controlled week predicted at least Partly Controlled asthma the following week (≥80% probability). The better the control, the lower the risk of an Uncontrolled week. The probability of an exacerbation was related to current state and was lower with budesonide/formoterol maintenance and reliever therapy.

Conclusions

Current control predicts future risk of instability and exacerbations. Budesonide/formoterol maintenance and reliever therapy reduces exacerbations versus comparators and achieves at least similar control.

Section snippets

Studies and population

All long-term, double-blind, randomized, parallel-group clinical studies (6–12 months in duration) investigating the efficacy of budesonide/formoterol maintenance and reliever therapy (Symbicort SMART; AstraZeneca AB, Lund, Sweden) with comparator therapies (higher maintenance dose budesonide plus a SABA as needed [higher maintenance dose ICS plus SABA],14, 15 same maintenance dose budesonide/formoterol [Symbicort; AstraZeneca] plus SABA as-needed [same maintenance dose ICS/LABA plus SABA]14, 18

Studies and population

Baseline characteristics were comparable between the 4 treatment groups within this pooled analysis (Table I). At baseline, patients had a mean FEV₁, percentage predicted normal of 71.6% to 72.3%; 35% to 49% of patients were using a LABA at entry.

Time course to achieve GINA control targets

The percentage of patients achieving a week of Controlled or Controlled/Partly Controlled asthma, as defined by GINA criteria, increased throughout the study periods, irrespective of treatment used, although most of the increase occurred during the

Discussion

The management of chronic diseases requires an approach to both the current manifestations and the long-term effects of disease. The focus of asthma management has shifted from treatment of an acute disease to that of long-term control and prevention of future risks. With improvements in controller therapy, it is now recognized that highly satisfactory levels of current control can be achieved and maintained for long periods.²³ It is thus relevant to consider different strategies for

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: Supported by AstraZeneca AB, Lund, Sweden.

: Disclosure of potential conflict of interest: E. D. Bateman is on advisory boards for and has received speakers' honoraria from AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim; is on advisory boards for Nycomed, Merck, ALK-Abelló, Hoffmann la Roche (Data Safety Board), and Almirall/Forest Pharmaceuticals; and has received research support from AstraZeneca, GlaxoSmithKline, Merck, Morris Pharmaceuticals, Pfizer, Replidyne Inc, Almirall, Aeras, and Eumedic Inc. P. M. O'Byrne is on advisory boards for and has received speakers' honoraria from AstraZeneca and GlaxoSmithKline; is on advisory boards for Topigen, Wyeth, and Schering; and has received research support from AstraZeneca, GlaxoSmithKline, Merck, Wyeth, Schering, and Alexion. M. R. Sears holds a chair endowed by AstraZeneca; has received consultation fees from AstraZeneca, Merck Frosst, and Schering-Plough; and has received research support from GlaxoSmithKline. T. W. Harrison has received honoraria from AstraZeneca and has received research support from GlaxoSmithKline and Boehringer Ingelheim. R. Buhl has received speakers' fees and consultants' fees, as well as reimbursement for attending scientific conferences from AstraZeneca, and his department has received research support from the Deutsche Forschungsgemeinschaft, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis. S. Quirce is on advisory boards for and has received speakers' honoraria from AstraZeneca and has received research support from Ciber de Enfermedades Respiratorias (CIBERES), Madrid. G. Eriksson, S. Peterson, and O. Östlund are employed by AstraZeneca. M. Humbert has consulted for Actelion, AstraZeneca, Amgen, Chiesi, GlaxoSmithKline, MSD, Novartis, and Pfizer. C. Jenkins has received speakers' honoraria from GlaxoSmithKline, Novartis, and AstraZeneca and has received research support from GlaxoSmithKline and AstraZeneca. H. K. Reddel is on advisory boards for and has received research support from AstraZeneca and GlaxoSmithKline and has received speakers' honoraria from AstraZeneca, Getz Pharma, and MerckSharp & Dohme.

^∗: Symbicort SMART and Turbuhaler are trademarks owned by AstraZeneca. Neither the Symbicort SMART posology nor the dry powder formulation Turbuhaler are currently approved in the United States.

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Asthma and lower airway diseaseOverall asthma control: The relationship between current control and future risk

Background

Objective

Methods

Results

Conclusions

Section snippets

Studies and population

Studies and population

Time course to achieve GINA control targets

Discussion

Chest

Chest

J Allergy Clin Immunol

Chest

Clin Ther

Chest

Respir Med

Lancet

Respir Med

Respir Med

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

A new perspective on concepts of asthma severity and control

Eur Respir J

An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice

Am J Respir Crit Care Med

Asthma and lower airway disease
Overall asthma control: The relationship between current control and future risk