Asthma outcomes: Exacerbations

https://doi.org/10.1016/j.jaci.2011.12.983Get rights and content

Background

The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining “exacerbation” or about how to characterize an episode’s severity.

Objective

National Institutes of Health institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies.

Methods

We used comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health–organized workshop in March 2010 and finalized in September 2011.

Results

No dominant definition of “exacerbation” was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalizations, and (3) use of short-acting β-agonists as quick-relief (sometimes referred to as “rescue” or “reliever”) medications.

Conclusions

The working group participants propose that the definition of “asthma exacerbation” be “a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome.” As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Furthermore, they propose the development of a standardized, component-based definition of “exacerbation” with clear thresholds of severity for each component.

Section snippets

Definition and methodology for measurement

Almost no 2 studies define “asthma exacerbation” in the same way. The most commonly included exacerbation outcomes were the need for systemic corticosteroids, urgent unscheduled care, specifically ED or urgent care (UC) visits, and hospitalizations for asthma.

The subcommittee proposes the following definition, primarily based on the ATS/ERS statement: “An exacerbation is a worsening of asthma requiring the use of systemic corticosteroids (or for patients on a stable maintenance dose, an

A component-based definition of “asthma exacerbation”

Many definitions of “asthma exacerbation” combine multiple components, such as change in symptoms, lung function, and SABA use. The subcommittee believes that this approach should be pursued with the goal of developing and validating a standard, component-based definition. There has been increasing awareness of heterogeneity of the underlying disease processes in asthma. Recent reports have highlighted the importance of different asthma phenotypes and their natural history.124, 125, 126, 127,

Definition and methodology for measurement

There are differences in the way exacerbations are currently measured in different age groups. In addition to the use of systemic (or increase in inhaled) corticosteroids, other frequently used measures for diagnosing an asthma exacerbation in a pediatric population include documentation of respiratory signs and symptoms, symptom scores, use of SABAs, and response to SABAs. Objective measures, including pulse oximetry, and exhaled Feno also have been used for defining exacerbations in children

References (133)

  • S.J. Szefler et al.

    Characterization of within-subject responses to fluticasone and montelukast in childhood asthma

    J Allergy Clin Immunol

    (2005)
  • C.A. Sorkness et al.

    Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial

    J Allergy Clin Immunol

    (2007)
  • T.W. Guilbert et al.

    The Prevention of Early Asthma in Kids study: design, rationale and methods for the Childhood Asthma Research and Education network

    Control Clin Trials

    (2004)
  • E. Bateman et al.

    Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma

    Chest

    (2006)
  • J. Bousquet et al.

    Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone

    Respir Med

    (2007)
  • W. Busse et al.

    Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma

    J Allergy Clin Immunol

    (2001)
  • R. Engelstatter et al.

    Once-daily ciclesonide via metered-dose inhaler: similar efficacy and safety with or without a spacer

    Respir Med

    (2009)
  • G. Huchon et al.

    Lung function and asthma control with beclomethasone and formoterol in a single inhaler

    Respir Med

    (2009)
  • P. Niphadkar et al.

    Comparison of the efficacy of ciclesonide 160 microg QD and budesonide 200 microg BID in adults with persistent asthma: a phase III, randomized, double-dummy, open-label study

    Clin Ther

    (2005)
  • D.S. Pearlman et al.

    Once-daily ciclesonide improves lung function and is well tolerated by patients with mild-to-moderate persistent asthma

    J Allergy Clin Immunol

    (2005)
  • R.S. Zeiger et al.

    Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial

    Am J Med

    (2005)
  • E. Israel et al.

    Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial

    Lancet

    (2004)
  • R.J. Martin et al.

    The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial

    J Allergy Clin Immunol

    (2007)
  • S.J. Szefler et al.

    Significant variability in response to inhaled corticosteroids for persistent asthma

    J Allergy Clin Immunol

    (2002)
  • E.D. Bateman et al.

    Efficacy and safety of roflumilast in the treatment of asthma

    Ann Allergy Asthma Immunol

    (2006)
  • W. Busse et al.

    Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial

    J Allergy Clin Immunol

    (2001)
  • A.H. Morice et al.

    Comparable long-term safety and efficacy of a novel budesonide/formoterol pressurized metered-dose inhaler versus budesonide/formoterol Turbuhaler in adolescents and adults with asthma

    Pulm Pharmacol Ther

    (2008)
  • D.R. Naimi et al.

    Adolescents and asthma: why bother with our meds?

    J Allergy Clin Immunol

    (2009)
  • D.M. Gries et al.

    A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone to treat asthma exacerbations in young children

    J Pediatr

    (2000)
  • F. Qureshi et al.

    Comparative efficacy of oral dexamethasone versus oral prednisone in acute pediatric asthma

    J Pediatr

    (2001)
  • B. Pitt et al.

    Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial–the Losartan Heart Failure Survival Study ELITE II

    Lancet

    (2000)
  • M.H. Gorelick et al.

    Performance of a novel clinical score, the Pediatric Asthma Severity Score (PASS), in the evaluation of acute asthma

    Acad Emerg Med

    (2004)
  • A.B. Becker et al.

    The Pulmonary Index. Assessment of a clinical score for asthma

    Am J Dis Child

    (1984)
  • S.R. Smith et al.

    Validation of the Pulmonary Score: an asthma severity score for children

    Acad Emerg Med

    (2002)
  • S. Mattke et al.

    Quality of care for childhood asthma: estimating impact and implications

    Pediatrics

    (2009)
  • H.K. Reddel et al.

    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

    (2009)
  • Global strategy for asthma management and prevention. Updated 2010

    Bethesda (MD): Global Initiative for Asthma (GINA)

    (2010)
  • Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma, Full Report 2007

    (2007)
  • A. Escribano et al.

    Clinical comparability between the CFC and HFA budesonide pressurised metered-dose inhalers in paediatric patients with asthma: a randomised controlled trial

    Curr Med Res Opin

    (2006)
  • D.M. Fleming et al.

    Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma

    Pediatr Infect Dis J

    (2006)
  • H. Milgrom et al.

    Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab)

    Pediatrics

    (2001)
  • A. von Berg et al.

    Efficacy and safety of ipratropium bromide plus fenoterol inhaled via Respimat Soft Mist Inhaler vs. a conventional metered dose inhaler plus spacer in children with asthma

    Pediatr Pulmonol

    (2004)
  • W.J. Morgan et al.

    Results of a home-based environmental intervention among urban children with asthma

    N Engl J Med

    (2004)
  • M. Kattan et al.

    A randomized clinical trial of clinician feedback to improve quality of care for inner-city children with asthma

    Pediatrics

    (2006)
  • R.J. Wright et al.

    Community violence and asthma morbidity: the Inner-City Asthma Study

    Am J Public Health

    (2004)
  • G.T. O’Connor et al.

    Acute respiratory health effects of air pollution on children with asthma in US inner cities

    J Allergy Clin Immunol

    (2008)
  • R.C. Strunk et al.

    Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study

    J Allergy Clin Immunol

    (2008)
  • T.W. Guilbert et al.

    Long-term inhaled corticosteroids in preschool children at high risk for asthma

    N Engl J Med

    (2006)
  • L.B. Bacharier et al.

    Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing

    J Allergy Clin Immunol

    (2008)
  • design, rationale, and methods. Childhood Asthma Management Program Research Group

    Control Clin Trials

    (1999)
  • Cited by (243)

    View all citing articles on Scopus

    The Asthma Outcomes workshop was funded by contributions from the National Institute of Allergy and Infectious Diseases; the National Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Institute of Environmental Health Sciences; the Agency for Healthcare Research and Quality; and the Merck Childhood Asthma Network, as well as by a grant from the Robert Wood Johnson Foundation. Contributions from the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Institute of Environmental Health Sciences; and the US Environmental Protection Agency funded the publication of this article and all other articles in this supplement.

    Disclosure of potential conflict of interest: A. Fuhlbrigge is on the Merck Respiratory Advisory Board and is a consultant for the Lovelace Respiratory and Research Institute. D. Peden has received research support from the NIH/NIAID, MedImmune, the US Environmental Protection Agency, and Aquinox Pharmaceuticals. A. J. Apter has received research support from the NHLBI and is on the AAAAI Board of Directors. H. A. Boushey has provided ad-hoc consultation for Kalobics; is on the Pharmaxis advisory committee; is on the ad-hoc advisory committee for Merck and GlaxoSmithKline; has provided consultation for Genentech and Johnson & Johnson; and has received research support from GlaxoSmithKline and Genentech. C. A. Camargo, Jr, is a consultant for Dey, Genentech, Merck, Novartis, and Pfizer; and has received research support from GlaxoSmithKline and Sanofi-Aventis. J. Gern is on the Scientific Advisory Board and has stock options in 3V Biosciences, and has received consulting fees from Centocor, Boehringer Ingelheim, GlaxoSmithKline, Biota, MedImmune, and Theraclone. P. W. Heymann has received research support from the NIH and Novartis. F. D. Martinez has consulted for MedImmune and received lecture honorarium from Abbott. W. G. Teague is a speaker for Merck and Genentech, and has received research support from the NIH/NHLBI and the American Lung Association. C. Blaisdell is on the American Academy of Pediatrics Executive Board and is an abstract reviewer for the Pediatric Academic Society. The rest of the authors declare that they have no relevant conflicts of interest.

    View full text