Risk Factors for Asthma Exacerbation and Treatment Failure in Adults and Adolescents with Well-controlled Asthma during Continuation and Step-Down Therapy

Ann Am Thorac Soc. 2018 Aug;15(8):955-961. doi: 10.1513/AnnalsATS.201711-886OC.


Rationale: Although national and international guidelines recommend reduction of asthma controller therapy or "step-down" therapy in patients with well-controlled asthma, it is expected that some individuals may experience worsening of asthma symptoms or asthma exacerbations during step-down. Characteristics associated with subsequent exacerbations during step-down therapy have not been well defined. The effect of environmental tobacco smoke exposure on risk of treatment failure during asthma step-down therapy has not been reported.

Objectives: To identify baseline characteristics associated with treatment failure and asthma exacerbation during maintenance and guideline-based step-down therapy.

Methods: The present analysis uses data collected from a completed randomized controlled trial of optimal step-down therapy in patients with well-controlled asthma taking moderate-dose combination inhaled corticosteroids/long-acting β-agonists. Participants were 12 years or older with physician-diagnosed asthma and were enrolled between December 2011 and May 2014.

Results: An emergency room visit in the previous year was associated with subsequent treatment failure (hazard ratio, 1.53; 95% confidence interval, 1.06-2.21). For every 10% increase in baseline forced expiratory volume in one second percent predicted, the hazard ratio of treatment failure was 14% lower (hazard ratio, 0.86; 95% confidence interval, 0.74-0.99). There was no difference in the risk of treatment failure between adults and children, nor was the duration of asthma associated with the risk of treatment failure. Age of asthma onset was not associated with an increased risk of treatment failure. Unexpected emergency room visit in the previous year was the only risk factor significantly associated with subsequent asthma exacerbations requiring systemic corticosteroids. Time to treatment failure or exacerbation did not differ in participants with and without self-report of environmental tobacco smoke exposure.

Conclusions: The present findings can help clinicians identify adults and adolescents with asthma who are more likely to develop treatment failure and exacerbations and who may therefore require closer monitoring during asthma step-down treatment. Those with reduced pulmonary function, a history of exacerbations, and early-onset disease, even if otherwise well controlled, may require closer observation to prevent treatment failures and asthma exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT01437995).

Keywords: asthma control; asthma exacerbation; asthma treatment failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenal Cortex Hormones / therapeutic use
  • Adrenergic beta-Agonists / administration & dosage*
  • Adrenergic beta-Agonists / therapeutic use
  • Adult
  • Age of Onset
  • Aged
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Deprescriptions*
  • Disease Progression
  • Emergency Service, Hospital / statistics & numerical data
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Tobacco Smoke Pollution / statistics & numerical data
  • Treatment Failure
  • Young Adult


  • Adrenal Cortex Hormones
  • Adrenergic beta-Agonists
  • Anti-Asthmatic Agents
  • Tobacco Smoke Pollution

Associated data

  • ClinicalTrials.gov/NCT01437995