title: Stepping down from combination asthma therapy: The predictors of outcome.
abstract: Stepping down from combination asthma therapy (inhaled corticosteroids (ICS) + long-acting β2 agonists (LABA)) is often avoided due to fear of exacerbations, which may lead to overmedication in well-controlled asthma. A better knowledge about the predictors of outcome might encourage clinicians to start stepping down more often than previously.
  
  
  
  In 55 subjects with well controlled asthma and combination therapy, LABAs were discontinued first, followed by ICS dose halving, and then cessation, in six weeks' intervals. The ability of Juniper's asthma control questionnaire (ACQ), ambulatory peak flow monitoring, spirometry, and hypertonic saline challenge to predict the outcomes of medication reductions were assessed.
  
  
  
  The proportions of subjects experiencing an exacerbation at each step were: 4 out of 55 subjects (7%) after LABA cessation, 4 out of 25 subjects (16%) after ICS dose halving, and 21 out of 46 subjects (46%) after ICS cessation. All exacerbations could be managed on an outpatient basis. There were 126 step-downs altogether. ACQ score < 0.29 (likelihood ratio 2.30 (1.05-5.05)), ACQ without spirometry < 0.15 (2.17 (0.96-4.90)) and FEV1 > 96% of predicted (2.18 (1.03-4.61)) predicted a successful outcome after step-down. Cough responsiveness to saline, bronchoconstrictive responsiveness to saline, and peak flow variation were not associated with the outcome.
  
  
  
  Combination therapy can often be reduced in controlled asthma but total cessation of ICSs must be carefully considered. Simple investigations, namely asthma control assessment by validated questionnaire and spirometry, help to predict the outcome of stepping down.
  
  
  
  The study was registered in ClinicalTrials.gov database (https://clinicaltrials.gov, KUH5801124).
authors: Unit for Medicine and Clinical Research, Pulmonary Division, Kuopio University Hospital, Kuopio, Finland; School of Medicine, Institute of Clinical Sciences, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland. Electronic address: heikki.koskela@kuh.fi.
authors: Heikki O
authors: HO
authors: Koskela
authors: Unit for Medicine and Clinical Research, Pulmonary Division, Kuopio University Hospital, Kuopio, Finland.
authors: Minna K
authors: MK
authors: Purokivi
authors: Unit for Medicine and Clinical Research, Pulmonary Division, Kuopio University Hospital, Kuopio, Finland.
authors: Jouko
authors: J
authors: Kokkarinen
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D003371:Cough / Q000188:drug therapy / Q000453:epidemiology; D018450:Disease Progression; D004359:Drug Therapy, Combination / Q000379:methods*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D000069342:Medical Overuse / Q000517:prevention & control; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D012462:Saline Solution, Hypertonic / Q000009:adverse effects / Q000494:pharmacology; D013147:Spirometry / Q000379:methods; D014797:Vital Capacity / Q000187:drug effects; D028761:Withholding Treatment
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D012462:Saline Solution, Hypertonic
keywords: Asthma; Asthma control; Asthma medication; Combined asthma therapy; Exacerbation; Therapy reduction