title: Symptom- and fraction of exhaled nitric oxide-driven strategies for asthma control: A cluster-randomized trial in primary care.
abstract: BACKGROUND
  Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (Feno), allow further tailoring of treatment.
  
  
  OBJECTIVE
  We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or Feno-driven controlled asthma (FCa).
  
  
  METHODS
  In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score <1.50); (2) aiming at Ca (ACQ score <0.75); and (3) aiming at FCa (ACQ score <0.75 and Feno value <25 ppb). During 12 months' follow-up, treatment was adjusted every 3 months by using an online decision support tool. Outcomes were incremental cost per quality-adjusted life year gained, asthma control (ACQ score), quality of life (Asthma Quality of Life Questionnaire score), asthma medication use, and severe exacerbation rate.
  
  
  RESULTS
  Six hundred eleven participants were allocated to the PCa (n = 219), Ca (n = 203), or FCa (n = 189) strategies. The FCa strategy improved asthma control compared with the PCa strategy (P < .02). There were no differences in quality of life (P ≥ .36). Asthma medication use was significantly lower for the PCa and FCa strategies compared with the Ca strategy (medication costs: PCa, $452; Ca, $551; and FCa, $456; P ≤ .04). The FCa strategy had the highest probability of cost-effectiveness at a willingness to pay of $50,000/quality-adjusted life year (86%; PCa, 2%; Ca, 12%). There were no differences in severe exacerbation rate.
  
  
  CONCLUSIONS
  A symptom- plus Feno-driven strategy reduces asthma medication use while sustaining asthma control and quality of life and is the preferred strategy for adult asthmatic patients in primary care.
authors.affiliation: Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: P.J.Honkoop@lumc.nl.
authors.forename: Persijn J
authors.initials: PJ
authors.lastname: Honkoop
authors.affiliation: Department of General Practice, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Rik J B
authors.initials: RJ
authors.lastname: Loijmans
authors.affiliation: Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Evelien H
authors.initials: EH
authors.lastname: Termeer
authors.affiliation: Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jiska B
authors.initials: JB
authors.lastname: Snoeck-Stroband
authors.affiliation: Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wilbert B
authors.initials: WB
authors.lastname: van den Hout
authors.affiliation: Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Moira J
authors.initials: MJ
authors.lastname: Bakker
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands; Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Willem J J
authors.initials: WJ
authors.lastname: Assendelft
authors.affiliation: Department of General Practice, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Gerben
authors.initials: G
authors.lastname: ter Riet
authors.affiliation: Department of Pulmonology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Tjard R J
authors.initials: TR
authors.lastname: Schermer
authors.affiliation: Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Sont
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000191:economics* / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000191:economics* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000191:economics* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D003362:Cost-Benefit Analysis; D019468:Disease Management; D016903:Drug Monitoring; D045853:Exhalation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D011795:Surveys and Questionnaires
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D009569:Nitric Oxide
keywords: Quality of life; asthma control; asthma exacerbations; cost-effectiveness; fraction of exhaled nitric oxide; online decision support