Monday, October 19, 2020

12:07 AM

BA

1. Steroid
   1. Oral - At STEP 5 but with cautious
   2. Inhaled
      1. ICS SOS with SABA in step 01
         • Two RCTs showed reduced exacerbations compared with SABA-only treatment
           • BEST, in adults, with combination ICS-SABA (Papi, NEJMed 2007)
           • TREXA, in children/adolescents, with separate inhalers (Martinez, Lancet 2011)

• Three RCTs showed similar or fewer exacerbations compared with maintenance ICS
  • TREXA, BEST
  • BASALT in adults, separate inhalers, vs physician-adjusted treatment (Calhoun, JAMA 2012)

1. As-needed low dose ICS (budesonide)-formoterol
   • Indirect evidence from SYGMA 1 of large reduction in severe exacerbations (2018)
   • Formoterol is quick acting but long lasting bronchodilator

SYGMA 1In patients with mild asthma, as-needed budesonide–formoterol provided superior asthma-symptom control to as-needed terbutaline, assessed according to electronically recorded weeks with well-controlled asthma, but was inferior to budesonide maintenance therapy. Exacerbation rates with the two budesonide-containing regimens were similar and were lower than the rate with terbutaline. Budesonide–formoterol used as needed resulted in substantially lower glucocorticoid exposure than budesonide maintenance therapy   post-hoc analysis of the SYGMA 1 study)In mild asthma, as-needed budesonide–formoterol reduces the short-term risk of severe exacerbations after a single day of higher use (more than two as-needed inhalations), even when overall use is infrequent. Use of an anti-inflammatory reliever might reduce the risk of short-term severe exacerbations by the timely provision of increased doses of as-needed inhaled corticosteroids and formoterol when symptoms occur.  SYGMA 2In patients with mild asthma, budesonide–formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms.Patients in the budesonide–formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group.

1. Daily ICS is no longer listed as a Step 1 option
   • This was included in GINA 2014-18, but with high probability of poor adherence
   • Now replaced by more feasible as-needed controller options for Step 1

• LTRA - Added in Step 02, No value in acute Ex

• BA
  1. SABA - Quick acting
     1. SABA only can increase exacerbation risk, Why?
        • b-receptor downregulation (tachyphylaxis)
        • decreased bronchoprotection
        • rebound hyperresponsiveness
        • decreased bronchodilator response
        • Increased allergic response
        • increased eosinophilic airway inflammation

1. Higher use of SABA is associated with adverse clinical outcomes, Why?

   1. 3 /year - increase ED admission

   2. 12 /year - increase Death

1. How to minimize this prob?
   1. Adding ICS to BA, 1st consider in 2014 update to limit the use of SABA only strategy.
      1. START study (2003) - post hoc analysis found that ICS halved the risk of serious exacerbations even in patients with symptoms 0-1 days a week at entry (2017)
      2. As-needed low dose ICS (budesonide)-formoterol

Indirect evidence from SYGMA 1 of large reduction in severe exacerbations (2018)

1. NOW SABA ONLY IS NOT RECOMONDED EVEN IN STEP 1 (2019)

This decision was based on evidence that SABA-only treatment increases the risk of severe on pollexacerbations, and that adding any ICS significantly reduces the risk