Table 1

Characteristics of included studies

StudySample sizeDescription of intervention and control arms
Calhoun et al 35 FeNO group n=115
Control group
Control group: National Heart, Lung and Blood Institute guidelines
FeNO group: <22 ppb treatment stepped down
22 to 35 maintain treatment
>35 increase treatment
Cao et al 22 EOS strategy n=20
Control group n=21
Control strategy: ‘Standard clinical guidelines’
EOS strategy: decrease ICS <1% eosinophils, keep ICS the same 1%–3% eosinophils, increase ICS if eosinophils >3%
Chlumsky et al 23 EOS strategy n=30
Standard strategy n=25
Standard strategy arm: GINA guidelines
EOS strategy: decrease ICS if ≤3%, keep same if 4%–8%, increase ICS if ≥8%
de Jongste et al 30 FeNO group n=75
Symptom group n=72
All participants scored asthma symptoms in an electronic diary over 30 weeks. Aim to keep FeNO <20 ppb
Symptom group based on symptom score: below range (<10)=step down/discontinue, range 10 to 60=no change and range >60=step up
Fleming et al 26 Inflammatory group n=27
Symptom group n=28
Symptom group: based on number of major exacerbations in the preceding 3 months and SABA use in preceding 2 weeks
Inflammatory group: treatment aimed to keep sputum eosinophil counts <2.5%
Fritsch et al 19 FeNO group n=22
Control group n=25
FeNO group: therapy was based on symptoms, beta-agonist use, lung function and FeNO
Control group: therapy based on symptoms, beta-agonists and lung function only
Green et al 24 Sputum management group n=37
BTS group n=37
Sputum management group: anti-inflammatory treatment was based on maintenance of sputum eosinophil count below 3% with a minimum dose of anti-inflammatory treatment
BTS management group: BTS/SIGN guidelines
Hashimoto et al 36 Internet strategy n=51
Conventional strategy n=38
Internet strategy: had steroid dose adjusted based on the three components: electronic diary, in-built algorithm (which includes FeNO levels) and monitoring support
Conventional strategy: GINA guidelines for the treatment of severe asthma
Honkoop et al 37 FeNO group n=189
Controlled asthma group n=203
Cluster randomisation (at general practice level)
FeNO strategy: treatment targeted to keep FeNO <50 ppb
Symptom strategy: ACT used including lung function
Jayaram et al
Sputum strategy group n=50
Clinical strategy group n=52
Sputum strategy: guided solely by induced sputum eosinophils to keep <2%
Clinical strategy: Canadian Asthma Consensus Group Guidelines
Malerba et al 25 Sputum strategy n=14
Clinical strategy n=14
Sputum strategy: treatment based on sputum eosinophil (%) and FeNO (ppb)
Decrease ICS <2% and ≤10 pbb
Keep same 2%–3% and 11–20 ppb
Increase ICS >3% and ≥20 ppb
Symptom strategy: symptom scores, use of SABA and night-time symptoms
Peirsman et al 34 FeNO group n=49
Control group n=50
FeNO group: treatment aimed to keep FeNO below 20 ppb
Control group: GINA guidelines
Petsky et al 28 FeNO group n=31
Symptom group n=32
FeNO group: treatment adjusted based on FeNO level and atopy status Elevated FeNO defined as:
≥10 ppb with no positive SPT
≥12 ppb with one positive SPT
≥20 ppb with ≥2 positive SPT
Control group: symptom diary cards
Pijnenburg et al 18 FeNO group n=39
Symptom group n=46
FeNO group: FeNO guided ICS dosing according to predetermined algorithm
Symptom group: symptom scores influenced ICS dosing
Pike et al 32 FeNO group n=44 Standard management group n=46FeNO group: FeNO measurements and symptom control
Standard management group: symptom control as per blinded clinician (reliever use, FEV1)
Powell et al 27 FeNO group n=111
Control group n=109
FeNO group: sequential process, first FeNO concentrations used to adjust ICS dose, and second ACT score used to adjust the LABA dose
Clinical group: Juniper ACT cut-off points defined as well-controlled asthma (ACT<0.75), partially controlled asthma (0.75 to 1.50) and uncontrolled asthma (>1.5)
Shaw et al 38 FeNO group n=58
Control group n=60
FeNO group: FeNO >26 ppb, ICS was increased. If FeNO <16 ppb or <26 ppb on two separate occasions, treatment was decreased
Control group: treatment was doubled if Juniper Asthma Control Score (JACS) >1.57 and treatment halved if JACS <1.57 for two consecutive months
Smith et al 21 97 patients randomised from 110 patientsFeNO group: based to keep FeNO <15 ppb at 250 mL/s
Control group: dose adjustment based on asthma symptoms, night-time waking, bronchodilator use, variation in PEFR and FEV1
Syk et al 39 FeNO group n=87
Control group n=78
FeNO group: keep FeNO level <24 ppb for women and <26 ppb for men
Control group: treatment adjusted based on patient-reported symptoms, SABA use, physical examination and spirometry results
Szefler et al 29 FeNO group n=276
Control group n=270
FeNO group: standard treatment modified on the basis of measurements of FeNO
Control group: National Asthma Education and Prevention Programme  guidelines
Verini et al 20 FeNO group n=32 GINA group n=32FeNO group at 6-month visit only: step treatment up if >12 ppb
Control group: GINA guidelines
Voorend-van Bergen et al 33 FeNO group n=92
Standard care group n=89
FeNO group: treatment adjusted according to FeNO levels and ACT results
If ACT ≥20 and:
FeNO <25=step down
FeNO ≥25 to <50=no change
FeNO ≥50= step up
If ACT <20 and:
FeNO ≥25=step up
FeNO <25=no change
Control group: treatment adjusted based on ACT results
<20=step up
≥20=no change or step down
  • ACT, Asthma Control Test; BTS, British Thoracic Society; EOS, eosinophils; FeNO, fractional exhaled nitric oxide; GINA, Global Initiative for Asthma; ICS, inhaled corticosteroids; LABA, long acting beta-agonist; PEFR, peak expiratory flow rate; SABA, short acting beta-agonist; SIGN, Scottish Intercollegiate Guidelines Network; SPT, skin prick test.