Characteristics of included studies
| Study | Sample size | Description of intervention and control arms |
| Calhoun et al 35 | FeNO group n=115 Control group n=114 | 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 31 | 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=46 | FeNO 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 patients | FeNO 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=32 | FeNO 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.