TABLE 2.

Methodological details of randomised clinical trials which have intervened with fractional exhaled nitric oxide (F_ENO) to guide asthma treatment

First author, year [reference]	Primary outcome(s)	Age years	Participants	Atopy as inclusion criterion?	FEV1 <80% also used in treatment algorithm?	FENO cut-off(s) (ppb) used to step-up/-down treatment	How often was FENO measured after initial assessment?	What did the trial find? (FENO treatment compared to standard care)
de Jongste, 2009 [59]	Symptom-free days	FENO group 11.6±2.6 Control group 11.8±4.3	151	Yes	No	20 for 6–10-year-olds 25 for older children	Daily measurements over 3 months	No difference in outcomes
Fritsch, 2006 [60]	FEV1	11.5±3.1	47	Yes	Yes	20	6, 12, 18 and 24 weeks	Higher mid-expiratory flow, higher dose of ICS
Peirsman, 2014 [61]	Symptom-free days	10.7±2.1	99	Yes	Yes	20	3, 6, 9 and 12 months	Reduced exacerbations, increased LTRA and ICS dose No difference in primary outcome
Petsky, 2015 [62]	Exacerbations	10.0±3.2	63	No	No	10 for nonatopic 12 with 1 PSPT 20 for >1 PSPT	1, 2, 3, 4, 6, 8, 10 and 12 months	Reduced exacerbation, increased ICS dose
Pijnenburg, 2005 [63]	Cumulative ICS dose	12.3±2.8	85	No	No	30	3, 6, 9 and 12 months	Reduced FENO and bronchial hyperresponsiveness No increase in ICS dose
Pike, 2013 [64]	ICS dose and exacerbation frequency	10.9±2.6	90	No	No	≤15 and ≥25	2, 4, 6, 8, 10 and 12 months	No differences in outcomes
Szefler, 2008 [65]	Days with asthma symptoms	14.4±2.1	546	Yes	Yes	20, 30 and 40	6, 14, 22, 30, 38 and 46 weeks	Reduced exacerbations, increased ICS dose No difference in primary outcome
Turner, 2022 [54]	Exacerbation	10.1±2.6	509	No	No	>50% change	3, 6, 9 and 12 months	No differences in outcomes
Verini, 2010 [66]	Exacerbation, symptoms and therapy score	FENO group 10.7±2.4 Control group 11.3±2.1	64	Yes	No	12	6 and 12 months	The FENO group were less likely to have an exacerbation at 6 and 12 months
Voorend-van Bergen, 2015 [67]	Proportion of symptom-free days	10.2±3.0	181#	Yes	No	20 and 50	4, 8 and 12 months	Increased asthma control, but not the primary outcome

Data are presented as mean±sd or n, unless otherwise stated. FEV₁: forced expiratory volume in 1 s; ICS: inhaled corticosteroid; LTRA: leukotriene receptor antagonist; PSPT: positive skin-prick test. ^#: although 272 children were included in the study, the 91 participants randomised to a web-based intervention did not have F_ENO measurements and are not included here