Domain  

Instructions (Check all that apply)  

Judgement  

Comments (optional)  

PICO components  

1. Did the research questions and inclusion criteria for the review include the components of PICO?  

For Yes:     

☒ Population    

☒ Intervention    

☒ Comparator group    

☒ Outcome  

Optional (recommended)  

☒ Timeframe for follow up   

☒Yes  

☐No  

Protocol  

2. Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?  

For Partial Yes:  

The authors state that they had a written protocol or guide that included ALL the following:   

☒ review question(s)   

☒ a search strategy   

☒ inclusion/exclusion criteria   

☒ a risk of bias assessment  

For Yes:   

As for partial yes, plus the protocol should be registered and should also have specified:   

☒ a meta-analysis/synthesis plan, if appropriate, and  

☒ a plan for investigating causes of heterogeneity   

☒ justification for any deviations from the protocol 

☒Yes  

☐Partial Yes  

☐No  

This is a Cochrane review and the protocol was not obtained, however all Cochrane reviews have a protocol that meets extensive criteria and the review had a section describing deviations from the protocol.  

Study design explanation 

3. Did the review authors explain their selection of the study designs for inclusion in the review?  

For Yes, the review should satisfy ONE of the following:   

☐ Explanation for including only RCTs   

☐ OR Explanation for including only NRSI   

☐ OR Explanation for including both RCTs and NRSI 

☐Yes  

☒No 

Authors did not provide an explanation for excluding NRSI. 

Comprehensive  

search strategy  

4. Did the review authors use a comprehensive literature search strategy?  

For Partial Yes (all the following):   

☒ searched at least 2 databases (relevant to research question)  

☒ provided key words and/or search strategy  ☒ justified publication restrictions (e.g. language)  

For Yes, should also have (all the following):   

☒ searched the reference lists / bibliographies of included studies   

☒ searched trial/study registries   

☒ included/consulted content experts in the field   

☒ where relevant, searched for grey literature   

☒ conducted search within 24 months of completion of the review 

☒Yes  

☐Partial Yes  

☐No 

Duplicate study selection 

5. Did the review authors perform study selection in duplicate?  

For Yes, either ONE of the following:  

☒ at least two reviewers independently agreed on selection of eligible studies and achieved consensus on which studies to include   

☐ OR two reviewers selected a sample of eligible studies and achieved good agreement (at least 80 percent), with the remainder selected by one reviewer. 

☒Yes  

☐No 

Duplicate data extraction 

6. Did the review authors perform data extraction in duplicate?  

For Yes, either ONE of the following: 

☐at least two reviewers achieved consensus on which data to extract from included studies  

☐ OR two reviewers extracted data from a sample of eligible studies and achieved good agreement (at least 80 percent), with the remainder extracted by one reviewer. 

☐Yes  

☒No 

Study characteristics were extracted by one reviewer and checked by a second 

reviewer. Outcome data were extracted by two reviewers independently. 

Details of excluded studies 

7. Did the review authors provide a list of excluded studies and justify the exclusions?  

For Partial Yes:   

☒ provided a list of all potentially relevant studies that were read in full-text form but excluded from the review  

For Yes, must also have:   

☒ Justified the exclusion from the review of each potentially relevant study 

☒Yes  

☐Partial Yes  

☐No 

Description of included studies 

8. Did the review authors describe the included studies in adequate detail?  

For Partial Yes (ALL the following):   

☒ described populations   

☒ described interventions   

☒ described comparators   

☒ described outcomes   

☒ described research designs  

For Yes, should also have ALL the following:   

☒ described population in detail   

☒ described intervention in detail (including doses where relevant)   

☒ described comparator in detail (including doses where relevant)   

☒ described study’s setting   

☒ timeframe for follow-up 

☒Yes  

☐Partial Yes  

☐No 

Risk of bias assessment (RCTs) 

9. Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review?  

For Partial Yes, must have assessed RoB from   

☒ unconcealed allocation, and   

☒ lack of blinding of patients and assessors when assessing outcomes  

(unnecessary for objective outcomes such as all cause mortality) 

For Yes, must also have assessed RoB from:   

☒ allocation sequence that was not truly random, and   

☒ selection of the reported result from among multiple measurements or analyses of a specified outcome 

☒Yes  

☐Partial Yes  

☐No  

☐Includes only NRSI 

Risk of bias assessment (NRSI) 

10. Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review?  

For Partial Yes, must have assessed RoB:   

☐ from confounding, and   

☐ from selection bias  

For Yes, must also have assessed RoB:   

☐ methods used to ascertain exposures and outcomes, and   

☐ selection of the reported result from among multiple measurements or analyses of a specified outcome 

☐Yes  

☐Partial Yes  

☐No  

☒Includes only RCTs 

Funding sources 

11. Did the review authors report on the sources of funding for the studies included in the review?  

For Yes   

☒ Must have reported on the sources of funding for individual studies included in the review. Note: Reporting that the reviewers looked for this information but it was not reported by study authors also qualifies 

☒Yes  

☐No 

Reported as part of risk of bias assessment. 

Meta-analyses (RCTs) 

12. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?  

For Yes:   

☒ The authors justified combining the data in a meta-analysis   

☒ AND they used an appropriate weighted technique to combine study results and adjusted for heterogeneity if present.   

☒ AND investigated the causes of any heterogeneity 

☒Yes  

☐No  

☐No meta-analysis conducted  

☐Includes only NRSI 

Meta-analyses (NRSI) 

13. If meta-analysis was performed did the review authors use appropriate methods for statistical combination of results?  

For Yes:   

☐ The authors justified combining the data in a meta-analysis   

☐ AND they used an appropriate weighted technique to combine study results, adjusting for heterogeneity if present   

☐ AND they statistically combined effect estimates from NRSI that were adjusted for confounding, rather than combining raw data, or justified combining raw data when adjusted effect estimates were not available   

☐ AND they reported separate summary estimates for RCTs and NRSI separately when both were included in the review 

☐Yes  

☐No  

☐No meta-analysis conducted  

☒Includes only RCTs 

Impact of bias on meta-analysis 

14. If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?  

For Yes:   

☐ included only low risk of bias RCTs   

☒ OR, if the pooled estimate was based on RCTs and/or NRSI at variable RoB, the authors performed analyses to investigate possible impact of RoB on summary estimates of effect. 

☒Yes  

☐No  

☐No meta-analysis conducted 

A sensitivity analysis was conducted excluding studies at high risk of bias. 

Risk of bias and interpretation results 

15. Did the review authors account for RoB in individual studies when interpreting/ discussing the results of the review?  

For Yes:   

☐ included only low risk of bias RCTs   

☒ OR, if RCTs with moderate or high RoB, or NRSI were included the review provided a discussion of the likely impact of RoB on the results 

☒Yes  

☐No 

Heterogeneity 

16. Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?  

For Yes:   

☐ There was no significant heterogeneity in the results  

☒ OR if heterogeneity was present the authors performed an investigation of sources of any heterogeneity in the results and discussed the impact of this on the results of the review 

☒Yes  

☐No 

Publication bias 

17. If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?  

For Yes:   

☐ performed graphical or statistical tests for publication bias and discussed the likelihood and magnitude of impact of publication bias 

☐Yes  

☒No  

☐No meta-analysis conducted 

Formal tests were not possible due to low number of studies, and this was not further discussed in the discussion. 

Conflicts of interest 

18. Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?  

For Yes:   

☒ The authors reported no competing interests OR   

☐ The authors described their funding sources and how they managed potential conflicts of interest 

☒Yes  

☐No 

Study reference 

Study characteristics 

Patient characteristics  

Intervention (I) 

Comparison / control (C)

Follow-up 

Outcome measures and effect size  

Comments 

De Jongste, 2008 

Type of study: Randomised controlled trial 

Setting and country: Secondary asthma care, The Netherlands and Italy 

Funding: 

The study was supported by the company (Aerocrine AB, Sweden) who manufactured the FeNO analyser. 

Conflict of interest:

Inclusion criteria:

Participants aged 6 to 18 yrs, stable mild-moderate asthma, diagnosed according 
to GINA guidelines, treatment with 200 μg to 1000 μg of inhaled budesonide or equivalent daily for 2 
months prior to randomisation, and RAST class ≥ 2, or a positive SPT to ≥ 1 airborne allergen. 

Exclusion criteria:

Active smoking, previous admission to an ICU for asthma and concomitant disease 
that might affect FeNO. 

N total at baseline:

Intervention: 75 

Control: 72 

Important prognostic factors:

For example 

age ± SD: 

I: 11.6 ± 2.6 

C: 11.8 ± 4.3 

Sex (% male) 

I: 61.3% male 

C: 75% male 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO self-monitoring 

Describe control (treatment/procedure/test): 

Symptom-based 

Length of follow-up:

30 weeks 

Loss-to-follow-up:

4 randomised participants (2 in FeNO group, 2 in symptom group) were excluded from final results due 
to severe non-compliance (2), inappropriate inclusion (no allergy 1) and moving abroad (1). 

Outcome measures and effect size (include 95%CI and p-value if available): 

Quality of life: 

Mean difference: 0 (95% CI; -0.24 to 0.24) 

Dinh-Thi-Dieu, 2020 

Type of study: 

Randomised controlled trial 

Setting and country:  

Various clinical departments of health centers in Vietnam 

Source of funding:  

Not reported 

Competing interests:  

All the authors declare no conflict of interests. 

Inclusion criteria: 

All children with uncontrolled asthma, who were between the ages of 6–17 years and under discontinued asthma treatment in the previous months or who had untreated asthma were included.” The children had high level of FeNO. “The diagnosis of asthma was based on the criteria recommended by GINA for children over five years. 

Exclusion criteria: 

Asthmatic children having one of the following features were excluded: other significant chronic or acute non-respiratory diseases, acute respiratory infections, severe asthma exacerbations needing systemic corticosteroid therapy (oral or injection) at inclusion, or who were unable to do a laboratory test. Asthmatic children with non-reproducible FEV1 and FENO measurements were also excluded in the present study. 

N total at baseline: 

Intervention: 108 

Control: 116 

Important prognostic factors: 

Age ± SD: 

I: 11 ± 5 

C: 10 ± 4 

Sex (% male) 

I: 63.8% 

C:62.0% 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO + GINA 

Describe control (treatment/procedure/test): 

GINA 

Length of follow-up:

Loss-to-follow-up:

Intervention:  (%) 

Reasons (describe)  

Control:  (%) 

Reasons (describe) 

Incomplete outcome data:  

Intervention:  (%) 

Reasons (describe)  

Control:  (%) 

Reasons (describe)  

Outcome measures and effect size (include 95%CI and p-value if available): 

Number of exacerbations per patient: 

I: 0.8 ( 95% CI; 0.7 to 0.9) 

C: 1.4 (95% CI; 1.3 to 1.5) 

Asthma Control Test: 

I: 23.0 (95% CI; 22.4 to 23.6) 

C: 22.0 (95% CI; 21.4 to 22.6) 

Petsky, 2015 

Type of study: Randomised controlled trial 

Setting and country: Secondary asthma care, Australia and Hong Kong 

Funding:  

Conflict of interest:  

None mentioned 

Inclusion criteria: 

Children aged > 4 yrs with persistent asthma, prescribed anti-inflammatory asthma 
treatment and receiving their care primarily through 2 hospitals (Brisbane and Hong Kong). 

Exclusion criteria: 

underlying cardio-respiratory illnesses such as bronchiectasis or tracheomalacia, 
inability to take ICS or LABA, or previous poor adherence to medications as documented in medical charts. 

N total at baseline: 

Intervention: 31 

Control: 32 

Important prognostic factors: 

Age 

I: Median age 10.17 yrs (IQR 6.56 to 12.69), 

C: Median age 10.08 yrs (IQR 6.25 to 12.44), 

Sex (% male) 

I: 58.1% male 

C:40.6% male 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO + atopic status 

Describe control (treatment/procedure/test): 

Symptom-based 

Length of follow-up: 

12 months 

Loss-to-follow-up: 

8 children did not complete the study (4 in FeNO group and 4 in control group).)  

Outcome measures and effect size (include 95%CI and p-value if available): 

Number of exacerbations per patient: 

I: 0.39 (95% CI; 0.13 to 0.65) 

C: 0.78 (95% CI; 0.39 to 1.17) 

Quality of life:

Mean difference: 0.33 (95% CI; -0.39 to 1.05) 

Pike, 2013 

Type of study: Randomised controlled trial 

Setting and country: Secondary asthma care, UK 

Funding: 

None reported 

Conflict of interest:

None reported.  

Inclusion criteria: 

: aged 6 to 17 yrs, clinical diagnosis of asthma and treatment with beclomethasone 
dipropionate/budesonide ≥ 400 μg/day or fluticasone ≥ 200 μg/day. Asthma diagnosed upon a history 
of symptoms, ≥ 15% increase in FEV1 with bronchodilator or diurnal PEF variability ≥ 15%. 

Exclusion criteria:

None reported. 

N total at baseline: 

Intervention: 28 

Control: 35 

Important prognostic factors: 

Age ± SD: 

I: 10.51 yrs (SD 2.62), 

C:11.42 yrs (SD 2.69) 

Sex (% male) 

I: 47.7% 

C: 65.2% 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO + symptom-based 

Describe control (treatment/procedure/test): 

Symptom-based 

Length of follow-up: 

12 months 

Loss-to-follow-up: 

13 children did not complete the study; 10 in FeNO group (8 withdrew, 1 non-adherence to protocol, 1 
life-threatening exacerbation) and 3 withdrew in Standard management group. 

Outcome measures and effect size (include 95%CI and p-value if available): 

Number of exacerbations per patient: 

I: 3.71 (95% CI; 2.73 to 4.69) 

C: 3.20 (95% CI; 2.48 to 3.92) 

Szefler, 2008 

Type of study: Randomised controlled trial 

Setting and country: Secondary asthma care, USA 

Funding:

Conflict of interest: 

Inclusion criteria: 

Aged 12 to 20 yrs, diagnosed with asthma by their physician, symptoms of persistent 
asthma or evidence of uncontrolled disease as defined by NAEPP guidelines, and residents of urban 
census tracts in which at least 20% of households had incomes below the federal poverty threshold. 

Exclusion criteria: 

None reported 

N total at baseline: 

Intervention: 276  

Control: 270 

Important prognostic factors: 

Age ± SD: 

I: 14.4 years 

C: 14.4 years 

Sex (% male) 

I: 52.9% 

C: 52.6% 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO + symptoms, FEV1 

Describe control (treatment/procedure/test): 

NAEPP 

Length of follow-up: 

46 weeks 

Loss-to-follow-up: 

12 randomised participants were lost to follow-up before the first outcome data were collected. During 
the 46-week follow-up, 17 participants in FeNO group dropped out and 23 in the control group. 

Outcome measures and effect size (include 95%CI and p-value if available): 

Number of exacerbations per patient: 

I: 0.66 (95% CI; 0.49 to 0.83) 

C: 0.84 (95% CI; 0.67 to 1.00) 

Asthma Control Test: 

I: 21.89 (95% CI; 21.65 to 22.13) 

C: 21.83 (95% CI; 21.59 to 22.07) 

Turner, 2022 

Type of study: Randomised controlled trial 

Setting and country: Secondary asthma care, UK 

Funding: 

The project was funded by the Efficacy and Mechanism Evaluation (EME) programme, 
a MRC and National Institute for Health and Care Research (NIHR) partnership. 

Conflict of interest: Steve Turner reports that Circassia (Oxford, UK) lent 
16 NIOX VERO® devices to measure nitric oxide in study participants and provided, at no cost, associated 
consumables for these devices. Seonaidh Cotton reports grants from the National Institute for Health 
and Care Research (NIHR) Health Technology Assessment (HTA) programme outside the submitted 
work. Graham Scotland reports non-financial support from Merck KgaA (Darmstadt, Germany) outside 
the submitted work. Graeme MacLennan reports grants from the NIHR HTA programme outside the submitted work. John Norrie reports grants from the University of Aberdeen and the University of Edinburgh during the conduct of the study and declares membership of the following NIHR boards: CPR Decision-making Committee (2016), HTA Commissioning Board (2010–16), HTA Commissioning Sub-Board (EOI) (2012–16), HTA Funding Boards Policy Group (2016), HTA General Board (2016–19), HTA Post-Board funding teleconference (2016–19), NIHR Clinical Trials Unit Standing Advisory Committee (2017–present), NIHR HTA and Efficacy and Mechanism Evaluation (EME) Editorial Board 
(2014–19), and the Pre-exposure Prophylaxis Impact Review Panel (2017–present). Erol Gaillard reports consultancy work for Boehringer Ingelheim (Ingelheim am Rhein, Germany), with money paid 

to the institution (University of Leicester); an investigator-led research grant from Circassia, Gilead (Foster City, CA, USA) and Chiesi Ltd (Manchester, UK); and research collaboration with Medimmune 
(Gaithersburg, MD, USA). David Price has board membership with AstraZeneca (Cambridge, UK), Boehringer Ingelheim, Chiesi, Mylan (Canonsburg, PA, USA), Novartis (Basel, Switzerland), Regeneron 
Pharmaceuticals (Tarrytown, NY, USA), Sanofi Genzyme (Cambridge, MA, USA), Thermofisher (Waltham, 
MA, USA) and Zentiva (Sanofi Generics) (Prague, Czech Republic); holds consultancy agreements with Airway Vista Secretariat (Seoul, South Korea), AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd (Kent, UK), FIECON Ltd (St Albans, UK), Fieldwork International (London, UK), GlaxoSmithKline (Brentford, UK), Mylan, Mundipharma (Limburg an der Lahn, Germany), Novartis,OM Pharma SA (Meyrin, Switzerland), PeerVoice (London, UK), Phadia AB (Uppsala, Sweden), Spirosure Inc. (Pleasanton, CA, USA), Strategic North Ltd (Hale, UK), Synapse Research Management Partners (Barcelona, Spain), Talos Health Solutions (Brussels, Belgium), Theravance (South San Francisco, CA, USA) and WebMD Global LLC (New York, NY, USA); has received grants and unrestricted funding for 
investigator-initiated studies [conducted through Observational and Pragmatic Research Institute Pte Ltd (Norwich, UK)] from AKL Research and Development Ltd (Stevenage, UK), AstraZeneca, Boehringer Ingelheim, British Lung Foundation (London, UK), Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, 
Respiratory Effectiveness Group (Ely, UK), Sanofi Genzyme, Theravance, UK NHS and Zentiva (Sanofi Generics); has received payment for lectures/speaking engagements from AstraZeneca, Boehringer 
Ingelheim, Chiesi, Cipla (Mumbai, India), GlaxoSmithKline, Kyorin, Merck (Kenilworth, NJ, USA),Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme and Zentiva (Sanofi Generics); has received payment for travel/accommodation/meeting expenses from AstraZeneca, 
Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; has received stock/stock options 
from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); has a 5% shareholding in Timestamp (Tel Aviv-Yafo, Israel), which develops adherence monitoring technology; is peer reviewer for the grant committees of 
the UK EME and HTA programmes; and was an expert witness for GlaxoSmithKline. 

Inclusion criteria: 

- Asthma diagnosed or confirmed by consultant paediatrician or respiratory/asthma specialist nurse 
(or Read code for asthma if recruited in primary care). 
l Aged ≥ 6 years and not reached the date of their 16th birthday (generally children below the age of 
6 find it difficult to provide FeNO measurements). 
l Currently prescribed ICs in a device that can be fitted with a smart inhaler [within the study the 
smart inhalers used were Adherium Haile ® sensors (Adherium Ltd, Auckland, New Zealand)]. For the 
purposes of the study, the maximum dose for children aged < 12 years was 1000 μg of budesonide 
equivalent per day; the maximum dose for children aged ≥ 12 years was 2000 μg of budesonide 
equivalent per day. 
l Parent-/patient-reported asthma exacerbation treated with at least one course of OCs in the 
12 months prior to recruitment. 

Exclusion criteria: 

Unable to provide FeNO measurement at the baseline assessment (expected prevalence of < 5%). 
l Other chronic respiratory conditions that also have exacerbations and may be confused with an 
asthma exacerbation. 
l Current treatment with maintenance oral steroids, given that treatment cannot be increased 
any further. 

N total at baseline: 

Intervention: 255 

Control: 251 

Important prognostic factors2: 

For example 

age ± SD: 

I: 10.7 years 

C: 10.7 years 

Sex:  

I: 61.2% male 

C: 58.8% male 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO-guided treatment escalated either anti-inflammatory medication (algorithm 1, elevated FeNO) or early intervention with bronchodilators (algorithm 2, FeNO not elevated). The response to increasing ICs or the addition of LABA or LTRA is known to be heterogeneous in children, and this algorithm uses FeNO to stratify treatment with early escalation of IC treatment or early addition of LABA and LTRA ‘add-on’ therapies, an approach that has been proven in a FeNO trial in pregnant mothers.  
l Inhaled corticosteroid was increased only once in controlled children with elevated FeNO, and only 
if their IC dose had not been increased since their asthma exacerbation and they were adherent. 
l In accordance with the BTS/SIGN 2016 guideline, 51 poor adherence was also considered (and 
discussed) before escalating treatment. Elevated FeNO is a result of airway inflammation but does 
not identify the cause of airway inflammation, and poor adherence is an important mechanism for 
persisting airway inflammation; therefore, adherence was part of the algorithm. Adherence was a 
continuous measure of a complex outcome, and a single cut-off value to prompt a discussion about 
adherence was arbitrary but needed. Poor adherence was defined as < 70%; an audit of children attending the asthma clinic in Aberdeen found that 48% had collected ≥ 70% of their IC treatment from their GP over 12 months (data from unpublished NHS Grampian audit by Dr Steve Turner). 
l Interpretation of FeNO on the first visit relied on population norms, rather like lung function or height, but at subsequent visits it was interpreted as a percentage change from the 
previous measurement. 
l Asthma control was defined as ACT score of ≥ 20. We know from two previous FeNO intervention 
trials and one observational study of children attending secondary care asthma clinics 56 that 75% of children with asthma have an ACT score of ≥ 20 at any one time. 

Describe control (treatment/procedure/test): 

Asthma treatment was guided by symptoms alone. 

Length of follow-up: 

12 months 

Loss-to-follow-up:

Intervention: 0 (0%) 

Reasons (describe) NA 

Control: 0 (0%) 

Reasons (describe) NA 

Incomplete outcome data:  

Intervention: 0 (0%) 

Reasons (describe) NA 

Control: 3 (1.2%) 

Reasons (describe) Missing primary outcome data 

Outcome measures and effect size (include 95%CI and p-value if available): 

Total number of exacerbations: 

I: 254 

C: 255 

Asthma Control Test: 

Median ACT score 

I: 22.0 (IQR; 18 – 24) 

C: 21.0 (IQR; 18 – 24) 

Author comments:  

In children with asthma being cared for in secondary care asthma clinics, the addition of FeNO to 
symptom-guided treatment did not reduce the OR for an asthma exacerbation. 

Verini, 2010 

Type of study: Randomised controlled trial 

Setting and country: Secondary asthma care, Italy 

Funding:

No information provided 

Conflict of interest: 

No information provided 

Inclusion criteria: 

all children had been admitted for allergic asthma and the diagnosis physician based 
according to ATS/ERS criteria. 

Exclusion criteria: 

None reported 

N total at baseline: 

Intervention: 32 

Control: 32 

Important prognostic factors: 

Age ± SD: 

I: 10.7 (SD 2.4) 

C: 11.3 (SD 2.1) 

Sex (% male) 

I: 56.3% 

C: 56.3% 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO + sympoms, lung function 

Describe control (treatment/procedure/test): 

Symptoms, lung function 

Length of follow-up: 

12 months 

Loss-to-follow-up:

All children completed the study  

Outcome measures and effect size (include 95%CI and p-value if available): 

Number of exacerbations per patient:

I: 0.83 (95% CI; 0.48 to 1.18) 

C: 1.85 (95% CI; 1.37 to 2.33) 

Voorend- Van Bergen, 2015 

Type of study: Randomised controlled trial 

Setting and country: Secondary asthma care, The Netherlands 

Funding:

Conflict of interest:

Inclusion criteria:

Aged 4 to 18 yrs, atopic asthma based on clinical symptoms, previous bronchodilator 
response > 9% increase in FEV1, previous airway hyper-responsiveness to methacholine. 

Exclusion criteria:

None reported 

N total at baseline:

Intervention: 92  

Control: 89 

Important prognostic factors:

Age ± SD: 

I: 10.3 yrs (SD 2.9) 

C: 10.1 9SD 3.2) 

Sex (% male) 

I: 67.4%  

C: 68.5% 

Groups comparable at baseline? 

Yes 

Describe intervention (treatment/procedure/test): 

FeNO + asthma control 

Describe control (treatment/procedure/test): 

Asthma control 

Length of follow-up:

Loss-to-follow-up:

All patients completed the intervention  

Outcome measures and effect size (include 95%CI and p-value if available): 

Asthma Control Test:

I: 22.4 (95% CI; 21.7 to 23.1) 

C: 21.4 (95% CI; 20.6 to 22.2) 

Quality of life:

Mean difference: 0.17 (95% CI; -0.09 to 0.43)