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Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
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Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Forest plot of comparison:1 Exacerbations, outcome: 1.1 Number of subjects who had one or more exacerbations over the study period.
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Figure 2

Forest plot of comparison:1 Exacerbations, outcome: 1.1 Number of subjects who had one or more exacerbations over the study period.

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In the symptom control group 30 people out of 100 had one of more exacerbations over the study period (Adults) over 52 weeks, compared to 27 (95% CI 12 to 51) out of 100 for the FeNO group.
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Figure 3

In the symptom control group 30 people out of 100 had one of more exacerbations over the study period (Adults) over 52 weeks, compared to 27 (95% CI 12 to 51) out of 100 for the FeNO group.

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Forest plot of comparison: 1 Exacerbations, outcome: 1.2 Exacerbation rates.
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Figure 4

Forest plot of comparison: 1 Exacerbations, outcome: 1.2 Exacerbation rates.

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Forest plot of comparison: 2 Objective data, outcome: 2.1 FEV1 % predicted at final visit [%Predicted].
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Figure 5

Forest plot of comparison: 2 Objective data, outcome: 2.1 FEV1 % predicted at final visit [%Predicted].

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Forest plot of comparison: 2 Objective data, outcome: 2.2 FeNO at final visit.
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Figure 6

Forest plot of comparison: 2 Objective data, outcome: 2.2 FeNO at final visit.

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Forest plot of comparison: 3 Symptom based data, outcome: 3.1 Symptom score.
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Figure 7

Forest plot of comparison: 3 Symptom based data, outcome: 3.1 Symptom score.

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Forest plot of comparison: 4 Medications, outcome: 4.4 ICS dose at final visit.
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Figure 8

Forest plot of comparison: 4 Medications, outcome: 4.4 ICS dose at final visit.

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In the symptom control group 36 people out of 100 had one of more exacerbations over the study period (children) over 26‐52 weeks, compared to 30 (95% CI 24 to 36) out of 100 for the FeNO treatment group.
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Figure 9

In the symptom control group 36 people out of 100 had one of more exacerbations over the study period (children) over 26‐52 weeks, compared to 30 (95% CI 24 to 36) out of 100 for the FeNO treatment group.

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Forest plot of comparison: 2 Objective data, outcome: 2.3 Geometric mean change in FeNO from baseline (control/FeNO level).
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Figure 10

Forest plot of comparison: 2 Objective data, outcome: 2.3 Geometric mean change in FeNO from baseline (control/FeNO level).

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Comparison 1 Exacerbations, Outcome 1 Number of subjects who had one or more exacerbations over the study period.
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Analysis 1.1

Comparison 1 Exacerbations, Outcome 1 Number of subjects who had one or more exacerbations over the study period.

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Comparison 1 Exacerbations, Outcome 2 Mean number of exacerbations per 52 weeks.
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Analysis 1.2

Comparison 1 Exacerbations, Outcome 2 Mean number of exacerbations per 52 weeks.

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Comparison 2 Objective data, Outcome 1 FEV1 % predicted at final visit.
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Analysis 2.1

Comparison 2 Objective data, Outcome 1 FEV1 % predicted at final visit.

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Comparison 2 Objective data, Outcome 2 FeNO at final visit.
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Analysis 2.2

Comparison 2 Objective data, Outcome 2 FeNO at final visit.

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Comparison 2 Objective data, Outcome 3 Geometric mean change in FeNO from baseline (control/FeNO level).
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Analysis 2.3

Comparison 2 Objective data, Outcome 3 Geometric mean change in FeNO from baseline (control/FeNO level).

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Comparison 3 Symptom based data, Outcome 1 Symptom score.
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Analysis 3.1

Comparison 3 Symptom based data, Outcome 1 Symptom score.

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Comparison 4 Medications, Outcome 1 ICS dose at final visit.
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Analysis 4.1

Comparison 4 Medications, Outcome 1 ICS dose at final visit.

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Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

Patient or population: Adults and children with asthma

Settings:

Intervention: Tailored intervention based on FeNO

Comparison: Intervention based on clinical symptoms

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Intervention based on clinical symptoms

Tailored intervention based on FeNO

Number of subjects who had one or more exacerbations over the study period in adults
(follow‐up: 52 weeks)

30 per 100

27 per 100
(12 to 51)

OR 0.85
(0.3 to 2.43)

197
(2)

⊕⊕⊕⊝
moderate1

Number of subjects who had one or more exacerbations over the study period in children and adolescents
(follow‐up: 26‐52 weeks)

36 per 100

30 per 100
(24 to 36)

OR 0.75
(0.55 to 1.01)

782
(3)

⊕⊕⊕⊝
moderate2,3,4

Number of exacerbations per 52 weeks in adults
(follow‐up: mean 52 weeks)

The mean number of exacerbations per 52 weeks in adults in the control groups was
0.66

The mean Number of exacerbations per 52 weeks in adults in the intervention groups was
0.14 lower
(0.41 lower to 0.12 higher)

197
(2)

⊕⊕⊕⊝
moderate1

Number of exacerbations per 52 weeks in children and adolescents
(follow‐up: mean 52 weeks)

The mean number of exacerbations per 52 weeks in children and adolescents in the control groups was
0.84

The mean Number of exacerbations per 52 weeks in children and adolescents in the intervention groups was
0.18 lower
(0.42 lower to 0.06 higher)

546
(1)

⊕⊕⊕⊝
moderate3,4

ICS dose at final visit in adults
(follow‐up: 52 weeks)

The mean ics dose at final visit in adults in the control groups was
1088 mcg/day (budesonide equivalent)

The mean ICS dose at final visit in adults in the intervention groups was
450 lower
(677 to 223 lower)

197
(2)

⊕⊕⊕⊝
moderate5

ICS dose at final visit in children and adolescents
(follow‐up: 26‐52 weeks)

The mean ics dose at final visit in children and adolescents in the control groups was
804 mcg/day (budesonide equivalent)

The mean ICS dose at final visit in children and adolescents in the intervention groups was
140 higher
(29 to 251 higher)

777
(3)

⊕⊕⊝⊝
low3,6,7

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; OR: Odds ratio;

GRADE Working Group grades of evidance
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Confidence intervals are wide and include clinically important benefit and harm

2 One study (deJongste 2008) design was open‐label which may have introduced bias.

3 Studies reported technical difficulties with FeNO analysers as reported in risk of bias table.

4 Medication increased prior to commencement of study.

5 In one study the overall dose of ICS was higher with FeNO based interventions even though the final ICS dose was lower

6 One study presented in these results was single blinded with intervention arm analysing FeNO only.

7 Final inhaled corticosteroid doses were quite varied. With one study having particularly high doses.

Figuras y tablas -
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Comparison 1. Exacerbations

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of subjects who had one or more exacerbations over the study period Show forest plot

5

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Adults

2

197

Odds Ratio (M‐H, Random, 95% CI)

0.85 [0.30, 2.43]

1.2 Children and adolescents

3

782

Odds Ratio (M‐H, Random, 95% CI)

0.75 [0.55, 1.01]

2 Mean number of exacerbations per 52 weeks Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 Adults

2

197

Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.41, 0.12]

2.2 Children and adolescents

1

546

Mean Difference (IV, Fixed, 95% CI)

‐0.18 [‐0.42, 0.06]
Figuras y tablas -
Comparison 1. Exacerbations
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Comparison 2. Objective data

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 FEV1 % predicted at final visit Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Adults

1

94

Mean Difference (IV, Fixed, 95% CI)

3.80 [‐4.50, 12.10]

1.2 Children and adolescents

3

778

Mean Difference (IV, Fixed, 95% CI)

1.81 [‐0.64, 4.25]

2 FeNO at final visit Show forest plot

4

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 Adults

2

197

Std. Mean Difference (IV, Fixed, 95% CI)

0.03 [‐0.25, 0.31]

2.2 Children and adolescents

2

635

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.02 [‐0.18, 0.13]

3 Geometric mean change in FeNO from baseline (control/FeNO level) Show forest plot

2

Geometric mean (Fixed, 95% CI)

1.17 [0.98, 1.39]

3.1 Children and adolescents

2

Geometric mean (Fixed, 95% CI)

1.17 [0.98, 1.39]
Figuras y tablas -
Comparison 2. Objective data
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Comparison 3. Symptom based data

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Symptom score Show forest plot

4

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Adults

2

197

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.42, 0.14]

1.2 Children and adolescents

2

631

Std. Mean Difference (IV, Fixed, 95% CI)

0.04 [‐0.11, 0.20]
Figuras y tablas -
Comparison 3. Symptom based data
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Comparison 4. Medications

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 ICS dose at final visit Show forest plot

5

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Adults

2

197

Mean Difference (IV, Fixed, 95% CI)

‐450.03 [‐676.73, ‐223.34]

1.2 Children and adolescents

3

777

Mean Difference (IV, Fixed, 95% CI)

140.18 [28.94, 251.43]
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Comparison 4. Medications
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