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. 2016 Feb 4;47(3):751–768. doi: 10.1183/13993003.01882-2015

TABLE 5.

Exacerbations and inhaled corticosteroid (ICS) use in adult patients with or without fractional exhaled nitric oxide (FeNO)-guided management

First author [ref.] Time of outcome Definition of outcomes Subjects n Exacerbations per person year Between group comparison ICS use Between group difference#
Smith [24] 3–12 months optimisation (exacerbation rates not reported for this period) plus 12 months titration Minor: global daily asthma score of two on ≥2 consecutive days 94 Intervention group+: 0.36
Control group+: 0.75
p=0.24 Final value ICS use§
Intervention
 Baseline: mean  411 μg per day  (95% CI 344–478)
 End of phase 2:  mean 370 µg  per day  (95% CI 263–477)
Control
 Baseline: mean  491 μg per day  (95% CI 403–579)
 End of phase 2:  mean 641 µg  per day  (95% CI 526–756)
Mean difference −270 µg per day (95% CI −112– −430, p=0.003)
Major: global daily asthma score of three on ≥2 consecutive days (or in 1 day, in the context of a minor exacerbation)
Major exacerbation or medical emergency: global daily asthma score of four in 1 day
Intervention group+: 0.13
Control group+: 0.14
p=0.91
Any minor or major exacerbation Intervention group: 0.49 (95% CI 0.20–0.78)
Control group: 0.90 (95% CI 0.31–1.49)
−45.6% (95% CI −78.6–54.5, p=0.27) NS
Course of oral prednisone Intervention group: 0.48
Control group: 0.60
p=0.60
Shaw [25] 12 months Course of OCS or antibiotics 118 Intervention group: 0.33 (sd 0.69)
Control group: 0.42 (sd 0.79)
−21% (95% CI −57–43%, p=0.43) Final value ICS useƒ
Intervention: 557 µg
Control: 895 µg
Mean difference −338 µg per day (95% CI −640– −37 µg, p= 0.028)
Total used in study (AUC):
11% greater in FeNO group (95% CI −15–37%)
Syk [14] End-points analysed from visit 2 to visit 6 (2–4 weeks, 12 months) Moderate exacerbation: need to step-up controller treatment for at least 2 days with or without clinic visit
Prophylactic use before pollen season excluded
165 Intervention group: 0.1
Control group: 0.325
NR ICS use¶¶
Intervention
 Median 0  (IQR −400–400)
 Baseline: mean  604 (se 370)
 Final value:  586 (se 454)
Control
 0 (IQR −200– 200)
 Baseline: mean  626 (se 391)
 Final value:  540 (se 317)
0.945
Severe exacerbation ##: worsening requiring a course of OCS Intervention group: 0.113
Control group: 0.0875
NS
Moderate or severe exacerbation Intervention group: 0.22
Control group: 0.41
p=0.024
Calhoun [13] 9 months Exacerbation: unscheduled medical contact for increased asthma symptoms that results in the use of OCS, increased ICS or additional medication for asthma 229 Intervention group: 0.21 (97.5% CI 0.1–0.32)
Control group: 0.23 (97.5% CI 0.1–0.37)
“Did not differ” ICS use (unclear if mean over whole study or final value)ƒ
Intervention
 Mean 1617 µg·month−1
Control
 Mean 1610 µg·month−1
NR
Treatment failure defined as exacerbation or loss of control++ Intervention group: 0.27 (97.5% CI 0.14–0.39)
Control group: 0.43 (97.5% CI 0.23–0.64)
“Were not different”
Honkoop [16] 12 months Severe exacerbation: course of oral prednisone, hospitalisation and/or emergency department visit 611 Intervention group: 0.19 (95% CI 0.11–0.29)
Control group
Strict: 0.29 (95% CI 0.17–0.40)
Sufficient: 0.29 (95% CI 0.15–0.43)
Odds ratio versus
Strict: 0.64 (95% CI 0.27–1.56)
Sufficient: 0.79 (95% CI 0.32–1.92)
NR NR
Unscheduled healthcare utilisation: hospitalisation and/or emergency department visit Number of visits
Intervention group: 3
Controlled asthma: strict 5
Partly controlled asthma: sufficient 9
Odds ratio versus
Strict: 0.61 (95% CI 0.14–2.58)
Sufficient: 0.37 (95% CI 0.10–1.38)

NS: nonsignificant difference; OCS: oral corticosteroid; AUC: area under curve; NR: not reported; IQR: interquartile range; PEFR: peak expiratory flow rate. #: Expressed as intervention minus control (negative values indicate lower FeNO). : Asthma scores were as follows. 0 (stable): morning PEFR >75% of best PEFR in 14-day run-in period without deterioration in any symptom scores. 1 (mildly unstable): one or more of the following a) bronchodilator use on two or more occasions in 24 h more than the rounded mean number of occasions during the run-in period; b) increase in symptom score of 1 point or more as compared with rounded mean during run-in period; c) onset of or increase in nocturnal waking by one or more times in the previous seven nights more than rounded mean number of times during the run-in period, or morning PEFR of 61–75% without deterioration in any of the above categories. 2 (minor deterioration): morning PEFR of 61–75% of best PEFR during the run-in period and one or more criteria for an asthma score of 1; or morning PEFR of 41–60% without deterioration in any criteria for an asthma score of 1. 3 (major deterioration): morning PEFR of 41–60% of best PEFR during run-in period and one or more criteria for an asthma score of 1. 4 (major exacerbation or medical emergency): morning PEFR of 40% or less than best PEFR during run-in period regardless of symptoms, or attendance at clinician's office or emergency department because of severe asthma. +: Estimated off graph. §: Fluticasone or the equivalent. ƒ: Beclomethasone diproprionate or equivalent. ##: American Thoracic Society/European Respiratory Society Task Force Criteria 2009. ¶¶: Budesonide equivalent. ++: At-home measurements: 1) Pre-bronchodilator AM peak expiratory flow (PEF) of <65% of baseline on two consecutive mornings, scheduled measurements. 2) Post-bronchodilator PEF of <80% of baseline despite 60 min of rescue β-agonist treatment. 3) Post-bronchodilator PEF may be taken at any time of day, an increase in albuterol use of more than 8 puffs per 24 h over baseline use for a period of 48 h, or more than 16 puffs per 24 h for more than 48 h. In-clinic measurements: 1) Pre-bronchodilator forced expiratory volume in 1 s (FEV1) values on two consecutive sets of spirometric determinations, measured 24–72 h apart, that are <80% of the baseline pre-bronchodilator value (baseline value for adherence period: FEV1 value at visit 3; baseline for randomisation period: FEV1 value at visit 4). All participants found to have an FEV1 of <80% of baseline at any centre visit but who are not considered to meet treatment failure or exacerbation criteria must be seen again within 72 h to have FEV1 measured. 2) Physician judgment for patient safety. 3) Patient dissatisfaction with asthma control achieved by study regimen. 4) Requirement for open-label ICSs or another (nonsystemic corticosteroid) new asthma medication (e.g. montelukast) without the addition of systemic corticosteroids.