Study and population characteristics

First author  [ref.]Country, funding  detailsStudy designInclusion/exclusion criteriaSubjects analysed/  recruited n/NAge yearsMales n/N (%)SpirometrySeverityFeNOSmokers;
Medication use
Smith [24]New Zealand,
Mixed funding# including equipment from Aerocrine
RCT: single blind, single centre, placebo-controlledChronic asthma [27] managed in primary care; regular ICS for ≥6 months, no dose change in previous 6 weeks. If could not tolerate removal of LABA during run-in allowed to participate if could tolerate a fixed dose.
Exclusions: ≥4 courses oral prednisone in previous 12 months; admission to hospital for asthma in previous 6 months; ever admitted to IC for asthma; smokers (current or ex-) with a history of >10 pack-years.
WBR: 13;
Intervention group: 46/48
Control group: 48/49
Mean age 44.8 (range 12–73)41/110 (37.3%)Mean (range) FEV1 % pred  Intervention  group:  86.4 (80.6–92.2)
 Control  group: 83.1  (76.5–89.7)
Mean (95% CI) symptom score  Intervention  group: 0.6  (0.4–0.8)
 Control  group:  0.8(0.6–1.1)
GM (95% CI) FeNO 250 mL+ Intervention  group:  7.8 (6.6–9.3)
 Control group:  6.4 (5.5–7.5)
Smokers: None
Atopic: NR
Medication use: Bronchodilator use,  mean per day over  the previous  7 days (95% CI)
 Intervention group:  0.5 (0.2–0.8)
 Control group:  0.6 (0.3–0.8)
 ICS use NR
Shaw  [25]UK,
Asthma UK grant, speakers fees reported, but not from Aerocrine
RCT: single blind, parallel groupGP diagnosis of asthma with ≥1 prescription for anti-asthma medication in the past 12 months. Current nonsmokers with a past smoking history of <10 pack-years.
Exclusions: poorly compliant; those with a severe asthma exacerbation (needing prednisolone) in the previous 4 weeks.
118 (ITT LOCF)/119
WBR: 1
Intervention group: 58
Control group: 60
Adults >18 years
Mean age NR
54/118 (46%)Mean±sd FEV1 % pred  Intervention  group:  81.4±20.9
 Control group:  84.9±20.1
Mean±sd FEV1/FVC
 Intervention  group:  71±10.7
 Control group:  72±9.9
Mean±sd Juniper score  Intervention  group:  1.32±0.65
 Control  group:  1.26±0.75
GM (68% CI) log FeNO
 Intervention  group: 29.2  (14.0–61.0)
 Control  group: 31.2  (13.3–73.1)
 Intervention  group: 22%
 Control group: 25%
Atopic:78 (66.1%) out of 118
Medication use:
Mean±sd ICS daily dose
 Intervention group:  697±708 µg
 Control group:  652±533 μg
Syk [14]Sweden,
Mixed funding#, some from Aerocrine
RCT: open label, parallel group, multicentreDoctor's diagnosis of asthma and ICS treatment for ≥ 6 months, IgE sensitisation to at least one major airborne perennial allergen. Nonsmokers for ≥1 year and with smoking history of <10 pack-years. Patients all had mild to moderate asthma.165/187
WBR: 6
Intervention group: 87/93
Control group: 78/88
Adults (18–64 years)
Mean±sd 41±12.4
94/181 (51.9%)Mean±sd FEV1 % pred
 Intervention  group: 84.3±14.1
 Control group:  83.7±12.5
Mean±sd FEV1/FVC
 Intervention  group: 0.78±0.08
 Control group:  0.79±0.08
NRGM (95% CI) FeNO ppb
 Intervention  group: 22.0  (19.3–25.2)
 Control  group: 21.6  (18.7–25.0)
Smokers: None
Atopic:165 (100%) out of 165
Medication use:
Median (IQR) budesonide equivalent ICS dose 400 (400–800) µg·day−1
LABA before study entry 54 (30.0%) out of 180
Calhoun  [13]USA,
 Mixed funding#, equipment from Aerocrine
RCT: multiply-blinded, multicentre studyMild to moderate asthmatics, well controlled persistent asthma with compliance rates ≥75%, who could tolerate treatment of two puffs twice daily of beclomethasone HFA (40 μg·puff−1) during the 2 week run-in period.363 recruited to trial
WBR: 21
Intervention group: 115/115§
Control group:  114/114ƒ
Other study arm (not included in review): 113/113
Mean±sd: Intervention  group:  34.8±11.3;
 Control group:  34.2±11.9
75/229 (32.8%)Mean±sd FEV1 % pred
 Intervention  group:  86.3±10.4
 Control group:  87.7±12.1
Mean±sd ACQ score  Intervention  group:  0.79±0.54
 Control group:  0.72±0.50
Mean±sd AQLQ score
 Intervention  group:  6.16±0.77
 Control group:  6.27± 0.76
Mean±sd ASUI score
 Intervention  group:  0.88±0.12
 Control group:  0.90±0.10
GM±sd FeNO ppb
 Intervention  group:  18.88±0.66
 Control group:  21.38±0.62
Smokers: NR
Atopic: 196 (85.6%) out of 229
Medication use:
Albuterol rescue use median (IQR)
 Intervention  group:  0.07 (0–0.43)
 Control group:  0.04 (0–0.29)
Honkoop [16]The Netherlands,
Mix of non-commercial grants and funding from Aerocrine
RCT; cluster designFrom protocol: doctor's diagnosis of asthma; who need ICS as controller medication (step 2–4 GINA guidelines); ICS ≥3 months in the previous year; no exacerbation of asthma within 1 month before entry. Exclusions: daily or alternate day oral corticosteroid therapy for at least 1 month before entering into the study.611 randomised
Other data NR
Intervention group: 189/205
Controlled asthma: 219/232
Partly controlled asthma: 203/210
Mean±sd age:
Intervention group: 39.5±9.3
Controlled asthma: 38.9±9.3
Partly controlled asthma: 39.9±9.8
190/611 (31%)
Intervention group: 27.7%
Controlled asthma: 31.6%
Partly controlled asthma: 34.2%
Mean±sd FEV1 % pred
 Intervention  group:  93.1±17.0
 Controlled  asthma:  92.4±17.2
 Partly controlled  asthma:  93.0±17.0
Mean±sd ACQ score
 Intervention  group:  0.99±0.73
 Controlled  asthma:  1.08±0.84
 Partly  controlled  asthma:  0.93±0.80
Mean±sd FeNO ppb
 Intervention  group:  24.5±21.7
 Controlled  asthma:  27.3±30.4
 Partly  controlled  asthma:  24.7±29.8
 Intervention  group: 14%
 Controlled  asthma: 13%
 Partly controlled  asthma: 16%
Atopic: 322 (54%) out of 611
Medication use:
 Intervention  group: 47%
 Controlled  asthma: 49%
 Partly controlled  asthma: 52%
Mean±sd beclomethasone equivalent dose:
 Intervention  group: 853±642 μg
 Controlled  asthma:  831±701 μg
 Partly controlled  asthma: 825±639 μg
Powell [26]Australia,
Mixed funding, lecture fees from Aerocrine Powell [26]
RCT: double-blind, parallel group, multicentreDoctor's diagnosis confirmed by respiratory physician's diagnosis of asthma. Nonsmoking pregnant women between 12 and 20 weeks gestation with doctor's diagnosis of asthma and who were using inhaled therapy in last year.203/242 WBR: 22
Intervention group: 100/111
Control group: 103/109
Pregnant adults >18 years
Mean±sd age 28±5.4
0/220 (0%)Mean (95% CI) FEV1 % pred
 Intervention  group: 95.1  (92.8–97. 4)
 Control  group: 96.1  (93.5–98.7)
Mean (95% CI) FEV1/FVC
 Intervention  group: 79.7  (75.4–78.0)
 Control  group: 80.63  (79.3–82.0)0/220 (0%)
Median (IQR) AQLQ-M
 Intervention  group: 0.8  (0.4–1.5)
 Control group:  1.0 (0.5–1.6)
Mean ACQ score (read off graph)
 Intervention  group: 0.98
 Control  group: 1.01
Median (IQR) FeNO ppb
 Intervention  group: 13.9  (6.6–32.0)
 Control  group: 13.1  (7.5–24.0)
Ex-smokers: 80 (39.4%) out of 203
Atopic: 156 (75.7%) out of 206
Medication use:
Median (IQR) days β2-agonist in the past week
 Intervention group:  1.0 (0–5)
 Control group:  2.0 (0–6)
ICS users
 Intervention group:  46 (41.4%) out of 111
 Control group:  47 (43.1%) out of 109
Median (IQR) BDP equivalent ICS dose (µg per day)
 Intervention group:  800 (400–800)
 Control group: 800  (400–1600)
  • FeNO: fractional exhaled nitric oxide; RCT: randomised controlled trial; ICS: inhaled corticosteroid; LABA: long-acting β2-agonist; IC: intensive care; WBR: withdrew before randomisation; FEV1: forced expiratory volume in 1 s; GM: geometric mean; NR: not reported; GP: general practitioner; ITT: intention to treat; LOCF: last observation carried forward; FVC: forced vital capacity; IQR: interquartile range; HFA: hydrofluoroalkanes; ACQ: Asthma Control Questionnaire; AQLQ: Asthma Quality of Life Questionnaire; ASUI: Asthma Symptom Utility Index; GINA: Global Initiative for Asthma; AQLQ-M; Asthma Quality of Life Questionnaire-Marks; BDP: beclomethasone dipropionate. #: mix of industry and non-industry funding, e.g. research council grants. : daily score over the previous 7 days. Asthma symptoms were scored for each 24-h period as follows: 0, indicated no symptoms; 1, symptoms for one short period; 2, symptoms for two or more short periods; 3, symptoms most of the time that did not affect normal daily activities; 4, symptoms most of the time that did affect normal daily activities; and 5, symptoms so severe as to disrupt daily activities. +: FeNO measured at 250 mL·s−1 gives lower values than FeNO at 50 mL·s−1. §: 37 withdrew, imputation method NR. ƒ: 13 withdrew, imputation method NR.