TABLE 2.
First author [ref.] | Country, funding details | Study design | Inclusion/exclusion criteria | Subjects analysed/ recruited n/N | Age years | Males n/N (%) | Spirometry | Severity | FeNO |
Smokers; Atopic; Medication use |
Smith [24] | New Zealand, Mixed funding# including equipment from Aerocrine |
RCT: single blind, single centre, placebo-controlled | Chronic 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. |
94/110 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 group | GP 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) |
Ex-smokers: 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, multicentre | Doctor'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 |
NR | GM (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 study | Mild 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 design | From 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: 39.4±9.5 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 |
Smokers: Intervention group: 14% Controlled asthma: 13% Partly controlled asthma: 16% Atopic: 322 (54%) out of 611 Medication use: LABA: 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, multicentre | Doctor'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.