The Airsonett temperature-controlled laminar airflow device for persistent allergic asthma

Study component

Description

Objectives/hypotheses

To determine whether environmental control using the Airsonett device could improve the quality of life of patients with persistent atopic asthma.

Study design

Phase III, multicentre, randomised, placebo‑controlled, parallel‑group trial. Follow‑up assessment at 1, 3, 6, 9 and 12 months of the treatment.

Setting

19 European asthma clinics.

Inclusion/exclusion criteria

Inclusion criteria were: a physician's diagnosis of asthma ≥1 year prior to study; age 7–70 years; AQLQ (mini‑AQLQ for aged ≥12 years and PAQLQ for aged <12 years) score ≤5.5 at inclusion; allergic sensitisation to a pet allergen (cat or dog) or house dust mite demonstrated by specific IgE level ≥0.70 kU/litre or positive skin prick test (weal diameter ≥histamine control); daily inhaled corticosteroid ≥200 micrograms/day budesonide/beclomethasone or ≥100 micrograms/day fluticasone for last 6 months; and features of partly controlled asthma according to GINA 2006.

Exclusion criteria were: current active or passive cigarette smoke exposure; inclusion in another allergen avoidance programme or drug trial; treatment with allergen immunotherapy or omalizumab in previous 2 years (1 year for children); inhaled corticosteroid dose >1200 micrograms/day budesonide/beclomethasone or >1000 micrograms/day fluticasone. A history of frequent severe asthma exacerbations was not an inclusion criterion for the study.

Primary outcomes

Quality of life assessed with the mini‑AQLQ (or with the PAQLQ in children ≤11 years). A change of 0.5 is considered clinically significant, and the primary outcome analysed was the proportion of patients with a significant increase in mini‑AQLQ or PAQLQ score ('responders') after 1 year of treatment.

Statistical methods

The intention‑to‑treat population in this study was defined as all patients who had ≥1 day of device treatment following randomisation. Last observation carried forward was used for missing data. Per protocol analyses excluded patients with major protocol violations or documented treatment compliance <80%. The host country, patient gender, years since asthma diagnosis, GINA treatment step and AQLQ at baseline were adjusted. ANCOVA analyses were used for continuous data and logistic regression for binary data. The sample size was calculated based on a minimum difference of 20% between treatment groups in the proportion of responders (increase in AQLQ ≥0.5 points over the 12‑month intervention), and a responder rate of 20% in the placebo group. Subgroup analyses were undertaken by age and asthma treatment intensity at baseline.

Participants

312 patients aged 7–70 years with inadequately controlled persistent atopic asthma who met the inclusion criteria.

Results

In all patients who had at least 1 day of treatment with the device, there was a significantly higher proportion with an improved quality of life (measured as an increase of ≥0.5 points in AQLQ score) after 1 year of active Airsonett treatment compared with placebo (OR 1.92, 95% CI 1.09 to 3.38; p=0.02). There was a similarly significant difference in the following patient groups: those aged <12 years (OR 5.57, 95% CI 1.13 to 27.48; p=0.02); those with high treatment intensity (GINA 4) at baseline (OR 2.42, 95% CI 1.05 to 5.60; p=0.04); those with poor symptom control (ACT <18) at baseline (OR 3.45, 95% CI 1.66 to 7.2; p<0.001); and those with both GINA 4 and ACT<18 at baseline (OR 4.47, 95% CI 1.48 to 15.19; p=0.009).

The difference was not significant in patients aged ≥12 years on which the study was powered.

When measured as an increase of ≥1 point in AQLQ score, the improvement with the active Airsonett device compared with placebo was only significant in those with ACT<18 (OR 2.78, 95% CI 1.36 to 5.67; p=0.005) and those with both ACT<18 and GINA 4 (OR 8.81, 95% CI 2.14 to 36.32; p=0.003).

No statistically significant difference was demonstrated between active and placebo groups in standard asthma medication use and asthma exacerbation.

No treatment‑related adverse events were observed.

Conclusions

The Airsonett device may be an effective treatment option for patients with inadequately controlled persistent allergic asthma to improve quality of life and airway inflammation.

Abbreviations: ACT, Asthma Control Test; AQLQ, Asthma Quality of Life Questionnaire; ANCOVA, analysis of covariance; CI, confidence interval; GINA, Global Initiative for Asthma; FENO, fractional exhaled nitric oxide; IgE, immunoglobulin E; kU/L, kilo‑units of antibody per litre; OR, odds ratio; PAQLQ, paediatric asthma quality of life questionnaire; SE, standard error; SD, standard deviation.

TLA

Placebo

Analysis

Randomised

n=207

n=105

Primary outcome

Proportion of patients with an increase of ≥0.5 points in AQLQ score after 1 year of treatment

76%

(143/189)

61%

(56/92)

Difference=14.8%

95% CI 3.1 to 26.5

OR=1.92

95% CI 1.09 to 3.38

p=0.02

77%

(106/136)

61%

(40/61)

Difference=16.6%

95% CI 3 to 30

OR=2.22

95% CI 1.11 to 4.40

p=0.02

80%

(37/46)

64%

(14/22)

Difference=16.8%

95% CI 8% to 38%

OR=5.57

95% CI 1.13 to 27.48

p=0.02

74%

(106/134)

60%

(42/70)

Difference=14.1%

95% CI 0.6 to 27.7

OR=1.89

95% CI 0.98 to 3.65

p=0.059

77%

(63/82)

62%

(29/47)

Difference=15.1%

95% CI 2% to 31%

OR=2.42

95% CI 1.05 to 5.60

p=0.04

74%

(93/125)

52%

(30/58)

Difference=22.7%

95% CI 8% to 38%

OR=3.45

95% CI 1.66 to 7.2

p<0.001

75%

(43/57)

50%

(15/30)

Difference=25.4%

95% CI 4% to 47%

OR=4.74

95% CI 1.48 to 15.19

p=0.009

Proportion of patients with an increase of ≥1 point in AQLQ score after 1 year of treatment

63%

(119/189)

51%

(47/92)

Difference=14.8%

95% CI 3 to 26

OR=1.58

95% CI 0.93 to 2.65

p=0.09

65%

(89/136)

50%

(33/66)

Difference=15.4%

95% CI 1% to 30%

OR=1.85

95% CI 0.97 to 3.53

p=0.06

72% (33/64)

50% (11/22)

Difference=21.7%

95% CI −3% to 46%

OR=4.40

95% CI 0.99 to 19.57

p=0.05

60%

(86/143)

51%

(36/70)

Difference=8.7%

95% CI −5 to 23

OR=1.37

95% CI 0.74 to 2.52

p=0.31

62%

(51/82)

51%

(24/47)

Difference=15.1%

95% CI 2% to 31%

OR=1.96

95% CI 0.87 to 4.40

p=0.10

62%

(77/125)

41%

(24/58)

Difference=20.2%

95% CI 5% to 35%

OR=2.78

95% CI 1.36 to 5.67

p=0.005

65%

(37/57)

37%

(11/30)

Difference=28.2%

95% CI 7% to 49%

OR=8.81

95% CI 2.14 to 36.32

p=0.003

Selected secondary outcomes

Change from baseline in AQLQ score after 3 months of treatment ^d

n=189

n=92

Difference=0.09

p=0.44

n=125

n=58

Difference=0.21

p=0.12

n=103

n=50

Difference=0.84

p=0.01

n=57

n=30

Difference=0.64

p=0.01

Change from baseline in AQLQ score after 12 months of treatment

n=189

n=92

Difference=0.21

p=0.12

n=125

n=58

Difference=0.52

p=0.005

n=103

n=50

Difference=0.88

p=0.001

n=57

n=30

Difference=0.79

p=0.002

Changes in the symptom domain of AQLQ score

1.3 (1.23)

0.99 (1.38)

Difference=0.31

95% CI 0.01 to 0.61

p=0.04

1.34 (1.14)

0.96 (1.34)

Difference=0.36

95% CI 0.01 to 0.71

p=0.04

1.46 (1.36)

0.93 (1.49)

Difference=0.38

95% CI −0.34 to 1.10

p=0.29

1.27 (1.18)

1.01 (1.36)

Difference=0.28

95% CI −0.62 to 0.05

p=0.10

1.45 (1.14)

1.00 (1.44)

Difference=0.47

95% CI 0.03 to 0.9

p=0.04

1.41 (1.24)

0.95 (1.60)

Difference=0.58

95% CI 0.17 to 0.98

p=0.006

1.45 (1.15)

0.86 (1.70)

Difference=0.70

95% CI 0.13 to 1.26

p=0.02

Use of standard pharmaceutical treatment

Baseline:

0.72 (0.46);

3–12 months:

0.74 (0.53)

Baseline:

0.77 (0.47);

3–12 months:

0.77 (0.49)

Difference=0.03 (0.04)

p=0.38

Baseline:

0.20 (0.40);

3–12 months:

0.19 (0.25)

Baseline:

0.22 (0.39);

3–12 months:

0.22 (0.41)

Difference=0.02 (0.02)

p=0.39

Baseline:

0.51 (0.51);

3–12 months:

0.52 (0.48)

Baseline:

0.53 (0.48);

3–12 months:

0.55 (0.47)

Difference=−0.01 (0.03)

p=0.77

Baseline:

0.29 (0.46);

3–12 months:

0.31 (0.53)

Baseline:

0.24 (0.41);

3–12 months:

0.28 (0.43)

Difference=−0.00 (0.02)

p=0.88

13.2% (25/189)

12.9% (12/93)

p=0.94

0.17 (0.53)

0.24 (0.83)

p=0.50

Asthma exacerbations (mean)

0.17

0.24

p=0.50

0.18

0.34

p=0.28

0.24

0.4

p=0.23

0.23

0.57

p=0.07

Changes in FENO from baseline

−4.88

95% CI −9.3 to −0.4

2.82

95% CI −3.5 to 9.2

Difference=−7.13

95% CI −13.6 to −0.7

p=0.03

−27.3

95% CI −37.6 to −17.0

−2.53

95% CI −24.0 to 18.9

Difference=−29.7

95% CI −47.2 to −12.2

p=0.001

Safety

n=189

n=93

Not applicable

Patients reporting serious adverse events (none treatment‑related)

17% (32/189)

15% (14/93)

Reported as no significant difference

Upper respiratory tract infection ^f

61.9% (117/189)

66.7% (62/93)

Not reported

Upper respiratory tract symptoms ^f

28.6%

(54/189)

23.7%

(22/93)

Not reported

General symptoms ^f

22.8%

(43/189)

20.4%

(19/93)

Not reported

Abbreviations: ACT, Asthma Control Test; AQLQ, Asthma Quality of Life Questionnaire; CI, confidence interval; GINA, Global Initiative for Asthma; FENO, fractional exhaled nitric oxide; ICS, inhaled corticosteroid; ITT, intention to treat; n, number of patients; p, p value; PAQLQ, Paediatric Asthma Quality of Life Questionnaire; RR, relative risk; SE, standard error; SD, standard deviation; TLA, temperature‑controlled laminar airflow.

^a ITT in this study was defined as the analysis that consists of all randomised patients who have had at least 1 treatment day with the intervention.

^b Per protocol analysis: consists of all randomised patients who have used the intervention minimum 80% of the 1-year study period, as recorded on a data chip in the machine and 80% of the last 3 weeks prior to visit month 3 and 12.

^c The study was powered on the patients aged ≥12 years for the analysis of treatment response rate.

^d Data from the manufacturer's report.

^e All medication does are expressed as mean (SD) proportion of the 'defined daily dose'; difference = mean (SE) of [(active during 3–12 months) – (active at baseline)] – [(placebo during 3–12 months) – (placebo at baseline)].

^f Adverse events affecting ≥5% of patients on ≥1 occasion.

Description

Objectives/hypotheses

To examine the treatment with the Airsonett device in teenagers and young adults with mild to moderate allergic asthma during night sleep. The researchers hypothesised that the decreased allergen exposure during the night would have an effect on bronchial inflammation and quality of life.

Study design

Randomised, 2‑centre, double‑blind, placebo‑controlled crossover trial. (No details on the randomisation and blinding methods were reported). A total of 22 patients entered the trial to receive either active or placebo treatment for 10 weeks (number of patients randomised to each group was not reported), followed by a 2‑week washout phase in which the patients did not use the device. Following the washout period patients were switched to the other treatment group for another 10 weeks. Clinical assessments including FENO, spirometry, physical examination and urine sample were conducted at baseline (week 0) and the end of the study (week 22). FENO and spirometry assessments were conducted at visit weeks 5, 10, 12 and 17 during the study.

Setting

Sweden. The device was placed in the patients' bedroom and used during night‑time sleep.

Inclusion/exclusion criteria

Inclusion criteria: perennial allergic asthmatic adolescents and young adults, 12–33 years of age, taking a daily maintenance dose of at least ≥400 mg/day of budesonide or 200 mg/day of fluticasone and short‑acting beta 2‑agonist treatment on less than 4 days per week. Asthma diagnosis was confirmed by lung function testing and/or bronchial provocation test (metacholine or cold dry air).

Exclusion criteria: current active or passive cigarette smoke exposure; inclusion in another allergen avoidance programme or drug trial; treatment with allergen immunotherapy or omalizumab in previous 2 years (1 year for children); inhaled corticosteroid dose >1200 mg/day budesonide/beclomethasone or >1000 mg/day fluticasone; a history of frequent severe asthma exacerbations.

Primary outcomes

The change in quality of life between active versus placebo treatment assessed on the mini‑AQLQ. The change in quality of life as the difference in the mini‑AQLQ summary score was defined as from start to end (10 weeks) of each study period. Mini‑AQLQ scores range from 0 to 7, where 7 is no symptoms. A change of 0.5 was considered clinically significant.

Statistical methods

The study hypothesis was tested by examining the difference in change in mini‑AQLQ score, FENO and spirometry during active versus placebo treatment periods. All patients who completed measurements at both baseline and end point of each treatment period were analysed. Results were summarised by treatment periods as mean scores with confidence interval. Changes from baseline within each treatment period (active or placebo) were analysed using paired t‑tests. An ANOVA model was used to compare the changes (measured as least square mean with confidence interval) between the 2 treatment periods. The country and baseline scores were varieties. It was calculated that a sample size of 20 would have a 62% power to detect a 30% improvement of mini‑AQLQ for active treatment compared with placebo, with the error set at 0.05 and SD based on a previous pilot study.

Participants

28 children and young adults (aged 12 to 33 years) with mild to moderate allergic asthma who fulfilled the inclusion criteria.

Results

22 patients completed measurements at baseline and endpoint of both treatment periods. Active treatment resulted in an improved mini‑AQLQ score that was statistically significant compared with placebo (mean score 0.54, p<0.05, n=20). An effect on bronchial inflammation was detected with significantly lower FENO values during the active treatment period (mean −6.95 ppb, p<0.05, n=22). Both effects were evident after 5 weeks. No statistically significant changes in lung function were observed.

Conclusions

Laminar airflow of purified air directed to the breathing zone during night sleep, as provided by the Airsonett device, may have a positive effect on bronchial inflammation in patients with perennial allergic asthma.

Abbreviations: ANOVA, analysis of variance; AQLQ, Asthma Quality of Life Questionnaire; CI, confidence interval; FENO, fractional exhaled nitric oxide; n, number of patients; SD, standard deviation.

Active TLA

Placebo

Analysis

Randomised

n=22

n=22

Efficacy

n=22

n=22

Primary outcome: mean mini‑AQLQ score

Baseline:

5.36

95% CI 4.82 to 5.90

End:

5.92

95% CI 5.56 to 6.28

Baseline:

5.69

95% CI 5.23 to 6.14

End:

5.70

95% CI 5.19 to 6.22)

Difference in change, mean (SEM):

0.54

(0.28)

p<0.05

(n=20)

Selected secondary outcomes

FENO (ppb)

Baseline:

29.2

95% CI 18.9 to 39.5

End:

22.2

95% CI 14.8 to 29.7

Baseline:

29.0

95% CI 18.2 to 39.8

End:

28.5

95% CI 16.4 to 40.6

Difference in change, mean (SEM):

‑6.4

(2.5)

p<0.05

(n=22)

Change in lung function: mean percentage difference in FEV₁

Not reported

Not reported

1.14%

Not significant

Change in lung function: mean percentage difference in PEF

Not reported

Not reported

3.44%

Not significant

Safety

Not reported

Not reported

Not reported

Patients reporting serious adverse events

Not reported

Not reported

Not reported

Abbreviations: AQLQ, Asthma Quality of Life Questionnaire; CI, confidence interval; FENO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ITT, intention to treat; n, number of patients; PEF, peak expiratory flow rate; RR, relative risk; SEM, standard error of mean; TLA, temperature‑controlled laminar airflow.

Study

Study design

Population

Intervention

Outcome measure

Finding

Vincenzo et al. (2010)

RCT

9 children with moderate to severe dust mite allergic asthma who lived in a dust mite‑free environment (Dolomites‑Alps) for > 3 months

Asthma symptoms; FENO level, eosinophils count in sputum and lung function

FENO level

Sputum eosinophils

Lung function:

Mohan et al. (2011)

RCT

52 children aged 8–16 years with allergic asthma and rhinitis sensitised to a perennial allergen

Sleep quality assessed using the parent reported PSQ, the self‑reported CSHQ and wristwatch actigraphy, after 1 year treatment.

TLA vs placebo: mean fall in PSQ 0.12 vs 0.12; p=0.96;

mean fall in CSHQ 1.82 vs 2.81; p=0.57

Moffatt et al. (2011)

RCT

52 children aged 8–16 years with allergic asthma and mild to moderate rhinitis sensitised to a perennial allergen

Rhinitis related quality of life using the RQLQ and nasal airflow measured using PNIF meters after 1 year treatment.

RQLQ score: mean difference 0.17 points in favour of TLA, 95% CI −0.47 to 0.80; p=0.597.

Improvement in the sleep domain of the RQLQ: mean difference 1.41 points in favour of TLA, 95% CI 0.25 to 2.56; p=0.019.

Reduction in overnight nasal congestion measured as [evening PNIF − morning PNIF]: mean difference 22.6 l/min in favour of TLA, 95% CI −0.3 to 45.6; p=0.053

Svensson (2005)

Case series

7 adults patients with asthma and verified allergy for animal dander, dust mites and several other allergens

The Airsonett device

Quality of life measured with mini‑AQLQ after 4 weeks' treatment

Mean (SD) maximum change of the total sum of mini‑AQLQ: 22.4% (9.1).

The medication was not changed during the study.

Abbreviations: CSHQ, Child's Sleep Habits Questionnaire; FENO, fractional exhaled nitric oxide; PSQ, Paediatric Sleep Questionnaire; PNIF, peak nasal inspiratory flow; RQLQ, Rhinoconjunctivitis Quality of Life Questionnaire; TLA, temperature‑controlled laminar airflow; vs, versus.

Trial ID

Status

Title

PICO

Study design

Publication

ISRCTN46346208

Ongoing

Laminar Airflow in Severe Asthma for Exacerbation Reduction (LASER)

P: adults (aged 18–75) with severe, poorly controlled asthma.

I: the Airsonett device

C: placebo device

O: clinically significant exacerbations over the 12‑month period

Multicentre randomised double‑blind placebo‑controlled parallel group trial of 12 months duration with a 4‑month internal pilot

Not applicable

NCT00986934

Completed

Effect of Temperature Controlled Laminar Airflow on the Peripheral Bronchial Airway in Asthma

P: asthma patients aged 7–70 years

I: the Airsonett device

C: placebo device

O: measurements of lung clearing index (weeks 0, 12 and 52)

Phase III, randomised, controlled, double‑blind, parallel group trial with 52‑week follow‑up

Not identified

ISRCTN67027605

Completed

A Pilot Proposal to Determine the Effect of the Airsonett Airshower on Sleep Quality

P: patients aged 18–65 years with doctor‑diagnosed allergic rhinitis

I: 4 nights of study, 2 with placebo Airsonett device and 2 with active Airsonett device

C: allerguard pillow protectors to be used on all 4 nights

O: total nasal symptom score

Single‑blind placebo‑controlled trial

Not identified

NCT00986388

Completed

Effect of Temperature Controlled Laminar Airflow on Bronchial Inflammation in Asthma

P: patients with perennial allergic asthma, age 7–70 years

I: the Airsonett device

C: placebo device

O: concentration of inflammatory cells and mediators in induced sputum (weeks 0, 4, 12 and 52)

Phase III, randomised, controlled, double‑blind, parallel group trial, with 52‑week follow‑up

Not identified

Abbreviations: PICO, participants, intervention, control, outcome.