Nocturnal temperature-controlled laminar airflow device for adults with severe allergic asthma: the LASER RCT

Abstract

Background Severe asthma exacerbations are costly to patients and the NHS, and occur frequently in severely allergic patients. Objective To ascertain whether or not nocturnal temperature-controlled laminar airflow (TLA) device usage over 12 months can reduce severe exacerbations and improve asthma control and quality of life compared with a placebo device, while being cost-effective and acceptable to adults with severe allergic asthma. Design A pragmatic, multicentre, randomised, double-blind, placebo-controlled, parallel-group, superiority trial with qualitative interviews. The trial included an internal pilot with qualitative focus groups. Setting Fourteen hospitals in the UK that manage patients with severe asthma. Participants Adults (16–75 years) with severe, poorly controlled, exacerbation-prone asthma despite high-intensity treatment, and who are sensitised to a perennial indoor aeroallergen. Intervention Nocturnal, home-based TLA treatment using an Airsonett® (Airsonett AB, Ängelholm, Sweden) device. The comparator was a placebo device that was identical to the active device except that it did not deliver the laminar airflow. Participants were allocated 1 : 1 to TLA therapy or placebo, minimised by site, origin of case, baseline severe exacerbation frequency, maintenance oral corticosteroid use and pre-bronchodilator forced expiratory volume in 1 second. Main outcome measures Primary outcome – frequency of severe asthma exacerbations occurring within the 12-month follow-up period, defined as worsening of asthma requiring systemic corticosteroids [≥ 30 mg of prednisolone or equivalent daily (or ≥ 50% increase in dose if on maintenance dose of ≥ 30 mg of prednisolone)] for ≥ 3 days. Secondary outcomes – changes in asthma control, lung function, asthma-specific and global quality of life for participants, adherence to the intervention, device acceptability, health-care resource use and cost-effectiveness. Results Between May 2014 and January 2016, 489 patients consented to participate in the trial, of whom 249 failed screening and 240 were randomised (n = 119 in the treatment group and n = 121 in the placebo group); all were analysed. In total, 202 participants (84%) reported use of the device for 9–12 months. Qualitative analyses showed high levels of acceptability. The mean [standard deviation (SD)] rate of severe exacerbations did not differ between groups [active 1.39 (1.57), placebo 1.48 (2.03); risk ratio 0.92, 95% CI 0.66 to 1.27; p = 0.616]. There were no significant differences in secondary outcomes for lung function, except for a reduction in mean daily peak expiratory flow [mean (SD) difference 14.7 l/minute (7.35 l/minute), 95% CI 0.32 to 29.1 l/minute; p = 0.045) for those in the active device group. There were no differences in asthma control or airway inflammation and no serious harms related to the device. No significant difference between the groups in quality-adjusted life-years gained over 1 year was observed. In addition, there was no difference in generic or disease-specific health-related quality of life overall, although statistically significant higher quality of life at month 6 was observed. Increases in quality of life were not sufficient to offset the annual costs associated with use of the TLA device. Limitations Missing outcome data could have resulted in an underestimation of exacerbations and rendered the study inconclusive. Conclusions Within the limits of the data, no consistent benefits of the active device were demonstrated, and the differences observed were not sufficient to make the device cost-effective. The types of patients who may benefit from the TLA device, and the reasons for large reductions in exacerbation frequency in severe asthma trials, which also incorporate other methods of recording exacerbations, need to be explored. Trial registration Current Controlled Trials ISRCTN46346208. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 29. See the NIHR Journals Library website for further project information.

Effect of nocturnal Temperature-controlled Laminar Airflow on the reduction of severe exacerbations in patients with severe allergic asthma: a meta-analysis

“…The current study is a post-hoc analysis of data from the LASER trial (Kapoor et al, ClinicalTrials.gov NCT02813811) [16] and the 4A asthma trial (Boyle et al, ClinicalTrials.gov NCT00986323) [9]. In the following text, the LASER trial will be referred to as Study A and the full 4A asthma trial as Study B1.…”

“…The original studies, Study A and Study B1 [9,16] were both phase III multicentre, double-blind, placebocontrolled, parallel-group trials in which patients were randomised to receive add-on treatment with TLA (Airsonett AIR4, Airsonett AB, Ängelholm; Sweden) or a placebo device for 1 year. In Study A and B1 all participants were evaluated during the study at baseline and after 3, 6, 9, and 12 months, and via completion of a diary.…”

“…In Study A, patients with a clinical diagnosis of asthma were aged 16-75 years, treated according to GINA 4/5, severe asthma defined by requirement for high-dose ICS plus a second controller and/or systemic corticosteroids, poorly controlled asthma demonstrated by two or more severe asthma exacerbations, requiring systemic corticosteroids in the preceding 12 months plus an Asthma Control Questionnaire (ACQ)7 score >1, and atopic status, defined as sensitisation to ≥1 perennial indoor aeroallergens [16]. In Study B1, patients with physician-diagnosed asthma were aged 7-70 years, with asthma treated according to GINA 2-4/5, defined by daily use of inhaled corticosteroids (ICS) for the last 6 months, poorly controlled asthma demonstrated by AQLQ-score ≤5.5 at inclusion, and atopic status, defined by sensitisation to a pet allergen (cat and/or dog) and/or house dust mite.…”

“…Both studies defined severe exacerbations in accordance with the American Thoracic Society/European Respiratory Society (ATS/ ERS) guidelines [17]. For further details regarding the collection of severe exacerbations, see the papers by Boyle et al [9] and Kapoor et al [16].…”

“…For patients with symptomatic severe asthma defined as GINA 4/5 and Asthma Control Test (ACT)<18 (n = 87), a 59% reduction of severe exacerbations was demonstrated (annual exacerbation rate: 0.23 for TLA vs 0.57 for placebo; RR = 0.41; p = 0.07) [7,9]. Recently, a one-year study (LASER) by Kapoor et al [16] in patients treated according to GINA step 4/5 showed no significant effect on severe exacerbations (RR = 0.92; p = 0.62) between TLA and placebo. The study demonstrated a high placebo response, especially in the patients with better symptom control, while the difference in effect between TLA and placebo descriptively increased for patients with more symptoms.…”