Temperature-controlled Laminar Airflow Research Articles

Temperature-controlled Laminar Airflow (TLA) in symptomatic severe asthma – a post hoc analysis of severe exacerbations, quality of life and health economics

PurposeUncontrolled severe asthma constitutes a major economic burden to society. Add-ons to standard inhaled treatments include inexpensive oral corticosteroids and expensive biologics. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett®) could be an effective, safe and cheaper alternative. The potential of TLA in reducing severe asthma exacerbations was addressed in a recent randomised placebo-controlled trial (RCT) in patients with severe asthma (Global Initiative for Asthma (GINA) step 4/5), but the results were inconclusive. We re-analysed the RCT with severe exacerbations stratified by the level of baseline asthma symptoms and Quality of Life.MethodsMore uncontrolled patients, defined by Asthma Control Questionnaire 7 (ACQ7) > 3, EuroQoL 5-Dimension Questionnaire Visual Analogue Scale (EQ5D-VAS) ≤ 65 and Asthma Quality of Life Questionnaire (AQLQ) ≤ 4 were selected for re-analysis. The rates of severe asthma exacerbations, changes in QoL and health-economics were analysed and compared between TLA and placebo.ResultsThe study population included 226 patients (113 TLA / 113 placebo.) The rates of severe asthma exacerbations were reduced by 33, 31 and 25% (p = 0.083, 0.073, 0.180) for TLA compared to placebo, dependent on selected control measures (ACQ7, EQ5D-VAS, AQLQ, respectively). For patients with less control defined by AQLQ≤4, the difference in mean AQLQ0-12M between TLA and placebo was 0.31, 0.33, 0.26 (p = 0.085, 0.034, 0.150), dependent on selected covariate (AQLQ, EQ5D-VAS, ACQ7, respectively). For patients with poor control defined by ACQ7 > 3, the difference in EQ5D-5 L utility scores between TLA and placebo was significant at 9 and 12 months with a cost-effective ICER. The results from the original study did not demonstrate these differences.ConclusionThis post hoc analysis demonstrated an effect of TLA over placebo on severe exacerbations, asthma control and health economics in a subgroup of patients with more symptomatic severe allergic asthma. The results are consistent with the present recommendations for TLA. However, these differences were not demonstrated in the full study. Several explanations for the different outcomes have been outlined, which should be addressed in future studies.FundingNIHR Health Technology Assessment Programme and Portsmouth Hospitals NHS Trust.

081 Observational study on temperature-controlled laminar airflow in atopic dermatitis patients

In atopic dermatitis (AD) patients aeroallergens such as house dust mite contribute profoundly to the disease severity. Temperature-controlled laminar airflow (TLA) has been developed to reduce indoor allergen exposure during the night’s sleep by filtering the surrounding atmosphere. To investigate the clinical and immunological effects of TLA in adults with AD, we conducted an observational study with ten patients with moderate to severe AD sensitized to house dust mite. The patients used TLA for three months and were able to participate in a nine months extension phase. Physician’s Global Assessment (PGA), SCORAD (41.96 ±9.78 vs. 34.15 ± 9.69, p = .037), and EASI (10.01 ± 3.94 vs 8.41 ± 3.76, P = .038) were significantly reduced after three months. Subjective scores such as sleeplessness and life quality measured by dermatology life quality index improved significantly. Investigating immunological effects, analysis of HDM stimulated PBMCs from patients revealed that the proliferative responses of total T cells, CD4+ T cells, skin-homing CD4+ T cells, and CD8+ T cells were significantly decreased after 3 months of TLA usage. Type 2 inflammation cytokines measured in patients’ serum were reduced in tendency after three months of TLA usage. After 12 months, consistent results were seen according to clinical disease scores and in vitro analyses. This is the first study suggesting beneficial effects of three months use of TLA in HDM sensitized adult AD patients regarding objective, subjective and in vitro parameters. Effects were consistent over one year of TLA. In sensitized AD patients, TLA may contribute to disease control and improvement as a potential add-on treatment.

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

ABSTRACT Background: Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA) has been shown to provide a significant reduction in the exposure to allergens in the breathing zone, leading to a long-term reduction in airway inflammation and improvement in Quality of life (QoL). Allergic asthma patients symptomatic on Global Initiative for Asthma (GINA) step 4/5 were found to benefit the most as measured by Asthma Quality of Life Questionnaire (AQLQ). However, the effect of TLA on severe asthma exacerbations is uncertain and therefore a meta-analysis was performed. Methods: Patients with severe allergic asthma (GINA 4/5) were extracted from two 1-year randomised, double-blind, placebo-controlled trials conducted with TLA. A meta-analysis of the effect on severe exacerbations was performed by negative binomial regression in a sequential manner, defined by baseline markers of asthma control (symptoms and QoL scores). Results: The pooled dataset included 364patients. Patients with more symptoms at baseline (ACT<18 or ACQ7>3; N=179), had a significant mean 41% reduction in severe exacerbations (RR=0.59 (0.38-0.90); p=0.015) in favour of TLA. Higher ACQ7 cut-points of 3.5-4.5 resulted in significant reductions of 48-59%.More uncontrolled patients based on AQLQ total and symptom domains ≤3.0 at baseline also showed a significant reduction in severe exacerbations for TLA vs. placebo ((47% (p=0.037) and 53% (p=0.011), respectively). The meta-analysis also confirmed a significant difference in AQLQ-responders ((Minimal Clinically Important Difference)≥0.5; 74% vs. 43%, p=0.04). Conclusion: This meta-analysis of individual patient data shows a beneficial effect on severe exacerbations and quality of life for TLA over placebo in more symptomatic patients with severe allergic asthma. These outcomes support the national management recommendations for patients with symptomatic severe allergic asthma. The actual effect of TLA on severe exacerbations should be confirmed in a prospective study with larger numbers of patients.

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

Severe asthma exacerbations are costly to patients and the NHS, and occur frequently in severely allergic patients. 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. 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. Fourteen hospitals in the UK that manage patients with severe asthma. Adults (16-75 years) with severe, poorly controlled, exacerbation-prone asthma despite high-intensity treatment, and who are sensitised to a perennial indoor aeroallergen. 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. 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. 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. Missing outcome data could have resulted in an underestimation of exacerbations and rendered the study inconclusive. 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. Current Controlled Trials ISRCTN46346208. 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.

Use of temperature-controlled laminar airflow in the management of atopic asthma: clinical evidence and experience.

Avoidance of allergens in the treatment of asthma has hitherto not achieved significant benefit despite the strong evidence that allergy both increases severity and contributes to exacerbations of asthma. House dust mite, cat and dog allergens are the most common perennial allergic triggers and most avoidance strategies have focused on reducing exposures in bedrooms. Cochrane reviews have suggested that they neither significantly reduce allergen levels nor improve asthma. While the lack of efficacy may be assumed to be a consequence of exposures occurring outside the bedroom, prolonged sleep is associated with increased susceptibility to bronchospasm and airway inflammation. Thus, if efficient reductions in allergen exposure could be achieved during sleep, it might be expected that this would result in significant improvements in control of asthma. The temperature-controlled laminar airflow (TLA) is a system which can be employed over beds in a domestic environment and results in massive reductions in particulate exposure of recumbent subjects, including highly respirable allergens such as Fel. D1 from cats. Trials of TLA have demonstrated highly significant improvements in asthma quality of life and reductions on airway inflammation as monitored by exhaled nitric oxide levels. Furthermore, in patients with the worst disease, severe exacerbation frequency was significantly reduced. Based on UK health-service costs, the use of TLA falls well below the National Institute for Health and Care Excellence (NICE) threshold for the incremental cost effectiveness ratio (ICER) per quality adjusted life year (QALY). Indeed, for those with frequent exacerbations, it is cost saving and should be prescribed for such allergic asthmatic patients.

Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma

IntroductionChronic asthma is a significant burden for individual sufferers, adversely impacting their quality of working and social life, as well as being a major cost to the National Health Service...

Temperature-controlled laminar airflow in severe asthma for exacerbation reduction (The LASER Trial): study protocol for a randomised controlled trial

BackgroundAsthma affects more than 5 million patients in the United Kingdom. Nearly 500,000 of these patients have severe asthma with severe symptoms and frequent exacerbations that are inadequately controlled with available treatments. The burden of severe asthma on the NHS is enormous, accounting for 80 % of the total asthma cost (£1 billion), with frequent exacerbations and expensive medications generating much of this cost.Of those patients with severe asthma, 70 % are sensitised to indoor aeroallergens, and the level of exposure to allergens determines the symptoms; patients exposed to high levels are therefore most at risk of exacerbations and hospital admissions.The LASER trial aims to assess whether a new treatment, temperature controlled laminar airflow (TLA) delivered by the Airsonett™ device, can reduce the frequency of exacerbations in patients with severe allergic asthma by reducing exposure to aeroallergens overnight.MethodsThis multicentre study is a placebo-controlled, blinded, randomised controlled, parallel group trial. A total of 222 patients with a new or current diagnosis of severe allergic asthma will be assigned with a random element in a 1:1 ratio to receive either an active device for one year or a placebo device. The primary outcome is the frequency of severe asthma exacerbations occurring over a 12-month period, defined in accordance with the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Secondary outcomes include changes in asthma control, lung function, asthma-specific and global quality of life for participants and their carers, adherence to intervention, healthcare resource use and costs, and cost-effectiveness. Qualitative interviews will be conducted to elicit participant’s and their partner’s perceptions of the treatment.DiscussionEffective measures of allergen avoidance have, to date, proved elusive. The LASER trial aims to address this. The study will ascertain whether home-based nocturnal TLA usage over a 12-month period can reduce the frequency of exacerbations and improve asthma control and quality of life as compared to placebo, whilst being cost-effective and acceptable to adults with poorly controlled, severe allergic asthma. The results of this study will be widely applicable to the many patients with allergic asthma both in the UK and internationally.Trial registrationCurrent controlled trials ISRCTN46346208 (Date assigned 22 January 2014).

Early qualitative analysis to enhance trial processes

The LASER Trial is an RCT of the effectiveness of the use of a Temperature-controlled Laminar Airflow (TLA) device in adults with severe allergic asthma. The trial is funded by the NIHR-HTA. The trial aims to determine whether home-based nocturnal treatment with a TLA device can reduce the frequency of asthma exacerbations over a one year period. In order to inform decisions about implementation of the device should it be shown to be effective, participant's experience of using the TLA device is being assessed by means of qualitative interviews. We conducted telephone interviews with 10 trial participants in the first 4 months of the trial in order to determine participant's thoughts, values and opinions of trial processes and the treatment device. This early qualitative evaluation as part of the larger experimental study has provided us with an opportunity to address different questions (What is happening? How is it happening?) than otherwise would be possible with quantitative data collection alone. We have been able to provide feedback to develop and enhance subsequent trial processes including recruitment and retention of participants. Experience from conducting this early evaluation is that the qualitative interviews and subsequent analysis have provided a useful insight into the difficulties that patients have experienced and what is important to them. As a result we have a better understanding and this has resulted in an informed plan of how to address these learning points with actions to enhance the experience of taking part in the trial for future participants.

Recruitment to clinical trials - the use of social media

The LASER Trial is an NIHR-HTA funded, multicentre, randomised controlled trial of an allergen intervention, (Temperature-controlled Laminar Airflow,) for patients with severe allergic asthma. To meet our challenging recruitment targets, we have adopted a number of different social media based recruitment strategies to ensure that the trial delivers on time. Asthma UK and Allergy UK have advertised the trial on their websites and shared the trial with their social media networks via Facebook and Twitter. Asthma UK alone has 27,000 Twitter followers and 35,000 Facebook ‘likes.’ This has raised the profile of the trial and lead to a significant increase in traffic to the trial website where patients can register their interest in participating. We set up a social media advertising campaign using paid adverts to target asthma patients living within 50km of our recruiting centres. Adverts appear in Facebook and Twitter feeds inviting people to find out more about the trial, directing them to the trial website. This campaign has reached nearly 50,000 people/month and has resulted in a further increase in patient registrations. We also employed an online recruitment company, Trialbee (http://www.trialbee.com.) Trialbee advertise the trial on social media platforms inviting patients to visit their website where they are screened and, if eligible, referred on to their nearest recruiting centre for screening. Our social media recruitment strategies have augmented recruitment alongside more traditional means of recruiting patients from the clinical setting. Social media has the potential to revolutionise recruitment to clinical trials and is currently an underused resource.

Allergen reduction by nightly temperature controlled laminar airflow (TLA) decreases exacerbation rate in severe allergic asthma

It has earlier been shown that TLA significantly reduces allergen exposure and airway inflammation and improves quality of life in poorly controlled allergic asthma patients.

Improved asthma control in patients with severe, persistent allergic asthma after 12 months of nightly temperature-controlled laminar airflow: an observational study with retrospective comparisons

IntroductionContinuous or episodic allergen exposure is a major risk factor of frequent symptoms and exacerbations for patients with allergic asthma. It has been shown that temperature-controlled laminar airflow (TLA) significantly reduced allergen exposure and airway inflammation and improved quality of life of patients with poorly controlled allergic asthma.ObjectiveThe objective was to evaluate the effects of nighttime TLA when used during real-life conditions for 12 consecutive months in addition to the patients’ regular medication.MethodsThis multicenter, pre- and postretrospective observational study included patients with inadequately controlled moderate-to-severe allergic asthma who received add-on treatment with TLA for 12 consecutive months. Data on medication use, asthma control, asthma symptoms, lung function, use of hospital resources, and exacerbations were collected after 4 and 12 months and compared with corresponding data collected retrospectively from medical records during the year prior to inclusion in the study.ResultsData from 30 patients (mean age 28; range 8–70) completing 4 months and 27 patients completing 12 months of TLA use are presented. The mean number of exacerbations was reduced from 3.6 to 1.3 (p<0.0001), and the ratio of asthma-related emergency room visits or hospitalizations diminished from 72.4 to 23.3% (p=0.001) or from 44.8 to 20.0% (p<0.05), respectively, after 12 months of TLA use. The Asthma Control Test index increased from 14.1 to 18.5 (p<0.0001). After 4 months of TLA use, clear improvements can be shown for most variables in line with the data collected after 12 months.ConclusionsThe addition of TLA to the patients’ regular medication significantly reduced exacerbations, asthma symptoms, and the utilization of hospital resources. The data support that TLA may be an important new non-pharmacological approach in the management of poorly controlled allergic asthma.

Effect of a novel temperature-controlled laminar airflow device on personal breathing zone aeroallergen exposure.

Temperature-controlled laminar airflow improves symptoms in atopic asthmatics, but its effects on personal allergen exposure are unknown. We aimed to evaluate its effects on personal cat allergen and particulate exposures in a simulated bedroom environment. Five healthy volunteers lay under an active and an inactive temperature-controlled laminar airflow device for 175min, in a simulated bedroom containing bedding from a cat owner. Total airborne particles (≥0.5 - ≥10μm diameter) were quantified with a laser particle counter. Airborne allergen was sampled with Institute of Occupational Medicine filters. Inhaled exposure was sampled with nasal air samplers. Allergen-containing particles were quantified by immunoassay. Treatment reduced total airborne particles (>0.5μm diameter) by >99% (P<0.001) and reduced airborne allergen concentration within the breathing zone (ratio of median counts=30, P=0.043). Treatment reduced inhaled allergen (ratio of median counts=7, P=0.043). Treatment was not associated with a change in airborne allergen concentration outside of the breathing zone (P=0.160). Temperature-controlled laminar airflow treatment of individuals in an allergen-rich experimental environment results in significant reductions in breathing zone allergenic and non-allergenic particle exposure, and in inhaled cat allergen exposure. These findings may explain the clinical benefits of temperature-controlled laminar airflow.

Nocturnal temperature controlled laminar airflow for treating atopic asthma: a randomised controlled trial

ObjectiveTo determine whether environmental control using nocturnal temperature controlled laminar airflow (TLA) treatment could improve the quality of life of patients with persistent atopic asthma.DesignRandomised, double-blind, placebo-controlled, parallel-group trial.SettingNineteen European...

P27 Personal allergen exposures are increased by changes in sleep position and improved by temperature-controlled laminar airflow

<h3>Introduction and Objectives</h3> Aeroallergens are released directly from bedding into the breathing zone, and contribute importantly to asthma symptoms. Adults change their sleep position between 3 and 45 times per night. The effect of these turns on inhaled particulate exposures is unknown. We aimed to investigate the effects of changing position on breathing zone particulate exposures and the effect of a novel Temperature-controlled Laminar Airflow (TLA) device on reducing such exposures. <h3>Methods</h3> A simulated bedroom was constructed containing bedding from a cat owner. Five healthy volunteers lay recumbent under an active and an inactive TLA device for 175 min. Volunteers made scheduled turns in bed to simulate normal sleep. Real-time total particle levels (≥0·5 μm diametre) within the breathing zone were measured by laser particle counting. Inhaled cat allergen exposure was measured by nasal air sampling. Time series analysis was used to evaluate changes in particulate exposures with turning. <h3>Results</h3> A greater proportion of larger particles than smaller ones were disturbed by turning over (F=20.6, df=5, p&lt;0.001). With the TLA switched off, 9% (95% CI 4 to 18) of total overhead particles &gt;10 μm diametre were accounted for by turning over, compared with 0.2% (95% CI 0.07 to 0.5) of particles &gt;0.5 μm diameter. TLA treatment reduced total particle numbers (size &gt;0.5 μm) by 3010-fold (p&lt;0.001) and significantly reduced the turn-associated increase for all particle sizes (Abstract P27 Figure 1, p&lt;0.015). Similar turn-associated increases in nasal air sampler cat particle counts were seen. TLA treatment reduced nasal cat allergen exposures by sevenfold (p=0.043). <h3>Conclusions</h3> Turning over in bed causes a significant increase in breathing zone exposures to particulates which are within the respirable size range. TLA treatment dramatically reduces overhead breathing zone total particulate exposures and also reduces nasal cat allergen exposure. TLA treatment attenuates the increase in particulate exposures caused by turning over. Treatments which result in better sleep quality and a reduced number of bodily turns may result in a reduction in personal breathing zone particulate exposures in bed.