Laminar Airflow in Severe Asthma for Exacerbation Reduction - 48 Month Follow-up.

Study Overview
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Brief Summary
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Temperature-controlled Laminar Airflow (TLA) treatment delivered by the Airsonett treatment device is a new treatment for patients with allergic asthma. The LASER Trial (temperature-controlled Laminar Airflow in Severe asthma for Exacerbation Reduction - LASER) is a trial, currently evaluating whether the Airsonett device is able to reduce the frequency of asthma attacks in patients with allergic asthma. (www.lasertrial.co.uk) Participants who successfully complete at least 6 months of follow-up in the LASER trial are eligible for the post trial provision of 4 years of an active TLA treatment device. To date there is no long term performance data available to show whether there is any sustained benefit from the long term use of the Airsonett device, whether any improvement in asthma control or quality of life is maintained and whether patients will continue to use the treatment device beyond 12 months (the length of the longest previous trials of TLA treatment.) The investigators plan to assess the performance of the Airsonett device by recording the frequency of asthma attacks in patients over a 4-year period (48 months.) The investigators also wish to evaluate the effect of long term TLA treatment on asthma control, quality of life, healthcare resource use and patient acceptability of longer term use of the Airsonett device. Participants will be sent and asked to complete a series of questionnaires on a 6 monthly basis over the 48 month study period. Questionnaires will be returned by post to a single study centre based in Portsmouth, UK. Participants will also be contacted by telephone on a 6 monthly basis by a member of the trial team to collect information about their medication, healthcare resource use and whether they have had any asthma attacks since their last contact. Participants will not be expected to visit the study centre during the trial.

Detailed Description
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Asthma affects over 5.4 million people in the UK with nearly 500,00 experiencing 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 total asthma cost. In 2009 there were 1131 deaths due to asthma, with those whose asthma remains poorly-controlled facing the greatest risk. Patients with severe asthma bear the greatest burden of asthma morbidity and experience more frequent and severe exacerbations which reduce their quality of life, impair their ability to work and place an enormous burden of anxiety on them and their families. There is also an increased risk of significant depression. 1 in 5 asthmatics in the UK report serious concerns that their next asthma attack will kill them. As highlighted in the 2010 Asthma UK report, 'Fighting for Breath,' these patients also face discrimination from employers, healthcare professional s and society as a whole as a result of their asthma. Current treatments including oral corticosteroids, 'steroid-sparing' immunosuppressants and monoclonal antibody therapies are often of limited efficacy and have potentially serious side effects (steroids, immunosuppressive agents) or are prohibitively expensive (monoclonal antibodies). The adverse effects of long-term oral steroids include adrenal suppression, decreased bone mineral density, diabetes and increased cardiovascular mortality. The anti-IgE treatment Omalizumab® has been shown to reduce exacerbations by up to 50% and improve quality of life in severe allergic asthma but costs up to £26,640 per year, which is substantially more than the current annual rental cost of a TLA device (£2,088). Patients with poorly controlled, severe, allergic asthma are left with a significant unmet clinical need and a specific requirement for cost-effective therapies which reduce systemic steroid exposure by reducing the frequency of severe exacerbations. The Department of Health Outcomes Strategy for COPD and Asthma (2011) recognised the huge burden that poorly-controlled asthma places on people's lives and the NHS, and spelt out the political commitment to improve asthma control and reduce asthma related emergency healthcare needs and deaths. The 2013 British Thoracic Society (BTS) and Scottish Intercollegiate Guidelines Network (SIGN) national asthma guidelines and 2010 WHO consultation on severe asthma have highlighted an urgent need for research in severe asthma, acknowledging the limitations of available treatments in severe asthma and the dearth of clinical trials upon which to base management recommendations. Asthma UK emphasised in its research strategy for 2012 document that new therapies able to reduce symptoms and prevent exacerbations will improve clinical outcomes and patient well-being and reduce the cost of treating severe asthma within the NHS. More than 70% of severe asthmatic patients are sensitised to common aeroallergens and/or moulds and the level of allergen exposure determines symptoms; those exposed to high allergen levels are at increased risk of exacerbations and hospital admissions. Domestic exposure to allergens is also known to act synergistically with viruses in sensitised patients to increase the risk and severity of exacerbations. Allergen avoidance has been widely recognised as a logical way of treating these patients . In controlled conditions, long-term allergen avoidance in sensitised asthmatics reduces airway inflammation with consequent symptomatic improvement, further supported by high-altitude, clean-air studies. Unfortunately, effective methods of allergen reduction have proved elusive, with current measures unable to reduce allergen load sufficiently to yield a consistent clinical improvement, thus leaving a significant gap in the potential strategies for reducing asthma severity through allergen reduction. At night airborne particles are carried by a persistent convection current established by the warm body, transporting allergens from the bedding area to the breathing zone . Proof-of-concept studies have shown the TLA device reduces the total number of airborne particles >0.5μm in the breathing zone by 3000-fold (p<0.001), cat allergen exposure by 7-fold (p=0.043) and significantly reduces the increase in particles generated when turning in bed for all particle sizes . When compared to a best in class traditional air cleaners TLA is able to reduce exposure to potential allergens by a further 99%30. We postulate that this highly significant reduction in nocturnal exposure, targeted to the breathing zone, explains why TLA may succeed in an area where so many other measures, including air filters, have failed. The TLA device when compared to placebo, has proven efficacy on asthma-related quality of life and bronchial inflammation (measured by exhaled nitric oxide) in a pan European multicentre Phase III study , (n=282, age range 7-70 years). The greatest benefit was seen in the more severe asthma patients requiring higher intensity treatment (GINA Steps 4-5) and in patients with poorly controlled asthma (Asthma Control Test <18). GINA Steps 4-5 are consistent with BTS/SIGN Guideline treatment Steps 4-5 (inhaled corticosteroid dose ≥1000µg/day beclomethasone (BDP) equivalent plus an additional controller medication such as a long acting ß2-agonist, leukotriene receptor antagonist or a sustained release theophylline). Whilst not powered to ascertain an effect on exacerbations, a post-hoc analysis showed a decreased exacerbation rate in more severe patients treated with TLA when compared with placebo with a trend towards significance (mean 0.23 TLA; 0.57 placebo p=0.07). A cost-effectiveness analysis based on the results from this trial also found no significant differences in ED visits, hospitalisation days, medication usage, and therefore overall costs between the two study groups . This lack of significant findings probably reflected the fact that the trial was not powered to detect differences in exacerbations, a predictor of increased asthma healthcare resource use and costs . Despite the lack of a significant reduction in healthcare resource use and associated costs, subsequent economic modelling showed that TLA would be cost-effective in Sweden at the current monthly rental price (SEK 2,000, ≈ £167), mainly due to increases in quality of life. In order to address this important research question in severe allergic asthma, The LASER Trial, a multi-centre, randomised, double blind, placebo-controlled, parallel group trial is currently assessing whether nocturnal use of the TLA treatment device Airsonett® is able to reduce the frequency of severe asthma exacerbations in patients with poorly controlled, severe, allergic asthma. The LASER Trial received funding from the National Institute for Health Research Health Technology Assessment Programme. In the LASER Trial, participants receive 12 months of treatment. Half of the participants receive an active TLA device and half receive a device which has been deactivated (a 'placebo' device.) Neither the patients nor researchers will know which device an individual participant has received. All participants who complete at least 6 months of follow-up within the LASER trial will be eligible for treatment with an active TLA device for 4 years regardless of whether they received an active or placebo device during the trial. LASER-48 is the follow on study from The LASER Trial where the investigators will ask participants to continue to report their asthma attacks and symptoms during a 4 year (48-month) follow-up period by means of questionnaires to monitor whether the treatment device has an impact on their asthma symptoms and quality of life. To reduce the burden on study participants, they will not be required to visit a hospital clinic for follow-up appointments but they will be contacted on a 6 monthly basis to gather information about their asthma symptoms, their asthma medications and whether they have been required to visit their GP or hospital for their asthma. Participants will be free to withdraw from the study at any time without giving a reason for doing so. At the end of the study after the last participant has completed their 48 months of follow-up, the data will be analysed to help determine whether longer term treatment with the TLA (Airsonett) device is able to reduce the frequency of asthma attacks, improve asthma symptoms, improve asthma related quality of life and remain a cost-effective and acceptable treatment for patients with severe allergic asthma.

Official Title
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A Prospective, Single Arm, Cohort Study of Nocturnal Temperature-controlled Laminar Airflow (TLA) Treatment (Airsonett®) in Patients With Allergic Asthma to Determine the Effect of Long-term Treatment on Exacerbation Frequency.

Conditions
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Asthma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant must meet ALL of the following criteria to be considered eligible for the study: Male or Female, aged 16 years or above. Using the TLA treatment device, Airsonett®, for the treatment of asthma. Participant is willing and able to give informed consent for participation in the study. Exclusion Criteria: The participant may not enter the study if ANY of the following apply: • Unable to comprehend the study and provide informed consent, e.g. insufficient command of English in the absence of someone to adequately interpret.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of severe asthma exacerbations over the 48-month follow up period. | Severe asthma exacerbations are defined in accordance with ATS/ERS guidelines as a worsening of asthma requiring systemic corticosteroids, ≥30mg prednisolone or equivalent daily (or ≥50% increase in dose if maintenance 30mg prednisolone or above) for 3 or more days. Courses of corticosteroids separated by ≥7 days will be treated as separate severe exacerbations. Participants will keep a record of their asthma exacerbations. They will be asked to record systemic corticosteroid use, dose of systemic corticosteroids and length of treatment course. This information will be collected from participants at 6, 12, 18, 24, 30, 36, 42 and 48 months. | 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Current asthma control | Current asthma control will be recorded at 6, 12, 18, 24, 30, 36, 42 and 48 months. This will be measured using the Asthma Control Questionnaire. | 6, 12, 18, 24, 30, 36, 42 and 48 months | 
| Exacerbation Frequency | Risk of adverse asthma outcomes will be recorded over the 48 month study period at 6, 12, 18, 24, 30, 36, 42 and 48 months | 48 months | 
| Oral Corticosteroid Use | Risk of adverse asthma outcomes will be recorded over the 48 month study period at 6, 12, 18, 24, 30, 36, 42 and 48 months | 6, 12, 18, 24, 30, 36, 42 and 48 months | 
| Frequency of Hospital Admissions for Asthma | Risk of adverse asthma outcomes will be recorded over the 48 month study period at 6, 12, 18, 24, 30, 36, 42 and 48 months | 6, 12, 18, 24, 30, 36, 42 and 48 months | 
| Health Related Quality of Life - Mini Asthma Quality of Life Questionnaire | This will be measured using the mini Asthma Quality of Life Questionnaire (miniAQLQ) at 6, 12, 18, 24, 30, 36, 42 and 48 months. | 6, 12, 18, 24, 30, 36, 42 and 48 months | 
| Health Related Quality of Life - EQ-5D-5L health questionnaire | This will also be measured using the the EQ-5D-5L health questionnaire at 6, 12, 18, 24, 30, 36, 42 and 48 months. | 6, 12, 18, 24, 30, 36, 42 and 48 months | 
| Sino-nasal Symptoms | This will be measured using the SNOT-22 (Sino-Nasal Outcome Test questionnaire at 6, 12, 18, 24, 30, 36, 42 and 48 months. | 6, 12, 18, 24, 30, 36, 42 and 48 months | 
| Health Economics | Healthcare resource use and cost will be measured and participants will complete the Work Productivity and Activity Impairment (WPAI(A)) Questionnaire. | 48 months | 
| TLA Treatment Acceptability | Time to withdrawal of treatment and participants perception of the TLA device will be recorded at 12, 24, 36 and 48 months. | 12, 24, 36 and 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Temperature-controlled Laminar Airflow, Exacerbation frequency