Newer nebulisers cut treatment times for people with cystic fibrosis

Key message: Nebulisers don’t all perform the same. Some newer types such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems including significantly shorter treatment time

Nebulisers are devices that allow medicines to be breathed in as a mist. People with cystic fibrosis (CF) are amongst those living with chronic conditions who use them to take medicines which help control their symptoms. Taking medicines this way may take a few minutes or as much as forty minutes each time and nebulised treatment has been found to significantly add to the burden of treatment for people with CF.

boy with nebuliser

Some nebulisers take longer to deliver medicines than others

There are lots of different types of nebulisers but which work best? A team from the Cochrane Cystic Fibrosis and Genetic Disorders Group has now done the first systematic review to look at the evidence on this. They wanted to know how effective and safe different types of nebulisers are, what impact they have in terms of treatment burden and how well people using them follow their prescribed treatment regime.

The nebuliser systems being compared were conventional systems, adaptive aerosol delivery (ADD) with and without vibrating mesh technology (VMT), VMT systems and ultrasonic nebuliser systems. The medicines were tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other aerosolised medicines.

They found twenty studies to include, in which 1936 children and adults with CF had taken part, and results from all but two could be combined.

What did they find?

  • Nebulisers using newer technologies such as AAD or VMT deliver the medicine faster and get more of it into the lungs than conventional systems
  • The newer systems are safe when used with the correct priming dose, which may be different from the dose used in conventional systems
  • People seem to stick to the treatment regime as well or better using the newer types of nebulisers
  • Some systems using VMT may go wrong more often

How good was the evidence?

There are a number of gaps. There were only a few studies available for each type of system and medicine and some combinations (of system and medicine) where no evidence was found

In almost all the studies details of the way the studies were designed and run (such as how people were randomized to their treatment groups) were not described

Four studies were available only as abstracts and supply only limited detail of methods and results. The authors have been asked for more information but this is currently missing from the review; if provided it can be included in a later version of the review. Three other studies did not report on missing data. Missing data is a source of bias in reviews and we know that negative or unfavourable results are more likely to remain unpublished

What should future trials consider?

As is so often the case, the review team have identified a need for future trials to explore outcomes which matter to patients. Specifically they highlight the need for evidence on the impact of newer nebuliser systems on quality of life and burden of treatment for people with CF, as well as on safe and effective dosing levels, clinical outcomes such as hospital admissions and the need for antibiotics and an economic evaluation of their use.

If you are someone with CF using nebulisers, what matters most to you and what would you like to see researchers investigating? You might be interested in the comments left below one of our earlier blogs (here), which was about a review on antibiotics for COPD but prompted interesting responses from Oli Rayner, who has CF, and Nikki Jahnke, the Managing Editor of the Cochrane Cystic Fibrosis and Genetic Disorders Group.


Daniels T, Mills N, Whitaker P. Nebuliser systems for drug delivery in cystic fibrosis. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD007639. DOI: 10.1002/14651858.CD007639.pub2.

Cochrane summary


7 thoughts on “Newer nebulisers cut treatment times for people with cystic fibrosis

  1. Interesting review which, as you say, points to the need for more, better quality studies. It may be obvious what a good nebuliser looks like but perhaps there are things which researchers would not know unless they actually use them day-to-day or ask the right questions of those who do. Here are the criteria I would use if I was doing a Which? guide. Some of the factors probably relate more to the drug than the device but, from the patient perspective, it is the overall experience that matters and determines whether the treatment gets done properly:

    – Efficacy in delivering the drug: this goes without saying but, in practice, some drug escapes into the air rather than going into the airways. A good nebuliser design would minimise the risk of this happening in order to deliver a fixed dose. (This is another advantage of breath-activated inhalers by the way.)

    – How long it takes to deliver the drug;

    – How long it takes to prepare the drug and whether it requires special equipment (e.g. sharps);

    – Whether the drug needs to be stored in a fridge;

    – How easy it is and how long it takes to wash / sterilise and dry the nebuliser mouthpieces, particularly where you need to do this multiple times back-to-back in order to get all the nebulised treatments done (i.e. you have more treatments, in a given cycle, than nebuliser mouthpieces);

    – Whether you need a tap with clean water;

    – Whether you need a power source and, if so, will the equipment work properly in foreign countries;

    – How big/heavy is the equipment and how portable is it;

    – Does the system need special “exhaust” arrangements e.g. an elephant tube out of a window or (expensive) filter pads or is it “self-contained”;

    – Can you use the device for all the nebulised treatments you have to do or do you need different devices for different drugs; and

    – Does using the device mean you have to periodically buy expensive replacement parts or consumables.

    Clearly most of these factors relate to convenience. There is a quality of life aspect but there is also an adherence aspect. It is hard to fit all the treatments into the day so inconvenient treatments are less likely to get done than convenient ones. By reducing the overall treatment burden, a nebuliser that does well on these criteria would help patients get all their treatments done each day, stay healthy and avoid exacerbations.

    It would be worth building these kinds of explicit criteria into trials rather than relying on the standard Quality of Life questionnaires, which don’t appear to capture these important aspects. Investing in trials like this would surely lead to better health outcomes and consequential NHS savings.


    • Thanks for taking the time to post this thoughtful response here, Oli, as well as engaging through Twitter. This is the nitty gritty from the coal face, isn’t it? I imagine others who also need to use nebulisers daily would agree with this (perhaps we will hear from some here!). Absolutely right that convenience is a big factor in treatment adherence. I like your suggestion that trials should look at these kinds of specifics; perhaps as well as using quality of life questionnaires?

  2. Oli thanks for taking the time to read and to comment on our review. The points that you make are really important; after all there is no point in a nebuliser being the best ever in terms of giving the medication if it is so big, heavy, difficult and time consuming to use and clean that no-one actually uses it. We recognised some of these issues when we developed the review and included the outcomes: quality of life, burden of treatment and patient satisfaction/preference (which included nebuliser weight, dimensions, time taken to clean equipment, noise levels, power supply, average number of doses per fully charged batteries, cleaning regimen, nebuliser system and consumables availability, customer support). These outcomes cover some of the points that you mention and we will take the other points on board for future updates of the review.

    We were disappointed that, despite including these outcomes, we found little information about these outcomes within the trials and were therefore unable to fully compare the different nebuliser systems in a way that is meaningful to people with CF who need to use them. On the positive side treatment time did feature heavily as an outcome measure within the included trials and so this was something that we could compare confidently between the systems. It was just a shame that setup and cleaning time wasn’t included within this. We completely agree that future research trials need to measure more ‘people focused’ outcomes like the ones you’ve mentioned above.

    • That’s great. This may not be the right forum but it seems to me “Quality of life” is a big and vague label that covers a broad range of unrelated things. It is often referred to as if it’s a luxury but not a genuine medical factor. I think it would be helpful to disaggregate QoL into more specific components i.e. “does CF stop you seeing your friends as much as you would like?” is a very different kind of question to “how long does nebuliser A take you to do and how easy is it?”. There are some which clearly have an impact on “whether the treatment gets done” rather than having to do with “impact on life when the treatment is done”. This goes to the heart of effectiveness vs efficacy. It seems to me there is a missing link. NHS buys things recommended by NICE, NICE recommends things which look “cost-effective.” things only appear “cost-effective” when there is data to show it and that only happens if trials are designed to produce the data. So if a company developed a new nebuliser that was amazingly convenient and user-friendly, they could only get the NHS to buy it if they could show how the amazing convenience and user-friendliness helped in terms of cost-effectiveness. In fact, there is good data to show that poor adherence causes additional exacerbations/hospitalisations (presented by Riekert at the NACFC 2012) and we know that exacerbations are very costly to the healthcare system (and of course to patients’ disease trajectory). So, it ought to be possible to show that a new product is more effective in the real world (vs efficacious), due to its impact on adherence, and therefore that it saves the NHS money by avoiding exacerbations and hospitalisations. If a new product could prevent one or two exacerbations per year, it would probably save the NHS £30,000-40,000 per patient per year, leaving aside the benefits to the patient’s health and quality of life which would be significant but hard to quantify in a way that NICE/QALY will recognise. It feels like the dots are all there but people don’t bother to join them up. It also illustrates the difference between designing trials to get a licence (i.e. show the FDA/EMA what they want to see) versus designing trials to give payers/clinicians/patients what they need to see. Incidentally, better trials would make much more use of real world data and remote monitoring; and the data collection/review would not stop on marketing authorisation. Fortunately, it seems the established link between adherence and frequency of exacerbations could provide a way forward i.e. a way to get the NHS to pay for products which are “good” and not just “licensed” and therefore justify the investment on better trials. Whoever sees this and acts on it will do very well for themselves and make a big difference to the lives of patients and their families.

      • Hi Oli, you are right the dots are there and when we take a step back and look at the bigger picture it seems just to be common sense that anything that can encourage people to stick with their treatment has got to be worthwhile investing in. Hopefully the current movement to increased patient involvement in research will also filter through to trial design. Groups like the James Lind Alliance, CFUnite and (of course) Cochrane are working to make this a reality.

  3. Efficacy is more important than Time for us
    My son is 11 and touch wood is still very compliant
    We use an EFlow Rapid, and find it great
    We still use the old Pari Turbo Boy for Hypertonic Saline for 2 reasons
    HS needs to be done for 20 mins, it starts working after 10 mins
    and the high amount of salt isn’t good for the very expensive heads
    (when I say ‘old’ I mean we’ve had it for a few years)
    Cost of Neb
    Cost of Replacement Posts/Heads

  4. Thank you for taking the time to read and comment on our review. We looked at a number of outcomes when comparing the nebuliser systems because we know that different outcomes are important to different people at different times. Efficacy is more important to you as a family now but changes such as becoming more independent with treatment, exams, starting college, university or work may mean that other outcomes such as time become more important for you in the future.

    None of the studies that we identified compared the delivery of hypertonic sodium chloride through different types of nebuliser systems so, based on the review, it’s difficult to comment on your reasons for using the Pariboy for this medication. However my opinion is that it is important to use a system that the person feels comfortable with in terms of being able to take the medication and that they feel that it works well for them. I think though that it is unlikely that the effectiveness of hypertonic is based on nebulising it for a minimum time. For example, nebulising it for twenty minutes with a conventional nebuliser would deliver a very different amount to the lungs than twenty minutes with an AAD nebuliser.

    Picking up on the issue of cost, this was an outcome that we wanted to look at but unfortunately it wasn’t included in any of the studies that we found so we were unable to compare the nebuliser systems based on cost. We recognise that the cost of the nebuliser itself, replacement parts and extra items that are needed to maintain the nebuliser system are important to people with CF who may have to pay for these items and also to healthcare providers where these items are provided to the person with CF free of charge. We hope that researchers will take note of this gap in research and will carry out studies comparing the costs of using each type of nebuliser system that we can include in a future update of the review.

    Linked with cost is the issue that you raised about the lifespan of the parts of some nebuliser systems and whether the use of some medications shorten this lifespan so leading to more expense. We looked at the reliability of nebuliser systems as an outcome and found that some types of vibrating mesh system are less reliable than other systems but we didn’t specifically look at the lifespan of nebuliser systems and their parts. This is something that we will consider looking at when the review is due for an update.

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