Key messages
1. Newer technologies have advantages over conventional systems in terms of treatment time, the amount of drug reaching the lung, preference, and adherence.
2. Not all medications used in treating cystic fibrosis can be delivered by the same nebuliser, and data are lacking for some of the different nebuliser and drug combinations.
3. Long-term studies are needed to evaluate different nebuliser systems to determine patient-focused outcomes (such as quality of life, effective dosing levels, and hospitalisations).
What is cystic fibrosis?
People with cystic fibrosis have sticky mucus in their lungs which is difficult to get rid of and which can cause infection if it builds up.
How are nebulisers used as part of cystic fibrosis treatment?
Nebulisers are used to deliver medications to the lungs to control the symptoms and the progression of disease. They change a liquid medication into a mist, so it can be breathed in. Different types of nebuliser systems are used with different medications.
1. Conventional systems - a machine pushes out a constant mist of medication at high speed.
2. Adaptive aerosol delivery systems - like conventional systems, also monitor breathing and only deliver the medication while the person is breathing in.
3. Vibrating mesh technology systems move the liquid medication through a metal mesh to generate a mist with similar-sized droplets which is delivered constantly.
4. Adaptive aerosol delivery systems with vibrating mesh technology combination between the two systems.
5. Ultrasonic systems use a crystal to vibrate the liquid medication at a high frequency and turn it into a mist which is delivered constantly.
What did we want to find out?
How well do the different nebuliser systems deliver each inhaled medication (how much medication is delivered into the lungs, and what is the impact on lung function)? Are they safe or do they have any side effects? We also wanted to know how these nebuliser systems affect people with cystic fibrosis in terms of treatment burden, adherence to treatment regimen and their quality of life.
What did we do?
We assessed 33 studies (2270 adults and children)and compared different types of nebuliser systems for delivering: tobramycin; colistin; dornase alfa; hypertonic saline; and other nebulised medications.
What did we find?
Conventional systems which have faster air flows and smaller medication droplets decrease treatment time and deliver more medication into the lung than other conventional systems, which have slower air flows and larger medication droplets. Nebulisers use newer technologies, e.g. adaptive aerosol delivery system or vibrating mesh technology, deliver the medication faster and may deliver more of the medication into the lung. These newer systems appear safe when used with the correct amount of medication, which may be different to that used in a conventional system. Some studies suggest that people with cystic fibrosis may prefer these newer systems and may take more of their medication when using them.
However, more research is needed into what dose of medication is needed for the different systems, which medications suit which technologies best and how these newer nebuliser technologies affect quality of life, burden of treatment, additional treatment needed (such as oral or intravenous antibiotics) and treatment costs.
What are the limitations of the evidence?
There were lots of different systems studied, and often we only had a few studies for each comparison. Also, the studies we found were quite small and results varied. We had concerns around at least some aspects of the design of every study which affected our confidence in the results.
How up to date is this evidence?
We last looked for evidence on 9 August 2023.
Newer technologies e.g. AAD and VMT have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, preference and adherence.
Data are lacking for all varieties of medications which are used in CF care, including different inhaled antibiotics or hypertonic saline, with all delivery (nebuliser system) possibilities. Long-term RCTs are needed to evaluate different nebuliser systems to determine patient-focused outcomes (such as QoL and burden of care), safe and effective dosing levels of a wide variety of medications, clinical outcomes (such as hospitalisations and need for antibiotics), and an economic evaluation of their use.
There are insufficient data to establish whether one nebuliser system is better than another overall. Clinicians should be aware of the variability in the performance of different nebuliser systems, compatibility with specific nebulised medication, and they must work with their patients to choose the best nebuliser system for each individual. This is likely to be an ongoing process as the needs and circumstances of each individual change over time.
Nebuliser systems are used to deliver medications to the lungs, to control the symptoms and the progression of lung disease in people with cystic fibrosis (CF). There are many different nebulised-medications prescribed for people with CF and there are many different types of nebuliser systems. Some of these nebulised medications are licenced for, and can be taken via only one type of nebuliser system; some are licensed for, and can be taken via more than one type of nebuliser system. This is an update to a previous systematic review.
To assess the time efficiency, effectiveness, safety, cost and impact of use (e.g. burden of care, adherence, quality of life (QoL)) of different nebuliser systems, when used with different inhaled medications for people with CF.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books containing conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. We also searched online trial registries.
Date of the most recent search: 9 August 2023.
Randomised controlled trials (RCTs) or quasi-RCTs comparing nebuliser systems, including conventional nebulisers, vibrating mesh technology (VMT) systems, adaptive aerosol delivery (AAD) systems and ultrasonic nebuliser systems.
Two review authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third review author assessed studies where agreement could not be reached. They assessed the certainty of the evidence using GRADE.
The search identified 216 studies with 33 of these (2270 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic saline and other solutions through the different nebuliser systems in children and adults with CF. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. The certainty of the evidence ranged from low to very low.
Some conventional nebuliser systems providing higher flows, higher respirable fractions, and smaller particles decrease treatment time, increase deposition (the amount of drug reaching the lung), and may be preferred by people with CF, as compared to other conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles.
Newer nebuliser systems using AAD, or VMT (or both) reduce treatment time compared to conventional systems. Deposition (as a percentage of priming dose) with AAD is greater than with conventional systems. VMT systems may give greater deposition than conventional systems when measuring sputum levels. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved and that individuals prefer AAD or VMT systems, but also that some nebuliser systems using VMT may be subject to increased system failures.
There is limited, unclear evidence on the impact of different nebuliser systems on lung function and a lack of data on the impact of different nebuliser systems on our outcomes of quality of life (QoL), adverse effects, respiratory exacerbations and related implications, adherence, satisfaction, cost and device reliability.