Review question
What are the benefits and risks of using non-invasive positive pressure ventilation (NIPPV) to treat people with cystic fibrosis (pwCF)?
Key messages
Based on current available evidence, we are not sure:
- whether one type of NIPPV is better than another;
- in which situations it helps the most;
- or for which specific purposes it works best in pwCF.
The results are also uncertain about the effects of NIPPV on mortality and quality of life. Some people found NIPPV helpful and preferred using it, while others stopped because they felt uncomfortable or could not tolerate the mask; the evidence about this is still very uncertain. Regarding safety, most studies did not report serious problems (serious adverse events). However, some described situations such as swallowing air (aerophagia) and air trapped in the lung (pneumothorax).
What is CF?
CF is a disease that is present from birth, and affects multiple body systems, especially the respiratory system. Common symptoms are persistent cough with thick mucus, frequent lung infections, and breathing difficulties. CF worsens with age, causing complications due to constant infections that damage airways, reduce lung function, and may lead to death.
What is NIPPV, and how can it assist in the treatment of pwCF?
NIPPV is a treatment where a machine is used to help the person breathe. During NIPPV therapy, the person breathes using a mask that forces the air into the lungs, keeping the airways open and requiring less effort from the individual. There are two main types of NIPPV:
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Continuous positive airway pressure (CPAP): this type of NIPPV forces air into the lungs constantly (during inhalation and exhalation).
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Bilevel positive airway pressure (BiPAP): this type of NIPPV forces air into the lungs more during inhalation and less during exhalation.
Studies suggest that NIPPV, combined with techniques to clear lung mucus, may ease breathlessness and improve oxygen levels in the blood. It can enhance sleep quality, reduce daytime sleepiness, and lessen fatigue during exercise, allowing people to exercise for more time. However, some people feel anxious and uncomfortable with a breathing mask. Most of these studies involved individuals with other lung diseases, so it remains unclear if NIPPV can help pwCF live longer or better, or if it might come with any risks for them.
What did we want to find out?
How the different types of NIPPV, used alone or combined with other treatments, can help pwCF.
What did we do?
We searched the main databases and analyzed all relevant studies available.
What did we find?
We found 14 studies with 261 children and adults at different stages of CF (including times when symptoms suddenly worsen, indicating the person is in crisis; and when symptoms remain the same as previously, meaning that the disease is stable or under control). NIPPV was compared to standard treatments, to other airway clearance methods (such as PEP mask or directed coughing), and to oxygen therapy. In some trials, it was also combined with other treatments. The duration of the treatments varied, from a single session to repeated use for up to three months.
Main results
In pwCF, the effects of BiPAP during pulmonary crises (exacerbations) are still uncertain. It is not clear whether BiPAP is better or worse than a PEP mask (a mask that creates resistance when breathing out) or guided coughing (a technique to help clear lung secretions) in terms of the amount of phlegm (thick sticky mucus) cleared and the tiredness felt by patients. The effects of BiPAP compared to oxygen therapy (air with a higher concentration of oxygen), or when used together with airway clearance techniques to shorten hospital stays, improve comfort, or reduce side effects, are also unclear.
In pwCF who are stable, the evidence is also very uncertain. We do not know whether BiPAP, compared to a PEP mask alone or in combination with other treatments, improves lung function (the amount of air the lungs can breathe in and out), sleep quality, or patient acceptance. Another device, CPAP, has also been studied in combination with airway clearance techniques (methods to loosen and clear mucus from the lungs), but the results remain uncertain.
What are the limitations of the evidence?
All studies included few participants, which may not have been sufficient to show the real effects. There are also doubts about how these studies were conducted. The confidence intervals were wide, which means that the true effect may be quite different from what appeared in the results. No study evaluated the long-term effects of the interventions, mainly focusing on immediate effects, such as one or two sessions.
Overall, we had only low to very low confidence in the results. Further larger, better‐quality trials are needed to clarify the effects of NIPPV.
How up-to-date are these findings?
The evidence is current to 2 April 2025.
Read the full abstract
Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis by providing ventilatory support and avoiding tracheal intubation. Using non-invasive ventilation, in the appropriate situation or individuals, can improve lung mechanics through increasing airflow and gas exchange and decreasing the work of breathing. Non-invasive ventilation thus acts as an external respiratory muscle. This is an update of a previously published review.
Objectives
To assess the effects, acceptability and individual preference of NIPPV for pwCF.
Search strategy
On 2 April 2025, we conducted searches in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register. Additionally, we consulted clinical trial registry databases and checked the reference lists of included studies.
Selection criteria
Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation used for airway clearance or during sleep or exercise in people with acute or chronic respiratory failure in cystic fibrosis.
Data collection and analysis
Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data.
Main results
Ten trials met the inclusion criteria with a total of 191 participants. Seven trials evaluated single treatment sessions, one evaluated a two-week intervention, one evaluated a six-week intervention and one a three-month intervention. It is only possible to blind trials of airway clearance and overnight ventilatory support to the outcome assessors. In most of the trials we judged there was an unclear risk of bias with regards to blinding due to inadequate descriptions. The six-week trial was the only one judged to have a low risk of bias for all other domains. One single intervention trial had a low risk of bias for the randomisation procedure with the remaining trials judged to have an unclear risk of bias. Most trials had a low risk of bias with regard to incomplete outcome data and selective reporting.
Six trials (151 participants) evaluated non-invasive ventilation for airway clearance compared with an alternative chest physiotherapy method such as the active cycle of breathing techniques or positive expiratory pressure. Three trials used nasal masks, one used a nasal mask or mouthpiece and one trial used a face mask and in one trial it is unclear. Three of the trials reported on one of the review's primary outcome measures (quality of life). Results for the reviews secondary outcomes showed that airway clearance may be easier with non-invasive ventilation and people with cystic fibrosis may prefer it. We were unable to find any evidence that non-invasive ventilation increases sputum expectoration, but it did improve some lung function parameters.
Three trials (27 participants) evaluated non-invasive ventilation for overnight ventilatory support compared to oxygen or room air using nasal masks (two trials) and nasal masks or full face masks (one trial). Trials reported on two of the review's primary outcomes (quality of life and symptoms of sleep-disordered breathing). Results for the reviews secondary outcome measures showed that they measured lung function, gas exchange, adherence to treatment and preference, and nocturnal transcutaneous carbon dioxide. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between non-invasive ventilation compared with oxygen or room air except for exercise performance, which significantly improved with non-invasive ventilation compared to room air over six weeks.
One trial (13 participants) evaluated non-invasive ventilation on exercise capacity (interface used was unclear) and did not reported on any of the review's primary outcomes. The trial found no clear differences between non-invasive ventilation compared to no non-invasive ventilation for any of our outcomes.
Three trials reported on adverse effects. One trial, evaluating non-invasive ventilation for airway clearance, reported that a participant withdrew at the start of the trial due to pain on respiratory muscle testing. One trial evaluating non-invasive ventilation for overnight support reported that one participant could not tolerate an increase in inspiratory positive airway pressure. A second trial evaluating non-invasive ventilation in this setting reported that one participant did not tolerate the non-invasive ventilation mask, one participant developed a pneumothorax when breathing room air and two participants experienced aerophagia which resolved when inspiratory positive airway pressure was decreased.
Authors' conclusions
Current evidence on the effects of NIPPV in patients with CF, both in people experiencing a pulmonary exacerbation and in stable conditions, is still uncertain. The studies included few participants, assessed few critical outcomes, and presented methodological limitations, resulting in substantial uncertainties. High-quality studies with longer interventions are needed to better estimate the effects of NIPPV on airway clearance, during nocturnal ventilation, during exercise, or for other applications in patients with CF.
Funding
The authors of the 2025 update did not receive financial support. This review was previously supported by the National Institute for Health & Care Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group.
Registration
This is an update of a Cochrane Review previously published in 2003, 2007, 2011, 2013 and 2017.
