RATIONALE: Improved understanding and treatment of cystic fibrosis (CF) has led to longer life expectancy, which is accompanied by an increasingly complex regimen of treatments. Suboptimal adherence to the treatment plan, in the context of respiratory disease, is associated with poorer health outcomes. With digital technology being more accessible, it can be used to monitor adherence to inhaled therapies via chipped nebulisers, mobile phone applications and web-based platforms. This technology can allow monitoring of adherence, as well as clinical outcomes, and allow feedback to both the person with CF and their healthcare team.
OBJECTIVES: To assess the effects of using digital technology to monitor adherence to inhaled therapies and health status in adults and children with CF.
SEARCH METHODS: We searched the Cochrane CF Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched Embase and three clinical trial registries, and checked the references of included studies. The date of last search was 27 February 2025.
ELIGIBILITY CRITERIA: We searched for randomised controlled trials (RCTs) looking at the effects of digital technology for monitoring adherence to inhaled therapies of children and adults with CF.
OUTCOMES: We assessed available data (at up to three months in one study, and up to 12 months in the second) for adherence to the inhaled treatment, treatment burden, quality of life (QoL) and the change from baseline in forced expiratory volume in one second (FEV). We assessed the number of pulmonary exacerbations by the end of each study. 1
RISK OF BIAS: Using Cochrane's Risk of Bias 2 tool, we assessed the risk of bias within each of the included trials and for each outcome from the randomisation process, deviations from intended interventions, missing outcome data, measurement of the outcome and selection of the reported result.
SYNTHESIS METHODS: Two review authors screened the search results for studies eligible for inclusion in the review and extracted their data. Due to the difference in the studies' interventions, we analysed the data separately. We assessed the overall certainty of the evidence using GRADE.
INCLUDED STUDIES: We included two studies with 628 participants aged five to 41 years. There was one study in each of two different comparisons.
SYNTHESIS OF RESULTS: Nebuliser target inhalation mode versus standard inhalation mode One parallel study was carried out over 10 weeks after a run-in period of four to six weeks. The study compared the effects of a digitally enhanced inhalation mode (target inhalation mode) for nebulised antibiotics compared to standard mode in children attending a regional CF clinic in the UK. The primary outcome was the time taken to complete the inhaled treatment, but the study authors also reported on adherence to therapy. The results showed that adherence may improve when using the target inhalation mode (mean difference (MD) 24.0%, 95% confidence interval (CI) 2.95 to 45.05; 1 study, 20 participants; low-certainty evidence). The target inhalation mode may make little or no difference to FEV% predicted (MD 1.00%, 95% CI -9.37 to 11.37; 1 study, 20 participants; low-certainty evidence). The study did not report on treatment burden, QoL or pulmonary exacerbations. We downgraded the certainty of the evidence for imprecision due to the small sample size, and for indirectness as the study was carried out in children and the results may not be applicable to adults. eNebuliser with digital support versus eNebuliser without support One large multicentre RCT monitored adherence via data-tracking nebulisers for 12 months. The intervention group also received access to an online web-based platform, CFHealthHub, which offered tailored, flexible support from the study authors as well as access to their adherence data, educational and problem-solving information. Compared to usual care, the digital intervention probably improves adherence to inhaled therapy (MD 18%, 95% CI 12.90 to 23.10; 1 study, 588 participants; moderate-certainty evidence); probably leads to slightly reduced treatment burden (MD 5.10, 95% CI 1.79 to 8.41; 1 study, 539 participants; moderate-certainty evidence); and may lead to slightly improved FEV% predicted (MD 3.70%, 95% CI -0.23 to 7.63; 1 study, 556 participants; low-certainty evidence). There is probably little or no difference in the incidence of pulmonary exacerbations or QoL between the two groups. We downgraded the certainty of the evidence for indirectness as the intervention was only assessed in an adult population and therefore may not apply to children. 1 1
AUTHORS' CONCLUSIONS: Digital monitoring plus tailored support via an online platform probably improves adherence to inhaled therapies and reduces treatment burden (but without a corresponding change in QoL) in the medium term (low- and moderate-certainty evidence). In a shorter timeframe, technological enhancement of inhaling antibiotics may improve adherence to treatment (low-certainty evidence). There may be little or no effect on lung function with either intervention, and online monitoring probably makes no difference to pulmonary exacerbations. Future research should assess the effect of digital technology on adherence to inhaled therapies in both children and adults. Consideration of adherence to the total treatment regimen is also important, as improved adherence to inhaled therapies could come at the cost of adherence to other parts of the treatment regimen.
FUNDING: The original review was supported by Cochrane Infrastructure funding from the National Institute for Health Research (NIHR). The review was updated with Cochrane CF funding from the CF Foundation and the UK CF Trust.
REGISTRATION: Protocol (2020) DOI: 10.1002/14651858.CD013733 Original review (2023) DOI: 10.1002/14651858.CD013733.pub2.
