Randomised cross-over trial evaluating the short-term effects of non-invasive ventilation as an adjunct to airway clearance techniques in adults with cystic fibrosis.

Introduction: Non-invasive ventilation (NIV) is used in cystic fibrosis (CF) to support airway clearance techniques (ACTs) by augmenting tidal volumes and reducing patient effort. However, the evidence base for this is limited. We hypothesised that NIV, in addition to usual ACT, would increase sputum clearance. In addition, we investigated ease of sputum clearance (EoC), work of breathing (WoB) and NIV tolerability. Methods: Adults with CF (16+ years) at the end of hospitalisation for a pulmonary exacerbation were randomised to a cross-over trial of NIV-supported ACT or ACT alone in two consecutive days. No other changes to standard care were made. The primary outcome was the total 24-hour expectorated sputum wet weight after the intervention. Spirometry was completed pre-treatment and post-treatment. Oxygen saturations were measured pre-treatment, during treatment and post-treatment. EoC and WoB were assessed using Visual Analogue Scale. Results: 14 subjects completed the study (7 male, mean age 35 [SD 17] years, mean forced expiratory volume in 1 s [FEV1] 49 [20] % predicted). The difference between treatment regimens was -0.98 g sputum (95% CI -11.5 to 9.6, p=0.84) over 24 hours. During treatment oxygen saturations were significantly higher with NIV-supported ACT (mean difference 2.0, 95% CI 0.9 to 2.6, p=0.0004). No other significant differences were found in post-treatment FEV1, EoC, WoB, oxygen saturations or subject preference. Conclusions: There was no difference in treatment effect between NIV-supported ACT and ACT alone, although the study was underpowered. Oxygen saturations were significantly higher during NIV-supported ACT, but with no effect on post-treatment saturations. NIV was well tolerated. Trial registration number: NCT01885650.

Inhaled therapy in cystic fibrosis: agents, devices and regimens.

KEY POINTS: There have been significant advances in both inhalation medicines and delivery devices with "intelligent nebulisers" and "dry-powder inhalers" becoming commonplace in CF care.Inhaled medicines generate high levels of a drug within the airways with limited systemic effects, offering safe and convenient antibiotic and mucolytic therapy for individuals with CF.Variations in adherence are not unique to CF; however, treatment burden is high and therefore fast inhaled drug delivery devices may assist individuals in completing the prescribed treatment regimes.Prescribers of inhaled medicines have a responsibility to consider, in addition to efficacy, the appropriated drug/device combination for each individual in order to promote adherence and achieve the desired clinical benefit. SUMMARY: The recognised mainstay daily treatments for cystic fibrosis (CF) focus on inhaled and oral medications, airway clearance and optimised nutrition. This review discusses recent advances in inhaled therapies for the management of CF, including devices such as intelligent nebulisers, drug formulations and supporting evidence for inhaled antibiotics (for the management of chronic Pseudomonas aeruginosa) and muco-active drugs. We include practical advice for clinicians regarding the optimisation of inhalation technique and education. The influence of adherence on the use of inhaled therapies in CF is also reviewed. EDUCATIONAL AIMS: To inform readers about the history and progression of inhaled therapies for people with CF with reference to the literature supporting current practice.To highlight the factors that may impact the success of inhaled therapies, including those which are device specific such as drug deposition and those which influence adherence.

Positive pressure--analysing the effect of the addition of non-invasive ventilation (NIV) to home airway clearance techniques (ACT) in adult cystic fibrosis (CF) patients.

BACKGROUND: There is no published literature on the frequency of use of non-invasive ventilation (NIV) with airway clearance techniques (ACT) throughout the cystic fibrosis (CF) population; 3.9% (191 people of 5062 registered) of the United Kingdom CF population older than 16 years are reported to use NIV in registry data; however, it is not specified if this is for ACT or respiratory failure. Using NIV with ACT decreases work of breathing and fatigue during in-patient admissions for CF patients. We hypothesised these effects could be replicated at home, potentially reducing hospital admissions. METHOD: Fourteen adult patients with CF scored ease of clearance and breathlessness with ACT before and after addition of NIV to normal ACT routine using a visual analog scale. Patient views on NIV with ACT were collected via a structured interview. Number of home intravenous (IV) antibiotic courses and days in hospital was collected for one year pre- and post-NIV provision. RESULTS: Patients reported statistically significant improvements in ease of clearance (p = 0.011) and reduced breathlessness during ACT using NIV (p = 0.011). Structured interview results indicated patient reports of sputum clearance improved. In-patient days were lower, while home IV days were higher after NIV was set up, although not statistically significant. CONCLUSION: This study is limited by small numbers; however, trends towards less hospital admissions and greater patient ease while using NIV with ACT warrant further investigation.