Patients with bronchiectasis (BE) suffer from a persistent cough, daily sputum expectoration, recurrent chest infections, and a poor health-related quality of life. Current guidelines for the management of BE highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum-removal as part of standard care. The investigators hypothesise that mucoactive agents (HTS or cabocisteine, or a combination of both) are effective in reducing exacerbations over a 52-week period, compared to usual care.

Mucus hypersecretion is a clinical feature of BE. This mucus-retention aids bacterial infection that can lead to pulmonary exacerbations, which further develops the "viscous cycle" of mucus-retention, infection, inflammation and tissue damage. Mucoactive drugs target this cycle by potentially increasing the ability to expectorate sputum and/or decrease mucus hypersecretion.

The current guidelines indicate that mucoactives in combination with airway clearance may be considered to enhance sputum expectoration in BE, but the evidence to support their use is limited. Furthermore, evidence for the effectiveness of hypertonic saline (HTS) and carbocisteine is insufficient to recommend them within the management of BE. However, EMBARC/BRONCH-UK data show that BE centres do prescribe mucoactives. This is important because adherence to therapies in BE in general is low, decreases as the number of prescribed medications increases, and is also related to poorer patient outcomes, including the number of pulmonary exacerbations and quality of life. Therefore, it is essential that only those drugs that are effective should be prescribed for patients with BE. There are cost considerations associated with mucoactives, and there is a risk of polypharmacy side effects.

Unlike BE, relatively strong evidence exists to favour the use of both HTS and carbocisteine within other respiratory conditions. Therefore, this trial will answer important clinical questions about whether similar benefits can be demonstrated in BE by using a pragmatic design to explore the specific effects of mucoactive agents, and directly support, or refute, more targeted use of these drugs.

Patients will be randomised to one of four treatment groups: (i) standard care and twice daily nebulised HTS (6%), (ii) standard care and carbocisteine, (iii) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (iv) standard care alone.

Inclusion Criteria:

• Diagnosis of BE on high resolution computed tomography(HRCT)/computed tomography (CT) scans
• BE must be the primary respiratory diagnosis
• One or more pulmonary exacerbations in the last year requiring antibiotics*
• Production of daily sputum
• Stable for 14 or more days before the first study visit with no changes to treatment
• Willing to continue any other existing chronic medication throughout the study
• Female subjects must be either surgically sterile, postmenopausal or agree to use effective contraception during the treatment period of the trial *This can include patient reported exacerbations

Exclusion Criteria:

• Age <18 years old
• Patients with cystic fibrosis (CF)
• Patients with COPD as a primary respiratory diagnosis
• Current smokers, female ex-smokers with greater than 20 pack years and male ex-smokers with greater than 25 pack years.
• Forced expiratory volume in one second (FEV1) <30%
• If being treated with long term macrolides, on treatment for less than one month before joining study
• Patients on regular isotonic saline
• Treatment with HTS, carbocisteine or any mucolytics within the past 30 days
• Known contraindication or intolerance to hypertonic saline or carbocisteine
• Hypersensitivity to any of the active ingredients or the excipients of carbocisteine
• Active peptic ulceration
• Any heredity galactose intolerance, the Lapp-Lactase deficiency or glucose-galactose malabsorption
• Patients unable to swallow oral capsules
• Women who are pregnant or lactating
• Participation in other trials of investigational products within 30 days

Requests for data sharing will be reviewed on an individual basis by the Chief Investigator (CI) and the Trial Management Group (TMG).