Bactek­O Sublingual Vaccine Treatment in Bronchiectasis - A Pilot Study

INTERVENTION: Single centre, double‐blinded, randomised, placebo‐controlled study in patients with non‐cystic fibrosis bronchiectasis. Patients aged over 18 years with non‐cystic fibrosis bronchiectasis diagnosed by high‐resolution CT scan. Bactek‐O is a commercially available polyvalent bacterial preparation (Immunotek Laboratories, Madrid, Spain). It is administered in liquid form as a spray, sublingually. It contains different species of inactivated bacteria that are frequently present in the respiratory tract: Streptococcus pyogenes (15%), Moraxella catarrhalis (15%), Haemophilus influenzae (35%), Streptococcus pneumoniae (35%). The other excipients are glycerol, pineapple essence to improve taste, sodium chloride and water for injection Bactek‐O vaccine and a placebo will be identically packaged and delivered sublingually. Eligible subjects will be randomised to Bactek‐O vaccine or placebo with the following regime: day 1, one sublingual spray and thereafter, up to day 180, two sublingual sprays daily. The total duration of treatment is therefore 6 months. The dose is 2 x 100 µL sprays. In terms of active ingredients, there is 10^9 bacteria/mL so each spray would have 10^8 b/mL. Adherence will be monitored and measured by keeping and reviewing the bottles both through visual inspection and weight assessment. Patient's adherence with the proper use of the study drug or placebo will be assessed at visits 3 and 4, and patients will be reminded to bring all study medication pack(s) (used or unused) and completed diaries to these visits CONDITION: Non‐cystic fibrosis bronchiectasis PRIMARY OUTCOME: Sputum procalcitonin SECONDARY OUTCOME: Bactek‐O vaccine safety ; ‐ safety will be measured by regularly assessing for adverse events or side effects. This will be performed at study visits (week 0, 4, 12 and 24). There will also be phone calls on week 1, 3, 6, 10, 16 and 22. ; ‐ Patients will also be requested to documents any symptoms or concerns in their diary cards provided throughout the study. Batek‐O tolerance and adherence ; ‐ these will be assessed by weighing medication bottles and asking patients to return empty bottles. They will also document daily administration in their diary cards. Effect on lung and nasopharyngeal microbiome ; • Microbiome analysis from nasopharyngeal swab and sputum at baseline and 6 months ; • Ecological network analyses to look at bacterial co‐occurrence and potential deterrence within the airway microbiome Health‐related Quality of Life in bronchiectasis patients ; • St. George’s Respiratory Questionnaire (SGRQ) ; • Bronchiectasis Health Questionnaire (BHQ) ; • The Leicester Cough Questionnaire (LCQ) Lung function (FEV1, FVC) which will be measured using spirometry. Pulmonary exacerbations ‐ this is defined in relation to the recent ERS consensus definition. This requires "a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is require". INCLUSION CRITERIA: • Aged 18 years or over. • Able to provide written informed consent. • Able to provide spontaneous sputum sample at visit 2 (week 0). • High‐resolution CT scan (HRCT) diagnosis of bronchiectasis; CT scan performed within the past 5 years • History of at least one pulmonary exacerbation requiring antibiotic treatment in the past 12 months. Patients with asthma and COPD will be included if the primary diagnosis is bronchiectasis. ; ‐ This will be assessed during study visits and phone calls. The diary card also contains all of these components which will allow us to determine the suitability of antibiotic prescription in the community. ; ‐ Both number of exacerbations and time to first exacerbation will be assessed. Sputum and plasma cytokines – interferon, IL‐4 IL‐5, IL‐6, IL‐8, IL‐10, TNF‐a Systemic inflammation using plasma CRP and blood neutrophil counts • Clinically stable during baseline period, which is 4 weeks prior to randomisation (as defined by the absence of clinical worsening beyond normal daily variation, with no need for increasing habitual medications or taking antibiotics or prednisone and stable spirometry).