Post Authorization Efficacy and Safety Study (PAES) to Confirm and Collect More Clinical Data of Buccalin® Tablets In the Prophylaxis of Recurrent Lower Respiratory Tract Infections (RLRTIs).

Inclusion criteria

• Patients willing and able to provide voluntary informed consent and to follow protocol requirements.
• Male or females from 18 to 99 years old, (Adult, Older Adult).
• Patients with Recurrent LRTIs including tracheitis, tracheobronchitis, acute bronchitis and exacerbations of chronic lung disease (asthma and/or COPD and/or bronchiectasis), who present with both of the following:

a) ≥2 episodes within 12 months prior to the run-in period based on patient reported medical history (to access the run-in period) b) ≥2 episodes during the run-in period documented by appropriate microbiological diagnostic test (to access the treatment period)

• Patients:

• not vaccinated or
• vaccinated against the most common pathogens for respiratory infectioan (within 12 months prior to the run-in period or during the run-in period, but not during the treatment period)*:

• Anti-pertussis vaccination

• Covid-19 vaccination

• Respiratory Syncytial Virus vaccination

• Influenza vaccination

• Pneumococcal vaccination

• Patients vaccinated with other types of vaccines that have no effect on the lower respiratory tract (e.g. hepatitis b vaccination, shingles/herpes zoster vaccination, papilloma virus vaccine), in addition to the ones listed above, may also be included.

Exclusion criteria

RUN-IN period

• Female patient: pregnant, lactating or planning pregnancy (Female of child-bearing potential will undergo urine pregnancy test).
• Female of potential child-bearing that does not use at least one effective contraceptive method for the entire study.
• Contraindication or known hypersensitivity to the active ingredients of bacterial lysates or any excipients listed in the ingredients.
• Pneumonia (based on the EMA Referral Procedure EMEA/H/A-31/1465).
• Known history of tuberculosis and/or cystic fibrosis.
• Known history of immunodeficiency diseases (e.g., HIV infection, AIDS, or any type of congenital or iatrogenic immune deficiency, including IgA deficiency).
• Severe heart failure (NYHA class III and IV).
• Haematologic diseases including severe anaemia (defined according to the National Cancer Institute as Hemoglobin < 8.0 g/dL).
• Renal failure (eGFR < 30 mL/min).
• History of known liver damages defined by the METAVIR classification (F1-F4)*.
• Malignancies with a remission period of < 5 years.
• Wheezing documented to be caused by gastroesophageal reflux**.
• Patient legally or mentally incapacitated unable to give informed consent for the participation in this study.
• Patient who is unable or unwilling to comply with the appointments or with all the requirements of the Protocol.
• History of autoimmune diseases and acute intestinal infections, as reported in Buccalin® SmPC.

• This criterion only applies to patients with known liver disease who can produce valid fibroscan and/or biopsy results and bring them for demonstration.

• The criterion can only be applied if the patient presents clinically reliable documentation that the wheezing is not due to a lung disease (i.e. gastroscopy).

TREATMENT period

• Female patient: pregnant, lactating or planning pregnancy (Female of child-bearing potential will undergo urine pregnancy test).
• Female of potential child-bearing that does not use at least one effective contraceptive method for the entire study.
• Contraindication or known hypersensitivity to the active ingredients of bacterial lysates or any excipients listed in the ingredients.
• Pneumonia (based on the EMA Referral Procedure EMEA/H/A-31/1465).
• Known history of tuberculosis and/or cystic fibrosis.
• Known history of immunodeficiency diseases (e.g., HIV infection, AIDS, or any type of congenital or iatrogenic immune deficiency, including IgA deficiency).
• Severe heart failure (NYHA class III and IV).
• Haematologic diseases including severe anaemia (defined according to the National Cancer Institute Hemoglobin < 8.0 g/dL).
• Renal failure (eGFR < 30 mL/min).
• History of known liver damages defined by the METAVIR classification (F1-F4)*.
• Malignancies with a remission period of < 5 years.
• Injection or oral administration of steroids within 4 weeks prior to randomization**.
• Use of immunosuppressants, immunostimulants, or gamma globulins within 6 months prior to randomization.
• Previous use within 6 months prior to randomization or ongoing use of bacterial lysates.
• Any major surgery within the last 3 months prior to randomization.
• Wheezing documented to be caused by gastroesophageal reflux***.
• Patient legally or mentally incapacitated unable to give informed consent for the participation in this study.
• Patient who is unable or unwilling to comply with the appointments or with all the requirements of the Protocol.
• History of autoimmune diseases and acute intestinal infections, as reported in Buccalin® SmPC.

• This criterion only applies to patients with known liver disease who can produce valid fibroscan and/or biopsy results and bring them for demonstration.

• In these instances, patients may undergo a washout period of 4 weeks to qualify for the treatment period.

• The criterion can only be applied if the patient presents clinically reliable documentation that the wheezing is not due to a lung disease (i.e. gastroscopy).