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).

RUN-IN period

1. Female patient: pregnant, lactating or planning pregnancy (Female of child-bearing potential will undergo urine pregnancy test).

2. Female of potential child-bearing that does not use at least one effective contraceptive method for the entire study.

3. Contraindication or known hypersensitivity to the active ingredients of bacterial lysates or any excipients listed in the ingredients.

4. Pneumonia (based on the EMA Referral Procedure EMEA/H/A-31/1465).

5. Known history of tuberculosis and/or cystic fibrosis.

6. Known history of immunodeficiency diseases (e.g., HIV infection, AIDS, or any type of congenital or iatrogenic immune deficiency, including IgA deficiency).

7. Severe heart failure (NYHA class III and IV).

8. Haematologic diseases including severe anaemia (defined according to the National Cancer Institute as Hemoglobin \< 8.0 g/dL).

9. Renal failure (eGFR \< 30 mL/min).

10. History of known liver damages defined by the METAVIR classification (F1-F4)\*.

11. Malignancies with a remission period of \< 5 years.

12. Wheezing documented to be caused by gastroesophageal reflux\*\*.

13. Patient legally or mentally incapacitated unable to give informed consent for the participation in this study.

14. Patient who is unable or unwilling to comply with the appointments or with all the requirements of the Protocol.

15. 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

1. Female patient: pregnant, lactating or planning pregnancy (Female of child-bearing potential will undergo urine pregnancy test).

2. Female of potential child-bearing that does not use at least one effective contraceptive method for the entire study.

3. Contraindication or known hypersensitivity to the active ingredients of bacterial lysates or any excipients listed in the ingredients.

4. Pneumonia (based on the EMA Referral Procedure EMEA/H/A-31/1465).

5. Known history of tuberculosis and/or cystic fibrosis.

6. Known history of immunodeficiency diseases (e.g., HIV infection, AIDS, or any type of congenital or iatrogenic immune deficiency, including IgA deficiency).

7. Severe heart failure (NYHA class III and IV).

8. Haematologic diseases including severe anaemia (defined according to the National Cancer Institute Hemoglobin \< 8.0 g/dL).

9. Renal failure (eGFR \< 30 mL/min).

10. History of known liver damages defined by the METAVIR classification (F1-F4)\*.

11. Malignancies with a remission period of \< 5 years.

12. Injection or oral administration of steroids within 4 weeks prior to randomization\*\*.

13. Use of immunosuppressants, immunostimulants, or gamma globulins within 6 months prior to randomization.

14. Previous use within 6 months prior to randomization or ongoing use of bacterial lysates.

15. Any major surgery within the last 3 months prior to randomization.

16. Wheezing documented to be caused by gastroesophageal reflux\*\*\*.

17. Patient legally or mentally incapacitated unable to give informed consent for the participation in this study.

18. Patient who is unable or unwilling to comply with the appointments or with all the requirements of the Protocol.

19. 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).

What this study is about