Expert consensus on the role of OM-85 in the management of recurrent respiratory infections: A Delphi study

Figures & data

Table 1. Statements reaching consensus during the first round of voting.

Statement
Disease	% agreement (scores 4 + 5)	Mean score (SD)
1. Acute respiratory infections are the primary cause of morbidity in high-income countries (the USA, Canada, and Western Europe).	88	4.0 (0.9)
2. Respiratory tract infections are the most frequent cause of visit to the General Practitioner’s Office in autumn and winter.	83	4.4 (0.9)
4. Most respiratory tract infections in children are caused by viruses (rhinovirus, respiratory syncytial virus, adenovirus, and influenza virus).	100	4.7 (0.5)
5. Primary risk factors for respiratory tract infections in pediatric patients include tobacco smoke exposure, environmental pollution, no breast feeding, and daily care attendance.	96	4.6 (0.6)
6. Recurrent respiratory tract infections have a huge social and economic impact, caused by a higher number of medical consultations, health-care costs, school absenteeism, and absence of parents from work.	96	4.6 (0.6)
7. Recurrent respiratory tract infections are associated with decline in pulmonary function, antibiotic overuse, and quality of life impairment, both for patients and their families.	92	4.3 (0.6)
8. Recurrent respiratory tract infections cause an increase in corticoid (systemic or inhaled) use in children with post-viral wheezing.	100	4.5 (0.5)
11. A significant reduction in the number of recurrent respiratory tract infections is an important therapeutic target to reduce the social and economic burden of the disease, as well as to improve the QoL of children and their families and to limit the risk to develop chronic diseases with recurrent exacerbations.	100	4.6 (0.5)
Prevention
12. The currently recommended strategy to limit the burden of recurrent respiratory infections is the elimination of environmental triggering factors and the systematic use of available vaccines.	96	4.6 (0.6)
13. The use of vaccines against influenza, pneumococcus, pertussis, and measles is crucial to reduce the burden of respiratory tract infections.	96	4.7 (0.6)
14. The use of antibiotics to prevent and treat recurrent respiratory infections is inappropriate, considering their prevalent viral etiology.	96	4.6 (0.6)
15. The partial efficacy of vaccines in children and the progressive increase of MDR bacteria require new therapeutic and preventive approaches, which need to be both effective and safe.	79	4.0 (0.8)
16. The complete removal of environmental factors responsible for recurrent infections is actually impossible, although practices such as face masks, social distancing, and frequent handwashing during the current pandemic have reduced the incidence of recurrent respiratory infections.	92	4.5 (0.8)
17. Although influenza vaccination use has increased in recent years, its coverage is still far from recommended targets in at-risk categories (75% minimum and 95% optimal).	92	4.4 (0.7)
OM-85
18. OM-85 exerts a modulation effect which induces a pre-activation of the immune system, warranting an early protection against infectious agents, as well as a control of the inflammatory state, through the balanced release of anti-inflammatory cytokines and factors.	92	4.2 (0.6)
19. OM-85 is the most studied immunomodulating agent for infection prevention.	92	4.3 (0.6)
20. OM-85 was shown to be effective in reducing the number of recurrent respiratory tract infections in smokers and in patients with COPD and chronic rhinosinusitis.	88	4.3 (0.7)
22. Orally administered OM-85 (10 d/month for 3 months) is effective in reducing the risk of new infections in children with recurrent respiratory infections aged 1–13 y, with a good safety and tolerability profile.	88	4.3 (0.8)
23. Treatment with OM-85 reduces the frequency of recurrent upper and lower respiratory tract infections in children, with a higher protective effect in subject with an increased recurrence risk.	92	4.3 (0.8)
24. In children with respiratory tract infections, treatment with OM-85 reduces the number of recurrences, the use and duration of antibiotic therapy, days of illness, and school absenteeism.	88	4.3 (0.9)
25. In children with respiratory tract infections and post-viral wheezing, treatment with OM-85 reduces the number of nasopharyngitis and wheezing episodes, as well as antibiotic use over 12 months.	88	4.2 (0.8)
29. OM-85 protective effect is maintained after a second yearly course of administration, with unchanged tolerability profile	79	4.0 (0.8)
30. OM-85 is well tolerated and safe, and it is not associated with severe adverse events and has shown a good compliance level.	100	4.4 (0.5)
31. Efficacy and safety of OM-85 have been demonstrated also in association with influenza vaccine.	87	4.2 (0.8)
32. OM-85 was shown to be well tolerated and effective in reducing the number and duration of recurrent infections of upper respiratory tract (otitis, tonsillitis, and sinusitis) in children, favoring the reduction of antibiotic use, time devoted to medical treatment, and school absenteeism.	92	4.2 (0.7)
34. Nonspecific immunomodulation obtained with OM-85 bacterial lysate amplifies natural defenses against infections and reduces respiratory tract inflammation induced by infections and allergens, thereby representing a possible strategy for management of recurrent respiratory infections in at-risk individuals.	83	4.1 (0.8)
35. OM-85 efficacy in improving the immune response against recurrent viral infections of respiratory tract in children may be particularly useful in the current COVID-19 pandemic situation.	75	3.8 (0.8)
36. Thanks to its long-term efficacy and good safety profile, OM-85 can be recommended as first-choice prophylactic treatment for the prevention of respiratory tract infections in children, especially those at high risk of recurrence.	92	4.0 (0.6)
Future strategies
37. The simultaneous administration of OM-85 and influenza vaccine does not affect the immune response against influenza virus and is not associated with increased adverse events, representing an effective and safe approach to reduce the burden of recurrent respiratory tract infections in children.	96	4.3 (0.6)
39. OM-85 and influenza vaccine exert a synergic effect on the reduction of recurrent respiratory tract infections.	83	4.0 (0.9)
40. Since the incidence of new recurrences of respiratory tract infections is highest during winter and several courses of treatment with OM-85 are needed to obtain the highest protective effect, it is recommended to start OM-85 administration early in autumn, a few weeks before influenza vaccination.	96	4.4 (0.7)

Table 2. Statements not reaching consensus during the first round of voting.

Statement
Disease	% agreement (scores 4 + 5)	Mean score (SD)
3. Respiratory tract infections represent the primary cause of mortality in children in both industrialized and developing countries.	62	4.4 (1.1)
9. The occurrence of recurrent respiratory infections in the first years of life is an important risk factor for the development of asthma later in life.	67	3.9 (0.9)
10. The use of systemic corticosteroids to treat respiratory tract infections with viral etiology correlates with relevant and potentially severe adverse effects and does not modify the natural history of the disease.	66	3.8 (1.2)
OM-85
21. OM-85, associated with standard therapy, is currently recommended for all patients with chronic rhinosinusitis, based on its demonstrated efficacy in preventing recurrences and reducing symptoms in these patients.	63	3.8 (0.8)
26. Specifically referring to ORL infections, the use of OM-85 in addition to antibiotic therapy in children with subacute rhinosinusitis and recurrent respiratory infections reduces time to symptom relief and complete recovery in the subacute phase of treatment and the incidence of respiratory tract infections in the preventive phase.	67	3.9 (0.9)
27. In children with recurrent tonsillitis, treatment with OM-85 reduces the number of tonsillectomies.	63	3.8 (0.9)
28. Protection induced by 3-month prophylaxis with OM-85 is maintained for 9 months after the end of treatment.	62	3.6 (0.8)
33. In children with acute episodes of chronic rhinosinusitis, treatment with OM-85 can be used to relieve cough and nasal obstruction/congestion and secretion and reduce the time of medical care, as well as the number and duration of subsequent exacerbations.	63	3.7 (1.0)
Future strategies
38. The use of OM-85 in association with COVID-19 vaccination (and related boosters in the coming years) might potentiate individual immune response against recurrent viral infections, reducing symptoms potentially associated with pandemic infection (cough, fever, etc.).	71	3.9 (0.8)