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Challenging mucosal immunity with bacterial extracts to prevent respiratory infections: an old therapy revisited.

Prevention of recurrent infections of the upper and lower respiratory tracts, in both children and adults, is one of the traditional challenges of respiratory medicine in order to reduce an important burden on both the individual patient and the health system [1-3]. There is a wide spectrum of options, from general environmental measures (an historical example being the clean air act in UK in the late fifties) (4), to individual interventions, i.e. prevention of negative voluntary habits, such as tobacco smoking and excessive alcohol intake, to regular adherence to treatments in chronic disorders (such as COPD) [3], but the most popular measures are targeted to the immune system, in particular with vaccination or immunomodulators. In recent years, as demonstrated in the paper by E. Pozzi published in this issue of the journal [5], a very old treatment has been relaunched, i.e. oral bacterial lysates as immunostimulating agents to prevent recurrent respiratory infections [6]. Their mechanism of action relies on the ability of bacterial components to stimulate the gut associated lymphoid tissue (the Peyer’s patches in particular) and on the properties of the activated dendritic cells and lymphocytes to re-circulate selectively among the different sites of the MALT, the Mucosal Associated Lymphoid Tissue, including the upper and lower airways mucosa. As a consequence, the stimulation of one station alerts the whole MALT against the attack of foreign microrganisms. Quite a large body of evidence has been accumulated on the biological effects of bacterial lysates in animal models and in humans, in terms of e.g. phagocyte and lymphocyte activation, IgA increase, cytokine production [6, 7]. It would seem that bacterial extracts are also able to promote the shift of naive lymphocyte maturation preferentially to Th1 instead of Th2 subset. This property is under investigation in the prevention and treatment of allergic disorders [8]. Whether bacterial lysates act as vaccines or aspecific immune modulators or both is still a matter needing further research; the non-specific immune stimulation is well known, a production of specific antibodies has been demonstrated too, but whether they are protective or not is still under investigation [5, 6]. The demonstration of a correspondent clinical efficacy has also been obtained in different trials, using an appropriate experimental design and different outcome measures, such as number and length of exacerbations, use of health care resources (number and days of hospitalisation, antibiotic consumption) and indirect costs, e.g. work or school days lost [9-11]. A metanalysis showed a mean value of 0.6 prevented acute exacerbations of chronic obstructive pulmonary disease (COPD) per 6 months per patient, and a reduction of 9 days in antibiotic treatment per 6 months per patient; the effective costsavings per patient per 6 months were 51,095 Lira (= 26,39 Euro), with respect to antibiotic treatment alone. Even assuming 0.3 prevented exacerbations per 6 months per patient, the preventive treatment still proved to be cost effective [12]. Adverse events are in general very limited and mainly confined to the digestive tract or to mild exacerbation of the infectious episode [11]. In some cases a concomitant administration with vaccines has been proposed for an adjuvant effect in the prevention of influenza [13]. In conclusion, biological and clinical data in literature would support the efficacy of oral bacterial lysates in the prevention of recurrent respiratory infections, at least in immunocompetent subjects. On the other hand, a few discrepancies resulting from different papers should foster further research to better define which patients really can take advantage from oral bacterial extracts with regard to factors such as age, living environment, comorbidities, frequency of exacerbations etc, and which therapeutic schemes are best effective. Monaldi Arch Chest Dis 2004; 61: 1, 4-5.