COPD is a complex disease linked to chronic inflammation mediated by increased number of macrophages, neutrophils, and T lymphocytes. The mechanisms underlying the inflammatory response in airways include a combination of lipid mediators, inflammatory peptides, reactive oxygen, nitrogen species, chemokines, cytokines, growth factors, and proteolytic enzymes, which activate immune cells, cause elastolysis, and mucus hypersecretion (Barnes 2004). In contrast to asthma, inhaled corticosteroids in COPD have no significant impact on cellular inflammation and result in only small improvement in symptoms, exacerbation, and sputum production (Birrel et al. 2005). Additionally, inhaled corticosteroids raise the risk of respiratory tracks infections for COPD sufferers (Angata et al. 2013; Price et al. 2012). In the present study, we addressed the question of whether inhaled corticosteroids may modulate Siglec-5 and/or Siglec-14 expression in immune cells isolated from induced sputum of COPD patients. Both Siglec-5 and Siglec-14 bind to α2,3- and α2,8-linked sialic acid residues in glycoconjugates are widely expressed in pathogens and mammalian tissues (Varki and Crocker 2009). Most of CD33-related Siglecs, such as human Siglec-5, have tyrosine-based inhibitory motif (ITIM), which interacts with protein-based phosphatase SHP-1 and/or SHP-2 upon tyrosine phosphorylation resulting in cellular inhibition. In contrast, Siglec-14 lacks the ITIM domain and mediates ‘positive’ signaling via tyrosine-based activatory motifs – like the ITAM domain coupled to the DAP12 molecule (Crocker et al. 2007). Interestingly, Siglec-5 and Siglec-14 are characterized by extensive sequence similarity in the amino-terminal part, suggesting a partial conversion between Siglec-5 and Siglec-14 genes (Yamanaka et al. 2009). Homozygous wildtype individuals express only Siglec-14 and present a strong inflammatory response. In heterozygous wildtype both Siglec-5 and Siglec-14 are expressed, mediating the inflammatory response of intermediate strength. The weakest inflammatory response is observed in Siglec-14-null individuals with a single Siglec-5/14 fusion gene product, Siglec-5. In the European population, the prevalence of wildtype alleles is 90 % and may suggest a high risk of strong responses to infectious cues and elevated susceptibility to exacerbation in COPD patients (Yamanaka et al. 2009). To detect Siglec-5 and/or Siglec-14 expression in isolated sputum cells we used a specific monoclonal antibody recognizing these two receptors. We found Siglec-5 and/or Siglec-14 expression in macrophages and neutrophils in all samples. Monotherapy with formoterol and its combination with tiotropium retained Siglec receptors at the same level, while the addition of ICS significantly increased their expression. It is unclear which type of receptor has been up-regulated. However, our study was performed in European patients who have wildtype alleles and express predominantly Siglec-14. In this way, ICS may generally influence the inflammatory response to sialic acid-rich pathogens by changing of cell activation thresholds. Angata et al. (2013) described positive correlation between Siglec-14 expression and frequency of exacerbation in COPD. It is less possible that the observed effects of ICS concerned only the up-regulation of Siglec-5 receptor in patients with Siglec-5/Siglec-14 genes fusion, which account for only 10 % of the European population. In this group, the effect of ICS could be defined as a desirable and beneficial to the patient because it would be related to the immunosuppressive activity of these drugs. Our observations are in line with the general opinion that ICS are not of equal benefit to all patients and may raise the risk of harm to some individuals (Price et al. 2012). Diversified distribution of Siglec-5 and Siglec-14 genes and their products in human population confirms the need for individual characteristic of patients before ICS therapy recommendation.