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Combination of bronchial asthma (BA) and gastroesophageal reflux disease (GERD) is a widespread clinical situation. The two pathologies are known to influence each other leading to disturbances in immune responsiveness. We studied phenotypes and phenotypic plasticity of immune cells (alveolar macrophages) in patients with BA and GERD. It was shown that BA and GERD are largely associated with AM of proinflammatory M2 and anti-inflammatory M1 phenotypes respectively. Population of AM with MI phenotype increases in patients having both BA and GERD compared with that in BA alone. In vitro experiments showed that acidic milieu promotes shifting the phenotype toward the predominance of M1, i.e. simulates the situation characteristic of GERD. Combination of BA and GERD narrows the interval within which AM can change MI phenotype (i.e. makes them more "rigid") but broadens the range in which they can change M2 phenotype. Also, GERD promotes the development of morphological rigidity of AM. Patients with BA given steroid therapy undergo inversion of phenotypic plasticity of AM. These data characterize the immunological component of BA and/or GERD pathogenesis. They help to better understand mechanisms of development of broncho-pulmonary pathology in GERD patients and can be used to work out new methods for the treatment of these diseases.

The study of pathogenesis of bronchial asthma (BA) and gastroesophageal reflux disease (GERD) or their combination showed that the intensity of inflammation and the choice between Thl and Th2 immune responses are determined by macrophages (elements of congenital immunity). Lung surfactant protein D (SP-D) existing in various oligomneric forms (as monomer trimer, dodecamer, multimer) plays an important role in the mechanism of transformation ofalveolar macrophage phenotype. Patients with BA+GERD have higher SP-D level in the bronchoalveolar lavage fluid than those with GERD alone but lower than patients with BA. SP-D dodecamers were found only in BA patients given basaLtherapy with inhaled glucocorticoids (IGC). It suggests that the presence of dodecamers in the lavage fluid may result firom anti-inflammatory action of IGC. They are absent in patients with BA+GERD treated with IGC probably because GERD enhances inflammatoly changes in the lungs of BA patients despite basal therapy These data together with results of experimental acidification of lavage fluid from BA patients give reason to hypothesize that microaspiration of acidic gastric contents frequently associated with GERD is a cause of local decrease of pH in different segments of the bronchial tree triggering two pathogenetic mechanisms: (I) programming proinflammatory MI phenotype of alveolar macrophages, increased production of nitric oxide, nitrosation of SP-D and destruction of its anti-inflammatory multimers ; (b) direct destruction ofSP-D oligomers in the acid medium. Both mechanisms reduce the level of anti-inflammatory SP-D multimers and increase the level ofproinflammatory monomers. Thus, decreased pH in lower airways is a real pathogenetic factor of anti-inflammatory shift in the oligomeric SP-D composition accounting for the inflammatory reaction of lungs in GERD.