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Aim: To study the role of serum surfactant protein D (SP-D) as a biomarker of lung injury in scleroderma systematica (SDS) in relation to the presence of gastroesophageal reflux (GER)., Subjects and Methods: Fifty-six patients (mean age 46±14 years) with diffuse and circumscribed SDS were examined and underwent pulmonary functional tests, X-ray and, if lung injury was present, high-resolution computed tomography of the lung, echocardiography, gastroduodenoscopy, and barium X-ray of the esophagus; an enzyme-linked immunosorbent assay was used to determine serum SP-D levels., Results: SP-D concentrations significantly correlate with the presence of lung injury in SDS and are significantly higher in the presence of pulmonary fibrosis and the signs of frosted glass and honeycomb lung patterns. SP-D levels were higher in the patients with lung injury and SDS in the group of those with pulmonary fibrosis and GER than in the group of pulmonary fibrosis patients without the latter., Conclusion: Serum SP-D may be considered in a number of biomarkers for the severity of lung injury in SDS, including GER-associated lung injury.

Aim: To assess cytokine spectrum changes in different types of pulmonary sarcoidosis (PS)., Subjects and Methods: Twenty-seven PS patients without signs of pulmonary fibrosis and 14 patients with sarcoidosis complicated by pulmonary fibrosis were examined. Baseline serum Th1 and Th2 cytokine concentrations were studied. A control group comprised 30 healthy donors., Results: A higher interleukin (IL)-4/IL-2 ratio was found in the peripheral blood of the patients with pulmonary fibrosis-complicated sarcoidosis than in the other patients (326.4 +/- 122.6 and 88.2 +/- 28.6%, respectively; p = 0.002). The sarcoidosis patients with signs of pulmonary fibrosis and no symptoms of disease inflammatory activity had elevated blood IL-1 levels whereas an IL-1 receptor antagonist was decreased., Conclusion: In the patients with PS, the development and progression of pulmonary fibrosis occur with a shift in the Th1/Th2 balance towards Th2, which manifests itself as a higher IL-4/IL-2 ratio in the peripheral blood. At the same time, the signs of systemic inflammatory activity remain.

On the model of toxic diffuse pulmonary fibrosis induced by intratracheal administration of bleomycin, we studied reactions of the blood system, content of stem cells, committed hemopoietic and stromal progenitor cells in the bone marrow, spleen and peripheral blood of C57Bl/6 mice. It was shown that the development of diffuse pulmonary fibrosis was accompanied by hyperplasia of bone marrow hemopoiesis and leukocytosis in the peripheral blood. Activation of the erythroid and granulocytic hemopoietic stems was related to stimulation of hemopoietic stem cells (polypotent cells, granulocyte/erythroid/macrophage/megakaryocyte precursor cells) and committed erythroid and myeloid progenitor cells in the bone marrow. At the same time, the number of stromal precursors increased. Bleomycin increased the count of hemopoietic stem cells the peripheral blood and spleen and reduced the content of mesenchymal stem cells in the spleen and bone marrow.

Cryptogenic fibrosing alveolitis (CFA) is a severe autoimmune disease of unclear etiology and prognostically unfavorable. The complexity of the diagnostics of this disease makes it necessary to search for new methods; for this reason immunity in CFA patients must be studied. The study of humoral organ-specific, organ-unspecific and antibacterial immunity of CFA patients revealed that the latter differed from the members of the groups used for comparison by a higher frequency of positive reactions in EIA determinations of IgG antibodies to cytokeratin-8 and Moraxella catarrhalis antigens. In addition, only in CFA patients a high degree of correlation (r=0.88) between these results was established. This made it possible to propose to use these reactions for confirming the diagnosis of CFA and suggested the probable role of M. catarrhalis in triggering autoimmune reactions characteristic of this disease.

Aim: To determine the role of enhanced blood coagulation in pathogenesis of pulmonary hypertension (PH) at an early stage of fibrosing alveolitis (FA)., Material and Methods: Clinical, functional, roentgenological, coagulation and immunological examinations were performed in 17 patients with idiopathic FA (IFA), in 6 patients with exogenic allergic alveolitis (EAA), in 15 FA patients with diffuse diseases of the connective tissue (FA-DDCT). The diagnosis was verified with high resolution computed tomography (HRCT). Lesser circulation was assessed by Doppler echocardiography. Morphological impairment of the lungs was specified in all the patients using analysis of the bronchoalveolar lavage. In 9 FA patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy volunteers. Thrombin-antithrombin complex (TAT) and thrombocytic factor 4 (TF-4) were estimated with ELISA as stable, highly sensitive markers of thrombophilia., Results: The TF-4 level was elevated in all IPD patients (p < 0.05), the elevation being highest in FA-DDCT (p < 0.007). With FA progression, TF-4 concentration went down. A weak negative correlation (p < 0.047, r = -0.38) was found with average pressure in the pulmonary artery (PAAP). TAT was higher than control in all the groups (p < 0.05). Maximal TAT values were registered in EAA. If HRCT detected active inflammation and in development of irreversible fibrous changes TAT was higher vs control. A direct correlation between TAT level and PAAP was not found., Conclusion: Disorders in thrombocytic and plasmic links of hemostasis are detectable early in IPD. Stable markers of thrombophilia (TAT and TF-4) reflect activity of inflammation in FA. They can be also used as sensitive diagnostic tests for diagnosis of PH and diagnosis of patients with activated coagulation system in IPD.

Antibodies to cytokeratin-8 were detected by enzyme immunoassay (EIA) in sera of 135 patients with cryptogenic fibrosing alveiolitis, different rheumatic diseases, sarcoidosis and exogenous allergic alveolitis, 109 patients with inflammatory lung diseases and 74 donors of the Moscow Blood Transfusion Station. The results revealed that The frequency of positive EIA reactions among the donors was 7%, while in the group of patients with rheumatic diseases--from 5.9% (scleroderma) to 42.9% (fibrosing alveolitis). Positive reactions also occurred in patients with exogenous allergic alveolitis and sarcoidosis. In the group of patients with chronic inflammatory lung diseases, i.e. in pathologies of non-autoimmune origin, positive reactions occurred in 13.3-33.3% of cases. To improve diagnostics and to disclose the mechanisms of pathogenesis, more detailed study of anticytokeratin antibodies in cases of interstitial lesions and chronic inflammatory lung diseases are necessary.

Lipid peroxidation parameters, such as malonic dialdehyde and antioxidant defense (superoxide dismutase and catalase activities) were studied in healthy individuals, miners of different occupations, working at mines of different altitudes. The studies showed that increased lipid peroxidation and decreased antioxidant defense are connected with the altitude of work and exposure to the quartz-containing dust combined with hypobaric hypoxia. Malonic dialdehyde, the final toxic product of peroxidation, is accumulated as a result of it. Increased membranous lipid peroxidation results in death and lysis of cells. It becomes the principal pathogenetic component of pneumoconiosis formation and clarifies the mechanism of its early development, comparatively fast progressing, frequency of nodular forms in miners from the high and middle altitudes. That testifies the ability of hypobaric hypoxia to produce silicosis.

The content of blood plasma corticosterone, testosterone and estradiol, and receptors to corticosteroids, androgens and estrogens in pulmonary cytosol of normal male rats and those with fibrosing process in the lungs were experimentally studied by means of radioimmunoassay. With pulmonary fibrosis, a decrease in the concentration of blood plasma corticosterone and testosterone, and lower content of their pulmonary cytosol receptors to corticosteroids, androgens and estrogens are observed. As testosterone propionate was administered in the course of this experiment, there was a normalization of blood plasma corticosterone levels and those of the pulmonary cytosol receptors to androgens. The content of blood plasma testosterone and the pulmonary cytosol receptors to corticosteroids and estrogens was partially normalized. However, it was significantly different from the indices in the control group.

Blood testosterone, estradiol, hydrocortisone, iron, zinc, and copper levels in males and female patients with lung sarcoidosis, idiopathic fibrosing alveolitis and histiocytosis X were studied. The female patients were in the menopause. A significant decrease in the levels of testosterone and zinc and an increase in the levels of estradiol and copper were revealed in the patients with alveolitis and histiocytosis X. In the patients with lung sarcoidosis a significant decrease in the content of zinc and an increase in the contents of estradiol and copper were stated. There was a relationship between the magnitude of the changes in hormone and trace element levels and the respiratory failure severity.