[Vasaprostan treatment of fibrosing alveolitis in patients with pulmonary hypertension]. / Primenenie vazoprostana u bol'nykh legochnoi gipertoniei pri fibroziruiushchem al'veolite.

AIM: To study clinical efficacy of vasaprostan in patients with fibrosing alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on functional activity of platelets and endothelium, intensity of free radical processes. MATERIAL AND METHODS: Seven FA patients were examined. They had either idiopathic FA or FA with diffuse diseases of the connective tissues. The following methods were used to assess the effect: standard clinical tests, high resolution computer tomography, Doppler echocardiography, definition of the complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation of oxygen active forms by leukocytes was measured by luminol-dependent chemiluminescence. Morphological verification of the diagnosis was made by the results of open pulmonary biopsies. RESULTS: Vasaprostan reduced pressure in the pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25 +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4 (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced the ability of platelets to inhibit generation of active oxygen forms (from 0.9 +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid peroxidation. CONCLUSION: Good effect of vasaprostan on platelet activity, free radical processes validates its use in combined treatment of various FA forms for correction of PH, its complications and as an antifibrogenic agent.

[Role of endothelial dysfunction and coagulation disorders in the development of pulmonary fibrosis in patients with interstitial lung diseases]. / Rol' éndotelial'noi disfunktsii i koagulologicheskikh narushenii v razvitii legochnogo fibroza u bol'nykh insterstitsial'nymi bolezniami legkikh.

Thirty-two patients with different forms of interstitial lung diseases (ILD), such as idiopathic fibrosing alveolitis (IFA) (n = 17) and fibrosing alveolitis concurrent with diffuse connective tissue diseases (FA-DCTD), were examined. Clinical, echocardiographic, computed tomographic, coagulative, and immunological studies were performed. Enzyme immunoassay was used to determine the levels of a complex of thrombin and antithrombin III (TAT) and platelet factor IV (PF-IV). There were significant increases in the levels of PF-IV (4.36 +/- 0.25 mg/l) and TAT (10.87 +/- 3.8 mg/l) in patients with ILD as compared to the control (2.75 +/- 0.47 and 1.8 +/- 0.2 mg/l, respectively; p < 0.05). In patients with early FA-DCTD with the predominance of the milk glass syndrome during high-resolution CT (HRCT), the level of PF-IV was greater than the normal levels (p < 0.05) and decreased with the progression of the disease and with the formation of the honeycomb lung. If there were HRCT signs of active inflammation, the level of TAT was higher than that in the control; this was also in the development of irreversible fibrous changes.

[Markers of thrombophilia in pulmonary fibrosis complicated by pulmonary hypertension]. / Markery trombofilii pri legochnom fibroze, oslozhnennom legochnoi gipertoniei.

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.

[Role of certain neurohumoral factors in development of pulmonary hypertonia in patients with interstitial lung diseases]. / Rol' nekotorykh neirogumoral'nykh faktorov v razvitii legochnoi gipertonii u bol'nykh interstitsial'nymi bolezniami legkikh.

AIM: To ascertain the role of some neurohumoral factors--nitric oxide (NO), ACE, histamine--in development of pulmonary hypertension (PH) in patients with interstitial lung diseases (ILD). MATERIAL AND METHODS: A total of 32 ILD patients were examined. Of them 14 had idiopathic fibrosing alveolitis (IFA), 6 had exogenous allergic alveolitis (EAA) and 12 patients had ILD in diffuse disease of the connective tissue (ILD-DDCT). In addition to routine tests, those for NO, ACE, histamine, serotonin in plasma were performed; Doppler echocardiography and high-resolution computed tomography were conducted. In 9 patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy subjects. RESULTS: The highest mean pressure in the pulmonary artery (PmPA) was registered in IFA vs EAA and ILD-DDCT patients (p < 0.001). NO concentration in plasma was higher in ILD-DDCT than in control patients. In IFA and EAA the level of NO was like in controls. Concentration of NO in plasma of IDL patients correlated with high activity of the process. No correlation was found between ACE in plasma and PmPA, ACE levels were much higher in controls than in the ILD patients (p < 0.05). Histamine levels were higher in ILD patients than in controls being the highest in ILD-DDCT. Serotonin was insignificantly higher in ILD patients than in controls. CONCLUSION: Damage to the endothelium of the pulmonary arteries and imbalance of neurohumoral factors may be considered as a mechanism of development and stabilization of PH in ILD patients.

[Pulmonary hypertension in interstitial diseases of the lungs]. / Legochnaia gipertenziia pri interstitsial'nykh bolezniakh legkikh.

Clinical, functional, immunological and x-ray examinations were performed in 32 patients with interstitial pulmonary diseases (14 with idiopathic fibrosing alveolitis, 6 with exogenic allergic alveolitis and 12 with diffuse affection of the connective tissue). The diagnosis was verified using high resolution computed tomography. Lesser circulation was studied with doppler-echocardiography. In 9 patients the diagnosis was verified by thoracoscopic biopsy of the lung. Control group consisted of 16 healthy subjects. The highest pressure in the trunk of the pulmonary artery (31 +/- 4.3 mmHg) was registered in patients with idiopathic fibrosing alveolitis. The severity of pulmonary arterial hypertension correlated with that of respiratory disorders, clinical symptoms and changes in the lungs. Blood pressure in the pulmonary artery trunk tended to elevation with progression of alterations in the lungs registered by computed tomography.

[Combination of pulmonary lymphangioleiomyomatosis with skin leiomyomatosis and uterine leiomyoma]. / Sochetanie limfangioleiomiomatoza legkikh, leiomiomatoza kozhi i leiomiomy matki.

Clinical observation with morphological verification of the above combination in a 48-year-old patient is presented. Large cysts, dystelectasia, fibrosis and smooth muscle proliferation were found in the lungs. The characteristic feature of smooth muscle cells was their differentiation in the direction of myofibroblasts and expression of antigen interacting with HMB-45 antibodies as well as protein products involved in catecholamine metabolism and estrogen receptors.

[Clinico-morphological and molecular-biological characteristics of idiopathic fibrous alveolitis and lung sarcoidosis]. / Kliniko-morfologicheskie i molekuliarno-biologicheskie osobennosti idiopaticheskogo fibroziruiushchego al'veolita i sarkoidoza legkikh.

Lung biopsies of 16 patients with classic idiopathic fibrosing alveolitis (IFA) and 6 patients with sarcoidosis were studied immunohistochemically. It was found that adenomatous hyperplasia (AH) and fibrosing in IFA are potentiated by high expression of thrombocytic growth factor (TGF) and insulin-like growth factor type 1 (IGF-1). Tumor necrosis factor alpha (TNFa) in IFA is actively produced at early stages of the disease. TNFa is drastically reduced in IFA with atypical AH. High level of TNFa produced by alveolar macrophage, pneumocytes type 2 and by other cells is observed in the lungs in sarcoidosis. The level of transforming growth factor (B1-TGF) is rather low in sarcoidosis this being combined with weak interstitial fibrosis (3.75 against 5.06 in IFA). Sarcoidosis granuloma contains proliferating epithelioid cells (as judged by Ki-67), produces a high amount of FTN (4.66), moderate amount of cell fibronectin (2.7), fibroblast growth factor, beta-TGF and IGF-system (1.7; 1.1; 0.8, respectively). Thus, IFA and sarcoidosis are distinguished not only morphologically but by the cytokine profile as well. This implies different approaches to their diagnosis and treatment.

[Nature of pseudo-amyloid masses in lymphocytic pneumonitis]. / Priroda psevdoamiloidnykh mass pri limfotsitarnom pnevmonite.

The material of open lung biopsies from a female patient with lymphocytic pneumonitis affecting mainly lower parts of the lungs was studied light- and electron-microscopically, immunohistochemically. Diffuse lymphoplasmacytic infiltration with an admixture of macrophages, single giant multinuclear cells and pseudo-amyloid inclusions were found. Morphogenesis of pseudo-amyloid inclusions is related to processes of pulmonary fibro-atelectasis with subsequent imbibition by immunoglobulins (hyperglobulinemia was found in circulating blood).

[Intercellular interactions in morphogenesis of initial lesions and sclerosis in interstitial lung diseases]. / Mezhkletochnye vzaimodeistviia v morfogeneze initsial'nykh povrezhdenii i skleroza pri interstitsial'nykh bolezniakh legkikh.

A total of 117 patients with pulmonary interstitial diseases (PID) were examined. The functional activity of alveolar macrophages was assayed in the lavage fluid and in lung tissue biopsy specimens from the generation of active oxygen forms, the secretion of tumor necrosis factor, fibronectin, expression of c-fos- and c-sis-oncoprotein. The stereotypic value for various PID was the development of alveolitis running in 2 stages: 1) early one, including exudative inflammation and 2) late one, involving sclerotic changes up to the formation of the honeycomb lung. This results in the block of the blood-air barrier and progression of respiratory failure and hypoxia in patients. The morphogenesis of fibrosing alveolitis is formed of alveolar septal damages caused by etiological agents of various nature, which is frequently unclear, by active forms of oxygen, lipid peroxidation products, proteases, tumor necrosis factor, which are produced by activated alveolar macrophages and polymorphonuclear leukocytes. The alveolar macrophage that secretes growth factors, c-fos- and c-sis-oncoproteins plays the key role in the progression of sclerotic changes. Lung cancer may develop at the end of fibrosing alveolitis at the stage of the honeycomb lung.

[Interstitial lung diseases--the clinical aspects of the problem]. / Interstitsial'nye bolezni legkogo--klinicheskie aspekty problemy.

Upon analysis of 550 cases of different chronic diffuse pulmonary diseases included in a group of interstitial diseases of the lungs (IDL) the authors came to the conclusion that IDL incorporate such variants as alveolitis, pulmonary vasculitis and pulmonary hemorrhages; granulomatosis covers exogenic allergic alveolitis, alveolitis in chronic active hepatitis; vasculitis group includes such rare diseases as necrotizing sarcoid granulomatosis vasculitis and lymphoid granulomatosis; fibrosing alveolitis--secondary alveolitis in sclerodermia systematica, rheumatoid arthritis, Sjogren's disease, chronic active hepatitis. Knowledge of IDL etiology (environmental, occupational, induced by radionuclides, drugs, viruses, fungi) with focus on drug affection of the lungs is thought of value. Biopsy and bronchial lavage findings are compared clinically and morphologically. Mechanisms of pulmonary fibrosis and approaches to inhibition of pulmonary fibrosis progression are outlined.

[Variants and stages in the course of idiopathic fibrosing alveolitis]. / Varianty i stadii techeniia idiopaticheskogo fibroziruiushchego al'veolita.

Clinicomorphological analysis covered 41 cases of idiopathic fibrosing alveolitis (IFA). The comparison of the degree of respiratory insufficiency, hypoxia, survival of the patients with cytogram of the bronchoalveolar lavage, morphological findings, generation of active oxygen forms by alveolar macrophages and leukocytes has provided evidence on an important role of alveolar macrophage in interstitial alveolitis and fibrosis in IFA. Three variants of chronic IFA are distinguished: aggressive, persistent and slowly progressive. The variants have different prognosis and need individual therapeutic approach.

[The clinico-morphological characteristics of interstitial lung diseases]. / Kliniko-morfologicheskaia kharakteristika interstitsial'nykh boleznei legkikh.

Electron microscopic and immunohistochemical methods were employed to study composition of collagens in extracellular matrix and quantify oncoproteins c-sis and c-fos. It was established that interstitial pulmonary diseases of various etiology are characterized at early stages by alveolitis with activation of alveolar macrophages, at late stages by interstitial fibrosis with accumulation of collagens type I, III, IV and V and epithelial dysplasia which is likely to initiate bronchioloalveolar cancer.

[Lymphocytic interstitial pneumonia as a variant of a precancerous lung lesion]. / Limfotsitarnaia interstitsial'naia pnevmoniia kak variant predopukholevogo porazheniia legkikh.

The paper reports a rare case of 26-year-old female with diffuse infiltrative lesions in both lungs. Blood tests revealed hypergammaglobulinemia and fast ESR. Lung biopsies exhibited diffuse lymphoid infiltration with fibroatelectasis regions. Cytological and immunophenotypic studies of the lavage showed polyclonal composition of the cell population and prevalence of mature lymphocytes. The diagnosis was made of lymphocytic interstitial pneumonia (LIP). No progression of the condition was observed. In view of expected malignant transformation the case was followed up. Benign characteristics of lymphocytic infiltration, no negative shifts within 5 years allow avoiding active immunodepressive treatment in this stage of the disease which belongs to diffuse forms of pseudolymphoma and is considered to be a prelymphomatosis status.