Infectious complications of MM, including from the side of the bronchopulmonary system, are the main cause of mortality in these patients. The most frequent and serious infectious complications of paraproteinemic hemoblastosis are pneumonia . It was noted that pneumonia is found 5 times more often in patients receiving high-dose therapy than in the background of supportive therapy. The most important therapeutic measures taken in pneumonia, acute bronchitis and other infectious complications in patients with MM include effects on the causative agent and the elimination of infections. toxication; relief of the inflammatory response; restoration of the drainage function of the lungs; correction of violations of urodynamics; normalization of the immunobiological reactivity of the patient .

A.N. Sokolov, G.M. Galstyan and V.G. Savchenko (2007) described pneumonia in patients with hematological diseases. According to the authors, more than half of the patients who undergo high-dose, leading to prolonged myelosuppression, types of chemotherapy tolerate pneumonia. The following risk factors for the development of pneumonia in patients with neutropenia were identified: impaired normal microflora , damage to the mucous membrane of the respiratory tract by radiation or drug exposure , aspiration (in patients receiving drugs that cause impaired consciousness), microaspiration during vomiting. At the beginning of the neutropenic period, bacterial infections predominate. The main causative agents are K. pneumoniae, other Enterobacteriacae, P. aureginosa, S. aureus. Local pulmonary infiltrates that occur after the 7th day of empirical antibiotic therapy are in most cases caused by fungal processes, often aspergillous and candidal, less often by others. In this paper, the characteristics of the course of pneumonia caused by various pathogens on the background of neutropenia are described .

After visual inspection of the bronchial tree, the light guide probe of the device with a laser radiation wavelength of 0.63 μm was carried out through the fibrobronchoscope biopsy channel and, under visual control, was mounted on the mucous membrane 1.5 cm distal to the spur of the right upper lobe bronchus (Fig. 1). The rationale for the above localization was that there is no aortic pulsation in the right parts of the bronchial tree, which can interfere with the recording of Doppler, in addition, the right main bronchus is anatomically shorter and wider than the left, hence the installation of the light guide on the mucosa is simplified. The displacement of 1.5 cm in the distal direction from the spur of the upper lobe bronchus is optimal,since in this case the recording is made at some distance from the main vessels of interbronchial spurs and high activity of the tussogenic zones, thus minimizing the errors in the study. With this topic, the fixation of the probe is facilitated, since the installation on the spur is difficult due to the high probability of its “slippage”. In patients in the sitting position, they recorded the Doppler patterns for 3 minutes using an application computer program (LDF version 2.20.0 507WL) with the output of quantitative indicators on the monitor screen in real time. The following indicators were evaluated: PM – microhemocirculation parameter, σ – mean square deviation of PM, Kv – coefficient of variation, Ae – amplitude of oscillations in the endothelial range, An – amplitude of oscillations in the neurogenic range,Am is the amplitude of oscillations in the myogenic range, Hell is the amplitude of oscillations in respiratory range, Ac – amplitude of oscillations in the cardiac range, calculated using continuous wavelet transform (Fig. 1). To increase the efficiency of the data we obtained, the conditions for standardization of LDF, proposed by the European Contact Dermatitis Society, were observed.

Peak flowmetry was performed in order to monitor the state of the function of external respiration with the determination of peak expiratory flow rate in the morning, evening hours and the calculation of daily fluctuations.

Pneumotachography was performed to determine the magnitude of bronchial resistance (pneumotachograph of the Kazan Scientific Production Association “Medinstrument”).

Determination of CSF and blood gas composition was carried out using an automatic gas analyzer AVL-995 Hb (Austria) and EasyStat (USA). The following indicators were analyzed: the activity of hydrogen ions (pH); carbon dioxide partial pressure (pCO 2 ); oxygen partial pressure (pO 2 ); arterial-alveolar difference in partial pressure of O 2 (AaDO 2 ); hemoglobin oxygen saturation (O 2 sat); total oxygen content dissolved and bound in blood (O 2 cont).

Zonal rheography of the lungs was carried out according to the method of E.A. Free Nerman and L.I. Zhukovsky on the device REAN-131 (Russia). In the quantitative analysis of eographically curves obtained over the six zones of the lungs, the following indicators were taken into account: 1) respiratory rate (RR), 2) respiratory volume of rheographic (DOF; Ohm), 3) minute ventilation volume of rheographic (MVDP; Om / min), 4) erographic index of systolic blood filling (SCr; Ohm), 6) ECG heart rate; 7) minute pulsator blood flow (MPKr; Om / min), 8) diastole – systolic coefficient (DSC, relative units), 9) Q interval – the period from the beginning of the Q wave on the ECG to the beginning of the rise of systolic wave pulsation rheograms (s), 10) average blood filling rate of light (CCM; Ohm / s), 7) ventilation-perfusion ratio (HPE) = MOVr: MPKr.

The functional state of the diaphragm was determined using ultrasound scanning on Shimadzu SDU 500A and Aloka 650SSD (Japan) devices using the method of O. A. Mazharova and O. N. Sivyakova .

Immunological research methods. Immune status was evaluated using monoclonal antibodies. Serum immunoglobulins were studied by the method of immunoassay.

Morphological research methods. As the main methods for assessing the morphofunctional state of the objects under study, stereological methods were used, thanks to which, based on the study of sections, one can judge the real three-dimensional volumes [14, 15, 16]. In the morphometric study of segmental bronchi using an MOV ocular micrometer – 1–15 x and an ocular mesh for cytohistostereometry studies with 100 and 25 points determined the diameter of the bronchi, the thickness of the mucous membrane, the ratio of the number of boviform cells and ciliary epithelium cells, the degree of desquamation and epithelial proliferation relative to the remaining epithelium, the thickness of the basal membrane, the degree of blood supply to the vessels of the bronchial wall, the cellular composition of the infiltrate of the bronchial wall, the thickness of the muscle fibers and their fragmentation. In the submucosa – the number and size of the glands. The perimeter and area of ​​the alveoli was determined. Measurements were made of the thickness of the walls of the pulmonary vessels, the diameter and the index of the blood supply of the pulmonary vessels.

A morphometric study of the heart at a macroscopic level determined the mass of the heart (g); the thickness of the myocardium of the right ventricle (RV) (cm); the pure mass of the pancreas (CMLP), obtained by separately weighing the heart according to the Muller-Burblinger method; ventricular index (LM) is the ratio of the net mass of the pancreas to the left; the width of the pancreas (perpendicular, mentally lowered from the middle of the anterior interventricular groove to the anterior surface of the pancreas) (cm); the tricuspid valve perimeter (TSK) (cm). In the study of the myocardium of the pancreas at the microscopic level, the average diameter of the cross section of the cardiomyocyte was determined (μm); cardiomyocytes cross-sectional area S in (mm 2 ), Thoraya Ko calculated by the formula S a = πr 2 , where r is the average radius of the cross section of the cardiomyocyte; the cross-sectional area of ​​the core of the cardiomyocyte S i (μm 2 ), which is calculated by the same formula; nuclear-cytoplasmic ratio calculated by the area of ​​the cardiomyocyte and the nucleus; percentage ratio of stromal structures and cardiomyocytes (Mmpzh%,% stroma). Calculated indicators such as the absolute mass of the pancreas (Mmpzh), calculated according to the formula Mmpzh = (ChMPzh * Mmpzh%) / 100 (g); the relative length of cardiomyocytes Z RV , which is calculated by the formula Z RV = Mmpzh / lpzh (conv. units).

IWC vessels have been studied in a qualitative and quantitative direction [16, 92, 98, 181]. For a qualitative assessment of changes in arteries, D. Heath and G. Edwards’s classification was used, in which changes in arteries pass through a series of successive stages: Stage I – middle envelope hypertrophy, Stage II – middle envelope hypertrophy and formation of an intimal muscle layer, Stage III – joining of progressive sclerosis inti maximal muscular layer, stage IV – common sclerotic changes in the layers of the arteries of the wall; stage V – joining the blood stagnation in the capillaries and hemosiderosis of the lungs; Stage VI – development of fibrinoid necrosis of arterial walls and arterioles. Changes in venules and veins were evaluated according to O.O. Orekhova: Stage I – middle envelope hypertrophy, moderate hyperelastosis; Stage II – the addition of media hypertrophy, pronounced hyperelastosis, the appearance of smooth muscles in the intima; Stage III – the accession of progressive sclerosis and intima hyperelastosis with a narrowing of the vessel lumen; Stage IV – a combination of sclerosis of the vessel wall with focal enlargements of its lumen; Stage V – pronounced sclerosis and hyperelastosis of the entire vessel wall, the presence of aneurysms, blood clots and other changes characteristic of venous insufficiency of blood flow.For a quantitative assessment, the length of the LA circumference, the degree of vascular congestion, the Kernogan index — the ratio of the thickness of the muscle layer to the radius of the vessel lumen, the thickness of the intimal muscle layer of the terminal and respiratory branches of the LA.

To study the diaphragm, pieces were taken from its rib section and the diaphragm thickness (mm) was determined, the percentage ratio of large, medium, small myocytes, the cross-sectional area of ​​muscle fibers (μm 2 ), the stroma number .

Statistical methods. All digital data are subject to verification of the sample distribution for normality according to Kolmogorov – Smirnov criteria and omega-square (ω 2 ). In the case of normal (Gaussian) data distribution, parametric methods were used with the calculation of the sample mean (M), the error of the mean (m) and standard deviation. An end-to-end linear correlation analysis of all obtained indicators with the calculation of the Pearson correlation coefficient was carried out. The statistical significance of the differences between the compared values ​​and correlation coefficients was determined on the basis of Student’s criterion for independent samples. Differences between averages were considered statistically significant at P <0.05. To identify statistically significant indicators that indicate the presence of leukostasis in the vessels of the bronchopulmonary system in CLL and myelomatosis of the lungs in patients with MM, discriminant analysis was performed. Static computer processing was performed using the STATISTICA 6.0 program.

228 patients with CLL who were registered in the hematology office of the Amur regional consultative clinic in 1995 – 2007 were examined. In the diagnosis of B – CLL, clinical examination data, hemograms, myelograms, trephine biopsy of the Ilium, standard immunophenotype (CD5, CD19, CD20, CD22, CD23) were used. The prevalence of CLL in the Amur Region is in second place among hemoblastosis (18%), second only to acute leukemia. The average annual incidence of this leukemia in the Amur Region is 2 per 100,000 of the population (Table 1). But if we consider the structure of hemoblastosis among the adult population of the region, then CLL is in the first place – 22% of all hemoblastosis, exceeding the prevalence of all other acute and chronic leukemias.The incidence of CLL is detected mainly in the age group of 50–70 years (Table 2). The average age of patients at the time of detection of the disease – 58.5 ± 5.2 years. The distribution of CLL patients depending on gender revealed a slight predominance of men over women .

In Russia, they mainly use the classification of tumors of the lymphatic system proposed by A.I. Vorobiov et al. in 1985 – 2000 . In the classification of 2000. CLL is divided into 7 forms, which allows for differentiated therapy of hemoblastosis. Distribution of CLL patients living in the Amur region, according to the forms of the disease (according to the classification of AI Vorobyev et al. , 2000) .

The life expectancy of patients with a benign form of CLL was 1.5 – 2 decades or more. In these patients, for a long time it was possible to refrain from prescribing a course cytostatic therapy. However, progression of the disease was noted in 70% of patients by the 10th year of observation, and in this connection specific therapy was prescribed. In the past century, with progressive form of CLL, course therapy was administered with chlorambucil. The median survival rate of patients with progressive form of CLL was 94 of the month. In the 90s of the last century, the treatment of patients with the tumor form of CLL began with monotherapy with cyclophosphamide. If there was no effect, they switched to polychemotherapy programs – CP, СОР, СОР, САР. The median survival of patients with the tumor form of CLL was 56 months. Transformation to lymphosarcoma has often been noted.

In recent years, patients with tumor and progressive forms of CLL are treated with fludarabine both as monotherapy and in combination with other drugs: cyclophosphamide (FC), rituximab (FCR), mitoxantrone (FCM). In the overwhelming majority of patients treated according to these protocols as the first line of therapy, they managed to achieve complete or partial remission of CLL. Since treatment according to these protocols has been carried out over the past few years, the median overall survival in this cohort has not yet been reached.

An important role in the treatment of splenic CLL was assigned to splenectomy and radiation treatment, the median survival rate was 61 months. The treatment of the abdominal form was carried out similarly to the treatment of the tumor form. The bone marrow and prolymphocytic forms of CLL were very rare. The disease in these cases was malignant, was accompanied by profound anemia and thrombocytopenia, and a fatal outcome quickly occurred.

Life expectancy was primarily affected by the stage of the disease in which hemoblastosis was diagnosed (table 5). Patients whose CLL was diagnosed in stage A according to the Binet classification had a significantly longer life expectancy than patients with B and C stages at the time of detection of the disease. Patients who had a high expression of the CD38 marker at the time of diagnosis of the disease had a significantly lower survival rate.

Infectious complications were observed in 85% of patients with CLL. The most common diseases were the bronchopulmonary system (pneumonia, bronchitis, pleurisy, etc.) – 38.8% and pathology of upper respiratory tract – 28.6%; Herpes zoster was observed less frequently – 16.3%; abscesses, phlegmon, sepsis – 5.3%; erysipelas – 5.3%; mycoses – 5.7%. In 13 people, the disease was complicated by autoimmune hemolytic anemia (5.5% of the total number of CLL patients).

Note: Pulmonary tuberculosis and chronic bronchitis were attributed to comorbidities in cases where they were previously diagnosed with CLL. The accession of these diseases on the background of CLL was attributed to its complications.

The terminal stage of CLL was more often manifested by cachexia, transformation into lymphosarcoma, “prolymphocytic crisis” was observed only in two patients, “blast crisis” CLL was not registered. In the vast majority of cases, the bronchopulmonary complications of hemoblastosis were the direct cause of death – 59.9%. In 23.8% of cases, death was due to concomitant cardiovascular pathology (ischemic heart disease, myocardial infarction, hypertensive disease).

The classification of J. Binet (1981) is taken as a basis when dividing patients with CLL into three groups, since it allows staging of hemoblastosis taking into account the stages of tumor progression.

Group I (48 people) – CLL patients in stage A according to J. Binet classification. In 39 patients with CLL, blood samples showed moderate leukocytosis and absolute lymphocytosis, the lymph nodes of all groups were of normal size. In 9 patients, except for leukocytosis and lymphocytosis, an increase in peripheral lymph nodes (1-2 groups) up to 2 cm in diameter, soft-elastic consistency; but for many years they have not experienced progression of the disease. No patient in group I had splenomegaly, anemia and thrombocytopenia. Thus, group I consisted of patients with a benign form of the disease. Course cytostatic therapy was not prescribed to these patients. They were monitored dynamically, sometimes given primary restraint therapy with chlorambucil. The average age of patients of group I is 58.7 ± 2.0 years,longevity is the same as in the population.

Group II – 112 people. This group includes patients with stage B according to the classification of J. Binet. The majority of patients belonged to the progressive and splenic (partially tumor) forms according to A.I. Vorobyov et al. (1985 – 2005). These patients were characterized by high leukocytosis, increasing lymphadenopathy (an increase in more than three groups of lymph nodes), splenosis and hepatomegaly. In blood tests, Hb values> 100 g / l and platelets> 100 × 10 9 / l. Lymph nodes were of a soft-elastic consistency, painless, not welded between themselves and the surrounding tissues. With the progression of CLL, infectious complications developed. In 80 patients of group II, according to ERTGS and CT, an increase in mediastinal lymph nodes was diagnosed. The average age of patients in group II was 58.5 ± 3.2 years. The median survival is 97 months.

Group III included 68 patients. This group consisted of patients in stage C according to the classification of J. Binet. The majority of patients belonged to the A.I. Vorobyov et al. (1985 – 2000). This group included 6 patients with the spleen form of CLL, all patients with abdominal, bone marrow and pro-lymphocytic forms of hemoblastosis, as well as patients who at the time of the survey were diagnosed with Richter syndrome. In all patients, anemia was diagnosed in blood tests (HB <100 g / l), in 33 patients thrombocytopenia (Tr <100 × 10 9 / l) Patients of group III are characterized by increasing lymphadenopathy (the lymph nodes reached considerable size, had a dense elastic consistency, were soldered to conglomerates), hepato-and splenomegaly, the appearance of pronounced symptoms of tumor intoxication, frequent infectious complications, the development of auto-immune complications, often there was a transformation into large – cellular lymphoma. In a number of patients of the third group, high leukocytosis with atypical lymphocyte morphology was noted. In all patients of group III, CT and ERTG of the mediastinum were shown to show an enlarged lymph nodes. The average age of patients in group III was 61.2 ± 5.5 years. Median survival – 43 months.

The clinical characteristics of the bronchopulmonary system in patients with CLL, outside the administration of AML, depended on the stage of the disease. In patients of group I, peripheral lymph nodes were not enlarged and, according to x-ray studies, no increase in lymph nodes in the chest cavity was detected. In all patients of this group, the lower edge of the liver was palpated along the edge of the rib arc; the spleen was not detected by palpation. In patients of group I, the chest was the correct form, both of its halves equally participated in the act of breathing. A clear pulmonary sound was determined perkutorno over the entire lung surface, vesicular respiration was heard during auscultation, and there were no spurious respiratory sounds. In 4 patients with the presence of concomitant Nedo sufficiency blood circulation in the lower parts of the lungs during auscultation listened to wet fine bubbling rales, percussion determined the dullness of the pulmonary sound.

In 80 patients of group II (71%), according to x-ray methods, an increase in broncho-pulmonary and mediastinal lymph nodes was diagnosed. However, none of the patients showed clinical symptoms of compression of the bronchi and lung tissue due to an increase in the lymph nodes in the chest cavity. In 61 patients, an increase in the spleen and / or liver was diagnosed, but there were no clinical signs of compression syndrome. When viewed in 82 patients of group II, the chest was the correct form. In 72 patients, during a percussion, a clear pulmonary sound was detected over the entire lung surface, vesicular respiration was heard during auscultation, and there were no adverse respiratory sounds.In 10 patients with the presence of concomitant circulatory failure in the lower lung during auscultation listened to wet finely wheezing, percussion determined the dullness of the pulmonary sound.

All patients in group III were diagnosed with swollen lymph nodes, including in the chest cavity. Of these, 14, according to peripheral lymph node biopsy, were diagnosed with Richter syndrome (transformation into large cell lymphoma).

However, the clinical manifestations of compression syndrome in the chest cavity (shortness of breath, asphyxiation, cough, pain syndrome) were diagnosed only in 5 people with Richter syndrome. In 6 patients, the spleen occupied a large part of the abdominal cavity (splenic form of CLL); radiologically, these patients were diagnosed with a high standing of the diaphragm dome. In the terminal stage of the disease, such a spleen caused compression syndrome in the abdominal cavity, chest compression was observed, which was clinically manifested by shortness of breath. In 12 patients in the terminal stage of the disease, with a significant increase in the liver and spleen, which had a dense consistency, insufficiency of blood circulation developed. Clinically, this was manifested by the accumulation of fluid in the pleural cavities (transudate), shortness of breath, cough, ascites, edema in the lower extremities.In the presence of fluid in the pleural cavities, a significant weakening of breathing and voice tremor was determined over the zone of lesion of the pleura, dull pulmonary sound. In 6 patients in the lower parts of the lungs, moist rales were heard.

In 21 patients of group III (9.2%), in the terminal stage of the disease, a specific lymphoproliferative pleurisy was diagnosed as a manifestation of leukemic pleural infiltration. In the presence of initial manifestations of lymphoproliferative pleurisy, clinical symptoms were absent. As it progressed, clinical symptoms appeared: dyspnea (19 patients), weight loss (21 patients), anorexia (21 patients), fever (10 patients). Only 9 patients with lymphoproliferative pleurisy experienced chest pain; they characterized the pain as dull and aching. During auscultation of the lungs in such patients, a significant weakening of respiration was determined over the area of ​​pleural lesion, percussion – a dulling of pulmonary sound, and a weakening or strengthening of voice jitter was determined.When a large amount of exudate accumulated in the pleural cavity, a lag of the affected lung was noted during breathing.

Infectious complications occur from 75 to 80% in patients with CLL . As CLL progresses, the incidence of bacterial and viral infections increases . Specific lymphoid infiltration of the lung tissue and hyperplasia of the lymphoid follicles of the bronchial tree contribute to bronchopulmonary complications in CLL. All this leads to the development of atelectasis, impaired ventilation and gas exchange function of the lungs and the drainage function of the bronchi . At the same time, the lifetime diagnosis of leukemic infiltration with the use of rontgenological methods causes considerable difficulties. . The source of infiltration is lymphoid follicles located around the bronchi and large veins. In the phase of malignant transformation of CLL, the tumor can grow from the lymph nodes into the fatty tissue of the mediastinum, the lesion of the interalveolar septa of the lung, the wall of the bronchi and pleura .

Of course, one of the main methods for recording the prevalence of the tumor process in CLL is renn-tomography and tomography . As an example, we present one of the observations . Patient V., 62 years old. On the radiograph of the organs of the thoracic cavity in a direct projection (Fig. A), bilateral, moderately pronounced root lymphadenopathy is determined without infiltrative changes in the lung tissue. When the sighting ERTG determined specific lymphoid infiltration of the lung tissue, muftoobrazno covering the upper lobe bronchus and circularly narrows their Enlightenment Russian you . On the radiograph, these changes are not differentiated.

If we summarize the available information in the literature and our own experience, then it can be noted that radiologically much more often we have to diagnose complications of leukemia in the form of various kinds of pneumonia than the actual leukemic infiltrates. Specific leukemic infiltrates with traditional radiography are rarely diagnosed, because they do not reach significant sizes. With significant leukemic infiltration of the peribronchial tissues, it is possible to note a pronounced increase in the pulmonary pattern and its deformation, corresponding to the delicate mesh -looped structure .

As the process progresses against this background, small focal shadows appear, the anatomical substrate of which can be both specific and non-specific processes in the lungs. Focal shadows in some cases can be a display of peribronchial and perivascular couplings in their cross section. With a friend On the other hand, specific leukemic infiltrates that go to the alveoli and perform them form small foci, which can be radiologically similar in the form of foci. Concomitant pneumonia, among which quite often small-focal forms occur, is also sometimes an anatomical substrate of small focal-like shadows. X-ray manifestations of specific leukemic infiltration and the accompanying or self-induced pneumonia may be similar. This similarity is so pronounced that it is difficult to decide which elements of the shadow pattern are associated with inflammatory changes, which are caused by specific infiltration, even with the use of modern technology – CT and ERTG.

The introduction of X-ray computed tomography into practice, especially of high resolution, significantly improves the diagnosis of pulmonary manifestations of CLL. In 102 patients with CLL, chest CT was performed (during the polar phases of respiration, planimetric and densitometric measurements), pathology was detected in 85 patients (83%), radiographs and linear tomograms changes were detected only in 46 patients (45%). At CT scan the following changes were revealed: root and mediastinal lymphadenopathy – in 68 (66.7%); compression of the bronchi and lung tissue by the lymph nodes with Richter syndrome – in 15 (14.7%); pneumonia – in 45 (44.1%); lymphoid infiltration of the lungs – in 5 (4.7%); lymphoid infiltration of the pleura – in 14 (13.7%); pleurisy – in 28 (27.5%); pulmonary tuberculosis – 10 (9.8%); emphysema – in 78 (76.5%); pneumosclerosis – in 37 (36.3%); post-pneumonic pneumofibrosis – in 14 (13.7%).

The enlarged lymph nodes of the mediastinum, according to different authors, I diagnose in 25-64% of patients with CLL . For the most part, peripheral lymph nodes are larger than the intrathoracic, but reverse relationships can also be observed. The severity of mediastinal lymphadenopathy depends on the stage of development of the tumor process. Lymphoadenopathy in patients with CLL is mainly peripheral. On this occasion, it is mainly patients who go to the doctor. Only a few of them at this time radiographically determine the enlargement of the lymph nodes of the median. Later, in the advanced stage of the disease, mediastinal lymphadenopathy is detected in more than half of the patients, sometimes reaching considerable sizes. However, for the classical course of the disease, even with a significant increase in lymph nodes, compression syndrome is not characteristic .