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 .

It must be borne in mind that bronchopulmonary complications in MM more often develop on the background of neutropenia. With neutropenia, the diagnosis and treatment of pneumonia has a number of features. The decrease in the number of neutrophils significantly aggravates the immune response of the body already significantly suppressed by the tumor process . Often this does not allow the development of characteristic clinical manifestations, coughing and auscultatory wheezing develop several times less, and the results of X-ray examination of patients during this period can be negative, which makes it difficult to diagnose in time. . G.A. Klyasova (2008) recommends performing a computed tomography of the lungs in the presence of fever during neutropenia, regardless of the auscultatory picture and without prior radiography. Hyperthermia is often the only sign of an infectious process sufficient to prescribe adequate antibiotic therapy . According to the criteria of the American Society for Infectious Diseases, the term “febrile neutropenia” is used, which means that the body temperature rises above 38 ° C at least twice a day or a one-time temperature increase above 38.3 ° C in patients with a neutrophil content of less than 1000 per day. µl blood.

V.V. Ptushkin et al. (1998) identify the following features of the etiology of infection in patients with febrile neutropenia: 1) increased infection with gram-positive cocci and reduced detection of gram-negative bacteria, 2) increased frequency of systemic mycoses, 3) increased frequency of viral superinfection.

The principles of antibiotic therapy for febrile neutropenia are as follows: 1. Immediately initiate antibiotic therapy after diagnosis; 2. The choice of the first drug is carried out empirically, depending on the clinical and epidemiological situation; 3. After microbiological identification of a bacterial infection, anti-bacterial therapy is corrected; 4. The assessment of the correctness of the choice of antibiotic is carried out 3 days after its appointment. The main criterion of efficacy is considered to be the positive dynamics of fever and intoxication. Otherwise, the antibiotic is replaced in accordance with the results of bacteriological examination of sputum or reserve drugs are used; 5. For light or moderate pneumonia, the use of a single antibiotic is possible.In order to adequately cover all potential pathogens in patients with febrile neutropenia, it is advisable to prescribe empiric therapy, which may consist of monotherapy with broad-spectrum antibiotics (III-IV cephalosporins, carbapenema) or a combination of two-three antibiotics. It is obligatory to use drugs directed against dangerous gram-negative pathogens (Pus synergis) due to the severity and severity of infectious complications caused by these pathogens; 6. The duration of antibiotic therapy is 7 to 10 days. In patients with severe hospital pneumonia, its duration is extended to 2–3, and sometimescarbapenems) or from a combination of two – three antibiotics. It is obligatory to use drugs directed against dangerous gram-negative pathogens (Pus synergis) due to the severity and severity of infectious complications caused by these pathogens; 6. The duration of antibiotic therapy is 7 to 10 days. In patients with severe hospital pneumonia, its duration is extended to 2–3, and sometimescarbapenems) or from a combination of two – three antibiotics. It is obligatory to use drugs directed against dangerous gram-negative pathogens (Pus synergis) due to the severity and severity of infectious complications caused by these pathogens; 6. The duration of antibiotic therapy is 7 to 10 days. In patients with severe hospital pneumonia, its duration is extended to 2–3, and sometimes and more weeks .

The main etiological factor in the onset of pneumonia is pneumococcus, macrolides (dirithromycin, roxithromycin, clarithromycin, spiramycin, midecamycin, azithromycin) and penicillins serve as the drugs of choice in these situations. Cephalosporins of the II – IV generations and fluoroquinolones active against gram-positive and gram-negative microorganisms have been widely used. In severe cases of infectious complications, aminoglycosides of the second and third generations are used, but nephrotoxicity must be taken into account. Carbapenems are reserve drugs and are used for severe pneumonia and other infectious complications, which arise mainly against the background of developed deep cytostatic myelodepression. Pneumonia in neutropenia, granulocytopenia is often caused by gram-negative flora (E. Coli, P. aeruginosae).In this case, the drugs of choice are cephalosporins of the third generation in combination with aminoglycosides, as well as with co-trimoxazole ohm (septrin, biseptol) . Co-trimoxazole is active against Enterobacteriaceae and staphylococci, but P. aeruginosae and E. Faec alis are resistant to it . In case of pneumonia caused by S. aureus strains, it is advisable to assign a glycopeptide s (vancomycin, tekoplanin) . When it is not possible to use glycopeptide antibiotics, phosphomycin and amyoglycosides are used in high doses . For vancomycin-resistant enterococcal infections, it is more effective than nIvox (lineolide) .

The following treatment regimens are most common as empirical modes of antibiotic use: a combination of β-lactam antibiotics with aminoglycosides (preferably in cases of suspected or proven infection caused by gram-negative bacteria, in clinics where there is a high frequency of gram-negative bacteremia); two β-lactam antibiotics together (preferably in patients with MM with chronic renal failure). With a high probability of developing streptococcal infection, it is advisable to combine piperacillin / tazobactam or ticarcillin / clavula nat with an aminoglycoside . Monotherapy with a wide spectrum of β-lactam antibiotics (ceftazidime, imipenem, meropenem, maxipime, piperacillin / tazobactam) is also used. . Most strains of E. coli and Proteus are sensitive to carbenicillin and ampicillin given in large doses. Effective combinations of semi-synthetic penicillins with substances that interfere with the action of β-lactamase produced by microorganisms (clavulanic acid, sulbactam). Recently, many works have been devoted to β-lactamases, an extended spectrum of action, and modern β-lactam antibiotics in the treatment of severe infections, including the nose sock . The use of III generation cephalosporins, oxacephems and penicillins of the V generation is effective in patients with sepsis in the event of Friedlander sticks in blood and sputum, and most anaerobes are sensitive to benzene penicillin administered in high doses (up to 10 million U / day). Anti Biotic reserve for infections caused by strains of staphylococcus and other gram-positive pathogens, as well as anaerobic bacteria, is the combination of penicillin with clinda qin and lincomycin . Carbapenems are indicated in patients after bone marrow transplantation and infections caused by deep cytostatic myelodepression . The choice between monotherapy and combination therapy is based on which risk group the patients belong to and how long neutropenia is. In patients with a long duration of neutropenia, they are used for combined therapy .

In addition to bacterial infections, there are often fungal infections, as well as infections caused by protozoa. The number of patients who develop invasive mycoses is constantly increasing . Invasive mycoses develop against the background of a decrease in body resistance. The first step in the unprotectedness of patients from opportunistic fungi is neutropenia. Risk factors include violations of the integrity of the skin, the mucous membrane of the gastrointestinal tract, the use of broad-spectrum antibiotics, the use of glucocorticoids , and immunosuppressors . For candidal lesions, amphoglucamine or mycoheptin, amphotericin B, flucytazine or ketonazole are used, fluconazole (diflucan) is an effective antifungal drug .

The duration and severity of neutropenia can affect the outcome of the infectious process. The presence of long-term neutropenia and tissue infection (sepsis, pneumonia, abscess, etc.), with signs of infection of a vascular catheter, are grounds for adding hematopoietic colony-stimulating factors to anti-infective drugs .

General clinical trials included clinical blood analysis, urinalysis, biochemical blood analysis (total protein, glucose, creatinine, urea, sialic, sublimate, thymol samples, irubin, β – lipoproteins, cholesterol , amylase, calcium , phosphorus, alkaline phosphatase, transaminases, lactate dehydrogenase, fibrinogen, prothrombin).

Cytological examination (myelogram) was performed for all patients with myeloma to verify the diagnosis. Sternal puncture was prescribed to patients with CLL according to indications in most cases for the diagnosis of stage 0 of the disease (according to K. Rai classification, 1975). If during the initial diagnosis of CLL, an operative lymph node biopsy was performed, prints were prepared for cytological examination.

Intravital histological studies (surgical biopsy of the lymph node, trephine biopsy of the ilium) were performed by most patients with CLL to verify the diagnosis and differential diagnosis of CLL with mature lymphomas from B lymphocytes in the leukemia stage. A histological examination of the lymph node in patients with CLL also led to the diagnosis of Richter syndrome (transformation of CLL into a large cell lymphosarcoma). To verify the diagnosis of multiple focal MM and solitary myeloma, a histological study of material taken during surgical biopsy from a myeloma tumor or destruction was performed.

The function of external respiration was determined using the “Fukuda” apparatus (Japan) and included spirometry, computer analysis of the “flow-volume” loop. Criteria developed by N.V. Putovym and G.B. Fesedeev. The severity of ventilation disorders was assessed by a 3-point system: moderate (1 degree), significantly (2 degree) and sharply (3 degree) pronounced disorders.

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).

X-ray methods of examination: a survey X-ray; polypositional large-scale fluorography of the chest organs, including in the polar phases of respiration; electron roentgenography (ERTG), computed tomography (CT).

Comprehensive ultrasound of the heart was performed on Shimadzu SDU 500 A and Aloka 650SSD (Japan) devices in M-, B- and Doppler modes, using 3.5 MHz sensors, from the parasternal and apical approaches. by standard methods, with the definition of parameters of pulmonary and hemodynamic valuable tral: end-diastolic dimension of the right ventricle (KDR RV ), the front wall thickness of the myocardium of the right ventricle (RV) in diastole (TMPS RV ), end-diastolic volume of the prostate (BWW RV ), end-systolic volume of the prostate (CSR RV ) ary RV index (MI RV ), cardiac index RV (SI RV ) RV ejection fraction tion (EF RV ), the final systolic size of the left ventricle (LV) ( LV LCR ), the final diastolic LV size ( LV CRD ), the myocardium thickness of the LV posterior wall in the diastole (TMVF LV ), of course, the diastolic LV volume ( LV LV ), the finite systolic volume LV (CSR LV ), the minute volume of blood circulation ( LV LV ), the LV stroke volume ( LV LV ), the LV LV index ( LV LV ), the LV cardiac index ( LV LV ), the LV ejection fraction ( LV LV ), interventricular thickness partitions in diastole (TMZHP D ) [45, 46, 11 9, 273, 345]. The mean pressure in the pulmonary artery (SrDLA) was calculated using the formula A. Kitabatakae et. al. The normal value of the SrDLA index was 9–16 mm. Hg Art., pulmonary hypertension was discussed when SrDLA increased at rest more than 20 mm. Hg Art. [9, 10]. Evaluation of the diastolic function of the myocardium of the right and left ventricles was carried out by analyzing the spectrum of the transtrikuspidal and transmitral Doppler streams. The maximum blood flow velocity during the early (fast) diastolic filling of the right ventricle (E TC ), the maximum blood flow velocity during atrial systole during the late diastolic filling of the right ventricle (A TC ), the maximum blood flow velocity during the early (fast) diastolic filling of the left ventricle (E MK ), maximum blood flow velocity during atrial systole in the late diastolic filling phase of the left ventricle (A MK ), E / A RV and E / A LV ratio.

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.