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.

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.

The rapid growth of lymph nodes, their acquisition of stony density, compression and infiltration of neighboring organs and tissues, causing swelling and pain, are characteristic of sarcomas, malignant transformation of CLL – the so-called. Richter syndrome. At this stage of the disease, compression of the enlarged lymph nodes of the bronchi and lung tissue is possible, accompanied by impaired ventilation of the lungs and the drainage function of the bronchi. In the stage of malignant transformation, the germination of the lymph node tissue into the lung tissue and the lumen of the bronchi is possible, which is not typical for the classic course of CLL. For verification of Richter syndrome, a histological examination of sarcomotransformed lymph nodes is necessary. Operational biopsy is not difficult if the transformation occurs in the peripheral lymph nodes,and it is very difficult to defeat mediastinal or abdominal nodes. Without replacing the histological examination, CT can help in the diagnosis of sarcoma transformation. lymph nodes of the chest cavity. Development of a compression syndrome in the chest cavity, associated with enlarged lymph nodes and / or germination of the lymph node tissue into the surrounding tissues, favors the development of Richter syndrome . In patients with Richter syndrome due to impaired lung ventilation and drainage of the bronchi, infection of the bronchopulmonary system is a fairly common and very serious complication. But in addition to inflammatory infiltrates, in the stage of malignant transformation of CLL, specific leukemic infiltration may appear in the lungs, the differential diagnosis of which with inflammatory infiltrates is very difficult .

There are great prospects in the use of CT for the objectification of X-ray images and parameters characterizing the selective status of the ventilation function of light . Radiographic findings on the state of pulmonary pattern and emphysema are very subjective . A.V. Lenshin (2004) developed a method for quantitative assessment of X-ray data on CT using the Hitachi W-800 computerized tomograph using the Level Detect program. The most optimal AV Lenshin considers sections at the level of the trachea bifurcation, made with a deep breath (the level of the pulmonary artery stem) [159]. Experienced by examining 100 healthy patients, 57 – with COPD and 54 – with bronchial asthma, the author found that in the density range –950 …- 1000 units. HU is detected (“contrasted”) with emphysematous transformed lung tissue.Counting the selected pixels in fixed (dominant) areas of a particular axial tomographic slice allows to obtain quantitative (in% per unit area) diagnostic tests of pulmonary emphysema [159]. This technique was used by us in patients with CLL (Fig. 9). In the studied groups of CLL patients, the following results of the quantitative determination of pulmonary emphysema were obtained: in group I, the percentage of emphysematous tissue per unit. the average area was 27.24 ± 0.24; in group II – 34.27 ± 0.31%; in group III – 42.29 ± 0.21%.the average area was 27.24 ± 0.24; in group II – 34.27 ± 0.31%; in group III – 42.29 ± 0.21%.the average area was 27.24 ± 0.24; in group II – 34.27 ± 0.31%; in group III – 42.29 ± 0.21%.

Diagnostic fiberoptic bronchoscopy (FBS) was performed on 60 CLL patients who did not abuse smoking and outside the administration of AML (20 patients of group I, 20 patients of group II, and 20 patients of group III). All patients of group I had a bronchoscopic picture of a normal tracheobronchial tree. But 10 patients had vascular injection.

In 10 patients of the II group, when conducting PBS, bilateral diffuse endobronchitis was diagnosed, the intensity of inflammation (IW) of the I degree. Not marked hyperreactivity of the bronchi. These patients had no clinical manifestations of bronchitis. A bronchoscopic picture of a normal tracheobronchial tree was diagnosed in 10 patients of group II. In 15 patients of this group, plethora and vasodilation were noted.

In 14 patients of the third group, fibrobronchoscopy was diagnosed with bilateral diffuse endobronchitis, IV – 1 and II degrees (12 and 2 people, respectively). No bronchial hyperreactivity was detected. Only four patients noted a slight cough in the morning. Other patients had no clinical symptoms of bronchitis. A bronchoscopic picture of a normal tracheobronchial tree was observed in 6 patients of group III. Expansion and plethora of blood vessels were diagnosed in 16 patients , which in CLL is a manifestation of hemoblastosis, and not bronchopulmonary pathology.

Thus, during fibrobronchoscopic examination, 60% of patients with a progressive course of CLL (40% of the total number of patients with CLL) were diagnosed with a latent course of chronic non-obstructive bronchitis.

Endobronchial biopsy was performed on 10 patients of group I, 10 patients of group II, and 5 patients of group III. Topeka biopsy specimens – 1.5 cm distal to the spur of the right upper lobe bronchus. Patients of group I were diagnosed with moderate proliferation or dystrophy of the bronchial epithelium. In patients with benign CLL, no lymphoid infiltration of the bronchi was detected. In patients with groups II and III, the histological examination of biopsy specimens determined the signs of chronic inflammation, edema, atrophy of the bronchial mucosa, and focal squamous metaplasia of the epithelium was often noted. Under the basement membrane revealed diffuse lymphocytic infiltration of varying severity. Most lymphoid infiltration was expressed in patients of group III.

In patients of group I, there was a slight dilatation of capillaries, a plethora of arterioles, capillaries and venules. In patients with CLL in stage A, no leucostasis was found in the vessels of the microcirculatory bed of the bronchi. In patients with group II, dilatation and plethora of arterioles, capillaries, and venules were observed with varying degrees of severity. In 6 patients of group II, accumulations of lymphocytes with the formation of leuco- stasis were observed in the vessels of the microcirculatory bed. In patients with group III, dilatation of arterioles, capillaries and venules was also diagnosed with varying degrees of severity. All group III patients were diagnosed with leukostasis in the vessels of the microcirculatory bed.

In order to study microhemocirculation in the proximal parts of the bronchial tree, endobronchial laser Doppler flowmetry (LDF) was performed in 25 patients with CLL. The results were compared with the data of 20 people from the control group, who were conducted PBS and LDF. According to the research data in patients with CLL, in the process of tumor progression, various types and degree of severity of microcirculatory circulation were registered.

The LDF method is based on probing tissue by laser radiation and subsequent processing of radiation reflected from a tissue in accordance with the Doppler effect. The amount of probed tissue in the LDF method is determined by the geometry and optical parameters of the light probe. The amplitude of the reflected signal is formed as a result of the reflection of radiation from erythrocytes, moving at different speeds and differently quantitatively distributed in arterioles, capillaries, venules and arterial venous anastomosis. Thus, PM determines the change in blood flow per unit time in the volume of tissue being probed and is represented by the following expression: PM = K × Ner × Vav; where: PM – microhemocirculation parameter , K – proportionality coefficient, (K = 1), Ner – red blood cell count, Vav – average erythrocyte rate – tov in the probed volume . A decrease in the PM values ​​may be due to a change in the number of blood cells and their speed in the microvessels of the area being examined. In CLL, microhemocirculation in the lungs and bronchi is undoubtedly promoted by accumulations of lymphocytes in small caliber vessels and anemic syndrome. In order to minimize the effect of anemia on the PM, in patients with group III (stage C, according to the J. Binet classification), the anemic syndrome was stopped before the study. The hemoglobin level during LDF was not lower than 100 × 10 9 / l, the content of red blood cells was at least 3 × 10 9 / l. Thus, they tried to establish a decrease in the speed of red blood cells in the microvessels, which in CLL may be primarily due to the presence of vascular accumulations of lymphocytes.

The amplitudes of oscillations in the N-range (due to sympathetic effects on smooth muscle cells of arterioles and arterio-venular anastomoses) and in the M-range (characterizing the state of the muscle tone of the pre-capillaries regulating blood flow to the nutritive channel) did not have significant differences with control .

The amplitudes of oscillations in the D-range in patients of the first subgroup did not have significant differences compared with the control indicators; in the second subgroup, there was a decrease in the amplitudes of oscillations in the D-range (P <0.05). The decrease in the amplitudes of the respiratory waves is due to insufficient blood flow into the venules, which may be due to the presence of leucostasis in CLL patients in the later stages of the tumor progression.

The amplitudes of oscillations in the C-band decreased during the tumor progression, in the first subgroup they did not have significant differences compared with the control, in the second subgroup the cardiac wave indices decreased (P <0.01). A decrease in cardiac wave values ​​indicates a decrease in arterial blood flow into the microvasculature, which may be due to the presence of vascular accumulations of lymphocytes, in some cases completely blocking the gaps of small vessels.

Significant inverse correlations were found between the level of leukocytosis in peripheral blood and a decrease in the fluctuations in the D and C ranges (respectively, r = –0.64, P <0.01 and r = –0.68, P <0.01), between duration of illness and a decrease

It can be concluded that in patients with CLL, in the process of tumor progression, the parameters characterizing the passive factors of LDF grams (causing fluctuations in blood flow outside the microcirculation system) —the amplitudes of fluctuations in the heart and respiratory ranges (pulse wave from the arteries and suction action ” respiratory pump “from the veins). These oscillations propagate with the bloodstream into the probed area, since the microvasculature, which is an integral part of the circulatory system, is topographically located between the arteries and the veins. Thus, in patients with CLL in the late stages of tumor progression, the flow of arterial blood into the microvasculature and its outflow to the venules due to the presence of leukostasis decrease.Indicators of active factors controlling microcirculation (directly affecting the microcirculation system — amplitudes of vibration in the EH and M bands), modulating blood flow from the vessel wall and realized through its muscular component, change to a much lesser extent. One of the reasons for this can be the fact that active mechanisms create transverse oscillations of the blood flow as a result of alternation of contraction and relaxation of vascular muscles (alternating episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workermodulating blood flow from the vascular wall and implemented through its muscular component, change to a much lesser extent. One of the reasons for this can be the fact that active mechanisms create transverse oscillations of the blood flow as a result of alternation of contraction and relaxation of vascular muscles (alternating episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workermodulating blood flow from the vascular wall and implemented through its muscular component, change to a much lesser extent. One of the reasons for this can be the fact that active mechanisms create transverse oscillations of the blood flow as a result of alternation of contraction and relaxation of vascular muscles (alternating episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workerthat active mechanisms create transverse blood flow oscillations as a result of alternation of contraction and relaxation of vascular muscles (successive episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the workerthat active mechanisms create transverse blood flow oscillations as a result of alternation of contraction and relaxation of vascular muscles (successive episodes of vasoconstriction and vasodilatation); passive factors organize longitudinal blood flow oscillations, expressed in periodic changes in the blood volume in the vessel; in the arterioles, the nature of the volume change is determined by the pulse wave, in the venules the worker rhythm of the respiratory pump . Lecostasis in small vessels of the lungs and bronchi present in a significant number of CLL patients to a greater extent impede longitudinal fluctuations in blood flow.

All patients who underwent diffuse endobronchitis during PBS underwent therapeutic measures: active aspiration of the bronchial contents, selective / partial lavage with dioxidine solution, local administration of antibiotics, etc. Two to three weeks after the start of treatment, endobronchial LDF was re-performed in these patients. Changes in the microcirculatory blood flow in the mucous membrane of the proximal bronchi in CLL patients, after normalization of the bronchoscopic picture, were preserved, which is explained by the morphological changes in the microvasculature vessels in CLL patients.

Disruption of microhemocirculation leads to the development of tissue hypoxia, metabolic disturbances in the mucous membrane cells of the bronchi and, along with marked secondary immunodeficiency, contribute to the occurrence of the inflammatory process in the bronchi. Violation of microhemocirculation supports the inflammatory reaction in the bronchi, contributes to its recurrent course, the development of disturbances in gas exchange and the ineffectiveness of antibacterial therapy. In 60% of patients with a progressive course of CLL (40% of the total number of patients with CLL), with PBS, an inflammatory process in the bronchi has been diagnosed with no pronounced clinical manifestations. However, the presence of a chronic focus of infection may contribute to the development of pneumonia in patients with a progressive course of CLL. Considering the above, patients with a progressive course of CLL,in the absence of contraindications, diagnostic bronchoscopy is recommended, and in the presence of an inflammatory process in the bronchi, the appointment of therapeutic measures.

The presence of the inflammatory process in the bronchi, along with their leukemic infiltration, contributes to an increase in bronchial resistance in patients with CLL group III.

Violation of microhemocirculation indices is registered earlier than the clinical manifestations of the bronchopulmonary system lesions appear. Thus, the study of endobronchial microcirculation can help predict the occurrence of inflammatory diseases of the bronchopulmonary system in patients with CLL.