An ultrasound examination of the diaphragm in patients of group I showed no significant changes compared to controls. The thickness of the diaphragm did not change. The position, shape, echogenicity of the diaphragm also did not differ from the control. Excursion of the diaphragm with calm and forced breathing did not differ from control. In patients of group II, the thickness of the diaphragm did not change, but its echo structure became heterogeneous. Marked flattening of the dome of the diaphragm. Significantly decreased excursion of the diaphragm. In group III, the largest morphological changes in the diaphragm were revealed. Its dome was not clear, the echo structure became non-uniform. The mobility of the diaphragm significantly decreased. EDS and EDF were significantly reduced. Decrease in the expansion of the diaphragm and its morphological restructuring, with MM,specific myelomatous damage to the diaphragm (plasma cell and lymphoid infiltration, the presence of protein stasis in vessels with impaired microcirculation, etc.), impaired chest movements in patients with severe osteodestructive process, in the presence of renal failure – uremic defeat afragmal muscle .

In patients of group II, a significant correlation dependence was found between a decrease in EDF and a decrease in the MOB of the lower (r = 0.89; P <0.001) and middle zones of the lungs (r = 0.56; P <0.05), between decrease EDS and a decrease in the MVR of the lower (r = 0.62 P <0.05) and middle zones (r = 0.56; P <0.05) of the lungs. In group III patients, a clear correlation was found between a decrease in EDF and a decrease in the MOBP of the lower lung zones (r = 0.56; P <0.05), between a decrease in the EDS and a decrease in the MOP of the lower lung zones (r = 0.52; P < 0.05). At the same time, no reliable correlation was found between the EDF, EDS and MOVr indices of the upper and middle zones. lungs. Smaller correlation indicators (compared to group II) between the decrease in the excursion of the diaphragm and the ventilation capacity of the lower zones of the lungs, the lack of reliable links between the excursion rates of the diaphragm and the ventilation of the middle zones is explained by the fact that in violation of the ventilation of the lungs, specific bronchopulmonary manifestations of CRF — nephrogenic edema, pneumonitis, calcification, fluid accumulation in the pleural cavities — play.

A significant inverse correlation was established between the decrease in EDF and EDS and the increase in SrDLA in patients II (r = –0.69; P <0.01 and –0.61; P <0.05) and III (r = –0.52 ; P <0.05 and – 0.5; P <0.05) groups. A positive correlation was found between a decrease in the MOVR of the sums and a decrease in the pO 2 of blood in patients of the II (r = 0.89; P <0.001) and III (r = 0.82; P <0.001) groups. A reverse correlation was diagnosed between a decrease in blood pO 2 and an increase in SrDLA in patients of the II (r = –0.96; P <0.001) and III (r = –0.79; P <0.001) groups.

Thus, in patients with MM, impaired functional ability of the diaphragm leads to impaired ventilation of the middle and lower zones of the lungs, resulting in hypoxemia and pulmonary hypertension. However, in patients with MM complicated by CRF, this relationship is less pronounced, since the uremic damage of the bronchopulmonary system plays an important role in impaired respiratory function, and the pH of the blood and endothelial dysfunction of the vessels contribute to the development of PH.

As an example, here is an extract from the outpatient card No 4569. Patient S., born in 1947. Diagnosis: Multiple myeloma, diffuse focal form, secreting P IgG, stage IIIA was exposed in November 1997. In the myelogram, 19% of plasma cells, in the immunogram, IgG is 65 g / l, on radiographs of the skull, pelvic bones and edges multiple destruction. Mild anemia has occurred. During the initial hospitalization in the hospital, treatment was carried out according to the MR protocol. The plateau phase has been reached. She subsequently received maintenance therapy according to the MR protocol for 5 years. In 2002, a relapse of the disease was established. After conducting two courses of therapy under the protocol M 2 – VBMCP reached the second phase of the “plateau”, which lasted until 2006. In 2006 a relapse of the disease developed, which was accompanied by the destruction of flat bones, a pronounced pain syndrome and a pathological fracture of the left shoulder. Attempts to strengthen cytostatic therapy led to the development of serious complications: agranulocytosis, complicated by pneumonia; toxic hepatitis; thrombocytopenia and severe hemorrhagic syndrome. In July 2006 therapy started on the Velc + dexa protocol. A stable plateau phase has been reached.

Additional survey methods (July 2006). Roentgenograms of the bones of the skull, pelvis, and ribs – multiple destruction. In myelogram 40% of plasma cells. Immunogram: IgG – 75 g / l, IgA – 0.84 g / l, IgM – 0.58 g / l. Blood count: hemoglobin – 95 g / l, erythrocytes – 3.6 × 10 12 / l, platelets – 120 × 10 9 / l, leukocytes – 3.9 × 10 9 / l, segmented nucleus – 46%, lymphocytes – 45%, eosinophils – 3%, monocytes – 6%, ESR – 65 mm / h. Biochemical analysis of blood: total protein – 95 g / l, creatinine – 90 μm / l, urea – 6 μm / l, Ca – 2.6 mmol / l. Clinical analysis of urine – proteinuria 1000 mg / l. Spirography: VC – 64% D, FEV 1 – 70% D. During peak flowmetry, the PSV indicators were as follows: in the morning hours – 69% D, in the evening hours – 74% D. Daily fluctuations PSV was 5%. During pneumotachography, an increase in bronchial inhalation resistance was observed (3.2 cm water / l / s) and exhalation (3.5 cm water / l / s). When conducting PBS, a bilateral diffuse atrophic endobronitis was diagnosed. The results of endobronchial LDF before treatment with Velcade and Dexamethasone: PM – 35.63 PE; σ – 5.8 PE; Kv – 16.28%; Ae – 1.98 PE; An – 1.93 PE, Am – 3.04 PE; Hell – 2,850 PE; Ac – 1,460 PE. The data of endobronchial LDF in the stable plateau phase: PM — 65.1 PE; σ – 8.1 PE; Kv – 17.9%; Ae – 2.3 PE; An – 2.8 PE, Am – 3.2 PE; Hell – 3.6 PE; Ac – 2,9PE. Zone rheography of the lungs (July 2006). Dore of the right lung: upper zone – 0.5, middle zone – 0.38, lower zone – 0.8 ohm;The depth of the left lung is the upper zone — 0.46, the middle zone — 0.44, the lower zone — 0.44 ohms. Dob sum = 3.02 ohms. MEP of the right lung: upper zone – 8.3, middle zone – 6, lower zone – 11.2 ohm / min; MEP of the left lung: upper zone – 7, middle zone – 8, lower zone – 6.6 ohm / min. MOVr Sum – 47.1 ohm / min. The ratio of the MOV of the upper zones / MOV of the lower zones = 0.86. SCR of the right lung: in the upper zone – 0.09, in the middle zone – 0.05, in the lower zone – 0.1 ohm; The CR of the left lung – in the upper zone – 0.1, in the middle zone – 0.06, in the lower zone – 0.1 ohm. Scr sum = 0.5 ohm MPCr of the right lung: in the upper zone – 7.5, in the middle zone 3.5, in the lower zone 9.7; MPCr of the left lung: in the upper zone – 8.6, in the middle zone 4.5, in the lower zone 9.7 ohms / min. MPKr Sum = 43.5 ohm / min. Ventilation-perfusion ratio: right lung: upper zone 1.1, middle zone 1.7, lower zone 1.15; left lung: upper zone 0.8, middle zone – 1.77, lower zone 0.7. VPO of both lungs 1.1. IKC ultrasound data (July 2006): SrDLA – 23 mm. Hg Art., KDO PZh – 126 ml, KSO PZh – 67 ml, UI PZh – 49 ml / m 2 , SI PZH – 2.6 l / min / m 2 , EF PZH – 41%, E TC – 0.36 m / s, A TC 0.53 m / s, E / A – 0.7. Diagnosed the expansion of all cavities of the heart. Ultrasonic examination of the diaphragm: TD – 6 mm, EDS – 12 mm, EDf – 28 mm.

Morphometric studies were carried out in 50 patients who died of MM, 40 of them died with signs of renal failure and 10 with no signs of CRF. When performing a morphometric study of the lungs and bronchi, a comparative analysis was conducted with similar indicators of 30 absolutely healthy people, equivalent in age and sex, who died from injuries incompatible with life, and did not have a history of hemoblastosis and bronchopulmonary pathology (control group) .

A morphological study of the bronchi of different caliber in MM patients showed an increase in the number of neutrophils, eosinophils, lymphocytes, plasma and mast cells. Morphometric parameters of segmental bronchi are given. In most patients with MM, the height of the epithelium of the mucous membrane of the segmental bronchi is reduced, compared to the same indicator in the control, and a decrease in the thickness of the mucous membrane is diagnosed. In some patients, thinning of the basement membrane was noted, and growth of connective tissue in the submucosal layer.

Due to edema, lymphoid and plasma cell infiltration, an increase in the thickness of the interalveolar septa was observed in MM patients who died without renal failure – 59 ± 5.5 μm (P <0.001). In patients with MM who died in the presence of renal insufficiency, calcification, symptoms of uremic pneumonitis and edema of the interstitial lung tissue were associated with the above pathological processes, therefore the thickness of the alveolar partitions was even greater (80.3 ± 10 μm; P <0.001). In the control, this indicator is 40 ± 0.08 microns.

The reduction in the area of ​​part of the alveoli in patients with MM who died without CKD phenomena (95 ± 8 μm 2 ; P <0.01) is associated with a thickening of the interalveolar septa, manifestations of pulmonary paraproteinosis, and changes in the bronchi and blood vessels. In the presence of chronic kidney disease, swelling of the lung stroma, calcification, uremic pneumonitis. Therefore, in chronic renal failure, changes in the affected alveoli are more pronounced (area – 71.7 ± 5.5 μm 2 ; P <0.001). In the remaining parts of the lung, a compensatory expansion of the alveoli was observed (181 ± 15 μm 2 ; P <0.05).

In patients with MM with a pronounced osteo-destructive process of the chest and CRF (stage IIIA and stage II, stage IIIB), changes in the diaphragm were observed that were absent in the control group. Myocytes of medium size prevailed, but at the same time, the number of large and small myocytes increased. In these patients, a significant growth of the stroma around the vessels, in the intramuscular space, and large areas of lipomatosis were detected. The development of morphological changes in the diaphragm in patients with MM is promoted by its lymphoid and plasma cell infiltration, the presence of protein stasis in small vessels with impaired microhemocirculation and a decrease in the contractile ability of the diaphragm. In the presence of renal failure, uremic damage and edema of the diaphragmatic muscle also contribute to dystrophic changes. .

Direct radiographic signs of specific myelomatous lesion of the lungs (the presence of paraproteinosis of the lungs, amyloidosis, plasma cell and lymphoid infiltration) could not be detected in any patient, since they rarely reach such marked sizes when they can be determined radiographically. However, when carrying out the proposed complex of additional instrumental studies with a high degree of probability, it can be concluded that there is a specific myelomatosis lesion of the lungs. In order to identify statistically significant indicators that could indicate the presence of myelomatous lesions of the bronchopulmonary system, discriminant analysis was performed. In the study accompanying these patients instrumental examination of the bronchopulmonary system,after autopsy, morphological changes in the lungs and bronchi are studied. 
 The results of the discriminant analysis are as follows.

Statistically significant signs (P <0.05): 1) interstitial changes on radiographs and CT images (p = 0.000001), 2) decrease in PM, during endobronchial LDF <50PE (p = 0.000058), 3) decrease in VC during spirography <80% D (p = 0.025), 4) High level of M-component (IgG> 70 g / l, IgA> 50 g / l) (p = 0.00015), 5) decrease in hemoglobin less 85 g / l (p = 000362), 6) blood creatinine level> 170 μm / l (p = 0.0086). The combination of the above indicators with a high degree of probability may indicate the presence of myelomatous lesions of the bronchopulmonary system. Strengthening and deformation of the pulmonary pattern is explained by the stagnation of blood in small vessels and the development of pneumosclerosis, since due to the increased plasma viscosity, blood flow in the pulmonary capillaries slows down. Violation of microhemocirculation in the vessels The ICC is also explained by the hyperviscosity of the plasma, due to paraproteinemia. A high level of the M-component and a decrease in hemoglobin of less than 85 g / l are observed in patients with stage III myeloma, when there is a large tumor mass and visceral manifestations of the disease. Reduction of VC is a consequence of the defeat of the bronchopulmonary system in patients with MM (Chapter 4). Lymphoid and / or plasma cell infiltration, paraproteinosis and / or amyloidosis were diagnosed in the majority of deceased patients with MM in the presence of CRF in the lungs. In addition, severe bronchopulmonary complications develop in uraemia: uremic pulmonary edema, pneumonitis and metastatic calcification.

Statistically insignificant signs (p> 0.05): 1) the presence of multiple bone destruction on radiographs (p = 0.980), included patients who did not have pulmonary in vivo complete illness was performed. All 2) the presence of visceral lesions of other organs and systems (liver, spleen, etc.) (p = 0.205), 3) decrease in FEV 1
<80% D, during spirography (p = 0.437), 4) significant chest deformity (p = 0.551), 5) difficulty breathing (p = 0.959), 6) serum calcium level> 2.6 µm / l (p = 0.159), 7) daily proteinuria BJ> 4 g per day (p = 0.576). The lack of significant significance of such indicators as difficulty breathing is explained by the fact that the clinical manifestations of myelomatous lung lesions were very rare, only in some patients with uremic pulmonary edema. None of the patients with spirography showed a violation of obstructive type VFL, a decrease in FEV 1 was observed only in patients with a decrease in VOL (a violation of VFL in a mixed type).

The coefficients of classifying functions are given. Classifying functions: group 1 – patients without myelomatosis of the bronchopulmonary system; group 2 – patients with myelomatous lesions of the bronchopulmonary system.

The resulting classification functions can be used to assign a new patient to group 1 or group 2. For this, the values ​​of the indicators received from the newly admitted patient are entered into the classification functions for groups 1 and 2. Then the classification functions are calculated, and The patient belongs to the group for which the calculation gave a greater value.

As an example, here is an extract from the case history No 23145. Patient B. 1951, born The diagnosis “Multiple myeloma, diffuse focal form with PIgG secretion, stage IIIIA” was revealed in 2000. Myelogram contains 70% of plasma cells. On the roentgenogram, multiple destruction in the ribs, skull, spine, pelvic bones. The secretion of serum immunoglobulin G – 90 g / l. Bens-Jones proteinuria, protein – 5000 g / ml. In the clinical analysis of blood, hemoglobin decrease is 90 g / l, ESR acceleration is 60 mm / h. Therapy was carried out according to the MP protocol, after which the “plateau” phase was achieved, which lasted until 2003. In the spring of 2003 – a relapse of the disease. He received treatment according to polychemotherapy protocols at the beginning of the first line, then according to the VAD protocol and VAD-like protocols. In September 2003, chronic renal failure joined. In August 2004, death was ascertained. 
 Data from lifetime instrumental examination

respiratory system: on radiographs – increased pulmonary pattern, emphysema, pneumosclerosis; spirography – VC 82% D, FEV 1 84% D; endobronchial LDF – PM 29 PE, zone lung rheography – MOVr (sum) – 65 ohm / min, MPKr (sum) – 45 ohm / min, Ultrasonic diaphragm scan: TD – 5.7 mm., EDS – 11 mm ., EDF – 29 mm.

A macroscopic examination revealed pulmonary edema. Marked adhesions of the interlobar pleura, parietal and visceral pleura. A fluid (transudate) was found in both pleural cavities. The lung tissue to the touch was a testy consistency, differed by its low airiness, had a net-like pattern on the cut. Histological examination of the lungs revealed lymphoid and plasma cell infiltration in the form of cords in the interalveolar septa, along the vascular adventitia, in the submucosal bronchi and in the peribronchial spaces, manifestations of pulmonary paraproteinosis (the protein masses filling the pulmonary alveoli created carnivorous spaces. lungs impregnated thickened, hyalinized interalveolar partitions and filled small vessels), pneumosclerosis,the presence of uremic lesions – pneumonitis (small focal nature of the lesion, extending to 5-20 alveoli, the presence of one and the same the source of circulatory disorders , edema and fibrinous inflammation), calcification. The thickness of the diaphragm is 3.9 mm. Medium sized myocytes prevailed. But an increase in large and small sized myocytes was noted (15 and 38%, respectively). There was a significant growth of the stroma around the vessels, in the intermuscular space (28%) and large areas of lipomatosis. Revealed protein stasis in small vessels of the diaphragm.

The data of regional ventilation and blood flow were analyzed and compared with morphological changes in the lungs in patients with MM. In patients with group II (stage IIIIA), paraproteinosis of the lungs and amyloidosis, lymphoid and plasma cell infiltration of the lungs and bronchi, pneumosclerosis, localized compensatory emphysema, microcirculation disorders and diaphragm function were diagnosed. The leading factor contributing to the development of microcirculatory disorders in this group is the plasma hyperhazard. Due to the pathology of the microvasculature, tissue trophicity is disturbed, local metabolism suffers, and tissue hypoxia develops. Thinning occurs, sclerosis of the bronchial mucosa. In 40% of patients with MM, bilateral diffuse atrophic endobronchitis develops.Against this background, due to immunodeficiency, bronchopulmonary infections acquire a severe and prolonged course. In case of myelomatosis of the diaphragm and violation of the chest excursion, the mobility of the primary respiratory muscle decreases. These pathological changes explain the decrease in general and regional ventilation, pulmonary blood flow in patients with MM.

In group III (with the addition of renal failure) in the lungs and bronchi, manifestations of nephrogenic edema, uremic pneumonitis and calcinosis are revealed, microhemocirculation and hemodynamic disorders of the ICC are progressing, which further aggravates the pulmonary ventilation.

The presence of specific myelomatous and uremic changes in the lungs, severe and prolonged course of bronchopulmonary infections, impaired lung ventilation function and bronchial drainage function, impaired chest excursion due to destruction of the ribs and spine lead to the development and progression of hypoxemia. In patients with MM in stage IIIA and with accession of chronic renal failure, endothelial dysfunction occurs . Patients with renal insufficiency develop acidosis. Hypoxemia, endothelial dysfunction, myocardial dystrophy and acidosis contribute to an increase in pressure in the pulmonary artery system with MM.

Along with a pronounced secondary immunodeficiency, the identified morphological and functional changes contribute to the development of infectious complications of the bronchopulmonary system in patients with CLL.

Pneumonia in CLL deserves special attention, since they are the most serious complication that plays a major role in the outcome of the disease. Of the 95 people who died in 54 people (56.4%), pneumonia was the immediate cause of death. Of the 228 patients examined, CLL pneumonia was registered in 103 patients (45%). The incidence of pneumonia depended on the severity of the tumor process. A large incidence was noted in patients of group III (58 patients), less often in patients of groups II and I (36 and 9 people, respectively). Relapses of pneumonia were recorded in 16 patients in the II and in 45 patients in the III group. A total of 103 patients with CLL had 150 cases of pneumonia.

Predominantly affected lower lobes of both lungs. In most cases, pneumonia began as focal, but often there was a tendency for rapid expansion, the emergence of new pneumonic foci, often merging with each other. Lobar pneumonia was diagnosed in 14 cases (9.3%).

Nosocomial pneumonia (NP) occurred at different times in 40 CLL patients (39% of the total number who had pneumonia). Of the 150 cases of pneumonia, 54 (36%) began in the inpatient unit. In patients with a benign course of CLL, NP was not registered. In group II, NPs were noted in 13 patients, in group III, in 31 people.

An analysis of the causes of NP showed that in most cases they developed after a course of cytostatic therapy, especially after polychemotherapy, against a background of a significant decrease in the number of leukocytes. Course treatment with cyclophosphamide, chlorambucil and monotherapy with fludarabine rarely preceded the occurrence of pneumonia (4, 1 and 3 cases, respectively). More often, this was facilitated by treatment with fludarabine in combination with rituximab (FCR) (6 cases) and mitoxantrone (FCM) (8 cases). The combination of fludarabine with cyclophosphamide preceded the appearance of NP in 4 cases. The course of polychemotherapy according to the protocols CP, COP, CHOP, CAP preceded the occurrence of NP in 24 cases. In four cases, NPs developed after local radiation therapy, against the background of a sharp decrease in the number of leukocytes.At the same time, according to these statistics, one can only indirectly judge the impact of certain protocols. chemotherapy for the occurrence of infections in patients with CLL. We have been actively using treatment with fludarabine for the past few years. In the 90s of the past century, patients with CLL were treated with cyclophosphamide, chlorambucil, CP, COP, CHOP, CAP polychemotherapy courses, according to these protocols, more patients were treated. Polychemotherapy courses are conducted in most cases in patients with rapidly progressive CLL. In these patients, immunodeficiency is more pronounced, which also contributes to the occurrence of inflammatory processes in the lungs. In addition, the occurrence of pneumonia contributes to comorbidities: diabetes mellitus, COPD, coronary heart disease, arterial hypertension, etc.

Emergence of community-acquired pneumonia was preceded by influenza, ARVI, acute bronchitis, exacerbation of chronic infections of the upper respiratory tract. The causative agent in most cases was pneumococcus. In 12 patients with community-acquired pneumonia, a combined flora was sown. In 45 cases, it was not possible to establish the etiological diagnosis of pneumonia, despite the use of modern methods of laboratory diagnostics.

Gram-negative flora is 56% of pathogens NP and 23.6% of community-acquired pneumonia.

Speaking about the laboratory manifestations of pneumonia in CLL, it should be noted that due to the nature of the disease (leukocytosis, absolute lymphocytosis) in the peripheral blood tests, these patients do not have a neutrophilic shift in the leukocyte formula. The lack of neutrophils in CLL patients explains the absence or doubtful radiological data in 10 patients, since a dense inflammatory focus is not always formed, giving a clear physical and X-ray picture. In 10 patients, a lesion in the lung was detected only with computer tomography. Neutrophil deficiency is an important cause of atypical pneumonia in patients with granulocytopenia.

An important feature of pneumonia in CLL patients is the occurrence of an inflammatory focus in places of lymphoid infiltration of the lung tissue. In 30 patients who died of CLL, the inflammatory focus was localized in the area of ​​light leukemic infiltration. These were patients in in the terminal stage of the disease, a prolonged, recurrent course of pneumonia was characteristic of all, with frequent involvement in the process of the pleura, difficult to respond to antibiotic therapy. The appearance of extramedullary foci of hematopoiesis is a sign of the terminal stage of CLL, therefore the constantly recurring course of pneumonia involving the lung sections in the inflammatory process was typical for most patients of group III. In patients with group II, recurrence of pneumonia was less common (16 patients). In group I, there was no recurrent pneumonia.

An important cause leading to the occurrence of pneumonia and largely determining its course is secondary immunodeficiency. The analysis of the main immunological parameters of 80 patients with pneumonia was carried out. The immunogram was studied in the period of the developed clinical picture of pneumonia, and after its resolution.

As can be seen from the presented study, after the resolution of pneumonia, there is no significant improvement in cellular and humoral immunity indices. Humoral protection carries IgA and IgG, lymphoid cells, macrophages of broncho-associated lymphoid tissue and lymph nodes . IgA ensures the agglutination of bacteria and neutralizes their toxins. IgG of the lower respiratory tract agglutinates and opsonizes bacteria, activates complement, accelerating chemotaxis of neutrophils and macrophages, neutralizes bacterial toxins . Therefore, hypoimmunoglobulinemia, characteristic of all patients with C – CLL and aggravated as the tumor process develops, is an important factor contributing to the occurrence of pneumonia, their severe and protracted course.

An important factor in the occurrence, severity and protracted course of pneumonia in CLL patients is impaired microcirculation in the lungs and bronchi in the process of tumor progression, accompanied by impaired trophism of tissues and local metabolism, developed tissue hypoxia .

The main clinical symptoms of pneumonia were: pain in the chest on the affected side, shortness of breath, cough with mucopuric sputum, febrile temperature, tachycardia, hypotension, weakened breathing, wet or dry rales. Unspecific, atypical course of pneumonia is noted in 40 cases (26.7% of the total number of pneumonia). The characteristics of the course of pneumonia in these patients were: 1) mild physical symptoms; 2) frequent absence of acute onset of the disease and pain; 3) the prevalence of extrapulmonary manifestations of pneumonia in the form of bacterial toxic shock, severe intoxication; 4) long-term resorption of pulmonary infiltrate, recurrence of the disease; 5) fever was observed in 10 people, without radiographic signs of pulmonary inflammation.

Severe pneumonia was noted in 75 patients with CLL in 90 cases, of which 54 people were found to be fatal. The most often severe course was observed in patients of group III (52 patients), later in patients of group II (23 patients). In patients with group I, severe pneumonia was not observed.

Among pulmonary complications, pneumonia was diagnosed with acute respiratory failure (45 cases), exudative pleurisy (40 cases), destruction of the lungs (10 cases), abscess of the lungs (10 cases), and lung disease (38 cases). Among extrapulmonary complications, infectious-toxic shock was noted – 45 cases, sepsis – 15 cases, pericarditis – 11 cases, psychosis – 7 cases, meningitis – 1 case.

In all CLL patients, when pneumonia was attached, a significant decrease in capillary blood pO 2 , a decrease in hemoglobin oxygen saturation and total oxygen in the blood were noted . A decrease in pO 2 is more pronounced in patients with a widespread involvement of the lung tissue in the inflammatory process. In many patients during the period of developed clinical manifestations of pneumonia, moderate hypercapnia occurred .

In the treatment of pneumonia in patients with CLL, the basic rules for the treatment of pneumonia in patients with neutropenia were followed . There was a significant difference between patients of CLL of the three groups in the regression of the clinical manifestations of pneumonia. Faster positive dynamics was observed in patients of group I. Not a single patient in this group had a prolonged course of pneumonia. Among 36 patients of group II, a prolonged course of pneumonia was observed in 15 people (41.7% of the total number of patients who had pneumonia in this group). In group III, a prolonged course of pneumonia was observed in 40 patients (69%).

In patients of groups I and II of CLL, there were no significant differences in the time of stopping the clinical manifestations of pneumonia as compared with patients with pneumonia without hemoblastosis (2nd control group). In patients with group III, cough, fever, tachycardia, wheezing, accelerated erythrocyte sedimentation rate were preserved for a much longer time, there was a slow radiological dynamics .

A feature of pneumonia in patients with CLL is a long-term X-ray dynamics. After stopping the main clinical manifestations of pneumonia, on radiographs long-term infiltration persists, which resolves very slowly, despite active antibacterial therapy. This causes the attending physician to conduct a differential diagnosis between inflammatory and leukemic infiltration of the lung tissue. Making a differential diagnosis in this situation is very difficult, even using modern bronchoscopic and radiological ( CT and MRI) techniques. . Puncture biopsy of the lesion in the lung, in most cases, is not feasible due to the presence of thrombocytopenia. Diagnostics helps with X-ray examination over time, inflammatory infiltration with antibacterial therapy resolves over time. In cases of the development of a lethal outcome in all patients with persistently recurrent, prolonged pneumonia, an inflammatory focus was detected in places with lymphocytic infiltration, which could only be diagnosed by histological examination.

Atypical, severe and TIGHTENING Nome pneumonia in pain GOVERNMENTAL CLL promote: a pronounced secondary immunodeficiency conducted this patient courses of chemotherapy and hormonal TE rapii, older age of most patients, lymphoid infiltration of the lungs and bronchi, impaired microcirculation and trophic tissue, presence of concomitant diseases (COPD, ischemic heart disease, diabetes mellitus, arterial hypertension, etc.), compression syndrome in the chest cavity in patients with Richter syndrome.

High resistance of pneumococcus to gentamine, cephalexin, oxacillin is noted . In many patients, pneumococcus retains sensitivity to penicillin, erythromycin, linkocomycin, cefazolin, cefotaxime. Hemophilus bacillus maintains minimal resistance to lincomycin, erythromycin, amoxicillin, oxacillin, cefazolin, cefoxime; significant resistance to gentamicin, penicillin. Staphylococcus aureus retains a high resistance to methicillin, penicillin, lincomycin, and carbenicillin. Among gram-negative microorganisms, there is high resistance to gentamicin, penicillin, amoxicillin. There is a high sensitivity to ciprofloxacin, cefoxime. Most gram-negative and gram-positive pathogens were sensitive to meropenem, fortum, cefepime, methicillin.

In the Far Eastern region, in the etiological structure of pathogens of community-acquired pneumonia in elderly patients (not suffering from lymphoproliferative diseases), along with pneumococcus and hemophilus bacilli, aerobic gram-negative bacteria (20%) and golden staphylococcus (8.5%) occupy a special place; Gram-negative microflora is the leading etiological factor in the development of NP (75.5%). The literary flora plays an important role in the occurrence of pneumonia in CLL patients, most of whom are elderly. In accordance with the occurrence of pneumonia in the hospital or outside the hospital, the suspected causative agent, the clinical and pathogenetic situation and the presence of underlying diseases, an empirical treatment algorithm for pneumonia in patients with CLL isin the period until the causative agent is detected and its sensitivity to antibiotics is determined, as well as for those situations when it is impossible to establish the etiological diagnosis of pneumonia It is possible .

In 54 patients with CLL complicated by pneumonia, a fatal outcome was noted. In 30 of them, during the histological study, an inflammatory focus was identified in the sites of lung lymphoid infiltration. Pneumonia, which was of a barbaric nature, was located mainly in the posterior sections of the lungs. In a macroscopic study, one or several lung lobes were enlarged. The tissue of the affected lung was sealed in gray, pink-gray or red. Large areas of airless tissue with hemorrhages were detected. The cut surface was grainy or smooth. In all cases, there was exudative pleurisy. Histological examination of lymphocytic infiltration in the bronchioles and alveolar passages revealed a loose exudate consisting of a serous or hemorrhagic fluid,fibrin and neutrophils. Due to the characteristics of CLL, the number of neutrophils in the exudate was reduced.

Macroscopically, focal, focal-confluent, and polysegmental pneumonia, on the background of pronounced pulmonary edema, looked like compaction areas ranging in size from 1 to 5 cm in diameter, from grayish-red to dark-red. These areas protruded above the surface of the incision of the lungs. Histologically, in the alveoli, exudates with a predominance of fibrin and a small number of neutrophils were found. There were signs of circulatory disorders on the periphery of the alveoli filled with exudate. A number of patients were diagnosed with resorption of fibrinopurulent exudate and growth in these areas of granulation and connective tissue in the form of Masson’s bodies (carnification, organization). Changes in the bronchi were local in the area of ​​chronic inflammation. Peribronchial changes prevailed: peribronchial tissue thickening,deformation and constriction of the bronchi with unevenly expanded gaps. In areas of carnification, clusters of alveolar macrophages and desquamated type 2 alveolocytes, the formation of granulation tissue inside the alveoli and respiratory bronchioles, and focal pulmonary fibrosis were detected in the lumen of the alveoli. The organization of exudate in the alveoli was detected against the background of marked infiltration of the interalveolar septa with lymphocytes. Clutches of lymphocytes were formed around small vessels. Often, interlobular, intersegmental, peribronchial fibrosis and obliteration of the terminal and respiratory bronchioles were noted. Microscopic examination of lymphoid infiltration of interalveolar septa, signs of “organizing pneumonia” and obliterating bronchiolitis were detected by microscopic examination of the majority of patients who died of CLL with severe pneumonia.In blood vessels of various calibers, leukostasis was noted with infiltration of the vessel walls with lymphocytes. In the centers of carnification and pneumosclerosis, cavities having a rounded or convoluted shape were often detected. These cavities were islands of preserved alveoli. In the areas of granulation tissue, the formation of a large number of capillaries was noted. In a number of pneumosclerosis foci, in a number of patients, vascular reduction and the appearance of arteriovenous anastomoses were detected. Morphological changes in the lungs (lymphoid infiltration of the interalveolar septa, impaired microhemocirculation and tissue trophism, “organized pneumonia”, bronchiolitis obliterans) contributed to the severe and prolonged course of pneumonia in these patients.In the centers of carnification and pneumosclerosis, cavities having a rounded or convoluted shape were often detected. These cavities were islands of preserved alveoli. In the areas of granulation tissue, the formation of a large number of capillaries was noted. In a number of pneumosclerosis foci, in a number of patients, vascular reduction and the appearance of arteriovenous anastomoses were detected. Morphological changes in the lungs (lymphoid infiltration of the interalveolar septa, impaired microhemocirculation and tissue trophism, “organized pneumonia”, bronchiolitis obliterans) contributed to the severe and prolonged course of pneumonia in these patients.In the centers of carnification and pneumosclerosis, cavities having a rounded or convoluted shape were often detected. These cavities were islands of preserved alveoli. In the areas of granulation tissue, the formation of a large number of capillaries was noted. In a number of pneumosclerosis foci, in a number of patients, vascular reduction and the appearance of arteriovenous anastomoses were detected. Morphological changes in the lungs (lymphoid infiltration of the interalveolar septa, impaired microhemocirculation and tissue trophism, “organized pneumonia”, bronchiolitis obliterans) contributed to the severe and prolonged course of pneumonia in these patients.In a number of pneumosclerosis foci, in a number of patients, vascular reduction and the appearance of arteriovenous anastomoses were detected. Morphological changes in the lungs (lymphoid infiltration of the interalveolar septa, impaired microhemocirculation and tissue trophism, “organized pneumonia”, bronchiolitis obliterans) contributed to the severe and prolonged course of pneumonia in these patients.In a number of pneumosclerosis foci, in a number of patients, vascular reduction and the appearance of arteriovenous anastomoses were detected. Morphological changes in the lungs (lymphoid infiltration of the interalveolar septa, impaired microhemocirculation and tissue trophism, “organized pneumonia”, bronchiolitis obliterans) contributed to the severe and prolonged course of pneumonia in these patients.

In all CLL patients who died when pneumonia was attached, there was an increase in the lymph nodes in the chest cavity, 14 of them had sarcomal transformation of these lymph nodes. Enlarged, sarcomotransformed, dense lymph nodes with Richter syndrome squeezed the lung tissue and bronchi, which contributed to impaired lung ventilation function, bronchial drainage function and the emergence of the inflammatory process.

As an example, here are two extracts from archival case histories.

Extract from the case history No 14267. Patient G., born in 1936. Diagnosis: chronic lymphocytic leukemia, tumor form, stage C according to the classification of J. Binet. The diagnosis of CLL was made in 2002, confirmed by histological examination of the lymph node and immunophenotyping of peripheral blood lymphocytes (CD5 +, CD19 +, CD20 +, CD22 +, CD23 +). Concomitant diseases: ischemic heart disease, circulatory failure IIA.

Upon admission to the hospital (March 12, 2006), there is an increase in the lymph nodes of all peripheral groups up to 5–6 cm in diameter with a densely elastic consistency, soldered between each other, form “packages”, with surrounding tissues are not soldered, without painful. Packings of enlarged abdominal lymph nodes are palpable through the anterior abdominal wall. The lower edge of the liver is palpated 8 cm below the costal arch. The spleen is palpable 13 cm below the left costal margin. In the lungs, vesicular breathing and wheezing are not heard. Heart sounds are muffled, the rhythm is right. Blood pressure 150/90 mm. Hg Art.HR – 88 beats per minute. A blood test (from 13.03.2006): hemoglobin – 68 g / l, red blood cells – 2.7 × 10 12 / l, leukocytes – 166.7 × 10 9 / l, platelets – 90 × 10 9 / l, lymphocytes – 98%, segmented – 2%, ESR – 10 mm / h. CCFG: lungs without focal and infiltrative shadows, the roots of the lungs are enlarged. ERTGS – an increase in mediastinal lymph nodes. Immunogram: CD 3 – 29.0%, CD 4 – 19.1%, CD 8 – 19.0%, CD 4 / CD 8 – 1.0, CD 20 – 63.1%, CD 22 – 30.2 %, immunoglobulins: A – 1.1 g / l, M – 1.0 g / l, G – 8.0 g / l. The patient underwent a course of therapy with fludararabine (Fludar tablet tablets, at a dose of 30 mg / m 2 , 1 – 5 days) in combination with cyclophosphate (at a dose of 200 mg / m 2 , 1 – 5 days), red blood cell transfusions, etc. Positive dynamics was observed: the lymph nodes of all peripheral groups decreased to 2–2.5 cm in diameter. The size of the liver and spleen has decreased. The lower edge of the liver protrudes 5 cm from the edge of the costal arch, the lower edge of the spleen is palpable 4 cm below the left costal edge. A blood test (from March 25, 2006): hemoglobin – 104 g / l, erythrocytes – 3.3 × 10 12 / l, leukocytes – 27.9 × 10 9 / l, platelets – 100 × 10 9 / l, lymphocytes – 96%, segmented – 4%, ESR – 18 mm / h. The patient notes improvement in well-being, preparing for discharge. On March 28, 2006, the temperature suddenly rose to 39 С. Chills. Tachycardia up to 120 beats per minute. Severe weakness, indisposition, shortness of breath at rest, feeling of lack of air. A decrease in blood pressure to 100 and 50 mm Hg is noted. During auscultation in the lower parts of the right lung moist rales are heard. An x-ray examination of the lungs was performed (March 29, 2006). Conclusion: focal-confluent pneumonia in the lower lobe of the right lung. In the clinical analysis of blood from March 29, 2006, the number of leukocytes decreased to 2.5 × 10 9 / l. KHS and blood gas composition: pH – 7,323; pCO 2 – 48.6 mm. Hg Art., pO 2 – 56.6 mm. Hg Art., O 2 SAT – 88%, O 2 CONT – 12.7 vol /%, AaDO 2 – 44.9 mm. Hg Art. In the sputum and bronchial washings, the pathogen was not detected in the pathogenic titer. Empirical therapy with broad-spectrum antibiotics was performed. Initially, the combination of ciprofloxacin (0.4 × 2 p / day, IV drip) and medocef (2.0 × 2 p / day, IV drip) was prescribed, followed by the combination of sulperazone (4.0 × 2 p / day, iv drip) and amikacin (1.5 g. 1p. per day). Immunomodulatory (immunoglobulins), antimycotic (mycosyst, mycoflucan) and detoxification therapy were prescribed. Blood pressure values ​​normalized on the fifth day, dyspnea stopped on the 10th day of treatment, the temperature returned to normal on the 18th day, wheezing stopped listening on the 16th day. Weakness, malaise persisted. 04/29/2006, a repeated X-ray of the lungs was taken.On control radiographs in the frontal and lateral projections, a decrease in pneumonic infiltration in the lower part of the right lung was determined (S 4-5-10). Conclusion: right-sided foci-confluent pneumonia in the resolution stage. For 4 weeks, pneumonia was not completely resolved, took a protracted course. The treatment was continued – a combination of fortum (2g. × 2 p / day, intravenous droplet) and ciprofloxacin in the same dose (given the good effect of prescribing this antibiotic). Immunomodulatory and detoxification therapy was continued. On radiographs from 13.05.2006, infiltration is not determined. As a complication, the development of focal pneumofibrosis is noted. Full normalization of well-being (the absence of all extrapulmonary manifestations of pneumonia) was also noted at the beginning of May 2006.In this case, classical nosocomial pneumonia took place in a patient with CLL that developed after a course of polychemotherapy, which has a heavy and protracted course.

Extract from the case history No 4239. Patient K., born in 1955. Diagnosis: Chronic lymphocytic leukemia, progressive form, stage C according to the J. Binet classification. CLL was diagnosed in 2004. Clinical blood test from 2004. – hemoglobin – 135g / l, erythrocytes – 3.9 × 10 12 / l, leukocytes – 35 × 10 9 / l, lymphocytes 73%, choke-core – 2%, segmented core – 20%, monocytes – 5%, platelets – 180 × 10 9 / l. Immunophenotype of peripheral blood lymphocytes – CD5 +, CD19 +, CD20 +, CD22 +, CD23 +. Expressed expression of CD38 was not observed at that time. Peripheral lymph nodes of all groups in 2004 did not exceed 1.5 – 2 cm. Liver, spleen were not enlarged. At that time, the stage A CLL was classified according to the Binet classification. Within two years, there was no significant progression of hemoblastosis, cytostatic therapy was not prescribed, and patients were monitored dynamically. Deterioration since September 2006: peripheral lymph nodes, liver, spleen began to increase; leukocytosis increased progressively; anemia and thrombocytopenia increased. Blood count: hemoglobin – 89g / l, erythrocytes – 2.78 × 10 12 / l, leukocytes – 134.16 × 10 9 / l, lymphocytes 86%, prolymphocytes – 8%, segment-nuclear – 6%, platelets – 70 × 10 9 / l. The patient was prescribed mono-therapy with fludarabine, subsequently the FCR protocol. But a persistent therapeutic effect was not observed. In June 2007 Clinical and X-ray studies diagnosed destructive pneumonia in the S 6 segment. left. Pulmonary tuberculosis was excluded (sputum and bronchial lavages at KUM, CT of the lungs were repeatedly examined, consultation with a phthisiologist). From the bronchial washings, S. pneumoniae and neisseria were sown. In the treatment of pneumonia, a combination of broad-spectrum antibiotics was used to identify the causative agent; after the causative agent was detected, antibiotic therapy was corrected taking into account its sensitivity. Immunomodulatory, antimycotic, anti-inflammatory therapy was prescribed. Fully clinical and radiological manifestations of pneumonia resolved in August 2007. October 18, 2007 He was taken to the therapeutic department of the CRH (at the place of residence) by an ambulance in a critical condition. There was an increase in body temperature to 39 – 40 ̊С, a decrease in blood pressure, severe shortness of breath. Clinical blood test:red blood cells – 2.4 × 10 12 / l, hemoglobin – 67 g / l, leukocytes – 274 × 10 9 / l, lymphocytes – 87%, prolymphocytes – 10%, segmented cells – 3%, platelets – 50 × 10 9 / l, ESR – 61 mm / h . During the X-ray examination, pneumonia was again diagnosed in the S 6 segment on the left. Despite the conduct of adequate antibacterial, anti-inflammatory, immunomodulating, detoxification therapy, 20.10.2007. a lethal outcome was established with the phenomena of bacterial toxic shock. Histological examination of tissue S 6 the left lung revealed lymphoid infiltration of the pulmonary interstitium; in the alveoli exudate was found with a significant predominance of fibrin, a small number of neutrophils, accumulations of bacteria. In this case, the focus of inflammation was localized in the area of ​​lymphocytic infiltration of the lung, which, along with pronounced immunodeficiency, caused severe and recurrent pneumonia.

Based on a study of the clinical and morphological features of the course of pneumonia in CLL patients, the following conclusion can be drawn : 1. Pneumonia is the most common infectious complication of CLL (103 patients out of 228 examined, which is 45%). As CLL progresses, the incidence of pneumonia increases. Patients with CLL have a high incidence of nosocomial pneumonia (36%).
 
 
 For patients with CLL, the prevalence of prolonged (53.4%), severe (60%) and atypical (27.6%) course of pneumonia is characteristic. The causes of atypical, severe, and protracted pneumonia in CLL are: a) pronounced secondary immunodeficiency, primarily neutrophil deficiency and hypo-immunoglobulinemia, b) courses of chemotherapy and glucocorticoid therapy, which contribute to the development of an ammunition deficit, aggravating the development of the ammunition and corticosteroids, which contribute to the development of an inadequate case of chemotherapy and glucocorticoid therapy, which contribute to the inadequacy of cortical diseases, which contribute to the development of an obstructive, severe and prolonged course of pneumonia in CLL; lung tissue and bronchi, d) significant microcirculation in the lungs and bronchi, e) pulmonary ventilation disturbance and perfusion, e) elderly rast of most CLL patients, g) presence of concomitant diseases (COPD, IHD, diabetes, etc.), pulmonary ventilation function and bronchial drainage function. Gram-negative flora occupies an important place among pneumonia pathogens in patients with CLL – 56% of the total number of hospital pneumonia and 26.3% of cases of community-acquired pneumonia. In accordance with the occurrence of pneumonia in the hospital or outside the hospital, the suspected causative agent, the clinical and pathogenetic situation and the presence of underlying diseases, an empirical antibiotic therapy of pneumonia has been compiled in patients with CLL
 identifying the pathogen and determining its sensitivity to antibiotics, as well as for those situations when it is impossible to establish the etiological diagnosis of pneumonia.

Regional ventilation and lung perfusion were studied using reopulmonography. MEP of the right lung: in the upper zone – 8.3, in the middle zone – 7.8; in the lower zone – 7.2 ohm / min; MOPP of the left lung: in the upper zone – 8.1, in the middle zone – 7.7; in the lower zone – 7.6 ohm / min. MOVr sum = 46.7 ohm / min. The ratio of MOV of the upper zones / MOV of the lower zones = 1.1, which indicates a significant redistribution of ventilation from the lower zones of the lungs to the upper ones. MPCr of the right lung: in the upper zone – 10, in the middle zone 8.2, in the lower zone 6.8; MPCr of the left lung: in the upper zone – 9, in the middle zone 8.6, in the lower zone 6.1 Om / min; MPKr sum 48.7 ohm / min. Reprinted pulmonary blood flow from the lower zones to the upper ones due to the increase in vascular resistance in the lower and middle zones and its decrease in the upper zones. VPO were distributed as follows: right lung – upper zone 0.83, middle zone 0.95, lower zone 1.0; left lung – upper zone 0.9, middle zone – 0.9, lower zone 1.2. The total index of the HPE of the right lung is 0.9, the left lung is 1, both lungs are 0.95. The data of ultrasound IWC: SrDLA – 24 mm. Hg Art., KDO PZh – 135 ml, CSR PZh – 51 ml, UI PZh – 72 ml / m 2 , SI PZH – 4.3 l / min / m 2 , EF RV – 54%, E TK – 0.44 m / s, A TK 0.70 m / s, E / A – 0.63. Diagnosed the expansion of all cavities of the heart. Ultrasonic examination of the diaphragm: TD – 5 mm, EDS – 8 mm, EDf – 13 mm. A decrease in the excursion of the diaphragm with quiet and forced breathing was diagnosed, which is due to its compression by significantly increased liver and spleen.

After analyzing the data of spirography, peak flow measurements, pneumotachography, and zonal rheography of the lungs, these studies of endobronchial LDF, pulmonary and intracardiac hemodinamics in patients with CLL, we can conclude:

1. In the process of tumor progression in CLL, indices of endobronchial microhemocirculation decrease. Important causes of endobronchial microcirculation disorders in CLL are high leukocytosis in the peripheral blood, contributing to the formation of leucostasis; in patients with anemic syndrome, a decrease in the number of erythrocytes.

2. Disruption of microhemocirculation in patients with CLL contributes to disruption of tissue trophism, development of tissue hypoxia, local metabolic disorder, resulting in the onset of a severe and prolonged inflammatory process in the lungs and bronchi and an increase in pressure in the small circle of the circulation. When conducting a fibrobronchoscopic study in 60% of patients with a progressive course of CLL, the latent course of chronic non-obstructive bronchitis was diagnosed (40% of the total number of CLL patients).

3. As the tumor process develops in CLL, violations of general and regional ventilation and lung perfusion are progressed, which is characterized by a decrease in these indicators in each zone separately and in general in both lungs. There is a redistribution of ventilation and blood flow from the lower and middle zones to the upper zones of both lungs. These changes are due to the presence of infectious complications and leukemic bronchopulmonary manifestations of CLL, a violation of the diaphragm excursion.

4. In patients with CLL in the later stages of the tumor progression, bronchial resistance increases due to severe and severe inflammatory processes, leukemic infiltration of the lungs and bronchi, impaired endobronchial micro-hemocirculation, compression of the bronchial tree by increased mediastinal lymph nodes.

5. As the CLL progresses, there are impaired systolic and diastolic functions of the right and left ventricles.

6. Violation of the contractile ability of the diaphragm in patients with CLL is promoted by its leukemic lesion and compression by the enlarged liver and spleen.

7. In 37% of patients with CLL in the late stages of tumor progression without a concomitant broncho-obstructive process, hypoxemia and pulmonary hypertension are diagnosed. A disturbance in the expansion of the diaphragm, a severe course of infectious complications and leukemic lesions of the bronchopulmonary system, rheological disorders in the ICC vessels, and myocardial dystrophy contribute to an increase in pressure in the LA system in these patients.