(DIFFUSE PARENCYMATOUS DISEASES OF THE LUNG)
Lung diseases caused by external factors
E 83.5 Alveolar microlithiasis
J 98.2 Interstitial emphysema
Q 33.0 Bronchogenic cysts – polycystic lung disease
D 86.0 Sarcoidosis
Main disease.
M 31.3 Wegener's granulomatosis: malignant granuloma of the nose, necrotizing vasculitis of small and medium-sized vessels of the lungs and kidneys
Complications.
Main disease.
D 76.0 Langerhans cell histiocytosis
(histiocytosis X, eosinophilic granuloma) with predominant damage to the lungs:
diffuse focal interstitial granulomatosis, multiple cysts and areas of bullous emphysema in the upper and middle lobes of the lungs.
Main disease.
D 48.1 Lymphangioleiomyomatosis of the lungs: multiple foci of smooth muscle proliferation, small cystic (honeycomb) lungs.
Complications. Bilateral chylothorax (600 ml each).
Main disease.
Complications.
Main disease.
Q 33.0. Bilateral subtotal polycystic pulmonary disease or bronchogenic cysts in segments 1-3 of the right and segments 4-8 of the left lung.
Complications. Focal confluent bronchopneumonia in 6-10 segments of the left lung.
Main disease.
Q 33.0. Intralobar sequestration in 7-10 segments of the left lung (in persons over 20 years old, 60% of the left lung is affected).
Complications. Focal confluent bronchopneumonia in the 6th segment of the left lung.
Main disease.
Q 33.0. Congenital adenomatoid malformation (specify one of 4 types) of the right lung.
Complications. Secondary arterial pulmonary hypertension with cor pulmonale.
CONCLUSION
A pathological diagnosis in pulmonology is not a list of nosological forms, syndromes and symptoms identified in a patient; it must be of a logical pathogenetic nature. The diagnosis should highlight the underlying disease, its complications and concomitant diseases. When constructing a pathological diagnosis and identifying nosological forms, one should be guided by the international nomenclature of diseases (List of diseases of the lower respiratory tract, 1979). Nosological forms in the diagnosis should be coded in accordance with ICD-10.
Standardization of principles and rules for constructing diagnoses will improve the formulation of pathological diagnosis, evaluation of treatment and statistical recording, especially such nosologies as pneumonia, COPD, bronchial asthma, interstitial (diffuse parenchymal) lung diseases.
LITERATURE
1. Avtandilov G.G. Preparation of a pathological diagnosis. M., 1984.-25p.
2. Avtandilov G.G. Problems of pathogenesis and differential pathoanatomical diagnosis of diseases in aspects of morphometry. M.: Medicine., 1984.-288p.
3. Avtandilov G.G. Fundamentals of pathological practice. M., 1994.-512 p.
4. Avtandilov G.G., Raynova L.V., Preobrazhenskaya T.M. Basic requirements for drawing up a pathological diagnosis and issuing a death certificate. M., 1987.-25p.
5. Bilichenko T.N., Chuchalin A.G., Son I.M. The main results of the development of specialized medical care for pulmonary patients in the Russian Federation for the period 2004-2010/Pulmonology.2012. No. 3. from 5-16.
6. Biopsy-section course. - Educational and methodological instructions for practical and independent work of students of the Faculty of Medicine / Edited by Professor O.D. Mishnev/. M., 1995.-70 p.
7. Davydovsky I.V. Pathological anatomy and pathogenesis of human diseases. M., 1956.- vol. 1, 2.
8. Disseminated processes in the lungs (edited by N.V. Putov) - USSR - GDR - M.: Medicine, 1984 - 224 p.
9. Zairatyants O.V., Kaktursky L.V. Formulation and comparison of the final clinical and pathological diagnoses. Directory. 2nd ed. Reworked and additional MIA., 2011. 506 p.
10. International statistical classification of diseases and related health problems. - Tenth revision in 3 volumes, WHO, Geneva. - Medicine Publishing House, 1995.
11. Ministry of Health of the Russian Federation. Department of Monitoring, Analysis and Strategic Development of Healthcare. Federal State Budgetary Institution "Central Research Institute of Organization and Informatization of Health Care" of the Russian Ministry of Health. Morbidity rate in the adult population of Russia in 2013: Statistical materials. M.; 2014; Part III.
12. Ministry of Health of the Russian Federation. Department of Monitoring, Analysis and Strategic Development of Healthcare Department of Monitoring, Analysis and Strategic Development of Healthcare. Federal State Budgetary Institution "Central Research Institute for Organization and Informatization of Health Care" of the Ministry of Health of the Russian Federation. Medical and demographic indicators of the Russian Federation. 20123: Statistical materials. M.; 2014.
13-11. Sarkisov D.S. Selected lectures on the course of general pathology. Some questions of modern teaching about the disease. -Issue 3. Moscow: NIO "Quartet", 1993. -P.99-123.
14 -12. Smolyannikov A.V., Avtandilov G.G., Uranova E.V. Principles of making a pathological diagnosis. - M.: TSOLIUV, 1977. - P.68.
15-13. Tsinzerling A.V. Modern infections: pathological anatomy and issues of pathogenesis. - St. Petersburg: Sotis, 1993. -363 p.
16-14. Tsinzerling V.A. Pneumonia and other respiratory infections in adults. In kN. Cellular biology of the lungs in normal and pathological conditions. Hand. For doctors. (ed. V.V. Erokhin, L.K. Romanova) – M.: Medicine. 2000.- p. 329-350.
17-15. Chuchalin A.G. Encyclopedia of Rare Diseases. Ed. GEOTAR-Media group, 2014.- 672 p.
16. Encyclopedic Dictionary of Medical Terms, 1988, vol. 1, p. 148.
18-17. GINA Updated 2015, www.ginastma.org; Gold 2014 www.goldcopd.org.
Diffuse parenchymal lung disease in a 24-year-old patient
K.S. Voitkovskaya, M.V. Samsonova, A.L. Chernyaev
Patient F., 24 years old, was in the hospital from January 17, 2012. Upon receipt of a complaint of shortness of breath during moderate physical activity, attacks of dry cough during the day. In February 2008, after hypothermia, an X-ray examination revealed a disseminated process in the lung. Consulted with a phthisiatrician, pulmonary tuberculosis was excluded. After 3 months, the patient began to complain of polyuria and polydipsia. Diabetes insipidus was diagnosed and replacement therapy was prescribed. During dynamic observation, disseminated nodular-reticular changes in the lungs, as well as mediastinal lymphadenopathy, persisted. The clinical picture of the disease was regarded as a manifestation of stage II sarcoidosis with damage to the lungs, mediastinal lymph nodes and, possibly, the pituitary gland.
Smoking history: smoker with 10 pack-years of smoking history. The professional history is not burdensome.
Objective research. On admission general state satisfactory. The physique is normosthenic. Skin and visible mucous membranes are clean, physiological in color. There is vesicular breathing over the lungs, no wheezing. The pulse is rhythmic, well filled, with a frequency of 76 beats/min. Blood pressure 120/80 mm Hg. Art. The abdomen is symmetrical, soft on palpation, painless in all parts. The lower border of the liver is along the edge of the costal arch; the spleen is not palpable. The effleurage symptom is negative on both sides. Physiological functions are normal.
Clinical analysis blood: leukocytes 4.8 x 109/l, erythrocytes 5.3 x 1012/l, hemoglobin 135.0 g/l, platelets 253.0 x 109/l, ESR 12 mm/h. Biochemical blood parameters are normal. General analysis urine without any features. The Wasserman reaction was negative; no antibodies to HIV were detected. There are no markers for hepatitis B and C.
Ksenia Sergeevna Voitkovskaya - resident at the Research Institute of Human Morphology of the Russian Academy of Medical Sciences, Moscow.
Maria Viktorovna Samsonova - Dr. honey. sciences, head Laboratory of Pathological Anatomy and Immunology, Research Institute of Pulmonology, FMBA of Russia, Lead. scientific co-workers Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences, Moscow.
Andrey Lvovich Chernyaev - professor, head. Department of Pathology, Research Institute of Pulmonology, Federal Medical and Biological Agency of Russia, leading. scientific co-workers Research Institute of Human Morphology of the Russian Academy of Medical Sciences.
The ECG shows sinus rhythm, heart rate 70 per minute, normal position electrical axis of the heart. According to spirography, there is moderate impairment of pulmonary function of the restrictive type.
With high-resolution multislice computed tomography (MSCT) of organs chest in the parenchyma of both lungs, single thin-walled air cavities were detected in the upper and middle lobes of both lungs and multiple small reticular nodules, in places associated with small bronchi (Fig. 1). A diagnostic video-thoracoscopy was performed: a lateral mini-thoracotomy on the right in the fifth intercostal space, 6 cm long. During inspection of the pleural cavity, it was determined that there were no adhesions, no effusion, enlarged lymph nodes measuring up to 1.5 cm were identified in the upper mediastinum. The lung tissue was compacted and rigid when instrumental palpation. Excision of the mediastinal lymph node and atypical resections of the lower and upper lobes of the lung were performed. The wound is sutured in layers. An aseptic dressing is applied.
Pathohistological examination. Macroscopic description of the material:
1) two marginal fragments of the lungs measuring up to 2.8 x 1.7 x 0.4 cm, on the section the lung tissue is airy, without reliably detectable foci of compaction;
Rice. 1. MSCT of the chest organs. Multiple round thin-walled cavities and single nodules with a diameter of 5-7 mm in the upper lobes of the lungs.
50 AtmvsferA. Pulmonology and allergology 4*2012 http://atm-press.ru
2) two small fragments of gray tissue (lymph nodes) measuring 0.4 x 0.3 x 0.2 cm.
Microscopic description of the drug:
1) in both fragments of the lung there is a picture of venous plethora. Part of the alveoli are destroyed, macrophages and hemosiderophages are visible in the lumen. In single interalveolar septa of individual acini, a few lymphoid infiltrates are detected. A section of the parenchyma of one of the lung fragments in a state of distelectasis. The interalveolar septa in this area are thickened due to edema, focal sclerosis, and infiltration with lymphohistiocytic elements. In the lumen of the alveoli, desquamated alveolocytes, hemosiderophages, and weakly eosinophilic exudate are determined. In some alveoli, polymorphic alveolocytes with large hyperchromic nuclei and single giant multinucleated cells, characteristic of viral infections. The bronchioles are spasmed, and inflammatory infiltrates with a predominance of lymphocytes are observed in the lumen of some of them. Mild peribronchial sclerosis and weak scattered lymphoid infiltration around the bronchioles are noted. The pleura of both fragments has areas of thickening due to the growth of granulation tissue on the surface, sclerosis and proliferation of mesotheliocytes;
2) lymph nodes with signs of sinus histiocytosis.
Conclusion: the morphological picture (lymphocytic bronchiolitis and focal alveolar lesions) most closely corresponds to a viral (most likely respiratory syncytial) infection of the lungs.
Due to the uncertainty of the diagnosis and the discrepancy between the clinical picture of the disease and the results of the pathohistological report, the patient was sent for consultation to the Pulmonology Research Institute of the Federal Medical and Biological Agency of Russia.
Repeated histological examination of lung tissue: the interalveolar septa are thin, the alveoli are dilated in places, there are a small number of macrophages in the lumens of the alveoli, some of them with brown cytoplasm. In the walls of some terminal bronchioles and around them there are infiltrates consisting of lymphocytes, histiocytes, brown (pigmented) macrophages in the form of small foci and granuloma-like accumulations of irregular shape; the same infiltration partially extends to the adjacent interalveolar septa (Fig. 2, 3). Immunohistochemical examination revealed CD1a-positive histiocytes in the infiltrates (Fig. 4).
Based on clinical and radiological data and the results of pathohistological examination, a diagnosis was formulated: Langerhans cell histiocytosis of the lungs, mediastinal lymph nodes and pituitary gland.
Rice. 2. Lung biopsy. Along the periphery of the terminal bronchiole there are accumulations of lymphocytes with an admixture of eosinophils (1), pigmented macrophages (2), and histiocytes. Hematoxylin and eosin staining. x100.
Rice. 3. Lung biopsy. Along the periphery of the terminal bronchiole there is an infiltrate represented by lymphocytes, pigmented macrophages, histiocytes (indicated by arrows), single dendritic cells and eosinophils. Hematoxylin and eosin staining. x400.
Rice. 4. Lung biopsy. Large clusters of dendritic cells staining positive for anti-CD1a antibodies. Immunohistochemical study. x100.
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Discussion
Langerhans cell histiocytosis (LCH) is a heterogeneous group of diseases characterized by the accumulation of Langerhans cells in various organs and tissues with the formation of granulomas with eosinophilic infiltration.
According to the classification of the Histiocytic Society (1997), histiocytic diseases are divided into three groups. Langerhans cell histiocytosis belongs to the first group of histiocytic diseases. The second group is formed by histiocytosis of mononuclear phagocytes (nelan-gergan cell) - Erdheim-Chester disease, Rosai-Dorfman disease. The third group includes malignant histiocytic diseases.
In turn, LCH is classified according to the extent of the lesion and clinical manifestations. Damage to one organ - bone, brain or lung - is usually observed in adults young. Multi-system damage with acute onset (Letterer-Siwe disease) occurs mainly in children and has a relatively unfavorable prognosis. Hen-da-Schüller-Christian syndrome is observed in children and adolescents and is also characterized by multiple organ damage, but has a more favorable prognosis. Thus, pulmonary LCH can develop as an independent disease or as a manifestation of a multisystem lesion. In adults, predominantly isolated pulmonary LCH occurs, but in 15% of cases there is multisystem involvement.
Langerhans cell istiocytosis is a rare disease. Its true prevalence has not yet been established. According to the Histiocytosis Association of Canada, in adults LCH of the lungs occurs with a frequency of 1 in 560,000 people and is more often detected at the age of 20-40 years, mainly in smokers (more than 90%). Men and women get sick equally often. The etiology of LCH is unknown.
With LCH of the lungs, patients complain of a nonproductive cough and shortness of breath. Sometimes the disease is asymptomatic and is detected only by chest x-ray. Complications of LCH include recurrent spontaneous pneumothorax and pulmonary arterial hypertension(PAH), which, as a rule, has a more severe course compared to PAH in other diffuse interstitial lung diseases, which is associated with the direct involvement of arterioles and venules in the pathological process.
In 70% of patients with lung LCH, function tests external respiration a decrease in diffusion is detected
lung capacity. In addition to restrictive changes, obstructive or mixed types of pulmonary function disorders may occur, while lung volume is usually preserved or even increased.
Chest radiography and MSCT most often reveal bilateral symmetrical nodules up to 1 cm in diameter, mainly in the upper and middle parts of the lungs. As the disease progresses, reticular and cystic changes appear with a decrease in the number of nodules.
The “gold standard” for the pathological and anatomical diagnosis of LCH is an open lung biopsy.
A pathognomonic microscopic sign of LCH is the detection of palmate granulomas containing Langerhans cells, lymphocytes, eosinophils, fibroblasts and plasma cells. The key morphological features that help distinguish Langerhans cells from other cells are their large size (15-25 µm), eosinophilic cytoplasm with poorly defined boundaries, a convoluted nuclear membrane, a characteristic bean-shaped nucleus, and the absence of nucleoli. Transmission electron microscopy reveals racket-shaped cytoplasmic inclusions - Birbeck granules - a pathognomonic sign of Langerhans cells.
Positive staining in an immunological study with antibodies to CD1a and S100 makes it possible to detect Langerhans cells infiltrating the walls and epithelium of bronchioles in the early stages of the disease. In addition, microscopically in the early stages of LCH, a picture of destructive bronchiolitis is noted with the formation of bronchocentric and peribronchiolar granulomas with the accumulation of pigmented alveolar macrophages.
A peculiarity of this observation is the combination of lung LCH with damage to the mediastinal lymph nodes and diabetes insipidus. Probably, the damage to the pituitary gland is also histiocytic in nature. Damage to several organs in LCH has been described in a number of cases in adults; this leads to a less favorable prognosis of the disease.
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Among them, the main one is fibrosing (fibrous) alveolitis- a heterogeneous group of lung diseases, characterized by a primary inflammatory process in the interalveolar pulmonary interstitium - pneumonitis- with the development of bilateral diffuse pneumofibrosis.
Classification. There are three nosological forms of fibrosing alveolitis:
1) idiopathic fibrous alveolitis, acute forms of which are called Hamman-Rich disease;
2) exogenous allergic alveolitis;
3) toxic fibrosing alveolitis.
Fibrosing alveolitis, which serves as a manifestation of other diseases, primarily systemic connective tissue diseases (rheumatic diseases) and viral chronic active hepatitis, is called Hamman-Rich syndrome.
Idiopathic fibrosing alveolitis accounts for 40-60% of all diffuse pulmonary fibrosis. Its chronic forms predominate; Hamman-Rich disease is much less common. Exogenous allergic alveolitis widespread among those employed in agriculture (farmer's lung), poultry farming (poultry lung), and livestock production, as well as in the textile and pharmaceutical industries. Toxic fibrosing alveolitis became more frequent among persons in contact with herbicides, mineral fertilizers, and those undergoing treatment in oncology and hematology hospitals.
Etiology. The cause of idiopathic fibrosing alveolitis has not been established; its nature is assumed to be viral. Among the etiological factors of exogenous allergic alveolitis, a number of bacteria and fungi, dust containing antigens of animal and plant origin, and medications are of great importance. The development of toxic fibrosing alveolitis is associated mainly with exposure to drugs that have a toxic pneumotropic effect (alkylating cytostatic and immunosuppressive drugs, antitumor antibiotics, antidiabetic drugs, etc.).
Pathogenesis. Immunopathological processes are of primary importance in the pathogenesis of fibrosing alveolitis. They are represented by immune complex damage to the capillaries of the interalveolar septa and lung stroma, to which cellular immune cytolysis is added. In idiopathic fibrosing alveolitis, damage to the pulmonary interstitium does not exclude the significance of autoimmunization and hereditary failure of lung stroma collagen. In toxic fibrosing alveolitis, the immunopathological mechanism of damage can be combined with a toxic one (direct pneumotropic effect of the pathogenic factor).
Pathological anatomy. Based on the study of lung biopsies, three stages of morphological changes in the lungs with fibrosing alveolitis (pneumonitis) have been established:
1) alveolitis (diffuse, or granulomatous);
2) disorganization of alveolar structures and pneumofibrosis;
3) formation of a honeycomb lung.
IN alveolitis stage, which may exist long time, there is an increasing diffuse infiltration of the interstitium of the alveoli, alveolar ducts, walls of the respiratory and terminal bronchioles with neutrophils, lymphocytes, macrophages, and plasma cells. In such cases we talk about diffuse alveolitis. Often the process takes on a focal granulomatous character rather than a diffuse one. Macrophage granulomas are formed both in the interstitium and in the wall of blood vessels. Then they talk about granulomatous alveolitis. Cellular infiltration leads to thickening of the alveolar interstitium, compression of capillaries, and hypoxia.
Stage of disorganization of alveolar structures and pneumofibroea, as its name suggests, is characterized by deep damage to the alveolar structures - destruction of endothelial and epithelial membranes, elastic fibers, as well as increased cellular infiltration of the alveolar interstitium, which spreads beyond its boundaries and affects blood vessels and perivascular tissue. In the interstitium of the alveoli, the formation of collagen fibers increases, and diffuse pneumofibrosis develops.
IN stages of honeycomb lung formation Alveolar-capillary block and panacinar emphysema, bronchiolectasis develop, and cysts with fibrous-altered walls appear in place of the alveoli. As a rule, hypertension develops in the pulmonary circulation. Hypertrophy of the right heart, which appears in the second stage, intensifies, and finally cardiopulmonary failure develops.
Pneumosclerosis (pneumocirrhosis)- this is the proliferation of connective tissue in the lung due to an inflammatory or dystrophic process, resulting in a violation of the elasticity and gas exchange function of the affected areas. Connective tissue in the lung leads to deformation of the bronchi, sharp compaction and wrinkling of lung tissue. The lung becomes airless, dense and decreases in size. Pneumosclerosis can occur at any age, but this disease is more common in men.
No esophagus.
Diseases of the esophagus are few. The most common causes are diverticula, inflammation (esophagitis) and tumors (cancer).
Esophageal diverticulum- this is a limited blind protrusion of its wall, which can consist of all layers of the esophagus ( true diverticulum) or only the mucous and submucosal layer protruding through the cracks of the muscular layer ( muscular diverticulum). Depending from location and topography distinguish farngoeophagal, bifurcation, epinephric and multiple diverticula, and from characteristics of origin- adhesive diverticula, which arise as a result of inflammatory processes in the mediastinum, and relaxation ones, which are based on local relaxation of the esophageal wall. An esophageal diverticulum can be complicated by inflammation of its mucous membrane - diverticulitis.
The causes of diverticulum formation may be congenital(inferiority of connective and muscular tissues of the wall of the esophagus, pharynx) and acquired(inflammation, sclerosis, cicatricial narrowing, increased pressure inside the esophagus).
Esophagitis- inflammation of the mucous membrane of the esophagus - usually develops secondary to many diseases, rarely - primary. It can be acute or chronic. Acute eeophagitis observed under the influence of chemical, thermal and mechanical factors, with a number of infectious diseases (diphtheria, scarlet fever, typhus), allergic reactions, maybe catarrhal, fibrinous, phlegmonous, ulcerative, gangrenous. A special form of acute esophagitis is membranous when the cast of the mucous membrane of the esophagus is rejected. After deep membranous esophagitis, which develops from chemical burns, cicatricial stenosis of the esophagus. At chronic esophagitis, the development of which is associated with chronic irritation of the esophagus (the effects of alcohol, smoking, hot food) or impaired blood circulation in its wall (venous congestion during cardiac decompensation, portal hypertension), the mucous membrane is hyperemic and swollen, with areas of epithelial destruction, leukoplakia and sclerosis. For specific chronic eeophagitis, found in tuberculosis and syphilis, is characterized by a morphological picture of the corresponding inflammation.
In a special form they allocate reflux esophagitis, in which inflammation, erosion and ulcers (erosive, ulcerative esophagitis) are found in the mucous membrane of the lower esophagus due to regurgitation of gastric contents into it.
Esophageal carcinoma most often occurs at the border of the middle and lower thirds, which corresponds to the level of tracheal bifurcation. It is much less common in the initial part of the esophagus and at the entrance to the stomach. Esophageal cancer accounts for 2-5% of all malignant neoplasms.
Etiology. Chronic irritation of the mucous membrane (hot rough food, alcohol, smoking), scar changes after a burn, chronic gastrointestinal infections, anatomical disorders (diverticula, ectopia of the cylindrical epithelium and gastric glands, etc.) predispose to the development of esophageal cancer. Among the precancerous changes highest value have leukoplakia and severe dysplasia of the mucosal epithelium.
Pathological anatomy. The following are distinguished: macroscopic forms of esophageal cancer: ring-shaped dense, papillary and ulcerated. Ring-shaped solid cancer is a tumor formation that circularly covers the wall of the esophagus in a certain area. The lumen of the esophagus is narrowed. When the tumor disintegrates and ulcerates, the patency of the esophagus is restored. Papillary r Esophageal cancer is similar to fungal cancer of the stomach. It breaks down easily, resulting in the formation of ulcers that penetrate into neighboring organs and tissues. Ulcerated cancer is a cancerous ulcer that is oval in shape and extends along the esophagus.
Among microscopic forms of esophageal cancer carcinoma is distinguished squamous cell carcinoma, adenocarcinoma, glandular squamous cell, glandular cystic, mycoepidermal and undifferentiated cancer.
Metastasis Esophageal cancer occurs predominantly lymphogenously.
Complications associated with germination into neighboring organs - trachea, stomach, mediastinum, pleura. Esophageal-tracheal fistulas form, aspiration pneumonia, abscess and gangrene of the lung, pleural empyema, and purulent mediastinitis develop. With esophageal cancer, cachexia appears early.
GASTRITIS.
Gastritis(from Greek gaster - stomach) - inflammatory disease gastric mucosa. There are acute and chronic gastritis.
Acute gastritis.
Etiology and pathogenesis. In development acute gastritis the role of irritation of the mucous membrane by abundant, difficult to digest, spicy, cold or hot food, alcoholic beverages, medications (salicylates, sulfonamides, corticosteroids, biomycin, digitalis, etc.), chemicals (occupational hazards) is great. Microbes (staphylococcus, salmonella) and toxins, products of impaired metabolism, also play a significant role. In some cases, for example, with alcohol poisoning, substandard food products, pathogenic factors directly affect the gastric mucosa - exogenous gastritis, in others - this action is indirect and is carried out using vascular, nervous, humoral and immune mechanisms - endogenous gastritis, which include infectious hematogenous gastritis, elimination gastritis with uremia, allergic, congestive gastritis, etc.
Pathological anatomy. Inflammation of the mucous membrane can cover the entire stomach ( diffuse gastritis) or certain parts of it ( focal gastritis). In this regard, there is a distinction fundal, antral, pyloroantral and pyloroduodenal gastritis.
Depending on the characteristics of morphological changes in the gastric mucosa, the following forms of acute gastritis are distinguished: catarrhal (simple); fibrinous; purulent (phlegmous); necrotic (corrosive).
At catarrhal (simple) gastritis The gastric mucosa is thickened, swollen, hyperemic, its surface is abundantly covered with mucous masses, multiple small hemorrhages and erosions are visible. Microscopic examination reveals dystrophy, necrobiosis and desquamation of the surface epithelium, the cells of which are characterized by increased mucus production. Shedding of cells leads to erosion. In cases where there are multiple erosions, they speak of erosive gastritis. The glands change slightly, but their secretory activity is suppressed. The mucous membrane is permeated with serous, serous-mucosal or serous-leukocyte exudate. Its own layer is plethoric and edematous, infiltrated with neutrophils, and diapedetic hemorrhages occur.
At fibrinous gastritis a fibrinous film of gray or yellow-brown color forms on the surface of the thickened mucous membrane. The depth of necrosis of the mucous membrane can be different, and therefore there are lobar(superficial necrosis) and diphtheritic(deep necrosis) variants of fibrinous gastritis.
At purulent, or phlegmonous gastritis, the wall of the stomach becomes sharply thickened, especially due to the mucous membrane and submucosal layer. The folds of the mucous membrane are rough, with hemorrhages, fibrinous-purulent deposits. A yellow-green purulent fluid drains from the cut surface. A leukocyte infiltrate containing a large number of microbes diffusely covers the mucous membrane, submucosal and muscular layers of the stomach and the peritoneum covering it. Therefore, with phlegmon gastritis, they often develop perigastritis And peritonitis. Cellulitis of the stomach sometimes complicates injury; it also develops with chronic ulcers and ulcerated stomach cancer.
Necrotizing gastritis usually occurs when chemicals (alkali, acid, etc.) enter the stomach, cauterizing and destroying the mucous membrane ( corrosive gastritis). Necrosis can involve superficial or deep parts of the mucous membrane, and can be coagulative or colliquative. Necrotic changes usually result in the formation of erosions and acute ulcers, which can lead to the development of phlegmon and gastric perforation.
Exodus acute gastritis depends on the depth of damage to the mucous membrane (wall) of the stomach. Catarrhal gastritis can result in complete restoration of the mucous membrane. At frequent relapses it can lead to development chronic gastritis. After significant destructive changes, characteristic of phlegmonous and necrotic gastritis, atrophy of the mucous membrane and sclerotic deformation of the stomach wall develops - gastric cirrhosis.
Differential diagnosis and treatment of diffuse (interstitial disseminated) lung lesions. Rare lung diseases. State Budgetary Educational Institution of Higher Professional Education SOGMA Ministry of Health of Russia Department of Internal Medicine No. 4 Vladikavkaz, 2015
ILD unites a heterogeneous group of diseases characterized by damage to the respiratory parts of the lung and progressive respiratory failure. A variety of pathological processes accompanied by damage (toxic, mechanical, inflammatory) to the alveolar structures throughout from the cells of the alveolar lining to the endothelium of the pulmonary capillaries, as a rule, lead to the development of diffuse interstitial fibrosis of the lungs.
ILD is a heterogeneous group of diseases and pathological conditions, characterized to varying degrees parenchymal non-infectious inflammation (like alveolitis and/or granulomatosis) with subsequent development of fibrosis. (Ilkovich, 2002)
About 200 diseases are known that have signs of IPD, which accounts for 20% of all lung diseases, half of them are of unknown etiology. All these diseases are united by a similar radiological (CT) picture of pulmonary dissemination, manifested by widespread changes in both lungs of a nodular, reticular or mixed nature. and the same clinical manifestations.
Diagnostic errors in these patients amount to 75-80%, and adequate specialized care is provided to them 1.5-2 years after the onset of the first signs of the disease." E. I. Shmelev, Research Institute of Tuberculosis of the Russian Academy of Medical Sciences "More than 80% of patients with ELISA in the clinic was unreasonably diagnosed bilateral pneumonia and erroneously prescribed antibiotics, which often worsen the prognosis of ILD.
The most common terms for this group of diseases are disseminated lung diseases, granulomatous lung diseases, interstitial lung diseases, and diffuse parenchymal lung diseases. None of these synonyms gives a complete picture, since in DLD the parenchyma, interstitial tissue of the lungs and stroma are affected, and there may or may not be granulomatous lesions of the lung tissue.
In the concept of “diffuse parenchymal lung diseases”, only one definition is confusing - “diffuse”, since pathomorphologists, as a rule, talk about mosaic lesions, and not about diffuse ones. Lung damage becomes diffuse as the disease progresses and a picture of a “honeycomb” lung forms.
A significant number of IBLs are associated with diffuse infiltration not limited to anatomical boundaries lung tissue pathological contents The morphological substrate can be: fluid (transudate, exudate, blood), cellular elements (inflammation, tumor), fibrosis and a number of other rarer causes.
The pulmonary pattern is formed by arteries and, to a lesser extent, venous vessels Bronchi, bronchial arteries, lymphatic vessels and the pulmonary interstitium do not participate in the formation of a normal pulmonary pattern. The image of blood vessels disappears at a distance of 11.5 cm from the visceral pleura.
IN vertical position the volume of blood flow in the upper parts of the lungs is less than in the lower ones; the ratio of the apexes to the base is 1: 3; in the horizontal – 3: 1
The lung consists of successively smaller anatomical units that have a similar structure: lobe, segment, secondary lobule, acinus. At each level, the anatomical unit is organized around a peculiar root - the bronchus and artery, located in the center, and is surrounded by the visceral pleura or connective tissue septum
Secondary pulmonary lobule Irregular shape, polygonal Size 11-17 mm Root of the lobule - bronchiole, artery, lymphatic vessels The interlobular septum contains lymphatic vessels and veins The pulmonary lobule consists of acini, the number of which does not exceed 10.
Acinus - part of the pulmonary parenchyma located distal to the terminal bronchiole Contains respiratory bronchioles alveolar ducts alveolar sacs and alveoli Average sizes of acini 6 -7 mm
Pulmonary interstitium Central - fibers surrounding the vessels and bronchi Peripheral - a direct continuation of the fibers of the visceral pleura, forms interlobular septa Septal - forms septa between the acini inside the secondary pulmonary lobules These three parts form a kind of lung skeleton that supports the lung from the roots to the pleural layers
General signs, combining ILD: Progressive shortness of breath Various dysfunctions of external respiration pathological signs - PATTERN (pattern) Widespread, bilateral changes in X-ray and CT examination, for example. For IPF these are the lower parts, for sarcoidosis these are the upper parts.
Diffuse parenchymal lung diseases (DPLD) DPLD of known etiology (CTD, drugs, etc.) IPF IIP Granulomatous DPLD (sarcoidosis, etc.) Other DPLD (LAM, HC X, etc.) Others. IIP (non-IPF) DIP OIP NSIP RBIZL COP LIP ATS/ERS Multidisciplinary Consensus Classification of IIPs. Am J Respir Crit Care Med 2002; 165: 277 -304 19
Since the etiology of most DLD is unknown, and to clarify the diagnosis in most cases there is a need for histological verification, it is advisable to classify DLD according to morphological criteria. Based on morphological features, DLD can be divided into three groups: ILD, diseases of storage and dissemination of a tumor nature
Rare forms of DPL: Goodpasture's syndrome. Idiopathic pulmonary hemosiderosis. Alveolar proteinosis. Leiomyomatosis of the lungs. Primary amyloidosis of the lungs.
“DIFFERENTIAL DIAGNOSTICS OF DISSEMINATED PROCESSES IN THE LUNG” The main components of the differential diagnosis of DLD are: anamnesis examination, assessment of clinical symptoms, X-ray and CT examination, functional examination, laboratory examination, biopsy examination.
Key issues to be carefully studied when collecting anamnesis in patients with ILD: Factors of environmental aggression Smoking Heredity Coexisting diseases Use of medications in connection with concomitant diseases Assessing the sequence, speed of onset and development of symptoms Establishing the time of onset of the disease - archival radiographs Response to initial therapy for ILD
Shortness of breath - main symptom IBL. With ELISA it appears early, often even before the onset of radiological signs of the disease, is inspiratory in nature and steadily progresses. In patients with sarcoidosis, shortness of breath is a late symptom. Often in patients with sarcoidosis, there is a discrepancy between the severity of radiological dissemination and the complete absence of shortness of breath. For patients with EAA, shortness of breath is usually of a mixed nature, its occurrence is associated with a causative factor (allergen) and is wave-like. In patients with histiocytosis X, moderate shortness of breath is combined with recurrent pneumothorax.
Cough is observed in many ILDs. However, isolated damage to the alveoli is not accompanied by a cough due to the lack of corresponding nerve endings in them, and therefore cough in most cases is a sign of irritation of the airways. For EAA and sarcoidosis, cough is a manifestation of a bronchocentric process.
Hemoptysis is a sign of destruction of lung tissue. Hemoptysis is most typical for pulmonary tuberculosis, Wegener's granulomatosis, Goodpasture's syndrome, pulmonary hemosiderosis, and for fibrosing alveolitis in rheumatic diseases. With ELISA - a late sign, manifested in 13% of cases. In patients with tuberculosis and necrotizing vasculitis, hemoptysis is combined with fever from an associated secondary infection. Goodpasture syndrome is characterized by hemoptysis in combination with symptoms
Damage to the pleura. Pleural effusion is most often observed in rheumatic diseases, drug-induced lung damage, asbestosis, and leiomyomatosis. Pneumothorax is characteristic of histiocytosis-X and leiomyomatosis.
Cyanosis that occurs or worsens with physical activity; Increase in temperature to subfebrile or febrile levels (non-permanent sign); Crepitating wheezing on inspiration (not a constant sign); Shortening of percussion tone over the affected area;
X-ray diagnostics. A survey radiograph is the main technique for suspected respiratory disease; it produces up to 50% of errors in ILD. High-resolution computed tomography (CT) is the main x-ray technique for ILD, which allows you to assess not only the extent of the process, but also monitor its dynamics.
1) 2) 3) 4) 5) Tasks X-ray examination patients with ILD; primary identification of pathology; determination of the nosological form of the pathological process; clarification of its morphological features (localization, prevalence, combined changes in the pleura and mediastinum, etc.); determination of the need, type and location of a biopsy; study of the dynamics of changes in the lungs under the influence of treatment
Main functional signs of ILD Reduced static lung volumes Reduced lung compliance Increased respiratory rate Alveolar hypoventilation Impaired ventilation-perfusion relationships Reduced diffusion capacity of the lungs Hypoxemia, increasing with physical activity
Studies of biopsy material As a result of morphological verification, a number of fibrosing alveolitis are identified, previously grouped under the heading ELISA: usual interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis associated with IPD, nonspecific interstitial pneumonia, acute interstitial pneumonia (Hamman-Rich syndrome), idiopathic bronchiolitis with organizing pneumonia. A common feature of these diseases is the mosaic pattern of morphological changes in the lung parenchyma.
Fibrosing alveolitis Idiopathic, exogenous allergic, toxic, fibrosing alveolitis as a syndrome in collagen diseases, as a complication of chronic active hepatitis and other diseases)
Idiopathic fibrosing alveolitis (idiopathic pulmonary fibrosis) Etiology and pathogenesis are unclear Develops in persons aged 40-50 years, much less often in persons old age, extremely rare in children
Ordinary interstitial pneumonitis - predominance of fibrosis over cellular infiltration Desquamative interstitial pneumonitis - ground glass zones (accumulation of macrophages in the lumen of the alveoli) Nonspecific interstitial pneumonitis - cellular infiltration of the interalveolar septa
Prednisolone (or analogs) – 0.5 mg/kg (lean body weight) per day per os for 4 weeks, – 0.25 mg/kg (LBW) per day per os for 8 weeks, and then reduce the dose to 0.125 mg /kg per day or 0.25 mg/kg every other day Azathioprine or Cyclophosphamide – 2-3 mg/kg LBW per day per os. – Start with a dose of 25–50 mg – Increase the dose slowly, by 25 mg, every 7-14 days until the maximum dose is reached (150 mg/day)
Standard SEPAR 2004 Protocol Prednisolone (or equivalents) § 4 weeks – 1 mg/kg/s (maximum up to 80 mg/s) § Reduce dose by 10 mg every 15 days to a dose of 20 mg/s § 2 weeks – 20 mg/kg § dose reduction to 5 mg/s (or 10 mg every other day) until clinical improvement If there is no response to steroids, add azathioprine
Prednisolone: treatment regimen for SOP Prednisolone § 4 weeks – 0. 75 mg/kg/s § 4 weeks – 0. 5 mg/kg/s § 4 weeks – 20 mg/s § 6 weeks – 10 mg/s § 6 weeks – 5 mg/s In acute situations, start with methylprednisolone 2 mg/kg/s IV for 3-5 days When the dose is reduced, relapses are in 58% For relapses: § 12 weeks – 20 mg/s § 6 weeks – 10 mg/s from § 6 weeks – 5 mg/s
She has been ill for 2-3 years, complaining of shortness of breath at the slightest physical exertion, cough with sputum difficult to separate.
EXOGENOUS ALLERGIC ALVEOLITIS is a group of diseases characterized by the development allergic reaction in the lungs as a result of hypersensitivity to organic or inorganic dust antigens. An example of exogenous allergic alveolitis is a disease called “farmer's lung”, caused by thermophilic actinomycetes, which occurs when working with moldy hay. Currently, more than 20 diseases with a similar pathogenesis are known, united by the term “exogenous allergic alveolitis”: “poultry farmer’s lung”, “furrier’s lung”, “vinegrower’s lung”,
Systemic diseases that cause ILD: Rheumatoid diseases: rheumatoid polyarthritis, systemic lupus erythematosus, dermatomyositis. Liver diseases: CAH, primary biliary cirrhosis Blood diseases: autoimmune hemolytic anemia, chronic lymphocytic leukemia, idiopathic thrombocytopenic purpura Hashimoto's trioiditis Miastenia gravis Intestinal diseases: Whipple's disease, ulcerative colitis, Crohn's disease Chronic heart disease: with left ventricular failure, with left-to-right shunting chronic renal failure
Collagenoses - group chronic diseases-can affect the lungs and pleura -caused by immunological factors X-ray changes are nonspecific! It is impossible to differentiate between different collagen vascular diseases distinguish them from each other by radiographs from ordinary infections and congestive conditions
Changes in the lungs with rheumatoid arthritis In the cortical regions, mainly in the posterior segments, reticular changes are detected in the form of uneven thickening of intralobular septa and areas of increased density like ground glass
Granulomatosis Pulmonary sarcoidosis, histiocytosis X, Wegener's granulomatosis and other necrotizing angiitis, idiopathic pulmonary hemosideosis, Goodpasture's syndrome)
Morphology of sarcoidosis in the early stages with damage to the lungs reveals many whitish nodules in the interstitial tissue and subpleural in the later stages - conglomerates of nodes, fibrosis, bullous emphysema
Clinical course: acute form and chronic The acute form occurs with high fever, pain in the joints, skin changes reminiscent of erythema nodosum. The chronic form develops from an acute one, but more often the disease proceeds as a chronic form from the very beginning. Clinical signs are minimal: low-grade fever is rarely observed, sometimes a dry cough, scant sputum production; a blood test may show be monocytosis and eosinophilia
Scanty clinical manifestations and the absence of complaints in sarcoidosis do not correspond to the pronounced changes detected by X-ray examination
Stages of sarcoidosis Stage 0. No changes on the chest x-ray Stage I - enlargement of the mediastinal and hilar lymph nodes without involvement of the pulmonary parenchyma Stage II - lymphadenopathy of the roots of the lungs and mediastinum. Pathological changes in the lung parenchyma Stage III – pathology of the pulmonary parenchyma without lymadenopathy Stage IV – irreversible pulmonary fibrosis
SARCOID GRANULOMA Giant multinucleated Pirogov-Langhans cell The giant Pirogov-Langhans cell in the central part of this granuloma is surrounded by epithelioid cells. Pay attention to the nuclei located along the periphery of the giant cell. http://www. meddean. luc. edu/lumen/Med. Ed/Radio/sarcpath. htm
The variety of manifestations of sarcoidosis and the significant frequency of atypical forms complicate diagnosis. Due to the importance of timely establishment of a reliable diagnosis for the appointment of adequate treatment, puncture transbronchial and transparietal biopsy is currently widely used
WHEN DO WE SUGGEST SARCOIDosis? ? ? 1. According to the results of radiation examination (x-ray, fluorogram) - syndromes of hilar lymphadenopathy of dissemination 2. According to complaints: unexplained weakness, fatigue, joint pain, decreased vision, heartbeat, dry cough, increasing shortness of breath. 3. For other changes: erythema nodosum, joint swelling, Bel's palsy, changes in the skin, lymph nodes, hypercalcemia, uveitis, refractory rhythm disturbances and
Sarcoidosis stage 1 enlargement of mediastinal and hilar lymph nodes without involvement of the pulmonary parenchyma in the process
Examination of a patient with sarcoidosis: RADIATION EXAMINATION of lymphadenopathy of the roots of the lungs and mediastinum. Pathological changes in the lung parenchyma http: //brighamrad. harvard. edu/Cases/bwh/hcache/149/full. html
CT scan of the SAME PATIENT Stage II sarcoidosis. Diffuse changes in both lungs with the presence of multiple polymorphic foci, with peribronchial couplings and areas of increased density like ground glass http: //brighamrad. harvard. edu/Cases/bwh/hcache/149/full. html
X-ray, X-ray computed tomogram and photograph of a changed area of skin in a 45-year-old patient. Diagnosis of sarcoidosis of the intrathoracic lymph nodes and mild sarcoidosis of the skin. Histologically verified (observations
Sarcoidosis stage 3 Sharlaimova I. R. 57 years old, the lesion was discovered in 1999, thoracotomy - sarcoidosis (no lymph nodes)
Sarcoidosis, stage 4 Signs of fibrosis, reduction in the volume of the posterior segments of the upper lobes, posterior displacement of the bronchi, appearance
1. Because the rate of spontaneous remission is high, treatment is not indicated for asymptomatic patients with stage 1 sarcoidosis [Evidence Level B]. 2. Because the remission rate is high, treatment is not indicated for asymptomatic patients with sarcoidosis II and Stage III for mild pulmonary dysfunction and stable condition [D]. 3. Oral corticosteroids are first-line drugs in patients with a progressive course of the disease according to X-ray and functional breathing studies, with severe symptoms or extrapulmonary manifestations requiring treatment [B].
4. Treatment with prednisolone (or an equivalent dose of another corticosteroid) is prescribed at a dose of 0.5 mg/kg/day for 4 weeks, then the dose is reduced to a maintenance dose to control symptoms and disease progression for 6-24 months [D]. 5. Bisphosphonates should be used to reduce steroid-induced osteoporosis [D]. 6. Inhaled corticosteroids have no value in either initial or maintenance therapy [B]. They may be used in selected subgroups of patients with severe cough [D]. 7. Other immunosuppressive and anti-inflammatory drugs have limited value in the treatment of sarcoidosis, but they should be considered as an alternative treatment when SCS do not control the disease or severe intolerance adverse reactions develop. The current drug of choice is methotrexate [C]. 8. For end-stage sarcoidosis, lung transplantation should be considered [D].
Histiocytosis, a granulomatous disease of unknown etiology, develops in young and middle-aged people. In more than half of patients, only the lungs are affected, in 20%, combined changes are detected in the bones, in 20%, changes are localized simultaneously in several organs
Clinical manifestations are not specific or absent at all. Spontaneous pneumothorax occurs in 1/5 of patients. The course is benign; in isolated cases, a honeycomb lung is formed
Morphologically, histiocytic granulomas and cysts are revealed; some granulomas may have small cavities. The X-ray picture is diffuse bilateral interstitial infiltration with small focal shadows measuring 2-3 mm, often in the upper and middle sections
A number of studies have shown unusual dynamics of changes in histiocytosis: an increase in solitary small foci to larger ones with cavities in the center, the appearance of cysts with thick walls, a decrease in the size of cysts and even their complete disappearance during dynamic observation
CT scan showing histiocytosis with Langerhans cells. A-diffuse centrilobular nodules and microcystic changes B-multiple small cysts, some of them confluent, isolated subpleural nodules. The parenchyma located between them is compacted like frosted glass. D - progressive destruction of parenchyma with the formation of fibrosis D - outcome
Pulmonary alveolar proteinosis X - pathological filling of the alveoli with protein material, Diagnosis - lavage water.
Goodpasture syndrome is an immunoinflammatory disease of the small vessels of the lungs and kidneys. Etiology unknown; rare; can affect any age; young men are more often affected
Goodpasture's syndrome Clinical manifestations are associated primarily with damage to the lungs - cough, hemoptysis, slight shortness of breath. In the majority, signs of glomerulonephritis are recorded from the first days of the disease. The classic triad is characteristic: pulmonary hemorrhages, glomerulonephritis and antibodies to antigens of the main membrane of the capillaries of the lungs and kidneys
Morphologically, hemorrhages into the cavity of the alveoli with or without a picture of alveolitis in the renal glomeruli, pathology from focal proliferative changes to necrotic glomerulonephritis is observed. X-ray picture of infiltrates of varying sizes in both lungs, especially in the hilar zones
Goodpasture's syndrome Alveolar type of infiltration, mainly in the hilar regions in the upper, middle and lower fields
Wegener's granulomatosis Etiology is unclear Develops slowly, over the course of years Morphologically necrotic granulomas in the upper respiratory tract and in the lungs, necrotizing vasculitis affecting arteries and veins, glomerulonephritis with necrosis and thrombosis of glomerular loops
Clinic: fever, cough, suffocation, hemoptysis. It begins with a purulent runny nose, pain in the maxillary sinuses, a necrotic process affects bones and cartilage, maybe. deformation of the face Progression leads to damage to the trachea, large bronchi and lung tissue X-ray picture strengthening of the pulmonary pattern with small focal shadows foci of compaction of the lung tissue with decay cavities
Wegener's granulomatosis Multiple thin-walled cavities in the posterior-basal regions of round and oval shape, in the subpleural regions they turn into granulomatous compactions
Wegener's disease A-diffuse confluent acinar foci of compaction due to hemorrhage B-chronic changes after resorption of hemorrhage into the lung tissue C-node with a thin-walled cavity and a horizontal fluid level D-cavity with thick walls
TREATMENT OF HISTIOCYTOSIS. 1. Conservative treatment consists of prescribing corticosteroids for a course of up to 12 months in an amount of 0.5−1 mg/kg body weight, followed by a gradual reduction in dosage. When the process progresses and there is no effect from corticosteroids, cytostatics are used, for example, methotrexate, vinblastine, cyclophosphamide. 2. Surgical methods are used for localized forms of histiocytosis in combination with radiation therapy. They consist of removal of histiocytic infiltrates, lobectomy, pneumonectomy, pleurectomy, and in especially severe cases with the development respiratory failure held
Malignant diseases of the blood system Lymphogranulomatosis (Hodgkin's disease) is a disease that occurs with tumor-like growths of the lymph nodes, characterized by a wave-like increase in temperature, sweating, itching of the skin and gradually increasing cachexia. Damage to the spleen, liver and bone marrow, which gives this disease a systemic character.
Morphological changes: proliferation of atypical reticular cells with the formation of giant forms typical of the disease - Berezovsky-Stenberg-Guide cells, the presence of which is mandatory for diagnosis. In most cases, the lymph nodes of the mediastinum and roots of the lungs are involved in the process, and then the lung tissue and pleura. The appearance of pulmonary changes is a sign of further generalization of the process and significantly worsens the prognosis.
X-ray semiotics Forms of LGM: Mediastinal Mediastinal-pulmonary Pulmonary Mediastinal-pulmonary-pleural The first three forms are the most common.
Mediastinal form Expansion of the cardiovascular shadow with enlarged lymph nodes The contours on the affected side are clear, polycyclic, individual arches protrude unevenly due to the unequal size of the lymph nodes. The anterior superior lymph nodes are most often affected. The lesion can be unilateral or bilateral
With right-sided localization, the process is diagnosed faster and more confidently: against the background of the air lung, even not sharply enlarged lymph nodes are visible. On tomograms there is no shadow of the azygos vein, and a dense ribbon-like shadow is visible along the wall of the trachea. With left-sided localization, diagnostic difficulties arise due to the presence of vascular arches, the angle between the shadow of the aortic arch and the pulmonary artery disappears.
With bilateral lesions, the median shadow is expanded in both directions, this is a picture known as the “pipe sign”. If the enlarged l/s are located at different depths, then they form polycyclic contours, a “scenes” pattern. The clarity of the outlines of the mediastinum is maintained as long as there is a capsule of enlarged nodes. When the granuloma grows, it spreads into the surrounding tissues and the clarity of the contours is erased.
In addition to the mediastinal lymph nodes, lymph nodes of the bronchopulmonary group are involved in the process (according to various authors from 20.7% to 29.6%). Differential diagnosis: with nonspecific and tuberculous bronhadenitis - the entire group is enlarged, with LGM - one or two lymph nodes
The most difficult diagnosis is with combined unilateral lesions of the lymph nodes of the mediastinum and the bronchopulmonary group, when a tumor node is detected in the root zone in the presence of enlarged lymph nodes in the mediastinum on the same side.
Preservation of the bronchial lumen distinguishes this form of LGM from bronchogenic cancer. An invisible (small) lung tumor with metastases to the mediastinal and bronchopulmonary lymph nodes may have a similar picture. Lymphogranulomatous growths can grow into the bronchi, causing complete occlusion
Mediastinal-pulmonary form Characterized by a combination of lesions of the intrathoracic lymph nodes and lung tissue due to: direct ingrowth of lymphogranuloma into the mediastinal pleura into the lung tissue through metastasis through the lymphatic and blood vessels
Scheme of radiological manifestations of mediastinal-pulmonary LGM Mediastinal form Enlarged intrathoracic lymph nodes Direct ingrowth into adjacent parts of the lungs Metastasis (lymphogenous, hematogenous) Medistinal-pulmonary form Enlarged intrathoracic lymph nodes combined with Common processes and - Interstitial nodular, nodular foci of infiltrative compaction Limited processes Single nodular formation, segmentitis, lobititis, infiltrate
Common processes have a characteristic x-ray picture: the shadow of the enlarged vascular bundle does not have clear boundaries and in the form of rough transverse strands passes into the lung tissue; changes are localized at any level; they correspond to the location of the enlarged lymph nodes; and linear shadows are a reflection of lymphogranulomatous muffs enveloping the vessels and bronchi in rare cases, a picture of specific lymphangitis may be observed
Nodular changes in the shadow of a round shape, ranging in size from 1.5 cm to 3-5 cm with clear or unclear (depending on the growth phase of the lymphogranuloma) contours of any localization from the subpleural regions to the hilar regions; their merging can be observed; they are often located at a considerable distance from each other, as a rule, they are localized on one side; as the process progresses, the fusion of lymphogranulomas forms massive infiltrates
Nodular changes manifest themselves: as multiple clearly defined shadows, often located in the basal segments against the background of pronounced compaction of the interstitial tissue of the lung, with progression, large nodes or massive infiltrates are formed
Foci of infiltrative compaction of an irregularly shaped shadow, 3-4 cm in size without clear boundaries, resembles a focus of inflammatory compaction of the lung tissue in the hilar zone, is not limited to one anatomical structure, “bricks up” the bronchi, the lumen of which narrows, but patency remains, progression can lead to the formation of large nodular formations, damage to a segment, lobe
Limited processes single nodular formation in the lung, round, homogeneous with clear contours, localization can be any (peripheral parts, hilar zone, deep in the parenchyma) enlarged lymph nodes of the root and mediastinum In the absence of peripheral lymph nodes, such a radiological picture is regarded as a manifestation of primary lung cancer or tumor metastases of another organ, since with LGM such a picture is rarely observed.
Segmentitis and lobitis are detected when the pulmonary parenchyma and alveolar apparatus grow into granulomatous tissue. X-ray picture: compaction of a segment or lobe without their volume reduction, the lumen of the bronchi is preserved in the thickness of the compacted tissue, localization - according to the anatomical structure
Isolated pulmonary form is extremely rare Clinical symptoms: cough, chest pain P picture: clearly defined homogeneous shadows in the lower parts with the same frequency in the right and left lungs. Changes can be single or multiple; in the latter case, around a single node there are small nodules in the same lung and large nodes on the other side.
Mediastinal-pulmonary-pleural form Involvement of the pleura in the process is observed when subpleurally located granulomas grow into it. The frequency of pleural damage ranges from 2% to 27.2%. Characteristic is the rapid accumulation of large amounts of fluid despite its removal. In pleural effusion, specific cells are found extremely rarely. The appearance of pleural effusion may be due to blockage of the lymph nodes of the roots of the zone by granulomatous tissue.
The pleural form is rare. Some authors doubt the possibility of isolated damage to the pleura and consider changes in the pleura in connection with microgranulomas located in the subpleural regions. X-ray can reveal a thickened pleura with an unclear internal contour (indicating the involvement of the parenchyma in the process), there may be free fluid in the pleural cavities.
Lymphosarcoma and reticulosarcoma have many common radiological manifestations when the process is localized in various organs, including in the chest cavity - lungs, mediastinum, pleura. With careful examination, it is always possible to establish the primary focus of tumor growth, indicating that these tumors are not a primary generalized process.
The disease manifests itself by the formation of an isolated single tumor node, which is often not detected and then the disease is diagnosed in the generalization phase. The primary localization of reticulo- and lymphosarcoma is observed mainly in the lymph nodes of the mediastinum. the lungs and pleura are involved in the process even with generalization much less frequently. lesions of the mediastinal lymph nodes are observed approximately 2 times more often in reticulosarcoma
The X-ray picture depends on the nature of tumor growth and the degree of enlargement of the lymph nodes and manifests itself: in some cases, these are large spherical shadows with a diameter of 4-6 cm with clear contours, located in the mediastinum, pushing back the mediastinal pleura, there may be a unilateral or bilateral lesion in others - there may be expansion of the vascular shadow in both directions, and, on the one hand, the contour can be straightened and all arches are smoothed, and on the other, it can have a polycyclic appearance, merging with the enlarged lymph nodes of the root, forming a single conglomerate with clear outlines
The X-ray picture with an increase in the lymph node in the anteroposterior direction does not show a significant expansion of the shadow of the vascular bundle, only a study in the lateral projection shows a darkening of the retrosternal space; in the phase of infiltrative growth, rough heavy shadows appear coming from a conglomerate of enlarged lymph nodes that accompany the vessels and bronchi
The X-ray picture on tomograms shows the ingrowth of tumor masses into the wall of the bronchi and the narrowing of their lumen; when the process generalizes, metastasis occurs in the lung tissue: from small nodular dissemination to segmentitis and lobita with clearly visible lumens of the bronchi, large clearly defined shadows from 1 cm, infiltrates up to 3 -3 , 5 cm without clear boundaries.
With reticulosarcoma, lung tissue is affected in 67%, with lymphosarcoma - very rarely. The X-ray picture of pulmonary changes does not have specific features that make it possible to differentiate lymphosarcoma and reticulosarcoma.
Periarteritis nodosa is an allergic disease (collagenosis) in which all layers of the walls are affected. blood vessels mainly arteries Morphology: changes in the vessels develop like endarteritis with the development of multiple small aneurysms (therefore, the name “allergic polyarteritis” more accurately reflects the essence of the disease) Clinic for lung damage: cough, hemoptysis, pain when breathing. In some cases, changes in the lungs are the leading part of the clinical symptom complex.
X-ray symptoms 1) bilateral symmetrical lesion 2) hilar compactions fan-shaped diverging from the roots in the form of thin stringy shadows (vasculitis, perivascular infiltration due to increased vascular permeability) 3) there may be a diffuse increase in the pulmonary pattern with small focal shadows (from 2-3 mm to 1 cm) mainly in the middle and lower fields (often leads to erroneous diagnosis of tuberculosis)
X-ray symptoms 4) with damage to large trunks, a picture of pulmonary infarction is observed, maybe 5) with decay - a picture of pulmonary abscess, 6) there may be miliary dissemination, 7) with damage to the pleural vessels - pleurisy develops (rarely)
Systemic lupus erythematosus Morphogenesis: vasculitis with changes in interstitial tissue. Mainly small arteries and arterioles are affected; fibrinoid is deposited in their walls, the amount of which gradually increases, which leads to the destruction of the muscular and elastic elements of the wall and the formation of aneurysms
X-ray picture of SLE: strengthening and deformation of the pulmonary pattern, the shadows of the vessels are wide, tortuous with uneven contours in places, focal-like shadows; the high standing of the domes of the diaphragm is caused by damage to its muscles and a decrease in tone, in some cases - thickening of the pulmonary pattern and disc-shaped atelectasis with predominant damage to the interstitial tissue the pulmonary pattern has a reticular appearance
X-ray picture of SLE: due to frequent kidney damage in SLE, interstitial edema is often observed in the lungs; pleural effusion is regarded as a manifestation of polyserositis - a classic sign of SLE. Serous fibrinous pleurisy is characterized by a tendency to develop adhesive processes with a small amount of effusion and the addition of a secondary infection leads to the development of pneumonia, abscesses, lung gangrene, and pleural empyema.
For quotation: Avdeev S.N., Chikina S.Yu., Kapustina V.A., Samsonova M.V., Brodskaya O.N. Diffuse parenchymal lung diseases: what new did we learn in 2011? // RMJ. 2012. No. 6. P. 265
Idiopathic pulmonary fibrosis
Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by a poor prognosis and high mortality rate. Activation of tyrosine kinase receptors plays a significant role in the pathogenesis of the disease, so certain hopes are placed on the use of inhibitors of these receptors in the treatment of IPF. The aim of this study was to compare the efficacy and safety of 4 different doses of BIBF 1120, an intracellular tyrosine kinase inhibitor, in patients with IPF.
A 12-month multicenter, randomized, double-blind, placebo-controlled study (phase II) enrolled 428 patients with IPF (320 men, mean age 65 years, mean forced vital capacity lungs (FVC) - 80.2%, average diffusivity for carbon monoxide (DLCO) - 3.6 mmol/min./kPa). Patients included in the study were randomized to receive placebo or BIBF 1120 at one of the following dosages: 50 mg 1 time/day, 50 mg 2 times/day, 100 mg 2 times/day. or 150 mg 2 times / day. within 52 weeks.
Treatment of patients with BIBF 1120 at a maximum dose of 150 mg 2 times a day. was accompanied by a reduction in annual FVC decline of 68.4% compared with placebo (0.06 L vs 0.19 L, p=0.01). After repeated statistical analysis stratified by BIBF 1120 dosage group at the end of the study, the rate of annual decline in FVC was still lower in the group of patients taking 150 mg twice a day compared to the placebo group (0.04 L vs 0.19 l) (Fig. 1). The change in total lung volume (TLV) when compared with baseline values was more pronounced among those receiving placebo than when treated with BIBF 1120 at a dose of 150 mg 2 times / day. (−0.24 l vs 0.12 l, p< 0,001). Изменение SpO2 в покое от baseline for groups of patients receiving the drug 100 mg 2 times a day. (+0.1%) and 150 mg 2 times/day. (−0.2%) was significantly different from the dynamics of SpO2 in the placebo group (−1.3%). Neither treatment regimen was associated with significant changes in DLCO and distance walked in the 6-minute walk test (6-MW).
Proportion of patients with clinical significant change Quality of life scores according to the St. George's Respiratory Questionnaire (SGRQ) (≥ 4 points) were significantly higher among those taking the study drug at a dose of 100 mg 2 times a day. and 150 mg 2 times / day, compared with the placebo group (32.6 and 29.1% vs 16.1%, respectively). The number of exacerbations of IPF was the smallest in the group receiving BIBF 1120 at a dose of 150 mg 2 times / day, and the largest in the group receiving placebo (2.4 vs 15.7 per 100 patient-years, p = 0.02) (Fig. 2). There were no differences in overall mortality among the compared groups.
The total number of adverse events did not differ significantly between groups. The proportion of patients with serious adverse events was lower among those taking the study drug at a dose of 150 mg 2 times/day. compared with those taking placebo (27.1 vs 36.0%), however, in the same group there was a higher rate of discontinuation of the drug due to the development of adverse events than in the placebo group (30.6 vs 25.9%) .
Thus, the phase II study demonstrated acceptable efficacy and safety of the new tyrosine kinase inhibitor BIBF 1120 in the treatment of patients with IPF. Thus, the use of maximum doses of the drug (150 mg 2 times/day) was accompanied by a decrease in the annual fall in FVC along with an improvement in a number of other indicators: a decrease in the number of exacerbations of IPF and an associated improvement in the quality of life of patients according to the SGRQ questionnaire. The most common side effects were gastrointestinal, and their severity was mild or moderate.
Therapy for gastroesophageal reflux
associated with increased survival in idiopathic pulmonary fibrosis
There is a high prevalence of gastroesophageal reflux (GER) in patients with IPF. The prevalence of proximal and distal GER, assessed using esophageal pH-metry, is 67-88 and 30-71%, respectively. The pathophysiological significance of GER in IPF remains unclear. The present study examined the relationship between GER and IPF in a large cohort of well-defined patients.
The study included 204 patients with IPF (69% men, mean age 70 years, mean body mass index 29 kg/m2, 71% of study participants were active or former smokers, mean FVC 69%, mean DLCO 47% ).
Symptoms of GER were detected in 34% of patients, and a history of GER was present in 45% of patients. By the time IPF was diagnosed, approximately half of the patients were taking medications to treat GER (86 people - proton pump inhibitors, 12 people - H2-histamine blockers), 11 patients underwent Nissen fundoplication surgery due to GER.
Median survival in this cohort was 1079 days. In univariate analysis, predictors of better survival were: female gender (odds ratio (OR) 0.64), higher FVC (OR 0.97), TLC (OR 0.97), DLCO (OR 0.97), presence of symptoms GER (OR 0.62), established diagnosis of GER (OR 0.57), taking medications for GER (OR 0.51), Nissen fundoplication (OR 0.29).
In both adjusted models, greater FVC (OR 0.98), DLCO (OR 0.98), and use of medications to treat GER (OR 0.47) were associated with better survival. Among patients receiving therapy for GER, there were more women (39% vs. 23%), a higher prevalence of cough (92% vs. 81%), and less fibrosis (14% vs. 19%).
In summary, the present study demonstrates that use of medications to treat GER in patients with IPF is associated with less pulmonary fibrosis and better survival. This observation supports the hypothesis that GER and chronic microaspiration may play an important role in the pathophysiology of IPF.
Progression of idiopathic pulmonary fibrosis: asymmetrical lesions
In IPF, the distribution of fibrous changes between the right and left lungs and the distribution of these changes in lung tissue over time are unknown. Asymmetric IPF (aIPF) provides a unique opportunity to better understand the pathogenesis and progression of IPF. This article presents the results of a case-control study that describes the clinical characteristics of aIPF, especially the association of the disease with GER; radiological and functional features, disease outcomes including progression on high-resolution computed tomography (HRCT), exacerbations and mortality, and a comparison of asymmetric and symmetric IPF is provided. Thirty-two patients with aIPF were compared with 64 control patients with symmetrical IPF.
The aIPF group consisted of 26 men and 6 women, the average age at the time of diagnosis of IPF was 69 years. IPF was asymmetric already at the first examination in 29 (90.6%) patients and initially symmetrical in 3 (9.4%) patients. When included in the study, pulmonary fibrosis was more pronounced in the right lung in 20 (62.5%) patients and in the left lung in 12 (37.5%) patients. GER was diagnosed in 20 (62.5%) patients. Compared with control patients, patients with aIPF were significantly older (69±7 vs. 63±12 years), more often suffered from GER (62.5 vs. 31.3%) and had more preserved DLCO (52±19 vs. from 43±13%).
In patients with aIPF, the average HRCT asymmetry index was 0.50, that is, the percentage of fibrosis in the most affected lung was 3 times higher than in the second lung. Pulmonary fibrosis was clearly unilateral in 2 patients. Emphysema was detected in 9 (28%) patients. Four patients had a special form of aIPF with severe fibrosis in one lung and emphysema in the other.
A significant correlation was revealed between the total percentage of fibrosis and FVC (% of predicted): r=-0.52. When HRCT was repeated (after 32±26 months), it was noted that the overall percentage of fibrosis significantly increased in all patients by an average of 13.3%. Pulmonary fibrosis remained clearly asymmetrical in 20 (86.9%) patients and became symmetrical in 3 (13.1%) patients after bilateral exacerbations.
Survival rates for patients with aIPF and symmetric IPF were similar, with survival probabilities at 1, 3, and 5 years: 75% versus 87%, 53% versus 63.3%, and 50% versus 51.4%, respectively.
Thus, aIPF can be caused by several underlying conditions, including GER. GER can contribute to both the progression of IPF and the development of exacerbations.
Viral infection in acute exacerbation of idiopathic pulmonary fibrosis
IPF is a progressive disease of unknown etiology associated with the development of pulmonary fibrosis that is difficult to treat. Despite the constant progression of functional indicators, clinical picture characterized by a relatively stable course and episodes of sudden deterioration, which are often fatal. Such episodes are called “exacerbation”. The purpose of this study is to show whether exacerbation of IPF is associated with viral infection.
The study included 43 patients with exacerbation of IPF. The median time from the onset of the disease to the development of exacerbation was 85 days. In 28% of patients, during the development of an exacerbation, virus-like symptoms occurred - fever and myalgia. In 4 patients (9%) with exacerbation PCR method respiratory viruses were identified (in 2 - rhinovirus, in 1 - coronavirus-OS43 and in 1 - parainfluenza virus-1). Viruses were not detected in any of the patients with stable IPF. Using DNA microarrays, the presence of transfusion-transmitted virus (TTV) and human herpes viruses was detected. When performing genome-specific PCR analysis, another 15 positive samples BALL. Among these viruses, only TTV was significantly more common in the group with exacerbation of IPF compared to controls (28% vs. 0%, p=0.0003). In four samples, 2 viruses were detected (2 - TTV and rhinovirus, 1 - TTV and parainfluenza-1 virus, and 1 - TTV and herpes simplex virus). Thus, in 33% of cases of exacerbation, viruses were detected, while in cases of stable disease, viruses were not detected in any of the samples (p<0,0001). Достоверных различий в частоте лихорадки и миалгии у вирус-положительных и вирус-отрицательных пациентов выявлено не было.
When comparing TTV-positive and TTV-negative patients, it was revealed that in the former the disease was more severe, of which 58% required mechanical ventilation, while in the TTV-negative group only 29% had such (p = 0. 09). In addition, in the TTV-positive group, 75% died within 60 days, and in the TTV-negative group, the proportion of deaths was 42% (p = 0.06). Median survival among TTV-positive patients was 29 days (versus 88 days among TTV-negative patients (p=0.19)), but the presence of a TTV-positive test was not a predictor of survival in this group of patients. In 27% of patients with exacerbation of IPF and in 16% of patients with stable IPF, the PCR test for TTV in the blood serum was positive, but there was no correlation between this indicator in the blood serum and BAL fluid. TTV infection was detected in BAL fluid in 24% of patients with ALI, and no significant differences were found between the frequency of TTV detection in patients with ALI and exacerbation of IPF.
Thus, the pathogenetic role of TTV in exacerbation of IPF is unclear. It is possible that the development of TTV infection leads to acute alveolar damage and the development of exacerbation. If so, this process is not unique to IPF, since this virus is found with approximately equal frequency among patients with ALI. Although a role for TTV in the pathogenesis of exacerbations in IPF cannot be ruled out, it is also possible that acute alveolar damage triggers local viral replication or may lead to increased microvascular permeability and infection in the lungs. In this case, the presence of TTV in the pulmonary space is more a consequence of inflammation in the lungs than its cause.
Exogenous allergic alveolitis
Morphological diversity of chronic disease of pigeon breeders: clinical picture and survival
Exogenous allergic alveolitis (EAA) is a diffuse parenchymal lung disease associated with the development of an immune response to the inhalation of various organic particles. In Mexico, one of the most common antigens causing the development of EAA is avian proteins, which provoke the development of the so-called “pigeon disease” (PD). The most common histopathological change observed in EAA is granulomatous interstitial bronchiolocentric pneumonitis, characterized by marked interstitial mononuclear infiltration with the presence of non-necrotizing ill-defined granulomas. In the chronic stage, fibrosis of varying severity may occur. However, other morphological changes have been described, including relatively homogeneous interstitial inflammation and fibrosis, reminiscent of nonspecific interstitial pneumonia (NSIP), as well as peripheral fibrosis with the formation of fibroblastic foci, reminiscent of usual interstitial pneumonia (UIP).
In the present study, in 110 patients diagnosed with GD, the clinical picture was described and survival was assessed in different morphological types of EAA: organizing pneumonia (OP), bronchocentric fibrosis (BCF) and unclassified EAA.
The average age of the patients was 45±12 years, the average duration of symptoms was 25±32 months. All patients noted the presence of shortness of breath and cough; changes in the terminal phalanges of the fingers like “drum sticks” were detected in 56% of patients. All patients had restrictive functional changes (FVC 54.5±17% of predicted), hypoxemia at rest (SpO2 85.7±6.7% of patients), worsening with physical activity (SpO2 72±8%).
A typical histological variant of EAA was identified in 58 patients, NSIP-like - in 22, AIP-like - in 10, mixed - in 9, organizing pneumonia - in 3, BCF - in 3 and unclassified - in 5. Fibroblastic foci were found in 20 % with typical EAA, 30% with NSIP-like variant and in all observations with AIP-like EAA. HRCT revealed that the inflammatory nature of the changes predominated in 75% of patients with typical EAA, 69% with NSIP-like, 14% with AIP-like variants of HD (p<0,05).
When analyzing survival, differences were revealed between the morphological groups of HD (Fig. 3). Thus, the OR for mortality for the group of patients with AIP-like variant compared with typical EAA was 4.19 (p<0,004). Напротив, выживаемость в группе с НСИП-подобным вариантом по сравнению с типичным ЭАА была выше - ОШ 0,18 (p<0,03). Таким образом, в настоящем исследовании показано, что при ЭАА имеет место разнообразие гистологических изменений, их оценка важна для определения прогноза выживаемости пациентов.
Hypersensitivity pneumonitis
and contamination with mycobacteria
metalworking fluids
EAA can be caused by the action of various antigens, including bacterial ones. There is evidence in the literature about the possible occurrence of EAA upon contact with metalworking fluids (MLFs). Fast-growing mycobacteria (FGM) are one of the etiological factors in the development of EAA caused by contact with MOG. The purpose of this study is to identify an antigen that may be associated with the development of EAA caused by exposure to MFA.
The study included 13 patients with MOG-associated EAA, confirmed according to clinical, biological and radiological criteria, 12 persons who had contact with MOG (working in the same factories and performing the same work as patients with EAA) in the absence of clinical symptoms , 18 healthy volunteers.
The average age of EAA patients was 46.3 years. All 13 patients showed improvement in clinical symptoms one year after cessation of contact with MOG. A serological test was performed to detect antigens against Aspergillus fumigatus and Pseudomonas, the results were negative. M. immunogenum was isolated from 40% of MOG samples, Bacillus spp. - from 42%, gram-negative bacteria (excluding Pseudomonas spp.) - from less than 12% of samples, fungi - from 11% of samples. Electrosyneresis analysis was performed on fluid samples to detect precipitins against M. immunogenum, F. solani, and B. simplex. For the M. immunogenum antigen, the number of precipitin arches was significantly higher in patients with MOS-associated EAA than in the control group who had contact with MOS. At a threshold of 5 precipitation arches, the sensitivity of the test was 77% and the specificity was 92%. M. immunoge-num-specific IgG was also significantly increased in this group of patients.
Thus, the presence of M. immunogenum in more than 40% of MOG samples, as well as the identification of specific precipitins to M. immunogenum in the blood serum of patients with MOG-associated EAA, indicates that contact with contaminated MOG may be the cause of the development of EAA. Regular testing of MMF samples and adequate protection of workers exposed to MMF will prevent the development of EAA in this population.
Cystic lung diseases
Efficacy and safety of sirolimus
with lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare systemic disease characterized by cystic destruction of lung tissue, chylous pleural effusion, and abdominal tumors (renal angiomyolipomas). Most patients develop respiratory disorders, recurrent pneumothorax and hypoxemia within 10 years from the onset of the disease. Smooth muscle cells infiltrating lung tissue also circulate in the blood and contain biallelic mutations that inactivate the TSC gene. Loss of TSC gene function triggers the mTOR signaling pathway, which regulates numerous cellular functions, including cell growth, motility, and cell survival. The drug sirolimus blocks the activation of mTOR and restores the functioning of the defective TSC gene.
This article presents the results of an international multicenter, randomized, double-blind, placebo-controlled study that examined the effect of one-year therapy with the mTOR inhibitor sirolimus on pulmonary function in patients with LAM.
Patients were recruited to participate in the study with the help of the LAM Foundation. The study included a screening visit, a 12-month treatment period, and a 12-month passive observation period during which patients did not receive the study drug. Patients were randomly assigned in a 1:1 ratio to receive oral sirolimus at an initial dose of 2 mg/day. or placebo. During each visit, the concentration of sirolimus in the blood was measured and the dose of the drug was changed to maintain its concentration within the range of 5–15 pg/ml.
A total of 89 patients were randomized: 43 to placebo and 46 to sirolimus. In the placebo group, FEV1 decreased over 12 months. by 12±2 ml/month. from the initial level. In the sirolimus group, the decrease in FEV1 was 1±2 ml/month, which meant stabilization of pulmonary function during treatment. The absolute difference in the average change in FEV1 during the treatment period between the groups was 153 ml (the differences are significant) (Fig. 4). The decrease in FVC during treatment was −11±3 ml/month. in the placebo group and +8±3 ml/month. in the sirolimus group, which meant a significant improvement in pulmonary function during active therapy. The absolute difference in mean change in FVC during therapy between groups was 226 ml (Fig. 4).
The quality of life according to the Functional Performance Inventory questionnaires and the EuroQOL visual analogue scale in the sirolimus group significantly improved over 12 months. treatment as opposed to the placebo group. Mean levels of the LAM-specific lymphogenous factor vascular endothelial growth factor D (VEGF-D) were similar in both groups at baseline, but at 6 and 12 months. in the sirolimus group were significantly lower than in the placebo group.
Over the subsequent year of passive observation, FEV1 decreased in both groups (by 8±2 ml/month in the placebo group and by 14±3 ml/month in the sirolimus group, the differences were not significant). Similarly, no significant differences were obtained in the dynamics of FVC over 24 months. Average VEGF-D level at 24 months. remained elevated in the placebo group (2107±2146 pg/ml) and decreased in the sirolimus group (930±461 pg/ml).
The most common side effects during the treatment period included inflammation of the mucous membranes of the gastrointestinal tract, diarrhea, nausea, hypercholesterolemia, skin rash and edema of the lower extremities. In the sirolimus group, side effects related to bone marrow and blood, gastrointestinal events, dermatological problems, metabolic disorders or changes in laboratory parameters, musculoskeletal disorders, and side effects related to soft tissue were significantly more common; pain and neurological syndromes, visual impairment or other ophthalmological problems.
Thus, treatment of patients with LAM with sirolimus for 1 year stabilized FEV1, improved quality of life and some functional characteristics. The positive effect on bronchial patency disappeared after discontinuation of the drug. Treatment with sirolimus was associated with a higher incidence of side effects than placebo, although serious side effects occurred at a similar rate in both groups.
Pulmonary manifestations of the syndrome
Burt-Hogg-Dubé': cystic changes
and pulmonary histiocytoma
Burt-Hogg-Dubé syndrome (BHD) is an autosomal dominant genodermatosis that predisposes to the development of follicular hamartomas of the skin, cystic changes in the lungs, pneumothorax and renal neoplasms. FCD syndrome is caused by a mutation in the FCD gene (FLCN), which is localized in the short arm of chromosome 17 (17p11.2) and encodes the synthesis of the tumor suppressor protein folliculin. Typical skin lesions for BCD syndrome are fibrofolliculoma (FF) and trichodiscoma (TD), which are multiple small papules on the skin of the face, neck and upper torso. Most patients develop cystic lung disease, often with recurrent pneumothorax. Kidney damage is manifested by various histological variants of renal cell carcinoma. This article describes lung lesions associated with BCD syndrome in 12 patients with BCD syndrome in three families living in the UK and Italy.
Skin lesions were diagnosed in 7 patients, kidney lesions in 2 patients, cystic lung lesions in 9 (75%) patients. The mean age at diagnosis was 44.6 years; 8 (66%) patients were male. 4 (33%) patients (age 47-57 years) developed recurrent pneumothorax (from one to three episodes). Pulmonary thin-walled cysts of round or oval shape, 3-57 mm in size (larger ones were located in the lower parts of the lungs), surrounded by unchanged lung tissue, with a wall thickness ranging from invisible to 2 mm, were detected by HRCT in small numbers throughout all lung fields in 9 (75 %) of patients aged 24-85 years (Fig. 5).
Histological examination revealed cystic dilatation of the alveolar ducts ranging from microscopic to several millimeters in diameter. Thin-walled cysts were lined with cubic epithelium in the absence of fibrous or smooth muscle tissue in their walls. In one patient, a single nodule 12 mm in diameter was identified in the lower lobe of the left lung, which was resected; Histiocytoma was diagnosed morphologically and immunophenotypically.
Thus, BCD syndrome is one of the cystic lesions of the lungs, which must be taken into account when making a differential diagnosis of cystic lung diseases (which also includes LAM, histiocytosis X, pneumonia caused by Pneumocystis, lymphocytic interstitial pneumonia and metastatic lesions of the lungs in adenocarcinomas and poorly differentiated sarcomas ).
Bronchiolitis
Severe chronic bronchiolitis
as the initial manifestation of the primary
Sjögren's syndrome
Sjögren's syndrome is an autoimmune disease characterized by lymphoid infiltration of the exocrine glands. A distinction is made between primary Sjögren's syndrome, a systemic disease of unknown etiology, and secondary Sjögren's syndrome, which accompanies other autoimmune diseases. The disease most often manifests itself by the development of asthenia and “dry” syndrome (xerostomia and xerophthalmia), less often by systemic manifestations, including damage to the respiratory system.
It is known that in almost half of the patients, lymphoplasmacytic infiltration of the wall of the airways can be detected during biopsy and bronchial hyperreactivity during FVD. Clinically significant damage to the respiratory system occurs, according to some authors, only in 9% of patients with primary Sjögren's syndrome.
This paper describes 5 clinical cases of patients with severe bronchiolitis and chronic respiratory failure associated with primary Sjogren's syndrome. Among the patients there were 4 women and 1 man, the average age at the time of diagnosis ranged from 38 to 70 years (58 years on average). In all patients, the dominant complaints were shortness of breath lasting from 1 to 144 months. (10 months on average), chronic cough and sputum production. Four patients required long-term oxygen therapy due to severe hypoxemia. Three had a history of recurrent upper respiratory tract infections.
When analyzing HRCT of the chest organs, moderately severe bronchiectasis was visualized in all patients against the background of multiple diffuse small-nodular lung lesions. At the time of diagnosis, 3 patients showed signs of alveolitis, which disappeared after antibiotic therapy and physiotherapy. According to the FVD data, all patients were diagnosed with bronchial obstruction. Microbiological examination of the bronchial tree aspirate revealed the growth of Pseudomonas aeruginosa in 1 patient and Staphylococcus aureus in another 1 patient. In 4 cases, bronchoalveolar lavage (BAL) was performed, which revealed increased cytosis, mainly due to neutrophils (80%). Antinuclear antibodies were detected in all patients, and anti-SSA antibodies were detected in 2 patients. All patients received inhaled glucocorticosteroids (ICS) and long-acting β2-agonists, as well as physical therapy to improve bronchial drainage. During the entire observation period, significant improvement was noted in 3 patients; recurrent respiratory infection was detected in 3 patients, of whom 1 died from pneumonia.
Thus, practitioners should not forget about the risk of developing respiratory damage against the background of systemic diseases. The administration of macrolides, ICS and bronchodilators can significantly improve the course of severe bronchiolitis obliterans.
Interstitial diseases
lungs and smoking
Lung volumes and emphysema in smokers with interstitial changes
Currently, more and more information is accumulating that tobacco smoking, in addition to COPD, can cause the formation of areas of increased lung density - interstitial changes (IS), detected by HRCT. The extent to which these impairments are associated with less emphysema and less total lung capacity (TLC) decline with continued smoking is unknown. The purpose of this study was to study the relationship between signs of IS, AEL and emphysema determined by HRCT in a cohort of smokers with an experience of more than 10 pack-years.
The study included 2508 smokers with a smoking history of at least 10 pack-years, aged 45-80 years, from 21 centers in the United States. The study did not include persons with pulmonary diseases other than asthma, COPD and emphysema.
HRCT was performed in 2416 patients, of whom 1171 were women, 613 were black, 1060 were active smokers, and 1002 had COPD. In 1361 (56%) patients, no IS was detected on HRCT, 861 (36%) had indeterminate (less than 5% of the lung area) IS, and 194 (8%) were identified as IS. Compared with individuals without IS, patients with IS were older (64 vs. 60 years), had a higher body mass index (28 vs. 27), and had a longer smoking history (44 pack-years vs. 40). Patients with IS were less likely to suffer from COPD (32% vs. 41%), have a lower TLC (5.02 L vs. 5.7 L) and a lower tidal volume (2.67 L vs. 3.13 L).
In the adjusted model, total pulmonary volume and tidal volume were reduced in patients with IS compared with the group without such changes. The severity of emphysema was also less in individuals with IS. The odds of having COPD in patients with IS were 47% lower than in those without IS.
Stratification of patients based on the presence or absence of COPD revealed that AIs are associated with a decrease in TLC in both patients with COPD (−12% predicted) and without COPD (−7% predicted). The severity of emphysema was also less in the presence of IS in patients with COPD (−7%) and without COPD (−0.6%). After adjusting for the prevalence of emphysema, the reduction in TLC was almost the same in the group with COPD (−7%) and without COPD (−6%). This means that a decrease in TLC in COPD with IS is associated with both a restrictive defect and a lesser severity of emphysema.
Of 194 patients with IS, 37 (19%) had centrilobular changes, 107 (55%) had subpleural changes, 38 (20%) had mixed centrilobular and subpleural changes, and 12 (6%) had radiological signs of interstitial lung diseases. The greatest decrease in TLC was observed with the subpleural variant of IS (−0.481), mixed variant (−0.416), the smallest decrease was observed with the centrilobular location of IS (−0.133). Active smoking was associated with centrilobular nodule formation (odds ratio 4.82).
In summary, the present study demonstrated that HRCT could detect interstitial changes in 8% of smokers. AIs are associated with a decrease in TLC and less severity of emphysema; the amplitude of this decrease is maximum in patients with COPD. The study authors suggest that smoking can cause two different types of lung damage - emphysema and IS.
