pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2016-26-3-345-351pulmo-726Research ArticleОБЗОРЫREVIEWПерспективные направления в изучении патогенеза эмпиемы плеврыPerspective investigations of empyema pathogenesisКосареваП. В.KosarevaP. V.

д. м. н., главный научный сотрудник отдела морфологических и патофизиологических исследований ЦНИЛ, заведующая курсом клинической лабораторной диагностики, доцент кафедры микробиологии, вирусологии с курсом КЛД ГБОУ ВПО «Пермский государственный медицинский университет им. акад. Е.А.Вагнера» Минздрава России; тел.: (342) 2171031

MD, Principal Researcher at Division of Morphological and Pathophysiological Investigations, Central Research Laboratory; Head of Course of Clinical Laboratory Diagnostics; Associate Professor at Department of Microbiology, Virusology and Clinical Laboratory Diagnostics, E.A.Vagner Perm State Medical University, Healthcare Ministry of Russia; tel.: (342) 2171031

rector@psma.ruХоринкоА. В.KhorinkoA. V.

заведующий Первым химиотерапевтическим отделением ГБУЗ ПК «Пермский краевой онкологический диспансер»; тел.: (342) 2201657

Head of the 1st Chemotherapeutic Department, Perm State Territorial Oncology Institution; tel.: (342) 2201657

permcancer@yandex.ruАмарантовД. Г.AmarantovD. G.

д. м. н., доцент кафедры нормальной, топографической и клинической анатомии, оперативной хирургии ГБОУ ВПО «Пермский государственный медицинский университет им. акад. Е.А.Вагнера» Минздрава России; тел.: (342) 2171031

MD, Associate Professor at Department of General, Topographic and Clinical Anatomy, and Operative Surgery, E.A.Vagner Perm State Medical University, Healthcare Ministry of Russia; tel.: (342) 2171031;

rector@psma.ruГБОУ ВПО «Пермский государственный медицинский университет им. акад. Е.А.Вагнера» Минздрава России: 614990, Пермь, Петропавловская, 26РоссияE.A.Vagner Perm State Medical University, Healthcare Ministry of Russia; 26, Petropavlovskaya str., Perm, 614990, RussiaRussian FederationГБУЗ ПК «Пермский краевой онкологический диспансер»: 614066, Пермь, ул. Баумана, 15РоссияPerm State Territorial Oncology Institution; 15, Baumana str., Perm, 614066, RussiaRussian Federation201627072016263345351Copyright © Косарева П.В., Хоринко А.В., Амарантов Д.Г., 20162016Косарева П.В., Хоринко А.В., Амарантов Д.Г.Kosareva P.V., Khorinko A.V., Amarantov D.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/726

Острая неспецифическая эмпиема плевры (ОНЭП) является одной из наиболее тяжелых из всех существующих гнойных патологий. Несмотря на положительные результаты лечения больных эмпиемами плевры (ЭП), на сегодняшний день остается необходимость совершенствования тактики лечения и методов ее прогнозирования. Перспективным в этом отношении является дальнейшее изучение патологической анатомии ОНЭП и определение гистологических критериев острого и хронического гнойного плеврита, плеврогенного пневмосклероза, поскольку морфологические характеристики играют важную роль в определении прогноза и выборе оптимальной тактики лечения. Однако в клинической практике полноценное гистологическое исследование висцеральной плевры и легкого затруднительно, т. к. любое повреждение пораженного легкого грозит формированием бронхиального свища. Между тем макроскопические характеристики плевральной полости и гистологические изменения в висцеральной плевре и легком взаимосвязаны. Углубленное исследование этой взаимосвязи и доказательство морфологической идентичности патоморфологических изменений в париетальной плевре и висцеральной плевре и легком при ЭП позволит повысить диагностическую эффективность торакоскопии и разработать методику торакоскопической экспресс"диагностики гистологических изменений, а также обозначить принципиально новые пути совершенствования подходов в лечении ЭП. При этом актуален поиск оптимальных для гистологической экспресс"диагностики молекулярных медиаторов плеврального фиброза. Выявленные закономерности могут помочь и в разработке новых методов лечения и профилактики плеврогенного пневмосклероза. В статье дается обзор современных представлений об основных механизмах ремоделирования внеклеточного матрикса при плевральном фиброзе и вызывающих его факторах. Анализ этих процессов может определять новые механизмы ремоделирования внеклеточного матрикса и путей его устранения при плеврогенном пневмосклерозе, а также использовать определение выявленных «ключевых посредников» плеврального фиброза в экспресс"диагностике стадий ОНЭП

Pleural empyema is one of the most serious septic diseases. Despite favorable outcome, therapeutic and prognostic strategies in empyema are needed to be improved. Further investigation of pathology and diagnostic histological criteria of acute and chronic purulent pleural inflammation and fibrosis is a perspective research direction, as morphological characteristics are important for prognosis and the optimal treatment choice. However, complete histological examination of the lung tissue and the visceral pleura is difficult in real clinical practice, because any lung damage can cause bronchial fistula. Nevertheless, histological features of the visceral pleura and the lungs are closely related to macroscopic characteristics of the pleura. Detailed study of this relationship and the search of morphological similarity of lesions in parietal pleura, visceral pleura, and the lung in patients with empyema could improve the diagnostic value of thoracoscopy, contribute to a rapid histological diagnosis and improve therapeutic approach to empyema. Current approach to the basic mechanisms and risk factors of remodeling of the extracellular matrix in pleural fibrosis was reviewed in the article. Analysis of this process could determine new mechanisms of extracellular matrix remodeling and ways to avoid fibrosis development in the adjacent lung tissue that, in turn, could underlie staging the empyema.

эмпиема плеврымедиаторы плеврального фиброзатрансформирующий фактор ростаматриксные металлопротеиназыempyemapleuramediators of pleural fibrosistransforming growth factormatrix metalloproteinasesReferencesМакаров В.В. Современные аспекты санации плевральной полости у больных с острой эмпиемой плевры. Буковинский медицинский вестник. 2008; 12 (3): 39–41. /Makarov V.V. Current aspects of pleural draining in acute empyema. Bukovinskiy meditsinskiy vestnik 2008; 12 (3): 39–41 (in Russian).Макаров В.В. Современные аспекты санации плевральной полости у больных с острой эмпиемой плевры. Буковинский медицинский вестник. 2008; 12 (3): 39–41. /Makarov V.V. Current aspects of pleural draining in acute empyema. Bukovinskiy meditsinskiy vestnik 2008; 12 (3): 39–41 (in Russian).Дударев А.А., Сухоруков А.М., Большаков В.Н. и др. Оценка гемостазиологических сдвигов у больных с острой неспецифической эмпиемой плевры. В кн.: Материалы III Съезда хирургов Сибири и Дальнего Востока. Томск; 2009: 86–87. / Dudarev A.A., Sukhorukov A.M., Bol'shakov V.N. et al. Haemostatic change in patients with acute non"specific empyema. In: Proceedings of the 3rd Congress of Surgeons of Syberia and the Far East. Tomsk; 2009: 86–87 (in Russian).Дударев А.А., Сухоруков А.М., Большаков В.Н. и др. Оценка гемостазиологических сдвигов у больных с острой неспецифической эмпиемой плевры. В кн.: Материалы III Съезда хирургов Сибири и Дальнего Востока. Томск; 2009: 86–87. / Dudarev A.A., Sukhorukov A.M., Bol'shakov V.N. et al. Haemostatic change in patients with acute non"specific empyema. In: Proceedings of the 3rd Congress of Surgeons of Syberia and the Far East. Tomsk; 2009: 86–87 (in Russian).Никольский В.И., Логинов С.Н., Баженов М.С., Семисаженов О.А. Динамическая торакоскопия с применением торакопорта в лечении больных с неспецифической эмпиемой плевры. Известия высших учебных заведений. Поволжский регион. 2010; 4 (16): 99–107. / Nikol'skiy V.I., Loginov S.N., Bazhenov M.S., Semisazhenov O.A. Dynamic thoracoscopy in patients with acute non-specific empyema using thoracoport. Izvestiya vysshikh uchebnykh zavedeniy. Povolzhskiy region. 2010; 4 (16): 99–107 (in Russian).Никольский В.И., Логинов С.Н., Баженов М.С., Семисаженов О.А. Динамическая торакоскопия с применением торакопорта в лечении больных с неспецифической эмпиемой плевры. Известия высших учебных заведений. Поволжский регион. 2010; 4 (16): 99–107. / Nikol'skiy V.I., Loginov S.N., Bazhenov M.S., Semisazhenov O.A. Dynamic thoracoscopy in patients with acute non-specific empyema using thoracoport. Izvestiya vysshikh uchebnykh zavedeniy. Povolzhskiy region. 2010; 4 (16): 99–107 (in Russian).Lee S.F., Lawrence D., Booth H. et al. Thoracic empyema: current opinions in medical and surgical management. Curr. Opin. Pulm. Med. 2010; 16 (3): 194–200.Lee S.F., Lawrence D., Booth H. et al. Thoracic empyema: current opinions in medical and surgical management. Curr. Opin. Pulm. Med. 2010; 16 (3): 194–200.Черкасов В.А., Хусейн Х.С. Лечение больных эмпиемой плевры. Пермский медицинский журнал. 2009; 26 (2): 15–19. / Cherkasov V.A., Khuseyn Kh.S. Treatment of patients with empyema. Permskiy meditsinskiy zhurnal 2009; 26 (2): 15–19 (in Russian).Черкасов В.А., Хусейн Х.С. Лечение больных эмпиемой плевры. Пермский медицинский журнал. 2009; 26 (2): 15–19. / Cherkasov V.A., Khuseyn Kh.S. Treatment of patients with empyema. Permskiy meditsinskiy zhurnal 2009; 26 (2): 15–19 (in Russian).Проценко А.В. Выбор способа торакопластики при бронхиальном свище и эмпиеме плевры после пульмонэктомии. Анналы хирургии. 2009; 2: 40–42. / Protsenko A.V. A choice of thoracoplastics method in post"pneumonectomy bronchial fistula and empyema. Annaly khirurgii 2009; 2: 40–42 (in Russian).Проценко А.В. Выбор способа торакопластики при бронхиальном свище и эмпиеме плевры после пульмонэктомии. Анналы хирургии. 2009; 2: 40–42. / Protsenko A.V. A choice of thoracoplastics method in post"pneumonectomy bronchial fistula and empyema. Annaly khirurgii 2009; 2: 40–42 (in Russian).Dudarev А.А., Sukhorukov А.М., Bolshakov V.N. et al. Use of thoracoscopy in local treatment of nonspecific pleural empyema. Bull. Intern. Sci. Surg. Ass. 2010; 5 (1): 11–12.Dudarev А.А., Sukhorukov А.М., Bolshakov V.N. et al. Use of thoracoscopy in local treatment of nonspecific pleural empyema. Bull. Intern. Sci. Surg. Ass. 2010; 5 (1): 11–12.Cheah Y.L., Ng T., Shah K. et al. Video"assisted Thoracoscopic Surgery (VATS) drainage of salmonella enteritidis empyema and needle"localization for retrieval of a dropped gallstone. Surg. Laparosc. Endosc. Percutan. Tech. 2010; 20 (4): 265–268.Cheah Y.L., Ng T., Shah K. et al. Video"assisted Thoracoscopic Surgery (VATS) drainage of salmonella enteritidis empyema and needle"localization for retrieval of a dropped gallstone. Surg. Laparosc. Endosc. Percutan. Tech. 2010; 20 (4): 265–268.Лукомский Г.И. Неспецифические эмпиемы плевры. М.: Медицина; 1976. / Lukomskiy G.I. Non"specific empyema. Moscow: Meditsina; 1976 (in Russian).Лукомский Г.И. Неспецифические эмпиемы плевры. М.: Медицина; 1976. / Lukomskiy G.I. Non"specific empyema. Moscow: Meditsina; 1976 (in Russian).Capelozzi V.L., da Rosa D.C., da Silva A.S.F. The value of cytology and pleural biopsy in the differential diagnostic of nonspecific pleural effusions. J. Pneumol. 2003; 29 (4): 225–234. On"line version: http://dx.doi.org/10.1590/S010235862003000400012.Capelozzi V.L., da Rosa D.C., da Silva A.S.F. The value of cytology and pleural biopsy in the differential diagnostic of nonspecific pleural effusions. J. Pneumol. 2003; 29 (4): 225–234. On"line version: http://dx.doi.org/10.1590/S010235862003000400012.Olgac G., Fazlioglu M., Kutlu C.A. VATS decortication in patients with stage 3 empyema. Thorac. Cardiovasc. Surg. 2005; 53 (5): 318–320.Olgac G., Fazlioglu M., Kutlu C.A. VATS decortication in patients with stage 3 empyema. Thorac. Cardiovasc. Surg. 2005; 53 (5): 318–320.Vyhnánek F., Fanta J., Jirava D., Ocadlík M. Contemporary approach to treatment of the posttraumatic empyema of the thorax. Rozhl. Chir. 2006; 85 (1): 4–8.Vyhnánek F., Fanta J., Jirava D., Ocadlík M. Contemporary approach to treatment of the posttraumatic empyema of the thorax. Rozhl. Chir. 2006; 85 (1): 4–8.Koh D."M., Burke S., Davies N., Padley S.P.G. Transthoracic US of the chest: clinical uses and applications. RadioGraphics. 2002; 22 (1): e1. DOI: http://dx.doi.org/ 10.1148/radiographics.22.1.g02jae1e1.Koh D."M., Burke S., Davies N., Padley S.P.G. Transthoracic US of the chest: clinical uses and applications. RadioGraphics. 2002; 22 (1): e1. DOI: http://dx.doi.org/ 10.1148/radiographics.22.1.g02jae1e1.Andrews N.C., Parker E.F., Shaw R.R. et al. Management of nontuberculous empyema. Am. Rev. Respir. Dis. 1962; 85: 935–936.Andrews N.C., Parker E.F., Shaw R.R. et al. Management of nontuberculous empyema. Am. Rev. Respir. Dis. 1962; 85: 935–936.Вагнер Е.А., Перепелицын В.Н., Субботин В.М. и др. Эндоскопическая окклюзия культи главного бронха при ее несостоятельности. Грудная и сердечно#сосудистая хирургия. 1990; 2: 46–49. / Vagner E.A., Perepelitsyn V.N., Subbotin V.M.et al. Endoscopic occlusion of the main bronchus cuff in a case of its failure. Grudnaya i serdechno-sosudistaya khirurgiya 1990; 2: 46–49 (in Russian).Вагнер Е.А., Перепелицын В.Н., Субботин В.М. и др. Эндоскопическая окклюзия культи главного бронха при ее несостоятельности. Грудная и сердечно#сосудистая хирургия. 1990; 2: 46–49. / Vagner E.A., Perepelitsyn V.N., Subbotin V.M.et al. Endoscopic occlusion of the main bronchus cuff in a case of its failure. Grudnaya i serdechno-sosudistaya khirurgiya 1990; 2: 46–49 (in Russian).Light R.W. Parapneumonic effusions and empyema. Proc. Am. Thorac. Soc. 2006; 3 (1): 75–80.Light R.W. Parapneumonic effusions and empyema. Proc. Am. Thorac. Soc. 2006; 3 (1): 75–80.Порханов В.А., Коровин А.Я. Новые возможности лечения постпневмонэктомической острой эмпиемы плевры со свищами главных бронхов: В кн.: Материалы III Конгресса ассоциации хирургов им. Н.И.Пирогова. М.; 2001: 122–124. / Porkhanov V.A., Korovin A.Ya. Novel approaches to treatment of acute post"pneumonectomy empyema and bronchial fistula of the main bronchus. In: Proceedings of the 3rd Congress of N.I.Pirogov Association of Surgeons. Moscow; 2001: 122–124 (in Russian).Порханов В.А., Коровин А.Я. Новые возможности лечения постпневмонэктомической острой эмпиемы плевры со свищами главных бронхов: В кн.: Материалы III Конгресса ассоциации хирургов им. Н.И.Пирогова. М.; 2001: 122–124. / Porkhanov V.A., Korovin A.Ya. Novel approaches to treatment of acute post"pneumonectomy empyema and bronchial fistula of the main bronchus. In: Proceedings of the 3rd Congress of N.I.Pirogov Association of Surgeons. Moscow; 2001: 122–124 (in Russian).Decologne N., Kolb M., Margetts P.J. et al. TGF"β1 induces progressive pleural scarring and subpleural fibrosis. J. Immunol. 2007; 179 (9): 6043– 6051.Decologne N., Kolb M., Margetts P.J. et al. TGF"β1 induces progressive pleural scarring and subpleural fibrosis. J. Immunol. 2007; 179 (9): 6043– 6051.Owens S., Jeffers A., Boren J. et al. Mesomesenchymal transition of pleural mesothelial cells is PI3K and NF"κB dependent. Am. J. Physiol. Lung Cell. Mol. Physiol. 2015; 308 (12): 1265–1273.Owens S., Jeffers A., Boren J. et al. Mesomesenchymal transition of pleural mesothelial cells is PI3K and NF"κB dependent. Am. J. Physiol. Lung Cell. Mol. Physiol. 2015; 308 (12): 1265–1273.Heldin C."H., Miyazono K., Dijke P. TGF"b signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997; 390: 465–471.Heldin C."H., Miyazono K., Dijke P. TGF"b signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997; 390: 465–471.Chena L."J., Yeb H., Zhanga Q. et al. Bleomycin induced epithelial"mesenchymal transition (EMT) in pleural mesothelial cells. Toxicol. Appl. Pharmacol. 2015; 283 (2): 75–82.Chena L."J., Yeb H., Zhanga Q. et al. Bleomycin induced epithelial"mesenchymal transition (EMT) in pleural mesothelial cells. Toxicol. Appl. Pharmacol. 2015; 283 (2): 75–82.Mutsaers S.E., Birnie K., Lansley S. et al. Mesothelial cells in tissue repair and fibrosis. Front. Pharmacol. 2015; 6: 113.Mutsaers S.E., Birnie K., Lansley S. et al. Mesothelial cells in tissue repair and fibrosis. Front. Pharmacol. 2015; 6: 113.Lee Y.C., Malkerneker D., Devin C.J. et al. Comparing transforming growth factor β"2 and fibronectin as pleurodesing agents. Respirology. 2001; 6: 281–286.Lee Y.C., Malkerneker D., Devin C.J. et al. Comparing transforming growth factor β"2 and fibronectin as pleurodesing agents. Respirology. 2001; 6: 281–286.Lee Y.C., Lane K.B., Zoia O. et al. Transforming growth factor"b induces collagen synthesis without inducing IL"8 production in mesothelial cells. Eur. J. Respir. 2003; 22: 197–202.Lee Y.C., Lane K.B., Zoia O. et al. Transforming growth factor"b induces collagen synthesis without inducing IL"8 production in mesothelial cells. Eur. J. Respir. 2003; 22: 197–202.Kunz C.R., Jadus M.R., Kukes G.D. et al. Intrapleural injection of transforming growth factor"[beta] antibody inhibits pleural fibrosis in empyema. Laboratory and animal investigations. Chest. 2004; 126 (5): 1636–1644. http://business.highbeam.com/137522/article#1G1#125648645/intrapleu ral#injection#transforming#growth#factorbetaKunz C.R., Jadus M.R., Kukes G.D. et al. Intrapleural injection of transforming growth factor"[beta] antibody inhibits pleural fibrosis in empyema. Laboratory and animal investigations. Chest. 2004; 126 (5): 1636–1644. http://business.highbeam.com/137522/article#1G1#125648645/intrapleu ral#injection#transforming#growth#factorbetaQing"qing Z., Geng"Yun S. Transforming growth factor"β and pleural fibrosis. Intern. J. Respir. 2009; 29 (10): 609–612.Qing"qing Z., Geng"Yun S. Transforming growth factor"β and pleural fibrosis. Intern. J. Respir. 2009; 29 (10): 609–612.Leask A. Signaling in fibrosis: targeting the TGF beta, endothelin"1 and CCN2 axis in scleroderma. Front. Biosci. 2009; 1: 115–122.Leask A. Signaling in fibrosis: targeting the TGF beta, endothelin"1 and CCN2 axis in scleroderma. Front. Biosci. 2009; 1: 115–122.Итмезех А. Механизмы формирования пневмосклероза при хроническом эндотоксикозе (экспериментальное исследование): Дисс. … канд. мед. наук. Волгоград; 2006. / Itmezekh A. Mechanisms of the lung tissue fibrosis in chronic endotoxicosis: Diss. Volgograd; 2006 (in Russian).Итмезех А. Механизмы формирования пневмосклероза при хроническом эндотоксикозе (экспериментальное исследование): Дисс. … канд. мед. наук. Волгоград; 2006. / Itmezekh A. Mechanisms of the lung tissue fibrosis in chronic endotoxicosis: Diss. Volgograd; 2006 (in Russian).Xaubet A., Marin"Arguedas A., Lario S. et al. Transforming growth factor"beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2003; 168: 431–435.Xaubet A., Marin"Arguedas A., Lario S. et al. Transforming growth factor"beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2003; 168: 431–435.Lawson W.E., Crossno P.F., Polosukhin V.V. et al. Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. Am. J. Physiol. Lung Cell. Mol. Physiol. 2008; 294: 1119–1126.Lawson W.E., Crossno P.F., Polosukhin V.V. et al. Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. Am. J. Physiol. Lung Cell. Mol. Physiol. 2008; 294: 1119–1126.Datta A., Scotton C.J., Chambers R.C. Novel therapeutic approaches for pulmonary fibrosis Pulmonary fibrosis. Br. J. Pharmacol. 2011; 163: 141– 172.Datta A., Scotton C.J., Chambers R.C. Novel therapeutic approaches for pulmonary fibrosis Pulmonary fibrosis. Br. J. Pharmacol. 2011; 163: 141– 172.Moore B.B., Murray L., Das A. et al. The role of CCL12 in the recruitment of fibrocytes and lung fibrosis. Am. J. Respir. Cell. Mol. Biol. 2006; 35: 175–181.Moore B.B., Murray L., Das A. et al. The role of CCL12 in the recruitment of fibrocytes and lung fibrosis. Am. J. Respir. Cell. Mol. Biol. 2006; 35: 175–181.Mehrad B., Burdick M.D., Strieter R.M. Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis. Int. J. Biochem. Cell. Biol. 2009; 41: 1708–1718.Mehrad B., Burdick M.D., Strieter R.M. Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis. Int. J. Biochem. Cell. Biol. 2009; 41: 1708–1718.Batra H., Antony V.B. Pleural mesothelial cells in pleural and lung diseases. J. Thorac. Dis. 2015; 7 (6): 961–963. http://www.jthoracdis.com/article/view/4274/htmlBatra H., Antony V.B. Pleural mesothelial cells in pleural and lung diseases. J. Thorac. Dis. 2015; 7 (6): 961–963. http://www.jthoracdis.com/article/view/4274/htmlScotton C.J., Chambers R.C. Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest. 2007;132: 1311–1321.Scotton C.J., Chambers R.C. Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest. 2007;132: 1311–1321.Moodley Y.P., Scaffidi A.K., Misso N.L. et al. Fibroblasts isolated from normal lungs and those with idiopathic pulmonary fibrosis differ in interleukin"6/gp130"mediated cell signaling and proliferation. Am. J. Pathol. 2003; 163: 345–354.Moodley Y.P., Scaffidi A.K., Misso N.L. et al. Fibroblasts isolated from normal lungs and those with idiopathic pulmonary fibrosis differ in interleukin"6/gp130"mediated cell signaling and proliferation. Am. J. Pathol. 2003; 163: 345–354.Moodley Y.P., Caterina P., Scaffidi A.K. et al. Comparison of the morphological and biochemical changes in normal human lung fibroblasts and fibroblasts derived from lungs of patients with idiopathic pulmonary fibrosis during FasLinduced apoptosis. J. Pathol. 2004; 202: 486–495.Moodley Y.P., Caterina P., Scaffidi A.K. et al. Comparison of the morphological and biochemical changes in normal human lung fibroblasts and fibroblasts derived from lungs of patients with idiopathic pulmonary fibrosis during FasLinduced apoptosis. J. Pathol. 2004; 202: 486–495.Kogan E., Тuong V., Demoura S. Mechanism of bronchoalveolar duct junction (BADJ) remodeling in idiopathic pulmonary fibrosis (IPF) as base for new pathogenetic therapy. Eur. Respir. J. 2008; 32 (Suppl. 52): 3489.Kogan E., Тuong V., Demoura S. Mechanism of bronchoalveolar duct junction (BADJ) remodeling in idiopathic pulmonary fibrosis (IPF) as base for new pathogenetic therapy. Eur. Respir. J. 2008; 32 (Suppl. 52): 3489.Tuong V., Demoura S., Kogan E. Markers of cell proliferation, apoptosis and angiogenesis in remodeling of bronchoalveolar duct junctions. Polish Histochemichal et Cytological Society. Folia Histochemica et Cytobiologica.Tuong V., Demoura S., Kogan E. Markers of cell proliferation, apoptosis and angiogenesis in remodeling of bronchoalveolar duct junctions. Polish Histochemichal et Cytological Society. Folia Histochemica et Cytobiologica.; 46 (2): 68.; 46 (2): 68.Scotton C.J., Krupiczojc M.A., Konigshoff M. et al. Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. J. Clin. Invest. 2009; 119: 2550–2563.Scotton C.J., Krupiczojc M.A., Konigshoff M. et al. Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. J. Clin. Invest. 2009; 119: 2550–2563.Scotton C.J., Chambers R.C. Pulmonary fibrosis. Br. J. Pharmacol. 2011; 163: 141–172.Scotton C.J., Chambers R.C. Pulmonary fibrosis. Br. J. Pharmacol. 2011; 163: 141–172.Sun Z."M., Li F."Y., Wang L. et al. Expression of fibroblast specific protein"1 in pleural tuberculosis and its clinical biological significance. World J. Surg. Oncol. 2014; 12: 151.Sun Z."M., Li F."Y., Wang L. et al. Expression of fibroblast specific protein"1 in pleural tuberculosis and its clinical biological significance. World J. Surg. Oncol. 2014; 12: 151.Miles S.E., Sandrini A., Johnson A.R., Yates D.H. Clinical consequences of asbestos"related diffuse pleural thickening: A review. J. Occup. Med. Toxicol. 2008; 3: 1–10.Miles S.E., Sandrini A., Johnson A.R., Yates D.H. Clinical consequences of asbestos"related diffuse pleural thickening: A review. J. Occup. Med. Toxicol. 2008; 3: 1–10.Huang S.X.L., Jaurand M."C., Kamp D.W. et al. Role of Mutagenicity in asbestos fiber"induced carcinogenicity and other diseases. J. Toxicol. Environment. Health. Part B. Crit. Rev. 2011; 14 (1–4): 179–245.Huang S.X.L., Jaurand M."C., Kamp D.W. et al. Role of Mutagenicity in asbestos fiber"induced carcinogenicity and other diseases. J. Toxicol. Environment. Health. Part B. Crit. Rev. 2011; 14 (1–4): 179–245.Broaddus V.C., Everitt J.I., Black B., Kane A.B. Non"neoplastic and neoplastic pleural endpoints following fiber exposure. J. Toxicol. Environ. Health. Part B. Crit. Rev. 2011; 14 (1–4): 153–178.Broaddus V.C., Everitt J.I., Black B., Kane A.B. Non"neoplastic and neoplastic pleural endpoints following fiber exposure. J. Toxicol. Environ. Health. Part B. Crit. Rev. 2011; 14 (1–4): 153–178.Sasse S.A., Jadus M.R., Kukes G.D. Pleural fluid transforming growth factor"β1 correlates with pleural fibrosis in experimental empyema. Am. J. Respir. Crit. Care Med. 2003; 168: 700–705.Sasse S.A., Jadus M.R., Kukes G.D. Pleural fluid transforming growth factor"β1 correlates with pleural fibrosis in experimental empyema. Am. J. Respir. Crit. Care Med. 2003; 168: 700–705.Papaioannou A.I., Kostikas K., Kollia P., Gourgoulianis K.I. Clinical implications for vascular endothelial growth factor in the lung: friend or foe? Respir. Res. 2006; 7: 128.Papaioannou A.I., Kostikas K., Kollia P., Gourgoulianis K.I. Clinical implications for vascular endothelial growth factor in the lung: friend or foe? Respir. Res. 2006; 7: 128.Compernolle V., Brusselmans K., Acker T. et al. Loss of HIF"2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat. Med. 2002; 8 (7): 702–710.Compernolle V., Brusselmans K., Acker T. et al. Loss of HIF"2alpha and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat. Med. 2002; 8 (7): 702–710.Kazi A.S., Lotfi S., Goncharova E.A. et al. Vascular endothelial growth factor"induced secretion of fibronectin is ERK dependent. Am. J. Physiol. Lung Cell. Mol. Physiol. 2004; 286 (3): 539–545.Kazi A.S., Lotfi S., Goncharova E.A. et al. Vascular endothelial growth factor"induced secretion of fibronectin is ERK dependent. Am. J. Physiol. Lung Cell. Mol. Physiol. 2004; 286 (3): 539–545.Mura M., dos Santos C.C., Stewart D., Liu M. Vascular endothelial growth factor and related molecules in acute lung injury. J. Appl. Physiol. 2004; 97 (5): 1605–1617.Mura M., dos Santos C.C., Stewart D., Liu M. Vascular endothelial growth factor and related molecules in acute lung injury. J. Appl. Physiol. 2004; 97 (5): 1605–1617.Grove C.S., Lee Y.C. Vascular endothelial growth factor: the key mediator in pleural effusion formation. Curr. Opin. Pulm. Med. 2002; 8 (4): 294–301.Grove C.S., Lee Y.C. Vascular endothelial growth factor: the key mediator in pleural effusion formation. Curr. Opin. Pulm. Med. 2002; 8 (4): 294–301.Mohammed K.A., Nasreen N., Hardwick J. et al. Bacterial induction of pleural mesothelial monolayer barrier dysfunction. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001; 281 (1): 119–125.Mohammed K.A., Nasreen N., Hardwick J. et al. Bacterial induction of pleural mesothelial monolayer barrier dysfunction. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001; 281 (1): 119–125.Humadi H.Y.A. Matrix Metalloproteinases and TIMPs Expression in Pleural Effusion of Different Origins. Thesis submitted for fulfillment of Master Degree in Pulmonology. Faculty of Medicine Cairo University; 2012.Humadi H.Y.A. Matrix Metalloproteinases and TIMPs Expression in Pleural Effusion of Different Origins. Thesis submitted for fulfillment of Master Degree in Pulmonology. Faculty of Medicine Cairo University; 2012.Oikonomidi S., Kostikas K., Kalomenidis I. et al. Matrix metalloproteinase levels in the differentiation of parapneumonic pleural effusions. Respiration. 2010; 80: 285–291.Oikonomidi S., Kostikas K., Kalomenidis I. et al. Matrix metalloproteinase levels in the differentiation of parapneumonic pleural effusions. Respiration. 2010; 80: 285–291.El Margoushya N.M., Khaleel A.T. Metalloproteinase and tissue inhibitor of metalloproteinase in tuberculosis and malignant pleural effusion. Egypt. J. Chest Dis. Tub. 2013; 62 (2): 235–240.El Margoushya N.M., Khaleel A.T. Metalloproteinase and tissue inhibitor of metalloproteinase in tuberculosis and malignant pleural effusion. Egypt. J. Chest Dis. Tub. 2013; 62 (2): 235–240.Yamashita C.M., Dolgonos L., Zemans R.L. et al. Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis. Am. J. Pathol. 2011; 179( 4): 1733–1745.Yamashita C.M., Dolgonos L., Zemans R.L. et al. Matrix metalloproteinase 3 is a mediator of pulmonary fibrosis. Am. J. Pathol. 2011; 179( 4): 1733–1745.Kim J.Y., Choeng H.C., Ahn C. Cho S."H. Early and late changes of MMP"2 and MMP"9 in bleomycin"induced pulmonary fibrosis. Yonsei Med. J. 2009; 50 (1): 68–77.Kim J.Y., Choeng H.C., Ahn C. Cho S."H. Early and late changes of MMP"2 and MMP"9 in bleomycin"induced pulmonary fibrosis. Yonsei Med. J. 2009; 50 (1): 68–77.Sheen P., O’Kane C.M., Chaudhary K. et al. High MMP"9 activity characterises pleural tuberculosis correlating with granuloma formation. Eur. Respir. J. 2009; 33 (1): 134–141.Sheen P., O’Kane C.M., Chaudhary K. et al. High MMP"9 activity characterises pleural tuberculosis correlating with granuloma formation. Eur. Respir. J. 2009; 33 (1): 134–141.

The authors declare that there are no conflicts of interest present.