Научная статья на тему 'Features of the immune status of patients with community-acquired viral pneumonia which was complicated by development of the acute respiratory distress syndrome'

Features of the immune status of patients with community-acquired viral pneumonia which was complicated by development of the acute respiratory distress syndrome Текст научной статьи по специальности «Фундаментальная медицина»

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Ключевые слова
COMMUNITY-ACQUIRED VIRAL PNEUMONIA / ACUTE RESPIRATORY DISTRESS SYNDROME / ARDS / IMMUNE RESPONSE

Аннотация научной статьи по фундаментальной медицине, автор научной работы — Sviatlitskaya Volha Ivanauna

30 patients with community-acquired viral pneumonia with laboratory confirmed diagnoses virus of an influenza A H1N1 (n=17) and a parainfluenza (n=13), complicated by the development of the acute respiratory a distress syndrome are examined. At these patients was established: decrease of proliferative activity of T lymphocytes, of quantity of serum immunoglobulins of a class M and G and active formation of immune complexes. At the died patients direct correlation dependence of quantity of the mononuclear cells which entered an apoptosis with the relative number of natural killers and absolute quantity of CD8+ of cytotoxic T-lymphocytes is established (R=0,71 and R=0,67 respectively, р < 0,05). It confirms a role of cellular immune reactions in development of the activation induced death of lymphocytes at serious viral pneumonia

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Текст научной работы на тему «Features of the immune status of patients with community-acquired viral pneumonia which was complicated by development of the acute respiratory distress syndrome»

Summarizing the existing evidences of this study about quality of life indicators we can conclude:

Multiple Sclerosis reduces real choices and opportunities to individuals, restricting individual actions and independence with a direct impact on quality of life.

The fulfillment of social roles and functions is linked to the degree of disability. Lack of solidarity as an important societal value show that families and communities has lost the important role of the past even in Albanian society.

The analysis of the data also highlighted a trend manifestation of isolation by the interviewed subjects leading to the reduction of social relations and social exclusion.

Disability in Multiple sclerosis was not directly correlated with age of patients but there was a correlation between disability and disease duration. Low levels of MSSS score are recorded in patients suffering from years by multiple sclerosis.

A multidisciplinary rehabilitation and intervention program improve the quality of life of people with multiple sclerosis and reduce the grade of disability. The presence of clinicists, psychologists, sociologists, social workers, physioterapists as an multidisiplinary team in clinical unit can improve the overall quality of life of patients with multiple scleorosis.

References:

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2. Stevenson V. L., Playford E. D. Rehabilitation and MS. Int MS J. - 2007. - September; - 14 (3):85-92.

3. Amato M. P., Goretti B, Ghezzi A., Lori S., Zipoli V., Portaccio E. et al. Cognitive and psychosocial features of childhood and juvenile MS. Neurology. - 2008. - May 13; - 70 (20):1891-7. - doi: 10.1212/01.

4. Lanzillo R., Chiodi A., Carotenuto A., Magri V., Napolitano A., Liuzzi R. et al. Quality oflife and cognitive functions in early onset multiple sclerosis. Eur J Paediatr Neurol. - 2016. - Jan; - 20 (1):158-63. - doi: 10.1016/j. ejpn.2015.08.005. - Epub - 2015. - September 3.

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7. Kurtzke J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. - 1983. - Novbrer; - 33 (11):1444-52.

8. Sherbourne C. D., Stewart A. L. The MOS Social Support Survey. Soc Sci Med. - 1991; - 32 (6):705-14.

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DOI: http://dx.doi.org/10.20534/ELBLS-17-1-39-42

Sviatlitskaya Volha Ivanauna, MD, Associate professor of Belarusian Medical Academy of Post-Graduate Education E-mail: goodlife@tut.by

Features of the immune status of patients with community-acquired viral pneumonia which was complicated by development of the acute respiratory distress syndrome

Abstract: 30 patients with community-acquired viral pneumonia with laboratory confirmed diagnoses virus of an influenza A H1N1 (n=17) and a parainfluenza (n=13), complicated by the development of the acute respiratory a distress syndrome are examined. At these patients was established: decrease of proliferative activity of T lymphocytes, of quantity of serum immunoglobulins of a class M and G and active formation of immune complexes. At the died patients direct correlation dependence of quantity of the mononuclear cells which entered an apoptosis with the relative number of natural killers and absolute

quantity of CD8+ of cytotoxic T-lymphocytes is established (R=0,71 and R=0,67 respectively, p < 0,05). It confirms a role of cellular immune reactions in development of the activation induced death of lymphocytes at serious viral pneumonia.

Keywords: community-acquired viral pneumonia, acute respiratory distress syndrome, ARDS, immune response.

Relevance of the topic

Viral lower respiratory tract infections are the most frequent reason of a case rate among children and adults. Now among the most frequent originators of community-acquired viral pneumonia an influenza virus, a parainfluenza and human respiratory syncytial virus (RS-virus) takes the leading positions. At the same time, viruses cause a damage to a bronchial or alveolar epithelium, disturbance of a nervous regulation of a bronchial tonus and microcirculation, and suppression of factors of nonspecific and specific antibacterial protection. These disturbances not only promote a bacterial infecting of a pulmonary tissue, but also increase risk of serious injury of lungs with development of the acute respiratory distress syndrome (ARDS).

Unfortunately, most often failures in treatment of serious community-acquired viral pneumonia are bound to development ofARDS. Despite development of medical technologies, the mortality at ARDS remains high, making from 24 to 75% and more at development of multiple organ dysfunction syndrome, averaging 40-46%.

In modern references, the immunologic status of patients with severe community-acquired viral pneumonia is presented generally by the quantitative characteristic of subpopulation of the T-cells link of immunity, proteins of an acute phase of an inflammation and immunoglobulins. At the same time, in development of serious injury of lungs the role of natural killers (NK) — the main effector cells of congenital immunity, minor populations of lymphocytes (NKT lymphocytes, yST-cells), and processes of the induced death of the activated lymphocytes is insufficiently studied [1; 2; 3].

In this context, the purpose of our research was to estimate a condition of systemic immunity and markers of the programmed cellular death (an apoptosis and a necrosis) in patients with community-acquired viral pneumonia that was complicated by development of ARDS.

Materials and methods

Thirty patients with severe forms of the community-acquired viral pneumonia with laboratory confirmed diagnoses of influenza A H1N1 (n=17) and parainfluenza viral infections (n=13), complicated by the development of ARDS who were treated in the ICU of City clinical hospital of emergency medical care ofMinsk, and

13 practically healthy persons (control group) were examined. Average age of patients made 46,1±12,6 years; 18 men (60%) and 12 women (40%). The mortality made 16,6% (n=5). The control group was comparable on gender and age to the studied group of patients.

The study included patients who meet the following criteria: acute onset of the disease; time of onset (fer-vescence > 38 ° C) prior to the development of ARDS is not more than 7 days; diffuse bilateral infiltration on radiographs; respiratory index (RI, PaO2/FiO2) < 300 mm Hg; no signs of cardiogenic pulmonary edema; the need for respiratory support.

Exclusion criteria in the study were as follows: age of patients less than 18 years old and over 80 years; if the patient has severe concomitant respiratory diseases: chronic obstructive pulmonary disease, asthma and others.

Hypoxemia has been quantified by the PaO2/FiO2 ratio (the ratio of pulmonary arterial oxygen tension to the fraction of inspired oxygen concentration). Determination of arterial blood gases were performed in patients at the time of admission to the ICU, after transfer to the ventilator, in the process of selection of the ventilation mode setting, but at least 2 times a day with the use of modular analyzer «ABL800 FLEX», Radiometer (Denmark).

The research of subpopulation structure of immunocompetent cells was conducted by method of flowing cytometry with use of monoclonal antibodies to superficial antigens of CD3, CD4, CD8, CD56, CD19 (Beckman Coulter, USA). Assessment of markers of the programmed cellular death was carried out with use of stains annexin V and a propidium iodide (Beckman Coulter, USA).

Statistical analysis of the results of research carried out on a computer (Windows 8) using the software package Microsoft Excel. Check the normality of the distribution of the results was carried out using W-Shapiro-Wilk test. Since most of the studied parameters characterized nonparametric distribution, the results are expressed as median and interquartile range (Me [q25-q75]). Significant differences were assessed using the U-Mann Whitney test. The difference compared indicators recognized significant at a value of p < 0,05 and p < 0,01.

Results and discussion

At patients of the main group were found: relative and absolute lymphopenia, thrombocytopenia and anemia. Similar changes in indicators of a blood are characteristic of systemic inflammatory process at patients with a serious viral infection. Also in a leukocyte formula reveal shift to the left to band, juvenile form of leucocytes and, in some cases, myelocytes and toxic granularity of neutrophils.

At a research of functional activity of polymorphonuclear neutrophils, depression of a phagocytic coefficient and coefficient of completeness of phagocytosis at patients of the main group in comparison with control group is established. Observed oppression of the absorption and digesting ability of neutrophils can be result as disturbance of processes of capture and a killing of cells, the reduced activity of enzymatic system and activity of the receptor device, and because of an exit of unripe forms of neutrophils in a peripheral blood.

At patients of the main group discovered decrease of absolute quantity of all subpopulations of T lymphocytes (CD3+, CD3+4+ and CD3+8+ of cells) and a tendency to decrease of absolute number of natural killers (CD56+) owing to an absolute lymphopenia what corresponds to the data obtained by other authors [1, 3]. At the same time, against the background of a lymphopenia at patients it was enlarged relative quantity of

NKT cells (CD3+56+) — a unique subclass of T-cells to which phenotypical features of T-lymphocytes and natural killers are inherent. This subclass of cells participates both in cytotoxic reactions, and in adjustment of production of the major cytokines defining a current of an immune response at this pathology.

At patients with ARDS find out decrease of level of serum immunoglobulins of the classes G and M along with augmentation of quantity of the circulating immune complexes is established that it is characteristic of a productive phase of an immune response on the antigenic stimulation, which is followed, by an active antibody formation and formation of immune complexes. In the main group of patients the enlarged concentration of an immunoglobulin A is also taped that reflects involvement mucous in inflammatory process.

The comparative analysis ofthe proliferative response of T-lymphocytes to nonspecific activation at cultivation in the presence of a phytohemagglutinin as indicator of functional activity of cells, the mitogen — the induced proliferation of T-cells at the studied group ofpatients on comparison with healthy donors 9,6 (8,16-10,65) c. u. showed reliable depression of an index of stimulation 5,8 (3,66-8,0) c. u.

Indicators of the immune status of patients with community-acquired viral pneumonia that was complicated by development of ARDS are presented in table 1.

Table 1. - The immune status of patients with community-acquired viral pneumonia that was complicated by development of ARDS

Parameters Control group (n=13) Main group (n=30)

1 2 3

Total leukocyte,10 9/L 5,9 (3,2*7,6) 7,0 (1,8*14,1)

Lymphocyte,% 27,4 (15,1*33,3) 12,4 (5,2*27,1)*

Lymphocyte, 10 9/L 1,6 (0,6*2,0) 0,9 (0,2-1,7)*

CD3+ T-lymphocyte,% 66,2 (63,3*74,3) 70,7 (53,9*78,8)

CD3+ T-lymphocyte, 10 9/L 1,1 (0,5*1,5) 0,6 (0,1*1,3)*

CD3+4+ T-helper cells,% 62,6 (58,9*73,9) 64,3 (50,9*78,0)

CD3+4+ T-helper cells, 10 6/L 703,1 (303,5*859,7) 345,8 (112,8*716,8)*

CD3+8+ CTL,% 25,9 (23,0*29,4) 27,9 (18,0*46,4)

CD3+8+ CTL, 10 6/L 220,9 (190,2*480,1)* 149,9 (42,2*550,1)*

CD4+/CD8+, c. u. 2,29 (1,7*3,3) 2,23 (0,9*4,5)

CD56+ NK T cells,% 15,27 (13,5*18,4) 11,8 (4,4*35,7)

CD56+ NK T cells, 10 6/L 182,8 (118,0*393,6) 136,6 (35,5*256,1)

CD3+56+ NK T cells,% 0,21 (0,08*0,5) 0,72 (0,2*5,4)*

CD3+56+ NK T cells, 10 6/a 2,29 (0,5*5,7) 2,68 (0,5*19,2)

CD19+ B- lymphocyte,% 12,20 (5,7*14,6) 11,21 (1,7*26,7)

CD19+ B- lymphocyte, 10 6/L 134,17 (89,3*179,5) 99,41 (68,9*233,6)

Ig G, g/L 14,4 (10,2*16,8) 8,5 (4,7*16,6) *

Ig M g/L 1,8 (1,3*2,8) 0,67 (0,1*1,27) *

1 2 3

Ig A, g/L 1,7 (0,9+2,0) 3,07 (1,3+13,1)

Circulating immune complexes, c. u. 57(33+70) 105 (89+157)*

Phagocytic index,% 76,7 (70,0+81,1) 62,5 (43,0+76,0)*

Completion rate of phagocytosis, c.u 1,1 (0,9+1,2) 0,9 (0,5+1,1)*

Note: * — index of reliability in relation to parameters of patients with obesity (P < 0.05).

It is known that NK cells are the most dynamic population of lymphocytes localized generally in a peripheral blood. It is considered that these cells possess rather wide range of a reactivity and reflect a condition of nonspecific cellular reactions before development of a specific immune response. At the initial stages after a becoming infected, there is an exit of NK cells from lymph nodes in a peripheral blood. During a productive stage of immune process depression of their level to the minimum values results from migration in the lesion center. The taped variability of this population of lymphocytes can serve as effective criterion of monitoring of a course of a disease.

At patients with the community-acquired viral pneumonia complicated by an nosocomial infection higher percent of CD8+ of specific cytotoxic T lymphocytes (CTL) in comparison with patients with pneumonia, uncomplicated nosocomial infection became perceptible 41,3 (28,0-46,2)% and 18,6 (16,5-27,6)%, respectively, (p < 0,05).

Intensity of processes of a destruction at the systemic level is estimated by definition of markers of the programmed cellular death of mononuclear of a peripheral blood. We established reliable augmentation of quantity of cells with apoptosis signs 14,7 (10,8+25,2)% and a secondary necrosis 6,8 (1,5+14,8)% at patients of the main group regardless

of a disease outcome in comparison with similar indicators of healthy donors 6,9 (5,6+8,4)% and 0,4 (0,2+0,97)%, respectively.

However, at the died patients direct correlation dependence of quantity of the mononuclear cells which entered an apoptosis with the relative number of natural killers and absolute quantity of CD8+ of cytotoxic T lymphocytes is established (R=0,71 and R=0,67 respectively, p < 0,05). It confirms a role of cellular immune reactions in development of the activation induced death of lymphocytes at serious viral pneumonia.

Conclusions

Thus, at patients with community-acquired viral pneumonia, wich complicated by the development of the ARDS is observed: decrease of proliferative activity of T lymphocytes, of quantity of serum immunoglobulins of a class M and G and active formation of immune complexes. It corresponds to the productive phase of an immune response aimed on elimination of an antigen from an organism. Lability specific and nonspecific the NK cells, correlating with cellular death, and depression of completeness of phagocytosis by neutrophils can be the cornerstone of development of methodological approaches of monitoring of a course of an infectious disease.

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2. McGill J. Innate immune control and regulation of influenza virus infections/J. McGill J. W. Heusel, K. L. Legge//J. Leukoc. Biol. - 2009. - Vol. 86, - No 4. - P. 803-12.

3. Tamura S. Defense mechanisms against influenza virus infection in the respiratory tract mucosa/S. Tamura, T. Kurata//Jpn. J. Infect. Dis. - 2004. - Vol. 57. - P. 236-47.

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