Luận án nghiên cứu đặc điểm lâm sàng, cận lâm sàng, vi khuẩn gây bệnh và biến đổi cytokine huyết thanh ở bệnh nhân viêm phổi cộng đồng nhập viện tại hải phòng tt

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENSE MILITARY MEDICAL UNIVERSITY LE THI DIEU HIEN STUDY ON CLINICAL, SUBCLINICAL CHARACTERISTICS, BACTERIAL PATHOGEN, SERUM CYTOKINE IN COMMU[.]

MILITARY MEDICAL UNIVERSITY

LE THI DIEU HIEN

STUDY ON CLINICAL, SUBCLINICAL

CHARACTERISTICS, BACTERIAL PATHOGEN, SERUM CYTOKINE IN COMMUNITY ACQUIRED PNEUMONIA PATIENTS ADMITTED AT

HOSPITAL IN HAI PHONG

Specialization: Internal medicine

Number : 9720107

SUMMARY OF DOCTOR THESIS

HA NOI - 2022

Academic supervisor:

1 Assoc Prof TA BA THANG, MD, PhD

2 Assoc Prof MAI XUAN KHAN

Reviewer 1: Assoc Prof Phan Thu Phương, MD, PhD

Reviewer 2: Assoc Prof Phạm Quốc Hoàn, MD, PhD

Reviewer 3: Assoc Prof Nguyễn Viết Nhung, MD, PhD

The thesis will defend the Committee of Military MedicalUniversity

Time : Hour date month year

Location for search the thesis:

2 Military Medical University Library

Community-acquired pneumonia (CAP) is one of the lowerrespiratory tract infections with high morbidity and mortalityworldwide, especially in the elderly and with chronic comorbidities.Currently, the common cause of CAP is still caused by bacteria, inwhich the leading cause is caused by typical bacteria (S pneumoniaeand H Influenzae) However, there are changes in the distribution ofbacteria as well as antibiotic susceptibility according to geography,the degree of pneumonia as well as the patient's location Viet Tiep-Hai Phong Hospital is the central general hospital of the provinceand the last line of the northern coastal provinces There have beensome studies on clinical, subclinical and etiology of CAP at somehospitals in Hai Phong, but there has not been any in-depth research

on CAP caused by bacteria Cytokines such as Tumor necrosisfactor-α (TNF-α), Interleukine-6 (IL-6), Interleukine-10 (IL-10) play

a major role in the inflammatory mechanism in CAP Changes inthese cytokines are associated with the severity of pneumonia as well

as treatment outcomes However, the results on the changes of serumcytokines are still different in the studies, and there are no specificresults on their changes in the group of patients with bacterial CAP

For this reason, we carried out the study "Study on clinical, subclinical characteristics, bacterial pathogen and serum cytokine in community acquired pneumonia patients admitted at hospital in Hai Phong" This study aimed including:

1 Clinical, subclinical characteristics and antibiotic resistance of bacteria in CAP patients at hospital in Hai Phong.

2 Evaluation of changes of levels TNF-α, IL-6, and IL-10 in serum and the relationship with clinical and subclinical characteristics in CAP patients at hospital in Hai Phong.

2 The summary of new main scientific contribution of the thesis

The research results of the thesis have some contributions to therespiratory specialty as follows:

- Characteristics of patients with community-acquired bacterialpneumonia hospitalized at Viet Tiep Friendship Hospital - Hai

Phong: the age group ≥60 mainly encountered (74.3%); Theproportion of male patients is higher than female The rate of co-morbidities is high (60.2%) The severity of the disease was found in44.8% On chest X-ray, diffuse lesions accounted for the majority(82.0%) The result of sputum culture was that Gram-negativebacteria accounted for the majority (84.6%), of which K.pneumoniae30.7%, P.aeruginosa 24.3% The percentage of Gram-positivebacteria was 15.4% The rate of antibiotic-sensitive bacteria was57.6%, antibiotic resistance 42.3% (resistance to 1 antibiotic was7.6%, resistance to multiple antibiotics was 34.5%).

- Serum levels of TNF-α, IL-6 and IL-10 at the time of admissionwere all higher than those of healthy subjects Serum IL-6concentration on day 7 after treatment decreased significantlycompared to the time of admission Increased levels of cytokinesTNF-α, IL-6 were correlated with the average lesion area on chest X-ray In the group of patients who isolated Gram-positive bacteria, theaverage serum IL-10 concentration on day 1 was higher than that inthe group of patients who isolated Gram-negative bacteria (p<0.05).The percentage of patients with increased serum IL-6 levels on day 1

in the group of patients with good progress was higher than in thegroup of patients with severe progression (p<0.05)

The research results contribute to improving the efficiency ofdiagnosis, treatment and prognosis of CAP caused by hospitalizedbacteria

3 The structure of the thesis

The major of the thesis was 143 pages: Introduction (2pages), Overview (43 pages), Subjects and methods (23 pages),Results (42 pages), Discussion (30 pages), Conclusion (2 pages),Recommendations (1 pages) This thesis was 34 tables, 10 figures,and 155 references (30 Vietnamese references, 121 Englishreferences; 58 references within last 5 years) and Appendix list ofresearch subjects and medical records

Chapter 1: OVERVIEW 1.1 COMMUNITY – ACQUIRED PNEUMONIA

1.1.1 Definition of community – acquired pneumonia

1.1.2 Epidemiology of community – acquired pneumonia

1.1.3 Pathogenesis of community – acquired pneumonia

1.1.4 Symptoms of community – acquired pneumonia

1.1.5 Subclinical symptoms of community – acquired pneumonia 1.1.6 Diagnosis of community – acquired pneumonia

1.2 ETOLOGY BACTERIA AND CHARECTERICS OF ANTIBIOTIC RESISTANCE OF BACTERIA CAUSING COMMUNITY – ACQUIRED PNEUMONIA

1.2.1 Bacterial causes of community-acquired pneumonia

1.2.2 Bacterial detection methods

1.2.3 Antibiotic resistance of bacteria causing acquired pneumonia

community-1.3 ROLES OF CYTOKINE IN COMMUNITY-ACQUIRED PNEUMONIA

1.3.1 The concept, role, and origin of cytokines

1.3.2 Origin of TNF-Alpha, IL-6, and IL-10

1.3.2.1 TNF- α (Tumour Necrosis Factor- Alpha)

1.3.2.2 Interleukine-6 (IL-6)

1.3.2.3 Interleukine-10 (IL-10)

1.3.3 Cytokine test method

1.4 RESEARCH RELATED TO THIS RESEARCH THEME

1.4.1 Research on clinical, bacteriological characteristics and prognosis of community-acquired pneumonia

1.4.2 Research on changes of levels of cytokine in serum

Chapter 2: RESEARCH SUBJECTS AND METHODS 2.1 RESEARCH SUBJECTS

- Disease group: 78 adult patients with community-acquiredbacterial pneumonia, hospitalized for inpatient treatment at Viet Tiepgeneral Hospital - Hai Phong, from January 2017 to December 2019

- Control group: 34 people who came hospital for health check-up atthe medical examination department of Hai Phong MedicalUniversity Hospital from January 2017 to December 2019 Thepeople in control group were tested levels of cytokines in serum as avalue for comparing to disease group

2.1.1 Subjects

2.1.1.1 Selection criteria for disease group

- The patient was diagnosed with CAP according to the diagnosticcriteria of the American Thoracic Society 2001 [27] and updatedversion 2014 [28]:

+ The symptoms of lower respiratory infection: cough, sputum,sputum with dark color, shortness of breath, with or without fever.+ Hear crackles in the lungs

+ Chest X-ray showed infiltrates

- Patients with results of sputum quantitative bacterial culture

- 16 years old or older

- Agree for participating this research

2.1.1.2 Selection criteria for control group

- People who were healthy in the past and present, and they did nothave immunodeficiency diseases, cancer, autoimmune diseases,chronic diseases, and infections

- Agree for participating this research

2.1.2 Exclusion criteria

2.1.2.1 Disease group

- The patients who have another co-morbidity regarding respiratorydisease such as tuberculosis, bronchiectasis, chronic obstructivepulmonary disease (COPD)

- With diseases such as cancer, autoimmune diseases, otherinfections

- Using corticosteroid for treatment within one month

2.1.2.2 Control group

- With an acute infection within one month

- Did not agree to participate in the research

2.2 RESEARCH CONTENTS

2.2.1 Clinical, paraclinical characteristics and antibiotic resistance in patients with community-acquired bacterial pneumonia

- Clinical: general characteristics of the patients, functionalsymptoms, physical symptoms, complications, disease severity,treatment results

- Subclinical: results of blood tests, blood biochemistry, chest X-ray,inflammatory markers (CRP and PCT)

- Results of sputum quantitative bacterial culture and antibioticresistance of pathogenic bacteria

2.2.2 Evaluation of changes of levels TNF-α, IL-6, and IL-10 in serum and their relationship with clinical and paraclinical charecteriistics

- Valuate the changes of TNF-α, IL-6, IL-10 in serum and each type

of cytokine among the disease group compared with the controlgroup

- Assess the relationship between cytokines with fever symptoms,age group, severity of disease, complications, treatment results

- Evaluate the relationship between cytokines with amount of whiteblood cells (WBCs), chest X-ray, results of bacterial isolation

2.3 METHODS 

2.3.1 Study design

Cross-sectional study, longitudinal follow-up study

2.3.2 Study location and period

The study was conducted at the department of respiratorymedicine - Viet Tiep general Hospital, Hai Phong and the department

of medical examination - Hai Phong Medical University Hospital,from January 2017 to December 2019

2.3.3 Sample size

Sample size: we selected a convenient sample Subjects wasadult patients diagnosed with CAP, hospitalized for inpatienttreatment at Viet Tiep general Hospital - Hai Phong, from January

2017 to December 2019

Sampling method: The subjects was collected by aconvenient method After the patient is admitted to the hospital, theywere asked participation this research and they was accumulatingduring the research period The patients who met the researcheligibility in both inclusion criteria and exclusion criteria such aswith diagnosed CAP and hospitalized for treatment at theRespiratory Department - Viet Tiep general Hospital, Hai Phongwere selected in the sample

During the study period from 1/2017 to 12/2019, wecollected 215 patients with CAP, in which 78 patients met theresearch criteria for analysis (with isolated bacteria in phlegmspecimens)

Chapter 3: RESEARCH RESULTS 3.1 CLINICAL, SUBCLINICAL CHARATERISTICS AND ANTIBIOTIC RESISTANCE OF BACTERIA IN CAP PATIENTS AT HOSPITAL

3.1.1 Characteristics of patients

Table 3.1 Age and gender characteristics of patients

3.1.2 Clinical characteristics of patients

Table 3.4 Physical symptoms of patients

Table 3.5 Systemic symptoms of study subjects

Table 3.6 Respiratory physical symptoms of the study subjects

Figure 3.2 Complications of patients

The figure indicated that pleural effusion was 10.3% andacute respiratory distress syndrome was 6.4%

Figure 3.3 Severity score according to CURB-65

This figure showed the patients with CURB-65 < 2 were43(55.12%) and the patients with CURB-65 ≥ 2 were 44.88%

3.1.3 Subclinical characteristics of paitients

Table 3.9 Blood biochemical and inflammatory markers

Table 3.11 Characteristic of chest X-ray

This result showed that the damage in chest X-ray in the right lungwas most common with 43(55.1%) and the damage in chest X-ray inboth was 12.8%

Figure 3.6 The result of antibiogram of Klebsiella pneumoniae

Klebsiella pneumoniae indicated a resistant to most cephalosporins.

The carbapenem group was also resistant up to 1/24 (4.1%)

Figure 3.7 The result of antibiogram of Acinetobacter baumannii

The percentage of resistance of Acinetobacter baumannii

bacteria was high with the Cephalosporin group

Figure 3.10 The results of antibiogram of Streptococcus pneumonia

The result showed that the Streptocosus pneumonia has a high

susceptibility to antibiotics

3.2 EVALUATION OF CHANGES OF LEVELS TNF-α IL-6 and IL-10 IN SERUM AND RELATIONSHIP WITH CLINICAL AND SUBCLINICAL CHARACTERISTICS IN CAP PATIENTS AT HOSPITAL IN HAI PHONG

3.2.1 The changes of levels of cytokine in serum

Table 3.16 Changes in mean levels of serum cytokines Cytokin

Day 7n=78 (3)TNF-α

(pg/mL)

0.350.18-1.00

0.760.43-1.42

1.010.55-2.37

p1.2=0.020*p2.3=0.107**IL- 6

(pg/mL)

1.110.79-1.92

2.150.79-6.98

1.120.70-2.66

p1.2=0.022*p2.3=0.003**IL- 10

(pg/mL)

1.090.65-1.63

1.180.45-2.58

1.110.74-1.91

p1.2=0.349*p2.3=0.084**

* Mann Whitney test ** Wilcoxon signrank test

The mean serum TNF-α levels on days 1 and 7 were higher than that

of healthy subject, but there was no difference between days 1 and 7

3.2.2 Relationship between levels of cytokine with symptoms Table 3.22 Relationship between average cytokine levels on day 1

with severity score

Cytokin CURB-65 <2 CURB-65 ≥2 n=43 % n=35 % p

TNF-α

(pg/ NormalHigh 1132 68.7551.61 305 31.25 0.219*48.39

ml) (p25-p75)Median 0.25-1.290.71 0.53-1.450.81 0.245**IL-6

(pg/

ml)

NormalHigh 1528 57.6953.85 1124 42.31 0.747*46.15Median

(p25-p75) 0.76-14.791.89 0.96-5.432.55 0.912**IL-10

(pg/

ml)

NormalHigh 2023 57.1453.49 1520 42.86 0.747*46.51Median

(p25-p75) 0.41-1.991.15 0.51-3.221.58 0.310**

* Chi-Square test ** Wilcoxon rank-sum test

The result showed that there was no significant between levels ofTNF-α, IL-6 và IL-10 and the median CURB-65 score (p>0.05)

3.2.3 Relationship between levels of cytokin with subclinical characteristics

Bảng 3.26 The relationship between levels of cytokine at the 1 day

and chest X-ray

Cytokin Large Lesion of chest X-ray Moderate Small p

Median

(p25-p75)

0.680.38-10.92 0.55-1.560.77 0.24-1.350.71 0.557**

Median

(p25-p75)

2.80.55-14.57 1.19-7.833.93 0.7-2.311.22 0.053**IL-10

(pg/ Normal 5 41.67 20 50 10 38.46 0.635*

* Chi-Square test **Kruskal-Wallis test

In the group of patients with moderate lung lesions on X-ray, themedian levels of TNF-α, IL-6 was higher than that of patients withlarge and small lung lesion, but the result did not show significantly(p>0.05)

3.2.4 Multivariate logistic regression analysis on high cytokin status analysis and factors of history, pathological symptom and lesions on X-ray

Bảng 3.30 Multiple logistic regression analysis on gender, sputum,

Chest X-ray, blood test and TNF-α

Variables OR Increase levels of TNF- α p 95%CI

Gender (men=0 women=1) 2.18 0.234 0.6-7.91Sputum (yes=1; no=0) 3.34 0.315 0.317-35.29Pleural effusion (yes=1 no=0) 4.35 0.072 0.88-21.65

There was relationship between high TNF-α with levels ofCRP (OR=1.01; p<0.05)

Bảng 3.31 Multivariate logistic regression analysis on gender.

Sputum, Chest X-ray, blood test, and high IL-6

Variable OR Increase levels of IL-6 p 95%CI

Gender (men=0 women=1) 0.55 0.27 0.18-1.61

Pleural effusion (yes=1 no=0) 1.76 0.41 0.46-6.78

Bảng 3.32 Multivariate logistic regression analysis on gender.

Sputum, Chest X-ray, blood test, and high IL-10

Variable OR Increase levels of IL-10 p 95%CI

Gender (men=0 women=1) 1.07 0.89 0.41-2.79

Pleural effusion (yes=1 no=0) 0.9 0.87 0.26-3.18

There was not relationship between high IL-10 with gender,Sputum, pleural effusion, zone of lesions on the chest X-ray, levels

of Ure and CRP (p>0.05)