CN109001457A - A kind of molecular marker combines the application in the risk assessment of patients with pneumonia - Google Patents

Abstract

The present invention relates to immunodiagnosis fields, and in particular to a kind of molecular marker combines the application in the risk assessment of patients with pneumonia.Molecular marker combination in the present invention includes PCT and CRP, PCT the and CRP content of different old age in course of disease stage infectious pneumonia patient's bodies is distinguished with otherness, and the AUC value of PCT is that the AUC value of 0.868, CRP is 0.790.In the present invention, the molecular marker combined content in the patients with pneumonia serum of the different courses of disease has significant difference, facilitates auxiliary diagnosis to the detection of molecular marker combination, disease classification, instructs antibiotic treatment, examination of curative effect and prognosis evaluation.

Description

A kind of molecular marker combines the application in the risk assessment of patients with pneumonia

Technical field

The present invention relates to immunodiagnosis fields, and in particular to a kind of risk assessment of the molecular marker combination in patients with pneumonia In application.

Background technique

Biomarker (Biomarker) refers to can be with tagging system, organ, tissue, cell and subcellular structure or function The biochemical indicator of change or the change that may occur of energy, has very extensive purposes.Biomarker can be used for disease and examine Break, judge staging or for evaluating the safety and efficacy of new drug or new treatment in target group.

The Procalcitonin (PCT) of serum is can to compare to accurately reflect respiratory tract patient sense as the one kind developed in recent years The bion marker for contaminating situation, under normal metabolism, the endocrine cell of parafollicular cells of thyroid gland and lungs can be generated PCT, and make its activation at calcitonin.Content < 0.05 μ g/L of normal its blood-serum P of adult CT, and the elderly and chronic The patient etc. of disease, concentration > 0.05 μ g/L of blood-serum P CT, has been even up to individually 0.1 μ g/L, while general patients serum The concentration of PCT is no more than 0.3 μ g/L.And inside and outside toxin produced by bacterium and other cell factors etc. can induce patient The various kinds of cell of whole body expresses PCT.Have relevant the study found that the PCT of patient is opened after being infected the 4h of bacterium Begin expression increase occur, and reaches a peak value in the 8h of infection, and when infection conditions are controlled, PCT starts to be removed, The removing half-life period of usual blood plasma is 1d or so.Therefore, by the PCT concentration of serum can prompt bacterium infection occur and The degree of infection.

C reactive protein (CRP): being the plasma protein generated by liver, it is a kind of thin with activating complement and promotion grain The acute phase protein of the phagocytosis of born of the same parents and macrophage, under normal circumstances, content denier, in acute injury and infection When its concentration in blood steeply rise, the CRP concentration especially in blood plasma is in acute myocardial infarction AMI, wound, infection, inflammation It is significantly increased rapidly when disease, surgical operation, cancer infiltration, 2000 times for even up to arriving normal level.Therefore it is dense by serum CA125 The case where degree measurement can also prompt organism infection.

Pneumonia (pneumonia) is to betide a kind of inflammation of terminal air flue, alveolar and interstitial lung.It can be by the micro- life of cause of disease Object, chemical factors, immunologic mjury, allergy and drug-induced.Present Global every country has relatively very high with pneumonia in area Incidence probability.In the current of antibiotic application, bacterial pneumonia is maximum to the health threat of children and the elderly, antibiotic Occur and development once declined pneumonia case fatality rate significantly.But in recent years, although apply strength antibiotic and effectively Vaccine, the case fatality rate of pneumonia does not reduce to be increased instead.

Research finds that old group, often can companion since the aging of body causes immunity degradation, compensatory capacity gradually to lose Other kinds of underlying disease, among especially with senile pneumonia be typical case.Senile pneumonia is usually fallen ill, and hurried, the state of an illness is tight The features such as development of weight and the course of disease is fast, especially for patient with severe symptoms, the case fatality rate to suffer from an inflammation of the lungs is sharply increased.Due to old group Particularity, symptom is mostly heavier in the pneumonia caused by different type pathogenic factor, lethality be also mostly it is higher, because And it is easy to obscure.But the therapeutic scheme for being different pneumonia caused by pathogen is different.Therefore, for pneumonia pathogen sense Contaminating the determination of type and holding the specific severity of the pneumonia state of an illness is one for early diagnosing pneumonia, early treatment pneumonia A primary condition.

The elderly is weak and sickly, and pneumonia is often in chronic delay, falls ill hurried, therefore how after gerontal patient is admitted to hospital, especially In the case where lacking effective clinical laboratory, imaging data, how clinician, which is patient, provides correctly examine earlier It is disconnected, it can be obtained in first after patient is admitted to hospital part checklist more to the effective information that diagnoses the illness, and evaluate old The risk of year infectious pneumonia patient becomes healing senile pneumonia, alleviates symptom, reduces the key of the death rate.In early stage Gerontal patient is targetedly treated, is developed by reasonably using antibiotic just can effectively control disease.But In current clinical position for the diagnosis of pneumonia often depend on clinical manifestation, imageological examination, Bacteria Culture and Immune coherence check etc..But specificity, sensibility existing for above method are relatively low, as a result report relatively late, Wu Fajin Timely, the effective clinical diagnosis of row, it could even be possible to delaying the development of the state of an illness.

Summary of the invention

In view of the above shortcomings of the prior art, the present invention provides a kind of combination of molecular marker and comments in the risk of patients with pneumonia Application in estimating, evaluation and timely targeted drug treatment tool of giving to patient's gradient of infection are very helpful, the present invention The marker combination of offer also can be applied to examination of curative effect, prognostic evaluation of patients with pneumonia etc..

In order to achieve the above object, the technical scheme is that

A kind of molecular marker combines the application in the risk assessment and diagnosis of old infectious pneumonia patient, and described point Sub- marker combination includes PCT and CRP；

The detection method of the molecular marker combination is: fluoroimmunoassay, immunoturbidimetry or protein chip；

Data analysing method is after the detection of the molecular marker combination: by Receiver Operating Characteristics (ROC) curve The diagnosis capability of single albumen is assessed with the calculating of area under the curve (AUC).

Further, in above-mentioned application, it is characterized in that: the AUC value of PCT is that the AUC value of 0.868, CRP is 0.790.

Further, above-mentioned application includes auxiliary diagnosis, disease classification, antibiotic treatment, examination of curative effect and prognosis is instructed to comment Estimate.

The utility model has the advantages that

The elderly's body immune ability reduces, and weakens to the resistivity of bacterium, is easy to suffer from infectious pneumonia, traditional Pneumonia detection means efficiency is lower, and time-consuming, and detection process is cumbersome, damages to the body of the elderly's weakness.Antibiotic Be excessively used, cause emerging in multitude for drug-fast bacteria, for the elderly, can not excessive use antibiotic, then how fast The severity of evaluation the elderly's infectious pneumonia of fast science? molecular marker is the key that the institute that solves the above problems ?.

The content of PCT and CRP seriously has significant difference, the AUC of PCT with the slight intracorporal content of sufferer in the course of disease Value is that the AUC value of 0.868, CRP is 0.790, and according to the content of PCT in patients serum and CRP, doctor can quickly judge patient Pneumonia severity；Over the course for the treatment of, PCT and CRP can be used as the monitoring index and antibiolics for the treatment of effectiveness evaluation Object instructs index, prevents abuse of antibiotics, conducive to the disease treatment of the elderly.

Detailed description of the invention

Fig. 1 is the result of PCT and CRP to the ROC analysis curve of bacterial infection pneumonia diagnosis.

Specific embodiment

In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with implementation of the invention Example, technical scheme in the embodiment of the invention is clearly and completely described.Based on the embodiments of the present invention, this field Those of ordinary skill's every other embodiment obtained without making creative work, belongs to protection of the present invention Range.

Embodiment one

Molecular marker combines the application in the risk assessment of patients with pneumonia

1. subjects and grouping

It collects 65 years old that in January, 2015 in December, 2017 First Affiliated Hospital of Kunming Medical University's division of respiratory disease is accepted for medical treatment in hospital The retrospective analysis of Senile Patients with Pneumonia 400 expansion.Collected subjects are divided into three groups, grouping and grouping standard are such as Under:

A group: (1) haemocyte increases, and neutrophil leucocyte has shift to left mostly 80% or more；(2) lower respiratory tract tissue Culture, Grain stain and capsule stain microscopy such as find typical Gram-positive, diplococcus or streptococcus with pod membrane, Tentatively it is used as etiological diagnosis.The timely inspection of sample is required simultaneously, is acquired after gargling before antibiotic application, takes deep purulence Property phlegm or rusty expectoration.If positive rate is lower, taking polymerase chain reaction (PCR) and fluorescent labeled antibody to detect can be improved cause of disease Learn diagnosis；(3) x-ray is shown in that early stage increased bronchovascular shadows, or the lung section of involvement, the lobe of the lung slightly obscure.Simultaneously by above-mentioned patient according to English Association of division of chest disease of state CURB-65 level is divided into: it is light, in, weigh three subgroup levels, wherein patients with mild 47, moderate patient 46, Severe 37.A group has 130 cases, wherein male patient 67, and female patient 63, patient age 65~80 years old, average year Year in age (69.31 ± 3.77).

B group: (1) clinical symptoms are more anxious, and the constitutional symptoms such as fever, headache, Muscular stiffness, burnout are prominent；(2) laboratory is examined Look into: white blood cell count(WBC) is normal, slightly higher or relatively low, erythrocyte sedimentation rate usually in the normal range, leucocyte seen in patient's sputum smear and Monocyte is in the majority.The visible enhanced lung markings of chest X ray, ground glass shade, strip infiltration, consolidation, serious patient show Double lung diffusivity nodositas invade profit, but great Ye consolidation and pleural effusion person are rare；(3) such as positive rate is lower, then passes through inspection Specific IgG antibodies are surveyed, further confirm that whether be viral sense by complement fixation test (CFT), hemagglutination-inhibition test, neutralization test Dye.In 140 cases of B group, male patient 72, female patient 68, patient age 65~80 years old, average age (69.45 ± 4.22) year.

C group: (1) clinical manifestation is mostly: onset is lighter, is mainly shown as out of strength, pharyngalgia, headache, cough, fever, appetite Depressed, diarrhea, DOMS etc.；(2) cough is mostly that irritation is choked cough, can a small amount of mucus.Fever is general to continue 2-3 weeks, body temperature It may be still with cough after restoring normal.Occasionally there is retrosternal pain；(3) laboratory checks: blood leukocytes sum is normal or slightly increases Height, based on neutrophil leucocyte.About 2/3 cold agglutination test of some patients is positive, titre >=1:32, if titre gradually rises, More there is diagnostic value.It, can further really if serum mycoplasma IgM antibody >=1:64 or convalescence antibody titer have 4 times of raisings It examines；(4) see in combination with X-ray film inspection: variform infiltrates shadow, is distributed in segmental, is marched off into political wilderness more than one piece, is had attached from hilus pulumonis with lung Closely flex outward.Lesion often voluntarily dissipates after 3-4 weeks.There is a small amount of pleural effusion in some patientss.In 130 data of C group, male Property patient 66, female patient 64, patient age 65~79 years old, average age (69.25 ± 4.07) year.

Control group: it gives the same period and hospitalizes the agematched patient for being diagnosed as non-pneumococcal disease being admitted to hospital, and exclude it The patient of his position inflammation infection.Male 75 in control group, women 75, the age is 60~80 years old, average age (69.37 ± 4.19) year.

All research objects are voluntarily to participate in this research in this research.

To tri- groups of patients of A, B, C through being the clinical symptoms described by the case-data in comparison hospital HIS system, and tie Synthorax portion X, CT and laboratory, which check, is diagnosed as pneumonia, at the same A group, B group, C group patient exclude there are bacterium, mycoplasma and (or) virus mixed infection, it accepts for medical treatment to be admitted to hospital after patients acuity onset and just starts to treat, and do not carried out in illness 2 weeks Such as antibacterial anti-inflammatory drug therapy.It studies simultaneously and excludes to merge the inflammation for suffering from other positions, such as hectic or tumour weight Big Disease, all research objects only carry out this project content in the course of the research, are not involved in other researchs. Research passes through the confirmation of Ethics Committee of institute and ratifies to carry out.

2. the detection of the PCT and CRP of pair serum

For A, B, C, control group patient accepts for medical treatment to be admitted to hospital the 2nd day and is acquired under fasting state to venous blood in it, adopts Integrate amount as 5ml, while the non-patients with pneumonia of control group being admitted to hospital the same day in it, 5ml venous blood is acquired under fasting state, is set simultaneously 1500 turns of progress, 10 minutes centrifugal treatings, isolated serum in the heparin tube of vacuum.Inspection for PCT and CRP It surveys.It needs to be placed in -20 DEG C of refrigerator for cannot timely carry out test sample to save in the middle.Blood-serum P CT detection application The matched reagent of French 15 immunity analysis instrument of Mei Liai VIDAS fluorescence (French Mei Liai company) and the instrument, calibration object measurement. Serum CA125 detection is using the matched reagent of II protein analyzer of SIEMENS BN (German SIMENS company) and the instrument, calibration Product measurement.

3 statistical procedures

Processing analysis, serum metering are carried out to the detected data of this research institute using the statistics software of SPSS16.0 Related data applies (mean ± standard deviation), and (x ± s) is indicated, and examines for comparing t, mean value compares application side between multiple groups Difference analysis, if the results of analysis of variance is significant, with " post-hoc tests " i.e. group between group two-by-two compared with SNK examine.Pass through P < 0.05 Indicate that the difference of comparison has conspicuousness, there are statistical meanings.Water is expressed with the PCT of control group serum and CRP simultaneously It is flat to compare value, the analysis of specificity and sensitivity is carried out using ROC curve.

4 interpretations of result

The result of 4.1 blood-serum P CT and the detection of CRP level

A group blood-serum P CT level compared with B group, C group in, difference is statistically significant (P < 0.01).The PCT water of B group, C group Flat to compare with control group, difference is statistically significant (P < 0.05), but B group, compared between C group PCT level, difference is not There are statistical significance (P > 0.05).A group serum CRP level compared with B group, C group, difference there are statistical significance (P < 0.01), and B group, C group CRP level with the comparison of control group, difference is statistically significant (P < 0.05), B group and C group CRP level Between compare, difference be not present statistical significance (P > 0.05).It is shown in Table 1 in detail.

The result of 1 blood-serum P CT of table and the detection of CRP level

Compared two-by-two between group SNK inspection, *: P < 0.05, a compared with A group: P < 0.05, b compared with B group: compared with C group P < 0.05。

Blood-serum P CT and the CRP horizontal analysis of 3 sub-group of patients of 4.2A group

Slight, 3 sub-group of patients of moderate and severe the blood-serum P CT expression and CRP table of bacterial pneumonia (A group) Up to level, in comparison two-by-two, there are the differences of conspicuousness, as a result have statistical significance (each group compares P < 0.05), while serum PCT expression and CRP expression are increased with the exacerbation of the state of an illness.It is shown in Table 2 in detail.

The blood-serum P CT and CRP of 2 A group of table, 3 sub-group of patients is horizontal

SNK inspection is compared between group two-by-two, a: P < 0.05, b compared with moderate group: P < 0.05, c and severe compared with slight group Group compares P < 0.05.

Value analysis of the 4.3PCT and CRP in diagnosis bacterial infection pneumonia

ROC analysis Dependence Results (Fig. 1) display by PCT and CRP to bacterial infection pneumonia diagnosis, PCT diagnosis The credibility interval that area under the curve (AUC) is 0.868, while 95% is 0.762~0.902, P < 0.001；And the song of CRP diagnosis Area is (AUC) 0.790 under line, while 95% credibility interval is 0.713~0.912, P < 0.001.As a result with the μ of PCT >=0.5 G/L and CRP >=10mg/L is shown in Table 3 to each group patients with pneumonia positive rate as positive threshold value.If with patients with lower respiratory tract The tissue bacterial culture positive is as diagnosis bacterial infection pneumonia goldstandard, and blood-serum P CT and CRP is to bacterial infection pneumonia Sensitivity is respectively as follows: 90.9% and 86.8%, between the sensitivity of blood-serum P CT and CRP difference there is no statistical significance (P > 0.05)；But blood-serum P CT and CRP specificity is respectively 90.4% and 77.5%, blood-serum P CT specificity is significantly higher than CRP, Difference has statistical significance (P < 0.01).

The diagnosis of table 3 PCT and CRP is for bacterial pneumonia value analysis

Result above shows that PCT and CRP increase with expression quantity of the aggravation in serum, the heavier A group of the state of an illness PCT the and CRP content detected is most, and B, C content are few, between no significant difference.As can be seen from the results, by detecting PCT and CRP Content in serum quickly can carry out risk assessment by the condition to sufferer, adjoint to exhale according to the content of PCT and CRP Road symptom checking is inhaled, doctor can be helped quickly to judge and assess conditions of patients, the pathologic finding that patients with mild is cumbersome is avoided, make Patient with severe symptoms quickly carries out testing in depth testing.During inflammation treatment, the index value of PCT and CRP, which are also used as doctor, to be made Index is instructed with antibiotic, reduces being excessively used for antibiotic.

Claims (3)

1. a kind of molecular marker combines the application in the risk assessment and diagnosis of old infectious pneumonia patient, feature exists In:

The molecular marker combination includes PCT and CRP；

The detection method of the molecular marker combination is: fluoroimmunoassay, immunoturbidimetry or protein chip；

Data analysing method is after the detection of the molecular marker combination: assessing single egg by the calculating of ROC curve and AUC White diagnosis capability.

2. molecular marker combination according to claim 1 is in the risk assessment and diagnosis of old infectious pneumonia patient Application, it is characterized in that: the AUC value of PCT is that the AUC value of 0.868, CRP is 0.790.

3. molecular marker combination according to claim 1 is in the risk assessment and diagnosis of old infectious pneumonia patient Application, it is characterized in that: the application include auxiliary diagnosis, disease classification, instruct antibiotic treatment, examination of curative effect and prognosis to comment Estimate.