Method for prediction of chronic dust bronchitis in coal mine workers

FIELD: medicine.

SUBSTANCE: method for prediction of a risk of chronic dust bronchitis in coal mine workers consists in blood examination for genetic markers. It involves the genetic markers of systems: haptoglobin (HP), group-specific component (GC), fluorescent esterase (EsD), erythrocyte acid phosphatase (AcP). A prognostic coefficient (PC) score is calculated. If the marker 1-1 is found in the HP system, the PC is specified to be equal to (+1.5); the marker 1-2 makes the PC to be equal to (+0.1), while the marker 2-2 shows the PC (-1.1). If the marker 1-1 is found in the GC system, the PC is specified to be equal to (-1.9); the marker 1-2 makes the PC to be equal to (+1.7), while the marker 2-2 shows the PC (+5.5). If the marker 1-1 is found in the EsD system, the PC is specified to be equal to (-1.2); the marker 1-2 makes the PC to be equal to (+2.3), while the marker 2-2 shows the PC (+3). If the AcP system comprises the marker (aa), the PC is equal to (-5); the marker (ab) shows the PC equal to (0); the marker (bb) provides the PC to be equal to (+3.6); the marker (ac) - the PC equal to (+2.2), the marker (bc) - the PC equal to (-2.4), the marker (ee) - the PC equal to (-3.5). The PC for all the markers are summed up; total PC being (+5) and more enables predicting the propensity for chronic dust bronchitis, while total PC equal (-5) and less shows resistance to chronic dust bronchitis.

EFFECT: use of the declared method enables higher accuracy of prediction of chronic dust bronchitis in coal mine workers.

1 tbl, 4 ex

 

The invention relates to medicine, in particular to the pathology. One of the most common occupational diseases in workers of coal mines, especially in underground coal mining, is a chronic dust bronchitis (Occupational diseases / Izmerov NF, Minenkova A.M., Artamonova VG etc. // ed Nefazodone. - M.: Medicine, 1996. - In 2 volumes. Vol.2. S-139). The incidence of chronic dust bronchitis (HPB) of employees in other sectors of the mining industry is according to different researchers from 18.4%to 78%, depending on the age and experience of the workers, but also on the levels of dust in the working environment. Of some importance is the lack of uniform diagnostic criteria of this disease.

To date, thoroughly described in the etiology of the disease, its pathogenesis and pathological anatomy (Cytology and histology, the structure of the endoscopic mucous membrane and architectonics of the bronchial tree when exposed to industrial aerosols, particularly immunological and biochemical composition of the secretion of the bronchi, the severity of the morphological changes in various structures of the bronchial wall, depending on the development of the inflammatory process). Also described clinical symptoms of bronchitis caused by dust, stipulated by the major General laws, typical of this nosological form and features, determined by the nature of the professional factor (Velichkovsky BT // Pulmonology. - 1995. No. 3. - P.6-19; Gromov KG Biological aggressiveness of coals. Kemerovo: Kuzbassvuzizdat, 2005. - 184 S.; Izmerov NF, Kasparov A.A. occupational Medicine. Introduction to the field. - M.: Medicine, 2002. - 392 S.; Babanov S.A., Gailis the PV Pneumoconiosis from exposure to industrial dust varying degrees of fibrogenesis. - Hard case.- 2010. No. 5. - P.1-12; A.V. Zhestkov Clinical and immunological manifestations of dust-induced lung diseases: author. dis...Prof. the honey. Sciences. - Samara, 2000; 32 C.).

The disadvantages of these methods of diagnosis HPB is that they describe the clinic already developed the disease, i.e. the situation when the disease is already there and question her treatment. But the priority of modern occupational medicine is the prevention of occupational diseases, based on timely, prenosological diagnosis, assessing the likelihood of its development. In addition, these indicators are dynamic over time and not always stable and adequately reflect the state of the organism.

A method of early diagnosis HPB based on the use of indicators of function of external respiration. Screened spend the camping twice with an interval of 1 year. This allows to assess the degree of negative dynamics of the state of the external respiratory function and to predict the likelihood of HPB (lutay A.V. Efimov, Mrs x, eagles RB method for the diagnosis of chronic dust bronchitis. Patent RU No. 2161800. Published 10.01.2001). The disadvantage of this method is the long time (1 year) to predict the probability of developing the disease.

The approach described is based on the study of genetic predisposition to the development HPB. Genetic markers (blood groups, biochemical markers - proteins, DNA sequence) in the vast majority of cases remain the same from birth to death. If any token is statistically more common in the group of patients compared with healthy, we can assume that its presence (directly or indirectly) associated with the development of this disease (Ivanova L.A., Bezrukavnikov L., Kuzmin, L.P. Prospects biochemical monitoring of genetic effects in human exposure to harmful factors in the working environment // occupational Medicine and prom. ecology. - 1995. No. 5. - P.23-26). This is generally the right approach for predicting the risk of developing any disease associated with exposure to xenobiotics, but we need to assess the genetic risk of developing a specific work-related disease is evania in particular sanitary and hygienic conditions of work, for example, the development of silicosis or chronic bronchitis.

A prototype of this invention is the assessment of the risk professionally driven viscerate in workers exposed to dust professions and in patients with chronic dust disease (Sands S.A., poteryaeva EL, Maslennikov A.B. and others the Importance of molecular genetic markers to assess individual risk viscerate in workers exposed to dust professions /occupational Medicine and prom. ecology. - 2008. No. 11. - P.40-45). In this work the risk factors attributed to the presence of different genotypes and alleles of the MTHFR gene and mutation of the gene F5. It was shown that the highest risk of development and progression professionally driven viscerate and/or occupational lung disease, the development of multiple organ lesions, is the carrier genotype T/T in the MTHFR locus and the R506Q mutation in the F5 locus, or the presence of the allele T gene T and mutation R506Q F5 gene. The disadvantage of this method is the use of only two molecular-genetic markers of genes MTHFR and F5, and F5 gene is subprimary, and the frequency of its main allele 1691G of the total sample of healthy and sick persons amounted to 0,9826, and the frequency of the minor allele 1691A (Leiden) - 0,0174, i.e. less than 2%. When close to the monomorphic frequencies of genotypes and alleles to predict the risk of development of such enough of the soap the common diseases, as viscerate, very difficult. Typically used for this highly polymorphic genetic system.

The disadvantages can be attributed to the relative high cost of the equipment and biochemical kits for the determination of molecular-genetic markers and higher requirements for the sterility of operations.

The objective of the invention is to improve the accuracy of predicting the risk of chronic dust bronchitis in workers of the coal industry by increasing the number of genetic markers.

This object is achieved as follows.

The workers of coal mines carried out a blood test to determine the genetic markers. Determine genetic marker systems: haptoglobin (HP), group-specific component (GC), fluorescent esterase (EsD), acid phosphatase erythrocytes (ASR). For each token to determine prognostic factor (PC) scores. When detecting in the system of HP token 1-1 installing PC is equal to (+1.5), a marker 1-2 is equal to (+0,1), token 2-2 is equal to (-1,1). When detecting in the system GC marker 1-1 installing PC equal (-1,9), token 1-2 is equal to (+1,7), token 2-2 is equal to (+5,5). When detecting the EsD marker 1-1 installing PC is (-1,2), token 1-2 - equal (+2,3), token 2-2 - equal (+3). When detecting in the system ASR marker (AA) established which indicate the PC is equal to (-5), marker (ab) - equal (0), token (bb) - equal (+3.6), and marker (AU) - equal (+2,2), token (b) - equal (-2,4) marker (SS) - equal (is 3.5). Summarize the PC all markers with account of the sign, and when the amount of PC is equal to (+5) and higher scores predict a predisposition to develop chronic dust bronchitis, when the amount of PC (-5) and less points predict resistance to chronic dust bronchitis.

The novelty of the method is to increase the number of new tokens systems: haptoglobin (HP), group-specific component (GC), fluorescent esterase (EsD), acid phosphatase erythrocytes (ASR).

The technical result of the invention is to improve the accuracy and informative way prediction.

The method consists in the following.

Determine the genotypes of the following systems: haptoglobin HP (HP 1-1, 1-2 HP, HP 2-2), group-specific component of the complement GC (GC 1-1, 1-2 GC, GC 2-2), fluorescent esterase EsD (EsD 1-1, 1-2 EsD, EsD 2-2), acid phosphatase erythrocytes (ASR (ASR AA, ACP ab, ASR bb, ACP AC, ACP b, ACP SS). The phenotypes determined by electrophoresis in polyacrylamide and starch gels with subsequent histochemical staining (Spitsyn VA Biochemical polymorphism of human (anthropological aspects). - M.: Moscow state University, 1985. - 216 C.).

It was further determined whether there are significant differences in the frequencies of genotypes between patients and health the new entities under the criteria χ 2and OR (Artamonova VG Actual problems of industrial ecology and prevention of occupational tasks // Bulletin of the Russian Academy of medical Sciences. - 1998. No. 1. - Ñ.38-42; Pearce N. What does the odds ratio estimate in a case-control study? // Int. J. Epidemiol. - 1993. - V.26, No. 6. - P.1189-1192).

χ2=[N(ad-b)2]/[(a+b)(a+c)(b+d)(c+d)], where a - patients carriers of the genotype (for example, HP 1-1), b - healthy individuals, carriers of the same genotype, with a sick person, do not carry this genotype (for example, HP 1-1), d - healthy persons who do not carry this genotype, N is the total number of surveyed persons.

OR (odds ratio the odds ratio) - shows how many times more often, this token is found among patients in comparison with healthy.

Or SIG(a/b)/(C/D), where

A - number (percentage) of people with this genotype (genotypes) in the group of patients;

With - a-number (percentage) of people with this genotype (genotypes) in the healthy group;

In the number (percentage) of individuals without this genotype (combination of genotypes) in the group of patients;

D - number (percentage) of individuals without this genotype (combination of genotypes) in the healthy group.

When analyzing the distribution of markers among patients with chronic dust bronchitis and healthy individuals revealed that patients statistically significantly more often markers: GC 2-2, 1-2 EsD, AcP bb, AcP bc.

For each marker was calculated prognostic factor (PC) scores for four is OLE:

PC=10 1g(P1/P2),

where P1 is the prevalence of the marker in patients;

P2 - the prevalence of the marker in healthy.

According to this data was compiled table of prognostic factors and values OR for different genotypes in patients with chronic dust bronchitis (Table 1).

The use of this predictive system is the summation of the values of all PC considering the sign (plus markers PC is added, and a negative subtracted from the total value of the PC). When the amount of PC all markers 5 points and above is projected predisposition to develop chronic dust bronchitis, and when the amount of PC -5 points and lower resistance to chronic dust bronchitis. Accordingly, the higher the total amount of PC, the higher its prognostic value. At intermediate numbers from -5 to +5 predicting the likelihood of developing the disease is uncertain.

Thanks to the operation taking the logarithm, we get either a negative value PC (in the case of resistance to the disease)or a positive value (in case of predisposition)that facilitates the obtaining total values of PCs in case of different values of separate PC and gives more reliable results.

Table 1
Prognostic factors (PC) and values OR for different genotypes in patients with chronic dust bronchitis
GenotypeValue PCOR
HP 1-1+1,51,6
HP 1-2+0,11,06
HP 2-2-1,10,68
GC 1-1-1,90,36
GC 1-2+1,71,82
GC 2-2+5,54,04
EsD 1-1-1,20,43
EsD 1-2+2,3to 2.06
EsD 2-2+32,11
AcP aa-50,28
AcP ab00,97
AcP bb +3,63,19
AcP ac+2,21,70
AcP bc-2,40,49
AcP ccis 3.50,44

The survey is conducted once defined 15 genetic markers, the data is then analyzed using table 1. If the sum PC +5 and above points recommended treatment and preventive measures aimed at preventing dust bronchitis. Examined resistant to the development of dust bronchitis PC -5 and less points, can be recommended for occupations with a high risk of dust bronchitis in coal, metallurgical industry.

Example 1.

Patient A., born in 1963, Ds. - chronic dust bronchitis.

Identified markers:

HP 1-1, PC=(+1,5),

GC 1-2, PC=(+1,7),

EsD 2-2, PC=(+3),

ACP AC, PC=(+2,2).

The amount of PC was: 1,5+3+1,7+2,2=8,4

For this patient at high risk of developing chronic dust bronchitis (8,4>5) was implemented.

Example 2.

Patient B., born in 1960, Ds. - chronic dust bronchitis.

Identified markers:

HP 1-2, PC=(+0,1),

GC 2-2, PC=(+5,5),

EsD 1-2, PC=(+2,3),

ACP ab, PC=(0).

The amount of PC was: 0,1+5,5+2,3=7,9

D is I the patient at high risk of developing chronic dust bronchitis (7,9> 5) is implemented.

Example 3.

Patient C., born in 1964, the control group, healthy.

Identified markers:

HP 2-2, PC=(-1,1),

GC 1-1, PC=(-1,9),

EsD 1-1, PC=(-1,2),

ACP ab, PC=(0).

The amount of PC was: (-1,1)+(-1,9)+(-1,2)+0=(-4,2).

For the patient there is a very low risk (-4,2<5) development of chronic dust bronchitis, which did not materialize.

Example 4.

Patient G., born in 1961, the control group, healthy.

Identified markers:

HP 1-2, PC=(+0,1),

GC 1-1, PC=(-1,9),

EsD 1-1, PC=(-1,2),

ASR bc, PC=(-2,4).

The amount of PC was: (+0,1)+(-1,9)+(-1,2)+(-2,4)=(-5,4).

The patient is resistant to the development of chronic dust bronchitis (PC=-5,4), which he also did not materialize.

These examples show that using our predictive system using genetic markers can distinguish individuals susceptible or resistant to the development of dust bronchitis.

A method for predicting the risk of chronic dust bronchitis in workers of coal mines by blood tests with determination of genetic markers, wherein define genetic marker systems: haptoglobin (HP), group-specific component (GC), fluorescent esterase (EsD), acid phosphatase erythrocytes (ASR), then for each token define prog is eticheski coefficient (PC) scores, namely, when the detection system HP token 1-1 installing PC is equal to (+1.5), a marker 1-2 is equal to (+0,1), token 2-2 is equal to (-1,1), the detection system GC marker 1-1 installing PC equal (-1,9), token 1-2 - equal (+1,7), token 2-2 is equal to (+5,5), when detecting the EsD marker 1-1 installing PC is (-1,2), token 1-2 - equal (+2,3), token 2-2 - equal (+3), the detection system Billing token (AA) install PC is equal to (-5), marker (ab) - equal (0), token (bb) - equal (+3.6), and marker (AU) - equal (+2,2), token (be) - equal (-2,4) marker (its) - equal (for 3,5) summarize the PC all markers with regard to sign and when the amount of PC is (+5) and higher scores predict a predisposition to develop chronic dust bronchitis, when the amount of PC (-5) and less points predict resistance to chronic dust bronchitis.



 

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