RU2608548C1 - Differential diagnostic technique for acute bronchitis and acute pneumonia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to therapy, and can be used for differential diagnostics of acute bronchitis and acute pneumonia. Essence of method: in patient with clinical presentation of acute respiratory infections, accompanied by bronchial-pulmonary syndrome, content of acetic acid, isocapronic and valeric acids are determined in salvia. Values of discriminator functions D1 and D2 are calculated by formulas. If D1 is greater than D2, acute bronchitis is diagnosed, if D2 is greater than D1, acute pneumonia is diagnosed.

EFFECT: invention provides simplification, safety (non-invasiveness) for patient and surrounding ones due to elimination of radiation exposure at provision of reliability, specificity of differential diagnostics of acute pneumonia and acute bronchitis, starting from early stages of disease; reduced time of differential diagnostics of acute pneumonia and acute bronchitis, thus reducing time for determining optimal treatment schedule, making it possible to reduce risk of complications and adverse prediction of developing diseases.

1 cl, 2 ex

Description

The invention relates to medicine, namely to therapy, and can be used for the differential diagnosis of acute bronchitis and acute pneumonia.

Existing methods for differential diagnosis of pneumonia and bronchitis are based on the assessment of medical history, the results of a physical examination of the patient, as well as laboratory x-ray functional studies. However, the incidence of erroneous diagnoses is 20-70% [Principi N., Esposito S. Management of severe community - acquired pneumonia of children in developing and developed countries. Thorax. 2011; 66: 815-822], which entails the unreasonable prescription of broad-spectrum antibacterial drugs and, as a result, an increased risk of undesirable side effects of treatment.

On the one hand, the differential diagnosis of pneumonia and bronchitis is still difficult, and later confirmation of the diagnosis of pneumonia leads to the development of possible complications with the destruction of lung tissue and the development of pleurisy.

One of the important components in the differential diagnosis of bronchitis and pneumonia is an X-ray examination of the chest organs [Molotkov Z.N. Differential diagnosis of acute pneumonia, pulmonary tuberculosis and cardiogenic pneumonia // Therapist. archive. - 1979. - N 2, - S. 30-35.]. However, the assessment of the results of an x-ray examination of the chest organs varies significantly even among qualified radiologists [Neuman M.I., Lee E.Y., Bixby S. et al. Variability of the interpretation of chest radiographs for the diagnosis of pneumonia in children. J. Hosp. Med. 2011.]. In addition, unjustified radiation exposure increases the risk of cancer [Namazova-Baranova L.S., Kulichenko T.V., Malakhova A.E., Starovoitova E.V., Bakradze M.D., Chashchina I.L., Mityushin I.L. Pneumococcal infection in children. Questions of modern pediatrics. 2012; 11 (4): 65-72.]. However, early diagnosis of pneumonia is important from the point of view of the timely appointment of antibacterial drugs, which will help reduce the number of complications.

A method for the cytological study of leukocytes and the contents of the tracheobronchial pathways is developed and used for the differential diagnosis of bronchitis and bronchopneumonia and pneumonia, in which, when the ratio of the permeability index of lysosome membranes in leukocytes, the contents of the tracheobronchial pathways to the value of the permeability index of lysosome membranes in blood leukocytes (from 0.05 to 0.75 units) diagnose the presence of pneumonia, with a ratio of indicators from 0.76 to 1.15 units. diagnose the presence of bronchopneumonia, and with a ratio of indicators from 1.16 to 10.0 units. diagnose the presence of bronchitis [Kazantseva V.N. Cytological and some cytoenzymological characteristics of sputum in chronic non-specific lung diseases. Archive of Pathology, 1980, v. 4, p. 63-78 (54) (57)] (prototype).

However, the known method does not have sufficient specificity for reliable differential diagnosis of acute pneumonia and acute bronchitis, especially in the early stages of the disease.

A known method for the differential diagnosis of diseases of the bronchopulmonary system according to the ratio of fatty acids C _{16: 0} / C _{19: 0} in the condensate of exhaled air by gas-liquid chromatography (RU 2117290, C1, BS Khyshiktuev, 08/10/1998). This method involves the calculation of a certain coefficient, and if its value is in the range of 1.5-2.5, chronic non-specific lung diseases are diagnosed, 2.5-4.5 - benign tumors, and with values less than 1.0 - lung cancer . However, this method cannot differentiate between acute bronchitis and acute pneumonia.

The inventors set the task - to develop a reliable non-invasive method for the differential diagnosis of acute bronchitis and acute pneumonia, starting from the early stages of the disease.

The technical result achieved by the implementation of the claimed invention consists in:

- simplification, safety (non-invasiveness) for the patient and others by eliminating radiation exposure while ensuring reliability, specificity of the differential diagnosis of acute pneumonia and acute bronchitis, starting from the early stages of the disease;

- reducing the time for differential diagnosis of acute pneumonia and acute bronchitis and thereby reducing the time to determine the optimal treatment regimen, which reduces the risk of complications and an unfavorable prognosis of the development of diseases.

The massive spread of molecular biological and physico-chemical methods for studying microbiocenoses contributes to the wider promotion of new approaches to the diagnosis of diseases in which microbiocenosis is a sensitive sensor that can form disease markers at an early stage. Such approaches are united by the common name omix technology. Metagenome is studied by metagenomics, epigenomics. Post-genomic research, the study of the protein composition of microbiocenosis deals with proteomics. Markers of metabolic nature are studied by metabolomics, and in the case of studies of part of the metabolome - by metabolonomics. The study of metabolites is carried out by multivariate regression methods - discriminant analysis, which is designed to classify samples from patients with various diagnoses according to the decisive rule.

The authors first established that a change in the concentration of short-chain fatty acids in the saliva of patients with symptoms of acute respiratory infection, accompanied by bronchopulmonary syndrome, caused, among other things, by the activity of microorganisms that cause acute pneumonia or acute bronchitis, allows for reliable differential diagnosis of these diseases.

The invention consists in the following.

For the differential diagnosis of acute pneumonia and acute bronchitis in a patient with a clinical picture of acute respiratory infection accompanied by bronchopulmonary syndrome, the content of acetic, valerianic and isocaproic acids is determined in saliva. Calculate the value of discriminant functions by the formulas:

D1 = -6.13238 + 0.50752 × C2-1.15227 × C5-3.88032 × IC6

D2 = -0.80473 + 0.113286 × C2 + 1.0909195 × C5 + 0.119217 × IC6,

Where:

C2 — concentration of acetic acid, mmol / g;

C5 — concentration of valerianic acid, mmol / g;

IC6 is the concentration of isocaproic acid, mmol / g.

If D1 is greater than D2, acute bronchitis is diagnosed, and if D2 is greater than D1, acute pneumonia is diagnosed.

In the particular case, the content of acetic, valerianic and isocaproic acids in saliva is determined by gas-liquid chromatography.

The method is as follows.

The determination of the concentration of volatile fatty acids (VFA) in saliva is carried out by gas-liquid chromatography and by direct injection of the supernatant of an acidified saliva solution in 0.1 N an aqueous solution of hydrochloric acid in an evaporator chromatograph.

To determine the VFA, the supernatant of the saliva sample was used. Getting it takes place according to the following scheme:

1. In a disposable plastic tube, 2-3 grams of saliva was weighed on an analytical balance accurate to the 3rd sign.

2. 1 ml of 0.1N hydrochloric acid and 1 ml of a standard substance (dimethylbutyric acid) were added to the sample. The mixture was homogenized by vigorous shaking in a closed tube.

3. A test tube with a homogeneous mixture was centrifuged for 10 minutes at 6000 rpm.

4. The resulting supernatant was clear and had an acid reaction (pH 2-3).

For chromatography, a Crystal 5000.2 gas-liquid chromatograph with an FFPA capillary column d 0.25 mm L 32 m and a flame-ionization type detector was used. The carrier gas is nitrogen.

The order of work on the chromatograph.

1. The chromatograph was brought to the mode:

- thermostat temperature, ° C 155 - detector temperature, ° C 250 - evaporator temperature, ° C 250 - carrier gas velocity, cm / sec 60 - carrier gas pressure kPa 136 - dividing the carrier gas stream 1:35

2. A supernatant sample was taken from a plastic tube using a 1 μl chromatographic syringe and introduced into the chromatograph evaporator. Peaks in VFA concentrations were determined by retention time. Retention times were determined based on the separation of a standard sample — a mixture of monocarboxylic acids of the homologous series from acetic to caproic acids.

Retention Times:

Acetic acid, min 1.36 Propionic acid, min 1,59 Isobutyric acid, min 1,69 Butyric acid, min 1.94 Isovalerianic acid, min 2.16 Standard substance (dimethylbutyric acid), min 2,39 Valerianic acid, min 2.6 Isocaproic acid, min 3.16 Caproic acid, min 3.6

When processing chromatograms, the calculation of peaks was carried out using the computer program of the device by analyzing the sequence of peaks, their boundaries and heights. Peak areas are defined as the areas of triangles with a base equal to the width of the peak and a height equal to the height of the peak. Based on the peak area of the standard (dimethylbutyric acid) with the known concentration and the ratio of the areas of the analyzed peaks, the concentration of each component of the VFA mixture was calculated. Combustion coefficients, which are the conversion factors of the molar concentration to the weight, were also used in the calculation formula. The concentration of the individual components was calculated by the formula:

Where

C _i, C _v. - concentrations of standard and component,

S _i , S _Art . - peak areas,

K _i - conversion factor.

For calculations, we used the formulas of the classification equation of discriminant analysis.

D1 = -6.13238 + 0.50752 × C2-1.15227 × C5-3.88032 × IC6

D2 = -0.80473 + 0.113286 × C2 + 1.0909195 × C5 + 0.119217 × IC6,

where: C2 - concentration of acetic acid in saliva, mmol / g; C5 — concentration of valerianic acid in saliva, mmol / g; IC6 is the concentration of isocaproic acid in saliva, mmol / g.

If D1 is greater than D2, acute bronchitis was diagnosed, and if D2 is greater than D1, acute pneumonia is diagnosed.

To prove the possibility of realizing the claimed purpose and achieving the specified technical result, we provide the following data.

Example 1

Patient A., aged 10 years old, was admitted to the hospital with complaints of weakness, coughing. Body temperature was 38.9 degrees Celsius. Auscultatory breathing is hard, weakened on the right, wheezing is not heard. BH - 21 per minute.

Analysis of the concentrations of short chain fatty acids in saliva showed the following concentrations (mmol / g): 15.10425 for acetic acid, 0.06312 for valerianic, 0.031578 for isocaproic acid. The obtained values were multiplied by the coefficients of the linear discriminant classification equations and added up taking into account the sign in accordance with the proposed formulas of the patented method. The obtained values were compared among themselves.

D1 = -6.13238 + 0.50752 × 15.10425-1.15227 × 0.06312-3.88032 × 0.031578 = 1.34

D2 = -0.80473 + 0.113286 × 15.10425 + 1.909195 × 0.06312 + 0.119217 × 0.031578 = 1.03

The maximum value of 1.34 corresponded to the acute bronchitis equation. The presumptive diagnosis is acute bronchitis, symptomatic and antiviral therapy are prescribed, it was decided to abstain from antibacterial therapy prior to the chest x-ray. According to an X-ray examination of the chest: there are no focal and infiltrative shadows, there are no swelling of the pulmonary fields, the roots of the lungs are not dilated, the domes of the diaphragm are clear, the sinuses are free. According to a general blood test, leukocytosis of 14.5 thousand, accelerated ESR of 19 mm / h. The final diagnosis is acute bronchitis. Thus, the diagnosis made using the proposed method was confirmed.

Example 2

Patient S., age 14, was admitted to the hospital with complaints of weakness, coughing. Body temperature was 39.9 degrees Celsius.

Auscultatory breathing is hard, weakened on the right, dry and wet rales of different sizes in the lower parts of the lungs, BH - 20 per minute. Analysis of the concentrations of short chain fatty acids in saliva showed the following concentrations (mmol / g): 1.564954 for acetic acid, 0.09552 for valerianic, 0.181464 for isocaproic acid. The obtained values were multiplied by the coefficients of the linear discriminant classification equations and added up taking into account the sign (by the proposed method). The obtained values were compared among themselves.

D1 = -6.13238 + 0.50752 × 1.564954-1.15227 × 0.09552-3.88032 × 0.181464 = -6.15

D2 = -0.80473 + 0.113286 × 1.564954 + 1.909195 × 0.09552 + 0.119217 × 0.181464 = -0.42.

The maximum value of -0.42 corresponded to the acute pneumonia equation. In accordance with the proposed method, the presumptive diagnosis is acute pneumonia, antibacterial treatment has been prescribed. The clinical and laboratory diagnosis of acute pneumonia was confirmed: a focal-infiltrative shadow was found in the lower lobe of the right lung radiographically, there was no swelling of the pulmonary fields, the roots of the lungs were widened, the dome of the diaphragm was clear, the sinuses were free; in the general analysis, leukocytosis is 19.2 thousand, accelerated ESR (32 mm / h).

The proposed differential diagnosis of acute bronchitis and acute pneumonia was used in 60 patients with presumptive diagnoses of acute bronchitis and acute pneumonia. The diagnoses made using the proposed method were confirmed by direct identification of the pathogen by the bacteriological method and the polymerase chain reaction method. The sensitivity of the method was 100%, specificity 96.6%.

Claims (9)

1. A method for the differential diagnosis of acute bronchitis and acute pneumonia, characterized in that in a patient with a clinical picture of acute respiratory infection accompanied by bronchopulmonary syndrome, the content of acetic, valerianic and isocaproic acids is determined in saliva, and the discriminant functions are calculated using the formulas: D1 = -6.13238 + 0.50752 × C2-1.15227 × C5-3.88032 × IC6 D2 = -0.80473 + 0.113286 × C2 + 1.0909195 × C5 + 0.119217 × IC6, Where: C2 is the concentration of acetic acid, mmol / g; C5 — concentration of valerianic acid, mmol / g; IC6 is the concentration of isocaproic acid, mmol / g; and if D1 is greater than D2, acute bronchitis is diagnosed, and if D2 is greater than D1, acute pneumonia is diagnosed. 2. The method according to p. 1, characterized in that the content of acetic, valerianic and isocaproic acids in saliva is determined by gas-liquid chromatography.