A kit for non-invasive diagnosis of type 2 chronic rhinosinusitis with nasal polyps

Abstract

The present invention discloses a kit for non-invasive diagnosis of type 2 chronic rhinosinusitis with nasal polyps. One technical solution protected by the present invention is the application of a system for detecting the content of inflammatory factors in the preparation of a product for diagnosing or assisting in diagnosing whether a patient with chronic rhinosinusitis with nasal polyps is a patient with type 2 chronic rhinosinusitis with nasal polyps. The inflammatory factors may be interleukin-5, CC chemokine ligand 5 and CC chemokine ligand 26, or interleukin-5, CC chemokine ligand 5, CC chemokine ligand 24, CC chemokine ligand 26 and periostin. The diagnostic AUC of the kit and device for non-invasive rapid diagnosis of type 2 CRSwNP before treatment provided by the present invention is 0.862 or 0.856, both of which are higher than the current clinical indicators for diagnosing type 2 CRSwNP, and can provide a basis for selecting the correct treatment plan, reasonable drugs, biological agents or surgical methods for treating refractory CRSwNP clinically.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and particularly to a kit for non-invasive diagnosis of type 2 chronic rhinosinusitis with nasal polyps. Background Art

[0002] Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the nasal and sinus mucosa. CRS can be divided into two clinical phenotypes: simple sinusitis and chronic rhinosinusitis with nasal polyps (CRSwNP). According to the expression of inflammatory factors in tissues, it can be further divided into different CRSwNP endotypes. Patients with CRSwNP have high heterogeneity, and the treatment regimens and treatment effects of patients with different clinical endotypes are different. It mainly includes type 2 CRSwNP patients with increased inflammatory factors such as interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) in nasal polyp tissues, and non-type 2 CRSwNP with increased inflammatory factors such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) (type 1 CRSwNP) or IL-17 and IL-22 (type 3 CRSwNP). Retrospective analysis found that CRSwNP patients with increased type 2 inflammatory factors (IL-4, IL-5, and IL-13) in nasal polyp tissues are very difficult to treat, and the recurrence rate of type 2 CRSwNP patients after treatment with the standard treatment regimen is 16.7%-96.1%.

[0003] Currently, the diagnosis of type 2 CRSwNP mainly relies on CRSwNP tissues obtained during surgery. CRSwNP patients with positive IL-5 (≥12.98 pg / mL) in CRSwNP tissues are considered type 2 CRSwNP patients. Although studies have found that extensive surgical methods such as completely removing the diseased mucosa of the paranasal sinuses can reduce the recurrence rate of type 2 CRSwNP patients, it also leads to over-surgical treatment of non-type 2 CRSwNP patients, resulting in adverse events such as empty nose syndrome; while some type 2 CRSwNP patients undergo functional endoscopic sinus surgery (FESS), and the patients relapse quickly, increasing the economic losses and physical and mental burdens of the patients. In addition, the application of biological agents that antagonize type 2 inflammatory responses also greatly depends on the clear diagnosis of type 2 CRSwNP. Currently, there is a lack of a preoperative, non-invasive, and effective diagnostic method for type 2 CRSwNP in clinical practice.

[0004] Developing a non-invasive, rapid and accurate diagnosis of type 2 CRSwNP will enable doctors to promptly and as early as possible select appropriate treatment plans according to the patient's condition, reduce patient recurrence, and improve the patient's quality of life. This is a technical problem that urgently needs to be solved. Summary of the Invention

[0005] The technical problem to be solved by this invention is how to develop a kit for non-invasively, accurately and rapidly diagnosing patients with type 2 chronic rhinosinusitis with nasal polyps.

[0006] To solve the above technical problem, the present invention first provides the application of a system for detecting the content of inflammatory factors in the preparation of a product for diagnosing or assisting in diagnosing whether a patient with chronic rhinosinusitis with nasal polyps is a patient with type 2 chronic rhinosinusitis with nasal polyps.

[0007] In the above application, the inflammatory factor may be inflammatory factor A or inflammatory factor B.

[0008] The inflammatory factor A may be interleukin 5, C-C motif chemokine ligand 5 and C-C motif chemokine ligand 26. The inflammatory factor B may be interleukin 5, C-C motif chemokine ligand 5, C-C motif chemokine ligand 24, C-C motif chemokine ligand 26 and periostin.

[0009] In the above application, the system may be system A or system B.

[0010] The system A may be a system including detecting the content of three inflammatory factors, namely interleukin 5, C-C motif chemokine ligand 5 and C-C motif chemokine ligand 26.

[0011] The system B may be a system including detecting the content of five inflammatory factors, namely interleukin 5, C-C motif chemokine ligand 5, C-C motif chemokine ligand 24, C-C motif chemokine ligand 26 and periostin.

[0012] The above-mentioned system may be a product.

[0013] In the above application, the product may include a liquid-phase chip and reagents or instruments required for detecting the content of the inflammatory factors through the liquid-phase chip.

[0014] The liquid-phase chip may be a Luminex liquid-phase chip. The Luminex liquid-phase chip may be a Luminex liquid-phase chip for respectively detecting interleukin 5, C-C motif chemokine ligand 5, C-C motif chemokine ligand 24, C-C motif chemokine ligand 26 and periostin.

[0015] The product may include interleukin-5, CC chemokine ligand 5, CC chemokine ligand 24, CC chemokine ligand 26, and / or periostin. Interleukin-5, CC chemokine ligand 5, CC chemokine ligand 24, CC chemokine ligand 26, and / or periostin in the product serve as standards for preparing a standard curve. To solve the above technical problems, the present invention also provides a device for non-invasive diagnosis or auxiliary diagnosis of type 2 chronic rhinosinusitis with nasal polyps. The device may include a data receiving module and a data processing module. The data receiving module may be configured to receive the content of inflammatory factors, age, and the total CT score of rhinosinusitis in the nasal secretions of a patient with chronic rhinosinusitis with nasal polyps to be tested. The data processing module may be used to convert the content of the inflammatory factors and age from the data receiving module into a risk value of the patient with chronic rhinosinusitis with nasal polyps to be tested having type 2 chronic rhinosinusitis with nasal polyps, and predict whether the patient with chronic rhinosinusitis with nasal polyps to be tested has type 2 chronic rhinosinusitis with nasal polyps based on the risk value.

[0016] In the device described above, the inflammatory factors may be interleukin-5, CC chemokine ligand 5, CC chemokine ligand 24, CC chemokine ligand 26, and periostin.

[0017] In the device described above, the data processing module may be configured to calculate the risk value of a patient with chronic rhinosinusitis with nasal polyps to be tested having type 2 chronic rhinosinusitis with nasal polyps according to Equation I:

[0018] y = -0.0156age - 0.0029CCL5 + 0.0012CCL26 - 0.000178CCL24 + 0.000028periostin + 0.339IL-5 - 0.00782CT score Equation I;

[0019] In Equation I, IL-5 represents the content of interleukin-5 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL. CCL5 represents the content of CC chemokine ligand 5 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL. CCL26 represents the content of CC chemokine ligand 26 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL. CCL24 represents the content of CC chemokine ligand 24 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL. periostin represents the content of periostin in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL. The age represents the age of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of years. CT score is the total CT score of the patient's rhinosinusitis. y represents the risk value of the patient with chronic rhinosinusitis with nasal polyps to be tested having type 2 chronic rhinosinusitis with nasal polyps.

[0020] The age unit of the patient described above can be years old.

[0021] In the device described above, when the y is greater than -0.371, the patient with chronic rhinosinusitis with nasal polyps to be tested can be a patient with type 2 chronic rhinosinusitis with nasal polyps. When the y is less than or equal to -0.371, the patient with chronic rhinosinusitis with nasal polyps to be tested can be a patient with non-type 2 chronic rhinosinusitis with nasal polyps.

[0022] The patient with non-type 2 chronic rhinosinusitis with nasal polyps can be a patient with type 1 chronic rhinosinusitis with nasal polyps or a patient with type 3 chronic rhinosinusitis with nasal polyps.

[0023] The device for non-invasive diagnosis or auxiliary diagnosis of type 2 chronic rhinosinusitis with nasal polyps can be a device for diagnosing or assisting in diagnosing whether a patient with chronic rhinosinusitis with nasal polyps is a patient with type 2 chronic rhinosinusitis with nasal polyps.

[0024] To solve the above technical problems, the present invention also provides a kit for non-invasive diagnosis or auxiliary diagnosis of type 2 chronic rhinosinusitis with nasal polyps.

[0025] The kit can include a parameter detection device. The parameter detection device can be used to detect the content of inflammatory factors in the nasal secretions of a patient with chronic rhinosinusitis with nasal polyps to be tested. The inflammatory factors can be interleukin 5, C-C motif chemokine ligand 5, and C-C motif chemokine ligand 26.

[0026] In the kit described above, the parameter detection device can be a parameter detection device for detecting the concentrations of interleukin 5, C-C motif chemokine ligand 5, and C-C motif chemokine ligand 26.

[0027] The kit described above can also include a readable carrier. The readable carrier can record the following content:

[0028] When the content of interleukin 5 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested is greater than 4.805 pg / mL, the output result of the readable carrier is 1.

[0029] When the content of interleukin 5 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested is less than or equal to 4.805 pg / mL, and the content of C-C motif chemokine ligand 26 is greater than 13.35 pg / mL and the content of C-C motif chemokine ligand 5 is less than or equal to 87.78 pg / mL, the output result of the readable carrier is 1.

[0030] When the concentrations of interleukin 5, C-C motif chemokine ligand 26, and C-C motif chemokine ligand 5 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested do not meet the above conditions, the output result of the readable carrier is 0.

[0031] When the output result of the readability carrier is 1, the patient with chronic rhinosinusitis with nasal polyps to be tested is a patient with type 2 chronic rhinosinusitis with nasal polyps. When the output result of the readability carrier is 0, the patient with chronic rhinosinusitis with nasal polyps to be tested is not a patient with type 2 chronic rhinosinusitis with nasal polyps.

[0032] In the above-mentioned kit, the parameter detection device may include a liquid-phase chip and reagents or instruments required for detecting the content of the inflammatory factors through the liquid-phase chip.

[0033] To solve the above technical problems, the present invention also provides a device for non-invasive diagnosis or auxiliary diagnosis of type 2 chronic rhinosinusitis with nasal polyps. The device may include a data receiving module and a data processing module; the data receiving module may be configured to receive the content of the inflammatory factors in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested. The data processing module may be used to convert the content of the inflammatory factors from the data receiving module into the risk value of the patient with chronic rhinosinusitis with nasal polyps to be tested suffering from type 2 chronic rhinosinusitis with nasal polyps, and whether the patient with chronic rhinosinusitis with nasal polyps to be tested has type 2 chronic rhinosinusitis with nasal polyps can be predicted according to the risk value.

[0034] The inflammatory factors may be interleukin-5, C-C motif chemokine ligand 26, and C-C motif chemokine ligand 5.

[0035] In the above-mentioned device, the data processing module may be configured to calculate the risk value z of the patient with chronic rhinosinusitis with nasal polyps to be tested suffering from type 2 chronic rhinosinusitis with nasal polyps according to the output result of the readability carrier described above.

[0036] When the output result of the readability carrier is 1, the z is 1, and the patient with chronic rhinosinusitis with nasal polyps to be tested may be a patient with type 2 chronic rhinosinusitis with nasal polyps. When the output result of the readability carrier is 0, the z is 0, and the patient with chronic rhinosinusitis with nasal polyps to be tested may be a patient with non-type 2 chronic rhinosinusitis with nasal polyps.

[0037] The patient with non-type 2 chronic rhinosinusitis with nasal polyps may be a patient with type 1 chronic rhinosinusitis with nasal polyps or a patient with type 3 chronic rhinosinusitis with nasal polyps.

[0038] The readability carrier described above may be the instruction manual of the kit. The content of the above-mentioned formula Ⅰ may be printed on a card.

[0039] The application of interleukin-5, C-C motif chemokine ligand 26, and C-C motif chemokine ligand 5 as three inflammatory factors as biomarkers in the preparation of products for detecting patients with type 2 chronic rhinosinusitis with nasal polyps also belongs to the protection scope of the present invention.

[0040] The use of five inflammatory factors, interleukin-5, CC chemokine ligand-5, CC chemokine ligand-24, CC chemokine ligand-26, and periostin, as biomarkers in the preparation of a product for detecting patients with type 2 chronic rhinosinusitis with nasal polyps also falls within the protection scope of the present invention.

[0041] In the above-mentioned use, the product may be a reagent, a kit, and / or a device.

[0042] To solve the above technical problems, the present invention also provides any one of the following uses:

[0043] P1. The use of the above-mentioned device or the above-mentioned kit in detecting patients with type 2 chronic rhinosinusitis with nasal polyps.

[0044] P2. The use of the above-mentioned device or the above-mentioned kit in the preparation of a product for detecting patients with type 2 chronic rhinosinusitis with nasal polyps.

[0045] P3. The use of three inflammatory factors, interleukin-5, CC chemokine ligand-26, and CC chemokine ligand-5, as biomarkers in detecting patients with type 2 chronic rhinosinusitis with nasal polyps.

[0046] P4. The use of five inflammatory factors, interleukin-5, CC chemokine ligand-5, CC chemokine ligand-24, CC chemokine ligand-26, and periostin, as biomarkers in detecting patients with type 2 chronic rhinosinusitis with nasal polyps.

[0047] To solve the actual clinical difficulties, based on the expression of inflammatory factors in the nasal secretions of patients with chronic rhinosinusitis with nasal polyps, the present invention screens clinical indicators and secretion inflammatory indicators that can be used for diagnosing type 2 CRSwNP through machine learning including decision trees and logistic regression, and establishes a model for non-invasive, accurate, and rapid diagnosis of type 2 CRSwNP patients, a diagnostic kit based on the model, and related devices, which is conducive to doctors selecting the correct treatment plan in clinical practice to treat refractory CRSwNP.

[0048] During the above-mentioned establishment process, random oversampling is used to handle class imbalance, and the best parameters suitable for each model are as follows:

[0049] Decision tree: The criterion is the entropy coefficient, the maximum number of leaves is 40, the minimum number of samples at a node is 2, the AUC is 0.899±0.050, the sensitivity is 0.832±0.083, and the specificity is 0.966±0.056

[0050] Logistic regression: The penalty coefficient C is 0.05, L1 regularization is used, the AUC is 0.800±0.053, the sensitivity is 0.678±0.092, and the specificity is 0.915±0.080

[0051] The AUC of the diagnostic model established by the decision tree is 0.862, the sensitivity is 68.1%, and the specificity is 100%.

[0052] The AUC value of the diagnostic model established by logistic regression is 0.856, the sensitivity is 79.3%, and the specificity is 85.2%.

[0053] The beneficial effects of the present invention compared with the prior art are as follows:

[0054] Currently, the area under the receiver operating characteristic curve (AUC) of clinical indicators for diagnosing type 2 CRSwNP, such as peripheral blood eosinophil count, eosinophil percentage, and the ratio of computed tomography (CT) ethmoid sinus and maxillary sinus scores (E / M), are all below 0.7. The AUC of the diagnostic model for type 2 CRSwNP established by machine learning decision tree of the present invention is 0.862, the sensitivity is 68.1%, and the specificity is 100% ( Figure 1 ), and the AUC of the diagnostic model for type 2 CRSwNP established by the logistic regression model is 0.856, the sensitivity is 79.3%, and the specificity is 85.2%, all of which are higher than the currently commonly used clinical indicators. The present invention provides a non-invasive kit and device for rapid pre-treatment diagnosis of type 2 CRSwNP with high sensitivity and specificity, which can provide a basis for clinicians to select reasonable treatment regimens such as drugs, biological agents, or surgical methods. Description of the Drawings

[0055] Figure 1 This is the prediction effect of using the decision tree model in a cohort of 162 patients of the present invention. IL-5, CCL5, and CCL26 refer to the concentration (pg / mL) of the inflammatory factor in the secretion.

[0056] Figure 2 This is the ROC curve established using the decision tree and logistic regression models.

[0057] Figure 3 This is the ROC curve for diagnosing type 2 CRSwNP using other commonly used clinical indicators.

[0058] Figure 4 This is the ROC curve for diagnosing type 2 CRSwNP using a single secretion index. Detailed Embodiments

[0059] The present invention will be further described in detail below in conjunction with the specific embodiments. The provided embodiments are only for clarifying the present invention, rather than limiting the scope of the present invention. The following provided embodiments can be used as a guide for those of ordinary skill in the art to make further improvements, and do not limit the present invention in any way.

[0060] In the following examples, the experimental methods are conventional methods unless otherwise specified, and are carried out according to the techniques or conditions described in the literature in this field or according to the product instructions. The materials, reagents, etc. used in the following examples can be obtained from commercial sources unless otherwise specified.

[0061] The receiver operating characteristic (ROC) reflects the balance between sensitivity and specificity. The area under the ROC curve is an important indicator of test accuracy. The larger the area under the ROC curve, the greater the diagnostic value of the test.

[0062] Sensitivity (true positive rate): The percentage of patients who actually have the disease and are correctly judged to have the disease according to the test standard. The greater the sensitivity, the better. The ideal sensitivity is 100%.

[0063] Specificity (true negative rate): The percentage of patients who actually do not have the disease and are correctly judged to not have the disease according to the test standard. The greater the specificity, the better. The ideal specificity is 100%.

[0064] Example 1: Establish a diagnostic model for type 2 CRSwNP using a machine learning scheme

[0065] The experimental data of the present invention comes from 162 CRSwNP patients hospitalized in the Department of Otorhinolaryngology and Allergy of Beijing Tongren Hospital, Capital Medical University. Inclusion criteria: ① According to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS2012), the diagnosis of CRSwNP is clear. ② Glucocorticoids or antibiotics have not been taken 4 weeks before surgery. ③ Informed consent has been signed.

[0066] 1. Collection of experimental data

[0067] 1.1 Collection of nasal secretions and data measurement

[0068] Nasopharyngeal secretions and concentrated nasopharyngeal secretions of 162 CRSwNP patients were collected using polyvinyl alcohol (PVA). The concentrations of interleukin 5 (IL-5), C-C motif chemokine ligand 5 (CCL5), C-C motif chemokine ligand 26 (CCL26), C-C motif chemokine ligand 24 (CCL24), and periostin in the nasopharyngeal secretions were measured using a Luminex liquid chip (R&D). Among them, the catalog number of the Luminex liquid chip for measuring the content of IL-5 in nasopharyngeal secretions is LUHM000, and an IL-5 standard curve was made using IL-5 as the standard product (the abscissa is the concentration of IL-5, and the ordinate is the fluorescence intensity). The catalog number of the Luminex liquid chip for measuring the content of CCL5 in nasopharyngeal secretions is LXSAHM, and a CCL5 standard curve was made using CCL5 as the standard product (the abscissa is the concentration of CCL5, and the ordinate is the fluorescence intensity). The catalog number of the Luminex liquid chip for measuring the content of CCL26 in nasopharyngeal secretions is LXSAHM, and a CCL26 standard curve was made using CCL26 as the standard product (the abscissa is the concentration of CCL26, and the ordinate is the fluorescence intensity). The catalog number of the Luminex liquid chip for measuring the content of CCL24 in nasopharyngeal secretions is LXSAHM, and a CCL24 standard curve was made using CCL24 as the standard product (the abscissa is the concentration of CCL24, and the ordinate is the fluorescence intensity). The catalog number of the Luminex liquid chip for measuring the content of periostin in nasopharyngeal secretions is LXSAHM, and a periostin standard curve was made using periostin as the standard product (the abscissa is the concentration of periostin, and the ordinate is the fluorescence intensity). The method for collecting nasopharyngeal secretions from patients using the PVA method is as follows:

[0069] The patient's nasal cavity was cleaned with normal saline, and an expandable sponge made of polyvinyl alcohol (Jingxi Import and Export Co., Ltd.) was placed in the bilateral middle nasal meatus of the patient for 5 minutes, and then transferred to a test tube containing 3 ml of normal saline and stored at 4°C for 2 hours. The contents of the test tube (nasopharyngeal secretions) were placed in a syringe. The liquid was centrifuged at 1500 g at 4°C for 5 minutes, and the supernatant was taken, and the concentration of inflammatory factors in the nasopharyngeal secretions was immediately detected (or stored at -80°C until the concentration of inflammatory factors was measured). The concentrations of inflammatory factors IL-5, CCL5, CCL24, CCL26, and periostin in the secretions were detected using a Luminex liquid chip from R&D.

[0070] 1.2 Collection of Other Clinical Data

[0071] Record the gender, age, Body Mass Index (BMI), eosinophil count in nasal cytology smear, smoking status, presence of asthma, history of sinus surgery, blood leukocyte count, peripheral blood eosinophil count, total CT score of sinusitis (CTscore), and the ratio of ethmoid sinus to maxillary sinus score (E / M) of 162 CRSwNP patients (Table 1).

[0072] Among them, the eosinophil count in nasal cytology smear was obtained by scraping cells from the middle part of the bilateral inferior turbinates of the patients with a nasal curette onto a glass slide, and after Gram staining, the number of eosinophils in the nasal cytology smear was calculated according to the Meltzer semi - quantitative scale.

[0073] Among them, the total CT score of sinusitis and the E / M ratio were obtained by using a Computed Tomography (CT) machine (Philips, Netherlands) to acquire the sinus imaging data of the patients, and the total CT score of sinusitis and E / M of the patients were calculated according to the Lund - Mackay scale.

[0074] The blood eosinophil and leukocyte counts were obtained by using an automatic blood cell analyzer.

[0075] Table 1. Basic information of 162 CRSwNP patients

[0076]

[0077] Note: Age and nasal secretion inflammatory factors are expressed as median (lower quartile - upper quartile).

[0078] 2. Establish a diagnostic model for type 2 CRSwNP using a machine learning model

[0079] Based on the data of 162 CRSwNP patients collected and measured in step 1, including the eosinophil count in nasal cytology smear, and the concentrations of inflammatory factors IL - 5, CCL5, CCL24, CCL26, and periostin in each CRSwNP patient; gender, age, BMI, smoking status, presence of asthma, history of sinus surgery; blood leukocyte count, blood eosinophil count, total CT score of sinusitis, and the ratio of ethmoid sinus to maxillary sinus score (E / M) data, establish machine learning models, including decision tree and logistic regression, and finally establish a diagnostic model for type 2 CRSwNP.

[0080] Random oversampling was used to handle class imbalance, and nested cross-validation was used to obtain an unbiased estimate of AUC. In the outer cross-validation, the data of 162 CRSwNP patients were divided into a training set (data of 130 patients) and a test set (data of 32 patients) at a ratio of 4:1. In the inner cross-validation, the training set was divided into another training set (data of 104 patients) and a validation set (data of 26 patients) at a ratio of 4:1. The best parameters were searched by grid search in the training set for training, and the parameters corresponding to the maximum AUC in the validation set were selected. 100 times of nested cross-validation were performed, and the average results on 500 test sets were reported. The finally determined best hyperparameters were the parameters with the maximum AUC on the test set (Table 2).

[0081] Table 2 Diagnostic effects of different machine learning models on type 2 CRSwNP

[0082]

[0083] The best parameters based on decision tree were trained in the overall cohort and pruned by restricting the maximum tree depth. The final model was that when IL-5 > 4.805 pg / mL in the secretion; or IL-5 ≤ 4.805 pg / mL, and CCL26 > 13.35 pg / mL, CCL5 ≤ 87.78 pg / mL, it was type 2 CRSwNP, and in other cases it was non-type 2 CRSwNP. The ROC curve of this model is as Figure 2 shown, with an AUC value of 0.862, a sensitivity of 68.1%, and a specificity of 100%( Figure 1 ).

[0084] The best parameters based on logistic regression were trained in the overall cohort, y = -0.0156age - 0.0029CCL5 + 0.0012CCL26 - 0.000178CCL24 + 0.000028periostin + 0.339IL-5 - 0.00782CT score; when y > -0.371, it was considered as type 2 CRSwNP.

[0085] Among them, CCL5, CCL26, CCL24, periostin, and IL-5 are the concentrations of the corresponding inflammatory factors in nasal secretions, with the unit of pg / mL; age is the patient's age; CTscore is the total CT score of the patient's sinusitis.

[0086] The ROC curve of this model is as Figure 2 shown, with an AUC value of 0.856, a sensitivity of 79.3%, and a specificity of 85.2%.

[0087] Among them, AUC is the area under the receiver operating characteristic curve, sensitivity = number of true positives / (number of true positives + number of false negatives), and specificity = number of true negatives / (number of true negatives + number of false positives).

[0088] 3. Comparison of the results of diagnosing type 2 CRSwNP with existing technologies

[0089] The effects of other clinical indicators were verified in 162 CRSwNP patients. Currently, the non-surgical clinical indicators for detecting type 2 CRSwNP include blood eosinophil count (EOS%), eosinophil count (EOS#), the ratio of the computed tomography (CT) scores of the ethmoid sinus and maxillary sinus (E / M), etc. The areas under the receiver operating characteristic curves (AUC) of the three clinical indicators for diagnosing type 2 CRSwNP patients were 0.682, 0.700, and 0.630 respectively, and the results were all lower than the AUC values detected by the decision tree and logistic regression models ( Figure 3 ).

[0090] Among them, the blood eosinophil count (EOS%) is the number of eosinophils / the number of blood white blood cells.

[0091] The eosinophil count (EOS#) is the number of eosinophils per liter of peripheral blood (×10 9 ).

[0092] Among the clinical indicators, there were no differences in indicators such as gender, age, BMI, whether smoking, whether combined with asthma, whether having a history of sinus surgery, blood white blood cell count, and the total score of sinusitis CT in the two groups (i.e., type 2 and non-type 2 CRSwNP).

[0093] Among them, the detection methods of EOS% and E / M are the same as those in step 1.2.

[0094] At the same time, the effects of a single nasal secretion index and the decision tree and logistic regression models in diagnosing type 2 CRSwNP patients were compared in 162 CRSwNP patients. The AUC values of the corresponding ROC curves of CCL5, CCL26, CCL24, periostin, and IL-5 in the secretion were 0.613, 0.802, 0.664, 0.731, and 0.820 respectively, and the results were also all lower than the AUC values detected by the decision tree and logistic regression models ( Figure 4 ).

[0095] The above has described the present invention in detail. For those skilled in the art, without departing from the gist and scope of the present invention and without the need for unnecessary experiments, the present invention can be implemented within a relatively wide range under equivalent parameters, concentrations, and conditions. Although specific embodiments of the present invention are given, it should be understood that the present invention can be further improved. In short, according to the principle of the present invention, this application intends to cover any modifications, uses, or improvements to the present invention, including those that depart from the scope disclosed in this application but are made using conventional techniques known in the art. The application of some basic features can be made within the scope of the appended claims below.

Claims

1. A device for non-invasive diagnosis or auxiliary diagnosis of type 2 chronic rhinosinusitis with nasal polyps, characterized in that: The device includes a data receiving module and a data processing module; the data receiving module is configured to receive the content of inflammatory factors, age, and the total CT score of sinusitis of a patient with chronic rhinosinusitis with nasal polyps to be tested, and the data processing module is used to convert the content of the inflammatory factors and age from the data receiving module into the risk value of the patient with chronic rhinosinusitis with nasal polyps suffering from type 2 chronic rhinosinusitis with nasal polyps through logistic regression training, and predict whether the patient with chronic rhinosinusitis with nasal polyps to be tested has type 2 chronic rhinosinusitis with nasal polyps according to the risk value; The inflammatory factors are interleukin 5, C-C motif chemokine ligand 5, C-C motif chemokine ligand 24, C-C motif chemokine ligand 26, and periostin; The calculation formula of the risk value is as follows: Formula I y = -0.0156 age - 0.0029 CCL5 + 0.0012 CCL26 - 0.000178 CCL24 + 0.000028 periostin + 0.339 IL-5 - 0.00782 CT score Formula I; In Formula I, IL-5 represents the content of interleukin 5 in the nasal secretion of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL; CCL5 represents the content of C-C motif chemokine ligand 5 in the nasal secretion of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL; CCL26 represents the content of C-C motif chemokine ligand 26 in the nasal secretion of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL; CCL24 represents the content of C-C motif chemokine ligand 24 in the nasal secretion of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL; periostin represents the content of periostin in the nasal secretion of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of pg / mL; age represents the age of the patient with chronic rhinosinusitis with nasal polyps to be tested, with the unit of years; CT score represents the total CT score of sinusitis of the patient with chronic rhinosinusitis with nasal polyps to be tested; y represents the risk value of the patient with chronic rhinosinusitis with nasal polyps to be tested suffering from type 2 chronic rhinosinusitis with nasal polyps.

2. A device for non-invasive diagnosis or auxiliary diagnosis of type 2 chronic rhinosinusitis with nasal polyps, characterized in that: The device includes a data receiving module and a data processing module; the data receiving module is configured to receive the content of inflammatory factors in the nasal secretion of a patient with chronic rhinosinusitis with nasal polyps to be tested, and the data processing module is used to convert the content of the inflammatory factors from the data receiving module into the risk value of the patient with chronic rhinosinusitis with nasal polyps suffering from type 2 chronic rhinosinusitis with nasal polyps through decision tree training, and predict whether the patient with chronic rhinosinusitis with nasal polyps to be tested has type 2 chronic rhinosinusitis with nasal polyps according to the risk value; The inflammatory factors are interleukin 5, C-C motif chemokine ligand 26, and C-C motif chemokine ligand 5; When the inflammatory factor meets the following condition A1) or A2), the risk value is 1, and the patient with chronic rhinosinusitis with nasal polyps to be tested has type 2 chronic rhinosinusitis with nasal polyps; when the inflammatory factor does not meet the following conditions A1) and A2), the risk value is 0, and the patient with chronic rhinosinusitis with nasal polyps to be tested does not have type 2 chronic rhinosinusitis with nasal polyps; A1) The content of interleukin-5 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested is greater than 4.805 pg / mL; A2) The content of interleukin-5 in the nasal secretions of the patient with chronic rhinosinusitis with nasal polyps to be tested is less than or equal to 4.805 pg / mL, and the content of CC chemokine ligand 26 is greater than 13.35 pg / mL and the content of CC chemokine ligand 5 is less than or equal to 87.78 pg / mL.

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