Method for diagnosing acute exacerbation of bronchiectasis and kit therefor

Abstract

The present invention relates to a method for predicting acute exacerbation of bronchiectasis, and a kit therefor. When the method and the kit according to the present invention are used, acute exacerbation of bronchiectasis can be easily diagnosed through a quantitative index.

Description

A method for diagnosing acute exacerbation of bronchiectasis and a kit therefor

[0001] This invention claims priority to Republic of Korea Patent Application No. 10-2023-0145128, filed with the Korean Intellectual Property Office on October 26, 2023, the disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a method for predicting acute exacerbation of bronchiectasis and a kit therefor.

[0003]

[0004] Bronchiectasis is a condition in which the airways are permanently dilated to the point where they cannot return to their original size. This condition can be localized or widespread throughout the lungs, and the affected airways exhibit a variety of changes, including inflammation, mucosal edema, ulceration, neovascularization of bronchial arterioles, scarring, and bronchial tortuosity due to repeated infections. Bronchial obstruction by airway secretions can lead to pneumonia, which can in turn cause temporary or permanent damage to the lung parenchyma. Factors that contribute to bronchiectasis include: 1) infectious insult, 2) airway obstruction, 3) impaired mucus and secretion clearance, and 4) impaired host defense mechanisms.

[0005] Meanwhile, bronchiectasis is caused by inflammation and destruction of the elements that make up the bronchial wall. The most common cause of inflammation is infection, and some microorganisms secrete pigments, proteolytic enzymes, and toxins that damage the respiratory epithelium and reduce the mucus-clearing ability of cilia. The host's inflammatory response primarily damages the epithelium through mediators secreted by neutrophils. A weakened resistance to infection allows bacterial colonization and growth to occur more readily in the dilated bronchi. Consequently, the inflammatory response leads to airway damage, a decreased ability to clear microorganisms, and the subsequent infection, which can lead to an even more severe inflammatory response.

[0006] Methods for diagnosing bronchiectasis include a physical examination, including auscultation of the chest to assess changes in breath sounds and dyspnea, simple chest X-rays, high-resolution chest computed tomography (CT), sputum cultures, bronchoscopy, bronchography, and pulmonary function tests. However, no objective, quantitative screening method exists for bronchiectasis.

[0007] Bronchiectasis presents with a wide range of clinical presentations, from those with minimal respiratory symptoms to those with frequent acute exacerbations and severe structural lung damage requiring lung transplantation. Consequently, patients may present with a wide range of prognoses. Recent studies have shown an increasing prevalence of bronchiectasis and a rising rate of disease-related hospitalizations, making it a disease with a significant burden of illness. Therefore, an objective and useful severity classification system that accurately reflects the prognosis of patients with bronchiectasis is necessary for the appropriate treatment and management of these patients. Recently, several indices have been developed that effectively assess the severity of bronchiectasis by considering various clinical factors along with radiological findings.

[0008] Meanwhile, regardless of the severity of bronchiectasis, acute exacerbations can occur in patients with mild to severe disease. Acute exacerbations in patients with bronchiectasis can be characterized by increased sputum production, increased purulence, or bloody sputum, and prominent systemic symptoms, including fever. However, it is difficult to determine whether the onset of these symptoms is due to an acute exacerbation, and no diagnostic kit has been developed to identify this condition before or during the early stages of an acute exacerbation.

[0009] Numerous papers and patents are referenced and cited throughout this specification. The disclosures of these cited papers and patents are incorporated herein by reference in their entirety to provide a clearer understanding of the state of the art and the scope of the present invention.

[0010]

[0011] The present inventors have diligently researched and developed a method and diagnostic kit capable of diagnosing acute exacerbations of bronchiectasis using objective, quantitative indicators. As a result, we confirmed that patients with acute exacerbations (AEs) of bronchiectasis commonly had sputum MPO concentrations exceeding a predetermined level. Furthermore, we demonstrated that this indicator can be used to objectively and quantitatively assess the state of acute exacerbations of bronchiectasis, thereby completing the present invention.

[0012] Accordingly, an object of the present invention is to provide a method for providing information for diagnosing acute exacerbation of bronchiectasis.

[0013] Another object of the present invention is to provide a diagnostic kit for diagnosing acute exacerbation of bronchiectasis.

[0014]

[0015] According to one aspect of the present invention, the present invention provides a method for providing information for diagnosing acute exacerbation of bronchiectasis, comprising the step of measuring the concentration of myeloperoxidase (MPO) in a biological sample isolated from a subject; wherein, if the measured MPO concentration exceeds 50 ng / ml, it is determined that the condition is an acute exacerbation of bronchiectasis.

[0016] The present inventors have conducted extensive research to develop a method and diagnostic kit capable of diagnosing acute exacerbations of bronchiectasis using objective, quantitative indicators. As a result, we confirmed that sputum MPO concentrations commonly exceeded a predetermined level in patients with acute exacerbations (AEs) of bronchiectasis. This finding demonstrated that this indicator could be used to objectively and quantitatively assess the severity of acute exacerbations of bronchiectasis.

[0017] In one embodiment of the present invention, the “subject” means a specimen suspected of being in an acute exacerbation state of bronchiectasis, and a mammal capable of developing bronchiectasis may be the subject, and more specifically, includes a human patient suspected of having developed bronchiectasis or diagnosed with having developed bronchiectasis.

[0018] In one embodiment of the present invention, the "subject" is a subject suffering from bronchiectasis. Since the information provision method of the present invention can be advantageously utilized to determine whether a subject with bronchiectasis is experiencing an acute exacerbation, the aforementioned "subject" can be effectively used for patients diagnosed with bronchiectasis.

[0019] In one embodiment of the present invention, the “subject” is a subject who has not experienced an acute exacerbation within 3 weeks. In the information providing method of the present invention, in the case of a subject who has experienced an acute exacerbation within 3 weeks from the time of performing the step of measuring the MPO (myeloperoxidase) concentration in a biological sample isolated from the subject, the MPO concentration standard for determining whether the subject has stabilized from an acute exacerbation to a stable state may be a value higher than 50 ng / ml.

[0020] The term “biological sample” in this specification may be any one selected from sputum, saliva, blood, serum or alveolar lavage fluid collected from the subject described above by various methods.

[0021] In one embodiment of the present invention, the "biological sample" is sputum. Acute exacerbations of bronchiectasis are typically accompanied by an increase in the production or amount of sputum. In this case, an acute exacerbation may be suspected, and sputum may be collected from the patient for objective and quantitative confirmation of the presence of an acute exacerbation, which may be usefully used as a biological sample in one embodiment of the present invention.

[0022] The term "MPO (myeloperoxidase)" in this specification is also called myeloperoxidase. It is the most abundant protein in neutrophils and is one of the major enzymes secreted outside the cells when neutrophils are activated, and is therefore used as an indicator of neutrophil activity. MPO can contribute to the process of neutrophils migrating to the site of inflammation and can cause alveolar damage when excessive inflammation occurs in the lungs because it catalyzes the process of generating hypochlorous acid, a strong oxidizing agent, from hydrogen peroxide and chloride ions. Although MPO concentrations are known to increase in inflammatory situations or in damaged lungs, the correlation between acute exacerbations that can occur in patients from the onset of the disease to the progression to severe disease, regardless of the severity of bronchiectasis, and MPO concentrations is unknown.

[0023] The MPO of the present invention may be a protein having an amino acid sequence represented by SEQ ID NO: 1 or a protein having an amino acid sequence having 90% or more, 95% or more, or 98% or more homology with the amino acid sequence of SEQ ID NO: 1. SEQ ID NO: 1 may be composed of a sequence corresponding to UNIPROT ID P05164.

[0024] [Sequence number 1]

[0025] MGVPFFSSLRCMVDLGPCWAGGLTAEMKLLLALAGLLAILATPQPSEGAAPAVLGEVDTSLVLSSMEEAKQLVDKAYKERRESIKQRLRSGSASPMELLSYFKQPVAATRTAVRAADYLHVALDLLERKLRSLWRRPFNVTDVLTPAQLNVLSKSSGCAYQDVGVTCPEQDKYRTITGMCNNRRSPTLGASNRAFVRWLPAEYEDGFSLPYGWTPGVKRNGFPVALARAVSNEIVRFPTDQLTPDQERSLMFMQWGQLLDHDLDFTPEPAARASFVTGVNCETSCVQQPPCFPLKIPPNDPRIKNQADCIPFFRSCPACPGSNITIRNQINALTSFVDASMVYGSEEPLARNLRNMSNQLGLLAVNQRFQDNGRALLPFDNLHDDPCLLTNRSARIPCFLAGDTRSSEMPELTSMHTLLLREHNRLATELKSLNPRWDGERLYQEARKIVGAMVQIITYRDYLPLVLGPTAMRKYLPTYRSYNDSVDPRIANVFTNAFRYGHTLIQPFMFRLDNRYQPMEPNPRVPLSRVFFASWRVVLEGGIDPILRGLMATPAKLNRQNQIAVDEIRERLFEQVMRIGLDLPALNMQRSRDHGLPGYNAWRRFCGLPQPETVGQLGTVLRNLKLARKLMEQYGTPNNIDIWMGGVSEPLKRKGRVGPLLACIIGTQFRKLRDGDRFWWENEGVFSMQQRQALAQISLPRIICDNTGITTVSKNNIFMSNSYPRDFVNCSTLPALNLASWREAS

[0026] The term “acute exacerbation” in the present invention specifically refers to acute exacerbation of bronchiectasis, and clinically, acute exacerbation refers to the worsening of symptoms such as cough, change in sputum, and dyspnea in patients with bronchiectasis. Hill et al. (Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, et al. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J 2017;49.) defined acute exacerbation of bronchiectasis for clinical research as follows through a systematic review and discussion of papers by several bronchiectasis experts. In a patient with bronchiectasis, if three or more of the following worsening symptoms persist for more than 48 hours: (i) cough, (ii) changes in sputum volume and viscosity, (iii) purulent sputum, (iv) dyspnea and / or decreased exercise capacity, (v) fatigue and / or weakness, and (vi) hemoptysis, and the physician decides to change the treatment of bronchiectasis. The acute exacerbation of bronchiectasis of the present invention refers to a state that is expected to be clinically judged to be an acute exacerbation state based on the above criteria.

[0027] According to an information providing method according to one embodiment of the present invention, when the MPO concentration measured from the biological sample described above exceeds 50 ng / ml, it can be confirmed that the subject is in an acute exacerbation state of bronchiectasis. The present inventors have objectively determined whether acute exacerbation or stable state has occurred in patients diagnosed with bronchiectasis according to current clinical judgment criteria using the quantitative indicator of MPO concentration in biological samples collected from patients, and have clarified that an acute exacerbation state can be determined when the MPO concentration in the biological sample exceeds 50 ng / ml. In addition to demonstrating a correlation between the MPO concentration in the biological sample and the acute exacerbation state of bronchiectasis, an objective judgment standard has been presented for the first time. According to a specific embodiment of the present invention, the MPO concentration in the biological sample evaluated as an acute exacerbation state can be basically defined as a value exceeding 50 ng / ml, but can be presented as a changed value to reflect various characteristics of the patient group. Specifically, for example, in order to determine whether a group of patients who have suffered an acute exacerbation will recover to a normal state within a short period of time, for example, within 1 week, 2 weeks, 3 weeks, or 4 weeks, the upper limit of the MPO concentration can be defined as a value higher than 50 ng / ml, and for example, 60 ng / ml, 65 ng / ml, 70 ng / ml, 75 ng / ml, or 80 ng / ml can be used as the upper limit, and a case having an MPO concentration below that standard can be determined to be in a normal state.

[0028] In one embodiment of the present invention, the step of measuring the MPO (myeloperoxidase) concentration can be performed by the following steps:

[0029] (a) mixing the biological sample with a detection buffer containing a first anti-MPO antibody labeled with a fluorescent element;

[0030] (b) reacting the mixture of step (a) on a membrane coated with a second anti-MPO antibody; and

[0031] (c) A step of measuring the MPO concentration in the biological sample through fluorescence detection of the fluorescent element after step (b).

[0032] The first anti-MPO antibody and the second anti-MPO antibody of one embodiment of the present invention can use various antibodies capable of specifically binding to MPO without limitation, and in addition to existing commercialized anti-MPO antibodies, an antibody newly designed and manufactured based on the MPO protein sequence according to SEQ ID NO: 1 can be preferably used.

[0033] In the above-described embodiment, the first anti-MPO antibody and the second anti-MPO antibody may be of a different or homologous type, and their types are not particularly limited. Specifically, for example, commercially available anti-MPO antibodies at the time of completion of the present invention may be preferably used, and it is self-evident that anti-MPO antibodies developed in the future may also be preferably used for the practice of the present invention.

[0034] In one embodiment of the present invention, the following steps may be additionally performed prior to performing step (a):

[0035] (pre-a) Step of diluting the biological sample with dilution buffer.

[0036] By diluting a biological sample with a dilution buffer, the biological sample can be further stabilized. Specifically, for example, when sputum is used as a biological sample, due to the high viscosity of sputum, the accuracy of MPO concentration measurement can be improved by diluting it with a dilution buffer.

[0037] In one specific example of the present invention, the above-described step (pre-a) may be diluting the biological sample and the dilution buffer in a volume ratio of 1:5 (v / v) to 1:20 (v / v). More specifically, for example, the above-described biological sample and the dilution buffer may be diluted in a volume ratio of 1:5 to 1:15 (v / v), 1:8 to 1:12 (v / v), and most specifically, 1:10 (v / v), but is not limited thereto.

[0038] The detection buffer of step (a) of the present embodiment can be mixed with the above-described biological sample or the above-described biological sample and dilution buffer mixture at a volume ratio of 1:5 (v / v) to 1:20 (v / v). However, the above-described volume ratio corresponds to a range arbitrarily set for ease of detection and is not necessarily limited thereto.

[0039] The term “fluorescent element” in this specification can be understood to mean any fluorescent element known to be usable for immunofluorescence analysis, and is not particularly limited thereto.

[0040] In one embodiment of the present invention, the fluorescent element is selected from the group consisting of Indocyanine green (ICG), IRDye 800CW carboxylate (IRDye 800CW), Alexa fluor-355, Alexa Fluor 488, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor-555, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, Alexa Fluor 780, Flamma 749, Flamma 774, Flamma 800, FSD FluorTM 647, FSD FluorTM 680, FSD FluorTM 750, FSD FluorTM 800, sulfo-cyanine 3.5 carboxylic acid Any one selected from the group consisting of sulfo-cyanine 5 carboxylic acid (Cy3.5), sulfo-cyanine 5.5 carboxylic acid (Cy5.5), sulfo-cyanine 7 carboxylic acid (Cy7) or sulfo-cyanine 7.5 carboxylic acid (Cy7.5), Texas Red, Pacific Blue, Oregon Green 488, JOE, Lissamine, Rhodamine Green, BODIPY, fluorescein isothiocyanate (FITC), carboxy-fluorescein (FAM), Allophycocyanin (APC), phycoerythrin (PE), rhodamine, dichlororhodamine (dRhodamine), carboxy tetramethylrhodamine (TAMRA), carboxy-X-rhodamine (ROX), PicoGreen, and RiboGreen can be used.

[0041] According to another aspect of the present invention, the present invention provides a kit for diagnosing acute exacerbation of bronchiectasis, comprising a membrane coated with an anti-MPO antibody or an antigen-binding fragment thereof, wherein the diagnostic kit is provided in the form of a cartridge for immunofluorescence measurement.

[0042] For example, by utilizing a sandwich immunoassay method in which antibodies bind to antigens, and quantitatively analyzing the luminescence caused by a fluorescent element bound to a detection antibody, it is possible to determine whether bronchiectasis is worsening.

[0043] In one embodiment of the present invention, the kit may include a specimen pad capable of depositing a mixture of a biological sample and a detection antibody, an absorbent pad capable of absorbing the solution and moving the biological sample, and a test line having an anti-MPO antibody immobilized thereon. Furthermore, the kit may further include a control line capable of detecting a control protein.

[0044] In one embodiment of the present invention, the membrane on the kit may be a nitrocellulose membrane. A nitrocellulose membrane is a material suitable for coating and immobilizing antibodies, and can be usefully used in one embodiment of the present invention.

[0045] “Acute exacerbation diagnosis kit for bronchiectasis” as one embodiment of the present invention is a diagnostic kit for use in implementing “Method for providing information for diagnosing acute exacerbation of bronchiectasis” as another embodiment of the present invention described above, and duplicate descriptions are omitted to avoid excessive complexity of the description in this specification.

[0046]

[0047] The features and advantages of the present invention are summarized as follows:

[0048] (a) The present invention provides a method for providing information for diagnosing acute exacerbation of bronchiectasis.

[0049] (b) The present invention provides a diagnostic kit for diagnosing acute exacerbation of bronchiectasis.

[0050] (c) When using the method and kit of the present invention, acute exacerbation of bronchiectasis can be easily diagnosed through quantitative indicators.

[0051]

[0052] Figure 1 shows the study population. The abbreviation AE indicates acute exacerbation. Three patients in the stable group and one patient in the AE group were absent at the first visit or had too little sputum to be measured.

[0053] Figure 2 shows the results comparing MPO concentrations between the stable group and the AE group. AE stands for acute exacerbation, and MPO stands for myeloperoxidase.

[0054] Figure 3 shows changes in MPO concentration according to changes in bronchiectasis status. (a) shows changes in MPO concentration in the stable / stable group, (b) shows changes in MPO concentration in the stable / AE group, (c) shows changes in MPO concentration in the AE / stable group, and (d) shows changes in MPO concentration in the AE / AE group. Patients were classified into four groups according to their disease status at the first and second visits: stable / stable, stable / AE, AE / stable, and AE / AE. The abbreviation AE stands for acute exacerbation, and MPO stands for myeloperoxidase.

[0055] Figure 4 shows the correlation between disease severity in bronchiectasis and MPO concentrations in the stable group. Abbreviations MPO stands for myeloperoxidase, BSI stands for bronchiectasis severity index score, FACED stands for forced expiratory volume in 1 second (F), age (A), presence of chronic colonization with Pseudomonas aeruginosa (C), radiographic enlargement (number of affected lung lobes) (E), and dyspnea (D).

[0056]

[0057] Hereinafter, the present invention will be described in more detail through examples. These examples are intended solely to illustrate the present invention more specifically, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples, in accordance with the gist of the present invention.

[0058]

[0059] Example

[0060] Example 1: Subject Specificity

[0061] Seventy-two patients with bronchiectasis who visited a hospital were prospectively enrolled. All participants underwent sputum examination at study enrollment. Patients in the stable group and the acute exacerbation (AE) group were followed for 3 months and 1–3 weeks, respectively. At the second visit, the patient's condition was reassessed and sputum examination was performed. Accordingly, patients were classified into four groups according to their disease status at the first and second visits (Fig. 1a). Patients in the stable group at the first visit who were stable and those in the AE group at the second visit were classified into the stable / stable group and the stable / AE group, respectively. Similarly, patients in the AE group at the first visit who were stable and those in the AE group at the second visit were classified into the AE / stable group and the AE / AE group, respectively. An acute exacerbation of bronchiectasis is defined as three or more major symptoms lasting more than 48 hours, requiring a change in treatment (Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, Chalmers JD, De Soyza A, Dimakou K, Elborn JS et al. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. The European respiratory journal 2017; 49).The clinical status and severity of bronchiectasis were assessed using the FACED (forced expiratory volume in 1 second [FEV1] % predicted, age, chronic colonization, dilation, and dyspnea) and Bronchial Encephalopathy Severity Index (BSI) scores as previously described (Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, Davidson J, Poppelwell L, Salih W, Pesci A, Dupont LJ. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med 2014; 189: 576-85.). Sputum MPO functional profiles were measured using AnyLab F Myeloperoxydase (Z-Biotech, South Korea), an immunofluorescence-based point-of-care (POCT) test. The primary study outcome was to evaluate whether sputum MPO concentrations differed according to disease status in patients with bronchiectasis.

[0062]

[0063] Example 2: Correlation Analysis between Acute Exacerbations (AEs) and MPO Concentrations

[0064] The mean age of the study group was 66 years (interquartile range [IQR], 59–72 years), and the patients included 40 men (55.6%) and 50 non-smokers (69.4%). The mean body mass index (BMI) was 21.3 kg / m 2 (IQR, 19.5–23.3 kg / m 2) was the most common comorbidity. COPD (33.3%) was the most common, followed by tuberculosis (27.8%) and nontuberculous mycobacterial lung disease (25.0%). Microorganisms were identified in 48.6% of patients, with Pseudomonas aeruginosa (23.6%) being the most common. The median modified Reiff, FACED, and BSI scores were 8 (IQR, 5–13), 2 (IQR, 1–3), and 8 (IQR, 6–9), respectively. There were no significant differences between groups in age, sex, BMI, smoking history, comorbidities, lung function, microbiology, modified Reiff score, BSI score, FACED score, and laboratory results.

[0065] However, baseline MPO concentrations were significantly higher in the AE group than in the stable group (median 195.8 ng / mL [107.7-832.7] vs. 33.0 ng / mL, [IQR 8.2-131.1], p<0.001) (Fig. 1b). In the stable / stable group, there was no significant change in MPO concentrations between the first and second measurements (median 30.8 ng / mL [IQR 6.4-218.0] vs. 49.9 ng / mL [IQR 15.8-231.7], p=0.898). In contrast, in the stable / AE group, the second MPO concentration was increased compared to the first MPO concentration (median 741.7 ng / mL [IQR 108.4-1194.3] vs. 42.6 ng / mL [IQR 22.4-59.0]), although not statistically significant (p=0.250) (Fig. 1c). In the AE / stable group, the second MPO concentration was significantly decreased compared to the first MPO concentration (median 261.5 ng / mL [IQR 127.7-1042.9] vs. 75.0 ng / mL [IQR 26.1-522.7], p=0.026). In contrast, there was no significant change in MPO concentration in the AE / AE group (median 306.1 ng / mL [IQR 89.9–450.0] vs. 890.3 mg / dL [IQR 517.0–818.5], p=0.447) (Fig. 1c). As shown in Fig. 1d, there was no statistically significant correlation between MPO concentrations in the stable group and both BSI and FACED scores (p>0.05 for both indices).

[0066] Analysis of the above results allowed us to derive MPO concentrations for assessing acute exacerbation (AE) status. In the stable group, MPO concentrations were above 50 ng / ml. However, among patients diagnosed with acute exacerbation within 3 weeks prior to MPO measurement and who subsequently recovered to normal, a median value of 75 ng / ml was observed.

[0067] This study reflects the first investigation into whether changes in sputum MPO concentrations can reflect the disease status of bronchiectasis. We observed no significant correlation between sputum MPO concentrations and disease severity, as measured by the BSI and FACED scores. However, sputum MPO concentrations were a good indicator of both the current disease status and the change in disease status in patients with bronchiectasis, suggesting that they are a potential biomarker reflecting the disease status (e.g., whether an acute exacerbation (AE) has occurred) of bronchiectasis. In this study, we demonstrated that sputum MPO concentrations are a biomarker reflecting disease status (e.g., whether an acute exacerbation has occurred) rather than disease severity. We observed no correlation between sputum MPO concentrations and disease severity, as assessed using the BSI and FACED scores. In contrast, sputum MPO concentrations were significantly correlated with bronchiectasis status. Thus, sputum MPO concentrations may reflect the severity of neutrophilic inflammation, which is correlated with the AE status of bronchiectasis. Additionally, MPO may contribute to airway obstruction and increased sputum production in bronchiectasis, which may be associated with AE.

[0068] The present invention has two important clinical implications. First, because sputum MPO concentrations were measured using a POCT method, our results demonstrate that sputum MPO concentrations can be used as a POCT biomarker to assess AE status and recovery in patients with bronchiectasis. MPO-guided assessment of AEs in bronchiectasis can inform clinical decisions regarding antibiotic prescribing, potentially helping to reduce unnecessary antibiotic use. Second, MPO may represent a novel neutrophil-modulating therapeutic target for the treatment of AEs in patients with bronchiectasis. Recently, brensocatib, a novel dipeptidyl peptidase 1 inhibitor, has been shown to reduce AEs in bronchiectasis associated with modulation of neutrophil elastase 3. Similarly, MPO inhibitors may be used as novel agents to reduce AEs in bronchiectasis.

[0069] In conclusion, there was a significant correlation between changes in disease status (whether acute exacerbation of bronchiectasis occurred or not) and MPO concentrations.

[0070] While specific aspects of the present invention have been described in detail above, it is clear to those skilled in the art that these specific descriptions are merely preferred implementation examples and that the scope of the present invention is not limited thereto.

Claims

1. A method for providing information for diagnosing acute exacerbation of bronchiectasis, comprising the step of measuring the concentration of myeloperoxidase (MPO) in a biological sample isolated from a subject: In the above, if the measured MPO concentration exceeds 50 ng / ml, it is judged to be an acute worsening state of bronchiectasis.

2. In paragraph 1, The above subject is a method for providing information for diagnosing acute exacerbation of bronchiectasis, wherein the subject is suffering from bronchiectasis.

3. In paragraph 1, A method for providing information for diagnosing acute exacerbation of bronchiectasis, wherein the subject has not experienced an acute exacerbation within 3 weeks.

4. In paragraph 1, The above biological sample is sputum, a method for providing information for diagnosing acute exacerbation of bronchiectasis.

5. In the first paragraph, the step of measuring the MPO (myeloperoxidase) concentration is performed by the following steps: a method for providing information for diagnosing acute exacerbation of bronchiectasis: (a) mixing the biological sample with a detection buffer containing a first anti-MPO antibody labeled with a fluorescent element; (b) reacting the mixture of step (a) on a membrane coated with a second anti-MPO antibody; and (c) A step of measuring the MPO concentration in the biological sample through fluorescence detection of the fluorescent element after step (b).

6. In paragraph 5, A method for providing information for diagnosing acute exacerbation of bronchiectasis, which additionally performs the following steps prior to performing step (a) above: (pre-a) Step of diluting the biological sample with dilution buffer.

7. In paragraph 6, A method for providing information for diagnosing acute exacerbation of bronchiectasis, wherein the above step (pre-a) is to dilute a biological sample and a dilution buffer in a volume ratio of 1:5 (v / v) to 1:20 (v / v).

8. In paragraph 5, The fluorescent element is Indocyanine green (ICG), IRDye 800CW carboxylate (IRDye 800CW), Alexa fluor-355, Alexa Fluor 488, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor-555, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 647, Alexa Fluor 660, Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, Alexa Fluor 780, Flamma 749, Flamma 774, Flamma 800, FSD FluorTM 647, FSD FluorTM 680, FSD FluorTM 750, FSD FluorTM 800, sulfo-cyanine 3.5 carboxylic acid (cy3.5), A method for providing information for diagnosing acute exacerbation of bronchiectasis, wherein the method comprises any one selected from the group consisting of sulfo-cyanine 5 carboxylic acid (Cy5), sulfo-cyanine 5.5 carboxylic acid (Cy5.5), sulfo-cyanine 7 carboxylic acid (Cy7), or sulfo-cyanine 7.5 carboxylic acid (Cy7.5), Texas Red, Pacific Blue, Oregon Green 488, JOE, Lissamine, Rhodamine Green, BODIPY, fluorescein isothiocyanate (FITC), carboxy-fluorescein (FAM), Allophycocyanin (APC), phycoerythrin (PE), rhodamine, dichlororhodamine (dRhodamine), carboxy tetramethylrhodamine (TAMRA), carboxy-X-rhodamine (ROX), PicoGreen, and RiboGreen.

9. A kit for diagnosing acute exacerbation of bronchiectasis comprising a membrane coated with an anti-MPO antibody or an antigen-binding fragment thereof, The above diagnostic kit is a kit for diagnosing acute exacerbation of bronchiectasis, provided in the form of a cartridge for immunofluorescence measurement.

10. In paragraph 9, The above membrane is a nitrocellulose membrane, a kit for diagnosing acute exacerbation of bronchiectasis.

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