Questionnaire, questionnaire set, and assessment system

Abstract

This questionnaire comprises a question column where question items are listed and a column for answers to the question items. The question items include the following question items (1) to (5). Question item (1): a question about the presence or absence of asthma history. Question item (2): a question about the presence or absence of wheezing. Question item (3): a question about the presence or absence of breathing difficulty at rest. Question item (4): a question about the presence or absence of awakening at night due to breathlessness or coughing. Question item (5): a question about the presence or absence of symptoms such as coughing or shortness of breath depending on weather or season.

Description

Technical Field

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[0006]

[0001] The present invention relates to a questionnaire, a questionnaire set, and a determination system. This application claims priority based on U.S. Provisional Application No. 63 / 446,029, filed in the United States on February 16, 2023, the content of which is incorporated herein by reference.

Background Art

[0002] Conventionally, in order to diagnose whether a patient with COPD (Chronic Obstructive Pulmonary Disease) has ACO (Asthma and COPD Overlap, asthma - chronic obstructive pulmonary disease overlap) complicated with asthma, a plurality of clinical tests have been required.

[0003] For example, Non - Patent Document 1 describes that for the diagnosis of ACO in cases diagnosed with COPD and undergoing treatment, FeNO, airway reversibility test, and blood test are to be performed.

Prior Art Documents

Non - Patent Documents

[0004]

Non - Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, there is a problem that performing a plurality of clinical tests places a great burden on COPD patients. Also, there is a problem that clinical tests cannot be performed in general practice clinics due to insufficient equipment.

[0006] In addition, during the COVID-19 era, there was the problem of difficulty in performing multiple clinical tests on patients while preventing infection between clinical testers and patients.

[0007] This invention has been made in view of these circumstances, and aims to provide a questionnaire, a set of questionnaires, and a determination system that can easily and accurately determine the possibility of an ACO in a COPD patient. [Means for solving the problem]

[0008] To solve the above problems, one aspect of the present invention includes the following aspects.

[0009] [1] A questionnaire comprising a question section in which question items are listed and a section for answering the question items, wherein the question items consist of the following question items (1) to (5). Question (1): Questions regarding a history of asthma. Question (2): Questions regarding the presence or absence of wheezing. Question (3): Questions regarding the presence or absence of shortness of breath at rest. Question (4): Questions regarding nighttime awakenings due to shortness of breath or cough. Question (5): Questions regarding the presence or absence of cough or shortness of breath symptoms that are weather or season-dependent.

[0010] [2] The questionnaire described in [1], which recommends that the respondent be treated for asthma-chronic obstructive pulmonary disease overlap if the answer to question (1) is "yes" and one or more answers to questions (2) to (5) are "yes", or if the answer to question (1) is "no" and three or more answers to questions (2) to (5) are "yes".

[0011] [3] A questionnaire as described in [1] or [2] in which a clinical examination is recommended to the respondent if the answer to question (1) is "Yes" and the answers to questions (2) to (5) are all "No", or if the answer to question (1) is "No" and one or two of the answers to questions (2) to (5) are "Yes".

[0012] [4] A questionnaire as described in any one of [1] to [3], further comprising a score column for recording the total score of the answers given in the answer columns for which the answer was "yes", and a judgment column, wherein the answer column for question item (1) is pre-filled with "2 points", the answer columns for question items (2) to (5) are pre-filled with "1 point", and the judgment column contains a statement that if the score in the score column is 3 points or more, the respondent is recommended to be treated as asthma-chronic obstructive pulmonary disease overlap, and if the score in the score column is 1 point or 2 points, the respondent is recommended to undergo a clinical examination.

[0013] [5] A questionnaire for asthma-chronic obstructive pulmonary disease overlap, intended for patients with chronic obstructive pulmonary disease, which is one of the questionnaires listed in [1] to [4].

[0014] [6] A questionnaire, which is one of the questionnaires listed in [1] to [5].

[0015] [7] A questionnaire posted on a webpage, which is one of the following: [1] to [5].

[0016] [8] A questionnaire that is designated as a questionnaire for patients diagnosed with COPD at a medical institution, and is one of the questionnaires listed in [1] to [7].

[0017] A set of questionnaires, including one of the questionnaires described in [9] [1] to [8], and a questionnaire for screening patients with chronic obstructive pulmonary disease.

[0018]

[10] A determination system for determining whether or not a patient with chronic obstructive pulmonary disease has asthma-chronic obstructive pulmonary disease overlap, comprising: a presentation means for presenting the following question items (1) to (5) to the respondent; an input means for the respondent to input answers to question items (1) to (5); and a control unit for outputting a recommendation message to the presentation means based on the answers input using the input means, Question (1): Questions regarding a history of asthma. Question (2): Questions regarding the presence or absence of wheezing. Question (3): Questions regarding the presence or absence of shortness of breath at rest. Question (4): Questions regarding nighttime awakenings due to shortness of breath or cough. Question (5): Questions regarding the presence or absence of cough or shortness of breath symptoms that are weather or season-dependent. A determination system in which, if the answer to question item (1) is "Yes" and there is one or more "Yes" answers to questions (2) to (5), or if the answer to question item (1) is "No" and there are three or more "Yes" answers to questions (2) to (5), the control unit determines that it is an asthma-chronic obstructive pulmonary disease overlap, and outputs a recommendation message to the presentation means recommending treatment for asthma-chronic obstructive pulmonary disease overlap, and presents it to the respondent.

[0019]

[11] The judgment system according to

[10] , wherein a "yes" answer to question item (1) is assigned "2 points", a "yes" answer to question items (2) to (5) is assigned "1 point", and a "no" answer to each question item (1) to (5) is assigned "0 points", the control unit comprises a calculation means for calculating the total score based on the answers entered by the input means, and if the total score is 3 points or more, the control unit causes the presentation means to output and display a recommendation message recommending treatment as asthma-chronic obstructive pulmonary disease overlap, and if the total score is 1 point or 2 points, the control unit causes the presentation means to output and display a recommendation message recommending clinical testing. [Effects of the Invention]

[0020] According to the present invention, it is possible to provide a questionnaire, a set of questionnaires, and a determination system that can easily and accurately determine the possibility of a COPD patient having ACO. [Brief explanation of the drawing]

[0021] [Figure 1A] This drawing shows a questionnaire according to a preferred embodiment of the present invention. [Figure 1B]A drawing showing another aspect of the questionnaire. [Figure 2] A block diagram showing a determination system according to a preferred embodiment of the present invention. [Figure 3] FIG. 3 is a flowchart showing message selection control of the control unit. [Figure 4] A drawing showing the breakdown of ACO diagnosis for COPD patients in the affiliated hospital of Teikyo University School of Medicine. [Figure 5] A graph showing the relationship between 10 candidate items and type 2 inflammation biomarkers obtained by clinical examination. [Figure 6] A graph showing the results of a multivariate analysis showing the relationship between 9 candidate items excluding symptoms dependent on work or stress and whether the diagnosis of COPD patients is ACO or not. [Figure 7] A graph showing the number of ACO patients and the number of Non-ACO patients for each score in COPD patients in the affiliated hospital of Teikyo University School of Medicine. [Figure 8] A graph showing the ROC curves of ACO-Q, COPD-PS, and COPD-Q in COPD patients in the affiliated hospital of Teikyo University School of Medicine. [Figure 9] A graph comparing the predictive ability of ACO determination by only ACO-Q, ACO diagnosis by only FeNO measurement, and ACO diagnosis by blood eosinophil count. [Figure 10] A graph showing the number of ACO patients and the number of Non-ACO patients for each score in COPD patients in the affiliated Mizoguchi Hospital of Teikyo University School of Medicine, which is a verification group. [Figure 11] A graph showing the ROC curve of ACO-Q in COPD patients in the affiliated Mizoguchi Hospital of Teikyo University School of Medicine, which is a verification group.

Mode for Carrying Out the Invention

[0022] Hereinafter, preferred embodiments of the present invention will be described in detail, sometimes referring to the drawings.

[0023] <<Questionnaire>> Figure 1A is a drawing showing a questionnaire according to a preferred embodiment of the present invention.

[0024] The questionnaire shown in Figure 1A is designed for COPD patients to determine the likelihood of having ACO (in other words, to screen for ACO patients). The person using this questionnaire to determine the likelihood of a COPD patient having ACO may be the COPD patient themselves, or another person such as a doctor.

[0025] As shown in Figure 1A, the questionnaire comprises a question field A1 containing the following five question items (1) to (5), an answer field A2 for question items (1) to (5), and a score field A2a. The score field A2a is where the sum of the scores recorded in answer field A2 for each question item answered "Yes" is entered. Question item (1): A question asking about the presence or absence of a history of asthma (past medical history of asthma). Question item (2): A question asking about the presence or absence of wheezing. Question item (3): A question asking about the presence or absence of shortness of breath at rest. Question item (4): A question asking about the presence or absence of nighttime awakenings due to shortness of breath or cough. Question item (5): A question asking about the presence or absence of cough or shortness of breath symptoms that depend on the weather or season. The order in which the above questions (1) to (5) are written is not particularly limited, and the order in which the above questions (1) to (5) are written can be changed at will.

[0026] The above questionnaire recommends that the respondent be treated for ACO (Asthma-Chronic Obstructive Pulmonary Disease Overlap) if the answer to question (1) is "Yes" and one or more answers to questions (2) to (5) are "Yes", or if the answer to question (1) is "No" and three or more answers to questions (2) to (5) are "Yes". It is not necessarily required that the above two cases be specified in the questionnaire by the number of "yes" or "no" answers, etc. As will be explained in detail later, the above two cases may be specified in the questionnaire by the total score (e.g., 3 points or more), and treatment as ACO may be recommended in those two cases.

[0027] Furthermore, in the two cases mentioned above, instead of recommending that the respondent be treated as having ACO, it is acceptable to state that there is a possibility of ACO, or that there is a high probability of ACO.

[0028] The above questionnaire states that if the answer to question (1) is "yes" and the answers to questions (2) through (5) are all "no", or if the answer to question (1) is "no" and one or two of the answers to questions (2) through (5) other than (1) are "yes", then the respondent should be recommended to undergo clinical testing (biomarker testing).

[0029] COPD patients who respond to this questionnaire can easily determine their likelihood of having ACO without clinical testing. The questionnaire according to this embodiment will be described in detail below.

[0030] In the questionnaire according to this embodiment, as indicated in answer field A2, 2 points are awarded if the answer to question (1) is "yes" (indicating a history of asthma), and 1 point is awarded for each question (2) to (5) for which the answer is "yes". Answers of "no" for each of the questions (1) to (5) receive 0 points (in other words, no points are awarded).

[0031] Respondents will answer "Yes" or "No" to questions (1) through (5), then calculate the total score for questions (1) through (5) and enter it in the score column (total score column) A2a.

[0032] Furthermore, as stated at the bottom of the questionnaire above, if the total score (the score in the A2a score column) is 3 points or higher, treatment for ACO is recommended for the respondent.

[0033] In contrast, if the total score (the score in score column A2a) is 1 or 2 points, the respondent is recommended to undergo clinical testing (biomarker testing). If the total score is 0 points, it is considered unlikely that the respondent has ACO.

[0034] In the following, the questionnaire used for COPD patients, which has a section with the five questions listed above, and recommends treatment as ACO if the total score is 3 points or more, will also be referred to as the "ACO-Q".

[0035] For example, if a respondent who is a COPD patient answers "Yes" to question (1), "No" to question (2), "No" to question (3), "Yes" to question (4), and "No" to question (5), their total score would be 3 points. As a result, treatment for ACO would be recommended for this respondent.

[0036] Furthermore, if a respondent who is a COPD patient answers "Yes" to question (1), "No" to question (2), "No" to question (3), "No" to question (4), and "No" to question (5), their total score will be 2 points. As a result, clinical testing will be recommended for that respondent.

[0037] Furthermore, if a respondent who is a COPD patient answers "No" to question (1), "Yes" to question (2), "Yes" to question (3), "Yes" to question (4), and "No" to question (5), the total score will be 3 points. As a result, treatment for ACO is recommended for this respondent.

[0038] Recommended clinical tests (biomarker tests) for patients with a total score of 1 or 2 include, but are not limited to, exhaled nitric oxide concentration testing (FeNO), airway reversibility testing, and blood tests.

[0039] Examples of blood tests include total serum IgE level tests and specific IgE level tests.

[0040] The ACO-Q may be an ACO questionnaire for COPD patients. Furthermore, there are no particular limitations on the form (medium) in which the ACO-Q is presented; it may be written on a questionnaire sheet or posted (displayed) on a web page.

[0041] If the ACO-Q is structured as a questionnaire written on paper, the questionnaire may be placed, for example, in a hospital examination room.

[0042] If the ACO-Q is posted on a webpage, respondents who are COPD patients may access the webpage containing the ACO-Q and answer it. In this case, when the respondent answers "Yes" or "No" on the webpage, the response data is sent to the server, a total score is calculated, and the server sends data containing the total score and a recommendation message corresponding to that total score to the respondent's device (tablet, computer, etc.), so that the total score and recommendation message are automatically displayed on the respondent's device. Note that it is not necessarily required for the respondent's device to send data to the server.

[0043] The ACO-Q may include a statement indicating that it is a questionnaire specifically for patients diagnosed with COPD at a medical institution, or it may include a statement indicating that it is a questionnaire intended for patients diagnosed with COPD at a medical institution.

[0044] On the other hand, while long-acting bronchodilators are the first-line treatment for patients with COPD, these are contraindicated in asthma patients due to the increased risk of severe exacerbations and death.

[0045] Furthermore, the introduction of ICS (inhaled corticosteroids) is essential for patients with ACO. Therefore, accuracy is required in diagnosing ACO, and as will be detailed in the examples below, the ACO-Q test described above has high discriminatory ability and reproducibility.

[0046] Figure 1B shows another form of the questionnaire. The questionnaire 10 shown in Figure 1B includes a question-and-answer section A, a judgment section 12, and an optional comment section 11. The question-and-answer section A includes a question section A1 containing five question items (1) to (5), an answer section A2 for question items (1) to (5), and a score section (total score section) A2a for recording the sum of the points recorded in the answer section A2. Respondents should enter their answers to question A1 in answer field A2 and their self-assessed total score in score field A2a.

[0047] Judgment section 12 states that if the total score entered in score section A2a is 3 points or more, the respondent is recommended to undergo treatment as an ACO.

[0048] Furthermore, in judgment column 12, it is stated that if the total score entered in score column A2a is 1 or 2 points, the respondent is recommended to undergo clinical testing (biomarker testing). In judgment column 12, you may optionally write that if the total score is 0, the likelihood of it being ACO is low.

[0049] The optional comment section 11 is for writing any message to the respondent. Examples of optional messages include: "If you have been diagnosed with COPD by a doctor in the past, you may have asthma and be at risk of asthma-chronic obstructive pulmonary disease overlap (ACO). Try the following questionnaire to see if you suspect you have ACO," or "This questionnaire is intended for people who have been diagnosed with COPD by a doctor in the past."

[0050] <<Questionnaire Set>> The questionnaire set of this embodiment includes the above-mentioned questionnaire (ACO-Q) and a questionnaire for screening COPD patients (in other words, for determining the likelihood of being a COPD patient and recommending treatment for COPD patients).

[0051] There are no particular limitations on the types of questionnaires used to screen COPD patients, but examples include the COPD Assessment Test (CAT), the COPD Screening Questionnaire (COPD-Q), the COPD Population Screening Questionnaire (COPD-PS, see the website of the GOLD Japan Committee), and the International Primary Care Airway Group Questionnaire (COPD-IPAG).

[0052] The questionnaire set includes the ACO-Q and a questionnaire for screening COPD patients. Respondents can use the COPD screening questionnaire to determine whether or not they have COPD, and if so, they can then use the ACO-Q to determine whether or not they have ACO. Therefore, it becomes possible to provide appropriate treatment for ACO to many patients who actually have ACO but have not been diagnosed with COPD or ACO.

[0053] <<Judgment System>> Figure 2 is a block diagram showing a determination system 1 according to a preferred embodiment of the present invention.

[0054] The judgment system 1 shown in Figure 2 is a judgment system that determines whether or not a COPD patient has ACO (Acute Cholesterol Occlusion).

[0055] The determination system 1 includes a presentation means 2 that presents the above-mentioned question items (1) to (5) to the respondent, an input means 3 in which the respondent inputs answers to question items (1) to (5), and a control unit 4 that performs message selection control to determine whether or not it is ACO based on the answers input using the input means 3 and output a recommendation message to the presentation means 2.

[0056] If the answer to question (1) is "Yes" and there is one or more "Yes" answers to questions (2) to (5), or if the answer to question (1) is "No" and there are three or more "Yes" answers to questions (2) to (5), the control unit 4 determines that it is ACO and has the presentation means 2 output and display a recommendation message recommending treatment for ACO. If the answer to question (1) is "Yes" and the answers to questions (2) to (5) are all "No", or if the answer to question (1) is "No" and there is one or two "Yes" answers to questions (2) to (5), the control unit 4 has the presentation means 2 output and display a recommendation message recommending clinical testing.

[0057] The following provides a detailed explanation of the judgment system 1.

[0058] Presentation means 2 is composed of a well-known display such as a liquid crystal display or a plasma display.

[0059] Input means 3 consists of a mouse, keyboard, touch panel, etc., but is not limited to these. A single touch panel may also constitute both input means 3 and presentation means 2.

[0060] The control unit 4 is composed of a well-known computer or server including a CPU and memory. The CPU performs message selection control by reading and executing various programs stored in memory.

[0061] The input means 3 is connected to the input side of the control unit 4, and the presentation means 2 is connected to the output side of the control unit 4. The connection between the control unit 4 and the input means 3, and the connection between the control unit 4 and the presentation means 2, may be a wired connection, a wireless connection, or a connection via a communication network such as the Internet.

[0062] The control unit 4 includes a calculation means 4a that calculates the total score based on the answers entered by the input means 3.

[0063] Figure 3 is a flowchart showing the message selection control of the control unit 4.

[0064] When response data for question items (1) to (5) is input from the input means 3 to the control unit 4 based on the respondent's actions (step S1), the calculation means 4a calculates the total score T based on the received response data (step S2).

[0065] A "yes" answer to question (1) is assigned "2 points", a "yes" answer to questions (2) to (5) is assigned "1 point", and a "no" answer to each question is assigned "0 points". The calculation means 4a calculates the total value T based on these settings and the response data.

[0066] Once the calculation means 4a calculates the total score T, the control unit 4 determines whether the total score T is 3 points or more (step S3).

[0067] If the result of the judgment is that the total score T is 3 points or more, the control unit 4 stores judgment data indicating that it is ACO in the memory and outputs a recommendation message 1 to the presentation means 2 recommending that it be treated as ACO, and has the respondent present it (step S4).

[0068] In response to this, if the result of the judgment is that the total score is less than 3 points, the control unit 4 determines whether the total score T exceeds 0 points (step S5).

[0069] If the result of the judgment indicates that the total score T exceeds 0, the control unit 4 stores judgment data indicating that there is a possibility of ACO in the memory, and outputs a recommendation message 2 recommending a clinical examination to the presentation means 2 for the respondent to present (step S6).

[0070] In response to this, if the result of the judgment is that the total score T is 0, the control unit 4 stores judgment data indicating that it is Non-ACO in the memory and outputs a negative message indicating that the possibility of it being ACO is low to the presentation means 2 for the respondent to present (step S7).

[0071] According to this embodiment, respondents can easily determine whether or not they are ACO simply by answering five questions (1) to (5) using the input means 3.

[0072] <<Other Embodiments>> As another embodiment of the present invention, the following questionnaire is provided.

[0073] The questionnaire comprises a question section, an answer section for the question items listed in the question section, and a score section for recording the total value of the points recorded in the answer section. The question items consist of the following question items (1) to (5). Question item (1): Questions regarding the history of asthma. Question item (2): A question asking about the presence or absence of wheezing. Question item (3): A question asking about the presence or absence of shortness of breath at rest. Question item (4): A question asking about the presence or absence of nighttime awakenings due to shortness of breath or cough. Question item (5): A question asking about the presence or absence of cough or shortness of breath symptoms that depend on the weather or season. The answer field for question (1) is pre-filled with "2 points," and the answer fields for questions (2) to (5) are pre-filled with "1 point."

[0074] The above questionnaire may further include a judgment column, in which it may state that if the score in the score column is 3 points or more, the respondent is recommended to be treated for asthma-chronic obstructive pulmonary disease overlap syndrome, and if the score in the score column is 1 point or 2 points, the respondent is recommended to undergo clinical testing.

[0075] In yet another embodiment, the present invention provides the following determination system. The assessment system determines whether a patient with chronic obstructive pulmonary disease (COPD) has asthma-COPD overlap and includes a presentation means that presents the respondent with the following questions (1) to (5), and an input means for the respondent to input their answers to questions (1) to (5). Answers to question (1) are assigned "2 points," and answers to questions (2) to (5) are assigned "1 point," with points predetermined. Based on the answers entered by the input means, a calculation means calculates the total score. If the total score is 3 points or more, the system determines that the respondent may have asthma-COPD overlap syndrome and recommends treatment for asthma-COPD overlap syndrome. Question item (1): Questions regarding the history of asthma. Question item (2): A question asking about the presence or absence of wheezing. Question item (3): A question asking about the presence or absence of shortness of breath at rest. Question item (4): A question asking about the presence or absence of nighttime awakenings due to shortness of breath or cough. Question item (5): A question asking about the presence or absence of cough or shortness of breath symptoms that depend on the weather or season.

[0076] Although preferred embodiments have been described in detail above, the present invention is not limited to these embodiments, and various modifications are possible within the scope of the invention as described in the claims.

[0077] For example, in each embodiment shown in Figures 1A to 3, question (1) was counted as 2 points, and questions (2) to (5) were each counted as 1 point. If the total score was 3 points or more, it was determined to be ACO, and if the score was 1 or 2 points, a clinical examination was recommended. However, it is sufficient to recommend a clinical examination if the answer to question (1) is "Yes" and there is one or more "Yes" answers in questions (2) to (5), or if the answer to question (1) is "No" and there are three or more "Yes" answers in questions (2) to (5), and if the answer to question (1) is "Yes" and there is one or two "Yes" answers in questions (2) to (5). The points assigned to each question and the cutoff value are not particularly limited.

[0078] For this reason, for example, a "yes" answer to question (1) could be counted as 20 points, and a "yes" answer to questions (2) to (5) could be counted as 10 points each. If the total score is 30 points or more, it could be determined to be ACO, and if the total score is 10 points or 20 points, clinical testing could be recommended. [Examples]

[0079] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.

[0080] In figures and tables, unless otherwise specified, "*" indicates statistical significance as p<0.05 and "**" indicates p<0.01, and data are shown as mean ± standard deviation. Statistical analysis was performed using JMP(R)16Pro software (SAS Institute Japan) and Prism(R) 8 (GraphPad Software).

[0081] <<Creating a Questionnaire>> (Creating candidate items) Table 1 below shows a list of possible question items.

[0082] [Table 1]

[0083] First, we created the above 10 candidate items to be included in the questionnaire.

[0084] The ten candidate items shown in Table 1 were created by three respiratory specialists as candidate items for a self-administered questionnaire, based on the characteristics described in the asthma guidelines (Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2022. Available from www.ginasthma.org.) or the ACO guidelines (Hashimoto S., et al., Asthma and Chronic Obstructive Pulmonary Disease Overlap According to the Japanese Respiratory Society Diagnostic Criteria: The Prospective, Observational ACO Japan Cohort Study. Adv Ther, 38, 1168-1184, 2021.).

[0085] A history of asthma (Q1-1) and allergic rhinitis (Q1-2) is listed in the ACO guidelines.

[0086] Regarding Q2-2, generally speaking, COPD patients are characterized by experiencing shortness of breath during exertion but not at rest. Therefore, shortness of breath at rest suggests ACO (Acute COPD).

[0087] In cases of variable or paroxysmal symptoms, symptoms triggered by diurnal or seasonal variations (Q3-1, Q3-3), nocturnal awakenings (Q3-2), changes in weather (Q3-3), or exercise (Q3-4) increase the likelihood of diagnosing asthma.

[0088] Mental disorders, including stress, and occupational substances (Q3-5) may be associated with the onset or exacerbation of asthma.

[0089] (Verification of questionnaire items in COPD patients) 106 COPD patients from the outpatient clinic of Teikyo University Hospital were sequentially registered, and 6 patients who could not answer the questions were excluded. The remaining 100 COPD patients were then diagnosed as having ACO (Acute Occlusive Cortex).

[0090] This study was approved by the Research Ethics Committee of the Faculty of Medicine, Teikyo University (19-179, 19-179-2). Written informed consent was obtained from all participants. This study was conducted in accordance with the principles of the Declaration of Helsinki.

[0091] COPD and ACO were diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria and the Japanese Respiratory Society ACO Management Guidelines 2018.

[0092] In detail, ACO was defined as a patient having fixed airflow limitation [FEV1 (forced expiratory volume in one second) / FVC (forced vital capacity) < 70%] and at least one COPD feature (history of smoking, emphysema on chest CT, impaired pulmonary diffusion capacity) and two or more asthma features (variable respiratory symptoms, history of asthma before age 40, FeNO > 35 ppb, or at least two of the following: concomitant rhinitis, airway reversibility, eosinophilia in the serum, high total IgE levels or high specific IgE levels).

[0093] Figure 4 is a diagram showing the breakdown of ACO diagnoses among COPD patients at Teikyo University Hospital.

[0094] As shown in Figure 4, among 100 COPD patients, of the 46 patients analyzed for all of the above characteristics, 21 were diagnosed with ACO, and 25 were diagnosed with Non-ACO (not having ACO).

[0095] Furthermore, of the 60 individuals whose characteristics were analyzed, 32 were diagnosed with ACO, and 22 were diagnosed with Non-ACO (not having ACO).

[0096] Therefore, of the 100 COPD patients who underwent a diagnosis of whether or not they had ACO, 53 (53%) were diagnosed with ACO, and 47 were diagnosed as non-ACO.

[0097] Specific IgE levels were measured using a panel IgE test with Thermo Fisher Diagnostics' View Allergy 39 or the ImmunoCAP method, with class 1 or higher being considered positive.

[0098] FeNO was measured using a NIOX VERO from Aerocrine.

[0099] COPD patients completed the COPD Assessment Test (CAT), the COPD Screening Questionnaire (COPD-Q), the COPD Population Screening Questionnaire (COPD-PS), and the International Primary Care Airway Group Questionnaire (COPD-IPAG).

[0100] Table 2 below shows a comparison of patient characteristics between ACOs and non-ACOs.

[0101] [Table 2]

[0102] As shown in Table 2, patients with ACO had significantly higher body mass index compared to patients without ACO.

[0103] Furthermore, patients with ACO had significantly higher serum total IgE, FeNO, and Der p-specific IgE levels than patients without ACO.

[0104] Furthermore, patients with ACO had significantly higher COPD-Q scores and COPD-PS scores compared to patients without ACO. This suggests that patients with ACO exhibit stronger COPD characteristics and more severe symptoms than patients without ACO.

[0105] COPD patients at Teikyo University School of Medicine's Mizoguchi Hospital were asked to answer the 10 candidate items shown in Table 1 above using a binary choice of "Yes" or "No".

[0106] Subsequently, Pearson's chi-squared test was used to compare the positive rates of the ACO COPD group and the non-ACO COPD group for each candidate item.

[0107] We also examined the relationship between candidate items and the levels of type 2 inflammatory biomarkers such as FeNO, serum eosinophil count, serum total IgE, and Der p-specific IgE.

[0108] Table 3 below shows the positive rates for the above 10 candidate items in patients with ACO and patients without ACO.

[0109] [Table 3]

[0110] As shown in Table 3, in patients with ACO, the positive rates for all items related to medical history (Q1), symptoms (Q2), and changes in respiratory symptoms (Q3) were significantly higher than in patients without ACO, with the exception of a history of allergic rhinitis (Q1-2).

[0111] Next, we analyzed the relationship between 10 candidate items and the levels of type 2 inflammatory biomarkers related to asthma.

[0112] Figure 5 is a graph showing the relationship between 10 candidate items and type 2 inflammatory biomarkers obtained through clinical tests. In Figure 5, the further to the right you move in the graph for each item, the stronger the relationship.

[0113] As shown in Figure 5, a history of asthma, a family history of asthma, and work- and stress-dependent symptoms significantly contributed to an increase in FeNO ≥ 35 ppb.

[0114] Furthermore, a history of allergic rhinitis was significantly associated with positive Der p-specific IgE levels.

[0115] Most candidate parameters tended to contribute to elevated blood eosinophil counts and total serum IgE levels.

[0116] These results suggest that the positive rates for candidate items related to changes in medical history and symptoms reflect elevated levels of type 2 inflammatory biomarkers.

[0117] Based on the above results, a multivariate analysis using a logistic regression model was performed on the candidate items. As mentioned above, in patients with ACO, the positive rates for 9 of the 10 candidate items, excluding a history of allergic rhinitis, were significantly higher. Furthermore, a history of allergic rhinitis was significantly associated with positive Der p-specific IgE. Therefore, all 10 candidate items were subjected to multivariate analysis.

[0118] Figure 6 is a graph showing the results of a multivariate analysis relating the nine candidate items to whether or not the diagnosis for COPD patients is ACO. Note that data on work- or stress-dependent symptoms are not shown in the Non-ACO group of patients, as no patients in this group answered "yes" to having work- or stress-dependent symptoms.

[0119] As shown in Figure 6, of the nine candidate items, five items—a history of asthma, wheezing, dyspnea at rest, nocturnal awakenings, and weather- and season-dependent symptoms—significantly contributed to the diagnosis of ACO.

[0120] Furthermore, in order to reduce the number of items in the questionnaire, stepwise logistic regression analysis was used to analyze the contribution of the above five items to the diagnosis of ACO. However, since the set including all five items achieved the best BIC (Bayesian Information Criterion) value (BIC = 108.7), it was decided to include all five items—history of asthma, wheezing, dyspnea at rest, nocturnal awakenings, and weather- and season-dependent symptoms—in the questionnaire.

[0121] (Scoring of a questionnaire consisting of 5 items) After selecting the five items mentioned above, a score-based questionnaire was created based on a logistic regression equation.

[0122] Table 4 below shows various scoring systems for the five questionnaire items.

[0123] [Table 4]

[0124] For scoring each item, scaled estimates calculated using the least squares regression method with JMP(R)16Pro software (manufactured by SAS Institute Japan) were used.

[0125] Subsequently, the scaled estimate was multiplied by 10 and replaced with the nearest integer to facilitate the calculation of the total score. As a result, a history of asthma was assigned a score of 2, while the other items were assigned a score of 1.

[0126] Based on the determined scoring method, the 100 COPD patients mentioned above were asked to complete a questionnaire, and the total score for each patient was calculated.

[0127] (Determination of the total score for determining ACO) Figure 7 is a graph showing the number of patients with ACO and Non-ACO (Acute Occlusive Disease) by score among COPD patients at Teikyo University Hospital.

[0128] Of the 36 patients with a total score of 0, 33 (91.7%) were diagnosed as Non-ACO based on the above definition of ACO using clinical tests, while the remaining 3 were diagnosed as ACO using clinical tests.

[0129] Furthermore, all patients with a total score of 3 or higher were diagnosed with ACO based on the above definition of ACO, using clinical tests.

[0130] Based on these results, we determined that it is appropriate to classify patients with a total score of 3 or higher as having ACO (Acute Care Occlusion).

[0131] (Usefulness of questionnaires) To evaluate the efficiency of ACO-Q in determining whether a patient is ACO or Non-ACO, ROC curves were created for ACO-Q, COPD-PS, and COPD-Q.

[0132] Figure 8 is a graph showing the ACO-Q, COPD-PS, and ROC curves for COPD-Q in COPD patients at Teikyo University Hospital.

[0133] The area under the curve (AUC) of the ROC curve in ACO-Q was 0.883 (95% CI: 0.806-0.933).

[0134] As mentioned above, patients with ACO had significantly higher COPD-Q and COPD-PS scores compared to patients without ACO. However, the area under the curve for COPD-PS and COPD-Q were significantly smaller than the area under the curve for ACO.

[0135] Therefore, it has become clear that among ACO-Q, COPD-PS, and COPD-Q, ACO-Q is the best tool for determining ACO.

[0136] Furthermore, the ROC curve for ACO-Q shows that the discriminative power of ACO is higher when the cutoff value for the total score is set to 1.

[0137] Figure 9 is a graph comparing the predictive ability of ACO diagnosis based solely on ACO-Q, ACO diagnosis based solely on FeNO measurement, and ACO diagnosis based on blood eosinophil count.

[0138] The area under the curve (AUC) for ACO-Q was significantly larger than that of FeNO (0.691, 95% CI: 0.576–0.786, p<0.01) and serum eosinophil count (0.613, 95% CI: 0.495–0.719, p<0.01). Therefore, this suggests the superiority of using ACO-Q alone compared to a single biomarker.

[0139] Table 5 below shows the validity of each cutoff value for the total ACO-Q score calculated using the Youden index. [Table 5]

[0140] As shown in Table 5, the best cutoff value estimated by the Youden index was 1 point due to its high sensitivity and specificity, but a score of 3 or higher resulted in a positive predictive value of 100%.

[0141] (Reproducibility of ACO-Q) As a validation group, 53 COPD patients from Teikyo University School of Medicine's Mizoguchi Hospital were enrolled and analyzed using the same method as described above. Note that the patients and their attending physicians at Teikyo University School of Medicine's Mizoguchi Hospital were different from those at Teikyo University School of Medicine's affiliated hospital.

[0142] Figure 10 is a graph showing the number of patients with ACO and Non-ACO for each score among COPD patients at Teikyo University School of Medicine Mizoguchi Hospital, which was the validation group.

[0143] Of the 26 patients with a total score of 0, 25 (96.2%) were diagnosed as Non-ACO based on the above definition of ACO using clinical tests, while the remaining 3 were diagnosed as ACO using clinical tests.

[0144] Furthermore, all patients with a score of 4 or higher were diagnosed with ACO using clinical tests based on the above definition of ACO.

[0145] Figure 11 is a graph showing the ROC curve of ACO-Q for COPD patients at Teikyo University School of Medicine's Mizoguchi Hospital, which was the validation group.

[0146] The area under the ROC curve shown in Figure 11 was 0.904 (95% CI: 0.815-0.993), which was equivalent to the area under the ROC curve in the original group at Teikyo University Hospital (see Figure 8). This suggests that the accuracy of the ACO-Q assessment is reproducible. [Industrial applicability]

[0147] According to the present invention, the possibility of being ACO can be determined simply and accurately, making it suitable for industrial use. [Explanation of Symbols]

[0148] 1: Judgment system, 2: Presentation means, 3: Input means, 4: Control unit, 4a: Calculation means, A1: Question field, A2: Answer field, A2a: Score field

Claims

1. A questionnaire for determining whether or not a patient with chronic obstructive pulmonary disease has asthma-chronic obstructive pulmonary disease overlap, It comprises a question field in which questions are listed, and a field for answering the said questions, The aforementioned questionnaire consists of the following questions (1) to (5), Question item (1): A question asking about the history of asthma. Question item (2): A question asking about the presence or absence of wheezing. Question item (3): A question asking about the presence or absence of shortness of breath at rest. Question item (4): A question asking about the presence or absence of nighttime awakenings due to shortness of breath or cough. Question item (5): A question asking about the presence or absence of cough or shortness of breath symptoms that depend on the weather or season. The system includes a score column for recording the total score of the points recorded in the answer column for each of the above question items (1) to (5) where the answer was "Yes", and a judgment column. The answer field for question (1) is pre-filled with "2 points," and the answer fields for questions (2) to (5) are pre-filled with "1 point." The aforementioned judgment column states that if the score in the aforementioned score column is 3 points or higher, the respondent is recommended to be treated for asthma-chronic obstructive pulmonary disease overlap. A questionnaire in which, if the score in the aforementioned score column is 1 or 2 points, a clinical examination is recommended for the respondent.

2. A questionnaire, as described in claim 1.

3. A questionnaire as described in claim 1, posted on a webpage.

4. The questionnaire according to claim 1, which includes a statement indicating that it is a questionnaire specifically for patients diagnosed with COPD at a medical institution.

5. A questionnaire set comprising the questionnaire described in claim 1 and a questionnaire for screening patients with chronic obstructive pulmonary disease.

6. A determination system for determining whether or not a patient with chronic obstructive pulmonary disease has asthma-chronic obstructive pulmonary disease overlap, A means of presenting the respondent with the following questions (1) to (5), An input method for respondents to input their answers to question items (1) to (5), The system includes a control unit that outputs a recommended message to the presentation means based on the answer entered using the input means, Question item (1): A question asking about the history of asthma. Question item (2): A question asking about the presence or absence of wheezing. Question item (3): A question asking about the presence or absence of shortness of breath at rest. Question item (4): A question asking about the presence or absence of nighttime awakenings due to shortness of breath or cough. Question item (5): A question asking about the presence or absence of cough or shortness of breath symptoms that depend on the weather or season. A determination system in which, if the answer to question item (1) is "Yes" and there is one or more "Yes" answers to questions (2) to (5), or if the answer to question item (1) is "No" and there are three or more "Yes" answers to questions (2) to (5), the control unit determines that it is an asthma-chronic obstructive pulmonary disease overlap, and outputs a recommendation message to the presentation means recommending treatment for asthma-chronic obstructive pulmonary disease overlap, and presents it to the respondent.

7. A "yes" answer to question (1) is assigned "2 points", a "yes" answer to questions (2) to (5) is assigned "1 point", and a "no" answer to any of the questions (1) to (5) is assigned "0 points". The control unit includes a calculation means that calculates the total score based on the answers entered by the input means. If the total score is 3 points or more, the control unit causes the display means to output and display a recommendation message recommending treatment for asthma-chronic obstructive pulmonary disease overlap. The determination system according to claim 6, wherein if the total value is 1 or 2 points, the control unit causes the presentation means to output and present a recommendation message recommending a clinical examination.

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