# US 2022/0120760 A1 · Treatment stratification for an exacerbation of inflammation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2022/0120760 A1 - Document ID: US20220120760A1 - Status: Published application - Kind: A1 - Application number: 17/310,757 - Filed: 2020-02-21 - Published: 2022-04-21 - Earliest claimed: 2019-02-22 - Assignees: Mologic Limited - Applicants: Mologic Limited - Inventors: Paul DAVIS; Gita PAREKH; Annelyse DUVOIX - Web page: https://patentgrep.com/patent/US20220120760A1 ## CPC - G01N 33/6884: {from lung} - G01N 33/6893: {related to diseases not provided for elsewhere} - G01N 33/5091: {for testing the pathological state of an organism} - G01N 33/573: for enzymes or isoenzymes - G01N 33/88: involving prostaglandins {or their receptors} - G16H 10/40: for data related to laboratory analysis, e.g. patient specimen analysis - G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients - G01N 2333/8125: Alpha-1-antitrypsin - G01N 2333/908: acting on hydrogen peroxide as acceptor (1.11) - G01N 2333/914: Hydrolases (3) - G01N 2333/96494: Matrix metalloproteases, e. g. 3.4.24.7 - G01N 2333/966: Elastase - G01N 2333/988: Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase - G01N 2800/122: Chronic or obstructive airway disorders, e.g. asthma COPD - G01N 2800/24: Immunology or allergic disorders - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA ## Abstract Provided are methods of analysing markers of eosinophil levels and/or markers of neutrophil levels in a blood sample from a patient suffering from an exacerbation of inflammation of a respiratory condition to determine the levels of eosinophils and/or neutrophils respectively. The methods may involve selecting an appropriate treatment. Systems and kits for performing the analysis are also provided. ## Claims ### Claim 1 A method for selecting a treatment to be administered to a patient suffering from an exacerbation of inflammation of a respiratory condition, the method comprising determining the levels of at least 3 markers of eosinophil levels and at least 3 markers of neutrophil levels in a blood sample taken from the patient suffering from an exacerbation of inflammation of a respiratory condition wherein: (i) perturbed levels of the at least 3 markers of eosinophil levels and no perturbation in the levels of the at least 3 markers of neutrophil levels result in selection of corticosteroids to be administered as the treatment for the exacerbation of inflammation; (ii) perturbed levels of the at least 3 markers of neutrophil levels and no perturbation in the levels of the at least 3 markers of eosinophil levels result in selection of antibiotics to be administered as the treatment for the exacerbation of inflammation; or (iii) perturbed levels of the at least 3 markers of eosinophil levels and the at least 3 markers of neutrophil levels result in selection of corticosteroids and antibiotics to be co-administered as the treatment for the exacerbation of inflammation; wherein determining the levels of the at least 3 markers of eosinophil levels comprises determining the levels of at least Eosinophil-derived neurotoxin (EDN), Myeloperoxidase (MPO) and Eosinophil cationic protein (RNASE3); and wherein determining the levels of the at least 3 markers of neutrophil levels comprises determining the levels of at least (i) Matrix metallopeptidase 9 (MMP9) and Eosinophil-derived neurotoxin (EDN); and (ii) at least one of leukotriene B4 (LTB4), C-reactive protein (CRP), Soluble urokinase-type plasminogen activator receptor (SuPAR), and/or Alpha-1-antitrypsin (A1AT), preferably LTB4. ### Claim 2 (depends on 1) The method according to claim 1 wherein determining the levels of the at least 3 markers of eosinophil levels further comprises determining the levels of at least 1 or 2 further markers selected from Human neutrophil elastase (HNE), Soluble urokinase-type plasminogen activator receptor (SuPAR), and/or Calprotectin. ### Claim 3 (depends on 1) The method according to claim 1 wherein determining the levels of the at least 3 markers of eosinophil levels further comprises determining the levels of Soluble urokinase-type plasminogen activator receptor (SuPAR), and HNE. ### Claim 4 (depends on 1) The method according to claim 1 wherein determining the levels of the at least 3 markers of neutrophil levels comprises determining the levels of at least MMP9, EDN and LTB4. ### Claim 5 (depends on 1) The method according to claim 1 wherein determining the levels of the at least 3 markers of neutrophil levels further comprises determining the levels of MBP. ### Claim 6 (depends on 1) The method according to claim 1 wherein determining the levels of the at least 3 markers of neutrophil levels further comprises determining the levels of at least 1 or 2 further (different) marker(s) selected from CRP, SuPAR, A1AT and/or LTB4. ### Claim 7 (depends on 1) The method according to claim 1 wherein the levels of at least 5 markers of eosinophil levels and at least 5 markers of neutrophil levels are determined in the blood sample, wherein the markers of eosinophil levels are preferably EDN, RNASE3, SuPAR, HNE and MPO; and wherein the markers of neutrophil levels are preferably (i) MMP9 and EDN; and (ii) at least 3 markers selected from LTB4, A1AT, SuPAR and/or CRP; for example wherein the markers of neutrophil levels are MMP9, EDN, SuPAR, LTB4 and A1AT; or MMP9, C-reactive protein (CRP), EDN, A1AT and LTB4; or MMP9, EDN, CRP, SuPAR and A1AT. ### Claim 8 A method for selecting corticosteroids to be administered as a treatment to a patient suffering from an exacerbation of inflammation of a respiratory condition, the method comprising determining the levels of at least 3 markers of eosinophil levels in a blood sample taken from the patient suffering from an exacerbation of inflammation of a respiratory condition, wherein perturbed levels of the at least 3 markers of eosinophil levels results in selection of corticosteroids to be administered as the treatment for the exacerbation of inflammation of a respiratory condition, wherein determining the levels of the at least 3 markers of eosinophil levels comprises determining the levels of EDN, MPO and RNASE3; optionally wherein determining the levels of the at least 3 markers of eosinophil levels further comprises determining the levels of HNE, SuPAR, and/or Calprotectin, preferably HNE and SuPAR. ### Claim 9 A method for selecting antibiotics to be administered as a treatment to a patient suffering from an exacerbation of inflammation of a respiratory condition, the method comprising determining the levels of at least 3 markers of neutrophil levels in a blood sample taken from the patient suffering from an exacerbation of inflammation of a respiratory condition wherein perturbed levels of at least 3 markers of neutrophil levels results in selection of antibiotics to be administered as the treatment for the exacerbation of inflammation, wherein determining the levels of the at least 3 markers of neutrophil levels comprises determining the levels of at least (i) Matrix metallopeptidase 9 (MMP9) and Eosinophil-derived neurotoxin (EDN); and (ii) at least one of leukotriene B4 (LTB4), C-reactive protein (CRP), Soluble urokinase-type plasminogen activator receptor (SuPAR), and/or Alpha-1-antitrypsin (A1AT), preferably LTB4, optionally at least 2 or 3 of these markers. ### Claim 10 (depends on 1) A method for selecting and monitoring treatment of a patient suffering from an exacerbation of inflammation of a respiratory condition, the method comprising: (i) selecting a treatment to be administered to the patient using a method as defined in claim 1; and (ii) with respect to the at least 3 markers for which levels were perturbed when determining the treatment to be administered of step (i), determining the levels of said at least 3 markers in a further blood sample taken from the patient at a later time point wherein: (a) perturbed levels of the at least 3 markers in the further sample indicate that the treatment should continue or be altered; or (b) a return to non-perturbed levels of the at least 3 markers in the further sample indicate or predict successful treatment of the exacerbation of inflammation; wherein optionally the method comprises a step of administering the selected treatment to the patient. ### Claim 11 A system or test kit for selecting a treatment to be administered to a patient suffering from an exacerbation of inflammation of a respiratory condition, comprising: a. one or more testing devices for determining the levels of at least 3 markers of eosinophil levels and at least 3 markers of neutrophil levels in a blood sample taken from the patient suffering from an exacerbation of inflammation of a respiratory condition; b. a processor; and c. a storage medium comprising a computer application that, when executed by the processor, is configured to: i. Access and/or calculate the determined levels of the at least 3 markers of eosinophil levels and the at least 3 markers of neutrophil levels in a blood sample on the one or more testing devices; ii. Calculate whether there is a perturbed level of the at least 3 markers of eosinophil levels and the at least 3 markers of neutrophil levels in the blood sample; and iii. Output from the processor the treatment to be administered to the patient suffering from an exacerbation of inflammation, wherein: perturbed levels of the at least 3 markers of eosinophil levels and no perturbation in the levels of the at least 3 markers of neutrophil levels result in selection of corticosteroids to be administered as the treatment for the exacerbation of inflammation; or perturbed levels of the at least 3 markers of neutrophil levels and no perturbation in the levels of the at least 3 markers of eosinophil levels result in selection of antibiotics to be administered as the treatment for the exacerbation of inflammation; or perturbed levels of the at least 3 markers of eosinophil levels and the at least 3 markers of neutrophil levels result in selection of corticosteroids and antibiotics to be co-administered as the treatment for the exacerbation of inflammation; wherein the at least 3 markers of eosinophil levels comprise at least EDN, MPO and RNASE3; and wherein the at least 3 markers of neutrophil levels comprise at least (i) MMP9 and EDN; and (ii) at least one of leukotriene B4 (LTB4), C-reactive protein (CRP), Soluble urokinase-type plasminogen activator receptor (SuPAR), and/or Alpha-1-antitrypsin (A1AT), preferably LTB4. ### Claim 12 A system or test kit for selecting corticosteroids to be administered as a treatment to a patient suffering from an exacerbation of inflammation of a respiratory condition, comprising: a. one or more testing devices for determining the levels of at least 3 markers of eosinophil levels in a blood sample taken from the patient suffering from an exacerbation of inflammation of a respiratory condition; b. a processor; and c. a storage medium comprising a computer application that, when executed by the processor, is configured to: i. Access and/or calculate the determined levels of the at least one marker of eosinophil levels in a blood sample on the one or more testing devices; ii. Calculate whether there is a perturbed level of the at least one marker of eosinophil levels in the blood sample; and iii. Output from the processor that corticosteroids are selected to be administered as the treatment for the exacerbation of inflammation if there is a perturbed level of the at least one marker of eosinophil levels in the blood sample, wherein the at least 3 markers of eosinophil levels comprise at least Eosinophil-derived neurotoxin (EDN), Myeloperoxidase (MPO) and Eosinophil cationic protein (RNASE3), and optionally the levels of HNE, SuPAR and/or Calprotecin are also determined. ### Claim 13 A system or test kit for selecting antibiotics to be administered as a treatment to a patient suffering from an exacerbation of inflammation, comprising: a. one or more testing devices for determining the levels of at least one marker of neutrophil levels in a blood sample taken from the patient suffering from an exacerbation of inflammation; b. a processor; and c. a storage medium comprising a computer application that, when executed by the processor, is configured to: i. Access and/or calculate the determined levels of the at least one marker of neutrophil levels in a blood sample on the one or more testing devices; ii. Calculate whether there is a perturbed level of the at least one marker of neutrophil levels in the blood sample; and iii. Output from the processor that antibiotics are selected to be administered as the treatment for the exacerbation of inflammation if there is a perturbed level of the at least one marker of neutrophil levels in the blood sample; wherein the at least 3 markers of neutrophil levels comprise at least (i) MMP9 and EDN; and (ii) at least one of leukotriene B4 (LTB4), C-reactive protein (CRP), Soluble urokinase-type plasminogen activator receptor (SuPAR), and/or Alpha-1-antitrypsin (A1AT), preferably LTB4. ### Claim 14 (depends on 11) The system or test kit according to claim 11 further comprising a display for the output from the processor and/or wherein the one or more testing devices are disposable single use devices and/or wherein the one or more testing devices comprise lateral flow test strips, optionally comprising a lateral flow test strip for each marker that is determined. ### Claim 15 (depends on 1) A method for selecting initial treatment of a patient suffering from an exacerbation of inflammation of a respiratory condition as defined in claim 1, said method comprising (i) using antibodies to detect one or more or all of the markers; (ii) using a lateral flow assay to detect one or more or all of the markers; and/or (iii) using a system or test kit to detect one or more or all of the markers. ### Claim 16 (depends on 1) The method according to claim 1 wherein: (i) the treatment will be the first treatment to be administered to the patient suffering from an exacerbation of inflammation; and/or (iii) the subject is suffering from a respiratory disorder, optionally wherein the respiratory disorder is chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) or asthma, preferably COPD. ### Claim 17 (depends on 11) A computer application as defined in claim 11. ### Claim 18 (depends on 10) A method for selecting and monitoring initial treatment of a patient suffering from an exacerbation of inflammation of a respiratory condition as defined in claim 10, said method comprising (i) using antibodies to detect one or more or all of the markers; (ii) using a lateral flow assay to detect one or more or all of the markers; and/or (iii) using a system or test kit to detect one or more or all of the markers.