US 12,716,898 B2Granted

Method for measuring COPD biomarkers

AssigneeSt. John's University

InventorsMichael Fagiola, Jerome Cantor

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Abstract

The invention pertains to the use of a specific biomarker of elastin degradation (desmosine) that measures the extent and progression of chronic obstructive pulmonary disease (COPD). In addition to potentially serving as a screening procedure for COPD, it provides a real-time measure of COPD drug efficacy and may therefore supersede the use of less sensitive tests such as pulmonary function studies and computed tomography. Equally important, the current invention constitutes a marked improvement for measuring desmosine in tissues and body fluids by greatly shortening the time for detection of this molecule in liquid chromatography-tandem mass spectrometry (LC-MS-MS) assays that are the gold standard for such measurements. Unlike previous methods, the invention allows for the use of LC-MS-MS without modification, so the method can be applied to any laboratory that uses this equipment for other measurements. This would include forensic facilities that need to determine if undiagnosed COPD played a role in the loss of life.

Claims18

Dependent claims

A method of treatment for a disease in a subject suspected of having elastic fiber injury, comprising:

using non-ion-paired liquid chromatography combined with mass spectrometry to measure only the amount of free desmosine and free isodesmosine in a sample from the subject, the sample being at least one member selected from the group consisting of connective tissue matrices, urine, plasma, sputum, bronchoalveolar lavage fluid and exhaled breath condensate;
and
correlating the measured amount of free desmosine and free isodesmosine to an established range of normal values of free desmosine and free isodesmosine derived from nonsmoking healthy individuals to identify the elastic fiber injury;
determining that the subject suffers from a disease selected from the group consisting of atherosclerosis, aortic aneurysm, skin lesions, cystic fibrosis, pulmonary hypertension, bronchiectasis, chronic obstructive pulmonary disease (COPD), COPD exacerbations and alpha-1 antitrypsin deficiency (AATD);
and
treating the disease, wherein
said treatment for atherosclerosis comprises a change in diet or exercise, administering a statin or other cholesterol drug, aspirin or medications to lower blood pressure, or angioplasty, endarterectomy, fibrinolytic therapy or coronary artery bypass graft surgery,
said treatment for aortic aneurysm comprises open-chest surgery, aortic root surgery or endovascular aortic aneurysm repair,
said treatment for skin lesions comprises cryosurgery, excisional surgery, Mohs surgery, curettage and electrodesiccation, cryotherapy, radiation therapy, chemotherapy, photodynamic therapy or biological therapy,
said treatment for cystic fibrosis comprises administering antibiotics, anti-inflammatories, hypertonic saline, bronchodialators, oral pancreatic enzymes, stool softeners, acid-reducing medications, drugs for diabetes or liver disease, or cystic fibrosis transmembrane conductance regulator modulators,
said treatment for pulmonary hypertension comprises right heart catheterization, atrial septostomy, lung or heart-lung transplant, or administering vasodilators, guanylate cyclase stimulators, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, calcium channel blockers, blood thinners, digoxin, diuretics or oxygen therapy,
said treatment for bronchiectasis comprises administering oral or intravenous antibiotics,
said treatment for COPD and COPD exacerbations comprises cessation of smoking, administering bronchodilators, inhaled steroids, oral steroids, phosphodiesterase-4 inhibitors, theophylline or antibiotics, oxygen therapy, pulmonary rehabilitation, use of bilevel positive airway pressure breathing devices, lung volume reduction surgery, lung transplant or bullectomy.

10 more elements

A method of treatment for an elastic fiber injury, comprising the steps of:

obtaining a specimen of tissue from a subject;
homogenizing said specimen to release free desmosine and free isodesmosine from the tissue;
centrifuging the homogenized specimen to produce a supernatant with sedimented solid material;
adding a desmosine-d4 standard to the supernatant;
separating the free desmosine and free isodesmosine from said supernatant using cation exchange chromatography and obtaining a chromatographic eluent;
applying the chromatographic eluent to a non-ion paired chromatography column;
measuring only free desmosine and free isodesmosine in the chromatographic eluent using tandem mass spectrometry;
and
comparing measured levels of free desmosine and free isodesmosine in the chromatographic eluent to an established range of normal values of free desmosine and free isodesmosine derived from nonsmoking healthy individuals to identify the elastic fiber injury, wherein
said treatment comprises at least one of a change in diet or exercise, administering a statin, aspirin or medication to lower blood pressure, angioplasty, endarterectomy, fibrinolytic therapy, coronary artery bypass graft surgery, open-chest surgery, aortic root surgery, endovascular aortic aneurysm repair, cryosurgery, excisional surgery, Mohs surgery, curettage and electrodesiccation, curettage and cryotherapy, radiation therapy, chemotherapy, photodynamic therapy, biological therapy, administering antibiotics, anti-inflammatoires, hypertonic saline, bronchodialators, oral pancreatic enzymes, stool softeners, acid-reducing medications, drugs for diabetes or liver disease, cystic fibrosis transmembrane conductance regulator (CFTR) modulators, right heart catheterization, atrial septostomy, lung-transplant or heart-lung transplant, administering vasodilators, guanylate cyclase stimulators, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, calcium channel blockers, blood thinners, digoxin, diuretics, oxygen therapy, oral or intravenous antibiotics, cessation of smoking, inhaled steroids, oral steroids, phosphodiesterase-4 inhibitors, theophylline, pulmonary rehabilitation, bilevel positive airway pressure breathing devices, lung volume reduction surgery or bullectomy.

7 more elements

A method of treatment for an elastic fiber injury in a tissue from a subject, comprising the steps of:

procuring a suitable specimen of tissue from a subject;
homogenization said tissue to release free desmosine and free isodesmosine therefrom;
centrifuging the homogenized tissue to obtain a supernatant;
adding a desmosine-d4 standard to the supernatant;
separating the free desmosine and free isodesmosine from said supernatant and obtain a chromatographic eluent using cation exchange chromatography;
applying the chromatographic eluent to a non-ion paired chromatography column;
measuring only the free desmosine and free isodesmosine from the non-ion paired chromatography column using tandem mass spectrometry;
and
comparing measured levels of free desmosine and free isodesmosine in the chromatographic eluent to an established range of normal values of free desmosine and free isodesmosine derived from nonsmoking healthy individuals to identify the elastic fiber injury, wherein
said treatment comprises at least one of a change in diet or exercise, administering a statin, aspirin or medication to lower blood pressure, angioplasty, endarterectomy, fibrinolytic therapy, coronary artery bypass graft surgery, open-chest surgery, aortic root surgery, endovascular aortic aneurysm repair, cryosurgery, excisional surgery, Mohs surgery, curettage and electrodesiccation, curettage and cryotherapy, radiation therapy, chemotherapy, photodynamic therapy, biological therapy, administering antibiotics, anti-inflammatorypertonic saline, bronchodialators, oral pancreatic enzymes, stool softeners, acid-reducing medications, drugs for diabetes or liver disease, cystic fibrosis transmembrane conductance regulator (CFTR) modulators, right heart catheterization, atrial septostomy, lung-transplant or heart-lung transplant, administering vasodilators, guanylate cyclase stimulators, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, calcium channel blockers, blood thinners, digoxin, diuretics, oxygen therapy, oral or intravenous antibiotics, cessation of smoking, inhaled steroids, oral steroids, phosphodiesterase-4 inhibitors, theophylline, pulmonary rehabilitation, bilevel positive airway pressure breathing devices, lung volume reduction surgery and bullectomy.

7 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/821,672Filed 23 Aug 2022 · continuation
Priority: 28 Jul 2021
Published: US 2023/0030026 A12 Feb 2023
Granted: 25 Aug 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

G01N 33/6848
General methods of protein analysis not limited to specific proteins or families of proteins: methods of protein analysis involving mass spectrometry
G01N 33/6887
Involving proteins, peptides or amino acids: from muscle, cartilage or connective tissue
G01N 1/4077
Concentrating samples: by other techniques involving separation of suspended solids
G01N 30/7233
Mass spectrometers: interfaced to liquid or supercritical fluid chromatograph