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The aim of the study is to assess if chronic cough leads to injury and remodelling of the airways. We plan to analyse bronchial injury and remodelling in patients with refractory chronic cough lasting longer than 12 month . Assessment of injury mediators will be performed in blood and bronchoalveolar lavage fluid. Remodelling features will be analysed based on chest CT scan and pathologic specimens. Injury of epithelium will be assessed in bronchial biopsy specimens. The relationship between the duration, severity of chronic cough, and bronchial inflammation, damage, remodelling will be analysed.
Cough is a physiological defensive reflex which decreases the risk of aspiration to the lower airways and allows to remove sputum and excessive mucus from the airways. However, in some cases, persisting intensive cough may result in many complications and decrease in patients' quality of life. Damage of the airway epithelium due to infection, chemical or mechanical injury leads to an increase in the frequency or intensity of cough.
The aim of the study is to assess if chronic cough leads to damage and remodelling of the airways. We plan to analyse bronchial injury and remodelling in patients with refractory chronic cough lasting longer than 12 months. Assessment of injury mediators will be performed in blood and BALF. Remodelling will be analysed based on chest CT scan and pathologic specimens. Injury of epithelium will be assessed in pathologic specimens of bronchial biopsy. The relationship between the duration, severity of chronic cough and bronchial inflammation, damage, remodelling will be analysed.
Patients with refractory chronic cough and clinical indications for bronchoscopy (such as: productive cough, mucus plugs or bronchiectasis in chest CT, suspected extensive dynamic airway collapse (EDAC), assessment of eosinophilic airway inflammation when induced sputum could not be obtained, or any suspicion or high risk of malignancy) will be invited to take part in the study.
We plan to enroll 40 non-smoking patients with chronic cough lasting longer than 12 months, who had already been unsuccessfully treated because of cough. Thorough diagnostics of cough reason will be performed. Besides parameters of bronchial inflammation, remodelling and injury will be analysed in serum and BALF. Injury and remodelling will also be assessed in bronchial biopsy and in chest CT.
The results of the study will assess if refractory chronic cough is associated with any type of airway inflammation, bronchial injury or remodeling.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 40 patients with refractory chronic cough lasting more than 6 months. | Patients were eligible for inclusion if they: were 18-75 years old; had chronic cough lasting more than 12 months unresponsive to previous treatment presented with a normal or near normal chest radiograph or only abnormalities irrelevant to cough; and had clinical indications for bronchoscopy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| chest computed tomography and bronchoscopy | Diagnostic Test | Assessment of airway remodeling features on chest CT in patients with chronic cough. Evaluation of airway injury and remodeling based on biological specimens obtained from the lower airways during bronchoscopy.Bronchoscopy is performed if clinically indicated. |
| Measure | Description | Time Frame |
|---|---|---|
| assessment of the severity of epithelial damage and inflammation in the bronchial biopsy | Bronchial biopsy will be analysed for airway inflammation and remodeling features such as proportion of epithelial shedding basement membrane thickening, infiltration of inflammatory cells and subbasement membrane (SBM) thickening. | baseline |
| assessment of airway inflammation and remodeling in the airways in chest CT | The CT scans will be evaluated for the presence, extent, and severity of bronchial wall thickening, bronchiectasis, mucus plugs, centrilobular abnormalities, air trapping or mosaic attenuation. | baseline |
| Assessment of biomarkers of inflammation in serum and BALF | Assessment of cellular composition and inflammatory biomarkers in serum and BALF ( IL-2, IL4, IL-5, IL-8, PGE2, periostin, TSLP), | baseline |
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Inclusion criteria for the study group:
Exclusion Criteria:
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In 30 patients referred to the cough clinic for refractory chronic cough lasting more than 6 months
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marta Dabrowska, MD, PhD | Contact | +48 501157765 | mdabrowska@mp.pl | |
| Karolina Klimowicz, MD | Contact | +48 507045417 | mdabrowska@mp.pl |
| Name | Affiliation | Role |
|---|---|---|
| Rafał Krenke, MD, PhD, Prof | Department of Internal Medicine, Pulmonary Diseases and Allergy, Warsaw Medical University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw | Recruiting | Warsaw | Masovian Voivodeship | 02-097 | Poland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35773287 | Result | Chung KF, McGarvey L, Song WJ, Chang AB, Lai K, Canning BJ, Birring SS, Smith JA, Mazzone SB. Cough hypersensitivity and chronic cough. Nat Rev Dis Primers. 2022 Jun 30;8(1):45. doi: 10.1038/s41572-022-00370-w. | |
| 28502417 | Result | Macedo P, Zhang Q, Saito J, Liang Z, Ffolkes L, Nicholson AG, Chung KF. Analysis of bronchial biopsies in chronic cough. Respir Med. 2017 Jun;127:40-44. doi: 10.1016/j.rmed.2017.04.001. Epub 2017 Apr 4. |
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| ID | Term |
|---|---|
| D000096822 | Chronic Cough |
| ID | Term |
|---|---|
| D003371 | Cough |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D012818 | Signs and Symptoms, Respiratory |
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| ID | Term |
|---|---|
| D001999 | Bronchoscopy |
| ID | Term |
|---|---|
| D003948 | Diagnostic Techniques, Respiratory System |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D004724 | Endoscopy |
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blood bronchoalveolat lavage fluid bronchial biopsy
|
|
| Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw | Recruiting | Warsaw | Warsaw | 02-097 | Poland |
|
| Medical University of Warsaw | Recruiting | Warsaw | 02-091 | Poland |
|
| Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw | Recruiting | Warsaw | 02-097 | Poland |
|
| 26426314 | Result | Gibson P, Wang G, McGarvey L, Vertigan AE, Altman KW, Birring SS; CHEST Expert Cough Panel. Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report. Chest. 2016 Jan;149(1):27-44. doi: 10.1378/chest.15-1496. Epub 2016 Jan 6. |
| 26285610 | Result | Dabrowska M, Grabczak EM, Arcimowicz M, Domeracka-Kolodziej A, Domagala-Kulawik J, Krenke R, Maskey-Warzechowska M, Tarchalska B, Chazan R. Causes of Chronic Cough in Non-smoking Patients. Adv Exp Med Biol. 2015;873:25-33. doi: 10.1007/5584_2015_153. |
| 29080708 | Result | Irwin RS, French CL, Chang AB, Altman KW; CHEST Expert Cough Panel*. Classification of Cough as a Symptom in Adults and Management Algorithms: CHEST Guideline and Expert Panel Report. Chest. 2018 Jan;153(1):196-209. doi: 10.1016/j.chest.2017.10.016. Epub 2017 Nov 10. |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003949 | Diagnostic Techniques, Surgical |
| D019060 | Minimally Invasive Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D013510 | Pulmonary Surgical Procedures |
| D019616 | Thoracic Surgical Procedures |