Remodelling of the Lower Airways in Chronic Cough

Официальное название

Does Chronic Cough Lead to Injury and Remodelling of the Lower Airways?

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест chest computed tomography and bronchoscopy
  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.

Первичные конечные точки

• assessment of the severity of epithelial damage and inflammation in the bronchial biopsy [Срок оценки: baseline]
• assessment of airway inflammation and remodeling in the airways in chest CT [Срок оценки: baseline]
• Assessment of biomarkers of inflammation in serum and BALF [Срок оценки: baseline]

Критерии участия

Inclusion criteria for the study group:

• age between 18 and 75 years,
• chronic cough of at least one year duration, with no previous treatment (at least 2 previous unsuccessful attempts at pharmacological treatment of cough)
• negative history of smoking (at least 6 months of abstinence),
• negative history of treatment with angiotensin-converting enzyme inhibitors (ACEI),
• normal chest radiograph or with changes not relevant to cough formation,
• no respiratory tract infections in the past 6 weeks,
• written consent from the patient to participate in the study.

Критерии исключения

• patients less than 18 and more than 75 years of age,
• cough lasting less than 12 months,
• active smoking or abstinence period of less than 6 months,
• respiratory tract infection 6 weeks prior to inclusion or at the time of study conduct - retry inclusion after 6 weeks,
• cancer or interstitial lung disease,
• contraindications to functional testing, sputum induction or bronchoscopy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Польша · 4 центра

• Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of War — Warsaw
• Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of War — Warsaw
• Medical University of Warsaw — Warsaw
• Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of War — Warsaw

Публикации

• 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. PMID 35773287
• 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. PMID 28502417
• 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. PMID 26426314
• 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. PMID 26285610
• 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. PMID 29080708

Идентификаторы

NCT: NCT07659860 · Remodelling in CC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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