Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of Losartan on cigarette smoke-induced lung injury in smokers and ex-smokers with and without chronic obstructive pulmonary disease (COPD).

Official Title
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Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis

Conditions
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COPD, Chronic Bronchitis

Intervention / Treatment
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* Drug: Losartan 50 mg
* Drug: Losartan 100 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfill one of the group definitions above Age between 35 and 75 years old Clinical diagnosis of chronic bronchitis, defined as productive cough for at least 3 months per year for at least two consecutive years Stable maintenance of all current medication therapy for 3 months, including ARBs for treated groups Exclusion criteria Current therapy with Angiotensin-converting-enzyme (ACE) inhibitor,or Intolerance to Angiotensin II receptor blockers (ARB) Women of child bearing potential Current use of nonsteroidal antiinflammatory drugs or potassium supplementation, treatment with aliskiren, anticoagulation COPD exacerbation requiring treatment within 6 weeks of the screening visit Oral corticosteroid use within 6 weeks of the screening visit Significant hypoxemia (oxygen saturation <90% on room air), chronic respiratory failure by history (pCO2 > 45 mmHg) and forced expiratory volume in 1 second (FEV1) below 40%, clinical evidence of cor pulmonale Untreated arterial hypertension (systolic blood pressure >140 mm Hg, diastolic blood pressure > 90 mm Hg) Ability to understand and willingness to sign consent documents Blood pressure less than 100 mm Hg systolic or 70 mm Hg diastolic while standing at the screening visit Cardiac, renal, hepatic (LFTs > 3x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases that are at the discretion of the investigator, to interfere with participation in study History of renal artery stenosis Concomitant airway disorders other than COPD and chronic bronchitis, such as bronchiectasis and asthma (history and reversible airflow obstruction by American Thoracic Society (ATS) criteria) History of pulmonary malignancies, and any other malignancies in the last 5 years History of thoracic surgery. Acute pulmonary exacerbation within 6 weeks from the Screening Visit. Subjects with no airflow obstruction by spirometry but with a decrease in diffusing capacity of lung for carbon monoxide(DLco) possibly indicating emphysema. Significant exposure to environmental tobacco smoke or atmospheric or occupational pollutants Urine pregnancy positive test at the Screening Visit.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy non-smokers<br>10 healthy non-smokers will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks. | Drug: Losartan 50 mg<br>* 50 mg Losartan taken orally once daily for 4 consecutive weeks.<br>* Other names: Cozaar;Drug: Losartan 100 mg<br>* 50 mg Losartan taken orally twice daily for 4 consecutive weeks.<br>* Other names: Cozaar;|
| Experimental: Smokers without COPD<br>10 smokers without COPD will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks. | Drug: Losartan 50 mg<br>* 50 mg Losartan taken orally once daily for 4 consecutive weeks.<br>* Other names: Cozaar;Drug: Losartan 100 mg<br>* 50 mg Losartan taken orally twice daily for 4 consecutive weeks.<br>* Other names: Cozaar;|
| Experimental: Ex-smokers with COPD<br>10 ex-smokers with COPD will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks. | Drug: Losartan 50 mg<br>* 50 mg Losartan taken orally once daily for 4 consecutive weeks.<br>* Other names: Cozaar;Drug: Losartan 100 mg<br>* 50 mg Losartan taken orally twice daily for 4 consecutive weeks.<br>* Other names: Cozaar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Nasal Potential Difference (NPD). | NPD were assessed from nasal cells collected using sterile cytology brushes. | Baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IL-8 Concentrations | Interleukin (IL)-8 concentrations were analyzed from samples on nasal lavage | Baseline, 8 weeks | 
| Percent Change in TGF-ß mRNA Expression | Transforming Growth Factor (TGF)-ß messenger ribonucleic acid (mRNA) expression were analyzed from nasal cells samples. | Baseline, 8 weeks |