Small Airway Chronic Obstructive Disease Syndrome Following Exposure to WTC Dust

Study Overview
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Brief Summary
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Many Survivors in the World Trade Center (WTC) clinical program have a clinical syndrome characterized by chronic obstruction in small airways and persistence of lower respiratory symptoms despite therapy. This study will test the hypothesis that persistent symptoms in WTC Survivors are associated with abnormal small airways whose dysfunction is amplified during exercise and is associated with biologic evidence of inflammation and remodeling. The results from this study will have important treatment implications for our WTC population with potential applicability to larger populations with either inhalational lung injury and/or airway diseases such as asthma and chronic obstructive pulmonary disease.

Official Title
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Small Airway Chronic Obstructive Disease Syndrome Following Exposure to WTC Dust

Conditions
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Chronic Obstructive Pulmonary Disease, Lower Respiratory Disease

Intervention / Treatment
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* Other: Cardio-Pulmonary Exercise Testing (CPET)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sACOS patients Previously participated in ULRS study and signed consent to be recontacted, or Patient in the WTC EHC and signed consent to be recontacted Onset of lower respiratory symptoms (LRS) after 9/11/01 ACT < 20 at WTC EHC Monitoring visit Presence of LRS on Study Visit 1 ACT<20 at Study Visit 1 FEV1 > 70% predicted Study Visit 1 Using ICS/LABA (Advair HFA equivalent > 115/21 mcg bid) or Fluticasone (110 mcg bid or equivalent) for at least 1 month before Study Visit 1 CXR without parenchymal abnormalities Control Patient in the WTC EHC and signed consent to be recontacted of lower respiratory symptoms on WTC EHC Monitoring Visit of WTC EHC Absence of lower respiratory symptoms on Study Visit 1 FEV1 > 70% predicted on monitoring Not on any ICS/LABA/LAMA Exclusion Criteria: sACOS >10py tobacco use Unstable cardiac disease Systolic BP > 180 mmHg or Diastolic BP > 120 mmHg Oxygen saturation < 90% Uncontrolled HTN, DM Musculoskeletal inability to exercise Use of long acting muscarinic antagonist in the past 2 weeks Current use of oral corticosteroids Other pulmonary disease, including sarcoidosis, ILD Currently pregnant or with plans to become pregnant or lactating History of narrow angle glaucoma Known prostate hyperplasia or bladder-neck obstruction Control >10py tobacco use Unstable cardiac disease Systolic BP > 180 mmHg or Diastolic BP > 120 mmHg Oxygen saturation < 90% Uncontrolled HTN, DM Musculoskeletal inability to exercise Use of ICS/LABA/SABA/LAMA individually or in combined formulation Current use of oral corticosteroids Other pulmonary disease, including sarcoidosis, ILD Currently pregnant or with plans to become pregnant or lactating History of narrow angle glaucoma Known prostate hyperplasia or bladder-neck obstruction

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Healthy Controls who were not in the WTC program (n = 20) Uncontrolled Lower Respiratory Symptoms in WTC Surivivors; ULRS study) with persistent LRS (n = 40)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Controls<br> | Other: Cardio-Pulmonary Exercise Testing (CPET)<br>* This test helps determine if the decreased tolerance to exercise or shortness of breath with activity a patient is experiencing is caused by a cardiac disease, versus a pulmonary disease.<br>|
| Experimental: Survivors<br> | Other: Cardio-Pulmonary Exercise Testing (CPET)<br>* This test helps determine if the decreased tolerance to exercise or shortness of breath with activity a patient is experiencing is caused by a cardiac disease, versus a pulmonary disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting Lung Function using Spirometry following Forced Oscillation Techniques | functional impairment at rest and with increased respiratory frequency (spirometry and forced oscillation techniques; FOT). | 4 Months | 
| Measure of Lung Function using spirometry after inhalation of a targeted anti-muscarinic agent. | Spirometry (meaning the measuring of breath) is the most common of the pulmonary function tests (PFTs), measuring lung function, specifically the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. | 4 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of measure of serum marker IL-6 | Inflammation is caused by extra protein released from the site of inflammation that circulates in the bloodstream. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and plasma viscosity (PV) blood tests are commonly used to detect this increase in protein. In this way they are used as markers of inflammation. | 4 Months | 
| Comparison of measure of serum marker IL-8 | Inflammation is caused by extra protein released from the site of inflammation that circulates in the bloodstream. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and plasma viscosity (PV) blood tests are commonly used to detect this increase in protein. In this way they are used as markers of inflammation. | 4 Months | 
| Comparison of measure of serum marker CRP | Inflammation is caused by extra protein released from the site of inflammation that circulates in the bloodstream. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and plasma viscosity (PV) blood tests are commonly used to detect this increase in protein. In this way they are used as markers of inflammation. | 4 Months | 
| Th2 inflammation By measure of fibrinogen | Inflammation is caused by extra protein released from the site of inflammation that circulates in the bloodstream. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and plasma viscosity (PV) blood tests are commonly used to detect this increase in protein. In this way they are used as markers of inflammation. | 4 Months | 
| Th2 inflammation By measure of periostin | Inflammation is caused by extra protein released from the site of inflammation that circulates in the bloodstream. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and plasma viscosity (PV) blood tests are commonly used to detect this increase in protein. In this way they are used as markers of inflammation. | 4 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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World Trade Center, World Trade Center Survivors