Uncontrolled Lower Respiratory Symptoms in the WTC Survivor Program

Study Overview
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Brief Summary
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The purpose of this study is to understand why patients in the World Trade Center program have continuing breathing problems. This study will improve investigators understanding of breathing problems among individuals with World Trade Center exposure by allowing them to review and monitor medication use, lung function, and examine other conditions that can contribute to problems with breathing. The findings from the study will help investigators understand why some people have persistent lower respiratory symptoms (breathing problems) after their exposure to World Trade Center dust and fumes, and may help guide better management and treatment of these symptoms.

Detailed Description
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Investigators will conduct a clinical study with aggressive treatment for lower respiratory symptoms in patients in the World Trade Center Environmental Health Center. Patients in the WTC EHC with uncontrolled LRS at visit 1 will be identified and placed on high-dose inhaled corticosteroids and long-acting beta agonists for three months. Adherence will be assessed at monthly visits. Patients will perform spirometry and oscillometry at baseline and after 3 months of treatment. They will also be assessed for markers of airway inflammation, bronchial hyperresponsiveness and co-morbid conditions including depression,anxiety,post-traumatic stress disorder, gastroesophageal reflux, paradoxical vocal cord motion and rhinosinusitis.

Official Title
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Uncontrolled Lower Respiratory Symptoms in the World Trade Center Survivor Program

Conditions
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Lung Diseases, Medication Compliance

Intervention / Treatment
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* Drug: Fluticasone propionate 230mcg for 3 Months
* Drug: Current Treatment or no treatment
* Drug: Salmeterol 21mcg for 3 Months


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years and <75 Meet criteria for World Trade Center Environmental Health Center enrollment Onset of lower respiratory symptoms after 9/11/01 Persistent lower respiratory symptoms (> 2 times per week) Pre-bronchodilator forced expiratory volume in one second (FEV1) within normal limits < 5 pack-year tobacco history Not current smoker Asthma Control Test Score ≤ 19 Normal chest x-ray Exclusion Criteria: Age < 18 years and ≥75 Lower respiratory symptoms or asthma history pre 9/11/01 No persistent lower respiratory symptoms pre-bronchodilator FEV1 within normal limits > 5 pack year tobacco Current smoker Abnormal Chest X-Ray or parenchymal changes on high resolution computed tomography Uncontrolled major chronic illness (diabetes mellitus, congestive heart failure, cancer) History of significant non-World Trade Center occupational or environmental exposure Allergy to study drug Pregnancy, lactation or plans to become pregnant Chronic oral corticosteroid use High risk of fatal or near-fatal asthma within the previous 2 years Other lung disease (Idiopathic pulmonary fibrosis,sarcoid, etc.)

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Uncontrolled LRS<br>Patients who have uncontrolled lower respiratory symptoms (ACT < 20) at time of Visit 1 will be provided with study Advair (Fluticasone propionate 230mcg/salmeterol 21mcg) for a total of 3 months and receive medication adherence counseling Patients who have uncontrolled LRS at V1, but do not fit criteria for Step 3,4 or 5 asthma therapy according to NIH EPR III asthma guidelines will be deferred from the study until they have been seen by their physician and tried on ICS therapy. | Drug: Fluticasone propionate 230mcg for 3 Months<br> <br> * Other names: Advair HFA;Drug: Salmeterol 21mcg for 3 Months<br> <br> |
| Other: Controlled LRS<br>Patients who had symptoms at monitoring visit but are now controlled at V1 will be asked to continue their current treatment (or no treatment) and will continue with the study. They will not be provided with any medications. | Drug: Current Treatment or no treatment<br>* Patients who had symptoms at monitoring visit but are now controlled at V1 will be asked to continue their current treatment (or no treatment) and will continue with the study. They will not be provided with any medications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Oscillation Technique (FOT) Measures | Small airway function measured pre/post BD (bronchodilator) impulse oscillometry at resistance 5 Hz (R5) and 5-20 Hz (R5-20). | Week 12 | 
| Spirometry Measures | Measured pre/post BD (bronchodilator). Reported as ratio: %FEV1(Liters)/FVC(Liters). FEV1 = forced expiratory volume at 1 second FVC = forced vital capacity | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Level of Bronchial Hyperreactivity (BHR) | To test whether bronchial Hyperreactivity (BHR), assessed by methacholine challenge, is associated with uncontrolled lower respiratory symptoms. | Week 12 | 
| Number of Participants With Positive Level of Paradoxical Vocal Fold Movement (PVFM) | measured by laryngoscopic visualization at rest or after provocation with various odors or exercise. | Week 12 | 
| Total IgE (Immunoglobulin E) Levels | IgE levels were obtained by blood test - the total amount of blood drawn is 30 mL. | Week 1 | 
| Total EoS (Eosinophil) Counts | EoS counts were obtained by blood test - the total amount of blood drawn is 30 mL. | Week 1 | 
| Levels of Fractional Exhaled Nitric Oxide (FeNO) | Measured using a portable device that measures the level of nitric oxide in parts per billion (PPB) in the air slowly exhaled out of the patient's lungs. | Week 12 | 
| Score on Voice Handicap Index 10 (VHI-10) | Voice Handicap Index 10 is a measure of laryngeal dysfunction or hypersensitivity to capture the overall state of voice handicap. The normative value for this instrument is 2.83, with a score > 11 considered abnormal. There are 10 statements that are scored between 0 and 4 (0= never, 4= always). The total range is 0-40, where 40 is highest level of dysfunction. | Week 12 | 
| Rhinosinusitis Score on International Classification of Sleep Disorders (ICSD) | For rhinosinusitis symptoms, the ICSD scoring system was used, with a likert scale of 1-10 for each symptom (total range of scale = 1-60, with higher scores reflecting more symptoms). | Week 12 | 
| Score on Leicester Cough Questionnaire (LCQ) | For rhinosinusitis symptoms, the Leicester Cough Questionnaire (LCQ) was used - a cough-specific health status questionnaire that assesses the physical, psychological, and social domains of cough. The LCQ is made up of 19 items; the total score range is 3-21; a higher score is associated with better health. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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World Trade Center Disaster, Environmental Exposure, Respiratory Physiology, Inflammation, Gastrointestinal Diseases, Sinus Symptoms, PTSD, Anxiety, Depression, Hypersensitivity, Spirometry, Oscillometry