Lung Diseases, Medication Compliance
Conditions
Keywords
World Trade Center Disaster, Environmental Exposure, Respiratory Physiology, Inflammation, Gastrointestinal Diseases, Sinus Symptoms, PTSD, Anxiety, Depression, Hypersensitivity, Spirometry, Oscillometry
Brief summary
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
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.
Interventions
DRUGFluticasone propionate 230mcg for 3 Months
DRUGCurrent Treatment or no treatment
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.
DRUGSalmeterol 21mcg for 3 Months
Sponsors
National Institute for Occupational Safety and Health (NIOSH/CDC)
NYU Langone Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Oscillation Technique (FOT) Measures | Week 12 | Small airway function measured pre/post BD (bronchodilator) impulse oscillometry at resistance 5 Hz (R5) and 5-20 Hz (R5-20). |
| Spirometry Measures | Week 12 | Measured pre/post BD (bronchodilator). Reported as ratio: %FEV1(Liters)/FVC(Liters). FEV1 = forced expiratory volume at 1 second FVC = forced vital capacity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total IgE (Immunoglobulin E) Levels | Week 1 | IgE levels were obtained by blood test - the total amount of blood drawn is 30 mL. |
| Total EoS (Eosinophil) Counts | Week 1 | EoS counts were obtained by blood test - the total amount of blood drawn is 30 mL. |
| Levels of Fractional Exhaled Nitric Oxide (FeNO) | Week 12 | 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. |
| Number of Participants With Positive Level of Bronchial Hyperreactivity (BHR) | Week 12 | To test whether bronchial Hyperreactivity (BHR), assessed by methacholine challenge, is associated with uncontrolled lower respiratory symptoms. |
| Rhinosinusitis Score on International Classification of Sleep Disorders (ICSD) | Week 12 | 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). |
| Score on Leicester Cough Questionnaire (LCQ) | Week 12 | 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. |
| Score on Voice Handicap Index 10 (VHI-10) | Week 12 | 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. |
| Number of Participants With Positive Level of Paradoxical Vocal Fold Movement (PVFM) | Week 12 | measured by laryngoscopic visualization at rest or after provocation with various odors or exercise. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Visit 1 Uncontrolled LRS Patients who have uncontrolled LRS (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.
Fluticasone propionate 230mcg for 3 Months
Salmeterol 21mcg for 3 Months | 49 |
| Visit 1 Controlled LRS 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.
Current Treatment or no treatment: 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. | 11 |
| Total | 60 |
Baseline characteristics
| Characteristic | Visit 1 Controlled LRS | Total | Visit 1 Uncontrolled LRS |
|---|---|---|---|
| Age, Continuous | 56 years | 56.5 years | 57 years |
| Race/Ethnicity, Customized Asian and Other | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 4 Participants | 30 Participants | 26 Participants |
| Race/Ethnicity, Customized NH-Black | 3 Participants | 15 Participants | 12 Participants |
| Race/Ethnicity, Customized NH-White | 1 Participants | 11 Participants | 10 Participants |
| Region of Enrollment United States | 11 participants | 60 participants | 49 participants |
| Sex: Female, Male Female | 10 Participants | 42 Participants | 32 Participants |
| Sex: Female, Male Male | 1 Participants | 18 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 11 |
| other Total, other adverse events | 0 / 49 | 0 / 11 |
| serious Total, serious adverse events | 0 / 49 | 0 / 11 |
Outcome results
Primary
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).
Time frame: Week 12
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Visit 1 Uncontrolled LRS | Forced Oscillation Technique (FOT) Measures | Pre BD R5 | 4.4 resonant frequency |
| Visit 1 Uncontrolled LRS | Forced Oscillation Technique (FOT) Measures | Pre BD R5-20 | 1.0 resonant frequency |
| Visit 1 Uncontrolled LRS | Forced Oscillation Technique (FOT) Measures | Post BD R5 | 4.1 resonant frequency |
| Visit 1 Uncontrolled LRS | Forced Oscillation Technique (FOT) Measures | Post BD R5-20 | 0.8 resonant frequency |
| Visit 1 Controlled LRS | Forced Oscillation Technique (FOT) Measures | Post BD R5-20 | 0.6 resonant frequency |
| Visit 1 Controlled LRS | Forced Oscillation Technique (FOT) Measures | Pre BD R5 | 3.7 resonant frequency |
| Visit 1 Controlled LRS | Forced Oscillation Technique (FOT) Measures | Post BD R5 | 4.0 resonant frequency |
| Visit 1 Controlled LRS | Forced Oscillation Technique (FOT) Measures | Pre BD R5-20 | 0.6 resonant frequency |
Primary
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
Time frame: Week 12
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Visit 1 Uncontrolled LRS | Spirometry Measures | Pre-BD FEV1/FVC | 78.5 % FEV1(Liters)/FVC(Liters) |
| Visit 1 Uncontrolled LRS | Spirometry Measures | Post-BD FEV1/FVC | 78.3 % FEV1(Liters)/FVC(Liters) |
| Visit 1 Controlled LRS | Spirometry Measures | Pre-BD FEV1/FVC | 81.2 % FEV1(Liters)/FVC(Liters) |
| Visit 1 Controlled LRS | Spirometry Measures | Post-BD FEV1/FVC | 77.7 % FEV1(Liters)/FVC(Liters) |
Secondary
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.
Time frame: Week 12
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Levels of Fractional Exhaled Nitric Oxide (FeNO) | 17.8 parts per billion (ppb) |
| Visit 1 Controlled LRS | Levels of Fractional Exhaled Nitric Oxide (FeNO) | 13 parts per billion (ppb) |
Secondary
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.
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Number of Participants With Positive Level of Bronchial Hyperreactivity (BHR) | 18 Participants |
| Visit 1 Controlled LRS | Number of Participants With Positive Level of Bronchial Hyperreactivity (BHR) | 6 Participants |
Secondary
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.
Time frame: Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Number of Participants With Positive Level of Paradoxical Vocal Fold Movement (PVFM) | 21 Participants |
| Visit 1 Controlled LRS | Number of Participants With Positive Level of Paradoxical Vocal Fold Movement (PVFM) | 6 Participants |
Secondary
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).
Time frame: Week 12
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Rhinosinusitis Score on International Classification of Sleep Disorders (ICSD) | 35 score on ICSD scale |
| Visit 1 Controlled LRS | Rhinosinusitis Score on International Classification of Sleep Disorders (ICSD) | 26 score on ICSD scale |
Secondary
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.
Time frame: Week 12
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Score on Leicester Cough Questionnaire (LCQ) | 12 score on LCQ scale |
| Visit 1 Controlled LRS | Score on Leicester Cough Questionnaire (LCQ) | 15.6 score on LCQ scale |
Secondary
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.
Time frame: Week 12
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Score on Voice Handicap Index 10 (VHI-10) | 7 score on VHI-10 scale |
| Visit 1 Controlled LRS | Score on Voice Handicap Index 10 (VHI-10) | 1 score on VHI-10 scale |
Secondary
Total EoS (Eosinophil) Counts
EoS counts were obtained by blood test - the total amount of blood drawn is 30 mL.
Time frame: Week 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Total EoS (Eosinophil) Counts | .10 eosiniphils *10^9/Liter |
| Visit 1 Controlled LRS | Total EoS (Eosinophil) Counts | .10 eosiniphils *10^9/Liter |
Secondary
Total IgE (Immunoglobulin E) Levels
IgE levels were obtained by blood test - the total amount of blood drawn is 30 mL.
Time frame: Week 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Visit 1 Uncontrolled LRS | Total IgE (Immunoglobulin E) Levels | 41 ng/mL |
| Visit 1 Controlled LRS | Total IgE (Immunoglobulin E) Levels | 31 ng/mL |