COPD, Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
COPD is characterized by lung injury and inflammation caused by noxious particles and gases, including those emanating from cigarette smoke and air pollution. Despite the clear detrimental impact of poor air quality on respiratory outcomes, regardless of smoking status, to investigators' knowledge, there are no studied environmental interventions targeting indoor air quality to improve respiratory health of smokers, thus ignoring a potential target for harm reduction. Investigators propose a randomized controlled intervention trial to test whether targeted reductions of multiple indoor pollutants (PM, SHS and NO2) in homes of smokers with COPD will improve respiratory outcomes. Investigators have chosen a potent, multimodal intervention (active air cleaners + Motivational intervention for SHS reduction) in order to maximize the opportunity to prove that there is a health benefit to active smokers with COPD from indoor air pollution reduction.
Detailed description
People with COPD who have higher exposure to indoor pollutants, including particulate matter (PM), second hand smoke (SHS), and nitrogen dioxide (NO2) have worse respiratory morbidity including a higher risk of exacerbations. These effects are not obscured by smoking habit. Unfortunately, despite the clear detrimental impact of poor air quality on respiratory outcomes, regardless of smoking status, to investigators' knowledge, there are no studied environmental interventions targeting indoor air quality to improve respiratory health of smokers, thus ignoring a potential target for harm reduction. Investigators propose a randomized controlled intervention trial to test whether targeted reductions of multiple indoor pollutants (PM, SHS and NO2) in homes of smokers with COPD will improve respiratory outcomes. Investigators have chosen a potent, multimodal intervention in order to maximize the opportunity to prove that there is a health benefit to active smokers with COPD from indoor air pollution reduction. After a one-month run in period in which all participants will receive smoking cessation strategies including Motivational Interviewing (MI) and nicotine replacement therapy, participants unable to quit smoking (n=120) will have 1:1 randomization to receive either 1) multi-component environmental intervention (active high-efficiency particulate air(HEPA) air cleaners + MI intervention for SHS reduction) or 2) sham air cleaners. Referrals to community resources for additional support will also be provided. Investigators aim to determine whether a multi-component environmental intervention (targeting PM, SHS and NO2 reduction) will improve respiratory morbidity (i.e., symptoms, quality of life, lung function and exacerbation risk) (Specific Aim #1) and intermediate outcome measures (i.e., markers of airway and systemic inflammation and oxidative stress) (Specific Aim #2) in smokers with COPD. Investigators anticipate that results from this study will inform clinical practice guidelines and health care policies aimed at reducing COPD morbidity and may have broader implications for indoor environmental recommendations for smokers with chronic disease.
Interventions
DEVICEActive HEPA Air Cleaner
The active treatment arm will receive two active air cleaners with HEPA and carbon filters to support a home smoking ban and SHS reduction.
BEHAVIORALMotivational interviewing
The active treatment arm will receive 4 sessions of phone based motivational interviewing to support a home smoking ban and SHS reduction (in addition to the smoking cessation counseling received by all study participants). The Control arm will receive only continued counseling for smoking cessation.
DEVICESham Air Cleaner
The Control arm will receive sham air cleaners
Sponsors
National Institute of Environmental Health Sciences (NIEHS)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 40 years, * Physician diagnosis of COPD, * Global Initiative for Obstructive Lung Disease (GOLD) Stage II-IV disease with Forced Expiratory Volume (FEV1)/ Forced Vital Capacity (FVC) \<70% and FEV1 (% predicted) \<80%. IF FEV1/FVC \<70% and FEV1 (% predicted) ≥ 80%, additional requirement will apply/will be asked: COPD Assessment Test (CAT) score ≥ 10 OR exacerbation history during the last 12 months. * Tobacco exposure ≥ 10 pack-years * Current smoker with an exhaled Carbon Monoxide (eCO) ≥ 7 ppm to confirm smoking status. We will employ a combination of self-report and a biochemical marker to identify former-smokers. (If no eCO performed due to COronaVIrus Disease-19 (COVID-19) pandemic safety reasons, we will rely on self-report smoking status and self-report 7-day abstinence questionnaire answers) * No home smoking ban. IF smoking is not allowed indoor (inside participant's home) then a home air quality assessment visit may be done.
Exclusion criteria
* Chronic systemic corticosteroids, * Other chronic lung disease including asthma, * Living in location other than home (e.g., long term care facility) * Home owner or occupant planning to move or change residence within study period. * Air Cleaners drop off (home visits temporary criteria due to COVID-19).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Dyspnea as Assessed by the University of California San Diego Shortness of Breath Questionnaire (SDSOBQ) | Baseline and 6 months | Dyspnea will be assessed using the University of California San Diego Shortness of Breath Questionnaire (SDSOBQ). The SDSOBQ scoring will range from 0 to 120 (with higher scores indicating greater difficulty breathing). |
| Change in Quality of Life -St. George's Respiratory Questionnaire (SGRQ) | Baseline and 6 months | St. George's Respiratory Questionnaire (SGRQ). The total score is from 0 to 100. Higher scores indicate more quality of life limitations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Dyspnea (Breathlessness) as Assessed by the Modified Medical Research Council Questionnaire (mMRC) | Change from baseline and 6 months post-randomization | Dyspnea (breathlessness) assessed by the modified Medical Research Council questionnaire (mMRC). Mean Score range is 0-4. Higher scores indicate worse COPD control. |
| Difference in the Proportion (Probability) of Health Care Utilization Due to COPD-related Exacerbations | From Baseline to 6 months | Questionnaire administered to collect participant's self report of Health Care Utilization (HCU) episodes due to COPD-related exacerbation (including need for oral corticosteroids or antibiotics for worsening respiratory symptoms, emergency department (ED) visit or hospitalization). This questionnaire will be administered at baseline and during the 6 months of follow-up. The HCU number could range from 0 (zero/no episode reported) to 1 (1 or more episodes reported) during the 6 months follow-up. |
| Change in COPD Health Status Will be Assessed by the COPD Assessment Test (CAT) | Baseline and 6 months | Change in COPD health status will be assessed by the COPD assessment test (CAT). The total score is from 0 to 40. Higher scores indicate worse COPD control. |
| Lung Function as Assessed by the Post Forced Expiratory Volume in 1 Second (FEV1%) Predicted | Baseline and 6 months | Pulmonary function testing will be assessed as FEV1% predicted, that is FEV1, adjusted for age, height, race and sex |
| Change in the Clinical COPD Questionnaire (CCQ) | Baseline and 6 months | The Clinical COPD Questionnaire (CCQ) will be administered to evaluate health status in patients with COPD. The CCQ is a 10-item questionnaire, health-related quality of life questionnaire (HRQoL) with good psychometric properties. The total score ranges from 0 to 6, where a higher scores indicates a worse health status. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Systemic Markers of Inflammation in Serum (C-reactive Protein) | Baseline and 6 months | Change in Systemic markers of inflammation in serum (C-reactive protein) will be measured by C-reactive protein concentration in serum and it will be expressed in: mg/l |
| Change in Systemic Markers of Inflammation in Serum (Interleukin-8) | Baseline and 6 months | Change in systemic markers of inflammation in serum (Interleukin-8) will be measured by Interleukin-8 concentration in serum (units/mg). |
| Change in Markers of Oxidative Stress in Urine (8-isoprostane) | Baseline and 6 months | Change in Markers of oxidative stress in urine (8-isoprostane) will be measured by 8-isoprostane concentration in urine (pg/ml). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited in the Baltimore/Washington are (MD, USA) between June 2019 and January 2024.
Pre-assignment details
Of the 144 enrolled participants, 121 met inclusion criteria. 1 of those participants dropped out prior to completing the baseline visit and was excluded from analysis.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment The active treatment arm will receive two portable active HEPA air cleaners as well as 4 sessions of phone based motivational interviewing to support a home smoking ban and SHS reduction (in addition to the smoking cessation counseling received by all study participants).
Active HEPA Air Cleaner: The active treatment arm will receive two active air cleaners with HEPA and carbon filters to support a home smoking ban and SHS reduction.
Motivational interviewing: The active treatment arm will receive 4 sessions of phone based motivational interviewing to support a home smoking ban and SHS reduction (in addition to the smoking cessation counseling received by all study participants).
The Control arm will receive only continued counseling for smoking cessation. | 59 |
| Control Arm Homes in the control group will receive Sham air cleaners that have the internal HEPA filter removed, but which will run normally, including similar noise, airflow and overall appearance compared to active air cleaners, thus blinding participants to filter status. The control arm will not receive phone based motivational interviewing to support a home smoking ban and SHS reduction, they will receive only smoking cessation counseling.
Sham Air Cleaner: The Control arm will receive sham air cleaners | 61 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Cancer diagnosis | 1 | 0 |
| Overall Study | Change residence | 1 | 2 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Evicted from home | 1 | 0 |
| Overall Study | Incomplete clinical visit at 6 months due to illness | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Unblinded | 2 | 3 |
Baseline characteristics
| Characteristic | Total | Active Treatment | Control Arm |
|---|---|---|---|
| Age, Continuous | 62.88 years STANDARD_DEVIATION 7 | 63.59 years STANDARD_DEVIATION 8 | 62.18 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants | 34 Participants | 40 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 20 Participants | 21 Participants |
| Sex: Female, Male Female | 75 Participants | 35 Participants | 40 Participants |
| Sex: Female, Male Male | 45 Participants | 24 Participants | 21 Participants |
| Some College Education or Above | 44 Participants | 19 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 59 | 1 / 61 |
| other Total, other adverse events | 3 / 59 | 1 / 61 |
| serious Total, serious adverse events | 4 / 59 | 3 / 61 |
Outcome results
Primary
Change in Dyspnea as Assessed by the University of California San Diego Shortness of Breath Questionnaire (SDSOBQ)
Dyspnea will be assessed using the University of California San Diego Shortness of Breath Questionnaire (SDSOBQ). The SDSOBQ scoring will range from 0 to 120 (with higher scores indicating greater difficulty breathing).
Time frame: Baseline and 6 months
Population: The difference in the overall number of participants analyzed is due to participants not having the University of California San Diego Shortness of Breath Questionnaire (SDSOBQ) data collected n either baseline and/or 6 months period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Treatment | Change in Dyspnea as Assessed by the University of California San Diego Shortness of Breath Questionnaire (SDSOBQ) | -4.8 score on a scale |
| Control Arm | Change in Dyspnea as Assessed by the University of California San Diego Shortness of Breath Questionnaire (SDSOBQ) | 1.3 score on a scale |
p-value: 0.061Generalized Linear Mixed Model (GLMM)
Primary
Change in Quality of Life -St. George's Respiratory Questionnaire (SGRQ)
St. George's Respiratory Questionnaire (SGRQ). The total score is from 0 to 100. Higher scores indicate more quality of life limitations.
Time frame: Baseline and 6 months
Population: The difference in the overall number of participants analyzed is due to participants not having SGRQ data collected in either baseline and/or 6 months period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Treatment | Change in Quality of Life -St. George's Respiratory Questionnaire (SGRQ) | -2.9 score on a scale |
| Control Arm | Change in Quality of Life -St. George's Respiratory Questionnaire (SGRQ) | 1.5 score on a scale |
p-value: 0.02595% CI: [-8.2, -0.5]Generalized Linear Mixed Model (GLMM)
Secondary
Change in COPD Health Status Will be Assessed by the COPD Assessment Test (CAT)
Change in COPD health status will be assessed by the COPD assessment test (CAT). The total score is from 0 to 40. Higher scores indicate worse COPD control.
Time frame: Baseline and 6 months
Population: The difference in the overall number of participants analyzed is due to participants not having the COPD assessment test (CAT) data collected in either baseline and/or 6 months period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Treatment | Change in COPD Health Status Will be Assessed by the COPD Assessment Test (CAT) | -1.8 score on a scale |
| Control Arm | Change in COPD Health Status Will be Assessed by the COPD Assessment Test (CAT) | 1.0 score on a scale |
Secondary
Change in Dyspnea (Breathlessness) as Assessed by the Modified Medical Research Council Questionnaire (mMRC)
Dyspnea (breathlessness) assessed by the modified Medical Research Council questionnaire (mMRC). Mean Score range is 0-4. Higher scores indicate worse COPD control.
Time frame: Change from baseline and 6 months post-randomization
Population: The difference in the overall number of participants analyzed is due to participants not having the modified Medical Research Council questionnaire (mMRC) data collected in either baseline and/or 6 months period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Treatment | Change in Dyspnea (Breathlessness) as Assessed by the Modified Medical Research Council Questionnaire (mMRC) | -0.3 score on a scale |
| Control Arm | Change in Dyspnea (Breathlessness) as Assessed by the Modified Medical Research Council Questionnaire (mMRC) | 0.1 score on a scale |
Secondary
Change in the Clinical COPD Questionnaire (CCQ)
The Clinical COPD Questionnaire (CCQ) will be administered to evaluate health status in patients with COPD. The CCQ is a 10-item questionnaire, health-related quality of life questionnaire (HRQoL) with good psychometric properties. The total score ranges from 0 to 6, where a higher scores indicates a worse health status.
Time frame: Baseline and 6 months
Population: The difference in the overall number of participants analyzed is due to participants not having the Clinical COPD Questionnaire (CCQ) data collected in either baseline and/or 6 months period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Treatment | Change in the Clinical COPD Questionnaire (CCQ) | -0.2 score on a scale |
| Control Arm | Change in the Clinical COPD Questionnaire (CCQ) | -0.8 score on a scale |
Secondary
Difference in the Proportion (Probability) of Health Care Utilization Due to COPD-related Exacerbations
Questionnaire administered to collect participant's self report of Health Care Utilization (HCU) episodes due to COPD-related exacerbation (including need for oral corticosteroids or antibiotics for worsening respiratory symptoms, emergency department (ED) visit or hospitalization). This questionnaire will be administered at baseline and during the 6 months of follow-up. The HCU number could range from 0 (zero/no episode reported) to 1 (1 or more episodes reported) during the 6 months follow-up.
Time frame: From Baseline to 6 months
Population: The difference in the overall number of participants analyzed is due to participants not completing (data not collected) the exacerbation survey between baseline and 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Active Treatment | Difference in the Proportion (Probability) of Health Care Utilization Due to COPD-related Exacerbations | Severe Exacerbations | 0.11 Proportion of events |
| Active Treatment | Difference in the Proportion (Probability) of Health Care Utilization Due to COPD-related Exacerbations | Moderate Exacerbations | 0.07 Proportion of events |
| Control Arm | Difference in the Proportion (Probability) of Health Care Utilization Due to COPD-related Exacerbations | Severe Exacerbations | 0.09 Proportion of events |
| Control Arm | Difference in the Proportion (Probability) of Health Care Utilization Due to COPD-related Exacerbations | Moderate Exacerbations | 0.19 Proportion of events |
Secondary
Lung Function as Assessed by the Post Forced Expiratory Volume in 1 Second (FEV1%) Predicted
Pulmonary function testing will be assessed as FEV1% predicted, that is FEV1, adjusted for age, height, race and sex
Time frame: Baseline and 6 months
Population: The difference in the overall number of participants analyzed is due to participants not having FEV1 data collected in either baseline and/or 6 months period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active Treatment | Lung Function as Assessed by the Post Forced Expiratory Volume in 1 Second (FEV1%) Predicted | -1.2 FEV1 percent predicted |
| Control Arm | Lung Function as Assessed by the Post Forced Expiratory Volume in 1 Second (FEV1%) Predicted | -0.8 FEV1 percent predicted |
Other Pre-specified
Change in Markers of Oxidative Stress in Urine (8-isoprostane)
Change in Markers of oxidative stress in urine (8-isoprostane) will be measured by 8-isoprostane concentration in urine (pg/ml).
Time frame: Baseline and 6 months
Other Pre-specified
Change in Systemic Markers of Inflammation in Serum (C-reactive Protein)
Change in Systemic markers of inflammation in serum (C-reactive protein) will be measured by C-reactive protein concentration in serum and it will be expressed in: mg/l
Time frame: Baseline and 6 months
Other Pre-specified
Change in Systemic Markers of Inflammation in Serum (Interleukin-8)
Change in systemic markers of inflammation in serum (Interleukin-8) will be measured by Interleukin-8 concentration in serum (units/mg).
Time frame: Baseline and 6 months