Residential Cleaning of Indoor Air to Reduce Acute Exacerbations of COPD (CARE): A Pilot Randomized Crossover Trial
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Sponsor: University of Rochester

Version Date: 18Dec2019 
Page 1 of 15 
 
A pilot randomized crossover trial of cleaning indoor air to reduce acute 
exacerbations of COPD (CARE) study 
 
 
 
Principal Investigator: 
Daniel Croft MD, MPH1 
Coinvestigators: 
David Rich Sc.D3; Anthony Pietropaoli MD, MPH1; Daniel 
Lachant DO1; Mark Frampton MD1; Mark Utell1,4; Phil 
Hopke PhD3; Kelly Thevenet-Morrison3; Sally Thurston 
PhD5 
Study coordinator: 
Carl Johnston, PhD6 Amy Rovitelli1 
 
1. Division of Pulmonary and Critical Care, Department of Medicine, University of 
Rochester 
2. Division of Infectious Disease. University of Rochester Medical Center, Rochester, 
New York 
3. Department of Public Health Sciences, University of Rochester Medical Center, 
Rochester, New York 
4. Department of Environmental Medicine, University of Rochester Medical Center, 
Rochester, New York 
5. Department of Biostatistics and Computational Biology, University of Rochester, 
Rochester, New York 
6. Department of Pediatrics, University of Rochester, Rochester, New York 
 
 
Corresponding PI: 
Daniel P. Croft MD, MPH 
University of Rochester Medical Center 
Pulmonary and Critical Care Division 
601 Elmwood Avenue Box 692 
Rochester, NY 14642 
Phone: 585 275 4161 Fax: 585 271 1171 
Email: 
daniel_croft@urmc.rochester.edu 
 
NCT: NCT03750292 

Version Date: 18Dec2019 
Page 2 of 15 
 
1. Purpose of the Study: 
Given the importance of indoor air pollution as a contributor to acute exacerbations of 
COPD (AECOPD), we will study the health impact of reducing indoor air pollution in 
patients with COPD using high-efficiency particulate air (HEPA) filtration units. 
 
Specifically we will explore whether 2 months of home air cleaning with the 
HEPAirX® air filtration system in the living room and bedroom of each subject’s 
home results in: 
 
1. Improved functional status measured by: 
a. St. George's Respiratory Questionnaire (SGRQ) and 
b. Daily step counts (measured by Fitbit® wearable sensor) 
 
2. Reduced levels of systemic inflammation, 
a. Plasma C-reactive protein (CRP) levels as a biomarker 
 
3. Reduced risk for AECOPD 
a. Using healthcare encounter data 
 
2. Background: 
B.1. COPD and Indoor air pollution: Descriptions, sources, and health effects of 
indoor air pollution have been summarized previously.(Weschler 2011; Zhang and Smith 2003) PM10 
(particles <10 µm), PM2.5 (particles <2.5 µm), ultrafine particles (particles <0.1 µm; UFP) 
as well as gaseous pollutants including carbon monoxide (CO), volatile organic 
compounds (VOC), and ozone (O3), among many other pollutants, are found indoors. 
All of these particulate and gaseous pollutants are either emitted from an indoor source 
(e.g. cooking, other open flames, or leaks in the home heating system), are secondary 
products of pollutants emitted indoors, or directly infiltrate from outside.(Li and Hopke 1991) 
While all these pollutants can contribute to AECOPD, the size of the particle pollutants 
(PM10, PM2.5 and UFP) determines how deep in the respiratory tract particles can 
penetrate, with PM10 depositing in the trachea causing, PM2.5 reaching the alveoli and 
UFP entering the systemic circulation.(Pope and Dockery 2006) 
Both filtration of particles (e.g. PM10, PM2.5, and UFP) and ventilation with outdoor air to 
reduce gaseous pollutant concentrations have been shown to improve human health 
and functional status.(Fisk and Brunner 2012; Fisk 2013; Seppanen and Fisk 2004) The HEPAirX filtration 
and ventilation device is a trademarked, patented (U.S. Patent # 7,802,443), U.S. FDA 
approved Class II medical re-circulating air cleaner, built by Air Innovations, Inc. (North 
Syracuse, NY). We have previously shown it to be proficient in reducing levels of 
several gaseous pollutants (via ventilation) and PM (via filtration); (see Preliminary 
evidence section for a full description of the HEPAirX). 
 
B.2. Indoor air pollution and inflammation: Both local (pulmonary) and systemic 
inflammation play key roles in airways diseases such as COPD. We and others have 
extensively assessed airway inflammation during air pollution studies (Huang et al. 2012; AP 
Pietropaoli et al. 2004; Zuurbier et al. 2011) and in COPD patients specifically have shown airway 
inflammation following increases in air pollution concentration over the previous 
days.(Adamkiewicz et al. 2004; A Pietropaoli et al. 2004) Air pollution also appears to induce systemic 

Version Date: 18Dec2019 
Page 3 of 15 
 
inflammation. (Brook et al. 2010; Croft et al. 2017) Plasma C-reactive protein (CRP) is a 
measure of systemic inflammation, and is an acute phase protein known to increase 
in the hours and days following an inflammatory stimulus. Persistently increased CRP 
after an AECOPD has been previously associated with an increased risk for recurrent 
AECOPD (Perera et al. 2007) and increased mortality from COPD.(Leuzzi et al. 2017) While the 
clinical significance of reducing CRP levels in COPD patients following AECOPD is not 
established, decreased systemic inflammation related to decreased levels of indoor air 
pollution is expected to lower the risk for recurrent AECOPD. 
 
B.3. Impaired functional status: Pulmonary and systemic inflammation contribute 
to the characteristic findings of AECOPD including increased respiratory 
symptoms of cough, sputum production, dyspnea and reduced functional status 
(defined as an inability to perform daily activities, fulfill usual roles, and maintain well- 
being).(Perera et al. 2007; Society 2013) The St. Georges Respiratory Questionnaire (SGRQ) is an 
established, clinically relevant measure of respiratory symptoms, activity level, and 
impacts on daily life, and is a measure of functional status regularly used and validated 
in COPD patient populations.(Jones et al. 1992) The questionnaire is a fixed format 50 item 
survey completed by the study subject asking questions in three parts: 1) levels of 
symptomatology including frequency (over the course of a week) of wheezing, cough, 
sputum production, and breathlessness, including the duration of episodes of wheeze 
and breathlessness, 2) physical activities (e.g. housework) that may be caused or are 
limited by breathlessness, and 3) impacts of these symptoms (e.g. employment, 
inhaler/medication needs, panic, disturbances of daily life, etc.). It is a self-assessment 
of respiratory symptoms and functional status, and provides a quantification of the 
impacts of airflow limitation on health and well-being. Previously, in a study of severe 
COPD patients, increased indoor residential PM2.5 concentrations were associated with 
impaired functional status measured by the SGRQ.(Osman et al. 2007) 
Consumer level wearable sensors are increasingly being used in clinical trials for 
mobility and functional status outcomes.(Izmailova et al. 2017) We will use a Fitbit® brand step 
counter as a secondary measure of functional status, due to its superior performance to 
other devices in an observational study examining patients’ movement after 
AECOPD.(Prieto-Centurion et al. 2016) 
 
C. Significance, Impact and Anticipated Outcomes 
This pilot study is significant and likely to have a high impact on URMC and its clinical 
treatment of COPD patients for several reasons. First, if we show that indoor air 
cleaning improves functional status, reduces systemic inflammation as well as the 
number of AECOPD encounters, we will provide an easy to use, relatively inexpensive 
treatment option that URMC and other medical facilities can use to protect their COPD 
patients against air pollution mediated health effects and hospital re-admissions. 
Second, having fewer hospital re-admissions for these COPD patients would reduce 
the treatment expenses of medical facilities such as the URMC providing their clinical 
care. Given the need of the URMC and other medical facilities to reduce their risk- 
adjusted 30-day COPD hospital re-admission rate to <20% or else face financial 
penalties from the Center for Medicare and Medicaid Services (CMS), this study is 
particularly timely. Third, if we find that indoor air cleaning protects COPD patients from 
AECOPD and/or improves their functional status, then a larger NIH funded study to 

Version Date: 18Dec2019 
Page 4 of 15 
 
confirm these findings, investigate pathophysiologic mechanisms, and examine whether 
specific components of pollutant mixtures are driving any health response(s) will be 
warranted. 
However, if we find that air cleaning using the HEPAirX does not reduce AECOPD 
and/or improve functional status in these COPD patients, then other in-home strategies 
to reduce COPD patients’ exposures to indoor air pollution may need to be 
investigated. For example, more comprehensive whole home filtration and air cleaning 
systems (which arguably would be much more expensive than the 2 air cleaners/home 
we will study here) could be installed in the homes of COPD patients to protect them 
from indoor air pollution exposure. Other options for these COPD patients upon initial 
hospital discharge may also need to be considered, including social work assistance to 
consider different residential locations in areas with lower levels of indoor and outdoor 
air pollutants and second hand smoke exposure. 
 
D. HEPAirX Air Cleaning System. The second 
generation HEPAirX integrated energy recovery 
ventilator and air cleaner (Figure 1) improves on older 
and other current devices through combined high- 
efficiency filtration (reduced particles) and ventilation 
(reduced gaseous pollutants). It is a trademarked, 
patented (U.S. Patent # 7,802,443), U.S. FDA 
approved Class II medical re-circulating air cleaner, 
built by Air Innovations, Inc. (North Syracuse, NY) to 
provide improved indoor air quality in the bedrooms of 
asthmatic children. The device is being used in the 
current study in the FDA-approved manner. Units to be 
used in the proposed study have a 99.97% efficient 
filter for particles 0.3 µm in size. The device provides a 
clean air delivery rate (CADR) of 9 per hour with 1.8 of them being outdoor air. Using the 
initial version of this system, mounted in bedroom windows, we reduced PM10, CO, 
CO2, and VOC concentrations in the bedrooms, decreased pulmonary inflammation, 
and improved pulmonary function in pediatric asthma patients.(Xu et al. 2009) Using the 
second-generation units we again substantially improved air quality in bedrooms (CO: 
-55%, VOC: -59% and PM10: -54%) with the HEPAirX system in full operation (unit 
on) compared to the placebo mode (unit on, but no filtration or ventilation). In this 
study, a placebo mode was added to the HEPAirX to provide only recirculation (without 
filtration or ventilation using outdoor air) and temperature control of the room air. This 
same placebo mode of the second generation device, which allows a comparison of 
health effects associated with air filtration and ventilation and the expected pollutant 
reductions will be used in our proposed study. 
The HEPAirX device fits into a standard double hung window (Figure 2) and provides the 
heating or cooling required to maintain a constant, comfortable room temperature. A built- 
in air-to-air heat exchanger captures the energy in the exhaust air to pre-condition the 
incoming outside air. Please see the letter from Michael Wetzel (CEO: Air Innovations; 
Manufacturer of HEPAirX) for his support of this study, and the provision of 20 HEPAirX air 
cleaning devices at no cost other than the HEPA filters used during the study. 
Figure 1. HEPAirX integrated energy 
recovery ventilator and air cleaner 

Version Date: 18Dec2019 
Page 5 of 15 
 
 
3.1. Study Population. We will recruit a total of 20 adult (≥18 years of age) men and 
women with severe COPD (forced expiratory volume (FEV1) < 50%), who live in Monroe 
County (New York), have completed pulmonary rehabilitation for over 1 month, and have 
suffered from an AECOPD in the past year. 
 
Number of Subjects: 
We will enroll a total of 20 patients in our study who have completed pulmonary 
rehabilitation in Monroe County, New York. 
 
Gender of Subjects: There are no restrictions on gender for this study with approximately 
60% of subjects expected to be female. 
 
Age of Subjects: All adults over the age of 18 will be included in the study with the 
average age of subjects enrolled expected to be around 65 years old. 
 
Racial and ethnic origin: There are no restrictions on race/ethnicity for participation in the 
study. We anticipate enrollment demographics in the study will be similar to our clinic 
population, of which 85% of patients are white, 10% African American, and 5% from other 
groups. 
 
Inclusion criteria: We will prospectively recruit a total of 20 adult (≥18 years of age) men 
and women with severe COPD (FEV1 < 50%), who live in Monroe County, have completed 
pulmonary rehabilitation (over 1 month since completion), and have suffered from an 
AECOPD in the past year. Subjects must have standard sized windows in their bedroom 
and living room amenable to installation of the HEPAirX® device. All subjects must also 
expect to sleep each night of the 4 months (2 months of Period 1, and 2 months of period 
2) in either their bedroom or living room for at least 6 hours/night, and not use other air 
filtering devices during the study. 
 
Exclusion criteria: Exclusion criteria include subjects who are under age 18 and do not 
meet the inclusion criteria as defined above. Exclusion criteria include subjects under age 
18, those who were smoking at the time of their prior COPD exacerbation, current 
smokers, those who live with an active smoker, homes with wood burning appliances, 
patients on chronic systemic corticosteroids (>3 months continuous use in past 1 months), 
those who are planning to move in the next 12 months, those with an occupation that has a 
high pollutant exposure (e.g. professional drivers), those who already have a home air 
filtration device(other than basic furnace filter) and those who do not meet the inclusion 
criteria as defined above. 
 
Vulnerable subjects: We do not plan to enroll vulnerable subjects. 
 
Discussion of subject population: We plan to enroll patients who have disease severe 
enough that an intervention of indoor air quality may benefit their health in a perceivable 
(Aims 1-3) way. This population is also more mobile than a homebound population making 
it safer/less disruptive to travel for blood draws at the University. 

Version Date: 18Dec2019 
Page 6 of 15 
 
4. Subject ID, Recruitment and Consent: 
We will enroll eligible patients (severe COPD and exacerbation history) who have 
completed the University of Rochester Pulmonary Rehabilitation program over 1 month 
prior to enrollment into our study. 
Contact will be made by telephone to determine their 
level of interest by the PI or coordinator of the study (Croft or Johnston). For those 
expressing a desire to participate during that phone call, potential subjects will be 
scheduled to come in to review the study in more detail.  Once the study has been 
reviewed with the subject in detail and all of their questions have been answered, written 
informed consent will be obtained by a study team member before the study procedures 
begin. All subjects will have capacity to consent for themselves. Subjects will be provided 
with a copy of the signed consent form for their records. Please see attached consent form 
for full details. 
 
 
 
 
 
 
 
5. Study Activities 
 
Summary of Project Methods and Study Procedures 
We propose a double-blind, randomized crossover trial (both study participant and 
clinical staff are blinded to randomized group) to assess whether 2 months of bedroom and 
living room air cleaning, in the homes of COPD patients with AECOPD in the past year, 
improves functional status, lowers systemic inflammation, and decreases the risk for 
AECOPD when compared to a 2 month period using a ‘sham filter’ (i.e. placebo mode 

Version Date: 18Dec2019 
Page 7 of 15 
 
described above). Descriptions of our study population, protocol and statistical analyses 
are provided below. 
E.1. Study Population. We will recruit a total of 20 adult (≥18 years of age) men and 
women with severe COPD (FEV1 < 50%), who live in Rochester, NY, have completed 
pulmonary rehabilitation, and have suffered from an AECOPD in the past year. E.2. Health 
Outcomes. Our primary endpoints will be the symptom score from the St. George’s 
Respiratory Questionnaire (SGRQ; marker of functional status) described above in Section 
B.3 and the average daily count of steps taken using a Fitbit® brand wearable sensor (Aim 
1). Our secondary endpoints are Plasma CRP measurements (Aim 2) and healthcare 
contacts for AECOPD (Aim 3). The subjects will wear the Fitbit® watch around their wrist 
during waking hours, which will automatically collect the daily count of steps and report this 
electronically to the research team via a secure account (Described below). The subjects 
will travel to the URMC lab at the specified time (described below) to have their plasma 
CRP drawn. 
E.3. Study Protocol. We will conduct a randomized, blinded, crossover trial, where 
each of the 20 total subjects will be randomly assigned to Group A (Period 1 = 8 weeks of 
filtration/ventilation mode, 3 week washout period, Period 2 = 8 weeks of placebo mode 
[device runs but no filtration/ventilation]) or Group B (Period 1 = 8 weeks of placebo mode, 
3 week washout period, Period 2 = 8 weeks of filtration/ventilation mode). Subjects will be 
blinded to which group they are randomly assigned, and only staff installing and monitoring 
the HEPAirX device and air pollution monitoring equipment, and not staff collecting or 
analyzing health outcomes, will know the assigned group. In the placebo mode of 
operation, the HEPAirX unit operates in exactly the same way (i.e. will look and sound the 
same), but it does not filter air to remove particles or have outdoor air exchanges to reduce 
gaseous pollutants. With 20 HEPAirX machines available and 2 required per subject, the 
timing of enrollment will be split into 2 groups of 10 patients (Two 19 week periods). 
After getting informed consent from each study participant, we will schedule the 1st 
home visit within 2 weeks. Once consent to participate in the study has been obtained, we 
will provide subjects with: 
• Five simple indoor air quality monitors which the subject will plug into an electrical 
outlet and set on a tabletop in a low traffic area of their living room and bedroom. 
• Subjects will also be given a Fitbit® activity tracker at this time, which will be worn on 
their wrist during waking hours. 
• Subjects will also be given a smartphone to use for syncing the Fitbit watch 
(charged every 4 days as well). 
Period 1: (First 8 week intervention: Either filtering/ventilation mode or sham mode): 
Subjects will visit the main URMC lab to have plasma CRP drawn (Blood Draw 1 of 4, 
perform a 6 minute walk test with their Fit Bit and wearable sensors. Study staff will then 
visit the subject’s home, check on the indoor air quality pollution monitors, and install and 
turn the HEPAirX® devices “On” to start Period 1 (Visit 1). At this time (Visit 1) the subjects 
will complete the SGRQ (survey 1 of 5). Washout Period: After 8 weeks of either filtration 
or placebo operation, the subject will have another blood draw for CRP at our URMC lab 
(2 of 4), perform a 6 minute walk test with their Fit Bit and wearable sensors and study 
staff will return (Visit 
2) to turn off the two devices for a 3 week Washout period. A SGRQ will also be 
administered at this time (Survey 2 of 5). This 3 week period was included to ensure that 
the Pre-filtering Period 2 health measurements are not impacted by the Period 1

Version Date: 18Dec2019 
Page 8 of 15 
 
filtration/ventilation. While previous studies suggest a 1 week washout is adequate for PM 
and other pollutant levels to return to baseline levels, we chose a 3 week washout period to 
ensure that the subjects’ functional status will also return to baseline levels. 
Period 2: (Second 8 week intervention): After the washout period, the subject will again 
have drawn at our URMC lab (Blood Draw 3 of 4), perform a 6 minute walk test with their 
Fit Bit and wearable sensors and they will complete another SGRQ (Survey 3 of 5). Study 
staff will then return to the subject’s home (Visit 3) to change the HEPAirX® device to the 
appropriate setting depending on the subjects’ Group (A or B). 
After 8 weeks of operation, staff will return to the subject’s home (Visit 4) to retrieve the 
HEPAirX® device, Fitbit® activity tracker, smartphone and air quality monitor. At this time, 
another SGRQ will be administered (Survey 4 of 5) and the subject will also submit their 
final blood sample for CRP (Blood Draw 4 of 4), perform a 6 minute walk test with their Fit 
Bit and wearable sensors. The subject will complete their final survey (Survey 5 of 5) three 
months after Visit 4 (week 31), concluding the study. 
Each subject will receive a total of $620 in personal checks (over the course of the study) 
to offset electricity costs to run the HEPAirX®  and costs for travel to URMC for blood 
draws. Checks will be given at each home visit for the portions of the study completed at 
that time point. Leftover blood from CRP analysis will be stored for the duration of the study 
and banked for future analysis, which will include the possibility for genetic analysis (See 
Blood collection section below for details). During the two eight week blocks, we will check 
in by phone 4 weeks into the study to make sure no problems have arisen and will be 
available to visit the home as needed during this period. 
To keep the subject blinded with regard to mode of the HEPAirX® during Periods 1 and 
2 (i.e. Filtration mode or Placebo mode), the device will be sealed to prevent the subject 
from opening it. Further, with or without the filter, there are no differences in temperature 
control, air flow (device still conducts 9 air changes per hour, recirculating indoor air 
without filtering or ventilating with outside air), or noise. Subjects will keep the device 
running constantly during both 8 week intervention periods, with temperature being the one 
variable the subject can control. We can determine its usage using an elapsed time meter 
on each unit. Subjects will keep a time-activity diary, particularly noting when cooking or 
cleaning occurs and when they are in the bedroom. This diary will also include instances of 
when patients feel symptoms of upper or lower respiratory infection (sinus congestion, 
runny nose, cough, increased sputum production) 
PROTOCOL (METHODS AND PROCEDURES) 
We will record patient information from the medical record into a secure database after the 
patient has given written informed consent. 
1) Blood Collection: Blood will be collected from a peripheral vein at the URMC lab 
(10mL total) using their standard technique to assess (1) plasma for CRP 
measurements (5ml) at the aforementioned intervals and 2) separate tube (5ml) 
of blood will be drawn for storage and may be used for genetic analysis. This 
blood will be stored (banked) for future analysis under a separate RSRB protocol 
(#00004357). 
 
2) Home Activity Monitoring: We will ask participants to wear a wristband step 
counter (FitBit®; Wavelet health, Mountain View, Ca) while at home which will 
measure continuous activity in the form of steps. It will also collect data on heart 

Version Date: 18Dec2019 
Page 9 of 15 
 
rate which will also be a proxy for activity. Participants will be dispensed a 
wristband (and charger) to wear at home for the entire study period. This Fitbit® 
will be synced to our secure tablet computer at the home visit intervals and we 
will access the data on the secure web-based portal. We will manage the 
accounts for each Fitbit®, but the subjects will have temporary access to the 
accounts. Subjects will be provided with a smartphone which will have only Wi- 
Fi capabilities and the Fitbit app installed. Subjects will sync their Fitbit with this 
device on a weekly basis. In this case, the wristband uploads the data to the app 
through blue tooth technology and ultimately onto a secure HIPAA compliant 
cloud. Subjects will be given the charging cord and instructed to charge the Fitbit® 
device every 7 days. When the study is complete, the FitBit® and smartphone will 
be collected at the final home visit. If the patient is not able to coordinate this data 
collection, we will help them sync their watch during home visits and will be 
available to help as needed through the study. 
 
3) Home air quality monitoring 
The simple corded air quality monitors (for particles and CO2, provided once 
consent has been obtained, will be placed in the subjects’ home and will take 
continuous measurements over the course of the study. This will be checked at 
the midpoint of the study and collected at the conclusion of the study. The 
monitors, will be sent to AirViz so they can extract the anonymized raw data from 
the air quality monitors and review the information captured to ensure data quality. 
Once QA review is complete, the data will be forwarded to us for our research 
analysis at the end of the study. AirViz Inc. will not receive any information that 
identifies the subjects, nor will they take part in analyzing or interpreting the 
results of the air quality data. Furthermore, after removal from subject homes, the 
filters from the HEPAirX® devices will be retained (not discarded) and will be used 
in a future analysis with links retained to subject ID and current study outcomes. 
 
4) Clinical Data Collection. The patients will receive standard of care diagnostic 
testing and treatment throughout the period of the study. We will collect  relevant 
data to the evaluation and ongoing management of COPD into a secure, web-
based data portal. We will maintain identifying information so that we could later 
add to the database as new diagnostic testing or new insights relevant to old 
diagnostic testing become available. 
 
5) Subject Withdrawals: This is described to the participant in the consent form. 
Subjects can withdraw at any point in the trial. If the subject withdraws prior to the 
installation of the air quality monitor, they will be replaced by another participant. 
 
6) Additional community resources: If agreeable, patients will be able to consent to 
having their name released to our partners in Community Health who will contact 
them to consider whether they are eligible to participate in the Rochester Healthy 
Homes Partnership, 

Version Date: 18Dec2019 
Page 10 of 15 
 
 
6. Risks and Benefits: 
Risks: This study is minimal risk, as we are simply implementing an intervention that will 
clean the indoor air of our subjects. The blood draws will impose a small amount of 
physical pain to the subject. The activity monitor is a noninvasive device worn around the 
wrist. The SGRQ should have minimal risk for psychological stress. For the outcome of 
measuring exacerbations, we will be using already existing information on these patients 
located in the medical record. There is a small risk of loss of confidentiality and a small risk 
of loss of privacy due to our accessing of your identifiable information including lab work 
and our entry into your home for installation of the indoor air cleaners.   Please see our 
data storage and confidentiality plan for our methods to protect against these potential 
losses of confidentiality and privacy. Having an indoor air cleaner may expose the subjects 
to the stress of thinking of the dangers of indoor air quality 
 
Benefits: There will be at most a transient benefit to the individual subjects. 
Compensation 
 
Payment to Subjects 
Each subject will receive a total of $580 in the form of a check to offset electricity costs to 
run the HEPAirX and travel for blood draws. 
 
1. Compensation for driving to the lab (using a compensation of $0.565 per mile 
with a uniform estimate of 30 miles travel for each of 4 CRP): 
$80 per study 
subject 
2. Compensation for scheduled home visits: $25 per visit = $100 per study subject 
3. Compensation for energy costs: $400 for study = $400 per study subject 
Total compensation per subject = 
$580 
 
 
Costs to Subjects 
There is a possible risk that the energy costs from the use of HEPAirX device will exceed 
the energy cost estimated by our technical team. To help protect subjects from this 
additional cost, we will have subjects submit their prior month’s utility bill to help with 
estimation. We will be able to provide reasonable additional compensation to the subjects. 
 
7. Data Storage and Confidentiality: 
 
Any confidential and private data will be protected and stored in a separate dataset at the 
University of Rochester in specified and protected locations (protected institutional 
SMDNAS drive of Dr. Daniel Croft), distinct from the main analysis dataset. The data from 
the air quality monitoring device within the home will only be collected at the end of each of 
the two periods (whether filter or placebo). At the end of the study, these air quality data 
will be aggregated and sent to the analyst Kelly Thevenet-Morrison study in a blinded 
fashion. Similarly the Fitbit monitoring data will be downloaded from the devices at least at 
the end of each period (though patients will be syncing data throughout the study every 4 
days). The Fitbit username and password will be managed by the investigators (Daniel 
Croft, Carl Johnston and Sanjna Prasad). For blinding purposes, the identifying information 

Version Date: 18Dec2019 
Page 11 of 15 
 
indicating the order of intervention will be located in a separate password protected file and 
will be managed by Kelly Thevenet-Morrison. Other than files with personal health 
information which will be password protected on the secure SMDNAS drive of the Principal 
Investigator Dr. Daniel Croft with access granted to, Dr. David Rich, Mrs. Kelly Thevenet- 
Morrison (analyst/programmer), Dr. Carl Johnston, Sanjna Prasad, Amy Rovitelli and Dr. 
Philip Hopke only. Also, we will utilize the date/time of any possible hospital admission 
and/or date/time of emergency department evaluation for COPD exacerbations to use in 
matching specific date/times of air pollution measurements. Identifying information will be 
retained for future analyses. 
 
8. Data Analysis: 
 
E.4. Statistical Analysis. We will generate descriptive statistics for each subject, 
indoor air pollutant concentrations during each filtering/placebo mode session, and our 
main outcomes in Aim 1-Aim 3 (Aim 1: SGRQ symptom score and average daily step 
count; Aim 2: plasma level of CRP; Aim 3: number of healthcare encounters for AECOPD), 
comparing the change in each between the filtration and placebo groups. Given the 
crossover design, each subject will serve as their own control. Our statistical analyses are 
described below. 
We will fit a random effects ANOVA model regressing the 8-week (Post-filtering SGRQ 
score (Aim 1) against the Pre-filtering SGRQ score, period (‘Period 1’ versus ‘Period 2’), 
and filtering mode (‘filter/ventilation mode’ versus ‘placebo mode’). If necessary, we will 
transform both post-filtering and pre-filtering SGRQ score to better satisfy model 
assumptions. Subjects will contribute two observations to the analysis and subjects will be 
included as random effects, recognizing correlations due to repeated measures on the 
same subject. Filtering mode will test whether the ‘filtration/ventilation mode’ produced a 
significant effect on subsequent SGRQ score than the ‘placebo mode’. Next, the final 
survey 3 months after the 19 week intervention period concludes will be compared to 
survey 4 to explore the duration of observed changes. We expect that in view of the 
“washout period” between Period 1 and Period 2, there will be no carry-over of the effect of 
the intervention in Period 1 on the results for Period 2. Including period in the model allows 
us to assess the plausibility of this assumption. This same analysis used for Aim 1 will also 
be used for Aim 2, plasma CRP. 
We will repeat the random effects ANOVA model, regressing the 8 week in Fitbit® 
measured average daily step count (Aim 1) (Post-filtering average daily step count) against 
the Pre-filtering average daily step count, period and filtering mode. Specifically the 
intervals selected for this analysis will be the week prior to Phase 1 compared to the final 
week of Phase 1 and the final week of the washout period compared with the final week of 
Phase 2. Indoor PM2.5 concentration will be analyzed similarly with the ANOVA model and 
will also use these same time intervals. We will repeat the random effects ANOVA model 
for average resting heart rate at the same time intervals. 
 
For Aim 3, the number of healthcare encounters for AECOPD, we will fit a Poisson 
regression of the number of COPD exacerbations in 8 weeks as a function of filtering mode 
(Filtering versus Placebo) and period. Should there be very few healthcare encounters, 
instead we will use a logistic regression to model whether there were any healthcare 
encounters. This model will allow us to evaluate the impact of filtering model on healthcare 

Version Date: 18Dec2019 
Page 12 of 15 
 
encounters, while adjusting for period (e.g. Group A (Filtration followed by Placebo) or 
Group B (Placebo followed by Filtration) to determine if the order of intervention affected 
the outcome). Next we will compare healthcare encounters for AECOPD at the 3 month 
follow up period with Phase 2 outcomes in a similar way. Since this is a pilot study, power 
calculations are not provided, and effect estimates from the regression analyses described 
above will be used as preliminary data in an application for a larger, adequately powered 
R01 funded study. 
 
Post hoc analyses: 
1. Autonomic function: In addition to average resting heart rate, we will determine if the 
data are robust enough to calculate heart rate variability. 
2. Genetic response: As mentioned, the stored blood may be used in a future analysis 
on the genetic response to air pollution related to respiratory outcomes 
3. Particle Chemistry: The particles on the filters will be analyzed in the future for 
composition and potentially even included in cell exposure studies to determine the 
mechanistic impact of the pollutants. 
 
SAFETY AND REPORTABLE EVENTS 
Adverse Event Definition 
An adverse event is any symptom, sign, illness, or experience, which develops or worsens 
during the course of the study, whether or not the event is considered related to study 
drug. 
 
Serious Adverse Event 
A serious adverse event is defined as any adverse medical experience that results in any 
of the following outcomes: 
• 
death; 
• 
is life-threatening; 
• 
requires inpatient hospitalization or prolongation of existing hospitalization; 
• 
results in persistent or significant disability/incapacity; 
• 
is a congenital anomaly/birth defect; or 
• 
requires medical or surgical intervention to prevent permanent impairment or 
damage. 
 
Recording Adverse Events 
At each subject visit the site study staff will assess adverse events by recording all 
voluntary complaints of the subject and by assessment of clinical and laboratory features. 
At each study visit, the subject should be questioned directly regarding the occurrence of 
any adverse experience since his/her last visit. 
 
While the subject is enrolled in the study, all adverse events, whether observed by the 
Investigator, elicited from or volunteered by the subject, should be documented. Each 
adverse event will include a brief description of the experience, the date of onset, the date 
of resolution, the duration and type of experience, the severity, and the relationship to any 
of the study procedures or devices, contributing factors, and any action taken with respect 
to the study procedures. 

Version Date: 18Dec2019 
Page 13 of 15 
 
 
Responsibilities for Reporting Serious Adverse Events 
The Investigator will record all serious adverse experiences that occur during the study 
period in the appropriate source documents and/or AE log as applicable from the time of 
signing consent to final study visit. The Investigator will also comply with regulations and 
RSRB policy regarding the reporting of adverse events. 
 
 
9. References: 
 
1. Adamkiewicz G, Ebelt S, Syring M, Slater J, Speizer FE, Schwartz J, et al. 2004. 
Association between air pollution exposure and exhaled nitric oxide in an elderly 
population. Thorax 59:204-209. 
2. Brook RD, Rajagopalan S, Pope CA, 3rd, Brook JR, Bhatnagar A, Diez-Roux AV, et 
al. 2010. Particulate matter air pollution and cardiovascular disease: An update to 
the scientific statement from the american heart association. Circulation 121:2331- 
2378. 
3. Croft DP, Cameron SJ, Morrell CN, Lowenstein CJ, Ling F, Zareba W, et al. 2017. 
Associations between ambient wood smoke and other particulate pollutants and 
biomarkers of systemic inflammation, coagulation and thrombosis in cardiac 
patients. Environ Res 154:352-361. 
4. Fisk WB, Brunner G. 2012. Changing ventilation rates in u.S. Offices: Implications 
for health, work performance, energy, and associated economics. Building and 
Environment 47:368-372. 
5. Fisk WJ. 2013. Health benefits of particle filtration. Indoor air 23:357-368. 
6. Huang W, Wang G, Lu SE, Kipen H, Wang Y, Hu M, et al. 2012. Inflammatory and 
oxidative stress responses of healthy young adults to changes in air quality during 
the beijing olympics. Am J Respir Crit Care Med 186:1150-1159. 
7. Izmailova ES, Wagner JA, Perakslis ED. 2017. Wearable devices in clinical trials: 
Hype and hypothesis. Clinical Pharmacology & Therapeutics. 
8. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. 1992. A self-complete measure 
of health status for chronic airflow limitation. The st. George's respiratory 
questionnaire. Am Rev Respir Dis 145:1321-1327. 
9. Leuzzi G, Galeone C, Taverna F, Suatoni P, Morelli D, Pastorino U. 2017. C- 
reactive protein level predicts mortality in copd: A systematic review and meta- 
analysis. Eur Respir Rev 26. 
10. Li CS, Hopke PK. 1991. Efficacy of air cleaning systems in controlling indoor radon 
decay products. Health Phys 61:785-797. 
11. Osman LM, Douglas JG, Garden C, Reglitz K, Lyon J, Gordon S, et al. 2007. Indoor 
air quality in homes of patients with chronic obstructive pulmonary disease. Am J 
Respir Crit Care Med 176:465-472. 
12. Perera WR, Hurst JR, Wilkinson TM, Sapsford RJ, Mullerova H, Donaldson GC, et 
al. 2007. Inflammatory changes, recovery and recurrence at copd exacerbation. Eur 
Respir J 29:527-534. 
13. Pietropaoli A, Frampton MW, Oberdorster G, Cox C, Huang L-S, Marder V, et al. 
2004. Blood markers of coagulation and inflammation in healthy human subjects exposed 
to carbon ultrafine particles. In: Effects of air contaminants on the respiratory tract - 

Version Date: 18Dec2019 
Page 14 of 15 
 
interpretations from molecular to meta analysis, (Heinrich U, ed). Stuttgart, 
Germany:NIS Monographs, Fraunhofer IRB Verlag, 181-194. 
14. Pietropaoli AP, Frampton MW, Hyde RW, Morrow PE, Oberdorster G, Cox C, et al. 
2004. Pulmonary function, diffusing capacity, and inflammation in healthy and 
asthmatic subjects exposed to ultrafine particles. Inhal Toxicol 16 Suppl 1:59-72. 
15. Pope CA, 3rd, Dockery DW. 2006. Health effects of fine particulate air pollution: 
Lines that connect. Journal of the Air & Waste Management Association 56:709- 
742. 
16. Prieto-Centurion V, Bracken N, Norwick L, Zaidi F, Mutso AA, Morken V, et al. 2016. 
Can commercially available pedometers be used for physical activity monitoring in 
patients with copd following exacerbations? Chronic Obstructive Pulmonary 
Diseases: Journal of the COPD Foundation 3:636-642. 
17. Seppanen OA, Fisk WJ. 2004. Summary of human responses to ventilation. Indoor 
Air 14 Suppl 7:102-118. 
18. Society AT. 2013. Functional status. Available: http://qol.thoracic.org/sections/key- 
concepts/functional-status.html 2013]. 
19. Weschler CJ. 2011. Chemistry in indoor environments: 20 years of research. Indoor 
Air 21:205-218. 
20. Xu Y, Raja S, Ferro AR, Jaques PA, Hopke PK, Gressani C, et al. 2009. 
Effectiveness of hvac/hepa unit on iaq and asthmatic children’s health. Building and 
Environment 45:330-337. 
21. Zhang J, Smith KR. 2003. Indoor air pollution: A global health concern. Br Med Bull 
68:209-225. 
22. Zuurbier M, Hoek G, Oldenwening M, Meliefste K, van den Hazel P, Brunekreef B. 
2011. Respiratory effects of commuters' exposure to air pollution in traffic. 
Epidemiology 22:219-227. 

Version Date: 18Dec2019 
Page 15 of 15 
 
Appendix: Data collection form 
Study Number 
Sex 
Age 
Race 
Ethnicity 
Home Address 
Comorbidities (OSA, sinus, DM, CHF, COPD, CRF) 
Smoking 
Vaccines 
FEV1 Forced expiratory volume 
FVC Forced vital capacity 
FEV1/FVC ratio 
DLCO (diffusion capacity) 
TLC (total lung capacity) 
Inhalers 
Inhaled steroid use 
Systemic steroid use 
Chronic Azithromycin Use 
 
Number of hospitalizations in past year 
Home O2 use (in Liters) 
CPAP/BiPAP use at night 
Statin use 
Symptoms (i.e. Cough, shortness of breath) 
 
SGRQ baseline 
SGRQ Period 1 end 
SGRQ Period 2 start 
SGRQ Period 2 end 
SGRQ 3 months from the end of period 2 
 
CRP at baseline 
CRP Period 1 Week 1 
CRP Period 1 end 
CRP Period 2 start 
CRP Period 2 week 
CRP Period 2 end 
 
Exacerbation count end of period 2 
Time to exacerbation 
Exacerbation count at 3 months from period 2