Cardiometabolic Biomarker Improvements Associated With Reduction in Air Pollution Exposure Via Home Air Filtration
Phase: NA
Conditions: Cardiovascular Diseases
Sponsor: NYU Langone Health

Official Title: 
Cardiometabolic Biomarker Improvements Associated With Reduction 
in Air Pollution Exposure Via Home Air Filtration  
NCT Number:
NCT05379400
Study Number:
22-00045 
Document Type:
Study Protocol and Statistical Analysis Plan
Date of the 
Document: 
 
September 14, 2023 

Page i
 
CARDIOMETABOLIC BIOMARKER IMPROVEMENTS ASSOCIATED 
WITH REDUCTION IN AIR POLLUTION EXPOSURE VIA HOME AIR 
FILTRATION. 
 
Principal Investigators:
Jonathan D. Newman, MD, MPH, FAHA, FACC 
Eugene Braunwald MD Assistant Professor of Medicine 
The Leon H. Charney Division of Cardiology  
And The Center for the Prevention of Cardiovascular Disease 
NYU School of Medicine 
 
 
 
Additional Investigators:
Sharine Wittkopp, MD, PhD
Post-Doctoral Fellow 
The Leon H. Charney Division of Cardiology  
NYU School of Medicine 
 
Terry Gordon, PhD 
Professor 
Department of Environmental Medicine 
NYU School of Medicine 
 
Jiyuan Hu, PhD 
Assistant Professor, Division of Biostatistics 
Department of Population Health 
Assistant Director, NYU Biostatistics Resource 
NYU School of Medicine 
 
Lorna Thorpe, PhD 
Professor 
Director of Division of Epidemiology 
Vice Chair of Strategy and Planning, Department of Population 
Health 
NYU School of Medicine 
NYULMC Study Number: 
s22-00045 
Funding Sponsor:
NYU Clinical and Translational Science Institute
Initial version: 01/25/2022 
Updated:  
04/07/2022 
Updated:  
09/07/2023 
 
 

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Statement of Compliance
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), any other applicable US government research regulations, and 
institutional research policies and procedures. The Principal Investigator will assure that no deviation 
from, or changes to the protocol will take place without prior agreement from the sponsor and 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the study participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection Training. 
 
 

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Table of Contents 
PROTOCOL SUMMARY .............................................................................................................................. 1
SCHEMATIC OF STUDY DESIGN ............................................................................................................... 4
1
KEY ROLES......................................................................................................................................... 5
2 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....................... 5
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ................................................................ 5
2.2
RATIONALE....................................................................................................................................6
2.3 
POTENTIAL RISKS & BENEFITS ........................................................................................................ 6
2.3.1 
Known Potential Risks ............................................................................................................. 6
2.3.2
Known Potential Benefits ........................................................................................................ 7
3 
OBJECTIVES AND PURPOSE ........................................................................................................... 7
3.1 
PRIMARY OBJECTIVE ...................................................................................................................... 7
4
STUDY DESIGN AND ENDPOINTS.................................................................................................... 8
4.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................... 8 
4.2 
STUDY ENDPOINTS......................................................................................................................... 9 
4.2.1 
Primary Study Endpoints ......................................................................................................... 9
4.2.2 
Exploratory Endpoints ............................................................................................................. 9
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................................... 9
5.1 
INCLUSION CRITERIA ...................................................................................................................... 9
5.2 
EXCLUSION CRITERIA ................................................................................................................... 10
5.3 
VULNERABLE SUBJECTS............................................................................................................... 10
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION .......................................................................... 10
5.4.1 
Use of DataCore/Epic Information for Recruitment Purposes .............................................. 11
5.5 
STUDY PARTICIPATION ................................................................................................................. 11
5.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES ................................................................................ 11
5.7 
PARTICIPANT WITHDRAWAL OR TERMINATION................................................................................ 11
5.7.1 
Reasons for Withdrawal or Termination ................................................................................ 11
5.7.2 
Handling of Participant Withdrawals or Termination ............................................................. 12
5.7.3 
Premature Termination or Suspension of Study ................................................................... 12
6 
STUDY AGENT .................................................................................................................................. 12
6.1 
STUDY AGENT(S) AND CONTROL DESCRIPTION.............................................................................. 14
6.1.1
Acquisition .............................................................................................................................11
6.1.2 
Formulation, Appearance, Packaging, and Labeling ............................................................ 11
6.1.3 
Preparation ............................................................................................................................ 11
6.1.4 
Duration of Therapy ............................................................................................................... 11
7 
STUDY PROCEDURES AND SCHEDULE ....................................................................................... 12
7.1 
STUDY PROCEDURES/EVALUATIONS ............................................................................................. 14
7.1.1 
Study Specific Procedures .................................................................................................... 11
7.1.2 
Standard of Care Study Procedures ..................................................................................... 11
7.2 
LABORATORY PROCEDURES/EVALUATIONS ................................................................................... 14
7.2.1 
Other Assays or Procedures ................................................................................................. 11
7.2.2 
Specimen Preparation, Handling, and Storage ..................................................................... 11
7.2.3 
Specimen Shipment .............................................................................................................. 11
7.3 
STUDY SCHEDULE........................................................................................................................ 14
7.3.1 
Screening .............................................................................................................................. 11
7.4 
ENROLLMENT/BASELINE ............................................................................................................... 14
7.5 
VIDEO VISIT................................................................................................................................. 15
7.6 
FINAL STUDY VISIT ....................................................................................................................... 15

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7.7 
WITHDRAWAL VISIT...................................................................................................................... 15
7.8
UNSCHEDULED VISIT....................................................................................................................15
8 
ASSESSMENT OF SAFETY .................................................. ERROR! BOOKMARK NOT DEFINED.
9 
CLINICAL MONITORING ....................................................... ERROR! BOOKMARK NOT DEFINED.
10
STATISTICAL CONSIDERATIONS ..................................................................................................15
10.1
STUDY HYPOTHESES .................................................................................................................... 15
10.2
ANALYSIS DATASETS .................................................................................................................... 15
10.3
STATISTICAL METHODS ................................................................................................................15
10.4
SAMPLE SIZE............................................................................................................................... 16
10.5
MEASURES TO MINIMIZE BIAS ....................................................................................................... 16 
10.5.1
Enrollment/Randomization/Masking Procedures..............................................................16
11
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................. 17
12
QUALITY ASSURANCE AND QUALITY CONTROL ....................................................................... 17
13
ETHICS/PROTECTION OF HUMAN SUBJECTS.............................................................................17
13.1
ETHICAL STANDARD ..................................................................................................................... 17
13.2
INSTITUTIONAL REVIEW BOARD..................................................................................................... 17
13.3
INFORMED CONSENT PROCESS .................................................................................................... 17
13.3.1 
Consent/Assent and Other Informational Documents Provided to Participants ............... 17
13.3.2 
Consent Procedures and Documentation ......................................................................... 18
13.4
PARTICIPANT AND DATA CONFIDENTIALITY .................................................................................... 18
13.4.1 
Research Use of Stored Human Samples, Specimens, or Data ...................................... 19
13.5
FUTURE USE OF STORED SPECIMENS ........................................................................................... 19
14
DATA HANDLING AND RECORD KEEPING ................................................................................... 20
14.1
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .............................................................. 20
14.2
STUDY RECORDS RETENTION ....................................................................................................... 21
14.3
PROTOCOL DEVIATIONS ............................................................................................................... 21
14.4
PUBLICATION AND DATA SHARING POLICY..................................................................................... 21
15
STUDY FINANCES ............................................................................................................................ 21
15.1
FUNDING SOURCE ........................................................................................................................ 21
15.2
COSTS TO THE PARTICIPANT ......................................................................................................... 21
15.3
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................ 21
16
STUDY ADMINISTRATION ............................................................................................................... 22
16.1
STUDY LEADERSHIP .....................................................................................................................22
17
CONFLICT OF INTEREST POLICY .................................................................................................. 22
18
REFERENCES ................................................................................................................................... 22
19
ATTACHMENTS ............................................................................................................................... XX

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List of Abbreviations  
 
BMI 
Body Mass Index 
BNP
Brain Natriuretic Peptide
BP
Blood Pressure
CBRD 
Center for Biospecimen Research and Development 
CDC 
Center for Disease Control 
CRP 
C-reactive protein 
CTSI 
Clinical Translational Science Institute 
EDTA 
Ethylene diamine tetraacetic acid 
EHR 
Electronic Health Record 
EPA 
Environmental Protection Agency 
GCP 
Good clinical practices 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices  
HEPA 
High Efficiency Particulate Air 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICAM-1 
Intercellular Adhesion Molecule-1 
ICMJE
International Committee of Medical Journal Editors 
IL-6 
Interleukin-6
IRB 
Institutional Review Board 
MCIT  
Medical Center Information Technology 
NCATS 
National Center for Advancing Translational Science 
NIH 
National Institutes of Health 
NYU 
New York University 
PAC 
Portable Air Cleaner 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PHI 
Protected Health Information 
PI 
Principle Investigator 
PM 
Particulate Matter 
PM2.5
Particulate Matter <2.5 
Tumor Necrosis Factor-alpha
TP 
Treating physician 
TRB 
Translational Research Building 
VCAM-1 
Vascular Cell Adhesion Molecule
 

1 
 
Protocol Summary
Title 
Cardiometabolic Biomarker improvements associated with reduction in air 
pollution exposure via home air filtration: a pilot trial. 
Short Title 
Cleaner air for better cardiac biomarkers 
Brief Summary 
In this research, we will conduct a double-blind, sham-controlled, randomized 
trial to examine the impact on cardiometabolic biomarkers of air pollution 
exposure reduction using home portable air cleaners (PACs) in a cohort of 
current adult patients at NYU Langone Health. This study is funded by CTSI 
(NIH/NCATS UL1TR001445) with two primary aims and two 
secondary/exploratory aims. In Aim 1, we will evaluate associations with PAC 
use with a priori specified biomarker of inflammation, tumor necrosis factor 
ll determine if 4 weeks of home air filtration with PACs 
concentrations when measured before and after intervention. Blood samples 
will be collected from 44 study participants before and after 4 weeks of PAC 
use (true and sham) for biomarker concentration measurement. In Aim 2, we 
PM2.5) as a continuous variable are associated with significant reductions 
-week period. In Exploratory Aim 1, we will 
explore associations between PAC use and concentrations of 
cardiometabolic biomarkers using a targeted proteomic panel, the Olink 
Explore 384 Cardiometabolic panel, measured before and after 4 weeks of 
intervention. This will be a hypothesis-generating analysis to identify possible 
novel biomarkers and pathways that may have importance in the 
physiological responses and clinical outcomes associated with air pollution 
exposure. In Exploratory Aim 2, we will explore if biomarkers identified in 
Exploratory Aim 1 with significant reductions after 4 weeks of PAC partially 
mediate the association between reductions in PM2.5 and changes in daily 
home blood pressure (BP)  measurements. Participants will be given home 
BP monitors to transmit de-identified daily morning BP measurements to a 
secure database during the 4 week intervention period. Changes in morning 
systolic (BP) will be analyzed as the outcome of interest, with changes in 
biomarker concentrations evaluated as a mediator of the relations between 
pollution reduction and changes in BP.  
 

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Objectives 
The primary objective of this research is to examine how PACs that reduce 
air pollution exposure affect cardiometabolic biomarkers and how those may 
mediate relationships with cardiovascular risk factors such as hypertension. 
Specific Aim 1: To determine if 4 weeks of home air filtration with PACs 
compared to sham is associated with significant reductions i
concentrations when measured before and after intervention.  
 
Specific Aim 2: To determine if reductions in PM2.5 are associated with 
-week period. 
 
Exploratory Aim 1: To identify novel biomarkers of the cardiometabolic effects 
of PM2.5 exposure with PAC use with a targeted proteomic panel, the Olink 
Explore 384 Cardiometabolic panel, measured before and after 4 weeks of 
intervention. 
 
Exploratory Aim 2: To determine if novel biomarkers identified in Exploratory 
Aim 1 are mediators of the relationship between PAC use and home BP 
reductions after 4 weeks of PAC use. 
 
Methodology 
Randomized, double-blind, sham-controlled pilot study 
Endpoint 
Aim 1 primary endpoint: 
 
Aim 2 primary endpoint: Change in indoor PM2.5 concentration  
 
Exploratory Aim 1 primary endpoint: Change in concentration of 384 
circulating biomarkers associated with cardiometabolic risk  
 
Exploratory Aim 2 primary endpoint: Change in average AM systolic blood 
pressure over study period  
 
Study Duration 
4 weeks 
Participant Duration 
Maximum: 4 weeks 
Population 
We will perform a randomized, double-blind, sham-controlled trial of continuous 
(24 hours/day) bedroom PAC use in an outpatient cohort English and Spanish 
medication changes in prior 
mm Hg without antihypertensive medications, or diagnosis of hypertension in 
medical records). Per guidelines, this range is considered safe to monitor 
without changes in antihypertensive medications. Additional inclusion criteria 
require participants to measure home blood pressure twice daily, participate in 
video conference for home equipment setup, and ability to visit clinic for blood 
draws before and after the study period. Participants will be excluded if they 
are current smokers, currently have known coronary artery disease, have 
known systemic inflammatory conditions (such as rheumatoid arthritis, 
inflammatory bowel disease, cancer), or are currently taking any anti-
inflammatory medications or medications that target inflammatory cytokines. 
We aim to enroll 44 participants, randomized in a 1:1 ratio to PAC with HEPA 
filtration versus sham filtration.

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Study Sites
Participants will be consented and enrolled at NYU outpatient clinic facilities 
in Manhattan. At this visit, patients will have baseline blood drawn and will 
receive all study equipment. Participants will set up air pollution monitor and 
PAC in their homes with video chat guidance. PAC will be run continuously in 
participant bedrooms for 4 weeks. Participants will have follow-up visit to NYU 
Langone hospital clinical lab for post-intervention blood collection and 
equipment return.  
Number of participants 
To achieve 44
participants from the electronic health record (EHR) in NYU clinics. There will 
be 22 participants per arm (sham versus active filtration). 
Statistical Analysis 
For all Aims: descriptive summary statistics, such as mean and standard 
deviation (or median and inter quartile range) will be reported for continuous 
variables and counts and proportions for categorical variables. Graphical 
displays of all variables will be examined, with attention to assessing balance 
in these characteristics by intervention group, and with assessment of the 
distribution of variables, relevant to the choice of statistical tests. Statistical 
comparisons between the PAC and sham groups will be performed using a 
two-group two-sided t-test or nonparametric Wilcoxon test for continuous 
variables and Chi-square test for categorical variables. Distributions of 
biomarker concentrations will be examined and non-normally distributed 
concentrations will be log-transformed, as needed.  
 
The analysis of our primary outcome for Aim 1 will use linear mixed-effects 
models with the change in prespecified biomarker, from pre-intervention to 
post-intervention, concentrations as the dependent variable and treatment 
arm as the independent variable. While randomization should obviate the 
need for additional adjustment, models will be adjusted for age, gender and 
BMI, as these are known to be related to inflammatory biomarker 
concentrations. These models use subject-specific random intercepts to 
account for heterogeneity between subjects and will account for within subject 
correlation between biomarker observations.  
 
For Aim 2, we will also utilize similar models incorporating PM2.5 as the 
independent variable. This will be assessed as the difference between pre-
intervention baseline PM2.5 concentration and the time-weighted average 
concentration of PM2.5 from the 14-day intervention period.  
 
For Exploratory Aim 1, we will evaluate the Olink panel results using mixed-
effects models for the remaining biomarkers that were not prespecified. 
These will be the same models as for Aims 1 and 2, adjusted for age, gender, 
and BMI. For Exploratory Aim 2, we will evaluate associations of PAC use 
and PM2.5 reduction with measured AM systolic blood pressure in this clinical 
cohort. We will perform mediation analysis using biomarkers with significant 
associations in Exploratory Aim 1 as mediators of the relations between PM2.5 
reduction and change in blood pressure.  
 
 

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Schematic of Study Design
N= 22 active PAC intervention (True)
N= 22 PAC intervention (Sham)
N=300 Non-smoking adults with Hypertension and no excluding 
comorbidities, identified through EHR screening
N=44 Eligible, Interested;
Obtain informed consent; Enroll 
in Pilot 
Randomization
Participants will set up equipment: PAC, PM monitor and BP monitor
14-Day intervention: Participants will turn on PAC and run continuously for 24 
hours/day. Participants will measure AM blood pressure. 
Final Blood Draw
Baseline Blood Draw
Prior to 
Enrollment
Clinic 
Visit 1
Clinic 
Visit 2
Video 
Visit

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1
Key Roles
Principal Investigator  
Jonathan Newman, MD, MPH, Eugene Braunwald M.D. Assistant Professor of Medicine (Cardiology) 
Division of Cardiology, Department of Medicine 
Center for the Prevention of Cardiovascular Disease 
NYU School of Medicine 
TRB Ste 853, NYU School of Medicine 
227 E 30th, NY, NY 10016
212.263-9393 
Jonathan.Newman@nyulangone.org 
 
co-Investigator  
Sharine Wittkopp, MD, PhD  
Division of Cardiology, Department of Medicine 
NYU School of Medicine 
TRB Ste 817A, NYU School of Medicine 
227 E 30th, NY, NY 10016 
646-501-8212 
Sharine.Wittkopp@nyulangone.org 
 
co-Investigator 
Terry Gordon, PhD, Professor 
Department of Environmental Medicine, NYU School of Medicine 
341 East 25th St, NY, NY 10010 
646-754-9450 
Terry.Gordon@nyulangone.org 
 
co-Investigator 
Jiyuan Hu, PhD 
Assistant Professor, Division of Biostatistics 
Department of Population Health 
Assistant Director, NYU Biostatistics Resource 
180 Madison Avenue, 2nd Flr, NY, NY 10016 
6465013639 
Jiyuan.Hu@nyulangone.org 
 
co-Investigator 
Lorna Thorpe, PhD MPH, Professor 
Director of Division of Epidemiology, Vice Chair of Strategy and Planning, Department of Population 
Health, NYU School of Medicine 
650 First Avenue, room 516, New York, NY 10016 
212-263-3327 
Lorna.Thorpe@nyulangone.org 
 
 
2 Introduction, Background Information and Scientific Rationale 
2.1
Background Information and Relevant Literature 
Fine particulate matter air pollution (PM
2.5) exposure is associated with 
increased blood pressure.1, 2 Proposed mechanisms include increases in inflammation and oxidative 
stress leading to increased sympathetic tone and impaired vasomotor regulation.3, 4 We have identified 
gene expression changes in inflammatory pathways in association with increased particulate matter 

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pollution.5 
inflammatory biomarkers.6-8 Controlled human exposure studies show that exposure to air pollution 
9 in vivo and in vitro
and remodeling linked with increases in blood pressure and the development of hypertension.10 Given this 
 with fine particulate matter 
air pollution exposure.    
 
While it is clear that increases in PM2.5 exposure are associated with increases in inflammation, evidence 
is less well-established that reducing PM2.5 exposure will reduce inflammation. Natural experiments 
in Beijing during the 2008 Olympics showed that reductions in PM2.5 due to regulations for the event were 
associated with reductions in concentrations of circulating inflammatory biomarkers compared to the 
months immediately before and after.11 There are also limited studies of reducing cardiovascular risk factors 
by decreasing particulate matter exposure with the use of HEPA filtration by portable air cleaners (PACs). 
For example, in a meta-analysis of the effect of PAC use on blood pressure, our group showed a significant 
12
More recently, we also showed by meta-analysis that residential PAC use by adults is associated with 
reductions in circulating concentrations of CRP (10 studies, total N=570) and IL-6 (9 studies, total N=379).13
In these studies, active PAC use was associated with statistically significant 7% lower CRP and 13% lower 
IL-
statistical significance (5 studies, N=215). Multiple biomarkers have data supporting their associations with 
air pollution exposure. For example, recent studies have shown that PM2.5 exposure was associated with 
significant changes in Angiopoetin-1, ICAM-1 and VCAM-1,14 and increased expression of CRP, IL-6, 
-1, fibrinogen, p-selectin.6-8 PCSK9 is an important pharmacologic target that has been 
shown to increase in association with increased particulate matter exposure.15 Soluble platelet selectin (sP-
selectin) has been shown to increase with PM exposure; a small trial of 29 adults showed that sP-selectin 
decreased with PAC use versus sham.16 BNP increases were shown in human exposure trials using diesel 
exhaust, with reductions in BNP when exhaust was filtered.17 The data from these studies support 
connections with exposure and biomarker outcomes, but there are limited data from few small studies 
describing associations with PAC use. Given the important role in cardiovascular disease, and data showing 
relationships with pollutant exposure, we will primarily evaluate cha
use versus sham; and also will explore associations with Angiopoetin-1, ICAM-1, VCAM-1, PCSK9, sP-
selectin, and BNP and other panel biomarkers. There is a dearth of data on how personal interventions 
to reduce air pollution exposure affect cardiometabolic biomarkers and how those may mediate 
relationships with cardiovascular risk factors such as hypertension. To address this gap we have 
proposed a randomized, double-blind, sham-controlled pilot trial to evaluate the changes in inflammation 
over 4 weeks of PAC use.  
2.2
Rationale
Because PAC use has been associated with decreases in concentrations of circulating CRP and IL-6, we 
hypothesize the following: (1) Among adults with hypertension recruited from an outpatient clinical setting, 
4 weeks of continuous home PAC use, compared with sham PACs, will be associated with decreased 
2.5 
from PAC use wil
. 
2.3
Potential Risks & Benefits
2.3.1 Known Potential Risks 
This is a minimal risk study, with no physical risks associated with the study design. Potential minimal 
risks are as follows:  
 (1) Risk of PAC use: In our published review of the effect of personal air cleaners (PACs) on blood 
pressure control, no risks were reported.12 While it is possible that use of a PAC might disrupt sleep, it 
is unlikely. In fact, frequently PACs have been used to generate “white noise” associated with 
improved sleep latency and duration in a variety of settings.  

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(2) Risk of monitoring air pollution: There are no known risks to participants with monitoring the 
amount of air pollution exposure. At conclusion of the 3-month study, data on air pollution exposure 
will be provided to study participants. There is no risk to participants in ongoing air pollution exposure 
during this time interval. 
(3) Risk of blood collection. There are minimal risks associated with a standardized venipuncture for 
blood collection. These risks include pain, discomfort and superficial bleeding or bruising. All 
participants in the clinical cohort will provide consent for standard blood collection, in which these 
minimal risks will be described. For participants in the clinical cohort, up to <15 
1 tablespoons and 
3% of a standard blood donation) of blood will be collected at the baseline visit and 4-week visit. The 
total amount of blood collected will be <30 mL for the main study. For participants opting into 
<50 mL for the 
entire study. This presents minimal risk to study participants.  
(4) Risk of monitoring home blood pressure and ambulatory blood pressure. There are no known 
direct risks to participants associated with the use of home blood pressure monitors are ambulatory 
monitors. These devices are routinely prescribed for self-monitoring and clinician-assisted decision 
making for hypertension. There is a potential risk of increased anxiety due to self-monitoring of blood 
pressure. Study coordinators will discuss any concerns regarding home blood pressure monitoring at 
video visit with study participants and will refer any concerns on recorded blood pressure values to 
participants’ managing physician.  
(5) Risk of discomfort with staff visualizing participants’ homes during video visit for equipment setup 
(6) Loss of time related to study participation: to minimize this risk, staff will schedule video visits at 
participants’ preferred times, and coordinate 4-week intervention period to facilitate clinic visits at 
convenient times for participants.  
 
2.3.2 Known Potential Benefits 
This research will significantly advance our understanding of the relationship between PAC use and 
inflammation, and potentially with blood pressure health outcomes. Using a sham-controlled design, the 
proposed study will provide robust evidence to enhance the existing knowledge on this subject and inform 
future research questions. 
 
Though individual study participants may experience the above mentioned direct potential risks through 
their participation in this study, study participants may also benefit from the study: study participants will 
receive and keep their own personal PAC and BP monitor, these may result in lasting improvements in 
participant health via continued air filtration or enhanced awareness of their BP. Participants will also 
receive a small remuneration for each blood draw.  
 
3 Objectives and Purpose 
3.1 Primary Objective
The primary objective of this research is to examine the effectiveness of PAC use in improving 
inflammation related to cardiovascular disease. 
Specific Aim 1: To determine if 4 weeks of home air filtration with PACs compared to sham is associated 
 
Specific Aim 2: To determine if reductions in PM2.5 as a continuous variable are associated with 
-week period. 
 
Exploratory Aim 1: To explore associations between PAC use and concentrations of cardiometabolic 
biomarkers using a targeted proteomic panel, the Olink Explore 384 Cardiometabolic panel, measured 
before and after 4 weeks of intervention.  
 

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Exploratory Aim 2: To explore if changes 
partially mediate the effects of PACs on home blood pressure. 
4 Study Design and Endpoints 
4.1
Description of Study Design
In this research, we will conduct a randomized, double-blind, sham-controlled pilot trial to study the effect 
of PAC use on the concentrations of circulating biomarkers of inflammation in outpatient adults within the 
NYU Langone Health system.  
Aim 1: To determine if 4 weeks of home air filtration with PACs compared to sham is associated 
 
Data collection will begin Q2 2022 with a total of two time points 4 weeks apart, pre- and post-
intervention. The study design utilizes purposeful selection of 74 adults with stable hypertension within 
the NYU Langone heath system outpatient cohort. We will define stable hypertension as no medication 
changes in prior 30 
medications, or diagnosis of hypertension in medical records. Per guidelines, this range is considered 
safe to monitor without changes in antihypertensive medications. At the initial clinic visit, blood will be 
collected and stored for analysis. We will measure circulating concentrations of 
using the Olink 
Explore 384 Cardiometabolic panel for this a priori specified analysis; this panel will also measure the 
concentrations of other biomarkers that we will explore further in Exploratory Aims 1 and 2. The Olink 
analysis uses a Proximity Extension Assay that has been shown to have high specificity and accuracy to 
allow for assessment of changes in concentrations between repeated samples over time.18, 19  
 
We will randomize participants to receive PAC with either true or sham filtration (HEPA filter removed). 
Equipment will be shipped to participant homes or given to participant at clinical visit along with written 
instructions for setup and use. Active and sham PACs, and pollution monitors, will be positioned in the 
bedroom where each participant sleeps. We will video conference with participants for initial setup of 
equipment, though prior data suggests that written instructions along are effective in aiding participants in 
this process. We will use a commercially available portable air cleaner with a “true HEPA” filter for the true 
arm. For the sham arm, the same model will be used with HEPA filter removed, and has identical 
appearance and sound. After enrollment and baseline blood draw, Home BP will be monitored using 
commercially available device with a paired data hub that transmits BP measurements to an online 
dashboard in real time. We will monitor participant adherence to PAC use with electricity consumption 
monitors. Participants will be scheduled for a clinic visit after 4 weeks of PAC use to return data hubs, 
electricity monitors and pollution monitors to the study team, and will undergo post-treatment blood draw. 
A second blood draw will be performed and blood will be stored for analysis. Participants will receive 
reimbursement after equipment is returned and second blood draw is complete. Participants randomized 
to sham PAC arm will receive HEPA filters to install and keep.  
 
Aim 2: To determine if reductions in PM2.5 as a continuous variable are associated with significant 
-week period. For Aim 2, the design is identical to above; 
however in addition, we will collect PM2.5 data using commercially available PM sensors placed in the 
same bedroom as PAC. While it has been shown that PACs significantly lower indoor PM2.5 
concentrations, these data will allow us to examine the effect of PM as a continuous variable in addition to 
the binary variable of PAC use (active versus sham). Commercially available PM monitors will record 
indoor PM2.5 concentrations using dual (backup) sensors, which store measurements on internal SD 
cards. Commercially available PM sensors have been well validated and use laser particle counters to 
count the number of particles at varying sizes with a sampling frequency of 2 minutes. PM monitors will 
be returned and data will be retrieved from SD cards at the post-intervention blood draw visit. These data 
will be measured for the entire cohort.  
 
 

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Exploratory Aim 1: To explore associations between PAC use and concentrations of 
cardiometabolic biomarkers using a targeted proteomic panel, the Olink Explore 384 
Cardiometabolic panel, measured before and after 4 weeks of intervention. For this Aim, we will 
utilize additional data generated from the Olink panel. The Olink Explore Cardiometabolic panel is for 
research use only and will not be used toward FDA approval or diagnostic purposes. It will generate no 
clinically actionable results. The panel measures 369 protein biomarkers associated with cardiovascular 
and metabolic disease. This panel has been used to investigate cardiovascular disease treatment and 
prevention in various adult populations. 18, 19 18, 19 18,19 18, 19 The pathways represented in the 
cardiometabolic panel include angiogenesis, cell activation, cell adhesion, coagulation, complement 
activation, extracellular matrix organization, response to hypoxia, and others. We will explore associations 
between PAC use (active vs. sham) and changes in circulating concentrations of Angiopoetin-1, ICAM-1, 
VCAM-1, PCSK9, sP-selectin, and BNP and other panel biomarkers. This Exploratory Aim will require no 
additional action on the part of participants.  
 
Exploratory Aim 2: To explore if changes in 
 
partially mediate the effects of PACs on home blood pressure. For this Aim, participants will monitor 
blood pressure daily during the 4-week intervention period using commercially available BP monitor with 
a paired data hub that transmits BP measurements to an online dashboard in real time. Participants will 
receive written and verbal instructions for proper BP recording technique at the baseline visit. They will 
record two measurements in a seated position each morning and evening during the study periods. The 
outcome of interest will be the mean of two AM systolic blood pressure measures. We will perform 
mediation analysis to analyze the direct and indirect effects of changes in significant biomarkers and 
PM2.5 changes on AM systolic BP. Based on our own pilot study of the effect of PAC use on AM systolic 
BP, we anticipate up to 30% missing BP measurements. We surveyed our prior pilot cohort regarding 
reasons for missing measurements and the predominant reported reason was forgetting; participants 
noted that they would have liked daily reminders. We will offer participants the option to receive daily text 
message reminders to record BP. These have been reported to be effective in other studies of home BP 
as well.  
 
4.2 Study Endpoints 
4.2.1 Primary Study Endpoints 
-week 
intervention period calculated as:  
([
]
[
])
[
]
100% 
Because the baseline biomarker concentration for an individual is compared to post-intervention 
irrespective of range, percent change is a useful metric to compare reported results across assays.  
 
 
4.2.2 Exploratory Endpoints 
Exploratory Aim 1: The endpoints for Exploratory Aim 1 will be the % change in concentration of 
biomarkers from the Olink Explore Cardiometabolic panel over the 4-week intervention period calculated 
as:  
([
]
[
])
[
]
100% 
Exploratory Aim 2: The endpoint for Exploratory Aim 2 will be the change in AM systolic BP (mm Hg) as a 
function of the change in PM2.5
 
5 Study Enrollment and Withdrawal 
5.1
Inclusion Criteria 

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To be eligible to participate in the pilot, individuals must meet all of the following criteria: 
1. 
 
1. Participant and members of household are reported to be non-smokers (defined as no household 
members are currently known to smoke cigarettes or use other tobacco products including e-
cigarettes) 
2. Participant is to understand/speak English or Spanish 
3. Participant can understand study procedures and give informed consent 
4. Participant has stable hypertension: no medication changes in prior 30 days, systolic BP <160 
hypertension in medical records 
5. Able to measure home blood pressure twice daily 
6. Able to participate in video conference for home equipment setup 
7. Able to visit clinic for blood draws before and after the study period  
8. Do not intend to sleep anywhere outside of primary bedroom for more than 48 consecutive hours 
or a total of 7 days during the study period.  
9. Ability to lift, or access to assistance with lifting, 20 lb to set up PAC in bedroom.   
5.2
Exclusion Criteria
Any individual who meets any of the following criteria will be excluded from participation in the pilot:  
1. Participants who are unable to provide a minimum of at least one blood pressure measurement 
per day 
2. Participants with average home blood pressure monitor readings of a systolic blood pressure 
(SBP) >160 mmHg over any 10-day period during the study. This will be considered evidence of 
uncontrolled hypertension and will require study termination.  
3. Participants with known coronary artery disease 
4. Participants with known systemic inflammatory conditions (such as rheumatoid arthritis, 
inflammatory bowel disease, cancer) 
5. Participants currently taking any anti-inflammatory medications or medications that target 
inflammatory cytokines 
6. Pregnancy 
7. Participants with known or suspected Covid-19 in the prior 30 days 
8. Participants with post-covid sequelae (a.k.a “Long covid”)  
9. Participants who are already utilizing HEPA filtration (PAC or within HVAC) in bedrooms 
5.3
Vulnerable Subjects
The study does not intend to enroll children, pregnant women, prisoners, or other vulnerable populations.
5.4
Strategies for Recruitment and Retention 
To achieve 44 
from the electronic health record (EHR) in NYU clinics and plan to enroll and randomize 44 participants. 
Utilizing support from DataCore and NYU Medical Center Information Technology, we will use SlicerDicer 
and other Epic tools to review EHR for eligibility. The team will request MCIT DataCore to generate a 
report identifying potential subjects that meet criteria and have upcoming office visit appointments. The 
study team, including principal investigator, co-investigators, and research assistants, will have access to 
the Epic search results and verify eligibility of potential subjects. The search results will include PHI- such 
as medical record numbers. Patients will then be contacted by phone, email, or MyChart portal using an 
IRB approved message or script. Subjects will also be approached during office visits to introduce the 
research project and be invited to participate in the study. In addition, the Clinical and Translational 
Science Institute (CTSI) Recruitment and Retention Core at NYU will be engaged to provide expert 
consultation. 
 
Interested and eligible participants that have an upcoming clinic appointment will be met at the visit for 
consent and enrollment. If no clinic visits are upcoming, participants will be invited for a research only 

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visit. Participants will meet with a research coordinator to review eligibility and provide informed 
consent. Informed consent will include specific language regarding laboratory testing for the Olink 
biomarker panel and a separate consent subsection for participation in providing samples for future 
research. Study discussion and consenting will occur following a clinic visit in a secure private location 
in either the outpatient clinics or Clinical and Translational Research Institute of NYU Medical Center. 
Participant will be randomized to true or sham arm of the trial and baseline blood draw will occur at this 
clinic visit. Blood will be collected and stored for analysis. Participants will receive partial reimbursement 
for the initial blood draw, and the remainder of remuneration will be giving at the final blood 
draw/equipment return. 
 
Inclusion of Women and Minorities: Women will be included as study participants (approximately 64% 
of enrolled participants). Minorities will also be included as study participants. Among NYU Langone 
Health outpatients, African Americans, Hispanic/Latinx, and Asian outpatients represent 16%, 17%, and 
5%, respectively, of the potential pool of study participants. 
5.4.1 Use of DataCore/Epic Information for Recruitment Purposes 
This study will utilize Epic to identify subjects. We will work with DataCore and NYU Medical Center 
EHR in NYU clinics. We will use 
SlicerDicer and other Epic tools to review EHR for eligibility. The team will request MCIT DataCore 
generate a report identifying potential subjects that meet criteria and have upcoming office visit 
appointments. The study team, including principal investigator, co-investigators, and research assistants, 
will have access to the EPIC search results and verify eligibility of potential subjects. 
 
Any recruitment information sent by email will utilize Send Safe email.  
 
Once potential subjects have been identified, the study team will notify the treating physician (TP) that 
they have patients eligible to participate as follow:  
 
TP has been notified that the study team will contact potential subjects directly, by letter, phone, 
email, or the MyChart portal etc. 
 
Once contact is made, approved recruitment language will be used to communicate the reason they are 
being contacted and subjects will be asked if they are interested in participating in this specific study. 
Should the potential subjects agree, the study team will provide the subjects with information regarding 
the next steps for participation.  
 
If a subject requests information regarding opting out of further recruitment for all research, subjects will 
be directed to contact research-contact-optout@nyumc.org or 1-855-777-7858. 
5.5 Study Participation 
For the initial clinical visit, participant’s participation will last approximately 30 minutes for consent and 
blood draw. The video visit for equipment set up will require 15 minutes. Daily participation will consist of 
5-7 minutes for BP monitoring each morning and evening. The final clinical visit for the post-intervention 
blood draw will last approximately 10-15 minutes. 
5.6 Total Number of Participants and Sites  
This pilot study will be conducted at NYU Langone Health Main Campus. Recruitment will end when we 
have consented and enrolled 74 adults, of which we expect 90% to complete the trial.   
5.7
Participant Withdrawal or Termination
5.7.1 Reasons for Withdrawal or Termination 
This is a minimal risk study, so we do not expect participants to withdraw for a safety related issue. 
However, participants are free to withdraw from participation in the study at any time upon request. If 
patients need to sleep elsewhere than their own bedroom for any unanticipated reason during the trial, 

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they should notify the research team and study endpoints (exposures and SBP) will be excluded from 
analyses during this period. Participants that unexpectedly require sleeping 2 or more consecutive nights 
away from their home (or a total of 7 days altogether) during the study period will need to drop from the 
study and their data will not be used in analyses. They can re-enroll at a later date.  
Reasons for withdrawal may be moving from the area or simply not interested in participating further. 
5.7.2 Handling of Participant Withdrawals or Termination 
Participation is voluntary and all study participants may withdraw from the study at any time without 
penalization. Participants may request removal and destruction of their blood samples from storage for 
future research without withdrawal from the remainder of the study. Participants may request termination 
from the study separate from withdrawal from future research.  
No replacement of participants who withdraw or discontinue early will occur. Data including date and 
reason for withdrawal will be recorded.  
A participant is considered lost to follow-up after 10 attempts to contact them by phone and 10 attempts 
by Epic messaging. 
5.7.3
Premature Termination or Suspension of Study
This study may be suspended or prematurely terminated if there is sufficient reasonable cause. Written 
notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to the study principal investigators (Newman, Wittkopp). If the study is 
suspended or prematurely terminated the PIs will promptly inform the IRB and will provide the reason(s) 
for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Insufficient compliance to protocol requirements 
 
Loss of institutional political will to examine health effects of the national policy 
 
Determination that the study procedures are too invasive 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and 
satisfy the sponsor and/or IRB. 
6 Study Agent (Study drug, device, biologic, vaccine etc.) and/or 
Procedural Intervention  
This study will utilize a portable air cleaner as an intervention for the potential reduction of air pollution-
associated inflammation. This commercially available device has no significant risks. We plan to use a 
commercially available PAC with a “true HEPA” filter for the true arm. For the sham arm, the same model 
will be used with HEPA filter removed, and has identical appearance and sound. We will use a PAC 
designed to filter air in rooms up to approximately 350 ft2, with minimal noise on the lowest setting.   
6.1 Study Agent(s) and Control Description
This study will utilize a sham PAC as a control. PAC will be delivered to participants as active or sham 
PAC in blinded fashion. The study team with receive the new devices and remove filters from sham 
PACs. Filters will be stored in our research office until the participant completes the protocol, at which 
time participants will return study equipment at receive filters to keep. Filter status indicator lights on the 
PAC will be covered with black electrical tape on all devices (active and sham) to preserve blinding.  
6.1.1 Acquisition 
PACs will be ordered online and delivered to the study team research office for preparation.  

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6.1.2
Formulation, Appearance, Packaging, and Labeling
This is a commercially available product and will be delivered to participants in original packaging, which 
will have been opened to prepare and blind devices.  
6.1.3
Preparation
Commercially available PACs contain carbon filters that reduce volatile organic carbons and can reduce 
odors. Because of this, we will remove the carbon filters from all air purifiers to preserve blinding. Sham 
PACs will also have HEPA filters removed. This will be done by unblinded research staff and devices will 
be labelled with an ID number to preserve blinding of the rest of the research team.  
6.1.4
Duration of Therapy
The PACs will be run continuously (24 hours per day) in participants’ bedrooms for 4 weeks. 
7
Study Procedures and Schedule
7.1 Study Procedures/Evaluations 
7.1.1
Study Specific Procedures
History will be obtained via participant medical records and confirmed with questionnaire. Medical 
comorbidity information collected will include: history of hypertension, duration of hypertension, history of 
diabetes; history of inflammatory conditions including Crohn’s disease, ulcerative colitis, rheumatoid 
arthritis, vasculitides such as Kawasaki disease and giant cell arteritis, cancer and current status (no 
evidence of disease, ongoing treatment, cured, etc). We will also collect current prescription medications 
and assess for any planned medication changes during the study period. We will collect blood pressure, 
BMI and waist circumference at the initial visit. We will collect <15 mL of blood for evaluation of 
inflammatory biomarkers at both the initial visit and the final visit. An additional ~10 mL of blood will be 
drawn from participants opting in to storage for future research. 
7.1.2 Standard of Care Study Procedures 
Regular standard of care procedures will be performed by clinical providers at the initial clinical visit and 
data will be recorded to RedCAP for research purposes by research staff at the time of enrollment. These 
data include measurement of blood pressure, height and weight and waist circumference. Medication 
reconciliation performed for the clinical visit will be confirmed by research staff as well.  
7.2 Laboratory Procedures/Evaluations
7.2.1 Other Assays or Procedures 
We will evaluate biomarkers of inflammation using the Olink Explore 384 Cardiometabolic panel. This 
panel will be performed by Olink. The Olink analysis uses a Proximity Extension Assay that has been 
shown to have high specificity and accuracy to allow for assessment of changes in concentrations 
between repeated samples over time. 
7.2.2 Specimen Preparation, Handling, and Storage 
Blood samples will be processed for both cardiometabolic biomarker measurement and storage for future 
research. Samples for Olink will be collected into EDTA coated tubes and centrifuged within 1 hour and 
samples will be placed in 96-well PCR plate (ThermoFisher Scientific #AB0800 with MicroAmp seal 
#4306311 from ThermoFisher Scientific). Samples will be randomized within plates using random-number 
generator and stored at -80C until shipped on dry ice to Olink for analysis of biomarker concentrations. 
Olink will not receive any participant identifying information. The remainder of blood will be stored in a 
secured laboratory in the Cardiology Division Science Building Laboratories.  

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7.2.3
Specimen Shipment
Specimens will be stored at -80C until shipped on dry ice to Olink when 96-well plates are filled until all 
data is collected. After all data is collected, remaining specimens for participants who have not opted in to 
future research will be discarded by the lab.  
 
7.3
Study Schedule
7.3.1 Screening 
Screening will occur with support from DataCore/MCIT   
 
Obtain list of potential participants in NYU Langone Health System 
 
Review list of potential participants to identify those with upcoming clinical visits (during Q2-3 of 
2022) 
 
Review potential participant charts to confirm likely eligibility 
 
Message eligible participants’ providers to coordinate staff visit at clinical appointment  
 
MyChart messages will be used to contact potential research participants. 
7.4
Enrollment/Baseline 
Enrollment/Baseline Visit (Visit 1) 
 
Verify inclusion/exclusion criteria 
 
Answer questions from potential participants regarding the air monitors, PACs and BP monitors to 
verify interest in participating 
 
Obtain written consent from eligible participant  
 
Schedule study visits (video visit for setup and clinical visit 2 for second blood draw) for 
individuals who are eligible and available to participate for the full duration of the study   
 
Record participant BP, height, weight, and waist circumference if not done as part of clinical visit 
 
Collect blood for baseline biomarker measurement pre-intervention: <15 mL for all, additional ~10 
mL for participants opting into future research. 
7.5
Video Visit 
Video visit for equipment setup 
 
Conduct video visit at a mutually agreeable time to instruct participants in equipment setup 
o 
Place PAC in an acceptable location in bedroom with recommended air space 
surrounding PAC, and PAC plugged into electricity monitor  
o 
Place PM monitor in an acceptable location in bedroom with adequate space between 
PAC and PM monitor to ensure representative sample 
o 
Connect PM monitor to WiFi if available 
 
Supervise participant self-measuring BP once to ensure real-time data transmission  
 
PAC must 
 
7.6
Final Study Visit
Final Study Visit (Visit 2: 4 weeks after PAC turned on) 
 
Participants return study equipment: PM monitors, BP monitor data hubs, electricity monitors 
 
Collect blood for post-intervention biomarker measurement: <15 mL for all, additional ~10 mL 
for participants opting into future research.
 
 

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7.7
Withdrawal Visit
Subjects may withdraw from the study at any time and visit will be scheduled to return any study 
equipment that has been received (PM monitors, BP monitor data hubs, electricity monitors). No 
withdrawal visit is required for withdrawal from future research. 
7.8
Unscheduled Visit
Participants may request an unscheduled video visit to troubleshoot equipment-related issues if needed.
8 Assessment of Safety
This study involves the use of commercially available products associated with no known risks to 
consumers. The Principle Investigator and Co-Investigator, Drs. Newman and Wittkopp, will monitor data 
safety of the overall study. We will review safety events related to blood pressure monitoring and blood 
draws at weekly team meetings with biweekly participant reviews complied by study coordinators. Given 
the established safety of all commercially available equipment used in this protocol, there are no 
predefined stopping rules for the study (no superiority/futility). After data safety assessments, study team 
will be notified via email of any changes in protocol.  
 
9 Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the 
trial follows the currently approved protocol/amendment(s), and with applicable regulatory requirement(s). 
This is a single-site study; data, training, procedures, and practices will be monitored continuously 
throughout the study period by study PIs. A quality management plan will be developed if needed.  
10 Statistical Considerations 
10.1 Statistical Hypotheses 
Aim 1: 
Hypothesis: Among adults with hypertension recruited from an outpatient clinical setting, 4 weeks of 
continuous home PAC use, compared with sham PACs, will be associated with decreased concentrations 
 
 
Aim 2: 
Hypothesis: Reductions in measured PM2.5 from PAC use will be associated with decreased 
 
10.2 Analysis Datasets
These analyses will be conducted as Intention-to-Treat dataset. Per-Protocol Analysis will be explored if 
electricity monitor data indicates poor compliance with PAC usage (if electricity monitor recordings indicate 
kilowatt-hour usage that is lower than expected by 50%.   
10.3 Statistical Methods 
Aim 1 Analysis.  
Descriptive summary statistics, such as mean and standard deviation (or median and inter quartile range) 
will be reported for continuous variables and counts and proportions for categorical variables. Graphical 
displays of all variables will be examined, with attention to assessing balance in these characteristics by 
intervention group, and with assessment of the distribution of variables, relevant to the choice of statistical 
tests. Statistical comparisons between the PAC and sham groups will be performed using a two-group 
two-sided t-test or nonparametric Wilcoxon test for continuous variables and Chi-square test for 

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categorical variables. Distributions of biomarker concentrations will be examined, and non-normally 
distributed concentrations will be log-transformed, as needed.  
 
The analysis of our primary outcome will use linear mixed-effects models with the change in prespecified 
biomarker, from pre-intervention to post-intervention, concentrations as the dependent variable and 
treatment arm as the independent variable. While randomization should obviate the need for additional 
adjustment, models will be adjusted for age, gender and BMI, as these are known to be related to 
inflammatory biomarker concentrations.20, 21 These models use subject-specific random intercepts to 
account for heterogeneity between subjects and will account for within subject correlation between 
biomarker observations. The proposed model is:  
 
= 
+
(
 
) +
(
) + 
(
) +
(
) +
 
We will also utilize similar models incorporating PM2.5 as the independent variable in place of PAC arm. 
This will be assessed as the difference between pre-intervention baseline PM2.5 concentration and the 
time-weighted average concentration of PM2.5 from the 14-day intervention period. For our exploratory 
aim we will evaluate the Olink panel results using mixed-effects models for the remaining biomarkers that 
were not prespecified. Additionally, we will explore associations of PAC use with measured blood 
pressure in this clinical cohort that likely differs from our current pilot cohort recruited from a community 
setting.  Because this pilot will integrate with our larger R01 trial, for which blood pressure is the primary 
outcome of interest, we will incorporate this biomarker data into that trial for a secondary exploratory 
analysis of biomarkers as mediators in the association between PAC use and blood pressure reductions. 
 
In our exploratory analysis, there will be multiple testing bias due to utilizing a panel of 369 
possible biomarker outcomes. With this size pilot cohort, it will be unlikely to achieve statistical 
significance if strict adjustments for multiple testing are undertaken. However, we will use the Holm 
procedure to evaluate for significance. Overall, these exploratory analyses will be hypothesis-generating 
and can help inform the design and sample size of future cohorts. 
10.4 Sample Size  
Power Analysis: While we do not expect substantial participant dropout over this short trial, our power 
analyses include adjustment for up to 10% dropout in each arm. Based on our meta-analysis of 
biomarkers22, we estimate a 10% change in concentration of biomarkers with PAC use versus sham. 13 13 
13 13 Using a basic multiple regression model incorporating age, BMI, and gender, along with our exposure 
(active PAC vs sham), we will have greater than 80% power to reject the null hypothesis of zero effect size 
at the significance level (alpha) of 0.05, with a sample size of 66. As such, our enrollment goal of 44 
participants, limited by budgetary contraints, may provide sufficient power to detect significant changes in 
biomarker concentrations. However, in the event that we are not able to reach statistical significance with 
the changes we detect, these results will still be informative for developing future studies. We will include 
baseline-only data for participants who do not complete the protocol.  
10.5 Measures to Minimize Bias
10.5.1 Enrollment/Randomization/Masking Procedures 
We will block randomize participants for a net 1:1 allocation to active- versus sham-PAC arms. We will 
have one unblinded PI and one unblinded research coordinator; the remainder of the research staff will 
be blinded to each participant’s treatment arm until the final visit (at which time, those in the sham PAC 
arm will receive HEPA filters). The allocation sequence file will be securely stored in an internal NYU 
OneDrive in a password protected file to which only the unblinded PI and unblinded research coordinator 
will have access.  
PAC devices will be modified by unblinded research coordinator and/or unblinded PI; all PACs will have 
indicator lights covered, sham-PACs will have HEPA filters removed. PACs will be assigned a tracking ID 
number that will be printed on PACs, and PAC boxes. Blinded staff will only know the PAC ID number 
assigned to a participant but not the randomization of the device.  

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Unblinded research coordinator and PI will assess enrollment goals.   
Blood samples will be assigned to PCR plate locations using a random number generator. 
Data from PM monitors will be downloaded after participant has completed protocol. Research team 
members performing data processing of PM measurements will be blinded to PAC status of participant.  
11 Source Documents and Access to Source Data/Documents 
Source data include all study-related forms, including: completed surveys, checklists, interview 
transcripts, consent forms, air monitor documentation, and study personnel tracking sheets.   
Access to study records will be limited to IRB-approved members of the study team. The investigator will 
permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government 
regulatory bodies, and University compliance and quality assurance groups of all study related 
documents. 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
12 Quality Assurance and Quality Control 
QC procedures will be implemented beginning with the data entry system and data QC checks that will be 
run on the database will be generated. Any missing data or data anomalies will be communicated to the 
site(s) for clarification/resolution. 
Following written SOPs, the monitors will verify that the clinical trial is conducted, and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory 
requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 
13 Ethics/Protection of Human Subjects 
13.1 Ethical Standard
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46. 
13.2 Institutional Review Board
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether previously consented participants 
need to be re-consented. 
13.3 Informed Consent Process
13.3.1 Consent/Assent and Other Informational Documents Provided to Participants 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting intervention. Forms 

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contain all regulatory consent text/content. The following consent materials are submitted with this 
protocol: 
 
1. Consent for participation (including PAC use, pollution monitoring, BP monitoring and blood 
draws, and optional consent for blood collection/storage for future use)  
13.3.2 Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants and their families. Consent forms will be IRB-
approved and the participant will be asked to read and review the document. The investigator will explain 
the research study to the participant and answer any questions that may arise. All participants will receive 
a verbal explanation in terms suited to their comprehension of the purposes, procedures, and potential 
risks of the study and of their rights as research participants. Participants will have the opportunity to 
carefully review the written consent form and ask questions prior to signing. The participants should have 
the opportunity to discuss the study with their surrogates or think about it prior to agreeing to participate. 
The participant will sign the informed consent document prior to any procedures being done specifically 
for the study. The participants may withdraw consent at any time throughout the course of the trial. A 
copy of the signed informed consent document will be given to the participants for their records. The 
rights and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
A copy of the signed informed consent document will be stored in the subject’s research record. The 
consent process, including the name of the individual obtaining consent, will be thoroughly documented in 
the subject’s research record. Any alteration to the standard consent process (e.g. use of a translator, 
consent from a legally authorized representative, consent document presented orally, etc.) and the 
justification for such alteration will likewise be documented.  
13.4 Participant and Data Confidentiality
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
 What protected health information (PHI) will be collected from subjects in this study 
 Who will have access to that information and why 
 Who will use or disclose that information  
 The rights of a research subject to revoke their authorization for use of their PHI.  
 
If a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the ability to 
use all information collected prior to the revocation of subject authorization.  For subjects that have 
revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect at 
least vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
 
This personal information will be retained, and all participants who enroll in the study will receive a unique 
study ID. Subsequent information will utilize this study ID instead of the participant’s name, and the key 
linking the study IDs and personal information will be retained on the secured server, accessible only to 
the study PIs, data manager, and field staff communicating with those participants. 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to the clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No information 
concerning the study, or the data will be released to any unauthorized third party without prior written 
approval of the sponsor. 
 

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The study monitor, other authorized representatives of the sponsor, or representatives of the IRB may 
inspect all documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s 
contact or identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems used by 
clinical sites and by NYU Langone Medical Center research staff will be secured and password protected. 
At the end of the study, all study databases will be de-identified and archived at the NYU Langone 
Medical Center. 
 
13.4.1 Research Use of Stored Human Samples, Specimens, or Data 
Participants will have blood drawn, some of which will be used for biomarker measurement. The 
remaining portion of blood samples from participants will be stored in a secured laboratory in the 
Cardiology Division Science Building Laboratories. 
 Intended Use: Samples and data collected under this protocol may be used to study additional 
pathways related to blood pressure and/or air pollution exposure.  
 Storage: Access to stored samples will be limited to the study team only. Samples and data will be 
stored using codes assigned by the investigators. Data will be kept in password-protected 
computers. Only investigators will have access to the samples and data. 
 Tracking: Data will be tracked using internal tracking datasheets stored in password protected file 
on NYU internal OneDrive. Study PIs will have password.  
o 
Disposition at the completion of the study: All samples will be stored in in a secured 
laboratory in the Cardiology Division Science Building Laboratories. Study participants 
who request destruction of samples will be notified of compliance with such request and 
all supporting details will be maintained for tracking.  
13.5 Future Use of Stored Specimens
We will request participation in storage of blood samples collected for continued analyses of this study, 
for studies as new scientific discoveries are made, to allow for retesting if necessary and for future 
research related to cardiovascular risk. We will give subjects who participate in the study the option to opt 
into storage for future research as there are many unknowns about cardiovascular risk in patients with air 
pollution exposure, and being able to maintain the samples will allow us to build upon the knowledge we 
gain from this initial study. Patients will be informed of this during the consent process. Future research 
will not stray from the purpose of the original application, and optional participation in the storage of 
samples for future research will remain separated from the primary protocol. For optional future research, 
 
 
Blood samples for future analysis will be assigned a unique code number and stored in a dedicated 
freezer storage by the PI without any identifying information other than a code number. The unique code 
number will not be based on any information that could be used to identify the subject (for example, social 
security number, initials, or birth date). We will use freezer-safe labels and store samples in freezers with 
emergency backup power. The master list linking names to code numbers will be kept in a locked file 
cabinet, separate from all research information, under double lock and key. Only the NYU PI will have 
access to the linking key between subject ID and subject identity. All confidential data will be stored with a 
unique code as an identifier and will be protected by a double electronic lock. All physical data will be kept 
under double physical lock. Only the PI and Co-Is will have access to the banked samples. 

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Samples will be stored for no more than 20 years. The specimens for future analysis may be analyzed 
upon completion of the study for RNA, microRNA, and DNA. The blood specimens may be analyzed upon 
completion of the study for RNA, microRNA, and DNA profiling. This may include detailed molecular 
profile study, describing genetic arrays of patterns associated with cardiometabolic risk. We will not be 
performing whole genome sequencing, only genetic testing as it relates to cardiovascular risk described 
above. Because there is no potential for clinically actionable genetic incidental findings because of this 
testing, genetic information will not be disclosed to anyone, including the participants and their physicians. 
Samples could also be used for testing other potential biomarkers in patient plasma and/or serum related 
to diabetes and CVD that may occur with exception of those which are already part of the protocol. 
Results of the future research will not be shared with the subjects or their physician, and will not become 
part of the participants’ medical records.  
 
In the future, other institutions, or future collaborators at or outside of NYU Medical Center may want to 
study a portion of these samples. If that happens, samples would be sent to other places so other people 
interested in studying these diseases and conditions could do that. The samples sent to other 
researchers will be de-identified without PHI. Samples will be stored for no more than 20 years following 
completion of the study. At the end of the 20-year period, all samples will be destroyed. 
 
Subjects can request for withdrawal of samples at any time by contacting PI Dr. Newman in writing. His 
mailing address is NYU Translational Research Building, 227 E. 30th St, Suite 853, NEW YORK 10016. 
Withdrawing Authorization only affects uses and sharing of information after written request has been 
received, and subject may not withdraw his/her Authorization for uses or disclosures that have previously 
been made or must continue to complete analyses or report data from the research. 
 
14 Data Handling and Record Keeping 
14.1 Data Collection and Management Responsibilities
Data collection is the responsibility of the study staff at the site under the supervision of the site PIs. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 
documents should be consistent with the source documents or the discrepancies should be explained 
and captured in a progress note and maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into RedCAP. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
 
For questionnaires confirming inclusion/exclusion criteria, data will be entered on an iPad with a data 
plan, provided by NYUMC, and stored using REDCap. No identifiable information will be entered or will 
be able to be accessed by field staff. In addition, iPads with be programmed to limit access to only 
REDCap prior to data collection. Back-up paper forms will be used in the event of technology issues. 
After data cleaning and quality assurance procedures are completed, pertinent sets of data will be 
converted into SAS format for statistical analyses. Only authorized research staff will have access to the 
files. 

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14.2 Study Records Retention
Study documents will be retained for at least 5 years after final reporting/publication. No records will be 
destroyed without the written consent of the sponsor. 
14.3 Protocol Deviations
All deviations in protocol will be addressed in study source documents, reported to the NYULMC IRB.
14.4 Publication and Data Sharing Policy
This study will comply with the NIH Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical 
trials registration policy as a condition for publication. The ICMJE defines a clinical trial as any research 
project that prospectively assigns human subjects to intervention or concurrent comparison or control 
groups to study the cause-and-effect relationship between a medical intervention and a health outcome. 
Medical interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care 
changes, and the like. Health outcomes include any biomedical or health-related measures obtained in 
patients or participants, including pharmacokinetic measures and adverse events. The ICMJE policy, and 
the Section 801 of the Food and Drug Administration Amendments Act of 2007, requires that all clinical 
trials be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the National 
Library of Medicine. Other biomedical journals are considering adopting similar policies. For interventional 
clinical trials performed under NIH IC grants and cooperative agreements, it is the grantee’s responsibility 
to register the trial in an acceptable registry, so the research results may be considered for publication in 
ICMJE member journals. The ICMJE does not review specific studies to determine whether registration is 
necessary; instead, the committee recommends that researchers who have questions about the need to 
register err on the side of registration or consult the editorial office of the journal in which they wish to 
publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal investigator) register 
and report results of certain "applicable clinical trials": 
 
 Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I investigations 
of a product subject to FDA regulation; 
 Trials of Devices: Controlled trials with health outcomes of a product subject to FDA regulation 
(other than small feasibility studies) and pediatric postmarket surveillance studies. 
 NIH grantees must take specific steps to ensure compliance with NIH implementation of FDAAA. 
 
15 Study Finances 
15.1 Funding Source 
This study is financed through a pilot grant from the NYU CTSI under grant number NIH/NCATS 
UL1TR001445 
15.2 Costs to the Participant 
No costs will incur as a result of participating in the study. 
15.3 Participant Reimbursements or Payments
Individual participants will be remunerated for blood draws as follows: Participants will receive $25 after 
the baseline blood draw. Upon completing the study, participants will be allowed to keep the air cleaner, 

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and will be given a true filter if assigned to the “sham” group; participants will also keep the blood 
pressure cuff. Participants will receive $75 after all other equipment is returned (electricity monitor, air 
pollution monitor and blood pressure data hub) and the final blood draw is completed.  
16 Study Administration
16.1 Study Leadership
This protocol describes a co-PI collaborative pilot project bringing together a well-established investigator 
and a post-doctoral research fellow with complementary skills and expertise, a shared commitment to the 
objectives of this study and a history of collaboration.  
 
The PI of the study is Dr. Jonathan Newman, the Eugene Braunwald M.D. Assistant Professor of 
Cardiology (Medicine). Dr. Newman has a Master’s in Public Health in clinical research methodology and
has substantial experience leading clinical trials, including the ISCHEMIA trial, the TACT2 trial, NYU 
(REPAIR). Dr. Newman has led recent investigations into the environmental effects of air pollution 
exposure, including a recent NIH/CDC/EPA white paper defining strategies to reduce the 
cardiopulmonary impact of particulate air pollution. The Co-PI of the study is Dr. Sharine Wittkopp, MD, 
PhD, Cardiology research fellow. Dr. Wittkopp has a Master’s in Biomedical Science on mitochondrial 
biochemistry and oxidative stress, with experience studying inflammation and air pollution exposure in 
human subjects cohorts in the CHAPS study of the Los Angeles air basin.   
Drs. Newman and Wittkopp recently collaborated with Co-investigators Drs. Thorpe and Gordon on a 
feasibility study on the use of PACs and home BP monitoring in a community cohort. The team’s work on 
this recent feasibility study has informed the design of the current pilot study presented herein.  
17 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence is critical. Therefore any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this study will be disclosed and managed. Furthermore, persons who have a perceived conflict of 
interest will be required to have such conflicts managed in a way that is appropriate to their participation 
in the study. The study leadership has established policies and procedures for all study group members 
to disclose all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest.  
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Committee with a Committee-sanctioned conflict management plan that has 
been reviewed and approved by the study sponsor prior to participation in this study. All NYULMC 
investigators will follow the applicable conflict of interest policies. 
18 References 
1. 
Yang BY, Qian Z, Howard SW, et al. Global association between ambient air pollution and blood 
pressure: A systematic review and meta-analysis. Environ Pollut. Apr 2018;235:576-588. 
doi:10.1016/j.envpol.2018.01.001 
2. 
Liang R, Zhang B, Zhao X, Ruan Y, Lian H, Fan Z. Effect of exposure to PM2.5 on blood 
pressure: a systematic review and meta-analysis. J Hypertens. Nov 2014;32(11):2130-40; discussion 
2141. doi:10.1097/HJH.0000000000000342 
3. 
Brook RD, Brook JR, Urch B, Vincent R, Rajagopalan S, Silverman F. Inhalation of fine 
particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation. 
Apr 2 2002;105(13):1534-6. doi:10.1161/01.cir.0000013838.94747.64 

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4. 
Brook RD, Urch B, Dvonch JT, et al. Insights into the mechanisms and mediators of the effects of 
air pollution exposure on blood pressure and vascular function in healthy humans. Hypertension. Sep 
2009;54(3):659-67. doi:10.1161/HYPERTENSIONAHA.109.130237 
5. 
Wittkopp S, Staimer N, Tjoa T, et al. Nrf2-related gene expression and exposure to traffic-related 
air pollution in elderly subjects with cardiovascular disease: An exploratory panel study. J Expo Sci 
Environ Epidemiol. Mar-Apr 2016;26(2):141-9. doi:10.1038/jes.2014.84 
6. 
Pope CA, 3rd, Hansen ML, Long RW, et al. Ambient particulate air pollution, heart rate variability, 
and blood markers of inflammation in a panel of elderly subjects. Environ Health Perspect. Mar 
2004;112(3):339-45. doi:10.1289/ehp.6588 
7. 
Calderon-Garciduenas L, Villarreal-Calderon R, Valencia-Salazar G, et al. Systemic inflammation, 
endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants. Inhal 
Toxicol. Mar 2008;20(5):499-506. doi:10.1080/08958370701864797 
8. 
Liu C, Cai J, Qiao L, et al. The Acute Effects of Fine Particulate Matter Constituents on Blood 
Inflammation and Coagulation. Environ Sci Technol. Jul 18 2017;51(14):8128-8137. 
doi:10.1021/acs.est.7b00312 
9. 
Tornqvist H, Mills NL, Gonzalez M, et al. Persistent endothelial dysfunction in humans after diesel 
exhaust inhalation. Am J Respir Crit Care Med. Aug 15 2007;176(4):395-400. doi:10.1164/rccm.200606-
872OC 
10. 
Lamb FS, Choi H, Miller MR, Stark RJ. TNFalpha and Reactive Oxygen Signaling in Vascular 
Smooth Muscle Cells in Hypertension and Atherosclerosis. Am J Hypertens. Oct 21 2020;33(10):902-913. 
doi:10.1093/ajh/hpaa089 
11. 
Rich DQ, Kipen HM, Huang W, et al. Association between changes in air pollution levels during 
the Beijing Olympics and biomarkers of inflammation and thrombosis in healthy young adults. JAMA. May 
16 2012;307(19):2068-78. doi:10.1001/jama.2012.3488 
12. 
Walzer D, Gordon T, Thorpe L, et al. Effects of Home Particulate Air Filtration on Blood Pressure: 
A Systematic Review. Hypertension. Jul 2020;76(1):44-50. doi:10.1161/HYPERTENSIONAHA.119.14456 
13. 
Wittkopp S, Walzer D, Thorpe L, et al. Meta-Analysis of Residental Portable Air Cleaner Use and 
Circulating Inflammatory Biomarkers. Abstract presented at: AHA Scientific Sessions; 11/13/2021 2021; 
Boston, MA. Session Exercise, Diet and Lifestyle Influences on CVD.  
14. 
Riggs DW, Zafar N, Krishnasamy S, et al. Exposure to airborne fine particulate matter is 
associated with impaired endothelial function and biomarkers of oxidative stress and inflammation. 
Environ Res. Jan 2020;180:108890. doi:10.1016/j.envres.2019.108890 
15. 
Macchi C, Ferri N, Favero C, et al. Long-term exposure to air pollution raises circulating levels of 
proprotein convertase subtilisin/kexin type 9 in obese individuals. Eur J Prev Cardiol. Apr 2019;26(6):578-
588. doi:10.1177/2047487318815320 
16. 
Zhao Y, Xue L, Chen Q, et al. Cardiorespiratory responses to fine particles during ambient PM2.5 
pollution waves: Findings from a randomized crossover trial in young healthy adults. Environ Int. Jun 
2020;139:105590. doi:10.1016/j.envint.2020.105590 
17. 
Vieira JL, Guimaraes GV, de Andre PA, Cruz FD, Saldiva PH, Bocchi EA. Respiratory Filter 
Reduces the Cardiovascular Effects Associated With Diesel Exhaust Exposure: A Randomized, 
Prospective, Double-Blind, Controlled Study of Heart Failure: The FILTER-HF Trial. JACC Heart Fail. Jan 
2016;4(1):55-64. doi:10.1016/j.jchf.2015.07.018 
18. 
deFilippi C, Lo J, Christenson R, et al. Novel mediators of statin effects on plaque in HIV: a 
proteomics approach. AIDS. Apr 24 2018;32(7):867-876. doi:10.1097/QAD.0000000000001762 
19. 
Alonso A, Chen LY, Rudser KD, Norby FL, Rooney MR, Lutsey PL. Effect of Magnesium 
Supplementation on Circulating Biomarkers of Cardiovascular Disease. Nutrients. Jun 6 
2020;12(6)doi:10.3390/nu12061697 
20. 
Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J. Systemic inflammation, adipose tissue tumor 
necrosis factor, and leptin expression. Obes Res. Apr 2003;11(4):525-31. doi:10.1038/oby.2003.74 
21. 
Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to 
age-associated diseases. J Gerontol A Biol Sci Med Sci. Jun 2014;69 Suppl 1:S4-9. 
doi:10.1093/gerona/glu057 
22. 
Wittkopp S, Walzer D, Thorpe L, et al. Portable Air Cleaner Use and Biomarkers of Inflammation: 
A Systematic Review and Meta-Analysis. American Heart Journal. in review 2022; 
 
 

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19 Attachments
These documents are relevant to the protocol, but they are not considered part of the protocol. They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendments. 
 
 
Attachment A: Comorbidity and medication questionnaire 
 
Attachment B: Instructions for BP recording 
 
Attachment C: Instructions for Equipment Setup 
 
 

 
26 
 
Attachment A : Air Filter Pilot Study Questionnaire 
Pre-Intervention Questionnaire: 
 
Height and Weight Measurements (self-reported measures): 
Enter the respondent’s weight (lbs.) here. Weight to the nearest 0.2 lb.: XXX 
Enter the respondent’s height (inches) here. Height to the nearest 0.5 in.: XXX 
1.
How long have you had high blood pressure?  
a. 0-2 years 
b. 2-5 years 
c. 5-10 years 
d. >10 years 
e. Don’t know/refused 
 
2. How long as it been since you last had your blood pressure taken by a doctor or other health 
professional? Was it… 
a. Within the past month? 
b. 1-6 months ago?  
c. 6-12 months ago?  
d. Over 1 year ago?  
e. Don’t know/refused 
 
3. Have you ever been told to take prescription medicine because of high blood pressure? 
a. Yes 
b. No 
c. Don’t know/refused 
 
4. Have you been told to take or continue taking prescription medicine because of high blood 
pressure/hypertension in the past 12 months? 
a. Yes  
b. No 
c. Don’t know/refused 
 
5. [If yes to Q3/Q4]: Are you now taking prescription medicine? 
a. Yes 
b. No 
c. Don’t know/refused 
 
6. Have you ever been told you have an inflammatory disorder such as rheumatoid arthritis, 
inflammatory bowel disease, cancer? 
a. Yes 
b. No 
c. Don’t know/refused 
 
7. If you take medications to lower your blood pressure, have any of these medications changed in the 
last month? 
a. Yes 
b. No 
c. Don’t know/refused 
 
8. In the past month, how often have you checked your blood pressure at home? 
a. Never 
b. Less than weekly 
c. Weekly 

 
 
 
27 
 
d. More than weekly 
 
9. Have you ever had, or been told you had, a heart attack? 
a. Yes 
b. No 
c. Don’t know/refused 
 
10. Have you ever had, or been told you had, a stroke? 
a. Yes 
b. No 
c. Don’t know/refused 
 
11. How concerned are you about the effects of air pollution on your health? 
a. Extremely concerned 
b. Very concerned 
c. Somewhat concerned 
d. Mildly concerned 
e. Not concerned 
 
(On Day 0, trained field staff will enter participant’s home, and place field equipment inside their home, providing 
detailed demonstration on how to measure blood pressure. Trained field staff will also manually record 
participant’s height and weight (lbs.) using a digital scale)  
 
Post-Intervention Questionnaire:  
Now that you have an air filter, I have some questions for you:  
1. How much time each day did you spend checking your BP for the study?  
a. 2-5 minutes 
b. 5-10 minutes 
c. 10-15 minutes 
 
2. On average, how much time did you run the filter each day?  
a. I kept it on for 24 hours a day 
b. I ran it for most of the day (18-24 hours) 
c. I ran it for more than half of the day (12-18 hours) 
d. I ran it for part of the day (6-12 hours) 
e. I ran it for a few hours (0-6 hours) 
 
3. How much did you notice noise from the filter? 
a. Extremely noisy 
b. Very noisy 
c. Somewhat noisy 
d. Minimal noise 
e. I didn’t hear it at all 
 
4. How likely is it that you will buy replacement filters in the future? [Likert scale] 
a. Very likely 
b. Somewhat likely 
c. Not very likely 
d. Not likely at all 
 
5. [If less than very likely….] What are some of the reasons why you might not buy replacement air 
filters (check all that apply)? 
a. Too costly 
b. Too inconvenient 
c. Don't know where to buy them 
d. Too noisy 

 
 
 
28 
 
e. Not sure they are effective 
f. 
Other: ____________ 
 
6. During the study period did you have a change in your blood pressure medication?  
a. Yes 
b. No 
c. Don’t know/refused 
 
7. How concerned are you about the effects of air pollution on your health?  
a. Very concerned 
b. Somewhat concerned 
c. Not very concerned 
d. Not concerned at all 
 
8. Would you be interested in continuing to participant in this study and check your BP twice daily for 3 
months?  
a. Yes 
b. No 
c. Don’t know/refused 
 
9. If this study continued for 6 months, would you be interested in continuing to participate and check 
your BP daily? 
a. Yes 
b. No 
c. Don’t know/refused 
 
 
 
 

 
 
 
29 
 
Attachment B: Participant Instructions for Measuring Blood Pressure
 
Checking your blood pressure at home is an important part of this study and helps you know when 
your blood pressure is high.  Here is a quick guide on how to check your blood pressure at home.  
 
1. Please take two blood pressure readings 1 minute apart in the morning and two readings 1 minute apart 
in the evening for every day for 2 weeks (for a total of 4 per day, and 64 readings over the 2 weeks).  
 
2. Make sure the air plug of the blood pressure cuff is placed tight into the machine before taking your blood 
pressure. 
 
3. Remove tight-fitting clothing from the left upper arm.  
 
4. Sit in a chair with your feet flat on the floor. Put your left arm on a table or armrest so the cuff is about the 
same height as your heart. Sit for at least 5 minutes prior to taking your first blood pressure reading. 
 
5. Place the blood pressure cuff on the left upper arm so that the white stripe is on the inside of the arm. 
Place the bottom of the blood pressure cuff about 1/2 inch above the elbow. Make sure that the air tube is 
pointed downward – it should run down the inside of your forearm and be in line with your middle finger 
(with the palm up). See next page for a diagram.  
 
6. Make sure that you are comfortable, and your left arm is not tense. Keep your left hand open.  
 
7. Press the Start/Stop button once with your other hand to take a measurement. You should feel the blood 
pressure cuff tighten when the blood pressure is being taken. Do not move or talk, and stay relaxed. Wait 
until the cuff deflates and your blood pressure is showing on the display. Once that has occurred, remove 
the blood pressure cuff.  
 
You can use this table to keep track of whether or not you have measured your blood pressure at these 
times (Example: place 2X’s under Day 1 AM after you’ve collected your two morning readings) 
 

 
 
 
30 
 
 
Week 1 (date range:     /    /      to     /    /      )
 
 Day 1 
Day 2
Day 3 
Day 4
Day 5 
Day 6 
Day 7 
AM
PM
 
 
 
 
 
 
Week 2 (date range:   /  /    to     /  /    )
 
Day 8
Day 9
Day 10
Day 11 
Day 12 
Day 13 
Day 14 
AM
PM
 
 
 
 
 
 
Week 3 (date range:   /  /    to     /  /    )
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
AM
 
 
 
 
 
 
PM
 
 
 
 
 
 
Week 4 (date range:   /  /    to     /  /    )
 
Day 8
Day 9
Day 10
Day 11 
Day 12 
Day 13 
Day 14 
AM
 
 
 
 
 
 
PM
 
 
 
 
 
 
 
 
 

31
HOW TO APPLY CUFF
Put your arm through the cuff loop.
Insert your arm as indicated by the 
marker.
Position the arm correctly.
1/2”
Close the fabric (Velcro) fastener FIRMLY.
1
2
3
4
a) The air tube should run down the inside of your forearm 
and be in line with your middle finger.
b) The bottom of the cuff should be 
approximately 1/2” above your 
elbow.
c) Make sure that the blue 
stripe is on the inside of the 
arm and aligned with the 
middle finger (with the palm 
up).

32
Attachment C: Participant Instructions for Equipment Setup