Particulate Matter, Blood Pressure, and the Sympathetic Nervous System

The investigators will enroll 50 healthy nonsmoking adults (20-65 years old) into a protocol
involving 2 separate 5 day long "study blocks". Each block will consist of 5 separate 2
hour-long "exposure periods" conducted 5 days in a row (Monday - Friday; start: 8 am to end:
10 am) (Table 2: Study flow chart). Investigators will enroll 2 patients to undergo the trial
study blocks simultaneously (one subject starting block 1 in the active intervention by
wearing the facemask and the other wearing no facemask to begin block 1). Day 1 (Monday) of
each study block will occur in a non-polluted clean indoor setting (Research Exam Room, Suite
A 1310; Lobby A, Dominos Farms). All subsequent exposure periods (days 2-5, Tuesday through
Friday) of each study block will all take place at the same designated "exposure site", an
Ann Arbor Transportation Association (AATA) parking lot area nearby several busy roadways in
Ann Arbor MI. To complete the entire study, each subject will perform 2 separate study
blocks. Minimal total study duration is 2 weeks (washout period = 2 days over weekend) to a
maximal period of 6 weeks (wash out period = 5 weeks). During one block, subjects will wear
an N-95 respirator facemask (active intervention) during all exposure periods (days 1-5, even
during day 1 indoor exposures). Subjects will remove the mask at the end of the study day
after all testing is completed. Active versus control intervention ordering will be performed
in a randomized single-blind cross-over order. During the other block subjects will wear no
facemask (control) during exposure periods. While subjects will necessarily be aware of the
intervention type, the study investigators responsible for evaluating the results will be
blinded to the intervention type during all data analyses (i.e., single blind trial).
Throughout all exposure periods, subjects will wear ambulatory BP monitors (ABPM) and ECG
Holter monitors to determine brachial BP/aortic hemodynamics measured every 10 minutes and
heart rate variability (HRV) metrics measured continuously and averaged into 10 minute epochs
corresponding to same time periods as the BP levels, respectively. Air pollution exposures
(PM2.5, black carbon (BC), and ultrafine particle (UFP) count), ambient temperature levels,
and noise intensity will be measured continuously at the near-roadway exposure site during
all exposure periods (Days 2-5). All environmental exposure metrics will also be averaged
into 10 minute epochs during the exposure periods corresponding to the health outcome times.
Following completion of exposure periods on day 4 (Thursday), subjects will have endothelial
function measured by endoPAT (RHI) immediately post-exposures at the near-roadway site, after
lying supine resting 5 minutes on a portable support. Patients will wear facemask throughout
RHI testing when in the active intervention block. On the final day 5 of each study block,
all subjects will have blood drawn. A sub-group (n=20) of subjects (enrolled on a first-come
basis) will have SNS activity measured by MSNA. After blood draws on each study visit day
subjects will remove the facemasks and can thereafter carry on with their routine daily
activities. However, subjects will be asked to not deviate from their usual lifestyle during
each study block. Subjects will be specifically directed to not significantly change their
lifestyle (e.g., diet, sleep patterns) and/or any routine activity (e.g., exercise regimen,
work, commutes, travel) throughout each study block.

Inclusion Criteria:

- 1. Age 18-65 years old. People older than 65 years are excluded as the impact of PM2.5
on their BP is not known from our prior studies (which included younger individuals)
and they have age-related increases in BP and SNS activity which may alter their
associations with PM2.5 exposures and thus produce too heterogeneous a population to
evaluate the linkages between PM2.5 and health outcomes.

- 2. Self-reported nonsmoker (100% abstinence for at least 1 year) living in non-smoking
households (no one living in the household that smokes indoors) and no known routine
exposures to air pollutants by known point sources at home, travel or occupationally
(e.g., fumes, dust, secondhand smoke). Smoking and other exposures may alter any
effect that ambient PM2.5 has on the health outcomes.

- 3. Able to understand the informed consent, legally provide informed consent, and able
to participate for the entire duration of the study.

Exclusion Criteria:

- 1. Any facial hair (beard or mustache) that does not allow for proper fitting and air
tight seal of the N95 facemask during the study that would compromise the ability of
the mask to prevent exposures.

- 2. Any prior cardiovascular diseases (coronary artery disease (CAD), congestive heart
failure (CHF), stroke, peripheral arterial disease (PAD), aneurysms, any
revascularization)*

- 3. Prior diagnosis of hypertension, diabetes, sleep apnea*

- 4. Prior diagnosis of chronic lung diseases (asthma, chronic obstructive lung disease
(COPD))*

- 5. Prior diagnosis of neurological disorders (Parkinson's disease, autonomic failure,
peripheral neuropathy, seizure disorder) or other conditions at discretion of
investigators*

- 6. Prior diagnosis of chronic kidney disease, any type of dialysis*

- 7. Active or history of any known cancer*

- 8. History of HIV*

- 9. Being treated for any infection with antibiotics within past month*

- 10. Mental health issue(s) including anxiety disorders, mood disorders, schizophrenia,
or other conditions at discretion of investigators*

- 11. Prior diagnosis of any other chronic or acute medical condition(s) at discretion
of investigators that may lead to alteration of baseline SNS activity, BP, or insulin
sensitivity and thereby potentially impact the association of PM2.5 with study
outcomes.

- 12. Medications for high BP or that alter BP. Any medications for cholesterol (e.g.,
statins). Any medications that alter blood glucose (e.g., diabetes medication)*.

- 13. Any medications or over the counter pills that may alter the association between
ambient PM2.5 and the health outcomes of BP, SNS activity and insulin sensitivity by
discretion of investigators*. No over the counter pills taken on routine basis (>2
times per week as standing dosage) including: anti-oxidants (vitamin C, E), NSAIDS,
fish oil supplements, folic acid supplements, multivitamins, or other over the counter
pills, herbs, or complimentary therapies under the discretion of the investigators.
These pills can be stopped for 3 months on an elective basis and then the individual
can enter the study. Other medications for chronic stable conditions that are not
listed in exclusion criteria and that are not likely to influence the study results
can be taken or continued as long as their doses have been stable for 3 months prior
to entering the study. Estrogen or birth control can be used (any type) as long as the
dosing has been stable for past 3 months. Medications or over the counter drugs used
on an as needed basis (such as Tylenol or aspirin) are fine as long as not routinely
taken >2 times per week)* Planned major change in lifestyle including work, activity,
exercise, diet, weight during course of study*

- 14. Screening visit BP ≥140/90 mm Hg (as measured by the automated office BP device-
BpTru)

- 15. Screening visit arm circumference ≥17 inches (makes home BP monitoring inaccurate
as the cuff of the commercially-available devices will not fit).

- 16. Screening visit pregnancy (positive urine pregnancy test in women <50 years of
age) and any plan to become pregnant during the study period