Particulate Matter, Blood Pressure, and the Sympathetic Nervous System
Particulate Matter, Blood Pressure, and the Sympathetic Nervous System
Healthy volunteers will be exposed to ambient air near a roadway under the conditions of with
 and without a facemask and their responses will be evaluated.
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