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Societies become increasingly urban - more than half the world's population now lives in cities. Urbanization elevates anthropogenic (man-made) exposure to air pollutants. A clear association exists between exposure to air pollutants and exacerbations (worsening) of pre-existing asthma, incidence of nighttime asthma, difficulties with asthma control and increased disease risk. In 2012, the Public Health Management Corporation's Community Health Data Base estimated that 19.4% of adults in Philadelphia had asthma compared to a national prevalence of 7%.
Asthma has a clear temporal signal. A majority of asthma patients, up to 75%, reports nighttime awakenings due to worsened cough, wheeze and dyspnea. This time-of-day-dependent exacerbation of symptoms, coined nocturnal asthma, is associated with poorer disease control, more frequent medication, and higher asthma-related morbidity and mortality. Consequently, several pathophysiological mechanisms proposed for nocturnal asthma relate to circadian clock biology.
Lung function oscillates over the course of 24 hours, peaking around noon and reaching its nadir during early morning hours. Concentrations of air pollutants show oscillating patterns in urban settings.
In this clinical research study, the investigators start to address how spatiotemporal fluctuations in air pollutants relate to asthma. Mechanistically, the investigators wish to address the hypothesis that microRNAs (miRs) act as interface between asthma phenotypes, circadian clocks and environmental exposure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Asthma |
| ||
| Healthy | Matched controls |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Observational | Other | Observational deep phenotyping physiological readouts |
|
| Measure | Description | Time Frame |
|---|---|---|
| Difference in expression levels of miR-142-3p in induced sputum from asthmatics versus controls | Relative expression normalized to housekeeping genes (GAPDH, ACTB) plotted by Expression levels of miR-142-3p will be averaged from several measurements (morning, afternoon, evening, night with target times of 08:00, 14:00, 20:00, 02:00 +/- 1 hour) scheduled over 48 hours | 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of ozone | Concentrations of this air pollutant will be averaged in increments of one hour over the course of 48 hours | 48 hours |
| Concentration of the air pollutants CO, CO2, formaldehyde, particulate matter (PM) 1, PM2, PM10, tVOC (total volatile organic compounds) |
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Inclusion Criteria:
Exclusion Criteria:
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Cohort 1: asthmatic patients (case); Cohort 2: matched healthy volunteers (control).
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| Name | Affiliation | Role |
|---|---|---|
| Garret FitzGerald, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania School of Medicine | Philadelphia | Pennsylvania | 19104 | United States |
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| Label | URL |
|---|---|
| Researcher Carsten Skarke, MD | View source |
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To be determined
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D057832 | Watchful Waiting |
| ID | Term |
|---|---|
| D017063 | Outcome Assessment, Health Care |
| D010043 | Outcome and Process Assessment, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
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saliva, blood, urine
Concentrations of these air pollutants will be averaged in increments of one hour over the course of 48 hours |
| 48 hours |
| Disease expression of asthma measured how frequent asthma medication is used | The number of uses of asthma medication will determine severity of asthma | 4 weeks |
| Circadian phase of cortisol | Concentrations of cortisol in saliva will be determined in the morning, afternoon, evening, and night with target times of 08:00, 14:00, 20:00, 02:00 +/- 1 hour scheduled over 48 hours. Cosinor analysis will determine the circadian phase. | 48 hours |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |