Air Pollution, Asthma and Circadian Clocks

NCT03406351 | Active Not Recruiting

• 1 other identifier: IRB828728
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma; Healthy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Concentration of ozone

  48 hours

• Concentration of the air pollutants CO, CO2, formaldehyde, particulate matter (PM) 1, PM2, PM10, tVOC (total volatile organic compounds)

  48 hours

• Disease expression of asthma measured how frequent asthma medication is used

  4 weeks

• Circadian phase of cortisol

  48 hours

Study Arms (2)

Asthma

Other: Observational

Healthy

Matched controls

Other: Observational

Interventions

Observational OTHER

Observational deep phenotyping physiological readouts

Asthma; Healthy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Cohort 1: asthmatic patients (case); Cohort 2: matched healthy volunteers (control).

You may qualify if:

• \>18 years of age,
• Physician's diagnosis of asthma,
• Prescribed an inhaled-steroid-containing medication for asthma (ensuring the patient is believed to have at least moderate reversible airways obstruction by their physician),
• severe persistent asthma according to the NHLBI Guidelines,
• evidence of reversible airflow obstruction: (a) forced expiratory volume in 1 second (FEV1) \<80% predicted at the time of or within 3 years of screening, and (b) improvement with bronchodilator: either (i) an increase of ≥15% and 200mL in FEV1 with asthma treatment over the previous 3 years or (ii) after 4 puffs of albuterol by MDI (or 2.5 mg by nebulizer), an increase in FEV1 or FVC ≥12% and 200 mL in FEV1 within 30 min at screening,
• Own a smartphone.

You may not qualify if:

• Severe psychiatric or cognitive problems (obvious mania, schizophrenia, significant mental retardation) making study conduct impossible. Formal psychiatric evaluations are outside of the scope; however, research coordinators will be trained to identify such cases followed by review of the PI. Patients can be referred to mental health facilities.
• Past diagnosis of gastroesophageal reflux disease or obstructive sleep apnea,
• Transmeridian travel across ≥2 time zones in the past month,
• Planned transmeridian travel across more than ≥2 time zones during the planned study activities;
• Use of oral or intravenous antibiotics in the past 6 months,
• Episodes of bronchospasm in response to ultrasonic nebulizer treatment (to induce sputum collection non-invasively),
• Any contraindication listed below in the separate paragraph "Contraindications for the use of CorTemp® Disposable Temperature Sensors";
• Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening;
• \> 2 drinks of alcohol per day;
• Use of illicit drugs;
• Smoking;
• Pregnant or nursing;
• Avoid over-the-counter NSAID use 2 weeks prior to 48 hour session \& during 48 hour session (Visit 3, Visit 4 \& Visit 5);
• Avoid Alcohol use 2 weeks prior to the 48 hour session and during the 3 day session (Visit 3, Visit 4 \& Visit 5);
• Vitamins use 1 week prior to and during the 48 hour session.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Researcher Carsten Skarke, MD

Biospecimen

Retention: SAMPLES WITH DNA

saliva, blood, urine

MeSH Terms

Conditions

Asthma

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Garret FitzGerald, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor

Study Record Dates

• First Submitted: January 14, 2018
• First Posted: January 23, 2018
• Study Start: January 15, 2018
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)