Asthma
Conditions
Keywords
Asthma in children, Asthma attack
Brief summary
To study the change from baseline in IL-1β (interleukin 1 beta) concentrations in the nasal airway during acute asthma exacerbation, specifically to measure the degree of change and identify the timing of peak IL-1β concentration. This information will allow the investigators to estimate effect size and guide decisions about the optimal timing of anakinra administration for the future study.
Detailed description
The study team will recruit 60 teens and young adults with persistent asthma who are at high risk for future exacerbation from the University of North Carolina at Chapel Hill (UNC) Children's Allergy and Asthma Center in Raleigh, NC. Participants will complete 13 study visits: an initial in-person visit (the study team will make every attempt to coordinate this visit with a scheduled clinic visit) and 12 monthly virtual follow up visits. Participants will be asked to use an at home spirometer once daily in the evening and will also complete an electronic asthma survey each night. Participants will also be provided with a sensor that tracks their rescue medication use throughout the study. Participants will undergo collection of nasal epithelial lining fluid (NELF) at the baseline visit. During the 12 months of study, participants will self-collect NELF samples if certain prespecified criteria for asthma exacerbation are met. Samples will be analyzed for IL-1β, interleukin receptor antagonist (IL-1RA) and other mediators associated with acute asthma exacerbation. Virtual follow up visits using a video platform will occur monthly for 12 months. Participants will self-report healthcare utilization and prescription for systemic corticosteroids. Spirometry and symptom survey data will be matched to subject-reported asthma exacerbations. The study design is adapted to minimize in-person visits, using web-based platforms for virtual visits and self-collection of samples to prioritize safety during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
Interventions
None listed
Sponsors
University of North Carolina, Chapel Hill
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Inclusion criteria
* Ages 12 to 21 years, inclusive, of both genders * Physician diagnosis of persistent asthma or symptoms consistent with persistent asthma based on expert guidelines for diagnosis and management of asthma (1). * Current use of a controller therapy such as an inhaled corticosteroid (ICS), ICS in combination with long-acting beta agonist (LABA), or leukotriene receptor antagonist (LTRA). * Asthma is "not well controlled" (participant must have ≥1 of the following): * Asthma Control Test (ACT) score \<20, * FEV1 \<80% of predicted, * Meets Global Initiative on Asthma (GINA) criteria for partly controlled or uncontrolled asthma (2): In the past 4 weeks, has the patient had: * Daytime symptoms \>2x/week? * Any night waking due to asthma? * SABA reliever needed \>2x/week? * Any activity limitation due to asthma? * \[0 = Well controlled; 1-2 = Partly controlled; 3-4 = Uncontrolled\] * A history of at least one exacerbation requiring systemic corticosteroids (oral, IM or IV) in the past 24 months * Access to a smartphone * Wireless internet access in the participant's home * Access to a standard freezer in the home
Exclusion criteria
* Systemic corticosteroid-dependent asthma (i.e. people who take oral steroids such as prednisone daily for asthma control). Use of other immunomodulator medications (such as biologics for asthma like omalizumab, etc) is allowable so long as the participant has been on a stable dose of the medication for at least 3 months. * Participants whose asthma is sufficiently severe that the participants routinely require rescue albuterol multiple times a day for symptom relief (not including pre-exercise albuterol use). * Pulmonary disease other than asthma that in the opinion of investigators may affect the interpretation of spirometry data, including but not limited to vocal cord dysfunction, restrictive lung disease, or cystic fibrosis. * Inability to perform spirometry. * History of spirometry-induced bronchoconstriction. * Pregnancy or nursing a baby. Due to the effect of hormonal changes of pregnancy/lactation on airway inflammation, participants who are pregnant or nursing will be excluded from study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Nasal IL-1β (pg/mL) Concentrations During Asthma Exacerbation | Baseline and up to 5 days from the time asthma exacerbation is diagnosed (Months 1-12) | Nasal epithelial lining fluid (NELF) is collected during a period of wellness (baseline) and daily during acute asthma exacerbation (defined by pre-specified criteria) for 5 days. This outcome is defined as the percent change from baseline in nasal IL-1β concentration during acute asthma exacerbation, calculated by comparing the peak concentration observed during the exacerbation to the baseline concentration (i.e., \[(peak value of IL-1β during exacerbation - baseline value of IL-1β)/baseline value of IL-1β\] x100). Results are summarized using the median and interquartile range. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Forced Expiratory Volume in the First Second (FEV1) in Liters During Asthma Exacerbation | Baseline and up to 5 days from the time asthma exacerbation is diagnosed (Months 1-12) | FEV1 will be measured during a period of wellness (baseline) and daily during acute asthma exacerbation defined by pre-specified criteria for 5 days. This outcome is defined as the percent change from baseline in FEV1 during acute asthma exacerbation, calculated by comparing the maximum decline in FEV1 observed during the exacerbation to the baseline FEV1 \[(max decline of FEV1 during exacerbation - baseline value of FEV1)/baseline value of FEV1\] x100). |
| Percentage Change From Baseline in Nasal IL-1RA (pg/mL) Concentration During Asthma Exacerbation | Baseline and up to 5 days from the time asthma exacerbation is diagnosed (Months 1-12) | Nasal epithelial lining fluid (NELF) is collected during a period of wellness (baseline) and daily during acute asthma exacerbation defined by pre-specified criteria for 5 days. This outcome is defined as the percent change from baseline in nasal IL-1RA concentration during acute asthma exacerbation, calculated by comparing the peak concentration observed during the exacerbation to the baseline concentration (i.e., \[(peak value of IL-1RA during exacerbation - baseline value of IL-1RA)/baseline value of IL-1RA\] x100). Results are summarized using the median and interquartile range. |
| Correlation Over Time Between Percentage Change in Nasal IL-1β Concentration From Baseline and Percentage Change in FEV1 From Baseline During Asthma Exacerbation | Baseline and up to 5 days from the time asthma exacerbation is diagnosed (Months 1-12) | Assess the relationship between the asthma exacerbation-induced percentage change from baseline in NELF IL-1β concentrations and the asthma exacerbation-induced percentage change from baseline in FEV1. Pearson's correlation coefficient will be calculated to evaluate the relationship between peak percentage increase in IL-1b levels from baseline and maximum percentage decline in FEV1 from baseline during exacerbation |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAllison Burbank, MD
University of North Carolina, Chapel Hill
Participant flow
Recruitment details
A convenience sample of adolescent and young adult patients receiving asthma specialty care in pulmonology and/or allergy clinics was enrolled at a single institution.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 37 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Forced expiratory volume in 1 second (FEV1) | 98 percent |
| Interleukin-1b (IL-1b) | 29.7 picograms per milliliter |
| Interleukin-1 receptor antagonist (IL-1RA) | 187397.6 picograms per milliliter |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 20 / 40 |
| serious Total, serious adverse events | 1 / 40 |
Outcome results
None listed