RITA: Role of microRNAs in T Cell-Driven Inflammation in Asthma

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT01484691
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 55
• Location: 1
• Arms: 3
• Actual Duration (Months): 42
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This will be a single center study of asthmatic subjects and healthy controls which will investigate mechanisms of asthma through detailed molecular analysis of airway tissues and fluids. The primary goal will be investigate the role of microRNAs in Th2-driven inflammation in asthma. The investigators hypothesize that asthma is associated with abnormal expression of miRNAs in T cells which favors differentiation into Th2-cells. The investigators further hypothesize that asthma is heterogeneous based on the presence and absence of Th2-driven inflammation and that abnormalities in T cell miRNA expression will be most prominent in a subgroup with high levels of Th2-driven inflammation (as assessed using molecular markers that the investigators have previously established). Finally, the investigators hypothesize that inhaled corticosteroids will normalize the T-cell miRNA abnormalities observed in asthma, as corticosteroids treat Th2-driven inflammation. The samples collected will also facilitate the pursuit of secondary analyses designed to investigate mechanisms of inflammation and remodeling in asthma as well as molecular phenotypes of asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Budesonide	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Role of miRNAs in Th2-driven Inflammation in Asthma
• Actual Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Healthy non-asthmatic controls Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression.
Active Comparator: Asthmatics (treatment) Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids.	Drug: Budesonide; Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks; Other Names: Pulmicort
No Intervention: Asthmatics (no treatment) Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids.

Outcome Measures

Primary Outcome Measures

1. Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls [Baseline (cross-sectional analysis)]

   Identification of T cell miRNAs which are differentially expressed in asthma as compared to healthy controls. The investigators will measure a panel of ~200 miRNAs by qPCR (yielding normalized copy numbers for each miR) and identify differential expressed based on a false discovery rate <0.05. Normalized copy numbers from this qPCR experiment were established using the "global mean-normalization" approach as described in the paper by Barbara D'haene et al. entitled "miRNA expression profiling - from reference genes to global mean normalization" published in MicroRNA Expression profiling Methods and Protocols, Springer Verlag, Feb 2011.

2. Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment [8 weeks after randomization to inhaled corticosteroids or no treatment]

   Identification of T cell miRNAs which were reduced in asthmatics who were randomized to inhaled corticosteroids as compared to those randomized to no treatment. The investigators will measure the same miRNAs by qPCR as identified in the other Primary Outcome and define a significant change using a multiple comparison adjusted p-value (false discovery rate <0.05).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Group A:

Inclusion Criteria:

• Male and female subjects between the ages of 18 and 70 years

Group B:

Inclusion Criteria:

• Male and female subjects between the ages of 18 and 70 years

• History of asthma

• No use of oral or inhaled corticosteroids for the treatment of asthma in the past 6 weeks

• Hyperreactivity to methacholine (PC20FEV1 Methacholine ≤ 8.0 mg/mL)

• At least one of the following symptoms, beta agonist use, or FEV1 criteria:

• Asthma symptoms on at least two days per week; OR

• Beta agonist use on at least two days per week; OR

• FEV1 < 85% predicted

Groups A & B:

Exclusion Criteria:

• Current smokers (smoking within the last 12 months) or former smokers who have a total pack-year smoking history greater than 10

• Pregnant women

• Subjects with a history of lung disease other than asthma

• Subjects with a history of a medical disease, which in the opinion of the investigator may put the subject at extra risk from study-related procedures or because the disease may influence the results of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

• University of California, San Francisco
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Prescott G Woodruff, MD, MPH, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UCSF Airway Clinical Research Center

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01484691
• Other Study ID Numbers: 11-07039
• First Posted: Dec 2, 2011
• Last Update Posted: Jun 24, 2022
• Last Verified: Jun 1, 2022

• Additional relevant MeSH terms: Asthma; Inflammation; Budesonide

Study Results

Participant Flow

Arm/Group Title	Healthy Non-asthmatic Controls	Asthmatics (Treatment)	Asthmatics (no Treatment)
Arm/Group Description	Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression.	Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids. Budesonide: Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids.
Period Title: Overall Study
STARTED	21	22	12
COMPLETED	20	19	10
NOT COMPLETED	1	3	2

Baseline Characteristics

Arm/Group Title	Healthy Non-asthmatic Controls	Asthmatics (Treatment)	Asthmatics (no Treatment)	Total
Arm/Group Description	Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression.	Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids. Budesonide: Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids.	Total of all reporting groups
Overall Participants	20	19	11	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.05 (5.34)	26.15 (5.01)	32.72 (13.49)	29.16 (7.63)
Sex: Female, Male (Count of Participants)
Female	11 55%	12 63.2%	5 45.5%	28 56%
Male	9 45%	7 36.8%	6 54.5%	22 44%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 10%	5 26.3%	1 9.1%	8 16%
Not Hispanic or Latino	15 75%	12 63.2%	8 72.7%	35 70%
Unknown or Not Reported	3 15%	2 10.5%	2 18.2%	7 14%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	5 25%	3 15.8%	2 18.2%	10 20%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	4 20%	1 5.3%	0 0%	5 10%
White	9 45%	9 47.4%	6 54.5%	24 48%
More than one race	0 0%	3 15.8%	0 0%	3 6%
Unknown or Not Reported	2 10%	3 15.8%	3 27.3%	8 16%
Region of Enrollment (participants) [Number]
United States	20 100%	19 100%	11 100%	50 100%
FEV1 (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	3.68 (0.93)	3.41 (1.01)	3.52 (0.97)	3.54 (0.99)

Outcome Measures

1. Primary Outcome

Title	Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls
Description	Identification of T cell miRNAs which are differentially expressed in asthma as compared to healthy controls. The investigators will measure a panel of ~200 miRNAs by qPCR (yielding normalized copy numbers for each miR) and identify differential expressed based on a false discovery rate <0.05. Normalized copy numbers from this qPCR experiment were established using the "global mean-normalization" approach as described in the paper by Barbara D'haene et al. entitled "miRNA expression profiling - from reference genes to global mean normalization" published in MicroRNA Expression profiling Methods and Protocols, Springer Verlag, Feb 2011.
Time Frame	Baseline (cross-sectional analysis)

Outcome Measure Data

Analysis Population Description

The study enrolled two groups of subjects: 1. Healthy Non-asthmatic Controls, 2. Asthmatics (who were subsequently randomized to inhaled corticosteroids or no treatment). This analysis compares pre-randomization values in group 1 healthy non-asthmatics controls to group 2 asthmatics because the scientific goal is to identify miRNAs differentially expressed in asthma.

Arm/Group Title	Healthy Non-asthmatic Controls	Asthmatics (Baseline)
Arm/Group Description	Healthy non-asthmatic controls who underwent bronchoscopy at one time point and served as a control group for the asthmatics group for evaluation of T-cell miRNA expression.	All steroid-naïve asthmatics. These subjects were studied before and after randomization to study drug or no treatment. The pre-randomization data were collected on these asthmatics as one uniform group for comparison to healthy controls. These subjects then underwent bronchoscopy and T-cell miRNA measurement at pre-randomization and again 8 weeks after randomization to inhaled corticosteroids or no treatment.
Measure Participants	19	25
mir1	13.2 (5.5)	10.2 (3.0)
mir107	13.6 (4.5)	11.7 (3.2)
mir128	17.0 (5.9)	16.5 (3.9)
mir141	14.6 (4.5)	13.3 (2.0)
mir148b	14.5 (5.2)	11.9 (3.3)
mir181b	11.5 (5.5)	10.8 (2.6)
mir185	12.7 (5.0)	10.7 (2.4)
mir194	11.5 (8.1)	8.7 (3.5)
mir19a	13.8 (7.1)	10.4 (2.5)
mir200a	14.9 (7.2)	14.9 (3.1)
mir22	14.2 (6.2)	12.3 (2.9)
mir223	12.3 (4.6)	10.7 (1.4)
mir23a	14.2 (5.0)	13.6 (2.8)
mir26a	10.2 (6.7)	9.4 (2.8)
mir320b	13.8 (3.4)	12.4 (2.6)
mir598	12.4 (2.1)	13.4 (2.2)
mir720	12.1 (5.2)	11.6 (5.1)
mir1915	7.7 (1.6)	8.8 (1.1)
mir1978	11.7 (3.7)	13.1 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.04
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir107
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.91
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir128
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.47
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir141
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.42
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir148b
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.55
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir181b
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir185
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.94
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir194
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.77
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir19a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.38
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir200a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir22
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.92
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir223
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.57
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir23a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.52
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir26a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir320b
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.39
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir598
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.92
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir720
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir1915
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir1978
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.35
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment
Description	Identification of T cell miRNAs which were reduced in asthmatics who were randomized to inhaled corticosteroids as compared to those randomized to no treatment. The investigators will measure the same miRNAs by qPCR as identified in the other Primary Outcome and define a significant change using a multiple comparison adjusted p-value (false discovery rate <0.05).
Time Frame	8 weeks after randomization to inhaled corticosteroids or no treatment

Outcome Measure Data

Analysis Population Description

This analysis population had two groups: 1. Asthmatics who were randomized to treatment with inhaled corticosteroids, 2. Asthmatics who were randomized to no treatment.

Arm/Group Title	Asthmatics (Treatment)	Asthmatics (no Treatment)
Arm/Group Description	Asthmatics randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at pre-randomization (before corticosteroids) and again after treatment with inhaled corticosteroids. Budesonide: Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Asthmatics randomized to no treatment with inhaled corticosteroids for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at pre-randomization and again 8 weeks after randomization to no treatment with inhaled corticosteroids.
Measure Participants	14	7
mir1	1.5 (4.6)	-3.0 (4.5)
mir107	0.86 (4.4)	-3.7 (4.0)
mir128	2.0 (3.6)	-1.6 (2.2)
mir141	1.2 (3.0)	1.7 (3.7)
mir148b	1.5 (5.0)	-3.1 (4.4)
mir181b	-0.12 (4.9)	-1.7 (4.3)
mir185	0.72 (3.8)	-2.2 (3.4)
mir194	-0.73 (5.3)	-0.37 (2.8)
mir19a	0.053 (3.8)	-2.4 (3.0)
mir200a	-1.4 (3.9)	-2.2 (2.4)
mir22	0.059 (4.6)	-2.7 (3.7)
mir223	0.90 (3.3)	-1.0 (3.0)
mir23a	1.5 (3.8)	-2.8 (1.5)
mir26a	1.2 (3.6)	-0.43 (5.4)
mir320b	0.86 (7.6)	1.8 (3.7)
mir598	-0.20 (3.3)	-3.5 (3.0)
mir720	-1.9 (6.6)	-0.87 (4.3)
mir1915	-0.49 (2.1)	0.26 (1.7)
mir1978	2.3 (5.1)	-1.5 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.53
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir107
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.52
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir128
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.57
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir141
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir148b
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.57
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir181b
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.56
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir185
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.90
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir194
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir19a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.48
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir200a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir22
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.78
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir223
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.91
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir23a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir26a
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.66
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir320b
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.91
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir598
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.32
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir720
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.99
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir1915
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.75
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Healthy Non-asthmatic Controls, Asthmatics (Baseline)
	Comments	mir1978
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.77
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Participants were monitored for adverse events during their study participation, which ranged from 2 weeks to 10 weeks depending on the group to which they were assigned.
Arm/Group Title	Healthy Non-asthmatic Controls		Asthmatics (Treatment)		Asthmatics (no Treatment)
Arm/Group Description	Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression.		Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids. Budesonide: Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks		Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids.
All Cause Mortality
	Healthy Non-asthmatic Controls		Asthmatics (Treatment)		Asthmatics (no Treatment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/22 (0%)		0/12 (0%)
Serious Adverse Events
	Healthy Non-asthmatic Controls		Asthmatics (Treatment)		Asthmatics (no Treatment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		1/22 (4.5%)		0/12 (0%)
Injury, poisoning and procedural complications
Medication error during bronchoscopy	0/21 (0%)	0	1/22 (4.5%)	1	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Healthy Non-asthmatic Controls		Asthmatics (Treatment)		Asthmatics (no Treatment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/21 (14.3%)		1/22 (4.5%)		2/12 (16.7%)
Respiratory, thoracic and mediastinal disorders
Decreased systolic blood pressure from sedation	0/21 (0%)		0/22 (0%)		1/12 (8.3%)
Decreased lung function post-procedure	3/21 (14.3%)		1/22 (4.5%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.