Flunisolide HFA in Children With Small Airway Disease

Not Applicable

Completed

Brief Summary: The purpose of this study is to see how two doses of Flunisolide HFA (an FDA approved inhaled medication to treat asthma) affect the small airways in children with asthma.

Detailed Description: This is a prospective, randomized, parallel, open label study. The primary aim is to compare the average change in spirometric values (Forced expiratory volume 1 (FEV1) and Forced Expiratory Flow 25-75% (FEF 25-75%) and Impulse Oscillometry System (IOS) values (Resistance at 5 Hz (R5), Resistance at 20 Hz (R20), Area of reactance (AX), Resonant frequency (Fres)) from baseline to week 6 from participants randomized flunisolide hydrofluoroalkane (HFA) 1 inhalation BID and to flunisolide HFA 2 inhalations BID. The change in scores from baseline to six week follow up will initially be compared using paired t-tests and Chi-squared tests for trend. Repeated measurements will be analyzed using generalized linear mixed-effects regression modeling (GLMM) techniques. For continuous outcomes (e.g. FEV1, FEF 25-75%, Fres, reactance at 5 Hz (X5), AX, R5-R20). The identity link function and normal distribution will be used. For count data (e.g., use of Beta-agonists, episodes of coughing, episodes of wheezing, etc.) the log link function and the Poisson distribution will be used. If we dichotomize outcomes (e.g., a Beta-agonist was used, coughing occurred, etc.) the logit link function and Bernoulli distribution will be used.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of asthma
Informed consent by parent or legal guardian
6 years to 18 years of age at screening visit
ability to comply with medication use, study visits and study procedures as judged by the site investigator
FEF 25-75% <65% of predicted as a marker for small airway disease

Exclusion Criteria

Acute wheezing at screening visit or at Baseline visit
Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset in 1 week preceding screening visit or 3 weeks preceding baseline visit
Oxygen saturation <95% at screening visit or at Baseline visit
Clinically significant upper airway obstruction as determined by the Site Investigator (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed obstructive sleep apnea.
Severe gastroesophageal reflux, defined as persistent frequent emesis despite anti-reflux therapy
Physical findings that would compromise the safety of the subject or the quality of the study data as determined by site investigator
Inhaled Corticosteroids (ICS) use within 7 days of Baseline visit; systemic steroids within 30 days
Cystic Fibrosis, Interstitial lung disease (ILD) history of severe Bronchopulmonary dysplasia (BPD) or other underling significant respiratory disease apart from asthma
Potential subjects who are pregnant may not enroll in the study

Arm && Interventions

Group	Intervention	Description
Flunisolide 320 mcg per day	Flunisolide HFA	Patients will receive inhaled Flunisolide HFA 160 mcg twice per day for a total of 320 mcg per day over the 6 week study period
Flunisolide 160 mcg per day	Flunisolide HFA	Patients will receive inhaled Flunisolide HFA 80 mcg twice per day for a total of 160 mcg per day over the 6 week study period

Primary Outcome Measures

Name	Time	Method
Spirometry Forced Expiratory Volume 1 (FEV1) After Flunisolide	Before and after treatment at baseline and six week followup	the most used outcome in respiratory studies
Impulse Oscillometry (IOS) Area of Reactance (AX) After Flunisolide Treatment	Baseline and six week followup	A composite measure of small airway dysfunction. A reduction in IOS scores indicate an improvement.
Spirometry Forced Expiratory Flow 25-75% (FEF 25-75%)	baseline and six week followup	Indirectly assess small airway function.
Impulse Oscillometry (IOS) Resistance 5 (R5)	initial visit and six week followup	Resistance of the respiratory system at 5 Hz is a measure of total airway resistance. Elevated value is indicative of respiratory dysfunction.