Improvement of FeNO and FEF25-75 After Inhaled Corticosteroid Treatment of Asthma

Concurrent Improvement of Exhaled Nitric Oxide and FEF25-75 After Treatment With Inhaled Corticosteroid in Children With Controlled Asthma

Abnormal lung function and high exhaled nitric oxide (FeNO) have been reported in asymptomatic patients with asthma. The investigators aimed to assess whether FeNO and FEF25-75 improve concurrently after treatment with inhaled corticosteroid (ICS) in patients with controlled asthma. Geometric mean (GM) FeNO and spirometric values in patients 8 to 16 years of age who maintained asthma control without controller medication were compared with healthy controls and patients with uncontrolled asthma who were also not receiving controller medications. Patients with controlled asthma and high FeNO (> 25 ppb) were randomized to ICS treatment or to remain untreated. Changes in spirometric values and GM FeNO from baseline were evaluated after 6 weeks.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Budesonide

Detailed Description

Current guideline-defined asthma control cannot be applied to the level of airway inflammation because neither symptoms nor the results of basic pulmonary function tests can reflect ongoing airway inflammation.Consequently, asymptomatic or minimally symptomatic patients are usually considered to have controlled asthma even if they have subclinical airway inflammation. Measures of airway inflammation are thus required to identify patients with silent airway inflammation which does not manifest itself as symptoms or impaired lung function. In addition, measurement should be easy to perform, reproducible, and associated with a high degree of acceptance by patients. In this regard, the advent of FeNO measurements represents a significant advance in monitoring airway inflammation of asthmatic patients. High FeNO values above certain cut-point may indicate active eosinophilic airway inflammation and the likelihood of deterioration in asthma control. However, it is still unclear that high FeNO in asymptomatic patients implies the need for the anti-inflammatory treatment.

Current guidelines for asthma management recommended forced expiratory volume in the first second (FEV1) as a principle spirometric parameter to assess airflow limitation. However, asthmatic subjects have air trapping in the presence of normal FEV1. Air trapping in asthmatic subjects has been demonstrated to be better correlated with forced expiratory flow between 25% and 75% of vital capacity % predicted (FEF25-75 % predicted) than FEV1 % predicted. In fact, impaired FEF25-75 is one of the most common abnormalities in pulmonary function in cross-sectional studies in asymptomatic patients. In addition, high FeNO in asymptomatic or minimally symptomatic patients may be accompanied by impairment of FEF25-75 because both parameters have been suggested to be measures of residual small airway disease. Therefore, there is a possibility that the improvement of FEF25-75 happens concomitantly with the decrease of FeNO during the anti-inflammatory treatment. In this study, we recruited previously well-documented atopic asthmatic children who required no medication to maintain asthma control for more than 3 months and had high FeNO levels (> 25 ppb). We aimed to assess whether the decrease of FeNO occurs simultaneously with improvement of FEF25-75 after treatment with inhaled corticosteroid (ICS) in these patients.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chungbuk
    • Cheongju, Chungbuk, Korea, Republic of, 361-711
      • Chungbuk National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• sensitized to aeroallergens and previously diagnosed to have asthma based on the documentation of airway hyperresponsiveness (methacholine PC20 ≤ 8 mg/mL) and/or reversible airflow obstruction (≥ 12% improvement in FEV1 in response to inhaled beta 2-agonist)
• maintained asthma control without controller medication for 3 months or more
• FeNO > 25 ppb

Exclusion Criteria:

• who had significant pulmonary disease other than asthma or a history of gastroesophageal reflux

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Budesonide; Patients with FeNO level greater than 25 ppb were randomly allocated to one of two groups. Randomisation was stratified by baseline FeNO. In one group (treatment group), participants were assigned to once daily treatment with 400 µg budesonide. In the other group (non-treatment group), participants did not receive any medication.	Drug: Budesonide; once daily inhalation with 400 µg budesonide (dry powder)during 6 weeks
No Intervention: remain untreated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FeNO	FeNO was measured at week 6 in the treatment and non-treatment groups.	6 weeks after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spirometric values(FEF25-75,FEV1,FEV1/FVC)	Spirometric values were evaluated at week 6 in the treatment and non-treatment groups.	6 weeks
Asthma control test scores	Asthma control test scores were evaluated at week 6 in the treatment and non-treatment groups.	6 weeks

Collaborators and Investigators

• Sponsor: Chungbuk National University
• Investigators: Principal Investigator: Youn-Soo Hahn, MD, PhD, Department of Pediatrics, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: April 20, 2011
• First Posted (Estimate): April 22, 2011

Study Record Updates

• Last Update Posted (Estimate): April 22, 2011
• Last Update Submitted That Met QC Criteria: April 20, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Asthma; children; exhaled nitric oxide; inhaled corticosteroid; FEF25-75
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: WC asthma treatment based FeNO