Bronchodilator Response in 4-12 Years Chinese Controller Naive Asthmatic Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Capital Institute of Pediatrics, China
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
caoling, Capital Institute of Pediatrics, China
ClinicalTrials.gov Identifier:
NCT01500525
First received: December 23, 2011
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

Objectives:

Our goal is trying to identify an ideal BDR cutoff point for Chinese controller-naïve asthmatic children. In order to achieve this, several steps need to taken.

  1. To observe BDR distribution curve for Chinese non-asthmatic children from 4-12 years
  2. To observe BDR distribution curve for Chinese controller-naïve asthmatic children from 4-12 years
  3. To compare BDR values between non-asthmatic group and controller-naïve asthmatic group, and analyze appropriate cut-off point value

Hypothesis:

  1. Publications and our clinical experience indicate BDR value is affected by ethnicity, and children are less responded to bronchodilator compared with adult patients. From this aspect, data from Chinese children may be different from data included in the guidelines which mostly determined by studies in adults
  2. Reversible bronchospasm is a characteristic in asthma patients. Between asthmatics and non-asthmatics, different response to BDR test would be observed, and there would be a cutoff point with good sensitivity and specificity to differentiate asthmatics from non-asthmatics

Background and rationale:

According to the guideline of global initiative for asthma, global strategy for asthma management and prevention (GINA) and guideline of United States National Asthma Education and Prevention Program (NAEPP) guidelines spirometry, including baseline forced expiratory volume in 1 second (FEV1) and the bronchodilator response (BDR) to short acting beta agonists (SABA), should be used in children as objective measures to establish the diagnosis and severity of bronchial asthma. Spirometry is necessary because not every child came to the clinic with typical symptoms and the objective measurement can improve diagnosis confidence. Baseline FEV1, the so called "gold standard" for evaluating airway obstruction in adults, is usually in the normal range (greater than 80% predicted) in children, regardless of asthma severity. This substantially limits its value for diagnosis and assessment of response to treatment. Because of this, several other objective measures have been suggested for diagnosis and treatment in children, including the response to a bronchodilator, which reflects not only airway reversibility, but also a marker of airway inflammation.

The current definition for a positive BDR is >12% reversibility and >200 ml increase from initial FEV1 after short acting beta-agonist (SABA) has been used. However, recent reports and our clinical observation revealed that, in a significant part of Chinese asthmatic children, their BDR value cannot achieve 12% in the evaluation.

It has been suggested that the cutoff point of 12% is too conservative for pediatric patients. In the study carried out by Galant et al among 51 non-asthmatic children and 346 controller naïve asthmatic children between 4-17 years, the BDR value could achieve 12% in only 30.6% asthmatic children, across all severity. Meanwhile, when observing BDR value in the above study, results were 2.2% (95% CI, 0.2-4.3) in the non-asthmatic group compared with 8.6% (95% CI, 7.5-9.8) in the asthmatic group. The range seen was 7.6% (95% CI, 5.8-9.5) for mild asthma to 10.1% (95% CI, 7.6-12.6) in the severe persistent group. Also, in a study among 142 children between 5-10 years in UK, 9% increase in FEV1 after bronchodilator use was suggested as the cutoff point with good sensitivity and specificity. Moreover, in a study carried out among 3052 children in rural area between 8-15 years in Anhui Province in China, results showed BDR was 3 +/- 5% in non-asthmatic children, and 7 +/- 9% in asthmatic children.

Difference between the proposed study to be carried out in our hospital and the one in Anhui Province is that subjects in this proposed study are from 4-12 years old, which is the largest patient segment in our clinic including preschool and school students. And most importantly, the main purpose of study in Anhui is to observe the BDR range of the non-asthmatic children and asthmatic children, while in our study, besides this objective,our will tentatively calculate a BDR cutoff point by using receiver operating characteristic (ROC curve). And the cutoff point can be used as a reference indicator in asthma diagnosis and long-term management.

The current BDR cutoff point of 12% that is not ideal for children can also be reflected in the clinical management. It has been shown that a persistent BDR value, even less than 12%, in asthmatic children suggests poor clinical outcome. In a 4 years study among 1041 asthmatic children in America carried out by Sharma et al, it showed that compared with individuals who had a BDR of 12% and 200ml, individuals who had a BDR of 10% had similar poor clinical outcomes (e.g. more hospital visits, more prednisone bursts, increased nocturnal awakenings, and missing more days of school). Same results were also obtained in Galant et al study among 679 asthmatic children among 5-18 years.


Condition
Asthma

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: A Prospective Observational Study in a Tertiary Pediatric Hospital in Beijing to Understand the Accuracy of Bronchodilator Response (BDR) in Chinese Controller Naive Asthmatic Children Between the Age of 4~12 Years Old

Resource links provided by NLM:


Further study details as provided by Capital Institute of Pediatrics, China:

Primary Outcome Measures:
  • bronchodilator response in asthmatic children [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
    1. To observe BDR distribution curve for Chinese non-asthmatic children from 4-12 years
    2. To observe BDR distribution curve for Chinese controller-naïve asthmatic children from 4-12 years
    3. To compare BDR values between non-asthmatic group and controller-naïve asthmatic group, and analyze appropriate cut-off point value


Estimated Enrollment: 600
Study Start Date: December 2011
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
asthmatic children
children diagnosed by a specialist as asthmatic patients
non-asthmatic children
children who are healthy and who do not have respiratory syndrom

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   4 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

300 asthmatic children and 300 non-asthmatic children will be recruited

Criteria

-Non-asthmatic group: healthy children from 4-12 years will be recruited from the Capital Institute of Pediatrics nearby schools

Inclusion criteria:

  1. Willingly attend this investigation
  2. Chest physical tests are normal

Exclusion criteria:

  1. The child had been hospitalized for any severe respiratory condition
  2. A physician had ever stated that the child had asthma, reactive airway diseases, or the child had taken antiasthma medications for symptoms
  3. The child was diagnosed with congenital heart disease requiring surgery or medications for management
  4. There are positive responses concerning other serious chest problems, chest surgery, chronic productive cough, recurrent intractable wheezing, and shortness of breath
  5. The children can not finish the test that met American Thoracic Society criteria for preschool children in a maximum of 6 attempts and are unable to successfully complete post-bronchodilator (BD) spirometry

    • Asthmatic group: 4-12 years old asthmatic children will be recruited from the asthma clinic of the Capital Institute of Pediatrics

Inclusion criteria:

  1. Diagnose asthma by specialist of asthma (based on symptoms): criteria for the diagnosis of asthma made by the asthma specialist included a history of recurrent coughing, wheezing, or shortness of breath at rest or with exercise, symptomatic improvement after bronchodilator use, and exclusion of other diagnoses
  2. Asymptomatic or mild symptomatic with no physical signs of wheeze at the time of testing
  3. Not receiving controller medication 6 weeks prior to the initial evaluation
  4. Willing to attend this investigation

Exclusion criteria:

  1. Using short β2 agonists within 6 hours
  2. Using long acting β2 agonists within 24 hours
  3. Can not finish the test that met American Thoracic Society criteria for preschool children in a maximum of 6 attempts and are unable to successfully complete post-bronchodilator spirometry.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01500525

Contacts
Contact: Ling Cao, MD 86-13910610319 caoling9919@yahoo.com.cn

Locations
China, Beijing
Capital Institute of Pediatrics Recruiting
Beijing, Beijing, China
Contact: Ling Cao, MD    86-13910610319    caoling9919@yahoo.com.cn   
Sponsors and Collaborators
Capital Institute of Pediatrics, China
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Ling Cao, MD Capital Institute of Pediatrics
  More Information

No publications provided

Responsible Party: caoling, Director of Pulmonary Department, Director of Asthma Center, Capital Institute of Pediatrics, China
ClinicalTrials.gov Identifier: NCT01500525     History of Changes
Other Study ID Numbers: MISP 40467
Study First Received: December 23, 2011
Last Updated: February 25, 2013
Health Authority: China: SFDA

Keywords provided by Capital Institute of Pediatrics, China:
asthma
children
accuracy of bronchodilator response

Additional relevant MeSH terms:
Bronchodilator Agents
Anti-Asthmatic Agents
Autonomic Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014