Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04125316 |
| Other study ID # |
FeNO_study_protocol V1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 15, 2019 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
February 2023 |
| Source |
Chinese University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This study aims to assess the level of FeNO in Chinese asthma patients with respect to the
different levels of asthma control over 1 year.
Description:
Introduction Measurement of fractional nitric oxide (NO) concentration in exhaled breath
(FeNO) has been shown to be a non-invasive, quantitative biomarker related to airway
inflammation. Although there is inadequate evidence to support the use of FENO to aid the
diagnosis of asthma, recent studies demonstrate the usefulness of FENO in phenotyping and
management of asthma. American Thoracic Society (ATS) Clinical Practice Guideline recommended
the use of FeNO in the diagnosis of eosinophilic airway inflammation and in determining the
likelihood of steroid responsiveness in individuals with chronic respiratory symptoms
possibly due to airway inflammation. The guideline recommends in adults with FENO less than
25 parts per billion (ppb) indicates eosinophilic inflammation and responsiveness to
corticosteroids are less likely, and greater than 50 ppb indicates eosinophilic inflammation
and, in symptomatic patients, responsiveness to corticosteroids are likely.
However, a validation study of ATS guideline showed almost one-fourth of patients had
intermediate FENO values (i.e. 25-50ppb), which may limit the clinical usefulness of the ATS
FeNO cut-points. Furthermore, FENO values are affected by multiple factors. In a recent study
that assessed the determinants of FENO in men and women without lung diseases using data from
25 centres across 11 European countries and Australia involving 3881 subjects, it was found
that gender, smoking status, height, IgE sensitization would affect the FeNO level measured.
A prior study also showed the FeNO levels of healthy Chinese children and adult without
significant lung diseases are higher than the Caucasian population. An earlier genotyping
findings of nitric oxide synthase genes suggested that the frequencies of minor alleles
associated with nitric oxide production were substantially lower in Chinese subjects.
Therefore, ethnic-specific references must be considered when setting the cut-off values for
assessing asthma status in different populations.
There are many studies on the cut-off of FeNO for making a diagnosis of asthma. There are,
however, not much information on the level of FeNO in Chinese asthma patients with different
levels of asthma control in a real-life setting and whether the ATS clinical practice
guideline is applicable for Chinese asthma subjects given that the healthy subjects had a
higher FeNO than the Caucasian population.
The aim of this study is to assess the level of FeNO in Chinese asthma patients with respect
to the different levels of asthma control over a period of 1 year.
Method Subject recruitment This is an observational study in which FeNO was measured in
Chinese adults asthma patients in Hong Kong. Subjects will be recruited from the general
medical and respiratory clinic of the Prince of Wales Hospital in Hong Kong. After an
explanation of the study, the investigator will obtain the written informed consent from all
the patients who meet the inclusion criteria and with no exclusion criteria.
Inclusion criteria:
• Chinese subjects aged between 18 and 90 years and have a diagnosis of asthma according to
The Global Initiative for Asthma (GINA) guideline 2019. Asthma is defined as those with a
consistent history and prior documented evidence of variable airflow obstruction, with
evidence of an increase in FEV1 greater than 12% or 200 mL following bronchodilator or
bronchial hyperresponsiveness on bronchial provocation testing, when stable.
Exclusion criteria:
- Patients with respiratory diseases with other known respiratory diseases including
chronic obstructive pulmonary disease, bronchiectasis, tuberculosis (TB)-destroyed lung
parenchyma, history of lung resection and lung cancer
- Individuals older than 40 years with a smoking history of more than 10 pack-years
- Patients currently randomized in other clinical studies
- Pregnant women
In addition, healthy subjects with no respiratory symptoms and asthma as defined above, and
other significant lung diseases, such as chronic obstructive pulmonary disease, history of
tuberculosis and bronchiectasis) with normal CXR will be recruited as control subjects.
Assessment of the subjects:
After recruitment, asthma patient will be followed up in the research clinic every 4 months
for one year. Patients will have the following assessment in each visit.
1. Demographic characteristics of the subjects Demographic characteristics of the subjects
will include age, body weight and height, symptoms, age of onset of disease,
exacerbations or hospital admission in the past 12 months for asthma, medications taking
and vaccinations in the past 12 months.
2. FeNO measurement FeNO will be measured before spirometry. FeNO will be measured online
using a NIOX VERO (Circassia, Oxford, UK) according to ATS/ERS recommendations. Subjects
will be in the sitting position (with no nose clip), exhale to residual volume, insert a
mouthpiece, inhale to total lung capacity, and then exhale for 10 seconds at a constant
flow rate of 50mL/s. The measurement will be repeated until three FeNO values varied
less than 10% or two values varied less than 5%. The mean FeNO (in ppb) will then be
recorded. All subjects have to refrain from strenuous physical activity or exercise for
at least 30 minutes prior to FeNO measurement. In addition, subjects shall avoid eating
for 1 hour and caffeine ingestion for 6 hours before the test. Subjects will not be
tested within 4 weeks of an upper or lower respiratory tract infection.
3. Spirometry pre- and post-bronchodilator Spirometry pre- and post-bronchodilator
according to the American Thoracic Society and European Respiratory Society standards
will be performed.14 The updated predicted spirometry values for Hong Kong Chinese will
be used to calculate the predicted lung function.ong Kong Chinese will be used to
calculate the predicted lung function.
4. Home peak expiratory flow rate (PEFR) monitoring Patients will be asked to measure their
home PEFR using a PEFR monitoring meter (Mini-Wright, Clement Clarke International Ltd,
Essex, UK) and will be asked to record their PEFR as the best of three recordings in the
morning before the use of inhalers. Mean PEFR is the mean of the daily PEFR for the 2
weeks before the follow-up. PEFR variability was calculated using the Min%Max index
(minimum PEFR, expressed as a percent of the best PEFR over 2 weeks before follow up).
5. Forced Oscillatory assessment of airway resistance Airway resistance and reactance will
be assessed using the TremoFlo C-100 (Thrasys, Halifax, Canada). Forced oscillatory
measures the resistance and reactance of the respiratory system during tidal breathing
by superimposing a gentle multi-frequency airwave onto the patient's respiratory
airflow. The parameters of airway resistance measured will include low-frequency
resistance at 5 Hz denoted as R5 and difference from 5 Hz to 19 Hz denoted as R5 to R19.
Low-frequency reactance at 5 Hz is denoted as X5, resonant frequency when elasticity
balances inertia (i.e. Fres) and the low-frequency reactance area (i.e. ALX) are
reactance parameters being assessed in the study.
6. Blood test Routine blood test, including blood eosinophil count and total IgE level as
determined by clinical need.
7. Skin prick test Skin prick test was performed with a panel of allergen extracts
including cat, dog, dermatophagoides pteronyssinus and D. farinae, Aspergillus, Mold
Mix, Tree Mix and cockroach. A minimum wheal size of 3 mm will be defined as a positive
response.
8. Assessment of asthma control Asthma control in the past 4 weeks will be assessed. They
will be evaluated and classified into different levels of asthma symptom control,
according to GINA 201914 (appendix 1). The asthmatic attacks that required courses of
systemic steroid or hospitalization will be documented (by asking the patient and also
checking with health records). In addition, Asthma Control Test and Asthma control
questionnaire will be used to assess asthma control.
For control subject, they will attend the research clinic once to have assessments of
demographic characteristics, FENO level, spirometry, airway resistance, blood and skin test
as described above.
Primary endpoint of the study: FeNO level in Chinese asthma of different levels of asthma
control.
Secondary endpoint: FeNO level and risk of exacerbation in the subsequent 12 months,
correlation of FeNO with makers of atopy and lung function including skin prick test, IgE
level, eosinophil level and lung function parameters (spirometry and airway resistance).
Statistics Data will be analyzed by the Statistical Package of the Social Science Statistical
software (SPSS) for Window, Version 22.0.0 (IBM SPSS Inc, IL, USA). The clinical
characteristics of the subjects will be expressed as mean (SD) for normally distributed
parameters or median (IQR) for non-normally distributed ones. FeNO levels between different
levels of asthma control will be assessed by one-way ANOVA, while within individual
variations with regard to the level of control and over time will be assessed by ANOVA with
repeated measures, adjusted by age, sex, height and presence of atopy. Comparison of the FeNO
levels of the asthma and control group will be assessed by independent sample t-test. Levels
of FENO and time to first exacerbation will be assessed by Cox proportional-hazards model and
log-rank test as appropriate. A p-value < 0.05 was considered statistically significant.
