MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY NGUYEN TRAN NGOC HIEU STUDY OF ASTHMA CONTROL STATUS IN CHILDREN WITH BRONCHIAL ASTHMA AND ALLERGIC RHIN
Trang 1MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH
HANOI MEDICAL UNIVERSITY
NGUYEN TRAN NGOC HIEU
STUDY OF ASTHMA CONTROL STATUS
IN CHILDREN WITH BRONCHIAL ASTHMA
AND ALLERGIC RHINITIS
Major: Pediatrics Code: 9720106
SUMARRY OF MEDICAL DOCTORAL THESIS
HANOI, 2022
The study was completed in:
HANOI MEDICAL UNIVERSITY
Sicence advisors:
1 A/Prof PhD Nguyen Thi Dieu Thuy
2 PhD Luong Cao Dong
Reviewer 1:
Reviewer 2:
Reviewer 3:
Thesis will be defended at The Commission for PhD thesis assessment
of Ha Noi Medical University
At …., date…., 2022
Thesis can be consulted at:
- National Library of Vietnam
- Library of Hanoi Medical University
Trang 2RELATED PUBLICATIONS
1 Nguyen Tran Ngoc Hieu, Nguyen Thi Dieu Thuy, Lương
Cao Don Applying of CARATkids questionaire for
assessment of asthma control in children with asthma
combined allergic rhinitis Journal of 108 - Clinical Medicine
and Pharmacy 2020; 15(3): 63-67
2 Nguyen Tran Ngoc Hieu, Luong Cao Dong and Nguyen Thi
Dieu Thuy Role of airway nitric oxide for asthma controls in
children with asthma combined allergic rhinitis Journal of
Medical Research Ha Noi Medical University 2020; 131(7):
141 - 147
3 H Nguyen - Tran - Ngoc, Th Nguyen - Thi - Dieu, D Luong -
Cao et al Study of asthma control status in children with
bronchial asthma and allergic rhinitis Journal of Functional
Ventilation and Pulmonology 2021; 37(12): 7-12
INTRODUCTION Bronchial asthma (BA) and allergic rhinitis (AR) are the most common chronic airway diseases in children For the purpose to help evaluate BA control in patients with co-morbidity of AR, the Control allergic rhinitis and asthma test for children (CARATkids) was developed to in 2010 for simultaneous control of both asthma and allergic rhinitis (BA-AR) in children This asthma control toolkit is relatively easy to use, but the results are quite subjective, depending on the awareness and care about the disease by the parents and the children with the disease
Both BA and AR are chronic inflammatory diseases of airways, and airway nitric oxide levels objectively reflect the airway inflammation Measuring Nasal Nitric Oxide (nNO) and Fractional Exhaed Nitric Oxide (FeNO) is a non-invasive exploratory method to assess airway inflammation in both upper and lower respiratory airways In Vietnam, there have only few studies been on the value of the CARATkids questionnaire as well as its correlation with the nitric oxide in the upper airways in patients with BA, especially in children with asthma and allergic rhinitis In order to evaluate the correlation between nNO concentration and asthma control status, we conducted the project "Study
of asthma control status in children with bronchial asthma and allergic rhinitis" with the following objectives:
1 Determining nasal nitric oxide threshold value in children with asthma and allergic rhinitis at Vietnam National Children's Hospital in the period 2016 - 2019
2 Evaluating asthma control status in children with asthma and allergic rhinitis
3 Determining asthma phenotype in children with asthma and allergic rhinitis
NEW FINDINGS OF THE THESIS Focus of the Thesis is studying the bronchial asthma in children with allergic rhinitis, which is a new problem in Vietnam Determining the nasal nitric oxide threshold value in children with asthma and allergic rhinitis and assess the status of asthma control in this subject Confirming the value of the questionnaire in assessing the simultaneous control of both asthma and allergic rhinitis in children (CARATkids) in Vietnamese children Identifying airway inflammation and asthma
Trang 3phenotype in children with asthma and allergic rhinitis provides the
clinicians with a basis for the decisive diagnosis and prevention of
bronchial asthma with allergic rhinitis
THESIS STRUCTURE
The thesis consists of 126 pages, including: introduction (2 pages),
literature review (36 pages), subjects and method (22 pages), results (32
pages), discussion (30 pages), conclusion (2 trang), some limitations of
the study (1 page), recommendations (1 page) There are 27 tables, 15
figures, 19 graphs, 4 diagrams, 2 appendices, 151 references in the
thesis
Chapter 1 LITERATURE REVIEW 1.1 Overview of Asthma and Allergic Rhinitis
1.1.1 Defination of asthma and allergic rhinitis
Defination of asthma: The Global Initiative for Asthma (GINA)
2020difined “Asthma is a heterogeneous desease, usually characterized
by chronic airway inflammation It is defined by the history of
respiratory symptoms such as wheeze, shortness of breath, chest
tightness and cough that vary over time and in intensity, together with
variable expiratory airflow limitation
Definition of allergic rhinitis: According to Allergic Rhinitis and
its Impact on Asthma (ARIA) 2008, rhinitis is defined as an
inflammation of the lining of the nose and is characterized by nasal
symptoms including anterior or posterior rhinorrhoea, sneezing, nasal
blockage and/or itching of the nose These symptoms occur during two
or more consecutive days for more than 1 hour on most days Allergic
rhinitis is clinically defined as a symptomatic disorder of the nose
induced after allergenexposure by an IgE-mediated inflammation
1.1.2 Epidemiology of Bronchial Asthma (BA) and Allergic Rhinitis (AR)
Epidemiological studies have shown that AR and BA often coexist in
the same patient Patients with moderate - severe persistent allergic rhinitis
have a higher risk of asthma than those with intermittent mild asthma Most
patients with asthma have symptoms of allergic rhinitis Rhinitis is an
independent allergic factor in asthma risks
1.1.3 Risks factors for bronchial asthma and allergic rhinitis
Asthma and allergic rhinitis often share common disease risk factors,
such as indoor and outdoor allergens, or medications like aspirin
1.1.4 The pathogenetic relationship between bronchial asthma and allergic rhinitis
There are now many controversial opinions about the pathogenesis of
BA, but it is agreed by most that BA is a complex disease characterized by airway chronic inflammation, hyperresponsiveness and structural changes, resulting in obstruction of airflow
Allergic rhinitis and bronchial asthma share the type 1 of allergy mechanism with the participation of IgE antibody Asthma and allergic rhinitis share the same allergen as a trigger factor The nasal and bronchial mucosa are similar, so they have similar reactivity
Both diseases are inflammatory airway diseases, with the same inflammatory cells and inflammatory mediators that are released by allergen exposure Asthma and rhinitis both cause airway obstruction
In addition, the upper airway has a protective role of the lower airway 1.1.5 Controlling allergic rhinitis helps to control bronchial asthma Children with asthma and allergic rhinitis are more likely to be hospitalized and incur higher treatment costs than the patients with asthma alone Allergic rhinitis greatly affects the life quality of children with bronchial asthma Therefore, good treatment of allergic rhinitis can contribute to well controlled of asthma
1.2 Asthma phenotype in children over 5 years old and adults The term “phenotype” (PNT) is intended to describe recognizable clinical features that are not directly related to the underlying pathophysiology In bronchial asthma, asthma phenotype describes the clinical features and inflammatory morphology as well as the responses
to treatment
In 2020, GINA classified asthma phenotypes as follows: allergic asthma; non-allergic asthma; late-onset asthma; asthma with persistent airflow limitation; asthma with obe sity
1.3 Diagnosis of bronchial asthma and allergic rhinitis 1.3.1 Diagnosis of asthma in children older than 5 years Diagnostic criteria of asthma in children older than 5 years old according to GINA 2016:
- Typical symptoms are wheeze, shortness of breath, chest tightness and cough
- Confirmed variable expiratory airflow limitation:
+ At least once during diagnostic process when FEV1 is low, confirm that FEV1/FVC is reduced
Trang 4+ An evidence of lung function changes compared with healthy
subjects:
• Increase in FEV1 of >12% predicted after administration of
bronchodilator
• Average daily diurnal PEF variability >13%
• Increase in FEV1 by >12% and >200 mL (or PEF† by >20%)
from baseline after 4 weeks of treatment, outside respiratory infections
+ Bronchial reconstitution test may be repeated when symptoms
are present in the morning or after bronchodilator administration
- Personal and family history: The child's history of previous recurrent
respiratory symptoms; the child may have allergic rhinitis or eczema
- Clinical examination: Clinical examination of asthmatic patients
usually shows no symptoms unless the patient is in an acute asthma
attack If a child has persistent asthma, the chest cavity may become
deformed
1.3.2 Diagnosis of allergic rhinitis
Diagnosis of allergic rhinitis according to ARIA 2008
- Personal and family history of allergies
- Functional symptoms: Having at least 2 of the following
symptoms (occurring frequently, lasting at least 1 hour/day): Clear
rhinorrhea; uninterrupted sneezing; stuffy nose; itchy nose; allergies in
the conjunctiva such as red, itchy eyes
- Physical symptoms: mucus excess on the floor of the inferiror
and middle sulcus rhinalis; enlarged and wet turbinates, especially
inferior turbinates; pale nasal mucosa; nasal polyps may exist
- Subclinical: Prick test may be positive for respiratory allergens;
specific IgE quantification; stimulation test with specific allergen
1.4 Treatment of bronchial asthma having allergic rhinitis
1.4.1 Targeted treatment of asthma having allergic rhinitis
- Control the current asthma symptoms
- Control the current allergic rhinitis symptoms
- Reduce the future risk of asthma and allergic rhinitis
1.4.2 Treatment regimen for asthma having allergic rhinitis
- Preventive treatment of plasma to GINA 2016 Asthma Treatment
Recommendations in children older than 5 years
- Treatment of allergic rhinitis to ARIA 2008 Allergic Rhinitis
Treatment Recommendations
- Simultaneous treatment regimen of asthma with allergic rhinitis: combination of both asthma and allergic rhinitis treatment regimens in which priority is given to drugs capable of simultaneously controlling asthma with allergic rhinitis such as LTRA, omalizumab, etc on request
1.4.3 Assessment of asthma and allergic rhinitis control
- Assessment of asthma control to GINA 2016
- Assessment of asthma control to the Asthma Control Test (ACT)
- Assessment of asthma and allergic rhinitis control to the Control allergic rhinitis and asthma test for children (CARATkids)
- Assessment of asthma control by exhaled nitric oxide level of the American Thoracic Society (ATS)
1.5 Role of nitric oxide in bronchial asthma and allergic rhinitis 1.5.1 Nitric oxide biosynthesis
The endogenous nitric oxide (NO) molecule is derived from the reaction between oxygen and nitrogen of the amino acid L-Arginin under the action of the enzyme NO synthase (NOS) There are three types of NOS enzymes in the bronchi participating in NO synthesis: NOS-1, NOS-2, and NOS-3 In which NOS-1 and NOS-3 always exist and produce NO continuously in small quantities, called basic NOS enzyme NOS-2 known as inducible NOS or iNOS is found in airway epithelial cells and some inflammatory cells, producing NO at a slower rate but in large quantities 1.5.2 Origin of nasal nitric oxide
Nasal nitric oxide (nNO) is produced in the nose and paranasal sinuses Each of these regions can contribute to the generation of nNO
In addition, nNO is produced by the nasal mucosal epithelium and inflammatory cells (eosinophils) involved in up-regulation of inducible nitric oxide (iNOS) enzymes The nasal cavity has a special vascular system that causes changes in nasal cavity volume and changes in the flow and/or volume of blood from nose, which could theoretically affect nNO production and absorption
1.5.3 Origin of bronchial nitric oxide Exhaled nitric oxide (FeNO) originates mainly from the bronchial epithelium In the presence of airway inflammation, NOS-2 is activated by airway epithelial cells and inflammatory cells increasing endogenous NO levels Under normal physiological conditions, the bronchial epithelium produces approximately 0.05 pico liters per second (pl/s) of NO over an area
of 1 cm2 In the presence of an inflammatory response, the airway epithelium
Trang 5produces approximately 7.4 pico liters per second per 1 cm2 area The
phenomenon of NO proliferation can last from 7-10 days
1.5.4 Role of nitric oxide in asthma and allergic rhinitis
FeNO levels provide a direct assessment of airway inflammation
associated with eosinophilia The change in FeNO levels manifests as early
as 1-2 weeks compared with the change in FEV1 after many months With
the eosinophilic asthma phenotype, FeNO significantly reduces in asthmatic
patients after corticosteroids administration This means, FeNO can assess
the severity of the inflammatory process as well as the degree of treatment
response to corticosteroids in asthmatic patients
nNO levels increase in people with allergic rhinitis Patients suffering
from allergic rhinitis with or withour bronchial asthma have statistically higher
levels of FeNO and nNO than those with vasomotor rhinitis and the controls
Several studies have shown a decrease in nNO level with topical
corticosteroids The nNO value is closely related to the outcome of asthma
control, especially in patients with asthma and allergic rhinitis nNO levels
have been suggested as a predictor of poor asthma control
1.5.5 Methods for measuring airway nitric oxide
Nowadays, there are three different techniques used to measure
exhaled nitric oxide: electrochemical sensors, chemiluminescence
sensors, and laser spectroscopy
FeNO and nNO levels are given in ppb (parts per billion) There are two
methods of measuring FeNO: online measurement and offline measurement
The most common method of measuring nNO is to insert a cannula into the
nasal cavity through the nostrils, aspirating the internal airflow (5 mL/s) while
the patient holding breath (10s) in order to have direct analysis of nitric oxide
level in the nose Another method is to measure nNO during air flow
circulating when the patient is still breathing normally through one nostril, air is
withdrawn through the other nostril at a rate of 5mL/s nNO can also be
measured through nasal mask with a single nasal exhalation at a fixed flow rate
using hand-held devices
1.6 Some studies on nitric oxide concentration and control of
bronchial asthma and allergic rhinitis in the World and Vietnam
1.6.1 Studies in the World
In 2005, Struben et al: study of the normal value of nNO in
children aged 6 to 17 years
2014, Kumar et al: Study of the correlation between FeNO, nNO
and allergic status in asthma and allergic rhinitis
In 2017, Amaral et al.: Study of the validation and the cutoff values
of the Control of Allergic Rhinitis and Asthma Test for children (CARATkids) in Brazil
1.6.2 Studies in Vietnam
In 2017, Duong Quy Sy et al.: Study of nNO concentrations in the diagnosis of allergic rhinitis in subjects with and without bronchial asthma
In 2018, Pham Khac Tiep: Study of applying the CARATkids scale
in asthma and allergic rhinitis control in children aged 6-12 at the Department of Immunology - Allergy - Rheumatology, Vietnam National Children's Hospital
In 2019, Duong Quy Sy et al.: Study of the therapeutic effect on nasal nitric oxide in patients with persistent allergic rhinitis
CHAPTER 2 SUBJECTS AND STUDY METHODS 2.1 Study Subjects
2.1.1 Patients with asthma and allergic rhinitis
- 124 patients diagnosed with bronchial asthma and allergic rhinitis who visited hospital for medical examination and treatment at Vietnam National Children's Hospital were invited to participate in the study
- Selection criteria
BA patients with AR: the patients diagnosed with bronchial asthma according to GINA 201654 and allergic rhinitis according to ARIA
2008 + Patients between 6 and 15 years old
+ Patients with BA diagnosed for the first time
+ Patients diagnosed with BA but has not received preventive treatment
+ Patients with BA that have quit prophylactic therapy for more than 3 months
+ Patients with allergic rhinitis symptoms, previously or currently examined and diagnosed with allergic rhinitis
+ Patients not in an acute asthma attack + Patients undergo the study with consent and supervision of the parents or regular caregivers
- Exclusion criteria + Patients classified as having stage 1 asthma with no indication for asthma prophylaxis
Trang 6+ Patients with asthma having other diseases such as congenital
heart disease, hepato-biliary disease, kidney and urinary tract
disease, neurological disorders, cognitive disorders, etc
+ Patients unable to understand and follow instructions when
participating in respiratory function and airway NO
concentration measurements
2.1.2 Controls
- Asthmatic patients without allergic rhinitis from 6 to 15 years of age
have the selection and exclusion criteria similar to those with bronchial asthma
having allergic rhinitis, but they don’t have allergic rhinitis
- Healthy children aged 6 -15 years old These children absolutely
have no history of wheezing, allergic rhinitis or other allergic
conditions; no systemic diseases No parents or siblings as family’s
history with asthma or allergic rhinitis
2.1.3 Study Location
- The study was conducted at the Department of Immunology -
Allergy - Rheumatology, Vietnam National Children's Hospital
2.1.4 Research time
- The study was conducted from October 1, 2016 to December 31,
2019
2.2 Study Methods
Study design:
- Objective 1: Cross-sectional descriptive study
- Objective 2: Longitudinal follow-up study, comparing before and
after treatment
- Objective 3: Descriptive study
Every asthmatic child with or without allergic rhinitis had been
invited to participate in the study four times:
1st time: at the first visit (T0)
2nd time: re-examination after 1 month (T1)
3rd time: re-examination after 3 months (T3)
4th time: re-examination after 6 months (T6)
Healthy children were invited to participate in the study once (T0):
children were examined and measured for airway nitric oxide levels and
respiratory function
2.2.1 Study sample size
- Applying the convenient sampling method: all children qualified
for selection and visited the Department of Immunology - Allergy -
Rheumatology during the study period were invited to participate in the study
Bronchial asthma group with allergic rhinitis
- Sample size for objective 1: Apply the formula to estimate the average index:
n = 2
(X )2
n: number of patients studied
With confidence interval 0,95 (α = 0,05) 2
ε : the relative deviation between the sample parameter and the population parameter, ranging from 0,05-0,5 (0,2-0,3)
S: variance
According to Struben's study, the value of nNO in healthy 6-17 years oldsis 449 ± 115 (ppb)91
1152
n = 1,962 * - = 101 (449x0,05)2
- Sample size for objectives 2 and 3: choose a convenient sample size
- At least 101 children with BA with AR were estimated to participate in the study
Asthmatic children without allergic rhinitis: As the percentage
of asthmatic children without allergic rhinitis is low, we purposefully selected 30 qualified asthmatic children without allergic rhinitis from 6
to 15 years old (22 boys; 8 girls) for the study
Healthy children: we selected 30 healthy children aged from 6 to
15 years old (19 boys; 11 girls) whose parents and they themselves agreed to participate in the study These are children who have regular health check-ups at the Vietnam National Children's Hospital
2.2.2 Study Steps Step 1: Selecting patients for the study (T0)
Patients visiting the National Children's Hospital for medical examination were asked about their illness, clinically examined, and tested to confirm the diagnosis of bronchial asthma (with and without accompanying allergic rhinitis)
Asthmatic children and their parents were interviewed for assessment of pre-treatment asthma control according to GINA criteria
Trang 7and ACT questionnaire, and asthmatic children with allergic rhinitis
were interviewed with a CARATkids questionnaire
Patients were appointed for blood count tests, IgE, respiratory
function measurement (CNHH), FeNO, nNO, prick test with respiratory
allergens
The healthy children were measured CNHH, FeNO, nNO
Step 2: Bronchial asthma was treated according to GINA 2016,
allergic rhinitis to ARIA 2008
Step 3: Re-examination, assessment of asthma control - allergic
rhinitis and adjustment of preventive medicine
- Time of re-examination:
After 1 month of treatment (T1), After 3 months of treatment (T3) After 6 months of treatment (T6)
- Clinical examination, checking for treatment adherence and
spraying method
- Interviewing the asthma control tables according to GINA, ACT
and CARATkids (for athmatic children with allergic rhinitis)
- Measuring FeNO, nNO and CNH
- Adjusting asthmatic prophylaxis according to GINA 2016
guidelines and allergic rhinitis controller according to ARIA 2008
Step 4: Input and process data
2.3 Data collection methods
2.3.1 General information and related factors
Ask and do a physical exam to gather the following information:
- Age
- Gender: male, female
- Weight and height
- BMI by age and sex
- Age of onset of wheezing
- Age at diagnosis of asthma
- Exposure to tobacco smoke
- Personal and family allergy history
- Level of asthma control according to GINA 2016
- Level of asthma control according to the ACT scale
- Control asthma and allergic rhinitis according to the CARATkids
scale
2.3.2 Paraclinical indicators
- Checking the blood count using automatic counter Sysmex
XN-3000 Quantifying IgE in blood by Cobus 6000 Prick testing with respiratory allergens using allergen preparations made by Stallergenes - France
- Measuring the respiratory function and testing for bronchial rehabilitation by KOKO device made in the US Measuring FeNO and nNO by HYPAIR FeNO of Medisoft, Belgium
2.4 Data processing The collected data was coded in a unified form; entered and analyzed using SPSS 16.0 software; suitable statistical algorithms were used
2.5 Study ethics Comply with the study ethics The study has been approved by the Ethics Committee of Hanoi Medical University, the Decision No 101/HĐĐĐHYHN
CHAPTER 3 STUDY RESULTS
- During the study period, there were 124 children with asthma and allergic rhinitis, 30 asthmatic children without allergic rhinitis and 30 healthy children aged from 6-15 years old who were eligible to participate
in the study
3.1 Characteristics of nasal nitric oxide in children with bronchial asthma having allergic rhinitis
*Nasal nitric oxide concentrations in children with asthma and allergic rhinitis, asthma without allergic rhinitis and healthy children
Trang 8The nNO concentration in children with BA-AR was 1594.5 (104 -
3674) ppb, higher than that in children with BA was 444.5 (105 - 2971)
ppb ((p<0.001), and 1055 (149 - 2090) ppb (p = 0.001) in healthy
children The concentration of nNO in the healthy children was higher
than that in group BA without AR, but the difference was not
statistically significant with p=0.053
* Area under the ROC curve of nasal nitric oxide in children with
asthma and allergic rhinitis
Area under
the ROC curve of nNO 95% confidence intervals Cut-off p
< 0,001
Se = 85,5%; Sp = 66,7%
The diagnostic value of allergic rhinitis in patients with BA with the
area under the ROC curve of nNO was 0.81; with the threshold value nNO =
605.5 ppb, the sensitivity was 85.5%, the specificity was 66.7%, p < 0.001
* Nasal nitric oxide concentration according to severity of allergic rhinitis
All children with BA and AR had high level of nNO In which, the
highest concentration of nNO in those with severe intermittent allergic
rhinitis was 2110 (367 - 3674) ppb and the lowest in those with mild intermittent allergic rhinitis was 1196 (104 - 2546) ppb The difference was statistically significant with p = 0.046
* The relationship between nNO concentration and certain factors
- There was no difference in nNO concentration by age, gender and weight in children with allergic rhinitis
- There was no association between cigarette smoke exposure and nNO concentration
- nNO concentration has a strong positive relationship with FEV1 (p = 0.01), FEV1/FVC (p = 0.02) and FeNO (p < 0.001)
3.2 Asthma control in children with asthma and allergic rhinitis
* Changes in average number of times using SABA per month
- The average number of times using SABA in a month in BA and
AR group decreased from 3.25 times to 1.70 ± 1.61 times after 1 month
of treatment, 1.03 ± 1.08 times after 3 months of treatment and 1.01 ± 1.26 times (p<0.001) after 6 months of treatment
* Changes in respiratory function during preventive treatment in children with asthma and allergic rhinitis
Values of repiratory function parameters
Before treatment (n=124)
X ± SD
1 month after treatment (n=97)
X ± SD
3 months after treatment (n=84)
X ± SD
6 months after treatment (n=77)
X ± SD
p
FVC 92,2 ± 18,4 98,6 ± 12,3 97,5 ± 13,3 96,8 ± 11,4 0,057 FEV1 85,6 ± 16,0 94,9 ± 12,7 93,8 ± 13,9 92,2 ± 12,2 0,007 FEV1/FVC 93,2 ± 10,4 96,9 ± 7,9 97,2 ± 7,9 96,2 ± 10,1 < 0,001 FEF25-75 70,3 ± 19,4 82,6 ± 17,9 83,1 ± 21,2 83,3 ± 20,1 < 0,001 PEF 67,7 ± 16,3 76,1 ± 13,0 78,1 ± 16,6 78,1 ± 16,2 < 0,001 All indicators of respiratory function improved with time of preventive treatment
* Results of asthma control in children with bronchial asthma and allergic rhinitis
- According to GINA, the number of children with well controlled asthma after 1 month is 45.4%; 65.5% after 3 months and 67.5% after 6 months, p<0.001
Trang 9- According to the ACT scale, the rate of asthma well controlled
after 1 month was 89.7%, 96.4% after 3 months and 96.1% after 6
months, p < 0.001
- According to the CARATkids scale with reference value of
Amaral et al (2017): the rate of well asthma and allergic rhinitis control
increased from 49.5% after 1 month of treatment to 66.2% after 6
months of treatment The rate of uncontrolled asthma and allergic
rhinitis decreased from 82.2% to 15.5% after 1 month of treatment;
5.2% after 6 months of treatment, p < 0.001
- According to FeNO concentration, the rate of asthma completely
controlled after 1 month, 3 months and 6 months of treatment was
61.8%, 78.6% and 76.6% respectively, 37.9% higher than before
treatment, p<0.001
* Cut-off point of CARATkids in uncontrolled asthma group after 1
month of treatment
Area under the curve 95% confidence intervals Cut-off p
Se = 100,0%; Sp = 79,8%
With CARATkids = 4.5 points, this limit was to define
uncontrolled asthma in children with asthma and allergic rhinitis; with
area under the curve of 0.957, the sensitivity was 100%, the specificity
was 79.8%, p < 0.001
* Changes in airway nitric oxide levels after asthma and allergic
rhinitis controls
- FeNO concentration before treatment was 29.8 ppb, and it was
decreased to 14.7 ppb after 6 months of preventive treatment, p<0.001
- The median nNO concentration decreased from 1592 (106 - 3302) ppb before treatment to 769 (100 - 2673) ppb after 6 months of treatment, p < 0.001
3.3 Asthma phenotype in chidlren with bronchial asthma and allergic rhinitis
* Asthma phenotype according to severity of allergic rhinitis
Characteristics
Severity of Allergic Rhinitis
p Mild AR
(n = 47)
Moderate-Seveve
AR (n = 77) FEV1 (%) (X ± SD) 87,7 ± 13,9 84,3 ±17,1 0,24 FEV1/FVC (%) (X ± SD) 93,1 ± 9,5 93,3 ± 10,9 0,89
Quantity of BCAT (BC/µl)
ICS dose (µg/day) (X ±
Number of patients after 6
ICS dose (µg/day) (X ± SD) after 6 months 267,7 ± 158,7 238,5 ± 123,5 0,63 SABA (X ± SD) after 6
FEV1 (%) (X ± SD) after 6
FEV1/FVC (%) (X ± SD) after 6 months 95,0 ± 10,2 96,7 ± 10,1 0,44
AR was divided into 2 groups: mild AR and moderate - severe AR The concentration of FeNO in asthmatic group with moderate-severe AR was higher than that in the group with mild AR, p < 0.001 The rate of well asthma control according to ACT was lower in the asthmatic group with moderate-severe AR, p < 0.05 The concentration of nNO, the number of eosinophils, the dose of ICS in the group with mild AR tended to be lower than in the group with moderate - severe AR After 6 months of preventive
Trang 10treatment, the group with moderate-severe AR had a higher average number
of SABA adminstration in a month (p = 0.02)
* Asthma phenotype according to nasal nitric oxide concentration
Characteristics
nNO
p
<605 ppb (n=18)
≥605 ppb (n=106) FEV1 (%) (X ± SD) 80,6 ± 16,1 86,4 ± 15,9 0,19
FEV1/FVC (%) (X ± SD) 91,1 ± 9,8 93,6 ± 10,5 0,28
Quantity of BCAT (BC/µl)
IgE in blood (IU/ml) (median) 390,4 910,6 0,002
ICS dose (µg/day) (X ± SD) 347,2 ± 125,4 318,0 ± 123,9 0,36
Number of patients after 6
ICS dose (µg/day) (X ± SD)
after 6 months 300,0 ± 158,1 239,9 ± 131,3 0,25
SABA (X ± SD) after 6 months 1,0 ± 1,33 0,57 ± 1,32 0,36
FEV1 (X ± SD) after 6 months 87,0 ± 14,3 93,0 ± 11,8 0,34
FEV1/FVC (X ± SD) after 6
Classification of asthma phenotypes by nNO showed that the group
with nNO concentration < 605ppb had lower FeNO concentration (p =
0.009), lower number of eosinophils (p = 0.03) and IgE concentration (p =
0.002) compared with the group with nNO concentration ≥ 605ppb There
was no difference in the results of asthma control according to ACT between
the 2 groups before treatment However, the indicators FEV1, FEV1/FVC
improved markedly after 6 months of preventive treatment
* Asthma phenotype according to FEV1 values
<80 % (n=38) 80-90 % (n=37) >90% (n=49) FVC (%) (X ± SD) 79,6 ± 25,2 91,8 ± 8,3 102,2 ± 9,7 <0,001 FEV1/FVC (%)
(X ± SD) 86,5 ± 11,1 93,7 ± 8,3 98,0 ± 8,4 <0,001
IgE in blood (IU/ml)
Number of eosinophils
ACT ≥ 20 (%) 9 (23,7) 13 (35,1) 27 (55,1) 0,01 ICS dose (µg/day)
(X ± SD) 390,5 ± 127,4 332,6 ± 124,5 262,0 ± 88,6 < 0,001 Number of patients
ICS dose (µg/day) (X ± SD) after 6 months
277,2 ± 155,2 270,8 ± 125,9 201,4 ± 117,0 0,07
SABA (X ± SD) after
FEV1 (%) (X ± SD) after 6 months 88,5 ± 13,2 90,7 ± 12,7 96,9 ± 9,6 0,031 FEV1/FVC (%)
(X ± SD) after 6 months
93,6 ± 11,6 97,4 ± 9,5 97,5 ± 9,0 0,29 FEV1 was divided into 3 groups, the group with normal FEV1 (>90%), the group with slightly decreased FEV1 (80-90%) and the group with clearly reduced FEV1 (<80%) The group with clearly reduced FEV1 had the lowest FeNO and nNO (p = 0.06 and p = 0.03), and this group also had a higher demand for ICS treatment than the other 2 groups (p < 0.001) Before treatment, the rate of well controlled asthma by ACT in the group with clearly reduced FEV1 (<80%) was lower than that of the other two groups (p = 0.01) After 6 months of treatment, the group with low FEV1 had a higher average number of SABA administraton (p = 0.04) and a lower FEV1 indicator (p =