|Year : 2023 | Volume
| Issue : 1 | Page : 20-25
Virus infection and severe asthma exacerbations: A cross-sectional study in Children’s Hospital 1, Ho Chi Minh City, Vietnam
Thuy Van Thao Nguyen1, Tuan Anh Tran2, Vu Thuong Le3, Kien Gia To4
1 Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam; Department of General Internal Medicine 2, Children’s Hospital 1 at Ho Chi Minh City, Vietnam
2 Department of Respirology, Children’s Hospital 1 at Ho Chi Minh City, Vietnam
3 Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam; Department of Respiratory, University Medical Center at Ho Chi Minh City, Vietnam
4 Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam
|Date of Submission||16-Jan-2023|
|Date of Decision||03-Mar-2023|
|Date of Acceptance||08-Mar-2023|
|Date of Web Publication||07-Apr-2023|
Prof. Kien Gia To
Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang, District 5, Ho Chi Minh City
Source of Support: None, Conflict of Interest: None
Context: Virus infection is a well-known risk factor for asthma exacerbations in temperate and subtropical countries, particularly in atopic children. However, the risk has not been well-described in tropical countries including Vietnam. Aims: To compare the odds of virus infection in hospitalized children with severe versus moderate asthma exacerbations. Settings and Design: A cross-sectional study was conducted at Children’s Hospital 1, Ho Chi Minh City, Vietnam. Children who were admitted to the hospital and diagnosed with severe or moderate asthma exacerbations were recruited for the study. Materials and Methods: Data were collected from interviews and medical records. Virus infection was confirmed by multiplex real-time polymerase chain reaction. Inhalant allergy was confirmed by a skin prick test with common indoor aeroallergens. Statistical Analysis Used: Associations among age, gender, passive smoking, child’s history of eczema, family history of asthma, virus infection, and inhalant allergy with the odds of severe asthma exacerbations were tested by binary logistic regressions. Multivariable logistic regression was done to measure the association between virus infection with the odds of severe asthma exacerbations adjusted for passive smoking. The odds ratio (OR) and its 95% confidence interval (CI) were reported to show the strength of the associations. Results: Nearly half of the children were infected by a virus (48.5%) and had passive smoking (49.2%). The percentage of children with a positive skin prick test was 83%. The most common indoor aeroallergen was house dust mites (81.1%). The odds of severe asthma exacerbations in children with virus infection was three times higher than that in those without virus infection (OR: 3.21, 95% CI: 1.20‐8.60, P = 0.021). Conclusions: Immunization and other healthcare programs should be deployed to prevent asthmatic children from virus infection and passive smoking to reduce the risk of severe asthma exacerbations.
Keywords: Asthma exacerbations, hospital-based study, inhalant allergy, viral infection
|How to cite this article:|
Nguyen TV, Tran TA, Le VT, To KG. Virus infection and severe asthma exacerbations: A cross-sectional study in Children’s Hospital 1, Ho Chi Minh City, Vietnam. Pediatr Respirol Crit Care Med 2023;7:20-5
|How to cite this URL:|
Nguyen TV, Tran TA, Le VT, To KG. Virus infection and severe asthma exacerbations: A cross-sectional study in Children’s Hospital 1, Ho Chi Minh City, Vietnam. Pediatr Respirol Crit Care Med [serial online] 2023 [cited 2023 May 29];7:20-5. Available from: https://www.prccm.org/text.asp?2023/7/1/20/373839
| Key Messages:|| |
Virus infection increases the odds of severe asthma exacerbations.
| Introduction|| |
Asthma causes 5.1 million disability-adjusted life years among children aged 1‐19 years globally. Acute respiratory virus infection is the most common trigger of asthma exacerbations, accounting for 60%‐95% of pediatric asthma exacerbations in temperate and subtropical countries.,, Children with atopic asthma, the most prevalent type of childhood asthma, have a high risk of a virus-induced asthma exacerbation., However, the prevalence of virus infection as well as an association between virus infection and asthma exacerbations in tropical countries such as Vietnam has not been well-described. Therefore, the study was conducted to measure the odds of virus infection in inpatients with severe compared to those with moderate asthma exacerbations at Children’s Hospital 1, Vietnam.
| Subjects and Methods|| |
Study design and sample
The study was conducted at Children’s Hospital 1, a tertiary pediatric hospital, located in Ho Chi Minh City (HCMC) from July 2020 to April 2021. HCMC is the biggest city in the south of Vietnam with a tropical climate and 9 million inhabitants. It has two seasons including rainy (from May to November) and sunny (from December to April). The average temperature is 26.8‐27.3°C with a high humidity (64.5%‐85.9%) year-round. The study was approved by the Ethics Committee of University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam (Approval Number: 218/IRB-VN01002).
A researcher screened medical records of children at the time of admission for eligibility. Parents of eligible children were approached and explained the purpose of the study and persuaded to allow their children to join the study. If they agreed, they were asked to sign the consent forms before data were collected. All eligible children were consecutively recruited to the study to ensure a ratio of one severe to five moderate asthma exacerbations.
Children were included if they were 3‐15 years old, admitted to the hospital due to a moderate or severe asthma exacerbation, and their parents allowed them to join the study and receive both multiplex real-time polymerase chain reaction (mqPCR) and a skin prick test (SPT). An asthma exacerbation was identified based on a history of wheezing (at least two episodes of wheezing were applied to under-6-year-old children) related to airflow obstruction, which responded well to asthma rescue medication without other causes of wheezing., According to the Global Initiative for Asthma 2010 guideline, a severe asthma exacerbation was determined if a patient had at least two of the following signs including breathless at rest, talking in words, severe retractions of accessory muscles and peripheral oxygen saturation (SpO2) <92%. A moderate asthma exacerbation was determined if a patient had two of the following signs including breathless at talking, talking in phrases, moderate retractions of accessory muscles, and SpO2 92%‐95%. Children, who have neurologic, metabolic, or genetic diseases, chronic pulmonary diseases other than asthma, cardiopathy, or immuno-suppression, were excluded from the study.
Data collection and tool
Age, gender, passive smoking, family history of asthma, and child’s history of eczema were collected from interviews and cross-checked with medical records. Passive smoking was defined as a child inhaling smoke from family members daily. Child’s history of eczema was yes if the child’s parents confirmed that the child was diagnosed by a physician. Family history of asthma was yes if parents confirmed that they or the child’s siblings were diagnosed with asthma by a physician. mqPCR and SPT were performed by accredited laboratories following the standard procedures. Results were read by qualified microbiologists and allergists.
Detection of acute respiratory virus infection
All eligible children were taken nasopharyngeal swabs within 24 h of admission by a well-trained doctor following a standard protocol. All the specimens were placed in dedicated tubes stored in the fridge and then transferred to the micrology laboratory for the detection of respiratory viruses. A validated mqPCR assay and KingFisher™ Flex CFX-96 system were used to detect adenovirus, respiratory syncytial virus, influenza virus (A, B, C), parainfluenza virus (1, 2, 3), human metapneumovirus, enterovirus, human coronavirus, bocavirus, and human rhinovirus. The mqPCR has a sensitivity of 99.5% and specificity of 83.7% and is routinely used to diagnose etiologies of respiratory infection. The virus-positive specimen was coded as “pathogen positive.” Co-infection was defined as the presence of at least two pathogens in the specimens.
Detection of inhalant allergy
An SPT was used to diagnose children’s inhalant allergy. Its specificity and sensitivity were 70%‐95% and 80%‐97%, respectively. The participants’ thorough history and physical examination were taken before the procedure. The children were eligible for the SPT if they had stable asthma and did not use antihistamines or systemic corticosteroids within the previous week. The indoor allergen extracts, which included Dermatophagoides pteronyssinus, Dermatophagoides farinae, cockroach, cat, and dog dander, were used in the SPT. An allergen was positive if its wheal diameter was larger than 3 mm compared to that of the negative control.
Data were entered using Microsoft Excel 2010 (Redmond, Washington) and analyzed using IBM SPSS Statistics 24.0 (Armonk, New York). Age was described as mean and standard deviation (SD). Gender, child’s history of eczema, family history of asthma, passive smoking, virus infection, and inhalant allergy were described as frequency and percentage.
Chi-squared test was used to test the association between demographic, clinical, and laboratory characteristics with the odds of severe asthma exacerbations compared to moderate asthma exacerbations. Model 1, a binary logistic regression, was used to measure the associations between variables including age, gender, child’s history of eczema, family history of asthma, passive smoking, virus infection, and inhalant allergy with the odds of severe asthma exacerbations. The odds ratio (OR) and its 95% confidence interval (CI) were calculated to show the strength of the associations. A P value of 0.20 was used to select variables for a multivariable logistic regression. A P value of 0.05 was considered statistically significant.
| Results|| |
There were 224 records approached and screened for eligibility. Of these, 132 children satisfied the inclusion and had no exclusion criteria, including 23 severe and 109 moderate asthma exacerbations. The mean age of 132 children was 6.25 years (SD 2.64), ranging from 3 to 13.2 years old. A logistic regression showed that age was not associated with severe asthma exacerbations (P = 0.627). The percentage of preschool asthma was 51.5% in the whole sample, 53.2% in children with moderate asthma exacerbations and 43.5% in children with severe asthma exacerbations. Chi-squared test showed no significant difference in the percentage of preschool-aged children between moderate and severe groups (P = 0.396).
Male represented 62.1% of the sample, 62.4% of moderate asthma exacerbations, and 60.9% of severe asthma exacerbations. The percentage of children having a family history of asthma was 9.8% and parental history of asthma was the most common among these children. Compared to children with moderate asthma exacerbations, those with severe asthma exacerbations had no significant difference in gender (P = 0.892), child’s history of eczema (P = 0.336), and family history of asthma (P = 0.571).
Passive smoking was 49.2% in the sample, 45.9% in children with moderate asthma exacerbations, and 65.2% in those with severe asthma exacerbations. No significant difference was observed in passive smoking between the two groups (Chi-squared test, P = 0.092) [Table 1].
|Table 1: Demographic, clinical, and laboratory characteristics of the asthmatic children in the sample (N = 132)|
Click here to view
The children with virus infection are more prone to develop severe exacerbations than those without virus infection.
The percentage of nasopharyngeal specimens positive for any assayed virus was 48.5%, of which 94% were infected by one type of virus. The percentage of virus infection in the severe group was significantly higher than that in the moderate group (69.6% vs. 44%, P = 0.03).
The percentage of children having inhalant allergy was 82.6%. House dust mites were the most common (81.1%), followed by cockroach (24.2%), cat dander (9.8%), and dog dander (9.8%). Of those children who were allergic to house dust mites, D. farinae and Dermatophagoides pteronyssinus accounted for 93.5% and 90.7%, respectively. The percentage of asthmatic children having inhalant allergy was not different between moderate and severe groups (81.7% vs. 87%, P = 0.542). However, the percentage of children having both virus infection and inhalant allergy was significantly different between those with moderate asthma exacerbations and those with severe asthma exacerbations (34.9% vs. 60.9%, P = 0.02).
[Table 2] shows that the odds of severe asthma exacerbations in children with virus infection was 2.9 times higher than that of those without virus infection in a binary logistic regression (OR: 2.91, 95% CI: 1.11–7.63, P = 0.03). The adjusted OR (aOR) was 3.21 times higher in the multivariable logistic regression adjusted for passive smoking (aOR: 3.21, 95% CI: 1.20‐8.60, P = 0.02).
|Table 2: Binary and multiple logistic regression measure associations between exploratory variables with the severity of asthma exacerbations (N = 132)|
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| Discussion|| |
This study found that virus infection increased the odds of severe asthma exacerbations in asthmatic children with a moderate or severe asthma exacerbation admitted to a hospital that was consistent with previous evidence. The potential mechanism for this link is related to an upward expression of specific receptors of respiratory viruses such as intercellular adhesion molecule-1 in airway epithelium, deficient, and delayed innate antiviral immune responses, and destruction of the epithelium by cytokines and chemokines derived from responses to allergens.,, Apart from this, synergic impact of acute respiratory virus infection and inhalant allergy on asthma exacerbations was explained by the interaction between high-affinity IgE receptors “FcεRI” as well as anti-virus immune modulation, resulting in excessive inflammatory response., A previous study showed that the combination of virus infection and allergic sensitization increased the risk of hospital admission due to asthma exacerbations. Our study did not find any association of this combination, but virus infection was found to act as an independent risk of severe asthma exacerbations in the multivariable logistic regression. Further studies with bigger sample sizes should be conducted to clarify the association.
This study found that nearly 50% of asthmatic children were infected by a virus. This percentage was reported at 61.7% of Canadian children aged 1‐17 years, 92.2% of Australian children aged 2‐16 years., It may be partially related to different climates among regions. Our study was conducted during COVID-19 pandemic. Thus, good habits including washing hands more frequently, wearing masks, and social distancing probably contributed to a lower prevalence of acute respiratory infection.
Human rhinovirus has been found to be the major cause of asthma exacerbations in children older than three in some studies. However, the underlying mechanism remains uncertain. Immune dysregulation via aberrant immune responses, both deficient and exaggerated, as well as a viral affinity for specific receptors required for infection of airway cells, have been proposed as a mechanism for human rhinovirus-induced asthma exacerbations. Our study was unable to confirm whether human rhinovirus infection increases the odds of severe asthma exacerbations in asthmatic children, which was consistent with Merckx’s study. The Vietnam National Pediatric Hospital reported that the concentration of Th2-related cytokines, a biomarker of human rhinovirus infection, was higher in children with severe asthma exacerbations compared to those with mild or moderate asthma exacerbations. Another study conducted in Australia found that children with human rhinovirus infection had higher asthma severity scores than those without respiratory virus infection.
Indoor aeroallergens were found to increase the risk of severe asthma exacerbations in children with inhalant allergy. However, the association between inhalant allergy and severe asthma exacerbations was not significant in our study even though most of our children were sensitive to indoor aeroallergens. It is worth noting that the percentage of children having both virus infection and inhalant allergy was significantly higher in children with severe asthma exacerbations compared to those with moderate asthma exacerbations. These findings were consistent with Merckx’s study.
Half of our asthmatic children were at preschool age which was consistent with a previous study of the Children’s Hospital 1. It was reported that preschool children in the United Kingdom had the highest rate of asthma exacerbations. A significant increase of peripheral airway resistance was observed in asthmatic children, particularly during asthma exacerbations. The airway resistance is remarkably stronger in preschool children compared to older children. In addition, recent evidence showed that variants in cadherin-related family member 3 may increase the risk of severe asthma exacerbations in children aged 2–6 by altering the integrity of airway epithelium, thus promoting entry and replication of viruses. However, age was not associated with the odds of severe asthma exacerbations in this study.
Our study had some limitations. Firstly, the study was conducted at one hospital with a small sample size; therefore, the findings should be cautiously extrapolated to a more general population. Secondly, data were collected cross-sectionally, and time order of the association between virus infection and severe asthma exacerbation is questionable. The odds of severe asthma exacerbations was underestimated because the study did not include children with mild asthma exacerbations or stable asthma.
In conclusion, among children with a severe or moderate asthma exacerbation admitted to the Children’s Hospital 1 in Ho Chi Minh City, Vietnam, half of them had respiratory virus infection. The odds of severe asthma exacerbations was three times higher in children with virus infection compared to those without virus infection. Healthcare programs such as immunization and/or tobacco controls should be considered and focused on asthmatic children to reduce the severity of asthma exacerbations. Vaccines other than influenza viruses should be developed to prevent asthmatic people from virus infection thus reducing the risk of severe asthma exacerbations.
Doctors and nurses of the Department of Respirology and Department of General Internal Medicine 2, Children’s Hospital 1, Ho Chi Minh City, Vietnam should be thanked for their supports in enrolling participants and collecting data for the study. Children and their parents should be thanked for attending the study.
Financial support and sponsorship
Conflicts of interest
The authors declare no conflicts of interests.
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[Table 1], [Table 2]