|Year : 2018 | Volume
| Issue : 1 | Page : 11-15
Air pollution as a risk factor for increasing hospitalizations of preschool wheeze in Hong Kong
Ka-Ka Siu1, Chin-Pang Wong1, Rachel Shui-Ping Lee1, Jack Pak-Yeung Chan1, Shuk-Yu Leung1, Eric Yat-Tung Chan1, Ka-Li Kwok1, Ada Yuen-Fong Yip1, Rupert Phillips2, Daniel Kwok-Keung Ng1
1 Department of Paediatrics, Kwong Wah Hospital, Hong Kong SAR, China
2 Brighton and Sussex Medical School, Brighton, UK
|Date of Web Publication||5-Apr-2018|
Department of Paediatrics, Kwong Wah Hospital, Hong Kong SAR
Source of Support: None, Conflict of Interest: None
Background: Wheeze has been reported to affect one-third of preschoolchildren. While different wheeze patterns have been shown to predict future asthma risk, limited data are available on the risk factors for preschool wheeze in Asia. Methods: Preschool children admitted to hospitals through emergency departments for wheeze, from 2004 to 2015 in Hong Kong, were retrospectively identified. Potential risk factors for admissions over the same period were retrieved (i.e., air pollutants, preterm delivery, and maternal age). Results: A total of 46,258 patients meeting the inclusion criteria were identified during the 12-year period. The preschool wheeze admission rate increased by 34% over the past 12 years, with an average year-on-year rise of 4.2%. Environmental nitrogen dioxide (NO2) concentration was significantly associated with an increase in admission for preschool wheeze (r = 0.63, P = 0.028). Univariate regression analysis was performed on potential risk factors. Annual average NO2concentration (P = 0.007) and maternal age more than 40 years (P = 0.012) were significant risk factors. For multivariable regression analysis, annual average NO2concentration (β = 0.18, 95% confidence interval = 0.06–0.30) was the only independent factor associated with preschool wheeze admission. Conclusions: The increase of NO2concentration is a significant risk factor for the increase in hospitalizations for preschool wheeze in Hong Kong.
Keywords: Bronchiolitis, pollutants, wheezing
|How to cite this article:|
Siu KK, Wong CP, Lee RS, Chan JP, Leung SY, Chan EY, Kwok KL, Yip AY, Phillips R, Ng DK. Air pollution as a risk factor for increasing hospitalizations of preschool wheeze in Hong Kong. Pediatr Respirol Crit Care Med 2018;2:11-5
|How to cite this URL:|
Siu KK, Wong CP, Lee RS, Chan JP, Leung SY, Chan EY, Kwok KL, Yip AY, Phillips R, Ng DK. Air pollution as a risk factor for increasing hospitalizations of preschool wheeze in Hong Kong. Pediatr Respirol Crit Care Med [serial online] 2018 [cited 2021 Feb 27];2:11-5. Available from: https://www.prccm.org/text.asp?2018/2/1/11/229319
| Introduction|| |
Preschool wheeze in children aged 6 years or below is a heterogeneous disorder, including asthma, acute bronchitis, and acute bronchiolitis. It was reported to occur in one-third of all preschoolchildren, and there was a rising trend in different countries., Several birth cohort studies classified wheeze by temporal phenotypes.,,
In 2008, the European Respiratory Society Task Force  proposed classifying wheeze by symptoms into episodic viral wheeze (EVW) and multiple triggered wheeze (MTW). In EVW, the child wheezes only at the time of viral upper respiratory tract infection and is symptom free between viral colds. In MTW, the child wheezes at the time of viral colds, also between colds, for example, with excitement, aeroallergen, cold, and smoke exposure. Different patterns of preschool wheeze may have long-term implications on lung function and development of asthma.,,
Preschool wheeze in children was reported to occur in 33% of children aged 1–6 years. In the UK, Kuehni et al. reported a significant increase in wheeze admission from 1990 (6%) to 1998 (10%), while Green et al. reported an average of 1.8% per year rise for bronchiolitis in infants from 2005 to 2014.
Various risk factors were reported to be associated with preschool wheeze in previous studies, including climate factors such as temperature, rainfall, relative humidity, air pollution index,, frequency of preterm deliveries, and maternal age.
Prematurity was investigated in a recent meta-analysis of 147,000 European children, investigating the association of gestational age (<37 weeks), birth weight (<2500 g), and infant weight gain with childhood asthma outcomes. It was shown that preterm births were largely associated with preschool wheeze and asthma. Another known risk factor for preterm birth, advanced maternal age, was also studied, as preterm births are more likely among teen mothers and mothers ≥40 years of age. In 2013, 16% of preterm births were from mothers aged 40 to 44 years and 25% of preterm births were from mothers ≥45 years old. Particulate matter (PM10) and nitrogen dioxide (NO2) were reported to be associated with wheeze/asthma in children aged 2–18 years.
The aim of this study was to investigate the trend of preschool wheeze requiring hospitalization and to identify the significant risk factors.
| Methods|| |
Study design and patients
This was a retrospective review that utilized data from the Clinical Data Analysis and Reporting System (CDARS), an information system with analytical and reporting capacities, to support the analysis of clinical data for research in the Hong Kong Hospital Authority. It incorporated data including diagnoses, procedures performed, and drug data for all patients admitted to public hospitals, which accounted for 80% of hospital admissions in Hong Kong. Patients aged 0–6 years, with diagnoses of bronchiolitis, asthma, bronchitis, or wheeze, were included in the study from 2004 to 2015.
Since there is no International Classification of Diseases, Ninth Revision (ICD-9) code for preschool wheeze, admission data for children aged 0–6 years, with bronchiolitis (ICD-9 code 466), asthma (ICD-9 code 493), bronchitis (ICD-9 code 490, 491.20, 491.21), and wheeze (ICD-9 code 786.07), were retrieved for the study period from 2004 to 2015 from CDARS. For comparison, data for febrile convulsion admission during the study period were also retrieved to see if there was any change in admission policy.
The total number of admissions and the yearly admission rate per 1000 preschoolchildren were retrieved. Trend of hospital admissions for preschool wheeze was studied against potential risk factors, i.e., NO2, sulfur dioxide (SO2), PM10, maternal age, and preterm delivery, in Hong Kong from 2004 to 2015.
Data on preterm deliveries (gestation <36 weeks) were obtained from the Annual Obstetric Reports of the Hong Kong Hospital Authority. Data on maternal age were obtained from the Hong Kong Census and Statistics Department. Pollutants' data, i.e., the yearly average of NO2, SO2, and PM10, were obtained from Hong Kong Environmental Protection Department. Pollutants' data were obtained from three roadside monitoring stations throughout Hong Kong. The monitoring technique was certified by the Hong Kong Laboratory Accreditation Scheme.
Statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Inc., Armonk, NY, USA). The annual number of patients admitted for preschool wheeze was reported. Linear regression analysis was used for analyzing the trend of significance. Univariate linear regression analysis was performed to identify the potential risk factors for preschool wheeze emergency admission. Multivariable linear regression analysis was performed to identify the independent risk factors that had P < 0.2 in the univariate analysis. Variables were selected for inclusion in the final models with the use of a step-wise selection process. The data were used to investigate the correlation between each of the pollutants and emergency admissions using bivariate correlation. For all analyses, P < 0.05 was considered statistically significant.
| Results|| |
A total of 46,258 patients meeting the inclusion criteria were identified during the 12-year period. Admission for preschool wheeze rose significantly from 9.9/1000 preschoolchildren in 2004 to 19.1/1000 preschoolchildren in 2013, an increase of 93%. The average year-on-year rise was 6.2%. This was a significant rising trend, P = 0.001 [Figure 1]. Admissions for preschool wheeze fell from 2013 to 2015 from 19.1 to 13.3/1000 preschoolchildren. Overall, the preschool wheeze admission rate increased by 34% over the past 12 years, with an average year-on-year rise of 4.2%.
|Figure 1: Emergency admission rate for preschool and febrile convulsion versus NO2. *P < 0.05.|
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In comparison, febrile convulsion admission over the same period (2004–2015) in the same age group showed no significant change in trend (P = 0.797). Univariate regression analysis was performed on potential risk factors [Table 1]. Annual average NO2 concentration (P = 0.007) and maternal age more than 40 years (P = 0.012) were significant risk factors. For multivariable regression analysis, annual average NO2 concentration (β = 0.18, 95% confidence interval [CI] = 0.06–0.30) was the only independent factor associated with preschool wheeze admission [Table 1]. The correlation between NO2 and preschool wheeze emergency admission was significant, r = 0.63, P = 0.028 [Figure 2]. The rise and fall of preschool wheeze admission mirrored that of NO2[Figure 1].
|Table 1: Risk factors for emergency preschool wheeze admission by linear regression analysis|
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|Figure 2: Correlation between preschool wheeze admission rate and NO2 (2004–2015), *P < 0.05.|
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| Discussion|| |
This study looked at the risk factors for the increase in hospital admission for preschool wheeze in Hong Kong. Compared with other countries, the preschool wheeze admission rate in Hong Kong at 13.3/1000 children was lower than that in Canada (23–42/1000). This could be related to ethnic differences. A study performed in the United States showed that ethnic minority children (Blacks, Hispanics) with preschool asthma were twice as likely to have wheeze compared with Caucasian after controlling for disease severity, access to care, and environmental factors. The difference in ethnic origin may account for the difference in admission rates between Hong Kong and North America. Other possible factors accounting the differences included socioeconomic status, household smoking, allergens' exposure, and damp housing. These factors could not be identified in our study due to its retrospective design. Our study demonstrated a significant rising trend of preschool wheeze admission in Hong Kong. Preschool wheeze hospitalizations increased significantly from 9.9/1000 in 2004 to 19.1/1000 in 2013 and fell to 13.3/1000 in 2015. The only risk factor identified was environmental NO2. There was biological explanation for our findings. NO2 was demonstrated to cause formation of excessive amount of reactive oxygen species in airways and in experimental animals, leading to tissue inflammation and cell death. Oxidative stress has been linked to clinical phenotypes such as asthma and atherosclerosis.
Several studies demonstrated the effect of NO2 on childhood respiratory diseases. NO2 exposure was associated with lifetime asthma and wheeze among children with allergic disease in Toronto. A dose–response association was observed between asthma symptoms and self-reported exposure to truck traffic in the Phase 3 International Study of Asthma and Allergies in Childhood, representing more than 500,000 children across the globe. In addition, high traffic-related air pollution exposure at birth was significantly associated with both transient and persistent wheezing phenotypes (adjusted odds ratio [aOR] =1.64; 95% CI = 1.04–2.57 and aOR = 2.31; 95% CI = 1.28–4.15, respectively); exposure from birth to 1 year and 1–2 years was also associated with persistent wheeze in birth cohort of 762 children in Greater Cincinnati, Ohio, United States. Outdoor concentrations of traffic-related air pollutants (NO2, PM2.5, and soot) were found to be associated with asthmatic symptoms during the first 4 years of life in a birth cohort study of 4000 children. There was also a consistent positive association between PM10 and SO2 with the prevalence of wheeze and bronchodilator use in children aged 6–12. Our study demonstrated NO2 to be positively associated with preschool wheeze hospitalization in Hong Kong. During the study period, the Government of Hong Kong initiated a program of low sulfur fuel for vehicles and ships since 2008 and 2015, respectively, which resulted in a significant drop of NO2 since 2013.
Contrary to the literature, the current study did not show prematurity as a risk factor for preschool wheeze and it might be due to the fact that preterm delivery was also related to NO2. In view of the significant rising trend of preschool wheeze hospitalization and its significant association with higher NO2 levels, it seems to be reasonable for government to continue targeting NO2 in the next phase of clean air campaign in Hong Kong. For example, the UK Government will end the sale of all new conventional petrol and diesel cars and vans by 2040, in order to cut NO2 emission. Preschool wheeze was reported to be associated with emergency asthma admission for the school-age group, and the current results might predict a subsequent surge in asthma admission for school-age children when the preschool wheeze children got older if the current downward trend for NO2 did not continue. More importantly, the current study predicted a similar increase for preschool wheeze in China in the following year because China witnessed a fourfold increase in car ownership in the past decade.
This study had two limitations. First, we only included patients with wheeze severe enough to be admitted to public hospitals in Hong Kong. Patients who attended private hospitals for wheeze could not be traced and children with wheeze managed in the outpatient setting were not included. Second, this was a retrospective study and only limited number of risk factors for wheeze could be obtained. Further prospective studies are warranted to assess the relationships of preschool wheeze and other risk factors, i.e., presence of older siblings, day-care attendance, family history of atopy, maternal smoking, environment tobacco exposure, viral infection, and incense burning.
| Conclusions|| |
There was a 93% increase of emergency preschool wheeze admission from 2004 to 2013. The increase of NO2 concentration is the significant risk factor for this increase. Therefore NO2 should remain the main target of the clean air campaign in Hong Kong so as to ensure a continuous decline in preschool wheeze admission.
We thank Professor Andrew A. Colin, MD, Division of Pediatric Pulmonology, Miller School of Medicine, University of Miami, Miami, Florida, for advice on study presentation; Mr. FW Leung, Records and Death Documentation Office of Kwong Wah Hospital; the Hong Kong Census and Statistics Department; Ms. C Sing, Departmental Operations Manager of Obstetrics and Gynaecology Department, Kwong Wah Hospital, for support on data retrieval.
Financial support and sponsorship
This work was financially supported by the Tung Wah Group of Hospitals' Research Fund 2014/2015.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, et al.
Definition, assessment and treatment of wheezing disorders in preschool children: An evidence-based approach. Eur Respir J 2008;32:1096-110.
Ducharme FM, Tse SM, Chauhan B. Diagnosis, management, and prognosis of preschool wheeze. Lancet 2014;383:1593-604.
Peroni DG, Piacentini GL, Bodini A, Boner AL. Preschool asthma in Italy: Prevalence, risk factors and health resource utilization. Respir Med 2009;103:104-8.
Taussig LM, Wright AL, Holberg CJ, Halonen M, Morgan WJ, Martinez FD, et al.
Tucson children's respiratory study: 1980 to present. J Allergy Clin Immunol 2003;111:661-75.
Savenije OE, Granell R, Caudri D, Koppelman GH, Smit HA, Wijga A, et al.
Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA. J Allergy Clin Immunol 2011;127:1505-2.e14.
Collins SA, Pike KC, Inskip HM, Godfrey KM, Roberts G, Holloway JW, et al.
Validation of novel wheeze phenotypes using longitudinal airway function and atopic sensitization data in the first 6 years of life: Evidence from the Southampton women's survey. Pediatr Pulmonol 2013;48:683-92.
Kusel MM, de Klerk NH, Kebadze T, Vohma V, Holt PG, Johnston SL, et al.
Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol 2007;119:1105-10.
Sly PD, Boner AL, Björksten B, Bush A, Custovic A, Eigenmann PA, et al.
Early identification of atopy in the prediction of persistent asthma in children. Lancet 2008;372:1100-6.
Martinez FD. Development of wheezing disorders and asthma in preschool children. Pediatrics 2002;109:362-7.
Kuehni CE, Davis A, Brooke AM, Silverman M. Are all wheezing disorders in very young (preschool) children increasing in prevalence? Lancet 2001;357:1821-5.
Green CA, Yeates D, Goldacre A, Sande C, Parslow RC, McShane P, et al.
Admission to hospital for bronchiolitis in England: Trends over five decades, geographical variation and association with perinatal characteristics and subsequent asthma. Arch Dis Child 2016;101:140-6.
Sung RY, Chan RC, Tam JS, Cheng AF, Murray HG. Epidemiology and aetiology of acute bronchiolitis in Hong Kong infants. Epidemiol Infect 1992;108:147-54.
Park M, Luo S, Kwon J, Stock TH, Delclos G, Kim H, et al.
Effects of air pollution on asthma hospitalization rates in different age groups in metropolitan cities of Korea. Air Qual Atmos Health 2013;6:543-51.
Cai J, Zhao A, Zhao J, Chen R, Wang W, Ha S, et al.
Acute effects of air pollution on asthma hospitalization in Shanghai, China. Environ Pollut 2014;191:139-44.
Sonnenschein-van der Voort AM, Arends LR, de Jongste JC, Annesi-Maesano I, Arshad SH, Barros H, et al.
Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children. J Allergy Clin Immunol 2014;133:1317-29.
Esposito S, Galeone C, Lelii M, Longhi B, Ascolese B, Senatore L, et al.
Impact of air pollution on respiratory diseases in children with recurrent wheezing or asthma. BMC Pulm Med 2014;14:130.
Jones R, Lin S, Munsie JP, Radigan M, Hwang SA. Racial/ethnic differences in asthma-related emergency department visits and hospitalizations among children with wheeze in buffalo, New York. J Asthma 2008;45:916-22.
Mielck A, Reitmeir P, Wjst M. Severity of childhood asthma by socioeconomic status. Int J Epidemiol 1996;25:388-93.
Strachan DP, Cook DG. Health effects of passive smoking 6. Parental smoking and childhood asthma: Longitudinal and case-control studies. Thorax 1998;53:204-12.
Fisk WJ, Lei-Gomez Q, Mendell MJ. Meta-analyses of the associations of respiratory health effects with dampness and mold in homes. Indoor Air 2007;17:284-96.
Persinger RL, Poynter ME, Ckless K, Janssen-Heininger YM. Molecular mechanisms of nitrogen dioxide induced epithelial injury in the lung. Mol Cell Biochem 2002;234-235:71-80.
Chuang KJ, Chan CC, Su TC, Lee CT, Tang CS. The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. Am J Respir Crit Care Med 2007;176:370-6.
Dell SD, Jerrett M, Beckerman B, Brook JR, Foty RG, Gilbert NL, et al.
Presence of other allergic disease modifies the effect of early childhood traffic-related air pollution exposure on asthma prevalence. Environ Int 2014;65:83-92.
Brunekreef B, Stewart AW, Anderson HR, Lai CK, Strachan DP, Pearce N, et al.
Self-reported truck traffic on the street of residence and symptoms of asthma and allergic disease: A global relationship in ISAAC phase 3. Environ Health Perspect 2009;117:1791-8.
Brunst KJ, Ryan PH, Brokamp C, Bernstein D, Reponen T, Lockey J, et al.
Timing and duration of traffic-related air pollution exposure and the risk for childhood wheeze and asthma. Am J Respir Crit Care Med 2015;192:421-7.
Brauer M, Hoek G, Smit HA, de Jongste JC, Gerritsen J, Postma DS, et al.
Air pollution and development of asthma, allergy and infections in a birth cohort. Eur Respir J 2007;29:879-88.
Roemer W, Hoek G, Brunekreef B. Effect of ambient winter air pollution on respiratory health of children with chronic respiratory symptoms. Am Rev Respir Dis 1993;147:118-24.
Lavigne E, Yasseen AS 3rd
, Stieb DM, Hystad P, van Donkelaar A, Martin RV, et al.
Ambient air pollution and adverse birth outcomes: Differences by maternal comorbidities. Environ Res 2016;148:457-66.
Air Quality Plan for Nitrogen Dioxide (NO2) in UK (2017). Department of Environment, Food and Rural Affairs and Department of Transport; 26 July, 2017. https://www.gov.uk/government/publications/air-quality-plan-for-nitrogen-dioxide-no2-in-uk-2017. [Last accessed on 2018 Feb 13].
Yu PT, Chan JY, Poon F, Lee RS, Leung SY, Ng JP, et al
. The predictive factors in preschool wheezers for subsequent asthma hospitalization after the age of 6 years. Pediatr Respirol Crit Care Med 2017;1:11-6. [Full text]
[Figure 1], [Figure 2]