We finished a time-series larger population-based study on the acute effects of ambient air pollution on children's health in Guangzhou city of China. Overall, associations with pneumonia hospital admissions were strongest for CO and NO2. Increments of an IQR (279.10 µg/m3 and 28.42µg/m3 respectively) in the 7-day-average level of CO and NO2 were associated with a 26.17% (95%CI 1.40%-56.98%) and 25.09% (95%CI 0.54%-55.64%) increase in pneumonia hospitalizations for children aged 6-17, respectively. An IQR increase in CO concentrations (279.10 µg/m3) was associated with a 15.15% (95%CI 4.34%-27.08%) increase in pneumonia hospitalizations for children aged 1-5. These results are basically consistent with the previous conclusions which showing children hospital admissions for ARI associated with markers of primary traffic pollutants such as CO or NO2 .
In this study, parts of ambient air pollutions levels were relatively higher than WHO standards, especially in winter. During 2013 and 2018, daily mean PM2.5 levels ranged from 4.61µg/m3 to 155.00µg/m3 which exceeded the WHO guideline value (24-h mean is 25µg/m3) on 1184 days (69.36%), while daily mean PM10 levels ranged from 9.96µg/m3 to 208.29µg/m3 which exceeded recommended levels on 931 days (54.54%). Daily mean CO levels ranged from 479.30µg/m3 to 2610.00µg/m3 which exceeded the WHO guideline value (24-h mean is 2000µg/m3) on 5 days, daily mean NO2 levels ranged from 0.55µg/m3 to 163.25µg/m3 which exceeded the WHO guideline value (24-h mean is 40µg/m3) on 751 days, daily mean SO2 levels ranged from 2.00µg/m3 to 53.00µg/m3 which exceeded the WHO guideline value (24-h mean is 20µg/m3) on 190 days, and daily mean O3 levels ranged from 3.46µg/m3 to 139.21µg/m3 which exceeded the WHO guideline value (8-h mean is 100µg/m3) on 59 days.
Lots of epidemiological and clinical studies indicated that ambient particulate matter (PM) in air pollution was strongly associated with increased cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease and heart disease in urban residents . PM10 could be positively associated with increased pneumonia admissions in children in the dry season . Daily mean PM10 levels were associated with prolonged hospitalizations in children aged 2–5 years in Vietnam . Unexpectedly, we find that the associations between daily mean PM10 levels and pneumonia hospitalizations of children were not statistically significant in all age groups. Although, a study showed positive associations between ARI and both NO2 and PM10 during the dry season 2003-2005 , but the results were not statistically significant given the rather short series and limited statistical power . Another report pointed out that increased acute lower respiratory tract infection admissions in children under 18 were associated with low rainfall but not PM10 nor air pollutant index . So, why are the effects of PM10 completely different in different regions? Is it possible that the effect of PM10 is mainly related to climate factor, immunity and age? Sure, the differences of the effect of PM10 may also be determined by genetic predisposition. We interestingly find that air pollutants might exacerbate genetic variations associated with asthma, including GLUTATHIONE-S-TRANSFERASE M1 (GSTM1) and GLUTATHIONE-S-TRANSFERASE P1 (GSTP1) gene. Among them, GSTP1 modified the delayed effects of PM10 and Consistent with previous studies, early living in polluted atmospheric can damage lung function on an average of 24-h for three days, and enhanced the lung respiratory function of carriers. Individuals carrying G allele could reduce the adverse effects of air pollutant in children of South Africa . The gene expression level of white blood cells in Ostrava area polluted by high PM concentration had been measured. It was found that the cellular immune response pathway was affected by higher PM concentration. The expression of APURINIC/APYRIMIDINIC ENDONUCLEASE (APEX), ATAXIA-TELANGIECTASIA MUTATED (ATM), FAS CELL SURFACE DEATH RECEPTOR (FAS), GLUTATHIONE S-TRANSFERASE MU1 (GSTM1), INTERLEUKIN1 BETA (IL1B) and RAD21 HOMOLOG (Schizosaccharomyces pombe) (RAD21) decreased significantly in Ostrava subjects, and the pathways related to neurodegenerative diseases were significantly correlated with PM2.5 exposure in Prague subjects of the Czech Republic . In addition, there have been relatively few researchers studied on the gene-PM exposure interactions, and most have done on a small number of loci for genetic polymorphisms. The possible underlying molecular mechanisms for PM exposure induced increases of acute lower respiratory infections in children remain the mystery.
About 95% of children in this study population are under 5 years of age. And a larger proportion (e.g. 67.31%) of children are infants. Hence, our results mainly reflect the effects of air pollutants in children under 5 years of age. Generally, the tertiary general hospital has a Pediatric Department in China. But hospital beds for children and the numbers of pediatric doctors are limited almost in all hospitals. Guangzhou is a super city with a population of more than 10 million. Therefore, most children with conditions requiring hospitalization are likely admitted to GDMCHH. Normally, GDMCHH is the most crowded specialist children's hospital in Guangzhou city, and children under 5 years of age are prioritized. And older children are preferably transferred to other local hospitals. Our results showed that the RR was statistically significant only for PM2.5 in infants (RR =0.90, 95%CI 0.82-0.99). And a study findings suggested that parental exposure to PM2.5 could increase infant mortality differently by the timing of exposure and gender, which suggested a relation to fetal development in South Korea . Zwozdziak et al. reported a decrease in lung function parameters with increasing exposure of indoor PM1 in school children . This may be an indication that smaller size PMs induce stronger inflammatory responses, particularly the ultrafine particles that can penetrate deeply into lung alveoli or be transported to other organs [31,32]. These results also suggested that high smaller size PMs exposures might adversely influence both development of the innate immune system and development of lung function of infants. Hence, to protect infancy vulnerability of the rapid lung and immune system development from high levels of air pollution exposure is very important during the early months of life.
Our results demonstrated that the association of CO with hospital admissions due to pneumonia reached statistical significance in children aged 1-5 (RR =1.15, 95%CI 1.04–1.27). And the RR per IQR for CO was higher in the spring (RR=1.60, 95% CI 1.08-2.37). Estimates for CO were statistically significant among children aged 1-5 years in summer. While there was a diametrically opposite conclusion for CO in Hanoi, Vietnam . How to explain this contradiction is a vexed one. Although, daily mean CO levels just exceeded the WHO guideline value on 5 days in Guangzhou during October 28, 2013 to June 30, 2018. But, effects of CO were significantly higher in spring after inclusion of PM2.5, PM10, SO2 or NO2 in children aged 6-17 years.
We find that associations between air pollutants (CO, SO2, NO2 and O3) and pneumonia hospitalizations of children aged 6-17 years were statistically significant in Guangzhou city. Generally, Guangzhou children living in a super city should spend more time for going to schools and coming back home, the primary traffic pollutants concentrations such as PMs, CO or NO2 were the highest during that time. No doubt the timing of air pollutants exposure increased. An investigation showed that acute lower respiratory infection admissions among children under 5 years of age were generally positively associated with ambient levels of PM10, NO2, and SO2 during the dry season, but not the rainy season, and negative results in the rainy season could be driven by residual confounding present from May to October in Ho Chi Minh City, Vietnam . Daily concentration of SO2 was apparently associated with respiratory mortality in Xi’an city . Daily concentrations of CO, NO2, SO2, and PM10 were significantly associated with increased risk of both cardiovascular and respiratory hospital admissions, whereas O3 was associated with only respiratory hospital admission [33, 34]. The observed seasonal difference in hospital admissions is larger than what one expects based on the difference in air pollution alone. The latter is though only one out of many determinants of hospital admissions.
The results of two pollutant models are presented in Fig 2 and additional file 6. Basically, two-pollutant models could be used to evaluate the possible roles of single pollutants. Pneumonia related estimates for NO2 were higher after inclusion of PM2.5 and PM10 in summer and autumn, but stable after inclusion of SO2 and CO. Estimates for CO were statistically significant among children aged 1-5 years in summer. The two-pollutant models revealed consistent patterns across all outcomes luckily as shown in additional file 6.
Another feature of this study is to demonstrate associations between air pollutants and the clinical pathogenic microorganism inspection results in the cases of hospitalization due to pneumonia among Guangzhou children. The clinical pathogenic microorganism inspection results for pneumonia are shown in additional file 7. The detected cases of pulmonary Mycoplasma pneumoniae were the most predominant, accounting for 37.28% of total detected cases of microorganism inspection (TDCMI). The positive rate was the largest in the age group 1-5 years. The positive rate minimized in winter for all kinds of pathogenic microorganisms, except that for Chlamydia pneumoniae and Hemophilus. The Lasso regression model was derived for the daily cases of microbial detection due to pneumonia and air pollutants (lag 0-6), combined with meteorological factors. RCs of daily mean NO2 levels were always positive which indicated that NO2 had significantly positive effects on the daily cases of microbial detection for pneumonia. RCs of daily mean O3 levels were almost positive except for Flu B virus, Chlamydia pneumonia and Adenovirus. While RCs of daily mean SO2 levels were almost negative, except for Adenovirus, which indicated that daily mean SO2 levels had negative effects on the daily cases of microbial detection. We find out that RCs of daily mean PM10 levels were positive for Mycoplasma pneumonia, Parainfluenza virus and Haemophilus, which accounting for 37.27%, 6.65% and 1.62% of TDCMI in children aged 0-17, respectively; the detected cases of these three kinds of pathogenic microorganisms accounted for 45.56% of TDCMI in whole children population. RCs of daily mean PM2.5 levels were both positive for Flu A virus which accounting for 4.61% only in infants and 15.64% among the 1-5 year age group, and Flu B virus which accounting for 10.68% only in infants and 32.60% among the 1-5 year age group; the detected cases of these two kind of pathogenic microorganisms accounted for 25.74%. RCs of daily mean PM10, NO2, CO and O3 levels were positive to Mycoplasdema pneumonia which accounting for 24.89% in infants and 63.36% among the 1-5 year age group simultaneously. RCs of daily mean PM2.5 and NO2 levels were positive to Influenza A and B virus simultaneously. RCs of daily mean O3, PM2.5 and PM10 levels were mainly positive for children less than 5 years-old. RCs of daily mean SO2, NO2 and CO levels were mainly positive for children aged 6-17 years. The pneumonia hospitalizations due to Mycoplasma pneumonia, Flu A virus and Flu B virus in children aged 0-5 are apparently associated with the levels of air pollutants (i.e. PMs, NO2, CO and O3). And pathogenic microorganisms, such as Mycoplasma pneumonia, Flu A virus and Flu B virus, might be possibly carried by PMs, which increased risks of the acute lower respiratory infections in children aged 0-5 years. We fortunately found a study from Urumqi city of Western China, which reported that the microorganisms responsible for human allergy and respiratory disease carried by PM10 and PM1 had been analyzed during winter. Their results showed that the bacterial community was mainly composed of Proteobacteria, Firmicutes and Actinobacteria. The sequences of several pathogenic bacteria and opportunistic pathogens were also detected, such as Acinetobacter, Delftia, Serratia, Chryseobacterium, which might impact on immunocompromised populations (elderly, children and postoperative convalescence patients) . However, to our knowledge, no previous study has studied the association between outdoor air pollutants and daily cases of microbial detection for pneumonia in children. Nowadays, further investigations are warranted.
This study has some limitations. The GDMCHH is the tertiary hospital, children with severe diseases might make up a larger proportion than in other hospitals. No doubt, outpatients were excluded from our study. Therefore, to obtain a more convincing explanation of the effects of air pollutants among children aged 6-17 years, the data from other local tertiary hospitals would be used to analyze. The effect estimates in our model are based on the sample size. If our sample size was large enough, the conclusions should be more accurate.