Pollutants such as PM2.5 are polluting the environment seriously, causing numerous health problems[23]. Many time-series studies have used PM2.5 as an exposure indicator[24]. However, HFMD hospitalization caused by PM2.5 has been little reported so far. To our knowledge, the topic of the clinic demographic features by the LOS is scarce in Chinese children. Long LOS will not only seriously reduce the turnover rate of scarce bed resources in the hospitals and reduce the throughput of patients, but also increase the financial burden on the families of children[25, 26]. Analyzing the LOS of HFMD is important for hospital administrators to formulate countermeasures, improve hospital work efficiency, and control excessive medical expenses. Therefore, we described the clinic demographic features and the LOS of HFMD in children's hospital of Nanjing medical university during 2012–2017 in Nanjing, China. Meanwhile, we conducted the relationship between the exposure of PM2.5 and its components and the LOS of HFMD.
The incidence of HFMD in China has been reported to be 1-2 per 1,000 people[27]. In our research, the incidence of hospitalized HFMD peaked in children aged 1 year and then decreased with age, over 98% of hospitalized HFMD cases occur in children younger than 6 years of age, which was consistent with the findings in other studies[28–30]. Therefore, measures must be taken to prevent HFMD in these key population groups. There was a difference in gender-specific hospital admission, the same results were reported in previous study[31–33], Although infection rates between males and females are comparable, males are more likely to develop symptoms, more involved in the propagation of outbreaks, and more likely to be brought in for medical care than females[30], the reason for the differences observed in gender is not known exactly. The cases of hospitalized HFMD tended to arise in the warmer season (summer and autumn) of the year. Nanjing has strong sunshine, high temperature and heavy rainfall in summer and autumn, and it has a more serious greenhouse effect. We estimate the sunshine, temperature and humidity might explain the seasonality of HFMD[34, 35].
The cases of hospitalized HFMD were the highest in 2013, and then slightly decreased from 2014 to 2017, especially in 2017, the number of hospitalized HFMD was the lowest. The promulgations of the guidelines for HFMD can reduce the number of inpatients through standardized diagnosis and treatment in outpatient. Meanwhile, the guidelines introduce measures for personal protection, family protection, kindergarten or school prevention and management, thus reducing the incidence of hand foot and mouth disease[36]. EV71 infections are one of the main etiological agents of HFMD, on December 2015, the China Food and Drug Administration (CFDA) approved the first inactivated EV71 whole virus vaccine for preventing severe HFMD. EV71 vaccination could decrease HFMD incidence significantly among children aged two to five years[37]. In children, the EV71 vaccine elicited EV71-specific immune response, less EV71-associated HFMD cases have been observed. One real-world study provided evidence of EV71 vaccine effectiveness for preventing EV71 and "other" viruses associated with HFMD[38].
In our research, most of inpatient children with HFMD were hospitalized for less than 7 days, followed by 7 to 14 days, and few were hospitalized for more than 14 days. Children aged 1 year, illness onset in summer and 2012 were most likely to be hospitalized for more than 14 days. In 2012, the number of inpatient children with HFMD exceeded 14 days was the largest, followed by 2013 and 2014, then it decreased significantly since 2015, which was related to the gradual improvement of the diagnosis and treatment of HFMD. The number of children hospitalized for more than 14 days in summer may be related to the increase of nosocomial infections caused by high temperature and high humidity in summer[39]. The number of children hospitalized for more than 14 days is also higher in aged 1-6 than that of other age groups. In terms of hospitalization management, more attention should be paid to these individuals.
Previous studies showed that PM2.5 has a higher influence on hospital admission than other air pollutants[40]. PM2.5 was positively associated with LOS among children[41]. There was a short-term increase in hospital admission rates associated with PM2.5 for all of the health outcomes except injuries[42]. Our study showed that short-term exposure to PM2.5 was positively associated with the LOS of HFMD. Our findings were broadly consistent with those studies[16, 43]. It has been demonstrated that exposure to PM2.5 could adversely affect vascular endothelial function, the activity of the sympathetic nervous system, and systemic inflammation, leading to vasoconstriction, increased plasma viscosity, and a risk of blood clotting and thrombosis[44]. These adverse effects can exacerbate the child’s symptoms, therefore increase the LOS of HFMD.
In addition, in our research, SO42− was the most significantly associated component of PM2.5 with the LOS of HFMD followed by NH4+, SOIL, NIT and BC. SO42− and NH4+ were the secondary pollutants and mainly concentrated in power plants dust, motor vehicle exhaust and construction dust, generally higher values were found during summer and spring months. SO42− is mostly regionally transported in the summer, various studies have linked sulfate exposure with adverse respiratory and cardiovascular effects, as well as mortality[17].
The BC component of PM2.5 consists of soot, charcoal, char, and other light absorbing refractory matter. Although the health impacts of BC have been extensively studied[17, 45], its association with HFMD is not as well characterized. In Nanjing, we found an expected association between BC exposure and the LOS of HFMD, our research has enriched the epidemiological information on the health impacts of BC on HFMD. NIT is mainly a secondary particle found in the atmosphere, unlike the adverse health effects of BC exposure, NIT exposure have been less explored [46].
The SS originate Cl−, Na+, and Mg2+ and is variable during winter months because of unsettled weather conditions in winter season[47], in our study, the cases of hospitalized HFMD tended to arise in the warmer season. The OM is a highly complex mixture of hundreds of compounds such as organic carbon, polycyclic aromatic hydrocarbons, alkanes, and fatty acids, but the health effects of OM remain largely uncharacterized, we did not find the association between OM exposure and the LOS of HFMD, these findings need to be further confirmed.
Our study had advantages. We focused on the epidemiologic features of the LOS of HFMD in the Chinese population and the relationship between the exposure of PM2.5 and its components and the LOS of HFMD. This is a topic that has not received much attention and will provide a basis for hospital management. PM2.5 exposure is associated with the increased LOS of HFMD, and its components (BC, SO42−, NH4+, NIT and SOIL) of PM2.5 might play a key role in the prolonged LOS of HFMD. Our findings call for greater awareness of environmental protection and the implementation of effective measures to improve the quality of air, which may reduce the risks of adverse effects on children. Policy changes to reduce outdoor air pollutant exposure may lead to improved HFMD outcomes and substantial savings in healthcare spending.
Our study had limitations. Some covariates are unmeasured, such as the socioeconomic and educational status of the parents. Although our observational study was completed in a representative city in China and lasted for 7 years, the sample size included is still relatively small, and larger sample size is needed to support the research results. In our study, we focus on PM2.5, other air pollutants such as nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) might also contribute to the LOS of HFMD.