In this population-based longitudinal study, we demonstrated that Taiwanese children exposed to higher concentrations of THC, NMHC, and CH4 were at increased risk of developing AD, regardless of adjustment for potential confounding factors such as age, sex, monthly income, and urbanization level. Our cohort study also revealed a clear dose-response relationship between air pollution and AD. Overall, the current study is distinctive in several respects. First, we assessed the real-world data from the Children’ s file. Children, one of the most susceptible subgroups of the population due to their immature systems, are undoubtedly more vulnerable to the health effects of air pollution than adults . Second, our AD diagnosis was confirmed precisely by the physician, so the potential for selection bias was minimized. Third, in order to identify the dermatologic effect of a single component, our study could be one of the first to investigate the relationship between AD and an active greenhouse gas, CH4.
Taiwan is located in east Asia, the most polluted region of the world, and is now facing severe air pollution, especially in major urban areas, owing to the rapid increase in population and industrial development, as well as transportation demands . While the number of children with AD continues to increase in both developed and developing countries, the prevalence of AD in Taiwan appears to have grown dramatically over recent decades . According to the Taiwan National Study 2000 to 2007, the overall eight-year prevalence of AD is approximately 6.7%, and has roughly doubled since then . Due to such rapid growth in the number of AD cases with increased urbanization and industrialization, the role of environmental factors, especially airborne pollution, has drawn increasing attention. Over the past ten years, a number of studies have shown that air pollutants, such as PM, TRAP, VOCs, and ETS, are associated with the development and exacerbation of AD. Multiple comprehensive studies have been conducted in the pediatric age group with a large data set. For example, in a French study enrolling 4,907 children who had resided at their current addresses for 3 years or longer, lifetime AD was significantly associated with 3-year averaged concentrations of PM10, NO2, NOx, and CO (adjusted ORs 1.13, 1.23, 1.06, and 1.08, respectively,) . In a Munich prospective birth cohort study including 2,860 children at four years of age demonstrated that NO2 exposure (per 6.4 mg/m3) was associated with both physician-diagnosed AD and parental reports of symptoms for AD (OR 1.18 and 1.11, respectively,) . In a cross-sectional study during 2011-2012 in Shanghai enrolling 3,358 preschool children indicated that positive correlation between increased gestational and lifetime exposures to a mixture of SO2, NO2 and PM10 during total lifetime and childhood AD (ORs 1.78, and 1.87, respectively) . In a US National Survey of Children’s Health, 91,642 children found that moderate to severe eczema was associated with elevated levels of NO3 and PM2.5 (OR 1.249 and 1.070, respectively,) . A few studies also revealed that prenatal exposure to VOCs and ETS are likely to induce a TH2-dominant immune status or the development of AD after birth [25-27]. In our study, we found that the adjusted HRs for AD increased with the THC (from 1.65 to 10.6), NMHC (from 1.14 to 2.47), and CH4 (from 1.70 to 11.9) exposure concentrations compared with those exposed to the corresponding concentrations in Q1 level.
Rapid industrialization coupled with urbanization has led to accumulated global waste production because of the continuously increasing demand for energy. Hydrocarbons, organic chemical compounds consisting of hydrogen and carbon, form the basis of the majority of global energy production by fossil fuel combustion and evaporation of gasoline. Both NMHC and CH4 are composed of THCs. Most hydrocarbons on earth naturally occur from the decomposition of organic matter in petroleum and are generated by human activity. NMHCs, often referred to as VOCs, are unstable forms of substances, such as benzene and their derivatives.
A great number of animal and epidemiological studies have disclosed negative effects of VOCs on skin barrier function. A prospective study in Korea revealed that a 1-ppb increase in outdoor benzene and total VOC concentration were associated with, respectively, 27.38% and 25.86%, respectively, in AD symptoms . Kim et al. also found that exposure to airborne formaldehyde leads to an increase in TEWL and stratum corneum pH both in healthy and AD groups . A rat model of AD conducted by Han et al. showed that formaldehyde exposure aggravated pruritus and skin inflammation. These results suggest that formaldehyde penetrated the injured skin barrier and exacerbated Th1 responses and serum IgE levels in the AD rats . Certain VOCs and polycyclic aromatic hydrocarbons (PAHs) in several previous studies have been proposed to activate the ligand-activated transcription factor AhR, leading to downstream activation of inflammation and itch mediators such as artemin [29, 30]. CH4, a nontoxic greenhouse gas, is scarcely reported for other adverse health effects of direct exposure, except for high concentrations leading to suffocation. Our study first identified that CH4 exposure contributes to an increased risk of AD development. One possible reason for this might be that the extra production of CH4 from rapid industrialization and urbanization contributes to the higher potential for pathogen transmission . Microbial superinfection leads to an exacerbation of AD .
Although our study was a large-scale and population-based cohort, there were still several limitations. First, although AD is a complex and multifactorial disorder, we did not consider other environmental factors, including temperature, humidity, and ultraviolet light that might interact with airborne pollutants. Besides, other potential risk factors for AD, such as atopic family history, dietary factors, pet and prenatal exposure, and even severity of AD could not be estimated in this study due to the lack of information in the children’s files. Thirdly, according to our results, a total of 7304 children (2.96%) were diagnosed with AD during the study period. The relatively low prevalence might be attributable to the medical records we chose as our database. Patients with mild AD may neither seek medical services nor be coded for the clinical diagnosis of AD by a physician. In other words, our study population was considerably representative of moderate-to-severe AD presentation of intense itching and relapsing eczematous skin lesions for more than six months. Finally, we did not investigate indoor air pollution in our study because children have greater participation in the home environment .