key: cord-0018551-xfgzbn2g
authors: Li, Xiang; An, Shu-Jie; Liu, Xiao-Ling; Ji, Ai-Ling; Cao, Yi; Xiang, Ying; Ma, Xiang-Yu; Hu, Qin; Yuan, Zhi-Quan; Li, Ya-Fei; Lu, Yuan-Gang; Cai, Tong-Jian
title: The Association Between Short-Term Air Pollution Exposure and Post-Adolescent Acne: The Evidence from a Time Series Analysis in Xi’an, China
date: 2021-06-25
journal: Clin Cosmet Investig Dermatol
DOI: 10.2147/ccid.s320248
sha: 2d3e93fac476f7f9a4aacb624d365ac835d79071
doc_id: 18551
cord_uid: xfgzbn2g

BACKGROUND: Post-adolescent acne is a common skin disease faced by adults. However, whether air pollution (AP) serves as a risk factor for post-adolescent acne remains elusive. AIM: To determine the relationship between short-term AP exposure (within 7 days) and outpatient visits for post-adolescent acne. METHODS: Daily outpatient visit data for post-adolescent acne and routinely AP data between 2010 and 2013 were collected from Xi’an, China. A generalized additive regression model was used to analyze the relationship between outpatient visits for post-adolescent acne and short-term ambient AP exposure. The gender-specific analyses were conducted as well. RESULTS: Totally, 27,190 outpatient visits for post-adolescent acne were included. The results revealed that a 10 μg/m(3) increase in PM(10), SO(2), and NO(2) at lag 0–7 day was associated with the increase of outpatient visits for post-adolescent acne at 0.84% (95% CI: 0.53%, 1.16%), 1.61% (95% CI: 0.12%, 3.10%), and 3.50% (95% CI: 1.60%, 5.40%), respectively. The significant positive associations of PM(10), SO(2), and NO(2) were found at both single-lag models and moving average models. The gender-specific analyses showed that the effect estimates of PM(10) was stronger for females than for males, while there was no observed gender difference in the effects of SO(2) and NO(2). CONCLUSION: Short-term exposure to AP was associated with increased outpatient visits for post-adolescent acne, especially for females in the effects of PM(10).

Acne vulgaris, an inflammatory disease of the pilosebaceous follicles, has been traditionally considered a common skin disease for teenagers. 1 In recent years, the number of adults affected by new-onset acne or persistent acne is gradually rising. 2, 3 Approximately 61.9% of populations in the United States 4 and 41% of female individuals in France 5 were found to be affected by acne during their adulthood. It results in with lower qualities of life and negative psychosocial conditions for patients. 6, 7 Especially, acne of adults over 25 years of age is generally defined as postadolescent acne, which is considered to be a particular subtype of acne differing from adolescent acne. 8 It mainly occurs in females with mild-to-moderate severity. In addition, compared with adolescent acne, post-adolescent acne has more inflammatory lesions and less comedones. 9 Moreover, unlike adolescent acne, which always appears on the forehead, nose, and upper cheeks, post-adolescent acne predominantly occurs on the chin, jawline, and neck. 9 Many factors have been thought to be associated with the risk of acne, such as smoking habits, 10 body mass index (BMI), 11 genetic factors, 12, 13 and cosmetics, 14 etc. Recent studies stressed that air pollution (AP) has adverse impacts on people's health, especially cardiovascular and pulmonary systems. [15] [16] [17] [18] [19] [20] [21] [22] Some studies also take AP's effects into consideration of the induction and aggravation of acne, because AP could contribute to hyper-seborrhea and hyper-sebum, both of which have been found to be prevalent in acne lesions. [23] [24] [25] [26] [27] [28] However, given that the clinical features of postadolescent acne, including the vulnerable population, the degree of inflammation, and the primary parts of bodies, were different from those of adolescent acne, the risk factors reported for acne are necessary to be reclassified and reidentified for both adults and teenagers. 29 Attention should also be paid to the epidemiological evidence regarding the effect of AP on post-adolescent acne.

In this study, time-series analyses were conducted to investigate the association between outpatient visits for postadolescent acne and daily AP in Xi'an, a northwestern Chinese city with relatively heavy AP. Subgroup analyses were also carried out to investigate the potential gender difference in such association.

Daily outpatient visit data for post-adolescent acne between 1 October 2010 and 31 December 2013 were obtained from Xijing Hospital in Xi'an, a northwestern Chinese city with an area of 10,108 km 2 and a population of over 8 million in 2014. 30 It has distinct climate fluctuations with four seasons. The medical services of Xijing Hospital are accessible seven days a week. The diagnosis of acne vulgaris (ICD-10: L70) was defined by dermatologists according to Andrews' Diseases of the Skin-Clinical Dermatology (11th edition). Both new acne cases and the relapses of previous diagnosed patients whose residential areas were in Xi'an City and whose ages were over 25 years old were included. The informed consent of patients was not obtained because there was no individual interaction with patients. In addition, the Ethics Committee of Third Military Medical University (Army Military Medical University) approved this study, and the protocols complied with the Declaration of Helsinki.

AP data between 1 October 2010 and 31 December 2013 were acquired from the Environmental Monitoring Center of Xi'an, including particulate matter less than 10 μm in aerodynamic diameter (PM 10 ), sulfur dioxide (SO 2 ), and nitrogen dioxide (NO 2 ). The daily (24-h) mean concentrations were used as metrics of AP exposures, which were calculated by averaging hourly data across 13 monitoring stations covering Xi'an. The data of daily mean temperature and daily relative humidity during the study period were obtained from the local meteorological bureau.

Firstly, the descriptive analyses were performed to characterize the basic information of outpatient visits, AP data, and meteorological data. The generalized additive model (GAM) was conducted to investigate the association between daily AP and outpatient visits for postadolescent acne because daily outpatient visits followed quasi-Poisson distribution. In such models, the outpatient visits of post-adolescent acne were included as the dependent variable, while daily AP, temperature, and relative humidity were included as independent variables. The formula used for the analyses and the choosing of degrees of freedom (df) were described in detail in our previous studies, 31, 32 and the formula was as follows:

Gender-specific analyses were also conducted by Z-test. The estimated differences between gender subgroups were shown by the estimates of differences between groups and their 95% confidence intervals (95% CIs). Analyses were performed using the "mgcv" package in R 3.6.0 (http://www.r-project.org). The results were presented as the percentage increase of outpatient visits for post-adolescent acne with a 10 μg/m 3 increase of PM 10, SO 2 , and NO 2 per day. P-values less than 0.05 (P<0.05) were considered statistically significant. Table 1 shows demographic information of daily outpatient visits and environmental factors. Totally, 27,190 outpatient visits for post-adolescent acne were recorded, including 7,587 males and 19,603 females. The average daily outpatient visits were 22.9. During the period, the daily mean concentrations of PM 10 , SO 2 , NO 2 were 142.6 µg/m 3 , 44.7 µg/m 3 , and 48.5 µg/m 3 , respectively. The average daily temperature was 14.3°C and relative humidity was 62.4%. In Figure 1 , the time series of outpatient visits, air pollutants, and meteorological factors were shown. The outpatient visits for post-adolescent acne were increasing over time, especially those for female patients. AP was more severe during winter, and there were minor peaks of outpatient visits in the same period. The temperature had a significant undulation period over the year, which was higher during summers. However, the relative humidity showed no apparent seasonal trend.

In Figure 2 , the correlations between AP and daily post-adolescent acne outpatient visits in single-lag days (lag 0 to lag 7) and cumulative exposure days (lag 0-1 to lag 0-7) were shown. In single-lag models, the positive association was evidenced from lag 0 to lag 3 and at lag 6 for PM 10 , at lag 3 for SO 2 , and from lag 0 to lag 3 for NO 2 . In cumulative exposure models, both PM 10 and NO 2 showed significant positive associations with outpatient visits for post-adolescent acne from lag0-1 to lag 0-7, while SO 2 had such associations from lag 0-4 to lag 0-7. To be specific, every 10 μg/m 3 increase of PM 10 , SO 2 , and NO 2 was associated with the increase of outpatient acne visits at 0.84% (95% CI: 0.53%, 1.16%), 1.61% (95% CI: 0.12%, 3.10%), and 3.50% (95% CI: 1.60%, 5.40%) at lag 0-7 day, respectively. In gender-specific analyses, the significant association between PM 10 and female outpatient visits for post-adolescent acne was observed from lag 0 to lag 6 and from 0-1 to lag 0-7, but no significant association was found for males, suggesting that females were more susceptible than males. The results of Z-test also showed that the association of PM 10 was stronger in females than in males at lag 0-6 and lag 0-7 (Table S1 ). For NO 2 , the significant positive association was evidenced in both males and females. As for SO 2 , the significant positive association was only observed at lag 1 for males and at lag 0-7 for females. Thus, PM 10 , SO 2 and NO 2 concentrations were positively associated with the outpatient visits for post-adolescent acne, and the estimate effects of PM 10 were stronger in females. Figure 3 illustrates the exposure-response curves between air pollutants and outpatient-visits for postadolescent acne at lag 0-7 day. The relationships of both PM 10 and NO 2 were inverse S-shaped in the curves. Specifically, the association of PM 10 was linear when the concentrations were above 200 µg/m 3 or below 100 µg/ m 3 , with no observed lower-and upper-bounds. Interestingly, the relationship turned to be flat when PM 10 levels ranged from 100 µg/m 3 to 200 µg/m 3 . For NO 2 , the linear relationship was observed when the concentrations were above 70 µg/m 3 or below 40 µg/m 3 , with no observed lower-and upper-bounds. The relationship turned to be flatter when the its levels ranged from 40 µg/m 3 to 70 µg/m 3 . Compared with those of PM 10 and NO 2 , the exposure-response curve of SO 2 rose steadily in the entire range of pollutant concentrations, demonstrating its mild but still positive correlation with the risk of postadolescent acne. Table 2 reveals the effects of two-pollutant models (lag 0-7). After adjusting for PM 10 or NO 2 , the effect of SO 2 turned to be statistically insignificant. Moreover, the effect of NO 2 remained robust and statistically significant after adjusting for SO 2 (3.75%, 95% CI: 1.25%, 6.25%), but it turned to be insignificant after adjusting for PM 10 (0.90%, 95% CI: −1.38%, 3.19%). Furthermore, the effect of PM 10 Figure 1 Original plots of outpatients, AP, and meteorological factors over time. (A and B) shows the daily levels of PM 10 , SO 2 , and NO 2 , and the daily outpatient numbers for post-adolescent acne, respectively. (C) shows the monthly average temperature and relative humidity during the study period. increased slightly after adjusting for SO 2 (0.86%, 95% CI: 0.51%, 1.21%), while its effect mildly decreased but still obvious after adjusting for NO 2 (0.76%, 95% CI: 0.38%, 1.14%).

In this study, we provided novel evidence of the relationship between short-term AP exposure and outpatient visits for post-adolescent acne. Through time-series analyses, we found positive associations between outpatient visits for post-adolescent acne and short-term exposure to ambient PM 10 , SO 2 , and NO 2 . In gender subgroup analyses, the associations of PM 10 appeared to be more significant in females than in males. Although acne is typically recognized as an adolescent disorder, a series of studies have reported that the incidence of acne in adults over 25 years old has steadily grown over time. 2, 33, 34 A consistent rise in the outpatient visits for post-adolescent acne also has been found in Xi'an, China during the study period. The reason for such growth was complex and might be attributed to that some lifestyle factors associated with post-adolescent acne such as smoking 35 and western diet 36, 37 are gradually prevalent in adults. 38, 39 However, the outpatient visits for post-adolescent acne exhibited a season variation, peaking in winter and decreasing in summer. Such variation indicated that some factors vary with seasonal fluctuation, such as environmental factors, may also affect the 

incidence and the aggravation of post-adolescent acne. Especially, in the present study, the levels of air pollutants (PM 10 , SO 2 , NO 2 ) also showed season variations, which seem to have the same fluctuations with the outpatient visits for post-adolescent acne. Therefore, it's imperative to investigate the association between post-adolescent acne and ambient AP.

Our study observed an obvious relationship between short-term exposures to PM 10 , SO 2 , and NO 2 and outpatient visits for post-adolescent acne, which was consistent with previous studies investigating the associations between AP and some inflammatory skin diseases. For example, Guo et al 40 suggested that short-term exposure to AP, represented by PM, was significantly related to the outpatient visits for eczema and dermatitis. Li et al 41 found that shortterm elevations of PM 10 , SO 2 , and NO 2 were associated with the increased outpatient visits for eczema. Moreover, Kim et al 42 also indicated that the risk of atopic dermatitis symptoms in young children could be increased with shortterm exposure to PM 10 , NO 2 , and ozone (O 3 ). Such correlations were plausible from a biological perspective: skin, a barrier between internal and external environment, directly contacts air pollutants. Various airborne pollutants can permeate the epidermal barrier, and then trigger skin barrier dysfunction, 43 immune dysregulation, 44 and dermal inflammation. 45 In such processes, the induction of inflammatory cascade, generation of free radicals, activation of AhR (aryl hydrocarbon receptor), and alterations of cutaneous microflora resulted from air pollutants all may be involved in the inflammatory processes and immune responses of post-adolescent acne. 46, 47 Furthermore, our data showed that the association between post-adolescent acne outpatient visits and PM 10 was more evident in females than in males. One possible explanation was that exposure to PM could result in the imbalance of female hormones via interfering with estrogen-regulated pathways. 48, 49 Given that the severity of female acne could fluctuate with hormones in their lifespan, especially in the period of menstruation, pregnancy, and menopause, the irregular changes of hormones affected by AP, especially PM, may further enhance the possibility of the onset and aggravation of post-adolescent acne during female adulthood. 3, 50 This can also, at least partly, explain why post-adolescent acne is more prevalent in females than in males. 34, 51 In another perspective, males and females have physiological, chemical, and biophysical differences in skin. 52 Such gender difference of skin characteristics in terms of stratum corneum hydration, transepidermal water loss, sebum production, and skin thickness may contribute to their dissimilar abilities against environmental stressors, including AP. From this viewpoint, this study indicated that male skin seems to have stronger properties to counteract or prevent against AP-induced skin damages.

Although it is unavoidable for skin to exposure to air pollutants, many anti-pollutant strategies can be taken into consideration to decrease the risk of post-adolescent acne. To begin with, moisturizer can be utilized to accelerate the recovery of skin barrier and prevent contaminants from adhering directly to the skin. 53 Furthermore, oral or topical antioxidants such as vitamin E, 54 and anti-inflammatory drugs such as adapalene and benzoyl peroxide can be conducive to relieve pollution-induced skin oxidation and inflammation. 55 Lastly, governments should make specific policies to control AP and to reduce the exposure levels of air pollutants. [56] [57] [58] [59] This study has several major advantages. Firstly, this study was conducted with a large sample of postadolescent acne outpatients. Secondly, we provided the first evidence that short-term exposure to AP may contribute to the increased risk of post-adolescent acne. Thirdly, this research was conducted in Xi'an, a major metropolis in northwestern China with a considerably large population and relatively heavy pollution.

Nonetheless, this study has several limitations. Firstly, like other similar ecological studies, air pollutant levels from fixed site monitoring stations instead of individual exposure levels were included into the main analysis models, which can lead to exposure errors known as "ecological fallacy". Secondly, the data of other pollutants were not available, including particulate matter less than 2.5 μm in aerodynamic diameter (PM 2.5 ), O 3 , and carbon monoxide (CO). Thirdly, also owing to the limitation of the availability, more confounders which may have potential effects on the relationship between AP and post-adolescent acne were not included for analyses, such as stress status, body mass index, and drug history. 60, 61 Fourthly, our data were only collected from a single hospital, which may make our results less representative of the whole city. Therefore, more work is needed to confirm our results in the future.

In conclusion, short-term air pollution (PM 10 , SO 2, and NO 2 ) exposure was associated with the increased risk of outpatient visits for post-adolescent acne. More interestingly, females were more sensitive to PM 10 than men. This study provided https://doi.org/10.2147/CCID.S320248

Clinical, Cosmetic and Investigational Dermatology 2021:14 novel evidence regarding the relationship between short-term ambient AP exposure and post-adolescence acne, which may have an important bearing on the intervention and prevention of this disease. Abbreviation AP, air pollution; CO, carbon monoxide; DOW, day of the week; df, degree of freedom; GAM, generalized additive model; NO 2 , nitrogen dioxide; O 3 , ozone; PACF, partial autocorrelation function; PM 10 , particulate matter less than 10 μm in aerodynamic diameter; PM 2.5 , particulate matter less than 2.5 μm in aerodynamic diameter; SO 2 , sulfur dioxide.

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We would like to acknowledge the financial supports from the Outstanding Talent 

No potential conflict of interest was reported by the authors.

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