Transepidermal water loss (TEWL): Environment and pollution—A systematic review

Abstract Introduction Transepidermal water loss (TEWL) is an objective measurement of skin integrity measured as the amount of water lost across the stratum corneum. TEWL varies greatly across variables such as age and anatomic location, and disruptions in the skin barrier have been linked to inflammatory dermatoses such as psoriasis and atopic dermatitis. Impact of environmental conditions and pollution on TEWL has yet to be determined. Accordingly, this review summarizes effects of environmental conditions and pollution on TEWL. Methods A comprehensive literature search was performed using Embase, PubMed, and Web of Science to find human studies that provided data on environmental conditions and/or pollution and TEWL. Results In total, 15 studies were included, with 11 studies examining environmental and seasonal conditions on TEWL and four examining pollution. All studies examining pollution showed increased TEWL in people exposed to particulate matter or NO2. Contradictory results were found on the effects of season and climate across the 11 studies, with no consensus reached. Conclusion Exposure to pollution is reported to cause increases in TEWL, likely through free radical damage. Significant discrepancies exist among current literature as to the effects of season and climate on TEWL. There is a need to continue examining environmental variables other than temperature and relative humidity, such as atmospheric and steam pressure, that may impact TEWL.


| INTRODUCTION
Transepidemal water loss (TEWL) is a measurement that represents the amount of water that escapes from the stratum corneum per area of skin and has historically been used as a reflection of skin water barrier integrity. TEWL measurements are made by placing a probe at the surface of the skin that is able to measure any changes in water vapour density across a determined area of skin over time by sensing changes in local humidity above ambient humidity values. 1 Disruptions in the skin barrier have been linked to increased TEWL values in dermatologic diseases such as psoriasis and atopic dermatitis. 2 TEWL varies greatly between individuals and across anatomical locations as described extensively by Akdeniz et al. 3 Many factors likely contribute to anatomic variation in TEWL values, but increased sweat gland activity at locations such as the forehead compared to the forearm lead to increases in water vapour and TEWL measurements. 4 Additionally, the systematic review by Peer et al. 5 summarised additional factors that may impact TEWL and suggested that age and skin surface temperature may impact TEWL. Given such great variation, it is important to avoid adding to this variation by minimising measurement variation in experimental settings.
An additional factor not yet summarised is the impact of climate on TEWL. Imhof et al. 6 describe how the microclimate between the skin surface and measurement device contribute greatly to measurement accuracy, with rate of evaporation due to skin surface temperature contributing to potential error in measurement without proper calibration. In addition, the temperature of the probe itself can contribute to TEWL values, with higher TEWL values observed with a higher temperature probe. 7 The temperature and climate conditions at time of measurement are important variables that influence TEWL readings, so it is important to consider how chronic exposure to differing climate conditions in humans may affect skin integrity and TEWL values.
Discrepancies exist amongst the literature as to how great an affect environmental conditions such as temperature and relative humidity have on TEWL. Using a climatic chamber to control conditions, it was found that TEWL significantly increased with increasing temperature and decreased with increasing relative humidity. 8 This may explain why TEWL values have often been shown to be higher during summer months (higher temperatures) with skin hydration greatly improved, but seasonal variation in TEWL varies greatly by anatomic location. 9 However, other studies have found contradictory results showing TEWL values to be higher in the nasolabial region during cooler winter months compared to autumn. 10 Thus, it is important to review the effects of climate on TEWL to understand such contradictions.
In addition to climate conditions like temperature and humidity, chronic exposure to air pollution may also contribute to skin barrier disruption. Air pollution and particulate matter cause damage to the epithelial barrier through oxidation of reactive oxygen species. 11 Pollution may also worsen dermatologic conditions such as atopic dermatitis through this oxidative barrier disruption and immune system activation cascades. 12 These mechanisms of skin integrity damage are an important consideration for those living in industrialised regions, and in combination with climate conditions, it may help identify individuals at higher risk for transient increases in TEWL based on geographic location. Thus, our goal is to add to the literature on factors influencing TEWL outlined by Akdeniz et al. 3 and Honari and Maibach 13 and summarise recent literature on how climate and pollution affect TEWL in humans.

| METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were used to guide the methodology and reporting (Figure 1). 14 In September of 2021, a comprehensive literature search was performed using Embase, PubMed, and Web of Science using the terms ('TEWL' or 'transepidermal water loss' or 'trans-epidermal water loss') and ('anatomic variation' or 'regional variation' or 'variation'). Only studies after 2015 were included to add to the existing information presented in previous literature such as that done by Akdeniz et al. 3 and Honari and Maibach. 13 No geographic or language restrictions were employed. The final inclusion criteria included studies: (1) with quantitative data analysing environmental factors or pollution on TEWL, (2) published after 2015, (3) using in vivo human models.
Title and abstract were used as a first pass to screen articles by two researchers (Maxwell Green and Howard I. Maibach). Articles remaining after screening underwent full text review, and articles meeting inclusion criteria were included. The data were extracted from the literature by one researcher (Maxwell Green) and verified by two others (Nadia Kashetsky, Aileen Feschuk). Any discrepancies in data collection were settled by a fourth researcher (Howard I. Maibach). The final data collected reported on significant effects of environmental factors and pollution on TEWL values.

| Study characteristics
In total, 15 studies met all inclusion criteria and were therefore included in review ( Table 1). Majority of studies (n = 11) researched effects of climate condition and seasonal variation including the following variables: seasonal variation (n = 5), indoor humidity (n = 2), daily variation, climate conditions, altitude, geographical location (n = 1 each). Additionally, four studies studied the impact of pollution on TEWL.
What is already known about this topic? � Increases in TEWL have been linked to inflammatory dermatoses such as psoriasis and atopic dermatitis. � Factors such as age and anatomic location have been linked to variation in TEWL values across individuals.

What does this study add?
� This review summarises how both environment and pollution may impact TEWL values across individuals.

| Seasonal variation in TEWL
Five studies examined seasonal variation on TEWL with mixed results. Overall, one study found higher TEWL values in skin during summer conditions compared to other months 16 with one study showing increased TEWL in skin after being exposed to summer conditions. 17 These results are contradicted by two studies that show increased TEWL in spring and winter months compared to summer and fall. 18,19 Finally, one study found TEWL of the forehead was significantly lower during spring months. 20 First, Song et al. 16 examined how skin integrity differed between summer and winter in healthy Korean males. All 100 subjects rested in a room 20-24°C with humidity from 40% to 60% for 30 min. A Tewameter TM300 was then used to make measurements at the forehead, cheek and forearm once in June to reflect summer values and once in January to reflect winter months. The average temperature and humidity in June were 24.9°C and 74.2% respectively. The average temperature and humidity in January were −2.4°C and 59.7% respectively. Results showed significantly higher TEWL values on the forehead during the summer (21.41 � 4.99 g/h/m 2 ) compared to the winter (17.40 � 4.67 g/h/m 2 ), and although summer averages for TEWL were higher at other sites, no significant difference was observed at the cheek and forearm.
Second, Kim et al. 17 found similar results in a cohort of 20 Korean adult women. These subjects rested in a temperature and humidity controlled air-conditioned environment before spending 20 min outside during    18 also examined seasonal variability in TEWL values but found contradictory results to those described above. They recruited 206 healthy Chinese women and measured TEWL values of the forehead during Spring (March-May), Summer (June-August), Fall (September-November), and Winter (December-February). Authors note that winter temperatures in this region remain above 10°C. Subjects rested for 30 min in a room 21 � 1°C with humidity between 45% and 55% before each of the four measurements. A TM300 Tewameter was used to make measurements on the forehead of women at the same time of their menstrual cycle to minimise confounding variables. TEWL values in fall (17.4 � 4.2 g/m 2 /h) and winter (18.2 � 3.8 g/m 2 /h) were significantly higher than summer (9.9 � 3.9 g/m 2 /h) and spring (13.3 � 4.1 g/m 2 /h) with a significant negative association seen between TEWL and both temperature and humidity.
Yang et al. 19 also studied Chinese females examining TEWL variation across seasons; 100 adult women rested for 20 min in a room between 20 and 25°C and 45%-55% humidity. TEWL measurements were made using a Tewameter on the right cheek and right forearm. Measurements were made three consecutive times on each woman on each of the four seasons, with the average being used for results. Results mirrored those found by Wan et al., 18 with higher TEWL values observed in the spring and winter compared to summer and fall on the cheek. No significant trend was observed across seasons at the forearm.
Doleckova et al. 20 performed a similar study on Caucasian women, measuring TEWL during different seasons (Spring n = 85, Summer n = 93, Autumn n = 137, Winter n = 131). TEWL measurements were done after women rested for 30 min in a room 20-22°C with a humidity from 40 to 45; TEWL measurements were made on the forehead and cheek 10 consecutive times, with the average value being used for results. Results showed that TEWL values were significantly lower on the forehead during the spring (12.5 � 2.6 g/h/m 2 ) compared to summer (14.4 � 3.5 g/h/m 2 ), fall (14.1 � 3.3 g/h/m 2 ), and winter (14.2 � 3.2 g/h/m 2 ), with no significant difference seen at the cheek across seasons.

| Indoor humidity
Two studies examined effects of indoor humidity on TEWL. Overall, both studies showed no significant correlation between TEWL and relative humidity.
First, Jin et al. 21 determined how indoor humidity affected skin integrity of both younger and older adults during winter months. They recruited 11 college students and 11 nursing home residents for the study. Both groups followed a typical daily routine, with college students attending class, and the nursing home residents attending activities in their facility. TEWL measurements were made using a Tewameter TM300 at the right volar forearm on four occasions at the dorm halls or nursing facility: a non-intervened day between Feb 20 and Feb 26, an intervention with room humidity at 40%, a non-intervened day between Mar 9 to Mar 12, and an intervention with room humidity at 50%. Results showed no significant correlation between relative humidity of the room and TEWL in either the young or older adults.
Second, Jang et al. 22 also examined how humidity affects skin integrity in a cohort of 11 young women during sleep. The women first slept for greater than 7 h in a room with less than 30% humidity at 20 � 2°; TEWL measurements were made using a Vapometer on the cheek of women, with another measurement being done after five consecutive tape-strippings. These measurements were made before bed, immediately after waking, and after a face wash in the morning. The next night, the process was repeated in the same conditions at greater than 70% humidity. Results showed no significant difference in TEWL measurements between humidity levels. However, after a night in 30% humidity, TEWL was significantly increased after morning face-wash compared to baseline. Overall, both studies showed no significant correlation between TEWL and relative humidity.

| Pollution
Four studies analysed exposure to pollution and all concluded that exposure to either particulate matter or NO 2 can increase TEWL. Overall, one study showed a positive significant relationship between nitrogen dioxide (NO 2 ) exposure and TEWL, and three studies showed a significant relationship between particulate matter (PM) exposure and TEWL. First, Shamsipour et al. 26 recruited 25 participants aged 18-60 years old and followed them from April 2017 to April 2018. At six separate intervals across the study, a TEWAmeter was used to obtain TEWL measurements on subjects on the middle forehead and right upper arm. Then using local air quality data provided by Tehran monitoring stations, average daily exposure to various air pollutants was estimated for each person to calculate values of exposure for the 24 h prior to each of the six measurements or for multi-day averages prior to measurements. The pollutants of interest were PM 10 , PM 2.5 , carbon monoxide (CO), sulphur dioxide (SO 2 ), NO 2 , and ozone (O 3 ). Results showed that exposure to NO 2 showed a significant correlation with increased TEWL of the forehead in measurements 4, 5, and 6 and in the arm at measurements 1, 4, 5, and 6 based on linear models. Kim et al. 27 also looked at how chronic exposure to PM may negatively affect skin integrity in younger and older subjects. They recruited 50 younger women aged 25-35 years and 50 older women aged 55-65 years in an industrial region and compared them to an equivalent control population in Kunming, an area with much less pollution. TEWL measurements were made on the frontal cheek and inner forearm. Although no difference was shown in TEWL values of the cheek, both younger and older women in the industrial region showed significantly higher TEWL values compared to controls on the inner forearm. This suggests that chronic exposure to particulate matter may cause transient increases in TEWL values.
Similar results were observed by Huang et al. 28 in a study conducted that compared urban taxi drivers to rural taxi drivers. Sixty-six rural drivers from Chongming and 100 urban drivers from Shanghai between the ages of 28 and 55 who had been working as a driver for at least 5 years were recruited; after 1 h of the subjects resting in a testing room, TEWL measurements were made on the upper cheek using the Tewameter TM300. Five rounds of tape stripping on this same location were done using D-squame tapes with 225 g/cm 3 of pressure, and another TEWL measurement was done. Following 8 additional tape-strippings, a final TEWL measurement was made. The average TEWL value of the upper cheek was significantly lower in rural drivers (16.5 � 0.4 g/h/m 2 ) compared to urban drivers (18.8 � 0.5 g/h/m 2 ). This difference was shown to only increase after the 13 rounds of tape stripping, supporting the conclusions drawn by the authors that skin exposed to pollution may be more sensitive to physical trauma.
Oh et al. 29

| DISCUSSION
This review summarises the literature effects of climate and pollution on TEWL in humans after 2015 (n = 15 studies), providing an update to factors influencing TEWL in the literature by Akdeniz et al. 3 and Honari and Maibach. 13 Results for the effects of climate conditions and seasonal variation on TEWL values across 11 studies mirror mixed results literature prior to 2015. One study showed increased TEWL during summer months compared to winter, 16 with one additional study showing that TEWL increased in women after they went from indoor air-conditioned environments to outdoor summer weather. 17 However, two additional studies then showed increased TEWL in facial skin during fall and winter months compared to summer and spring months with significant decreases in TEWL with increasing temperature. 18,19 There was some consensus across studies in regard to indoor relative humidity, though, with no significant trend in association with TEWL across two studies.
Discrepancies on the effects of temperature and relative humidity across seasons and geographic locations on TEWL suggest other variables may be affecting TEWL readings. Liu et al. 23 also examined effects of atmospheric pressure and steam pressure and found that TEWL increases with increasing atmospheric pressure and decreases with increasing steam pressure. Very little research has looked more extensively into the effects of pressure in the atmosphere on skin integrity, but a study by Games et al 30 showed that increasing local pressure leads to transient increases in skin temperature. This may suggest why increases in atmospheric pressure were linked to increases in TEWL, as increasing skin temperature has shown a significant linear relationship with increasing TEWL. 31 The four studies studying the effect of pollution on TEWL all concluded that people residing in urban areas show higher TEWL values compared to those residing in rural areas and increasing TEWL values with increasing exposure to NO 2 and PM. Exposure to PM in particular has been linked to skin diseases such as atopic dermatitis, potentially due to transient increases in TEWL. 32 The mechanism of PM disturbances to skin integrity are not completely known, but they have been linked to epithelial oxidative stress and organelle dysfunction that can affect TEWL. 33 Nitrogen dioxide may cause disruption to skin by similar mechanisms, but additional research on NO 2 and other pollutants and how they affect barrier function is needed. Readers are directed to the Handbook of Cosmetic Science and Technology 5 th edition for a comprehensive overview of how pollution can affect properties of the skin.
Several limitations of this review must be considered. Firstly, only studies published after 2015 were included; this decision was made so that this review may add to the already existing information presented in years prior. In addition, the search terms were created to capture a wide range of variables that may influence TEWL across anatomic regions, and thus, specific search criteria for each variable of interest were not used. In addition, this review only looked at human models (in vivo), while animal models may be beneficial in understanding climate and pollution effects on skin barrier function. The use of in vitro models may benefit research on TEWL changes due to environmental and pollution variation, as they allow for more controlled environmental conditions. Further, seasonal variation variables were prominently studied in Asian countries with temperatures not nearly as variable as many other GREEN ET AL. climates across the world. This same limitation is observed with regards to altitude, with much greater variation in altitudes observed in many other countries. Also, heterogeneity in patient populations between studies makes direct comparison of the variable's impact on TEWL difficult. Finally, it is important to note that a statistically significant mathematical difference in TEWL values may not reflect differences in clinical presentation of the skin itself, and although significant differences may be shown in studies, many uncontrolled for variables likely impacted the differences in TEWL between individuals.

| CONCLUSION
Effects of climate and seasonal variation on TEWL are due to a wide range of variables and their interactions that cannot be exclusively accounted for by temperature and relative humidity. This is demonstrated by the large number of contradictions found between temperature, relative humidity, and seasonal variation and their effects on TEWL. Additional studies should focus on how climate conditions other than temperature and humidity, such as atmospheric and steam pressure, may impact TEWL. In addition, it is important to control for variables affecting TEWL in experimental settings that have been supported by the literature such as age and anatomic location to minimise confounding in TEWL measurement. 5 Pollution from particulate matter and NO 2 cause oxidative damage to epithelial cells to increase TEWL as concluded by four studies in this review. This may put individuals living in industrial zones at higher risk for conditions of impaired barrier function such as atopic dermatitis and psoriasis. Additional research is needed to understand how other air pollutants may disrupt barrier function to gain a greater understanding of the mechanisms behind pollutant-induced TEWL increases.