Green Space Exposure: A New Approach for the Prevention and Control of Rheumatoid Arthritis

Prevention of RA

Green space exposure has been demonstrated to result in reductions in inflammatory markers of relevance to RA such as interleukin (IL)-6.⁸ These immune changes may relate to exposure to bVOCs, more diverse environmental microbiota (microbes in the air and on surfaces), and/or reductions in air pollution. Dysbiosis of the oral and gut microbiota tend to appear in people with RA prior to the onset of symptoms, with such dysbioses leading to changes in a range of RA inflammatory markers, including IL-6, IL-17, and tumor necrosis factor.¹ Exposure to environmental microbiota provides one mechanism by which the human microbiota can be changed,⁹ with a recent systematic review demonstrating that green space exposure is associated with differences in the gut and oral microbiomes.¹⁰ Inhaling bVOCs has been shown to reduce inflammation and anxiety, and improve sleep in animal models¹¹; however, the dosages administered in these studies are likely higher than experienced by people in or near green spaces. Finally, exposure to high levels of air pollution is a known driver of RA.^12,13 Green spaces have been promoted as a means of reducing air pollution⁵; however, in the presence of primary air pollutants, the bVOCs may also react with these air pollutants to produce secondary pollutants,¹⁴ which could increase the risk of RA.^12,13 Appreciating the local environmental context may therefore be of particular importance when introducing or optimizing green spaces, or when encouraging people to use these spaces.

The effect of green space exposure on RA incidence has been investigated in 3 recent studies,^12,13,15 with the first published in 2022.¹⁵ These studies were conducted in China^12,13 and Indonesia,¹⁵ and all studies used the normalized difference vegetation index (NDVI) as a measure of green space exposure. One study also included the enhanced vegetation index (EVI)¹² and another the percentage of forest land cover.¹⁵ Each of the 3 studies reported that higher exposure to green space was associated with a lower risk of RA, and results were typically similar across various green space measures (eg, NDVI, EVI, and forest cover, and across different size buffer zones). The effect was modified by age, BMI (calculated as weight in kilograms divided by height in meters squared [kg/m²]), and exposure to particulate matter of < 2.5 μm (PM_2.5), indicating a greater effect of green space exposure on RA risk for those aged ≥ 65 years, with a BMI of ≤ 18.5,¹² and/or with exposure to higher levels of PM_2.5.^12,13 There was no such significant effect modification for sex, smoking, alcohol consumption, having a plant-based diet, marital status, occupation, literacy, and household income. Of interest, air pollution (PM_2.5) was not found to mediate the effect of green space exposure and RA risk.¹² One additional study¹⁶ using data from the UK Biobank found that exposure to blue space (waterbodies within 300 or 1000 meters) was associated with a lower risk of RA; green space exposure was a significant effect modifier, whereby the effect of green space exposure on RA risk was higher among people with lower exposure to green spaces.

These studies provide a promising indication of the potential protective role green space exposure may have against developing RA. There are, however, a number of limitations to the studies, including that none clearly reported details of the green space exposure metrics, only one used participants’ residential addresses to determine green space exposure (as opposed to the city centroid¹³ or green space in the province¹⁵), and one did not have any individual-level data (rather, using characteristics of the population within the province, including the RA outcome¹⁵). Importantly, none of the studies used a counterfactual framework; hence causal inferences cannot be drawn from these studies. Nonetheless, the current evidence base indicates there is a potential protective role for green space exposure in providing a possible new approach to preventing RA.

Management of RA

Based on the evidence above, it is possible that green space exposure could also assist in the management of RA; however, no studies to date have examined this potential effect. Exposure may reduce disease activity through the same mechanisms outlined above. For example, RA treatment partially restores the oral and gut microbiota,¹⁷ along with the targeted improvements in inflammatory markers. Further, physical activity reduces disease activity,¹⁸ and those living in close proximity to green spaces are typically more physically active.³ It has also been suggested that green space exposure may reduce the sensation of pain through exposure to the environmental microbiota, bVOCs, and the sights and sounds of nature.³ Other mechanisms may involve negative air ions, as well as increased sunlight exposure and social integration, which are higher in people who have green spaces in close proximity to their home.³ Due to green space exposure targeting multiple potential mechanisms for pain reduction, there may be particular benefits for people who have persistent pain despite well-managed RA from an inflammatory perspective. Finally, green space exposure may play a role in reducing many comorbidities in RA,¹⁹ including mental illness, respiratory conditions, cardiovascular disease, cancer,⁴ and osteoporosis.²⁰

Future research

Exposure to green spaces may provide a new approach to preventing and managing RA, either complementing or enhancing current practice. However, more evidence is required to develop a stronger evidence base if recommendations are to be made for enhancing policy and practice. Although we have theoretical support for the potential role of green space exposure in reducing the burden of RA, including early findings in support of the protective role against RA, studies are needed to examine the effect of green space exposure on specific outcomes for those with RA. Generating such evidence requires the use of more robust methods with clear reporting, underpinned by the counterfactual framework for observational studies, so that causal inferences may be drawn where trials cannot be conducted. By comparing different types of green spaces (eg, sports fields, nature reserves, and different levels of biodiversity), we can also work toward optimizing the structure of green space to maximize health-enhancing exposures. Where possible, more detailed exposure metrics should be used, including the intensity and duration of exposure—people’s actual time and activity in these spaces—rather than estimating exposure based on where the person lives. The optimization of both clinical and public health recommendations may also be further enhanced by investigating potential effect modifiers (eg, age, sex, level of disease activity), which may influence the relationship.