Air pollution, health and social deprivation: A fine-scale risk assessment.

Risk assessment studies often ignore within-city variations of air pollutants. Our objective was to quantify the risk associated with fine particulate matter (PM2.5) exposure in 2 urban areas using fine-scale air pollution modeling and to characterize how this risk varied according to social deprivation. In Grenoble and Lyon areas (0.4 and 1.2 million inhabitants, respectively) in 2012, PM2.5 exposure was estimated on a 10×10m grid by coupling a dispersion model to population density. Outcomes were mortality, lung cancer and term low birth weight incidences. Cases attributable to air pollution were estimated overall and stratifying areas according to the European Deprivation Index (EDI), taking 10µg/m(3) yearly average as reference (counterfactual) level. Estimations were repeated assuming spatial homogeneity of air pollutants within urban area. Median PM2.5 levels were 18.1 and 19.6µg/m(3) in Grenoble and Lyon urban areas, respectively, corresponding to 114 (5.1% of total, 95% confidence interval, CI, 3.2-7.0%) and 491 non-accidental deaths (6.0% of total, 95% CI 3.7-8.3%) attributable to long-term exposure to PM2.5, respectively. Attributable term low birth weight cases represented 23.6% of total cases (9.0-37.1%) in Grenoble and 27.6% of cases (10.7-42.6%) in Lyon. In Grenoble, 6.8% of incident lung cancer cases were attributable to air pollution (95% CI 3.1-10.1%). Risk was lower by 8 to 20% when estimating exposure through background stations. Risk was highest in neighborhoods with intermediate to higher social deprivation. Risk assessment studies relying on background stations to estimate air pollution levels may underestimate the attributable risk.

Designing local air pollution policies focusing on mobility and heating to avoid a targeted number of pollution-related deaths: Forward and backward approaches combining air pollution modeling, health impact assessment and cost-benefit analysis.

CONTEXT: Policies aiming at decreasing air pollutants (e.g., fine particulate matter, PM2.5) are often designed without targeting an explicit health benefit nor carrying out cost-benefit analyses. METHODS: We developed a transdisciplinary backward and forward approach at the conurbation level: from health objectives set by local decision-makers, we estimated which reductions in PM2.5 exposures and emissions would allow to reach them, and identified urban policies leading to these reductions (backward approach). We finally conducted health impact and cost-benefit analyses of these policies (forward approach). The policies were related to the most emitting sectors in the considered area (Grenoble, France), wood heating and transport sectors. The forward approach also considered the health impact and co-benefits of these policies related to changes in physical activity and CO2 emissions. FINDINGS: Decision-makers set three health targets, corresponding to decreases by 33% to 67% in PM2.5-attributable mortality in 2030, compared to 2016. A decrease by 42% in PM2.5 exposure (from 13.9 µg/m3) was required to reach the decrease by 67% in PM2.5-attributable mortality. For each Euro invested, the total benefit was about 30€ for policies focusing on wood heating, and 1 to 68€ for traffic policies. Acting on a single sector was not enough to attain a 67% decrease in PM2.5-attributable mortality. This target could be achieved by replacing all inefficient wood heating equipment by low-emission pellet stoves and reducing by 36% the traffic of private motorized vehicles. This would require to increase the share of active modes (walking, biking…), inducing increases in physical activity and additional health benefits beyond the initial target. Annual net benefits were between €484 and €629 per capita for policies with report on active modes, compared to between €162 and €270 without. CONCLUSIONS: Urban policies strongly reducing air pollution-attributable mortality can be identified by our approach. Such policies can be cost-efficient.

Photic sensitivity ranges of hamster pupillary and circadian phase responses do not overlap.

Mammalian retinal photoreceptors form an irradiance detection system that drives many nonvisual responses to light such as pupil reflex and resetting of the circadian clock. To understand the role of pupil size in circadian light responses, pupil diameter was pharmacologically manipulated and the effect on behavioral phase shifts at different irradiance levels was studied in the Syrian hamster. Dose-response curves for steady-state pupil size and for behavioral phase shifts were constructed for 3 pupil conditions (dilated, constricted, and control). Retinal irradiance was calculated from corneal irradiance, pupil size, retinal surface area, and absorption of ocular media. The sensitivity of photic responses to retinal irradiance is approximately 1.5 log units higher than to corneal irradiance. When plotted against corneal irradiance, pharmacological pupil constriction reduces the light sensitivity of the circadian system, but pupil dilation has no effect. As expected, when plotted against retinal irradiance all dose-response curves superimposed, confirming that the circadian system responds to photon flux on the retina. Pupil dilation does not increase the circadian response to increasing irradiance, since the response of the circadian system attains saturation at irradiance levels lower than those required to induce pupil constriction. The main finding shows that due to the different response sensitivities, the effect of pupil constriction on the light sensitivity of the circadian system in the hamster under natural conditions is virtually negligible. We further suggest the existence of distinct modulating mechanisms for the differential retinal irradiance sensitivity of the pupil system and the circadian system, which enables the different responses to be tuned to their specific tasks while using similar photoreceptive input.

Which decreases in air pollution should be targeted to bring health and economic benefits and improve environmental justice?

BACKGROUND: Fine particulate matter (PM2.5) exposure entails large health effects in many urban areas. Public measures aiming at decreasing air pollution are often designed without targeting an explicit health benefit. Our objective was to investigate the health and economic benefits and the social inequalities in exposure resulting from several scenarios of reduction of PM2.5 exposure, in order to support decisions about urban policies. MATERIAL AND METHODS: In the French conurbations of Grenoble and Lyon (0.4 and 1.4 million inhabitants, respectively), PM2.5 yearly average exposure was estimated on a 10-m grid by coupling a PM2.5 dispersion model to population density. Changes in death cases, life expectancy, lung cancer and term low birth weight incident cases as well as associated health economic costs were estimated for ten PM2.5 reduction scenarios differing in terms of amplitude of reduction and spatial extent. Changes in social differences in PM2.5 exposure were also assessed. RESULTS: During the 2015-2017 period, PM2.5 average exposure was 13.9 µg/m3 in Grenoble and 15.3 µg/m3 in Lyon conurbations. Exposure to PM2.5 led to an estimated 145 (95% Confidence Interval, CI, 90-199) and 531 (95% CI, 330-729) premature deaths, 16 (95% CI, 8-24) and 65 (95% CI, 30-96) incident lung cancers, and 49 (95% CI, 19-76) and 193 (95% CI, 76-295) term low birth weight cases each year in Grenoble and Lyon conurbations, respectively, compared to a situation without PM2.5 anthropogenic sources, i.e. a PM2.5 concentration of 4.9 µg/m3. The associated costs amounted to 495 (Grenoble) and 1767 (Lyon) M€/year for the intangible costs related to all-cause non-accidental mortality and 27 and 105 M€ for the tangible and intangible costs induced by lung cancer. A PM2.5 exposure reduction down to the WHO air quality guideline (10 µg/m3) would reduce anthropogenic PM2.5-attributable mortality by half while decreases by 2.9 µg/m3 (Grenoble) and 3.3 µg/m3 (Lyon) were required to reduce it by a third. Scenarios focusing only on the most exposed areas had little overall impact. Scenarios seeking to reach a homogeneous exposure in the whole study area were the most efficient in alleviating social inequalities in exposure. CONCLUSIONS: Reduction scenarios targeting only air pollution hotspots had little expected impact on population health. We provided estimates of the PM2.5 change required to reduce PM2.5-attributable mortality by one third or more. Our approach can help targeting air pollution reduction scenarios expected to entail significant benefits, and it could easily be transposed to other urban areas.

Responses of suprachiasmatic nucleus neurons to light and dark adaptation: relative contributions of melanopsin and rod-cone inputs.

The circadian oscillator in the suprachiasmatic nucleus (SCN) is entrained to the environmental light/dark cycle through photic information conveyed from the retina. The vast majority of projections to the SCN arise from melanopsin-expressing ganglion cells that are intrinsically light sensitive and that receive inputs from both rods and cones. To investigate the relative contributions of the different photoreceptive systems in shaping the photic signal influencing the circadian clock, we analyzed neuronal responses of single SCN neurons using extracellular electrophysiological recordings under different conditions of light adaptation. In the majority of neurons (78%), the spike rate is increased by light stimulation whereas the remainder are light-inhibited. The neuronal response to light is composed of several components distinguished by their temporal dynamics and degree of alteration after previous light exposure. SCN neurons display a sustained response to light followed by persistence of the response after light offset. These responses are sluggish and relatively unaffected by previous light exposures. Neurons also respond with a brisk, excitatory ON response and often an OFF response that is either excitatory or inhibitory. ON-OFF responses are transient and strongly reduced by previous bright white light exposure. Furthermore, two types of neuronal response patterns can be distinguished by the presence or absence of a slow-transient component that follows the transient ON response. The transient ON-OFF components express light adaptation properties characteristic of retinal channels involving cones, whereas the sustained and persistent components are consistent with in vitro response properties reported for melanopsin-expressing ganglion cells.

Melanopsin-dependent nonvisual responses: evidence for photopigment bistability in vivo.

In mammals, nonvisual responses to light have been shown to involve intrinsically photosensitive retinal ganglion cells (ipRGC) that express melanopsin and that are modulated by input from both rods and cones. Recent in vitro evidence suggests that melanopsin possesses dual photosensory and photoisomerase functions, previously thought to be a unique feature of invertebrate rhabdomeric photopigments. In cultured cells that normally do not respond to light, heterologous expression of mammalian melanopsin confers light sensitivity that can be restored by prior stimulation with appropriate wavelengths. Using three different physiological and behavioral assays, we show that this in vitro property translates to in vivo, melanopsin-dependent nonvisual responses. We find that prestimulation with long-wavelength light not only restores but enhances single-unit responses of SCN neurons to 480-nm light, whereas the long-wavelength stimulus alone fails to elicit any response. Recordings in Opn4-/- mice confirm that melanopsin provides the main photosensory input to the SCN, and furthermore, demonstrate that melanopsin is required for response enhancement, because this capacity is abolished in the knockout mouse. The efficiency of the light-enhancement effect depends on wavelength, irradiance, and duration. Prior long-wavelength light exposure also enhances short-wavelength-induced phase shifts of locomotor activity and pupillary constriction, consistent with the expression of a photoisomerase-like function in nonvisual responses to light.

Immunohistochemical evidence of a melanopsin cone in human retina.

PURPOSE: Melanopsin, expressed in a subset of intrinsically photosensitive ganglion cells that project to the suprachiasmatic nucleus (SCN), is involved in the photic entrainment of circadian rhythms and other non-image-forming functions (pupil light reflex, masking, acute heart rate response, and alertness). Melanopsin has recently been shown to be a "bireactive" photopigment that functions as a photosensory opsin using 11-cis retinaldehyde as a chromophore and has intrinsic photoisomerase activity. Melanopsin is widely distributed in the retina of vertebrates and, depending on the species, is expressed in ganglion, amacrine, horizontal, and photoreceptor cells. The present study was conducted to determine the distribution of this opsin in the human retina. METHODS: Human donor eyes were obtained from donors and fixed shortly after death. Immunohistochemistry was used to determine melanopsin expression in the retinas of three donors. The possible coexpression of this photopigment with other opsins was studied by double-labeling immunocytochemistry and confocal analysis. RESULTS: In addition to the expected labeling in ganglion cells of the inner retinal layers, an unexpected finding showed melanopsin-immunopositive label in the outer segments of cones that did not coexpress other known opsins. These melanopsin-expressing cones are extremely sparse (5-25 cones/mm2; 0.1%-0.5% of the entire cone population) and are located in the peripheral retina. CONCLUSIONS: The presence of melanopsin in human cones suggests image and non-image-forming roles in visual responses at both the cone input and ganglion cell output stages and their involvement in a broad spectrum of irradiance detection functions in the visual system.

Melanopsin bistability: a fly's eye technology in the human retina.

In addition to rods and cones, the human retina contains light-sensitive ganglion cells that express melanopsin, a photopigment with signal transduction mechanisms similar to that of invertebrate rhabdomeric photopigments (IRP). Like fly rhodopsins, melanopsin acts as a dual-state photosensitive flip-flop in which light drives both phototransduction responses and chromophore photoregeneration that bestows independence from the retinoid cycle required by rods and cones to regenerate photoresponsiveness following bleaching by light. To explore the hypothesis that melanopsin in humans expresses the properties of a bistable photopigment in vivo we used the pupillary light reflex (PLR) as a tool but with methods designed to study invertebrate photoreceptors. We show that the pupil only attains a fully stabilized state of constriction after several minutes of light exposure, a feature that is consistent with typical IRP photoequilibrium spectra. We further demonstrate that previous exposure to long wavelength light increases, while short wavelength light decreases the amplitude of pupil constriction, a fundamental property of IRP difference spectra. Modelling these responses to invertebrate photopigment templates yields two putative spectra for the underlying R and M photopigment states with peaks at 481 nm and 587 nm respectively. Furthermore, this bistable mechanism may confer a novel form of "photic memory" since information of prior light conditions is retained and shapes subsequent responses to light. These results suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulation of non-visual responses to light and highlights the ubiquitous nature of photoswitchable photosensors across living organisms.