Global guidance on environmental life cycle impact assessment indicators: impacts of climate change, fine particulate matter formation, water consumption and land use

Purpose Guidance is needed on best-suited indicators to quantify and monitor the man-made impacts on human health, biodiversity and resources. Therefore, the UNEP-SETAC Life Cycle Initiative initiated a global consensus process to agree on an updated overall life cycle impact assessment (LCIA) framework and to recommend a non-comprehensive list of environmental indicators and LCIA characterization factors for (1) climate change, (2) fine particulate matter impacts on human health, (3) water consumption impacts (both scarcity and human health) and 4) land use impacts on biodiversity. Methods The consensus building process involved more than 100 world-leading scientists in task forces via multiple workshops. Results were consolidated during a 1-week Pellston Workshop™ in January 2016 leading to the following recommendations. Results and discussion LCIA framework: The updated LCIA framework now distinguishes between intrinsic, instrumental and cultural values, with disability-adjusted life years (DALY) to characterize damages on human health and with measures of vulnerability included to assess biodiversity loss. Climate change impacts: Two complementary climate change impact categories are recommended: (a) The global warming potential 100 years (GWP 100) represents shorter term impacts associated with rate of change and adaptation capacity, and (b) the global temperature change potential 100 years (GTP 100) characterizes the century-scale long term impacts, both including climate-carbon cycle feedbacks for all climate forcers. Fine particulate matter (PM2.5) health impacts: Recommended characterization factors (CFs) for primary and secondary (interim) PM2.5 are established, distinguishing between indoor, urban and rural archetypes. Water consumption impacts: CFs are recommended, preferably on monthly and watershed levels, for two categories: (a) The water scarcity indicator “AWARE” characterizes the potential to deprive human and ecosystems users and quantifies the relative Available WAter REmaining per area once the demand of humans and aquatic ecosystems has been met, and (b) the impact of water consumption on human health assesses the DALYs from malnutrition caused by lack of water for irrigated food production. Land use impacts: CFs representing global potential species loss from land use are proposed as interim recommendation suitable to assess biodiversity loss due to land use and land use change in LCA hotspot analyses. Conclusions The recommended environmental indicators may be used to support the UN Sustainable Development Goals in order to quantify and monitor progress towards sustainable production and consumption. These indicators will be periodically updated, establishing a process for their stewardship

Advancements in Life Cycle Human Exposure and Toxicity Characterization

BACKGROUND: The Life Cycle Initiative, hosted at the United Nations Environment Programme, selected human toxicity impacts from exposure to chemical substances as an impact category that requires global guidance to overcome current assessment challenges. The initiative leadership established the Human Toxicity Task Force to develop guidance on assessing human exposure and toxicity impacts. Based on input gathered at three workshops addressing the main current scientific challenges and questions, the task force built a roadmap for advancing human toxicity characterization, primarily for use in life cycle impact assessment (LCIA). OBJECTIVES: The present paper aims at reporting on the outcomes of the task force workshops along with interpretation of how these outcomes will impact the practice and reliability of toxicity characterization. The task force thereby focuses on two major issues that emerged from the workshops, namely considering near-field exposures and improving dose-response modeling. DISCUSSION: The task force recommended approaches to improve the assessment of human exposure, including capturing missing exposure settings and human receptor pathways by coupling additional fate and exposure processes in consumer and occupational environments (near field) with existing processes in outdoor environments (far field). To quantify overall aggregate exposure, the task force suggested that environments be coupled using a consistent set of quantified chemical mass fractions transferred among environmental compartments. With respect to dose-response, the task force was concerned about the way LCIA currently characterizes human toxicity effects, and discussed several potential solutions. A specific concern is the use of a (linear) dose-response extrapolation to zero. Another concern addresses the challenge of identifying a metric for human toxicity impacts that is aligned with the spatiotemporal resolution of present LCIA methodology, yet is adequate to indicate health impact potential. CONCLUSIONS: Further research efforts are required based on our proposed set of recommendations for improving the characterization of human exposure and toxicity impacts in LCIA and other comparative assessment frameworks. https://doi.org/10.1289/EHP3871

A fugacity-based indoor residential pesticide fate model

Dermal and non-dietary pathways are potentially significant exposure pathways to pesticides used in residences. Exposure pathways include dermal contact with residues on surfaces, ingestion from hand- and object-to-mouth activities, and absorption of pesticides into food. A limited amount of data has been collected on pesticide concentrations in various residential compartments following an application. But models are needed to interpret this data and make predictions about other pesticides based on chemical properties. In this paper, we propose a mass-balance compartment model based on fugacity principles. We include air (both gas phase and aerosols), carpet, smooth flooring, and walls as model compartments. Pesticide concentrations on furniture and toys, and in food, are being added to the model as data becomes available. We determine the compartmental fugacity capacity and mass transfer-rate coefficient for wallboard as an example. We also present the framework and equations needed for a dynamic mass-balance model

Position paper: models of post-transplant care for individuals with cystic fibrosis

There is no consensus on the best model of care for individuals with CF to manage the non-pulmonary complications that persist after lung transplant. The CF Foundation virtually convened a group of international experts in CF and lung-transplant care. The committee reviewed literature and shared the post-lung transplant model of care practiced by their programs. The committee then developed a survey that was distributed internationally to both the clinical and individual with CF/family audiences to determine the strengths, weaknesses, and preferences for various models of transplant care. Discussion generated two models to accomplish optimal CF care after transplant. The first model incorporates the CF team into care and proposes delineation of responsibilities for the CF and transplant teams. This model is reliant on outstanding communication between the teams, while leveraging the expertise of the CF team for management of the non-pulmonary manifestations of CF. The transplant team manages all aspects of the transplant, including pulmonary concerns and management of immunosuppression. The second model consolidates care in one center and may be more practical for transplant programs that have expertise managing CF and have access to CF multidisciplinary care team members (e.g., located in the same institution). The best model for each program is influenced by several factors and model selection needs to be decided between the transplant and the CF center and may vary from center to center. In either model, CF lung transplant recipients require a clear delineation of the roles and responsibilities of their providers and mechanisms for effective communication.</p

Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children

Objectives We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO2) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved. Methods We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV1 in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (i-GSEA4GWAS) to identify plausible pathways. Results Two SNPs near the EPHA3 (rs13090972 and rs958144) and one in TXNDC8 (rs7041938) showed significant interactions with NO2 in Caucasians but we did not replicate this locus in African-Americans. SNP-CO interactions did not reach genome-wide significance. The i-GSEA4GWAS showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV1 changes. For NO2-related FEV1 responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses. Conclusion The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways

Ambient air pollution, lung function, and airway responsiveness in asthmatic children

Background: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthma are lacking. Objective: To investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. Methods: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide (NO2) and sulfur dioxide (SO2) levels in 1,003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to zip/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and FVC %predicted, FEV1/FVC and PC20, adjusting for seasonality and confounders. Results: Same-day and 1-week average CO levels were negatively associated with post-bronchodilator %predicted FEV1 (change(95%CI) per IQR: −0.33(−0.49, −0.16), −0.41(−0.62, −0.21), respectively) and FVC (−0.19(−0.25, −0.07), −0.25(−0.43, −0.07)). Longer-term four-month averages of CO were negatively associated with prebronchodilator %predicted FEV1 and FVC (−0.36(−0.62, −0.10), −0.21(−0.42, −0.01)). Four-month averaged CO and ozone levels were negatively associated with FEV1/FVC (p<0.05). Increased four-month average NO2 levels were associated with reduced post-bronchodilator FEV1 and FVC %predicted. Long-term exposures to SO2 were associated with reduced PC20 (%change(95%CI) per IQR:-6(-11,-1.5)). Treatment augmented the negative short-term CO effect on PC20. Conclusions: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications may not protect but worsens the CO effects on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication

Long-term safety and efficacy of tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study

Background: Tezacaftor-ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8-24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor-ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor-ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods: Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor-ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and 'tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor-ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov (NCT02565914). Findings: Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor-ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor-ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor-ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation: Tezacaftor-ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor-ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor-ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding: Vertex Pharmaceuticals Incorporated