Air Pollution Metabolomic Signatures and Chronic Respiratory Diseases Risk: A Longitudinal Study.

BACKGROUND: Although evidence has documented the associations of ambient air pollution with chronic respiratory diseases (CRDs) and lung function, the underlying metabolic mechanisms remain largely unclear. RESEARCH QUESTION: How does the metabolomic signature for air pollution relate to CRD risk, respiratory symptoms, and lung function? STUDY DESIGN AND METHODS: We retrieved 171,132 participants free of COPD and asthma at baseline from the UK Biobank, who had data on air pollution and metabolomics. Exposures to air pollutants (particulate matter with diameter ≤ 2.5 µm [PM2.5], particulate matter with a diameter ≤ 10 µm, nitrogen oxide [NOX], and NO2) were assessed for 4 years before baseline considering residential address histories. We used 10-fold cross-validation elastic net regression to identify air pollution-associated metabolites. Multivariable Cox models were used to assess the associations between metabolomic signatures and CRD risk. Mediation and pathway analysis were conducted to explore the metabolic mechanism underlying the associations. RESULTS: During a median follow-up of 12.51 years, 8,951 and 5,980 incident COPD and asthma cases were recorded. In multivariable Cox regressions, air pollution was positively associated with CRD risk (eg, hazard ratio per interquartile range increment in PM2.5, 1.09; 95% CI, 1.06-1.13). We identified 103, 86, 85, and 90 metabolites in response to PM2.5, particulate matter with a diameter ≤ 10 µm, NOX, and NO2 exposure, respectively. The metabolomic signatures showed significant associations with CRD risk (hazard ratio per SD increment in PM2.5 metabolomic signature, 1.11; 95% CI, 1.09-1.14). Mediation analysis showed that peripheral inflammatory and erythrocyte-related markers mediated the effects of metabolomic signatures on CRD risk. We identified 14 and 12 perturbed metabolic pathways (energy metabolism and amino acid metabolism pathways, etc) for PM2.5 and NOX metabolomic signatures. INTERPRETATION: Our study identifies metabolomic signatures for air pollution exposure. The metabolomic signatures showed significant associations with CRD risk, and inflammatory- and erythrocyte-related markers partly mediated the metabolomic signatures-CRD links.

Mediation Effect of Brain Volume on the Relationship Between Peripheral Inflammation and Cognitive Decline.

BACKGROUND: Studies have reported the associations between inflammation, brain volume, and cognition separately. It is reasonable to assume peripheral inflammation may contribute to cognitive decline through brain volume atrophy. OBJECTIVE: To examine the associations between peripheral inflammation, brain volume, and cognition among adults, and to investigate whether brain volume atrophy mediates the inflammation-cognition relationshipMethods:We retrieved 20,381 participants with available data on peripheral inflammation, brain volume, and cognition from the UK Biobank cohort. Cognitive function was assessed by performance on cognitive tasks probing various cognitive domains. Brain volumes were measured by magnetic resonance imaging (MRI). Multivariable linear models were used to investigate the associations between three peripheral inflammatory indexes (C-reactive protein, systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio), brain volume, and cognition. Mediation analyses were conducted to assess the potential mediating effect of brain volume atrophy. All results were corrected for multiple comparisons using the false-discovery rate (FDR). RESULTS: Peripheral inflammation was inversely associated with grey matter volume (GMV), white matter volume (WMV), and cognition after adjusting for potential covariates. For instance, CRP was associated with the GMV of left parahippocampal gyrus (ß= -0.05, 95% confidence interval [CI]: -0.06 to -0.04, pFDR =1.07×10-16) and general cognitive factor (ß= -0.03, 95% CI: -0. -0.04 to -0.01, pFDR = 0.001). Brain volume atrophy mediated the inflammation-cognitive decline relationship, accounting for 15-29% of the overall impact. CONCLUSION: In this cohort study, peripheral inflammation was associated with brain volume atrophy and cognitive decline. Brain atrophy may mediate the inflammation-cognitive decline relationship.

Global burden of chronic obstructive pulmonary disease attributable to ambient particulate matter pollution and household air pollution from solid fuels from 1990 to 2019.

We aimed to estimate the spatiotemporal trends in the global burden of chronic obstructive pulmonary disease (COPD) attributable to both household air pollution from solid fuels (HAP) and ambient particulate matter (APM) from 1990 to 2019 and compared the possible differences between the burdens attributable to APM and HAP. The number of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLLs) of COPD attributable to HAP from solid fuels and APM during 1990-2019 were extracted from the Global Burden of Diseases Study 2019. The proportion of YLLs in DALYs and average YLLs per COPD death were also calculated. Subgroup analyses by sex, age, and socio-demographic index (SDI) were conducted. The estimated annual percentage change (EAPC) was used to assess the temporal trend of age-standardized rate of mortality (ASMR) and DALYs (ASDR). Over the past 30 years, we observed a clear downward trend in COPD deaths attributable to HAP and an upward trend by 97.61% in COPD deaths attributable to APM. The global COPD burden attributable to APM in 2019 was higher than those due to HAP, except in low-SDI regions. For both HAP and APM, YLLs continued to predominate in DALYs of COPD, with an average YLLs per death of more than 10 years in different regions. The ASMR was higher in males and lower in high-SDI regions. The ASMR and ASDR attributable to HAP decreased globally in all age groups during 1990-2019, while those attributable to APM increased among people older than 80 years and in regions with lower SDI. Our study reveals an increasing trend in APM-attributable COPD burden over the past three decades. Comparatively, the global burden due to HAP decreased markedly, but it was still pronounced in low-SDI regions. Continued efforts on PM mitigation are needed for COPD prevention.