Association of blood eosinophils with corticosteroid treatment failure stratified by smoking status among inpatients with AECOPD.

BACKGROUND: Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far. OBJECTIVES: This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking. METHODS: We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure. RESULTS: There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses. CONCLUSION: Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD.

Air pollution, lung function and mortality: survival and mediation analyses in UK Biobank.

Background: Air pollution is associated with lower lung function, and both are associated with premature mortality and cardiovascular disease (CVD). Evidence remains scarce on the potential mediating effect of impaired lung function on the association between air pollution and mortality or CVD. Methods: We used data from UK Biobank (n∼200 000 individuals) with 8-year follow-up to mortality and incident CVD. Exposures to particulate matter <10 µm (PM10), particulate matter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) were assessed by land-use regression modelling. Lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio) was measured between 2006 and 2010 and transformed to Global Lung Function Initiative (GLI) z-scores. Adjusted Cox proportional hazards and causal proportional hazards mediation analysis models were fitted, stratified by smoking status. Results: Lower FEV1 and FVC were associated with all-cause and CVD mortality, and incident CVD, with larger estimates in ever- than never-smokers (all-cause mortality hazard ratio per FEV1 GLI z-score decrease 1.29 (95% CI 1.24-1.34) for ever-smokers and 1.16 (95% CI 1.12-1.21) for never-smokers). Long-term exposure to PM2.5 or NO2 was associated with incident CVD, with similar effect sizes for ever- and never-smokers. Mediated proportions of the air pollution-all-cause mortality estimates driven by FEV1 were 18% (95% CI 2-33%) for PM2.5 and 27% (95% CI 3-51%) for NO2. Corresponding mediated proportions for incident CVD were 9% (95% CI 4-13%) for PM2.5 and 16% (95% CI 6-25%) for NO2. Conclusions: Lung function may mediate a modest proportion of associations between air pollution and mortality and CVD outcomes. Results likely reflect the extent of either shared mechanisms or direct effects relating to lower lung function caused by air pollution.

Double trouble: The interaction of PM2.5 and O3 on respiratory hospital admissions.

The co-occurrence of fine particulate matter (PM2.5) and ozone (O3) pollution during the warm season has become a growing public health concern. The interaction between PM2.5 and O3 and its contribution to disease burden associated with co-pollution has not been thoroughly examined. We collected data on hospital admissions for respiratory diseases from a city-wide hospital discharge database in Beijing between 2013 and 2019. City-wide 24-h mean PM2.5 and daily maximum 8-h mean O3 were averaged from 35 monitoring stations across Beijing. Conditional Poisson regression was employed to estimate the interaction between warm-season PM2.5 and O3 on respiratory admissions. A model incorporating a tensor product term was used to fit the non-linear interaction and estimate the number of respiratory admissions attributable to PM2.5 and O3 pollution. From January 18, 2013 to December 31, 2019, 1,191,308 respiratory admissions were recorded. We observed multiplicative interactions between warm-season PM2.5 and O3 on upper respiratory infections (P = 0.004), pneumonia (P = 0.002), chronic obstructive pulmonary disease (P = 0.041), and total respiratory disease (P < 0.001). PM2.5-O3 co-pollution during warm season exhibited a super-additive effect on respiratory admissions, with a relative excess risk due to interaction of 1.65% (95%CI: 0.46%-2.84%). There was a non-linear pattern of the synergistic effect between PM2.5 and O3 on respiratory admissions. Based on the World Health Organization global air quality guidelines, 12,421 respiratory admissions would be reduced if both daily PM2.5 and O3 concentrations had not exceeded the target (PM2.5 15 µg/m3, O3 100 µg/m3). The number of respiratory admissions attributable to either PM2.5 or O3 pollution decreased by 48.7% from 2013 to 2019. Prioritizing O3 control during the warm season is a cost-effective strategy for Beijing. These findings underscore the significance of concurrently addressing both PM2.5 pollution and O3 pollution during the warm season to alleviate the burden of respiratory diseases.

The Prognostic Value of Blood Eosinophil Level in AECOPD is Influenced by Corticosteroid Treatment During Hospitalization.

Purpose: Blood eosinophil is a promising biomarker for phenotyping patients with acute exacerbation of COPD (AECOPD). We aimed to evaluate the prognostic value of eosinophil on short- and long-term outcomes stratified by corticosteroid treatment among AECOPD inpatients. Patients and Methods: In this retrospective cohort study, we included patients hospitalized for AECOPD from July 2013 to June 2021 in Beijing, China. Clinical data were collected from electronic medical records. The blood eosinophil count was measured within 24h after admission. Eosinophilic AECOPD was defined as having an eosinophil percentage ≥ 2%. The study outcomes were length of stay (LOS), treatment failure, and AECOPD readmission risk within 3 years of discharge. Multivariable models were used to analyze the associations between blood eosinophil count and outcomes stratified by corticosteroid treatment during hospitalization. Results: A total of 2406 AECOPD patients were included. The median LOS of AECOPD patients was 10 (interquartile range: 8-14) days. The eosinophil percentage was negatively associated with LOS (P-trend=0.014). Compared with the non-eosinophilic AECOPD group, the eosinophilic group had a 58% lower risk of treatment failure (OR=0.42, 95% CI: 0.20-0.89) in patients treated with systemic corticosteroids, but no association was observed in those treated with inhaled corticosteroids (ICS) only (OR=0.95, 95% CI: 0.60-1.52). The eosinophilic group had an increased risk of 90-day re-admission in patients treated with ICS only (HR=1.51, 95% CI: 1.00-2.29), but not in patients treated with systemic corticosteroids during hospitalization (HR=0.67, 95% CI: 0.39-1.15). No statistically significant results were found for 180-day, 1-year, or 3-year readmission risk. Conclusion: Elevated blood eosinophils in AECOPD were associated with shorter length of stay and improved response to treatment with systemic corticosteroids, but not inhaled corticosteroids. Our study suggested that a therapeutic approach of using systemic corticosteroid may benefit patients present with eosinophilic AECOPD.

The exposome in respiratory diseases: multiple preventable risk factors from early life to adulthood.

The increasing global burden of respiratory diseases over the last decades raises questions about the impact of environmental factors during industrialisation and urbanisation. Although the knowledge of environmental epidemiology is growing, it is still unclear what the most critical exposure windows are for respiratory health. In addition, the relationships between different environmental exposures can be complex. The exposome approach investigating all non-genetic factors on health has been developed in recent years but has been little applied in respiratory health to date. This journal club article reviews three recent publications investigating the effects of environmental exposures, considered separately or in an exposome approach with different exposure windows, on respiratory health outcomes. These three studies highlight targets for action in primary and secondary prevention. Two studies, using data from the INMA and RHINESSA cohorts, support the regulation and reduction of phthalates and air pollution, respectively. Moreover, the exposome approach conducted in the NutriNet-Santé cohort emphasises that risk reduction must involve a multi-interventional approach targeting both specific early-life risk factors and promotion of a healthy lifestyle in adulthood. These three articles also present research perspectives in environmental epidemiology.

Does air pollution confound associations between environmental noise and cardiovascular outcomes? - A systematic review.

BACKGROUND: Exposure to environmental noise is associated with adverse health effects, but there is potential for confounding and interaction with air pollution, particularly where both exposures arise from the same source, such as transport. OBJECTIVES: To review evidence on confounding and interaction of air pollution in relation to associations between environmental noise and cardiovascular outcomes. METHODS: Papers were identified from similar reviews published in 2013 and 2015, from the systematic reviews supporting the WHO 2018 noise guidelines, and from a literature search covering the period 2016-2022 using Medline and PubMed databases. Additional papers were identified from colleagues. Study selection was according to PECO inclusion criteria. Studies were evaluated against the WHO checklist for risk of bias. RESULTS: 52 publications, 36 published after 2015, were identified that assessed associations between transportation noise and cardiovascular outcomes, that also considered potential confounding (49 studies) or interaction (23 studies) by air pollution. Most, but not all studies, suggested that the associations between traffic noise and cardiovascular outcomes are independent of air pollution. NO2 or PM2.5 were the most commonly included air pollutants and we observed no clear differences across air pollutants in terms of the potential confounding role. Most papers did not appear to suggest an interaction between noise and air pollution. Eight studies found the largest noise effect estimates occurring within the higher noise and air pollution exposure categories, but were not often statistically significant. CONCLUSION: Whilst air pollution does not appear to confound associations of noise and cardiovascular health, more studies on potential interactions are needed. Current methods to assess quality of evidence are not optimal when evaluating evidence on confounding or interaction.

Long-Term Exposure to Road Traffic Noise and Incident Heart Failure: Evidence From UK Biobank.

BACKGROUND: Evidence on road traffic noise and heart failure (HF) is limited, and little is known on the potential mediation roles of acute myocardial infarction (AMI), hypertension, or diabetes. OBJECTIVES: The purpose of this study was to evaluate the impacts of long-term road traffic noise exposure on the risk of incident HF considering air pollution, and explore the mediations of the previously mentioned diseases. METHODS: This prospective study included 424,767 participants without HF at baseline in UK Biobank. The residential-level noise and air pollution exposure was estimated, and the incident HF was identified through linkages with medical records. Cox proportional hazard models were used to estimate HRs. Furthermore, time-dependent mediation was performed. RESULTS: During a median 12.5 years of follow-up, 12,817 incident HF were ascertained. The HRs were 1.08 (95% CI: 1.00-1.16) per 10 dB[A] increase in weighted average 24-hour road traffic noise level (Lden), and 1.15 (95% CI: 1.02-1.31) for exposure to Lden >65 dB[A] compared with the reference category (Lden ≤55 dB[A]), respectively. Furthermore, the strongest combined effects were found in those with both high exposures to road traffic noise and air pollution including fine particles and nitrogen dioxide. Prior AMI before HF within 2 years' time interval mediated 12.5% of the association of road traffic noise with HF. CONCLUSIONS: More attention should be paid and a preventive strategy should be considered to alleviate the disease burden of HF related to road traffic noise exposure, especially in participants who survived AMI and developed HF within 2 years.

Mediation of metabolic syndrome in the association between long-term co-exposure to road traffic noise, air pollution and incident type 2 diabetes.

OBJECTIVES: Recent studies have linked exposure to road traffic noise or air pollution with incident type 2 diabetes (T2D), but investigation on their co-exposure was limited and underlying mechanisms remain unclear. We hypothesized that long-term co-exposure to road traffic noise and air pollution increases the risk of incident T2D via the development of metabolic syndrome (MetS). METHODS: This prospective study included 390,834 participants in UK Biobank. Cumulative risk index (CRI), the health-based weighted levels of multiple exposures, was applied to characterize the co-exposure to 24-hour road traffic noise (Lden), particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), and nitrogen dioxide (NO2). Lden was modeled by the Common Noise Assessment Methods in Europe and air pollutant levels were measured by the Land Use Regression model at participants' residential addresses. Incident T2D was ascertained through linkages to inpatient hospital records. MetS was defined by five (central obesity, triglycerides, HDL cholesterol, glucose, and blood pressure) or six factors (C-reactive protein additionally). Cox proportional hazard models were used to assess the association between environmental exposures and incident T2D, and mediation analyses were applied to investigate the role of MetS. RESULTS: After a median of 10.9 years of follow-up, 13,214 (3.4%) incident T2D cases were ascertained. The exposure to Lden, PM2.5, and NO2, as well as their co-exposure, were significantly associated with an elevated risk of incident T2D, with HRs of 1.03 (95%CI: 1.00, 1.05) per 3.5 dB(A) increase in Lden, 1.05 (95%CI: 1.01, 1.10) per 1.3 µg/m3 increase in PM2.5, 1.07 (95%CI: 1.02, 1.11) per 9.8 µg/m3 increase in NO2, and 1.06 (95%CI: 1.02, 1.09) per interquartile range increase in CRI. MetS significantly mediated 43.5%- 54.7% of the CRI-T2D relationship. CONCLUSIONS: Long-term co-exposure to road traffic noise and air pollution is associated with an elevated risk of incident T2D, which may partly be mediated by MetS.

Road Traffic Noise and Incidence of Primary Hypertension: A Prospective Analysis in UK Biobank.

Background: The quality of evidence regarding the associations between road traffic noise and hypertension is low due to the limitations of cross-sectional study design, and the role of air pollution remains to be further clarified. Objectives: The purpose of this study was to evaluate the associations of long-term road traffic noise exposure with incident primary hypertension; we conducted a prospective population-based analysis in UK Biobank. Methods: Road traffic noise was estimated at baseline residential address using the common noise assessment method model. Incident hypertension was ascertained through linkage with medical records. Cox proportional hazard models were used to estimate hazard ratios (HRs) for association in an analytical sample size of over 240,000 participants free of hypertension at baseline, adjusting for covariates determined via directed acyclic graph. Results: During a median of 8.1 years follow-up, 21,140 incident primary hypertension (International Classification of Diseases-10th Revision [ICD-10]: I10) were ascertained. The HR for a 10 dB[A] increment in mean weighted average 24-hour road traffic noise level (L den ) exposure was 1.07 (95% CI: 1.02-1.13). A dose-response relationship was found, with HR of 1.13 (95% CI: 1.03-1.25) for L den >65 dB[A] vs ≤55 dB[A] (P for trend <0.05). The associations were all robust to adjustment for fine particles (PM2.5) and nitrogen dioxide (NO2). Furthermore, high exposure to both road traffic noise and air pollution was associated with the highest hypertension risk. Conclusions: Long-term exposure to road traffic noise was associated with increased incidence of primary hypertension, and the effect estimates were stronger in presence of higher air pollution.

Landscape fire smoke enhances the association between fine particulate matter exposure and acute respiratory infection among children under 5 years of age: Findings of a case-crossover study for 48 low- and middle-income countries.

BACKGROUND: Fine particulate matter (PM2.5) produced by landscape fires is thought to be more toxic than that from non-fire sources. However, the effects of "fire-sourced" PM2.5 on acute respiratory infection (ARI) are unknown. METHODS: We combined Demographic and Health Survey (DHS) data from 48 countries with gridded global estimates of PM2.5 concentrations from 2003 to 2014. The proportions of fire-sourced PM2.5 were assessed by a chemical transport model using a variety of PM2.5 source data. We tested for associations between ARI and short-term exposure to fire- and "non-fire-sourced" PM2.5 using a bidirectional case-crossover analysis. The robustness and homogeneity of the associations were examined by sensitivity analyses. We also established a nonlinear exposure-response relationship between fire- and non-fire-sourced PM2.5 and ARI using a two-dimensional spline function. RESULTS: The study included 36,432 children under 5 years who reported ARI symptoms. Each 1 µg/m3 increment of fire-sourced PM2.5 was associated with a 3.2 % (95 % confidence interval [CI] 0.2, 6.2) increment in the risk of ARI. This effect was comparable to that of each ∼5 µg/m3 increment in PM2.5 from non-fire sources (3.1 %; 95 % CI 2.4, 3.7). The association between ARI and total PM2.5 concentration was significantly mediated by the proportion of fire-sourced particles. Nonlinear analysis showed that the risk of ARI was increased by both fire- and non-fire-sourced PM2.5, but especially by the former. CONCLUSIONS: PM2.5 produced by landscape fire was more strongly associated to ARI among children under 5 years than that from non-fire sources.

Environmental noise and health in low-middle-income-countries: A systematic review of epidemiological evidence.

Evidence of the health impacts from environmental noise has largely been drawn from studies in high-income countries, which has then been used to inform development of noise guidelines. It is unclear whether findings in high-income countries can be readily translated into policy contexts in low-middle-income-countries (LMICs). We conducted this systematic review to summarise noise epidemiological studies in LMICs. We conducted a literature search of studies in Medline and Web of Science published during 2009-2021, supplemented with specialist journal hand searches. Screening, data extraction, assessment of risk of bias as well as overall quality and strength of evidence were conducted following established guidelines (e.g. Navigation Guide). 58 studies were identified, 53% of which were from India, China and Bulgaria. Most (92%) were cross-sectional studies. 53% of studies assessed noise exposure based on fixed-site measurements using sound level meters and 17% from propagation-based noise models. Mean noise exposure among all studies ranged from 48 to 120 dB (Leq), with over half of the studies (52%) reporting the mean between 60 and 80 dB. The most studied health outcome was noise annoyance (43% of studies), followed by cardiovascular (17%) and mental health outcomes (17%). Studies generally reported a positive (i.e. adverse) relationship between noise exposure and annoyance. Some limited evidence based on only two studies showing that long-term noise exposure may be associated with higher prevalence of cardiovascular outcomes in adults. Findings on mental health outcomes were inconsistent across the studies. Overall, 4 studies (6%) had "probably low", 18 (31%) had "probably high" and 36 (62%) had "high" risk of bias. Quality of evidence was rated as 'low' for mental health outcomes and 'very low' for all other outcomes. Strength of evidence for each outcome was assessed as 'inadequate', highlighting high-quality epidemiological studies are urgently needed in LMICs to strengthen the evidence base.

Relationships of Residential Distance to Major Traffic Roads with Dementia Incidence and Brain Structure Measures: Mediation Role of Air Pollution.

Background: Uncertainty exists regarding the operating pathways between near-roadway exposure and dementia incidence. We intend to examine relationships between proximity to major roadways with dementia incidence and brain MRI structure measures, and potential mediation roles of air and noise pollution. Methods: The cohort study was based on the UK Biobank. Baseline survey was conducted from 2006 to 2010, with linkage to electronic health records conducted for follow-up. Residential distance to major roadways was ascertained residential address postcode. A land use regression model was applied for estimating traffic-related air pollution at residence. Dementia incidence was ascertained using national administrative databases. Brain MRI measures were derived as image-derived phenotypes, including total brain, white matter, gray matter, and peripheral cortical gray matter. Results: We included 460,901 participants [mean (SD) age: 57.1 (8.1) years; men: 45.7%]. Compared with individuals living >1,000 m from major traffic roads, living ≤1,000 m was associated with a 13% to 14% higher dementia risk, accounting for 10% of dementia cases. Observed association between residential distance and dementia was substantially mediated by traffic-related air pollution, mainly nitrogen dioxide (proportion mediated: 63.6%; 95% CI, 27.0 to 89.2%) and PM2.5 (60.9%, 26.8 to 87.0%). The shorter residential distance was associated with smaller volumes of brain structures, which was also mediated by traffic-related air pollutants. No significant mediation role was observed of noise pollution. Conclusions: The shorter residential distance to major roads was associated with elevated dementia incidence and smaller brain structure volumes, which was mainly mediated by traffic-related air pollution.

Ambient Air Pollution and Respiratory Health in Sub-Saharan African Children: A Cross-Sectional Analysis.

Ambient air pollution is projected to become a major environmental risk in sub-Saharan Africa (SSA). Research into its health impacts is hindered by limited data. We aimed to investigate the cross-sectional relationship between particulate matter with a diameter ≤ 2.5 µm (PM2.5) and prevalence of cough or acute lower respiratory infection (ALRI) among children under five in SSA. Data were collected from 31 Demographic and Health Surveys (DHS) in 21 SSA countries between 2005-2018. Prior-month average PM2.5 preceding the survey date was assessed based on satellite measurements and a chemical transport model. Cough and ALRI in the past two weeks were derived from questionnaires. Associations were analysed using conditional logistic regression within each survey cluster, adjusting for child's age, sex, birth size, household wealth, maternal education, maternal age and month of the interview. Survey-specific odds ratios (ORs) were pooled using random-effect meta-analysis. Included were 368,366 and 109,664 children for the analysis of cough and ALRI, respectively. On average, 20.5% children had reported a cough, 6.4% reported ALRI, and 32% of children lived in urban areas. Prior-month average PM2.5 ranged from 8.9 to 64.6 µg/m3. Pooling all surveys, no associations were observed with either outcome in the overall populations. Among countries with medium-to-high Human Development Index, positive associations were observed with both cough (pooled OR: 1.022, 95%CI: 0.982-1.064) and ALRI (pooled OR: 1.018, 95%CI: 0.975-1.064) for 1 µg/m3 higher of PM2.5. This explorative study found no associations between short-term ambient PM2.5 and respiratory health among young SSA children, necessitating future analyses using better-defined exposure and health metrics to study this important link.

Road traffic noise and cardiovascular disease risk factors in UK Biobank.

AIMS: The aim of this study was to investigate the cross-sectional associations of modelled residential road traffic noise with cardiovascular disease risk factors [systolic (SBP) and diastolic blood pressure (DBP), C-reactive protein, triglycerides, glycated haemoglobin, and self-reported hypertension] in UK Biobank. METHODS AND RESULTS: The UK Biobank recruited 502 651 individuals aged 40-69 years across the UK during 2006-10. Road traffic noise (Lden and Lnight) exposure for 2009 was estimated at baseline address using a simplified version of the Common Noise Assessment Methods model. We used multivariable linear and logistic regression models, adjusting for age, sex, body mass index (BMI), smoking, alcohol intake, area- and individual-level deprivation, season of blood draw, length of time at residence, and nitrogen dioxide (main model), in an analytical sample size of over 370 000 participants. Exposure to road-traffic Lden >65 dB[A], as compared to ≤55 dB[A], was associated with 0.77% [95% confidence interval (CI) 0.60%, 0.95%], 0.49% (95% CI 0.32%, 0.65%), 0.79% (95% CI 0.11%, 1.47%), and 0.12% (95% CI -0.04%, 0.28%) higher SBP, DBP, triglycerides, and glycated haemoglobin, respectively. Removing BMI from the main model yielded significant positive associations with all five markers with elevated percent changes. The associations with SBP or DBP did not appear to be impacted by hypertension medication while a positive association with prevalent self-reported hypertension was seen in the non-medicated group who exposed to a Lden level of 60-65 dB[A] (odds ratio 1.07, 95% CI 1.00, 1.15). CONCLUSION: Exposure to road traffic noise >65 dB[A], independent of nitrogen dioxide, was associated with small but adverse changes in blood pressure and cardiovascular biochemistry.

The need for clean air: The way air pollution and climate change affect allergic rhinitis and asthma.

Air pollution and climate change have a significant impact on human health and well-being and contribute to the onset and aggravation of allergic rhinitis and asthma among other chronic respiratory diseases. In Westernized countries, households have experienced a process of increasing insulation and individuals tend to spend most of their time indoors. These sequelae implicate a high exposure to indoor allergens (house dust mites, pets, molds, etc), tobacco smoke, and other pollutants, which have an impact on respiratory health. Outdoor air pollution derived from traffic and other human activities not only has a direct negative effect on human health but also enhances the allergenicity of some plants and contributes to global warming. Climate change modifies the availability and distribution of plant- and fungal-derived allergens and increases the frequency of extreme climate events. This review summarizes the effects of indoor air pollution, outdoor air pollution, and subsequent climate change on asthma and allergic rhinitis in children and adults and addresses the policy adjustments and lifestyle changes required to mitigate their deleterious effects.