Ambient Air Pollutant Exposures and COVID-19 Severity and Mortality in a Cohort of Patients with COVID-19 in Southern California.

Rationale: Ecological studies have shown air pollution associations with coronavirus disease (COVID-19) outcomes. However, few cohort studies have been conducted. Objectives: To conduct a cohort study investigating the association between air pollution and COVID-19 severity using individual-level data from the electronic medical record. Methods: This cohort included all individuals who received diagnoses of COVID-19 from Kaiser Permanente Southern California between March 1 and August 31, 2020. One-year and 1-month averaged ambient air pollutant (particulate matter ⩽2.5 µm in aerodynamic diameter [PM2.5], NO2, and O3) exposures before COVID-19 diagnosis were estimated on the basis of residential address history. Outcomes included COVID-19-related hospitalizations, intensive respiratory support (IRS), and ICU admissions within 30 days and mortality within 60 days after COVID-19 diagnosis. Covariates included socioeconomic characteristics and comorbidities. Measurements and Main Results: Among 74,915 individuals (mean age, 42.5 years; 54% women; 66% Hispanic), rates of hospitalization, IRS, ICU admission, and mortality were 6.3%, 2.4%, 1.5%, and 1.5%, respectively. Using multipollutant models adjusted for covariates, 1-year PM2.5 and 1-month NO2 average exposures were associated with COVID-19 severity. The odds ratios associated with a 1-SD increase in 1-year PM2.5 (SD, 1.5 µg/m3) were 1.24 (95% confidence interval [CI], 1.16-1.32) for COVID-19-related hospitalization, 1.33 (95% CI, 1.20-1.47) for IRS, and 1.32 (95% CI, 1.16-1.51) for ICU admission; the corresponding odds ratios associated with 1-month NO2 (SD, 3.3 ppb) were 1.12 (95% CI, 1.06-1.17) for hospitalization, 1.18 (95% CI, 1.10-1.27) for IRS, and 1.21 (95% CI, 1.11-1.33) for ICU admission. The hazard ratios for mortality were 1.14 (95% CI, 1.02-1.27) for 1-year PM2.5 and 1.07 (95% CI, 0.98-1.16) for 1-month NO2. No significant interactions with age, sex or ethnicity were observed. Conclusions: Ambient PM2.5 and NO2 exposures may affect COVID-19 severity and mortality.

Particulate matter of air pollution may increase risk of kidney failure in IgA nephropathy.

IgA nephropathy (IgAN) is characterized by deposition of galactose-deficient IgA1 (Gd-IgA1) in glomerular mesangium associated with mucosal immune disorders. Since environmental pollution has been associated with the progression of chronic kidney disease in the general population, we specifically investigated the influence of exposure to fine particulate matter less than 2.5 µm in diameter (PM2.5) on IgAN progression. Patients with biopsy-proven primary IgAN were recruited from seven Chinese kidney centers. PM2.5 exposure from 1998 to 2016 was derived from satellite aerosol optical depth data and a total of 1,979 patients with IgAN, including 994 males were enrolled. The PM2.5 exposure levels for patients from different provinces varied but, in general, the PM2.5 exposure levels among patients from the north were higher than those among patients from the south. The severity of PM2.5 exposure in different regions was correlated with regional kidney failure burden. In addition, each 10 µg/m3 increase in annual average concentration of PM2.5 exposure before study entry (Hazard Ratio, 1.14; 95% confidence interval, 1.06-1.22) or time-varying PM2.5 exposure after study entry (1.10; 1.01-1.18) were associated with increased kidney failure risk after adjustment for age, gender, estimated glomerular filtration rate, urine protein, uric acid, hemoglobin, mean arterial pressure, Oxford classification, glucocorticoid and renin-angiotensin system blocker therapy. The associations were robust when the time period, risk factors of cardiovascular diseases or city size were further adjusted on the basis of the above model. Thus, our results suggest that PM2.5 is an independent risk factor for kidney failure in patients with IgAN, but these findings will require validation in more diverse populations and other geographic regions.

Fine particulate matter exposure during pregnancy and infancy and incident asthma.

BACKGROUND: Lung development is a multistage process from conception to the postnatal period, disruption of which by air pollutants can trigger later respiratory morbidity. OBJECTIVE: We sought to evaluate the effects of weekly average fine particulate matter (particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) exposure during pregnancy and infancy on asthma and identify vulnerable times to help elucidate possible mechanisms of the effects of PM2.5 on asthma symptoms. METHODS: A birth cohort study including 184,604 children born during 2004-2011 in Taichung City was retrieved from the Taiwan Maternal and Child Health Database and followed until 2014. A daily satellite-based hybrid model was applied to estimate PM2.5 exposure for each subject. A Cox proportional hazard model combined with a distributed lag nonlinear model was used to evaluate the associations of asthma with PM2.5 exposure during pregnancy and infancy. RESULTS: The birth cohort contained 34,336 asthmatic patients, and the mean age of children given a diagnosis of asthma was 3.39 ± 1.78 years. Increased exposure to PM2.5 during gestational weeks 6 to 22 and 9 to 46 weeks after birth were significantly associated with an increased incidence of asthma. The exposure-response relationship indicated that the hazard ratio (HR) of asthma increased steeply at PM2.5 exposure of greater than 93 µg/m3 during pregnancy. Additionally, the HRs remained significant with postnatal exposure to PM2.5 between 26 and 72 µg/m3 (range, 1.01-1.07 µg/m3), followed by a sharp increase in HRs at PM2.5 exposure of greater than 73 µg/m3. CONCLUSION: Both prenatal and postnatal exposures to PM2.5 were associated with later development of asthma. The vulnerable time windows might be within early gestation and midgestation and infancy.

The relationship between air pollution and COVID-19-related deaths: An application to three French cities.

Being heavily dependent to oil products (mainly gasoline and diesel), the French transport sector is the main emitter of Particulate Matter (PMs) whose critical levels induce harmful health effects for urban inhabitants. We selected three major French cities (Paris, Lyon, and Marseille) to investigate the relationship between the Coronavirus Disease 19 (COVID-19) outbreak and air pollution. Using Artificial Neural Networks (ANNs) experiments, we have determined the concentration of PM2.5 and PM10 linked to COVID-19-related deaths. Our focus is on the potential effects of Particulate Matter (PM) in spreading the epidemic. The underlying hypothesis is that a pre-determined particulate concentration can foster COVID-19 and make the respiratory system more susceptible to this infection. The empirical strategy used an innovative Machine Learning (ML) methodology. In particular, through the so-called cutting technique in ANNs, we found new threshold levels of PM2.5 and PM10 connected to COVID-19: 17.4 µg/m3 (PM2.5) and 29.6 µg/m3 (PM10) for Paris; 15.6 µg/m3 (PM2.5) and 20.6 µg/m3 (PM10) for Lyon; 14.3 µg/m3 (PM2.5) and 22.04 µg/m3 (PM10) for Marseille. Interestingly, all the threshold values identified by the ANNs are higher than the limits imposed by the European Parliament. Finally, a Causal Direction from Dependency (D2C) algorithm is applied to check the consistency of our findings.

Chemical characteristics of road dust PM2.5 fraction in oasis cities at the margin of Tarim Basin.

In order to understand the compositions characteristics of particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) fraction in road dust (RD2.5) of oasis cities on the edge of Tarim Basin, 30 road dust (RD) samples were collected in Kashi, Cele, and Yutian in the spring, 2018, and RD2.5 was collected using the resuspension approach. Eight water-soluble ions, 39 trace elements and 8 fractions of carbon-containing species in PM2.5 were analyzed. Ca2+ and Ca were the most abundant ions and elements in RD2.5 (7.1% and 9.5%). Cl- in RD2.5 was affected not only by attributed to saline-alkali soils in oasis cities of the Tarim Basin and dust from Taklimakan Desert but also by human activities. Moreover, the organic carbon/elemental carbon (OC/EC) ratio indicated that carbon components in RD2.5 in Cele town mainly come from fossil fuel combustion, while those in Yutian and Kashi mainly come from biomass combustion. It is noteworthy that high Ca in RD2.5 was seriously affected by anthropogenic emissions, and high Na and K contents in RD2.5 could be derived from soil and desert dust. It was estimated that Cd, Tl, Sn and Cr were emitted from anthropogenic emissions using the enrichment factor. The coefficients of divergence (COD) result indicated that the influence of local emission on road dust emission is greater than that of long-distance transmission. This study is the first time to comprehensively analyze the chemical characteristics of road dust in oasis cities, and the results provides the sources of road dust at the margin of Tarim Basin.

Changes in the relationship between childhood asthma and ambient air pollution in Taiwan: Results from a nationwide survey repeated 5 years apart.

BACKGROUND: Childhood asthma is a common disease whose prevalence is changing. Shift in environmental exposure was one of the plausible explanations. This study investigated changes in the association between childhood asthma and ambient air pollution occurring over time. METHOD: A nationwide questionnaire survey concerning respiratory illness and symptoms was administered to Taiwanese elementary and middle school students in 2011 and repeatedly in 2016-2017. During the study period, the concentrations of ambient air pollutants were obtained from the Environmental Protection Administration (EPA) monitoring stations. Generalized estimating equation models were applied to examine the association between air pollution in the past year and the risk of current asthma. RESULTS: A total of 6346 children from the 2011 survey and 11 585 children from the 2016-2017 survey attended schools located within a 1-km radius of Taiwan EPA monitoring stations. The prevalence of childhood current asthma (children with physician-diagnosed asthma and persistent asthma symptoms in the past year) increased from 7.5% to 9.6% during this period. The level of exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5 ) in the past year was found to be associated with current asthma both in the 2011 survey (odds ratio (OR): 1.90, 95% confidence interval (CI): 1.41-2.57) and in the 2016-2017 survey (OR: 1.24, 95% CI: 1.04-1.48). CONCLUSION: Improved air quality has reduced the effect of PM2.5 on childhood asthma, but air quality remains a health concern in Taiwan.

Changes in the relationship between ambient fine particle concentrations and childhood lung function over 5 years.

BACKGROUND: Exposure to ambient fine particles, particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5), is a public health concern. Concentrations of ambient PM2.5 have changed temporally in the past 10 years after a series of action policies for improving air quality were implemented in Taiwan. In this study, temporal changes in the relationship between PM2.5 and lung function among children were investigated. METHODS: A nationwide respiratory health survey was conducted among Taiwanese elementary and middle school students in 2011 and again in 2016-2017. A questionnaire was administered to students, for whom forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured using spirometry. During the study period, monthly concentrations of ambient PM2.5 were obtained from the monitoring stations of the Environmental Protection Administration. Lung function measurements were compared with ambient PM2.5 exposure using mixed-effects models. RESULTS: In the 2011 survey (mean PM2.5: 40.6 µg/m3), exposure to PM2.5 in the preceding 1-2 months was associated with a 2.2% decrease (95% confidence interval [CI]: -4.1%, -0.3%) in FVC and a 2.3% decrease (95% CI: -4.0%, -0.5%) in FEV1. By contrast, a significant relationship between PM2.5 concentrations and lung function was not observed in the 2016-2017 survey (mean PM2.5: 30.0 µg/m3). CONCLUSIONS: As improvement in air quality over time, the negative relationship between PM2.5 and childhood lung function tend to be not significant.

Maternal exposure to ambient fine particulate matter and risk of premature rupture of membranes in Wuhan, Central China: a cohort study.

BACKGROUND: The associations between maternal exposure to ambient PM2.5 during pregnancy and the risk of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) are controversial. And no relevant study has been conducted in Asia. This study aimed to determine the association between maternal exposure to ambient PM2.5 during pregnancy and the risk of (P)PROM. METHODS: A cohort study including all singleton births in a hospital located in Central China from January 2015 through December 2017 was conducted. Multivariable logistic regression models, stratified analysis, generalized additive model, and two-piece-wise linear regression were conducted to evaluate how exposure to ambient PM2.5 during pregnancy is associated with the risks of PROM and PPROM. RESULTS: A total of 4364 participants were included in the final analysis, where 11.71 and 2.34% of births were complicated by PROM and PPROM, respectively. The level of PM2.5 exhibited a degree of seasonal variation, and its median concentrations were 63.7, 59.3, 55.8, and 61.8 µg/m3 for the first trimester, second trimester, third trimester, and the whole duration of pregnancy, respectively. After adjustment for potential confounders, PROM was positively associated with PM2.5 exposure (per 10 µg/m3) [Odds Ratio (OR) = 1.14, 95% Confidence Interval (CI), 1.02-1.26 for the first trimester; OR = 1.09, 95% CI, 1.00-1.18 for the second trimester; OR = 1.13, 95% CI, 1.03-1.24 for the third trimester; OR = 1.35, 95% CI, 1.12-1.63 for the whole pregnancy]. PPROM had positive relationship with PM2.5 exposure (per 10 µg/m3) (OR = 1.17, 95% CI, 0.94-1.45 for first trimester; OR = 1.11, 95% CI, 0.92-1.33 for second trimester; OR = 1.19, 95% CI, 0.99-1.44 for third trimester; OR = 1.53, 95% CI, 1.03-2.27 for the whole pregnancy) Positive trends between the acute exposure window (mean concentration of PM2.5 in the last week and day of pregnancy) and risks of PROM and PPROM were also observed. CONCLUSIONS: Exposure to ambient PM2.5 during pregnancy was associated with the risk of PROM and PPROM.

Impact of ambient PM2.5 on adverse birth outcome and potential molecular mechanism.

PM2.5 (particulate matter ≤2.5 µm in aerodynamic diameter) refers to atmospheric particulate matter (PM) with an aerodynamic diameter of equal and less than 2.5 µm that tends to be suspended for long periods of time and travel over long distances in both outdoor and indoor atmospheres. PM2.5, along with the toxic compounds attached on it, may cause a wide range of disorders. The fetus is considered to be highly susceptible to a variety of toxicants including atmospheric pollutants such as PM2.5 through prenatal exposure. To better understand the relationship between maternal exposure to PM2.5 and adverse birth outcomes for reproduction and fetus development, we studied the published data on this issue including case-control studies, cohort studies and meta-analyses studies, and summarized the basic impact of ambient particulate matter on adverse birth outcomes. Research evidence indicates that PM2.5 has a potential to induce low birth weight (LBW), preterm birth (PTB), and stillbirth. A further in-depth analysis shows that oxidative stress, DNA methylation, mitochondrial DNA (mtDNA) content alteration, and endocrine disruptions may all play an important role in PM2.5 induced adverse effects to pregnant women and fetuses. In addition, PM2.5 exposure can cause male reproductive toxicity, leading to associated adverse pregnancy outcomes.

Short-term exposures to ambient air pollution and risk of recurrent ischemic stroke.

OBJECTIVE: To investigate the association between short-term changes in ambient pollution (particulate matter <2.5µm in aerodynamic diameter (PM2.5) and ozone (O3)) and the risk of recurrent ischemic stroke among individuals living in a bi-ethnic community. METHODS: We identified recurrent ischemic stroke cases from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project between 2000 and 2012. Associations between PM2.5 (mean 24-h) and O3 (maximal 8-h) levels, measured on the previous day, and odds of ischemic stroke were assessed using a time-stratified case-crossover design and modeled using conditional logistic regression. RESULTS: There were 317 recurrent ischemic strokes after excluding 41 strokes that occurred on days with missing air pollution data. Mean age was 72 years (SD=12) and median time to stroke recurrence was 1.1 years (IQR: 0.2-2.8 years). Median levels of PM2.5 and O3 over the study period were 7.7µg/m3 (IQR: 5.6-10.7µg/m3) and 35.2 ppb (IQR: 25.0-46.1 ppb), respectively. We observed no associations between previous-day PM2.5 and O3 and odds of recurrent stroke (OR=0.95 per 10µg/m3 of PM2.5, 95% CI: 0.71-1.28 and OR=0.97 per 10ppb of O3, 95% CI: 0.87-1.07) after adjusting for ambient temperature and relative humidity. Co-adjustment of both pollutants did not change the results. CONCLUSION: We found no evidence of associations between previous-day air pollution levels and recurrent ischemic stroke. Research on the influence of air pollutants on risk of stroke recurrence is still in its infancy, and more research is necessary in studies that are adequately powered to understand the relation.

In vitro/in vivo correlation and modeling of emitted dose and lung deposition of inhaled salbutamol from metered dose inhalers with different types of spacers in noninvasively ventilated patients.

Substituting spacer by another in noninvasive ventilation (NIV) involves many variables, e.g. total emitted dose (TED), mass median aerodynamic diameter (MMAD), type of spacer, total lung deposition and total systemic absorption, which must be adjusted to ensure patient optimum therapy. Data mining based on artificial neural networks and genetic algorithms were used to model in vitro inhalation process, predict and optimize bioavailability from inhaled doses delivered by metered dose inhaler (MDI) using different spacers in NIV. Modeling of data indicated that in vitro performance of MDI-spacer systems was dependent mainly on fine particle dose (FPD), fine particle fraction (FPF), MMAD and to lesser extent on spacer type. Ex vivo model indicated that amount of salbutamol collected on facemask filter was directly affected by FPF. In vivo model (24hQ) depended directly on spacer type, FPF and TED. Female patients showed higher 0.5hQ and 24hQ values than males. AeroChamber VC spacer demonstrated higher TED and 24hQ in vivo values. Results indicated suitability of MDI-spacer systems in achieving appropriate in vitro inhalation performance. The possibility of modeling and predicting both ex vivo and in vivo capabilities of MDI-spacer systems from knowledge of in vitro attributes enabled detailed focus on important variables required to deliver safe and accurate doses of salbutamol to ventilated patients.

Discriminating Ability of Abbreviated Impactor Measurement Approach (AIM) to Detect Changes in Mass Median Aerodynamic Diameter (MMAD) of an Albuterol/Salbutamol pMDI Aerosol.

This article reports on results from a two-lab, multiple impactor experiment evaluating the abbreviated impactor measurement (AIM) concept, conducted by the Cascade Impaction Working Group of the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of this experiment was to expand understanding of the performance of an AIM-type apparatus based on the Andersen eight-stage non-viable cascade impactor (ACI) for the assessment of inhalation aerosols and sprays, compared with the full-resolution version of that impactor described in the pharmacopeial compendia. The experiment was conducted at two centers with a representative commercially available pressurized metered dose inhaler (pMDI) containing albuterol (salbutamol) as active pharmaceutical ingredient (API). Metrics of interest were total mass (TM) emitted from the inhaler, impactor-sized mass (ISM), as well as the ratio of large particle mass (LPM) to small particle mass (SPM). ISM and the LPM/SPM ratio together comprise the efficient data analysis (EDA) metrics. The results of the comparison demonstrated that in this study, the AIM approach had adequate discrimination to detect changes in the mass median aerodynamic diameter (MMAD) of the ACI-sampled aerodynamic particle size distribution (APSD), and therefore could be employed for routine product quality control (QC). As with any test method considered for inclusion in a regulatory filing, the transition from an ACI (used in development) to an appropriate AIM/EDA methodology (used in QC) should be evaluated and supported by data on a product-by-product basis.

Oral inhalation of dacomitinib nanocarriers as a therapeutic strategy for non-small cell lung cancer.

Background: Development of an inhalable nanoformulation of dacomitinib (DMB) encapsulated in poly-(lactic-co-glycolic acid) nanoparticles (NPs) to improve solubility, facilitate direct lung delivery and overcome the systemic adverse effects.Methods: DMB-loaded poly-(lactic-co-glycolic acid) NPs were prepared using solvent evaporation and characterized for particle size, polydispersity index and zeta-potential. The NPs were evaluated for in vitro drug release, aerosolization performance and in vitro efficacy studies.Results: The NPs showed excellent particle characteristics and displayed a cumulative release of ∼40% in 5 days. The NPs demonstrated a mass median aerodynamic diameter of ∼3 µm and fine particle fraction of ∼80%. Further, in vitro cell culture studies showed improved cytotoxic potential of DMB-loaded NPs compared with free drug.Conclusion: The study underscores the potential of DMB-loaded NPs as a viable approach for non-small cell lung cancer treatment.

Characteristics of radioactive aerosols during the pre-decommission phase of the experimental shielding reactor.

The decommissioning of nuclear reactors is a global concern, in part because of the generation of radioactive aerosols that can lead to internal radiation exposure. At present, radioactive aerosols generated during nuclear decommissioning have not been actively studied, and data collected from the actual decommissioning are limited. This paper presents a study of radioactive aerosols generated during the pre-decommission phase of an experimental shielding reactor. Among all the on-site operations, cutting resulted in the highest levels of radioactivity. Plasma arc cutting, in particular, had a maximum gross α and ß radioactivity over 0.10 and 0.14 Bq/m3, respectively. Assumed AMAD (activity median aerodynamic diameter) values are employed to assess the impact of particle size on the internal exposure dose resulting from the inhalation of 137Cs aerosols. This assessment is based on the Human Respiratory Tract Model of International Commission on Radiological Protection. When cutting stainless steel by plasma arc, the internal exposure dose caused by 137Cs aerosols with an AMAD of 0.1 µm is estimated to be nearly four times as that of aerosols with an AMAD of 10 µm. Results show that the internal exposure dose is highly dependent on the AMAD, implying the importance of measuring size-related parameters of radioactive aerosols in the future nuclear decommissioning. This study has revealed some characteristics of radioactive aerosols released in decommissioning operations, which can serve as a valuable reference for controlling and removing aerosols during the decommissioning of nuclear facilities.

Association Between Particulate Matter Exposure and Preterm Birth in Women With Abnormal Preconception Thyrotropin Levels: Large Cohort Study.

Background: Prior research has linked exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) with preterm birth (PTB). However, the modulating effect of preconception thyroid stimulating hormone (TSH) levels on the relationship between PM2.5 exposure and PTB has not been investigated. Objective: This study aimed to assess whether preconception TSH levels modulate the impact of PM2.5 exposure on PTB. Methods: This cohort study was conducted in Guangdong, China, as a part of the National Free Pre-Pregnancy Checkups Project. PM2.5 exposure was estimated by using the inverse distance weighting method. To investigate the moderating effects of TSH levels on trimester-specific PM2.5 exposure and PTB, we used the Cox proportional hazards model. Additionally, to identify the susceptible exposure windows for weekly specific PM2.5 exposure and PTB, we built distributed lag models incorporating Cox proportional hazards models. Results: A total of 633,516 women who delivered between January 1, 2014, to December 31, 2019, were included. In total, 34,081 (5.4%) of them had abnormal preconception TSH levels. During the entire pregnancy, each 10-µg/m3 increase in PM2.5 was linked to elevated risks of PTB (hazard ratio [HR] 1.559, 95% CI 1.390-1.748), early PTB (HR 1.559, 95% CI 1.227-1.980), and late PTB (HR 1.571, 95% CI 1.379-1.791) among women with abnormal TSH levels. For women with normal preconception TSH levels, PM2.5 exposure during the entire pregnancy was positively associated with the risk of PTB (HR 1.345, 95% CI 1.307-1.385), early PTB (HR 1.203, 95% CI 1.126-1.285), and late PTB (HR 1.386, 95% CI 1.342-1432). The critical susceptible exposure windows were the 3rd-13th and 28th-35th gestational weeks for women with abnormal preconception TSH levels, compared to the 1st-13th and 21st-35th gestational weeks for those with normal preconception TSH levels. Conclusions: PM2.5 exposure was linked with a higher PTB risk, particularly in women with abnormal preconception TSH levels. PM2.5 exposure appears to have a greater effect on pregnant women who are in the early or late stages of pregnancy.

Race, socioeconomic status, and air pollution exposure in North Carolina.

BACKGROUND: Although studies suggest that exposure to pollutants is associated with race/ethnicity and socio-economic status (SES), many studies are limited to the geographic regions where monitoring stations are located. OBJECTIVES: This study uses modeled predictive surfaces to examine the relationship between air pollution exposure, race/ethnicity, and measures of SES across the entire State of North Carolina. METHODS: The daily predictions of particulate matter <2.5 µm in aerodynamic diameter (PM2.5) and ozone (O3) were determined using a spatial model that fused data from two sources: point air monitoring data and gridded numerical output. These daily predicted pollution levels for 2002 were linked with Census data. We examine the relationship between the census-tract level predicted concentration measures, SES, and racial composition. RESULTS: SES and race/ethnicity were related to predicted concentrations of both PM2.5 and O3 for census tracts in North Carolina. Lower SES and higher proportion minority population were associated with higher levels of PM2.5. An interquartile range (IQR) increase of median household income reduced the predicted average PM2.5 level by 0.10 µg/m3. The opposite relationship was true for O3. An IQR increase of median household income increased the predicted average O3 measure by 0.11 ppb. CONCLUSIONS: The analyses demonstrate that SES and race/ethnicity are related to predicted estimates of PM2.5 and O3 for census tracts in North Carolina. These findings offer a baseline for future exposure modeling work involving SES and air pollution for the entire state and not just among the populations residing near monitoring networks.

Dry Powder Formulations for Inhalation Require a Smaller Aerodynamic Diameter for Usage at High Altitude.

BACKGROUND: High Altitude Pulmonary Edema (HAPE) seriously threatens the health of people at high altitudes. There are drug treatments for HAPE, and dry powder formulations (DPFs) represent a rapid and accessible delivery vehicle for these drugs. However, there are presently no reports on the inhalability of DPFs in low-pressure environments. Given the reduced atmospheric pressure typical at high altitudes, conventional DPFs might not be suitable for inhalation. Therefore, it is necessary to elucidate the deposition behaviors of dry powder in the respiratory tract at low pressure, as well as to improve their pulmonary deposition efficiency via adjustments to their formulation and design. METHODS: The effect of air pressure, inspiratory velocity, and particle properties (such as size, density, and aerodynamic diameter) on pulmonary deposition of DPFs was calculated by a computational fluid dynamics (CFD)-coupled discrete phase model. DPFs of various aerodynamic diameters were prepared by spray drying, and the inhalability of these DPFs in a low-pressure environment was evaluated in mice. Finally, a mouse model of HAPE was established, and the treatment of HAPE by nifedipine-loaded DPFs with small aerodynamic diameter was validated. RESULTS: CFD results showed that low pressure decreased the deposition of DPFs in the lungs. At 0.5 standard atmosphere, DPFs with aerodynamic diameter of ∼2.0 µm could not enter the lower respiratory tract; however, a decrease in the physical diameter, density, and, consequently, the aerodynamic diameter of the DPFs was able to enhance pulmonary deposition of these powders. To validate the CFD results, three kinds of dry powder with aerodynamic diameters of 0.66, 0.98, and 2.00 µm were prepared by spray drying. Powders with smaller aerodynamic diameter could be inhaled into the lungs of mice more effectively, and, consequently could ameliorate the progression of HAPE more effectively than conventional powders. These results were consistent with the CFD results. CONCLUSIONS: Low atmospheric pressure can prevent the pulmonary deposition of DPFs at high altitudes. Compared with conventional DPFs, powders with smaller aerodynamic diameter can be effectively inhaled at these pressures and thus might be more suitable for the treatment the HAPE.

The effect of exhalation before the inhalation of dry powder aerosol drugs on the breathing parameters, emitted doses and aerosol size distributions.

Airway deposition of aerosol drugs is highly dependent on the breathing manoeuvre of the patients. Though incorrect exhalation before the inhalation of the drug is one of the most common mistakes, its effect on the rest of the manoeuvre and on the airway deposition distribution of aerosol drugs is not explored in the open literature. The aim of the present work was to conduct inhalation experiments using six dry powder inhalers in order to quantify the effect of the degree of lung emptying on the inhalation time, inhaled volume and peak inhalation flow. Another goal of the research was to determine the effect of the exhalation on the aerodynamic properties of the drugs emitted by the same inhalers. According to the measurements, deep exhalation before drug inhalation increased the volume of the inhaled air and the average and maximum values of the inhalation flow rate, but the extent of the increase was patient and inhaler specific. For different inhalers, the mean value of the relative increase in peak inhalation flow due to forceful exhalation was between 15.3 and 38.4% (min: Easyhaler®, max: Breezhaler®), compared to the case of normal (tidal) exhalation before the drug inhalation. The relative increase in the inhaled volume was between 36.4 and 57.1% (min: NEXThaler®, max: Turbuhaler®). By the same token, forceful exhalation resulted in higher emitted doses and smaller emitted particles, depending on the individual breathing ability of the patient, the inhalation device and the drug metered in it. The relative increase in the emitted dose varied between 0.2 and 8.0% (min: Foster® NEXThaler®, max: Bufomix® Easyhaler®), while the relative enhancement of fine particle dose ranged between 1.9 and 30.8% (min: Foster® NEXThaler®, max: Symbicort® Turbuhaler®), depending on the inhaler. All these effects and parameter values point toward higher airway doses due to forceful exhalation before the inhalation of the drug. At the same time, the present findings highlight the necessity of proper patient education on the importance of lung emptying, but also the importance of patient-specific inhaler-drug pair choice in the future.

Lockdown-induced Urban Aerosol Change over Changchun, China During COVID-19 Outbreak with Polarization LiDAR.

Depending on various government policies, COVID-19 (Corona Virus Disease-19) lockdowns have had diverse impacts on global aerosol concentrations. In 2022, Changchun, a provincial capital city in Northeast China, suffered a severe COVID-19 outbreak and implemented a very strict lockdown that lasted for nearly two months. Using ground-based polarization Light Detection and Ranging (LiDAR), we detected real-time aerosol profile parameters (EC, extinction coefficient; DR, depolarization ratio; AOD, aerosol optical depth), as well as air-quality and meteorological indexes from 1 March to 30 April in 2021 and 2022 to quantify the effects of lockdown on aerosol concentrations. The period in 2022 was divided into three stages: pre-lockdown (1-10 March), strict lockdown (11 March to 10 April), and partial lockdown (11-30 April). The results showed that, during the strict lockdown period, compared with the pre-lockdown period, there were substantial reductions in aerosol parameters (EC and AOD), and this was consistent with the concentrations of the atmospheric pollutants PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm) and PM10 (particulate matter with an aerodynamic diameter ≤ 10 µm), and the O3 concentration increased by 8.3%. During the strict lockdown, the values of EC within 0-1 km and AOD decreased by 16.0% and 11.2%, respectively, as compared to the corresponding period in 2021. Lockdown reduced the conventional and organized emissions of air pollutants, and it clearly delayed the time of seasonal emissions from agricultural burning; however, it did not decrease the number of farmland fire points. Considering meteorological factors and eliminating the influence of wind-blown dust events, the results showed that reductions from conventional organized emission sources during the strict lockdown contributed to a 30% air-quality improvement and a 22% reduction in near-surface extinction (0-2 km). Aerosols produced by urban epidemic prevention and disinfection can also be identified using the EC. Regarding seasonal sources of agricultural straw burning, the concentrated burning induced by the epidemic led to the occurrence of heavy pollution from increased amounts of atmospheric aerosols, with a contribution rate of 62%. These results indicate that there is great potential to further improve air quality in the local area, and suggest that the comprehensive use of straw accompanied by reasonable planned burning is the best way to achieve this.

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes.

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.