Organic Dust Research Articles

The effect of occupational exposure to organic dust on lung function parameters among African industrial workers: a systematic review and meta-analysis

The effect of occupational exposure to organic dust on lung function parameters among African industrial workers: a systematic review and meta-analysis

Tentative detection of cyclopropenylidene in comets

ABSTRACT We report the tentative detection of the ring molecule cyclopropenylidene (c-C$_3$H$_2$) in cometary comae. We observed three short-period comets: 73P/Schwassmann–Wachmann 3, 17P/Holmes, 103P Hartley 2, and two Oort Cloud comets: C/2007 N3 (Lulin) and C/2012 F6 (Lemmon) with the Arizona Radio Observatory Submillimeter Telescope (SMT) and the Atacama Large Millimeter/submillimeter Array (ALMA). We tentatively detected c-C$_3$H$_2$ in three of the comets, with molecule production rates in the range of $(0.2\!-\!3.8)\times 10^{25}$ molecules s$^{-1}$, and c-C$_3$H$_2$/H$_2$O mixing ratios of 0.01–0.19 per cent. Evidence from both the single-dish and interferometric data points to the presence of c-C$_3$H$_2$ being of a discrete transient nature and exhibiting an extended spatial distribution, indicating production from the decomposition of organic dust particles in the coma.

Aconitate decarboxylase 1 mediates the acute airway inflammatory response to environmental exposures.

Environmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung disease. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Aconitate decarboxylase 1 (Acod1) was one of the most upregulated genes following LPS (vs. saline) exposure of murine whole lungs with transcriptomic profiling of sorted lung monocyte/macrophage subpopulations also highlighting its significance. Given monocyte/macrophage activation can be tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator ACOD1 in environmental exposure-induced lung inflammation. Wild-type (WT) mice were intratracheally (i.t.) instilled with 10 μg of LPS or saline. Whole lungs were profiled using bulk RNA sequencing or sorted to isolate monocyte/macrophage subpopulations. Sorted subpopulations were then characterized transcriptomically using a NanoString innate immunity multiplex array 48 h post-exposure. Next, WT and Acod1-/- mice were instilled with LPS, 25% organic dust extract (ODE), or saline, whereupon serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. BALF metabolites of the tricarboxylic acid (TCA) cycle were quantified by mass spectrometry. Cytokines/chemokines and tissue remodeling mediators were quantitated by ELISA. Lung immune cells were characterized by flow cytometry. Invasive lung function testing was performed 3 h post-LPS with WT and Acod1-/- mice. Acod1-/- mice treated with LPS demonstrated decreased BALF levels of itaconate, TCA cycle reprogramming, decreased BALF neutrophils, increased lung CD4+ T cells, decreased BALF and lung levels of TNF-α, and decreased BALF CXCL1 compared to WT animals. In comparison, Acod1-/- mice treated with ODE demonstrated decreased serum pentraxin-2, BALF levels of itaconate, lung total cell, neutrophil, monocyte, and B-cell infiltrates with decreased BALF levels of TNF-α and IL-6 and decreased lung CXCL1 vs. WT animals. Mediators of tissue remodeling (TIMP1, MMP-8, MMP-9) were also decreased in the LPS-exposed Acod1-/- mice, with MMP-9 also reduced in ODE-exposed Acod1-/- mice. Lung function assessments demonstrated a blunted response to LPS-induced airway hyperresponsiveness in Acod1-/- animals. Acod1 is robustly upregulated in the lungs following LPS exposure and encodes a key immunometabolic regulator. ACOD1 mediates the proinflammatory response to acute inhaled environmental LPS and organic dust exposure-induced lung inflammation.

Study on the explosion mechanism of two-phase organic dust — Based on polypropylene/propylene hybrid explosions as an example

A two-phase organic dust explosion is more complex than a single dust or gas explosion and poses a more significant threat to industrial safety production. To elucidate the explosion mechanism of two-phase organic dust, this study investigated the characteristics of flame propagation in PP/propylene hybrid explosions and revealed the flame propagation mechanism. The research findings indicate that adding propylene makes the flame brighter and more continuous, and velocity and temperature increase significantly. The introduction of propylene shifts the control of flame propagation from a process dominated by pyrolysis explosion kinetics to one governed by premixed gas explosion kinetics. Dimensionless characteristic numbers Bi and Da were introduced further to analyze the control mechanism of the dust explosion process. It was found that the explosion process was mainly diffusion flame combustion and premixed gas phase combustion.

Valorization of treated wastewater from the soaking of baby alpaca skin fur

Baby alpaca fur industry generates considerable wastewater during the soaking process, which contains high levels of total suspended solids (TSSs), proteins, and salts, among other components. The valorization of wastewater after precipitation, coagulation–flocculation, and aeration treatments was evaluated for use in irrigation water, fertigation, groundwater recharge, concrete construction, and disposal. The precipitation treatment sludge and the coagulation–flocculation treatment were evaluated as a protein source, soil quality improvement, and disposal. The treatment system included evaluations of nine pH levels, seven coagulant doses, and seven aeration times. The contents of TSSs, chemical oxygen demand (COD), total Kjeldalh nitrogen (TKN), ammonia nitrogen (N–NH3), and oils and fats (O&G), among other parameters, were determined in the treated and untreated wastewater. Before entering the treatment system, the physicochemical characterization of the wastewater showed a high concentration of parameters related to organic matter and dust, such as O&G, five-day biological oxygen demand (BOD5), COD, TSSs, TKN, and N–NH3. The optimal removal parameters were pH 12 for the chemical precipitation of proteins, a dose of 480 mg/L FeCl3 as a coagulant for TSSs removal, and 150 min of aeration; removal efficiencies of 99.02 %, 77.49 %, 79.93 %, and 64.62 % for TSSs, Cod, TKN, and N–NH3, respectively, were obtained. The wastewater after treatment can be used for groundwater recharge and concrete construction, and the wastewater with 2 % dilution can be used for irrigation water and fertigation. The sludge after precipitation is rich in protein and can be used as a protein source or soil quality improver.

Is Farming a Risk Occupation for Cardio-cerebrovascular Diseases? A Scoping Review on Cardio-cerebrovascular Disease Risk in Farmers.

In the Republic of Korea, cardiocerebrovascular disease (CCVD) is recognized as an occupational disease when sufficient evidence of a work-related burden exists. In 2021, approximately 26.8% of the payments from occupational disease insurance under the Industrial Accident Compensation Insurance Act were allocated to CCVDs. However, due to the specific nature of insurance policies for farmers, CCVD is not acknowledged as an occupational disease in their case. We reviewed studies on the differences in the incidence, prevalence, and mortality rates of CCVDs between farmers and the general population or other occupations and described the exposure of farmers to risk factors for CCVDs. Several studies showed that farming is a high-risk occupation for CCVDs, with the following risk factors: long working hours, night work, lack of holidays, and strenuous physical labor; physical factors (noise, cold, heat, humidity, and vibration); exposure to hazardous gases (diesel exhaust, carbon monoxide, hydrogen sulfide, carbon disulfide, nitrogen oxides, and polycyclic aromatic hydrocarbons), pesticides, and dust (particulate matter, silica, and organic dust); exposure to a hypoxic environment; and job-related stress. Social isolation and lack of accessible medical facilities also function as additional risk factors by preventing farmers from receiving early interventions. Farmers are exposed to various risk factors for CCVDs and are an occupation at risk for CCVDs. More studies are needed in the future to elucidate this relationship. This study lays the groundwork for future research to develop guidelines for approving CCVDs as occupational diseases among farmers.

Long-term measurements of aerosol composition at rural background sites in France: Sources, seasonality and mass closure of PM2.5

Fine particulate matter (PM2.5) was monitored at five rural background locations in France from 2012 to 2021. Annual PM2.5 ranged from 5 to 15 μg m−3, all sites repeatedly exceeding the 2021 annual World Health Organization guideline. Chemical speciation including organic and elemental carbon (OC, EC), secondary inorganic aerosols (SIA: NO3−, SO42−, NH4+) and other major water-soluble ions (Cl−, Na+, Mg2+, Ca2+, K+) were monitored on 24-h filters covering 14% of the year. A source apportionment of OM was undertaken based on fine potassium and using representative ratios for domestic biomass burning (BB) and fossil fuel (FF) emissions. The latter dominated the EC fraction (55–60%) while BB was the main primary source of OM (27–54%). The average mass balance of PM2.5 at the French rural background atmospheric sites was: secondary organic aerosol (18–35%), BB (17–27%), non-sea-salt sulphate (12–17%), nitrate (6–22%), ammonium (7–11%), FF (4–6%), mineral dust (3–9%) and sea salt (1–2%). Secondary aerosols were the main component of PM2.5 through all seasons, with SIA dominating in spring episodes. The contribution of OM to PM2.5 was larger at the southern sites whereas the contribution of SIA was larger at the northern sites. The mean OC/EC ratio and the good correlations between OC, EC, and fine potassium suggested that BB was the main primary source contributing to carbonaceous aerosols, 27–54% to total OM depending on the site; and also, to PM2.5 (17–27%). Stronger regulations of OM sources including BB, nitrate from combustion, and ammonium from agricultural sources are needed to reduce PM2.5 at rural background sites on an annual and episodic basis, respectively.

Pattern of occupational lung disease among industrial workers attending a medical college of Eastern India.

Occupational lung diseases (OLDs) contribute a significant proportion to the global burden of pulmonary morbidities but are grossly misdiagnosed due to the relative lack of attribution given to occupational exposures. Obstructive lung diseases are known to be associated with long-lasting disability and loss of earning capacity (LOEC) among workers in industrial setups, thus reducing nationwide productivity. In this context, the study aimed to find out the pattern of OLD and factors associated with the severity of it among patients in a tertiary care hospital. The study was a record-based secondary data analysis conducted in the Medical Records Department of a Medical College in Kolkata. A computerized database of patients attending Special Medical Board (SMB) examinations from the Department of Medical Records was utilized for data collection. A data abstraction format was constructed to collect information on pulmonary morbidity, occupational exposure, and sociodemographic and behavioral variables. Extracted data were analyzed in Microsoft Excel and Statistical Package for Social Sciences (SPSS) software. After a review of records, it was shown that 62.3% (66 out of 106 people) of the study subjects had an obstructive type of OLD, the most common being Jute Byssinosis. A negative correlation (Spearman's ρ = -0.136) was found between pulmonary function (FEV1/FVC) and LOEC (%) in the study subjects. In the multivariable logistic regression, exposure to organic dust was found to be significantly associated with worsened lung function {adjusted-Odd's Ratio (95% Confidence Interval) =3.11 (1.1-8.8), P value = 0.03}. OLD is an understated health issue, especially in an industrial diaspora of developing countries, like India. Healthcare facilities should utilize their resources properly for the advancement of medical surveillance in industries where organic dust is produced. Health education of the stakeholders regarding the consequences of OLDs and the benefits of preventive primary approaches will go a long way in alleviating the burden of disease.

Effects of particulate matter (PM2.5) concentration and components on mortality in chronic kidney disease patients: a nationwide spatial–temporal analysis

Chronic kidney disease (CKD) is a major global public health issue and the leading cause of death in Thailand. This study investigated the spatial–temporal association between PM2.5 and its components (organic carbon, black carbon, dust, sulfate, and sea salt) and CKD mortality in Thailand from 2012 to 2021. The Modern-Era Retrospective analysis for Research and Application version 2 (MERRA-2), a NASA atmospheric satellite model, was assessed for the temporal data of PM2.5 concentration and aerosol components. Spatial resources of 77 provinces were integrated using the Geographical Information System (GIS). Multivariate Poisson regression and Bayesian inference analyses were conducted to explore the effects of PM2.5 on CKD mortality across the provinces. Our analysis included 718,686 CKD-related deaths, resulting in a mortality rate of 1107 cases per 100,000 population where was the highest rate in Northeast region. The average age of the deceased was 72.43 ± 13.10 years, with males comprising 50.46% of the cases. Adjusting for age, sex, underlying diseases, co-morbidities, CKD complications, replacement therapy, population density, and income, each 1 µg/m3 increase in PM2.5, black carbon, dust, sulfate, and organic carbon was significantly associated with increased CKD mortality across 77 provinces. Incidence rate ratios were 1.04 (95% CI 1.03–1.04) for PM2.5, 1.11 (95% CI 1.10–1.13) for black carbon, 1.24 (95% CI 1.22–1.25) for dust, 1.16 (95% CI 1.16–1.17) for sulfate, and 1.05 (95% CI 1.04–1.05) for organic carbon. These findings emphasize the significant impact of PM2.5 on CKD mortality and underscore the need for strategies to reduce PM emissions and manage CKD co-morbidities effectively.

UV light absorption at 370 nm by mineral dust, organic carbon, and elemental carbon in the Himalayas and Tibetan Plateau

The mass and light absorption contributions of organic carbon (OC), elemental carbon (EC), and mineral dust influence glacial melting and potentially contribute to climate change over the high Himalayas and Tibetan Plateau (HTP). Plateau-scale investigations of these components and their respective light absorption are limited due to the high altitude. In this study, we combined the analysis of major light-absorbing substances and their corresponding multiwavelength absorption to determine their specific contributions firstly. We investigated the spatial variations of total suspended particle (TSP) mass across the HTP, noting high contributions from dust, carbonaceous components, and secondary inorganic aerosols (SNA, including sulfate, nitrate, and ammonium). Enhanced levels of primary and secondary OC and SNA were observed in the marginal areas of the HTP, associated with high relative humidity (RH) and OX levels (O3+NO2). EC was the primary contributor to light absorption, accounting for approximately 68%, 46%, and 64% in Ngari, Qinghai Lake, and Beiluhe, respectively. We found higher light-absorbing contributions from carbonaceous aerosols in the marginal areas compared to the central HTP site, particularly during the heating seasons (∼90%). Fugitive dust significantly contributed to TSP mass but not to light absorption. The concurrent constraints on the mass and optical properties of OC, EC, and dust in this study can help reduce uncertainties in climate models specific to the HTP.

Occupational interstitial lung diseases

Avariety of workplace exposures (organic or inorganic dusts as well as gases, fumes, or vapors) can cause diffuse interstitial lung disease. The latency period until onset of the disease can exceed 30years. The disease course varies greatly and depends on the quantity of the inhaled substance and its fibrogenic effect. Pulmonary high-resolution computed tomography (HRCT) patterns do not differ significantly from those of interstitial lung diseases (ILD) of other etiologies. Therefore, without knowledge of the occupational history, work-related ILDs are often classified as idiopathic. In addition, there is increasing evidence in the recent literature that high exposure to silica dust can trigger autoimmune diseases (also involving the lungs). For this reason, aqualified occupational history is now an indispensable part of the interdisciplinary diagnosis of ILDs.

Zinc Protects against Swine Barn Dust-Induced Cilia Slowing.

Agricultural workers exposed to organic dust from swine concentrated animal feeding operations (CAFOs) have increased chances of contracting chronic lung disease. Mucociliary clearance represents a first line of defense against inhaled dusts, but organic dust extracts (ODEs) from swine barns cause cilia slowing, leading to decreased bacterial clearance and increased lung inflammation. Because nutritional zinc deficiency is associated with chronic lung disease, we examined the role of zinc supplementation in ODE-mediated cilia slowing. Ciliated mouse tracheal epithelial cells were pretreated with 0-10 µg/mL ZinProTM for 1 h, followed by treatment with 5% ODE for 24 h. Cilia beat frequency (CBF) and protein kinase C epsilon (PKCε) activity were assayed. ODE treatment resulted in cilia slowing after 24 h, which was reversed with 0.5 and 1.0 µg/mL ZinPro pre-treatment. No zinc protection was observed at 50 ng/mL, and ciliated cells detached at high concentrations (100 µg/mL). ZinPro alone produced no changes in the baseline CBF and showed no toxicity to the cells at concentrations of up to 10 µg/mL. Pre-treatment with ZinPro inhibited ODE-stimulated PKCε activation in a dose-dependent manner. Based on ZinPro's superior cell permeability compared to zinc salts, it may be therapeutically more effective at reversing ODE-mediated cilia slowing through a PKCε pathway. These data demonstrate that zinc supplementation may support the mucociliary transport apparatus in the protection of CAFO workers against dust-mediated chronic lung disease.

Snow survey within the copper ore deposits in the mining regions of the Urals

The paper presents the results of studies of dust residues of snow cover within various climatic zones and copper deposits of the Ural region. Snow cover research is one of the methods for environmental assessment of territories. This concerns the study of dust residues from snow cover samples, as shown by the example of the territories of the Northern and Southern Urals at different stages of work on copper deposits. The initial stage of study and development is considered using the example of porphyry copper deposits in the Chelyabinsk region, where snow samples reveal organic matter in dust residues, typical birch seeds, a small amount of minerals at a low dust load (P ˂ 100 kg/day per km2). For the deposits of the Ivdel region (Northern Urals), the dust residues largely contain organic dust, fragments of ore minerals (pyrite, chalcopyrite) and minerals of volcanic rocks and metasomatic rocks. The maximum value of the dust load is set for the Novo-Shemurskoye deposit currently being developed. A study of dust residues in the zone of influence of the Karabash copper smelter (before its reconstruction) has shown that in some parts of the sanitary protection zone the level of snow cover pollution is very high with dust load values up to 12,633 kg/day per km2, which is determined primarily by the widespread use of crushed copper smelting slag. In general, the study of dust residues of snow cover provides information about both the ecological state of the territories and the mineral composition of the residues, which must be used for practical purposes.

Dust Explosibility and Severity of Bayan and Tanito Coal

AbstractThe assessment of the explosibility and severity characteristics of Bayan coal and Tanito coal was investigated over various concentrations in a 20 L Siwek spherical explosion chamber. The coals tested in this study were also compared with other organic dusts such as palm‐based soap noodle, tea powder, black rice, and rice flour, which were tested using the same explosion chamber and procedures. The severity and explosibility of the coals increase as their concentration increases. The Pmax of Bayan coal (10.15 bar) is higher than that of Tanito coal (7.35 bar). The Kst of Bayan coal (48.04 bar m s−1) is also higher than that of Tanito coal (16.83 bar m s−1). Among all the dusts studied using the same chamber and procedures, palm‐based soap noodle has the highest Pmax at 16 bar, while tea powder has the lowest Pmax at 6.35 bar. The results show that the explosibility and severity of the coals increase as the concentrations increase, and the moisture content, coal ranking, and different types of organic dust have a significant influence on the severity characteristics of dust explosions.

Decoupling pyrolysis and combustion of organic powders to determine the laminar flame speed

AbstractDetermining the laminar flame speed of dusts is far from straightforward. A strong dependency on the experimental setup and the data treatment's high complexity makes it a true challenge. This work compares three complementary experimental setups to measure the laminar flame speed of organic dust (here, cellulose): a modified Hartmann tube, a 20 L sphere, and a micro‐fluidized bed (MFB) burner. The first two consider the flame propagation phenomenon in its globality, which means that numerous steps are involved simultaneously (particle heating, pyrolysis, oxidation, radiative transfer, flame stretching), while the third one decouples pyrolysis and combustion, to focus mainly on the oxidation rate. An MFB was conceived to generate pyrolysis products and burn them in a laminar flame. Unstretched flame velocities determined with the first two setups were consistent and equal to 22.0 and 26.6 cm ∙ s−1, respectively. Using Silvestrini's equation, values ranging between 14.0 and 33.4 cm ∙ s−1 were obtained according to the dust concentration. With the MFB burner, the flame speed was much higher (135–155 cm ∙ s−1), due to the higher temperature of the fresh mixture and the fact that only the oxidation of the pyrolysis gases is considered. A numerical simulation (Chemkin) confirmed these results since the range 135 to 231 cm ∙ s−1 was obtained for equivalence ratios of 0.6 and 1.2, respectively. The discrepancy between the laminar flame speed determined in the sphere or in the tube and that obtained in the MFB highlights the significant influence of particle heating and pyrolysis during a dust explosion.

Pollution characteristics, source apportionment, and health risk assessment of PM10 and PM2.5 in rooftop and kerbside environment of Lanzhou, NW China.

To investigate air pollution in the kerbside environment and its associated human health risks, a study was conducted in Lanzhou during December 2018, as well as in April, June, and September 2019. The research aimed to characterize the composition of PM10 and PM2.5, including elements, ions, and carbonaceous components, at both rooftop and kerbside locations. Additionally, source apportionment and health risk assessment were conducted. The results showed that the average mass concentrations of PM10 on the rooftop were 176.01 ± 83.23μg/m3, and for PM2.5, it was 94.07 ± 64.89μg/m3. The PM10 and PM2.5 levels at the kerbside are 2.21 times and 1.79 times, respectively, greater than those on the rooftop. Moreover, the concentrations of elements, ions, and carbonaceous components in kerbside PM were higher than those at the rooftop location. Chemical mass closure analysis identified various sources, including organic matter, mineral dust, secondary ions, other ions, elements, and other components. In comparison to rooftop particulate matter (PM), mineral dust makes a more substantial contribution to kerbside PM. Secondary ions show an opposite trend, making a greater contribution to rooftop PM. The contribution of organic components within PM of the same particle size remains relatively consistent. The outcome of the health risk assessment indicates that Co, Cd, and As in PM within the kerbside and rooftop environments do not pose a notable carcinogenic risk. However, Al and Mn do present specific non-carcinogenic risks, particularly in the kerbside environment. Furthermore, children experience elevated non-carcinogenic risk compared to adults. These findings can serve as a scientific foundation for formulating policies within the local health department.

Rapid detection of explosives in collected dust using ion mobility spectrometry

Vapor and particulate matter from explosives can be adsorbed onto dust, enabling their detection in security and military applications. In this study, model explosive-adsorbed dust specimens were prepared using four types of dust from two inorganic substances [silica (SL) and clay (CL)] and two organic materials [sawdust (SD) and cotton fabric (CF)]. Three explosives, namely 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX), and pentaerythritol tetranitrate (PETN), were investigated, along with two different collection filters of poly(tetrafluoroethylene) (PTFE) and lens cleansing paper (LCP). The dust was sprayed in a hood and collected using a cyclone collector. The explosive components present in the dust were rapidly detected using ion mobility spectrometry (IMS). The adsorption efficiencies of TNT, RDX, and PETN onto dust were 36 – 97, 45 – 76, and 37 – 90 %, respectively, and the values of the inorganic dusts were higher than those of the organic dusts. The dust collection rate ranged from 5 to 15 %, and decreased in the order of CL > CF > SL = SD. The factors influencing rapid explosive detection were the intrinsic vapor pressure of the explosive, interactions between the dust and the explosive, thermal conductivities of the dusts and collection filters, and structure of the collection filter. Due to the low vapor pressure of RDX, this explosive was detected later than TNT and PETN. In most cases, detection was more rapid when using the LCP than when using the PTFE because of the thicker and woven structure of the PTFE filter. The detection limits achieved using the LCP (0.049 – 1.17 μg) were lower than those of the PTFE (0.67 – 10.05 μg). When the PTFE was used, the detection limits for the organic dusts were lower than those for the inorganic dusts. Notably, the detection limits of the explosives adsorbed onto dust were significantly higher than those of the pure explosives.

Risk of hypersensitivity pneumonitis and other interstitial lung diseases following organic dust exposure

BackgroundOrganic dust is associated with hypersensitivity pneumonitis, and associations with other types of interstitial lung disease (ILD) have been suggested. We examined the association between occupational organic dust exposure and...

Allergen-specific immunotherapy for mold allergies

AbstractMolds are ubiquitous in our environment and are considered by the population to be the most important indoor pollutant problem [1]. The current 2023 update to the AWMF mold guideline [1] is intended to allay or channel fears and provide assistance for a sensible diagnosis and treatment decision.The detection of an IgE-mediated allergy implies for allergists Allergen immunotherapy (AIT) as an established treatment option. However, compared to the well-validated AIT with pollen and house dust mites, the decision to use AIT with mold extracts must be weighed more heavily between the benefits and risks.Spores of Alternaria alternata are found in high concentrations in the outdoor air. Due to the high allergenic potential and the small size of the spores, an Alternaria allergy often leads to bronchial asthma, especially in children. The effectiveness of AIT with Alternaria extracts has been tested in several studies; for other molds, especially those from the indoor environment, the efficacy and applicability is very limited.In terms of differential diagnosis, it must be borne in mind that molds can not only cause common allergic reactions but can also be responsible for allergic bronchopulmonary mycoses/aspergillosis (ABPA), Aspergillus bronchitis, exogenous allergic alveolitis (EAA), invasive aspergillosis, mycoses and rhinosinusitis. Very high concentrations, which can occur particularly in workplaces, can also result in toxic effects (“organic dust toxic syndrome”); molds are also held responsible for mucous membrane irritation, odor effects and mood disorders [1].

Targeting transitioning lung monocytes/macrophages as treatment strategies in lung disease related to environmental exposures

BackgroundEnvironmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited, transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear.MethodsCCR2 RFP+ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. Infiltrating lung cells including monocyte/macrophage subpopulations, neutrophils, and lymphocytes were characterized by flow cytometry. Lung histopathology, collagen content, vimentin, and post-translational protein citrullination and malondialdehyde acetaldehyde (MAA) modification were quantitated. Parametric statistical tests (one-way ANOVA, Tukey’smultiple comparison) and nonparametric statistical (Kruskal–Wallis, Dunn’s multiple comparison) tests were used following Shapiro–Wilk testing for normality.ResultsIntratracheal instillation of ODE, LPS, or PGN robustly induced the recruitment of inflammatory CCR2+ CD11cintCD11bhi monocytes/macrophages and both CCR2+ and CCR2− CD11c−CD11bhi monocytes at 48 h. There were also increases in CCR2+ CD4+ and CD8+ T cells and NK cells. Despite reductions in LPS-induced lung infiltrating CD11cintCD11bhi cells (54% reduction), CCR2 knockout (KO) mice were not protected against LPS-induced inflammatory and pro-fibrotic consequences. Instead, compensatory increases in lung neutrophils and CCL2 and CCL7 release occurred. In contrast, the depletion of circulating monocytes through the administration of intravenous clodronate (vs. vehicle) liposomes 24 h prior to LPS exposure reduced LPS-induced infiltrating CD11cintCD11bhi monocyte-macrophage subpopulation by 59% without compensatory changes in other cell populations. Clodronate liposome pre-treatment significantly reduced LPS-induced IL-6 (66% reduction), matrix metalloproteinases (MMP)-3 (36%), MMP-8 (57%), tissue inhibitor of metalloproteinases (61%), fibronectin (38%), collagen content (22%), and vimentin (40%). LPS-induced lung protein citrullination and MAA modification, post-translational modifications implicated in lung disease, were reduced (39% and 48%) with clodronate vs. vehicle liposome.ConclusionHighly concentrated environmental/occupational exposures induced the recruitment of CCR2+ and CCR2− transitioning monocyte-macrophage and monocyte subpopulations and targeting peripheral monocytes may reduce the adverse lung consequences resulting from exposures to LPS-enriched inhalants.