Respiratory Tract Exposure Research Articles

Long-term exposure to PM2.5 leads to mitochondrial damage and differential expression of associated circRNA in rat hepatocytes

Fine particulate matter (PM2.5) is one of the four major causes of mortality globally. The objective of this study was to investigate the mechanism underlying liver injury following exposure to PM2.5 and the involvement of circRNA in its regulation. A PM2.5 respiratory tract exposure model was established in SPF SD male rats with a dose of 20 mg/kg, and liver tissue of rats in control group and PM2.5-exposed groups rats were detected. The results of ICP-MS showed that Mn, Cu and Ni were enriched in the liver. HE staining showed significant pathological changes in liver tissues of PM2.5-exposed group, transmission electron microscopy showed significant changes in mitochondrial structure of liver cells, and further mitochondrial function detection showed that the PM2.5 exposure resulted in an increase in cell reactive oxygen species content and a decrease in mitochondrial transmembrane potential, while the expression of SOD1 and HO-1 antioxidant oxidase genes was upregulated. Through high-throughput sequencing of circRNAs, we observed a significant down-regulation of 10 and an up-regulation of 17 circRNAs in the PM2.5-exposed groups. The functional enrichment and pathway analyses indicated that the differentially expressed circRNAs by PM2.5 exposure were primarily associated with processes related to protein ubiquitination, zinc ion binding, peroxisome function, and mitochondrial regulation. These findings suggest that the mechanism underlying liver injury induced by PM2.5-exposure may be associated with mitochondrial impairment resulting from the presence of heavy metal constituents. Therefore, this study provides a novel theoretical foundation for investigating the molecular mechanisms underlying liver injury induced by PM2.5 exposure.

Application of SHEL Model in the Management of Respiratory Tract Exposure in Fangcang Shelter Hospitals for COVID-19.

To explore the application effect of the (software factors, hardware factors, environmental factors, parties and other factors, SHEL) model in respiratory tract exposure protection of staff in temporary COVID-19 hospitals. 207 Staff members working in the isolation units of Fangcang shelter hospitals between 20 May 2022 and 5 June 2022 were selected as research subjects. The SHEL model was used to protect and manage the respiratory exposure of the isolation unit staff to the novel coronavirus. The incidence of respiratory exposure among the staff in the isolation units was compared before the SHEL model's implementation (20 May 2022-28 May 2022) and afterwards the SHEL model's implementation (29 May 2022-5 June 2022). Before the implementation of the SHEL model, a total of nine cases (4.35%) from 207 workers had respiratory exposure. Occurrence location: six cases in the isolation room (one-out room, level-one protection zone) and three cases in the drop-off area for patients outside the ward. After implementation, a total of two cases (0.97%) of respiratory tract exposure occurred among the 207 staff members; both occurred in the unprotected zone (two-out room, level-two protection zone), and the difference was statistically significant before and after the implementation (P < 0.05). New coronary pneumonia Fangcang shelter hospitals should use the SHEL model to manage the respiratory exposure of their isolation unit staff to reduce the respiratory exposure risk to staff in isolation units.

Antibody protection from SARS-CoV-2 respiratory tract exposure and infection

The COVID-19 pandemic has underscored the need to understand the dynamics of SARS-CoV-2 respiratory infection and protection provided by the immune response. SARS-CoV-2 infections are characterized by a particularly high viral load, and further by the small number of inhaled virions sufficient to generate a high viral titer in the nasal passage a few days after exposure. SARS-CoV-2 specific antibodies (Ab), induced from vaccines, previous infection, or inhaled monoclonal Ab, have proven effective against SARS-CoV-2 infection. Our goal in this work is to model the protective mechanisms that Ab can provide and to assess the degree of protection from individual and combined mechanisms at different locations in the respiratory tract. Neutralization, in which Ab bind to virion spikes and inhibit them from binding to and infecting target cells, is one widely reported protective mechanism. A second mechanism of Ab protection is muco-trapping, in which Ab crosslink virions to domains on mucin polymers, effectively immobilizing them in the mucus layer. When muco-trapped, the continuous clearance of the mucus barrier by coordinated ciliary propulsion entrains the trapped viral load toward the esophagus to be swallowed. We model and simulate the protection provided by either and both mechanisms at different locations in the respiratory tract, parametrized by the Ab titer and binding-unbinding rates of Ab to viral spikes and mucin domains. Our results illustrate limits in the degree of protection by neutralizing Ab alone, the powerful protection afforded by muco-trapping Ab, and the potential for dual protection by muco-trapping and neutralizing Ab to arrest a SARS-CoV-2 infection. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”.

Prevalence of Comorbidities Among COPD Patients: A Comparative Case-Control Study in Kashmir

Background: COPD is a chronic inflammatory lung disease characterized by airflow limitation, which is a result of continuous and consistent use of tobacco smoke or exposure of respiratory tract to noxious stimuli or recurrent childhood respiratory tract infection. Methods: A cross section of population from one of the assembly constituencies of Srinagar city has been taken as an area of sampling. A sample size of about 400 subjects was taken from three different electoral wards based on random table method as per defined inclusion criteria. Results: Majority of the COPD patients accounting for (33.8%) were aging from 40 to 50 years, followed by (31.1%) falling in the age interval (61-70) years. The present study revealed that commonest comorbidities among COPD patients were hypertension (56.7%), Osteoporosis (41%), anxiety (32.4%), diabetes (24.3%) and HTN CVD (22.9%). Conclusion: The present study demonstrated that the prevalence of chronic diseases like hypertension, diabetes, HTN CVD, RA osteoporosis, anxiety, proximal myopathy, and insomnia are significantly higher among COPD cases compared to healthy controls. Keywords: Chronic obstructive pulmonary disease, respiratory tract infection, comorbidities

Glutathione reactivity with aliphatic polyisocyanates.

Isocyanate chemicals known to cause adverse health effects when inhaled are essential to making important products and are used in multiple industries. Glutathione (GSH), a major antioxidant of the lower airways with a well described role in xenobiotic metabolism, is a primary reaction target for di-isocyantes. However, GSHs reactivity with poly-isocyanates which have largely replaced diisocyanates (particularly aliphatic) in most end-user settings remains uncertain. We hypothesized aliphatic polyisocyanates would readily react with glutathione under physiologic conditions and the products could be identified using liquid chromatography (LC) coupled-mass spectrometry (MS) and tandem MS/MS. The data identified (tris)GSH-isocyanate adducts as the major reaction product of GSH with the most commonly used contemporary polymeric (tri-isocyanate) formulations of hexamethylene diisocyanate (HDI), the isocyanurate and biuret, as [M+H]+ ions of 1426.53 and 1400.55 m/z respectively in reverse phase LC-MS using electrospray in positive ion mode. The uretdione form of HDI, a stabilized dimer, formed two reaction products with GSH, a tris(GSH)-isocyanate reaction product recognized as a 1258.44 m/z [M+H]+ ion, and a bis(GSH)-isocyanate product identified as a 951.36 m/z [M+H]+ ion. Predicted structures for the newly described GSH-polyisocyanate reaction products, modeled based on collision induced dissociation (CID) fragmentation patterns in tandem MS/MS, support S-linkage of the GSH to N = C = O groups. In summary, industrially-used aliphatic polyisocyanates readily react with GSH to form primarily S-linked tris(GSH)-conjugates, a process that may play an important role in response to respiratory tract exposure.

Aerosol Transport Modeling: The Key Link Between Lung Infections of Individuals and Populations.

The recent COVID-19 pandemic has propelled the field of aerosol science to the forefront, particularly the central role of virus-laden respiratory droplets and aerosols. The pandemic has also highlighted the critical need, and value for, an information bridge between epidemiological models (that inform policymakers to develop public health responses) and within-host models (that inform the public and health care providers how individuals develop respiratory infections). Here, we review existing data and models of generation of respiratory droplets and aerosols, their exhalation and inhalation, and the fate of infectious droplet transport and deposition throughout the respiratory tract. We then articulate how aerosol transport modeling can serve as a bridge between and guide calibration of within-host and epidemiological models, forming a comprehensive tool to formulate and test hypotheses about respiratory tract exposure and infection within and between individuals.

The evaluation of maximum condyle-tragus distance can predict difficult airway management without exposing upper respiratory tract; a prospective observational study

BackgroundRoutine preoperative methods to assess airway such as the interincisor distance (IID), Mallampati classification, and upper lip bite test (ULBT) have a certain risk of upper respiratory tract exposure and virus spread. Condyle-tragus maximal distance(C-TMD) can be used to assess the airway, and does not require the patient to expose the upper respiratory tract, but its value in predicting difficult laryngoscopy compared to other indicators (Mallampati classification, IID, and ULBT) remains unknown. The purpose of this study was to observe the value of C-TMD to predict difficult laryngoscopy and the influence on intubation time and intubation attempts, and provide a new idea for preoperative airway assessment during epidemic.MethodsAdult patients undergoing general anesthesia and tracheal intubation were enrolled. IID, Mallampati classification, ULBT, and C-TMD of each patient were evaluated before the initiation of anesthesia. The primary outcome was intubation time. The secondary outcomes were difficult laryngoscopy defined as the Cormack-Lehane Level > grade 2 and the number of intubation attempts.ResultsThree hundred four patients were successfully enrolled and completed the study, 39 patients were identified as difficult laryngoscopy. The intubation time was shorter with the C-TMD>1 finger group 46.8 ± 7.3 s, compared with the C-TMD<1 finger group 50.8 ± 8.6 s (p<0.01). First attempt success rate was higher in the C-TMD>1 finger group 98.9% than in the C-TMD<1 finger group 87.1% (P<0.01). The correlation between the C-TMD and Cormack-Lehane Level was 0.317 (Spearman correlation coefficient, P<0.001), and the area under the ROC curve was 0.699 (P<0.01). The C-TMD < 1 finger width was the most consistent with difficult laryngoscopy (κ = 0.485;95%CI:0.286–0.612) and its OR value was 10.09 (95%CI: 4.19–24.28), sensitivity was 0.469 (95%CI: 0.325–0.617), specificity was 0.929 (95%CI: 0.877–0.964), positive predictive value was 0.676 (95%CI: 0.484–0.745), negative predictive value was 0.847 (95%CI: 0.825–0.865).ConclusionCompared with the IID, Mallampati classification and ULBT, C-TMD has higher value in predicting difficult laryngoscopy and does not require the exposure of upper respiratory tract.Trial registrationThe study was registered on October 21, 2019 in the Chinese Clinical Trial Registry (ChiCTR1900026775).

Letter: The Risk of COVID-19 Infection During Neurosurgical Procedures: A Review of Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) Modes of Transmission and Proposed Neurosurgery-Specific Measures for Mitigation.

Letter: The Risk of COVID-19 Infection During Neurosurgical Procedures: A Review of Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) Modes of Transmission and Proposed Neurosurgery-Specific Measures for Mitigation.

Acute toxicity of intratracheal arsenic trioxide instillation in rat lungs.

This study investigated the acute toxicity of different concentrations of arsenic trioxide (As2O3; ATO) on rat lungs. In total, 160 Wistar rats were randomly divided into the control, low‐, medium‐ and high‐dose groups, which were exposed to 0, 0.16, 1.60 and 16 μg/kg of ATO by intratracheal instillation, respectively. Samples were collected at 6, 12, 24, 48 and 72 hours after exposure and the dynamic changes indicative of acute lung toxicity were monitored. Compared with the control group, the exposure groups exhibited significant changes such as increased lung water content ratio and protein concentration in the bronchoalveolar lavage fluid, pulmonary interstitial thickening, cell membrane edema, increased inflammatory factor concentration, JNK and P38 were significantly activated, and the degree of phosphorylation was increased. Furthermore, all the changes in the exposure groups were exposure concentration‐dependent. ATO respiratory tract exposure can cause restrictive ventilatory disturbance in rats, and the degree of injury is exposure concentration‐dependent.

Estimating the time-varying generation rate of acetic acid from an all-purpose floor cleaner

Understanding the relationship between consumer product use and risk of adverse health outcomes facilitates appropriate risk management and product stewardship. A preferred method for estimating the systemic and respiratory tract exposure and dose tailored to cleaning products use has been proposed, refining previously issued exposure guidance. Consistent with other exposure and risk-assessment frameworks, it is dependent upon high-quality exposure determinant data that also serve as model inputs. However, as publicly available exposure determinant data are scarce, the risk assessor is left with the option of estimating determinants such as the generation rate or employing empirical methods to estimate them. When the exposure scenario involves a chemical mixture, estimating the generation rate may not be feasible. We present an approach for estimating the time-varying generation rate of an aqueous acetic acid mixture representative of the base formulation for many consumer and DIY cleaning products that was previously assessed in a screening-level assessment. The approach involved measuring the evaporation rate for a reasonable worst-case scenario under controlled conditions. Knowing the mass applied, a time-varying generation rate was estimated. To evaluate its portability, a field study was conducted in a home where measurements were collected in an all-purpose room with the exterior door open (Room 1) and closed (Room 2), and a bathroom (Room 3) using a portable Fourier Transform Infrared (FTIR) spectrophotometer. Acetic acid concentrations were modeled using two common indoor air models, the Well Mixed Room model. Measured and modeled acetic acid concentrations were compared, with the WMR 95% confidence intervals encompassing measured concentrations for all three rooms, supporting the utility of the approach used and portability of the generation rate derived from it.

Dilysine-Methylene Diphenyl Diisocyanate (MDI), a Urine Biomarker of MDI Exposure?

Biomonitoring of methylene diphenyl diisocyanate (MDI) in urine may be useful in industrial hygiene and exposure surveillance approaches toward disease (occupational asthma) prevention and in understanding pathways by which the internalized chemical is excreted. We explored possible urine biomarkers of MDI exposure in mice after respiratory tract exposure to MDI, as glutathione (GSH) reaction products (MDI-GSH), and after skin exposure to MDI dissolved in acetone. LC-MS analyses of urine identified a unique m/ z 543.29 [M + H]+ ion from MDI-exposed mice but not from controls. The m/ z 543.29 [M + H]+ ion was detectable within 24 h of a single MDI skin exposure and following multiple respiratory tract exposures to MDI-GSH reaction products. The m/ z 543.29 [M + H]+ ion possessed properties of dilysine-MDI, including (a) an isotope distribution pattern for a molecule with the chemical formula C27H38N6O6, (b) the expected collision-induced dissociation (CID) fragmentation pattern upon MS/MS, and (c) a retention time in reversed-phase LC-MS identical to that of synthetic dilysine-MDI. Further MDI-specific Western blot studies suggested albumin (which contains multiple dilysine sites susceptible to MDI carbamylation) as a possible source for dilysine-MDI and the presence of MDI-conjugated albumin in urine up to 6 days after respiratory tract exposure. Two additional [M + H]+ ions ( m/ z 558.17 and 863.23) were found exclusively in urine of mice exposed to MDI-GSH via the respiratory tract and possessed characteristics of previously described cyclized MDI-GSH and oxidized glutathione (GSSG)-MDI conjugates, respectively. Together the data identify urinary biomarkers of MDI exposure in mice and possible guidance for future translational investigation.

Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes

Although avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform the risk of infection, as well as the likely disease severity. Using the ferret model of H5N1 infection, we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus to upper respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection, but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was comparatively delayed and more focal than after TRT infection. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease. Risks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus could spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower after exposure to virus by this route than when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection, such as viremia, could help prioritize antiviral treatments for patients most at risk of succumbing to infection.

Systemic and behavioral effects of intranasal administration of silver nanoparticles

Use of silver nanoparticles (AgNPs) for their antimicrobial properties is widespread. Much of the previous work on the toxicity of AgNPs has been conducted in vitro or following oral or intravenous administration in vivo. Intranasal (IN) instillation of AgNPs mimics inhalation exposure and allows further exploration of the toxicity of these particles via respiratory tract exposure. The present study involved 1) single-dose exposures to assess tissue distribution and toxicity and 2) repeated exposures to assess behavioral effects of IN AgNP exposure (nominally uncoated 25nm AgNP). AgNP deposition was localized in the liver, gut-associated lymphoid tissue, and brain. Decrease cellularity in spleen follicles was observed in treated mice, along with changes in cell number and populations in the spleen. The splenic GSH:GSSG ratio was also reduced following AgNP exposure. Expression of the oxidative stress-responsive gene Hmox1 was elevated in the hippocampus, but not cortex of treated mice, as was the level of HMOX1 protein. Mice receiving 7days of IN exposure to 50mg/kg AgNPs exhibited similar learning- and memory-related behaviors to control mice, except that treated mice spent significantly less time in the target quadrant of the Morris Water Maze during the acquisition phase probe trial. These findings indicate systemic distribution and toxicity following IN administration of AgNPs.

Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs.

Objectives:With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs.Methods:Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis.Results:No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05).Conclusions:Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.

Sharing experience of managing outbreak flu incident at a psychiatry hospital

Purpose: Influenza is caused by viral infection.Type A, in particular, is the culprit for global pandemics for nearly a hundred years and also the main virus for cluster infection with flu in psychiatry over the past few years. Methods: 17 infection cases were reported over a period of 16 days starting January 9, 2014, including 16 patients and 1 staff member (service provider),the overall attack rate was 27.42%. Patients developed symptoms such as fever and upper respiratory tract infection, including 13 with fever. No one had vomit or diarrhea. Intervening infection control measures were adopted and healthcare professionals cooperated fully to keep patients in separate areas for centralized care and away from respiratory tract and contact exposure. The patients temperature was monitored on a daily basis. All the staff and patients wore surgical masks and practiced correct hand washing. Visitors were provided limited access. Group therapy events were suspended. The environment was cleaned and disinfected in order to keep the situation under control.Among the patients, 8 had a throat sampling swab. Flu Virus A H1 positive developed in the culture of 3 out of the 8 patients (37.5%). Results: No additional cases were reported after January 25. May be indicators of exposure to environmental cases of influenza virus infection, and infection through common environment interact to others. Conclusions: This event also shows the importance of flu vaccination. Those with a flu shot had mild symptoms upon infection and their symptoms quickly remitted. The flu vaccination rate in the patient ward was 46.00% among the patients and 53.85% among the staff, lower than the average in the hospital. Although no cases of flu complications, it is necessary to discuss again how to enhance the flu vaccination rate and early antiviral prophylaxis.

Hexamethylene diisocyanate (HDI) vapor reactivity with glutathione and subsequent transfer to human albumin

IntroductionAirway fluid glutathione (GSH) reactivity with inhaled vapors of diisocyanate, a common occupational allergen, is postulated to be a key step in exposure-induced asthma pathogenesis. MethodsA mixed (vapor/liquid) phase exposure system was used to model the in vivo reactivity of inhaled HDI vapor with GSH in the airway fluid. HDI–GSH reaction products, and their capacity to transfer HDI to human albumin, were characterized through mass spectrometry and serologic assays, using HDI-specific polyclonal rabbit serum. ResultsHDI vapor exposure of 10mM GSH solutions resulted in primarily S-linked, bis(GSH)–HDI reaction products. In contrast, lower GSH concentrations (100μM) resulted in mainly mono(GSH)–HDI conjugates, with varying degrees of HDI hydrolysis, dimerization and/or intra-molecular cyclization, depending upon the presence/absence of H2PO4−/HPO42− and Na+/Cl− ions. The ion composition and GSH concentration of the fluid phase, during HDI vapor exposure, strongly influenced the transfer of HDI from GSH to albumin, as did the pH and duration of the carbamoylating reaction. When carbamoylation was performed overnight at pH 7, 25 of albumin’s lysines were identified as potential sites of conjugation with partially hydrolyzed HDI. When carbamoylation was performed at pH 9, more rapid (within 3h) and extensive modification was observed, including additional lysine sites, intra-molecular cross-linkage with HDI, and novel HDI–GSH conjugation. ConclusionsThe data define potential mechanisms by which the levels of GSH, H2PO4−/HPO42−, and/or other ions (e.g. H+/OH−, Na+, Cl−) affect the reactivity of HDI vapor with self-molecules in solution (e.g. airway fluid), and thus, might influence the clinical response to HDI respiratory tract exposure.

Peptidoglycan from Staphylococcus aureus increases MUC5AC gene expression via RSK1-CREB pathway in human airway epithelial cells.

Respiratory tract exposure to viruses, air pollutants, or bacterial pathogens can lead to pulmonary diseases. The molecular mechanism of mucous overproduction increased by these pathogens provides the knowledge for developing new therapeutic strategies. There is established in vitro data demonstrating that the overexpression of MUC5AC is induced by peptidoglycan (PGN) derived from Staphylococcus aureus. However, the mechanisms by which PGN activates MUC5AC gene expression in the airway remain unclear. The aim of this study was to identify the mechanism of PGN-induced MUC5AC gene expression. We found that PGN could induce MUC5AC gene expressions in a time- and dose-dependent manner. Moreover, activations of ERK1/2 and JNK increased after treatment of cells with PGN, whereas phosporylation of p38 was undetected. Of these MAPKs, pharmacologic inhibition of ERK1/2 decreased PGN-induced MUC5AC gene expression. In addition, we checked the activation of p90 ribosomal S6 kinase 1 (RSK1) as a downstream signaling target of ERK1/2 in PGN signaling. The activation of RSK1 was prevented by pretreatment with PD98059. We also found that RSK1 mediated the PGN-induced phosphorylation of cAMP response element-binding protein (CREB) and the transcription of MUC5AC. Furthermore, the cAMP-response element (CRE) in the MUC5AC promoter appears to be important for PGN-induced MUC5AC gene expression in NCI-H292 cells.

Immune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

BackgroundMethylene diphenyl diisocyanate (MDI), a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation.MethodsMice exposed via the skin to varying doses (0.1-10% w/v) of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA), while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL). Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo.ResultsSkin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary) respiratory tract inflammation and eosinophilia depended upon the (primary) skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI). The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation.ConclusionsMDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma pathogenesis. MDI conjugation and antigenic modification of albumin at local (skin/respiratory tract) exposure sites may represent the common antigenic link connecting skin exposure to subsequent respiratory tract inflammation.

Swimming pool, respiratory health, and childhood asthma: Should we change our beliefs?

Swimming is often recommended as a sport because of its several benefits to health. It is also recommended in asthmatic children as a sport with a lower potential for prompting exercise-induced asthma. However, there is growing interest in the potentially harmful effects of repeated respiratory tract exposure to chlorinated products and the problem of possible swimming-related health hazards is gaining importance at international level. It is already known that acute exposure to chlorine gas as in swimming pool accidents causes lung damage and also that elite swimmers may have increased airway inflammation and bronchial hyperreactivity, probably as a result of repeated exposure to chlorine derivatives. Recently some studies have been conducted to investigate whether repeated exposure to chlorine by-products in recreational swimmers might also lead to lung damage. In addition, some studies have been lately published on the even more debated issue of the possible harmful effects of baby swimming on respiratory health. This article reviews and discusses data from the literature on the effects of chlorine derivatives in different categories of people routinely attending swimming pools. The need for longitudinal studies is emphasized to definitely clarify any role of chlorinated swimming pool attendance in the development of asthma in recreational swimmers.

Lead distribution in rats following respiratory exposure to lead-contaminated soils

Two preliminary experiments were performed to explore the use of an intratracheal instillation technique as a cost-effective method of determining the biokinetics of lead (Pb) following respiratory exposure to Pb-contaminated soils. A novel intratracheal instillation procedure was refined and used to deliver a defined dose of Pb-contaminated soil or PbAc to the lower respiratory tract of rats. In the first experiment, rats were sacrificed at numerous time intervals post-dosing, and liver, kidney, blood, and bone tissues were collected for Pb analysis. In the second experiment, rats were dosed with Pb-contaminated soil or PbAc via intratracheal instillation or gastric gavage. All rats were sacrificed 96 h after dose administration and tissues were collected for lead analysis. Data from these experiments indicate Pb is well-absorbed following intratracheal instillation of Pb-contaminated soil, and the intratracheal instillation technique could be used as a cost effective method for exploring the biokinetics of Pb in Pb-contaminated soils following respiratory tract exposure.