Hypoxaemia and risk of asphyxia during underground work in artisanal cobalt mines.

BACKGROUND: More than half the cobalt needed for vehicle electrification originates from the southern part of the Democratic Republic of the Congo (DRC), with a substantial part being extracted by artisanal miners. AIMS: To investigate oxygen saturation during underground work among cobalt artisanal miners. METHODS: In a field survey, we measured oxygen saturation (SpO2) and heart rate by pulse oximetry in 86 miners from two underground mines and 24 miners from a surface mine at four different time points: before descent into the mine (T1), at 50 minutes in the mine (T2), upon leaving the shaft (T3), and 10 minutes after having left the mine (T4). RESULTS: Miners working underground (-36 to -112 meters) were somewhat older (34.8 ±â€…6.7 years) than those working in the surface mine (32.0 ±â€…6.5 years), and they worked more hours daily (12.6 ±â€…1.2 hours) than controls (9.0 ±â€…0.0 hours). All participants had SpO2 >95% at T1 and T4. At T2, SpO2 dropped below 93% and 80% in 35% and 10% underground miners, respectively; SpO2 was still <93% at T3 in 13%. SpO2 remained stable among surface miners. Later, we showed that underground ambient oxygen levels decreased well below 21% in several pits. CONCLUSIONS: Pulse oximetry revealed relevant hypoxaemia during underground work in a substantial proportion of artisanal miners. Such hypoxaemia without evidence of underlying cardiovascular disease is indicative of low ambient oxygen, due to insufficient mine ventilation. This may cause deaths from asphyxia. The hazards of low ambient oxygen in artisanal mines must be prevented by appropriate technical measures ensuring the supply of sufficient fresh air.

Short-term health effects in the general population following a major train accident with acrylonitrile in Belgium.

BACKGROUND: Following a train derailment, several tons of acrylonitrile (ACN) exploded, inflamed and part of the ACN ended up in the sewage system of the village of Wetteren. More than 2000 residents living in the close vicinity of the accident and along the sewage system were evacuated. A human biomonitoring study of the adduct N-2-cyanoethylvaline (CEV) was carried out days 14-21 after the accident. OBJECTIVES: (1) To describe the short-term health effects that were reported by the evacuated residents following the train accident, and (2) to explore the association between the CEV concentrations, extrapolated at the time of the accident, and the self-reported short-term health effects. METHODS: Short-term health effects were reported in a questionnaire (n=191). An omnibus test of independence was used to investigate the association between the CEV concentrations and the symptoms. Dose-response relationships were quantified by Generalized Additive Models (GAMs). RESULTS: The most frequently reported symptoms were local symptoms of irritation. In non-smokers, dose-dependency was observed between the CEV levels and the self-reporting of irritation (p=0.007) and nausea (p=0.007). Almost all non-smokers with CEV concentrations above 100pmol/g globin reported irritation symptoms. Both absence and presence of symptoms was reported by non-smokers with CEV concentrations below the reference value and up to 10 times the reference value. Residents who visited the emergency services reported more symptoms. This trend was seen for the whole range of CEV concentrations, and thus independently of the dose. DISCUSSION AND CONCLUSION: The present study is one of the first to relate exposure levels to a chemical released during a chemical incident to short-term (self-reported) health effects. A dose-response relation was observed between the CEV concentrations and the reporting of short-term health effects in the non-smokers. Overall, the value of self-reported symptoms to assess exposure showed to be limited. The results of this study confirm that a critical view should be taken when considering self-reported health complaints and that ideally biomarkers are monitored to allow an objective assessment of exposure.

A chest physician's guide to mechanisms of sinonasal disease.

The upper and lower airways are closely linked from an anatomical, histological and immunological point of view, with inflammation in one part of the airways influencing the other part. Despite the concept of global airway disease, the upper airways tend to be overlooked by respiratory physicians. We provide a clinical overview of the most important and recent insights in rhinitis and rhinosinusitis in relation to lower airway disease. We focus on the various exogenous and endogenous factors that play a role in the development and aggravation of chronic upper airway inflammation. In addition to the classical inhaled allergens or microorganisms with well-defined pathophysiological mechanisms in upper airway disease, environmental substances such as cigarette smoke, diesel exhaust particles and occupational agents affecting lower airway homeostasis have recently gained attention in upper airway research. We are only at the beginning of understanding the complex interplay between exogenous and endogenous factors like genetic, immunological and hormonal influences on chronic upper airway inflammation. From a clinical perspective, the involvement of upper and lower airway disease in one patient can only be fully appreciated by doctors capable of understanding the interplay between upper and lower airway inflammation.

Acrylonitrile exposure in the general population following a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On Saturday May 4, 2013, a train transporting chemicals derailed in the village of Wetteren (Belgium) and caused a leak of acrylonitrile (ACN). OBJECTIVES: To assess the human exposure to acrylonitrile in the local population with the highest suspected exposure. METHODS: Between May 18-25, 242 residents participated in the study. N-2-cyanoethylvaline (CEV), a biomarker that is highly specific for ACN exposure, was measured in the blood. To account for potential influence by smoking, cotinine was determined in the urine. Participants also filled in a short questionnaire. RESULTS: In the evacuated zone, 37.3% of the non-smokers and 40.0% of the smokers had CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively, at the time of the train accident. Spatial mapping of the CEV concentrations depending on the residential address showed a distribution pattern following the sewage system. DISCUSSION AND CONCLUSION: The train derailment resulted in a highly atypical sequence-of-events. In addition to exposure in the direct vicinity of the site of the train derailment, exposure also occurred via the sewage system, into which acrylonitrile had entered shortly after the accident.

Acrylonitrile exposure assessment in the emergency responders of a major train accident in Belgium: a human biomonitoring study.

BACKGROUND: On May 4, 2013, a train transporting chemicals derailed in Wetteren, Belgium. Several tanks loaded with acrylonitrile (ACN) exploded, resulting in a fire and a leakage of ACN. OBJECTIVES: To determine exposure to ACN and to assess discriminating factors for ACN exposure in the emergency responders involved in the on-site management of the train accident. METHODS: The study population consisted of 841 emergency responders. Between May 21 and June 28, they gave blood for the determination of N-2-cyanoethylvaline (CEV) hemoglobin adducts and urine for the measurement of cotinine. They also filled in a short questionnaire. RESULTS: 163 (26%) non-smokers and 55 (27%) smokers showed CEV concentrations above the reference values of 10 and 200 pmol/g globin, respectively. The 95th percentile in the non-smokers was 73 pmol/g globin and the maximum was 452 pmol/g globin. ACN exposure among the non-smokers was predicted by (1) the distance to the accident, (2) the duration of exposure, and (3) the occupational function. DISCUSSION AND CONCLUSION: Emergency responders involved in the on-site management of the train accident were clearly exposed to ACN from the accident. However, the extent of exposure remained relatively moderate with CEV concentrations staying within the ranges described in literature as background for a smoking population. Moreover, the exposure was less pronounced in the emergency responders as compared to that in the local population.

EAACI position paper: irritant-induced asthma.

The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: (i) definite IIA, that is acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed-onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA.

Occupational upper airway disease: how work affects the nose.

Chronic inflammation of the upper airways is common and can arbitrarily be divided into rhinitis and rhinosinusitis. Infection and allergy represent two well-characterized and most frequently diagnosed etiologies of upper airway inflammation. Persistent upper airway inflammation caused by agents inhaled in the work environment represents a diagnostic challenge in clinical practice, and its pathophysiology has been little studied. Occupational rhinitis is a recognized medical condition with diagnostic and therapeutic guidelines. In contrast, only limited evidence is available about the relationship between work exposures and rhinosinusitis. This review aims at providing a comprehensive overview of the available literature on occupational upper airway disease with a focus on pathophysiological mechanisms and with an emphasis on the current unmet needs in work-related upper airway disease.

Papain-induced asthma: a man with dyspnea from dawn till dust.

A 52-year-old man, a current smoker (40 pack years) with unremarkable medical history, was referred to the outpatient pneumology clinic because of recent complaints of shortness of breath and wheezing, which were relieved by inhaled bronchodilators. Serial peak expiratory flow (PEF) measurements showed a clear rise in PEF during the weekend and a fall on the evening after the first day of the week. It also showed that evening values were always lower than morning values. During a holiday, a slow but persistent rise in PEF was observed. Such a pattern is highly suggestive for occupational asthma. A detailed description of his job revealed papain exposure. After a positive specific IgE and skin prick test for papain the diagnosis of papain induced asthma was made. When an allergy and serious lung function impairment is proven against products encountered in a work related situation, not improving after maximal preventive measures, the patient is advised to change job.

Lymphocytic bronchiolitis after lung transplantation is associated with daily changes in air pollution.

Acute rejection represents a major problem after organ transplantation, being a recognized risk for chronic rejection and mortality. Recently, it became clear that lymphocytic bronchiolitis (LB, B-grade acute rejection) is more important than previously thought, as it predisposes to chronic rejection. We aimed to verify whether daily fluctuations of air pollution, measured as particulate matter (PM) are related to histologically proven A-grade rejection and/or LB and bronchoalveolar lavage (BAL) fluid cellularity after lung transplantation. We fitted a mixed model to examine the association between daily variations in PM(10) and A-grade rejection/LB on 1276 bronchoscopic biopsies (397 patients, 416 transplantations) taken between 2001 and 2011. A difference of 10 µg/m(3) in PM(10) 3 days before diagnosis of LB was associated with an OR of 1.15 (95% CI 1.04-1.27; p = 0.0044) but not with A-grade rejection (OR = 1.05; 95% CI 0.95-1.15; p = 0.32). Variations in PM(10) at lag day 3 correlated with neutrophils (p = 0.013), lymphocytes (p = 0.0031) and total cell count (p = 0.024) in BAL. Importantly, we only found an effect of PM10 on LB in patients not taking azithromycin. LB predisposed to chronic rejection (p < 0.0001). The risk for LB after lung transplantation increased with temporal changes in particulate air pollution, and this was associated with BAL neutrophilia and lymphocytosis. Azithromycin was protective against this PM effect.

Negative impact of occupational exposure on surgical outcome in patients with rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a frequent condition that is treated by functional endoscopic sinus surgery (FESS) when medical treatment fails. Endogenous as well as exogenous factors may be responsible for persisting symptoms after FESS. The role of occupational exposures on success of FESS has never been investigated. METHODS: In this case-control study, we tested the hypothesis that the outcome of FESS procedures is related to exposures at work. Questionnaires were sent to 890 patients who had undergone one or more FESS procedures and to 182 controls. Three independent experts assessed blindly the reported work exposures to inhaled agents. The relationship between exposure and the number of FESS procedures was analyzed. RESULTS: Relevant occupational exposure was reported by 25% of all responding patients undergoing FESS (n = 467) and 12% of controls (n = 69). The prevalence of occupational exposures increased linearly with the number of FESS procedures from 21% in those who had one FESS to 44% in those who had four or more FESS (χ(2)  = 12.74, P < 0.001). Logistic regression analysis with adjustments for potential confounders, including smoking, atopy, and asthma, confirmed that the odds ratio (OR) for reporting occupational exposures was significantly higher in those needing more than one FESS (OR = 1.64) or more than two FESS (OR = 1.97). These results were mainly driven by exposure to low molecular weight agents. CONCLUSION: Exposure at work appears to be a risk factor for the occurrence of CRS and for its recurrence or persistence, as evidenced by the need for revision surgery.

Accuracy of office spirometry performed by trained primary-care physicians using the MIR Spirobank hand-held spirometer.

BACKGROUND: With the availability of compact, portable, effective microspirometers, pulmonary function tests no longer need to be performed only in specialized laboratories. However, the perception persists that small flow-sensing devices are less accurate than volume-sensing spirometers. OBJECTIVES: To study the accuracy of spirometry performed with the MIR Spirobank® and to investigate how accurately trained primary-care physicians can perform spirometry using a portable electronic spirometer. METHODS: Patients with suspected occupational asthma were submitted to specific bronchial challenge tests in the pulmonary function laboratory according to published recommendations. Serial measurements were performed with the Jaeger MasterScope device (reference standard) or the Spirobank device. Data were generated from 908 parallel measurements on 34 patients. Furthermore, 16 patients with documented moderate to severe COPD were examined in a carousel set-up by four trained physicians who each used his/her own Spirobank device coupled to a laptop computer. RESULTS: The Spirobank spirometer performed very well compared with the Jaeger MasterScope in a laboratory environment, displaying an underestimation of the forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity (FVC) of 2-5%. High correlations were found for the pulmonary function parameters. The highest correlation was for FEV(1) (r(2) = 0.949) and the lowest for the maximum expiratory flow at 25% of FVC (MEF(25)) (r(2) = 0.864). Only 2% of the observed variation in the measurement results could be explained by the type of device. CONCLUSIONS: The Spirobank device seems to be appropriate for research purposes if the standardized protocol is used correctly and the acceptability criteria are respected.

Air pollution-associated procoagulant changes: the role of circulating microvesicles.

BACKGROUND: Epidemiological studies suggest an association between exposure to particulate matter (PM) in air pollution and the risk of venous thromboembolism (VTE). OBJECTIVES: To investigate the underlying pathophysiological pathways linking PM exposure and VTE. PATIENTS AND METHODS: We assessed potential associations between PM exposure and coagulation and inflammation parameters, including circulating microvesicles, in a group of 233 patients with diabetes. RESULTS: The numbers of circulating blood platelet-derived and annexin V-binding microvesicles were inversely associated with the current levels of PM(2.5) or PM(10), measured on the day of sampling. Recent past exposure to PM(10), up to 1 week prior to blood sampling, estimated at the patients' residential addresses, was associated with elevated high-sensitivity C-reactive protein (CRP), leukocytes and fibrinogen, as well as with tissue factor (TF)-dependent procoagulant changes in thrombin generation assays. When longer windows of past exposure were considered, up to 1 year preceding blood sampling, procoagulant changes were evident from the strongly increased numbers of red blood cell-derived circulating microvesicles and annexin V-binding microvesicles, but they no longer associated with TF. Past PM exposure was never associated with activated partial thromboplastin time (aPTT), prothrombin time (PT), or factor (F) VII, FVIII, FXII or D-dimers. Residential distance to a major road was only marginally correlated with procoagulant changes in FVIII and thrombin generation. CONCLUSIONS: Increases in the number of microvesicles and in their procoagulant properties, rather than increases in coagulation factors per se, seem to contribute to the risk of VTE, developing during prolonged exposure to air pollutants.

Lung exposure to nanoparticles modulates an asthmatic response in a mouse model.

The aim of this study was to investigate the modulation of an asthmatic response by titanium dioxide (TiO2) or gold (Au) nanoparticles (NPs) in a murine model of diisocyanate-induced asthma. On days 1 and 8, BALB/c mice received 0.3% toluene diisocyanate (TDI) or the vehicle acetone-olive oil (AOO) on the dorsum of both ears (20 µL). On day 14, the mice were oropharyngeally dosed with 40 µL of a NP suspension (0.4 mg·mL⁻¹ (∼0.8 mg·kg⁻¹) TiO2 or Au). 1 day later (day 15), the mice received an oropharyngeal challenge with 0.01% TDI (20 µL). On day 16, airway hyperreactivity (AHR), bronchoalveolar lavage (BAL) cell and cytokine analysis, lung histology, and total serum immunoglobulin E were assessed. NP exposure in sensitised mice led to a two- (TiO2) or three-fold (Au) increase in AHR, and a three- (TiO2) or five-fold (Au) increase in BAL total cell counts, mainly comprising neutrophils and macrophages. The NPs taken up by BAL macrophages were identified by energy dispersive X-ray spectroscopy. Histological analysis revealed increased oedema, epithelial damage and inflammation. In conclusion, these results show that a low, intrapulmonary doses of TiO2 or Au NPs can aggravate pulmonary inflammation and AHR in a mouse model of diisocyanate-induced asthma.

Appearance of konzo in South-Kivu, a wartorn area in the Democratic Republic of Congo.

Konzo is an upper motor neuron disease characterized by sudden-onset and irreversible spastic paraparesis occurring in nutritionally compromised people. It is associated with consumption of insufficiently processed cyanogenic-toxic cassava. Cassava, the main caloric source in the Democratic Republic of Congo, has been safely consumed for decades in the Eastern Province of South-Kivu. However, in the context of long-lasting war and violent conflicts, cases of spastic paraparesis resembling konzo appeared in a populous area (Burhinyi). Two field surveys (2003 and 2005) identified 41 subjects meeting clinical criteria of konzo and suffering from (chronic) malnutrition. Their urinary thiocyanate concentrations (median 129, range 20-688, SD 146 µg/L), and cyanogen levels (median 20 ppm, range 5-300 ppm, SD 73 ppm) in cassava roots from their household stocks were high. The source of cyanogenic-toxicity was unprocessed fresh cassava roots during harvest period, but probably also insufficiently processed roots. This first report of konzo in South-Kivu concludes that occurrence of konzo was triggered by food shortages because of the longstanding state of insecurity. Contributory factors included the introduction of new varieties of (bitter) cassava, but konzo may actually be caused by a combination of factors that are yet to be understood.

Short-term exposure to particulate matter induces arterial but not venous thrombosis in healthy mice.

BACKGROUND: Epidemiological findings suggest an association between exposure to particulate matter (PM) and venous thrombo-embolism. OBJECTIVES: To investigate arterial vs. venous thrombosis, inflammation and coagulation in mice, (sub)acutely exposed to two types of PM. METHODS: Various doses (25, 100 and 200 µg per animal) of urban particulate matter (UPM) or diesel exhaust particles (DEP) were intratracheally (i.t.) instilled in C57Bl6/n mice and several endpoints measured at 4, 10 and 24 h. Mice were also repeatedly exposed to 100 µg per animal on three consecutive days with endpoints measured 24 h after the last instillation. RESULTS: Exposure to 200 µg per mouse UPM enhanced arterial thrombosis, but neither UPM nor DEP significantly enhanced venous thrombosis. Both types of PM induced dose-dependent increases in broncho-alveolar lavage fluid (BALF) total cell numbers (mainly neutrophils) and cytokines (IL-6, KC, MCP-1, RANTES, MIP-1α), with peaks at 4 h and overall higher values for UPM than for DEP. Systemic inflammation was limited to increased serum IL-6 levels, 4 h after UPM. Both types of PM induced similar and dose-dependent but modest increases in factor (F)VII, FVIII and fibrinogen. Three repeated instillations did not or only modestly enhance the proinflammatory and procoagulant status. CONCLUSIONS: Compared with DEP, UPM induced more pronounced pulmonary inflammation, but both particle types triggered similar and mild short-term systemic effects. Hence, acute exposure to PM triggers activation of primary hemostasis in the mouse, but no substantial secondary hemostasis activation, resulting in arterial but not venous thrombogenicity.

[Acute and subacute chemical pneumonitis]. / Pathologies respiratoires aiguës et subaiguës d'origine toxique.

Acute or subacute chemical-induced lung injury is rarely compound specific and is most often caused by an accidental occupational, domestic or environmental exposure to an inhaled chemical agent. The industrial disaster that happened in Bhopal in 1984, accidental poisoning with chlorine and petroleum hydrocarbons and also vesicant gases used during conflicts, are specific examples. Rarely, a chemical agent can cause lung damage by being ingested and reaching the lung through the systemic circulation (for example accidental or deliberate paraquat ingestion). Household accidents should not be underestimated. An important cause of household accidents is chlorine inhalation resulting from mixing bleach with acids such as the scale removers used to clean toilets. Chemical agents can provoke direct and/or indirect damage to the respiratory tract. The acute or subacute clinical manifestations resulting from inhalation of chemical agents are very varied and include inhalation fevers, acute non-cardiogenic pulmonary oedema, adult respiratory distress syndrome, reactive airways dysfunction syndrome and acute or subacute pneumonitis. The site and the severity of chemical-induced respiratory damage caused by inhaled chemical agents depend mainly on the nature and the amount of the agent inhaled. The immediate and long-term prognosis and possible sequelae are also variable. This review excludes infectious or immunologically induced acute respiratory diseases.