Presentation on theme: "Occupational lung disorders due to metals"— Presentation transcript:
1Occupational lung disorders due to metals Prof Tony CantrellNational Institute for Occupational Health &University of the WitwatersrandJohannesburgSouth Africa
2I hope that this talk will steer us away from the rigid way of thinking about toxic metals to new approaches for old problems.Dealing with some aspects from existing wisdom and also looking at what the future may come up with.This presentation is not meant to form a mini reference file on the subject of metals and lung disease, but should rather help us develop an approach to understanding what happens when we insult our lungs with metals at work and in the environment.
4Non-specific metal toxicity Metals are generally toxic in the human body, even if some are essential to our wellbeing in trace amountsAs soluble divalent cations, or in other chemical forms, they interact with susceptible sites on enzymes, proteins, active receptors, DNA, membranes etcWho are exposed? workers – children – hobbyists – the general populationGradually the environmental background of non-degradable toxins is building up as industrial volumes accelerate
5Some specific disease entities involving the lungs include: Irritation of the lungs, asthma, chronic bronchitis, COPD, cancersMetal Fume Fever – cutting, smelting, galvanizingCadmium fume causes pneumonitis distinct from Metal Fume FeverAcute chemical pneumonitis - gold amalgum retorters inhale mercury vapourThe ACGIH BEI for elemental mercury in urine is 35 microg Hg/litre.The patient was measured as excreting microg Hg/litre.Acute chemical pneumonitis, but died of kidney failureHard Metal DiseaseBeryllium Disease
6Lifetime [50 year] cumulative whole body dose of 1 sievert. Uranium induced malignancies - Slimes dams and old milled dust in air Concern was old cyanide!Lifetime [50 year] cumulative whole body dose of 1 sievert.An additional statistical risk of developing lung cancer = 5%
7Chromiun, Nickel, Vanadium Well known to cause variety of occupational asthma and lung cancers, and other occupational diseasesChromium: lung not the only target site septal defects, rodent ulcers, carcinoma of the tongue etc. Mechanism assumed to be via chronic irritant action [hexavalent ion]Nickel: Respiratory sensitizer, probable lung carcinogenVanadium: Respiratory irritant in association with SOx and ammonia
8Metal Fume FeverCaused by the inhalation of finely divided fume [<1 micron] of some non-ferrous metalsFrequently encounteredSelf limiting without interventionSymptomsFlu-like illness of short duration, metallic taste in mouth, throat irritation and dry cough , tight chest, cold shiversOnset: 3-10 hours post exposure, resolving on its own within 48 hoursFollwing an attack, a temporary period of tolerance for 1 or 2 days
9Metal Fume FeverCaused by heavy exposure to finely divided ZnO dust and fume during dip galvanizing of hot corrugated iron sheets, casting molten metal, flame cutting and weldingCopper and magnesium fume have similar effects. Brass ‘Foundrymans Ague’
10Cadmium pneumonitisAcute exposure at low concentrations > symptoms = MFF. Occupational history is critical for the differential DxIrritation of the URT with cough, irritation of the throat, metallic taste, dyspnea, chest painOnset may be delayed for 4-8 hoursAt higher exposure: pulmonary oedema, chemical pneumonitis, GIT and fluid balance problemsExposure for as little as a shift can lead to wheezing, chest pain, persistent cough and respiratory failure 3-7 days laterHigher exposures may lead to progressive pulmonary fibrosis and impaired lung function. At this stage multiple organ systems will also be affected
11Hard Metal DiseaseThis is a chronic interstitial lung disease caused by cobalt fume and dustaka - Giant cell interstitial pneumonitisAffects workers exposed to cobalt fume/dust while making or using tungsten/carbide hardened toolsLatency of 6-48 monthsPresent with dyspnea on exertion, cough , fatigueShow lung infiltrates and possibly restrictve lung function defect
12Hard Metal Disease Symptoms & Findings Chest tightness, cough Clubbing Diffuse, interstitial infiltratesExertional dyspneaInspiratory ralesRestrictive defectSputum productionWeight lossIf cobalt exposure continues, progressive fibrosis with respiratory failure may developCobalt may also > occupational asthma, bronchitis, bronchiolitis obliterans, and acute chemical pneumonitis at high cobalt exposure
13Welding exposes the worker to metal fumes of variable composition Millions worldwide use the processHigh temperatures up to 4000 oC produce hazardous fumes and gasesAn Antonini et al revue examined the effect of welding fume on respiratory health [Am J Resp Hlth :350]Full-time welders exhibitMetal fume feverAirway irritationLung function changesSusceptibility to lung infectionPossible increase in incidence of lung cancerBut mechanisms are not clear, and further work is needed
14Exposures associated with welding What causes Welders’ Lung? Iron siderosis, deposits in the lungManganese respiratory irritant, neurotoxicCr & Ni lung cancers,, septal defects, skin ulcersCu & Zn metal fume feverCd brown CdO fume, lung irritation, kidney, Ca prostate?Lead divalent ion [Pb2+] effects, lung cancers?Fluoride URT irritation, chronic bone disease, fluorosisOzone irritant, lung fibrosisNOx acute & chronic effects on lungs+ the effects of PPE, radiation, very hot air and high work rateMixed exposure at its worst!
15Does lead cause lung disease? Not the usual target organ [marrow, kidneys, CNS, sperm]Not a classical carcinogenYet the lung are the main portal of entry to the body. Non-specific divalent toxicity must have some negative effects!The IARC have classified Pb and its compounds as probable human carcinogens based on increased prevalence of lung, kidney and bladder tumors in workers occupationally exposed to lead.1 of 6 cohort studies on smelter workers showed a significant 2-fold increase in lung cancer.Is this playing with numbers?Confounders to consider include conditions in the industry, trace contaminants [alloys, recycling] and other factors
16The role of nanoparticles in the lungs Engineered nanoparticle technology is developing fast, with the attendant production and analytical skillsThis has generated new interest in ultrafine particles created in industrial processes and which can be inhaledTheir small size will affect retention, dwell time and fate in the lungsMay not necessarily damage the lung itself, but small size allows them to penetrate what is normally a defensive barrier. Affects toxicity, alters possible target organs. Affects a spectrum of exposure diseases.
17NIOH nickel case study: not known as IDLH till now Nanoparticles IISome Swedish workers postulate that very small Mn particles may track up nerve fibres into the brain. But this is only one form of exposure. Normal miners also develop Mn toxicity from exposure to much larger particles.Metallic nanoparticles in the workplace are generated at very high temperature, such as encountered in welding. This could include second stage fume formation from larger dust particles.Exposure to this type of vapour has been shown to result in increased heart rate, increased autonomic control in workers.American and Swedish laboratories are working on characterizing high temperature process aerosols for distribution in the URT.Need for new measurement methods for conceptual understanding of NP technology and its attendant hazardsNeed for different methods of hygiene, control and PPENIOH nickel case study: not known as IDLH till now
18Into the future with beryllium Beryllium is the second lightest metal which makes excellent alloys for components in a variety of aerospace, defense and other applications [Be/Cu]But inhalation of beryllium dust or fumes causes chronic beryllium disease [CBD] and lung cancerCBD is a rare disease characterized by diffuse interstitial pulmonary granulomatosis. Presents with dyspnea and dry coughCXR show fine granular shadows throughout the lungsCompromised lung function and blood gasesAccumulation of CD4(+) T cellsMimics sarcoidosis and must be considered in the differential Dx
19Recent work in the Netherlands and in the USA has shown that only 5-15 % of exposed workers get interstitial disease!The use of genomic analysis may explain why genetic and/or susceptibility variation may predispose certain individuals to CBeDiseaseSilver & Sharp [Occup Env Med (2006) 48:4, ] have reported that the predictive value of the HLA-DPB1-Glu69 marker for susceptibility to beryllium disease is 12%.Not yet at the stage of clinical application, such techniques are assisting occupational medicine to enter the 21st Century in style.The challenge to us is to keep abreast with modern technology!
20A genomic micro-array showing up and down regulated genes from a typical analysis