A report in 1980 by Beaumont and Weiss,4
on the mortality experience of 8,679 male members of a metal trades union employed in shipyards, metal fabrication shops and small boat yards, recorded a significant excess of deaths from pneumonia in welders relative to that expected from rates in all US men. Five years later, Newhouse et al5
also found a significant excess death rate from pneumonia, among welders employed at a shipyard in North East England relative to platers and electricians from the same site.
Most information on the mortality of welders has accrued, however, from the Decennial Supplements on occupational mortality for England and Wales. Successive analyses have demonstrated increased death rates from pneumonia in welders, in a pattern that can be followed back for more than five decades. During 1949-53, 70 deaths were observed as compared with 31 expected;6
in 1959-63 101 deaths with 54.9 expected;7
and in 1970-72 66 deaths versus 42.0 expected.8
In 1994, an analysis covering the extended period 1979-80 and 1982-90 (disrupted by a year of industrial action among the registrars of births and deaths) offered greater statistical power to explore potential determinants.9
This confirmed the association with welding but went further in clarifying that the excess was attributable largely to deaths from pneumonias other than bronchopneumonia (principally lobar pneumonia), and was, moreover, limited to men below the normal retirement age of 65 years (55 observed deaths from lobar pneumonia vs. 21.6 expected). Thus, excess risk existed for welders still in the occupation but not in men who had retired from it, making confounding by smoking and other non-occupational factors an unlikely explanation. Finally, the heightened risk was found to apply to several other occupations entailing exposure to metal fume, such as moulders and coremakers and furnacemen in foundries.9
When taken together, these findings suggested that inhalation of metal fume increases susceptibility to infectious pneumonia, and that the effect was reversible following cessation of exposure.
A subsequent mortality report extended observations with addition of data from the Registrar General’s Supplements for 1910-2, 1930-32 and 1949-53.10
As in previous analyses, occupations with potential exposure to metal fume, and particularly welders, moulders and coremakers and furnacemen, had significantly elevated mortality from pneumonia. Excesses were also apparent for metal grinders and polishers, although these were less marked. Once more the excess mortality from pneumonia in fume-exposed occupations was confined to men of working age, while the at-risk occupations were found not to have comparable excesses of lung cancer or of mortality from non-respiratory infections, adding to the evidence against confounding as an explanation.
In 1930-32 and 1949-53, unlike in later reports, workers in ferrous foundries were distinguished from foundrymen working other metals, and iron ore miners from miners of tin, copper and other metalliferous ores. When disaggregated in this way, it was found that the elevation of mortality from pneumonia was generally more marked in those working with ferrous metal, with no consistent differences in mortality from bronchitis. Similarly, in 1910-2 the risk of death from pneumonia in iron founders was twice that in brass founders, and that in iron miners and quarriers was 50% greater than in lead miners; but there was no corresponding excess mortality risk from bronchitis.10
Generally, the pattern was considered compatible with a specific hazard from iron, and multiple strands of evidence indicate that free iron can promote infections in biological systems, acting either as a growth nutrient for miscorganisms or a cause of free radical injury (for a full review see reference 10
). Iron is seldom “free” at body surfaces – instead most of the body’s stores are intracellular, in ferritin, haemosiderin and haem, and the extracellular fraction is bound to high affinity iron binding proteins (transferrin in serum and lactoferrin in external secretions) that keep the concentration of free iron in equilibrium as low as 10−18
M. However, a battle for free iron exists between host and microorganisms, the normal flora of the respiratory tract reflecting in part the nutrient-limited balance finally achieved. In situations where the balance is disturbed, as for example when exogenous supplies of iron exceed the capacity of the iron binding protein system, overgrowth of organisms may be encouraged or free radical injury of host defences against infection could ensue. Thus, an “iron hypothesis” has been mooted to explain the consistently higher risk of pneumonia in metal-fume exposed workers.10
Analysis of death certificates can only take matters so far, being limited for example in its capacity to explore the iron hypothesis, and whether risks are specific to certain metal(s) or more general to many metals, or to assess whether the excess risk applies to all categories of pneumonia or only to those caused by certain microorganisms. Another uncertainty is whether the effect of metal fume is on the incidence of disease (the risk of acquiring pneumonia) or on case fatality rate (the risk of dying once the disease has occurred).
To garner further information, a case-control study was conducted during 1996-1999 in Birmingham and the West Midlands (chosen because of the relatively high prevalence of occupational exposure to metal fume in the local population).11
In all, 525 working-aged men aged 20-64 years admitted to 11 hospitals with community-acquired pneumonia were interviewed about their lifetime occupational history, including exposure to metal fume, together with 1,122 controls, admitted to the same hospitals under the same medical teams with non-respiratory illness.
Consistent with the mortality data, pneumonia overall was found to be more common among welders and other workers with exposure to metal fume than in workers with non-exposed jobs; and risks were confined to exposures in the previous 12 months (adjusted odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.4), and not apparent if last exposure was more than a year before (OR 1.1). Also consistent with the mortality data, risks were higher where the X-rays (read blind to occupational history) showed shadowing in a lobar, segmental, or sub-segmental pattern than when the appearance was one of bronchopneumonia (ORs for exposure to any metal fume in the previous 12 months 1.8 and 1.8 respectively, vs. 1.3 for bronchopneumonia). And consistent with the iron hypothesis, they were highest of all when exposure in the past year was to ferrous fumes but not to other metals or alloys (OR for lobar pneumonia 3.0, 95%CI 1.4-6.7). Finally, in 43 cases where the pneumonia was confirmed as pneumococcal, by recovery of Streptococcus pneumoniae from blood and/or sputum, the OR for exposure to metal fume of any kind was 1.8 and for exposure specifically to ferrous fume was 3.1 (95%CI 1.0-9.5). The findings thus support the hypothesis of a hazard that is reversible following cessation of exposure, that affects the incidence of disease and not just its fatality, and which is linked in particular with recent exposure to ferrous metal fume and with lobar and pneumococcal pneumonia.
Useful though this information is, the study could not tie down precisely the timeframe of risk, as most workers who were exposed in the previous 12 months had also been exposed in the previous seven days. Nor did it exclude the possibility that other organisms could sometimes be involved, as in men infected with Legionella, Mycoplasma, or Haemophilus influenza the OR following exposure to ferrous fume was 2.1. Finally, too few men were exposed solely to non-ferrous metal fumes to allow confident exclusion of risks from these other sources of exposure.
Further corroboration of the findings came from a study of mortality12
in a large Swedish cohort of construction workers, including 30,427 men with exposure to metal fumes. Risks of death from pneumonia were elevated 2.3-fold overall, and by 3.7- and 5.8-fold respectively when lobar pneumonia and pneumococcal pneumonia were analysed as subgroups of interest; while the relative risk of infectious pneumonia was only 1.16 in retired workers with former exposure.
Bringing the story up to date are one more analysis of occupational mortality and a survey of patients hospitalised with IPD. In the first of these, Palmer et al
published risk estimates from the latest analysis of occupational mortality for ONS in England and Wales during 1991-2000.13
Confirming earlier observations, excesses of mortality were found from pneumococcal and lobar pneumonia (54 deaths vs. 27.3 expected) and from pneumonias other than bronchopneumonia (71 vs. 52.4), but no excess from these causes at older ages, or from bronchopneumonia at any age. Thus, despite potentially better workplace controls on exposure, the hazard remains manifest in the most recent national statistics. Elsewhere, a study by Wong et al
of cases of IPD confirmed at a microbiological reference laboratory in Alberta Canada, implied a rate among welders of 22.7/100000 population/year, 2.7 times higher than in the general adult population aged 18-65 years.
Deaths from pneumonia in young adults are comparatively rare, as is IPD,14,15
but the analysis by Palmer et al
found that the attributable mortality from metal fume (45.3 excess deaths) in England and Wales during 1991-2000 was not trivial in comparison with an estimated 62.6 deaths from occupational asthma over the same period.13
Using data from various sources, the HSE has since made a similar estimate of attributable mortality.16
It may be said that, although efforts to control welding fume exposure at source are ongoing, this long-standing hazard has been relatively under-appreciated in the UK, especially since the first report by Coggon et al
appeared in The Lancet
in 1994 under the title “Lobar pneumonia: an occupational disease in welders”. However, in 2001 the Norwegian Labour Inspection Authority (NLIA) issued a warning to Norwegian physicians about the potentially lethal risk of fumes from thermal metal work.17
The NLIA had received three independent reports of deaths from pneumonia with septicaemia among previously healthy men aged 50 to 55 years (all three exposed to welding fumes immediately before they fell ill), and had also identified nine cases of non-fatal pneumonia – three in workers exposed to fumes from cutting, grinding, and welding, who were hospitalised with lobar pneumonia, and six in workers engaged on reconstruction work inside a ship’s hull, who were managed as outpatients.18
Case reports linking fatal pneumonia in welders and metal fume exposed occupations with atypical micro-organisms also form a part of the record.19
The NLIA urged physicians to inquire about occupational exposures in working-aged patients with pneumonia; but the more direct and pressing need, to ensure effective controls, has been problematic for several reasons. Although some data suggest that that chronic exposure to metal fume blunts responsiveness to inhaled particulate matter (favouring the free radical injury hypothesis),20
the exact underlying mechanisms remain elusive, with mechanistic chamber experiments ongoing (K Palmer, personal communication). In the absence of suitable biomarkers of risk, the dose-response relationship and therefore the level below which exposures should be controlled have not yet been defined.