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Occupation and Pneumonia Kjell Torén, MD, PhD Professor, Section of Occupational and Environmental Medicine Institute of Medicine, Sahlgrenska Academy at University of Gothenburg Gothenburg, Sweden I have nothing to disclose in relation to this topic Norway 1923 Ferromanganese plant Sauda narrow valley 1

1939;3:2527-2533 Smoke from factory 80% manganese/ferromanganese First year six lethal cases of lobar pneumonia Coming 15 years 8 times higher mortality rate of lobar pneumonia Cases in the smoke direction. Relation production volume Workers? 2

1960s Exposure to manganese dust increase the risk for lobar pneumonia Established risk factors; Smoking Alcoholism Diabetes Immunodeficiencies Not mentioned; Occupational exposures?? Penumonia and occupation?? Literature search Very few studies *Associations with welding/metal fumes British studies *Associations with occupational exposures to gas, dust and fumes * Animals and excrements *Case reports Legionella pneumophilae Rhodococcus equi 3

Welders (Seattle area) SMR 167 Ship-yard workers from Bay area. 18% of the lobar pneumonia occurred among welders. But welders were 18% of the workforce. Welders, shipyard NE England SMR 184 Coggon et al Lancet 1994 Mortality (PMR) from lobar pneumonia Lobar Welders, cutters 255 Foundry-workers 292 Sheet-metal workers 190 Case-control study West Midlands Admitted to any of 11 hospitals 1996-1999 Men 20-64 yrs Symptoms + X-ray +(fever or leukocytosis) 525 cases 1122 controls (patients admitted for non-respiratory conditions) 4

Occupations Last exposure to metal fume (several items) Different exposures and morbidity from pneumonia with control for overlapping exposures Pneumonia OR Exposure N OR 95% CI >1 year before onset 1.1 (0.8-1.4) 8 days-1 year b. o. 1.8 (0.4-4.2) Within 7 days b. o. 1.6 (1.0-2.4) Metal fume 58 1.4 0.8-2.3 Metal dust 75 1.2 0.7-1.8 Wood dust 38 0.8 0.5-1.4 Cement dust 46 1.1 0.7-1.9 Asbest 26 1.2 0.7-2.1 Metal fume and morbidity from lobar pneumonia or bronchopneumonia Thorax 2009;64:983-986 Lobar Bronchopneu Exposure OR 95% CI OR 95% CI Any metal fume 1.8 1.0-3.3 1.3 0.8-2.3 No alloys 3.0 1.4-6.7 1.6 0.8-3.0 Welders Furnace operators Moulders/coremakers Other metal workers Sheet metal workers PMR (16-64 yrs) 242, p<0.05 96, NS 300, p<0.05 46, NS 268, p<0.05 5

1768 cases, of these 863 in working age 8.7/100 000 Occupation Cases Incidence OR All patients with invasive pneumococcal disease 2000-2004. Alberta, Canada Welder 18 22.7/100 000 2.6 (1.7-4.2) Electrician 6 12.2/100 000 1.4 (0.6-3.1) Farmer 7 3.1/100 000 0.4 (0.2-0.7) Day care worker 8 10.5/100 000 1.2 (0.6-2.4) Thorax 2011;66:992-996 Construction workers 6

Construction worker Study population 320 143 males occupationally exposed to inorganic dust, chemicals, metal fume (welding fumes, diesel exhaust and solvents 79 305 white collar workers Job exposure matrix Exposure medio 1970s 214 occupational codes Each factor exp/unexp Job exposure matrix Inorganic dust (MMMF, Cement dust, Concrete dust, Asbestos, Quartz) Chemicals (Epoxy, diisocyanates, organic solvents) Metal fume Wood dust 7

Swedish National Cause of Death Register Infectious pneumonia ICD 8-9 471, 481-483, 485-486, 487A ICD 10 J10-J16, J18 Lobar pneumonia ICD 8-9 481 ICD 10 J18.9 Pneumococcal pneumonia ICD 8-9 481 ICD 10 J13 Mortality 1971 2003 Incidence of death from pneumonia in the exposed and unexposed cohorts Standardised mortality rate ratios (SRR) Poisson regression models Stratifying for smoking, age (5 yrs). Risk for pneumonias in relation to occupational exposures Infectious Lobar Pneumococcal 20-64 yrs Inorganic dust 1.9 3.4 4.3 Chemicals 1.9 4.5 5.8 Metal fume 2.3 3.7 5.8 65-84 yrs Inorganic dust 1.4 N.a. N.a. Chemicals 1.4 N.a. N.a. Metal fume 1.2 N.a. N.a. 8

Risk for infectious pneumonia in relation to nonoverlapping exposures Exposure All 20-64 yrs 65-84 yrs Inorganic dust (n=350) 1.4 1.7 1.4 Chemicals (n=7) 1.1 N.A. N.A Metal fumes (n<3) N.A N.A. N.A Wood dust (n=51) 1.3 1.2 1.3 Referents (n=125) 1.0 1.0 1.0 Three cases of lobar pneumonia among welders Norwegian Labour Inspection Agency Three independent reports about deaths from pneumonia with septicemia Previously healthy men 50 to 55 years of age Welders Two shipyard welders Helper in a workshop for heavy trucks Conclusions (so far); Exposure to welding fumes/work as a welder increase the risk for pneumonia/lobar pneumonia. The effect of welding fumes may be an effect of exposure to inorganic dust. Probably a multifactorial etiology What do we know about dust exposure and risk for pneumonia? 9

Subjects aged 65 and older 717 cases 867 controls Two of; Temp>38 C, cough, chest påain, dysponoea, crackles on auskultation New opacity on a chest radiograph Interviews Multivariate regression models Exposure OR Immunosuppressive medications 15.1 (4.7-48.3) Smoking>100 cigarettes 2.0 (1.3-3.4) Second hand smoke 1.8 (1.0-2.9) Alcohol, 5 g/month 1.7 (1.1-2.6) Occupational exposure to VGDF 3.7 (2.4-5.8) Farr BM, et al Risk factors for community-acquired pneumonia diagnosed upon hospital admission. Respir Med 2000;94:954-963 BTS cohort of primary community-acquired pneumonia Two controls from the same catchment area Solvents or gasoline around home 3.3 (1.6-6.9) 10

Predictor OR 95% CI Unmarried 1.7 1.2-4.0 Unemployed 2.2 1.2-4.0 Dusty occupation 2.5 1.6-3.8 Heavy smoking 3.2 2.0-5.3 Manufacturing workers undergoing mandatory health examinations Men Cement, lime, plaster 1.5 3.2 Cast metals 1.6 ---- Women Conclusion; There is data supporting a relation with exposure to gas, dust and fumes and increased risk for pneumonia Exposure to livestock, animals and excrements seems to increase the risk for pneumonia 11

Exposures increasing the risk for pneumonia Work with pigeon loft and attending birth of piglets (Thomas 1994) Exposure to animals, excrements and visceras (Almirall 2008) Cases Laboratory confirmed tularemia cases (n=227) Controls - matched age, sex and residency Questionnaires All tularemia (n=227) Pneumonic cases (n=20) Outdoor activities 1.8 in forests Farming 2.3 Handling hay 6.6 Handling dead Animals 4.1 Mosquito bites 4.6 Exists in soils in cattle farm and stables Occupational risk factor among immunocompromised persons Cattle farmers, horse breeders, stable workers, cleaning animal pens 12

Pneumonias among working men and women. Search after an occupational exposure Especially welding fumes, inorganic dust and farming activities Be aware of the increased risk among immunocompromised subjects. Lobar pneumonia among men should be regarded as an occupational lung disease Mechanisms? Zhou and Kobzik: AJRCMB 2007 Alveolar macrophages internalization of bacteria Hampered by concentrated ambient particles (CAP) Soluble fraction Chelation of iron reversed the effect Soluble metals, especially iron, decreased the killing of Streptococcus pneumonie Lungs of mice was inoculated with Listeria. There were significantly more bacterial colonies in lungs of mice preexposed to welding fumes compared to control animals Lungs of mice was inoculated with Listeria. There were significantly more bacterial colonies in lungs of mice preexposed to welding fumes compared to control animals 13

Animal studies support the mechanism that exposure to welding fumes as well as ambient particles decrease the antibacterial function of the alveolar macrophages making animals more susceptible to bacterial inefctions Priming with interferon-γ and exposure to concentrated ambient particles caused loss of phagocytosis in alveolar macrophages Which of the following work exposures is not associated with increased epidemiologic risk of pneumonia? A. Welding fumes B. Inorganic dust C. Lead D. Manganese 14

Which of the following organisms has not been associated with increased epidemiologic risk of work related pneumonia? A. Hanta virus B. Pneumococcus C. Legionella D. Tularemia Occupational exposures have been associated with which pattern or type of pneumonia? A. Lobar pneumonia only B. Multi lobar only C. Pneumococcal pneumonia only D. Multiple organisms and various radiographic types 15