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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

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Smoke from factory 80% manganese/ferromanganese

1939;3:2527-2533

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?

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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

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Ship-yard workers from Bay area. 18% of the lobar pneumonia occurred among welders. But welders were 18% of the workforce. Welders (Seattle area) SMR 167 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)

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Occupations Last exposure to metal fume (several items) Pneumonia OR >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)

Different exposures and morbidity from pneumonia with control for overlapping exposures Exposure N OR 95% CI 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 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 Thorax 2009;64:983-986 PMR (16-64 yrs) Welders 242, p<0.05 Furnace operators 96, NS Moulders/coremakers 300, p<0.05 Other metal workers 46, NS Sheet metal workers 268, p<0.05

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All patients with invasive pneumococcal disease 2000-2004. Alberta, Canada

Occupation Cases Incidence OR 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)

1768 cases, of these 863 in working age 8.7/100 000

Thorax 2011;66:992-996

Construction workers

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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,

• rganic solvents)

Metal fume Wood dust

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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.

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Risk for infectious pneumonia in relation to non-

• verlapping 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

• f exposure to inorganic dust.

Probably a multifactorial etiology What do we know about dust exposure and risk for pneumonia?

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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) Solvents or gasoline around home 3.3 (1.6-6.9)

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

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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 Women Cement, lime, plaster 1.5 3.2 Cast metals 1.6

• 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

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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 Pneumonic (n=227) 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 immuno- compromised persons Cattle farmers, horse breeders, stable workers, cleaning animal pens

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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

• f Streptococcus pneumonie

Lungs of mice was inoculated with Listeria. There were significantly more bacterial colonies in lungs of mice pre- exposed to welding fumes compared to control animals Lungs of mice was inoculated with

• Listeria. There were

significantly more bacterial colonies in lungs of mice pre- exposed to welding fumes compared to control animals

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Priming with interferon-γ and exposure to concentrated ambient particles caused loss of phagocytosis in alveolar macrophages

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

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

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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