Conferencia Dr. Monsó. • It is healthy to live and work on a farm? Congreso SEPAR Sevilla 2006

It is healthy to live and work on a farm?

E Mons贸 Hospital Germans Trias i Pujol, Badalona, Spain.

Content • The hygiene hypothesis.

• Exposures and diseases.

• Farming in Europe.

• Enclosed workplaces: – Greenhouses.

– Confinement buildings.

Health Hygiene hypothesis • Early exposure to farming environments is associated with a low incidence of asthma, due to a predominant Th1 inmunologic response.

Health

Ernst. AJRCCM 2000

Health

Ernst. AJRCCM 2000

Health

Ernst. AJRCCM 2000

Health

Health

Illi. BMJ 2001

Health

Illi. BMJ 2001

Health

Illi. BMJ 2001

Health

Disease BHR+asthma

• • • • • • •

Farmers Agricultural workers Spray painters Cleaners Plastics Textiles ....

2.6(1.3-5.3) 1.8(1.0-3.2) ..... .... .... ....

asthma

1.7(1.0-3.0) 1.4(1.0-2.0) .... .... .... ....

Kogevinas. Lancet 1999;353:170

Work-related diseases • • • • • • • •

Rinitis.

Asthma.

Organic dust toxic syndrome.

Silo filler’s disease.

Farmer’s lung disease.

Chronic bronchitis.

Lung infection.

COPD.

Work exposures • Toxic gases – Ammonia, CO2, methane, Hydrogen sulfide, NO2, CO.

• Organic dust – Endotoxin, glucan, mycotoxin.

• Biologic agents – Bacteria, fungi, Mites.

• Inorganic dusts.

• Chemicals.

• Infectious microorganisms.

Work environments • Field work.

• Confinement house.

• Silo.

• Greenhouse.

Northamerican/European Study on Farmers’ Lung Health - Design • Cross-sectional study of the prevalence of respiratory symptoms in European and Californian farmers.

• Assessment of occupation and regionrelated risk factors for respiratory symptoms.

Monsó E. Eur Respir J 2003

Work-related diseases • • • • • • • •

Rinitis.

Asthma.

Organic dust toxic syndrome.

Silo filler’s disease.

Farmer’s lung disease.

Chronic bronchitis.

Lung infection.

COPD.

Method • Target sample: All subjects who participated in the studies on respiratory health in farmers performed in Europe and California in the nineties.

• Random selection from census and contact by mail, phone or home visit.

• Questionnaire on respiratory symptoms and occupation.

Monsó E. Eur Respir J 2003

Statistics

• Association between respiratory symptoms, occupation and region assessed using logistic regression.

– 1) Occupational model created for every respiratory symptom with sociodemographic factors and type of farming as independent variables.

– 2) Regional model including region in every occupational model as a risk factor.

Monsó E. Eur Respir J 2003

Respiratory Symptoms 30 25

*

California Europe

*

%

20

* p<.001

15

*

10

*

*

5 0

Smoking

Rhinitis

Asthma

Chronic bronchitis

ODTS

Results 1a Sociodemography and Symptoms California Europe N Age, mean (SD) Gender(women), n (%) Current smoking, n (%) Former smoking, n (%) Rhinitis, n (%) Asthma, n (%) Chronic bronchitis, n (%) ODTS, n (%)

1839 55 (13) 181 (10) 212 (11) 600 (33) 440 (24) 86 (5) 80 (4) 50 (3)

7188 48 (13) 1246 (17) 1602 (22) 1329 (18) 910 (12) 203 (3) 770 (11) 877 (12)

p <.001 <.001 <.001 <.001 <.001 <.001 <.001 <.001

Animal exposure 60

*

50

%

40

*

California Europe

*

* p<.001

30 20

*

10

*

0

Swine

Beef/Veal

Dairy

Poultry

Sheep

Rabbit

Results 1b Animal Exposure Swine, n (%) Beef/Veal, n (%) Dairy, n (%) Poultry, n (%) Sheep, n (%) Rabbit, n (%) One or more, n (%)

California

Europe

p

40 (2) 381 (21) 136 (7) 89 (5) 105 (6) 8 (1) 584 (32)

2337 (32) 3987 (55) 4037 (56) 692 (10) 522 (7) 212 (3) 6009 (84)

<.001 <.001 <.001 <.001 <.05 <.001 <.001

Crop exposure 60

*

*

50

California Europe

%

40

* p<.001

*

30 20

*

10

*

* *

*

0

Grain

Vegetables Tomatoes Root crops Oil plants

Fruits

Nuts

Flowers

Results 1c Crop Exposure Grain, n (%) Vegetables, n (%) Tomatoes, n (%) Root crops, n (%) Oil plants, n (%) Fruits/berries, n (%) Nuts, n (%) Flowers, n (%)

California

Europe

p

180 (10) 63 (3) 82 (5) 59 (3) 47 (3) 878 (47) 490 (26) 89 (5)

3754 (52) 943 (13) 516 (7) 1801 (25) 1235 (17) 563 (8) 287 (4) 311 (4)

<.001 <.001 <.001 <.001 <.001 <.001 <.001 <.001

Results 2a Risk factors-Animal farming Adjusted OR (95CI) Rhinitis Asthma

Swine Beef/Veal Dairy Poultry Sheep Rabbit

0.65 (0.56-0.76) -----1.13 (0.97-1.31) -----0.55 (0.47-0.64) 0.80 (0.62-1.03) 1.30 (1.06-1.60) 1.90 (1.34-2.68) ----------1.27 (0.88-1.85) ------

Results 2b Risk factors-Animal farming Adjusted OR (95CI) Chron. bronchitis ODTS

Swine Beef/Veal Dairy Poultry Sheep Rabbit

1.22 (1.03-1.43)

------

-----

0.76 (0.64-0.90)

-----

1.32 (1.11-1.57)

-----

1.25 (0.99-1.59)

1.27 (0.98-1.66)

1.31 (1.01-1.69)

1.68 (1.13-2.50)

1.89 (1.30-2.75)

Results 2c Risk factors-Crop farming Grain Vegetables Tomatoes Root crops Oil plants Fruits/berries Nuts Flowers

Adjusted OR (95CI) Rhinitis Asthma 1.13 (1.00-1.29) -----0.77 (0.61-0.97) 0.52 (0.32-0.83) 0.77 (0.57-1.04) ----------1.28 (0.94-1.75) ----------1.30 (1.10-1.54) -----1.23 (1.00-1.51) -----1.29 (0.98-1.70) 1.71 (1.06 -2.77) (1.06-2.77)

Results 2d Risk Factors-Crop Farming

Grain Vegetables Tomatoes Root crops Oil plants Fruits/berries Nuts Flowers

Adjusted OR (95CI) Chron. bronchitis ODTS 1.42 (1.21-1.67) 2.15 (1.82-2.53) -------------------------1.51 (1.28-1.77) 1.49 (1.22-1.81) 1.66 (1.39-1.98) 0.90 (0.72-1.12) 0.81 (0.64-1.01) 0.55 (0.40-0.77) -----1.67 (1.22-2.27) 1.75 (1.29-2.38)

Results Risk Factors-Farming Crops

Animals

Grain Vegetables Tomatoes Root crops Oil plants Fruits/berries Nuts Flowers

Swine Beef/Veal Dairy Poultry Sheep Rabbits

Results 4a Europe-California . Regional risk factors Non-smokers Adjusted OR (95CI) Sociodemograph. Occupational mod.

Rhinitis Asthma Chronic Br. ODTS

0.56 (0.47- 0.65) 0.96 (0.68- 1.35) 4.19 (3.08- 5.70) 7.93 (5.76-10.93)

0.58 (0.47-0.71) 0.95 (0.67-1.35) 3.61 (2.64-4.95) 4.14 (2.81-6.09)

Results 4b Europe-California . Regional risk factors Smokers

Adjusted OR (95CI) Sociodemograph. Occupational m.

Rhinitis 0.70 (0.47- 1.05) Asthma 1.92 (0.85- 4.37) Chronic Br. 2.82 (1.76- 4.53) ODTS 9.88 (4.23-23.10)

0.68 (0.42-1.12) 1.41 (0.68-3.27) 1.73 (1.05-2.86) 3.96 (1.65-9.51)

Results 5a - Europe Chronic bronchitis and indoor work Chronic bronchitis ODTS Adjusted OR (95CI)

yes

no

Non-smokers 28% 7% Smokers 40% 11%

5.17 (4.21- 6.34) 4.28 (3.01- 6.10)

Results 5b - Europe Chronic bronchitis and indoor work Chronic bronchitis Confinement building Adjusted OR (95CI)

yes Non-smokers Smokers

no

11% 8% 18% 11%

1.58 (1.27- 1.96) 1.98 (1.46- 2.68)

Results 5c - Europe Chronic bronchitis and indoor work Chronic bronchitis greenhouse Adjusted OR (95CI) yes

Non-smokers Smokers

no

15% 9% 14% 15%

1.59 (1.02- 2.48) 0.98 (0.45- 2.12)

Results 6a Non-smoking animal farmers n=112 Former smoking, n (%) Chronic bronchitis, n (%) in former smokers, n (%) in never smokers, n (%) Chronic bronchitis+COPD, n (%) in former smokers, n (%) in never smokers, n (%)

28 36 6 30 11 3 8

(25.0) (32.1) (5.4) (26.8) (10.7) (11.1) (10.5)

Conclusions - 1 â&#x20AC;˘

The prevalence of chronic bronchitis and ODTS is higher in European than in Californian farmers.

â&#x20AC;˘

The high prevalence of chronic bronchitis and ODTS in European farmers depends on the type of farming practiced in the region and is mainly related to work inside animal confinement buildings.

Background The European Farmersâ&#x20AC;&#x2122; Study demonstrated that the cultivation of flowers and ornamental plants is a risk factor for bronchial asthma and working inside greenhouses increases this risk.

MonsĂł E. Am J Respir Crit Care Med 2000; 162: 1246

European Farmersâ&#x20AC;&#x2122; Study 5.4% asthma prevalence in flower growers OR (95%CI) for asthma Flower growing

2.1 (1.1-3.9)

Greenhouse work

2.1 (0.9-4.5)

farmers with other cultivations as the reference

MonsĂł E. Am J Respir Crit Care Med 2000; 162: 1246

Flower greenhouse

Aim To determine the prevalence and the etiology of occupational asthma in crop farmers cultivating flowers and/or ornamental plants inside greenhouses.

Method - 1 Target population •Determination of a representative subsample from the population of greenhouse flower and/or ornamental plant growers who participated in the European Farmers’ Study.

•Selection of a random sample of 40 growers from this subsample for the present study.

Method - 2 Measurements • • • • •

Greenhouse characteristics Air contaminants.

Symptoms and occupational exposure.

Spirometry and reversibility testing.

Workplace bronchial provocation challenge for subjects reporting wheezing and/or asthma last year.

• Skin testing with workplace allergens.

Method - 3 Skin testing • Common allergens (Dermatophagoides, mixed trees, mixed grass, mixed graminae, Parietaria, cat and dog hair).

• Workplace allergens: • Moulds: Alternaria, Cladosporium, and Penicillium.

Aspergillus

Gladiolus, Hyacintus, Narcissus, Solidago, Chrysantemum and Heliantus.

• Flowers: •

Spider mite.

Results - 1 Population sample •73/85 greenhouse flower and/or ornamental plant growers participating in the European Farmers’ Study worked in Spain (86%) and were the target population.

•39 growers from the random sample of 40 subjects from the target population participated in the study (97.5%).

Population sample

Greenhouse area

Results - 2 Sociodemography and symptoms Age, m (SD) Gender (m/f) Smoking, n (%) Flower growers, n (%) Ornamental plant growers, n(%) Wheezing last year, n (%) Nasal allergies last year, n(%) Asthma attacks last year, n (%)

48.6 (10.2) 35/4 18 (46.2) 25 (64.1) 14 (35.9) 12 (30.8) 12 (30.8) 3 (7.7)

Results - 3 Greenhouse air contamination by moulds 100 90

% of observations

80 70

82

60 50 40

46

44

30 20 10 0

36

31 18 Cladosp.

Penicil.

18

15

Botryu. Acremon. Asperg. Alternar.

13 Geotric.

Other

Nonident.

Workplace bronchial challenge - 1 Control day

Greenhouse day

4,5

4

FEV1 (L)

3,5

3

2,5

*

2

*

1,5

* Decline FEV1 >20%

1 0

30

60

90

120

150

180

Minutes

210

240

270

300

330

360

Workplace bronchial challenge - 2 Control day

Greenhouse day

4,5

4

FEV1 (L)

3,5

3

2,5

2

*

1,5

* * Decline FEV1 >20%

1 0

30

60

90

120

150

180

Minutes

210

240

270

300

330

360

Workplace bronchial challenge - 3 Control day

Greenhouse day

4,5

4

FEV1 (L)

3,5

3

*

2,5

2

1,5

* Decline FEV1 >20%

1 0

30

60

90

120

150

180

Minutes

210

240

270

300

330

360

Results - 4 Occupational asthma and sensitization n (%) atopy (n=38) current asthma

16 (42.1) 5 (12.8)

- occupational

3 (7.7)

- non-occupational

2 (5.1)

Results - 4 Sensitization to workplace allergens n=38

n (%) moulds

7 (18.4)

flowers

8 (21.1)

spider mite

2 (5.3)

one or more allergens

13 (34.2)

Results - 5 Etiology of occupational asthma Prevalences Sensitization to workplace allergen

Occupational asthma

n

(%)

13/38 (34.2) 3/39

(7.7)

Sensitization to moulds (2)/ flowers (2)

Occupational asthma - Sensitized to workplace allergens

3/13 (23.1)

- Non-sensitized to workplace allergens

0/25

(0.0)

Conclusions - 2 â&#x20AC;˘One third of the greenhouse flower and/or ornamental plant growers are sensitized to workplace moulds and/or flowers. â&#x20AC;˘The cultivation of flowers and/or ornamental plants inside greenhouses causes occupational asthma in almost 8% of the growers, through sensitization to workplace antigens.

Pig farmers - Lung function decline

Iversen. ERJ 2000

Method 1 â&#x20AC;˘ Never-smoking subjects who participated in the European Farmersâ&#x20AC;&#x2122; Study and worked inside animal confinement buildings (n=105).

Age, mean (SD) Gender (women), n (%) Country Denmark, n (%) Germany, n (%) Switzerland, n (%) Spain, n (%)

45.1 (11.7) 21 (20.0) 14 (13.3) 65 (61.9) 20 (19.0) 6 (5.7)

Method - 2 Measurements • • • • •

Symptoms and occupational exposure.

Spirometry and reversibility testing.

FEV1 variability in a work day.

Confinement building characteristics.

Air contaminants: • Carbon dioxide • Ammonia • Dust • Endotoxin

Respiratory symptoms - animal farmers Type of farming Pig, n (%) Beef/Veal, n (%) Dairy, n (%) Poultry, n (%)

82 32 23 33

(78.1) (30.5) (21.9) (31.4)

Respiratory symptoms Wheeze last year, n (%) 58 (55.2) Chronic bronchitis, n (%) 48 (45.7) Wheeze or chronic bronchitis, n (%) 72 (68.6)

Lung function - animal farmers FEV1%, m (SD)

98.5 (21.0)

COPD, n (%) ($) mild, n (%) moderate/severe, n (%) +respiratory symptoms, n (%)

18 7 11 18

FEV1 variability>10%, m (SD) increase, n (%) decline, n (%)

20 (19.0) 7 (6.7) 13 (12.3)

COPD and FEV1 variability variability >10%, n (%) variab.>10% + wheeze, n(%)

(17.1) (6.7) (10.5) (17.1)

4 (3.8) 4 (3.8) ($) GOLD criteria

Building characteristics - Air contaminants Confinement building Area (m2 ) Temperature (ยบC) Humidity (%) CO2 (ppm) Ammonia (ppm) Total dust (mg/m3) Endotoxin (ng/m3)

168 (110-300) 18.0 (15.7-20.0) 81.3 (73.5-87.2) 1500 (1000-2000) 10.0 (5.0-17.0) 5.6 (2.3-9.4) 85.9 (35.3-275.4)

expressed as median (interquartile range)

COPD and building characteristics COPD, n (%) โ คmedian

>median

Crude OR(95%CI)

10 (18.9)

8 (15.4)

0.78 (0.28-2.17)

>0.25

Temperature (ยบC)

8 (14.8)

10 (19.6)

1.40 (0.50-3.89)

>0.25

Relative humidity (%)

7 (13.2)

11 (21.2)

1.76 (0.62-4.97)

>0.25

p

Measurement Area (m2 )

COPD and indoor contaminants - 1 COPD, n/n total (%) CO2 First quartile Second quartile Third quartile Fourth quartile Ammonia First quartile Second quartile Third quartile Fourth quartile

Adjusted OR(95%CI)

5/29 8/32 4/20 1/24

(17.2) (25.0) (20.0) (4.2)

1.00 1.08 (0.34-3.43) 0.54 (0.17-1.69) 0.18 (0.02-1.44)

3/28 8/32 3/21 4/24

(10.7) (25.0) (14.3) (16.7)

1.00 1.82 (0.48-7.00) 0.86 (0.30-2.48) 1.32 (0.35-4.89)

COPD and indoor air contaminants - 2 n=76

COPD, n/n total (%)

Total dust First quartile Second quartile Third quartile Fourth quartile Endotoxin First quartile Second quartile Third quartile Fourth quartile

Adjusted OR(95%CI)

1/17 2/21 2/19 6/19

(5.9) (9.5) (10.5) (31.6)

1.00 2.96 (0.34-25.98) 3.70 (0.79-17.27) 4.16 (1.01-17.14)

1/19 3/19 3/18 4/20

(5.3) (15.8) (16.7) (20.0)

1.00 4.03 (0.46-35.52) 1.98 (0.50-7.87) 1.15 (0.23-5.59)

Conclusions - 3 •COPD in never-smoking farmers working inside animal confinement buildings may reach moderate severity.

•Indoor exposure to organic dust in the workplace is related to COPD, and show a dose-response relationship.

•Endotoxin exposure is marginally related to COPD.

Final conclusions â&#x20AC;˘

The prevalence of chronic bronchitis is higher in European than in Californian farmers.

â&#x20AC;˘

Chronic bronchitis in Europe is related to work inside animal confinement areas and greenhouses.

Final Conclusions â&#x20AC;˘One third of the greenhouse flower growers are sensitized to workplace moulds and/or flowers. â&#x20AC;˘The cultivation of flowers inside greenhouses causes occupational asthma in almost 8% of the growers, through sensitization to workplace antigens.

Final Conclusions â&#x20AC;˘COPD in never-smoking farmers working inside confinement buildings is significant. â&#x20AC;˘Indoor exposure to organic dust in the workplace is related to COPD

Epidemiolog铆a de la enfermedad Ram贸n Magarolas Sandra Cabrera Marc Schenker Katja Radon Dennis Nowak Brigitta Danuser

Rosa Rein贸n Sandra Alonso Cathy Saiki Elena Riu Martin Iversen Josep Morera

Hospital Germans Trias i Pujol, Badalona, Spain University of California, Davis, California, USA I Poliklinik Arbeits-Umweltmedizin, Munchen, Germany