1. University of Texas, Houston School of Public Health
International Conference on Pesticide Exposure and Health July , 2002 NIH, Natcher Conference Center Bethesda, MD USA Respiratory Disease
Arch I. Carson, MD, PhD
University of Texas, Houston
School of Public Health

2. Effects of pesticides and pesticide preparations on respiratory function
Acute effects
Chronic effects
Vehicles and dispersants
Fumigants

3. Respiratory system

4. “Inert ingredients”
Vehicles (petroleum distillates, diesel fuel, ethylene glycol, aromatic hydrocarbons) respiratory irritation, pneumonia
Dispersants (silica, petroleum distillates) pulmonary fibrosis, lipoid pneumonia, etc.

5. Fumigants Sulfotep (Methner and Weldon, 1996) Methyl bromide
Aluminum phosphide (phosphine)
Etc.

6. Most epidemiological studies have been “generic”
Farming vs. non-farming households in Saskatchewan
Asthma, bronchitis, pneumonia, hay fever, > in children (Masley et al., 2000)
Greenhouse workers
Occupational asthma, respiratory symptoms (Illing, 1997)
Farmers and grain handlers
Cough, wheezing, breathlessness, chest tightness (doPico,1996)
Indonesian farmers
Dry throat, difficulty breathing, chest pain (Kishi et al., 1995)

7. Most epidemiological studies have been “generic” (cont.)
Chemical facility workers
Airway obstruction, chronic bronchitis, emphysema (Konieczny and Kossman, 1993)
Polish organochlorine/carbamate/triazine workers
Impaired PFT’s, Impaired neutrophil function (Sliwinski et al., 1991)
Indian mango orchard applicators
Pneumonitis (Srivastava et al., 1991) Restrictive defect (Garg et al., 1989)

8. Acetylcholinesterase inhibitors
Agricultural workers in East Africa
Respiratory symptoms (Ohayo-Mitoko et al., 2000)
Commercial flower growers
Hypersensitivity (carbamates), asthma, rhinitis (Ueda et al., 1995)
41 cases exposed to chlorpyrifos
Headaches, chest congestion, permanent disability (Sherman, 1995)
International exposure cases
Respiratory allergic symptoms, asthma (Ecobichon, 1995) (McDuffie and Senthilselvan, 1992)

9. Acetylcholinesterase inhibitors (cont.)
Environmental spill exposures
Irritant-induced asthma, exacerbation of pre-existing asthma (Wugofski, 1994)
Combined OP exposures
Intermediate syndrome with respiratory paresis (De Bleeker et al., 1992)
Trialkylphosphorothioates
Bronchiolar cell, Clara cell, and Type I pneumoocyte damage (Dinsdale, 1992)

10. Paraquat Nicaraguan applicators Costa Rican ag workers
Chronic nose bleeds, asthma, chronic bronchitis, chronic breathlessness (Castro-Gutierrez, 1997)
Costa Rican ag workers
Pulmonary edema and functional respiratory disorders (Hogstedt, 1997)

11. Respiratory cancer
Arsenicals
Hexamethylphosphoramide (rodents)

12. Few or no published studies
Organochlorines
Phenoxyacetate herbicides
Pyrethroids (mounting body of evidence for respiratory allergies)

13. Adverse respiratory function outcomes
Acute or persistent episodic airway obstruction in the chest (asthma)
Chronic obstructive pulmonary disease (COPD)
Chronic upper respiratory hyperresponsiveness (rhinitis, sinusitis, headaches)
Interstitial pulmonary fibrosis
Allergy (allergic rhinitis, asthma, pneumonitis)
Cancer

14. Pesticide-related respiratory morbidity
Largest number of pesticide-related respiratory health problems are short-term irritant or allergically mediated symptoms without permanent sequellae
Remaining chronic respiratory disease is mediated by direct acute toxicity with repair-related long-term dysfunction.

15. Case 36 y.o. male supervisor in a pesticide compounding facility
Childhood asthma until age 10. Completely asymptomatic, off medication, thereafter
3/26/96: Fire in the compounding unit, 30 minute exposure to thick, acrid smoke

16. Case
Immediate symptoms: watery eyes, burning sensation of nose and throat, chest tightness, dyspnea, wheezing, nausea, vomiting
Hospitalized for 24 hours
Persistent “wheezy” cough, nasal and sinus congestion, GERD symptoms. Cough worsened by exposure to ETS, cooking fumes, cologne.

17. Case: Irritant-induced Asthma
Physical examination (4/96): swollen nasal mucosa, white drainage, decreased nasal airflow. Clear lungs.
Spirometry: FVC-89% FEV1-96%
Methacholine challenge (5/96): 40% decrease in FEV1 at 0.5 mg/ml
Bronchoscopy (5/96): airway erythema
Sinus x-rays: moderate maxillary sinus mucosal thickening

18. Irritant-induced Occupational Asthma
Synonyms: non-immunological asthma, asthma without latency
Onset: 2 types
Sudden onset (RADS)
Not-so-sudden onset
Causal agents: a long list of respiratory irritants, including gases, fumes and chemicals (pesticides)

19. Asthma in the Workplace: A “broader” classification*
(*) Influenced by setting: clinical, surveillance, compensation systems.

20. Pathogenesis of Asthma
Source: Holgate, S.T. and NAEPP Expert Panel II, 1997

21. Cellular Mechanisms of Inflammation in Asthma
Source: NAEPP Expert Panel II, 1997

22. Pulmonary function tests

23. Non-specific bronchial challenge
FEV1
(% of
baseline)
albuterol

24. Peak Flow Variability in Asthma
Exposed
Not Exposed
Exposed
Serial Peak Flow Values:

25. Asthma Epidemiology: U.S.
14-15 million persons (5%) affected (5 million in the under 18 age group)
> 100 million days of restricted activity/yr
$6.2 billion in annual costs
From 1979 to 1992:
66% increase in prevalence
17% increase in hospitalization
58% increase in age-adjusted asthma deaths

26. How much of asthma is attributable to occupational exposures?
United States:
Among Social Security disability applicants: 15.4% (Blanc, 1987)
Among HMO members: 21% (Milton et al, 1998)
Japan: 15% (Kobayashi, 1974)
Spain: 6.7% (Kogevinas et al, 1996)
Finland: 4.8% (Reijula et al, 1996)
Meta-analysis: 9% [15% among high quality studies](Blanc and Toren, 1999)

27. Asthma: the bottom line
We are dealing with a disease of public health importance, with clearly worsening trends in prevalence and severity.

28. How much of the worldwide increase in asthma is due to environmental or occupational pesticide exposure?