International Conference on Pesticide Exposure and Health July 8 12, 2002 NIH, Natcher Conference Ce

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International Conference on Pesticide Exposure
and HealthJuly 8 - 12, 2002NIH, Natcher
Conference CenterBethesda, MD USA Respiratory
Disease

• Arch I. Carson, MD, PhD
• University of Texas, Houston
• School of Public Health

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Effects of pesticides and pesticide preparations
on respiratory function

• Acute effects
• Chronic effects
• Vehicles and dispersants
• Fumigants

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Respiratory system
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Inert ingredients

• Vehicles (petroleum distillates, diesel fuel,
  ethylene glycol, aromatic hydrocarbons)
  respiratory irritation, pneumonia
• Dispersants (silica, petroleum distillates)
  pulmonary fibrosis, lipoid pneumonia, etc.

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Fumigants

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

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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)

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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 PFTs, Impaired neutrophil function
  (Sliwinski et al., 1991)
• Indian mango orchard applicators
• Pneumonitis (Srivastava et al., 1991) Restrictive
  defect (Garg et al., 1989)

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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)

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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)

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Paraquat

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

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Respiratory cancer

• Arsenicals
• Hexamethylphosphoramide (rodents)

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Few or no published studies

• Organochlorines
• Phenoxyacetate herbicides
• Pyrethroids (mounting body of evidence for
  respiratory allergies)

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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

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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.

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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

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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.

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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

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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)

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Asthma in the Workplace A broader
classification
() Influenced by setting clinical,
surveillance, compensation systems.
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Pathogenesis of Asthma
Source Holgate, S.T. and NAEPP Expert Panel
II, 1997
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Cellular Mechanisms of Inflammation in Asthma
Source NAEPP Expert Panel II, 1997
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Pulmonary function tests
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Non-specific bronchial challenge
FEV1 ( of baseline)
albuterol
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Peak Flow Variability in Asthma
Exposed
Not Exposed
Exposed
Serial Peak Flow Values
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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

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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)

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Asthma the bottom line

• We are dealing with a disease of public health
  importance, with clearly worsening trends in
  prevalence and severity.

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