University of Texas, Houston School of Public Health International Conference on Pesticide Exposure and Health July 8 - 12, 2002 NIH, Natcher Conference Center Bethesda, MD USA Respiratory Disease Arch I. Carson, MD, PhD University of Texas, Houston School of Public Health

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

Respiratory system

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

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

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)

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)

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)

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)

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)

Respiratory cancer Arsenicals Hexamethylphosphoramide (rodents)

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

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

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.

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

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.

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

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)

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

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

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

Pulmonary function tests

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

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

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

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)

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

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