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Popcorn Packers' Pneumoconiosis

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Popcorn Packers' Pneumoconiosis There's an Epidemic in Jasper County: Popcorn Workers' Lung- The History, Biology and Occupational Medicine Occupational Heath Issues of Flavoring-Induced Bronchiolitis Obliterans (FIBO) • Prevent occupational illness and injury • Treat occupational illness and injury • Dedicated to promoting the health of Allen J. Parmet, MD, MPH workers through preventive medicine, 816-931-2501 clinical care, research, and education [email protected] Kansas City, MO History of a new illness Jasper, Missouri • Jasper, Missouri popcorn facility Small facility located in SW Missouri, packs • Biology of the lung popcorn. • Initial Clinical Cases Initially in 1980s, packed for home popping in • Epidemiology jars. • NIOSH Investigation In early 1990s, began packaging microwave packets. •Chemistry • Brochiolitis Obliterans Syndrome Popcorn Packaging Facility Facility Layout Popcorn Mixing Area Salt (Mezzanine) Packaging Final Product Boxing Area Oil Office Lines (Below) Seasoning 1 The airways decrease in individual BUT FIRST… size, increase in total cross section • A quick review of human/mammalian respiratory physiology • Out goes the bad air, in comes the good… Upper Airway Trachea Bronchus Bronchiole Alveolus bone structure cartilage rings muscular tubes sacs 2 cm2 100m2 Pulmonary Functions Pulmonary Functions Forced Expiratory Flow from the 25th to 75th Percentile FEF25-75) in Litres per second Forced Expiratory Forced Vital Volume in One VOLUME Tidal Volume VOLUME Capacity (FVC) in Second (FEV1) in Litres Litres 1s And Diffusing TIME TIME Capacity (DLCO) O2 (40) CO2(40) Initial Cases • Early 1990s, workers AIR O2 O2 + began noting difficulty CO2 Glucose breathing, particularly N O2 (100) 2 with certain product lines. CO2 CO2 + O2 Water + • Several became too ill to work and ENERGY developed asthma, respiratory illnesses of various sorts. Lung • Consultations at specialty centers did not CO2 (5) O2 (100) Cells provide a definitive diagnosis to individuals N2 - In Equilibrium by Blood Diffusion in all compartments 2 Holy Smokes! There’s an Epidemic Initial investigation of Bronchiolitis Obliterans in Jasper. • An attorney interviewed several former • Background incidence (rate of new cases employees, multiple diagnoses, multiple per year) of Bronchiolitis Obliterans treating physicians. ~1/40,000 people per year • Cases presented for medical review. • Rate in Jasper ~50/10,000 people/yr • Epidemics are defined as excessive rate of disease • So there is an epidemic in Jasper Patient Characteristics Patient 1 • Aged 29-50 • 40 y/o F, employed 6 months on packing • 5 Female/4 Male line. • 8 Non-Smokers • Non-smoker • Employed few months to several years • FVC=57% FEV1=21% FEF25-75=6% • Worked in various places and positions DLCO=51% around the plant • Additional exams: Bx: non-necrotizing • No time of year specified for onset granulomas. Awaiting lung transplant. Patient 7 Epidemiology • 50 y/o M, employed 18 months as an oil • May, 2000-Missouri Department of Health mixer. contacted. • Ex-smoker: 12 pk-yrs (stopped 15 years) • August, 2000-MDH, NIOSH meet with and • FVC=40% FEV1=19% FEF25-75=8% discuss investigation. • August, 2000-March, 2001-NIOSH site • Additional exams: Developed allergic investigation. dermatitis due to diacetyl, per KUMC. Claim denied. • August, 2001-Interim Report 3 Pulmonary Findings in Popcorn Pulmonary Findings in Popcorn Workers: Index Cases Workers: Index Cases • PFTs – Severe fixed airway obstruction in 6 of 8 • Wedge lung biopsy from 1 subject showed granulomatous bronchiolitis/pneumonitis – Well-preserved DLCO in 7 of 8 – This person had a normal BAL • Chest X-rays unremarkable in all – Is this a hypersensitivity response? • Initial diagnoses: bronchitis, pneumonia, • 1/2 given Cytoxan had objective improvement asthma, emphysema • 0/8 responded to corticosteriods • 4 are listed for lung transplantation – NIOSH Workshop Summary 8/25/01 – NIOSH Workshop Summary 8/25/01 Pulmonary Findings in Popcorn Pulmonary Findings in Popcorn Workers Workers • What exposure(s) caused these findings? • Have these exposures been associated with – Exposures at this plant consist of salt, lung disease in other settings? flavorings, oil and popcorn kernels – J. Lockey described a food flavoring plant – Flavorings used include a butter flavoring employee with fixed airway obstruction, air containing diacetyl trapping and normal DLCO on PFTs with • Diacetyl is the predominant ketone in butter bronchiolitis obliterans on open lung biopsy, flavoring later published as 5 cases. – NIOSH Workshop Summary 8/25/01 • NIOSH Workshop Summary 8/25/01, report 2002. Other Findings Bronchiolitis Obliterans • Eye irritation • Gross lung specimens notable for focal nodules, failure to deflate in the expected • Dermatitis time after biopsy is taken • Histologic appearance is that of organizing • Infertility association fibroblastic polyps – Usually extend from one side wall of a respiratory or terminal bronchiole, sometimes into an adjacent alveolar duct or sac 4 Bronchiolitis Obliterans Bronchiolitis Obliterans Differential Diagnosis • Lymphocytes and • Inhalation of toxic fumes, gases, dusts plasma cells – Cigarette smoke, irritant gases such as chlorine, silica, sometimes present grain dust etc. • Need a specimen • Infection obtained by VATS or – Influenza, CMV, RSV, other viruses open biopsy to make – Fungi the dx in a definitive – Bacteria manner • Bordetella pertussis • HRCT very useful – Mycoplasma Bronchiolitis Obliterans High Resolution CT Findings in Differential Diagnosis Bronchiolitis Obliterans – Drugs • Inspiratory film: areas of • Chemotherapeutic agents, including busulphan, low attenuation bleomycin • Amiodarone • Expiratory film: areas of air trapping, distinct from – Organ transplantation normal areas of increased – Connective tissue disease attenuation seen at end – Hypersensitivity pneumonitis expiration –Aspiration Pulmonary Findings in Popcorn Nebraska Popcorn Worker with Workers Cough • Is there supportive data from animal • 50+ yo popcorn packing facility manager studies? who developed corneal ulcerations, – Rats exposed to vapors from a butter flavoring worsening of his mild chronic cough 1 wk by NIOSH scientists developed necrosis of after starting to use a new low-fat butter airway epithelium from the nasal cavity to the flavoring (with more butter flavoring than lung usual recipe) – NIOSH Workshop Summary 8/25/01 – Non-smoking, no history of asthma – Hubbs 1-2002, Hubbs 2-2004 – 4 year work history, with duties including mixing of flavorings 5 Popcorn Worker with Cough Nebraska Popcorn Worker • Eye exam confirmed the corneal ulcerations • The plant was shut down for 2 weeks • Hoarseness • He developed Herpes zoster and was treated with prednisone 40 mg/day • Bibasilar rales on chest exam • 1 week later, he had resolution of his blurred • Inspiratory/expiratory high resolution CT: vision and his cough was decreasing in severity normal vs. mild air trapping • 6 weeks later, he denied pulmonary and eye • PFT’s showed mild fixed airway symptoms and had returned to full-time work at obstruction the popcorn packing facility Nebraska Popcorn Worker: Popcorn Worker’s Lung: Important Features Summary/Conclusions • Had acute onset with exposure to a new • Syndrome seen in workers who package flavoring microwave popcorn – Those who mix flavoring, pack at highest risk • Unique physical findings included corneal • Airway obstruction (mild to very severe) ulcerations, hoarseness – Not reversible with bronchodilator therapy • Rapid improvement with change in – Air trapping on inspiratory-expiratory high resolution exposure, corticosteroids CT scan – PFTs stabilize with cessation of exposure Popcorn Worker’s Lung: Popcorn Worker’s Summary/Conclusions Lung:Summary/Conclusions • Radiographs and PFTs c/w bronchiolitis • The microwave popcorn industry needs to obliterans but we do not yet fully control exposure to fumes from artificial understand the histology butter flavorings • Evidence points to flavoring agents – NIOSH is working with this industry to address containing diacetyl as a causative agent the problem using industrial hygiene measures • Diacetyl used widely as a butter flavoring, is present and use of PPE in butter • Await results of industrial hygiene studies, animal experiments 6 Interim Report Animal Exposure Study • 87% of employees evaluated by survey, • Rats inhalation exposed to butter seasoning spirometry, chest x-rays. at increasing doses. • Ees had 2.6 times rate of expected chronic cough compared to national average. 3.3 times rate of • Deaths occur at 1/36X workplace maximums. chronic bronchitis. • Suspect chemical: Diacetyl (2,2-Butanedione) • Non-smoking Ees had 5 times rate of expected – C H O vs Acetaldehyde C H O chronic cough compared to national average, 10.8 4 6 2 2 3 – Naturally occurring ketone in butter, coffee, bay times rate of chronic bronchitis. oils. O • Average loss of lung volume 200 ml/yr compared – FDA lists as GRAS to national average of 30 ml/yr. O The Suspects: NIOSH Summary • Diacetyl (2,2-Butanedione)CO 4H6O2 • Work Related Brochiolitis Obliterans Syndrome in Relation to exposures arising in the mixing room but widely disseminated O O throughout other areas of the plant. • Acetaldehyde C H O 2 3 • Recommend extensive primary, secondary and tertiary prevention efforts for all current and O former workers. • Acrolein (2 propenal) C3H4O Diacetyl was once used to treat recurrent pneumothorax by causing pleural scarring: Laforet & Hering, Intrapleural Insufflation of Diacetyl Phosphate to Promote
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