Microsoft powerpoint - 22_brautbar_occupational bronchiolitis obliterans (collegium
Occupational Bronchiolitis Obliterans in Food Flavoring
*Nachman Brautbar, M.D., *Ronald Zlotolow,
*University of Southern California, Los Angeles, California,
RAMAZZINI DAYS 2007 - JUBILEE CELEBRATION
25th Anniversary of the Collegium Ramazzini
Introduction
• Several recent studies reported severe
occupational lung disease in workers exposed to materials used in food flavoring. In those cases, airborne dust from butter flavoring such as diacetyl were causative (not exclusive to only diacetyl).
• The Center of Disease Control (CDC) and the
California OSHA issued a report (April 2007) indicating among others the need “to identify cases” and “reduce risk for lung disease”“from occupational exposure to flavoring”.
• We report here 4 patients, exposed to
powders, vapors and mists in food flavoring industry, with chronic bronchiolitis obliterans.
• To our knowledge, at least one patient was
initially misdiagnosed as “asthma”.
• Pulmonary function tests were done in
accordance with the American Thoracic Society criteria [ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003 Jan 15;167(2):211-77]. Case Report #1: 32-y.o. Male
– Machine operator and mixer at a food flavoring/powders
– Inhalation during mixing of heated flavoring powder;– Provided paper masks, described as ineffectual.
– Suffocating symptoms and respiratory complaints upon
– BP: 130/80;– Lung examination demonstrated diffuse wheezing. Case Report #1
– EKG, thyroid and urinalysis and chemistry panel were
– Hematology panel: RDW of 11.3, eosinophils of 9,
– Allergy test: Immunoglobin E of 684;– Chest x-ray: Normal– Spirometry: FVC of 43%, FEV
– Repeat spirometry: FVC of 35%, FEV of 22%;
– Repeat spirometry: FVC of 46%, FEV of 31%, diffusion
capacity of 85%, bronchodilation did not improve the FEV in all spirometric studies (effort was good; fixed
Case Report #1
– Proventil, Advair and Spiriva, with only a
Case Report #2: 38-y.o. Male
– Production worker at food flavoring company for 5
– Inhalation during mixing of heated flavoring powder.
– Shortness of breath, chest pain, cough and eye
irritation by the end of the second week on the job;
– Breathing problems worsened and was diagnosed with
– Given inhalers and oral prednisone, which were
– Asthma at age 8, resolved at age 9. Case Report #2
– Lung examination exhibited positive diffuse wheezing.
– EKG, urinalysis, chemistry panel, rheumatology and
collagen vascular panels were within normal limits;
– Hematology panel: Sedimentation rate of 33.
– Allergy test: Immunoglobin E of 217.
significant change post bronchodilator, bronchodilation did not improve FEV in all spirometric studies (effort
Case Report #2
– Oral prednisone (60 mg per day) with no
improvement, Proventil, Advair and home nebulizer, which are ineffectual, and 24-hour supplemental oxygen. Case Report #3: 50-y.o. Male
– Compounder for flood flavoring company for 6 years.
– Inhalation during mixing of flavoring powders and liquids
– Provided paper masks, described as ineffectual.
– Headaches upon inhalation of powder and fumes;– Cough after one year on the job, given diagnosis of
asthma by private physician and prescribed inhalers. Case Report #3
– Urinalysis revealed moderate leukocytes;– Hematology panel: Neutrophils of 40,
eosinophils of 7 and sedimentation rate of 20;
– Allergy test: Immunoglobin E was normal– EKG and chest x-ray were normal;– Spirometry: FVC of 50%, FEV of 37%, diffusion
– Repeat spirometry: FVC of 48%, FEV of 37%
and increased to 39% post-bronchodilator, bronchodilation did not improve FEV
spirometric studies (effort was good). Case Report #3
– Albuterol, Spiriva and Singular (with some
Case Report #4: 44-y.o. Female
– General laborer at food powder company for 10 years.
– Inhalation of fumes and dust while mixing chemicals for
concentrated fruit juices and candies.
– Provided paper masks, described as ineffectual.
– Shortness of breath, watery eyes and nasal congestion
Case Report #4
– EKG: sinus bradycardia;– Chemistry panel, hematology panel and thyroid panel
– Chest x-ray was within normal limits;– Methacholine challenge test (sometime in 2003):
FEV1 was 103% and decreased to 63% after methacholine, complained of worsening shortness of breath;
– Diagnosis at that time: occupational asthma– Her symptoms deteriorated and was re-evaluated in
– Repeat spirometry (about 3 years later): FVC of 36%,
FEV1 of 42% with good effort and no improvement post-bronchodilation. Case Report #4
– Initial diagnosis: reactive airway disease;
– Diagnosis three years later: bronchiolitis
Summary of Case Reports Discussion
The key diagnostic feature in our patients were:
1. History of exposure to food flavoring
2. Obstructive airway disease (FEV ↓) with
no improvement upon bronchodilation(fixed obstruction);
• In California, since April of 2006 a total of
obstructive airway disease, exposure to chemicals used in the food flavoring industry, lack of adequate protective devices and absence of other causes (i.e., preexisting asthma, cigarette smoking) and a mean age of 34 (range 27-44).
• Our findings in these 4 patients are
compatible with other studies (e.g., Kreiss, K. et al. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med. 2002 Aug 1;347(5):330-8):
– “Our findings of excess rate of lung disease and
associations between indexes of exposure to volatile organic chemicals and obstructive lung disease supports the conclusion that an agent in butter flavoring caused occupational bronchiolitis obliterans in exposed workers at this popcorn plant.”
Workers in food flavoring industry (probably not limited to production) are at increased risk for severe and progressive lung disease, bronchiolitis obliterans.
The condition is probably under-diagnosed (lack of occupational history by clinicians) and underreported (NIOSH and California OSHA hearings 2006, 2007).
Shortness of breath and obstructive airway disease in food flavoring industry and chain of distribution, i.e., bakeries, movies, etc., must be evaluated with a detailed occupational history and pulmonary function tests based on the American Thoracic Society criteria (CT scan of the chest may be important).
Meticulous follow-up and reporting to OSHA.NIOSH is mandatory.
Treatment: no evidence that steroids and immunosuppressive therapy is helpful. Conclusion
• Recent onset of shortness of breath, followed by
“asthma” in workers with a history of exposure to powders, vapors and mist used in the food flavoringindustry should be a red flag for bronchiolitis obliterans, asthma, bronchiolitis obliterans with organizing pneumonia, and pulmonary fibrosis.
• Fixed obstructive airway disease is a prime diagnostic
feature. CT scan of the chest is helpful. Lung biopsy is probably not helpful and it may not change the treatment nor the clinical outcime.
• In some patients who were diagnosed as “occupational
bronchodilation is mandatory (Case #4). Literature
• A cluster of severe bronchiolitis obliterans cases in a small
rural microwave popcorn plant (Kreiss, K.; et al. Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. N Engl J Med. 2002 Aug 1;347(5):330-8).
• Kanwal, R.; et al. Evaluation of flavorings-related lung
disease risk at six microwave popcorn plants. J Occup Environ Med. 2006 Feb;48(2):149-57.
• Centers for Disease Control and Prevention (CDC). Fixed
obstructive lung disease among workers in the flavor-manufacturing industry--California, 2004-2007. MMWRMorb Mortal Wkly Rep. 2007 Apr 27;56(16):389-93. Literature
• The spectrum of lung disease in flavoring workers may be
broader: asthma, bronchiolitis obliterans with organizing pneumonia, fibrosis, granulomatosis, pneumonia. “Perhaps bronchiolitis obliterans is a much more common finding than we think” -- Kreiss, K. Occupational Bronchiolitis Obliterans Masquerading as COPD. Am J Respir Crit Care Med. 2007 Sep 1;176(5):427-9.
• Exposure levels as low as 0.2 to 0.6 ppm -- Kreiss, K.
Flavoring-related bronchiolitis obliterans. Curr Opin AllergyClin Immunol. 2007 Apr;7(2):162-7.
• Federal agencies knew about diacetyl dangers and kept
quiet. -- OMB Watch. Federal Agencies Knew of Diacetyl Dangers and Kept Silent. Published: 9/11/2007. http://www.ombwatch.org/article/articleview/3970. Literature
• Industrial sputum evaluation in microwave popcorn
production workers demonstrate neutrophilic airway inflammation. -- Akpinar-Elci, M.; et al. Induced sputum evaluation in microwave popcorn production workers. Chest. 2005 Aug;128(2):991-7.
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