JASPER, MO—A severe occupational risk to respiratory health is now associated not with mining or agriculture but, surprisingly, with manufacture of food containing artificial butter flavoring. Eight cases of constrictive bronchiolitis obliterans (CBO) in former workers at a microwave popcorn packaging facility, four of whom await lung transplants, were reported to the Missouri Department of Health (MDH) in May 2000, prompting a joint investigation with the National Institute of Occupational Safety and Health (NIOSH).[1]

In CBO, “inflammatory and scar tissue are distributed throughout the small airways, but the alveoli are spared,” said Kay Kreiss, MD, Chief of the Division of Respiratory Disease Surveillance at the NIOSH Field Studies Branch in Morgantown, West Virginia. After some acute exposures to noxious fumes, “patients develop acute pulmonary edema and seem to recover, but over the next month or two, they develop CBO,” Dr. Kreiss emphasized. “But in this plant, cough and exertional dyspnea evolved without recognized overexposure or acute lung injury, sometimes within a few months of employment.”

After finding no recognized causes of the rare disorder at the plant, the MDH requested NIOSH assistance. Led by Dr. Kreiss, investigators measured airborne dust and volatile compounds from artificial butter, and they surveyed current plant employees with questionnaires, spirometry, diffusing capacity measurements, and chest films.

Overall, plant employees reported elevated rates of chronic cough, dyspnea, and asthma. Never-smoking employees had a 3.3-fold excess incidence of chronic bronchitis and a 10.8-fold excess incidence of obstructive spirometric abnormalities. Notably, the degree of airway obstruction correlated with workers’ cumulative exposure to dust and volatile fumes from heated artificial butter.

ARTIFICIAL BUTTER IMPLICATED

“We exposed rats at NIOSH to vapors from heated artificial butter flavoring. They had profound damage to the respiratory epithelium, but not alveolar damage.... Our toxicologist had never seen anything like this: The damage extended below the basement membrane,” Dr. Kreiss told PULMONARY REVIEWS. NIOSH has yet to identify a particular component of the flavoring mixture as the culprit.

IDENTIFYING CASES

“In fixed obstruction like this, there’s no bronchodilator response and minimal gas-exchange abnormalities. Chest x-rays appear normal, but inspiratory and expiratory high-resolution CT scans may show inhomogeneity in aeration,” said Dr. Kreiss. In cases like this, “it’s important to talk to an expert chest pathologist before biopsy,” she recommended. “Tissue samples require special elastin stains and sectioning techniques that follow airways down to the smallest levels to demonstrate CBO.”

“We’re dealing with something new: Permanent airway effects are associated with a substance that’s never been described as harmful,” Dr. Kreiss remarked. So far, NIOSH has noted “clusters of disease involved with manufacturing and using flavoring agents,” she said. “We know of four plants where cases of CBO have occurred. At one, … fixed airway obstruction was associated with exposure to butter flavoring.”

Therefore, “workers exposed to volatile flavorings should be protected with engineering controls and respirators and followed with serial spirometry for early identification of airways obstruction,” Dr. Kreiss recommended. She added, “If someone suspects a case associated with exposure to flavorings, it’s important to report it to NIOSH—this information can help us to identify hazards.”

—Mimi Zucker, PhD

Reference
1. Gomaa A, Kullmari G, Fedan K, et al. NIOSH Investigation of Gilster Mary Lee HETA#2000-0401 Technical Assistance to Missouri Department of Health. NIOSH Interim Report, August 25, 2001, available from Dr. Kreiss, National Institute of Occupational Safety and Health, Morgantown, WV.

Return to table of contents